Japan
MED-2513
Insights into the beneficial effect of caloric/ dietary restriction for a healthy and prolonged life
Over the last several years, new evidence has kept pouring in about the remarkable effect of caloric restriction (CR) on the conspicuous bedfellows- aging and cancer. Through the use of various animal models, it is now well established that by reducing calorie intake one can not only increase life span but, also, lower the risk of various age related diseases such as cancer. Cancer cells are believed to be more dependent on glycolysis for their energy requirements than normal cells and, therefore, can be easily targeted by alteration in the energy-metabolic pathways, a hallmark of CR. Apart from inhibiting the growth of transplantable tumors, CR has been also shown to inhibit the development of spontaneous, radiation, and chemically induced tumors. The question regarding the potentiality of the anti-tumor effect of CR in humans has been in part answered by the resistance of a cohort of women, who had suffered from anorexia in their early life, to breast cancer. However, human research on the beneficial effect of CR is still at an early stage and needs further validation. Though the complete mechanism of the anti-tumor effect of CR is far from clear, the plausible involvement of nutrient sensing pathways or IGF-1 pathways proposed for its anti-aging action cannot be overruled. In fact, cancer cell lines, mutant for proteins involved in IGF-1 pathways, failed to respond to CR. In addition, CR decreases the levels of many growth factors, anabolic hormones, inflammatory cytokines, and oxidative markers that are deregulated in several cancers. In this review, we discuss the anti-tumor effect of CR, describing experiments done in vitro in tumor models and in vivo in mouse models in which the tumor was induced by means of radiation or chemical exposure, expressing oncogenes or deleting tumor suppression genes. We also discuss the proposed mechanisms of CR anti-tumor action. Lastly, we argue the necessity of gene expression studies in cancerous versus normal cells upon CR.
MED-2502
Macronutrient balance and lifespan
Dietary restriction (DR) without malnutrition is widely regarded to be a universal mechanism for prolonging lifespan. It is generally believed that the benefits of DR arise from eating fewer calories (termed caloric restriction, CR). Here we argue that, rather than calories, the key determinant of the relationship between diet and longevity is the balance of protein to non-protein energy ingested. This ratio affects not only lifespan, but also total energy intake, metabolism, immunity and the likelihood of developing obesity and associated metabolic disorders. Among various possible mechanisms linking macronutrient balance to lifespan, the nexus between the TOR and AMPK signaling pathways is emerging as a central coordinator.
MED-2498
Dietary Restriction, Growth Factors and Aging: from yeast to humans
Dietary restriction (DR) and reduced growth factor signaling both elevate resistance to oxidative stress, reduce macromolecular damage, and increase lifespan in model organisms. In rodents, both DR and decreased growth factor signaling reduce the incidence of tumors and slow down cognitive decline and aging. DR reduces cancer and cardiovascular disease and mortality in monkeys, and reduces metabolic traits associated with diabetes, cardiovascular disease and cancer in humans. Neoplasias and diabetes are also rare in humans with loss of function mutations in the growth hormone receptor. DR and reduced growth factor signaling may thus slow aging by similar, evolutionarily conserved, mechanisms. We review these conserved anti-aging pathways in model organisms, discuss their link to disease prevention in mammals, and consider the negative side effects that might hinder interventions intended to extend healthy lifespan in humans.
MED-2504
Nutrient control of TORC1, a cell-cycle regulator.
It is well established that the target of rapamycin (TOR) protein kinase has pivotal roles in controlling cell functions (including protein synthesis, cell growth and cell proliferation) and is implicated in numerous human diseases. Mammalian TOR complex 1 (mTORC1) signalling is activated by hormones and growth factors, and is also stimulated by intracellular amino acids. Recent research has provided important new insight into the poorly understood mechanism by which amino acids activate mTORC1 signalling, showing that the protein kinase MAP4K3 and Rag GTPases have important roles in this. mTORC1 is known to control the G1/S transition of the cell cycle: new data show that (m)TORC1 also controls G2/M progression in yeast and mammals, albeit in contrasting ways.
MED-2505
Ten years of life: Is it a matter of choice?
BACKGROUND: Relative risk estimates suggest that effective implementation of behaviors commonly advocated in preventive medicine should increase life expectancy, although there is little direct evidence. OBJECTIVE: To test the hypothesis that choices regarding diet, exercise, and smoking influence life expectancy. METHODS: A total of 34 192 California Seventh-Day Adventists (75% of those eligible) were enrolled in a cohort and followed up from 1976 to 1988. A mailed questionnaire provided dietary and other exposure information at study baseline. Mortality for all subjects was ascertained by matching to state death tapes and the National Death Index. RESULTS: California Adventists have higher life expectancies at the age of 30 years than other white Californians by 7.28 years (95% confidence interval, 6.59-7.97 years) in men and by 4.42 years (95% confidence interval, 3.96-4.88 years) in women, giving them perhaps the highest life expectancy of any formally described population. Commonly observed combinations of diet, exercise, body mass index, past smoking habits, and hormone replacement therapy (in women) can account for differences of up to 10 years of life expectancy among Adventists. A comparison of life expectancy when these factors take high-risk compared with low-risk values shows independent effects that vary between 1.06 and 2.74 years for different variables. The effect of each variable is assessed with all others at either medium- or high-risk levels. CONCLUSIONS: Choices regarding diet, exercise, cigarette smoking, body weight, and hormone replacement therapy, in combination, appear to change life expectancy by many years. The longevity experience of Adventists probably demonstrates the beneficial effects of more optimal behaviors.
MED-2507
mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein ...
Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of "weak" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the "weak" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.
MED-5239
Leucine signaling in the pathogenesis of type 2 diabetes and obesity
Epidemiological evidence points to increased dairy and meat consumption, staples of the Western diet, as major risk factors for the development of type 2 diabetes (T2D). This paper presents a new concept and comprehensive review of leucine-mediated cell signaling explaining the pathogenesis of T2D and obesity by leucine-induced over-stimulation of mammalian target of rapamycin complex 1 (mTORC1). mTORC1, a pivotal nutrient-sensitive kinase, promotes growth and cell proliferation in response to glucose, energy, growth factors and amino acids. Dairy proteins and meat stimulate insulin/insulin-like growth factor 1 signaling and provide high amounts of leucine, a primary and independent stimulator for mTORC1 activation. The downstream target of mTORC1, the kinase S6K1, induces insulin resistance by phosphorylation of insulin receptor substrate-1, thereby increasing the metabolic burden of β-cells. Moreover, leucine-mediated mTORC1-S6K1-signaling plays an important role in adipogenesis, thus increasing the risk of obesity-mediated insulin resistance. High consumption of leucine-rich proteins explains exaggerated mTORC1-dependent insulin secretion, increased β-cell growth and β-cell proliferation promoting an early onset of replicative β-cell senescence with subsequent β-cell apoptosis. Disturbances of β-cell mass regulation with increased β-cell proliferation and apoptosis as well as insulin resistance are hallmarks of T2D, which are all associated with hyperactivation of mTORC1. In contrast, the anti-diabetic drug metformin antagonizes leucine-mediated mTORC1 signaling. Plant-derived polyphenols and flavonoids are identified as natural inhibitors of mTORC1 and exert anti-diabetic and anti-obesity effects. Furthermore, bariatric surgery in obesity reduces increased plasma levels of leucine and other branched-chain amino acids. Attenuation of leucine-mediated mTORC1 signaling by defining appropriate upper limits of the daily intake of leucine-rich animal and dairy proteins may offer a great chance for the prevention of T2D and obesity, as well as other epidemic diseases of civilization with increased mTORC1 signaling, especially cancer and neurodegenerative diseases, which are frequently associated with T2D.
MED-2509
Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR
DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.
MED-2519
Caloric restriction in humans: potential pitfalls and health concerns.
To date, the only intervention that has consistently been shown to slow the rate of aging, and to increase mean and maximum lifespan in short-lived species, is life-long calorie restriction. It is yet unclear whether long-term calorie restriction in longer lived species (i.e. primates and humans) will have a similar effect. In humans, several studies investigating short-term calorie restriction or "weight loss" programs suggest beneficial outcomes on parameters of cardiovascular disease. Studies on long-term calorie restriction are performed on a self-selected group of human subjects and show similar effects. However, few studies are currently investigating the quality of life and potential pitfalls of long-term calorie restriction in humans. It is likely that some of the physiological and psychological effects of caloric restriction that occur in animals may impact the human life very differently. For certain, calorie restriction has a plethora of health benefits in mammals, such as a reduction in age-related diseases such as cancer. However, despite the "magic" of CR, this intervention in humans may present itself with a number of health concerns, which may not be applicable to or impact the life of experimental animals, but may do so in humans. These potential pitfalls and "side effects" are not clearly addressed in the literature and will be a focus of this review.
MED-2510
Comparative and meta-analytic insights into life extension via dietary restriction.
Dietary restriction (DR) extends the lifespan of a wide range of species, although the universality of this effect has never been quantitatively examined. Here, we report the first comprehensive comparative meta-analysis of DR across studies and species. Overall, DR significantly increased lifespan, but this effect is modulated by several factors. In general, DR has less effect in extending lifespan in males and also in non-model organisms. Surprisingly, the proportion of protein intake was more important for life extension via DR than the degree of caloric restriction. Furthermore, we show that reduction in both age-dependent and age-independent mortality rates drives life extension by DR among the well-studied laboratory model species (yeast, nematode worms, fruit flies and rodents). Our results suggest that convergent adaptation to laboratory conditions better explains the observed DR-longevity relationship than evolutionary conservation although alternative explanations are possible. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
MED-2511
The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load.
Residents of Okinawa, the southernmost prefecture of Japan, are known for their long average life expectancy, high numbers of centenarians, and accompanying low risk of age-associated diseases. Much of the longevity advantage in Okinawa is thought to be related to a healthy lifestyle, particularly the traditional diet, which is low in calories yet nutritionally dense, especially with regard to phytonutrients in the form of antioxidants and flavonoids. Research suggests that diets associated with a reduced risk of chronic diseases are similar to the traditional Okinawan diet, that is, vegetable and fruit heavy (therefore phytonutrient and antioxidant rich) but reduced in meat, refined grains, saturated fat, sugar, salt, and full-fat dairy products. Many of the characteristics of the diet in Okinawa are shared with other healthy dietary patterns, such as the traditional Mediterranean diet or the modern DASH (Dietary Approaches to Stop Hypertension) diet. Features such as the low levels of saturated fat, high antioxidant intake, and low glycemic load in these diets are likely contributing to a decreased risk for cardiovascular disease, some cancers, and other chronic diseases through multiple mechanisms, including reduced oxidative stress. A comparison of the nutrient profiles of the three dietary patterns shows that the traditional Okinawan diet is the lowest in fat intake, particularly in terms of saturated fat, and highest in carbohydrate intake, in keeping with the very high intake of antioxidant-rich yet calorie-poor orange-yellow root vegetables, such as sweet potatoes, and green leafy vegetables. Deeper analyses of the individual components of the Okinawan diet reveal that many of the traditional foods, herbs, or spices consumed on a regular basis could be labeled "functional foods" and, indeed, are currently being explored for their potential health-enhancing properties.
MED-2644
p-Nonyl-phenol: an estrogenic xenobiotic released from "modified" polystyrene.
Alkylphenols are widely used as plastic additives and surfactants. We report the identification of an alkylphenol, nonylphenol, as an estrogenic substance released from plastic centrifuge tubes. This compound was extracted with methanol, purified by flash chromatography and reverse-phase high performance liquid chromatography, and identified by gas chromatography-mass spectrometry. Nonylphenol induced both cell proliferation and progesterone receptor in human estrogen-sensitive MCF7 breast tumor cells. Nonylphenol also triggered mitotic activity in rat endometrium; this result confirms the reliability of the MCF7 cell proliferation bioassay. The estrogenic properties of alkylphenols, specifically nonylphenols, indicate that the use of plasticware containing these chemicals in experimental and diagnostic tests may lead to spurious results, and these compounds as well as alkylphenol polyethoxylates may also be potentially harmful to exposed humans and the environment at large.
MED-2646
Do fast foods cause asthma, rhinoconjunctivitis and eczema? Global findings from the International Study of Asthma and Allergies in Childhood (ISAA...
BACKGROUND: Certain foods may increase or decrease the risk of developing asthma, rhinoconjunctivitis and eczema. We explored the impact of the intake of types of food on these diseases in Phase Three of the International Study of Asthma and Allergies in Childhood. METHODS: Written questionnaires on the symptom prevalence of asthma, rhinoconjunctivitis and eczema and types and frequency of food intake over the past 12 months were completed by 13-14-year-old adolescents and by the parents/guardians of 6-7-year-old children. Prevalence ORs were estimated using logistic regression, adjusting for confounders, and using a random (mixed) effects model. RESULTS: For adolescents and children, a potential protective effect on severe asthma was associated with consumption of fruit ≥3 times per week (OR 0.89, 95% CI 0.82 to 0.97; OR 0.86, 95% CI 0.76 to 0.97, respectively). An increased risk of severe asthma in adolescents and children was associated with the consumption of fast food ≥3 times per week (OR 1.39, 95% CI 1.30 to 1.49; OR 1.27, 95% CI 1.13 to 1.42, respectively), as well as an increased risk of severe rhinoconjunctivitis and severe eczema. Similar patterns for both ages were observed for regional analyses, and were consistent with gender and affluence categories and with current symptoms of all three conditions. CONCLUSIONS: If the association between fast foods and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is causal, then the findings have major public health significance owing to the rising consumption of fast foods globally.
MED-2651
Alkylphenols in human milk and their relations to dietary habits in central Taiwan.
The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.
MED-118
Alkylphenols in human milk and their relations to dietary habits in central Taiwan.
The aims of this study were to determine the concentrations of 4-nonylphenol (NP) and 4-octylphenol (OP) in 59 human milk samples and to examine related factors including mothers' demographics and dietary habits. Women who consumed over the median amount of cooking oil had significantly higher OP concentrations (0.98 ng/g) than those who consumed less (0.39 ng/g) (P < 0.05). OP concentration was significantly associated with the consumption of cooking oil (beta = 0.62, P < 0.01) and fish oil capsules (beta = 0.39, P < 0.01) after adjustment for age and body mass index (BMI). NP concentration was also significantly associated with the consumption of fish oil capsules (beta = 0.38, P < 0.01) and processed fish products (beta = 0.59, P < 0.01). The food pattern of cooking oil and processed meat products from factor analysis was strongly associated with OP concentration in human milk (P < 0.05). These determinations should aid in suggesting foods for consumption by nursing mothers in order to protect their infants from NP/OP exposure. 2010 Elsevier Ltd. All rights reserved.
MED-2652
Xeno-estrogenic compounds in precipitation.
The exposure to some chemicals can lead to hormone disrupting effects. Presently, much attention is focused on so-called xeno-estrogens, synthetic compounds that interact with hormone receptors causing a number of reactions that eventually lead to effects related to reproduction and development. The current study was initiated to investigate the presence of a number of such compounds in precipitation as a follow-up on a previous study in which pesticide concentrations in air and precipitation were determined. Rainwater samples were collected at about 50 locations in The Netherlands in a four week period. The samples were analysed for bisphenol-A, alkylphenols and alkylphenol ethoxylates, phthalates, flame retardants and synthetic musk compounds. The results clearly indicated the presence of these compounds in precipitation. The concentrations ranged from the low ng l(-1) range for flame retardants to several thousands of ng l(-1) for the phthalates. Bisphenol-A was found in 30% of the samples in concentrations up to 130 ng l(-1), while alkylphenols and alkylphenol ethoxylates were found in virtually all locations in concentrations up to 920 ng l(-1) for the individual compounds. Phthalates were by far the most abundant xeno-estrogens in the precipitation samples and were found in every sample. Di-isodecyl phthalate was found in a surprisingly high concentration of almost 100 000 ng l(-1). Polybrominated flame retardants were found in the low ng l(-1) range and generally in less than 20% of the samples. Noticeable was the finding of hexabromocyclododecane, a replacement for the polybrominted diphenyl ethers at one location in a concentration of almost 2000 ng l(-1). Finally, as expected, synthetic musk compounds were detected in almost all samples. This is especially true for the polycyclic musks HHCB and AHTN. Nitro musks were found, but only on a few locations. Kriging techniques were used to calculate precipitation concentrations in between actual sampling locations to produce contour plots for a number of compounds. These plots clearly show located emission sources for a number of compounds such as bisphenol-A, nonylphenol ethoxylate, phthalates and AHTN. On the contrary, the results for HHCB and some phthalates indicated diffuse emission patterns, probably as the result of the use of consumer products containing these compounds.
MED-2653
Nonylphenol and octylphenol in human breast milk.
Human milk is the most important form of nourishment for newborn children. Its consumption is strongly recommended by health authorities also for other important advantages. Unfortunately, in the last three decades a great number of investigations have shown the occurrence of several environmental contaminants in human milk, especially those with lipophilic properties. This study investigates the presence of nonylphenol, octylphenol (OP), nonylphenol monoethoxylate (NP1EO) and two octylphenol ethoxylates (OPEOs) (namely OP1EO and OP2EO), in human breast milk of Italian women. NP was the contaminant found at the highest levels with mean concentrations of 32 ng/mL, about two orders of magnitude higher than OP (0.08 ng/mL), OP1EO (0.07 ng/mL) and OP2EO (0.16 ng/mL). In the group of study a positive correlation among fish consumption and levels of NP in the milk was observed, in accordance with the evidence that seafood represents one of the most important sources of exposure to this group of contaminants in Italy. On the basis of the concentrations found in the breast milk samples, a maximum NP daily intake of 3.94 microg/kg/day can be calculated, which is close to the Tolerable Daily Intake (TDI) of 5 microg/kg body weight (bw) proposed by the Danish Institute of Safety and Toxicology. In the cases of OP no TDI is available, but its intake is at least six orders of magnitude lower than the NOAEL of 10 mg/kg/day derived from a two generation study on rats.
MED-2655
Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial
Background Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations. Aims To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association. Methods A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV1)) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period. Results Participants with little or no genistein intake had a lower baseline FEV1 than those with a moderate or high intake (2.26L vs. 2.53L and 2.47L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index. Conclusions In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.
MED-2659
European bans on surfactant trigger transatlantic debate.
U.S. and European regulators and researchers disagree over risks of a common class of surfactants.
MED-2661
Alkylphenols and alkylphenol ethoxylates contamination of crustaceans and fishes from the Adriatic Sea (Italy).
This paper presents the results of an investigation on the occurrence of alkylphenols (APs) and their ethoxylates (APEs) in 8 edible marine species from the Adriatic Sea and tries to estimate the corresponding intake for the Italian population. Two crustaceans, Nephrops norvegicus (Norway lobster) and Squilla mantis (spottail mantis shrimp), plus six fish species, Engraulis enchrascicolus (anchovy), Scomber scombrus (Atlantic mackerel), Merluccius merluccius (European hake), Mullus barbatus (red mullet), Solea vulgaris (common sole) and Lophius piscatorius (angler) were analyzed for their content of nonylphenol (NP), octylphenol (OP) and octylphenol polyethoxylates (OPEs). These compounds were found in all analysed samples. NP was detected at the highest concentrations: 118-399 and 9.5-1431 ng g(-1) fresh weight (fw) respectively in crustaceans and fish. OP was found at respective levels of 2.7-4.7 and 0.3-3.8 ng g(-1) fw in crustaceans and fish, whereas OPE was determined at respective concentrations of 1.2-16.8 and 0.2-21.1 ng g(-1) fw in the same species. These results, together with those from a previous study on 4 edible mollusc, allow to estimate respective daily intakes for NP, OP, and OPE of about 12, 0.1, and 0.1 microg day(-1) for an Italian adult living along the Adriatic Coast. In relation to NP and OP, these intakes are much lower than the doses associated with toxic effects in laboratory animals (9 mg kg(-1) bw for rats). Nevertheless, data of exposure from other sources to these chemicals and others with similar biological characteristics are needed.
MED-2662
Effects of xenoestrogenic environmental pollutants on the proliferation of a human breast cancer cell line (MCF-7).
A human breast cancer cell line (MCF-7) was used to develop an in vitro screening assay for the detection of xenoestrogenic environmental pollutants. MCF-7 cells were cultured in DMEM containing 5% fetal bovine serum (FBS). An estrogenic response was defined as an increase in the frequency of proliferating MCF-7 cells, and was measured using a thymidine analog, bromodeoxyuridine, and flow cytometry. Di-2-ethylhexyl phthalate (DEHP) and 4-n-nonylphenol (4-n-NP) were used as model chemicals. The proliferation rate of S-phase cells after 24 h of exposure to various concentrations of 17beta-estradiol and to model compounds was compared with a positive and a negative control, containing 1 nM 17beta-estradiol and 0.1% ethanol, respectively. DEHP and 4-n-NP increased the frequency of proliferating MCF-7 cells in a dose-dependent manner. The lowest concentration that significantly increased the proliferation of MCF-7 cells was 10 microM for DEHP and 1 microM for 4-n-NP. The results showed that the assay is accurate and quick to perform. It may prove a valuable tool for screening potential estrogen-mimicking environmental pollutants.
MED-4551
Maternal meat and fat consumption during pregnancy and suspected atopic eczema in Japanese infants aged 3-4 months: the Osaka Maternal and Child He...
Interest has increased in the possibility that maternal dietary intake during pregnancy might influence the development of allergic disorders in children. The present prospective study examined the association of maternal intake of selected foods high in fatty acids and specific types of fatty acids during pregnancy with the risk of suspected atopic eczema among Japanese infants aged 3-4 months. Subjects were 771 mother-child pairs. Information on maternal dietary intake during pregnancy was assessed with a validated self-administered diet history questionnaire. The term 'suspected atopic eczema' was used to define an outcome based on results of our questionnaire completed by mothers 3-4 months postpartum. The risk of suspected atopic eczema was 8.4% (n = 65). Higher maternal intake of meat during pregnancy was significantly associated with an increased risk of suspected atopic eczema in the offspring: the multivariate odds ratio (OR) for the highest vs. lowest quartile was 2.59 [95% confidence interval (CI): 1.15-6.17, p for trend = 0.01]. The positive association was strengthened when the definition of the outcome was confined to a definite physician's diagnosis of atopic eczema (n = 35): the multivariate OR between extreme quartiles was 3.53 (95% CI: 1.19-12.23, p for trend = 0.02). No material exposure-response relationships were observed between maternal intake of eggs, dairy products, fish, total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid consumption and the risk of suspected atopic eczema. Higher maternal meat intake may increase the risk of infantile atopic eczema, whereas we found no evidence that maternal intake of fish and n-3 polyunsaturated fatty acids are preventive against infantile atopic eczema. (c) 2009 John Wiley & Sons A/S
MED-2643
Endocrine-Disrupting Chemicals: Associated Disorders and Mechanisms of Action
The incidence and/or prevalence of health problems associated with endocrine-disruption have increased. Many chemicals have endocrine-disrupting properties, including bisphenol A, some organochlorines, polybrominated flame retardants, perfluorinated substances, alkylphenols, phthalates, pesticides, polycyclic aromatic hydrocarbons, alkylphenols, solvents, and some household products including some cleaning products, air fresheners, hair dyes, cosmetics, and sunscreens. Even some metals were shown to have endocrine-disrupting properties. Many observations suggesting that endocrine disruptors do contribute to cancer, diabetes, obesity, the metabolic syndrome, and infertility are listed in this paper. An overview is presented of mechanisms contributing to endocrine disruption. Endocrine disruptors can act through classical nuclear receptors, but also through estrogen-related receptors, membrane-bound estrogen-receptors, and interaction with targets in the cytosol resulting in activation of the Src/Ras/Erk pathway or modulation of nitric oxide. In addition, changes in metabolism of endogenous hormones, cross-talk between genomic and nongenomic pathways, cross talk with estrogen receptors after binding on other receptors, interference with feedback regulation and neuroendocrine cells, changes in DNA methylation or histone modifications, and genomic instability by interference with the spindle figure can play a role. Also it was found that effects of receptor activation can differ in function of the ligand.
MED-2645
Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment.
The development of the male reproductive ducts and external genitalia in vertebrates is dependent on elevated androgen concentrations during embryonic development and the period of postnatal growth. We have observed that a population of juvenile alligators living on Lake Apopka exhibit significantly smaller penis size (24% average decrease) and lower plasma concentrations of testosterone (70% lower concentrations) when compared to animals of similar size on Lake Woodruff. In addition to smaller phalli, no relationship exists between plasma testosterone concentrations and penile size in males from Lake Apopka, whereas a positive relationship exists for males from Lake Woodruff. The alligators on Lake Apopka are known to have elevated concentrations of the antiandrogenic DDT breakdown product p.p'-DDE stored in their fat. We suggest a number of hypotheses that could explain the modification in the phenotype of the juvenile male living in Lake Apopka. These modifications in phenotype include a smaller penis size, lower plasma androgen concentrations, and lack of responsiveness of the penis to the plasma androgens present.
MED-2656
Effects of intestinal microflora and the environment on the development of asthma and allergy.
The aim of previous research into the causes of allergic diseases, including asthma was mostly to identify potential risk factors in the environment. No major risk factors have been identified, however. Over the past 10 years, focus has, therefore, more been directed towards protective factors that could enhance the development of tolerance to allergens which were previously encountered early in life, but are now lost in modern affluent societies. In particular, the role of childhood infections has been discussed, but so far these studies have not been conclusive. Recent epidemiological studies and experimental research suggest that the microbial environment and exposure to microbial products in infancy modifies immune responses and enhances the development of tolerance to ubiquitous allergens. The intestinal microflora may play a particular role in this respect, as it is the major external driving force in the maturation of the immune system after birth, and animal experiments have shown it to be a prerequisite for normal development of oral tolerance. Recent studies have shown differences in the composition of the microflora between healthy and allergic infants in countries with a high and low prevalence of allergies and between healthy and allergic infants within such countries. These differences are apparent within the first week of life and thus precede clinical symptoms. The use of live microorganisms that might be beneficial to health has a long tradition and the safety is well documented. Very recently, several prospective intervention studies, modifying the gut flora from birth have yielded encouraging results and may suggest a new mode of primary prevention of allergy in the future.
MED-2657
Increasing prevalence of Japanese cedar pollinosis: a meta-regression analysis.
BACKGROUND: Japanese cedar pollinosis, caused by the pollen of the Japanese cedar tree (Cryptomeria japonica), is the commonest seasonal allergic disease in Japan. A number of epidemiological surveys have been reported on Japanese cedar pollinosis, but it has never been assessed systematically or quantitatively. To confirm the increasing prevalence of Japanese cedar pollinosis and related factors, we conducted a meta-regression analysis on population-based surveys in Japan. METHODS: We searched for data from population-based surveys in which serological methods were used to test all participants. Weighted regression of logit-transformed prevalence and sensitization rates were used to evaluate the effects of the year of survey, age, and degree of urbanization. We also analyzed the relationship between prevalence and sensitization rate. RESULTS: Thirty-eight reports with 27 subgroups for prevalence and 134 subgroups for sensitization rate were selected from the literature published in the years between 1986 and 2000. The Japanese cedar pollen sensitization rate was found to be significantly correlated with the year of survey, age, and degree of urbanization (adjusted R(2) = 0.55). The coefficient for the correlation between the prevalence and the sensitization rate revealed a statistically significant correlation (Pearson's r = 0.70, p < 0.001). CONCLUSIONS: The prevalence of Japanese cedar pollinosis among adolescents was predicted to be 28.7% in metropolitan areas and 24.5% in the general population in urban areas in the year 2004, derived from the estimated sensitization rate and the relationship between sensitization rate and prevalence. The prevalence of Japanese cedar pollinosis increased 2.6-fold between 1980 and 2000, and the prevalence differed considerably according to age and degree of urbanization. Copyright (c) 2005 S. Karger AG, Basel
MED-2658
Alkylphenols--potential modulators of the allergic response.
The prevalence of allergic diseases has increased in recent decades. Allergic diseases, particularly asthma, are complex diseases with strong gene-environment interactions. Epidemiological studies have identified a variety of risk factors for the development of allergic diseases. Among them, endocrine-disrupting chemicals (EDCs) play an important role in triggering or exacerbating these diseases. 4-Nonylphenol (NP) and 4-octylphenol (OP)--two major alkylphenols--have been recognized as common toxic and xenobiotic endocrine disrupters. Due to their low solubility, high hydrophobicity, and low estrogenic activity, they tend to accumulate in the human body and may be associated with the adverse effects of allergic diseases. Recently, new evidence has supported the importance of alkylphenols in the in vitro allergic response. This review focuses on the effects of alkylphenols on several key cell types in the context of allergic inflammation. Copyright © 2012. Published by Elsevier B.V.
MED-2660
Trends in nutritional intake and serum cholesterol levels over 40 years in Tanushimaru, Japanese men.
BACKGROUND: Rapid socioeconomic development in Japan since the beginning of the Seven Countries Study in 1958 has brought remarkable changes in lifestyle and dietary patterns. We investigated the relationship between time trends in nutrient intake and serum cholesterol levels in a Japanese cohort of the Seven Countries Study, in Tanushimaru, a typical farming town on Kyushu Island. METHODS: Subjects totaled 628 in 1958, 539 in 1977, 602 in 1982, 752 in 1989, and 402 in 1999, and all of the subjects were men aged 40-64 years. Eating patterns were evaluated by 24-hour dietary recall from 1958 through 1989, and by a food frequency questionnaire in 1999. We also measured serum cholesterol levels in each health examination. RESULTS: The total daily energy intake decreased from 2837 kcal in 1958 to 2202 kcal in 1999. The carbohydrate intake in percentage of total daily energy intake decreased markedly, from 84% in 1958 to 62% in 1999, in contrast to large increases during this period in protein intake (from 11% to 18%) and fat intake (from 5% to 20%). In proportion to the dramatic change in protein and fat intake, serum cholesterol levels showed large increases (from 152.5mg/dl to 194.2 mg/ dL). CONCLUSIONS: In spite of such big dietary changes toward a westernized diet, the incidence of coronary artery disease in a rural Japanese area remains low. However, careful surveillance is needed in the future because of the remarkably increasing intake of fats, especially saturated fatty acids.
MED-2649
Dietary meat and fat intake and prevalence of rhinoconjunctivitis in pregnant Japanese women: baseline data from the Kyushu Okinawa Maternal and Child Health Study
Background Dietary fat exerts numerous complex effects on proinflammatory and immunologic pathways. Several epidemiological studies have examined the relationships between intake of fatty acids and/or foods high in fat and allergic rhinitis, but have provided conflicting findings. The current cross-sectional study investigated such relationships in Japan. Methods Study subjects were 1745 pregnant women. The definition of rhinoconjunctivitis was based on criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age; gestation; region of residence; number of older siblings; number of children; smoking; secondhand smoke exposure at home and at work; family history of asthma, atopic eczema, and allergic rhinitis; household income; education; and body mass index. Results The prevalence of rhinoconjunctivitis in the past 12 months was 25.9%. Higher meat intake was significantly associated with an increased prevalence of rhinoconjunctivitis: the adjusted odds ratio between extreme quartiles was 1.71 (95% confidence interval: 1.25-2.35, P for trend = 0.002). No measurable association was found between fish intake and rhinoconjunctivitis. Intake of total fat, saturated fatty acids, monounsaturated fatty acids, n-3 polyunsaturated fatty acids, α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, n-6 polyunsaturated fatty acids, linoleic acid, arachidonic acid, and cholesterol and the ratio of n-3 to n-6 polyunsaturated fatty acid intake were not evidently related to the prevalence of rhinoconjunctivitis. Conclusions The current results suggest that meat intake may be positively associated with the prevalence of rhinoconjunctivitis in young adult Japanese women.
MED-2999
Western diseases and their emergence related to diet.
Many of the commonest diseases in the economically more developed communities are characteristic of modern Western culture. Evidence is presented suggesting that they represent a failure of adaptation to the dramatic changes in diet that have been associated with the emergence of modern Western culture. Dietary changes aimed at the alleviation and prevention of these diseases are discussed and recommended.
MED-2997
The Etiological Significance of Related Diseases
If disease patterns emerge which show that certain diseases can be related, this is a valuable pointer to a common cause. This article traces the principle of interpreting disease relationships, illustrated by several common conditions of western civilization, for which the common cause is postulated as being removal of fiber from the diet.
MED-2765
The value of current nutrition information.
To prevent or delay the occurrence of chronic diseases, scientific bodies from the cardiologic and oncologic disciplines have made recommendations regarding the daily dietary intake of certain macro- and micronutrients. This study assessed the knowledge of a random population of 2,305 individuals comprising members of the public, health care workers, university graduate students, and health club attendees. Segments of this population might be expected to have a greater understanding and ability to implement these dietary recommendations. We found that over 90% of the participants were unaware of the recommendations for calcium, salt, vitamin A, and fiber, and the fiber content in a high fiber cereal. Approximately 80% of the participants were unaware of the recommendations regarding fat intake and could not calculate the fat content of a food product. Almost half of the study population took a vitamin pill daily. Of the subjects who were aware of the correct unit measurement for vitamin A (IU), almost 25% of gave a response that exceeded the recommended daily intake. A majority of this study population were unaware of the dietary recommendations regarding the prevention of cardiovascular events and cancer. Subgroups of this study population that might be expected to have more information regarding these recommendations (i.e., having higher education or being a health care professional) did not display a satisfactory level of knowledge. To further compound the problems of adhering to the recommended guidelines, the labeling of many food products is misleading. The recommendations on dietary intake and the information on food product content must be transmitted to the public in a form that allows for ready application when purchasing and consuming food.
MED-3001
Towards a new system of health: the challenge of Western disease.
Over the last three decades, the concept of Western disease has become well established. Medicine has approached this group of diseases by searching for new cures but has achieved relatively little success. We argue that medicine should now accept the failure of this strategy and place a major emphasis on prevention. The key objective is to change the climate of opinion so that prevention is taken seriously by the general population. The chief activity should be a wide ranging public education campaign so as to persuade people to live a healthier lifestyle. Medicine will require restructuring in order to carry out this work. Medical education needs to be reformed so that medical students receive the necessary training. This must be done as part of an integrated approach in which government, industry and medical research all play a major role. Governments should use taxation and subsidies in areas such as food and tobacco so as to shift consumption patterns towards healthier products. Governments must also tighten laws on tobacco sales and advertising, support health education, and improve food labelling. Industry must be made far more responsive to the health needs of the population. This should be done both by public education, so as to alter demand, and by government action. Medical research should change its emphasis from studying the detailed mechanisms of disease ("complex research") to studying the role of lifestyle factors ("simple research").
MED-2769
Milk Intake in Early Life and Risk of Advanced Prostate Cancer
The authors investigated whether early-life residency in certain areas of Iceland marked by distinct differences in milk intake was associated with risk of prostate cancer in a population-based cohort of 8,894 men born between 1907 and 1935. Through linkage to cancer and mortality registers, the men were followed for prostate cancer diagnosis and mortality from study entry (in waves from 1967 to 1987) through 2009. In 2002–2006, a subgroup of 2,268 participants reported their milk intake in early, mid-, and current life. During a mean follow-up period of 24.3 years, 1,123 men were diagnosed with prostate cancer, including 371 with advanced disease (stage 3 or higher or prostate cancer death). Compared with early-life residency in the capital area, rural residency in the first 20 years of life was marginally associated with increased risk of advanced prostate cancer (hazard ratio = 1.29, 95% confidence interval (CI): 0.97, 1.73), particularly among men born before 1920 (hazard ratio = 1.64, 95% CI: 1.06, 2.56). Daily milk consumption in adolescence (vs. less than daily), but not in midlife or currently, was associated with a 3.2-fold risk of advanced prostate cancer (95% CI: 1.25, 8.28). These data suggest that frequent milk intake in adolescence increases risk of advanced prostate cancer.
MED-2770
The experience of Japan as a clue to the etiology of breast and ovarian cancers: relationship between death from both malignancies and dietary prac...
Although breast and ovarian cancers are rare in Japan compared with other developed countries, the death rates for both are increasing. In Japan, dramatic lifestyle changes occurred after World War II. Over the past 50 years (1947-1997), the age-standardized death rates of breast and ovarian cancers increased about 2- and 4-fold, respectively, and the respective intake of milk, meat, and eggs increased 20-, 10-, and 7-fold. The increase in the annual death rates from breast and ovarian cancers might be due to the lifestyle changes (increased consumption of animal-derived food) that occurred after 1945. Among the food, milk and dairy products should receive particular attention since they contain considerable amounts of estrogens.
MED-2771
Milk consumption is a risk factor for prostate cancer in Western countries: evidence from cohort studies.
We have previously found a positive association between milk consumption and prostate cancer risk using meta-analysis to analyze published case-control studies. In the present study, further meta-analysis was conducted to estimate the summary relative risk (RR) between the consumption of milk and dairy products and prostate cancer from cohort studies published between 1966- 2006. We found 18 relevant articles and 13 independent studies were available for our analysis. The summary RR was 1.13 (95% confidence interval = 1.02-1.24) when comparing the highest with the lowest quantile of consumption. The summary RRs by study stratification showed a positive association. A dose-response relationship was identified when combining the studies that partitioned the consumption by quintiles. We also evaluated the effects of some limitations, such as dairy classification, prostate cancer stages and publication bias, in the present study. These findings, together with the previous study, suggest that the consumption of milk and dairy products increases the risk of prostate cancer. This is biologically plausible since milk contains considerable amounts of fat, hormones, and calcium that are associated with prostate cancer risk.
MED-2772
Milk consumption is a risk factor for prostate cancer: meta-analysis of case-control studies.
Prostate cancer has become the most common cancer among men in the United States. Although milk consumption is considered to be a risk factor in some epidemiological studies, the results are inconsistent. A meta-analysis method was conducted to estimate the combined odds ratio (OR) between milk consumption and prostate cancer from case-control studies published between 1984 and 2003 using commercial software (comprehensive meta-analysis). The combined OR was 1.68 (95% confidence interval = 1.34-2.12) in the 11 published case-control studies. The combined OR varied little by study stratification. Additionally, we evaluated the possible risk factors in milk for prostate cancer. In conclusion, we found a positive association between milk consumption and prostate cancer. The underlying mechanisms, including fat, calcium, hormones, and other factors, should be investigated further. Copyright 2004 Lawrence Erlbaum Associates, Inc.
MED-2774
Milk stimulates growth of prostate cancer cells in culture.
Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes.
MED-2775
Incidence and mortality of testicular and prostatic cancers in relation to world dietary practices.
The incidence and mortality rates of testicular and prostatic cancers in 42 countries were correlated with the dietary practices in these countries using the cancer rates (1988-92) provided by the International Agency for Research on Cancer (IARC) and the food supply data (1961-90) provided by the Food and Agriculture Organization (FAO). Among the food items we examined, cheese was most closely correlated with the incidence of testicular cancer at ages 20-39, followed by animal fats and milk. The correlation coefficient (r) was highest (r = 0.804) when calculated for cheese consumed during the period 1961-65 (maternal or prepubertal consumption). Stepwise-multiple-regression analysis revealed that milk + cheese (1961-65) made a significant contribution to the incidence of testicular cancer (standardized regression coefficient [R] = 0.654). Concerning prostatic cancer, milk (1961-90) was most closely correlated (r = 0.711) with its incidence, followed by meat and coffee. Stepwise-multiple-regression analysis identified milk + cheese as a factor contributing to the incidence of prostatic cancer (R = 0.525). The food that was most closely correlated with the mortality rate of prostatic cancer was milk (r = 0.766), followed by coffee, cheese and animal fats. Stepwise-multiple-regression analysis revealed that milk + cheese was a factor contributing to mortality from prostatic cancer (R = 0.580). The results of our study suggest a role of milk and dairy products in the development and growth of testicular and prostatic cancers. The close correlation between cheese and testicular cancer and between milk and prostatic cancer suggests that further mechanistic studies should be undertaken concerning the development of male genital organ cancers. Copyright 2001 Wiley-Liss, Inc.
MED-2882
Blueberry anthocyanins: protection against ageing and light-induced damage in retinal pigment epithelial cells.
Retinal pigment epithelium (RPE) cells are vital for retinal health. However, they are susceptible to injury with ageing and exposure to excessive light, including UV (100-380 nm) and visible (380-760 nm) radiation. To evaluate the protective effect of blueberry anthocyanins on RPE cells, in vitro cell models of replicative senescent and light-induced damage were established in the present study. After purification and fractionation, blueberry anthocyanin extracts (BAE) were yielded with total anthocyanin contents of 31·0 (SD 0·5) % and were used in this study. Replicative senescence of RPE cells was induced by repeatedly passaging cells from the fourth passage to the tenth. From the fifth passage, cultured RPE cells began to enter a replicative senescence, exhibiting reduced cell proliferation along with an increase in the number of β-galactosidase-positive cells. RPE cells maintained high cell viability (P < 0·01) and a low (P < 0·01) percentage of β-galactosidase-positive cells when treated with 0·1 μg/ml BAE. In contrast, after exposure to 2500 (SD 500) lx light (420-800 nm) for 12 h, RPE cells in the positive control (light exposure, no BAE treatment) exhibited premature senescence, low (P < 0·01) cell viability and increased (P < 0·01) vascular endothelial growth factor (VEGF) release compared with negative control cells, which were not subjected to light irradiation and BAE exposure. Correspondingly, BAE is beneficial to RPE cells by protecting these cells against light-induced damage through the suppression of ageing and apoptosis as well as the down-regulation of the over-expressed VEGF to normal level. These results demonstrate that BAE is efficacious against senescence and light-induced damage of RPE cells.
MED-2899
Iris color and macular pigment optical density.
The present study was designed to assess the relationship between iris color and macular pigment optical density. Both melanin and carotenoids (responsible for iris color and macular pigment composition, respectively) appear to protect the retina through similar mechanisms and higher concentrations may reduce the incidence of retinal degenerations. To evaluate this relationship, 95 subjects were examined and the following variables were measured: iris color; macular pigment optical density (MP); plasma concentrations of lutein and zeaxanthin and beta-carotene; dietary intake of lutein and zeaxanthin and beta-carotene; and total fat intake. Iris color was determined by self assessment and classified as blue or gray (group I), green or hazel (group II) or brown or black (group III). MP density was measured psychophysically by measuring foveal and parafoveal sensitivities to lights of 460 and 550 nm, using the method of heterochromatic flicker photometry. Plasma carotenoid concentrations were measured using reverse-phase high-performance liquid chromatography. Dietary intake was determined by a detailed food-frequency questionnaire. Despite similarities in diet and in blood concentrations of carotenoids, significant differences in macular pigment density (P < 0.02) were found for different colored irises (group I, n = 38, MP = 0.25; group II, n = 26, MP = 0.32; group III, n = 31, MP = 0.38). The covariation of iris color and MP indicates that past epidemiologic studies have not adequately determined the independent effects of either factor. The relationship of MP and iris color may be the result of one or two factors: the evolution of a shared tendency to accumulate melanin and carotenoids due to similar environmental pressures (e.g. light and oxygen); and/or MP might be depleted due to the tendency for eyes with light irises to transmit more light than eyes with dark irises, thus causing increased oxidative stress.
MED-2894
Two-year randomized, placebo-controlled study of black currant anthocyanins on visual field in glaucoma.
AIM: To examine the influence of the black currant anthocyanins (BCACs) on the disease progression of open-angle glaucoma (OAG), a randomized, placebo-controlled, double-masked trial was made in 38 patients with OAG treated by antiglaucoma drops. METHODS: BCACs (50 mg/day, n = 19) or their placebos (n = 19) were orally administered once daily for a 24-month period. Systemic blood pressure, pulse rates, intraocular pressure (IOP), ocular blood circulation by laser-speckle flowgraphy, and Humphrey visual field mean deviation (MD) were measured during the 24-month period. RESULTS: As a main outcome measurement, we evaluated the difference between the groups in MD deterioration in the eye with a better MD from the trial's baseline through 24 months. A statistically significant difference was observed between the treatment groups in mean change from baseline in MD 24 months after therapy (p = 0.039, unpaired t test). Upon administration of BCACs, the ocular blood flows during the 24-month observational period increased in comparison with placebo-treated patients. However, no significant changes were observed in systemic and ocular conditions including IOP during the 24-month period. CONCLUSIONS: Our results suggest that oral administration of BCACs may be a safe and promising supplement for patients with OAG in addition to antiglaucoma medication. Copyright © 2012 S. Karger AG, Basel.
