Diabetes as a Disease of Fat Toxicity
MED-1716
A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors
Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and biochemical studies establish the role of insulin and hyperinsulinaemia in cancer risk and progression. Insulin-like growth factors, IGF-1 and IGF-2, secreted by visceral or mammary adipose tissue have significant paracrine and endocrine effects. These effects can be exacerbated by increased steroid hormone production. Structural studies elucidate how each of the three ligands, insulin, IGF-1, and IGF-2, interacts differently with isoforms A and B of the insulin receptor and with type I IGF receptor and explain how these protagonists contribute to diabetes-associated cancer. The above should inform appropriate treatment of cancers that arise in obese individuals and in those with diabetes mellitus type 2. Novel drugs that target the insulin and insulin-like growth factor signal transduction pathways are in clinical trial and should be effective if appropriate biomarker-informed patient stratification is implemented.
MED-1236
Pathogenesis of type 2 diabetes: tracing the reverse route from cure to cause.
The metabolic abnormalities of type 2 diabetes can be reversed reproducibly by bariatric surgery. By quantifying the major pathophysiological abnormalities in insulin secretion and insulin action after surgery, the sequence of events leading to restoration of normal metabolism can be defined. Liver fat levels fall within days and normal hepatic insulin sensitivity is restored. Simultaneously, plasma glucose levels return towards normal. Insulin sensitivity of muscle remains abnormal, at least over the weeks and months after bariatric surgery. The effect of the surgery is explicable solely in terms of energy restriction. By combining this information with prospective observation of the changes immediately preceding the onset of type 2 diabetes, a clear picture emerges. Insulin resistance in muscle, caused by inherited and environmental factors, facilitates the development of fatty liver during positive energy balance. Once established, the increased insulin secretion required to maintain plasma glucose levels will further increase liver fat deposition. Fatty liver causes resistance to insulin suppression of hepatic glucose output as well as raised plasma triacylglycerol. Exposure of beta cells to increased levels of fatty acids, derived from circulating and locally deposited triacylglycerol, suppresses glucose-mediated insulin secretion. This is reversible initially, but eventually becomes permanent. The essential time sequence of the pathogenesis of type 2 diabetes is now evident. Muscle insulin resistance determines the rate at which fatty liver progresses, and ectopic fat deposition in liver and islet underlies the related dynamic defects of hepatic insulin resistance and beta cell dysfunction. These defects are capable of dramatic reversal under hypoenergetic feeding conditions, completely in early diabetes and to a worthwhile extent in more established disease.
MED-1237
Banting Memorial Lecture 2012 Reversing the twin cycles of Type 2 diabetes
It has become widely accepted that Type 2 diabetes is inevitably life-long, with irreversible and progressive beta cell damage. However, the restoration of normal glucose metabolism within days after bariatric surgery in the majority of people with Type 2 diabetes disproves this concept. There is now no doubt that this reversal of diabetes depends upon the sudden and profound decrease in food intake, and does not relate to any direct surgical effect. The Counterpoint study demonstrated that normal glucose levels and normal beta cell function could be restored by a very low calorie diet alone. Novel magnetic resonance methods were applied to measure intra-organ fat. The results showed two different time courses: a) resolution of hepatic insulin sensitivity within days along with a rapid fall in liver fat and normalisation of fasting glucose levels; and b) return of normal beta cell insulin secretion over weeks in step with a fall in pancreas fat. Now that it has been possible to observe the pathophysiological events during reversal of Type 2 diabetes, the reverse time course of events which determine the onset of the condition can be identified. The twin cycle hypothesis postulates that chronic calorie excess leads to accumulation of liver fat with eventual spill over into the pancreas. These self-reinforcing cycles between liver and pancreas eventually cause metabolic inhibition of insulin secretion after meals and onset of hyperglycaemia. It is now clear that Type 2 diabetes is a reversible condition of intra-organ fat excess to which some people are more susceptible than others.
MED-1238
Relationship of dietary fat to glucose metabolism.
The relationship between dietary fat and glucose metabolism has been recognized for at least 60 years. In experimental animals, high fat diets result in impaired glucose tolerance. This impairment is associated with decreased basal and insulin-stimulated glucose metabolism. Impaired insulin binding and/or glucose transporters has been related to changes in the fatty acid composition of the membrane induced by dietary fat modification. In humans, high-fat diets, independent of fatty acid profile, have been reported to result in decreased insulin sensitivity. Saturated fat, relative to monounsaturated and polyunsaturated fat, appears to be more deleterious with respect to fat-induced insulin insensitivity. Some of the adverse effects induced by fat feeding can be ameliorated with omega-3 fatty acid. Epidemiological data in humans suggest that subjects with higher intakes of fat are more prone to develop disturbances in glucose metabolism, type 2 diabetes or impaired glucose tolerance, than subjects with lower intakes of fat. Inconsistencies in the data may be attributable to clustering of high intakes of dietary fat (especially animal fat) with obesity and inactivity. Metabolic studies suggest that higher-fat diets containing a higher proportion of unsaturated fat result in better measures of glucose metabolism than high-carbohydrate diet. Clearly, the area of dietary fat and glucose metabolism has yet to be fully elucidated.
MED-1474
Free fatty acids and skeletal muscle insulin resistance.
PURPOSE OF REVIEW: Acute exposure to fatty acids causes insulin resistance in muscle, and excess dietary lipid and obesity are also strongly associated with muscle insulin resistance. Relevant mechanisms, however, are still not fully elucidated. Here we examine the latest evidence as to why lipids might accumulate in muscle and the possible mechanisms for lipid-induced insulin resistance. RECENT FINDINGS: Muscle lipid metabolites such as long chain fatty acid coenzyme As, diacylglycerol and ceramides may impair insulin signalling directly. Crosstalk between inflammatory signalling pathways and insulin signalling pathways, mitochondrial dysfunction and oxidative stress have also been put forward as major contributors to the development or maintenance of lipid-induced insulin resistance in muscle. Several animal models with gene deletions in pathways of fatty acid synthesis and storage also show increased metabolic rate, reduced intramuscular lipid storage and improved insulin action when challenged with a high lipid load. SUMMARY: Studies in genetic and dietary obese animal models, genetically modified animals and humans with obesity or type 2 diabetes suggest plausible mechanisms for effects of fatty acids, lipid metabolites, inflammatory pathways and mitochondrial dysfunction on insulin action in muscle. Many of these mechanisms, however, have been demonstrated in situations in which lipid accumulation (obesity) already exists. Whether the initial events leading to muscle insulin resistance are direct effects of fatty acids in muscle or are secondary to lipid accumulation in adipose tissue or liver remains to be clarified.
MED-1992
Prediabetes: A high-risk state for developing diabetes
Summary Prediabetes (or “intermediate hyperglycaemia”), based on glycaemic parameters above normal but below diabetes thresholds is a high risk state for diabetes with an annualized conversion rate of 5%–10%; with similar proportion converting back to normoglycaemia. The prevalence of prediabetes is increasing worldwide and it is projected that >470 million people will have prediabetes in 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction, abnormalities that start before glucose changes are detectable. Observational evidence shows associations of prediabetes with early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores could optimize the estimation of diabetes risk using non-invasive parameters and blood-based metabolic traits in addition to glycaemic values. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention with evidence of a 40%–70% relative risk reduction. Accumulating data also suggests potential benefits from pharmacotherapy.
MED-1876
Consumption of whole grain reduces risk of deteriorating glucose tolerance, including progression to prediabetes.
