rapamycin
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-5237
mTOR: from growth signal integration to cancer, diabetes and ageing
Preface In all eukaryotes, the target of rapamycin (TOR) signaling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress, and, in metazoan, growth factors. Mammalian TOR complexes 1 and 2 (mTORC1 and mTORC2) exert their actions by regulating other important kinases, such as S6K and Akt. In the last few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed its critical involvement in the onset and progression of diabetes, cancer and ageing.
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-2518
Aging is not programmed
Aging is not and cannot be programmed. Instead, aging is a continuation of developmental growth, driven by genetic pathways such as mTOR. Ironically, this is often misunderstood as a sort of programmed aging. In contrast, aging is a purposeless quasi-program or, figuratively, a shadow of actual programs. “The brightest flame casts the darkest shadow.” -George Martin
MED-2520
TOR-driven aging: speeding car without brakes.
This article discusses that the traditional analogy of an aging organism with a rusting (albeit self-repairing) car is misleading. The true analogy is a speeding car that enters a low-speed zone and damages itself because it does not and cannot slow down. For such a car without brakes (and actually without a driver), aging from rusting never occurs. Using simple analogies (although turning gerontology upside down), this article discusses the origin of aging, how overactivation of the mTOR (Target of Rapamycin) pathway causes aging, why aging causes damage (organ damage) not damage causes aging, the link between aging and age-related diseases, slow aging versus aging tolerance and suppression of aging with rapamycin.
MED-2521
Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle.
A streptomycete was isolated from an Easter Island soil sample and found to inhibit Candida albicans, Microsporum gypseum and Trichophyton granulosum. The antibiotic-producing microorganism was characterized and identified as Streptomyces hygroscopicus. The antifungal principle was extracted with organic solvent from the mycelium, isolated in crystalline form and named rapamycin. Rapamycin is mainly active against Candida albicans; minimum inhibitory concentration against ten strains ranged from 0.02 to 0.2 mug/ml. Its apparent activity against Microsporum gypseum and Trichophyton granulosum is lower because of its instability in culture media on prolonged incubation required by these fungi. No activity was observed against gram-positive and gram-negative bacteria. Acute toxicity in mice is low.
MED-2127
Nutrient Signaling to mTOR and Cell Growth
The mammalian target of rapamycin (mTOR) is a conserved protein kinase involved in a multitude of cellular processes including cell growth. Increased mTOR activation is observed in multiple human cancers and inhibition of mTOR has proven efficacious in numerous clinical trials. mTOR comprises two complexes, termed mTORC1 and mTORC2. Both complexes respond to growth factors, whereas only mTORC1 is controlled by nutrients, such as glucose and amino acids. Since the discovery of mTOR, extensive studies have intricately detailed the molecular mechanisms by which mTORC1 is regulated. Somewhat paradoxically, amino acid induced mTORC1 activation—arguably the most essential stimulus leading to mTORC1 activation—is the least understood. Here we review the current knowledge of nutrient dependent regulation of mTORC1.
MED-2128
Sirolimus for Kaposi's sarcoma in renal-transplant recipients.
BACKGROUND: Recipients of organ transplants are susceptible to Kaposi's sarcoma as a result of treatment with immunosuppressive drugs. Sirolimus (rapamycin), an immunosuppressive drug, may also have antitumor effects. METHODS: We stopped cyclosporine therapy in 15 kidney-transplant recipients who had biopsy-proven Kaposi's sarcoma and began sirolimus therapy. All patients underwent an excisional biopsy of the lesion and one biopsy of normal skin at the time of diagnosis. A second biopsy was performed at the site of a previous Kaposi's sarcoma lesion six months after sirolimus therapy was begun. We examined biopsy specimens for vascular endothelial growth factor (VEGF), Flk-1/KDR protein, and phosphorylated Akt and p70S6 kinase, two enzymes in the signaling pathway targeted by sirolimus. RESULTS: Three months after sirolimus therapy was begun, all cutaneous Kaposi's sarcoma lesions had disappeared in all patients. Remission was confirmed histologically in all patients six months after sirolimus therapy was begun. There were no acute episodes of rejection or changes in kidney-graft function. Levels of Flk-1/KDR and phosphorylated Akt and p70S6 kinase were increased in Kaposi's sarcoma cells. The expression of VEGF was increased in Kaposi's sarcoma cells and even more so in normal skin cells around the Kaposi's sarcoma lesions. CONCLUSIONS: Sirolimus inhibits the progression of dermal Kaposi's sarcoma in kidney-transplant recipients while providing effective immunosuppression. Copyright 2005 Massachusetts Medical Society.
MED-2129
Amino acid sensing mechanisms: an Achilles heel in cancer?
The act of increasing mass, either in non-dividing cells or in dividing cells seeking to provide new material for daughter cells, depends upon the continued presence of extracellular nutrients in order to conserve mass. For amino acid nutrients, it appears that their insufficiency for new protein synthesis is actively monitored by both prokaryotic and eukaryotic cells, eliciting appropriate cellular responses that may depend not only on bulk nutrient supply, but also on the abundance of specific amino acids. © 2012 The Author Journal compilation © 2012 FEBS.
MED-2130
Deconvoluting mTOR biology
In metazoans, TOR is an essential protein that functions as a master regulator of cellular growth and proliferation. Over the past decade, there has been an explosion of information about this critical master kinase, ranging from the composition of the TOR protein complex to its ability to act as an integrator of numerous extracellular signals. Unfortunately, this plethora of information has also raised numerous questions regarding TOR function. Currently, the prevailing view is that mammalian TOR (mTOR) exists in at least two molecular complexes, mTORC1 and mTORC2, which are largely defined by the presence of either RAPTOR or RICTOR. However, additional co-factors have been identified for each complex, and their importance in mediating mTOR signals has been incompletely elucidated. Similarly, there are differences in mTOR function that reflect the tissue of origin. In this review, we present an alternative view to mTOR complex formation and function, which envisions mTOR regulation and signal propagation as a reflection of cell type- and basal state-dependent conditions. The re-interpretation of mTOR biology in this framework may facilitate the design of therapies most likely to effectively inhibit this central regulator of cell behavior.
MED-2132
mTORC1 signaling: what we still don't know.
The mammalian target of rapamycin (mTOR) is a protein kinase that plays key roles in cellular regulation. It forms complexes with additional proteins. The best-understood one is mTOR complex 1 (mTORC1). The regulation and cellular functions of mTORC1 have been the subjects of intense study; despite this, many questions remain to be answered. They include questions about the actual mechanisms by which mTORC1 signaling is stimulated by hormones and growth factors, which involves the small GTPase Rheb, and by amino acids, which involves other GTPase proteins. The control of Rheb and the mechanism by which it activates mTORC1 remain incompletely understood. Although it has been known for many years that rapamycin interferes with some functions of mTORC1, it is not known how it does this, or why only some functions of mTORC1 are affected. mTORC1 regulates diverse cellular functions. Several mTORC1 substrates are now known, although in several cases their physiological roles are poorly or incompletely understood. In the case of several processes, although it is clear that they are regulated by mTORC1, it is not known how mTORC1 does this. Lastly, mTORC1 is implicated in ageing, but again it is unclear what mechanisms account for this. Given the importance of mTORC1 signaling both for cellular functions and in human disease, it is a high priority to gain further insights into the control of mTORC1 signaling and the mechanisms by which it controls cellular functions and animal physiology.
MED-2134
mTOR and cancer therapy.
Proteins regulating the mammalian target of rapamycin (mTOR), as well as some of the targets of the mTOR kinase, are overexpressed or mutated in cancer. Rapamycin, the naturally occurring inhibitor of mTOR, along with a number of recently developed rapamycin analogs (rapalogs) consisting of synthetically derived compounds containing minor chemical modifications to the parent structure, inhibit the growth of cell lines derived from multiple tumor types in vitro, and tumor models in vivo. Results from clinical trials indicate that the rapalogs may be useful for the treatment of subsets of certain types of cancer. The sporadic responses from the initial clinical trials, based on the hypothesis of general translation inhibition of cancer cells are now beginning to be understood owing to a more complete understanding of the dynamics of mTOR regulation and the function of mTOR in the tumor microenvironment. This review will summarize the preclinical and clinical data and recent discoveries of the function of mTOR in cancer and growth regulation.
MED-2135
Fisetin regulates obesity by targeting mTORC1 signaling.
Fisetin, a flavonol present in vegetables and fruits, possesses antioxidative and anti-inflammatory properties. In this study, we have demonstrated that fisetin prevents diet-induced obesity through regulation of the signaling of mammalian target of rapamycin complex 1 (mTORC1), a central mediator of cellular growth, cellular proliferation and lipid biosynthesis. To evaluate whether fisetin regulates mTORC1 signaling, we investigated the phosphorylation and kinase activity of the 70-kDa ribosomal protein S6 kinase 1 (S6K1) and mTORC1 in 3T3-L1 preadipocytes. Fisetin treatment of preadipocytes reduced the phosphorylation of S6K1 and mTORC1 in a time- and concentration-dependent manner. To further our understanding of how fisetin negatively regulates mTORC1 signaling, we analyzed the phosphorylation of S6K1, mTOR and Akt in fisetin-treated TSC2-knockdown cells. The results suggested that fisetin treatment inhibits mTORC1 activity in an Akt-dependent manner. Recent studies have shown that adipocyte differentiation is dependent on mTORC1 activity. Fisetin treatment inhibited adipocyte differentiation, consistent with the negative effect of fisetin on mTOR. The inhibitory effect of fisetin on adipogenesis is dependent of mTOR activity, suggesting that fisetin inhibits adipogenesis and the accumulation of intracellular triglycerides during adipocyte differentiation by targeting mTORC1 signaling. Fisetin supplementation in mice fed a high-fat diet (HFD) significantly attenuated HFD-induced increases in body weight and white adipose tissue. We also observed that fisetin efficiently suppressed the phosphorylation of Akt, S6K1 and mTORC1 in adipose tissue. Collectively, these results suggest that inhibition of mTORC1 signaling by fisetin prevents adipocyte differentiation of 3T3-L1 preadipocytes and obesity in HFD-fed mice. Therefore, fisetin may be a useful phytochemical agent for attenuating diet-induced obesity. Copyright © 2013 Elsevier Inc. All rights reserved.
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-2137
Rapalogs in cancer prevention
Common cancer is an age-related disease. Slow aging is associated with reduced and delayed carcinogenesis. Calorie restriction (CR), the most studied anti-aging intervention, prevents cancer by slowing down the aging process. Evidence is emerging that CR decelerates aging by deactivating MTOR (Target of Rapamycin). Rapamycin and other rapalogs suppress cellular senescence, slow down aging and postpone age-related diseases including cancer. At the same time, rapalogs are approved for certain cancer treatments. Can cancer prevention be explained by direct targeting of cancer cells? Or does rapamycin prevent cancer indirectly through slowing down the aging process? Increasing evidence points to the latter scenario.
MED-2138
Caloric restriction and incidence of breast cancer.
CONTEXT: Restricting caloric intake is one of the most effective ways to extend lifespan and to reduce spontaneous tumor occurrence in experimental animals, but whether similar associations hold in humans has not been appropriately studied. OBJECTIVE: To determine whether caloric restriction in early life reduces the risk of invasive breast cancer. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study using data from the Swedish Inpatient Registry, the Swedish Cancer Registry, the Swedish Death Registry, and the Swedish Fertility Registry. Participants were 7303 Swedish women hospitalized for anorexia nervosa prior to age 40 years between 1965 and 1998. Women were excluded (n = 31) if they were diagnosed with cancer prior to their first discharge from hospitalization for anorexia nervosa. MAIN OUTCOME MEASURE: Incidence of invasive breast cancer. RESULTS: Compared with the Swedish general population, women hospitalized for anorexia nervosa prior to age 40 years had a 53% (95% confidence interval [CI], 3%-81%) lower incidence of breast cancer; nulliparous women with anorexia nervosa had a 23% (95% CI, 79% higher to 75% lower) lower incidence, and parous women with anorexia nervosa had a 76% (95% CI, 13%-97%) lower incidence. CONCLUSIONS: Severe caloric restriction in humans may confer protection from invasive breast cancer. Low caloric intake prior to first birth followed by a subsequent pregnancy appears to be associated with an even more pronounced reduction in risk.
MED-2139
Prognostic and therapeutic implications of mTORC1 and Rictor expression in human breast cancer.
The mammalian target of rapamycin (mTOR) plays a key role in the regulation of cellular metabolism, growth and proliferation. It forms two multi-protein complexes known as complex 1 (mTORC1) and 2 (mTORC2). Raptor and Rictor are the core proteins for mTORC1 and mTORC2, respectively. This study examines the relationship between mTORC1, Rictor and Raptor mRNA expression and human breast cancer. Furthermore, the correlation between mTORC1 and hTERT was investigated. Breast cancer tissues (n=150) and normal tissues (n=31) were analysed using reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. Higher mTOR expression was noted in breast cancer tissue (P=0.0018), higher grade tumours (grade 2 vs. 3, P=0.047), in ductal tumours (P=0.0014), and was associated with worse overall survival (P=0.01). Rictor expression was significantly higher in background breast tissues compared with tumours and was inversely related to the Nottingham Prognostic Index (NPI1 vs. 2, P=0.03) and tumour grade (grade 1 vs. 3, P=0.01) and was associated with better overall (P=0.037) and disease-free survival (P=0.048). The mRNA expression of Raptor was higher in tumours compared with normal tissues. Furthermore, the expression of Raptor was associated with a higher tumour grade (grade 1 vs. 3, P=0.027). A highly significant positive correlation between mTOR and hTERT (P<0.00001) was observed. These observations are consistent with the role of mTORC1 in the anti-apoptosis pathway and suggest that selective inhibitors of mTORC1 may be more efficacious in human breast cancer. Our findings support the hypothesis that mTORC1 is an important upregulator of telomerase in breast cancer.
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-2514
Why human lifespan is rapidly increasing: solving "longevity riddle" with "revealed-slow-aging" hypothesis
Healthy life span is rapidly increasing and human aging seems to be postponed. As recently exclaimed in Nature, these findings are so perplexing that they can be dubbed the 'longevity riddle'. To explain current increase in longevity, I discuss that certain genetic variants such as hyper-active mTOR (mTarget of Rapamycin) may increase survival early in life at the expense of accelerated aging. In other words, robustness and fast aging may be associated and slow-aging individuals died prematurely in the past. Therefore, until recently, mostly fast-aging individuals managed to survive into old age. The progress of civilization (especially 60 years ago) allowed slow-aging individuals to survive until old age, emerging as healthy centenarians now. I discuss why slow aging is manifested as postponed (healthy) aging, why the rate of deterioration is independent from aging and also entertain hypothetical use of rapamycin in different eras as well as the future of human longevity.
MED-2943
Long-term low-calorie low-protein vegan diet and endurance exercise are associated with low cardiometabolic risk.
BACKGROUND: Western diets, which typically contain large amounts of energy-dense processed foods, together with a sedentary lifestyle are associated with increased cardiometabolic risk. We evaluated the long-term effects of consuming a low-calorie low-protein vegan diet or performing regular endurance exercise on cardiometabolic risk factors. METHODS: In this cross-sectional study, cardiometabolic risk factors were evaluated in 21 sedentary subjects, who had been on a low-calorie low-protein raw vegan diet for 4.4 +/- 2.8 years, (mean age, 53.1 +/- 11 yrs), 21 body mass index (BMI)-matched endurance runners consuming Western diets, and 21 age- and gender-matched sedentary subjects, consuming Western diets. RESULTS: BMI was lower in the low-calorie low-protein vegan diet (21.3 +/- 3.1 kg/m(2)) and endurance runner (21.1 +/- 1.6 kg/m(2)) groups than in the sedentary Western diet group (26.5 +/- 2.7 kg/m(2)) (p < 0.005). Plasma concentrations of lipids, lipoproteins, glucose, insulin, C-reactive protein, blood pressure (BP), and carotid artery intima-media thickness were lower in the low-calorie low-protein vegan diet and runner groups than in the Western diet group (all p < 0.05). Both systolic and diastolic BP were lower in the low-calorie low-protein vegan diet group (104 +/- 15 and 62 +/- 11 mm Hg) than in BMI-matched endurance runners (122 +/- 13 and 72 +/- 9 mmHg) and Western diet group (132 +/- 14 and 79 +/- 8 mm Hg) (p < 0.001); BP values were directly associated with sodium intake and inversely associated with potassium and fiber intake. CONCLUSIONS: Long-term consumption of a low-calorie low-protein vegan diet or regular endurance exercise training is associated with low cardiometabolic risk. Moreover, our data suggest that specific components of a low-calorie low-protein vegan diet provide additional beneficial effects on blood pressure.
MED-5118
Effect of two types of soy milk and dairy milk on plasma lipids in hypercholesterolemic adults: a randomized trial.