MED-3136
Influence of frequent and long-term bean consumption on colonic function and fermentation.
The objective of this study was to determine the influence of frequent and long-term consumption of legume seeds on colonic function. Two groups of subjects were studied--one group habitually consumed legume seeds as part of their normal diet, a second group only infrequently consumed legumes. No differences between these groups could be detected for fecal output and frequency, intestinal transit time, VFA excretion or fecal pH during 23-day study periods in which subjects consumed either their usual diet or 100 g red kidney beans, daily. However, the addition of beans to the diets of both groups provided significantly more dietary fiber, and produced greater fecal output and a higher concentration of VFA in feces. Fecal output appeared to be determined by two independent parameters--dietary fiber intake and VFA excretion. Beans provided a physiologically useful source of dietary fiber and favorably influenced colonic function.
MED-3138
Perceptions of flatulence from bean consumption among adults in 3 feeding studies
Background Many consumers avoid eating beans because they believe legume consumption will cause excessive intestinal gas or flatulence. An increasing body of research and the 2010 Dietary Guidelines for Americans supports the benefits of a plant-based diet, and legumes specifically, in the reduction of chronic disease risks. The purpose of the current research was to investigate the perception of increased flatulence and gastrointestinal discomfort among participants who consumed a ½ cup of beans daily for 8 or 12 weeks. Methods Participants in three studies to test the effects of beans on heart disease biomarkers completed the same weekly questionnaire to assess gastrointestinal discomfort issues such as increased flatulence, stool changes, and bloating. Studies 1 and 2 were randomized crossover trials. Participants consumed ½ cup of pinto beans, black-eyed peas, and canned carrots as control (n = 17) in Study 1 for three randomized 8-week phases. For Study 2, participants ate ½ cup baked beans or canned carrots as control (n = 29) for two randomized 8-week phases. Study 3 was a parallel arm trial with 40 subjects receiving ½ cup pinto beans and 40 consuming a control soup for 12 weeks. Changes in the frequency of perceived flatulence, stool characteristics, and bloating were the primary outcome measures. Chi-square distributions were examined for the presence or absence of symptoms and demographic characteristics to determine differences by gender, age, body mass index (BMI), and bean type. Results Less than 50% reported increased flatulence from eating pinto or baked beans during the first week of each trial, but only 19% had a flatulence increase with black-eyed peas. A small percentage (3-11%) reported increased flatulence across the three studies even on control diets without flatulence-producing components. Conclusions People's concerns about excessive flatulence from eating beans may be exaggerated. Public health nutritionists should address the potential for gastrointestinal discomfort when increasing fiber intake from beans with clients. It is important to recognize there is individual variation in response to different bean types.
MED-3141
A bean-free diet increases the risk of all-cause mortality among Taiwanese women: the role of the metabolic syndrome.
OBJECTIVE: To evaluate the associations with chronic disease risk and mortality of the consequences of bean-free diets in Taiwanese adults with regard to gender. DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001 agreed to physical examination in the subsequent year. This group then took part in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and 2950 women were tracked by death registry over the 6·8 years of follow-up. RESULTS: Among 38,077 person-years, an average follow-up 6·5 years, 225 all-cause deaths were identified. Generalized linear models showed beans to be favourable for metabolic syndrome (other than for fasting glucose) in men; in women, beans were favourable for waist circumference and HbA1c. Cumulative logistic regression models for the effect of a bean-free diet on metabolic syndrome scores according to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-tw) gave adjusted odds ratios of 1·83 in men and 1·45 in women. Cox regression models for the bean-free diet showed an increased hazard ratio for all-cause mortality among women (1·98, 95% CI 1·03, 3·81) but not men (1·28, 95% CI 0·76, 2·16). CONCLUSIONS: A bean-free diet may play a role in developing the metabolic syndrome in both genders, and is a significant predictor of all-cause mortality in Taiwanese women but not men.
MED-3140
Legumes: the most important dietary predictor of survival in older people of different ethnicities.
To identify protective dietary predictors amongst long-lived elderly people (N= 785), the "Food Habits in Later Life "(FHILL) study was undertaken among five cohorts in Japan, Sweden, Greece and Australia. Between 1988 and 1991, baseline data on food intakes were collected. There were 785 participants aged 70 and over that were followed up to seven years. Based on an alternative Cox Proportional Hazard model adjusted to age at enrollment (in 5-year intervals), gender and smoking, the legume food group showed 7-8% reduction in mortality hazard ratio for every 20g increase in daily intake with or without controlling for ethnicity (RR 0.92; 95% CI 0.85-0.99 and RR 0.93; 95% CI 0.87-0.99, respectively). Other food groups were not found to be consistently significant in predicting survival amongst the FHILL cohorts.
MED-3443
Could dietary seaweed reverse the metabolic syndrome?
Incidence of the metabolic syndrome is increasing worldwide, with notable exceptions of some Asian countries where seaweeds are commonly consumed. 13 men (mean age 47.4+/-9.9 yr) and 14 women (average age 45.6+/-12.2 yr) with at least one symptom of the metabolic syndrome were recruited in Quito Ecuador to a randomized double-blinded placebo-controlled trial. Subjects were assigned to either Group 1 (1 m placebo, followed by 1 m 4 g/d seaweed [Undaria pinnatifida]) or Group 2 (1 m of 4 g/d seaweed, followed by 1 m of 6 g/d of seaweed). Blood pressure, weight, waist circumference, inflammation biomarkers, and lipids were measured monthly. Repeated measures analysis of variance with Tukey's multiple comparison tests were used for statistical analysis. In Group 2, systolic blood pressure decreased 10.5 mmHg after a month of 6 g/d seaweed (95% CI: 4.1, 16.8 mmHg; p<0.05), primarily in subjects with high-normal baseline blood pressure. Waist circumference changed only for women participants, with a 2.4 cm decrease in Group 1 after treatment with placebo (95% CI: 1.0, 3.7 cm; p<0.01). In Group 2, women had a mean decrease of 2.1 cm after 4 g/d (95% CI: 0.4, 3.7 cm; p<0.05) and a further 1.8 cm decrease after 1 m 6 g/d seaweed (95 % CI: 0.1, 3.4, p<0.05). No other changes were observed. Consumption of 4 to 6 g/d seaweed, typical for most people in Japan, may be associated with low metabolic syndrome prevalence.
MED-3444
Iodine and thyroid cancer risk among women in a multiethnic population: the Bay Area Thyroid Cancer Study.
Research on the relationship between iodine exposure and thyroid cancer risk is limited, and the findings are inconclusive. In most studies, fish/shellfish consumption has been used as a proxy measure of iodine exposure. The present study extends this research by quantifying dietary iodine exposure as well as incorporating a biomarker of long-term (1 year) exposure, i.e., from toenail clippings. This study is conducted in a multiethnic population with a wide variation in thyroid cancer incidence rates and substantial diversity in exposure. Women, ages 20-74, residing in the San Francisco Bay Area and diagnosed with thyroid cancer between 1995 and 1998 (1992-1998 for Asian women) were compared with women selected from the general population via random digit dialing. Interviews were conducted in six languages with 608 cases and 558 controls. The established risk factors for thyroid cancer were found to increase risk in this population: radiation to the head/neck [odds ratio (OR), 2.3; 95% confidence interval (CI), 0.97-5.5]; history of goiter/nodules (OR, 3.7; 95% CI, 2.5-5.6); and a family history of proliferative thyroid disease (OR, 2.5; 95% CI, 1.6-3.8). Contrary to our hypothesis, increased dietary iodine, most likely related to the use of multivitamin pills, was associated with a reduced risk of papillary thyroid cancer. This risk reduction was observed in "low-risk" women (i.e., women without any of the three established risk factors noted above; OR, 0.53; 95% CI, 0.33-0.85) but not in "high-risk" women, among whom a slight elevation in risk was seen (OR, 1.4; 95% CI, 0.56-3.4). However, no association with risk was observed in either group when the biomarker of exposure was evaluated. In addition, no ethnic differences in risk were observed. The authors conclude that iodine exposure appears to have, at most, a weak effect on the risk of papillary thyroid cancer.
MED-3441
Marine edible algae as disease preventers.
As modern lifestyles and new feeding habits settle in the world, noncommunicable diseases (NCDs) have evolved to be major causes of disability in developing as well as developed countries. As a concomitant effect, there is a growing interest in natural, healthy food and an increasing awareness of risk factors and determinants of disease. This chapter describes some nutritional facts about seaweeds, which have been used as food since ancient times in China, Japan, Egypt, and India and comments on the potential utilization of marine algae as functional foods. This concept and the description of metabolic syndrome are used as a basis to comprehension of seaweeds against two dreadful illnesses of our times: high blood pressure and cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
MED-3445
An epidemiologic study of thyroid cancer in Hawaii.
A population-based case-control interview study was designed to test the hypothesis that dietary iodine or the consumption of goitrogenic vegetables increases the risk of thyroid cancer. A total of 191 histologically confirmed cases (64 percent female) and 441 matched controls from five ethnic groups in Hawaii were available for analysis. Among women, intake of seafood (especially shellfish), harm ha (a fermented fish sauce), and dietary iodine were associated with an increased risk of cancer, whereas consumption of goitrogenic (primarily cruciferous) vegetables was associated with a decreased risk. Non-dietary risk factors included miscarriage (especially at first pregnancy), use of fertility drugs, family history of thyroid disease, obesity, and work as a farm laborer. The odds ratio for the combined effect of a high iodine intake and a first-pregnancy miscarriage was 4.8 (95 percent confidence interval [CI] = 1.2-19.2); and for high iodine intake and use of fertility drugs 7.3 (95 percent CI = 1.5-34.5). Among men, positive associations were found for obesity, work as a farm laborer, and a past history of benign thyroid disease. Although this study identified several dietary and non-dietary risk factors for thyroid cancer, it could not fully explain the exceptionally high incidence rates among Filipino women in Hawaii.
MED-3446
Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women.
Seaweed and soy foods are consumed daily in Japan, where breast cancer rates for postmenopausal women are significantly lower than in the West. Likely mechanisms include differences in diet, especially soy consumption, and estrogen metabolism. Fifteen healthy postmenopausal women participated in this double-blind trial of seaweed supplementation with soy challenge. Participants were randomized to 7 wk of either 5 g/d seaweed (Alaria) or placebo (maltodextrin). During wk 7, participants also consumed a daily soy protein isolate (2 mg isoflavones/kg body weight). After a 3-wk washout period, participants were crossed over to the alternate supplement schedule. There was an inverse correlation between seaweed dose (mg/kg body weight) and serum estradiol (E2) (seaweed-placebo = y = -2.29 x dose + 172.3; r = -0.70; P = 0.003), [corrected] which was linear across the range of weights. Soy supplementation increased urinary daidzein, glycitein, genistein, and O-desmethylangolensin (P = 0.0001) and decreased matairesinol and enterolactone (P < 0.05). Soy and seaweed plus soy (SeaSoy) increased urinary excretion of 2-hydroxyestrogen (2-OHE) (P = 0.0001) and the ratio of 2-OHE:16alpha-hydroxyestrone (16alphaOHE(1)) (P = 0.01). For the 5 equol excretors, soy increased urinary equol excretion (P = 0.0001); the combination of SeaSoy further increased equol excretion by 58% (P = 0.0001). Equol producers also had a 315% increase in 2:16 ratio (P = 0.001) with SeaSoy. Seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria.
MED-3442
A case-control study on seaweed consumption and the risk of breast cancer.
Gim (Porphyra sp.) and miyeok (Undaria pinnatifida) are the seaweeds most consumed by Koreans. We investigated the association between the intake of gim and miyeok and the risk of breast cancer in a case-control study. Cases were 362 women aged 30-65 years old, who were histologically confirmed to have breast cancer. Controls visiting the same hospital were matched to cases according to their age (sd 2 years) and menopausal status. Food intake was estimated by the quantitative FFQ with 121 items, including gim and miyeok. Conditional logistic regression analysis was used to obtain the OR and corresponding 95 % CI. The average intake and consumption frequency of gim in cases were lower than in controls. The daily intake of gim was inversely associated with the risk of breast cancer (5th v. 1st quintile, OR, 0.48; 95 % CI, 0.27, 0.86; P for trend, 0.026) after adjustment for potential confounders. After stratification analysis was performed according to menopausal status, premenopausal women (5th v. 1st quintile, OR, 0.44; 95 % CI, 0.24, 0.80; P for trend, 0.007) and postmenopausal women (5th v. 1st quintile, OR, 0.32; 95 % CI, 0.13, 0.80; P for trend, 0.06) showed similar inverse associations between gim intake and the risk of breast cancer after an adjustment for potential confounders except dietary factors. Miyeok consumption did not have any significant associations with breast cancer. These results suggest that high intake of gim may decrease the risk of breast cancer.
MED-3447
Seaweed prevents breast cancer?
To investigate the chemopreventive effects of seaweed on breast cancer, we have been studying the relationship between iodine and breast cancer. We found earlier that the seaweed, wakame, showed a suppressive effect on the proliferation of DMBA (dimethylbenz(a)anthracene)-induced rat mammary tumors, possibly via apoptosis induction. In the present study, powdered mekabu was placed in distilled water, and left to stand for 24 h at 4 degrees C. The filtered supernatant was used as mekabu solution. It showed an extremely strong suppressive effect on rat mammary carcinogenesis when used in daily drinking water, without toxicity. In vitro, mekabu solution strongly induced apoptosis in 3 kinds of human breast cancer cells. These effects were stronger than those of a chemotherapeutic agent widely used to treat human breast cancer. Furthermore, no apoptosis induction was observed in normal human mammary cells. In Japan, mekabu is widely consumed as a safe, inexpensive food. Our results suggest that mekabu has potential for chemoprevention of human breast cancer.
MED-3448
Seaweed consumption and the risk of thyroid cancer in women: the Japan Public Health Center-based Prospective Study.
Iodine is a suspected risk factor for thyroid cancer. Seaweed accounts for about 80% of Japanese people's iodine intake. We examined the association between seaweed consumption and the risk of thyroid cancer in Japanese women. Women participating in the Japan Public Health Center-based Prospective Study (n=52 679; age: 40-69 years) were followed up for a mean of 14.5 years; 134 new thyroid cancer cases, including 113 papillary carcinoma cases, were identified. Seaweed consumption was assessed using a food-frequency questionnaire and divided into three categories: 2 days/week or less (reference); 3-4 days/week; and almost daily. The Cox proportional hazards model was applied to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Seaweed consumption was clearly associated with an increased risk of papillary carcinoma (HR for almost daily consumption compared with 2 days/week or less=1.71; 95% CI: 1.01-2.90; trend P=0.04). After stratification for menopausal status, an increased risk was observed in postmenopausal women (papillary carcinoma HR for almost daily consumption compared with 2 days/week or less=3.81, 95% CI: 1.67-8.68; trend P<0.01), but not in premenopausal women (HR=0.91, 95% CI: 0.44-1.91; trend P=0.76). This study identified a positive association between seaweed consumption and the risk of thyroid cancer (especially for papillary carcinoma) in postmenopausal women.
MED-1318
Rice consumption is not associated with risk of cardiovascular disease morbidity or mortality in Japanese men and women: a large population-based, ...
BACKGROUND: Rice consumption has been associated with risk of type 2 diabetes, but its relation with cardiovascular disease (CVD) is limited. OBJECTIVE: We examined the association between rice consumption and risk of CVD incidence and mortality in a Japanese population. DESIGN: This was a prospective study in 91,223 Japanese men and women aged 40-69 y in whom rice consumption was determined and updated from 3 self-administered food-frequency questionnaires, each 5 y apart. Follow-up for incidence was from 1990 to 2009 in cohort I and 1993 to 2007 in cohort II and for mortality was from 1990 to 2009 in cohort I and 1993 to 2009 in cohort II. HRs and 95% CIs of CVD incidence and mortality were calculated according to quintiles of cumulative average rice consumption. RESULTS: In 15-18 y of follow-up, we ascertained 4395 incident cases of stroke, 1088 incident cases of ischemic heart disease (IHD), and 2705 deaths from CVD. Rice consumption was not associated with risk of incident stroke or IHD; the multivariable HR (95% CI) in the highest compared with lowest rice consumption quintiles was 1.01 (0.90, 1.14) for total stroke and 1.08 (0.84, 1.38) for IHD. Similarly, there was no association between rice consumption and risk of mortality from CVD; the HR (95% CI) for mortality from total CVD was 0.97 (0.84, 1.13). There were no interactions with sex or effect modifications by body mass index for any endpoint. CONCLUSION: Rice consumption is not associated with risk of CVD morbidity or mortality. © 2014 American Society for Nutrition.
MED-1319
Diet and chronic degenerative diseases: perspectives from China.
A comprehensive ecologic survey of dietary, life-style, and mortality characteristics of 65 counties in rural China showed that diets are substantially richer in foods of plant origin when compared with diets consumed in the more industrialized, Western societies. Mean intakes of animal protein (about one-tenth of the mean intake in the United States as energy percent), total fat (14.5% of energy), and dietary fiber (33.3 g/d) reflected a substantial preference for foods of plant origin. Mean plasma cholesterol concentration, at approximately 3.23-3.49 mmol/L, corresponds to this dietary life-style. The principal hypothesis under investigation in this paper is that chronic degenerative diseases are prevented by an aggregate effect of nutrients and nutrient-intake amounts that are commonly supplied by foods of plant origin. The breadth and consistency of evidence for this hypothesis was investigated with multiple intake-biomarker-disease associations, which were appropriately adjusted. There appears to be no threshold of plant-food enrichment or minimization of fat intake beyond which further disease prevention does not occur. These findings suggest that even small intakes of foods of animal origin are associated with significant increases in plasma cholesterol concentrations, which are associated, in turn, with significant increases in chronic degenerative disease mortality rates.
MED-1320
White Rice, Brown Rice, and Risk of Type 2 Diabetes in US Men and Women
Context Because of a different degree of processing and nutrient contents, brown rice and white rice may have different effects on risk of type 2 diabetes. Objective To prospectively examine white rice and brown rice consumptions in relation to type 2 diabetes risk in US men and women aged 26–87 yr. Design and Setting The Health Professionals Follow-up Study (1986–2006) and the Nurses’ Health Study I (1984–2006) and II (1991–2005). Participants We prospectively ascertained diet, lifestyle practices, and disease status among 39,765 men and 157,463 women in these cohorts. All participants were free of diabetes, cardiovascular disease, and cancer at baseline. Intake of white rice, brown rice, other foods, and nutrients was assessed at baseline and updated every 2–4 years. Results During 3,318,196 person-years of follow-up, we documented 10,507 incident cases of type 2 diabetes. After multivariate adjustment for age and other lifestyle and dietary risk factors, higher intake of white rice was associated with a higher risk of type 2 diabetes. The pooled relative risk (95% confidence interval) of type 2 diabetes comparing ≥5 servings/week with <1 serving/month of white rice was 1.17 (1.02, 1.36). In contrast, high brown rice intake was associated with a lower risk of type 2 diabetes: The pooled multivariate relative risk (95% confidence interval) was 0.89 (0.81, 0.97) for ≥ 2 servings/week of brown rice as compared with <1 serving/month. We estimated that replacing 50 grams/day (cooked, equivalent to ⅓ serving/day) intake of white rice with the same amount of brown rice was associated with a 16% (95% confidence interval: 9%, 21%) lower risk of type 2 diabetes, whereas the same replacement with whole grains as a group was associated with a 36% (95% confidence interval: 30%, 42%) lower diabetes risk. Conclusions Substitution of whole grains, including brown rice, for white rice may lower risk of type 2 diabetes. These data support the recommendation that most carbohydrate intake should come from whole grains rather than refined grains to facilitate the prevention of type 2 diabetes.
MED-1321
Phospholipids in rice: significance in grain quality and health benefits: a review.
Phospholipids (PLs) are a major class of lipid in rice grain. Although PLs are only a minor nutrient compared to starch and protein, they may have both nutritional and functional significance. We have systemically reviewed the literature on the class, distribution and variation of PLs in rice, their relation to rice end-use quality and human health, as well as available methods for analytical profiling. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and their lyso forms are the major PLs in rice. The deterioration of PC in rice bran during storage was considered as a trigger for the degradation of rice lipids with associated rancid flavour in paddy and brown rice. The lyso forms in rice endosperm represent the major starch lipid, and may form inclusion complexes with amylose, affecting the physicochemical properties and digestibility of starch, and hence its cooking and eating quality. Dietary PLs have a positive impact on several human diseases and reduce the side-effects of some drugs. As rice has long been consumed as a staple food in many Asian countries, rice PLs may have significant health benefits for those populations. Rice PLs may be influenced both by genetic (G) and environmental (E) factors, and resolving G×E interactions may allow future exploitation of PL composition and content, thus boosting rice eating quality and health benefits for consumers. We have identified and summarised the different methods used for rice PL analysis, and discussed the consequences of variation in reported PL values due to inconsistencies between methods. This review enhances the understanding of the nature and importance of PLs in rice and outlines potential approaches for manipulating PLs to improve the quality of rice grain and other cereals. Copyright © 2013 Elsevier Ltd. All rights reserved.
MED-1322
Whole grain and refined grain consumption and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of cohort studies.
Several studies have suggested a protective effect of intake of whole grains, but not refined grains on type 2 diabetes risk, but the dose-response relationship between different types of grains and type 2 diabetes has not been established. We conducted a systematic review and meta-analysis of prospective studies of grain intake and type 2 diabetes. We searched the PubMed database for studies of grain intake and risk of type 2 diabetes, up to June 5th, 2013. Summary relative risks were calculated using a random effects model. Sixteen cohort studies were included in the analyses. The summary relative risk per 3 servings per day was 0.68 (95% CI 0.58-0.81, I(2) = 82%, n = 10) for whole grains and 0.95 (95% CI 0.88-1.04, I(2) = 53%, n = 6) for refined grains. A nonlinear association was observed for whole grains, p nonlinearity < 0.0001, but not for refined grains, p nonlinearity = 0.10. Inverse associations were observed for subtypes of whole grains including whole grain bread, whole grain cereals, wheat bran and brown rice, but these results were based on few studies, while white rice was associated with increased risk. Our meta-analysis suggests that a high whole grain intake, but not refined grains, is associated with reduced type 2 diabetes risk. However, a positive association with intake of white rice and inverse associations between several specific types of whole grains and type 2 diabetes warrant further investigations. Our results support public health recommendations to replace refined grains with whole grains and suggest that at least two servings of whole grains per day should be consumed to reduce type 2 diabetes risk.
MED-1323
Low-carbohydrate diet scores and risk of type 2 diabetes in men
Background: Fat and protein sources may influence whether low-carbohydrate diets are associated with type 2 diabetes (T2D). Objective: The objective was to compare the associations of 3 low-carbohydrate diet scores with incident T2D. Design: A prospective cohort study was conducted in participants from the Health Professionals Follow-Up Study who were free of T2D, cardiovascular disease, or cancer at baseline (n = 40,475) for up to 20 y. Cumulative averages of 3 low-carbohydrate diet scores (high total protein and fat, high animal protein and fat, and high vegetable protein and fat) were calculated every 4 y from food-frequency questionnaires and were associated with incident T2D by using Cox models. Results: We documented 2689 cases of T2D during follow-up. After adjustments for age, smoking, physical activity, coffee intake, alcohol intake, family history of T2D, total energy intake, and body mass index, the score for high animal protein and fat was associated with an increased risk of T2D [top compared with bottom quintile; hazard ratio (HR): 1.37; 95% CI: 1.20, 1.58; P for trend < 0.01]. Adjustment for red and processed meat attenuated this association (HR: 1.11; 95% CI: 0.95, 1.30; P for trend = 0.20). A high score for vegetable protein and fat was not significantly associated with the risk of T2D overall but was inversely associated with T2D in men aged <65 y (HR: 0.78; 95% CI: 0.66, 0.92; P for trend = 0.01, P for interaction = 0.01). Conclusions: A score representing a low-carbohydrate diet high in animal protein and fat was positively associated with the risk of T2D in men. Low-carbohydrate diets should obtain protein and fat from foods other than red and processed meat.
MED-1324
Differential effect of protein and fat ingestion on blood glucose responses to high- and low-glycemic-index carbohydrates in noninsulin-dependent d...
Six noninsulin-dependent diabetic subjects received meals containing 25 g carbohydrate either as potato or as spaghetti. The meals were repeated with the addition of 25 g protein and with 25 g protein and 25 g fat. Blood glucose and insulin responses were measured for 4 h after the test meal. When carbohydrate was given alone, the blood glucose and serum insulin increments were higher for the potato meal. The addition of protein increased the insulin responses to both carbohydrates and slightly reduced the glycemic response to mashed potato (F = 2.04, p less than 0.05). The further addition of fat reduced the glycemic response to mashed potato (F = 14.63, p less than 0.001) without any change in the blood glucose response to spaghetti (F = 0.94, NS). The different responses to coingestion of protein and fat reduced the difference between the glycemic responses to the two carbohydrates.
MED-1612
Effect of protein ingestion on the glucose and insulin response to a standardized oral glucose load.
Type II diabetic subjects were given 50 g protein, 50 g glucose, or 50 g glucose with 50 g protein as a single meal in random sequence. The plasma glucose and insulin response was determined over the subsequent 5 h. The plasma glucose area above the baseline following a glucose meal was reduced 34% when protein was given with the glucose. When protein was given alone, the glucose concentration remained stable for 2 h and then declined. The insulin area following glucose was only modestly greater than with a protein meal (97 +/- 35, 83 +/- 19 microU X h/ml, respectively). When glucose was given with protein, the mean insulin area was considerably greater than when glucose or protein was given alone (247 +/- 33 microU X h/ml). When various amounts of protein were given with 50 g glucose, the insulin area response was essentially first order. Subsequently, subjects were given 50 g glucose or 50 g glucose with 50 g protein as two meals 4 h apart in random sequence. The insulin areas were not significantly different for each meal but were higher when protein + glucose was given. After the second glucose meal the plasma glucose area was 33% less than after the first meal. Following the second glucose + protein meal the plasma glucose area was markedly reduced, being only 7% as large as after the first meal. These data indicate that protein given with glucose will increase insulin secretion and reduce the plasma glucose rise in at least some type II diabetic persons.
MED-1326
Prevalence of diabetes among men and women in China.
BACKGROUND: Because of the rapid change in lifestyle in China, there is concern that diabetes may become epidemic. We conducted a national study from June 2007 through May 2008 to estimate the prevalence of diabetes among Chinese adults. METHODS: A nationally representative sample of 46,239 adults, 20 years of age or older, from 14 provinces and municipalities participated in the study. After an overnight fast, participants underwent an oral glucose-tolerance test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance). Previously diagnosed diabetes was determined on the basis of self-report. RESULTS: The age-standardized prevalences of total diabetes (which included both previously diagnosed diabetes and previously undiagnosed diabetes) and prediabetes were 9.7% (10.6% among men and 8.8% among women) and 15.5% (16.1% among men and 14.9% among women), respectively, accounting for 92.4 million adults with diabetes (50.2 million men and 42.2 million women) and 148.2 million adults with prediabetes (76.1 million men and 72.1 million women). The prevalence of diabetes increased with increasing age (3.2%, 11.5%, and 20.4% among persons who were 20 to 39, 40 to 59, and > or = 60 years of age, respectively) and with increasing weight (4.5%, 7.6%, 12.8%, and 18.5% among persons with a body-mass index [the weight in kilograms divided by the square of the height in meters] of < 18.5, 18.5 to 24.9, 25.0 to 29.9, and > or = 30.0, respectively). The prevalence of diabetes was higher among urban residents than among rural residents (11.4% vs. 8.2%). The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose (11.0% vs. 3.2% among men and 10.9% vs. 2.2% among women). CONCLUSIONS: These results indicate that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed. 2010 Massachusetts Medical Society
MED-1327
Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain.
Whole-grain and high fiber intakes are routinely recommended for prevention of vascular diseases; however, there are no comprehensive and quantitative assessments of available data in humans. The aim of this study was to systematically examine longitudinal studies investigating whole-grain and fiber intake in relation to risk of type 2 diabetes (T2D), cardiovascular disease (CVD), weight gain, and metabolic risk factors. We identified 45 prospective cohort studies and 21 randomized-controlled trials (RCT) between 1966 and February 2012 by searching the Cumulative Index to Nursing and Allied Health Literature, Cochrane, Elsevier Medical Database, and PubMed. Study characteristics, whole-grain and dietary fiber intakes, and risk estimates were extracted using a standardized protocol. Using random effects models, we found that compared with never/rare consumers of whole grains, those consuming 48-80 g whole grain/d (3-5 serving/d) had an ~26% lower risk of T2D [RR = 0.74 (95% CI: 0.69, 0.80)], ~21% lower risk of CVD [RR = 0.79 (95% CI: 0.74, 0.85)], and consistently less weight gain during 8-13 y (1.27 vs 1.64 kg; P = 0.001). Among RCT, weighted mean differences in post-intervention circulating concentrations of fasting glucose and total and LDL-cholesterol comparing whole-grain intervention groups with controls indicated significantly lower concentrations after whole-grain interventions [differences in fasting glucose: -0.93 mmol/L (95% CI: -1.65, -0.21), total cholesterol: -0.83 mmol/L (-1.23, -0.42); and LDL-cholesterol: -0.82 mmol/L (-1.31, -0.33)]. [corrected] Findings from this meta-analysis provide evidence to support beneficial effects of whole-grain intake on vascular disease prevention. Potential mechanisms responsible for whole grains' effects on metabolic intermediates require further investigation in large intervention trials.
MED-1328
Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global B...
BACKGROUND: In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. METHODS: We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). FINDINGS: Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. INTERPRETATION: Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. FUNDING: Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.
MED-1329
White rice-based food consumption and ischemic stroke risk: a case-control study in southern China.
White rice-based foods, which are high in refined carbohydrates, are widely consumed in China. A case-control study was conducted to investigate the association between white rice-based food consumption and the risk of ischemic stroke in the southern Chinese population. Information on diet and lifestyle was obtained from 374 incident ischemic stroke patients and 464 hospital-based controls. Logistic regression analyses were performed to assess the effects of rice-based foods on stroke risk. The mean weekly intake of rice foods appeared to be significantly higher in cases than in controls. Increased consumptions of cooked rice, congee, and rice noodle were associated with a higher risk for ischemic stroke after controlling for confounding factors. The corresponding adjusted odds ratios (with 95% confidence intervals) for the highest versus lowest intake level were 2.73 (1.31-5.69), 2.93 (1.68-5.13), and 2.03 (1.40-2.94), with significant dose-response relationships observed. The results provide evidence of a positive association between habitual rice food consumption and the risk of ischemic stroke in Chinese adults. Copyright © 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.
MED-1330
Diabetes prevalence and determinants in adults in China mainland from 2000 to 2010: a systematic review.
AIMS: To systematically review trends in diabetes mellitus (DM) prevalence in adults in China over the last 10 years and to identify the determinants of these trends. METHODS: A systematic search was conducted for studies published between 2000 and 2010. Studies reporting DM prevalence were included if they met the pre-determined criteria. The prevalence estimates and reported determinants of these studies were compared. RESULTS: Twenty-five manuscripts, reporting on 22 studies, were selected for inclusion in the review. There has been an increase in DM prevalence from 2.6% to 9.7% in China over the past decade. DM prevalence is strongly associated with age and is higher in urban residents compared with rural populations. Some studies found a difference in DM prevalence between males and females, but this finding was not consistent. Other commonly reported associations with DM included family history, obesity and hypertension. CONCLUSION: Over the period of 2000-2010, we identify a significant increase in DM prevalence at the national level. It is important for all levels of government to develop more effective strategies to prevent and manage this rising diabetes epidemic. There is also an important need for more large-scale studies of diabetes in the western and central regions of China. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
MED-1331
Dynamics of the nutrition transition toward the animal foods sector in China and its implications: a worried perspective.
Many changes in diet and in physical activity are occurring simultaneously in the developing world. These diet shifts include large increases in energy density, in the proportion of the population consuming a high fat diet and in animal product intake. Animal source foods (ASF) play a major role in these diet shifts. This article documents the large shifts in the composition of diets and obesity across the developing world and notes that these changes are accelerating. Using China as a case study, evidence of the speeding up of this process is presented in descriptive and more rigorous dynamic longitudinal analysis. The implications of these changes for dietary and obesity patterns and cardiovascular disease are great. Indeed, developing countries are at a point where the prevalence of obesity is greater than that of undernutrition and concerns related to intake of saturated fat and energy imbalance must be considered more seriously by the agriculture sector. Current agriculture development policy in many developing countries focuses on livestock promotion and does not consider the potential adverse health consequences of this strategy. Although linkages between ASF intake and obesity cannot be established as clearly as they are for high ASF intakes, heart disease and cancer, the potential adverse health effects linked with an increased ASF intake should no longer be ignored.
MED-1332
Incidence of Type 2 Diabetes in Japan: A Systematic Review and Meta-Analysis
Background The definition of incident type 2 diabetes varies across studies; hence, the actual incidence of type 2 diabetes in Japan is unclear. Here, we reviewed the various definitions of incident type 2 diabetes used in previous epidemiologic studies and estimated the diabetes incidence rate in Japan. Methods We searched for related literature in the MEDLINE, EMBASE, and Ichushi databases through September 2012. Two reviewers selected studies that evaluated incident type 2 diabetes in the Japanese population. Results From 1824 relevant articles, we included 33 studies with 386,803 participants. The follow-up period ranged from 2.3 to 14 years and the studies were initiated between 1980 and 2003. The random-effects model indicated that the pooled incidence rate of diabetes was 8.8 (95% confidence interval, 7.4–10.4) per 1000 person-years. We observed a high degree of heterogeneity in the results (I2 = 99.2%; p < 0.001), with incidence rates ranging from 2.3 to 52.6 per 1000 person-years. Three studies based their definition of incident type 2 diabetes on self-reports only, 10 on laboratory data only, and 20 on self-reports and laboratory data. Compared with studies defining diabetes using laboratory data (n = 30; pooled incidence rate = 9.6; 95% confidence interval = 8.3–11.1), studies based on self-reports alone tended to show a lower incidence rate (n = 3; pooled incidence rate = 4.0; 95% confidence interval = 3.2–5.0; p for interaction < 0.001). However, stratified analyses could not entirely explain the heterogeneity in the results. Conclusions Our systematic review and meta-analysis indicated the presence of a high degree of heterogeneity, which suggests that there is a considerable amount of uncertainty regarding the incidence of type 2 diabetes in Japan. They also suggested that laboratory data may be important for the accurate estimation of the incidence of type 2 diabetes.
MED-1333
Insulin secretion as a determinant of pancreatic cancer risk.
New epidemiology confirms that glucose intolerance is a risk factor for pancreatic cancer, and that this association cannot be accounted for by an adverse impact of early pancreatic cancer on beta cell function. Previous reports indicate that risk for pancreatic cancer is increased in adult-onset diabetics. Since streptozotocin diabetes inhibits carcinogen-mediated induction of pancreatic cancer in hamsters, the most reasonable interpretation of these findings is that insulin (or some other beta cell product) acts as a promoter for pancreatic carcinogenesis. This view is consistent with a report that human pancreatic adenocarcinomas express insulin receptors that can stimulate mitosis; an additional possibility is that high insulin levels indirectly promote pancreatic carcinogenesis by boosting effective IGF-I activity via hepatic actions. In international ecologic epidemiology, pancreatic cancer rates correlate tightly with dietary intake of animal products; this may reflect the fact that vegan diets are associated with low diurnal insulin secretion. There is also suggestive evidence that macrobiotic vegan diets, which are low in glycemic index, may increase mean survival time in pancreatic cancer. However, other types of diets associated with decreased postprandial insulin response, such as high-protein diets or 'Mediterranean' diets high in oleic acid, may also have the potential for pancreatic cancer prevention. The huge increases of age-adjusted pancreatic cancer mortality in Japan and among African-Americans during the last century imply that pancreatic cancer is substantially preventable; a low-insulin-response diet coupled with exercise training, weight control, and smoking avoidance, commendable for a great many other reasons, may slash pancreatic cancer mortality dramatically. Copyright 2001 Harcourt Publishers Ltd.
MED-1334
Program and Policy Options for Preventing Obesity in China
By 2002, China’s prevalence of overweight and obesity among adults was 18.9 percent and 2.9 percent, respectively. The Chinese traditional diet has been replaced by the “Western diet” and major declines in all phases of activity and increased sedentary activity as the main reasons explaining the rapid increase in overweight and obesity, bring major economic and health costs. The Nutrition Improvement Work Management Approach was released in 2010. Overweight and obesity prevention-related policies were added to national planning for disease prevention and control. The Guidelines for Prevention and Control of Overweight and Obesity of Chinese Adults and the School-age Children and Teenagers Overweight and Obesity Prevention and Control Guidelines in China were promulgated in 2003 and 2007, respectively. Few education programs have been implemented. Selected academic intervention research projects dominate with a focus on reducing child obesity and promoting healthier diets; increasing physical activity and reducing sedentary time; and facilitating changes in family, school, social, and cultural environments. Intervention samples are small and have not addressed the increasing rates of obesity throughout the entire population. Government provision of effective policy measures, multisectoral cooperation and increasing corporate social responsibility are keys to curb the trend toward overweight and obesity in China.
MED-1335
Glycaemic responses to glucose and rice in people of Chinese and European ethnicity.
AIMS: Diabetes rates are especially high in China. Risk of Type 2 diabetes increases with high intakes of white rice, a staple food of Chinese people. Ethnic differences in postprandial glycaemia have been reported. We compared glycaemic responses to glucose and five rice varieties in people of European and Chinese ethnicity and examined possible determinants of ethnic differences in postprandial glycaemia. METHODS: Self-identified Chinese (n = 32) and European (n = 31) healthy volunteers attended on eight occasions for studies following ingestion of glucose and jasmine, basmati, brown, Doongara(®) and parboiled rice. In addition to measuring glycaemic response, we investigated physical activity levels, extent of chewing of rice and salivary α-amylase activity to determine whether these measures explained any differences in postprandial glycaemia. RESULTS: Glycaemic response, measured by incremental area under the glucose curve, was over 60% greater for the five rice varieties (P < 0.001) and 39% greater for glucose (P < 0.004) amongst Chinese compared with Europeans. The calculated glycaemic index was approximately 20% greater for rice varieties other than basmati (P = 0.01 to 0.05). Ethnicity [adjusted risk ratio 1.4 (1.2-1.8) P < 0.001] and rice variety were the only important determinants of incremental area under the glucose curve. CONCLUSIONS: Glycaemic responses following ingestion of glucose and several rice varieties are appreciably greater in Chinese compared with Europeans, suggesting the need to review recommendations regarding dietary carbohydrate amongst rice-eating populations at high risk of diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.
MED-1795
Fruit consumption and risk of type 2 diabetes: results from three prospective longitudinal cohort studies
Objective To determine whether individual fruits are differentially associated with risk of type 2 diabetes. Design Prospective longitudinal cohort study. Setting Health professionals in the United States. Participants 66 105 women from the Nurses’ Health Study (1984-2008), 85 104 women from the Nurses’ Health Study II (1991-2009), and 36 173 men from the Health Professionals Follow-up Study (1986-2008) who were free of major chronic diseases at baseline in these studies. Main outcome measure Incident cases of type 2 diabetes, identified through self report and confirmed by supplementary questionnaires. Results During 3 464 641 person years of follow-up, 12 198 participants developed type 2 diabetes. After adjustment for personal, lifestyle, and dietary risk factors of diabetes, the pooled hazard ratio of type 2 diabetes for every three servings/week of total whole fruit consumption was 0.98 (95% confidence interval 0.96 to 0.99). With mutual adjustment of individual fruits, the pooled hazard ratios of type 2 diabetes for every three servings/week were 0.74 (0.66 to 0.83) for blueberries, 0.88 (0.83 to 0.93) for grapes and raisins, 0.89 (0.79 to 1.01) for prunes, 0.93 (0.90 to 0.96) for apples and pears, 0.95 (0.91 to 0.98) for bananas, 0.95 (0.91 to 0.99) for grapefruit, 0.97 (0.92 to 1.02) for peaches, plums, and apricots, 0.99 (0.95 to 1.03) for oranges, 1.03 (0.96 to 1.10) for strawberries, and 1.10 (1.02 to 1.18) for cantaloupe. The pooled hazard ratio for the same increment in fruit juice consumption was 1.08 (1.05 to 1.11). The associations with risk of type 2 diabetes differed significantly among individual fruits (P<0.001 in all cohorts). Conclusion Our findings suggest the presence of heterogeneity in the associations between individual fruit consumption and risk of type 2 diabetes. Greater consumption of specific whole fruits, particularly blueberries, grapes, and apples, is significantly associated with a lower risk of type 2 diabetes, whereas greater consumption of fruit juice is associated with a higher risk.
MED-1418
Hydrogen sulfide induces direct radical-associated DNA damage.
Hydrogen sulfide (H(2)S) is produced by indigenous sulfate-reducing bacteria in the large intestine and represents an environmental insult to the colonic epithelium. Clinical studies have linked the presence of either sulfate-reducing bacteria or H(2)S in the colon with chronic disorders such as ulcerative colitis and colorectal cancer, although at this point, the evidence is circumstantial and underlying mechanisms remain undefined. We showed previously that sulfide at concentrations similar to those found in the human colon induced genomic DNA damage in mammalian cells. The present study addressed the nature of the DNA damage by determining if sulfide is directly genotoxic or if genotoxicity requires cellular metabolism. We also questioned if sulfide genotoxicity is mediated by free radicals and if DNA base oxidation is involved. Naked nuclei from untreated Chinese hamster ovary cells were treated with sulfide; DNA damage was induced by concentrations as low as 1 micromol/L. This damage was effectively quenched by cotreatment with butylhydroxyanisole. Furthermore, sulfide treatment increased the number of oxidized bases recognized by formamidopyrimidine [fapy]-DNA glycosylase. These results confirm the genotoxicity of sulfide and strongly implicate that this genotoxicity is mediated by free radicals. These observations highlight the possible role of sulfide as an environmental insult that, given a predisposing genetic background, may lead to genomic instability or the cumulative mutations characteristic of colorectal cancer.
MED-1419
A diet high in fat and meat but low in dietary fibre increases the genotoxic potential of 'faecal water'.
To determine the effects of different diets on the genotoxicity of human faecal water, a diet rich in fat, meat and sugar but poor in vegetables and free of wholemeal products (diet 1) was consumed by seven healthy volunteers over a period of 12 days. One week after the end of this period, the volunteers started to consume a diet enriched with vegetables and wholemeal products but poor in fat and meat (diet 2) over a second period of 12 days. The genotoxic effect of faecal waters obtained after both diets was assessed with the single cell gel electrophoresis (Comet assay) using the human colon adenocarcinoma cell line HT29 clone 19a as a target. The fluorescence and length of the tails of the comet images reflects the degree of DNA damage in single cells. The mean DNA damage, expressed as the ratio of tail intensity (fluorescence in the tail) to total intensity of the comet after incubation with faecal water from volunteers consuming diet 1 was about twice as high as for diet 2. The susceptibility of the cells incubated with faecal water to DNA damage caused by additional hydrogen peroxide treatment showed no significant differences between the two diets. Generation of oxidized pyrimidine and purine bases revealed no differences after pretreatment with both types of faecal water. The results indicate that diets high in fat and meat but low in dietary fibre increase the genotoxicity of faecal water to colonic cells and may contribute to an enhanced risk of colorectal cancer.