BACKGROUND: High whole-grain intake has been reportedly associated with reduced risk of developing type 2 diabetes (T2D), which is an effect possibly subject to genetic effect modification. Confirmation in prospective studies and investigations on the impact on prediabetes is needed. OBJECTIVES: In a prospective population-based study, we investigated whether a higher intake of whole grain protects against the development of prediabetes and T2D and tested for modulation by polymorphisms of the TCF7L2 gene. DESIGN: We examined the 8-10-y incidence of prediabetes (impaired glucose tolerance, impaired fasting glucose, or the combination of both) and T2D in relation to the intake of whole grain. Baseline data were available for 3180 women and 2297 men aged 35-56 y. RESULTS: A higher intake of whole grain (>59.1 compared with <30.6 g/d) was associated with a 34% lower risk to deteriorate in glucose tolerance (to prediabetes or T2D; women and men combined). The association remained after adjustments for age, family history of diabetes, BMI, physical activity, smoking, education, and blood pressure (OR: 0.78; 95% CI: 0.63, 0.96). Risk reduction was significant in men (OR: 0.65; 95% CI: 0.49, 0.85) but not in women. Associations were significant for prediabetes per se (all, OR: 0.73; 95% CI: 0.56, 0.94; men, OR: 0.57; 95% CI: 0.40, 0.80). The intake of whole grain correlated inversely with insulin resistance (HOMA-IR). The impact of whole-grain intake was undetectable in men who harbored diabetogenic polymorphisms of the TCF7L2 gene. CONCLUSIONS: A higher intake of whole grain is associated with decreased risk of deteriorating glucose tolerance including progression from normal glucose tolerance to prediabetes by mechanisms likely tied to effects on insulin sensitivity. Effect modifications by TCF7L2 genetic polymorphisms are supported.
MED-1998
The early treatment of type 2 diabetes.
The growing epidemic of type 2 diabetes is one of the leading causes of premature morbidity and mortality worldwide, mainly due to the micro- and macrovascular complications associated with the disease. A growing body of evidence suggests that although the risk of developing complications is greater with glucose levels beyond the established threshold for diagnosis--increasing in parallel with rising hyperglycemia-individuals with glucose levels in the prediabetic range are already at increased risk. Early intervention, ideally as soon as abnormalities in glucose homeostasis are detected, is of great importance to minimize the burden of the disease. However, as the early stages of the disease are asymptomatic, diagnosing prediabetes and early overt type 2 diabetes is challenging. The aim of this article is to discuss these challenges, the benefits of early intervention--with emphasis on the prevention trials showing that progression to type 2 diabetes can be delayed by addressing prediabetes--and the existing evidence-based guidelines that have been drawn to optimize the standards of care at the prediabetes and overt type 2 diabetes stages. Copyright © 2013. Published by Elsevier Inc.
MED-1878
Crossing the Quality Chasm: A New Health System for the 21st Century
Excerpt Second in a series of publications from the Institute of Medicine's Quality of Health Care in America project Today's health care providers have more research findings and more technology available to them than ever before. Yet recent reports have raised serious doubts about the quality of health care in America. Crossing the Quality Chasm makes an urgent call for fundamental change to close the quality gap. This book recommends a sweeping redesign of the American health care system and provides overarching principles for specific direction for policymakers, health care leaders, clinicians, regulators, purchasers, and others. In this comprehensive volume the committee offers: A set of performance expectations for the 21st century health care system. A set of 10 new rules to guide patient-clinician relationships. A suggested organizing framework to better align the incentives inherent in payment and accountability with improvements in quality. Key steps to promote evidence-based practice and strengthen clinical information systems. Analyzing health care organizations as complex systems, Crossing the Quality Chasm also documents the causes of the quality gap, identifies current practices that impede quality care, and explores how systems approaches can be used to implement change. Copyright 2001 by the National Academy of Sciences. All rights reserved.
MED-1879
Daily flaxseed consumption improves glycemic control in obese men and women with pre-diabetes: a randomized study.
The study hypothesis was that fasting glucose, insulin, fructosamine, C-reactive protein, and interleukin-6 decrease and adiponectin increases with daily flaxseed consumption in overweight or obese individuals with pre-diabetes. In this randomized, cross-over study overweight or obese men and postmenopausal women (n = 25) with pre-diabetes consumed 0, 13, or 26 g ground flaxseed for 12 weeks. Glucose, insulin, homeostatic model assessment (HOMA-IR), and normalized percent of α-linolenic fatty acid (ALA) were significantly different by treatment (multiple analysis of variance, P = .036, P = .013, P = .008, P = .024 respectively). Paired t tests showed glucose decreased on the 13 g intervention compared to the 0 g period [13 g = -2.10 ± 1.66 mg/L (mean ± SEM), 0 g = 9.22 ± 4.44 mg/L, P = .036]. Insulin decreased on the 13 g intervention but not the 26 g (P = .021) and 0 g (P = .013) periods (13 g = -2.12 ± 1.00 mU/L, 26 g = 0.67 ± 0.84 mU/L, 0 g = 1.20 ± 1.16 mU/L). HOMA-IR decreased on the 13 g period but not on the 26 g (P = .012) and 0 g (P = .008) periods (13 g = -0.71 ± 0.31, 26 g = 0.27 ± 0.24, 0 g = 0.51 ± 0.35). The α-linolenic fatty acid decrease for the 0 g period was different than the 13 g (P = .024) and 26 g (P = .000) periods (13 g = 0.20 ± 0.04, 26 g = 0.35 ± 0.07, 0 g = -0.01 ± 0.07). Fructosamine, high sensitivity C-reactive protein, adiponectin, and high-sensitivity interleukin-6 had no significant differences. Flaxseed intake decreased glucose and insulin and improved insulin sensitivity as part of a habitual diet in overweight or obese individuals with pre-diabetes. Copyright © 2013 Elsevier Inc. All rights reserved.
MED-2405
Environmental contaminants as risk factors for developing diabetes.
The contribution of exposure to persistent organic pollutants (POPs) to the incidence of diabetes has received little attention until recently. A number of reports have emerged, however, concerning elevated diabetes in persons occupationally exposed to dioxin. United States (US) Air Force personnel in Vietnam who sprayed Agent Orange containing dioxin as a contaminant had elevated rates of diabetes, leading to US government compensation for diabetes in these veterans. Recent studies in populations exposed to polychlorinated biphenyls (PCBs) and chlorinated pesticides found a dose-dependent elevated risk of diabetes. An elevation in risk of diabetes in relation to levels of several POPs has been demonstrated by two different groups using the National Health and Nutrition Examination Survey (NHANES), a random sampling of US citizens. The strong associations seen in quite different studies suggest the possibility that exposure to POPs could cause diabetes. One striking observation is that obese persons that do not have elevated POPs are not at elevated risk of diabetes, suggesting that the POPs rather than the obesity per se is responsible for the association. Although a specific mechanism is not known, most POPs induce a great number and variety of genes, including several that alter insulin action. Because diabetes is a dangerous disease that is increasing in frequency throughout the world, further study of the possibility that exposure to POPs contributes to the etiology of diabetes is critical.