OBJECTIVE: To compare the effects of two commercially available soy milks (one made using whole soy beans, the other using soy protein isolate) with low-fat dairy milk on plasma lipid, insulin, and glucose responses. DESIGN: Randomized clinical trial, cross-over design. SUBJECTS: Participants were 30-65 years of age, n = 28, with pre-study LDL-cholesterol (LDL-C) concentrations of 160-220 mg/dL, not on lipid lowering medications, and with an overall Framingham risk score of <or=10%. INTERVENTION: Participants were required to consume sufficient milk to provide 25 g protein/d from each source. The protocol included three 4-week treatment phases, each separated from the next by a wash-out period of >or=4 weeks. RESULTS: Mean LDL-C concentration at the end of each phase (+/- SD) was 161 +/- 20, 161 +/- 26 and 170 +/- 24 mg/dL for the whole bean soy milk, the soy protein isolate milk, and the dairy milk, respectively (p = 0.9 between soy milks, p = 0.02 for each soy milk vs. dairy milk). No significant differences by type of milk were observed for HDL-cholesterol, triacylglycerols, insulin, or glucose. CONCLUSION: A 25 g dose of daily soy protein from soy milk led to a modest 5% lowering of LDL-C relative to dairy milk among adults with elevated LDL-C. The effect did not differ by type of soy milk and neither soy milk significantly affected other lipid variables, insulin or glucose.
MED-3226
Hypercalciuria Associated with High Dietary Protein Intake Is Not Due to Acid Load
Context and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins. Participants and Interventions: Eleven healthy volunteers were evaluated at the end of each of four phases while consuming metabolic diets with fixed calcium and sodium content. Phases 1 and 3 consisted of a control diet (CD). Phases 2 and 4 consisted of a eucaloric HPD (60 g/d animal proteins added to CD). Along with HPD in phases 2 and 4, subjects ingested 30 mEq twice daily of either potassium citrate (KCitrate, alkaline salt) or potassium chloride (KCl, control neutral salt). Results: KCitrate completely neutralized the acid load imparted by HPD (based on changes in urine pH and net acid excretion) and increased urinary citrate. Urinary calcium increased during both HPD phases compared with CD but was not significantly different between the HPD + KCl and HPD + KCitrate phases (182 ± 85 vs. 170 ± 85 mg/d; P = 0.28). Increased urinary saturation with respect to calcium oxalate and uric acid with HPD was abrogated by KCitrate. Conclusions: This study suggests that, at least in the short-term, mechanism(s) other than acid load account for hypercalciuria induced by HPD. The beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.
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-3374
Attractive names sustain increased vegetable intake in schools.
OBJECTIVE: This study will determine if the selective use of attractive names can be a sustainable, scalable means to increase the selection of vegetables in school lunchrooms. METHODS: Study 1 paired an attractive name with carrots in five elementary schools (n=147) and measured selection and consumption over a week compared to controls. Study 2 tracked food sales of vegetables in two elementary schools (n=1017) that were systematically attractively named or not named over a two-month period. Both studies were conducted in New York in 2011. RESULTS: Study 1 found that elementary students ate twice the percentage of their carrots if attractively named as "X-ray Vision Carrots," than if un-named or generically named as the "Food of the Day." Study 2 found that elementary school students were 16% more likely to persistently choose more hot vegetable dishes (p<0.001) when they were given fun or attractive names. DISCUSSION: Attractive names effectively and persistently increased healthy food consumption in elementary schools. The scalability of this is underscored by the success of Study 2, which was implemented and executed for negligible cost by a high school student volunteer. Copyright © 2012 Elsevier Inc. All rights reserved.
MED-4949
Public Health and Economic Consequences of Methyl Mercury Toxicity to the Developing Brain
Methyl mercury is a developmental neurotoxicant. Exposure results principally from consumption by pregnant women of seafood contaminated by mercury from anthropogenic (70%) and natural (30%) sources. Throughout the 1990s, the U.S. Environmental Protection Agency (EPA) made steady progress in reducing mercury emissions from anthropogenic sources, especially from power plants, which account for 41% of anthropogenic emissions. However, the U.S. EPA recently proposed to slow this progress, citing high costs of pollution abatement. To put into perspective the costs of controlling emissions from American power plants, we have estimated the economic costs of methyl mercury toxicity attributable to mercury from these plants. We used an environmentally attributable fraction model and limited our analysis to the neurodevelopmental impacts—specifically loss of intelligence. Using national blood mercury prevalence data from the Centers for Disease Control and Prevention, we found that between 316,588 and 637,233 children each year have cord blood mercury levels > 5.8 μg/L, a level associated with loss of IQ. The resulting loss of intelligence causes diminished economic productivity that persists over the entire lifetime of these children. This lost productivity is the major cost of methyl mercury toxicity, and it amounts to $8.7 billion annually (range, $2.2–43.8 billion; all costs are in 2000 US$). Of this total, $1.3 billion (range, $0.1–6.5 billion) each year is attributable to mercury emissions from American power plants. This significant toll threatens the economic health and security of the United States and should be considered in the debate on mercury pollution controls.
MED-2429
Statin use and risk of breast cancer: a meta-analysis of observational studies.
Emerging evidence suggests that statins' may decrease the risk of cancers. However, available evidence on breast cancer is conflicting. We, therefore, examined the association between statin use and risk of breast cancer by conducting a detailed meta-analysis of all observational studies published regarding this subject. PubMed database and bibliographies of retrieved articles were searched for epidemiological studies published up to January 2012, investigating the relationship between statin use and breast cancer. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Combined relative risk (RR) and 95 % confidence interval (CI) were calculated using a random-effects model (DerSimonian and Laird method). Subgroup analyses, sensitivity analysis, and cumulative meta-analysis were also performed. A total of 24 (13 cohort and 11 case-control) studies involving more than 2.4 million participants, including 76,759 breast cancer cases contributed to this analysis. We found no evidence of publication bias and evidence of heterogeneity among the studies. Statin use and long-term statin use did not significantly affect breast cancer risk (RR = 0.99, 95 % CI = 0.94, 1.04 and RR = 1.03, 95 % CI = 0.96, 1.11, respectively). When the analysis was stratified into subgroups, there was no evidence that study design substantially influenced the effect estimate. Sensitivity analysis confirmed the stability of our results. Cumulative meta-analysis showed a change in trend of reporting risk of breast cancer from positive to negative in statin users between 1993 and 2011. Our meta-analysis findings do not support the hypothesis that statins' have a protective effect against breast cancer. More randomized clinical trials and observational studies are needed to confirm this association with underlying biological mechanisms in the future.
MED-4264
Could increased time spent in a thermal comfort zone contribute to population increases in obesity?
Domestic winter indoor temperatures in the USA, UK and other developed countries appear to be following an upwards trend. This review examines evidence of a causal link between thermal exposures and increases in obesity prevalence, focusing on acute and longer-term biological effects of time spent in thermal comfort compared with mild cold. Reduced exposure to seasonal cold may have a dual effect on energy expenditure, both minimizing the need for physiological thermogenesis and reducing thermogenic capacity. Experimental studies show a graded association between acute mild cold and human energy expenditure over the range of temperatures relevant to indoor heating trends. Meanwhile, recent studies of the role of brown adipose tissue (BAT) in human thermogenesis suggest that increased time spent in conditions of thermal comfort can lead to a loss of BAT and reduced thermogenic capacity. Pathways linking cold exposure and adiposity have not been directly tested in humans. Research in naturalistic and experimental settings is needed to establish effects of changes in thermal exposures on weight, which may raise possibilities for novel public health strategies to address obesity. © 2011 The Authors. obesity reviews © 2011 International Association for the Study of Obesity.
MED-4918
Increased Prevalence and Mortality in Undiagnosed Celiac Disease
Background & Aims The historical prevalence and long-term outcome of undiagnosed celiac disease (CD) are unknown. We investigated the long-term outcome of undiagnosed CD and whether the prevalence of undiagnosed CD has changed during the past 50 years. Methods This study included 9,133 healthy young adults at Warren Air Force Base (sera were collected between 1948 and 1954) and 12,768 sex-matched subjects from 2 recent cohorts from Olmsted County, Minnesota, with either similar years of birth (n=5,558) or age at sampling (n=7,210) to that of the Air Force cohort. Sera were tested for tissue transglutaminase and, if abnormal, for endomysial antibodies. Survival was measured during a follow-up period of 45 years in the Air Force cohort. The prevalence of undiagnosed CD between the Air Force cohort and recent cohorts was compared. Results Of 9,133 persons from the Air Force cohort, 14 (0.2%) had undiagnosed CD. In this cohort, during 45 years of follow-up, all-cause mortality was greater in persons with undiagnosed CD than among those who were seronegative (hazard ratio=3.9; 95% CI, 2.0–7.5; P<.001). Undiagnosed CD was found in 68 (0.9%) persons with similar age at sampling and 46 (0.8%) persons with similar years of birth. The rate of undiagnosed CD was 4.5-fold and 4-fold greater in the recent cohorts (respectively) than in the Air Force cohort (both P ≤ .0001). Conclusions During 45 years of follow-up, undiagnosed CD was associated with a nearly 4-fold increased risk of death. The prevalence of undiagnosed CD appears to have increased dramatically in the United States during the past 50 years.
MED-1209
Adherence to healthy lifestyle habits in US adults, 1988-2006.
BACKGROUND: Lifestyle choices are associated with cardiovascular disease and mortality. The purpose of this study was to compare adherence to healthy lifestyle habits in adults between 1988 and 2006. METHODS: Analysis of adherence to 5 healthy lifestyle trends (>or=5 fruits and vegetables/day, regular exercise >12 times/month, maintaining healthy weight [body mass index 18.5-29.9 kg/m(2)], moderate alcohol consumption [up to 1 drink/day for women, 2/day for men] and not smoking) in the National Health and Nutrition Examination Survey 1988-1994 were compared with results from the National Health and Nutrition Examination Survey 2001-2006 among adults aged 40-74 years. RESULTS: Over the last 18 years, the percent of adults aged 40-74 years with a body mass index >or=30 kg/m(2) has increased from 28% to 36% (P <.05); physical activity 12 times a month or more has decreased from 53% to 43% (P <.05); smoking rates have not changed (26.9% to 26.1%); eating 5 or more fruits and vegetables a day has decreased from 42% to 26% (P <.05), and moderate alcohol use has increased from 40% to 51% (P <.05). Adherence to all 5 healthy habits has gone from 15% to 8% (P <.05). Although adherence to a healthy lifestyle was lower among minorities, adherence decreased more among non-Hispanic Whites over the period. Individuals with a history of hypertension/diabetes/cardiovascular disease were no more likely to be adherent to a healthy lifestyle than people without these conditions. CONCLUSIONS: Generally, adherence to a healthy lifestyle pattern has decreased during the last 18 years, with decreases documented in 3 of 5 healthy lifestyle habits. These findings have broad implications for the future risk of cardiovascular disease in adults.
MED-2383
The role of nuts in the optimal diet: time for a critical appraisal?
During the last decades, nuts have attracted the attention of researchers for their potential benefits in cardiovascular prevention. We discuss here some aspects of the assumed beneficial effects of nuts, weighing them against potential harm. Epidemiological observations and controlled intervention trials consistently suggest that nuts consumption is associated with improved serum lipid profile, thus helping decrease cardiovascular risk. Being nuts an energy dense food, their impact on energy balance and body weight should be considered. In particular, the claim that adding nuts to the habitual diet, thus increasing calorie intake, does not cause body fat accumulation still needs evidence and biological plausibility. The potential risk associated with the relatively frequent occurrence of allergic reactions following the consumption of nuts is also discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.
MED-2583
Effect of inositol hexaphosphate (IP(6)) on human normal and leukaemic haematopoietic cells.
Inositol hexaphosphate (IP(6)), a naturally polyphosphorylated carbohydrate, has been reported to have significant in vivo and in vitro anticancer activity against numerous tumours, such as colon, prostate, breast, liver and rhabdomyosarcomas. To confirm this activity in haematological malignancies and to characterize some of the mechanisms of IP(6) action, we analysed its effects on human leukaemic cell lines and fresh chronic myelogenous leukaemia (CML) progenitor cells using a combined cellular and molecular approach. IP(6) had a dose-dependent cytotoxic effect on all of the evaluated cell lines, with accumulation in the G2M phase in two out of five cell lines tested. At the molecular level, cDNA microarray analysis after IP(6) exposure showed an extensive downmodulation of genes involved in transcription and cell cycle regulation and a coherent upregulation of cell cycle inhibitors. Furthermore, IP(6) treatment of fresh leukaemic samples of bone marrow CD34+ CML progenitor cells significantly inhibited granulocyte-macrophage colony-forming unit (CFU-GM) formation (P = 0.0062) in comparison to normal bone marrow specimens, which were not affected. No differentiating effect on HL60 cells was observed. Taken together, our results confirm the antiproliferative activity of IP(6) and suggest that it may have a specific antitumour effect also in chronic myeloid leukaemias, via active gene modulation.
MED-4786
Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai Women's Health Study
Background: Soy food is a rich source of isoflavones—a class of phytoestrogens that has both antiestrogenic and anticarcinogenic properties. Objective: The objective was to evaluate the association of adolescent and adult soy food intake with breast cancer risk in a cohort of 73,223 Chinese women who participated in the Shanghai Women's Health Study. Design: A validated food-frequency questionnaire was used to assess usual dietary intake during adulthood and adolescence. After a mean follow-up of 7.4 y, 592 incident cases of breast cancer were identified for longitudinal analyses by using Cox regressions. Results: Adult soy food consumption, measured either by soy protein or isoflavone intake, was inversely associated with the risk of premenopausal breast cancer, and the association was highly statistically significant (P for trend < 0.001). The multivariate-adjusted relative risks (RRs) for the upper intake quintile compared with the lowest quintile were 0.41 (95% CI: 0.25, 0.70) for soy protein intake and 0.44 (95% CI: 0.26, 0.73) for isoflavone intake. High intake of soy foods during adolescence was also associated with a reduced risk of premenopausal breast cancer (RR: 0.57; 95% CI: 0.34, 0.97). Women who consumed a high amount of soy foods consistently during adolescence and adulthood had a substantially reduced risk of breast cancer. No significant association with soy food consumption was found for postmenopausal breast cancer. Conclusion: This large, population-based, prospective cohort study provides strong evidence of a protective effect of soy food intake against premenopausal breast cancer.
MED-5225
Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes
Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.
MED-4400
The influence of μ-opioid receptor agonist and antagonist peptides on peripheral blood mononuclear cells (PBMCs).
Milk is one of the main source of biologically-active peptides that may function as regulatory substances called food hormones. After passing the gut-blood barrier, the μ-opioid receptor agonist and antagonist peptides may become the new factors influencing various functions of the human organism. The aim of the conducted research was to determine the influence of μ-opioid receptor agonist peptides: human and bovine β-casomorphin-7 (h/bBCM-7) and antagonistic peptides: casoxin-6 and- D (CXN-6/D) on proliferation and cytokine secretion of human peripheral blood mononuclear cells (PBMCs). The PBMCs proliferation was measured by the use of the BrdU test, which assesses the DNA synthesis activity and the WST-1 test which assesses the activity of mitochondrial dehydrogenase enzymes. The influence of all the investigated peptides on secretion of IL-4, IL-8, IL-13 and IFN-γ was determined by the use of the ELISA tests. Incubating the cells with the peptides has not caused any changes to their enzymatic activity, which has been proved by a WST-1 test. When using a BrdU test, however, it has been observed that there appear changes to proliferation of PBMCs correlated to amounts of bromodeoxyuridine incorporated into the cellular DNA. Moreover, changes to secretion of IL-4 and IL-13 by the cells under the influence of agonists were detected, as well as changes to secretion of IFN-gamma under the influence of all the examined substances. The obtained results provide information on immunomodulatory effects of food-derived opioid peptides, which may be of clinical significance especially in the case of allergic diseases in newborns. Copyright © 2010 Elsevier Inc. All rights reserved.
MED-4678
Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women
The aim of this study was to obtain a better understanding of the role of hormonal factors in breast cancer risk and to determine whether the effect of reproductive events differs according to age at diagnosis. It analysed the effect of age at menarche, age at first full-term pregnancy, number of full-term pregnancies and number of spontaneous abortions both on the overall risk of breast cancer and on its pre- or postmenopausal onset, using the data on 1718 breast cancer cases, obtained from a large sample of around 100 000 French women participating in the E3N cohort study. The results provide further evidence that the overall risk of breast cancer increases with decreasing age at menarche, increasing age at first pregnancy and low parity. No overall effect of spontaneous abortions was observed. The effect of these reproductive factors differed according to menopausal status. Age at menarche had an effect on premenopausal breast cancer risk, with a decrease in risk with increasing age of 7% per year (P<0.05). Compared to those who had their first menstrual periods at 11 or before, women experiencing menarche at 15 or after had an RR of 0.66 (95% CI 0.45–0.97) in the premenopausal group. Age at first full-term pregnancy had an effect on both pre- and postmenopausal breast cancer risk, with significant tests showing increasing risk per year of increasing age (P=0.001 and P<0.05 respectively). A first full-term pregnancy above age 30 conveyed a risk of 1.63 (95% CI 1.12–2.38) and 1.35 (95% CI 1.02–1.78) in the pre- and postmenopausal groups respectively. A protective effect of high parity was observed only for postmenopausal breast cancer risk (P for trend test =0.001), with point estimates of 0.79 (95% CI 0.60–1.04), 0.69 (95% CI 0.54–0.88), 0.66 (95% CI 0.51–0.85) and 0.64 (95% CI 0.48–0.86) associated to a one, two, three and four or more full-term pregnancies. A history of spontaneous abortion had no significant effect on the risk of breast cancer diagnosed before or after menopause. Our results suggest that reproductive events have complex effects on the risk of breast cancer. British Journal of Cancer (2002) 86, 723–727. DOI: 10.1038/sj/bjc/6600124 www.bjcancer.com © 2002 Cancer Research UK
MED-5151
The emerging role of flavonoid-rich cocoa and chocolate in cardiovascular health and disease.