MED-1420
Nutrition and colonic health: the critical role of the microbiota.
PURPOSE OF REVIEW: To highlight mechanisms whereby diet affects colonic function and disease patterns. RECENT FINDINGS: Topical nutrients are preferentially used by the gut mucosa to maintain structure and function. With the colon, topical nutrients are generated by the colonic microbiota to maintain mucosal health. Most importantly, short chain fatty acids control proliferation and differentiation, thereby reducing colon cancer risk. In patients with massive loss of small intestine, short chain fatty acid production supports survival by releasing up to 1000 kcal energy/day. Human studies show that the microbiota synthesizes a large pool of utilizable folate which may support survival in impoverished populations. Unfortunately, the microbiota may also elaborate toxic products from food residues such as genotoxic hydrogen sulfide by sulfur-reducing bacteria in response to a high-meat diet. The employment of culture-free techniques based on 16S regions of DNA has revealed that our colons harbor over 800 bacterial species and 7000 different strains. Evidence suggests that the diet directly influences the diversity of the microbiota, providing the link between diet, colonic disease, and colon cancer. The microbiota, however, can determine the efficiency of food absorption and risk of obesity. SUMMARY: Our investigations have focused on a small number of bacterial species: characterization of microbiota and its metabolism can be expected to provide the key to colonic health and disease.
MED-1421
Contribution of dietary protein to sulfide production in the large intestine: an in vitro and a controlled feeding study in humans.
BACKGROUND: Hydrogen sulfide is a luminally acting, bacterially derived cell poison that has been implicated in ulcerative colitis. Sulfide generation in the colon is probably driven by dietary components such as sulfur-containing amino acids (SAAs) and inorganic sulfur (eg, sulfite). OBJECTIVE: We assessed the contribution of SAAs from meat to sulfide production by intestinal bacteria with use of both a model culture system in vitro and an in vivo human feeding study. DESIGN: Five healthy men were housed in a metabolic suite and fed a sequence of 5 diets for 10 d each. Meat intake ranged from 0 g/d with a vegetarian diet to 600 g/d with a high-meat diet. Fecal sulfide and urinary sulfate were measured in samples collected on days 9 and 10 of each diet period. Additionally, 5 or 10 g bovine serum albumin or casein/L was added to batch cultures inoculated with feces from 4 healthy volunteers. Concentrations of sulfide, ammonia, and Lowry-reactive substances were measured over 48 h. RESULTS: Mean (+/-SEM) fecal sulfide concentrations ranged from 0.22 +/- 0.02 mmol/kg with the 0-g/d diet to 3.38 +/- 0.31 mmol/kg with the 600-g/d diet and were significantly related to meat intake (P: < 0.001). Sulfide formation in fecal batch cultures supplemented with both bovine serum albumin and casein correlated with protein digestion, as measured by the disappearance of Lowry-reactive substances and the appearance of ammonia. CONCLUSION: Dietary protein from meat is an important substrate for sulfide generation by bacteria in the human large intestine.
MED-3964
Diet and risk of inflammatory bowel disease.
BACKGROUND: A better understanding of the environmental factors leading to inflammatory bowel disease should help to prevent occurrence of the disease and its relapses. AIM: To review current knowledge on dietary risk factors for inflammatory bowel disease. METHODS: The PubMed, Medline and Cochrane Library were searched for studies on diet and risk of inflammatory bowel disease. RESULTS: Established non-diet risk factors include family predisposition, smoking, appendectomy, and antibiotics. Retrospective case-control studies are encumbered with methodological problems. Prospective studies on European cohorts, mainly including middle-aged adults, suggest that a diet high in protein from meat and fish is associated with a higher risk of inflammatory bowel disease. Intake of the n-6 polyunsaturated fatty acid linoleic acid may confer risk of ulcerative colitis, whereas n-3 polyunsaturated fatty acids may be protective. No effect was found of intake of dietary fibres, sugar, macronutrients, total energy, vitamin C, D, E, Carotene, or Retinol (vitamin A) on risk of ulcerative colitis. No prospective data was found on risk related to intake of fruits, vegetables or food microparticles (titanium dioxide and aluminium silicate). CONCLUSIONS: A diet high in protein, particular animal protein, may be associated with increased risk of inflammatory bowel disease and relapses. N-6 polyunsaturated fatty acids may predispose to ulcerative colitis whilst n-3 polyunsaturated fatty acid may protect. These results should be confirmed in other countries and in younger subjects before dietary counselling is recommended in high risk subjects. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
MED-4342
Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study.
OBJECTIVES: Diet composition has long been suspected to contribute to inflammatory bowel disease (IBD), but has not been thoroughly assessed, and has been assessed only in retrospective studies that are prone to recall bias. The aim of the present study was to evaluate the role of dietary macronutrients in the etiology of IBD in a large prospective cohort. METHODS: The Etude Épidémiologique des femmes de la Mutuelle Générale de l'Education Nationale cohort consists of women living in France, aged 40-65 years, and free of major diseases at inclusion. A self-administered questionnaire was used to record dietary habits at baseline. Questionnaires on disease occurrence and lifestyle factors were completed every 24 months. IBDs were assessed in each questionnaire until June 2005, and subsequently validated using clinical and pathological criteria. We estimated the association between nutrients or foods and IBD using Cox proportional hazards models adjusted for energy intake. RESULTS: Among 67,581 participants (705,445 person-years, mean follow-up since completion of the baseline dietary questionnaire 10.4 years), we validated 77 incident IBD cases. High total protein intake, specifically animal protein, was associated with a significantly increased risk of IBD, (hazards ratio for the third vs. first tertile and 95% confidence interval being 3.31 and 1.41-7.77 (P trend=0.007), and 3.03 and 1.45-6.34 (P trend=0.005) for total and animal protein, respectively). Among sources of animal protein, high consumption of meat or fish but not of eggs or dairy products was associated with IBD risk. CONCLUSIONS: High protein intake is associated with an increased risk of incident IBD in French middle-aged women.
MED-1581
When can we cure Crohn's?
Crohn's disease is a life-long idiopathic inflammatory disease which affects the entire gastrointestinal tract and occasionally extra-intestinal organs. CD is thought to result from complex interactions between environmental factors, the gut microbes, and the genetic background and the immune system of the host. In the last decades research on these pathogenetic components, and especially on mucosal immunity, has led to the development of biologic agents and therapeutic strategies that have improved dramatically the treatment of CD but we are still far away from curing the disease. If there is a treatment for CD that will probably evolve through methodical steps towards integrating research on all the components involved in the pathogenesis of CD. This holistic and global approach may aid at unravelling the mysteries of CD and developing novel agents and therapeutic strategies which by targeting multiple pathogenetic pathways and at different stages of disease may lead hopefully to cure. Copyright © 2014 Elsevier Ltd. All rights reserved.
MED-1425
Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the inc...
We examined the correlation between the incidence of Crohn disease and dietary change in a relatively homogeneous Japanese population. The incidence and daily intake of each dietary component were compared annually from 1966 to 1985. The univariate analysis showed that the increased incidence of Crohn disease was strongly (P < 0.001) correlated with increased dietary intake of total fat (r = 0.919). animal fat (r = 0.880), n-6 polyunsaturated fatty acids (r = 0.883), animal protein (r = 0.908), milk protein (r = 0.924), and the ratio of n-6 to n-3 fatty acid intake (r = 0.792). It was less correlated with intake of total protein (r = 0.482, P < 0.05), was not correlated with intake of fish protein (r = 0.055, P > 0.1), and was inversely correlated with intake of vegetable protein (r = -0.941, P < 0.001). The multivariate analysis showed that increased intake of animal protein was the strongest independent factor with a weaker second factor, an increased ration of n-6 to n-3 polyunsaturated fatty acids. The present study in association with reported clinical studies suggests that increased dietary intake of animal protein and n-6 polyunsaturated fatty acids with less n-3 polyunsaturated fatty acids may contribute to the development of Crohn disease.
MED-1426
Influence of dietary protein supplements on the formation of bacterial metabolites in the colon.
BACKGROUND: To evaluate the influence of increased dietary protein intake on bacterial colonic metabolism in healthy volunteers. METHODS: Short chain fatty acids, ammonia, and volatile organic compounds in faecal samples, and phenols in the urine of five volunteers were measured after one week of basal nutrient intake and and after one week of a diet supplemented with a protein rich food (Fortimel; Nutricia, Zoetermeer, The Netherlands). Paired t tests and factor analysis were used for statistical analysis. RESULTS: Total energy and resistant carbohydrate intake remained unchanged in each study period. The percentage energy intake delivered as dietary protein, increased significantly (from 15.4% to 23.8%; p = 0.007) during supplement intake. A significant increase in faecal ammonia (p = 0.002), faecal valeric acid (p = 0.02), and urinary p-cresol (p = 0.04) was noted during supplementary protein intake. A total of 120 different volatile compounds were isolated from the faecal samples of which 10 increased significantly during dietary protein supplementation. The change in volatile pattern, especially for S containing metabolites, was clearly shown by a factor analysis model which made a distinction between the two dietary regimens for all volunteers. CONCLUSION: An increase in dietary protein leads to altered products formation by colonic metabolism, mainly reflected by an increase in faecal ammonia, faecal volatile S substances, and urinary p-cresol.
MED-1527
Vegetarian Dietary Patterns and Mortality in Adventist Health Study 2
Importance Some evidence suggests vegetarian dietary patterns may be associated with reduced mortality, but the relationship is not well established. Objective To evaluate the association between vegetarian dietary patterns and mortality. Design Prospective cohort study; mortality analysis by Cox proportional hazards regression, controlling for important demographic and lifestyle confounders. Setting Adventist Health Study 2 (AHS-2), a large North American cohort. Participants A total of 96 469 Seventh-day Adventist men and women recruited between 2002 and 2007, from which an analytic sample of 73 308 participants remained after exclusions. Exposures Diet was assessed at baseline by a quantitative food frequency questionnaire and categorized into 5 dietary patterns: nonvegetarian, semi-vegetarian, pesco-vegetarian, lacto-ovo–vegetarian, and vegan. Main Outcome and Measure The relationship between vegetarian dietary patterns and all-cause and cause-specific mortality; deaths through 2009 were identified from the National Death Index. Results There were 2570 deaths among 73 308 participants during a mean follow-up time of 5.79 years. The mortality rate was 6.05 (95% CI, 5.82–6.29) deaths per 1000 person-years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs non-vegetarians was 0.88 (95% CI, 0.80–0.97). The adjusted HR for all-cause mortality in vegans was 0.85 (95% CI, 0.73–1.01); in lacto-ovo–vegetarians, 0.91 (95% CI, 0.82–1.00); in pesco-vegetarians, 0.81 (95% CI, 0.69–0.94); and in semi-vegetarians, 0.92 (95% CI, 0.75–1.13) compared with nonvegetarians. Significant associations with vegetarian diets were detected for cardiovascular mortality, noncardiovascular noncancer mortality, renal mortality, and endocrine mortality. Associations in men were larger and more often significant than were those in women. Conclusions and Relevance Vegetarian diets are associated with lower all-cause mortality and with some reductions in cause-specific mortality. Results appeared to be more robust in males. These favorable associations should be considered carefully by those offering dietary guidance.
MED-1528
Effect of the vegetarian diet on non-communicable diseases.
A vegetarian diet generally includes plenty of vegetables and fruits, which are rich in phytochemicals, antioxidants, fiber, magnesium, vitamins C and E, Fe³⁺, folic acid and n-6 polyunsaturated fatty acid (PUFA), and is low in cholesterol, total fat and saturated fatty acid, sodium, Fe²⁺, zinc, vitamin A, B₁₂ and D, and especially n-3 PUFA. Mortality from all-cause, ischemic heart disease, and circulatory and cerebrovascular diseases was significantly lower in vegetarians than in omnivorous populations. Compared with omnivores, the incidence of cancer and type 2 diabetes was also significantly lower in vegetarians. However, vegetarians have a number of increased risk factors for non-communicable diseases such as increased plasma homocysteine, mean platelet volume and platelet aggregability compared with omnivores, which are associated with low intake of vitamin B₁₂ and n-3 PUFA. Based on the present data, it would seem appropriate for vegetarians to carefully design their diet, specifically focusing on increasing their intake of vitamin B₁₂ and n-3 PUFA to further reduce already low mortality and morbidity from non-communicable diseases. © 2013 Society of Chemical Industry.
MED-1529
Risk of hospitalization or death from ischemic heart disease among British vegetarians and nonvegetarians: results from the EPIC-Oxford cohort study.
BACKGROUND: Few previous prospective studies have examined differences in incident ischemic heart disease (IHD) risk between vegetarians and nonvegetarians. OBJECTIVE: The objective was to examine the association of a vegetarian diet with risk of incident (nonfatal and fatal) IHD. DESIGN: A total of 44,561 men and women living in England and Scotland who were enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study, of whom 34% consumed a vegetarian diet at baseline, were part of the analysis. Incident cases of IHD were identified through linkage with hospital records and death certificates. Serum lipids and blood pressure measurements were available for 1519 non cases, who were matched to IHD cases by sex and age. IHD risk by vegetarian status was estimated by using multivariate Cox proportional hazards models. RESULTS: After an average follow-up of 11.6 y, there were 1235 IHD cases (1066 hospital admissions and 169 deaths). Compared with nonvegetarians, vegetarians had a lower mean BMI [in kg/m(2); -1.2 (95% CI: -1.3, -1.1)], non-HDL-cholesterol concentration [-0.45 (95% CI: -0.60, -0.30) mmol/L], and systolic blood pressure [-3.3 (95% CI: -5.9, -0.7) mm Hg]. Vegetarians had a 32% lower risk (HR: 0.68; 95% CI: 0.58, 0.81) of IHD than did nonvegetarians, which was only slightly attenuated after adjustment for BMI and did not differ materially by sex, age, BMI, smoking, or the presence of IHD risk factors. CONCLUSION: Consuming a vegetarian diet was associated with lower IHD risk, a finding that is probably mediated by differences in non-HDL cholesterol, and systolic blood pressure.
MED-1530
Cardiovascular disease mortality and cancer incidence in vegetarians: a meta-analysis and systematic review.
BACKGROUND: Prospective cohort studies have examined mortality and overall cancer incidence among vegetarians, but the results have been inconclusive. AIMS: The objective of the present meta-analysis was to investigate cardiovascular disease mortality and cancer incidence among vegetarians and nonvegetarians. METHODS: Medline, EMBASE and Web Of Science databases were searched for cohort studies published from inception to September 2011. Studies were included if they contained the relative risk (RR) and corresponding 95% CI. Participants were from the UK, Germany, California, USA, the Netherlands and Japan. RESULTS: Seven studies with a total of 124,706 participants were included in this analysis. All-cause mortality in vegetarians was 9% lower than in nonvegetarians (RR = 0.91; 95% CI, 0.66-1.16). The mortality from ischemic heart disease was significantly lower in vegetarians than in nonvegetarians (RR = 0.71; 95% CI, 0.56-0.87). We observed a 16% lower mortality from circulatory diseases (RR = 0.84; 95% CI, 0.54-1.14) and a 12% lower mortality from cerebrovascular disease (RR = 0.88; 95% CI, 0.70-1.06) in vegetarians compared with nonvegetarians. Vegetarians had a significantly lower cancer incidence than nonvegetarians (RR = 0.82; 95% CI, 0.67-0.97). CONCLUSIONS: Our results suggest that vegetarians have a significantly lower ischemic heart disease mortality (29%) and overall cancer incidence (18%) than nonvegetarians. Copyright © 2012 S. Karger AG, Basel.
MED-1531
A Multicountry Ecological Study of Cancer Incidence Rates in 2008 with Respect to Various Risk-Modifying Factors
Observational and ecological studies are generally used to determine the presence of effect of cancer risk-modifying factors. Researchers generally agree that environmental factors such as smoking, alcohol consumption, poor diet, lack of physical activity, and low serum 25-hdyroxyvitamin D levels are important cancer risk factors. This ecological study used age-adjusted incidence rates for 21 cancers for 157 countries (87 with high-quality data) in 2008 with respect to dietary supply and other factors, including per capita gross domestic product, life expectancy, lung cancer incidence rate (an index for smoking), and latitude (an index for solar ultraviolet-B doses). The factors found to correlate strongly with multiple types of cancer were lung cancer (direct correlation with 12 types of cancer), energy derived from animal products (direct correlation with 12 types of cancer, inverse with two), latitude (direct correlation with six types, inverse correlation with three), and per capita gross national product (five types). Life expectancy and sweeteners directly correlated with three cancers, animal fat with two, and alcohol with one. Consumption of animal products correlated with cancer incidence with a lag time of 15–25 years. Types of cancer which correlated strongly with animal product consumption, tended to correlate weakly with latitude; this occurred for 11 cancers for the entire set of countries. Regression results were somewhat different for the 87 high-quality country data set and the 157-country set. Single-country ecological studies have inversely correlated nearly all of these cancers with solar ultraviolet-B doses. These results can provide guidance for prevention of cancer.
MED-1532
Trends in mortality from cancers of the breast, colon, prostate, esophagus, and stomach in East Asia: role of nutrition transition.
Although substantial nutrition transition, characterized by an increased intake of energy, animal fat, and red meats, has occurred during the last several decades in East Asia, few studies have systematically evaluated temporal trends in cancer incidence or mortality among populations in this area. Therefore, we sought to investigate this question with tremendous public health implications. Data on mortality rates of cancers of the breast, colon, prostate, esophagus, and stomach for China (1988-2000), Hong Kong (1960-2006), Japan (1950-2006), Korea (1985-2006), and Singapore (1963-2006) were obtained from WHO. Joinpoint regression was used to investigate trends in mortality of these cancers. A remarkable increase in mortality rates of breast, colon, and prostate cancers and a precipitous decrease in those of esophageal and stomach cancers have been observed in selected countries (except breast cancer in Hong Kong) during the study periods. For example, the annual percentage increase in breast cancer mortality was 5.5% (95% confidence interval: 3.8, 7.3%) for the period 1985-1993 in Korea, and mortality rates for prostate cancer significantly increased by 3.2% (95% confidence interval: 3.0, 3.3%) per year from 1958 to 1993 in Japan. These changes in cancer mortality lagged ∼ 10 years behind the inception of the nutrition transition toward a westernized diet in selected countries or regions. There have been striking changes in mortality rates of breast, colon, prostate, esophageal, and stomach cancers in East Asia during the last several decades, which may be at least in part attributable to the concurrent nutrition transition.
MED-2114
Potential role of FoxO1 and mTORC1 in the pathogenesis of Western diet-induced acne
Acne in adolescents of developed countries is an epidemic skin disease and has currently been linked to the Western diet (WD). It is the intention of this viewpoint to discuss the possible impact of WD-mediated nutrient signalling in the pathogenesis of acne. High glycaemic load and dairy protein consumption both increase insulin/insulin-like growth factor-1 (IGF-1) signalling (IIS) that is superimposed on elevated IGF-1 signalling of puberty. The cell's nutritional status is primarily sensed by the forkhead box transcription factor O1 (FoxO1) and the serine/threonine kinase mammalian target of rapamycin complex 1 (mTORC1). Increased IIS extrudes FoxO1 into the cytoplasm, whereas nuclear FoxO1 suppresses hepatic IGF-1 synthesis and thus impairs somatic growth. FoxO1 attenuates androgen signalling, interacts with regulatory proteins important for sebaceous lipogenesis, regulates the activity of innate and adaptive immunity, antagonizes oxidative stress and most importantly functions as a rheostat of mTORC1, the master regulator of cell growth, proliferation and metabolic homoeostasis. Thus, FoxO1 links nutrient availability to mTORC1-driven processes: increased protein and lipid synthesis, cell proliferation, cell differentiation including hyperproliferation of acroinfundibular keratinocytes, sebaceous gland hyperplasia, increased sebaceous lipogenesis, insulin resistance and increased body mass index. Enhanced androgen, TNF-α and IGF-1 signalling due to genetic polymorphisms promoting the risk of acne all converge in mTORC1 activation, which is further enhanced by nutrient signalling of WD. Deeper insights into the molecular interplay of FoxO1/mTORC1-mediated nutrient signalling are thus of critical importance to understand the impact of WD on the promotion of epidemic acne and more serious mTORC1-driven diseases of civilization.
MED-2115
Diet supplementation with donkey milk upregulates liver mitochondrial uncoupling, reduces energy efficiency and improves antioxidant and antiinflam...
Dietary PUFA, mainly those of the n-3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low-fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso-energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF-α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione-S-transferase NADH quinone oxidoreductase) in DM-treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid-related factor 2 pathway. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
MED-2116
Turning acne on/off via mTORC1
Over the past 10 years, the increase in comprehension of the mechanisms behind acne has been truly exponential. Starting with the ethnological work of Cordain, accelerated by the epidemiological work of Adebamowo, supported by the clinical trials of Smith and Mann, Kwon, DiLandro and others, the interface of diet and acne is coming into focus. Melnik now presents an exceptional pair of papers that illustrate for dermatologists what translational research is all about. The Western diet, the role of dairy, FoxO1 and mTORC1, the interplay of agonists and antagonists, therapeutics present and future – the jigsaw puzzle is coming together.
MED-2117
Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis.
Recent evidence underlines the role of Western diet in the pathogenesis of acne. Acne is absent in populations consuming Palaeolithic diets with low glycaemic load and no consumption of milk or dairy products. Two randomized controlled studies, one of which is presented in this issue of Acta Dermato-Venereologica, have provided evidence for the beneficial therapeutic effects of low glycaemic load diets in acne. Epidemiological evidence confirms that milk consumption has an acne-promoting or acne-aggravating effect. Recent progress in understanding the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1) allows a new view of nutrient signalling in acne by both high glycaemic load and increased insulin-, IGF-1-, and leucine signalling due to milk protein consumption. Acne should be regarded as an mTORC1-driven disease of civilization, like obesity, type 2 diabetes and cancer induced by Western diet. Early dietary counselling of teenage acne patients is thus a great opportunity for dermatology, which will not only help to improve acne but may reduce the long-term adverse effects of Western diet on more serious mTORC1-driven diseases of civilization.
MED-4896
Acne vulgaris: a disease of Western civilization.
BACKGROUND: In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95% of the adolescent population. In men and women older than 25 years, 40% to 54% have some degree of facial acne, and clinical facial acne persists into middle age in 12% of women and 3% of men. Epidemiological evidence suggests that acne incidence rates are considerably lower in nonwesternized societies. Herein we report the prevalence of acne in 2 nonwesternized populations: the Kitavan Islanders of Papua New Guinea and the Aché hunter-gatherers of Paraguay. Additionally, we analyze how elements in nonwesternized environments may influence the development of acne. OBSERVATIONS: Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade 1 with multiple comedones or grades 2-4) was observed. Of 115 Aché subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed. CONCLUSIONS: The astonishing difference in acne incidence rates between nonwesternized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing environmental factors. Identification of these factors may be useful in the treatment of acne in Western populations.
MED-2120
ACNE AND RISK OF PROSTATE CANCER
In a recent study, prostatectomy specimens from which Propionibacterium acnes was cultured were more likely to have inflammation than culture-negative specimens or specimens positive for other bacteria, leading the authors to hypothesize that P. acnes-mediated inflammation may contribute to prostate carcinogenesis. To indirectly explore associations between P. acnes and prostate cancer, we investigated severe acne, as measured by tetracycline use for four or more years, in relation to incident prostate cancer in the Health Professionals Follow-up Study. On the 1992 follow-up questionnaire, participants were asked whether they had ever used “tetracycline for at least two months at a time (e.g., for acne or other reason)” and their duration of use. Prostate cancer diagnoses were ascertained on each subsequent biennial questionnaire and confirmed by medical record review. Between 1992 and 2002, 2,147 cases of prostate cancer were reported among 34,629 eligible participants. Men who used tetracycline for four or more years had a significantly higher risk of prostate cancer (16 cases, 1,569 person-years) than men who did not use tetracycline (2,071 cases, 304,822 person-years, multivariable-adjusted RR=1.70, 95% CI:1.03–2.80). Although intriguing, this finding should be viewed cautiously because of the small number of exposed cases, indirect assessment of severe acne, and complex etiology of acne, which is not limited to P. acnes infection. Therefore, additional biologic and epidemiologic studies are necessary to determine and elucidate the possible role of P. acnes infection in prostate carcinogenesis.
MED-2121
Dietary intervention in acne
The purpose of this paper is to highlight the endocrine signaling of Western diet, a fundamental environmental factor involved in the pathogenesis of epidemic acne. Western nutrition is characterized by high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of insulin- and IGF-1-level elevating dairy proteins. Metabolic signals of Western diet are sensed by the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), which integrates signals of cellular energy, growth factors (insulin, IGF-1) and protein-derived signals, predominantly leucine, provided in high amounts by milk proteins and meat. mTORC1 activates SREBP, the master transcription factor of lipogenesis. Leucine stimulates mTORC1-SREBP signaling and leucine is directly converted by sebocytes into fatty acids and sterols for sebaceous lipid synthesis. Over-activated mTORC1 increases androgen hormone secretion and most likely amplifies androgen-driven mTORC1 signaling of sebaceous follicles. Testosterone directly activates mTORC1. Future research should investigate the effects of isotretinoin on sebocyte mTORC1 activity. It is conceivable that isotretinoin may downregulate mTORC1 in sebocytes by upregulation of nuclear levels of FoxO1. The role of Western diet in acne can only be fully appreciated when all stimulatory inputs for maximal mTORC1 activation, i.e., glucose, insulin, IGF-1 and leucine, are adequately considered. Epidemic acne has to be recognized as an mTORC1-driven disease of civilization like obesity, type 2 diabetes, cancer and neurodegenerative diseases. These new insights into Western diet-mediated mTORC1-hyperactivity provide a rational basis for dietary intervention in acne by attenuating mTORC1 signaling by reducing (1) total energy intake, (2) hyperglycemic carbohydrates, (3) insulinotropic dairy proteins and (4) leucine-rich meat and dairy proteins. The necessary dietary changes are opposed to the evolution of industrialized food and fast food distribution of Westernized countries. An attenuation of mTORC1 signaling is only possible by increasing the consumption of vegetables and fruit, the major components of vegan or Paleolithic diets. The dermatologist bears a tremendous responsibility for his young acne patients who should be advised to modify their dietary habits in order to reduce activating stimuli of mTORC1, not only to improve acne but to prevent the harmful and expensive march to other mTORC1-related chronic diseases later in life.
MED-2122
Metabolic disorders and breast cancer risk (United States).
OBJECTIVE: To clarify the hormonal context of breast cancer etiology we used data from a large, population-based case-control study to investigate the relationship between breast cancer risk and a history of diabetes mellitus, disorders associated with estrogen stimulation (uterine fibroids, endometriosis, gallstones), and disorders associated with androgen stimulation (acne, hirsutism, and polycystic ovaries). METHODS: Breast cancer patients between 50 and 75 years old were identified from state-wide tumor registries in Wisconsin, Massachusetts, and New Hampshire; controls were randomly selected from drivers' license lists (age less than 65) or Medicare enrollment files (age 65-74). Information on reproductive history, medical history, and personal habits was obtained by telephone interview. A total of 5659 cases and 5928 controls were interviewed and provided suitable data. RESULTS: There was no overall association between breast cancer risk and reported history of diabetes mellitus, endometriosis, uterine fibroids, gallstones, or cholecystectomy. However, the disorders with androgenic associations all conferred an increased risk: the overall odds ratio (OR) for a history of acne was 1.4 (95% CI 1.0-1.9), that for hirsutism was 1.2 (95% CI 0.81-1.8), and that for polycystic ovaries 1.6 (95% CI 0.8-3.2). Diabetes mellitus diagnosed before age 35 conferred an odds ratio of 0.52 (95% 0.25-1.1), while diabetes diagnosed at a later age was associated with an increased risk (OR = 1.2, 95% CI 1.0-1.4). CONCLUSIONS: Androgen-related phenomena are likely to be important in the etiology of breast cancer.
MED-2123
Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth
Milk has been recognized to represent a functionally active nutrient system promoting neonatal growth of mammals. Cell growth is regulated by the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is still a lack of information on the mechanisms of mTORC1 up-regulation by milk consumption. This review presents milk as a materno-neonatal relay system functioning by transfer of preferential amino acids, which increase plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) for mTORC1 activation. Importantly, milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes. Whereas human breast milk is the ideal food for infants allowing appropriate postnatal growth and species-specific metabolic programming, persistent high milk signaling during adolescence and adulthood by continued cow´s milk consumption may promote mTORC1-driven diseases of civilization.
MED-2124
Acne: risk indicator for increased body mass index and insulin resistance.
Acne appears to represent a visible indicator disease of over-activated mTORC1 signalling, an unfavour-able metabolic deviation on the road to serious common Western diseases of civilisation associated with increased body mass index and insulin resistance. Exaggerated mTORC1 signalling by Western diet explains the association of acne with increased body mass index, insulin resistance, and early onset of menarche. Both, a high glycaemic load and increased consumption of milk and milk products, staples of Western diet, aggravate mammalian target of rapamycin complex 1 signalling. This review of the literature summarises present evidence for an association between acne, increased body mass index, insulin resistance and Western diet. By dietary intervention with a Palaeolithic-type diet, the dermatologist has the chance to attenuate patients' increased mTORC1 signalling by reducing glycaemic load and milk consumption, which may not only improve acne but may delay the march to more serious mTORC1-driven diseases of civilisation.
MED-2136
The impact of cow's milk-mediated mTORC1-signaling in the initiation and progression of prostate cancer
Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrations by casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostate development and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.
MED-2126
Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity
Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1). Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.
MED-2445
Dietary polyphenols in the prevention and treatment of allergic diseases.
Allergic disorders encompass skin, food and respiratory allergies. Sensitization to a normally harmless allergen results in the immune system being biased to a predominant T-helper type 2 response. Re-exposure to the same allergen leads to a robust secretion of allergy-related mediators that eventually triggers symptoms. Our understanding of these disorders has enabled the search of therapeutic approaches that can either modulate the sensitization process or impact on allergic mediators, thus helping manage allergic symptoms. Polyphenols are one such class of compounds that are found in foods and plant sources and have been investigated for their anti-allergic effect in different disease models and in human clinical trials. Their anti-inflammatory profile is known to impact on the recruitment of immune cells to the skin and in preventing the development of secondary infections following disruption of the skin barrier. The interaction of polyphenols with proteins can modulate the process of allergic sensitization and their direct effect on allergic effector cells such as mast cells inhibit mediator release, resulting in the alleviation of symptoms. In addition, their endogenous anti-oxidant ability limits the extent of cellular injury from free radicals during the allergic insult. Overall, polyphenols hold promise as anti-allergy agents capable of influencing multiple biological pathways and immune cell functions in the allergic immune response and deserve further investigation. The objective of the current review is to summarize the key findings and progress made in studying polyphenols as anti-allergic ingredients. Special emphasis is placed in this review to highlight key physiological, cellular and signalling pathways implicated in the mechanism of action of different polyphenols in the context of allergic disorders and their manifestations. © 2011 Blackwell Publishing Ltd.
MED-2446
Dietary antioxidant intake, allergic sensitization and allergic diseases in young children.
BACKGROUND: Allergic diseases have risen in prevalence over recent decades. The aetiology remains unclear but is likely to be a result of changing lifestyle and/or environment. A reduction in antioxidant intake, consequent to reduced intake of fresh fruits and vegetables, has been suggested as a possible cause. OBJECTIVE: To investigate whether dietary antioxidant intake at age 5 was related to atopy at 5 and 8 years of age amongst children in an unselected birth cohort. METHODS: Children were followed from birth. Parents completed a validated respiratory questionnaire and children were skin prick tested at 5 and 8 years of age. Serum IgE levels were measured at age 5. At age 5, antioxidant intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). A nutrient analysis program computed nutrient intake, and frequency counts of foods high in the antioxidant vitamins A, C and E were assessed. RESULTS: Eight hundred and sixty-one children completed both the respiratory and FFQ. Beta-carotene intake was associated with reduced risk of allergic sensitization at age 5 [0.80 (0.68-0.93)] and 8 [0.81 (0.70-0.94)]. In addition, beta-carotene intake was negatively associated with total IgE levels (P = 0.002). Vitamin E intake was associated with an increased risk of allergic sensitization [1.19 (1.02-1.39)], only at age 5. There was no association between antioxidant intakes and wheeze or eczema. CONCLUSION: Increased beta-carotene intake was associated with a reduced risk of allergic sensitization and lower IgE levels, in 5- and 8-year-old children. Dietary antioxidants may play a role in the development of allergic sensitization.
MED-2458
Manipulating antioxidant intake in asthma: a randomized controlled trial.
BACKGROUND: Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. OBJECTIVE: The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. DESIGN: Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily; n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily; n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. RESULTS: After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91; P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. CONCLUSIONS: Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at http://www.actr.org.au as ACTRN012606000286549.
MED-2448
Clinical efficacy of apple polyphenol for treating cedar pollinosis.
A double-blind comparative study was conducted on cedar pollinosis patients in order to evaluate the treatment efficacy of apple polyphenol (Ap). Ap was administered (500 mg) once daily for 12 weeks, starting about 2 weeks prior to cedar pollen dispersion. Pollinosis symptoms during the study were evaluated according to the classification in the guidelines for allergic rhinitis diagnosis and treatment. The results show that the sneezing score was significantly lower for the Ap group than with the placebo group during the early period of pollen dispersion and during the main dispersion period. In addition, no adverse reactions were induced by Ap during the study. These results suggest that Ap may alleviate the symptoms of cedar pollinosis.
MED-2449
An evaluation of the clinical efficacy of tomato extract for perennial allergic rhinitis.
BACKGROUND: Recently, some common foods in daily life have been found to have anti-allergic effects. We have reported that tomato extract (TE) could possibly inhibit histamine release and mouse ear-swelling responses. Moreover, it is reported that TE could relieve the symptoms for Japanese cedar pollinosis. METHODS: To evaluate the anti-allergic effect of TE, we performed a randomized, double-blind, placebo-controlled study in 33 patients with perennial allergic rhinitis (PAR) using oral administration of TE (360 mg per day) or placebo for 8 weeks. RESULTS: We found that the sneezing score significantly decreased in the TE group at the end of the trial compared to the beginning (P < 0.05). There were decreasing tendencies of rhinorrhea and nasal obstruction in the TE group. The patients' quality of life was significantly improved in the TE group after 8 weeks of treatment (P < 0.05), but not in placebo group. A significant improvement in total symptom scores, combining sneezing, rhinorrhea and nasal obstruction, was observed after oral administration of TE for 8 weeks (P < 0.01). The safety of TE treatment was confirmed by laboratory tests and inspection of general conditions. CONCLUSIONS: TE can be expected to safely improve the nasal symptoms of PAR.
MED-2450
Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete
Background Atopy is not uncommon among children living in rural Crete, but wheeze and rhinitis are rare. A study was undertaken to examine whether this discrepancy could be attributed to a high consumption of fresh fruit and vegetables or adherence to a traditional Mediterranean diet. Methods A cross‐sectional survey was performed in 690 children aged 7–18 years in rural Crete. Parents completed a questionnaire on their child's respiratory and allergic symptoms and a 58‐item food frequency questionnaire. Adherence to a Mediterranean diet was measured using a scale with 12 dietary items. Children underwent skin prick tests with 10 common aeroallergens. Results 80% of children ate fresh fruit (and 68% vegetables) at least twice a day. The intake of grapes, oranges, apples, and fresh tomatoes—the main local products in Crete—had no association with atopy but was protective for wheezing and rhinitis. A high consumption of nuts was found to be inversely associated with wheezing (OR 0.46; 95% CI 0.20 to 0.98), whereas margarine increased the risk of both wheeze (OR 2.19; 95% CI 1.01 to 4.82) and allergic rhinitis (OR 2.10; 95% CI 1.31 to 3.37). A high level of adherence to the Mediterranean diet was protective for allergic rhinitis (OR 0.34; 95% CI 0.18 to 0.64) while a more modest protection was observed for wheezing and atopy. Conclusion The results of this study suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis. Diet may explain the relative lack of allergic symptoms in this population.
MED-2451
Diet, lung function, and lung function decline in a cohort of 2512 middle aged men
BACKGROUND—A prospective cohort study of 2512 Welshmen aged 45-59 living in Caerphilly in 1979-1983 was used to investigate associations between diet and lung function. METHODS—At baseline (phase I) and at five year follow up (phase II), forced expiratory volume in one second (FEV1) was measured using a McDermott spirometer and dietary data were obtained using a semi-quantitative food frequency questionnaire. RESULTS—Good lung function, indicated by high maximum FEV1 given age and height, was associated with high intakes of vitamin C, vitamin E, β-carotene, citrus fruit, apples, and the frequent consumption of fruit juices/squashes. Lung function was inversely associated with magnesium intake but there was no evidence of an association with fatty fish. Following adjustment for confounders including body mass index, smoking history, social class, exercise, and total energy intake, only the associations with vitamin E and apples persisted, with lung function estimated to be 39 ml (95% confidence interval (CI) 9 to 69) higher for vitamin E intakes one standard deviation (SD) apart and 138 ml higher (95% CI 58to 218) for those eating five or more apples per week compared with non-consumers. Decline in lung function between phases was not significantly associated with the changing intakes of apples or vitamin E. An association between high average apple consumption and slow decline in lung function lost significance after adjustment for confounders. CONCLUSIONS—A strong positive association is seen between lung function and the number of apples eaten per week cross sectionally, consistent with a protective effect of hard fruit rather than soft/citrus fruit. The recent suggestion that such effects are reversible was not supported by our longitudinal analysis.
MED-2452
A prospective study of diet and adult-onset asthma.
A role for diet in the pathophysiology of asthma may be mediated by altered immune or antioxidant activity with consequent effects on airway inflammation. We evaluated associations between several dietary factors assessed by a semiquantitative food frequency questionnaire, and incidence of asthma over a 10-yr period in 77,866 women 34 to 68 yr of age. Women in the highest quintile of vitamin E intake from diet, but not from supplements, had a risk of 0.53 (95% confidence interval [CI] = 0.33 to 0.86) compared with women in the lowest quintile. This relationship, however, was attenuated when the contribution from nuts, a major source of vitamin E in these data and a possible allergen, was removed (relative risk = 0.74 [0.50 to 1.10], p for trend = 0.007). Positive associations were found for vitamins C and E from supplements, but appeared to be explained by women at high risk of asthma initiating use of vitamin supplements prior to diagnosis. A nonsignificant inverse association with carotene intake was noted, but no clear relations with asthma were demonstrated for intake of linoleic acid or omega-3 fatty acids. These data suggest that antioxidant supplementation and intake of various fats during adulthood are not important determinants of asthma, although vitamin E from diet may have a modest protective effect.
MED-2453
Effect of fresh fruit consumption on lung function and wheeze in children
BACKGROUND: Fresh fruit consumption and vitamin C intake have been associated with improved lung function in adults. Whether this is due to enhancement of lung growth, to a reduction in lung function decline, or to protection against bronchospasm is unclear. METHODS: In a cross- sectional school based survey of 2650 children aged 8-11 from 10 towns in England and Wales the main outcome measure was forced expiratory volume in one second (FEV1) standardised for body size and sex. Exposure was assessed by a food frequency questionnaire to parents and by measurement of plasma levels of vitamin C in a subsample of 278 children. RESULTS: FEV1 was positively associated with frequency of fresh fruit consumption. After adjustment for possible confounding variables including social class and passive smoking, those who never ate any fresh fruit had an estimated FEV1 some 79 ml (4.3%) lower than those who ate these items more than once a day (95% CI 22 to 136 ml). The association between FEV1 and fruit consumption was stronger in subjects with wheeze than in non-wheezers (p = 0.020 for difference in trend), though wheeze itself was not related to fresh fruit consumption. Frequency of consumption of salads and of green vegetables were both associated with FEV1 but the relationships were weaker than for fresh fruit. Plasma vitamin C levels were unrelated to FEV1 (r = - 0.01, p = 0.92) or to wheeze and were only weakly related to fresh fruit consumption (r = 0.13, p = 0.055). CONCLUSIONS: Fresh fruit consumption appears to have a beneficial effect on lung function in children. Further work is needed to confirm whether the effect is restricted to subjects who wheeze and to identify the specific nutrient involved.
MED-2472
Vegan regimen with reduced medication in the treatment of bronchial asthma.
Thirty-five patients who had suffered from bronchial asthma for an average of 12 yr, all receiving long-term medication, 20 including cortisone, were subject to therapy with vegan food for 1 yr. In almost all cases, medication was withdrawn or drastically reduced. There was a significant decrease in asthma symptoms. Twenty-four patients (69%) fulfilled the treatment. Of these, 71% reported improvement at 4 months and 92% at 1 yr. There was a significant improvement in a number of clinical variables; for example, vital capacity, forced expiratory volume at one sec and physical working capacity, as well as a significant change in various biochemical indices as haptoglobin, IgM, IgE, cholesterol, and triglycerides in blood. Selected patients, with a fear of side-effects of medication, who are interested in alternative health care, might get well and replace conventional medication with this regimen.
MED-2517
mTOR is a key modulator of ageing and age-related disease
Many experts in the biology of ageing believe that pharmacological interventions to slow ageing are a matter of ‘when’ rather than ‘if’. A leading target for such interventions is the nutrient response pathway defined by the mechanistic target of rapamycin (mTOR). Inhibition of this pathway extends lifespan in model organisms and confers protection against a growing list of age-related pathologies. Characterized inhibitors of this pathway are already clinically approved, and others are under development. Although adverse side effects currently preclude use in otherwise healthy individuals, drugs that target the mTOR pathway could one day become widely used to slow ageing and reduce age-related pathologies in humans.
MED-2501
Amino acid sensing and regulation of mTORC1.
Amino acids play fundamental roles in the cell both as the building blocks of new proteins and as metabolic precursors. To adapt to their limitation during periods of protein starvation, multiple adaptive mechanisms have evolved, including a rapid cessation of new protein synthesis, an increase in amino acid biosynthesis and transport, and autophagy. Here, we discuss what we currently know about how amino acid limitation is sensed, and how this sensing might be transmitted to mTORC1 to regulate protein synthesis and autophagy. Copyright © 2012 Elsevier Ltd. All rights reserved.
MED-2506
Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on mor...
Long-term caloric restriction (CR) is a robust means of reducing age-related diseases and extending life span in multiple species, but the effects in humans are unknown. The low caloric intake, long life expectancy, and the high prevalence of centenarians in Okinawa have been used as an argument to support the CR hypothesis in humans. However, no long-term, epidemiologic analysis has been conducted on traditional dietary patterns, energy balance, and potential CR phenotypes for the specific cohort of Okinawans who are purported to have had a calorically restricted diet. Nor has this cohort's subsequent mortality experience been rigorously studied. Therefore, we investigated six decades of archived population data on the elderly cohort of Okinawans (aged 65-plus) for evidence of CR. Analyses included traditional diet composition, energy intake, energy expenditure, anthropometry, plasma DHEA, mortality from age-related diseases, and current survival patterns. Findings include low caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI, relatively high plasma DHEA levels at older ages, low risk for mortality from age-related diseases, and survival patterns consistent with extended mean and maximum life span. This study lends epidemiologic support for phenotypic benefits of CR in humans and is consistent with the well-known literature on animals with regard to CR phenotypes and healthy aging.
MED-2512
Extending healthy ageing: nutrient sensitive pathway and centenarian population
Ageing is a challenge for any living organism and human longevity is a complex phenotype. With increasing life expectancy, maintaining long-term health, functionality and well-being during ageing has become an essential goal. To increase our understanding of how ageing works, it may be advantageous to analyze the phenotype of centenarians, perhaps one of the best examples of successful ageing. Healthy ageing involves the interaction between genes, the environment, and lifestyle factors, particularly diet. Besides evaluating specific gene-environment interactions in relation to exceptional longevity, it is important to focus attention on modifiable lifestyle factors such as diet and nutrition to achieve extension of health span. Furthermore, a better understanding of human longevity may assist in the design of strategies to extend the duration of optimal human health. In this article we briefly discuss relevant topics on ageing and longevity with particular focus on dietary patterns of centenarians and nutrient-sensing pathways that have a pivotal role in the regulation of life span. Finally, we also discuss the potential role of Nrf2 system in the pro-ageing signaling emphasizing its phytohormetic activation.