MED-2406
Fish and Marine Omega-3 Polyunsatured Fatty Acid Consumption and Incidence of Type 2 Diabetes: A Systematic Review and Meta-Analysis
Objective. To examine the association between fish and marine long-chain omega-3 polyunsaturated fatty acid (LC n-3 PUFA) consumption and incidence of type 2 diabetes (T2D) in prospective cohort studies. Methods. Meta-analytic procedures were used to estimate the relative risk (RR) using random effects or fixed effects generic inverse variance model. Publication bias and study heterogeneity were assessed using Egger's test and I2 statistic. Results. We found no significant association between the intake of fish/seafood (pooled RR: 1.04; P = 0.63, 95% CI: 0.9 to 1.2, 549, 955 participants) or marine LC n-3 PUFA (pooled RR: 1.08, P = 0.39, 95% CI: 0.90 to 1.30, 346, 710 participants) and T2D risk. Significant study heterogeneity was observed in fish/seafood and marine LC n-3 PUFA studies (P < 0.00001). Subgroup analysis revealed no obvious sources for high heterogeneity. We also found a significant protective effect of oily fish intake on T2D risk (pooled RR = 0.89, P = 0.005, 95% CI: 0.82 to 0.96). Dose-response analysis suggested that every 80 g per day intake of oily fish may reduce 20% risk of T2D. Conclusion. We found no significant effect of fish/seafood or marine LC n-3 PUFA intake on risk of T2D but a significant effect of oily fish intake on risk of T2D.
MED-2407
Public health concern behind the exposure to persistent organic pollutants and the risk of metabolic diseases
Background Persistent organic pollutants (POPs) are hazardous chemicals omnipresent in our food chain, which have been internationally regulated to ensure public health. Initially described for their potency to affect reproduction and promote cancer, recent studies have highlighted an unexpected implication of POPs in the development of metabolic diseases like type 2 diabetes and obesity. Based on this novel knowledge, this article aims at stimulating discussion and evaluating the effectiveness of current POP legislation to protect humans against the risk of metabolic diseases. Furthermore, the regulation of POPs in animal food products in the European Union (EU) is addressed, with a special focus on marine food since it may represent a major source of POP exposure to humans. Discussion There is mounting scientific evidence showing that current POP risk assessment and regulation cannot effectively protect humans against metabolic disorders. Better regulatory control of POPs in dietary products should be of high public health priority. Summary The general population is exposed to sufficient POPs, both in term of concentration and diversity, to induce metabolic disorders. This situation should attract the greatest attention from the public health and governmental authorities.
MED-3028
Fish Consumption, Dietary Long-Chain n-3 Fatty Acids, and Risk of Type 2 Diabetes
OBJECTIVE The evidence on the association between fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes is inconsistent. We therefore performed a systematic review and meta-analysis of the available prospective evidence. RESEARCH DESIGN AND METHODS Studies were identified by searching the PubMed and EMBASE databases through 15 December 2011 and by reviewing the reference lists of retrieved articles. Prospective studies were included if they reported relative risk (RR) estimates with 95% CIs for the association between fish consumption and/or dietary long-chain n-3 fatty acids and incidence of type 2 diabetes. A dose-response random-effects model was used to combine study-specific RRs. Potential sources of heterogeneity were explored by prespecified stratifications. RESULTS Sixteen studies involving 527,441 participants and 24,082 diabetes cases were included. Considerable statistical heterogeneity in the overall summary estimates was partly explained by geographical differences. For each serving per week increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02–1.09), 1.03 (0.96–1.11), and 0.98 (0.97–1.00) combining U.S., European, and Asian/Australian studies, respectively. For each 0.30 g per day increment in long-chain n-3 fatty acids, the corresponding summary estimates were 1.17 (1.09–1.26), 0.98 (0.70–1.37), and 0.90 (0.82–0.98). CONCLUSIONS Results from this meta-analysis indicate differences between geographical regions in observed associations of fish consumption and dietary intake of long-chain n-3 fatty acids with risk of type 2 diabetes. In consideration of the heterogeneous results, the relationship warrants further investigation. Meanwhile, current public health recommendations on fish consumption should be upheld unchanged.
MED-2409
Marine N-3 Polyunsaturated Fatty Acids Are Inversely Associated with Risk of Type 2 Diabetes in Asians: A Systematic Review and Meta-Analysis
Background Prospective cohort studies in relation to the associations between n-3 polyunsaturated fatty acids (PUFA) and risk of type 2 diabetes (T2D) were inconsistent. Differences in tissue n-3 PUFA compositions in subjects with and without T2D were also inconsistent in both cohort and case-control studies. We conducted a systematic review and meta-analysis of prospective cohort studies to examine the associations of fish and n-3 PUFA intake with T2D risk. The differences in tissue n-3 PUFA compositions in subjects with and without T2D were investigated based on cohort and case-control studies. Methods and Findings PubMed, Embase, Cochrane library, China National Knowledge Infrastructure (CNKI) and Chinese VIP database up to January 2012 was used to identify relevant studies, and reference lists from retrieved studies were reviewed. Two authors independently extracted the data. Random-effects models were used to pool the summary relative risk (RR). Twenty-four studies including 24,509 T2D patients and 545,275 participants were identified. For cohort studies, the summary RR of T2D for the highest vs lowest categories of total fish, marine n-3 PUFA and alpha-linolenic acid intake was 1.07 (95% CI: 0.91, 1.25), 1.07 (95% CI: 0.95, 1.20) and 0.93 (95% CI: 0.81, 1.07), respectively. Subgroup analyses indicated that summary RR (highest vs lowest category) of T2D for fish and marine n-3 PUFA intake was 0.89 (95% CI: 0.81, 0.98) and 0.87 (95% CI: 0.79, 0.96) for Asian populations, and 1.20 (95% CI: 1.01, 1.44) and 1.16 (95% CI: 1.04, 1.28) for Western populations. Asian subjects with T2D had significantly lower tissue compositions of C22∶6n-3 (SMD: −1.43; 95% CI: −1.75, −1.12) and total n-3 PUFA (SMD: −1.41; 95% CI: −2.23, −0.59) compared with those without T2D. Conclusion This systematic review and meta-analysis provides evidence that marine n-3 PUFA have beneficial effects on the prevention of T2D in Asian populations.
MED-2410
Fish consumption, insulin sensitivity and beta-cell function in the Insulin Resistance Atherosclerosis Study (IRAS)
Background and aims Previous research on the association between fish consumption and incident type 2 diabetes has been inconclusive. In addition, few studies have investigated how fish consumption may be related to the metabolic abnormalities underlying diabetes. Therefore, we examined the association of fish consumption with measures of insulin sensitivity and beta-cell function in a multi-ethnic population. Methods and results We examined the cross-sectional association between fish consumption and measures of insulin sensitivity and secretion in 951 non-diabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS). Fish consumption, categorized as <2 vs. ≥2 portions/week, was measured using a validated food frequency questionnaire. Insulin sensitivity (SI) and acute insulin response (AIR) were determined from frequently sampled intravenous glucose tolerance tests. Higher fish consumption was independently associated with lower SI-adjusted AIR (β=−0.13 [−0.25, −0.016], p=0.03, comparing ≥ 2 vs. <2 portions/week). Fish consumption was positively associated with intact and split proinsulin/C-peptide ratios, however, these associations were confounded by ethnicity (multivariable-adjusted β=0.073 [−0.014, 0.16] for intact proinsulin/C-peptide ratio, β=0.031 [−0.065, 0.13] for split proinsulin/C-peptide ratio). We also observed a significant positive association between fish consumption and fasting blood glucose (multivariable-adjusted β=2.27 [0.68, 3.86], p=0.005). We found no association between fish consumption and SI (multivariable-adjusted β= −0.015 [−0.083, 0.053]) or fasting insulin (multivariable-adjusted β=0.016 [−0.066, 0.10]). Conclusions Fish consumption was not associated with measures of insulin sensitivity in the multi-ethnic IRAS cohort. However, higher fish consumption may be associated with pancreatic beta-cell dysfunction.