Cocoa and chocolate have recently been found to be rich plant-derived sources of antioxidant flavonoids with beneficial cardiovascular properties. These favorable physiological effects include: antioxidant activity, vasodilation and blood pressure reduction, inhibition of platelet activity, and decreased inflammation. Increasing evidence from experimental and clinical studies using cocoa-derived products and chocolate suggest an important role for these high-flavanol-containing foods in heart and vascular protection.
MED-2310
Fruit and Vegetable Intake, Physical Activity, and Mortality in Older Community-Dwelling Women
OBJECTIVES To examine the relationship between fruit and vegetable intake, physical activity, and all-cause mortality in older women. DESIGN Six Cox proportional hazards models examined independent and additive relationships between physical activity, carotenoids, and all-cause mortality. Additional models tested whether physical activity and carotenoids were conjointly related to mortality. Models were adjusted for age, education, and race and ethnicity. SETTING Baltimore, Maryland. PARTICIPANTS Seven hundred thirteen women aged 70 to 79 participating in the Women’s Health and Aging Studies. MEASUREMENTS Total serum carotenoids, a marker of fruit and vegetable intake, and physical activity were measured at baseline. Physical activity was measured according to kilocalorie expenditure. RESULTS During 5 years of follow-up, 82 (11.5%) participants died. Measured continuously, physical activity improved survival (HR = 0.52, 95% CI = 0.41–0.66, P < .001). The most active women were more likely to survive than the least physically active women (HR = 0.28, 95% CI = 0.13–0.59, P < .001). Continuous measures of carotenoids improved survival (HR = 0.67, 95% CI = 0.51–0.89, P = .01). Women in the highest tertile of total carotenoids were more likely to survive those in the lowest (HR = 0.50, 95% CI = 0.27–0.91, P = .03). When examined in the same model, continuous measures of physical activity (HR = 0.54, 95% CI = 0.42–0.68, P < .001) and carotenoids (HR = 0.76, 95% CI = 0.59–0.98, P = .04) predicted survival during follow-up. CONCLUSION The combination of low total serum carotenoids and low physical activity, both modifiable risk factors, strongly predicted earlier mortality. These findings provide preliminary support that higher fruit and vegetable intake and exercise improve survival.
MED-3534
Efficacy of a tart cherry juice blend in preventing the symptoms of muscle damage
Background Numerous antioxidant and anti‐inflammatory agents have been identified in tart cherries. Objective To test the efficacy of a tart cherry juice blend in preventing the symptoms of exercise induced muscle damage. Methods This was a randomised, placebo controlled, crossover design. Fourteen male college students drank 12 fl oz of a cherry juice blend or a placebo twice a day for eight consecutive days. A bout of eccentric elbow flexion contractions (2 × 20 maximum contractions) was performed on the fourth day of supplementation. Isometric elbow flexion strength, pain, muscle tenderness, and relaxed elbow angle were recorded before and for four days after the eccentric exercise. The protocol was repeated two weeks later with subjects who took the placebo initially, now taking the cherry juice (and vice versa). The opposite arm performed the eccentric exercise for the second bout to avoid the repeated bout protective effect. Results Strength loss and pain were significantly less in the cherry juice trial versus placebo (time by treatment: strength p<0.0001, pain p  =  0.017). Relaxed elbow angle (time by treatment p  =  0.85) and muscle tenderness (time by treatment p  =  0.81) were not different between trials. Conclusions These data show efficacy for this cherry juice in decreasing some of the symptoms of exercise induced muscle damage. Most notably, strength loss averaged over the four days after eccentric exercise was 22% with the placebo but only 4% with the cherry juice.
MED-5147
Immune effects of cocoa procyanidin oligomers on peripheral blood mononuclear cells.
There has been considerable work on the relationships between nutrition and the immune response, particularly on studies that have focused on adaptive responses. There is increasing recognition of the importance of innate immunity in host protection and initiation of cytokine networks. In this study, we examined the effect of select cocoa flavanols and procyanidins on innate responses in vitro. Peripheral blood mono-nuclear cells (PBMCs), as well as purified monocytes and CD4 and CD8 T cells, were isolated from healthy volunteers and cultured in the presence of cocoa flavanol fractions that differ from another by the degree of flavanol polymerization: short-chain flavanol fraction (SCFF), monomers to pentamers; and long-chain flavanol fraction (LCFF), hexamers to decamers. Parallel investigations were also done with highly purified flavanol monomers and procyanidin dimers. The isolated cells were then challenged with lipopolysaccharide (LPS) with quantitation of activation using CD69 and CD83 expression and analysis of secreted tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-10, and granulocyte macrophage colony-stimulating factor (GM-CSF). The chain length of flavanol fractions had a significant effect on cytokine release from both unstimulated and LPS-stimulated PBMCs. For example, there was a striking increase of LPS-induced synthesis of IL-1beta, IL-6, IL-10, and TNF-alpha in the presence of LCFF. LCFF and SCFF, in the absence of LPS, stimulated the production of GM-CSF. In addition, LCFF and SCFF increased expression of the B cell markers CD69 and CD83. There were also unique differential responses in the mononuclear cell populations studied. We conclude that the oligomers are potent stimulators of both the innate immune system and early events in adaptive immunity.
MED-4137
Prevalence of Yersinia enterocolitica in different phases of production on swine farms.
Swine have been identified as the primary reservoir of pathogenic Yersinia enterocolitica (YE), but little research has focused on the epidemiology of YE at the farm level. The objective of this study was to describe the prevalence of YE in different production phases on swine farms. In this cross-sectional study, individual pigs on eight swine operations were sampled for the presence of YE. On each farm, both feces and oral-pharyngeal swabs were collected from pigs in five different production phases: gestating, farrowing, suckling, nursery, and finishing. A pig was considered positive if either sample tested positive. Samples were cultured with cold enrichment followed by isolation on selective media plates. Presumptive isolates were confirmed as YE and assayed for the presence of ail with a multiplex PCR. Of the 2,349 pigs sampled, 120 (5.1%) tested positive, and of those, 51 were ail positive (42.5% of YE isolates). On all farms, there was a trend of increasing prevalence as pigs mature. Less than 1% of suckling piglets tested positive for YE. Only 1.4% (44.4% of which were ail positive) of nursery pigs tested positive, but 10.7% (48.1% of which were ail positive) of finishing pigs harbored YE. Interestingly, gestating sows had the second highest prevalence of YE at 9.1% (26.7% of which were ail positive), yet YE was never detected from the farrowing sows. These results represent the first on-farm description of YE in U.S. herds and provide the initial step for designing future studies of YE.
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-1273
Amyotrophic lateral sclerosis. A case-control study following detection of a cluster in a small Wisconsin community.
From 1975 to 1983, six cases of amyotrophic lateral sclerosis (ALS) were diagnosed in long-term residents of Two Rivers, Wis; the probability that this occurred due to chance was less than .05. To investigate potential risk factors for ALS, we conducted a case-control study using two control subjects matched to each case patient for age, gender, and duration of residence in Two Rivers. Physical trauma, the frequent consumption of freshly caught Lake Michigan fish, and a family history of cancer were reported more often by case patients than control subjects. These findings support previous studies proposing a role for trauma in ALS pathogenesis and suggest that the causative role of diet should be further explored. Continued surveillance for and epidemiologic investigation of ALS clusters with subsequent retrospective analysis may provide clues concerning the cause of ALS.
MED-3057
Brain PET imaging in obesity and food addiction: current evidence and hypothesis.
The ongoing epidemics of obesity is one main health concern of the present time. Overeating in some obese individuals shares similarities with the loss of control and compulsive behavior observed in drug-addicted subjects, suggesting that obesity may involve food addiction. Here, we review the contributions provided by the use of positron emission tomography to the current understanding of the cerebral control of obesity and food intake in humans. The available studies have shown that multiple areas in the brain are involved with the reward properties of food, such as prefrontal, orbitofrontal, somatosensory cortices, insula, thalamus, hypothalamus, amygdala, and others. This review summarizes the current evidence, supporting the concepts that i) regions involved in the somatosensory response to food sight, taste, and smell are activated by palatable foods and may be hyperresponsive in obese individuals, ii) areas controlling executive drive seem to overreact to the anticipation of pleasure during cue exposure, and iii) those involved in cognitive control and inhibitory behavior may be resistant to the perception of reward after food exposure in obese subjects. All of these features may stimulate, for different reasons, ingestion of highly palatable and energy-rich foods. Though these same regions are similarly involved in drug abusers and game-addicted individuals, any direct resemblance may be an oversimplification, especially as the heterogeneities between studies and the prevalent exclusion of sensitive groups still limit a coherent interpretation of the findings. Further work is required to comprehensively tackle the multifaceted phenotype of obesity and identify the role of food dependency in its pathophysiology. Copyright © 2012 S. Karger GmbH, Freiburg.
MED-1565
Adherence to the World Cancer Research Fund/American Institute for Cancer Research guidelines and risk of death in Europe: results from the Europea...
BACKGROUND: In 2007, the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) issued recommendations on diet, physical activity, and weight management for cancer prevention on the basis of the most comprehensive collection of available evidence. OBJECTIVE: We investigated whether concordance with WCRF/AICR recommendations is related to risk of death. DESIGN: The current study included 378,864 participants from 9 European countries enrolled in the European Prospective Investigation into Cancer and Nutrition study. At recruitment (1992-1998), dietary, anthropometric, and lifestyle information was collected. A WCRF/AICR score, which incorporated 6 of the WCRF/AICR recommendations for men [regarding body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods, and alcoholic drinks (score range: 0-6)] and 7 WCRF/AICR recommendations for women [plus breastfeeding (score range: 0-7)], was constructed. Higher scores indicated greater concordance with WCRF/AICR recommendations. Associations between the WCRF/AICR score and risks of total and cause-specific death were estimated by using Cox regression analysis. RESULTS: After a median follow-up time of 12.8 y, 23,828 deaths were identified. Participants within the highest category of the WCRF/AICR score (5-6 points in men; 6-7 points in women) had a 34% lower hazard of death (95% CI: 0.59, 0.75) compared with participants within the lowest category of the WCRF/AICR score (0-2 points in men; 0-3 points in women). Significant inverse associations were observed in all countries. The WCRF/AICR score was also significantly associated with a lower hazard of dying from cancer, circulatory disease, and respiratory disease. CONCLUSION: Results of this study suggest that following WCRF/AICR recommendations could significantly increase longevity.
MED-5193
Plasma and erythrocyte biomarkers of dairy fat intake and risk of ischemic heart disease.
BACKGROUND: The relation between dairy product intake and the risk of ischemic heart disease (IHD) remains controversial. OBJECTIVE: We aimed to explore biomarkers of dairy fat intake in plasma and erythrocytes and to assess the hypothesis that higher concentrations of these biomarkers are associated with a greater risk of IHD in US women. DESIGN: Among 32,826 participants in the Nurses' Health Study who provided blood samples in 1989-1990, 166 incident cases of IHD were ascertained between baseline and 1996. These cases were matched with 327 controls for age, smoking, fasting status, and date of blood drawing. RESULTS: Among controls, correlation coefficients between average dairy fat intake in 1986-1990 and 15:0 and trans 16:1n-7 content were 0.36 and 0.30 for plasma and 0.30 and 0.32 for erythrocytes, respectively. In multivariate analyses, with control for age, smoking, and other risk factors of IHD, women with higher plasma concentrations of 15:0 had a significantly higher risk of IHD. The multivariate-adjusted relative risks (95% CI) from the lowest to highest tertile of 15:0 concentrations in plasma were 1.0 (reference), 2.18 (1.20, 3.98), and 2.36 (1.16, 4.78) (P for trend = 0.03). Associations for other biomarkers were not significant. CONCLUSIONS: Plasma and erythrocyte contents of 15:0 and trans 16:1n-7 can be used as biomarkers of dairy fat intake. These data suggest that a high intake of dairy fat is associated with a greater risk of IHD.
MED-3844
Does antibacterial treatment for urinary tract infection contribute to the risk of breast cancer?
Low lignan status has been reported to be related to an elevated risk of breast cancer. Since lignan status is reduced by antibacterial medications, it is plausible to hypothesize that repeated use of antibiotics may also be a risk factor for breast cancer. History of treatment for urinary tract infection was studied for its prediction of breast cancer among 9461 Finnish women 19–89 years of age and initially cancer-free. During a follow-up in 1973–1991, a total of 157 breast cancer cases were diagnosed. Women reporting previous or present medication for urinary tract infection at baseline showed an elevated breast cancer risk in comparison with other women. The age-adjusted relative risk was 1.34 (95% confidence interval (CI) = 0.98–1.83). The association was concentrated to women under 50 years of age. The relative risk for these women was 1.74 (95% CI 1.13–2.68), whereas it was 0.97 (95% CI 0.59–1.58) for older women. The relative risk in the younger age-group was 1.47 (95% CI 0.73–2.97) during the first 10 years of follow-up, and 1.93 (95% CI 1.11–3.37) for follow-up times longer than 10 years. These data suggest that premenopausal women using long-term medication for urinary tract infections show a possible elevated risk of future breast cancer. The results are, however, still inconclusive and the hypothesis needs to be tested by other studies. © 2000 Cancer ResearchCampaign
MED-2291
Viscous versus nonviscous soluble fiber supplements: mechanisms and evidence for fiber-specific health benefits.
PURPOSE: This review focuses on the health benefits of viscous versus nonviscous soluble fibers, why symptoms can occur with increased fiber consumption, and how to avoid symptoms to improve adherence with a high-fiber diet. DATA SOURCES: Review of scientific literature as well as evidence-based guidelines and resources. CONCLUSIONS: While it is generally known that "fiber is good for you," it is less well known that specific health benefits are associated with specific fiber characteristics. Many of the health benefits of fiber can be directly correlated with the viscosity of soluble fibers when hydrated (i.e., gel-forming). A reduction in viscosity of a given fiber will attenuate these health benefits, and a nonviscous fiber does not exhibit these health benefits. IMPLICATIONS FOR PRACTICE: Increasing the viscosity of chyme with a viscous soluble fiber has been shown clinically to lower cholesterol for cardiovascular health, improve glycemic control in type 2 diabetes, normalize stool form in both constipation (softens hard stool) and diarrhea (firms loose/liquid stool), and improve the objective clinical measures of metabolic syndrome (glycemic control, lipoprotein profile, body mass index/weight loss, and blood pressure). ©2012 The Author(s) Journal compilation ©2012 American Academy of Nurse Practitioners.
MED-4200
Differences in postprandial inflammatory responses to a 'modern' v. traditional meat meal: a preliminary study.
A low-grade inflammatory response ('metaflammation') has been found to be associated with certain chronic diseases. Proposed inducers of this have been aspects of the modern lifestyle, including newly introduced foods. Plasma TAG, and the inflammatory cytokines C-reactive protein (CRP), TNF-alpha and IL-6 were compared in a randomised, cross-over trial using ten healthy subjects before and after eating 100 g of kangaroo, or a 'new' form of hybridised beef (wagyu) separated by about 1 week. Postprandial levels for 1 and 2 h of TAG, IL-6 and TNF-alpha were significantly higher after eating wagyu compared with kangaroo (P = 0.002 for TAG at 1 h, P < 0.001 at 2 h; P < 0.001 for IL-6 and TNF-alpha at 1 and 2 h). CRP was significantly higher 1 h postprandially after wagyu (P = 0.011) and non-significantly higher 2 h postprandially (P = 0.090). We conclude that the metaflammatory reaction to ingestion of a 'new' form of hybridised beef (wagyu) is indicative of a low-grade, systemic, immune reaction when compared with lean game meat (kangaroo). Further studies using isoenergetic intake and isolating fatty acid components of meats are proposed.
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-3927
Caffeine for treatment of Parkinson disease
Objective: Epidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). However, the symptomatic effects of caffeine in PD have not been adequately evaluated. Methods: We conducted a 6-week randomized controlled trial of caffeine in PD to assess effects upon daytime somnolence, motor severity, and other nonmotor features. Patients with PD with daytime somnolence (Epworth >10) were given caffeine 100 mg twice daily ×3 weeks, then 200 mg twice daily ×3 weeks, or matching placebo. The primary outcome was the Epworth Sleepiness Scale score. Secondary outcomes included motor severity, sleep markers, fatigue, depression, and quality of life. Effects of caffeine were analyzed with Bayesian hierarchical models, adjusting for study site, baseline scores, age, and sex. Results: Of 61 patients, 31 were randomized to placebo and 30 to caffeine. On the primary intention-to-treat analysis, caffeine resulted in a nonsignificant reduction in Epworth Sleepiness Scale score (−1.71 points; 95% confidence interval [CI] −3.57, 0.13). However, somnolence improved on the Clinical Global Impression of Change (+0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (−1.97; −3.87, −0.05). Caffeine reduced the total Unified Parkinson's Disease Rating Scale score (−4.69 points; −7.7, −1.6) and the objective motor component (−3.15 points; −5.50, −0.83). Other than modest improvement in global health measures, there were no changes in quality of life, depression, or sleep quality. Adverse events were comparable in caffeine and placebo groups. Conclusions: Caffeine provided only equivocal borderline improvement in excessive somnolence in PD, but improved objective motor measures. These potential motor benefits suggest that a larger long-term trial of caffeine is warranted. Classification of evidence: This study provides Class I evidence that caffeine, up to 200 mg BID for 6 weeks, had no significant benefit on excessive daytime sleepiness in patients with PD.