MED-2647
Dietary exposure to xenoestrogens in New Zealand.
Continuing evidence of the feminising effects of xenoestrogens on a range of wildlife species increases the need to assess the human health risk of these estrogen mimics. We have estimated the exposure of New Zealand males, females and young men to a range of naturally occurring and synthetic xenoestrogens found in food. Only estrogenic compounds that act by interaction with the estrogen receptor have been included. Theoretical plasma estrogen activity levels were derived from estrogen exposure estimates and estrogenic potency data. Theoretical plasma levels were compared with published data for specific xenoestrogens. There was surprisingly close agreement. Xenoestrogenicity from dietary intake was almost equally attributed to naturally occurring and synthetic xenoestrogens. Relative contributions for a male, for example were isoflavones (genistein and daidzein) (36%) and bisphenol A (34%) with smaller contributions from alkyl phenols (18%) and the flavonoids (phloretin and kaempferol) (12%). It is suggested that dietary xenoestrogens might have a pharmacological effect on New Zealand males and postmenopausal women, but are unlikely to be significant for pre-menopausal women.
MED-2648
Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals
The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17beta++-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17beta-Estradiol, 17alpha-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds--tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p'-DDT, p,p'-DDE, endosulfan, chlomequat chloride, and ethanol--varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods.
MED-2627
Human exposure to endocrine disrupters: carcinogenic risk assessment.
Human exposure to endocrine disrupters (EDs) is widespread and is considered to pose a growing threat to human health. Recent advances in molecular and genetic research and better understanding of mechanisms of blastic cell transformation have led to efforts to improve cancer risk assessment for populations exposed to this family of xenobiotics. In risk assessment, low dose extrapolation of cancer incidence data from both experimental animals and epidemiology studies has been largely based on models assuming linear correlation at low doses, despite existence of evidence showing otherwise. Another weakness of ED risk assessment is poor exposure data in ecological studies. Those are frequently rough estimates derived from contaminated items of local food basket surveys. Polyhalogenated hydrocarbons are treated as examples. There is growing sense of urgency to develop a biologically based dose response model of cancer risk, integrating emerging data from molecular biology and epidemiology to provide more realistic data for risk assessors, public, public health managers and environmental issues administrators.
MED-2650
Inadvertent exposure to xenoestrogens.
Over the last 40 years there have been constant reports concerning environmental chemicals with hormone-like effects in wildlife. An endocrine disruptor is an exogenous substance that causes adverse health effects in an intact organism or its progeny, secondary to changes in endocrine function. Endocrine disruptors of widely diverse chemical structures that have oestrogenic properties are known as oestrogenic xenobiotics or xenoestrogens. Some of these substances, such as phytoestrogens and mycoestrogens, can come from diet or from the environment. Although the oestrogenic activity of these substances is weaker than that of oestradiol, new chemicals with endocrine disrupting potential continue to be discovered, inadvertent forms of exposure are constantly being identified, and there is increasing concern about cumulative effects. Studies in the 1960s and 1970s characterized the oestrogenicity of a number of industrial compounds and the pesticides o,p-DDT, kepone, methoxychlor, phenolic derivatives and polychlorinated biphenyls (PCBs). In the last 5 years, several environmental chemicals have been added to the list of xenoestrogens, including the pesticides toxaphene, dieldrin and endosulphan, and several different compounds used in the food industry, antioxidants such a t-butylhydroxyanisole; plasticizers such as benzylbutylphthalate and 4-OH-alkylphenols; and substances used in dental restorations, such as bisphenol-A. The relevance of these newly discovered endocrine disruptors to human health is now starting to emerge. The few studies that have investigated their effect in humans point in the same direction: if there is indeed an association between exposure to substances with hormone-disruptive activity and certain disorders of endocrine organs, the incidence of such disorders would be greater in areas where exposure to agents with this activity is high. A closer scrutiny is required to determine whether these newly discovered endocrine disrupting chemicals contribute, together with oestrogenic pesticides, to the exposure of humans to xenoestrogens.
MED-2654
Endocrine disrupting nonylphenols are ubiquitous in food.
4-Nonylphenols (NPs) are common products of biodegradation of a widely used group of nonionic surfactants, the nonylphenol ethoxylates (NPEs). These compounds are known to be persistent, toxic, and estrogen active. There is a worldwide scientific and public discussion on the potential consequences of human long term dietary exposure to such endocrine disrupters. Despite numerous determinations of NPs in environmental samples no systematical reports exist relating to concentrations of NPs in food. We analyzed NPs in 60 different foodstuff commercially available in Germany. The results indicate that NPs are ubiquitous in food. The concentrations of NPs on a fresh weight basis varied between 0.1 and 19.4 microg/kg regardless of the fat content of the foodstuff. Based on data on German food consumption rates and these first analyses of NPs in food, the daily intake for an adult was calculated to be 7.5 microg/day NPs. For infants exclusively fed with breast milk or infant formulas daily intakes of 0.2 microg/day and 1.4 microg/day NPs, respectively, can be estimated.
MED-3000
Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer.
An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. Copyright © 2011 UICC.
MED-2773
The experience of Japan as a clue to the etiology of testicular and prostatic cancers.
In Japan dramatic lifestyle changes occurred after World War 2. To examine the experience of Japan as a clue to the etiology, trends in the mortality rates of testicular and prostatic cancers from 1947 to 1998 were related to changes in dietary practices. The male population born before 1945 had a peak in death from testicular cancer in their thirties or forties, whereas those born after 1946 had a peak in their twenties. The death rate of prostatic cancer increased 25-fold almost linearly after the war. The intake of milk, meat, and eggs increased 20-, 9-, and 7-fold, respectively, after the war. In connection with the development and growth of testicular and prostatic cancers in Japan, particular attention should be paid to milk, because the increase in its consumption in this country is a recent occurrence and because milk contains considerable amounts of estrogens plus saturated fats.
MED-2898
Macular pigment and risk for age-related macular degeneration in subjects from a Northern European population.
PURPOSE: Age and advanced disease in the fellow eye are the two most important risk factors for age-related macular degeneration (AMD). In this study, the authors investigated the relationship between these variables and the optical density of macular pigment (MP) in a group of subjects from a northern European population. METHODS: The optical density of MP was measured psychophysically in 46 subjects ranging in age from 21 to 81 years with healthy maculae and in 9 healthy eyes known to be at high-risk of AMD because of advanced disease in the fellow eye. Each eye in the latter group was matched with a control eye on the basis of variables believed to be associated with the optical density of MP (iris color, gender, smoking habits, age, and lens density). RESULTS: There was an age-related decline in the optical density of macular pigment among volunteers with no ocular disease (right eye: r(2) = 0.29, P = 0.0006; left eye: r(2) = 0.29, P < 0.0001). Healthy eyes predisposed to AMD had significantly less MP than healthy eyes at no such risk (Wilcoxon's signed rank test: P = 0.015). CONCLUSIONS: The two most important risk factors for AMD are associated with a relative absence of MP. These findings are consistent with the hypothesis that supplemental lutein and zeaxanthin may delay, avert, or modify the course of this disease.
MED-2884
A 12-wk egg intervention increases serum zeaxanthin and macular pigment optical density in women.
Two carotenoids found in egg yolk, lutein and zeaxanthin, accumulate in the macular retina where they may reduce photostress. Increases in serum lutein and zeaxanthin were observed in previous egg interventions, but no study measured macular carotenoids. The objective of this project was to determine whether increased consumption of eggs would increase retinal lutein and zeaxanthin, or macular pigment. Twenty-four females, between 24 and 59 y, were assigned to a pill treatment (PILL) or 1 of 2 egg treatments for 12 wk. Individuals in the PILL treatment consumed 1 sugar-filled capsule/d. Individuals in the egg treatments consumed 6 eggs/wk, containing either 331 microg (EGG 1) or 964 microg (EGG 2) of lutein and zeaxanthin/yolk. Serum cholesterol, serum carotenoids, and macular pigment OD (MPOD) were measured at baseline and after 4, 8, and 12 wk of intervention. Serum cholesterol concentrations did not change in either egg treatment group, but total cholesterol (P = 0.04) and triglycerides (P = 0.02) increased in the PILL group. Serum zeaxanthin, but not serum lutein, increased in both the EGG 1 (P = 0.04) and EGG 2 (P = 0.01) groups. Likewise, MPOD increased in both the EGG 1 (P = 0.001) and EGG 2 (P = 0.049) groups. Although the aggregate concentration of carotenoid in 1 egg yolk may be modest relative to other sources, such as spinach, their bioavailability to the retina appears to be high. Increasing egg consumption to 6 eggs/wk may be an effective method to increase MPOD.
MED-2885
Ultraviolet phototoxicity to the retina.
OBJECTIVE: This overview of ultraviolet (UV) phototoxicity considers the interaction of UVA and short-wavelength VIS light with the retina and retinal pigment epithelium. METHODS: The damage mechanisms underlying UV retinal phototoxicity are illustrated with a literature survey and presentation of experimental results. RESULTS: Depending on the wavelength and exposure duration, light interacts with tissue by three general mechanisms: thermal, mechanical, or photochemical. Although the anterior structures of the eye absorb much of the UV component of the optical radiation spectrum, a portion of the UVA band (315-400 nm) penetrates into the retina. Natural sources, such as the sun, emit energetic UV photons in relatively long durations, which typically do not result in energy confinement in the retina, and thus do not produce thermal or mechanical damage but are capable of inducing photochemical damage. Photochemical damage in the retina proceeds through Type 1 (direct reactions involving proton or electron transfers) and Type 2 (reactions involving reactive oxygen species) mechanisms. Commonly used drugs, such as certain antibiotics, nonsteroidal anti-inflammatory drugs, psychotherapeutic agents, and even herbal medicines, may act as photosensitizers that promote retinal UV damage, if they are excited by UVA or visible light and have sufficient retinal penetration. CONCLUSIONS: Although the anterior portion of the eye is the most susceptible to UV damage, the retina is at risk to the longer UV wavelengths that propagate through the ocular media. Some phototoxicity may be counteracted or reduced by dietary intake of antioxidants and protective phytonutrients.
MED-2886
Goji berry effects on macular characteristics and plasma antioxidant levels.
PURPOSE: Goji berry (Lycium barbarum L.) is purported to benefit vision because of its high antioxidant (especially zeaxanthin) content, although this effect has not been demonstrated in high-quality human studies. The purpose of this study was to evaluate the effects of daily supplementation with a proprietary milk-based formulation of goji berry, Lacto-Wolfberry (LWB), on macular characteristics and plasma zeaxanthin and antioxidant capacity levels in elderly subjects. METHODS: This was a double-masked, randomized, placebo-controlled trial in healthy elderly subjects (range, 65 to 70 years) receiving 13.7 g/d of LWB (n = 75) or placebo (n = 75) for 90 days. Subjects underwent direct ophthalmic examination to assess pigmentation and soft drusen count in the macula and a blood draw to measure plasma zeaxanthin level and total antioxidant capacity. RESULTS: The placebo group demonstrated hypopigmentation and soft drusen accumulation in the macula, whereas the LWB group remained stable. Both plasma zeaxanthin level and antioxidant capacity increased significantly in the LWB group, by 26% and 57%, respectively, but did not change in the placebo group. No product-related adverse events were reported in either group. CONCLUSIONS: Overall, daily dietary supplementation with goji berry for 90 days increases plasma zeaxanthin and antioxidant levels as well as protects from hypopigmentation and soft drusen accumulation in the macula of elderly subjects. However, the mechanism of action is unclear, given the lack of relationship between change in plasma zeaxanthin and change in macular characteristics.
MED-2888
Fasting plasma zeaxanthin response to Fructus barbarum L. (wolfberry; Kei Tze) in a food-based human supplementation trial.
Age-related macular degeneration (AMD) is a common disorder that causes irreversible loss of central vision. Increased intake of foods containing zeaxanthin may be effective in preventing AMD because the macula accumulates zeaxanthin and lutein, oxygenated carotenoids with antioxidant and blue light-absorbing properties. Lycium barbarum L. is a small red berry known as Fructus lycii and wolfberry in the West, and Kei Tze and Gou Qi Zi in Asia. Wolfberry is rich in zeaxanthin dipalmitate, and is valued in Chinese culture for being good for vision. The aim of this study, which was a single-blinded, placebo-controlled, human intervention trial of parallel design, was to provide data on how fasting plasma zeaxanthin concentration changes as a result of dietary supplementation with whole wolfberries. Fasting blood was collected from healthy, consenting subjects; fourteen subjects took 15 g/d wolfberry (estimated to contain almost 3 mg zeaxanthin) for 28 d. Repeat fasting blood was collected on day 29. Age- and sex-matched controls (n 13) took no wolfberry. Responses in the two groups were compared using the Mann-Whitney test. After supplementation, plasma zeaxanthin increased 2.5-fold: mean values on day 1 and 29 were 0.038 (sem 0.003) and 0.096 (sem 0.009) micromol/l (P<0.01), respectively, for the supplementation group; and 0.038 (sem 0.003) and 0.043 (sem 0.003) micromol/l (P>0.05), respectively, for the control group. This human supplementation trial shows that zeaxanthin in whole wolfberries is bioavailable and that intake of a modest daily amount markedly increases fasting plasma zeaxanthin levels. These new data will support further study of dietary strategies to maintain macular pigment density.
MED-2889
Cataract is a self-defence reaction to protect the retina from oxidative damage.
Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Cataract extraction is the most common surgical procedure in developed countries. Lutein (L) and zeaxanthin (Z), retinal carotenoids, are the most powerful retinal anti-oxidants and absorb the harmful blue light. The depletion of L+Z induces the development of the lens opacification-cataract. Cataract reduces the retinal oxidative stress (OS), which causes a reduction of the probability to develop AMD. Oxidative Stress at the retinal level is the common pathway in the development of AMD and cataract. AMD and cataract are not two independent processes. Cataract is a self-defense reaction of the retina to reduce OS and retinal damage. Restoring the anti-oxidative capabilities of the retina by increasing intake of L+Z reduces the likelihood of AMD and cataract. Extracting the opaque lens elevates the retinal OS and increases the rate of AMD. Copyright © 2011 Elsevier Ltd. All rights reserved.
MED-2890
Nearwork-induced transient myopia (NITM) and permanent myopia--is there a link?
Myopia is a worldwide public health problem. However, its understanding is incomplete, and many of its preventative and therapeutic aspects remain controversial. Nearwork is a primary, environmentally based factor in the aetiology of permanent myopia (PM), with nearwork-induced transient myopia (NITM) being a possible contributory component. A relationship between PM and NITM has been suggested, but that connection has remained somewhat indirect and elusive. However, based on recent converging evidence from clinical, laboratory and modelling studies, a five-fold argument will be advanced for a possible link between PM and NITM.
MED-2891
Variations in product choices of frequently purchased herbs: caveat emptor.
BACKGROUND: Patients who report use of herbs to their physicians may not be able to accurately describe the ingredients or recommended dosage because the products for the same herb may differ. The purpose of this study was to describe variations in label information of products for each of the 10 most commonly purchased herbs. METHODS: Products for each of 10 herbs were surveyed in a convenience sample of 20 retail stores in a large metropolitan area. Herbs were those with the greatest sales dollars in 1998: echinacea, St John's wort, Ginkgo biloba, garlic, saw palmetto, ginseng, goldenseal, aloe, Siberian ginseng, and valerian. RESULTS: Each herb had a large range in label ingredients and recommended daily dose (RDD) across available products. Strengths were not directly comparable because of ingredient variability. Among 880 products, 43% were consistent with a benchmark in ingredients and RDD, 20% in ingredients only, and 37% were either not consistent or label information was insufficient. Price per RDD was a significant predictor of consistency with the benchmark, but store type was not. CONCLUSIONS: Persons self-medicating with an herb may be ingesting ingredients substantially different from that recommended by a benchmark, both in quantity and content. Higher price per label RDD was the best predictor of consistency with a benchmark. This study demonstrates that health providers and consumers need to closely examine label ingredients of presumably the same or similar herbal products.
MED-2892
The effect of bilberry nutritional supplementation on night visual acuity and contrast sensitivity.
PURPOSE: The purpose of this study was to investigate the effect of bilberry on night visual acuity (VA) and night contrast sensitivity (CS). METHODS: This study utilized a double-blind, placebo-controlled, crossover design. The subjects were young males with good vision; eight received placebo and seven received active capsules for three weeks. Active capsules contained 160 mg of bilberry extract (25-percent anthocyanosides), and the placebo capsules contained only inactive ingredients. Subjects ingested one active or placebo capsule three times daily for 21 days. After the three-week treatment period, a one-month washout period was employed to allow any effect of bilberry on night vision to dissipate. In the second three-week treatment period, the eight subjects who first received placebo were given active capsules, and the seven who first received active capsules were given placebo. Night VA and night CS was tested throughout the three-month experiment. RESULTS: There was no difference in night VA during any of the measurement periods when examining the average night VA or the last night VA measurement during active and placebo treatments. In addition, there was no difference in night CS during any of the measurement periods when examining the average night CS or the last night CS measurement during active and placebo treatments. CONCLUSION: The current study failed to find an effect of bilberry on night VA or night CS for a high dose of bilberry taken for a significant duration. Hence, the current study casts doubt on the proposition that bilberry supplementation, in the forms currently available and in the doses recommended, is an effective treatment for the improvement of night vision in this population.
MED-2893
Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a systematic review and meta-analysis.
Lutein and zeaxanthin are thought to decrease the incidence of age-related macular degeneration (AMD); however, findings have been inconsistent. We conducted a systematic literature review and meta-analysis to evaluate the relationship between dietary intake of lutein and zeaxanthin and AMD risk. Relevant studies were identified by searching five databases up to April 2010. Reference lists of articles were retrieved, and experts were contacted. Literature search, data extraction and study quality assessment were performed independently by two reviewers and results were pooled quantitatively using meta-analysis methods. The potential sources of heterogeneity and publication bias were also estimated. The search yielded six longitudinal cohort studies. The pooled relative risk (RR) for early AMD, comparing the highest with the lowest category of lutein and zeaxanthin intake, was 0·96 (95 % CI 0·78, 1·17). Dietary intake of these carotenoids was significantly related with a reduction in risk of late AMD (RR 0·74; 95 % CI 0·57, 0·97); and a statistically significant inverse association was observed between lutein and zeaxanthin intake and neovascular AMD risk (RR 0·68; 95 % CI 0·51, 0·92). The results were essentially consistent among subgroups stratified by participant characteristics. The findings of the present meta-analysis indicate that dietary lutein and zeaxanthin is not significantly associated with a reduced risk of early AMD, whereas an increase in the intake of these carotenoids may be protective against late AMD. However, additional studies are needed to confirm these relationships.
MED-2895
Dietary modification of human macular pigment density.
PURPOSE: The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether MP density in the retina could be raised by increasing dietary intake of L and Z from foods. METHODS: Macular pigment was measured psychophysically for 13 subjects. Serum concentrations of L, Z, and beta-carotene were measured by high-performance liquid chromatography. Eleven subjects modified their usual daily diets by adding 60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150 g of corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary modification lasted up to 15 weeks. RESULTS: For the subjects fed spinach or spinach and corn, three types of responses to dietary modification were identified: Eight "retinal responders" had increases in serum L (mean, 33%; SD, 22%) and in MP density (mean, 19%; SD, 11%); two "retinal nonresponders" showed substantial increases in serum L (mean, 31%) but not in MP density (mean, -11%); one "serum and retinal nonresponder" showed no changes in serum L, Z, or beta-carotene and no change in MP density. For the two subjects given only corn, serum L changed little (+11%, -6%), but in one subject serum Z increased (70%) and MP density increased (25%). CONCLUSIONS: Increases in MP density were obtained within 4 weeks of dietary modification for most, but not all, subjects. When MP density increased with dietary modification, it remained elevated for at least several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical investigation appears to be feasible for many persons.
MED-3139
Soy food intake after diagnosis of breast cancer and survival: an in-depth analysis of combined evidence from cohort studies of US and Chinese women
Background: Soy isoflavones have antiestrogenic and anticancer properties but also possess estrogen-like properties, which has raised concern about soy food consumption among breast cancer survivors. Objective: We prospectively evaluated the association between postdiagnosis soy food consumption and breast cancer outcomes among US and Chinese women by using data from the After Breast Cancer Pooling Project. Design: The analysis included 9514 breast cancer survivors with a diagnosis of invasive breast cancer between 1991 and 2006 from 2 US cohorts and 1 Chinese cohort. Soy isoflavone intake (mg/d) was measured with validated food-frequency questionnaires. HRs and 95% CIs were estimated by using delayed-entry Cox regression models, adjusted for sociodemographic, clinical, and lifestyle factors. Results: After a mean follow-up of 7.4 y, we identified 1171 total deaths (881 from breast cancer) and 1348 recurrences. Despite large differences in soy isoflavone intake by country, isoflavone consumption was inversely associated with recurrence among both US and Chinese women, regardless of whether data were analyzed separately by country or combined. No heterogeneity was observed. In the pooled analysis, consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of all-cause (HR: 0.87; 95% CI: 0.70, 1.10) and breast cancer–specific (HR: 0.83; 95% CI: 0.64, 1.07) mortality and a statistically significant reduced risk of recurrence (HR: 0.75; 95% CI: 0.61, 0.92). Conclusion: In this large study of combined data on US and Chinese women, postdiagnosis soy food consumption of ≥10 mg isoflavones/d was associated with a nonsignificant reduced risk of breast cancer–specific mortality and a statistically significant reduced risk of recurrence. One of the studies included in the After Breast Cancer Pooling Project, the Women's Healthy Eating & Living Study, was registered at clinicaltrials.gov as NCT00003787.
MED-3142
Positive effects of soy isoflavone food on survival of breast cancer patients in China.
AIM: Soy foods are the major source of isoflavones, which are believed to play important roles in genesis of breast cancer and its progression. We here conducted a prospective study to evaluate the association of soy isoflavone food consumption with breast cancer prognosis. METHODS: A prospective study was performed from January 2004 and January 2006 in China. Trained interviewers conducted face-to-face interviews using a structured questionnaire to collect information on dietary habits and potential confounding factors. The relative risk [hazard ratio (HR)] and 95% CI were calculated from the Cox regression model for all significant predictors from cancer diagnosis to the endpoint of the study (event). RESULTS: After a median follow up of 52.1 months (range, 9-60 months), a total of 79 breast cancer related deaths were recorded in our study, risk being inversely associated with a high intake of soy isoflavone. With an average intake of soy isoflavone above 17.3 mg/day, the mortality of breast cancer can be reduced by about 38-36%. We also found the decreased breast cancer death with high soy protein intake, with a HR (95% CI) of 0.71 (0.52-0.98). Stratified analysis with reference to the ER status, further demonstrated a better prognosis of ER positive breast cancer with a high intake of soy isoflavone (HR 0.59, 0.40-0.93). CONCLUSION: Our study shows the soy food intake is associated with longer survival and low recurrence among breast cancer patients. A cohort study with a larger sample size and long term follow-up is now needed.
MED-3143
Gastrointestinal symptoms in 3181 volunteers ingesting snack foods containing olestra or triglycerides. A 6-week randomized, placebo-controlled trial.
BACKGROUND: Olestra is a nonabsorbable, energy-free fat substitute. Because it is not absorbed, it may cause digestive symptoms when consumed in large amounts. OBJECTIVE: To compare the frequency and impact of gastrointestinal symptoms in adults and children who freely consume snacks containing olestra or regular snacks in the home. DESIGN: 6-week, double-blind, randomized, parallel, placebo-controlled trial. SETTING: General community. PARTICIPANTS: 3181 volunteers 2 to 89 years of age. INTERVENTION: Households received identical packages labeled as containing olestra corn or potato chips. These packages contained either olestra or regular chips (control). MEASUREMENT: Gastrointestinal symptoms and their impact on daily activities were reported in a daily record. RESULTS: At least one gastrointestinal symptom was reported by 619 of 1620 (38.2%) persons in the olestra group and 576 of 1561 (36.9%) controls (difference, 1.3 percentage points [95% CI, -3.6 to 6.2 percentage points]; P = 0.60). In general, the groups did not differ significantly in the proportion of participants who reported individual gastrointestinal symptoms; however, more controls reported nausea (8.4% compared with 5.7%; difference, -2.7 percentage points [CI, -4.9 to -0.4 percentage points]; P = 0.02). The only difference between groups for the mean numbers of days on which symptoms were reported was that participants in the olestra group had 1 more symptom-day of more frequent bowel movements than did controls (3.7 symptom-days compared with 2.8 symptom days; difference, 0.9 symptom-days [CI, 0.1 to 1.8 symptom-days]; P = 0.04). The groups did not differ in the impact of symptoms on daily activities. CONCLUSIONS: Clinically meaningful or bothersome gastrointestinal effects are not associated with unregulated consumption of olestra corn and potato chips in the home.
MED-3623
Pediatric CT research elevates public health concerns: low-dose radiation issues are highly politicized.
This article presents an analysis of issues related to low-dose radiation, with a focus on pediatric computed tomography (CT). It references several early studies that are seldom quoted in radiation research papers, then quantifies the excess lifetime fatal cancer yield attributable to an estimated 6.5 million pediatric abdominal CT scans. The authors highlight an important policy document issued jointly by the National Cancer Institute and the Society for Pediatric Radiology--specifically, its conclusion that a small dose from CT represents "a public health concern." Finally, the article identifies several contentious issues and proposes policy initiatives that, if implemented, could result in significant reductions of future radiogenic cancers and chronic injuries. The authors call for discussions between professional radiology societies and public interest health organizations, thereby involving all stakeholders.
MED-3624
Estimated risks of radiation-induced fatal cancer from pediatric CT.
OBJECTIVE: In light of the rapidly increasing frequency of pediatric CT examinations, the purpose of our study was to assess the lifetime cancer mortality risks attributable to radiation from pediatric CT. MATERIALS AND METHODS: Organ doses as a function of age-at-diagnosis were estimated for common CT examinations, and estimated attributable lifetime cancer mortality risks (per unit dose) for different organ sites were applied. Standard models that assume a linear extrapolation of risks from intermediate to low doses were applied. On the basis of current standard practice, the same exposures (milliampere-seconds) were assumed, independent of age. RESULTS: The larger doses and increased lifetime radiation risks in children produce a sharp increase, relative to adults, in estimated risk from CT. Estimated lifetime cancer mortality risks attributable to the radiation exposure from a CT in a 1-year-old are 0.18% (abdominal) and 0.07% (head)-an order of magnitude higher than for adults-although those figures still represent a small increase in cancer mortality over the natrual background rate. In the United States, of approximately 600,000 abdominal and head CT examinations annually performed in children under the age of 15 years, a rough estimate is that 500 of these individuals might ultimately die from cancer attributable to the CT radiation. CONCLUSION: The best available risk estimates suggest that pediatric CT will result in significantly increased lifetime radiation risk over adult CT, both because of the increased dose per milliampere-second, and the increased lifetime risk per unit dose. Lower milliampere-second settings can be used for children without significant loss of information. Although the risk-benefit balance is still strongly tilted toward benefit, because the frequency of pediatric CT examinations is rapidly increasing, estimates that quantitative lifetime radiation risks for children undergoing CT are not negligible may stimulate more active reduction of CT exposure settings in pediatric patients.
MED-3625
Informed consent and communication of risk from radiological and nuclear medicine examinations: how to escape from a communication inferno
Short abstract Radiological and nuclear medicine examinations confer a definite (albeit low) long term risk of cancer, but patients undergoing such examinations often receive no or inaccurate information about these risks. Picano argues that this disregard of patient autonomy is no longer acceptable and suggests a practicable way of communicating risk
MED-3626
Justification of diagnostic medical exposures: some practical issues. Report of an International Atomic Energy Agency Consultation
Objectives The Radiation Protection of Patients Unit of the International Atomic Energy Agency (IAEA) is concerned about the effectiveness of justification of diagnostic medical exposures. Recent published work and the report of an initial IAEA consultation in the area gave grounds for such concerns. There is a significant level of inappropriate usage, and, in some cases, a poor level of awareness of dose and risk among some key groups involved. This article aims to address this. Methods The IAEA convened a second group of experts in November 2008 to review practical and achievable actions that might lead to more effective justification. Results This report summarises the matters that this group considered and the outcome of their deliberations. There is a need for improved communication, both within professions and between professionals on one hand, and between professionals and the patients/public on the other. Coupled with this, the issue of consent to imaging procedures was revisited. The need for good evidence-based referral guidelines or criteria of acceptability was emphasised, as was the need for their global adaptation and dissemination. Conclusion Clinical audit was regarded as a key tool in ensuring that justification becomes an effective, transparent and accountable part of normal radiological practice. In summary, justification would be facilitated by the “3 As”: awareness, appropriateness and audit.
MED-3627
Projected cancer risks from computed tomographic scans performed in the United States in 2007.
BACKGROUND: The use of computed tomographic (CT) scans in the United States (US) has increased more than 3-fold since 1993 to approximately 70 million scans annually. Despite the great medical benefits, there is concern about the potential radiation-related cancer risk. We conducted detailed estimates of the future cancer risks from current CT scan use in the US according to age, sex, and scan type. METHODS: Risk models based on the National Research Council's "Biological Effects of Ionizing Radiation" report and organ-specific radiation doses derived from a national survey were used to estimate age-specific cancer risks for each scan type. These models were combined with age- and sex-specific scan frequencies for the US in 2007 obtained from survey and insurance claims data. We estimated the mean number of radiation-related incident cancers with 95% uncertainty limits (UL) using Monte Carlo simulations. RESULTS: Overall, we estimated that approximately 29 000 (95% UL, 15 000-45 000) future cancers could be related to CT scans performed in the US in 2007. The largest contributions were from scans of the abdomen and pelvis (n = 14 000) (95% UL, 6900-25 000), chest (n = 4100) (95% UL, 1900-8100), and head (n = 4000) (95% UL, 1100-8700), as well as from chest CT angiography (n = 2700) (95% UL, 1300-5000). One-third of the projected cancers were due to scans performed at the ages of 35 to 54 years compared with 15% due to scans performed at ages younger than 18 years, and 66% were in females. CONCLUSIONS: These detailed estimates highlight several areas of CT scan use that make large contributions to the total cancer risk, including several scan types and age groups with a high frequency of use or scans involving relatively high doses, in which risk-reduction efforts may be warranted.
MED-3628
210Po in the marine environment with emphasis on its behaviour within the biosphere.
The distribution and behaviour of the natural-series alpha-emitter polonium-210 in the marine environment has been under study for many years primarily due to its enhanced bioaccumulation, its strong affinity for binding with certain internal tissues, and its importance as a contributor to the natural radiation dose received by marine biota as well as humans consuming seafoods. Results from studies spanning nearly 5 decades show that (210)Po concentrations in organisms vary widely among the different phylogenic groups as well as between the different tissues of a given species. Such variation results in (210)Po concentration factors ranging from approximately 10(3) to over 10(6) depending upon the organism or tissue considered. (210)Po/(210)Pb ratios in marine species are generally greater than unity and tend to increase up the food chain indicating that (210)Po is preferentially taken up by organisms compared to its progenitor (210)Pb. The effective transfer of (210)Po up the food chain is primarily due to the high degree of assimilation of the radionuclide from ingested food and its subsequent strong retention in the organisms. In some cases this mechanism may lead to an apparent biomagnification of (210)Po at the higher trophic level. Various pelagic species release (210)Po and (210)Pb packaged in organic biodetrital particles that sink and remove these radionuclides from the upper water column, a biogeochemical process which, coupled with scavenging rates of this radionuclide pair, is being examined as a possible proxy for estimating downward organic carbon fluxes in the sea. Data related to preferential bioaccumulation in various organisms, their tissues, resultant radiation doses to these species, and the processes by which (210)Po is transferred and recycled through the food web are discussed. In addition, the main gaps in our present knowledge and proposed areas for future studies on the biogeochemical behaviour of (210)Po and its use as a tracer of oceanographic processes are highlighted in this review. Copyright © 2010 Elsevier Ltd. All rights reserved.
MED-3629
Pacific bluefin tuna transport Fukushima-derived radionuclides from Japan to California
The Fukushima Dai-ichi release of radionuclides into ocean waters caused significant local and global concern regarding the spread of radioactive material. We report unequivocal evidence that Pacific bluefin tuna, Thunnus orientalis, transported Fukushima-derived radionuclides across the entire North Pacific Ocean. We measured γ-emitting radionuclides in California-caught tunas and found 134Cs (4.0 ± 1.4 Bq kg−1) and elevated 137Cs (6.3 ± 1.5 Bq kg−1) in 15 Pacific bluefin tuna sampled in August 2011. We found no 134Cs and background concentrations (∼1 Bq kg−1) of 137Cs in pre-Fukushima bluefin and post-Fukushima yellowfin tunas, ruling out elevated radiocesium uptake before 2011 or in California waters post-Fukushima. These findings indicate that Pacific bluefin tuna can rapidly transport radionuclides from a point source in Japan to distant ecoregions and demonstrate the importance of migratory animals as transport vectors of radionuclides. Other large, highly migratory marine animals make extensive use of waters around Japan, and these animals may also be transport vectors of Fukushima-derived radionuclides to distant regions of the North and South Pacific Oceans. These results reveal tools to trace migration origin (using the presence of 134Cs) and potentially migration timing (using 134Cs:137Cs ratios) in highly migratory marine species in the Pacific Ocean.
MED-3630
Radioactive fallout in the United States due to the Fukushima nuclear plant accident.
The release of radioactivity into the atmosphere from the damaged Fukushima Daiichi nuclear power plant started on March 12th, 2011. Among the various radionuclides released, iodine -131 ((131)I) and cesium isotopes ((137)Cs and (134)Cs) were transported across the Pacific Ocean and reached the United States on 17-18 March 2011. Consequently, an elevated level of fission products (131)I, (132)I, (132)Te, (134)Cs and (137)Cs were detected in air, water, and milk samples collected across the United States between March 17 and April 4, 2011. The continuous monitoring of activities over a period of 25 days and spatial variations across more than 100 sampling locations in the United States made it possible to characterize the contaminated air masses. For the entire period, the highest detected activity values ranged from less than 1 m Bq m(-3) to 31 m Bq m(-3) for the particulate (131)I, and up to 96 m Bq m(-3) for the gaseous (131)I fraction.
MED-3631
Increase of 210Po levels in human semen fluid after mussel ingestion.
Polonium-210 ((210)Po) radioactive concentrations were determined in human semen fluid of vasectomized non-smoker volunteers. The (210)Po levels ranged from 0.10 to 0.39 mBq g(-1) (mean: 0.23 ± 0.08 mBq g(-1)). This value decreased to 0.10 ± 0.02 mBq g(-1) (range from 0.07 to 0.13 mBq g(-1)) after two weeks of a controlled diet, excluding fish and seafood. Then, volunteers ate during a single meal 200 g of the cooked mussel Perna perna L., and (210)Po levels were determined again, during ten days, in semen fluid samples collected every morning. Volunteers continued with the controlled diet and maintained sexual abstinence through the period of the experiment. A 300% increase of (210)Po level was observed the day following mussel consumption, with a later reduction, such that the level returned to near baseline by day 4. Copyright © 2011 Elsevier Ltd. All rights reserved.
MED-3632
An unexpected mortality increase in the United States follows arrival of the radioactive plume from Fukushima: is there a correlation?
The multiple nuclear meltdowns at the Fukushima plants beginning on March 11, 2011, are releasing large amounts of airborne radioactivity that has spread throughout Japan and to other nations; thus, studies of contamination and health hazards are merited. In the United States, Fukushima fallout arrived just six days after the earthquake, tsunami, and meltdowns. Some samples of radioactivity in precipitation, air, water, and milk, taken by the U.S. government, showed levels hundreds of times above normal; however, the small number of samples prohibits any credible analysis of temporal trends and spatial comparisons. U.S. health officials report weekly deaths by age in 122 cities, about 25 to 35 percent of the national total. Deaths rose 4.46 percent from 2010 to 2011 in the 14 weeks after the arrival of Japanese fallout, compared with a 2.34 percent increase in the prior 14 weeks. The number of infant deaths after Fukushima rose 1.80 percent, compared with a previous 8.37 percent decrease. Projecting these figures for the entire United States yields 13,983 total deaths and 822 infant deaths in excess of the expected. These preliminary data need to be followed up, especially in the light of similar preliminary U.S. mortality findings for the four months after Chernobyl fallout arrived in 1986, which approximated final figures.
MED-3633
Semen quality of male idiopathic infertile smokers and nonsmokers: an ultrastructural study.
This retrospective study was aimed at evaluating the effects of cigarette consumption on semen parameters in a group of men with idiopathic infertility. The semen quality of 2 groups of men with idiopathic infertility, smokers (n = 118) and nonsmokers (n = 153), were compared. Conventional semen analysis was performed and sperm morphology was assessed by transmission electron microscopy (TEM). TEM data were elaborated by means of a mathematical formula based on a Bayesian technique able to furnish a fertility index (FI), and the percentages of sperm apoptosis, necrosis, and immaturity. Values of normality recommended by World Health Organization guidelines were used as a control for conventional semen analysis, and values from sperm of 25 men of proven fertility were used for TEM indices. Infertile smoker and nonsmoker patients showed similar sperm parameters, although sperm motility and TEM analysis values in both groups were significantly impaired compared with controls. Smoker patients were then classified as mild (>or=1 and <or=10 cigarettes/d), moderate (>10 and <20 cigarettes/day), or heavy smokers (>or=20 cigarettes/d). Sperm concentration and FI were significantly (P < .05) different among the 3 considered smoker classes. Comparing the pairs of smoker classes, sperm concentration and FI in heavy smokers were significantly lower (P < .05) than that observed in mild smoker and nonsmoker groups. Although semen quality in males with idiopathic infertility seems not to be dramatically affected by cigarette consumption, heavy smokers show significantly lower sperm concentration and FI: another strong reason to stop smoking.
MED-3634
Cigarette smoke radioactivity and lung cancer risk.
INTRODUCTION: To determine the tobacco industry's policy and action with respect to radioactive polonium 210 ((210)Po) in cigarette smoke and to assess the long-term risk of lung cancer caused by alpha particle deposits in the lungs of regular smokers. METHODS: Analysis of major tobacco industries' internal secret documents on cigarette radioactivity made available online by the Master Settlement Agreement in 1998. RESULTS: The documents show that the industry was well aware of the presence of a radioactive substance in tobacco as early as 1959. Furthermore, the industry was not only cognizant of the potential "cancerous growth" in the lungs of regular smokers but also did quantitative radiobiological calculations to estimate the long-term (25 years) lung radiation absorption dose (rad) of ionizing alpha particles emitted from the cigarette smoke. Our own calculations of lung rad of alpha particles match closely the rad estimated by the industry. According to the Environmental Protection Agency, the industry's and our estimate of long-term lung rad of alpha particles causes 120-138 lung cancer deaths per year per 1,000 regular smokers. Acid wash was discovered in 1980 to be highly effectively in removing (210)Po from the tobacco leaves; however, the industry avoided its use for concerns that acid media would ionize nicotine converting it into a poorly absorbable form into the brain of smokers thus depriving them of the much sought after instant "nicotine kick" sensation. CONCLUSIONS: The evidence of lung cancer risk caused by cigarette smoke radioactivity is compelling enough to warrant its removal.
MED-3635
Wet deposition of fission-product isotopes to North America from the Fukushima Dai-ichi incident, March 2011.
Using the infrastructure of the National Atmospheric Deposition Program (NADP), numerous measurements of radionuclide wet deposition over North America were made for 167 NADP sites before and after the Fukushima Dai-ichi Nuclear Power Station incident of March 12, 2011. For the period from March 8 through April 5, 2011, wet-only precipitation samples were collected by NADP and analyzed for fission-product isotopes within whole-water and filterable solid samples by the United States Geological Survey using gamma spectrometry. Variable amounts of (131)I, (134)Cs, or (137)Cs were measured at approximately 21% of sampled NADP sites distributed widely across the contiguous United States and Alaska. Calculated 1- to 2-week individual radionuclide deposition fluxes ranged from 0.47 to 5100 Becquerels per square meter during the sampling period. Wet deposition activity was small compared to measured activity already present in U.S. soil. NADP networks responded to this complex disaster, and provided scientifically valid measurements that are comparable and complementary to other networks in North America and Europe.
MED-3636
Death by polonium-210: lessons learned from the murder of former Soviet spy Alexander Litvinenko.
The medical response to radiation--whether the result of radiological warfare, terrorist deployment of improvised radiation dispersal weapons, political assassination, occupational or industrial accidents or the medically radiated patient remains one of the least taught among all disciplines within medical education. In the aftermath of 9/11 among medical vulnerabilities to toxicant threats, of all the categories of weapons of mass destruction (WMD)--whether using the CBRNE (chemical, biological, radiological, nuclear, explosive) or NBC (nuclear, biological, chemical) acronym--radiation is the least taught in professional schools, responder cultures or civil preparedness organizations. To date, few health care professionals (HCP) possess the fundamental knowledge or skills to identify and diagnose, let alone treat a radiation victim; this vulnerability made even more obvious in the aftermath of the high profile assassination of former Russian agent Alexander Litvinenko. He was poisoned with Polonium210. Radioactive substances are ubiquitous with radiation sources being in or transported through virtually every region nationwide. It is essential to increase preparedness among community and rural health care facilities as well as urban and university hospitals. Managing radiation injuries effectively requires access to specialized equipment and expertise. Radiation sickness is progressive and may require acute, critical and long-term care throughout the course of illness. Regardless of the source, preparedness rests upon acknowledging a threat exists and dedicating the resources to address the risks including the enhancement of training and equipment. Mass or individual exposures to radiation present unique challenges to the entire response continuum from law enforcement, first responders and emergency medical care. Increased education about and practice in responding to radiological threats is essential to enhance preparedness.
MED-3863
Sensitive skin: closing in on a physiological cause.
The phenomenon of 'sensitive skin' is a relatively recent complaint in which certain individuals report more intense and frequent adverse sensory effects than the normal population upon use of cosmetic (personal-care) products. Originally defined as a minority complaint, sensitive skin is now claimed by a majority of women in industrialized countries and nearly half of men. Sensitive skin is self-diagnosed and typically unaccompanied by any obvious physical signs of irritation, and the number of individuals who claim sensitivity has risen steadily with the number of consumer products targeted towards this supposedly uncommon group. Believed by many dermatologists, therefore, to be a 'princess and the pea' phenomenon, the problem of sensitive skin has largely avoided focussed research. Over the last few years, however, the evidence of documentable biophysical changes associated with the largely sensory symptoms of this disorder has accumulated, including some gained by improved methods of identifying subclinical signs of skin irritation. Although the understanding of the aetiology of this phenomenon is as yet incomplete, existing research now supports a biophysical origin for this disorder. Effective methods of diagnosis, intrinsic and extrinsic contributors to exaggerated neural sensitivity, and the specific mechanisms of the discomfort associated with the compliant are required, as are appropriate means of prevention and treatment.
MED-3864
Supplementation of flaxseed oil diminishes skin sensitivity and improves skin barrier function and condition.