MED-2411
Omega-3 Fatty Acids and incident Type 2 Diabetes: A Systematic Review and Meta-Analysis
The relationship between omega-3 polyunsaturated fatty acids (n-3 PUFA) from seafood (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) or plant (alpha-linolenic acid, ALA) sources and risk of type 2 diabetes mellitus (DM) remains unclear. We systematically searched multiple literature databases through June 2011 to identify prospective studies examining relations of dietary n-3 PUFA, dietary fish and/or seafood, and circulating n-3 PUFA biomarkers with incidence of DM. Data were independently extracted in duplicate by 2 investigators, including multivariate-adjusted relative risk (RR) estimates and corresponding 95% CIs. Generalized least-squares trend estimation was used to assess dose-response relationships, with pooled summary estimates calculated by both fixed-effect and random-effect models. From 288 identified abstracts, 16 studies met inclusion criteria, including 18 separate cohorts comprising 540,184 individuals and 25,670 cases of incident DM. Consumption of fish and/or seafood was not significantly associated with DM (n=13 studies; RR per 100g/d=1.12, 95% CI=0.94, 1.34); nor were consumption of EPA+DHA (n=16 cohorts; RR per 250mg/d=1.04, 95% CI=0.97, 1.10) or circulating levels of EPA+DHA biomarkers (n=5 cohorts; RR per 3% of total fatty acids=0.94, 95% CI=0.75, 1.17). Both dietary ALA (n=7 studies; RR per 0.5g/d=0.93, 95% CI=0.83, 1.04) and circulating ALA biomarker levels (n=6 studies; RR per 0.1% of total fatty acid=0.90, 95% CI=0.80, 1.00, P=0.06) were associated with non-significant trend towards lower risk of DM. Substantial heterogeneity (I2~80%) was observed among studies of fish/seafood or EPA+DHA and DM; moderate heterogeneity (<55%) was seen for dietary and biomarker ALA and DM. In unadjusted meta-regressions, study location (Asia vs. North America/Europe), mean BMI, and duration of follow-up each modified the association between fish/seafood and EPA+DHA consumption and DM risk (P-Interaction ≤ 0.02 each). We had limited statistical power to determine the independent effect of these sources of heterogeneity due to their high collinearity. The overall pooled findings do not support either major harms or benefits of fish/seafood or EPA+DHA on development of DM, and suggest that ALA may be associated with modestly lower risk. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation.
MED-2412
Fish oil supplementation in type 2 diabetes: a quantitative systematic review.
OBJECTIVE: To determine the effects of fish oil supplementation on lipid levels and glycemic control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: A comprehensive search of Medline, Embase, Lilacs, the Cochrane Clinical Trials Registry bibliographies of relevant papers, and expert input updated through September 1998 was undertaken. All randomized placebo-controlled trials were included in which fish oil supplementation was the only intervention in subjects with type 2 diabetes. Three investigators performed data extraction and quality scoring independently with discrepancies resolved by consensus. Eighteen trials including 823 subjects followed for a mean of 12 weeks were included. Doses of fish oil used ranged from 3 to 18 g/day The outcomes studied were glycemic control and lipid levels. RESULTS: Meta-analysis of pooled data demonstrated a statistically significant effect of fish oil on lowering triglycerides (-0.56 mmol/l [95% CI -0.71 to -0.41]) and raising LDL cholesterol (0.21 mmol/l [0.02 to 0.41]). No statistically significant effect was observed for fasting glucose. HbA1c total cholesterol, or HDL cholesterol. The triglyceride-lowering effect and the elevation in LDL cholesterol were most marked in those trials that recruited hypertriglyceridemic subjects and used higher doses of fish oil. Heterogeneity was observed and explained by the recruitment of subjects with baseline hypertriglyceridemia in some studies. CONCLUSIONS: Fish oil supplementation in type 2 diabetes lowers triglycerides, raises LDL cholesterol, and has no statistically significant effect on glycemic control. Trials with hard clinical end points are needed.
MED-2413
Association of fish and n-3 fatty acid intake with the risk of type 2 diabetes: a meta-analysis of prospective studies.
Results from observational studies on the association of fish and n-3 fatty acid consumption with type 2 diabetes mellitus (T2DM) risk are conflicting. Hence, a meta-analysis was performed to investigate this association from cohort studies. A comprehensive search was then conducted to identify cohort studies on the association of fish and/or n-3 fatty acid intake with T2DM risk. In the highest v. lowest categorical analyses, the fixed or random-effect model was selected based on the homogeneity test among studies. Linear and non-linear dose-response relationships were also assessed by univariate and bivariate random-effect meta-regression with restricted maximum likelihood estimation. In the highest v. lowest categorical analyses, the pooled relative risk (RR) of T2DM for intake of fish and n-3 fatty acid was 1·146 (95 % CI 0·975, 1·346) and 1·076 (95 % CI 0·955, 1·213), respectively. In the linear dose-response relationship, the pooled RR for an increment of one time (about 105 g)/week of fish intake (four times/month) and of 0·1 g/d of n-3 fatty acid intake was 1·042 (95 % CI 1·026, 1·058) and 1·057 (95 % CI 1·042, 1·073), respectively. The significant non-linear dose-response associations of fish and n-3 fatty acid intake with T2DM risk were not observed. The present evidence from observational studies suggests that the intake of both fish and n-3 fatty acids might be weakly positively associated with the T2DM risk. Further studies are needed to confirm these results.
MED-2973
Egg consumption and the risk of type 2 diabetes mellitus: a case-control study.
OBJECTIVE: Type 2 diabetes mellitus appears to involve an interaction between susceptible genetic backgrounds and environmental factors including highly calorific diets. As it is important to identify modifiable risk factors that may help reduce the risk of type 2 diabetes mellitus, the aim of the present study was to determine the association between egg consumption and the risk of type 2 diabetes mellitus. DESIGN: A specifically designed questionnaire was used to collect information on possible risk factors of type 2 diabetes mellitus. The odds ratios and 95 % confidence intervals for type 2 diabetes mellitus were calculated by conditional logistic regression. SETTING: A case-control study in a Lithuanian out-patient clinic was performed in 2001. SUBJECTS: A total of 234 cases with a newly confirmed diagnosis of type 2 diabetes mellitus and 468 controls free of the disease. RESULTS: Variables such as BMI, family history of diabetes, cigarette smoking, education, morning exercise and plasma TAG level were retained in multivariate logistic regression models as confounders because their inclusion changed the value of the odds ratio by more than 10 % in any exposure category. After adjustment for possible confounders more than twofold increased risk of type 2 diabetes mellitus was determined for individuals consuming 3-4·9 eggs/week (OR = 2·60; 95 % CI 1·34, 5·08) and threefold increased risk of the disease was determined for individuals consuming ≥5 eggs/week (OR = 3·02; 95 % CI 1·14, 7·98) compared with those eating <1 egg/week. CONCLUSIONS: Our data support a possible relationship of egg consumption and increased risk of type 2 diabetes mellitus.
MED-5124
Egg Consumption and Cardiovascular Disease and Mortality The Physicians' Health Study
Background Reduction in dietary cholesterol is recommended to prevent cardiovascular disease (CVD). Although eggs are important sources of cholesterol and other nutrients, limited and inconsistent data are available on the effects of egg consumption on the risk of CVD and mortality. Objectives To examine the association between egg consumption and the risk of CVD and mortality. Design Prospective cohort study of 21,327 participants from the Physicians' Health Study I. Egg consumption was assessed using a simple abbreviated food questionnaire. We used Cox regression to estimate relative risks. Results After an average follow up of 20 years, a total of 1,550 new myocardial infarction (MI), 1,342 incident strokes, and 5,169 deaths occurred in this cohort. Egg consumption was not associated with incident MI or stroke in a multivariable Cox regression. In contrast, adjusted hazard ratios (95% CI) for mortality were 1.0 (reference), 0.94 (0.87-1.02), 1.03 (0.95-1.11), 1.05 (0.93-1.19), and 1.23 (1.11-1.36) for egg consumption of <1, 1, 2-4, 5-6, and 7+ per week, respectively, (p for trend <0.0001). This association was stronger among diabetic subjects with a 2-fold increased risk of death comparing the highest to the lowest category of egg consumption than non-diabetic subjects (HR: 1.22 (1.09-1.35) (p for interaction 0.09). Conclusions Our data suggest that infrequent egg consumption does not influence the risk of CVD and only confers a modest increased risk for total mortality in male physicians. In addition, egg consumption was positively related to mortality and such relation was stronger among diabetic subjects in this selective population.