MED-1827
In vitro anti-metastatic activity of enterolactone, a mammalian lignan derived from flax lignan, and down-regulation of matrix metalloproteinases i...
BACKGROUND: Actin cytoskeleton is involved in actin-based cell adhesion, cell motility, and matrix metalloproteinases(MMPs) MMP2, MMP9, MMP11 and MMP14 are responsible for cell invasion in breast cancer metastasis. The dietary intake of lignan from flax seed gets converted to enterolactone (EL) and enterodiol in the human system. Here we show that the enterolactone has a very significant anti-metastatic activity as demonstrated by its ability to inhibit adhesion and invasion and migration in MCF-7 and MDA MB231 cell lines. MATERIALS AND METHODS: Migration inhibition assay, actin-based cell motility assay along with reverse transcriptase polymerase chain reaction (RT-PCR) for MMP2, MMP9, MMP11 and MMP14 genes were performed in MCF-7 and MDA MB 231 cell lines. RESULTS: Enterolactone seems to inhibit actin-based cell motility as evidenced by confocal imaging and photo documentation of cell migration assay. The results are supported by the observation that the enterolactone in vitro significantly down-regulates the metastasis-related metalloproteinases MMP2, MMP9 and MMP14 gene expressions. No significant alteration in the MMP11 gene expression was found. CONCLUSIONS: Therefore we suggest that the anti-metastatic activity of EL is attributed to its ability to inhibit cell adhesion, cell invasion and cell motility. EL affects normal filopodia and lamellipodia structures, polymerization of actin filaments at their leading edges and thereby inhibits actin-based cell adhesion and cell motility. The process involves multiple force-generating mechanisms of actin filaments i.e. protrusion, traction, deadhesion and tail-retraction. By down-regulating the metastasis-related MMP2, MMP9 and MMP14 gene expressions, EL may be responsible for cell invasion step of metastasis.
MED-4800
Detection and characterization of Clostridium difficile in retail chicken.
AIMS: This study was designed to evaluate the prevalence of Clostridium difficile contamination of retail chicken. METHODS AND RESULTS: Chicken legs, thighs and wings were purchased using a standardized method from retail outlets across Ontario, Canada. Selective culture was used for qualitative and quantitative detection of C. difficile. Clostridium difficile was isolated from 26/203 (12.8%) chicken samples; 10/111 (9.0%) thighs, 13/72 (18%) wings and 3/20 (15%) legs (P = 0.19). All isolates were ribotype 078, a strain that has been associated with food animals and potentially community-associated disease in humans. All positive samples were positive only on enrichment culture. CONCLUSIONS: Clostridium difficile could be found relatively commonly in retail chicken meat, albeit at low levels. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to report C. difficile in chicken meat. Contamination of meat with C. difficile strains implicated in human infections raises concerns about food as a source of C. difficile infection. The relevance of food contamination is completely unclear at this point but food should be investigated as a source of infection.
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-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-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-826
The polycystic ovary syndrome: a position statement from the European Society of Endocrinology.
Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS. © 2014 European Society of Endocrinology.
MED-1280
Diverse taxa of cyanobacteria produce β-N-methylamino-l-alanine, a neurotoxic amino acid
Cyanobacteria can generate molecules hazardous to human health, but production of the known cyanotoxins is taxonomically sporadic. For example, members of a few genera produce hepatotoxic microcystins, whereas production of hepatotoxic nodularins appears to be limited to a single genus. Production of known neurotoxins has also been considered phylogenetically unpredictable. We report here that a single neurotoxin, β-N-methylamino-l-alanine, may be produced by all known groups of cyanobacteria, including cyanobacterial symbionts and free-living cyanobacteria. The ubiquity of cyanobacteria in terrestrial, as well as freshwater, brackish, and marine environments, suggests a potential for wide-spread human exposure.
MED-1432
Do Sirtuins Promote Mammalian Longevity?: A Critical Review on Its Relevance to the Longevity Effect Induced by Calorie Restriction
Sirtuins (SIRTs), a family of nicotinamide adenine dinucleotide (NAD)-dependent deacetylases, are emerging as key molecules that regulate aging and age-related diseases including cancers, metabolic disorders, and neurodegenerative diseases. Seven isoforms of SIRT (SIRT1–7) have been identified in mammals. SIRT1 and 6, mainly localized in the nucleus, regulate transcription of genes and DNA repair. SIRT3 in the mitochondria regulates mitochondrial bioenergetics. Initial studies in yeasts, nematodes, and flies indicated a strong connection of SIRT with the life-prolonging effects of calorie restriction (CR), a robust experimental intervention for longevity in a range of organisms. However, subsequent studies reported controversial findings regarding SIRT roles in the effect of CR. This review describes the functional roles of mammalian SIRTs and discusses their relevance to mechanisms underlying the longevity effect of CR.
MED-3350
Effect of dietary sodium restriction on taste responses to sodium chloride: a longitudinal study.
Normotensive adults on low-sodium, weight-loss, and control diets recorded preferences and perceived saltiness for sodium chloride (NaCl) added to cream soup at intervals over 1 yr. Reduction in sodium intake and excretion accompanied a shift in preference toward less salt: preferred concentrations by ad libitum salting declined from 0.72% at the onset to 0.33% NaCl at week 24; hedonic scores for high concentrations of NaCl decreased significantly while scores for low concentrations increased. After 3 mo of sodium restriction, NaCl preferences readjusted to a lower level: ad libitum additions of NaCl were similar after 13, 24, and 52 wk. Less hedonic variation was observed among controls than among Na-restricted groups. The weight-loss group showed increased liking for mid-range NaCl levels. Mechanisms underlying preference changes, including physiological, behavioral, and context effects, may provide insights into maintenance of low-sodium diets for treatment and prevention of hypertension.
MED-4513
Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B₁₂ status in the elderly.
BACKGROUND: Vitamin B₁₂ deficiency is common among the elderly, and early detection is clinically important. However, clinical signs and symptoms have limited diagnostic accuracy and there is no accepted reference test method. METHODS: In elderly subjects (n = 700; age range 63-97 years), we investigated the ability of serum cobalamin, holotranscobalamin (holoTC), total homocysteine (tHcy), methylmalonic acid (MMA), serum and erythrocyte folate, and other hematologic variables to discriminate cobalamin deficiency, defined as red blood cell cobalamin <33 pmol/L. RESULTS: Serum holoTC was the best predictor, with area under the ROC curve (95% CI) 0.90 (0.86-0.93), and this was significantly better (P ≤ 0.0002) than the next best predictors; serum cobalamin, 0.80 (0.75-0.85), and MMA, 0.78 (0.72-0.83). For these 3 analytes, we constructed a 3-zone partition of positive and negative zones and a deliberate indeterminate zone between. The boundaries were values of each test that resulted in a posttest probability of deficiency of 60% and a posttest probability of no deficiency of 98%. The proportion of indeterminate observations for holoTC, cobalamin, and MMA was 14%, 45%, and 50%, respectively. Within the holoTC indeterminate zone (defined as 20-30 pmol/L), discriminant analysis selected only erythrocyte folate, which correctly allocated 65% (58/89) of the observations. Renal dysfunction compromised the diagnostic accuracy of MMA but not holoTC or serum cobalamin. CONCLUSIONS: This study supports the use of holoTC as the first-line diagnostic procedure for vitamin B₁₂ status.
MED-2298
A guide to exercise prescription.
Exercise is a fundamental component of good health. The American College of Sports Medicine and "Exercise is Medicine" recommend treating exercise as a vital sign, and assessing and prescribing physical activity at every medical visit. Meeting the recommended goals of physical activity results in a significant reduction in all-cause mortality. Physicians can improve health by prescribing exercise. Copyright © 2013 Elsevier Inc. All rights reserved.
MED-1680
Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.
BACKGROUND: Although more than 80% of the global burden of cardiovascular disease occurs in low-income and middle-income countries, knowledge of the importance of risk factors is largely derived from developed countries. Therefore, the effect of such factors on risk of coronary heart disease in most regions of the world is unknown. METHODS: We established a standardised case-control study of acute myocardial infarction in 52 countries, representing every inhabited continent. 15152 cases and 14820 controls were enrolled. The relation of smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins (Apo), and psychosocial factors to myocardial infarction are reported here. Odds ratios and their 99% CIs for the association of risk factors to myocardial infarction and their population attributable risks (PAR) were calculated. FINDINGS: Smoking (odds ratio 2.87 for current vs never, PAR 35.7% for current and former vs never), raised ApoB/ApoA1 ratio (3.25 for top vs lowest quintile, PAR 49.2% for top four quintiles vs lowest quintile), history of hypertension (1.91, PAR 17.9%), diabetes (2.37, PAR 9.9%), abdominal obesity (1.12 for top vs lowest tertile and 1.62 for middle vs lowest tertile, PAR 20.1% for top two tertiles vs lowest tertile), psychosocial factors (2.67, PAR 32.5%), daily consumption of fruits and vegetables (0.70, PAR 13.7% for lack of daily consumption), regular alcohol consumption (0.91, PAR 6.7%), and regular physical activity (0.86, PAR 12.2%), were all significantly related to acute myocardial infarction (p<0.0001 for all risk factors and p=0.03 for alcohol). These associations were noted in men and women, old and young, and in all regions of the world. Collectively, these nine risk factors accounted for 90% of the PAR in men and 94% in women. INTERPRETATION: Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity account for most of the risk of myocardial infarction worldwide in both sexes and at all ages in all regions. This finding suggests that approaches to prevention can be based on similar principles worldwide and have the potential to prevent most premature cases of myocardial infarction.
MED-1542
Status of Cardiovascular Health in US Adults: Prevalence Estimates from the National Health and Nutrition Examination Surveys (NHANES) 2003-2008
Background The American Heart Association's 2020 Strategic Impact Goals define a new concept, “cardiovascular (CV) health”; however, current prevalence estimates of the status of CV health in U.S. adults according to age, sex and race/ethnicity have not been published. Methods and Results We included 14,515 adults (≥20 years) from the 2003-2008 National Health and Nutrition Examination Surveys. Participants were stratified by young (20-39 years), middle (40-64 years), and older ages (65+ years). CV health behaviors (diet, physical activity, body mass index, smoking) and CV health factors (blood pressure, total cholesterol, fasting blood glucose, smoking) were defined as poor, intermediate, or ideal. Less than 1% of adults exhibited ideal CV health for all 7 metrics. For CV health behaviors, non-smoking was most prevalent (range:60.2-90.4%) while ideal Healthy Diet Score was least prevalent (range:0.2-2.6%) across groups. Prevalence of ideal BMI (range:36.5-45.3%) and ideal physical activity levels (range:50.2-58.8%) were higher in young adults compared to middle or older ages. Ideal total cholesterol (range:23.7-36.2%), blood pressure (range:11.9-16.3%) and fasting blood glucose (range:31.2-42.9%) were lower in older adults compared with young and middle age adults.Prevalence of poor CV health factors was lowest in young age but higher at middle and older ages. Prevalence estimates by age and sex were consistent across race/ethnic groups. Conclusions These prevalence estimates of CV health represent a starting point from which effectiveness of efforts to promote CV health and prevent CV disease can be monitored and compared in U.S. adult populations.
MED-4249
Crossover study of diets enriched with virgin olive oil, walnuts or almonds. Effects on lipids and other cardiovascular risk markers.
BACKGROUND AND AIMS: Virgin olive oil (VOO) and nuts are basic components of the Mediterranean diet, a heart-healthy dietary pattern. Nuts have well known cholesterol lowering effects, while evidence is unclear for VOO. We designed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40% of the fat in the background diet with VOO, walnuts or almonds. METHODS AND RESULTS: After a 4 week run-in period with a healthy diet, eligible candidates were randomized into three diet sequences in a crossover design, with a common background diet enriched with VOO, walnuts or almonds, lasting 4 weeks each. Outcomes were changes of serum lipids and oxidation and inflammation markers, measured by standard methods. Plasma fatty acids were determined by gas chromatography to assess compliance. In 18 participants completing the study (9 women, mean age 56 y, BMI 25.7 kg/m(2)), LDL-cholesterol was reduced from baseline by 7.3%, 10.8% and 13.4% after the VOO, walnut and almond diets, respectively (P = 0.001, Friedman test). Total cholesterol and LDL/HDL ratios decreased in parallel. LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets. No changes of other lipid fractions, oxidation analytes or inflammatory biomarkers were observed. Plasma fatty acid changes after each diet sequence supported good compliance. CONCLUSION: The results confirm the cholesterol lowering properties of nut-enriched diets. They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content, which clearly deserves further study. Copyright © 2010 Elsevier B.V. All rights reserved.
MED-748
Medical practice and social authority.
Questions of medical ethics are often treated as especially difficult casuistical problems or as difficult cases illustrative of paradoxes or advantages in global moral theories. I argue here, in opposition to such approaches, for the inseparability of questions of social history and social theory from any normative assessment of medical practices. The focus of the discussion is the question of the legitimacy of the social authority exercised by physicians, and the insufficiency of traditional defences of such authority in liberal societies (voluntarist, informed consent approaches), as well as traditional attacks on such strategies (ideology critique). Seeing such authority as institution bound and role based, it is argued, can help reframe, more broadly and more adequately, what is an "ethical problem" in medical practice and why.
MED-1818
Nutrient-based dietary patterns and pancreatic cancer risk.
PURPOSE: Few data are available on the role of combinations of foods and/or nutrients on pancreatic cancer risk. To add further information on dietary patterns potentially associated to pancreatic cancer, we applied an exploratory principal component factor analysis on 28 major nutrients derived from an Italian case-control study. METHODS: Cases were 326 incident pancreatic cancer cases and controls 652 frequency-matched controls admitted to hospital for non-neoplastic diseases. Dietary information was collected through a validated and reproducible food frequency questionnaire. Multiple logistic regression models adjusted for sociodemographic variables and major recognized risk factors for pancreatic cancer were used to estimate the odds ratios (OR) of pancreatic cancer for each dietary pattern. RESULTS: We identified four dietary patterns-named "animal products," "unsaturated fats," "vitamins and fiber," and "starch rich," that explain 75% of the total variance in nutrient intake in this population. After allowing for all the four patterns, positive associations were found for the animal products and the starch rich patterns, the OR for the highest versus the lowest quartiles being 2.03 (95% confidence interval [CI], 1.29-3.19) and 1.69 (95% CI, 1.02-2.79), respectively; an inverse association emerged for the vitamins and fiber pattern (OR, 0.55; 95% CI, 0.35-0.86), whereas no association was observed for the unsaturated fats pattern (OR, 1.13; 95% CI, 0.71-1.78). CONCLUSIONS: A diet characterized by a high consumption of meat and other animal products, as well as of (refined) cereals and sugars, is positively associated with pancreatic cancer risk, whereas a diet rich in fruit and vegetables is inversely associated. Copyright © 2013 Elsevier Inc. All rights reserved.
MED-1339
Calcium supplementation and bone mineral density in females from childhood to young adulthood: a randomized controlled trial.
BACKGROUND: Short-term studies established that calcium influences bone accretion during growth. Whether long-term supplementation influences bone accretion in young adults is not known. OBJECTIVE: This study evaluated the long-term effects of calcium supplementation on bone accretion among females from childhood to young adulthood. DESIGN: A 4-y randomized clinical trial recruited 354 females in pubertal stage 2 and optionally was extended for an additional 3 y. The mean dietary calcium intake of the participants over 7 y was approximately 830 mg/d; calcium-supplemented persons received an additional approximately 670 mg/d. Primary outcome variables were distal and proximal radius bone mineral density (BMD), total-body BMD (TBBMD), and metacarpal cortical indexes. RESULTS: Multivariate analyses of the primary outcomes indicated that calcium-supplementation effects vary over time. Follow-up univariate analyses indicated that all primary outcomes were significantly larger in the supplemented group than in the placebo group at the year 4 endpoint. However, at the year 7 endpoint, this effect vanished for TBBMD and distal radius BMD. Longitudinal models for TBBMD and proximal radius BMD, according to the time since menarche, showed a highly significant effect of supplementation during the pubertal growth spurt and a diminishing effect thereafter. Post hoc stratifications by compliance-adjusted total calcium intake and by final stature or metacarpal total cross-sectional area showed that calcium effects depend on compliance and body frame. CONCLUSIONS: Calcium supplementation significantly influenced bone accretion in young females during the pubertal growth spurt. By young adulthood, significant effects remained at metacarpals and at the forearm of tall persons, which indicated that the calcium requirement for growth is associated with skeletal size. These results may be important for both primary prevention of osteoporosis and prevention of bone fragility fractures during growth.