BACKGROUND: Skin sensitivity is a common problem in the Western population correlated with changes of skin properties like skin barrier function, hydration and skin physiology. Skin properties can be modulated by dietary fatty acids (FA), especially poly-unsaturated FA. The present study was performed to evaluate the effect of daily supplementation with flaxseed oil and safflowerseed oil on healthy volunteers with sensitive skin. METHODS: The study was designed as a randomized, double-blind 12-week intervention with 2 female treatment groups (n = 13). Plasma FA profile, skin sensitivity, skin hydration, transepidermal water loss (TEWL) and skin surface were evaluated on day 0, week 6 and week 12. RESULTS: Supplementation with flaxseed oil led to significant decreases in sensitivity (after nicotinate irritation), TEWL, skin roughness and scaling, while smoothness and hydration were increased. Concomitantly, the ratio of n-6/n-3 FA in plasma decreased. Upon supplementation with safflowerseed oil, only a significant improvement in skin roughness and hydration was observed; however, the effects were less pronounced and determined at a later point in time than with flaxseed oil. The plasma n-6/n-3 FA ratio increased. CONCLUSION: The data provide evidence that daily intake of flaxseed oil modulates skin condition. Copyright © 2010 S. Karger AG, Basel.
MED-3865
Sensitive skin in the American population: prevalence, clinical data, and role of the dermatologist.
INTRODUCTION: Sensitive skin is a complex dermatological condition, defined by abnormal sensory symptoms. The aim of this epidemiological survey was to assess the prevalence of sensitive skin and collect data on sensitive skin in the US population. METHODS: A phone survey was conducted in the USA by a poll institute in 2007. A sample was drawn from a representative national cohort of the American population at least 18years of age through the quota method. Data on demographic characteristics, environmental and climatic factors, skin characteristics, dermatological disorders, cosmetics use, and visits to the dermatologist were collected. RESULTS: Of 994 subjects who answered (495 men and 499 women), 44.6% declared having "sensitive" or "very sensitive" skin. Women were more concerned than men (50.9% vs. 38.2%, P<0.0001). There was no significant difference related to geographic localization, age, or ethnic distribution. Subjects with sensitive skin had mainly dry (34.5%) or mixed skin (35.7%), fair phototypes, dermatological disorders, higher skin reactivity to cosmetics and various environmental factors in comparison with subjects who stated having only a "slightly" sensitive or not sensitive skin. The dermatologist had a strong influence on subjects with "sensitive" or "very sensitive" skin through the prescription of skin care products. CONCLUSION: This study, based on a representative sample of the American population, reveals a high prevalence of sensitive skin in the USA. Sensitive skin is mainly associated with dry skin, fair phototype, reactivity to climatic and environmental factors, and cosmetics. American dermatologists seem largely involved in the care of this condition. © 2011 The International Society of Dermatology.
MED-3874
Flaxseed Supplementation (not Dietary Fat Restriction) Reduces Prostate Cancer Proliferation Rates in Men Presurgery
Background Prostate cancer affects one-out-of-six men during their lifetime. Dietary factors are postulated to influence the development and progression of prostate cancer. Low-fat diets and flaxseed supplementation may offer potentially protective strategies. Methods We undertook a multi-site, randomized controlled trial to test the effects of low-fat and/or flaxseed-supplemented diets on the biology of the prostate and other biomarkers. Prostate cancer patients (n=161) scheduled at least 21 days before prostatectomy were randomly assigned to one of the following arms: 1) control (usual diet); 2) flaxseed-supplemented diet (30 g/day); 2) low-fat diet (<20% total energy); or 4) flaxseed-supplemented, low-fat diet. Blood was drawn at baseline and prior to surgery and analyzed for prostate specific antigen (PSA), sex hormone binding globulin, testosterone, insulin-like growth factor-1 and binding protein-3, c-reactive protein, and total and low density lipoprotein cholesterol. Tumors were assessed for proliferation (Ki-67, the primary endpoint) and apoptosis. Results Men were on protocol an average of 30 days. Proliferation rates were significantly lower (P < 0.002) among men assigned to the flaxseed arms. Median Ki-67 positive cells/total nuclei ratios (x100) were 1.66 (flaxseed-supplemented diet) and 1.50 (flaxseed-supplemented, low-fat diet) vs. 3.23 (control) and 2.56 (low-fat diet). No differences were observed between arms with regard to side effects, apoptosis, and most serological endpoints; however, men on low-fat diets experienced significant decreases in serum cholesterol (P=0.048). Conclusions Findings suggest that flaxseed is safe, and associated with biologic alterations that may be protective for prostate cancer. Data also further support low-fat diets to manage serum cholesterol.
MED-3875
Effect of mammalian lignans on the growth of prostate cancer cell lines.
BACKGROUND: Mammalian lignans, enterolactone (EL) and enterodiol (ED), have been shown to inhibit breast and colon carcinoma. To date, there have been no reports of the effect of lignans on prostatic carcinoma. We investigated the effects of ED and EL on three human prostate cancer cell lines (PC-3, DU-145 and LNCaP). MATERIALS AND METHODS: Cells were treated with either 0.1% (v/v) DMSO (vehicle) or 10-100 microM of EL, ED or genistein (positive control) for 72 hours. Cell viability was measured by the propidium iodide nuclei staining fluorometric assay with each assay performed in triplicate. RESULTS: At 10-100 microM, EL significantly inhibited the growth of all cell lines, whereas ED only inhibited PC-3 and LNCaP cells. While EL was a more potent growth inhibitor than ED, both were less potent than genistein. The dose for 50% growth inhibition of LNCaP cells (IC50) by EL was 57 microM, whereas IC50 was 100 microM for ED, (the observed IC50 for genistein was 25 microM). CONCLUSION: ED and EL suppress the growth of prostate cancer cells, and may do so via hormonally-dependent and independent mechanisms.
MED-3876
Lignans and isoflavonoids in plasma and prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom.
BACKGROUND: Chinese men have lower incidences of prostate cancer compared to men from Europe and North America. Asians consume large quantities of soya, a rich source of isoflavanoids phyto-oestrogens and have high plasma and urinary levels of these compounds. The mammalian lignans, enterolactone and enterodiol, are another group of weak plant oestrogens and are derived from seeds, cereals and grains. Vegetarians have high plasma and urinary concentrations of lignans. METHODS: The concentrations lignans and isoflavonic phyto-oestrogens were determined by gas chromatography-mass spectrometry (GC-MS) in plasma and prostatic fluid from Portuguese, Chinese and British men consuming their traditional diets. RESULTS: In prostatic fluid the mean concentrations of enterolactone were 31, 162 and 20.3 ng/ml for Hong Kong, Portugal and Britain respectively. Very high levels of enterolactone (> 600 ng/ml) were observed in the prostatic fluid of some of the men from Portugal. High concentrations of equol (3270 ng/ml) and daidzein (532 ng/ml) were found in a sample of prostatic fluid from Hong Kong. Higher mean levels of daidzein were observed in prostatic fluid from Hong Kong at 70 ng/ml, compared to 4.6 and 11.3 ng/ml in samples from Portugal and Britain respectively. Mean levels of daidzein were higher in the plasma samples from Hong Kong (31.3 ng/ml) compared to those from Portugal (1.3 ng/ml) and Britain (8.2 ng/ml). In general, the mean plasma concentrations of enterolactone from the three centres were similar, at 6.2, 3.9 and 3.9 ng/ml in samples from Hong Kong Portugal and Britain respectively. CONCLUSIONS: Higher concentrations of the isoflavanoid phyto-oestrogens, daidzein and equol, were found in the plasma and prostatic fluid of men from Hong Kong compared to those from Britain and Portugal. However, the levels of the lignan, enterolactone, were very much higher in prostatic fluid of Portuguese men. Isoflavanoids and lignans have many interesting properties and may, in part, be responsible for lower incidences of prostate cancer in men from Asia and also some Mediterranean countries. The isoflavanoids from soya, which are present in high concentrations in the prostatic fluid of Asian men, may be protective against prostate disease.
MED-3877
Pilot study to explore effects of low-fat, flaxseed-supplemented diet on proliferation of benign prostatic epithelium and prostate-specific antigen.
OBJECTIVES: Dietary factors may influence the prostate and have an impact on prostatic growth and disease. A small number of studies have suggested that flaxseed-supplemented, fat-restricted diets may thwart prostate cancer growth in both animals and humans. Unknown, however, is the potential effect of such a diet on benign prostatic epithelium. METHODS: We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet affects the proliferation rates in benign epithelium. We also explored the effects on circulating levels of prostate-specific antigen (PSA), total testosterone, and cholesterol. Fifteen men who were scheduled to undergo repeat prostate biopsy were instructed to follow a low-fat (less than 20% kcal), flaxseed-supplemented (30 g/day) diet and were provided with a supply of flaxseed to last throughout the 6-month intervention period. The PSA, total testosterone, and cholesterol levels were determined at baseline and at 6 months of follow-up. Reports from the original and repeat biopsies were compared, and proliferation (MIB-1) rates were quantified in the benign prostatic epithelium. RESULTS: Statistically significant decreases in PSA (8.47 +/- 3.82 to 5.72 +/- 3.16 ng/mL; P = 0.0002) and cholesterol (241.1 +/- 30.8 to 213.3 +/- 51.2 mg/dL; P = 0.012) were observed. No statistically significant change was seen in total testosterone (434.5 +/- 143.6 to 428.3 +/- 92.5 ng/dL). Although 6-month repeat biopsies were not performed in 2 cases because of PSA normalization, of the 13 men who underwent repeat biopsy, the proliferation rates in the benign epithelium decreased significantly from 0.022 +/- 0.027 at baseline to 0.007 +/- 0.014 at 6 months of follow-up (P = 0.0168). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect the biology of the prostate and associated biomarkers. A randomized controlled trial is needed to determine whether flaxseed supplementation, a low-fat diet, or a combination of the two regimens may be of use in controlling overall prostatic growth.
MED-3878
Effect of Low-fat Diets on Plasma Levels of NFκB-regulated Inflammatory Cytokines and Angiogenic Factors in Men with Prostate Cancer
Diet, nutritional status, and certain dietary supplements are postulated to influence the development and progression of prostate cancer. Angiogenesis and inflammation are central to tumor growth and progression, but the effect of diet on these processes remains uncertain. We explored changes in 50 plasma cytokines and angiogenic factors (CAFs) in 145 men with prostate cancer enrolled in a pre-operative, randomized controlled phase-II trial with four arms: control (usual diet); low-fat (LF) diet; flaxseed-supplemented (FS) diet; and flaxseed-supplemented, low-fat diet. The mean duration of dietary intervention was 30–31 days. Among the individual arms, the largest number of significant changes (baseline vs pre-operative follow-up) was observed in the LF arm, with 19 CAFs decreasing and one increasing (p<.05). Compared to the control arm, 6 CAFs—including pro-angiogenic factors (stromal-cell derived-1α and myeloid factors (granulocyte-colony-stimulating factor, macrophage colony-stimulating factor — all decreased in the LF arm compared to controls; 3 and 4 CAFs changed in the FS and FS+LF arms, respectively. Weight loss occurred in the LF arms and significantly correlated with VEGF decreases (P <0.001). The CAFs that changed in the LF arm are all known to be regulated by nuclear factor-kappa B (NF-κB), and a pathway analysis identified NF-κB as the most likely regulatory network associated with these changes in the LF arm, but not in the FS-containing arms. These results suggest that a low-fat diet without flaxseed may reduce levels of specific inflammatory cytokines and angiogenic factors and suggests that the NF-κB pathway may be a mediator of these changes.
MED-4233
Pilot study of dietary fat restriction and flaxseed supplementation in men with prostate cancer before surgery: exploring the effects on hormonal l...
OBJECTIVES: Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS: Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS: The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS: These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.
MED-3971
Povidone iodine-induced overt hypothyroidism in a patient with prolonged habitual gargling: urinary excretion of iodine after gargling in normal su...
Iodine-induced hypothyroidism that develops in patients who gargle routinely with povidone iodine is well known. Usually the hypothyroidism is mild and resolves spontaneously upon cessation of gargling. Here, we report a 63-year-old patient with overt hypothyroidism that developed due to habitual gargling with povidone iodine for more than 10 years. The urinary excretion of iodine was estimated to be greater than 5 mg/day, based on values obtained from 18 normal subjects who gargled three times a day (4.6+/-2.1 mg, mean+/-SD). After discontinuation of the gargling, the patient has been euthyroid for more than 10 months.
MED-3972
Prevention of upper respiratory tract infections by gargling: a randomized trial.
BACKGROUND: Gargling to wash the throat is commonly performed in Japan, and people believe that such hygienic routine, especially with gargle medicine, prevents upper respiratory tract infections (URTIs). Its effectiveness, however, has not been established by clinical trials. DESIGN: Randomized controlled trial carried out in 2002-2003 winter season and analyzed in 2003 and 2004. PARTICIPANTS: Healthy volunteers (387) aged 18 to 65 years. INTERVENTION: Participants were randomly assigned to water gargling, povidone-iodine gargling, and usual care (control). Subjects in the two gargling groups were requested to gargle with water or diluted povidone-iodine at least three times a day. Participants were followed for 60 days. MAIN OUTCOME MEASURES: The primary outcome measure was first URTI incidence. Severity of URTI symptoms among incident cases was also evaluated. Both outcomes were assessed with a self-administered symptom record. Analyses were performed on an intention-to-treat basis. RESULTS: A total of 130 participants contracted URTIs. The incidence rate of first URTI was 0.26 episodes/30 person-days among control subjects. The rate decreased to 0.17 episodes/30 person-days in the water gargling group, and 0.24 episodes/30 person-days in the povidone-iodine gargling group. Respective incidence rate ratios against controls were 0.64 (95% confidence interval [CI]=0.41-0.99) and 0.89 (95% CI=0.60-1.33). A Cox regression (proportional hazard model) revealed the efficacy of water gargling (hazard ratio=0.60, 95% CI=0.39-0.95). Even when a URTI occurred, water gargling tended to attenuate bronchial symptoms (p=0.055). CONCLUSIONS: Simple water gargling was effective to prevent URTIs among healthy people. This virtually cost-free modality would appreciably benefit the general population.
MED-3973
Gargling for Oral Hygiene and the Development of Fever in Childhood: A Population Study in Japan
Background Fever is one of the most common symptoms among children and is usually caused by respiratory infections. Although Japanese health authorities have long recommended gargling to prevent respiratory infections, its effectiveness among children is not clear. Methods The children in this observational study were enrolled from 145 nursery schools in Fukuoka City, Japan. Children in the exposure group were instructed to gargle at least once a day. The endpoints of this study were incidence of fever during the daytime and incidence of sickness absence. Differences among gargling agents for each endpoint were also analyzed. Results A total of 19 595 children aged 2 to 6 years were observed for 20 days (391 900 person-days). In multivariate logistic regression, the overall odds ratio (OR) for fever onset in the gargling group was significantly lower (OR = 0.68). In age-stratified analysis, ORs were significantly lower at age 2 (OR = 0.67), 4 (OR = 0.46), and 5 (OR = 0.41) years. Regarding sickness absence, the overall OR was 0.92 (not significant) in the gargling group. In age-stratified analysis, ORs were significantly lower at age 4 (OR = 0.68), 5 (OR = 0.59), and 6 (OR = 0.63) years. In subgroup analysis, significantly lower ORs for fever onset were observed for children who gargled with green tea (OR = 0.32), functional water (OR = 0.46), or tap water (OR = 0.70). However, the ORs were not significant for sickness absence. Conclusions Gargling might be effective in preventing febrile diseases in children.
MED-3974
The economic burden of non-influenza-related viral respiratory tract infection in the United States.
BACKGROUND: Viral respiratory tract infection (VRTI) is the most common illness in humans. Despite the high incidence, the economic impact of non-influenza-related VRTI has not been rigorously explored. Our objectives were to obtain an updated incidence of non-influenza-related VRTI in the United States and to quantify the health care resource use (direct costs) and productivity losses (indirect costs) associated with these infections. METHODS: A nationwide telephone survey of US households (N = 4051) was conducted between November 3, 2000, and February 12, 2001 to obtain a representative estimate of the self-reported incidence of non-influenza-related VRTI and related treatment patterns. Direct treatment costs measured included outpatient clinician encounters, use of over-the-counter and prescription drugs, and associated infectious complications of non-influenza-related VRTI. Absenteeism estimates for infected individuals and parents of infected children were extrapolated from National Health Interview Survey data. RESULTS: Of survey respondents, 72% reported a non-influenza-related VRTI within the past year. Respondents who experienced a self-reported non-influenza-related VRTI averaged 2.5 episodes annually. When these rates are extrapolated to the entire US population, approximately 500 million non-influenza-related VRTI episodes occur per year. Similarly, if the treatment patterns reported by the respondents are extended to the population, the total economic impact of non-influenza-related VRTI approaches $40 billion annually (direct costs, $17 billion per year; and indirect costs, $22.5 billion per year). CONCLUSIONS: Largely because of the high attack rate, non-influenza-related VRTI imposes a greater economic burden than many other clinical conditions. The pending availability of effective antiviral therapies warrants increased attention be paid to this common and expensive illness.
MED-3975
Cost-effectiveness of gargling for the prevention of upper respiratory tract infections
Background In Japan, gargling is a generally accepted way of preventing upper respiratory tract infection (URTI). The effectiveness of gargling for preventing URTI has been shown in a randomized controlled trial that compared incidences of URTI between gargling and control groups. From the perspective of the third-party payer, gargling is dominant due to the fact that the costs of gargling are borne by the participant. However, the cost-effectiveness of gargling from a societal perspective should be considered. In this study, economic evaluation alongside a randomized controlled trial was performed to evaluate the cost-effectiveness of gargling for preventing URTI from a societal perspective. Methods Among participants in the gargling trial, 122 water-gargling and 130 control subjects were involved in the economic analysis. Sixty-day cumulative follow-up costs and effectiveness measured by quality-adjusted life days (QALD) were compared between groups on an intention-to-treat basis. Incremental cost-effectiveness ratio (ICER) was converted to dollars per quality-adjusted life years (QALY). The 95% confidence interval (95%CI) and probability of gargling being cost-effective were estimated by bootstrapping. Results After 60 days, QALD was increased by 0.43 and costs were $37.1 higher in the gargling group than in the control group. ICER of the gargling group was $31,800/QALY (95%CI, $1,900–$248,100). Although this resembles many acceptable forms of medical intervention, including URTI preventive measures such as influenza vaccination, the broad confidence interval indicates uncertainty surrounding our results. In addition, one-way sensitivity analysis also indicated that careful evaluation is required for the cost of gargling and the utility of moderate URTI. The major limitation of this study was that this trial was conducted in winter, at a time when URTI is prevalent. Care must be taken when applying the results to a season when URTI is not prevalent, since the ICER will increase due to decreases in incidence. Conclusion This study suggests gargling as a cost-effective preventive strategy for URTI that is acceptable from perspectives of both the third-party payer and society.
MED-4127
Aspartame-induced fibromyalgia, an unusual but curable cause of chronic pain.
We report for the first time an unusual musculoskeletal adverse effect of aspartame in two patients. A 50-year-old woman had been suffering from widespread pain and fatigue for more than 10 years leading to the diagnosis of fibromyalgia. During a vacation in a foreign country, she did not suffer from painful symptoms since she had forgotten to take her aspartame. All of the symptoms reappeared in the days following her return when she reintroduced aspartame into her daily diet. Thus, aspartame was definitively excluded from her diet, resulting in a complete regression of the fibromyalgia symptoms. A 43-year-old man consulted for a 3-year history of bilateral forearm, wrist, and hand and cervical pain with various unsuccessful treatments. A detailed questioning allowed to find out that he had been taking aspartame for three years. The removal of aspartame was followed by a complete regression of pain, without recurrence. We believe that these patients' chronic pain was due to the ingestion of aspartame, a potent flavouring agent, widely used in food as a calorie-saver. The benefit/ risk ratio of considering the diagnosis of aspartame-induced chronic pain is obvious: the potential benefit is to cure a disabling chronic disease, to spare numerous laboratory and imaging investigations, and to avoid potentially harmful therapies; the potential risk is to temporarily change the patient's diet. Thus, practitioners should ask patients suffering from fibromyalgia about their intake of aspartame. In some cases, this simple question might lead to the resolution of a disabling chronic disease.
MED-4124
Erythritol is a sweet antioxidant.
OBJECTIVE: Hyperglycemia, oxidative stress, and the onset and progression of diabetic complications are strongly linked. Reduction of oxidative stress could be of utmost importance in the long-term treatment of diabetic patients. The chronic nature of the disease calls for a mode of antioxidant intake that can be sustained easily, e.g., by the diet. Erythritol, a simple polyol, could be such a compound. It is orally available, well tolerated, and its chemical structure resembles that of mannitol, a well-known hydroxyl radical (HO*) scavenger. METHODS: We studied the antioxidant properties of erythritol in vitro and subsequently determined its antioxidant activity and its vasoprotective effect in the streptozotocin diabetic rat. RESULTS: Erythritol was shown to be an excellent HO* radical scavenger and an inhibitor of 2,2'-azobis-2-amidinopropane dihydrochloride-induced hemolysis but inert toward superoxide radicals. High-performance liquid chromatographic and electron spin resonance spectroscopy studies showed that the reaction of erythritol with hydroxyl radicals resulted in the formation of erythrose and erythrulose by abstraction of a carbon-bound hydrogen atom. In the streptozotocin diabetic rat, erythritol displayed an endothelium-protective effect and, in accordance with the in vitro experiments, erythrose was found in the urine of erythritol-consuming rats. CONCLUSION: Erythritol acts as an antioxidant in vivo and may help protect against hyperglycemia-induced vascular damage. Copyright 2010 Elsevier Inc. All rights reserved.
MED-4125
Human gut microbiota does not ferment erythritol.
Erythritol, a naturally occurring polyol, is gaining attention as a bulk sweetener for human nutrition. Industrially, it is produced from glucose by fermentation. From various studies it is known to be non-cariogenic. Moreover, it is rapidly absorbed in the small intestine and quantitatively excreted in the urine. Only about 10 % enters the colon. Earlier in vitro experiments showed that erythritol remained unfermented for a fermentation period of 12 h. In order to investigate whether fresh human intestinal microbiota is able to adapt its enzyme activities to erythritol, a 24 h lasting fermentation was carried out under well-standardised in vitro conditions. For comparison maltitol, lactulose and blank (faecal inoculum only) were incubated as well. Fermentation patterns were established by following total gas production, hydrogen accumulation, changes in pH value, SCFA production and substrate degradation. Taking all fermentation parameters into account, erythritol turned out to be completely resistant to bacterial attack within 24 h, thus excluding an adaptation within that period. Since under in vivo conditions more easily fermentable substrates enter the colon continuously, it seems very unlikely that erythritol will be fermented in vivo.
MED-4126
Formaldehyde, aspartame, and migraines: a possible connection.
Aspartame is a widely used artificial sweetener that has been linked to pediatric and adolescent migraines. Upon ingestion, aspartame is broken, converted, and oxidized into formaldehyde in various tissues. We present the first case series of aspartame-associated migraines related to clinically relevant positive reactions to formaldehyde on patch testing.
MED-4184
High concentrations of polybrominated diphenylethers (PBDEs) in breast adipose tissue of California women.
We measured major PBDEs and PCBs in breast adipose tissues of California women participating in a breast cancer study in the late 1990s. Samples were analyzed using gas chromatography with electron impact ionization and tandem mass spectrometry detection. The congener profile observed was: BDE47>BDE99>BDE153>BDE100>BDE154 and PCB153>PCB180>PCB138>PCB118. Whereas high correlations were observed within each chemical class, very weak correlations appeared between classes, pointing to different exposure pathways. Weak negative associations were observed for PBDE congeners and age. Our PBDE data are among the highest reported, exceeding data from the National Health and Nutrition Examination Survey and consistent with the high use of PBDEs in California. These data may be helpful in establishing a baseline for PBDE body burdens to gauge changes over time as a result of restrictions in the use of PBDE formulations. Copyright © 2010 Elsevier Ltd. All rights reserved.
MED-4216
Relationship of dietary protein and soy isoflavones to serum IGF-1 and IGF binding proteins in the Prostate Cancer Lifestyle Trial.
High levels of insulin-like growth factor 1 (IGF-1) are associated with increased risk of prostate cancer, whereas increased levels of some of its binding proteins (IGFBPs) seem to be protective. High intakes of dietary protein, especially animal and soy protein, appear to increase IGF-1. However, soy isoflavones have demonstrated anti-proliferative and apoptotic effects both in vitro and in vivo. We evaluated dietary intakes of total protein and soy isoflavones in relation to the IGF axis in prostate cancer patients making comprehensive lifestyle changes including a very low-fat vegan diet supplemented with soy protein (58 g/day). After one year, intervention group patients reported significantly higher intakes of dietary protein and soy isoflavones compared to usual-care controls (P < 0.001). IGF-1 increased significantly in both groups, whereas IGFBP-1 rose in the experimental group only (P < 0.01). Increases in vegetable protein over one year were associated with increases in IGFBP-1 among intervention group patients (P < 0.05). These results suggest that dietary protein and soy isoflavones, in the context of comprehensive lifestyle changes, may not significantly alter IGF-1. However, given the recent literature indicating that high intake of protein rich in essential amino acids (animal or soy protein) may increase IGF-1, it may be prudent for men with early stage prostate cancer not to exceed dietary protein recommendations.
MED-4211
Dietary soy and fats in relation to serum insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels in premenopausal Jap...
Circulating levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) have each been associated with premenopausal breast cancer risks. We analyzed data from a cross-sectional study of 261 premenopausal Japanese women aged 20-54 yr with adequate nutritional status to evaluate the relationships between concentrations of IGF-1 and IGFBP-3 in serum and dietary intakes of soy, fats and other nutrients. Diet was assessed by a semiquantitative food frequency questionnaire. There was no significant correlation between soy product as well as soy isoflavone intake and serum IGF-1 or IGFBP-3 levels after controlling for age, total energy, percent body fat, and education level. Total fat intake was significantly inversely correlated with serum IGFBP-3 level (r = -0.13, P = 0.04). The correlations of saturated and monounsaturated fats with serum IGFBP-3 were of borderline significance (r = -0.12, P = 0.06 and r = -0.11, P = 0.07, respectively).
MED-4212
Insulin-like growth factor-1 and binding protein-3 in a 2-year soya intervention among premenopausal women.
Soya foods may protect against the development of breast cancer. Insulin-like growth factor (IGF)-1 is under investigation as a possible link between nutrition and cancer. We examined the effect of soya foods on circulating IGF-1 and IGF binding protein (BP)-3 levels among 196 healthy premenopausal women in a 2-year randomised nutritional trial. The intervention group consumed two daily servings of soya foods including tofu, soya milk, soya nuts and soya protein powder (equivalent to 50 mg isoflavones and 5-22 g soya protein per serving); the controls maintained their regular diet. Five serum samples at baseline, 3, 6, 12, and 24 months were collected in the morning during the luteal phase and analysed for IGF-1 and IGFBP-3 by double-antibody ELISA. We applied mixed models to investigate the intervention effect and predictors of serum levels while considering the repeated measurement design. Adherence with the study regimen was high and dropout rates were acceptable. Randomisation resulted in similar mean IGF-1 and IGFBP-3 levels by group. We did not observe a significant intervention effect on IGF-1, IGFBP-3, and their molar ratio during the entire study period. However, urinary isoflavone excretion during the study period was positively associated with IGF-1 (P=0.04) and the IGF-1:IGFBP-3 ratio (P=0.06). The effect was consistent over time. Adding soya foods to the diet of premenopausal women does not appear to lower serum levels of IGF-1 and IGFBP-3; if anything, the greater protein intake from soya may lead to a small increase in IGF-1 serum levels.
MED-4886
Clinical events in prostate cancer lifestyle trial: results from two years of follow-up.
OBJECTIVES: Previous research has demonstrated that patients with prostate cancer participating in the Prostate Cancer Lifestyle Trial had a reduction in prostate-specific antigen (PSA) levels, inhibition of LNCaP cell growth, and fewer prostate cancer-related clinical events at the end of 1 year compared with controls. The aim of this study was to examine the clinical events in this trial during a 2-year period. METHODS: The Prostate Cancer Lifestyle Trial was a 1-year randomized controlled clinical trial of 93 patients with early-stage prostate cancer (Gleason score <7, PSA 4-10 ng/mL) undergoing active surveillance. The patients in the experimental arm were encouraged to adopt a low-fat, plant-based diet, to exercise and practice stress management, and to attend group support sessions. The control patients received the usual care. RESULTS: By 2 years of follow-up, 13 of 49 (27%) control patients and 2 of 43 (5%) experimental patients had undergone conventional prostate cancer treatment (radical prostatectomy, radiotherapy, or androgen deprivation, P < .05). No differences were found between the groups in other clinical events (eg, cardiac), and no deaths occurred. Three of the treated control patients but none of the treated experimental patients had a PSA level of >or=10 ng/mL, and 1 treated control patient but no treated experimental patients had a PSA velocity of >2 ng/mL/y before treatment. No significant differences were found between the untreated experimental and untreated control patients in PSA change or velocity at the end of 2 years. CONCLUSIONS: Patients with early-stage prostate cancer choosing active surveillance might be able to avoid or delay conventional treatment for at least 2 years by making changes in their diet and lifestyle.
MED-4466
Kale juice improves coronary artery disease risk factors in hypercholesterolemic men.
OBJECTIVE: To evaluate the effect of 3-month kale (Brassica oleracea acephala) juice supplementation on coronary artery disease risk factors among hypercholesterolemic men. METHODS: Thirty-two men with hypercholesterolemia (> 200 mg/dL) were recruited after annual health examinations among the faculty and staff at university. The subjects consumed 150 mL of kale juice per day for a 12-week intervention period. Dietary and anthropometric assessments were performed and blood samples were collected to evaluate biochemical profiles before and after supplementation. RESULTS: Serum concentrations of HDL-cholesterol, and HDL- to LDL-cholesterol ratio were significantly increased by 27% (P<0.0001) and 52% (P<0.0001), respectively. The LDL-cholesterol concentration and the atherogenic index were significantly reduced by 10% (P=0.0007) and 24.2% (P<0.0001), respectively without affecting body mass index, waist and hip circumferences, or nutrient intakes after three months of supplementation. While there was no difference in the concentration of malondialdehyde, significant increase in glutathione peroxidase activity (P=0.0005) were accompanied by a significant increase in the serum selenium level (P=0.0132). It was also found that the responses of these risk factors to kale juice administration were dependent on smoking status. CONCLUSION: Regular meals supplementation with kale juice can favorably influence serum lipid profiles and antioxidant systems, and hence contribute to reduce the risks of coronary artery disease in male subjects with hyperlipidemia.
MED-4625
Low-dose arachidonic acid intake increases erythrocytes and plasma arachidonic acid in young women.
Arachidonic acid (ARA) is considered to be a minor contributor to the diet. Previous reports regarding the effect of ARA supplementation on the composition of long-chain polyunsaturated fatty acids (LCPUFA) in the blood of humans are extremely limited. In the present study, we conducted a crossover double-blind, placebo-control study. Twenty-three young Japanese women consumed one capsule containing triacylglycerol enriched with 80 mg ARA, equivalent to the amount in one egg, daily for 3 weeks. Blood samples were drawn before and after treatment periods, and the compositions of the LCPUFA in blood lipid fractions were measured. The supplementation of ARA increased the composition of ARA, but did not decrease the composition of n-3LCPUFA in erythrocyte phospholipids and plasma phospholipids, esterified cholesterol, and triacylglycerol. We found that dietary ARA increased the ARA level in all lipid fractions of the blood, even at a very low dose. (c) 2010 Elsevier Ltd. All rights reserved.
MED-4626
Individual variation and intraclass correlation in arachidonic acid and eicosapentaenoic acid in chicken muscle
Chicken meat with reduced concentration of arachidonic acid (AA) and reduced ratio between omega-6 and omega-3 fatty acids has potential health benefits because a reduction in AA intake dampens prostanoid signaling, and the proportion between omega-6 and omega-3 fatty acids is too high in our diet. Analyses for fatty acid determination are expensive, and finding the optimal number of analyses to give reliable results is a challenge. The objective of the present study was i) to analyse the intraclass correlation of different fatty acids in five meat samples, of one gram each, within the same chicken thigh, and ii) to study individual variations in the concentrations of a range of fatty acids and the ratio between omega-6 and omega-3 fatty acid concentrations among fifteen chickens. Fifteen newly hatched broilers were fed a wheat-based diet containing 4% rapeseed oil and 1% linseed oil for three weeks. Five muscle samples from the mid location of the thigh of each chicken were analysed for fatty acid composition. The intraclass correlation (sample correlation within the same animal) was 0.85-0.98 for the ratios of total omega-6 to total omega-3 fatty acids and of AA to eicosapentaenoic acid (EPA). This indicates that when studying these fatty acid ratios, one sample of one gram per animal is sufficient. However, due to the high individual variation between chicken for these ratios, a relatively high number of animals (minimum 15) are required to obtain a sufficiently high power to reveal significant effects of experimental factors (e.g. feeding regimes). The present experiment resulted in meat with a favorable concentration ratio between omega-6 and omega-3 fatty acids. The AA concentration varied from 1.5 to 2.8 g/100 g total fatty acids in thigh muscle in the fifteen broilers, and the ratio between AA and EPA concentrations ranged from 2.3 to 3.9. These differences among the birds may be due to genetic variance that can be exploited by breeding for lower AA concentration and/or a more favorable AA/EPA ratio to produce meat with health benefits.
MED-4635
Globalization, diet, and health: an example from Tonga.
The increased flow of goods, people, and ideas associated with globalization have contributed to an increase in noncommunicable diseases in much of the world. One response has been to encourage lifestyle changes with educational programmes, thus controlling the lifestyle-related disease. Key assumptions with this approach are that people's food preferences are linked to their consumption patterns, and that consumption patterns can be transformed through educational initiatives. To investigate these assumptions, and policies that derive from it, we undertook a broad-based survey of food-related issues in the Kingdom of Tonga using a questionnaire. Data on the relationships between food preferences, perception of nutritional value, and frequency of consumption were gathered for both traditional and imported foods. The results show that the consumption of health-compromising imported foods was unrelated either to food preferences or to perceptions of nutritional value, and suggests that diet-related diseases may not be amenable to interventions based on education campaigns. Given recent initiatives towards trade liberalization and the creation of the World Trade Organization, tariffs or import bans may not serve as alternative measures to control consumption. This presents significant challenges to health policy-makers serving economically marginal populations and suggests that some population health concerns cannot be adequately addressed without awareness of the effects of global trade.
MED-4640
PASSCLAIM--gut health and immunity.
BACKGROUND: The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. AIM: To define normal function of the gut and immune system and describe available methods of measuring it. RESULTS: We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be "improved". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo. measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens. determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.
MED-4747
Hormonal growth promoting agents in food producing animals.
In contrast to the use of hormonal doping agents in sports to enhance the performance of athletes, in the livestock industry hormonal growth promoters ("anabolics") are used to increase the production of muscle meat. This leads to international disputes about the safety of meat originating from animals treated with such anabolics.As a consequence of the total ban in the EU of all hormonal active growth promoters ("hormones") in livestock production, in contrast to their legal use [e.g. of five such hormones (17beta-estradiol, testosterone, progesterone, trenbolone and zeranol) as small solid ear implants and two hormones as feed additives for feedlot heifers (melengestrol acetate) and for swine (ractopamine) in the USA], the regulatory controls also differ sharply between the EU and the USA.In the EU the treatment of slaughter animals is the regulatory offence that has to be controlled in inspection programs. In the USA testing for compliance of a regulatory maximum residue level in the edible product (muscle, fat, liver or kidney) is the purpose of the inspection program (if any).The EU inspection programs focus on sample materials that are more suitable for testing for banned substances, especially if the animals are still on the farm, such as urine and feces or hair. In the case of slaughtered animals, the more favored sample materials are bile, blood, eyes and sometimes liver. Only in rare occasions is muscle meat sampled. This happens only in the case of import controls or in monitoring programs of meat sampled in butcher shops or supermarkets.As a result, data on hormone concentrations in muscle meat samples from the EU market are very rare and are obtained in most cases from small programs on an ad hoc basis. EU data for natural hormones in meat are even rarer because of the absence of "legal natural levels" for these hormones in compliance testing. With the exception of samples from the application sites - in the EU the site of injection of liquid hormone preparations or the site of application of "pour on" preparations - the hormone concentrations observed in meat samples of illegally treated animals are typically in the range of a few micrograms per kilogram (ppb) down to a few tenths of a microgram per kilogram. In the EU dozens of illegal hormones are used and the number of active compounds is still expanding. Besides estrogenic, androgenic and progestagenic compounds also thyreostatic, corticosteroidal and beta-adrenergic compounds are used alone or in "smart" combinations.An overview is given of the compounds identified on the EU black market. An estimate is also given of the probability of consumption in the EU of "highly" contaminated meat from the application sites in cattle. Finally some data are presented on the concentration of estradiol in bovine meat from animals treated and not treated with hormone implants. These data are compared with the recent findings for estradiol concentrations in hen's eggs. From this comparison, the preliminary conclusion is that hen's eggs are the major source of 17alpha- and 17beta-estradiol in the consumer's daily "normal" diet.
MED-4748
Body fat and animal protein intakes are associated with adrenal androgen secretion in children.
BACKGROUND: Adrenarche is the increase in adrenal androgen (AA) production starting in childhood. Until now, it has been unknown whether or not nutritional factors modulate adrenarche. OBJECTIVE: The objective was to examine whether body composition and certain dietary intakes are associated with AA production in children after accounting for urinary indicators of major adrenarche-related steroidogenic enzymes. DESIGN: Androgen and glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry in 24-h urine samples of 137 healthy prepubertal children aged 3-12 y, for whom birth characteristics, growth velocity data, and 3-d weighed-diet record information were available. Associations of the sum of C19 metabolites (reflecting daily AA secretion) with nutritional factors [fat mass (FM), fat-free mass (FFM), nutrient intakes, glycemic index, and glycemic load] and AA-relevant estimates of steroidogenic enzyme were examined in stepwise multiple regression models adjusted for age, sex, urine volume, and total energy intake. Enzyme activity estimates were calculated by using specific urinary steroid metabolite ratios. RESULTS: Of the nutrition-relevant predictors, FM (P < 0.0001) explained most of the variation of AA secretion (R(2) = 5%). Animal protein intake was also positively associated with AA secretion (P < 0.05), which explained 1% of its variation. FFM (P = 0.1) and total protein intake (P = 0.05) showed positive trends. The difference in daily AA secretion between the lowest and highest quartile of FM was comparable to that between the lowest and highest estimated activity of one of the major steroidogenic enzymes. CONCLUSIONS: Body fat mass may relevantly influence prepubertal adrenarchal androgen status. In addition, animal protein intake may also make a small contribution to AA secretion in children.
MED-4749
Consequence of boar edible tissue consumption on urinary profiles of nandrolone metabolites. I. Mass spectrometric detection and quantification of ...
For the first time in the field of steroid residues in humans, demonstration of 19-norandrosterone (19-NA: 3alpha-hydroxy-5alpha-estran-17-one) and 19-noretiocholanolone (19-NE: 3alpha-hydroxy-5beta-estran-17-one) excretion in urine subsequent to boar consumption is reported. Three male volunteers agreed to consume 310 g of tissues from the edible parts (meat, liver, heart and kidney) of a boar. The three individuals delivered urine samples before and during 24 h after meal intake. After deconjugation of phase II metabolites, purification and specific derivatisation of target metabolites, the urinary extracts were analysed by mass spectrometry. Identification was carried out using measurements obtained by gas chromatography/high resolution mass spectrometry (GC/HRMS) (R = 7000) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) (positive electrospray ionisation (ESI+)). Quantification was realised using a quadrupole mass filter. 19-NA and 19-NE concentrations in urine reached 3.1 to 7.5 microg/L nearby 10 hours after boar tissue consumption. Levels returned to endogenous values 24 hours after. These two steroids are usually exploited to confirm the exogenous administration of 19-nortestosterone (19-NT: 17beta-hydroxyestr-4-en-3-one), especially in the antidoping field. We have thus proved that eating tissues of non-castrated male pork (in which 17beta-nandrolone is present) might induce some false accusations of the abuse of nandrolone in antidoping. Copyright 2000 John Wiley & Sons, Ltd.
MED-4750
Assessment of endogenous androgen levels in meat, liver and testis of Iranian native cross-breed male sheep and bull by gas chromatography-mass spe...
Androgenic steroids always exist in different animal tissues at trace level, with significant numbers of interfering compounds, which makes their determination difficult. To solve some of the problems in quantification of the natural steroids in those tissues, a new GC-MS method was developed in this study. By using a surrogate analyte approach, which was developed in the authors' previous studies, and extensive sample preparation procedure, which successfully eliminates many of the interfering compounds and resulting in a cleaner extract, accuracy, precision, sensitivity and selectivity of the method for the determination of steroids in complex matrices such as meat, liver and testis were improved. By aid of this method, the levels of androgens in different tissues of Iranian native cross-breed bulls and male sheep were determined. According to the results obtained in the present study, although the androgenic profile (contents and ratios of precursors and metabolites to the main hormones) is similar between the same tissues of both animals, the total androgenic content of each tissue is higher in the bull than the same tissue in male sheep. In addition, in both animals higher amount of androgens were found in liver in comparison with meat and testis.
MED-4751
The possible role of female sex hormones in milk from pregnant cows in the development of breast, ovarian and corpus uteri cancers.
The continued increase in incidence of some hormone-related cancers worldwide is of great concern. Although estrogen-like substances in the environment were blamed for this increase, the possible role of endogenous estrogens from food has not been widely discussed. We are particularly concerned about cows' milk, which contains a considerable quantity of estrogens. When we name cows' milk as one of the important routes of human exposure to estrogens, the general response of Western people is that "man has been drinking cows' milk for around 2000 years without apparent harm." However, the milk that we are now consuming is quite different from that consumed 100 years ago. Unlike their pasture-fed counterparts of 100 years ago, modern dairy cows are usually pregnant and continue to lactate during the latter half of pregnancy, when the concentration of estrogens in blood, and hence in milk, increases. The correlation of incidence and mortality rates with environmental variables in worldwide countries provides useful clues to the etiology of cancer. In this study, we correlated incidence rates for breast, ovarian, and corpus uteri cancers (1993-97 from Cancer Incidence in Five Continents) with food intake (1961-97 from FAOSTAT) in 40 countries. Meat was most closely correlated with the breast cancer incidence (r=0.827), followed by milk (0.817) and cheese (0.751). Stepwise multiple-regression analysis (SMRA) identified meat as the factor contributing most greatly to the incidence of breast cancer ([R]=0.862). Milk was most closely correlated with the incidence of ovarian cancer (r=0.779), followed by animal fats (0.717) and cheese (0.697). SMRA revealed that milk plus cheese make the greatest contribution to the incidence of ovarian cancer ([R]=0.767). Milk was most closely correlated with corpus uteri cancer (r=0.814), followed by cheese (0.787). SMRA revealed that milk plus cheese make the most significant contribution to the incidence of corpus uteri cancer ([R]=0.861). In conclusion, increased consumption of animal-derived food may have adverse effects on the development of hormone-dependent cancers. Among dietary risk factors, we are most concerned with milk and dairy products, because the milk we drink today is produced from pregnant cows, in which estrogen and progesterone levels are markedly elevated.
MED-4867
Evaluation of the genotoxicity of stevioside and steviol using six in vitro and one in vivo mutagenicity assays.
Stevioside, a constituent of Stevia rebaudiana, is commonly used as a non-caloric sugar substitute in Japan. The genetic toxicities of stevioside and its aglycone, steviol, were examined with seven mutagenicity tests using bacteria (reverse mutation assay, forward mutation assay, umu test and rec assay), cultured mammalian cells (chromosomal aberration test and gene mutation assay) and mice (micronucleus test). Stevioside was not mutagenic in any of the assays examined. The aglycone, steviol, however, produced dose-related positive responses in some mutagenicity tests, i.e. the forward mutation assay using Salmonella typhimurium TM677, the chromosomal aberration test using Chinese hamster lung fibroblast cell line (CHL) and the gene mutation assay using CHL. Metabolic activation systems containing 9000 g supernatant fraction (S9) of liver homogenates prepared from polychlorinated biphenyl or phenobarbital plus 5,6-benzoflavone-pretreated rats were required for mutagenesis and clastogenesis. Steviol was weakly positive in the umu test using S.typhimurium TA1535/pSK1002 either with or without the metabolic activation system. Steviol, even in the presence of the S9 activation system, was negative in other assays, i.e. the reverse mutation assays using S.typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and Escherichia coli WP2 uvrA/pKM101 and the rec-assay using Bacillus subtilis. Steviol was negative in the mouse micronucleus test. The genotoxic risk of steviol to humans is discussed.