MED-2975
Egg consumption and the risk of diabetes in adults, Jiangsu, China.
BACKGROUND: Although egg consumption has been associated with elevated plasma levels of cholesterol and triglyceride and with risk of cardiovascular disease in some populations, epidemiologic studies on egg consumption and the risk of diabetes are extremely sparse, particularly in the Chinese population. METHOD: Data from a household survey in the year 2002 among 2849 adults aged ≥20 y from a nationally representative sample in Jiangsu Province, China, were used. Dietary information was assessed by a validated food frequency questionnaire and 3 d weighed food records. Fasting blood specimens were collected. RESULTS: After the adjustment for age, total calorie intake, education, smoking, family history of diabetes, and sedentary activity, egg consumption was significantly and positively associated with diabetes risk, particularly in women. The odds ratios (OR) (95% CI) of diabetes associated with egg consumption <2/wk, 2-6/wk, and ≥1/d in the total sample were 1.00, 1.75, 2.28 (1.14-4.54), respectively (P for trend 0.029). Corresponding ORs (95% CI) in women were 1.00, 1.66, and 3.01 (1.12, 8.12), respectively (P for trend 0.022). Additional adjustment of body mass index attenuated the association, but it remained significant. There was a similar, however, not statistically significant association in men. In addition, plasma triglyceride and total cholesterol levels were significantly higher in women who consumed ≥2 eggs/wk than those who consumed eggs less often. CONCLUSION: Egg consumption was positively associated with the risk of diabetes among the Chinese, particularly in women. Copyright Â© 2011 Elsevier Inc. All rights reserved.
MED-2976
Egg consumption and risk of type 2 diabetes in older adults
Background: Type 2 diabetes (T2D) remains an important public health issue in the United States. There are limited and inconsistent data on the association between egg consumption and fasting glucose or incident diabetes. Objectives: We assessed the association between egg intake and incident diabetes in older adults. Design: In this prospective study of 3898 men and women from the Cardiovascular Health Study (1989–2007), we assessed egg consumption by using a picture-sorted food questionnaire and ascertained incident T2D annually by using information on hypoglycemic agents and plasma glucose. We used Cox proportional hazards models to estimate adjusted relative risks. Results: During a mean follow-up of 11.3 y, 313 new cases of T2D occurred. Crude incidence rates of T2D were 7.39, 6.83, 7.00, 6.72, and 12.20 per 1000 person-years in people who reported egg consumption of never, <1 egg/mo, 1–3 eggs/mo, 1–4 eggs/wk, and almost daily, respectively. In multivariable-adjusted models, there was no association between egg consumption and increased risk of T2D in either sex and overall. In a secondary analysis, dietary cholesterol was not associated with incident diabetes (P for trend = 0.47). In addition, egg consumption was not associated with clinically meaningful differences in fasting glucose, fasting insulin, or measures of insulin resistance despite small absolute analytic differences that were significant. Conclusion: In this cohort of older adults with limited egg intake, there was no association between egg consumption or dietary cholesterol and increased risk of incident T2D.
MED-2977
Egg Consumption and Risk of Type 2 Diabetes in Men and Women
OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of <1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend <0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend <0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.
MED-2978
High intakes of protein and processed meat associate with increased incidence of type 2 diabetes.
Diets high in protein have shown positive effects on short-term weight reduction and glycaemic control. However, the understanding of how dietary macronutrient composition relates to long-term risk of type 2 diabetes is limited. The aim of the present study was to examine intakes of macronutrients, fibre and protein sources in relation to incident type 2 diabetes. In total, 27 140 individuals, aged 45-74 years, from the population-based Malmö Diet and Cancer cohort, were included. Dietary data were collected with a modified diet history method, including registration of cooked meals. During 12 years of follow-up, 1709 incident type 2 diabetes cases were identified. High protein intake was associated with increased risk of type 2 diabetes (hazard ratio (HR) 1.27 for highest compared with lowest quintile; 95 % CI 1.08, 1.49; P for trend = 0.01). When protein consumption increased by 5 % of energy at the expense of carbohydrates (HR 1.20; 95 % CI 1.09, 1.33) or fat (HR 1.21; 95 % CI 1.09, 1.33), increased diabetes risk was observed. Intakes in the highest quintiles of processed meat (HR 1.16; 95 % CI 1.00, 1.36; P for trend = 0.01) and eggs (HR 1.21; 95 % CI 1.04, 1.41; P for trend = 0.02) were associated with increased risk. Intake of fibre-rich bread and cereals was inversely associated with type 2 diabetes (HR 0.84; 95 % CI 0.73, 0.98; P for trend = 0.004). In conclusion, results from the present large population-based prospective study indicate that high protein intake is associated with increased risk of type 2 diabetes. Replacing protein with carbohydrates may be favourable, especially if fibre-rich breads and cereals are chosen as carbohydrate sources.
MED-3866
Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design
Background Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Methods Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation. Results Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003). Conclusions The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.
MED-3867
High alpha-linolenic acid flaxseed (Linum usitatissimum): some nutritional properties in humans.
Although high alpha-linolenic acid flaxseed (Linum usitatissimum) is one of the richest dietary sources of alpha-linolenic acid and is also a good source of soluble fibre mucilage, it is relatively unstudied in human nutrition. Healthy female volunteers consumed 50 g ground, raw flaxseed/d for 4 weeks which provided 12-13% of energy intake (24-25 g/100 g total fat). Flaxseed raised alpha-linolenic acid and long-chain n-3 fatty acids in both plasma and erythrocyte lipids, as well as raising urinary thiocyanate excretion 2.2-fold. Flaxseed also lowered serum total cholesterol by 9% and low-density-lipoprotein-cholesterol by 18%. Changes in plasma alpha-linolenic acid were equivalent when 12 g alpha-linolenic acid/d was provided as raw flaxseed flour (50 g/d) or flaxseed oil (20 g/d) suggesting high bioavailability of alpha-linolenic acid from ground flaxseed. Test meals containing 50 g carbohydrate from flaxseed or 25 g flaxseed mucilage each significantly decreased postprandial blood glucose responses by 27%. Malondialdehyde levels in muffins containing 15 g flaxseed oil or flour/kg were similar to those in wheat-flour muffins. Cyanogenic glycosides (linamarin, linustatin, neolinustatin) were highest in extracted flaxseed mucilage but were not detected in baked muffins containing 150 g flaxseed/kg. We conclude that up to 50 g high-alpha-linolenic acid flaxseed/d is palatable, safe and may be nutritionally beneficial in humans by raising n-3 fatty acids in plasma and erythrocytes and by decreasing postprandial glucose responses.
MED-3868
Dietary milled flaxseed and flaxseed oil improve N-3 fatty acid status and do not affect glycemic control in individuals with well-controlled type ...