MED-3137
Americans Do Not Meet Federal Dietary Recommendations
A longstanding goal of dietary surveillance has been to estimate the proportion of the population with intakes above or below a target, such as a recommended level of intake. However, until now, statistical methods for assessing the alignment of food intakes with recommendations have been lacking. The purposes of this study were to demonstrate the National Cancer Institute’s method of estimating the distribution of usual intake of foods and determine the proportion of the U.S. population who does not meet federal dietary recommendations. Data were obtained from the 2001–2004 NHANES for 16,338 persons, aged 2 y and older. Quantities of foods reported on 24-h recalls were translated into amounts of various food groups using the MyPyramid Equivalents Database. Usual dietary intake distributions were modeled, accounting for sequence effect, weekend/weekday effect, sex, age, poverty income ratio, and race/ethnicity. The majority of the population did not meet recommendations for all of the nutrient-rich food groups, except total grains and meat and beans. Concomitantly, overconsumption of energy from solid fats, added sugars, and alcoholic beverages (“empty calories”) was ubiquitous. Over 80% of persons age ≥71 y and over 90% of all other sex-age groups had intakes of empty calories that exceeded the discretionary calorie allowances. In conclusion, nearly the entire U.S. population consumes a diet that is not on par with recommendations. These findings add another piece to the rather disturbing picture that is emerging of a nation’s diet in crisis.
MED-2228
Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials.
BACKGROUND: There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD). OBJECTIVE: The objective was to systematically review the effects of chocolate, cocoa, and flavan-3-ols on major CVD risk factors. DESIGN: We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) of chocolate, cocoa, or flavan-3-ols. We contacted authors for additional data and conducted duplicate assessment of study inclusion, data extraction, validity, and random-effects meta-analyses. RESULTS: We included 42 acute or short-term chronic (≤18 wk) RCTs that comprised 1297 participants. Insulin resistance (HOMA-IR: -0.67; 95% CI: -0.98, -0.36) was improved by chocolate or cocoa due to significant reductions in serum insulin. Flow-mediated dilatation (FMD) improved after chronic (1.34%; 95% CI: 1.00%, 1.68%) and acute (3.19%; 95% CI: 2.04%, 4.33%) intakes. Effects on HOMA-IR and FMD remained stable to sensitivity analyses. We observed reductions in diastolic blood pressure (BP; -1.60 mm Hg; 95% CI: -2.77, -0.43 mm Hg) and mean arterial pressure (-1.64 mm Hg; 95% CI: -3.27, -0.01 mm Hg) and marginally significant effects on LDL (-0.07 mmol/L; 95% CI: -0.13, 0.00 mmol/L) and HDL (0.03 mmol/L; 95% CI: 0.00, 0.06 mmol/L) cholesterol. Chocolate or cocoa improved FMD regardless of the dose consumed, whereas doses >50 mg epicatechin/d resulted in greater effects on systolic and diastolic BP. GRADE (Grading of Recommendations, Assessment, Development and Evaluation, a tool to assess quality of evidence and strength of recommendations) suggested low- to moderate-quality evidence of beneficial effects, with no suggestion of negative effects. The strength of evidence was lowered due to unclear reporting for allocation concealment, dropouts, missing data on outcomes, and heterogeneity in biomarker results in some studies. CONCLUSIONS: We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR. Larger, longer-duration, and independently funded trials are required to confirm the potential cardiovascular benefits of cocoa flavan-3-ols.
MED-4993
Effects of a low-salt diet on flow-mediated dilatation in humans.
BACKGROUND: The effect of salt reduction on vascular function, assessed by brachial artery flow-mediated dilatation (FMD), is unknown. OBJECTIVE: Our aim was to compare the effects of a low-salt (LS; 50 mmol Na/d) diet with those of a usual-salt (US; 150 mmol Na/d) diet on FMD. DESIGN: This was a randomized crossover design in which 29 overweight and obese normotensive men and women followed an LS diet and a US diet for 2 wk. Both diets had similar potassium and saturated fat contents and were designed to ensure weight stability. After each intervention, FMD, pulse wave velocity, augmentation index, and blood pressure were measured. RESULTS: FMD was significantly greater (P = 0.001) with the LS diet (4.89 +/- 2.42%) than with the US diet (3.37 +/- 2.10%), systolic blood pressure was significantly (P = 0.02) lower with the LS diet (112 +/- 11 mm Hg) than with the US diet (117 +/- 13 mm Hg), and 24-h sodium excretion was significantly lower (P = 0.0001) with the LS diet (64.1 +/- 41.3 mmol) than with the US diet (156.3 +/- 56.7 mmol). There was no correlation between change in FMD and change in 24-h sodium excretion or change in blood pressure. No significant changes in augmentation index or pulse wave velocity were observed. CONCLUSIONS: Salt reduction improves endothelium-dependant vasodilation in normotensive subjects independently of the changes in measured resting clinic blood pressure. These findings suggest additional cardioprotective effects of salt reduction beyond blood pressure reduction. The trial is registered with the Australian and New Zealand Clinical Trials Registry (unique identifier: ANZCTR12607000381482; http://www.anzctr.org.au/trial_view.aspx?ID=82159).
MED-2359
Anti-Gal titers in healthy adults and inflammatory bowel disease patients.
INTRODUCTION: ALPHA-GAL is a glycoconjugate present on cell membranes of mammals and bacteria but not humans who display anti-Gal antibodies (AB) in high titers provoked by the commensal gut flora. In the present study, we sought to determine the longitudinal course of alpha-Gal specific AB titers of all isotypes over 8 weeks among healthy adult subjects. Furthermore, we hypothesized that inflammatory bowel disease (IBD) patients display increased anti-Gal titers. MATERIALS AND METHODS: We drew serum from healthy probands (n=20) weekly for 8 weeks and obtained plasma samples of from patients suffering from Crohn's disease (n=20) and ulcerative colitis (n=20). We measured anti-Gal ABs of all isotypes and total immunoglobulin (Ig) content using an enzyme-linked immunosorbent assay technique. For statistical evaluation of the longitudinal titers, we calculated confidence intervals for the slopes of a random intercept model, comparing variances between and within the probands. For group comparisons, we performed paired student t-tests and Pearson correlations. RESULTS: Alpha-Gal specific IgG, IgM, IgD, and IgA titers remained unvaried within a narrow range upon longitudinal observation. Most probands did not display alpha-Gal specific IgE ABs. Crohn's disease patients showed highly increased alpha-Gal-specific IgA titers compared with control subjects (P<.01). CONCLUSION: Apart from IgE, alpha-Gal-specific ABs of all isotypes remained constant over longer time periods in healthy subjects. Thus, significant titer changes actually represent increased antigen exposure and a specific anti-alpha-Gal response. Crohn's disease patients display increased anti-Gal IgA titers compared with healthy controls, which reflects a chronically impaired mucosal gut barrier in this patient cohort. Copyright © 2011 Elsevier Inc. All rights reserved.
MED-1133
Prevalence of Kidney Stones in the United States
Background The last nationally representative assessment of kidney stone prevalence in the United States occurred in 1994. After a 13-yr hiatus, the National Health and Nutrition Examination Survey (NHANES) reinitiated data collection regarding kidney stone history. Objective Describe the current prevalence of stone disease in the United States, and identify factors associated with a history of kidney stones. Design, setting, and participants A cross-sectional analysis of responses to the 2007–2010 NHANES (n = 12 110). Outcome measurements and statistical analysis Self-reported history of kidney stones. Percent prevalence was calculated and multivariable models were used to identify factors associated with a history of kidney stones. Results and limitations The prevalence of kidney stones was 8.8% (95% confidence interval [CI], 8.1–9.5). Among men, the prevalence of stones was 10.6% (95% CI, 9.4–11.9), compared with 7.1% (95% CI, 6.4–7.8) among women. Kidney stones were more common among obese than normal-weight individuals (11.2% [95% CI, 10.0–12.3] compared with 6.1% [95% CI, 4.8–7.4], respectively; p < 0.001). Black, non-Hispanic and Hispanic individuals were less likely to report a history of stone disease than were white, non-Hispanic individuals (black, non-Hispanic: odds ratio [OR]: 0.37 [95% CI, 0.28–0.49], p < 0.001; Hispanic: OR: 0.60 [95% CI, 0.49–0.73], p < 0.001). Obesity and diabetes were strongly associated with a history of kidney stones in multivariable models. The cross-sectional survey design limits causal inference regarding potential risk factors for kidney stones. Conclusions Kidney stones affect approximately 1 in 11 people in the United States. These data represent a marked increase in stone disease compared with the NHANES III cohort, particularly in black, non-Hispanic and Hispanic individuals. Diet and lifestyle factors likely play an important role in the changing epidemiology of kidney stones.
MED-2723
Health and economic burden of the projected obesity trends in the USA and the UK.
Rising prevalence of obesity is a worldwide health concern because excess weight gain within populations forecasts an increased burden from several diseases, most notably cardiovascular diseases, diabetes, and cancers. In this report, we used a simulation model to project the probable health and economic consequences in the next two decades from a continued rise in obesity in two ageing populations--the USA and the UK. These trends project 65 million more obese adults in the USA and 11 million more obese adults in the UK by 2030, consequently accruing an additional 6-8·5 million cases of diabetes, 5·7-7·3 million cases of heart disease and stroke, 492,000-669,000 additional cases of cancer, and 26-55 million quality-adjusted life years forgone for USA and UK combined. The combined medical costs associated with treatment of these preventable diseases are estimated to increase by $48-66 billion/year in the USA and by £1·9-2 billion/year in the UK by 2030. Hence, effective policies to promote healthier weight also have economic benefits. Copyright © 2011 Elsevier Ltd. All rights reserved.
MED-4142
Human pathogens and tetracycline-resistant bacteria in bioaerosols of swine confinement buildings and in nasal flora of hog producers.
Swine confinement buildings in eastern Canada are enclosed and equipped with modern production systems to manage waste. Bioaerosols of these swine confinement buildings could be contaminated by human pathogens and antimicrobial resistant bacteria which could colonize exposed workers. We therefore wanted to analyze bioaerosols of swine confinement buildings and nasal flora of Canadian hog producers to evaluate possible colonization with human pathogens and tetracycline-resistant bacteria. Culturable and non-culturable human pathogens and tet genes were investigated in the bioaerosols of 18 barns. The nasal passages of 35 hog producers were sampled and total DNA was extracted from the calcium-alginate swabs to detect, by PCR, Campylobacter, C. perfringens, Enterococcus, E. coli, Y. enterocolitica, tetA/tetC, tetG and ribosomal protection protein genes. Airborne culturable C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were present in the bioaerosols of 16, 17, 11 and 6 of the 18 facilities. Aerosolized total (culturable/non culturable) Campylobacter, C. perfringens, Enterococcus, E. coli and Y. enterocolitica were detected in 10, 6, 15, 18 and 2 barns, respectively. Tet genes were found in isolates of culturable human pathogens. TetA/tetC, tetG and ribosomal protection protein genes were detected in the bioaerosols of all 18 studied buildings. Campylobacter, C. perfringens, Enterococcus, E. coli, and Y. enterocolitica were found respectively in 4, 9, 17, 14 and one nasal flora of workers. One and 10 workers were positive for tetA/tetC and tetG genes, respectively. In swine confinement buildings, hog producers are exposed to aerosolized human pathogens and tetracycline-resistant bacteria that can contaminate the nasal flora. Copyright © 2010 Elsevier GmbH. All rights reserved.
MED-3030
Do national advisories serve local consumers: an assessment of mercury in economically important North Carolina fish.
Consumption of marine fish provides both benefits (lean protein, omega-3 fatty acids and essential nutrients) and risks (main source of mercury (Hg) exposure for humans). Mercury is a potent neurotoxin and the source of more fish advisories nationwide than any other toxicant. Despite the widespread nature of Hg, it is unknown whether local Hg contamination reflects national and regional levels often used as bases to inform consumers of potential fish consumption risk. Thus, the objectives of our study were to examine Hg levels of six commonly consumed marine species harvested locally off the North Carolina coast and to compare our results to published regional (Monterey Bay Aquarium's Seafood Watch List) and national (Environmental Protection Agency, EPA, and Food and Drug Administration, FDA) Hg averages, action levels, and guidelines. We found significant differences in Hg concentrations among collected species, and we identified correlations between Hg concentration and fish length and trophic levels. Collected mahi mahi and triggerfish were below the EPA fish tissue action level (0.3ppm). Wahoo and grouper exceeded the EPA action level but were below the FDA action level (1.0ppm). King mackerel had the highest Hg concentration among targeted species, exceeding both EPA and FDA action levels. Further, our local results were not always consistent with calculated averages from EPA and FDA databases for the same species, and although many of our findings were consistent with Monterey Bay Aquarium's Seafood Watch List (southeast region), recommendations based on Hg levels would conflict with recommendations they provide based on sustainability. We find regional and national averages are not always reflective of local Hg contamination and suggest local data may be needed to accurately assess consumer risk.
MED-4256
A systematic review of waist-to-height ratio as a screening tool for the prediction of cardiovascular disease and diabetes: 0·5 could be a suitable...
This systematic review collated seventy-eight studies exploring waist-to-height ratio (WHtR) and waist circumference (WC) or BMI as predictors of diabetes and CVD, published in English between 1950 and 2008. Twenty-two prospective analyses showed that WHtR and WC were significant predictors of these cardiometabolic outcomes more often than BMI, with similar OR, sometimes being significant predictors after adjustment for BMI. Observations from cross-sectional analyses, forty-four in adults, thirteen in children, supported these predictions. Receiver operator characteristic (ROC) analysis revealed mean area under ROC (AUROC) values of 0·704, 0·693 and 0·671 for WHtR, WC and BMI, respectively. Mean boundary values for WHtR, covering all cardiometabolic outcomes, from studies in fourteen different countries and including Caucasian, Asian and Central American subjects, were 0·50 for men and 0·50 for women. WHtR and WC are therefore similar predictors of diabetes and CVD, both being stronger than, and independent of, BMI. To make firmer statistical comparison, a meta-analysis is required. The AUROC analyses indicate that WHtR may be a more useful global clinical screening tool than WC, with a weighted mean boundary value of 0·5, supporting the simple public health message 'keep your waist circumference to less than half your height'.
MED-836
The optimal diet for women with polycystic ovary syndrome?
An optimal diet is one that not only prevents nutrient deficiencies by providing sufficient nutrients and energy for human growth and reproduction, but that also promotes health and longevity and reduces the risk of diet-related chronic diseases. The composition of the optimal diet for women with polycystic ovary syndrome (PCOS) is not yet known, but such a diet must not only assist short term with weight management, symptoms and fertility, but also specifically target the long-term risks of type 2 diabetes, CVD and certain cancers. With insulin resistance and compensatory hyperinsulinaemia now recognised as a key factor in the pathogenesis of PCOS, it has become clear that reducing insulin levels and improving insulin sensitivity are an essential part of management. Diet plays a significant role in the regulation of blood glucose and insulin levels, yet research into the dietary management of PCOS is lacking and most studies have focused on energy restriction rather than dietary composition per se. On the balance of evidence to date, a diet low in saturated fat and high in fibre from predominantly low-glycaemic-index-carbohydrate foods is recommended. Because PCOS carries significant metabolic risks, more research is clearly needed.
MED-2097
Nutritional intervention in patients with periodontal disease: clinical, immunological and microbiological variables during 12 months.
The role of nutrition in onset, progression and treatment of periodontitis has not been thoroughly evaluated. In the present prospective clinical study, we investigated the influence of a nutritional intervention on changes in clinical, microbiological and immunological periodontal variables during a period of 12 months in patients with the metabolic syndrome and chronic periodontitis. Twenty female subjects with the metabolic syndrome and mild to moderate chronic periodontitis participated in a guided nutritional intervention programme. Examinations were assessed before, and at 2 weeks, 3, 6 and 12 months after intervention. Clinical measurements included probing depth, Löe and Silness gingival index and Quigley-Hein plaque index. In gingival crevicular fluid, periodontopathogens, levels of IL-1beta and IL-6 as well as the activity of granulocyte elastase were determined. In stimulated saliva, antioxidative and oxidative variables were measured. After 12 months the following significant changes could be observed: reduction of clinical probing depth (2.40 v. 2.20 mm; P < 0.001), reduction of gingival inflammation (gingival index 1.13 v. 0.9; P < 0.001), reduced concentrations of IL-1beta (4.63 v. 1.10 pg/ml per site; P < 0.001) as well as IL-6 (1.85 v. 0.34 pg/ml per site; P = 0.022) in gingival crevicular fluid. Bacterial counts in gingival crevicular fluid as well as oxidative and antioxidative variables in saliva showed no significant changes. Only salivary catalase showed a tendency to lower values. These findings indicate that in patients with the metabolic syndrome wholesome nutrition might reduce inflammatory variables of periodontal disease and promote periodontal health.
MED-1712
Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-defici...