MED-4868
Stevia (Stevia rebaudiana) a bio-sweetener: a review.
Studies revealed that Stevia has been used throughout the world since ancient times for various purposes; for example, as a sweetener and a medicine. We conducted a systematic literature review to summarize and quantify the past and current evidence for Stevia. We searched relevant papers up to 2007 in various databases. As we know that the leaves of Stevia plants have functional and sensory properties superior to those of many other high-potency sweeteners, Stevia is likely to become a major source of high-potency sweetener for the growing natural food market in the future. Although Stevia can be helpful to anyone, there are certain groups who are more likely to benefit from its remarkable sweetening potential. These include diabetic patients, those interested in decreasing caloric intake, and children. Stevia is a small perennial shrub that has been used for centuries as a bio-sweetener and for other medicinal uses such as to lower blood sugar. Its white crystalline compound (stevioside) is the natural herbal sweetener with no calories and is over 100-300 times sweeter than table sugar.
MED-4869
Evaluation of certain food additives.
This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular, flavouring agents). A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (asparaginase from Aspergillus niger expressed in A. niger, calcium lignosulfonate (40-65), ethyl lauroyl arginate, paprika extract, phospholipase C expressed in Pichia pastoris, phytosterols, phytostanols and their esters, polydimethylsiloxane, steviol glycosides and sulfites [assessment of dietary exposure]) and 10 groups of related flavouring agents (aliphatic branched-chain saturated and unsaturated alcohols, aldehydes, acids and related esters; aliphatic linear alpha,beta-unsaturated aldehydes, acids and related alcohols, acetals and esters; aliphatic secondary alcohols, ketones and related esters; alkoxy-substituted allylbenzenes present in foods and essential oils and used as flavouring agents; esters of aliphatic acyclic primary alcohols with aliphatic linear saturated carboxylic acids; furan-substituted aliphatic hydrocarbons, alcohols, aldehydes, ketones, carboxylic acids and related esters, sulfides, disulfides and ethers; miscellaneous nitrogen-containing substances; monocyclic and bicyclic secondary alcohols, ketones and related esters; hydroxy- and alkoxy-substituted benzyl derivatives; and substances structurally related to menthol). Specifications for the following food additives were revised: canthaxanthin; carob bean gum and carob bean gum (clarified); chlorophyllin copper complexes, sodium and potassium salts; Fast Green FCF; guar gum and guar gum (clarified); iron oxides; isomalt; monomagnesium phosphate; Patent Blue V; Sunset Yellow FCF; and trisodium diphosphate. Re-evaluation of flavouring agents for which estimated intake was based on anticipated poundage data was carried out for 2-isopropyl- N,2,3-trimethylbutyramide (No. 1595) and L-monomenthyl glutarate (No. 1414). Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives considered.
MED-5030
Association of Sleep Duration with Mortality from Cardiovascular Disease and Other Causes for Japanese Men and Women: the JACC Study
Study Objectives: To examine sex-specific associations between sleep duration and mortality from cardiovascular disease and other causes. Design: Cohort study. Setting: Community-based study. Participants: A total of 98,634 subjects (41,489 men and 57,145 women) aged 40 to 79 years from 1988 to 1990 and were followed until 2003. Interventions: N/A. Measurements and Results: During a median follow-up of 14.3 years, there were 1964 deaths (men and women: 1038 and 926) from stroke, 881 (508 and 373) from coronary heart disease, 4287 (2297 and 1990) from cardiovascular disease, 5465 (3432 and 2033) from cancer, and 14,540 (8548 and 5992) from all causes. Compared with a sleep duration of 7 hours, sleep duration of 4 hours or less was associated with increased mortality from coronary heart disease for women and noncardiovascular disease/noncancer and all causes in both sexes. The respective multivariable hazard ratios were 2.32 (1.19–4.50) for coronary heart disease in women, 1.49 (1.02–2.18) and 1.47 (1.01–2.15) for noncardiovascular disease/noncancer, and 1.29 (1.02–1.64) and 1.28 (1.03–1.60) for all causes in men and women, respectively. Long sleep duration of 10 hours or longer was associated with 1.5- to 2-fold increased mortality from total and ischemic stroke, total cardiovascular disease, noncardiovascular disease/noncancer, and all causes for men and women, compared with 7 hours of sleep in both sexes. There was no association between sleep duration and cancer mortality in either sex. Conclusions: Both short and long sleep duration were associated with increased mortality from cardiovascular disease, noncardiovascular disease/noncancer, and all causes for both sexes, yielding a U-shaped relationship with total mortality with a nadir at 7 hours of sleep. Citation: Ikehara S; Iso H; Date C; Kikuchi S; Watanabe Y; Wada Y; Inaba Y; Tamakoshi A. Association of sleep duration with mortality from cardiovascular disease and other causes for Japanese men and women: the JACC study. SLEEP 2009;32(3):259–301.
MED-4714
Vegetables, but not pickled vegetables, are negatively associated with the risk of breast cancer.
This study investigated the association between pickled vegetable consumption and the risk of breast cancer using a validated food frequency questionnaire. A total of 358 patients with breast cancer who were matched to 360 healthy controls by age (using a 5-yr age distribution) were recruited from the National Cancer Center in South Korea. After adjusting for nondietary risk factors, total vegetable intake was inversely associated with risk of breast cancer. However, unlike nonpickled vegetables, pickled vegetable intake and its proportion relative to total vegetables were positively associated with the risk of breast cancer, and this association was more profound and consistent when pickled vegetable intake was considered as a proportion relative to total vegetables (odds ratio [OR] = 6.24, 95% confidence interval [CI] = 3.55-10.97; P for trend <0.001 for highest vs. lowest quartiles of intake) than as the absolute consumed amount (OR = 2.47, 95% CI = 1.45-4.21; P for trend = 0.015 for highest vs. lowest quartiles of intake). These results suggest that not only the amount of total vegetable intake but also the amounts of different types of vegetable (i.e., pickled or nonpickled) and their proportions relative to total vegetables are significantly associated with the risk of breast cancer.
MED-1460
Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function
Insulin resistance condition is associated to the development of several syndromes, such as obesity, type 2 diabetes mellitus and metabolic syndrome. Although the factors linking insulin resistance to these syndromes are not precisely defined yet, evidence suggests that the elevated plasma free fatty acid (FFA) level plays an important role in the development of skeletal muscle insulin resistance. Accordantly, in vivo and in vitro exposure of skeletal muscle and myocytes to physiological concentrations of saturated fatty acids is associated with insulin resistance condition. Several mechanisms have been postulated to account for fatty acids-induced muscle insulin resistance, including Randle cycle, oxidative stress, inflammation and mitochondrial dysfunction. Here we reviewed experimental evidence supporting the involvement of each of these propositions in the development of skeletal muscle insulin resistance induced by saturated fatty acids and propose an integrative model placing mitochondrial dysfunction as an important and common factor to the other mechanisms.
MED-1949
Is very preterm birth a risk factor for adult cardiometabolic disease?
The first infants to experience modern pre- and neonatal care are now in their thirties, an age at which the incidence of cardiometabolic disease is low. However, data from cohorts born preterm prior to the introduction of modern care suggest an increased risk of type 2 diabetes. For young adult cohorts of former very small or very preterm infants, there is accumulating evidence of increased risk factors for later cardiovascular disease, including higher blood pressure, lower lean body mass, impaired glucose regulation, and perhaps a more atherogenic lipid profile. Regarding lifestyle, adults born very small or very preterm undertake less non-conditioning physical activity and may have a lower intake of fruit and milk products. Any intervention reducing risk factors, in particular blood pressure and low physical activity, would have a substantial potential to reduce the lifetime disease burden in small preterm infants. There are now enough data to warrant an expert evaluation of the level of evidence for cardiometabolic disease in individuals born very small or very preterm, which has possible public health implications. Copyright © 2013 Elsevier Ltd. All rights reserved.
MED-5260
Phenolic content of virgin olive oil improves ischemic reactive hyperemia in hypercholesterolemic patients.
OBJECTIVES: The goal of this study was to evaluate the effects of the phenolic content of virgin olive oil on endothelial reactivity. BACKGROUND: Endothelial-dependent vasodilatation is impaired during the postprandial state, and oxidative stress could play a key role in its development. METHODS: Twenty-one hypercholesterolemic volunteers received two breakfasts, using a randomized sequential crossover design. Both arms received the same olive oil, but one had its phenolic acid content reduced from 400 to 80 ppm. Ischemic reactive hyperemia (IRH) was measured with a laser-Doppler procedure at baseline and 2 h and 4 h after oil intake. Postprandial plasma concentrations of lipid fractions, lipoperoxides (LPO), 8-epi prostaglandin-F(2alpha), and nitrates/nitrites (NO(x)) were obtained at baseline and after 2 h of the fat meal. RESULTS: The intake of the polyphenol-rich breakfast was associated with an improvement in endothelial function, as well as a greater increase in concentrations of NO(x) (p < 0.001) and a lower increase in LPO (p < 0.005) and 8-epi prostaglandin-F2alpha (p < 0.001) than the ones induced by the low polyphenol fat meal. A positive correlation was found to exist between NO(x) and enhanced endothelial function at the second hour (r = 0.669; p < 0.01). Furthermore, a negative correlation was found between IRH and LPO (r = -0.203; p < 0.05) and 8-epi prostaglandin-F2alpha levels (r = -0.440; p < 0.05). CONCLUSIONS: A meal containing high-phenolic virgin olive oil improves ischemic reactive hyperemia during the postprandial state. This phenomenon might be mediated via reduction in oxidative stress and the increase of nitric oxide metabolites.
MED-3314
Occupation and risk of lymphoma: a multicentre prospective cohort study (EPIC).
OBJECTIVES: Evidence suggests that certain occupations and related exposures may increase the risk of malignant lymphoma. Farming, printing and paper industry, wood processing, meat handling and processing, welding, shoe and leather manufacturing and teaching profession are among the categories that have been implicated in previous studies. The relationship between occupation and malignant lymphoma has been investigated in a large European prospective study. METHODS: We investigated occupational risks for lymphomas in the European Prospective Investigation into Cancer and Nutrition (EPIC). The mean follow-up time for 348,555 subjects was 9 years (SD: 2 years). The analysis was based on 866 and 48 newly diagnosed cases of non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). These were identified in the EPIC subcohorts with occupational data. Data on 52 occupations were collected through standardised questionnaires. Cox proportional hazard models were used to explore the association between occupation and risk of malignant lymphoma. RESULTS: The following occupations were positively associated with malignant NHL after adjustment for study centre, age, sex, socioeconomic status (SES), smoking and alcohol: butchers (HR=1.53, 95% CI 1.05 to 2.48, including multiple myeloma/plasmacytoma; HR=1.30, 95% CI 1.00 to 2.66, excluding multiple myeloma/plasmacytoma) and car repair workers (HR=1.50, 95% CI 1.01 to 2.00, including multiple myeloma/plasmacytoma; HR=1.51, 95% CI 1.01 to 2.31, excluding multiple myeloma/plasmacytoma). HL was associated with gasoline station occupation (HR=4.59, 95% CI 1.08 to 19.6). CONCLUSION: The findings in this current study of a higher risk of NHL among car repair workers and butchers and a higher risk of HL among gasoline station workers suggest a possible role from occupationally related exposures, such as solvents and zoonotic viruses, as risk factors for malignant lymphoma.
MED-1703
The Projected Impact of Risk Factor Reduction on Alzheimer's Disease Prevalence
There are currently approximately 33.9 million individuals with Alzheimer's disease (AD) worldwide, and prevalence is expected to triple over the next 40 years. The goal of this review was to summarize the evidence regarding seven potentially modifiable AD risk factors: diabetes, mid-life hypertension, mid-life obesity, smoking, depression, low educational attainment and physical inactivity. In addition, we projected the impact of risk factor reduction on AD prevalence by calculating population attributable risks (PARs, the percent of cases attributable to a given factor) and the number of AD cases that could potentially be prevented by 10% and 25% risk factor reductions worldwide and in the US. Together, these factors contributed to up to half of AD cases globally (17.2 million) and in the US (2.9 million). A 10%–25% reduction in all seven risk factors could potentially prevent as many as 1.1–3.0 million cases worldwide and 184,000–492,000 cases in the US.
MED-4831
Effects of plant-based diets on plasma lipids.
Dyslipidemia is a primary risk factor for cardiovascular disease, peripheral vascular disease, and stroke. Current guidelines recommend diet as first-line therapy for patients with elevated plasma cholesterol concentrations. However, what constitutes an optimal dietary regimen remains a matter of controversy. Large prospective trials have demonstrated that populations following plant-based diets, particularly vegetarian and vegan diets, are at lower risk for ischemic heart disease mortality. The investigators therefore reviewed the published scientific research to determine the effectiveness of plant-based diets in modifying plasma lipid concentrations. Twenty-seven randomized controlled and observational trials were included. Of the 4 types of plant-based diets considered, interventions testing a combination diet (a vegetarian or vegan diet combined with nuts, soy, and/or fiber) demonstrated the greatest effects (up to 35% plasma low-density lipoprotein cholesterol reduction), followed by vegan and ovolactovegetarian diets. Interventions allowing small amounts of lean meat demonstrated less dramatic reductions in total cholesterol and low-density lipoprotein levels. In conclusion, plant-based dietary interventions are effective in lowering plasma cholesterol concentrations.
MED-5165
Watermelon consumption increases plasma arginine concentrations in adults.
OBJECTIVE: Watermelon is a rich source of citrulline, an amino acid that can be metabolized to arginine, a conditionally essential amino acid for humans. Arginine is the nitrogenous substrate used in the synthesis of nitric oxide and plays an essential role in cardiovascular and immune functions. No detailed studies have been conducted to evaluate plasma arginine response in humans after long-term feeding of citrulline from natural plant sources. This study investigated if watermelon juice consumption increases fasting concentrations of plasma arginine, ornithine, and citrulline in healthy adult humans. METHODS: Subjects (n = 12-23/treatment) consumed a controlled diet and 0 (control), 780, or 1560 g of watermelon juice per day for 3 wk in a crossover design. The treatments provided 1 and 2 g of citrulline per day. Treatment periods were preceded by washout periods of 2 to 4 wk. RESULTS: Compared with the baseline, fasting plasma arginine concentrations increased 12% after 3 wk of the lower-dose watermelon treatment; arginine and ornithine concentrations increased 22% and 18%, respectively, after 3 wk of the higher-dose watermelon treatment. Fasting citrulline concentrations did not increase relative to the control but remained stable throughout the study. CONCLUSION: The increased fasting plasma concentrations of arginine and ornithine and stable concentrations of plasma citrulline in response to watermelon juice consumption indicated that the citrulline from this plant origin was effectively converted into arginine. These results demonstrate that plasma concentration of arginine can be increased through intake of citrulline from watermelon.
MED-5252
Caffeine does not increase the risk of atrial fibrillation: a systematic review and meta-analysis of observational studies.
BACKGROUND: Atrial fibrillation (AF) is the most prevalent sustained arrhythmia, and risk factors are well established. Caffeine exposure has been associated with increased risk of AF, but heterogeneous data exist in the literature. OBJECTIVE: To evaluate the association between chronic exposure to caffeine and AF. DESIGN: Systematic review and meta-analysis of observational studies. DATA SOURCES: PubMed, CENTRAL, ISI Web of Knowledge and LILACS to December 2012. Reviews and references of retrieved articles were comprehensively searched. STUDY SELECTION: Two reviewers independently searched for studies and retrieved their characteristics and data estimates. DATA SYNTHESIS: Random-effects meta-analysis was performed, and pooled estimates were expressed as OR and 95% CI. Heterogeneity was assessed with the I(2) test. Subgroup analyses were conducted according to caffeine dose and source (coffee). RESULTS: Seven observational studies evaluating 115 993 individuals were included: six cohorts and one case-control study. Caffeine exposure was not associated with an increased risk of AF (OR 0.92, 95% CI 0.82 to 1.04, I(2)=72%). Pooled results from high-quality studies showed a 13% odds reduction in AF risk with lower heterogeneity (OR 0.87; 95% CI 0.80 to 0.94; I(2)=39%). Low-dose caffeine exposure showed OR 0.85 (95% CI 0.78 to 92, I(2)=0%) without significant differences in other dosage strata. Caffeine exposure based solely on coffee consumption also did not influence AF risk. CONCLUSIONS: Caffeine exposure is not associated with increased AF risk. Low-dose caffeine may have a protective effect.
MED-4363
From Barnyard to Food Table: the Omnipresence of Hepatitis E virus and Risk for Zoonotic Infection and Food Safety
Hepatitis E virus (HEV) is an important but extremely understudied pathogen. The mechanisms of HEV replication and pathogenesis are poorly understood, and a vaccine against HEV is not yet available. HEV is classified in the family Hepeviridae consisting of at least four recognized major genotypes. Genotypes 1 and 2 HEV are restricted to humans and associated with epidemics in developing countries, whereas genotypes 3 and 4 HEV are zoonotic and responsible for sporadic cases worldwide. The identification and characterization of a number of animal strains of HEV from pigs, chickens, rabbits, rats, mongoose, deer, and possibly cattle and sheep have significantly broadened the host range and diversity of HEV. The demonstrated ability of cross-species infection by some animal strains of HEV raises public health concerns for zoonotic HEV infection. Pigs are a recognized reservoir for HEV, and pig handlers are at increased risk of zoonotic HEV infection. Sporadic cases of hepatitis E have been definitively linked to the consumption of raw or undercooked animal meats such as pig livers, sausages, and deer meats. In addition, since large amounts of viruses excreted in feces, animal manure land application and runoffs can contaminate irrigation and drinking water with concomitant contamination of produce or shellfish. HEV RNA of swine origin has been detected in swine manure, sewage water and oysters, and consumption of contaminated shellfish has also been implicated in sporadic cases of hepatitis E. Therefore, the animal strains of HEV pose not only a zoonotic risk but also food and environmental safety concerns.
MED-2108
Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer. Nutrient intake.
A 3-day diary with portion sizes weighed by the subject and a 24-h recall were obtained on 50 sets of subjects: Seventh-day Adventist lacto-ovo-vegetarians and nonvegetarians, and general population nonvegetarians, matched on age (+/- 5 yr), sex, marital status, education, type of milk preferred, and an index of the frequency of dairy and egg product use. An additional 18 unmatched persons who follow a pure vegetarian dietary pattern (use no meat, fish, fowl, dairy, or egg products) were recruited into the study. The rational for the dietary methods used is presented and details of each of the methods used are given. The results of the nutrient analysis of the 24-h recall and 3-day diary are presented. The 3-day nutrient intake means for the four groups are compared to the sex-specific recommended daily allowance both with and without supplements. The contribution of nutritional supplements to the nutrient intake is discussed. All groups show adequate or excess intake levels of calories, protein, and fat when either the 24-h recall or the 3-day diary values are considered. The higher intake of calories noted among nonvegetarians can be explained by a higher intake of both fat and protein in these groups. A, B, and C vitamin levels (3-day dairy estimates) are adequate both with and without supplements. Calcium intake is much below recommended levels for pure vegetarian females. Iron intake is low for all females. A heme iron source does not improve the intake levels for nonvegetarian females. A comparison of these results with prior reports of nutrient intake among Seventh-day Adventists is presented.
MED-4173
Chronic disease and infant nutrition: is it significant to public health?
OBJECTIVE: To assess the public health significance of premature weaning of infants from breast milk on later-life risk of chronic illness. DESIGN: A review and summary of recent meta-analyses of studies linking premature weaning from breast milk with later-life chronic disease risk is presented followed by an estimation of the approximate exposure in a developed Western country, based on historical breast-feeding prevalence data for Australia since 1927. The population-attributable proportion of chronic disease associated with current patterns of artificial feeding in infancy is estimated. RESULTS: After adjustment for major confounding variables, current research suggests that the risks of chronic disease are 30-200 % higher in those who were not breast-fed compared to those who were breast-fed in infancy. Exposure to premature weaning ranges from 20 % to 90 % in post-World War II age cohorts. Overall, the attributable proportion of chronic disease in the population is estimated at 6-24 % for a 30 % exposure to premature weaning. CONCLUSIONS: Breast-feeding is of public health significance in preventing chronic disease. There is a small but consistent effect of premature weaning from breast milk in increasing later-life chronic disease risk. Risk exposure in the Australian population is substantial. Approximately 90 % of current 35-45-year-olds were weaned from breast-feeding by 6 months of age. Encouraging greater duration and exclusivity of breast-feeding is a potential avenue for reducing future chronic disease burden and health system costs.
MED-4131
Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens.
In this article we estimate the annual cost of illness and quality-adjusted life year (QALY) loss in the United States caused by 14 of the 31 major foodborne pathogens reported on by Scallan et al. (Emerg. Infect. Dis. 17:7-15, 2011), based on their incidence estimates of foodborne illness in the United States. These 14 pathogens account for 95 % of illnesses and hospitalizations and 98 % of deaths due to identifiable pathogens estimated by Scallan et al. We estimate that these 14 pathogens cause $14.0 billion (ranging from $4.4 billion to $33.0 billion) in cost of illness and a loss of 61,000 QALYs (ranging from 19,000 to 145,000 QALYs) per year. Roughly 90 % of this loss is caused by five pathogens: nontyphoidal Salmonella enterica ($3.3 billion; 17,000 QALYs), Campylobacter spp. ($1.7 billion; 13,300 QALYs), Listeria monocytogenes ($2.6 billion; 9,400 QALYs), Toxoplasma gondii ($3 billion; 11,000 QALYs), and norovirus ($2 billion; 5,000 QALYs). A companion article attributes losses estimated in this study to the consumption of specific categories of foods. To arrive at these estimates, for each pathogen we create disease outcome trees that characterize the symptoms, severities, durations, outcomes, and likelihoods of health states associated with that pathogen. We then estimate the cost of illness (medical costs, productivity loss, and valuation of premature mortality) for each pathogen. We also estimate QALY loss for each health state associated with a given pathogen, using the EuroQol 5D scale. Construction of disease outcome trees, outcome-specific cost of illness, and EuroQol 5D scoring are described in greater detail in a second companion article.
MED-2491
Arsenic and lead in juice: apple, citrus, and apple-base.
Exposure limits for arsenic and lead in drinking water have long been established by the U.S. Environmental Protection Agency and new regulations regarding the presence of these contaminants in bottled water went into effect in California in 2009. No comparable exposure limits or regulations are available, however, for juices and other beverages that may contain arsenic and lead. In the study described in this article, 20 apple juices (or ciders), 15 apple-containing juices, one grape, and one citrus juice were analyzed for arsenic and lead. Arsenic was detected in all juices while lead was detected in more than 94% of juices analyzed. Twelve samples (32%) demonstrated arsenic levels nearly at or above the drinking water exposure limit of 10 parts per billion. No juices contained lead above drinking water exposure limits. Expanding drinking water limits to include juices (and other frequently consumed beverages) would better protect consumers while regular testing of these juices would better inform consumers of the risks posed by specific juices and brands.
MED-998
Polybrominated Diphenyl Ethers (PBDEs) in Breast Milk and Neuropsychological Development in Infants
Background: There is increasing interest in the potential effects of polybrominated diphenyl ethers (PBDEs) on children’s neuropsychological development, but only a few small studies have evaluated such effects. Objectives: Our goal was to examine the association between PBDE concentrations in colostrum and infant neuropsychological development and to assess the influence of other persistent organic pollutants (POPs) on such association. Methods: We measured concentrations of PBDEs and other POPs in colostrum samples of 290 women recruited in a Spanish birth cohort. We tested children for mental and psychomotor development with the Bayley Scales of Infant Development at 12–18 months of age. We analyzed the sum of the seven most common PBDE congeners (BDEs 47, 99, 100, 153, 154, 183, 209) and each congener separately. Results: Increasing Σ7PBDEs concentrations showed an association of borderline statistical significance with decreasing mental development scores (β per log ng/g lipid = –2.25; 95% CI: –4.75, 0.26). BDE-209, the congener present in highest concentrations, appeared to be the main congener responsible for this association (β = –2.40, 95% CI: –4.79, –0.01). There was little evidence for an association with psychomotor development. After adjustment for other POPs, the BDE-209 association with mental development score became slightly weaker (β = –2.10, 95% CI: –4.66, 0.46). Conclusions: Our findings suggest an association between increasing PBDE concentrations in colostrum and a worse infant mental development, particularly for BDE-209, but require confirmation in larger studies. The association, if causal, may be due to unmeasured BDE-209 metabolites, including OH-PBDEs (hydroxylated PBDEs), which are more toxic, more stable, and more likely to cross the placenta and to easily reach the brain than BDE-209.
MED-3521
Sweet and sour cherry phenolics and their protective effects on neuronal cells.
The identification of phenolics from various cultivars of fresh sweet and sour cherries and their protective effects on neuronal cells were comparatively evaluated in this study. Phenolics in cherries of four sweet and four sour cultivars were extracted and analyzed for total phenolics, total anthocyanins, and their antineurodegenerative activities. Total phenolics in sweet and sour cherries per 100 g ranged from 92.1 to 146.8 and from 146.1 to 312.4 mg gallic acid equivalents, respectively. Total anthocyanins of sweet and sour cherries ranged from 30.2 to 76.6 and from 49.1 to 109.2 mg cyanidin 3-glucoside equivalents, respectively. High-performance liquid chromatography (HPLC) analysis revealed that anthocyanins such as cyanidin and peonidin derivatives were prevalent phenolics. Hydroxycinnamic acids consisted of neochlorogenic acid, chlorogenic acid, and p-coumaric acid derivatives. Glycosides of quercetin, kaempferol, and isorhamnetin were also found. Generally, sour cherries had higher concentrations of total phenolics than sweet cherries, due to a higher concentration of anthocyanins and hydroxycinnamic acids. A positive linear correlation (r2 = 0.985) was revealed between the total anthocyanins measured by summation of individual peaks from HPLC analysis and the total anthocyanins measured by the pH differential method, indicating that there was in a close agreement with two quantifying methods for measuring anthocyanin contents. Cherry phenolics protected neuronal cells (PC 12) from cell-damaging oxidative stress in a dose-dependent manner mainly due to anthocyanins. Overall results showed that cherries are rich in phenolics, especially in anthocyanins, with a strong antineurodegenerative activity and that they can serve as a good source of biofunctional phytochemicals in our diet.
MED-913
A literature review on the safety assessment of genetically modified plants.
In recent years, there has been a notable concern on the safety of genetically modified (GM) foods/plants, an important and complex area of research, which demands rigorous standards. Diverse groups including consumers and environmental Non Governmental Organizations (NGO) have suggested that all GM foods/plants should be subjected to long-term animal feeding studies before approval for human consumption. In 2000 and 2006, we reviewed the information published in international scientific journals, noting that the number of references concerning human and animal toxicological/health risks studies on GM foods/plants was very limited. The main goal of the present review was to assess the current state-of-the-art regarding the potential adverse effects/safety assessment of GM plants for human consumption. The number of citations found in databases (PubMed and Scopus) has dramatically increased since 2006. However, new information on products such as potatoes, cucumber, peas or tomatoes, among others was not available. Corn/maize, rice, and soybeans were included in the present review. An equilibrium in the number research groups suggesting, on the basis of their studies, that a number of varieties of GM products (mainly maize and soybeans) are as safe and nutritious as the respective conventional non-GM plant, and those raising still serious concerns, was currently observed. Nevertheless, it should be noted that most of these studies have been conducted by biotechnology companies responsible of commercializing these GM plants. These findings suggest a notable advance in comparison with the lack of studies published in recent years in scientific journals by those companies. All this recent information is herein critically reviewed. Copyright © 2011 Elsevier Ltd. All rights reserved.
MED-1221
Clostridium difficile in foods and animals: history and measures to reduce exposure.
Many articles have summarized the changing epidemiology of Clostridium difficile infections (CDI) in humans, but the emerging presence of C. difficile in foods and animals and possible measures to reduce human exposure to this important pathogen have been infrequently addressed. CDIs have traditionally been assumed to be restricted to health-care settings. However, recent molecular studies indicate that this is no longer the case; animals and foods might be involved in the changing epidemiology of CDIs in humans; and genome sequencing is disproving person-to-person transmission in hospitals. Although zoonotic and foodborne transmission have not been confirmed, it is evident that susceptible people can be inadvertently exposed to C. difficile from foods, animals, or their environment. Strains of epidemic clones present in humans are common in companion and food animals, raw meats, poultry products, vegetables, and ready-to-eat foods, including salads. In order to develop science-based prevention strategies, it is critical to understand how C. difficile reaches foods and humans. This review contextualizes the current understanding of CDIs in humans, animals, and foods. Based on available information, we propose a list of educational measures that could reduce the exposure of susceptible people to C. difficile. Enhanced educational efforts and behavior change targeting medical and non-medical personnel are needed.
MED-1035
How trustworthy are bowel histories? Comparison of recalled and recorded information.
One hundred and fifty hospital outpatients were questioned about their bowel habits and then asked to record these in diary booklets for two weeks. Overall, recalled and recorded figures for frequency of defecation agreed fairly closely, but in 16% of patients there was a discrepancy of three or more bowel actions per week. This was usually an exaggeration of the difference from the norm of one a day. Patients were bad at predicting episodes of changed bowel frequency. These findings cast doubt on the value of population surveys of bowel habit based solely on questionnaires. They also suggest that the irritable bowel syndrome might be correctly diagnosed more often if patients were routinely asked to record their bowel actions.
MED-1104
Multiple myeloma : recent progress in diagnosis and treatment.
Multiple myeloma (MM) has been the most intractable hematological disease for many years. Recently, basic and clinical research has advanced remarkably and a new therapeutic strategy has been established. The introduction of high-dose melphalan with autologous stem-cell transplantation and the availability of molecular-targeted novel agents such as immunomodulatory drugs and proteasome inhibitors have dramatically changed the treatment strategies for MM. Achievement of a high response rate resulted in the extension of overall survival, but further research and the development of more multimodality therapeutic approaches is warranted to cure this disease.
MED-4765
Dietary predictors of 5-year changes in waist circumference.
BACKGROUND: Previous studies on the association between macronutrient intake and the development of abdominal obesity, which carries an increased health risk, have not shown a consistent pattern, possibly due to mixed effects of other aspects of the food intake. OBJECTIVE: This study investigated the association between intake from 21 food and beverage groups and the subsequent 5-year difference in waist circumference. METHODS: The study population consisted of 22,570 women and 20,126 men, aged 50 to 64 years at baseline, with complete data on baseline and follow-up waist circumference, baseline diet (192 items food frequency questionnaire), body mass index, and selected potential confounders (eg, smoking status, sport activities, and intake of alcoholic beverages). Multiple linear regression analyses were performed. RESULTS: For women, 5-year difference in waist circumference was inversely related to intake from red meat, vegetables, fruit, butter, and high-fat dairy products, whereas intake from potatoes, processed meat, poultry, and snack foods was positively associated. For men, red meat and fruit intakes were inversely associated with 5-year difference in waist circumference, whereas snack foods intake was positively associated. Sex differences occurred for vegetables, high-fat dairy products, and processed meat. CONCLUSIONS: The results suggest that a diet low in fruits and red meat and high in snack foods was associated with larger waist circumference gains in both sexes. Furthermore, in women a diet low in vegetables, butter, and high-fat dairy products, and high in poultry, potatoes, and processed meat were likely determinants of subsequent gain at the waist.
MED-1937
Effects of turmeric on Alzheimer's disease with behavioral and psychological symptoms of dementia
We describe here three patients with the Alzheimer's Disease (AD) whose behavioral symptoms were improved remarkably as a result of the turmeric treatment, which is the traditional Indian medicine. Their cognitive decline and Behavioral and Psychological Symptoms of Dementia (BPSD) were very severe. All three patients exhibited irritability, agitation, anxiety, and apathy, two patients suffer from urinary incontinence and wonderings. They were prescribed turmeric powder capsules and started recovering from these symptoms without any adverse reaction in the clinical symptom and laboratory data. After 12 weeks of the treatment, total score of the Neuro-Psychiatric Inventory-brief questionnaire decreased significantly in both acuity of symptoms and burden of caregivers. In one case, the Mini-Mental State Examination (MMSE) score was up five points, from 12/30 to 17/30. In the other two cases, no significant change was seen in the MMSE; however, they came to recognize their family within 1 year treatment. All cases have been taking turmeric for more than 1 year, re-exacerbation of BPSD was not seen. The present cases suggest a significant improvement of the behavioral symptoms in the AD with the turmeric treatment, leading to probable benefit of the use of turmeric in individuals with the AD with BPSD.
MED-5007
Plasma adiponectin concentrations are associated with body composition and plant-based dietary factors in female twins.
Circulating adiponectin is emerging as an important link between obesity, type 2 diabetes, and cardiovascular disease (CVD). However, the spectrum of lifestyle factors that modulate the adiponectin concentration remains to be elucidated, particularly among women. We conducted a cross-sectional study of 877 female twin pairs from the TwinsUK adult twin registry. Using a co-twin design, we examined dietary and body composition influences on adiponectin by conducting matched, within-pair analyses to eliminate confounding. Following multivariable adjustment within-twin pairs, significant influences on adiponectin (log-transformed, percent change per SD of the dietary/body composition variable) were observed for nonstarch polysaccharides (3.25%; 95% CI: 0.06, 6.54; P < 0.05) and magnesium intake (3.80%; 95%CI: 0.17, 7.57; P < 0.05), with a trend toward an association for fruit and vegetable (F&V) intakes (2.55%; 95% CI: -0.26, 5.45; P = 0.08). These modest positive associations cannot be explained by confounding through other lifestyle factors shared by the twins. A significant relationship between adiponectin and 3 derived dietary patterns (F&V, dieting, traditional English), carbohydrate, protein, trans fat, and alcohol intake was also observed. Strong inverse associations with adiponectin were observed for BMI (-10.72%; 95% CI: -13.78, -7.55), total (-6.89%: 95% CI: -10.34, -3.30; P < 0.05), and central fat mass (-12.50%; 95% CI: -15.82, -9.05; P < 0.05); these relationships were significant both when twins were analyzed as individuals and when characteristics were contrasted within-twin pairs, suggesting a direct effect. We observed modest associations between dietary factors and adiponectin in female twins, independent of adiposity, and report strong inverse associations with body composition. These data reinforce the importance of weight maintenance and increasing consumption of diets rich in plant-based foods to prevent CVD and type 2 diabetes.
MED-4308
Effect of nutrient intake on premenstrual depression.
We examined the occurrence and coincidence of depressed mood and excessive carbohydrate intake in 19 patients who claimed to suffer from severe premenstrual syndrome and in nine control subjects, all as inpatients, during the early follicular and late luteal phases of their menstrual cycles. Mood was assessed with the Hamilton Depression Scale and an addendum that evaluated fatigue, sociability, appetite, and carbohydrate craving. Calorie and nutrient intakes were measured directly. The subjects with premenstrual syndrome significantly increased calorie intake during the late luteal phase (from 1892 +/- 104 to 2395 +/- 93 kcal, mean +/- SEM); carbohydrate intake increased by 24% from meals and by 43% from snacks. Protein intake failed to change, whereas intake of fat, a fixed constituent of all of the test foods, rose in proportion to calorie intake. The Hamilton Depression Scale and addendum scores rose from 2.0 +/- 0.5 to 21.2 +/- 0.8 (Hamilton Scale) and from 0.5 +/- 0.5 to 10.2 +/- 0.6 (addendum) among subjects with premenstrual syndrome during the luteal phase but failed to change among the controls (2.1 +/- 0.8 to 2.4 +/- 0.8, and 0.4 +/- 0.3 to 0.6 +/- 0.3). Consumption of a carbohydrate-rich, protein-poor evening test meal during the late luteal phase of the menstrual cycle improved depression, tension, anger, confusion, sadness, fatigue, alertness, and calmness scores (p less than 0.01) among patients with premenstrual syndrome. No effect of the meal was observed during the follicular phase or among the control subjects during either phase. Because synthesis of brain serotonin, which is known to be involved in mood and appetite, increases after carbohydrate intake, premenstrual syndrome subjects may overconsume carbohydrates in an attempt to improve their dysphoric mood state.
MED-2831
Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers
TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-α, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-α antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000–20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8
MED-1986
Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard Growth Study of 1922 to 1935.
BACKGROUND: Overweight in adults is associated with increased morbidity and mortality. In contrast, the long-term effect of overweight in adolescence on morbidity and mortality is not known. METHODS: We studied the relation between overweight and morbidity and mortality in 508 lean or overweight adolescents 13 to 18 years old who participated in the Harvard Growth Study of 1922 to 1935. Overweight adolescents were defined as those with a body-mass index that on two occasions was greater than the 75th percentile in subjects of the same age and sex in a large national survey. Lean adolescents were defined as those with a body-mass index between the 25th and 50th percentiles. Subjects who were still alive were interviewed in 1988 to obtain information about their medical history, weight, functional capacity, and other risk factors. For those who had died, information on the cause of death was obtained from death certificates. RESULTS: Overweight in adolescent subjects was associated with an increased risk of mortality from all causes and disease-specific mortality among men, but not among women. The relative risks among men were 1.8 (95 percent confidence interval, 1.2 to 2.7; P = 0.004) for mortality from all causes and 2.3 (95 percent confidence interval, 1.4 to 4.1; P = 0.002) for mortality from coronary heart disease. The risk of morbidity from coronary heart disease and atherosclerosis was increased among men and women who had been overweight in adolescence. The risk of colorectal cancer and gout was increased among men and the risk of arthritis was increased among women who had been overweight in adolescence. Overweight in adolescence was a more powerful predictor of these risks than overweight in adulthood. CONCLUSIONS: Overweight in adolescence predicted a broad range of adverse health effects that were independent of adult weight after 55 years of follow-up.
MED-5131
Vitamin B12 sources and bioavailability.
The usual dietary sources of vitamin B(12) are animal foods, meat, milk, egg, fish, and shellfish. As the intrinsic factor-mediated intestinal absorption system is estimated to be saturated at about 1.5-2.0 microg per meal under physiologic conditions, vitamin B(12) bioavailability significantly decreases with increasing intake of vitamin B(12) per meal. The bioavailability of vitamin B(12) in healthy humans from fish meat, sheep meat, and chicken meat averaged 42%, 56%-89%, and 61%-66%, respectively. Vitamin B(12) in eggs seems to be poorly absorbed (< 9%) relative to other animal food products. In the Dietary Reference Intakes in the United States and Japan, it is assumed that 50% of dietary vitamin B(12) is absorbed by healthy adults with normal gastro-intestinal function. Some plant foods, dried green and purple lavers (nori) contain substantial amounts of vitamin B(12), although other edible algae contained none or only traces of vitamin B(12). Most of the edible blue-green algae (cyanobacteria) used for human supplements predominantly contain pseudovitamin B(12), which is inactive in humans. The edible cyanobacteria are not suitable for use as vitamin B(12) sources, especially in vegans. Fortified breakfast cereals are a particularly valuable source of vitamin B(12) for vegans and elderly people. Production of some vitamin B(12)-enriched vegetables is also being devised.
MED-2201
New metrics of affordable nutrition: which vegetables provide most nutrients for least cost?
Measuring food prices per gram, rather than per calorie, is one way to make healthful vegetables appear less expensive. However, a better measure of affordability would take the nutrient content of vegetables into account. This study, based on analyses of US Department of Agriculture datasets, aimed to identify which vegetables, including juices and soups, provided the most nutrients per unit cost. Nutrient density was measured using the Nutrient Rich Foods (NRF) index, based on nine nutrients to encourage: protein; fiber; vitamins A, C, and E; calcium; iron; magnesium; and potassium; and on three nutrients to limit: saturated fat, added sugar, and sodium. Food cost in dollars was calculated per 100 g, per 100 kcal, per serving, and per nutrient content. One-way analyses of variance with post hoc tests were used to determine statistical significance. Results showed that tomato juices and tomato soups, dark green leafy and nonleafy vegetables, and deep yellow vegetables, including sweet potatoes, had the highest NRF scores overall. Highest NRF scores per dollar were obtained for sweet potatoes, white potatoes, tomato juices and tomato soups, carrots, and broccoli. Tomato sauces, raw tomatoes, and potato chips were eaten more frequently than were many other vegetables that were both more affordable and more nutrient-rich. These new measures of affordable nutrition can help foodservice and health professionals identify those vegetables that provide the highest nutrient density per unit cost. Processed vegetables, including soups and juices, can contribute to the quality and the affordability of the diet. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.
MED-3945
International multidimensional authenticity specification (IMAS) algorithm for detection of commercial pomegranate juice adulteration.
The pomegranate fruit ( Punica granatum ) has become an international high-value crop for the production of commercial pomegranate juice (PJ). The perceived consumer value of PJ is due in large part to its potential health benefits based on a significant body of medical research conducted with authentic PJ. To establish criteria for authenticating PJ, a new International Multidimensional Authenticity Specifications (IMAS) algorithm was developed through consideration of existing databases and comprehensive chemical characterization of 45 commercial juice samples from 23 different manufacturers in the United States. In addition to analysis of commercial juice samples obtained in the United States, data from other analyses of pomegranate juice and fruits including samples from Iran, Turkey, Azerbaijan, Syria, India, and China were considered in developing this protocol. There is universal agreement that the presence of a highly constant group of six anthocyanins together with punicalagins characterizes polyphenols in PJ. At a total sugar concentration of 16 degrees Brix, PJ contains characteristic sugars including mannitol at >0.3 g/100 mL. Ratios of glucose to mannitol of 4-15 and of glucose to fructose of 0.8-1.0 are also characteristic of PJ. In addition, no sucrose should be present because of isomerase activity during commercial processing. Stable isotope ratio mass spectrometry as > -25 per thousand assures that there is no added corn or cane sugar added to PJ. Sorbitol was present at <0.025 g/100 mL; maltose and tartaric acid were not detected. The presence of the amino acid proline at >25 mg/L is indicative of added grape products. Malic acid at >0.1 g/100 mL indicates adulteration with apple, pear, grape, cherry, plum, or aronia juice. Other adulteration methods include the addition of highly concentrated aronia, blueberry, or blackberry juices or natural grape pigments to poor-quality juices to imitate the color of pomegranate juice, which results in abnormal anthocyanin profiles. To adjust the astringent taste of poor-quality juice or peel extract, addition of nonpomegranate sugars is a commonly detected adulteration method. The profile generated from these analyses combined with information from existing databases and published literature has been integrated into a validated IMAS for PJ, which can be utilized to detect PJ adulteration. In this survey of commercial pomegranate juices, only 6 of 23 strictly met all of the IMAS criteria.