OBJECTIVE: To determine the effects of dietary consumption of milled flaxseed or flaxseed oil on glycemic control, n-3 fatty acid status, anthropometrics, and adipokines in individuals with type 2 diabetes. DESIGN: Thirty-four participants were randomized into a parallel, controlled trial. SUBJECTS: The participants were adults with type 2 diabetes (age 52.4 +/- 1.5 years, body mass index 32.4 +/- 1.0 kg/m(2), n = 17 men and 17 women). INTERVENTIONS: Participants consumed a selection of bakery products containing no flax (control group [CTL], n = 9), milled flaxseed (FXS, n = 13; 32 g/d), or flaxseed oil (FXO, n = 12; 13 g/d) daily for 12 weeks. The FXS and FXO groups received equivalent amounts of alpha-linolenic acid (ALA; 7.4 g/day). MEASURES OF OUTCOME: The primary outcome measures were fasting plasma hemoglobin A(1c), glucose, insulin, and phospholipid fatty acid composition. The secondary outcome measures were fasting circulating leptin and adiponectin, as well as body weight, body mass index, and waist circumference. Dietary intake assessment and calculations for homeostasis model assessment for insulin resistance and quantified insulin sensitivity check were also completed. RESULTS: The FXS and FXO groups had increases in plasma phospholipid n-3 fatty acids (ALA, eicosapentaenoic acid [EPA], or decosapentaenoic acid [DPA], but not docosahexaenoic acid), and the FXO group had more EPA and DPA in plasma phospholipids compared to the FXS group. All groups had similar caloric intakes; however, the CTL group experienced a 4% weight gain compared to baseline (p < 0.05), while both flax groups had constant body weights during the study period. All other parameters, including glycemic control, were unchanged by dietary treatment. CONCLUSIONS: Milled FXS and FXO intake does not affect glycemic control in adults with well-controlled type 2 diabetes. Possible prevention of weight gain by flax consumption warrants further investigation.
MED-3869
An open-label study on the effect of flax seed powder (Linum usitatissimum) supplementation in the management of diabetes mellitus.
Diabetes mellitus is characterized by hyperglycemia and associated with aberrations in the metabolism of carbohydrate, protein, and lipid that result in development of secondary complications. Extensive studies have indicated that nutritional therapy plays a pivotal role in the controlling or postponing of development of these secondary complications. Several functional foods have been shown to possess hypoglycemic and hypolipidemic properties. Flax seed (FS) is a functional food that is rich in omega 3 fatty acids and antioxidants and is low in carbohydrates. In exploratory studies, FS was incorporated in recipes, which resulted in a reduction in the glycemic index of the food items. These observations prompted us to investigate the efficacy of FS supplementation in type 2 diabetics (n = 29). Subjects were assigned to the experimental (n = 18) or the control group (n = 11) on the basis of their desire to participate in the study. The experimental group's diet was supplemented daily with 10 g of FS powder for a period of 1 month. The control group received no supplementation or placebo. During the study, diet and drug intake of the subjects remained unaltered. The efficacy of supplementation with FS was evaluated through a battery of clinico-biochemical parameters. Supplementation with FS reduced fasting blood glucose by 19.7% and glycated hemoglobin by 15.6%. A favorable reduction in total cholesterol (14.3%), triglycerides (17.5%), low-density lipoprotein cholesterol (21.8%), and apolipoprotein B and an increase in high-density lipoprotein cholesterol (11.9%) were also noticed. These observations suggest the therapeutic potential of FS in the management of diabetes mellitus.
MED-4543
Antitumour effects of Phyllanthus emblica L.: induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion o...
Phyllanthus emblica Linn. (PE) is a medicinal fruit used in many Asian traditional medicine systems for the treatment of various diseases including cancer. The present study tested the potential anticancer effects of aqueous extract of PE in four ways: (1) against cancer cell lines, (2) in vitro apoptosis, (3) mouse skin tumourigenesis and (4) in vitro invasiveness. The PE extract at 50-100 microg/mL significantly inhibited cell growth of six human cancer cell lines, A549 (lung), HepG2 (liver), HeLa (cervical), MDA-MB-231 (breast), SK-OV3 (ovarian) and SW620 (colorectal). However, the extract was not toxic against MRC5 (normal lung fibroblast). Apoptosis in HeLa cells was also observed as PE extract caused DNA fragmentation and increased activity of caspase-3/7 and caspase-8, but not caspase-9, and up-regulation of the Fas protein indicating a death receptor-mediated mechanism of apoptosis. Treatment of PE extract on mouse skin resulted in over 50% reduction of tumour numbers and volumes in animals treated with DMBA/TPA. Lastly, 25 and 50 microg/mL of PE extract inhibited invasiveness of MDA-MB-231 cells in the in vitro Matrigel invasion assay. These results suggest P. emblica exhibits anticancer activity against selected cancer cells, and warrants further study as a possible chemopreventive and antiinvasive agent. Copyright 2010 John Wiley & Sons, Ltd.
MED-4538
Effect of Amla fruit (Emblica officinalis Gaertn.) on blood glucose and lipid profile of normal subjects and type 2 diabetic patients.
The present study evaluated the anti-hyperglycemic and lipid-lowering properties of Emblica officinalis Gaertn. fruit in normal and diabetic human volunteers. The results indicated a significant decrease (P <  0.05) in fasting and 2-h post-prandial blood glucose levels on the 21st day in both normal and diabetic subjects receiving 1, 2 or 3 g E. officinalis powder per day as compared with their baseline values. Significant (P <  0.05) decreases were also observed in total cholesterol and triglycerides in both normal and diabetic volunteers on day 21 that were given either 2 or 3 g E. officinalis powder per day. However, diabetic volunteers receiving only 3 g E. officinalis powder exhibited a significant (P <  0.05) decrease in total lipids on day 21. Both normal and diabetic volunteers receiving 2 or 3 g E. officinalis powder significantly (P <  0.05) improved high-density lipoprotein-cholesterol and lowered low-density lipoprotein-cholesterol levels.
MED-975
Diverticular disease of the colon. The first of the Western diseases shown to be due to a deficiency of dietary fibre.
Diverticular disease of the colon is a new disease that appeared at the beginning of this century. It is now the commonest disease of the colon in the Western world, being found in 1 in 3 people of over 60 years of age. The pathogenesis of the disease involves excessive segmentation, but this does not explain its aetiology. The historical appearance of the disease on the clinical scene and its geographical distribution suggest that it is due to the removal of fibre from carbohydrates. The author treated 70 patients with symptomatic diverticular disease with a high-fibre diet. The results of this and the effects of bran are discussed.
MED-1980
Rapid Detection of Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae
Enterobacterial strains producing clavulanic-acid-inhibited extended-spectrum β-lactamases (ESBLs) are increasingly reported worldwide. Conventional detection of ESBL production remains time-consuming (24 to 48 h). Therefore, the ESBL NDP (Nordmann/Dortet/Poirel) test was developed for a rapid identification of ESBLs in Enterobacteriaceae. This biochemical test was based on the in vitro detection of a cephalosporin (cefotaxime) hydrolysis that is inhibited by tazobactam addition. The ESBL activity was evidenced by a color change (red to yellow) of a pH indicator (red phenol) due to carboxyl-acid formation resulting from cefotaxime hydrolysis that was reversed by addition of tazobactam (positive test). The ESBL NDP test was applied to cultured strains (215 ESBL producers and 40 ESBL nonproducers). Its sensitivity and specificity were 92.6% and 100%, respectively. Its sensitivity (100%) was excellent for detection of CTX-M producers. A few ESBL producers (n = 16) that remained susceptible to cefotaxime were not detected. The test was also evaluated on spiked blood cultures and showed excellent sensitivity and specificity (100% for both). The test was rapid (less than 1 h) and cost-effective. It can be implemented in any health care facility and is well adapted for infection control purposes in particular.