Diet contributes to over one-third of cancer deaths in the Western world, yet the factors in the diet that influence cancer are not elucidated. A reduction in caloric intake dramatically slows cancer progression in rodents, and this may be a major contribution to dietary effects on cancer. Insulin-like growth factor I (IGF-I) is lowered during dietary restriction (DR) in both humans and rats. Because IGF-I modulates cell proliferation, apoptosis, and tumorigenesis, the mechanisms behind the protective effects of DR may depend on the reduction of this multifaceted growth factor. To test this hypothesis, IGF-I was restored during DR to ascertain if lowering of IGF-I was central to slowing bladder cancer progression during DR. Heterozygous p53-deficient mice received a bladder carcinogen, p-cresidine, to induce preneoplasia. After confirmation of bladder urothelial preneoplasia, the mice were divided into three groups: (a) ad libitum; (b) 20% DR; and (c) 20% DR plus IGF-I (IGF-I/DR). Serum IGF-I was lowered 24% by DR but was completely restored in the IGF-I/DR-treated mice using recombinant IGF-I administered via osmotic minipumps. Although tumor progression was decreased by DR, restoration of IGF-I serum levels in DR-treated mice increased the stage of the cancers. Furthermore, IGF-I modulated tumor progression independent of changes in body weight. Rates of apoptosis in the preneoplastic lesions were 10 times higher in DR-treated mice compared to those in IGF/DR- and ad libitum-treated mice. Administration of IGF-I to DR-treated mice also stimulated cell proliferation 6-fold in hyperplastic foci. In conclusion, DR lowered IGF-I levels, thereby favoring apoptosis over cell proliferation and ultimately slowing tumor progression. This is the first mechanistic study demonstrating that IGF-I supplementation abrogates the protective effect of DR on neoplastic progression.
MED-3391
Safety of sildenafil citrate: review of 67 double-blind placebo-controlled trials and the postmarketing safety database
Aim: To review special safety topics associated with sildenafil and to document the tolerability of 50- and 100-mg doses, overall and by age, in men with erectile dysfunction (ED). Methods: Data were collated from 67 double-blind placebo-controlled (DBPC) trials (> 14,000 men) conducted by the manufacturer and from the manufacturer’s postmarketing safety database (39,277 patients). The DBPC data were stratified by dose, starting dose and age (≥ 65 and ≥ 75 years). Special safety topics included cardiovascular risk, priapism, non-arteritic anterior ischaemic optic neuropathy (NAION), impaired renal and hepatic function, drug interactions (i.e. nitrates, cytochrome P3A4 inhibitors, other ED therapies and α-blockers) and incorrect use. Results: Sildenafil was well tolerated at a dose of 50 or 100 mg in men with ED, overall, in those aged ≥ 65 years, and in those aged ≥ 75 years. Analyses of the databases did not reveal any causal link between sildenafil and cardiovascular events, or any new safety risks relating to cardiovascular events, priapism, NAION, hearing loss or drug interactions. In the small number of men with moderate impairment of renal function or hepatic function who were treated with sildenafil in DBPC trials, the safety profile was similar to that in men with no impairment of renal or hepatic function. Overdose with sildenafil was rare in the ED population. No new safety issues, emerging trends or adverse reactions were identified in conjunction with overdose, dependence, abuse or misuse. Conclusion: This collated review confirms generally the good tolerability and established safety profile of sildenafil 50 and 100 mg in men with ED and reveals no new safety issues.
MED-3558
Vitamin A, carotenoids, and risk of persistent oncogenic human papillomavirus infection.
Oncogenic human papillomavirus (HPV) infection is the main etiologic factor for cervical neoplasia, although infection alone is insufficient to produce disease. Cofactors such as nutritional factors may be necessary for viral progression to neoplasia. Results from previous studies have suggested that higher dietary consumption and circulating levels of certain micronutrients may be protective against cervical neoplasia. This study evaluated the role of vitamin A and carotenoids on HPV persistence comparing women with intermittent and persistent infections. As determined by the Hybrid Capture II system, oncogenic HPV infections were assessed at baseline and at approximately 3 and 9 months postbaseline. Multivariate logistic regression analysis was used to determine the risk of persistent HPV infection associated with each tertile of dietary and circulating micronutrients. Higher levels of vegetable consumption were associated with a 54% decrease risk of HPV persistence (adjusted odds ratio, 0.46; 95% confidence interval, 0.21-0.97). Also, a 56% reduction in HPV persistence risk was observed in women with the highest plasma cis-lycopene concentrations compared with women with the lowest plasma cis-lycopene concentrations (adjusted odds ratio, 0.44; 95% confidence interval, 0.19-1.01). These data suggest that vegetable consumption and circulating cis-lycopene may be protective against HPV persistence.
MED-4989
Effect of a high nutrient density diet on long-term weight loss: a retrospective chart review.
BACKGROUND: A high nutrient density (HND) vegetable-based diet offers a dietary model extremely low in saturated fat as well as refined carbohydrates and emphasizes a liberal intake of fresh fruits, vegetables, beans, and nuts. We conducted a retrospective chart review of patients who came to a family practice office seeking nutritional counseling for weight loss. All of these patients were prescribed an HND diet in an extended counseling session with a family physician. METHODS: A convenience sample (N = 56) of all patients seeking dietary counseling for weight loss from a family practice physician in a 3-year period was included in the chart review. No personal identifying data were recorded. The initial counseling sessions averaged 1 hour in length. Patients were provided with a sample HND daily meal plan and recipes and with verbal and written information about the rationale for the diet. Data recorded from patients' charts at 6-month intervals for up to 2 years of follow-up (when available) included weight, blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and cholesterol:HDL ratio. Non-parametric statistical testing using the Friedman rank order (exact) test for k-related samples was conducted. A follow-up survey on adherence and medication use was completed by 38 patients. RESULTS: Of the 33 patients who returned for follow-up after 1 year, the mean weight loss was 31 lbs (P = .000). Of the 19 patients who returned after 2 years, the mean weight loss was 53 lbs (P = .000), mean cholesterol fell by 13 points, LDL by 15 points, triglycerides by 17 points, and cardiac risk ratio dropped from 4.5 to 3.8. Changes in systolic and diastolic blood pressure were highly significant at all follow-up time intervals (P < or = .001). There was a significant correlation between adherence and degree of weight loss (P = .011). CONCLUSIONS: Weight loss was sustained in patients who returned for follow-up and was more substantial in those who reported good adherence to the recommendations. However, many patients were lost to follow-up. Favorable changes in lipid profile and blood pressure were noted. An HND diet has the potential to provide sustainable, significant, long-term weight loss and may provide substantial lowering of cardiac risk in patients who are motivated and provided with extended one-on-one counseling and follow-up visits. Development of tools to aid in patient retention is an area for possible further study. Clinical trials with long-term follow-up are needed to further test the therapeutic potential and to examine adherence and follow-up issues related to this dietary approach. An HND diet as demonstrated with this group may be the most health-favorable and effective way to lose weight for appropriately motivated patients.
MED-952
Cannabis and the lung.
The use of cannabis is embedded within many societies, mostly used by the young and widely perceived to be safe. Increasing concern regarding the potential for cannabis to cause mental health effects has dominated cannabis research and the potential adverse respiratory effects have received relatively little attention. Studies on cannabis are challenging and subject to confounding by concomitant use of tobacco and other social factors, and while many of the studies referred to in this review are beset by the difficulties inherent in undertaking epidemiological research of the effects of cannabis, there is an emerging concern among many chest physicians who would suggest that habitual smoking of cannabis may contribute to the development of chronic obstructive pulmonary disease, pneumothorax and respiratory infections, including tuberculosis. Special attention should be given to the risk of lung cancer, particularly as biological plausibility may precede epidemiology.
MED-884
Effect of different cooking methods on vegetable oxalate content.
Approximately 75% of all kidney stones are composed primarily of calcium oxalate, and hyperoxaluria is a primary risk factor for this disorder. Nine types of raw and cooked vegetables were analyzed for oxalate using an enzymatic method. There was a high proportion of water-soluble oxalate in most of the tested raw vegetables. Boiling markedly reduced soluble oxalate content by 30-87% and was more effective than steaming (5-53%) and baking (used only for potatoes, no oxalate loss). An assessment of the oxalate content of cooking water used for boiling and steaming revealed an approximately 100% recovery of oxalate losses. The losses of insoluble oxalate during cooking varied greatly, ranging from 0 to 74%. Because soluble sources of oxalate appear to be better absorbed than insoluble sources, employing cooking methods that significantly reduce soluble oxalate may be an effective strategy for decreasing oxaluria in individuals predisposed to the development of kidney stones.
MED-3436
How to save a life during a clinic visit for erectile dysfunction by modifying cardiovascular risk factors.
Erectile dysfunction (ED) is an early marker for systemic atherosclerosis and is a predictor for coronary artery disease and cardiac events. The aim of this paper is to convey the importance of addressing cardiovascular risk factors in patients with ED and to inform urologists as well as other physicians who are not specialized in cardiology how to carry out a basic cardiovascular evaluation, including history, physical examination and objective data. We review the evidence and pathophysiology linking ED to cardiovascular disease, and then describe how to carry out a basic cardiovascular evaluation. We present data from the literature showing that appropriate use of lifestyle modifications and medical therapy has a positive effect on mortality, on numerous cardiovascular end points and on ED. Suggestions of when to refer the ED patient to an internist or cardiologist are provided. Identifying and treating cardiovascular risk factors may not only benefit the patient's ED, but it might also save the patient's life.
MED-3890
Detection of a Common and Persistent tet(L)-Carrying Plasmid in Chicken-Waste-Impacted Farm Soil
The connection between farm-generated animal waste and the dissemination of antibiotic resistance in soil microbial communities, via mobile genetic elements, remains obscure. In this study, electromagnetic induction (EMI) surveying of a broiler chicken farm assisted soil sampling from a chicken-waste-impacted site and a marginally affected site. Consistent with the EMI survey, a disparity existed between the two sites with regard to soil pH, tetracycline resistance (Tcr) levels among culturable soil bacteria, and the incidence and prevalence of several tet and erm genes in the soils. No significant difference was observed in these aspects between the marginally affected site and several sites in a relatively pristine regional forest. When the farm was in operation, tet(L), tet(M), tet(O), erm(A), erm(B), and erm(C) genes were detected in the waste-affected soil. Two years after all waste was removed from the farm, tet(L), tet(M), tet(O), and erm(C) genes were still detected. The abundances of tet(L), tet(O), and erm(B) were measured using quantitative PCR, and the copy numbers of each were normalized to eubacterial 16S rRNA gene copy numbers. tet(L) was the most prevalent gene, whereas tet(O) was the most persistent, although all declined over the 2-year period. A mobilizable plasmid carrying tet(L) was identified in seven of 14 Tcr soil isolates. The plasmid's hosts were identified as species of Bhargavaea, Sporosarcina, and Bacillus. The plasmid's mobilization (mob) gene was quantified to estimate its prevalence in the soil, and the ratio of tet(L) to mob was shown to have changed from 34:1 to 1:1 over the 2-year sampling period.
MED-2027
Characterization of Adults With a Self-Diagnosis of Nonceliac Gluten Sensitivity.
Background: Nonceliac gluten sensitivity (NCGS), occurring in patients without celiac disease yet whose gastrointestinal symptoms improve on a gluten-free diet (GFD), is largely a self-reported diagnosis and would appear to be very common. The aims of this study were to characterize patients who believe they have NCGS. Materials and Methods: Advertising was directed toward adults who believed they had NCGS and were willing to participate in a clinical trial. Respondents were asked to complete a questionnaire about symptoms, diet, and celiac investigation. Results: Of 248 respondents, 147 completed the survey. Mean age was 43.5 years, and 130 were women. Seventy-two percent did not meet the description of NCGS due to inadequate exclusion of celiac disease (62%), uncontrolled symptoms despite gluten restriction (24%), and not following a GFD (27%), alone or in combination. The GFD was self-initiated in 44% of respondents; in other respondents it was prescribed by alternative health professionals (21%), dietitians (19%), and general practitioners (16%). No celiac investigations had been performed in 15% of respondents. Of 75 respondents who had duodenal biopsies, 29% had no or inadequate gluten intake at the time of endoscopy. Inadequate celiac investigation was common if the GFD was initiated by self (69%), alternative health professionals (70%), general practitioners (46%), or dietitians (43%). In 40 respondents who fulfilled the criteria for NCGS, their knowledge of and adherence to the GFD were excellent, and 65% identified other food intolerances. Conclusions: Just over 1 in 4 respondents self-reporting as NCGS fulfill criteria for its diagnosis. Initiation of a GFD without adequate exclusion of celiac disease is common. In 1 of 4 respondents, symptoms are poorly controlled despite gluten avoidance. © 2014 American Society for Parenteral and Enteral Nutrition.
MED-1259
Consumption of blueberries with a high-carbohydrate, low-fat breakfast decreases postprandial serum markers of oxidation.
We sought to determine whether consumption of blueberries could reduce postprandial oxidation when consumed with a typical high-carbohydrate, low-fat breakfast. Participants (n 14) received each of the three treatments over 3 weeks in a cross-over design. Treatments consisted of a high blueberry dose (75 g), a low blueberry dose (35 g) and a control (ascorbic acid and sugar content matching that of the high blueberry dose). Serum oxygen radical absorbance capacity (ORAC), serum lipoprotein oxidation (LO) and serum ascorbate, urate and glucose were measured at fasting, and at 1, 2 and 3 h after sample consumption. The mean serum ORAC was significantly higher in the 75 g group than in the control group during the first 2 h postprandially, while serum LO lag time showed a significant trend over the 3 h for both blueberry doses. Changes in serum ascorbate, urate and glucose were not significantly different among the groups. To our knowledge, this is the first report that has demonstrated that increased serum antioxidant capacity is not attributable to the fructose or ascorbate content of blueberries. In summary, a practically consumable quantity of blueberries (75 g) can provide statistically significant oxidative protection in vivo after a high-carbohydrate, low-fat breakfast. Though not tested directly, it is likely that the effects are due to phenolic compounds, either directly or indirectly, as they are a major family of compounds in blueberries with potential bioactive activity.
MED-3757
A duty to deceive: placebos in clinical practice.
Among medical researchers and clinicians the dominant view is that it is unethical to deceive patients by prescribing a placebo. This opinion is formalized in a recent policy issued by the American Medical Association (AMA [Chicago, IL]). Although placebos can be shown to be always safe, often effective, and sometimes necessary, doctors are now effectively prohibited from using them in clinical practice. I argue that the deceptive administration of placebos is not subject to the same moral objections that face other forms of deception in clinical practice and medical research. Although deception is normally objectionable on the grounds that it limits autonomy and breaches trust, these grounds do not apply to placebos when they are prescribed within appropriate ethical limits. Patients have reason to prefer that doctors can prescribe placebos in ethically responsible ways. Hence, the AMA has an obligation to endorse and to promote the responsible use of deceptive placebos in clinical practice.
MED-944
Nanomaterials in consumer products: a challenging analytical problem.
Many products used in everyday life are made with the assistance of nanotechnologies. Cosmetic, pharmaceuticals, sunscreen, powdered food are only few examples of end products containing nano-sized particles (NPs), generally added to improve the product quality. To evaluate correctly benefits vs. risks of engineered nanomaterials and consequently to legislate in favor of consumer's protection, it is necessary to know the hazards connected with the exposure levels. This information implies transversal studies and a number of different competences. On analytical point of view the identification, quantification and characterization of NPs in food matrices and in cosmetic or personal care products pose significant challenges, because NPs are usually present at low concentration levels and the matrices, in which they are dispersed, are complexes and often incompatible with analytical instruments that would be required for their detection and characterization. This paper focused on some analytical techniques suitable for the detection, characterization and quantification of NPs in food and cosmetics products, reports their recent application in characterizing specific metal and metal-oxide NPs in these two important industrial and market sectors. The need of a characterization of the NPs as much as possible complete, matching complementary information about different metrics, possible achieved through validate procedures, is what clearly emerges from this research. More work should be done to produce standardized materials and to set-up methodologies to determine number-based size distributions and to get quantitative date about the NPs in such a complex matrices.
MED-1953
Antimicrobial properties of Allium sativum (garlic).
Although garlic has been used for its medicinal properties for thousands of years, investigations into its mode of action are relatively recent. Garlic has a wide spectrum of actions; not only is it antibacterial, antiviral, antifungal and antiprotozoal, but it also has beneficial effects on the cardiovascular and immune systems. Resurgence in the use of natural herbal alternatives has brought the use of medicinal plants to the forefront of pharmacological investigations, and many new drugs are being discovered. This review aims to address the historical use of garlic and its sulfur chemistry, and to provide a basis for further research into its antimicrobial properties.
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-334
Differences among total and in vitro digestible phosphorus content of plant foods and beverages.
OBJECTIVE: Among plant foods, grain products, legumes, and seeds are important sources of phosphorus (P). Current data on P content and absorbability of P from these foods are lacking. Measurement of in vitro digestible P (DP) content of foods may reflect absorbability of P. The objective of this study was to measure both total phosphorus (TP) and DP contents of selected foods and to compare the amounts of TP and DP and the proportion of DP to TP among different foods. METHODS: TP and DP content of 21 foods and drinks of plant origin were measured by inductively coupled plasma optical emission spectrometry. In DP analysis, samples were digested enzymatically in principle in the same way as in the alimentary canal before P analyses. The most popular national brands were chosen for analysis. RESULTS: The highest amount of TP (667 mg/100 g) was found in sesame seeds with hull, which also had the lowest percentage of DP (6%) to TP. Instead, in cola drinks and beer, the percentage of DP to TP was 87 to 100% (13 to 22 mg/100 g). In cereal products, the highest TP content (216 mg/100 g) and DP proportion (100%) were present in industrial muffins, which contain sodium phosphate as a leavening agent. Legumes contained an average DP content of 83 mg/100 g (38% of TP). CONCLUSION: Absorbability of P may differ substantially among different plant foods. Despite high TP content, legumes may be a relatively poor P source. In foods containing phosphate additives, the proportion of DP is high, which supports previous conclusions of the effective absorbability of P from P additives. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
MED-4170
To breastfeed or not to breastfeed: a review of the impact of lactational exposure to polychlorinated biphenyls (PCBs) on infants.