MED-3787
11C-choline vs. 18F-FDG PET/CT in assessing bone involvement in patients with multiple myeloma
Background Multiple Myeloma (MM) is a B cell neoplasm causing lytic or osteopenic bone abnormalities. Whole body skeletal survey (WBSS), Magnetic resonance (MR) and 18F-FDG PET/CT are imaging techniques routinely used for the evaluation of bone involvement in MM patients. Aim As MM bone lesions may present low 18F-FDG uptake; the aim of this study was to assess the possible added value and limitations of 11C-Choline to that of 18F-FDG PET/CT in patients affected with MM. Methods Ten patients affected with MM underwent a standard 11C-Choline PET/CT and an 18F-FDG PET/CT within one week. The results of the two scans were compared in terms of number, sites and SUVmax of lesions. Results Four patients (40%) had a negative concordant 11C-Choline and 18F-FDG PET/CT scans. Two patients (20%) had a positive 11C-Choline and 18F-FDG PET/CT scans that identified the same number and sites of bone lesions. The remaining four patients (40%) had a positive 11C-Choline and 18F-FDG PET/CT scan, but the two exams identified different number of lesions. Choline showed a mean SUVmax of 5 while FDG showed a mean SUVmax of 3.8 (P = 0.042). Overall, 11C-Choline PET/CT scans detected 37 bone lesions and 18F-FDG PET/CT scans detected 22 bone lesions but the difference was not significant (P = 0.8). Conclusion According to these preliminary data, 11C-Choline PET/CT appears to be more sensitive than 18F-FDG PET/CT for the detection of bony myelomatous lesions. If these data are confirmed in larger series of patients, 11C-Choline may be considered a more appropriate functional imaging in association with MRI for MM bone staging.
MED-1697
Effect of Tomato Industrial Processing (Different Hybrids, Paste, and Pomace) on Inhibition of Platelet Function In Vitro, Ex Vivo, and In Vivo
Cardiovascular disease (CVD) is the leading cause of death worldwide. Healthy eating is among its safeguards, especially the daily intake of fruits and vegetables. In this context it has been shown that tomato (Solanum lycopersicum) presents antiplatelet activity. In the present study, we evaluated in vitro antiplatelet activity of fresh hybrid tomato process (nine hybrids: Apt 410, H 9888, Bos 8066, Sun 6366, AB3, HMX 7883, H 9665, H 7709, and H 9997), paste and its by-product of industrial processes (pomace). We assessed antiplatelet activity ex vivo and bleeding time in rats that ingested 0.1 and 1.0 g/kg of pomace each day. In studies in vitro, no significant differences in antiplatelet activity was observed in fresh tomato hybrids. Furthermore, the agro-industrial process did not affect the antiplatelet activity of paste and pomace. Likewise, pomace intake of 1.0 g/kg per day prolonged bleeding time and reduced ex vivo platelet aggregation in rats. The data obtained indicate that tomato has one or more compounds that caused antiplatelet activity. Regular consumption of tomato and its industrial derivatives could be part of a CVD prevention regimen.
MED-4164
Evidence that protein requirements have been significantly underestimated.
PURPOSE OF REVIEW: This review discusses recent evidence that suggests a significant underestimation of protein requirements in adult humans. RECENT FINDINGS: Traditionally, total protein requirements for humans have been determined using nitrogen balance. The recent Dietary Reference Intake recommendations for mean and population-safe intakes of 0.66 and 0.8 g/kg/day, respectively, of high-quality protein in adult humans are based on a meta-analysis of nitrogen balance studies using single linear regression analysis. We reanalyzed existing nitrogen balance studies using two-phase linear regression analysis and obtained mean and safe protein requirements of 0.91 and 0.99 g/kg/day, respectively. The two-phase linear regression analysis is considered more appropriate for biological analysis of dose-response curves. Considering the inherent problems associated with the nitrogen balance method, we developed an alternative method, the indicator amino acid oxidation technique, to determine protein requirements The mean and population-safe requirements in adult men were determined to be 0.93 and 1.2 g/kg/day and are 41 and 50%, respectively, higher than the current Dietary Reference Intakes recommendations. SUMMARY: The indicator amino acid oxidation-based requirement values of 0.93 and 1.2 g protein/kg/day and the reanalysis of existing nitrogen balance studies are significantly higher than current recommendations. Therefore, there is an urgent need to reassess recommendations for protein intake in adult humans.
MED-3936
Elevated Serum Pesticide Levels and Risk of Parkinson Disease
Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD.
MED-1440
SIRT1 Decrease Parallels the Accumulation of tau in Alzheimer Disease
Aging and metabolism-related disorders are risk factors for Alzheimer disease (AD). Since sirtuins may increase the lifespan through regulation of cellular metabolism, we compared the concentration of sirtuin 1 (SIRT1) in the brains of AD patients (n = 19) and controls (n = 22) using Western immunoblots and in situ hybridization. We report a significant reduction of SIRT1 (mRNA: −29%; protein: −45%) in the parietal cortex of AD patients, but not in the cerebellum. Further analyses in a second cohort of 36 subjects confirmed that cortical SIRT1 was decreased in the cortex of AD patients but not in individuals with mild cognitive impairment. SIRT1 mRNA and its translated protein correlated negatively with the duration of symptoms (mRNA: r2 = −0.367; protein: r2 = −0.326) and the accumulation of paired helical filament tau (mRNA: r2 = −0.230; protein: r2 = −0.119), but weakly with insoluble amyloid-β(Aβ42 (mRNA: r2 = −0.090; protein: r2 = −0.072). A significant relationship between SIRT1 levels and global cognition scores proximate to death was also found (r2 = +0.09; p = 0.049). In contrast, cortical SIRT1 levels remained unchanged in a triple-transgenic animal model of AD. Collectively, our results indicate that loss of SIRT1 is closely associated with the accumulation of Aβ and tau in the cerebral cortex of patients with AD.
MED-4721
Cannabinoid receptor localization in brain.
[3H]CP 55,940, a radiolabeled synthetic cannabinoid, which is 10-100 times more potent in vivo than delta 9-tetrahydrocannabinol, was used to characterize and localize a specific cannabinoid receptor in brain sections. The potencies of a series of natural and synthetic cannabinoids as competitors of [3H]CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in our in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience. Autoradiography of cannabinoid receptors in brain sections from several mammalian species, including human, reveals a unique and conserved distribution; binding is most dense in outflow nuclei of the basal ganglia--the substantia nigra pars reticulata and globus pallidus--and in the hippocampus and cerebellum. Generally high densities in forebrain and cerebellum implicate roles for cannabinoids in cognition and movement. Sparse densities in lower brainstem areas controlling cardiovascular and respiratory functions may explain why high doses of delta 9-tetrahydrocannabinol are not lethal.
MED-4818
Pork intake and human papillomavirus-related disease.
Clinical and ecological evidence supporting an association between human papillomavirus (HPV)-related tumors and dietary factors are presented. Abstinence from high intake of fried pork (600-1,000 g/day) was associated with regression of an urethral condyloma in a healthy 19-year-old man treated with interferon gamma. International correlations suggest that pork intake is positively associated with incidence of cervical cancer, a disease also related to HPV. Pork meat or dietary factors associated with pork meat consumption may be involved in the development of HPV-related diseases.
MED-5212
Surgical punctal occlusion with a high heat-energy releasing cautery device for severe dry eye with recurrent punctal plug extrusion.
PURPOSE: To report the rate of recanalization and the efficacy of punctal occlusion surgery with a high heat-energy-releasing cautery device in patients with severe dry eye disease and recurrent punctal plug extrusion. DESIGN: Prospective, interventional case series. METHODS: Seventy puncta from 44 eyes of 28 dry eye patients underwent punctal occlusion with thermal cautery. All patients had a history of recurrent punctal plug extrusion. A high heat-energy-releasing thermal cautery device (Optemp II V; Alcon Japan) was used for punctal occlusion surgery. Symptom scores, best-corrected visual acuity, fluorescein staining score, rose bengal staining score, tear film break-up time, and Schirmer test values were compared before and 3 months after the surgery. Rate of punctal recanalization also was examined. RESULTS: Three months after surgical cauterization, symptom score decreased from 3.9 ± 0.23 to 0.56 ± 0.84 (P < .0001). Logarithm of the minimal angle of resolution best-corrected visual acuity improved from 0.11 ± 0.30 to 0.013 ± 0.22 (P = .003). Fluorescein staining score, rose bengal staining score, tear film break-up time, and the Schirmer test value also improved significantly after the surgery. Only 1 of 70 puncta recanalized after thermal cauterization (1.4%). CONCLUSIONS: Punctal occlusion with the high heat-energy-releasing cautery device not only was associated with a low recanalization rate, but also with improvements in ocular surface wetness and better visual acuity. Copyright © 2011 Elsevier Inc. All rights reserved.
MED-3427
The link between erectile and cardiovascular health: the canary in the coal mine.
Lifestyle and nutrition have been increasingly recognized as central factors influencing vascular nitric oxide (NO) production and erectile function. This review underscores the importance of NO as the principal mediator influencing cardiovascular health and erectile function. Erectile dysfunction (ED) is associated with smoking, excessive alcohol intake, physical inactivity, abdominal obesity, diabetes, hypertension, and decreased antioxidant defenses, all of which reduce NO production. Better lifestyle choices; physical exercise; improved nutrition and weight control; adequate intake of or supplementation with omega-3 fatty acids, antioxidants, calcium, and folic acid; and replacement of any testosterone deficiency will all improve vascular and erectile function and the response to phosphodiesterase-5 inhibitors, which also increase vascular NO production. More frequent penile-specific exercise improves local endothelial NO production. Excessive intake of vitamin E, calcium, l-arginine, or l-citrulline may impart significant cardiovascular risks. Interventions discussed also lower blood pressure or prevent hypertension. Certain angiotensin II receptor blockers improve erectile function and reduce oxidative stress. In men aged <60 years and in men with diabetes or hypertension, erectile dysfunction can be a critical warning sign for existing or impending cardiovascular disease and risk for death. The antiarrhythmic effect of omega-3 fatty acids may be particularly crucial for these men at greatest risk for sudden death. In conclusion, by better understanding the complex factors influencing erectile and overall vascular health, physicians can help their patients prevent vascular disease and improve erectile function, which provides more immediate motivation for men to improve their lifestyle habits and cardiovascular health. Copyright © 2011 Elsevier Inc. All rights reserved.
MED-2721
Increased food energy supply is more than sufficient to explain the US epidemic of obesity.
BACKGROUND: The major drivers of the obesity epidemic are much debated and have considerable policy importance for the population-wide prevention of obesity. OBJECTIVE: The objective was to determine the relative contributions of increased energy intake and reduced physical activity to the US obesity epidemic. DESIGN: We predicted the changes in weight from the changes in estimated energy intakes in US children and adults between the 1970s and 2000s. The increased US food energy supply (adjusted for wastage and assumed to be proportional to energy intake) was apportioned to children and adults and inserted into equations that relate energy intake to body weight derived from doubly labeled water studies. The weight increases predicted from the equations were compared with weight increases measured in representative US surveys over the same period. RESULTS: For children, the measured weight gain was 4.0 kg, and the predicted weight gain for the increased energy intake was identical at 4.0 kg. For adults, the measured weight gain was 8.6 kg, whereas the predicted weight gain was somewhat higher (10.8 kg). CONCLUSIONS: Increased energy intake appears to be more than sufficient to explain weight gain in the US population. A reversal of the increase in energy intake of approximately 2000 kJ/d (500 kcal/d) for adults and of 1500 kJ/d (350 kcal/d) for children would be needed for a reversal to the mean body weights of the 1970s. Alternatively, large compensatory increases in physical activity (eg, 110-150 min of walking/d), or a combination of both, would achieve the same outcome. Population approaches to reducing obesity should emphasize a reduction in the drivers of increased energy intake.
MED-3595
Heavy Metals and Couple Fecundity, the LIFE Study
The effect of heavy metals at environmentally relevant concentrations on couple fecundity has received limited study despite ubiquitous exposure. In 2005–2009, couples (n=501) desiring pregnancy and discontinuing contraception were recruited and asked to complete interviews and to provide blood specimens for the quantification of cadmium (μg/L), lead (μg/dL) and mercury (μg/L) using inductively coupled plasma-mass spectrometry. Couples completed daily journals on lifestyle and intercourse along with menstruation and pregnancy testing for women. Couples were followed for 12 months or until pregnant. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated adjusting for age, body mass index, cotinine, and serum lipids in relation to female then male exposures. FORs <1 denote a longer time to pregnancy. In adjusted models, reduced FORs were observed for both female cadmium (0.78; 95% CI 0.63–0.97) and male lead (0.85; 95% CI 0.73–0.98) concentrations. When jointly modeling couples’ exposures, only male lead concentration significantly reduced the FOR (0.82; 95% CI 0.68, 0.97), though the FOR remained <1 for female cadmium (0.80; 95% CI 0.64, 1.00). This prospective couple based cohort with longitudinal capture of time to pregnancy is suggestive of cadmium and lead’s reproductive toxicity at environmentally relevant concentrations.
MED-4251
Nutraceutical supplements for weight loss: a systematic review.
Obesity is a global public health issue. Although the etiology of this global epidemic is multifactorial, most sufferers would be delighted to find a relatively effortless way to lose weight. Herbal "weight loss pills" can fit the bill. The authors systematically review the scientific evidence concerning various weight loss agents that are available over the counter or in food stores. The review provides a starting point to make informed choices among nutraceutical agents promoted for weight loss, as well as advice for incorporating healthy alternatives in the diet.
MED-2054
Prevalence, symptoms and outcome of constipation in infants and toddlers.
OBJECTIVE: To determine the prevalence of constipation in children <or=2 years, describe the symptoms of constipation, and review how often specific interventions were effective. STUDY DESIGN: Retrospective chart review. RESULTS: Of 4,157 children <2 years of age, 185 children had constipation. The prevalence rate for constipation in the first year of life was 2.9%, and in the second year of life, the rate was 10.1%. Functional constipation was the cause in 97% of the children. Boys and girls were affected with equal frequency. Constipation was caused by an underlying organic disease in 1.6% of cases, and 97% of the children had functional constipation. Dietary changes and corn syrup were the initial treatment suggestions for 116 children; 93% of these children underwent follow-up examinations, and the constipation resolved in 25% of the children. Of 100 children treated with milk of magnesia or polyethylene glycol 3350 without electrolytes, 93 children underwent follow-up examinations, and the constipation was resolved with treatment in 92% of the children. CONCLUSIONS: Dietary changes, corn syrup, or both resolved constipation in 25% of children, and laxatives resolved constipation in 92% of children. Both milk of magnesia and polyethylene glycol were efficient and safe in infants and toddlers.
MED-2038
Absence of somatization in non-coeliac gluten sensitivity.
OBJECTIVE: In contrast to coeliac disease (CD), the mechanism behind non-coeliac gluten sensitivity (NCGS) is unclear. The aims of the study were to measure the presence of somatization, personality traits, anxiety, depression, and health-related quality of life in NCGS individuals compared with CD patients and healthy controls, and to compare the response to gluten challenge between NCGS and CD patients. MATERIAL AND METHODS: We examined 22 CD patients and 31 HLA-DQ2+ NCGS patients without CD, all on a gluten-free diet. All but five CD patients were challenged orally for 3 days with gluten; symptom registration was performed during challenge. A comparison group of 40 healthy controls was included. Patients and healthy controls completed questionnaires regarding anxiety, depression, neuroticism and lie, hostility and aggression, alexithymia and health locus of control, physical complaints, and health-related quality of life. RESULTS: The NCGS patients reported more abdominal (p = 0.01) and non-abdominal (p < 0.01) symptoms after gluten challenge than CD patients. There were no significant differences between CD and NCGS patients regarding personality traits, level of somatization, quality of life, anxiety, and depressive symptoms. The somatization level was low in CD and NCGS groups. Symptom increase after gluten challenge was not related to personality in NCGS patients. CONCLUSIONS: NCGS patients did not exhibit a tendency for general somatization. Personality and quality of life did not differ between NCGS and CD patients, and were mostly at the same level as in healthy controls. NCGS patients reported more symptoms than CD patients after gluten challenge.
MED-4070
Intake of fried meat and risk of cancer: a follow-up study in Finland.
It has been suggested that mutagens in fried meat may be involved in the cancer process. Therefore the relationships between intake of fried meat and subsequent risk of cancers at different sites were studied among 9,990 Finnish men and women, 15-99 years of age and initially free of cancer. The baseline study was carried out in 1966-1972, and cases of cancer were identified through data linkage with the Finnish Cancer Registry. During a 24-year follow-up, 853 cancer cases were diagnosed. The intake of fried meat was estimated from a dietary history interview covering the total diet of the participants during the previous year. There was a positive association between fried meat intake and the risk of female-hormone-related cancers, i.e., cancer of the breast, endometrium and ovary combined. The relative risk of these cancers combined between persons in the highest and lowest tertiles of daily intake of fried meat adjusted for age, personal characteristics and intake of other main food groups was 1.77 (95% confidence interval = 1.11-2.84). Pancreatic and nervous system cancers also presented non-significant suggestive associations. No associations were observed with respect to other single cancer sites studied or to all sites of cancer combined. Further epidemiological efforts are needed to ascertain the potential link between fried-food mutagens and cancer risk.
MED-3598
A prospective study of intake of trans-fatty acids from ruminant fat, partially hydrogenated vegetable oils, and marine oils and mortality from CVD.
Trans-fatty acids (TFA) have adverse effects on blood lipids, but whether TFA from different sources are associated with risk of CVD remains unresolved. The objective of the present study was to evaluate the association between TFA intake from partially hydrogenated vegetable oils (PHVO), partially hydrogenated fish oils (PHFO) and ruminant fat (rTFA) and risks of death of CVD, CHD, cerebrovascular diseases and sudden death in the Norwegian Counties Study, a population-based cohort study. Between 1974 and 1988, participants were examined for up to three times. Fat intake was assessed with a semi-quantitative FFQ. A total of 71,464 men and women were followed up through 2007. Hazard ratios (HR) and 95 % CI were estimated with Cox regression. Energy from TFA was compared to energy from all other sources, carbohydrates or unsaturated cis-fatty acids with different multivariable models. During follow-up, 3870 subjects died of CVD, 2383 of CHD, 732 of cerebrovascular diseases and 243 of sudden death. Significant risks, comparing highest to lowest intake category, were found for: TFA from PHVO and CHD (HR 1.23 (95 % CI 1.00, 1.50)) and cerebrovascular diseases (HR 0.65 (95 % CI 0.45, 0.94)); TFA from PHFO and CVD (HR 1.14 (95 % CI 1.03, 1.26)) and cerebrovascular diseases (HR 1.32 (95 % CI 1.04, 1.69)); and rTFA intake and CVD (HR 1.30 (95 % CI 1.05, 1.61)), CHD (HR 1.50 (95 % CI 1.11, 2.03)) and sudden death (HR 2.73 (95 % CI 1.19, 6.25)) in women. These associations with rTFA intake were not significant in men (P interaction ≥ 0.01). The present study supports that TFA intake, irrespective of source, increases CVD risk. Whether TFA from PHVO decreases risk of cerebrovascular diseases warrants further investigation.
MED-2787
The effect of curcumin and placebo on human gall-bladder function: an ultrasound study.
BACKGROUND: The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall-bladder. AIMS: To compare the effect of 20 mg curcumin or placebo on the gall-bladder volume of healthy volunteers. METHODS: A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall-bladder volume. The data obtained was analysed by paired Student's t-test. RESULTS: The fasting gall-bladder volumes of 15.74 +/- 4.29 mL on curcumin and 15.98 +/- 4.08 mL on placebo were similar (P > 0.20). The gall-bladder volume was reduced within the period after curcumin administration. The percentage of gall-bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 +/- 6.9, 16.8 +/- 7.4, 22.0 +/- 8.5 and 29. 3 +/- 8.3%, respectively, which was statistically significant compared to placebo. CONCLUSION: On the basis of the present findings, it appears that curcumin induces contraction of the human gall-bladder.
MED-4188
Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot tr...
Depressive disorders are very common in clinical practice, with approximately 11.3 of all adults afflicted during any a year. Saffron is the world's most expensive spice and apart from its traditional value as a food additive, recent studies indicate several therapeutic effects for saffron. It is used for depression in Persian traditional medicine. Our objective was to compare the efficacy of hydro-alcoholic extract of Crocus sativus (stigma) with fluoxetine in the treatment of mild to moderate depression in a 6-week double-blind, randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM-IV and with mild to moderate depression participated in the trial. In this double-blind, single-center trial and randomized trial, patients were randomly assigned to receive capsules of saffron 30 mg/day (BD) (Group 1) and capsule of fluoxetine 20 mg/day (BD) (Group 2) for a 6-week study. Saffron at this dose was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F = 0.13, d.f. = 1, P = 0.71). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified.
MED-3532
Application of LC and LC-MS to the analysis of melatonin and serotonin in edible plants.
Melatonin is a neurohormone produced by the pineal gland of animals. Serotonin is a monoamine neurotransmitter and one of the precursors of melatonin biosynthesis. These two indoleamines have recently been reported to have widespread occurrence in many edible plants. Consuming foodstuffs containing melatonin and serotonin could raise their physiologic concentrations in blood and enhance human health. Literature concerning analytical methods suitable for determination of melatonin and serotonin in edible plants is limited, although several liquid chromatographic (LC) techniques have been used for their quantification. Liquid chromatography-mass spectrometry (LC-MS) methods combine selectivity, sensitivity, and high precision, and enable the simultaneous determination of melatonin and serotonin. This work reviews LC and LC-MS techniques used to determine melatonin and serotonin, and the available data on melatonin and serotonin levels in edible plants. © 2011 Crown Copyright
MED-4278
EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK.
OBJECTIVE: To describe the lifestyle characteristics and nutrient intakes of the Oxford cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: Cohort of men and women recruited through general practices or by post to include a high proportion of non meat-eaters. Dietary, anthropometric and lifestyle data were collected at baseline and four diet groups were defined. SETTING: United Kingdom. PARTICIPANTS: In total, 65 429 men and women aged 20 to 97 years, comprising 33 883 meat-eaters, 10 110 fish-eaters, 18 840 lacto-ovo vegetarians and 2596 vegans. RESULTS: Nutrient intakes and lifestyle factors differed across the diet groups, with striking differences between meat-eaters and vegans, and fish-eaters and vegetarians usually having intermediate values. Mean fat intake in each diet group was below the UK dietary reference value of 33% of total energy intake. The mean intake of saturated fatty acids in vegans was approximately 5% of energy, less than half the mean intake among meat-eaters (10-11%). Vegans had the highest intakes of fibre, vitamin B1, folate, vitamin C, vitamin E, magnesium and iron, and the lowest intakes of retinol, vitamin B12, vitamin D, calcium and zinc. CONCLUSIONS: The EPIC-Oxford cohort includes 31 546 non meat-eaters and is one of the largest studies of vegetarians in the world. The average nutrient intakes in the whole cohort are close to those currently recommended for good health. Comparisons of the diet groups show wide ranges in the intakes of major nutrients such as saturated fat and dietary fibre. Such variation should increase the ability of the study to detect associations of diet with major cancers and causes of death.
MED-5256
No Association of Coffee Consumption with Gastric Ulcer, Duodenal Ulcer, Reflux Esophagitis, and Non-Erosive Reflux Disease: A Cross-Sectional Study of 8,013 Healthy Subjects in Japan
Probably due to caffeine-induced gastric acid secretion, negative effects of coffee upon various upper-gastrointestinal diseases have been precariously accepted, despite the inadequate epidemiological evidence. Our aim is to evaluate the effect of coffee consumption on four major acid-related diseases: gastric ulcer (GU), duodenal ulcer (DU), reflux esophagitis (RE), and non-erosive reflux disease (NERD) based on the large-scale multivariate analysis. Of the 9,517 healthy adults, GU, DU, and RE were diagnosed by endoscopy, and NERD was diagnosed by the symptoms of heartburn and regurgitation without esophageal erosion. Associations between coffee consumption and the four disorders were evaluated, together with age, gender, body mass index (BMI), Helicobacter pylori (HP) infection status, pepsinogen I/II ratio, smoking, and alcohol. We further performed meta-analysis using the random effects model to redefine the relationship between coffee intake and peptic ulcer disease. The eligible 8,013 study subjects comprised of 5,451 coffee drinkers and 2,562 non-coffee drinkers. By univariate analysis, age, BMI, pepsinogen I/II ratio, smoking, and alcohol showed significant associations with coffee consumption. By multiple logistic regression analysis, positively correlated factors with significance were HP infection, current smoking, BMI, and pepsinogen I/II ratio for GU; HP infection, pepsinogen I/II ratio, and current smoking for DU; HP non-infection, male, BMI, pepsinogen I/II ratio, smoking, age, and alcohol for RE; younger age, smoking, and female for NERD. The meta-analyses could detect any association of coffee consumption with neither GU nor DU. In conclusion, there are no significant relationship between coffee consumption and the four major acid-related upper gastrointestinal disorders.
MED-4265
Microbial ecology: human gut microbes associated with obesity.
Two groups of beneficial bacteria are dominant in the human gut, the Bacteroidetes and the Firmicutes. Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people, and that this proportion increases with weight loss on two types of low-calorie diet. Our findings indicate that obesity has a microbial component, which might have potential therapeutic implications.
MED-4005
Effect of the fat composition of a single high-fat meal on inflammatory markers in healthy young women.
The aim of the present study was to examine the effect of a single high-fat meal with different fat quality on circulating inflammatory markers and gene expression in peripheral blood mononuclear cells (PBMC) to elucidate the role of fat quality on postprandial inflammation. A postprandial study with fourteen healthy females consuming three test meals with different fat quality was performed. Test days were separated by 2 weeks. Fasting and postprandial blood samples at 3 and 6 h after intake were analysed. The test meal consisted of three cakes enriched with coconut fat (43 % energy as saturated fat and 1 % energy as α-linolenic acid (ALA)), linseed oil (14 % energy as ALA and 30 % energy as saturated fat) and cod liver oil (5 % energy as EPA and DHA and 5 % energy as ALA in addition to 31 % energy as saturated fat). In addition, ex vivo PBMC experiments were performed in eight healthy subjects investigating the effects of EPA and ALA on release and gene expression of inflammatory markers. The IL-8 mRNA level was significantly increased after intake of the cod liver oil cake at 6 h compared with fasting level, which was significantly different from the effect observed after the intake of linseed cake. In contrast, no effect was seen on circulating level of IL-8. In addition, ALA and EPA were shown to elicit different effects on the release and mRNA expression levels of inflammatory markers in PBMC cultured ex vivo, with EPA having the most prominent pro-inflammatory potential.
MED-1606
Intake of fiber and fiber-rich plant foods is associated with a lower risk of renal cell carcinoma in a large US cohort
Background: Plant-based and fiber-rich diets high in vegetables, fruit, and whole grains are recommended to prevent cancer and chronic conditions associated with renal cell carcinoma (RCC), such as obesity, hypertension, and diabetes. Diet may play a role in the etiology of RCC directly and/or indirectly. Objective: In a large prospective cohort of US men and women, we comprehensively investigated dietary intake and food sources of fiber in relation to RCC risk. Design: Participants of the NIH-AARP Diet and Health Study (n = 491,841) completed a self-administered questionnaire of demographics, diet, lifestyle, and medical history. Over 9 (mean) years of follow-up we identified 1816 incident cases of RCC. HRs and 95% CIs were estimated within quintiles by using multivariable Cox proportional hazards regression. Results: Total dietary fiber intake was associated with a significant 15–20% lower risk of RCC in the 2 highest quintiles compared with the lowest (P-trend = 0.005). Intakes of legumes, whole grains, and cruciferous vegetables were also associated with a 16–18% reduced risk of RCC. Conversely, refined grain intake was positively associated with RCC risk in a comparison of quintile 5 with quintile 1 (HR: 1.19; 95% CI: 1.02, 1.39; P-trend = 0.04). The inverse association between fiber intake and RCC was consistent among participants who never smoked, had a body mass index [BMI (in kg/m2)] <30, and did not report a history of diabetes or hypertension. Conclusions: Intake of fiber and fiber-rich plant foods was associated with a significantly lower risk of RCC in this large US cohort. This trial was registered at clinicaltrials.gov as NCT00340015.
MED-3247
Evidence Report: The efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis
Objective: The chemotherapeutic agent mitoxantrone was approved for use in multiple sclerosis (MS) in 2000. After a review of all the available evidence, the original report of the Therapeutics and Technology Assessment Subcommittee in 2003 concluded that mitoxantrone probably reduced clinical attack rates, MRI activity, and disease progression. Subsequent reports of decreased systolic function, heart failure, and leukemia prompted the US Food and Drug Administration to institute a “black box” warning in 2005. This review was undertaken to examine the available literature on the efficacy and safety of mitoxantrone use in patients with MS since the initial report. Methods: Relevant articles were obtained through a review of the medical literature and the strength of the available evidence was graded according to the American Academy of Neurology evidence classification scheme. Results: The accumulated Class III and IV evidence suggests an increased incidence of systolic dysfunction and therapy-related acute leukemia (TRAL) with mitoxantrone therapy. Systolic dysfunction occurs in ∼12% of patients with MS treated with mitoxantrone, congestive heart failure occurs in ∼0.4%, and leukemia occurs in ∼0.8%. The number needed to harm is 8 for systolic dysfunction and 123 for TRAL. There is no new efficacy evidence that would change the recommendation from the previous report. Conclusions: The risk of systolic dysfunction and leukemia in patients treated with mitoxantrone is higher than suggested at the time of the previous report, although comprehensive postmarketing surveillance data are lacking. GLOSSARY
MED-2827
Soy protein may alleviate osteoarthritis symptoms.
Alternative and complementary therapeutic approaches, such as the use of a wide array of herbal, nutritional, and physical manipulations, are becoming popular for relieving symptoms of osteoarthritis (OA). The present study evaluated the efficacy of soy protein (SP) supplementation in relieving the pain and discomfort associated with OA. One hundred and thirty-five free-living individuals (64 men and 71 women) with diagnosed OA or with self-reported chronic knee joint pain not attributed to injury or rheumatoid arthritis were recruited for this double-blind, placebo-controlled, parallel design study. Study participants were assigned randomly to consume 40 g of either supplemental SP or milk-based protein (MP) daily for 3 months. Pain, knee range of motion, and overall physical activity were evaluated prior to the start of treatment and monthly thereafter. Serum levels of glycoprotein 39 (YKL-40), a marker of cartilage degradation, and insulin-like growth factor-I (IGF-I), a growth factor associated with cartilage synthesis, were assessed at baseline and at the end of the study. Overall, SP improved OA-associated symptoms such as range of motion and several factors associated with pain and quality of life in comparison to MP. However, these beneficial effects were mainly due to the effect of SP in men rather than women. Biochemical markers of cartilage metabolism further support the efficacy of SP in men as indicated by a significant increase in serum level of IGF-I and a significant decrease in serum level of YKL-40 compared to MP. This study is the first to provide evidence of possible beneficial effects of SP in the management of OA. Examining and verifying the long-term effects of SP on improving symptoms of OA, particularly in men, is warranted.
MED-3288
Outbreak of progressive inflammatory neuropathy following exposure to aerosolized porcine neural tissue.
In the fall of 2007, the Minnesota Department of Health was notified of 11 cases of an unexplained neurological illness, all linked to a pork processing plant, Quality Pork Processors, Inc., in Austin, MN. The cluster of workers had been experiencing similar symptoms, including fatigue, pain, numbness, and tingling in their extremities as well as weakness. The symptoms were described as more sensory than motor, and all patients had evidence of polyradiculoneuropathy with signs of nerve root irritation. An epidemiological investigation revealed that the only commonality between cases was their exposure to a pork brain extraction procedure involving compressed air. As relatives of the cases remained asymptomatic and all cultures for known pathogens were negative, the etiology of the syndrome seemed not to be infectious. Clinically, the syndrome was most akin to chronic inflammatory demyelinating polyneuropathy. Laboratory tests corroborated the clinical findings, revealing inflammation of peripheral nerves and nerve roots; however, these cases also had features clinically distinct from chronic inflammatory demyelinating polyneuropathy as well as laboratory testing revealing a novel immunoglobulin G immunostaining pattern. This suggested that the observed inflammation was the result of 1 or more unidentified antigens. This syndrome was ultimately dubbed progressive inflammatory neuropathy and was theorized to be an autoimmune reaction to aerosolized porcine neural tissue. Since the investigation's outset, 18 cases of progressive inflammatory neuropathy have been identified at the Minnesota pork processing plant, with 5 similar cases at an Indiana plant and 1 case at a Nebraskan plant. The plants in which cases have been identified have since stopped the use of compressed air in removing pork brains. All cases have stabilized or improved, with some requiring immunosuppressive and analgesic treatment. The study of progressive inflammatory neuropathy is ongoing, and the details of this investigation highlight the value of epidemiological principles in the identification and containment of outbreaks while researchers attempt to uncover the unique pathophysiology and potential etiology of the illness. Mt Sinai J Med 76:442-447, 2009. (c) 2009 Mount Sinai School of Medicine.
MED-4336
Regular consumption of dark chocolate is associated with low serum concentrations of C-reactive protein in a healthy Italian population.
Dark chocolate contains high concentrations of flavonoids and may have antiinflammatory properties. We evaluated the association of dark chocolate intake with serum C-reactive protein (CRP). The Moli-sani Project is an ongoing cohort study of men and women aged >/=35 y randomly recruited from the general population. By July 2007, 10,994 subjects had been enrolled. Of 4849 subjects apparently free of any chronic disease, 1317 subjects who declared having eaten any chocolate during the past year (mean age 53 +/- 12 y; 51% men) and 824 subjects who ate chocolate regularly in the form of dark chocolate only (50 +/- 10 y; 55% men) were selected. High sensitivity-CRP was measured by an immunoturbidimetric method. The European Prospective Investigation into Cancer and Nutrition FFQ was used to evaluate nutritional intake. After adjustment for age, sex, social status, physical activity, systolic blood pressure, BMI, waist:hip ratio, food groups, and total energy intake, dark chocolate consumption was inversely associated with CRP (P = 0.038). When adjusted for nutrient intake, analyses showed similar results (P = 0.016). Serum CRP concentrations [geometric mean (95% CI)] univariate concentrations were 1.32 (1.26-1.39 mg/L) in nonconsumers and 1.10 (1.03-1.17 mg/L) in consumers (P < 0.0001). A J-shaped relationship between dark chocolate consumption and serum CRP was observed; consumers of up to 1 serving (20 g) of dark chocolate every 3 d had serum CRP concentrations that were significantly lower than nonconsumers or higher consumers. Our findings suggest that regular consumption of small doses of dark chocolate may reduce inflammation.
MED-4443
Flaxseed: a potential source of food, feed and fiber.
Flaxseed is one of the most important oilseed crops for industrial as well as food, feed, and fiber purposes. Almost every part of the flaxseed plant is utilized commercially, either directly or after processing. The stem yields good quality fiber having high strength and durability. The seed provides oil rich in omega-3, digestible proteins, and lignans. In addition to being one of the richest sources of α-linolenic acid oil and lignans, flaxseed is an essential source of high quality protein and soluble fiber and has considerable potential as a source of phenolic compounds. Flaxseed is emerging as an important functional food ingredient because of its rich contents of α-linolenic acid (ALA), lignans, and fiber. Lignans appear to be anti-carcinogenic compounds. The omega-3s and lignan phytoestrogens of flaxseed are in focus for their benefits for a wide range of health conditions and may possess chemo-protective properties in animals and humans. This paper presents a review of literature on the nutritional composition of flaxseed, its health benefits, and disease-prevention qualities, utilization of flaxseed for food, feed, and fiber, and processing of flaxseed.
MED-3202
Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man.
1. The effects of grapefruit juice and naringenin on the activity of the human cytochrome P450 isoform CYP1A2 were evaluated using caffeine as a probe substrate. 2. In vitro naringin was a potent competitive inhibitor of caffeine 3-demethylation by human liver microsomes (Ki = 7-29 microM). 3. In vivo grapefruit juice (1.2 l day-1 containing 0.5 g l-1 naringin, the glycone form of naringenin) decreased the oral clearance of caffeine by 23% (95% CI: 7%-30%) and prolonged its half-life by 31% (95% CI: 20%-44%) (n = 12). 4. We conclude that grapefruit juice and naringenin inhibit CYP1A2 activity in man. However, the small effect on caffeine clearance in vivo suggests that in general the ingestion of grapefruit juice should not cause clinically significant inhibition of the metabolism of other drugs that are substrates of CYPIA2.
MED-306
Sensitivity of Continuous Performance Test (CPT) at Age 14 Years to Developmental Methylmercury Exposure
Hit Reaction Time latencies (HRT) in the Continuous Performance Test (CPT) measure the speed of visual information processing. The latencies may involve different neuropsychological functions depending on the time from test initiation, i.e., first orientation, learning and habituation, then cognitive processing and focused attention, and finally sustained attention as the dominant demand. Prenatal methylmercury exposure is associated with increased reaction time (RT) latencies. We therefore examined the association of methylmercury exposure with the average HRT at age 14 years at three different time intervals after test initiation. A total of 878 adolescents (87% of birth cohort members) completed the CPT. The RT latencies were recorded for 10 minutes, with visual targets presented at 1000 ms intervals. After confounder adjustment, regression coefficients showed that CPT-RT outcomes differed in their associations with exposure biomarkers of prenatal methylmercury exposure: During the first two minutes, the average HRT was weakly associated with methylmercury (beta (SE) for a ten-fold increase in exposure, (3.41 (2.06)), was strongly for the 3-to-6 minute interval (6.10 (2.18)), and the strongest during 7–10 minutes after test initiation (7.64 (2.39)). This pattern was unchanged when simple reaction time and finger tapping speed were included in the models as covariates. Postnatal methylmercury exposures did not affect the outcomes. Thus, these findings suggest that sustained attention as a neuropsychological domain is particularly vulnerable to developmental methylmercury exposure, indicating probable underlying dysfunction of the frontal lobes. When using CPT data as a possible measure of neurotoxicity, test results should therefore be analyzed in regard to time from test initiation and not as overall average reaction times.
MED-4693
Light-at-night, circadian disruption and breast cancer: assessment of existing evidence
Background Breast cancer incidence is increasing globally for largely unknown reasons. The possibility that a portion of the breast cancer burden might be explained by the introduction and increasing use of electricity to light the night was suggested >20 years ago. Methods The theory is based on nocturnal light-induced disruption of circadian rhythms, notably reduction of melatonin synthesis. It has formed the basis for a series of predictions including that non-day shift work would increase risk, blind women would be at lower risk, long sleep duration would lower risk and community nighttime light level would co-distribute with breast cancer incidence on the population level. Results Accumulation of epidemiological evidence has accelerated in recent years, reflected in an International Agency for Research on Cancer (IARC) classification of shift work as a probable human carcinogen (2A). There is also a strong rodent model in support of the light-at-night (LAN) idea. Conclusion If a consensus eventually emerges that LAN does increase risk, then the mechanisms for the effect are important to elucidate for intervention and mitigation. The basic understanding of phototransduction for the circadian system, and of the molecular genetics of circadian rhythm generation are both advancing rapidly, and will provide for the development of lighting technologies at home and at work that minimize circadian disruption, while maintaining visual efficiency and aesthetics. In the interim, there are strategies now available to reduce the potential for circadian disruption, which include extending the daily dark period, appreciate nocturnal awakening in the dark, using dim red light for nighttime necessities, and unless recommended by a physician, not taking melatonin tablets.
MED-4426
Riding in shopping carts and exposure to raw meat and poultry products: prevalence of, and factors associated with, this risk factor for salmonella...
Riding in a shopping cart next to raw meat or poultry is a risk factor for Salmonella and Campylobacter infections in infants. To describe the frequency of, and factors associated with, this behavior, we surveyed parents of children aged younger than 3 years in Foodborne Disease Active Surveillance Network sites. We defined exposure as answering yes to one of a series of questions asking if packages of raw meat or poultry were near a child in a shopping cart, or if a child was in the cart basket at the same time as was raw meat or poultry. Among 1,273 respondents, 767 (60%) reported that their children visited a grocery store in the past week and rode in shopping carts. Among these children, 103 (13%) were exposed to raw products. Children who rode in the baskets were more likely to be exposed than were those who rode only in the seats (odds ratio [OR], 17.8; 95% confidence interval [CI], 11.0 to 28.9). In a multivariate model, riding in the basket (OR, 15.5; 95% CI, 9.2 to 26.1), income less than $55,000 (OR, 1.8; 95% CI, 1.0 to 3.1), and Hispanic ethnicity (OR, 2.3; 95% CI, 1.2 to 4.5) were associated with exposure. Our study shows that children can be exposed to raw meat and poultry products while riding in shopping carts. Parents should separate children from raw products and place children in the seats rather than in the baskets of the cart. Retailer use of leak-proof packaging, customer placement of product in a plastic bag and on the rack underneath the cart, use of hand sanitizers and wipes, and consumer education may also be helpful.
MED-2239
A novel curcumin-based vaginal cream Vacurin selectively eliminates apposed human cervical cancer cells.
OBJECTIVE: Human papillomavirus (HPV) infections remain a leading cause of mortality worldwide. In the U.S. strategies via screening and vaccination prevent HPV-associated cervical neoplasms, but consume immense healthcare costs. The spice component curcumin has potent anticancer and antiviral properties, which have been difficult to harness as a treatment, due to its poor systemic bioavailability. This project tests the possibility of developing a curcumin-based therapy for cervical cancer. METHODS: Using four HPV(+) cervical cancer cell lines and normal fibroblasts we first tested the selectivity and potency of curcumin in eliminating HPV(+) cells. Subsequently, we developed a curcumin-based cervical cream and tested its efficacy in eliminating apposed HPV(+) cells and also its possible side effects on the vaginal epithelium of healthy mice. RESULTS: Curcumin selectively eliminates a variety of HPV(+) cervical cancer cells (HeLa, ME-180, SiHa, and SW756), suppresses the transforming antigen E6, dramatically inhibits the expression of the pro-cancer protein epidermal growth factor receptor (EGFR), and concomitantly induces p53. Additionally, Vacurin, a uniform colloidal solution of curcumin in a clinically used amphipathic vaginal cream, eliminates apposed HeLa cells while suppressing the expression of EGFR. In mice, daily intravaginal application of Vacurin for three weeks produced no change in body weight and when the mice were sacrificed, the vaginal tract epithelium showed no Vacurin-evoked adverse effects. CONCLUSION: We have developed a curcumin-based vaginal cream, which effectively eradicates HPV(+) cancer cells and does not affect non-cancerous tissue. Our preclinical data support a novel approach for the treatment of cervical HPV infection. Copyright © 2012 Elsevier Inc. All rights reserved.
MED-5105
Dioxins, dibenzofurans, dioxin-like PCBs, and DDE in U.S. fast food, 1995.
Food, especially dairy products, meat, and fish, is the primary source of environmental exposure to dioxins in the general population. Little data exists on dioxin levels in the popular and widely consumed "fast foods". Data presented in a previously published pilot study was limited to measuring only the levels of dioxins and dibenzofurans in three types of U.S. fast food. This study adds to the previous paper by presenting data, in addition to dioxins and dibenzofurans, on the closely related dioxin-like polychlorinated biphenyls (PCBs), and the persistent metabolite of DDT, 1,1-dichloro-2,2-bis (p-chlorophenyl) ethylene (DDE), in four types of popular U.S. fast food. These include McDonald's Big Mac Hamburger, Pizza Hut's Personal Pan Pizza Supreme, Kentucky Fried Chicken (KFC) three piece original recipe mixed dark and white meat luncheon package, and Häagen-Daz chocolate-chocolate chip ice cream. Dioxin plus dibenzofuran dioxin toxic equivalents (TEQ) ranged from 0.03 to 0.28 TEQ pg/g wet or whole weight for the Big Mac, from 0.03 to 0.29 for the Pizza, from 0.01 to 0.31 for the KFC, and from 0.03 to 0.49 TEQ pg/g for the ice cream. Daily TEQ consumption per kilogram body weight (kg/BW), assuming an average 65 kg adult and a 20 kg child, from one serving of each of these fast food ranged between 0.046 and 1.556 pg/kg in adults whereas in children the values were between 0.15 and 5.05 pg/kg. Total measured PCDD/Fs in the Big Mac, Personal Pan Pizza, KFC, and the Häagen-Daz ice cream varied from 0.58 to 9.31 pg/g. Measured DDE levels in the fast foods ranged from 180 to 3170 pg/g. Total mono-ortho PCB levels ranged up to 500 pg/g or 1.28 TEQ pg/g for the KFC and for di-ortho PCBs up to 740 pg/g or 0.014 TEQ pg/g for the pizza sample. Total PCB values in the four samples ranged up to 1170 pg/g or 1.29 TEQ pg/g for the chicken sample.