MED-720
The effect of oral alpha-galactosidase on intestinal gas production and gas-related symptoms.
Bloating, abdominal distention, and flatulence represent very frequent complaints in functional disorders but their pathophysiology and treatment are largely unknown. Patients frequently associate these symptoms with excessive intestinal gas and the reduction of gas production may represent an effective strategy. The aim was to evaluate the effect of alpha-galactosidase administration, in a randomized double-blind placebo-controlled protocol, on intestinal gas production and gas-related symptoms after a challenge test meal in healthy volunteers. Eight healthy volunteers ingested 300 or 1200 GalU of alpha-galactosidase or placebo during a test meal containing 420 g of cooked beans. Breath hydrogen excretion and occurrence of bloating, abdominal pain, discomfort, flatulence, and diarrhea were measured for 8 hr. The administration of 1200 GalU of alpha-galactosidase induced a significant reduction of both breath hydrogen excretion and severity of flatulence. A reduction in severity was apparent for all considered symptoms, but both 300 and 1200 GalU induced a significant reduction in the total symptom score. Alpha-galactosidase reduced gas production following a meal rich in fermentable carbohydrates and may be helpful in patients with gas-related symptoms.
MED-1151
Organic food consumption and the incidence of cancer in a large prospective study of women in the United Kingdom
Background: Organically produced foods are less likely than conventionally produced foods to contain pesticide residues. Methods: We examined the hypothesis that eating organic food may reduce the risk of soft tissue sarcoma, breast cancer, non-Hodgkin lymphoma and other common cancers in a large prospective study of 623 080 middle-aged UK women. Women reported their consumption of organic food and were followed for cancer incidence over the next 9.3 years. Cox regression models were used to estimate adjusted relative risks for cancer incidence by the reported frequency of consumption of organic foods. Results: At baseline, 30%, 63% and 7% of women reported never, sometimes, or usually/always eating organic food, respectively. Consumption of organic food was not associated with a reduction in the incidence of all cancer (n=53 769 cases in total) (RR for usually/always vs never=1.03, 95% confidence interval (CI): 0.99–1.07), soft tissue sarcoma (RR=1.37, 95% CI: 0.82–2.27), or breast cancer (RR=1.09, 95% CI: 1.02–1.15), but was associated for non-Hodgkin lymphoma (RR=0.79, 95% CI: 0.65–0.96). Conclusions: In this large prospective study there was little or no decrease in the incidence of cancer associated with consumption of organic food, except possibly for non-Hodgkin lymphoma.
MED-5222
Pharmaceutical and herbal products that may contribute to dry eyes.
BACKGROUND: Symptomatic dryness of the eyes is a most common blepharoplasty complication. The authors reviewed the medications and herbal products that may potentiate this complication. METHODS: The MEDLINE and PubMed databases were searched for the years 1991 to 2011. Search terms included "dry eye syndrome," "keratitis sicca," "keratoconjunctivitis sicca," "ocular side effects," "herbal supplements," "herbals and dry eye," "dry eye risk factors," "etiology of dry eye," "drugs side effects," "drugs and dry eye," "dietary supplements," "ocular toxicity," and "tear film." References from herbal product reviews and eligible medication reports were searched for additional articles. A manual search was also conducted based on citations in the published literature. RESULTS: Of 232 articles found to be related to dry eye syndrome and possible risk factors, 196 were excluded because they did not discuss medications or herbal products as risk factors in dry eye syndrome. Thirty-six articles that examined the pathophysiology and risk factors of dry eye were included. Nine books were reviewed that contained some information regarding the association of medications and herbal products with dry eye. These agents were then categorized based on mechanism of action and usage. Medications listed include antihistamines, decongestants, antidepressants, anticonvulsants, antipsychotics, antiparkinson drugs, beta-blockers, and hormone replacement therapy. The three main herbal products that contribute to dry eye are niacin, echinacea, and kava. There was a strong association between anticholinergic alkaloids and dry eye. CONCLUSION: This study identifies the medications and herbal products that should be considered when a patient undergoes blepharoplasty and complains of symptoms associated with dryness of the eyes.
MED-1258
The effect of combining plant sterols, soy protein, viscous fibers, and almonds in treating hypercholesterolemia.
Reductions in low-density lipoprotein-cholesterol (LDL-C) result from diets containing almonds, or diets that are either low in saturated fat or high in viscous fibers, soy proteins, or plant sterols. We have therefore combined all of these interventions in a single diet (portfolio diet) to determine whether cholesterol reductions could be achieved of similar magnitude to those reported in recent statin trials which reduced cardiovascular events. Twenty-five hyperlipidemic subjects consumed either a portfolio diet (n=13), very low in saturated fat and high in plant sterols (1.2 g/1,000 kcal), soy protein (16.2 g/1,000 kcal), viscous fibers (8.3 g/1,000 kcal), and almonds (16.6 g/1,000 kcal), or a low-saturated fat diet (n=12) based on whole-wheat cereals and low-fat dairy foods. Fasting blood, blood pressure, and body weight were obtained at weeks 0, 2, and 4 of each phase. LDL-C was reduced by 12.1% +/- 2.4% (P<.001) on the low-fat diet and by 35.0% +/- 3.1% (P<.001) on the portfolio diet, which also reduced the ratio of LDL-C to high-density lipoprotein-cholesterol (HDL-C) significantly (30.0% +/- 3.5%; P<.001). The reductions in LDL-C and the LDL:HDL-C ratio were both significantly lower on the portfolio diet than on the control diet (P<.001 and P<.001, respectively). Mean weight loss was similar on test and control diets (1.0 kg and 0.9 kg, respectively). No difference was seen in blood pressure, HDL-C, serum triglycerides, lipoprotein(a) [Lp(a)], or homocysteine concentrations between diets. Combining a number of foods and food components in a single dietary portfolio may lower LDL-C similarly to statins and so increase the potential effectiveness of dietary therapy.
MED-3794
Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms.
OBJECTIVE: To test the hypothesis that a low-fat, vegetarian diet reduces dysmenorrhea and premenstrual symptoms by its effect on serum sex-hormone binding globulin concentration and estrogen activity. METHODS: In a crossover design, 33 women followed a low-fat, vegetarian diet for two menstrual cycles. For two additional cycles, they followed their customary diet while taking a supplement placebo pill. Dietary intake, serum sex-hormone binding globulin concentration, body weight, pain duration and intensity, and premenstrual symptoms were assessed during each study phase. RESULTS: Mean (+/- standard deviation [SD]) serum sex-hormone binding globulin concentration was higher during the diet phase (46.7 +/- 23.6 nmol/L) than during the supplement phase (39.3 +/- 19.8 nmol/L, P < .001). Mean (+/- SD) body weight was lower during the diet (66.1 +/- 11.3 kg) compared with the supplement phase (67.9 +/- 12.1 kg, P < .001). Mean dysmenorrhea duration fell significantly from baseline (3.9 +/- 1.7 days) to diet phase (2.7 +/- 1.9 days) compared with change from baseline to supplement phase (3.6 +/- 1.7 days, P < .01). Pain intensity fell significantly during the diet phase, compared with baseline, for the worst, second-worst, and third-worst days, and mean durations of premenstrual concentration, behavioral change, and water retention symptoms were reduced significantly, compared with the supplement phase. CONCLUSION: A low-fat vegetarian diet was associated with increased serum sex-hormone binding globulin concentration and reductions in body weight, dysmenorrhea duration and intensity, and premenstrual symptom duration. The symptom effects might be mediated by dietary influences on estrogen activity.