Researchers have long debated the adverse effects of exposure to polychlorinated biphenyls (PCBs) on children versus the benefits of breastfeeding. In this article, the authors provide an overview of the known health effects of PCBs in children and examine the level of evidence regarding the risk of postnatal exposure via breastfeeding. The major source of PCBs is environmental, with over 90% of human exposure through the food chain. PCB exposure in infants is predominantly via breast milk, but limited evidence exists of significant toxicity associated with this mode of transmission. Breastfeeding should, therefore, continue to be encouraged on the basis of evidence of the benefits derived from human milk coupled with inconclusive proof that lactational PCB exposure has major detrimental effects on the overall health and development of infants.
MED-4159
Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Mem...
CONTEXT: The Women's Health Initiative Memory Study (WHIMS) previously found increased risk for dementia and no effect on mild cognitive impairment (MCI) in women treated with conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA). OBJECTIVE: To determine the effects of CEE alone and CEE plus MPA on incidence of probable dementia and MCI in older women. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled clinical trials of CEE (estrogen-alone trial) or CEE plus MPA (estrogen plus progestin trial) in community-dwelling women aged 65 to 79 years, conducted from June 1995 to July 8, 2002 (estrogen plus progestin; n = 4532), or to February 29, 2004 (estrogen-alone; n = 2947), in 39 of the 40 WHI clinical centers. INTERVENTIONS: In the estrogen-alone trial, 1 daily tablet containing either 0.625 mg/d of CEE vs matching placebo; in the estrogen plus progestin trial, 1 daily tablet containing CEE (0.625 mg/d) plus MPA (2.5 mg/d) vs matching placebos. MAIN OUTCOME MEASURES: Probable dementia and MCI. RESULTS: In the estrogen-alone trial, 47 participants were diagnosed with probable dementia, of whom 28 were assigned to CEE and 19 to placebo (hazard ratio [HR], 1.49; 95% confidence interval [CI], 0.83-2.66). Incidence rates for probable dementia in the estrogen-alone trial were statistically similar to those in the estrogen plus progestin trial (45 vs 22 per 10 000 person-years for CEE plus MPA vs placebo, respectively; P =.11). When data were pooled per the original WHIMS protocol, the overall HR for probable dementia was 1.76 (95% CI, 1.19-2.60; P =.005). After excluding participants with baseline Modified Mini-Mental State Examination scores at or below the screening cut point, the HR was 1.77 (95% CI, 0.74-4.23; P =.20) in the estrogen-alone trial and 2.19 (95% CI, 1.25-3.84; P =.006) in the pooled trials. In the estrogen-alone trial, 76 participants were diagnosed with MCI in the CEE group vs 58 in the placebo group (HR, 1.34; 95% CI, 0.95-1.89). In the combined trial data, the HR was similar (1.25; 95% CI, 0.97-1.60). In the estrogen-alone trial, 93 participants receiving CEE were diagnosed with either probable dementia or MCI vs 69 receiving placebo (HR, 1.38; 95% CI, 1.01-1.89; P =.04). CONCLUSIONS: Estrogen therapy alone did not reduce dementia or MCI incidence and increased the risk for both end points combined. Pooling data for estrogen alone and estrogen plus progestin resulted in increased risks for both end points. Use of hormone therapy to prevent dementia or cognitive decline in women 65 years of age or older is not recommended.
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-5341
Effects of a low-fat, high-fiber diet and exercise program on breast cancer risk factors in vivo and tumor cell growth and apoptosis in vitro.
The present study investigated the effects of a diet and exercise intervention on known breast cancer (BCa) risk factors, including estrogen, obesity, insulin, and insulin-like growth factor-I (IGF-I), in overweight/obese, postmenopausal women. In addition, using the subjects' pre- and postintervention serum in vitro, serum-stimulated growth and apoptosis of three estrogen receptor-positive BCa cell lines were studied. The women where placed on a low-fat (10-15% kcal), high-fiber (30-40 g per 1,000 kcal/day) diet and attended daily exercise classes for 2 wk. Serum estradiol was reduced in the women on hormone treatment (HT; n = 28) as well as those not on HT (n = 10). Serum insulin and IGF-I were significantly reduced in all women, whereas IGF binding protein-1 was increased significantly. In vitro growth of the BCa cell lines was reduced by 6.6% for the MCF-7 cells, 9.9% for the ZR-75-1 cells, and 18.5% for the T-47D cells. Apoptosis was increased by 20% in the ZR-75-1 cells, 23% in the MCF-7 cells, and 30% in the T-47D cells (n = 12). These results show that a very-low-fat, high-fiber diet combined with daily exercise results in major reductions in risk factors for BCa while subjects remained overweight/obese. These in vivo serum changes slowed the growth and induced apoptosis in serum-stimulated BCa cell lines in vitro.
MED-2011
Exploratory study of the relationship between hypertension and diet diversity among Saba Islanders.
The relationship between diet diversity and hypertension was examined in a cross-sectional exploratory study of 82 randomly selected adult residents of Saba Island, Netherlands Antilles, in the eastern Caribbean Basin. Blood pressure measurements, taken over 4 years, and the appropriate use of antihypertensive medications, were used to identify chronic hypertensives. A 24-hour dietary recall, semi-quantitative food frequency interviews, and ethnographic confirmation techniques were used to calculate diet diversity, a measure of the overall dietary pattern. Results suggest hypertension is associated with lack of an overall balance of food groups in the daily diet beyond any imbalance of a particular dietary cation such as sodium, potassium, or calcium. Bivariate analyses found a significant association between a poorly diversified diet and hypertension (odds ratio [OR] = 4.25, 95 percent confidence intervals [CI] = 1.47,12.30). Dietary intake of sodium, potassium, and calcium was also examined and found not to be associated with the presence of hypertension in bivariate analyses. Including these cations individually in logistic regression models, which also included diet diversity, did not diminish the diet diversity-hypertension association. Multiple logistic regression models in which other potential confounding variables were individually entered as a control variable (body fat, skin color, age, sex, perceived stress, alcohol intake, aerobic activity, and socioeconomic status) did not alter this result. Analysis of the presence or absence of individual food groups indicate a lack of legumes in the daily diet is also associated with the diagnosis of hypertension (OR = 4.71, 95 percent CI = [1.71,13.01]).
MED-4468
Effect of ascorbic acid and green tea on endogenous formation of N-nitrosodimethylamine and N-nitrosopiperidine in humans.
Many constituents present in the human diet may inhibit endogenous formation of N-nitroso compounds (NOC). Studies with human volunteers showed inhibiting effects of intake of ascorbic acid and green tea consumption on nitrosation using the N-nitrosoproline test. The aim of the present study was to evaluate the effects of ascorbic acid and green tea on urinary excretion of carcinogenic N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine (NPIP) in humans. Twenty-five healthy female volunteers consumed a fish meal rich in amines as nitrosatable precursors in combination with intake of nitrate-containing drinking water at the Acceptable Daily Intake level during 7 consecutive days. During 1 week before and after nitrate intake a diet low in nitrate was consumed. Using the same protocol, the effect of two different doses of ascorbic acid (250 mg and 1 g/day) and two different doses of green tea (2 g and 4 g/day) on formation of NDMA and NPIP was studied. Mean nitrate excretion in urine significantly increased from control (76+/-24) to 167+/-25 mg/24 h. Intake of nitrate and fish resulted in a significant increase in mean urinary excretion of NDMA compared with the control weeks: 871+/-430 and 640+/-277 ng/24 h during days 1-3 and 4-7, respectively, compared with 385+/-196 ng/24 h (p<0.0002). Excretion of NPIP in urine was not related to nitrate intake and composition of the diet. Intake of 250 mg and 1 g of ascorbic acid per day resulted in a significant decrease in urinary NDMA excretion during days 4-7 (p=0.0001), but not during days 1-3. Also, consumption of four cups of green tea per day (2 g) significantly decreased excretion of NDMA during days 4-7 (p=0.0035), but not during days 1-3. Surprisingly, consumption of eight cups of green tea per day (4 g) significantly increased NDMA excretion during days 4-7 (p=0.0001), again not during days 1-3. This increase is probably a result of catalytic effects of tea polyphenols on nitrosation, or of another, yet unknown, mechanism. These results suggest that intake of ascorbic acid and moderate consumption of green tea can reduce endogenous NDMA formation.
MED-5316
2,4-Dinitrophenol (DNP): A Weight Loss Agent with Significant Acute Toxicity and Risk of Death
2,4-Dinitrophenol (DNP) is reported to cause rapid loss of weight, but unfortunately is associated with an unacceptably high rate of significant adverse effects. DNP is sold mostly over the internet under a number of different names as a weight loss/slimming aid. It causes uncoupling of oxidative phosphorylation; the classic symptom complex associated with toxicity of phenol-based products such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea, eventually leading to death. Fatalities related to exposure to DNP have been reported since the turn of the twentieth century. To date, there have been 62 published deaths in the medical literature attributed to DNP. In this review, we will describe the pattern and pathophysiology of DNP toxicity and summarise the previous fatalities associated with exposure to DNP.
MED-1923
Loving-Kindness Meditation practice associated with longer telomeres in women.
Relatively short telomere length may serve as a marker of accelerated aging, and shorter telomeres have been linked to chronic stress. Specific lifestyle behaviors that can mitigate the effects of stress might be associated with longer telomere lengths. Previous research suggests a link between behaviors that focus on the well-being of others, such as volunteering and caregiving, and overall health and longevity. We examined relative telomere length in a group of individuals experienced in Loving-Kindness Meditation (LKM), a practice derived from the Buddhist tradition which utilizes a focus on unselfish kindness and warmth towards all people, and control participants who had done no meditation. Blood was collected by venipuncture, and Genomic DNA was extracted from peripheral blood leukocytes. Quantitative real time PCR was used to measure relative telomere length (RTL) (Cawthon, 2002) in fifteen LKM practitioners and 22 control participants. There were no significant differences in age, gender, race, education, or exposure to trauma, but the control group had a higher mean body mass index (BMI) and lower rates of past depression. The LKM practitioners had longer RTL than controls at the trend level (p=.083); among women, the LKM practitioners had significantly longer RTL than controls, (p=.007), which remained significant even after controlling for BMI and past depression. Although limited by small sample size, these results offer the intriguing possibility that LKM practice, especially in women, might alter RTL, a biomarker associated with longevity. Copyright © 2013 Elsevier Inc. All rights reserved.
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-4502
Lifestyle recommendations to reduce the risk of kidney stones.
Kidney stones are increasingly common in wealthy industrialized countries. The most frequent form (80%) is idiopathic calcium stone disease. Eating habits and lifestyle have a direct effect on the lithogenic urinary risk factors and the pathogenesis of this condition. A diet characterized by a high intake of fluids, fruits, and vegetables; a low consumption of salt and protein; and a balanced intake of calcium, fats, and carbohydrates constitutes an efficacious approach to the prevention and treatment of this illness. A correct body weight, regular exercise, and a reduction in stressful life events are also useful preventive actions. Copyright © 2011 Elsevier Inc. All rights reserved.
MED-4320
Higher bioaccessibility of iron and zinc from food grains in the presence of garlic and onion.
Bioavailability of micronutrients iron and zinc is particularly low from plant foods. Hence there is a need to evolve a food-based strategy to improve the same to combat widespread deficiencies of these minerals in a population dependent on plant foods. Dietary sulfur-containing amino acids have been reported to improve the mineral status of experimental animals. Our objective was to examine whether sulfur compound-rich Allium spices have a similar potential of beneficially modulating the mineral bioavailability. In this context, we examined the influence of exogenously added garlic and onion on the bioaccessibility of iron and zinc from food grains. Two representative cereals and pulses each were studied in both raw and cooked condition employing two levels of garlic (0.25 and 0.5 g/10 g of grain) and onion (1.5 and 3 g/10 g of grain). The enhancing effect of these two spices on iron bioaccessibility was generally evidenced in the case of both the cereals (9.4-65.9% increase) and pulses (9.9-73.3% increase) in both raw and cooked conditions. The two spices similarly enhanced the bioaccessibility of zinc from the food grains, the extent of increase in cereals ranging from 10.4% to 159.4% and in pulses from 9.8% to 49.8%. Thus, both garlic and onion were evidenced here to have a promoting influence on the bioaccessibility of iron and zinc from food grains. This novel information has the potential application in evolving a food-based strategy to improve the bioavailability of trace minerals and hence contributes to the human health benefit.
MED-2525
A global survey of physicians' perceptions on cholesterol management: the From The Heart study.
AIMS: Guidelines for cardiovascular disease (CVD) prevention cite high levels of low-density lipoprotein cholesterol (LDL-C) as a major risk factor and recommend LDL-C goals for various risk groups. Lifestyle changes are advised as first-line treatment for patients with high cholesterol, and statins are recommended in high-risk patients. The From The Heart study investigated current practice for the diagnosis and treatment of high cholesterol, and attitudes towards management of the condition. METHODS: Physicians were randomly selected from 10 countries, and completed a confidential, semi-structured questionnaire. RESULTS: Of 2790 physicians agreeing to participate, 750 (27%) responded. Physicians rated CVD as the leading cause of death, although physicians (80%) perceived that cancer was the most feared illness among patients. Physicians (71%) believed smoking to be the greatest CVD risk factor, while only 50% thought high cholesterol was the greatest risk. Most physicians (81%) used guidelines to set cholesterol goals, primarily their national guidelines (34%) or the National Cholesterol Education Program Adult Treatment Panel III guidelines (24%). Although only 47% of patients reached and maintained their cholesterol goals, 61% of physicians believed that a sufficient number of patients achieved goals, and 53% did not feel frustrated that they could not always effectively treat patients with CVD. CONCLUSION: Results indicate discrepancies between guideline recommendations and clinical practice. Although physicians appreciate the risk of CVD, the importance of achieving healthy cholesterol levels for CVD prevention does not seem to be widely endorsed. There is a need for improved communication regarding the importance of cholesterol lowering and investigation of initiatives to improve goal achievement among physicians.
MED-2591
Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular ...
Low-carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or the metabolic syndrome (MS), their net effect on arterial wall function remains unclear. The objective was to evaluate the relation between dietary macronutrient composition and the small artery reactive hyperaemia index (saRHI), a marker of small artery endothelial function, in a cohort of patients at increased cardiovascular (CV) risk. The present cross-sectional study included 247 patients. Diet was evaluated by a 3-d food-intake register and reduced to a novel low-carbohydrate diet score (LCDS). Physical examination, demographic, biochemical and anthropometry parameters were recorded, and the saRHI was measured in each patient. Individuals in the lowest LCDS quartile (Q1, 45 % carbohydrate; 20 % protein; 32 % fat) had higher saRHI values than those in the top quartile (Q4, 29 % carbohydrate, 24 % protein, 40 % fat; 1.66 (sd 0.41) v. 1.52 (sd 0.22), P= 0.037). These results were particularly strong in patients with the MS (Q1 = 1.82 (sd 0.32) v. Q4 = 1.61 (sd 027); P= 0.021) and T2D (Q1 = 1.78 (sd 0.31) v. Q4 = 1.62 (sd 0.35); P= 0.011). Multivariate analysis demonstrated that individuals in the highest LCDS quartile had a significantly negative coefficient of saRHI, which was independent of confounders (OR -0.85; 95 % CI 0.19, 0.92; P= 0.031). These findings suggest that a dietary pattern characterised by a low amount of carbohydrate, but high amounts of protein and fat, is associated with a poorer small artery vascular reactivity in patients with increased CV risk.
MED-4198
Insect food for astronauts: gas exchange in silkworms fed on mulberry and lettuce and the nutritional value of these insects for human consumption ...
In this study, silkworm moth (Bombyx mori L.) larvae were regarded as an animal protein source for astronauts in the bioregenerative life support system during long-term deep space exploration in the future. They were fed with mulberry and stem lettuce leaves during the first three instars and the last two instars, respectively. In addition, this kind of environmental approach, which utilised inedible biomass of plants to produce animal protein of high quality, can likewise be applied terrestrially to provide food for people living in extreme environments and/or impoverished agro-ecosystems, such as in polar regions, isolated military bases, ships, submarines, etc. Respiration characteristics of the larvae during development under two main physiological conditions, namely eating and not-eating of leaves, were studied. Nutrient compositions of silkworm powder (SP), ground and freeze-dried silkworms on the 3rd day of the 5th instar larvae, including protein, fat, vitamins, minerals and fatty acids, were measured using international standard methods. Silkworms' respiration rates, measured when larvae were eating mulberry leaves, were higher than those of similar larvae that hadn't eaten such leaves. There was a significant difference between silkworms fed on mulberry leaves and those fed on stem lettuce in the 4th and 5th instars (P<0.01). Amounts of CO2 exhaled by the silkworms under the two physiological regimes differed from each other (P<0.01). There was also a significant difference between the amount of O2 inhaled when the insects were under the two physiological statuses (P<0.01). Moreover, silkworms' respiration quotient under the eating regime was larger than when under the not-eating regime. The SP was found to be rich in protein and amino acids in total; 12 essential vitamins, nine minerals and twelve fatty acids were detected. Moreover, 359 kcal could be generated per 100 gram of SP (dry weight).