MED-3407
The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease
The Princeton Consensus (Expert Panel) Conference is a multispecialty collaborative tradition dedicated to optimizing sexual function and preserving cardiovascular health. The third Princeton Consensus met November 8 to 10, 2010, and had 2 primary objectives. The first objective focused on the evaluation and management of cardiovascular risk in men with erectile dysfunction (ED) and no known cardiovascular disease (CVD), with particular emphasis on identification of men with ED who may require additional cardiologic work-up. The second objective focused on reevaluation and modification of previous recommendations for evaluation of cardiac risk associated with sexual activity in men with known CVD. The Panel's recommendations build on those developed during the first and second Princeton Consensus Conferences, first emphasizing the use of exercise ability and stress testing to ensure that each man's cardiovascular health is consistent with the physical demands of sexual activity before prescribing treatment for ED, and second highlighting the link between ED and CVD, which may be asymptomatic and may benefit from cardiovascular risk reduction.
MED-5287
Candy consumption was not associated with body weight measures, risk factors for cardiovascular disease, or metabolic syndrome in US adults: NHANES...
There is limited research examining the relationship of candy consumption by adults on diet and health. The purpose of this study was to determine total, chocolate, or sugar candy consumption and their effect on energy, saturated fatty acid and added sugar intake, weight, risk factors for cardiovascular disease, metabolic syndrome (MetS), and diet quality in adults 19 years and older (n = 15,023) participating in the 1999-2004 National Health and Nutrition Examination Survey. Twenty-four-hour dietary recalls were used to determine intake. Covariate-adjusted means ± SE and prevalence rates were determined for candy consumption groups. Odds ratios were used to determine the likelihood of cardiovascular risk factors and MetS. A total of 21.8%, 12.9%, and 10.9% of adults consumed total, chocolate, and sugar candy, respectively. Mean daily per capita intake of total, chocolate, and sugar candy was 9.0 ± 0.3, 5.7 ± 0.2, and 3.3 ± 0.2 g, respectively; intake in consumers was 38.3 ± 1.0, 39.9 ± 1.1, and 28.9 ± 1.3 g, respectively. Energy (9973 ± 92 vs 9027 ± 50 kJ; P < .0001), saturated fatty acid (27.9 ± 0.26 vs 26.9 ± 0.18 g; P = .0058), and added sugar (25.7 ± 0.42 vs 21.1 ± 0.41 g; P < .0001) intake were higher in candy consumers than nonconsumers. Body mass index (27.7 ± 0.15 vs 28.2 ± 0.12 kg/m(2); P = .0092), waist circumference (92.3 ± 0.34 vs 96.5 ± 0.29 cm; P = .0051), and C-reactive protein (0.40 ± 0.01 vs 0.43 ± 0.01 mg/dL; P = .0487) levels were lower in candy consumers than nonconsumers. Candy consumers had a 14% decreased risk of elevated diastolic blood pressure (P = .0466); chocolate consumers had a 19% decreased risk of lower high-density lipoprotein cholesterol (P = .0364) and a 15% reduced risk of MetS (P = .0453). Results suggest that the current level of candy consumption was not associated with health risks. Copyright © 2011 Elsevier Inc. All rights reserved.
MED-1151
Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom
Background: Organically produced foods are less likely than conventionally produced foods to contain pesticide residues. Methods: We examined the hypothesis that eating organic food may reduce the risk of soft tissue sarcoma, breast cancer, non-Hodgkin lymphoma and other common cancers in a large prospective study of 623 080 middle-aged UK women. Women reported their consumption of organic food and were followed for cancer incidence over the next 9.3 years. Cox regression models were used to estimate adjusted relative risks for cancer incidence by the reported frequency of consumption of organic foods. Results: At baseline, 30%, 63% and 7% of women reported never, sometimes, or usually/always eating organic food, respectively. Consumption of organic food was not associated with a reduction in the incidence of all cancer (n=53 769 cases in total) (RR for usually/always vs never=1.03, 95% confidence interval (CI): 0.99–1.07), soft tissue sarcoma (RR=1.37, 95% CI: 0.82–2.27), or breast cancer (RR=1.09, 95% CI: 1.02–1.15), but was associated for non-Hodgkin lymphoma (RR=0.79, 95% CI: 0.65–0.96). Conclusions: In this large prospective study there was little or no decrease in the incidence of cancer associated with consumption of organic food, except possibly for non-Hodgkin lymphoma.
MED-4167
Influence of water and food consumption on inadvertent antibiotics intake among general population.
Antibiotic entry into the water environment has been of growing concern. However, few investigations have been performed to examine the potential for indirect human exposure to environmental antibiotic residues. We evaluated the contribution of drinking water and major food consumption to inadvertent intake of antibiotic residues among general human population in Korea. We estimated daily human intake of six antibiotics, i.e., sulfamethazine (SMZ), sulfamethoxazole (SMX), sulfathiazole (STZ), trimethoprim (TMP), enrofloxacin (EFX), and roxithromycin (RTM), by measuring the concentrations of the antibiotics and their major metabolites in urine from general population in Korea (n=541). In addition, we measured antibiotics from source water of drinking water as well as in tap water samples, and surveyed water consumption rates among the study population. To assess the contribution of dietary factor, we also surveyed consumption pattern for several major foods which are suspected of antibiotics residue. SMZ, Sulfamethazine-N4-acetyl (SMZ-N4), TMP, EFX, ciprofloxacin (CFX), and RTM were detected up to 448, 6210, 11,900, 6970, 32,400, and 151pg/ml in the urine samples, respectively. Estimates of daily intake of major antibiotics did not appear to be related with consumption of drinking water although antibiotics were frequently detected in source waters (10-67ng/l). Consumption of several foods correlated significantly with urinary excretion of several antibiotics. Daily intake estimates of EFX and CFX were associated with consumption of beef, pork, and dairy products; those of SMZ and TMP associated with pork and dairy products; and that of TMP related with raw fish. Daily antibiotics intake estimates however did not exceed the acceptable daily intake levels. Copyright 2010 Elsevier Inc. All rights reserved.
MED-3173
Natural mood foods: The actions of polyphenols against psychiatric and cognitive disorders
Objectives Polyphenols, natural compounds found in plant-based foods, possess special properties that can battle oxidative stress and stimulate the activation of molecules that aid in synaptic plasticity, a process that underlies cognitive function. Unlike many traditional treatments, polyphenols affect a broad range of mechanisms in the brain that can assist in the maintenance of cognitive and mental health, as well as the recovery from neurodegenerative diseases. Examining the molecular basis underlying the link between food intake and brain function has presented the exciting possibility of using diet as a viable method to battle cognitive and psychiatric disorders. Methods We will discuss the molecular systems that link polyphenols, the gut, and the brain, as well as introduce published human and animal studies demonstrating the effects of polyphenol consumption on brain plasticity and cognition. Results By influencing cellular energy metabolism and modulating the signaling pathways of molecules involved with brain plasticity, dietary factors – formerly recognized for just their effects on bodily systems – have emerged as affecters of the brain. Conclusion Thus, the consumption of diets enriched with polyphenols may present the potential of dietary manipulation as a non-invasive, natural, and inexpensive therapeutic means to support a healthy brain.
MED-2407
Public health concern behind the exposure to persistent organic pollutants and the risk of metabolic diseases
Background Persistent organic pollutants (POPs) are hazardous chemicals omnipresent in our food chain, which have been internationally regulated to ensure public health. Initially described for their potency to affect reproduction and promote cancer, recent studies have highlighted an unexpected implication of POPs in the development of metabolic diseases like type 2 diabetes and obesity. Based on this novel knowledge, this article aims at stimulating discussion and evaluating the effectiveness of current POP legislation to protect humans against the risk of metabolic diseases. Furthermore, the regulation of POPs in animal food products in the European Union (EU) is addressed, with a special focus on marine food since it may represent a major source of POP exposure to humans. Discussion There is mounting scientific evidence showing that current POP risk assessment and regulation cannot effectively protect humans against metabolic disorders. Better regulatory control of POPs in dietary products should be of high public health priority. Summary The general population is exposed to sufficient POPs, both in term of concentration and diversity, to induce metabolic disorders. This situation should attract the greatest attention from the public health and governmental authorities.
MED-3718
American Cancer Society Guidelines on Nutrition and Physical Activity for cancer prevention: reducing the risk of cancer with healthy food choices ...
The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the Department of Health and Human Services' 2005 Dietary Guidelines for Americans.
MED-2044
Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly?
Cancer incidence increases with advancing age. Over 60% of new cancers and 70% of cancer deaths occur in individuals aged 65 years or older. One factor that may contribute to this is immunosenescence - a canopy term that is used to describe age-related declines in the normal functioning of the immune system. There are multiple age-related deficits in both the innate and adaptive systems that may play a role in the increased incidence of cancer. These include decreased NK-cell function, impaired antigen uptake and presentation by monocytes and dendritic cells, an increase in 'inflammaging', a decline in the number of naïve T-cells able to respond to evolving tumor cells, and an increase in functionally exhausted senescent cells. There is consensus that habitual physical exercise can offer protection against certain types of cancer; however the evidence linking immunological mechanisms, exercise, and reduced cancer risk remain tentative. Multiple studies published over the last two decades suggest that exercise can mitigate the deleterious effects of age on immune function, thus increasing anti-cancer immunity. The potential ameliorative effect of exercise on these mechanisms include evidence that physical activity is able to stimulate greater NK-cell activity, enhance antigen-presentation, reduce inflammation, and prevent senescent cell accumulation in the elderly. Here we discuss the role played by the immune system in preventing and controlling cancer and how aging may retard these anti-cancer mechanisms. We also propose a pathway by which exercise-induced alterations in immunosenescence may decrease the incidence of cancer and help improve prognosis in cancer patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
MED-4790
The risks of copper toxicity contributing to cognitive decline in the aging population and to Alzheimer's disease.
It is a pleasure and an honor to contribute a paper to a special issue of the Journal of the American College of Nutrition honoring Stanley Wallach and Pearl Small. In this brief review I advance the hypothesis that copper toxicity is the major cause of the epidemic of mild cognitive impairment and Alzheimer's disease engulfing our aging population. This epidemic is recent, exploding in the last 50-60 years. The disease was virtually unknown 100 years ago. And it involves only developed countries that use copper plumbing. Something in our environment associated with development is poisoning the minds of our aged. The epidemic is associated with the use of copper plumbing, and the taking of copper in multi-mineral supplements. Food copper (organic copper) is processed by the liver and is transported and sequestered in a safe manner. Inorganic copper, such as that in drinking water and copper supplements, largely bypasses the liver and enters the free copper pool of the blood directly. This copper is potentially toxic because it may penetrate the blood/brain barrier. I review a web of animal and human data that tightens the noose around the hypothesis that copper toxicity is causing the epidemic of Alzeimer's disease and loss of cognition in our aging population.
MED-4318
Low-pH cola beverages do not affect women's iron absorption from a vegetarian meal.
Preliminary data in the literature indicate that iron absorption from a meal may be increased when consumed with low-pH beverages such as cola, and it is also possible that sugar iron complexes may alter iron availability. A randomized, crossover trial was conducted to compare the bioavailability of nonheme iron from a vegetarian pizza meal when consumed with 3 different beverages (cola, diet cola, and mineral water). Sixteen women with serum ferritin concentrations of 11-54 µg/L were recruited and completed the study. The pizza meal contained native iron and added ferric chloride solution as a stable isotope extrinsic label; the total iron content of the meal was ~5.3 mg. Incorporation of iron from the meal into RBC was not affected by the type of drink (9.9% with cola, 9.4% with diet cola, and 9.6% with water). Serum ferritin and plasma hepcidin were correlated (r = 0.66; P<0.001) and both were significant predictors of iron bioavailability, but their combined effect explained only 30% of the inter-individual variation (P<0.001) and illustrates the current lack of understanding of mechanisms responsible for the fine-tuning of iron absorption. Although there was no effect of low-pH drinks on iron bioavailability in healthy women, their effect on absorption of fortification iron that requires solubilization in dilute acid, such as reduced iron, and in individuals with low gastric acid production, such as older people and individuals with Helicobacter pylori infection, warrants further investigation.
MED-3604
US medical researchers, the Nuremberg Doctors Trial, and the Nuremberg Code. A review of findings of the Advisory Committee on Human Radiation Expe...
The Advisory Committee on Human Radiation Experiments (ACHRE), established to review allegations of abuses of human subjects in federally sponsored radiation research, was charged with identifying appropriate standards to evaluate the ethics of cold war radiation experiments. One central question for ACHRE was to determine what role, if any, the Nuremberg Code played in the norms and practices of US medical researchers. Based on the evidence from ACHRE's Ethics Oral History Project and extensive archival research, we conclude that the Code, at the time it was promulgated, had little effect on mainstream medical researchers engaged in human subjects research. Although some clinical investigators raised questions about the conduct of research involving human beings, the medical profession did not pursue this issue until the 1960s.
MED-1298
Increased interleukin-10 but unchanged insulin sensitivity after 4 weeks of (1, 3)(1, 6)-beta-glycan consumption in overweight humans.
Obesity-induced insulin resistance has been suggested to be a systemic inflammatory condition with activation of the innate immune system. Animal studies indicate that certain dietary fibers such as (1,3)(1,6)-beta-D-glycans (BDG) have potent effects on immune activity such as increasing the antiinflammatory cytokine interleukin-10 (IL-10) and reducing the secretion of inflammatory factors. Therefore, we hypothesized that BDG consumption improves inflammatory markers and insulin sensitivity in overweight and obese subjects with moderately increased levels of C-reactive protein, indicating subclinical inflammation. We screened 180 overweight and obese subjects for moderately increased C-reactive protein levels on 2 or more occasions, in the absence of any signs of acute infection. Twelve of the subjects met all inclusion criteria and were investigated in a randomized, double-blind, placebo-controlled, crossover design for 2 x 4 weeks (washout > or =4 weeks). Subjects ingested capsules containing 3 x 0.5 g of highly purified BDG or 3 x 0.5 g of placebo (waxy maize starch) daily. Maintenance of the normal diet of the participants and the correct intake of the capsules were monitored, using 6 x 3-day food recording and counting of the provided capsules. Predefined outcome measures were BDG-induced changes in pro and antiinflammatory markers in circulating blood and gene expression in adipose tissue and peripheral insulin sensitivity expressed as M value. The BDG consumption for 4 weeks significantly increased both circulating levels and adipose tissue messenger RNA (mRNA) expression of the antiinflammatory cytokine IL-10 in overweight and obese humans. Insulin sensitivity as well as circulating levels and mRNA expression of proinflammatory cytokines were unaffected by BDG treatment. Increased IL-10 after BDG consumption might be a contributing factor to the known beneficial effects of dietary fiber intake.
MED-1619
No evidence of insulin resistance in normal weight vegetarians. A case control study.
BACKGROUND: Diets rich in carbohydrates with a low glycemic index and with high fiber content are associated with flat post-prandial rises of blood glucose, minimal post-prandial insulin secretion and maintenance of insulin sensitivity. Protective food commodities in the prevention of cardiovascular disease, insulin resistance syndrome or diabetes are crucial components of the vegetarian diet. AIM OF THE STUDY: Insulin resistance values were assessed in relation to different nutrition. Metabolic abnormality is a predictor of age-related diseases and can be more pronounced in obese subjects. Insulin resistance values in normal weight subjects of two different nutritional habits were correlated with age. METHODS: Fasting concentrations of glucose and insulin as well as calculated values of insulin resistance IR (HOMA) were assessed in two nutritional groups of apparently healthy adult subjects (age range 19 - 64 years) with normal weight (body mass index 18.6 - 25.0 kg/m(2)): a vegetarian group (95 long-term lacto-ovo-vegetarians; duration of vegetarianism 10.2 +/- 0.5 years) and a non-vegetarian control group (107 subjects of general population on traditional western diet). Intake of energy and main nutrients (fats, saccharides, proteins) was similar in both groups. RESULTS: Glucose and insulin concentrations and IR (HOMA) values were significantly lower in vegetarians (glucose 4.47 +/- 0.05 vs. 4.71 +/- 0.07 mmol/l; insulin 4.96 +/- 0.23 vs. 7.32 +/- 0.41 mU/l; IR (HOMA) 0.99 +/- 0.05 vs. 1.59 +/- 0.10). IR (HOMA) dependence on age was only significant in subjects on a western diet. A significant increase of IR was found already in the age range 31-40 years, compared to vegetarians and it continued in later age decades. Age independent and low insulin resistance values in vegetarians are a consequence of an effective diet prevention by long-term frequent consumption of protective food. Vegetarians had a significantly higher consumption of whole grain products, pulses, products from oat and barley. CONCLUSION: The results of age independent and low values of insulin resistance document a beneficial effect of long-term vegetarian nutrition in prevention of metabolic syndrome, diabetes and cardiovascular disease.
MED-1246
Aromatherapy with peppermint, isopropyl alcohol, or placebo is equally effective in relieving postoperative nausea.
To determine whether aromatherapy can reduce postoperative nausea, the investigators studied 33 ambulatory surgery patients who complained of nausea in the PACU. After indicating the severity of nausea on a 100-mm visual analogue scale (VAS), subjects received randomized aromatherapy with isopropyl alcohol, oil of peppermint, or saline (placebo). The vapors were inhaled deeply through the nose from scented gauze pads held directly beneath the patients' nostrils and exhaled slowly through the mouth. Two and 5 minutes later, the subjects rated their nausea on the VAS. Overall nausea scores decreased from 60.6 +/- 4.3 mm (mean +/- SE) before aromatherapy to 43.1 +/- 4.9 mm 2 minutes after aromatherapy (P <.005), and to 28.0 +/- 4.6 mm 5 minutes after aromatherapy (P < 10(-6)). Nausea scores did not differ between the treatments at any time. Only 52% of the patients required conventional intravenous (IV) antiemetic therapy during their PACU stay. Overall satisfaction with postoperative nausea management was 86.9 +/- 4.1 mm and was independent of the treatment group. Aromatherapy effectively reduced the perceived severity of postoperative nausea. The fact that a saline "placebo" was as effective as alcohol or peppermint suggests that the beneficial effect may be related more to controlled breathing patterns than to the actual aroma inhaled.
MED-2303
Balancing life-style and genomics research for disease prevention.
Genetic and environmental factors, including diet and life-style, both contribute to cardiovascular disease, cancers, and other major causes of mortality, but various lines of evidence indicate that environmental factors are most important. Overly enthusiastic expectations regarding the benefits of genetic research for disease prevention have the potential to distort research priorities and spending for health. However, integration of new genetic information into epidemiologic studies can help clarify causal relations between both life-style and genetic factors and risks of disease. Thus, a balanced approach should provide the best data to make informed choices about the most effective means to prevent disease.
MED-3788
Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis
Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.
MED-943
Embryotoxic effects of pine needles and pine needle extracts.
A heat stable toxin present in needles of ponderosa pine was found to be soluble in methanol, ethanol, chloroform hexanes and 1-butanol. The embryotoxic effects of fresh green pine needles and a chloroform/methanol extract were determined by measuring embryo resorption in pregnant mice. Autoclaving the needles and extract for 1 hour prior to feeding enhanced the embryoresorptive effect by 28% and 32%, respectively. The results of this study revealed that the embryo resorptive dose (ERD50) of heat stable toxin for 1 mouse was 8.95 gms. for fresh green pine needles and 6.46 gms. for autoclaved green pine needles. In addition to embryocidal effects, feeding of the toxin resulted in significant weight loss in adult mice.
MED-5162
Antimutagenic effect of broccoli flower head by the ames salmonella reverse mutation assay.
A study was performed to investigate the antimutagenic effect of broccoli flower head by the Ames Salmonella reverse mutation assay. Broccoli flower head being the most highly edible part in the plant was analysed for its antimutagenic effect. Without isolating the phytomolecules, the crude ethanol extract of broccoli flower head was tested for suppressing the mutagenic effect induced by certain chemical mutagens. Three strains - TA 98, TA102 and TA 1535 were used in the study. The tester strains were challenged with their respective mutagens. These were challenged with the ethanol extract of broccoli flower head at concentrations of 23 and 46 mg/plate. The plates were incubated for 72 h and the revertant colonies were counted. The crude extract did not prove to be promutagenic. The ethanol extract of the broccoli flower head at 46 mg/plate suppressed the mutagenic effect induced by the corresponding positive mutagens on all the three tester strains used in this study. The crude extract of broccoli flower head alone was not cytotoxic even at the maximum concentration tested (46 mg/plate). In conclusion, the ethanol extract of broccoli at 46 mg/plate suggests their diverse antimutagenic potential against the mutagenic chemicals employed in this study. (c) 2007 John Wiley & Sons, Ltd.
MED-5039
Cocoa and cardiovascular health.
Epidemiological data demonstrate that regular dietary intake of plant-derived foods and beverages reduces the risk of coronary heart disease and stroke. Among many ingredients, cocoa might be an important mediator. Indeed, recent research demonstrates a beneficial effect of cocoa on blood pressure, insulin resistance, and vascular and platelet function. Although still debated, a range of potential mechanisms through which cocoa might exert its benefits on cardiovascular health have been proposed, including activation of nitric oxide and antioxidant and antiinflammatory effects. This review summarizes the available data on the cardiovascular effects of cocoa, outlines potential mechanisms involved in the response to cocoa, and highlights the potential clinical implications associated with its consumption.
MED-4942
Association of polychlorinated biphenyls with hypertension in the 1999-2002 National Health and Nutrition Examination Survey.
The association of 11 polychlorinated biphenyls (PCBs) with hypertension was investigated using the National Health and Nutrition Examination Survey (NHANES), 1999-2002. The unweighted number of participants assessed for hypertension ranged from 2074 to 2556 depending on the chemical(s) being analyzed. In unadjusted logistic regressions all 11 PCBs were associated with hypertension. After adjustment for age, gender, race, smoking status, body mass index, exercise, total cholesterol, and family history of coronary heart disease, seven of the 11 PCBs (PCBs 126, 74, 118, 99, 138/158, 170, and 187) were significantly associated with hypertension. The strongest adjusted associations with hypertension were found for dioxin-like PCBs 126 and 118. PCB 126>59.1 pg/g lipid adjusted had an odds ratio of 2.45 (95% CI 1.48-4.04) compared to PCB 126<or=26.1 pg/g lipid adjusted. PCB 118>27.5 ng/g lipid adjusted had an odds ratio of 2.30 (95% CI 1.29-4.08) compared to PCB 118<or=12.5 ng/g lipid adjusted. Moreover, participants with one or more elevated PCBs had an odds ratio of 1.84 (95% CI 1.25-2.70) compared to no PCBs elevated in an adjusted logistic regression. The prevalence of one or more elevated PCBs was 22.76% or 32 million of 142 million persons >or=20 years old in the non-institutionalized US population. We hypothesize that association of seven PCBs with hypertension indicates elevated PCBs are a risk factor for hypertension. What clinicians can do, given the results of this study, is limited unless the appropriate laboratory methods can be made more widely available for testing patients.
MED-4494
Associations of processed meat and unprocessed red meat intake with incident diabetes: the Strong Heart Family Study
Background: Fifty percent of American Indians (AIs) develop diabetes by age 55 y. Whether processed meat is associated with the risk of diabetes in AIs, a rural population with a high intake of processed meat (eg, canned meats in general, referred to as “spam”) and a high rate of diabetes, is unknown. Objective: We examined the associations of usual intake of processed meat with incident diabetes in AIs. Design: This prospective cohort study included AI participants from the Strong Heart Family Study who were free of diabetes and cardiovascular disease at baseline and who participated in a 5-y follow-up examination (n = 2001). Dietary intake was ascertained by using a Block food-frequency questionnaire at baseline. Incident diabetes was defined on the basis of 2003 American Diabetes Association criteria. Generalized estimating equations were used to examine the associations of dietary intake with incident diabetes. Results: We identified 243 incident cases of diabetes. In a comparison of upper and lower quartiles, intake of processed meat was associated with a higher risk of incident diabetes (OR: 1.63; 95% CI: 1.21, 2.63), after adjustment for potential confounders. The relation was particularly strong for spam (OR for the comparison of upper and lower quartiles: 2.06; 95% CI: 1.30, 3.27). Intake of unprocessed red meat was not associated with incident diabetes (OR for the comparison of upper and lower quartiles: 0.90; 95% CI: 0.59, 1.37). Conclusion: The consumption of processed meat, such as spam, but not unprocessed red meat, was associated with higher risk of diabetes in AIs, a rural population at high risk of diabetes and with limited access to healthy foods.
MED-2346
Anisakis simplex: from Obscure Infectious Worm to Inducer of Immune Hypersensitivity
Summary: Infection of humans with the nematode worm parasite Anisakis simplex was first described in the 1960s in association with the consumption of raw or undercooked fish. During the 1990s it was realized that even the ingestion of dead worms in food fish can cause severe hypersensitivity reactions, that these may be more prevalent than infection itself, and that this outcome could be associated with food preparations previously considered safe. Not only may allergic symptoms arise from infection by the parasites (“gastroallergic anisakiasis”), but true anaphylactic reactions can also occur following exposure to allergens from dead worms by food-borne, airborne, or skin contact routes. This review discusses A. simplex pathogenesis in humans, covering immune hypersensitivity reactions both in the context of a living infection and in terms of exposure to its allergens by other routes. Over the last 20 years, several studies have concentrated on A. simplex antigen characterization and innate as well as adaptive immune response to this parasite. Molecular characterization of Anisakis allergens and isolation of their encoding cDNAs is now an active field of research that should provide improved diagnostic tools in addition to tools with which to enhance our understanding of pathogenesis and controversial aspects of A. simplex allergy. We also discuss the potential relevance of parasite products such as allergens, proteinases, and proteinase inhibitors and the activation of basophils, eosinophils, and mast cells in the induction of A. simplex-related immune hypersensitivity states induced by exposure to the parasite, dead or alive.
MED-1360
Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder
Objective To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to standard antidepressant medication (sertraline) and greater reductions in depression compared to placebo controls. Methods Between October 2000 and November 2005, we performed a prospective, randomized controlled trial (SMILE study) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital. A total of 202 adults (153 women; 49 men) diagnosed with major depression were assigned randomly to one of four conditions: supervised exercise in a group setting; home-based exercise; antidepressant medication (sertraline, 50–200 mg daily); or placebo pill for 16 weeks. Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale (HAM-D). Results After 4 months of treatment, 41% of the participants achieved remission, defined as no longer meeting the criteria for major depressive disorder (MDD) and a HAM-D score of <8. Patients receiving active treatments tended to have higher remission rates than the placebo controls: supervised exercise = 45%; home-based exercise = 40%; medication = 47%; placebo = 31% (p = .057). All treatment groups had lower HAM-D scores after treatment; scores for the active treatment groups were not significantly different from the placebo group (p = .23). Conclusions The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD. Placebo response rates were high, suggesting that a considerable portion of the therapeutic response is determined by patient expectations, ongoing symptom monitoring, attention, and other nonspecific factors.
MED-1409
Changing prevalence of coronary heart disease risk factors and cardiovascular diseases in men of a rural area of Crete from 1960 to 1991.
This study compares the prevalence of coronary heart disease (CHD), risk factors (RF), and cardiovascular diseases (CVD) among Cretan men from a rural area examined in 1960 and 1991. The study population consisted of 148 men in 1960 and 42 men in 1991 of the same age group (fifty-five to fifty-nine years old) and from the same rural area. All men had a complete examination of the cardiovascular system and a resting electrocardiogram (ECG). Systolic BP (SBP) > or = 140 mmHg was found in 42.6% of the subjects in 1960 and in 45.2% in 1991 (NS). Diastolic BP > or = 95 mmHG was found in 14.9% of the subjects in 1960 as opposed to 33.3% in 1991 (P < 0.02). Total serum cholesterol (TSCH) > or = 260 mg/dL approximately 6.7 mmol/L) was found in 12.8% of the subjects in 1960 and in 28.6% in 1991 (P < 0.01). Heavy smokers ( > or = 20 cigarettes/daily) were 27.0% in 1960 as compared with 35.7% in 1991 (:NS); 5.4% of the subjects in 1960 had light physical activity (PA) as compared with 14.3% in 1991 (P < 0.01); 74.7% of the subjects were farmers in 1960 as compared with 43.6% in 1991 (P < 0.1). The prevalence of CHD was 0.7% in 1960 as compared with 9.5% in 1991 (P < 0.001). Hypertensive heart disease was found in 3.4% of the subjects in 1960 and 4.8% in 1991 (NS). The prevalence of all major CVD was much higher in 1991 (19.1%) as compared with 1960 (8.8%) (P < 0.01). In conclusion, the prevalence of CHD RF and CVD was much higher in 1991 than in 1960 for Cretan men of the same age group. This higher prevalence seems to be related to dietary and life-style changes that have taken place in Crete during the last thirty years.
MED-3708
Is the asthma epidemic still ascending?
Asthma is a phenotypically heterogeneous disorder of multifactorial origins that affects 300 million people suffering from asthma and more than 250,000 asthma-related deaths each year. Although treatment for asthma has improved, its prevalence continues to increase, particularly in low and middle income countries, or in some ethnic groups in which prevalence was previously low. Observed spatio-temporal variations in the increased prevalence of asthma depend on exposure to environmental factors. Recently, several arguments are also in favor of the involvement of host susceptibility and stress in the observed increase of asthma prevalence. Further investigations are warranted to better understand mechanisms underlying asthma increase or stagnation. Copyright © 2012 Elsevier Inc. All rights reserved.
MED-5089
Dietary acrylamide intake and the risk of renal cell, bladder, and prostate cancer.
BACKGROUND: Acrylamide, a probable human carcinogen, was recently detected in various heat-treated carbohydrate-rich foods. Epidemiologic studies on the relation with cancer have been few and largely negative. OBJECTIVE: We aimed to prospectively examine the association between dietary acrylamide intake and renal cell, bladder, and prostate cancers. DESIGN: The Netherlands Cohort Study on diet and cancer includes 120,852 men and women aged 55-69 y. At baseline (1986), a random subcohort of 5000 participants was selected for a case-cohort analysis approach using Cox proportional hazards analysis. Acrylamide intake was assessed with a food-frequency questionnaire at baseline and was based on chemical analysis of all relevant Dutch foods. RESULTS: After 13.3 y of follow-up, 339, 1210, and 2246 cases of renal cell, bladder, and prostate cancer, respectively, were available for analysis. Compared with the lowest quintile of acrylamide intake (mean intake: 9.5 microg/d), multivariable-adjusted hazard rates for renal cell, bladder, and prostate cancer in the highest quintile (mean intake: 40.8 microg/d) were 1.59 (95% CI: 1.09, 2.30; P for trend = 0.04), 0.91 (95% CI: 0.73, 1.15; P for trend = 0.60), and 1.06 (95% CI: 0.87, 1.30; P for trend = 0.69), respectively. There was an inverse nonsignificant trend for advanced prostate cancer in never smokers. CONCLUSIONS: We found some indications for a positive association between dietary acrylamide and renal cell cancer risk. There were no positive associations with bladder and prostate cancer risk.
MED-4851
Rheumatoid arthritis treated with vegetarian diets.
The notion that dietary factors may influence rheumatoid arthritis (RA) has been a part of the folklore of the disease, but scientific support for this has been sparse. In a controlled, single-blind trial we tested the effect of fasting for 7-10 d, then consuming an individually adjusted, gluten-free, vegan diet for 3.5 mo, and then consuming an individually adjusted lactovegetarian diet for 9 mo on patients with RA. For all clinical variables and most laboratory variables measured, the 27 patients in the fasting and vegetarian diet groups improved significantly compared with the 26 patients in the control group who followed their usual omnivorous diet throughout the study period. One year after the patients completed the trial, they were reexamined. Compared with baseline, the improvements measured were significantly greater in the vegetarians who previously benefited from the diet (diet responders) than in diet nonresponders and omnivores. The beneficial effect could not be explained by patients' psychologic characteristics, antibody activity against food antigens, or changes in concentrations of prostaglandin and leukotriene precursors. However, the fecal flora differed significantly between samples collected at time points at which there was substantial clinical improvement and time points at which there were no or only minor improvements. In summary, the results show that some patients with RA can benefit from a fasting period followed by a vegetarian diet. Thus, dietary treatment may be a valuable adjunct to the ordinary therapeutic armamentarium for RA.
MED-1819
Potentiation of gemcitabine by Turmeric Force in pancreatic cancer cell lines.
Gemcitabine is a first line cancer drug widely used for the treatment of pancreatic cancer. However, its therapeutic efficiency is significantly limited by resistance of pancreatic cancer cells to this and other chemotherapeutic drugs. We have investigated the cytotoxic effect of Turmeric Force (TF), a supercritical and hydroethanolic extract of turmeric, alone and in combination with gemcitabine in two pancreatic carcinoma cell lines (BxPC3 and Panc-1). TF is highly cytotoxic to BxPC3 and Panc-1 cell lines with IC50 values of 1.0 and 1.22 microg/ml, respectively with superior cytotoxicity than curcumin. Gemcitabine IC50 value for both of these cell line is 0.03 microg/ml; however, 30-48% of the pancreatic cancer cells are resistant to gemcitabine even at concentrations >100 microg/ml. In comparison, TF induced cell death in 96% of the cells at 50 microg/ml. The combination of gemcitabine and TF was synergistic with IC90 levels achieved in both pancreatic cancer cell lines at lower concentrations. CalcuSyn analysis of cytotoxicity data showed that the Gemcitabine + Turmeric Force combination has strong synergism with combination index (CI) values of 0.050 and 0.183 in BxPC3 and Panc-1 lines, respectively at IC50 level. This synergistic effect is due to the increased inhibitory effect of the combination on nuclear factor-kappaB activity and signal transducer and activator of transcription factor 3 expression as compared to the single agent.
MED-3526
Jerte Valley cherry-enriched diets improve nocturnal rest and increase 6-sulfatoxymelatonin and total antioxidant capacity in the urine of middle-a...
Tryptophan, serotonin, and melatonin, present in Jerte Valley cherries, participate in sleep regulation and exhibit antioxidant properties. The effect of the intake of seven different Jerte Valley cherry cultivars on the sleep-wake cycle, 6-sulfatoxymelatonin levels, and urinary total antioxidant capacity in middle-aged and elderly participants was evaluated. Volunteers were subjected to actigraphic monitoring to record and display the temporal patterns of their nocturnal activity and rest. 6-sulfatoxymelatonin and total antioxidant capacity were quantified by enzyme-linked immunosorbent assay and colorimetric assay kits, respectively. The intake of each of the cherry cultivars produced beneficial effects on actual sleep time, total nocturnal activity, assumed sleep, and immobility. Also, there were significant increases in 6-sulfatoxymelatonin levels and total antioxidant capacity in urine after the intake of each cultivar. These findings suggested that the intake of Jerte Valley cherries exerted positive effect on sleep and may be seen as a potential nutraceutical tool to counteract oxidation.
MED-4517
Fecal weight, colon cancer risk, and dietary intake of nonstarch polysaccharides (dietary fiber)
Low fecal weight and slow bowel transit time are thought to be associated with bowel cancer risk, but few published data defining bowel habits in different communities exist. Therefore, data on stool weight were collected from 20 populations in 12 countries to define this risk more accurately, and the relationship between stool weight and dietary intake of nonstarch polysaccharides (NSP) (dietary fiber) was quantified. In 220 healthy U.K. adults undertaking careful fecal collections, median daily stool weight was 106 g/day (men, 104 g/day; women, 99 g/day; P = 0.02) and whole-gut transit time was 60 hours (men, 55 hours; women, 72 hours; P = 0.05); 17% of women, but only 1% of men, passed < 50 g stool/day. Data from other populations of the world show average stool weight to vary from 72 to 470 g/day and to be inversely related to colon cancer risk (r = -0.78). Meta-analysis of 11 studies in which daily fecal weight was measured accurately in 26 groups of people (n = 206) on controlled diets of known NSP content shows a significant correlation between fiber intake and mean daily stool weight (r = 0.84). Stool weight in many Westernized populations is low (80-120 g/day), and this is associated with increased colon cancer risk. Fecal output is increased by dietary NSP. Diets characterized by high NSP intake (approximately 18 g/day) are associated with stool weights of 150 g/day and should reduce the risk of bowel cancer.
MED-3868
Dietary milled flaxseed and flaxseed oil improve N-3 fatty acid status and do not affect glycemic control in individuals with well-controlled type ...
OBJECTIVE: To determine the effects of dietary consumption of milled flaxseed or flaxseed oil on glycemic control, n-3 fatty acid status, anthropometrics, and adipokines in individuals with type 2 diabetes. DESIGN: Thirty-four participants were randomized into a parallel, controlled trial. SUBJECTS: The participants were adults with type 2 diabetes (age 52.4 +/- 1.5 years, body mass index 32.4 +/- 1.0 kg/m(2), n = 17 men and 17 women). INTERVENTIONS: Participants consumed a selection of bakery products containing no flax (control group [CTL], n = 9), milled flaxseed (FXS, n = 13; 32 g/d), or flaxseed oil (FXO, n = 12; 13 g/d) daily for 12 weeks. The FXS and FXO groups received equivalent amounts of alpha-linolenic acid (ALA; 7.4 g/day). MEASURES OF OUTCOME: The primary outcome measures were fasting plasma hemoglobin A(1c), glucose, insulin, and phospholipid fatty acid composition. The secondary outcome measures were fasting circulating leptin and adiponectin, as well as body weight, body mass index, and waist circumference. Dietary intake assessment and calculations for homeostasis model assessment for insulin resistance and quantified insulin sensitivity check were also completed. RESULTS: The FXS and FXO groups had increases in plasma phospholipid n-3 fatty acids (ALA, eicosapentaenoic acid [EPA], or decosapentaenoic acid [DPA], but not docosahexaenoic acid), and the FXO group had more EPA and DPA in plasma phospholipids compared to the FXS group. All groups had similar caloric intakes; however, the CTL group experienced a 4% weight gain compared to baseline (p < 0.05), while both flax groups had constant body weights during the study period. All other parameters, including glycemic control, were unchanged by dietary treatment. CONCLUSIONS: Milled FXS and FXO intake does not affect glycemic control in adults with well-controlled type 2 diabetes. Possible prevention of weight gain by flax consumption warrants further investigation.
MED-973
What is a high fiber diet?
There is no recognized definition of what constitutes a high fiber diet. Intakes of dietary fiber in different populations internationally vary widely from less than 20 g to more than 80 g per day. The types of foods contributing fiber also vary; in some countries cereals contribute the most fiber, in others leafy or root vegetables predominate. Vegetables have the highest fiber content per Kcal, and in most populations with fiber intakes over 50 g, vegetables contribute over 50% of total fiber intake. In rural Uganda, where the fiber hypothesis was first developed by Burkitt and Trowell, vegetables contribute over 90% of fiber intake. An experimental diet, the "Simian" diet, has been developed to mimic as closely as possible using human foods, the diet consumed by our simian ancestors the great apes. It is also similar to the Ugandan diet in containing large amounts of vegetables and 50 g fiber/1000 Kcal. Though nutritionally adequate, this diet is very bulky and not a suitable model for general recommendations. Dietary guidelines are that fat intake should be < 30% of energy, with a fiber intake of 20-35 g/d. These recommendations are inconsistent with a high fiber diet because, for people consuming more than about 2400 Kcal, low fiber choices for fruits and grains must be selected to keep dietary fiber intake within the range of 20-35 g. In a 30% fat, 1800 Kcal omnivorous diet, selection of wholemeal bread and whole fruit, results in a fiber intake over 35 g/d, and for and 1800 Kcal vegetarian diet, with substitution of modest amounts of peanut butter and beans for meats, dietary fiber intake goes up to 45 g/d. Thus, if it is desirable to promote the use of unrefined foods, the recommended dietary fiber intake should be a minimum of 15-20 g/1000 Kcal.
MED-4828
Association between statin-associated myopathy and skeletal muscle damage
Background Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. Methods We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury. Results Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10× the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3). Interpretation Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak.
MED-1188
Inflammatory bowel disease in rural sub-Saharan Africa: rarity of diagnosis in patients attending mission hospitals.
One hundred and eighteen missionaries working on 75 mission stations or hospitals in 24 sub-Saharan African countries provided information about their medical practice in the preceding year of 1981. Details were collected of the total number of patients seen and admitted during the year, and the number of cases of bloody diarrhoea, typhoid and inflammatory bowel disease. Over 1 million outpatients and about 190,000 inpatients were treated. These included 12,859 cases of bloody diarrhoea, of whom 1,914 had typhoid. Twenty-two cases of inflammatory bowel disease were also reported. Histological support was least available in West Africa and only 25% of hospitals had access to this facility. Nevertheless, the frequency with which inflammatory bowel disease in sub-Saharan Africa is difficult and limited by access to diagnostic facilities. It is likely to be some time before reliable estimates of the incidence and prevalence of Crohn's disease and ulcerative colitis in the rural African population can be made.
MED-1179
Organic foods: health and environmental advantages and disadvantages.
The US market for organic foods has grown from $3.5 billion in 1996 to $28.6 billion in 2010, according to the Organic Trade Association. Organic products are now sold in specialty stores and conventional supermarkets. Organic products contain numerous marketing claims and terms, only some of which are standardized and regulated. In terms of health advantages, organic diets have been convincingly demonstrated to expose consumers to fewer pesticides associated with human disease. Organic farming has been demonstrated to have less environmental impact than conventional approaches. However, current evidence does not support any meaningful nutritional benefits or deficits from eating organic compared with conventionally grown foods, and there are no well-powered human studies that directly demonstrate health benefits or disease protection as a result of consuming an organic diet. Studies also have not demonstrated any detrimental or disease-promoting effects from an organic diet. Although organic foods regularly command a significant price premium, well-designed farming studies demonstrate that costs can be competitive and yields comparable to those of conventional farming techniques. Pediatricians should incorporate this evidence when discussing the health and environmental impact of organic foods and organic farming while continuing to encourage all patients and their families to attain optimal nutrition and dietary variety consistent with the US Department of Agriculture's MyPlate recommendations. This clinical report reviews the health and environmental issues related to organic food production and consumption. It defines the term "organic," reviews organic food-labeling standards, describes organic and conventional farming practices, and explores the cost and environmental implications of organic production techniques. It examines the evidence available on nutritional quality and production contaminants in conventionally produced and organic foods. Finally, this report provides guidance for pediatricians to assist them in advising their patients regarding organic and conventionally produced food choices.
MED-2223
Evaluation of Antiradical Activity of Different Cocoa and Chocolate Products: Relation with Lipid and Protein Composition
Chocolate antioxidant properties are often claimed; however, they are frequently different from the parent natural sources due to the industry or artisan transformation. In particular, antioxidant property of chocolate and cocoa are not adequately taken into consideration by consumers who normally make use of this food just for its flavor and taste properties. In this study, we have investigated the antioxidant capacity and total phenolic content of cocoa nibs, cocoa masses, and corresponding chocolate bars with different percentages of cocoa from different origins. The antioxidant capacity of the different samples was measured by two different assays [1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) and ferric reducing antioxidant of potency (FRAP) tests]. The Folin–Ciocalteu reagent was used to assess the total phenolic content. The masses showed a higher antioxidant power than the nibs, and this has been attributed to the fact that in the nibs is still present the lipid part, which will form the cocoa butter. The influence of milk, whey, and soy proteins was also investigated. Our results showed that the extra dark cocoa bar, 100% cocoa chocolate, is the best in terms of total polyphenol content and in terms of antioxidant capacity according to the DPPH and FRAP tests. In addition, the bars of organic dark chocolate 80%, dark Tanzania 80%, and Trinidad 80% products are well performing in all respects. As highlighted by us, the antiradical properties of cocoa products are higher than many antioxidant supplements in tablets.