MED-1624
Direct and indirect cellular effects of aspartame on the brain.
The use of the artificial sweetener, aspartame, has long been contemplated and studied by various researchers, and people are concerned about its negative effects. Aspartame is composed of phenylalanine (50%), aspartic acid (40%) and methanol (10%). Phenylalanine plays an important role in neurotransmitter regulation, whereas aspartic acid is also thought to play a role as an excitatory neurotransmitter in the central nervous system. Glutamate, asparagines and glutamine are formed from their precursor, aspartic acid. Methanol, which forms 10% of the broken down product, is converted in the body to formate, which can either be excreted or can give rise to formaldehyde, diketopiperazine (a carcinogen) and a number of other highly toxic derivatives. Previously, it has been reported that consumption of aspartame could cause neurological and behavioural disturbances in sensitive individuals. Headaches, insomnia and seizures are also some of the neurological effects that have been encountered, and these may be accredited to changes in regional brain concentrations of catecholamines, which include norepinephrine, epinephrine and dopamine. The aim of this study was to discuss the direct and indirect cellular effects of aspartame on the brain, and we propose that excessive aspartame ingestion might be involved in the pathogenesis of certain mental disorders (DSM-IV-TR 2000) and also in compromised learning and emotional functioning.
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-4202
Non-nutrient causes of low-grade, systemic inflammation: support for a 'canary in the mineshaft' view of obesity in chronic disease.
A form of low-grade, systemic inflammation ('metaflammation') is linked to many types of chronic disease. Initially, this was thought to be causally related to weight gain and obesity and a possible explanation of the link between obesity and disease. However, several lifestyle-related inducers of such inflammation, some of which are associated with obesity, but some of which are not, have now been identified. The most common of these have been nutritive related, suggesting that there could still be a relationship, either directly or indirectly, with obesity. Here we provide evidence for non-nutritive inflammatory inducers, providing further support for an earlier suggestion that while obesity, beyond a point, may have a direct link with disease, this may be neither necessary nor sufficient to explain the current epidemic of chronic disease. A more ubiquitous cause encompassing all inflammatory inducers is the modern, post-industrial environment and lifestyles emanating from this. Obesity may thus be more of 'a canary in the mineshaft', warning of bigger global problems, than just a single pathway to modern environmentally driven disease. © 2010 The Authors. obesity reviews © 2010 International Association for the Study of Obesity.
MED-4607
Effects of sorbic acid and its salts on chromosome aberrations, sister chromatid exchanges and gene mutations in cultured Chinese hamster cells.
The ability of sorbic acid and its potassium and sodium salts to induce chromosome aberrations, sister chromatid exchanges (SCE) and gene mutations in cultured Chinese hamster V79 cells was examined. Sodium sorbate caused significant induction of chromosome aberrations and SCE, and also induced 6-thioguanine-resistant mutations in a dose-dependent manner. The clastogenic potency of sodium sorbate was found to be less than one hundredth of that of the potent clastogen N-methyl-N'-nitro-N-nitrosoguanidine. The induction of SCE by sodium sorbate was twice the control level, whereas that by methyl methanesulphonate, a potent inducer of SCE, was 14 times the control level. The mutagenic potency of sodium sorbate was less than one-tenth that of ethyl methanesulphonate, a potent inducer of mutation, when compared at an equitoxic level. Sorbic acid and its potassium salt induced chromosome aberrations, but only at the highest doses tested. These compounds also induced 1.2 times the control level of SCE, but neither compound induced 6-thioguanine-resistant mutations. The cytogenetic activity of sodium sorbate was concluded not to be due to the effect of osmotic pressure or an impurity. These results indicate that sodium sorbate is a genotoxic agent, although its potency seems to be weak, and that sorbic acid and potassium sorbate are less genotoxic than the sodium salt.
MED-1153
ATTENTION DEFICIT/HYPERACTIVITY DISORDER AND URINARY METABOLITES OF ORGANOPHOSPHATE PESTICIDES IN U.S. CHILDREN 8–15 YEARS
Context Exposure to organophosphate (OP) pesticides is common, and although these compounds have known neurotoxic properties, few studies examined risks for children in the general population. Objective To examine the association between the concentrations of urinary dialkyl phosphate (DAP) metabolites of OPs and attention deficit/hyperactivity disorder (ADHD) in children age 8 to 15 years. Participants and Methods Cross-sectional data from the National Health and Nutrition Examination Survey (2000–2004) were available for 1,139 children representative of the general U.S. population. A structured interview with a parent was used to ascertain ADHD diagnostic status, based on slightly modified criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV. Results One hundred nineteen children met the diagnostic criteria for ADHD. Children with higher concentrations of urinary DAPs, especially dimethyl alkylphosphates (DMAP), were more likely to be diagnosed with ADHD. A 10-fold increase in DMAP concentration was associated with an odds ratio (OR) of 1.55 (95% confidence intervals [CI], 1.14–2.10), after adjusting for sex, age, race/ethnicity, poverty-income ratio, fasting duration, and urinary creatinine concentration. For the most commonly detected DMAP metabolite, dimethylthiophosphate, children with levels higher than the median of detectable concentrations had double the odds of ADHD (adjusted OR, 1.93 [95% CI, 1.23–3.02]) compared with those with non-detectable levels. Conclusions These findings support the hypothesis that OP exposure, at levels common in U.S. children, may contribute to ADHD prevalence. Prospective studies are needed to establish whether this association is causal.
MED-4197
Natural compounds in the human diet and their ability to bind mutagens prevents DNA-mutagen intercalation.
Human diet may contain many mutagenic or carcinogenic aromatic compounds as well as some beneficial physiologically active dietary components, especially plant food phytochemicals, which act as mutagenesis or carcinogenesis inhibitors. This study compared the binding properties of natural compounds in the human diet (caffeine, theophylline, theobromine, and resveratrol) with a water-soluble derivative of chlorophyll to bind to acridine orange, a known mutagen. An analysis was conducted to determine which substances were effective binding agents and may thus be useful in prevention of chemical-induced mutagenesis and carcinogenesis. Data indicated that in order to bind 50% of the mutagen in a complex, less than twice the concentration of chlorophyllin was needed, the resveratrol concentration was 20-fold higher, while a 1000-fold or even 10,000-fold excess of xanthines were required to bind acridine orange.
MED-4337
The capacity of foodstuffs to induce innate immune activation of human monocytes in vitro is dependent on food content of stimulants of Toll-like r...
The ingestion of fatty meals is associated with a transient, low-grade systemic inflammatory response in human subjects, involving the activation of circulating monocytes and the secretion of pro-inflammatory cytokines. However, it is not yet clear how different foodstuffs may promote inflammatory signalling. In a screen of forty filter-sterilised soluble extracts from common foodstuffs, seven were found to induce the secretion of TNF-α and IL-6 from human monocytes in vitro. To investigate what may differentiate inflammatory from non-inflammatory food extracts, stimulants of Toll-like receptor (TLR) 2 and TLR4 were quantified using human embryonic kidney-293 cells transfected with each TLR, and calibrated with defined bacterial lipopeptide (BLP) and lipopolysaccharide (LPS) standards. These assays revealed that while most foods contained undetectable levels of TLR2 or TLR4 stimulants, all TNF-α-inducing foods contained stimulants of either TLR2 (up to 1100 ng BLP-equivalent/g) or TLR4 (up to 2700 ng LPS-equivalent/g) in both the soluble and insoluble fractions. TLR stimulants were present mainly in meat products and processed foods, but were minimal or undetectable in fresh fruit and vegetables. The capacity of food extracts to induce TNF-α secretion in monocytes correlated with the content of both TLR2 (r 0·837) and TLR4 stimulants (r 0·748), and was completely abolished by specific inhibition of TLR2 and TLR4. LPS and BLP were found to be highly resistant to typical cooking times and temperatures, low pH and protease treatment. In conclusion, apparently unspoiled foodstuffs can contain large quantities of stimulants of TLR2 and TLR4, both of which may regulate their capacity to stimulate inflammatory signalling.
MED-1170
Parental occupational exposure to pesticides as risk factor for brain tumors in children and young adults: a systematic review and meta-analysis.
OBJECTIVE: To examine the potential association between parental occupational exposure to pesticides and the occurrence of brain tumors in children and young adults. METHODS: Studies identified from a MEDLINE search through 15 January 2013 and from the reference lists of identified publications were submitted to a systematic review and meta-analysis. Relative risk estimates were extracted from 20 studies published between 1974 and 2010. Most of the retrieved studies involved farm/agricultural jobs. Summary ratio estimates (SR) were calculated according to fixed and random-effect meta-analysis models. Separate analyses were conducted after stratification for study design, exposure parameters, disease definition, geographic location and age at diagnosis. RESULTS: Statistically significant associations were observed for parents potentially exposed to pesticides in occupational settings and the occurrence of brain tumor in their offspring after combining all case-control studies (summary odds ratio [SOR]: 1.30; 95%: 1.11, 1.53) or all cohort studies (summary rate ratio [SRR]: 1.53; 95% CI: 1.20, 1.95). Significantly increased risks were seen for prenatal exposure windows, for either exposed parent, for exposure defined as to pesticides as well as by occupational/industry title, for astroglial brain tumors and after combining case-control studies from North America or cohort studies from Europe. CONCLUSIONS: This meta-analysis supports an association between parental occupational exposure to pesticides and brain tumors in children and young adults, and adds to the evidence leading to the recommendation of minimizing (parental) occupational exposure to pesticides. These results must, however, be interpreted with caution because the impact of work-related factors others than pesticide exposure is not known. Copyright © 2013 Elsevier Ltd. All rights reserved.
MED-1741
Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase
Roundup is a glyphosate-based herbicide used worldwide, including on most genetically modified plants that have been designed to tolerate it. Its residues may thus enter the food chain, and glyphosate is found as a contaminant in rivers. Some agricultural workers using glyphosate have pregnancy problems, but its mechanism of action in mammals is questioned. Here we show that glyphosate is toxic to human placental JEG3 cells within 18 hr with concentrations lower than those found with agricultural use, and this effect increases with concentration and time or in the presence of Roundup adjuvants. Surprisingly, Roundup is always more toxic than its active ingredient. We tested the effects of glyphosate and Roundup at lower nontoxic concentrations on aromatase, the enzyme responsible for estrogen synthesis. The glyphosate-based herbicide disrupts aromatase activity and mRNA levels and interacts with the active site of the purified enzyme, but the effects of glyphosate are facilitated by the Roundup formulation in microsomes or in cell culture. We conclude that endocrine and toxic effects of Roundup, not just glyphosate, can be observed in mammals. We suggest that the presence of Roundup adjuvants enhances glyphosate bioavailability and/or bioaccumulation.
MED-3435
Increased risk of stroke among men with erectile dysfunction: a nationwide population-based study.
INTRODUCTION: Previous cross-sectional studies have suggested that erectile dysfunction (ED) represents an independent risk factor for future cardiovascular events. However, very few studies have attempted to examine the association between ED and subsequent stroke. AIM: The aim of this study is to estimate the risk of stroke during a 5-year follow-up period after the first ambulatory care visit for the treatment of ED using nationwide, population-based data and a retrospective case-control cohort design in Taiwan. METHODS: This study used data sourced from the "Longitudinal Health Insurance Database." The study cohort comprised 1,501 patients who received a principal diagnosis of ED between 1997 and 2001 and 7,505 randomly selected subjects as the comparison cohort. Each patient (N = 9,006) was then individually tracked for 5 years from their index ambulatory care visit to identify those who had diagnosed episodes of stroke. MAIN OUTCOME MEASURE: Stratified Cox proportional hazard regressions were performed as a means of comparing the 5-year stroke-free survival rate for the two cohorts. RESULTS: Of the sampled patients, 918 (10.2%) developed stroke within the 5-year follow-up period, that is, 188 individuals (12.5% of the patients with ED) from the study cohort and 730 individuals (9.7% of patients in the comparison cohort) from the comparison cohort. The log-rank test indicated that patients with ED had significantly lower 5-year stroke-free survival rates than those in the comparison cohort (P < 0.001). After adjusting for the patient's monthly income, geographical location, hypertension, diabetes, coronary heart disease, peripheral vascular disease, atrial fibrillation, and hyperlipidemia, patients with ED were more likely to have a stroke during the 5-year follow-up period than patients in the comparison cohort (hazard ratio = 1.29, 95% confidence interval = 1.08 - 1.54, P < 0.01). CONCLUSIONS: These results suggest that ED is a surrogate marker for future stroke in men. © 2010 International Society for Sexual Medicine.
MED-5235
Meat consumption, diabetes, and its complications.
Several prospective studies have reported that risk of type 2 diabetes (T2DM) is elevated in meat consumers, especially when processed meats are consumed. Elevated risks of coronary heart disease (CHD) and stroke in meat consumers have also been reported. In this overview, the evidence regarding meat consumption and the risk of diabetes, both type 1 diabetes (T1DM) and T2DM and their macro- and microvascular complications, is reviewed. For T2DM, we performed a new meta-analysis including publications up to October 2012. For T1DM, only a few studies have reported increased risks for meat consumers or for high intake of saturated fatty acids and nitrates and nitrites. For T2DM, CHD, and stroke, the evidence is strongest. Per 100 g of total meat, the pooled relative risk (RR) for T2DM is 1.15 (95 % CI 1.07-1.24), for (unprocessed) red meat 1.13 (95 % CI 1.03-1.23), and for poultry 1.04 (95 % CI 0.99-1.33); per 50 g of processed meat, the pooled RR is 1.32 (95 % CI 1.19-1.48). Hence, the strongest association regarding T2DM is observed for processed (red) meat. A similar observation has been made for CHD. For stroke, however, a recent meta-analysis shows moderately elevated risks for meat consumers, for processed as well as for fresh meats. For the microvascular complications of diabetes, few prospective data were available, but suggestions for elevated risks can be derived from findings on hyperglycemia and hypertension. The results are discussed in the light of the typical nutrients and other compounds present in meat--that is, saturated and trans fatty acids, dietary cholesterol, protein and amino acids, heme-iron, sodium, nitrites and nitrosamines, and advanced glycation end products. In light of these findings, a diet moderate to low in red meat, unprocessed and lean, and prepared at moderate temperatures is probably the best choice from the public health point of view.
MED-3676
Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and...
In a previous clinical study, a probiotic formulation (PF) consisting of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 (PF) decreased stress-induced gastrointestinal discomfort. Emerging evidence of a role for gut microbiota on central nervous system functions therefore suggests that oral intake of probiotics may have beneficial consequences on mood and psychological distress. The aim of the present study was to investigate the anxiolytic-like activity of PF in rats, and its possible effects on anxiety, depression, stress and coping strategies in healthy human volunteers. In the preclinical study, rats were daily administered PF for 2 weeks and subsequently tested in the conditioned defensive burying test, a screening model for anti-anxiety agents. In the clinical trial, volunteers participated in a double-blind, placebo-controlled, randomised parallel group study with PF administered for 30 d and assessed with the Hopkins Symptom Checklist (HSCL-90), the Hospital Anxiety and Depression Scale (HADS), the Perceived Stress Scale, the Coping Checklist (CCL) and 24 h urinary free cortisol (UFC). Daily subchronic administration of PF significantly reduced anxiety-like behaviour in rats (P < 0·05) and alleviated psychological distress in volunteers, as measured particularly by the HSCL-90 scale (global severity index, P < 0·05; somatisation, P < 0·05; depression, P < 0·05; and anger-hostility, P < 0·05), the HADS (HADS global score, P < 0·05; and HADS-anxiety, P < 0·06), and by the CCL (problem solving, P < 0·05) and the UFC level (P < 0·05). L. helveticus R0052 and B. longum R0175 taken in combination display anxiolytic-like activity in rats and beneficial psychological effects in healthy human volunteers.
MED-4907
Black rice anthocyanins inhibit cancer cells invasion via repressions of MMPs and u-PA expression.
Tumor metastasis is the most important cause of cancer death and various treatment strategies have targeted on preventing the occurrence of metastasis. Anthocyanins are natural colorants belonging to the flavonoid family, and are wildly used for their antioxidant properties. Here, we provided molecular evidence associated with the anti-metastatic effects of peonidin 3-glucoside and cyanidin 3-glucoside, major anthocyanins extracted from black rice (Oryza sativa L. indica), by showing a marked inhibition on the invasion and motility of SKHep-1 cells. This effect was associated with a reduced expression of matrix metalloproteinase (MMP)-9 and urokinase-type plasminogen activator (u-PA). Peonidin 3-glucoside and cyanidin 3-glucoside also exerted an inhibitory effect on the DNA binding activity and the nuclear translocation of AP-1. Furthermore, these compounds also exerted an inhibitory effect of cell invasion on various cancer cells (SCC-4, Huh-7, and HeLa). Finally, anthocyanins from O. sativa L. indica (OAs) were evidenced by its inhibition on the growth of SKHep-1 cells in vivo.