MED-1061
Saturated fat intake and insulin resistance in men with coronary artery disease. The Stanford Coronary Risk Intervention Project Investigators and ...
BACKGROUND: To determine whether there is an association between diet and plasma insulin concentration that is independent of obesity, we studied the relation of dietary composition and caloric intake to obesity and plasma insulin concentrations in 215 nondiabetic men aged 32-74 years with angiographically proven coronary artery disease. METHODS AND RESULTS: After adjusting for age, the intake of saturated fatty acids and cholesterol were positively correlated (p less than 0.05) with body mass index (r = 0.18, r = 0.16), waist-to-hip circumference ratio (r = 0.21, r = 0.22), and fasting insulin (r = 0.26, r = 0.23). Carbohydrate intake was negatively correlated with body mass index (r = -0.21), waist-to-hip ratio (r = -0.21), and fasting insulin (r = -0.16). Intake of monounsaturated fatty acids did not correlate significantly with body mass index or waist-to-hip circumference ratio but did correlate positively with fasting insulin (r = 0.24). Intake of dietary calories was negatively correlated with body mass index (r = -0.15). In multivariate analysis, intake of saturated fatty acids was significantly related to elevated fasting insulin concentration independently of body mass index. CONCLUSIONS: These cross-sectional findings in nondiabetic men with coronary artery disease suggest that increased consumption of saturated fatty acids is associated independently with higher fasting insulin concentrations.
MED-2243
Turmeric and curcumin as topical agents in cancer therapy.
An ethanol extract of turmeric ("Curcuma longa") as well as an ointment of curcumin (its active ingredient) were found to produce remarkable symptomatic relief in patients with external cancerous lesions. Reduction in smell were noted in 90% of the cases and reduction in itching in almost all cases. Dry lesions were observed in 70% of the cases, and a small number of patients (10%) had a reduction in lesion size and pain. In many patients the effect continued for several months. An adverse reaction was noticed in only one of the 62 patients evaluated.
MED-5100
Public health guidance on cardiovascular benefits and risks related to fish consumption
Historically, concerns with fish consumption have addressed risks from contaminants (e.g., methylmercury (MeHg), and PCBs). More recently public health concerns have widened in appreciation of the specific benefits of fish consumption such as those arising from polyunsaturated fatty acids (PUFAs) in fish oil. Fish contains varying levels of PUFAs and MeHg. Since both address the same health outcomes (in opposite directions) and occur together in fish, great care must be exercised in providing public health guidance. Mozaffarian and Rimm in a recent article (JAMA. 2006, 296:1885–99) have made a strong case for the beneficial effects of PUFAs in reducing the risk of coronary heart disease, but at the same time, have also broadly discounted the increased risks of coronary heart disease posed by MeHg in fish, stating that "... among adults... the benefits of fish intake exceed the potential risks." This conclusion appears to be based on an inaccurate and insufficiently critical analysis of the literature. This literature is re-examined in light of their conclusions, and the available and appropriate public health options are considered.
MED-5175
Nutrition and lifestyle in relation to bowel movement frequency: a cross-sectional study of 20630 men and women in EPIC-Oxford.
OBJECTIVE: To investigate the relationships between nutritional and lifestyle factors and bowel movement frequency. DESIGN: Cross-sectional analysis using data from a prospective study. Mean numbers of bowel movements were calculated in relation to a range of factors. In addition, individuals were categorised according to frequency of bowel movements: fewer than 7 per week ('less than daily') versus 7 or more per week ('daily'), and odds ratios were calculated from logistic regression models. Results for each factor were adjusted for the other factors under consideration. SETTING: The European Prospective Investigation into Cancer and Nutrition, Oxford cohort (EPIC-Oxford), UK. PARTICIPANTS: In total, 20630 men and women aged 22-97 years at recruitment. Thirty per cent of the subjects were vegetarians or vegans. RESULTS: Women had fewer bowel movements on average than men, and were less likely to have daily bowel movements. Mean bowel movement frequency was higher in vegetarians (10.5 in men, 9.1 in women) and especially in vegans (11.6 in men, 10.5 in women) compared with participants who ate meat (9.5 in men, 8.2 in women). There were also significant positive associations between bowel movement frequency and body mass index (BMI), intakes of dietary fibre and non-alcoholic fluids, for both men and women. Vigorous exercise was positively associated with bowel movement frequency in women although results for men were less clear. Alcohol intake was positively associated with bowel movement frequency in men but not in women. CONCLUSION: Being vegetarian and especially vegan is strongly associated with a higher frequency of bowel movements. Moreover, having a high intake of dietary fibre and fluids and a high BMI are associated with an increase in frequency of bowel movements.
MED-5049
Association between soy and green tea (Camellia sinensis) diminishes hypercholesterolemia and increases total plasma antioxidant potential in dysli...
OBJECTIVE: To evaluate the hypolipemic and antioxidant effects of soy and green tea alone and/or in association in dyslipidemic subjects. METHODS: One hundred dyslipidemic individuals were allocated into four groups. The soy group ingested 50 g of soy (kinako) daily, and the green tea group ingested 3 g of green tea in 500 mL of water per day. A third group ingested 50 g of soy and 3 g of green tea daily, and the control group had a hypocholesterolemic diet. Evaluations were performed at baseline and after 45 and 90 d. Plasma levels of total cholesterol, high-density lipoprotein, and triacylglycerols were evaluated by automated methods. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. LDL was isolated by ultracentrifugation. Total plasma antioxidant capacity and plasma levels of total lipid hydroperoxides and those linked to LDL were evaluated by chemiluminescence. The results were expressed as median values and their 25th to 75th percentiles, with a 5% level of significance. RESULTS: No significant difference occurred in LDL, high-density lipoprotein cholesterol, and triacylglycerol levels across groups. However, a statistically significant difference in total cholesterol occurred within the soy/green tea group 45 and 90 d after intervention. No statistically significant difference occurred in plasma levels of lipid hydroperoxides or those linked to LDL in any of the groups studied. All the groups that used soy and/or green tea presented increased total plasma antioxidant potential. CONCLUSION: Soy and green tea, alone or in combination, increased the total antioxidant potential of hypercholesterolemic patients, whereas only the combination decreased total cholesterol levels.
MED-3847
Lignans in man and in animal species.
In our laboratories, for several years, two phenolic compounds have been detected during gas chromatographic-mass spectrometric analysis of urinary steroid extracts from human and animal species. Although features of the mass spectra of their trimethylsilyl (TMS) ether derivatives resembled those of oestrogens, they were atypical of steroids. The possibility that they were artefacts of the isolation procedures was discounted after careful studies with blanks, by varying the extraction method and because they were present almost exclusively as conjugates of glucuronic acid. Several of the general characteristics of the unknown compounds were reported after one (referred to as compound 180/442) was found to have a cyclic pattern of excretion during the menstrual cycle of an adult vervet monkey (Fig. 1). An investigation of the nature and distribution of the compounds has shown them to be urinary constituents in humans, baboons, vervet monkeys and rats, and further related compounds have been detected, so far only in vervet monkey urine. We now report spectroscopic and chemical studies that show the two original compounds to be lignans, which have a 2,3-dibenzylbutane skeleton as their basic structure. Unlike all previously known natural lignans, invariably of plant origin, the two mammalian compounds carry phenolic hydroxy groups only in the meta position of the aromatic rings.
MED-3498
Dietary acrylamide exposure of the French population: results of the second French Total Diet Study.
Acrylamide is a heat-induced carcinogen compound that is found in some foods consequently to cooking or other thermal processes. In the second French Total Diet Study (TDS), acrylamide was analysed in 192 food samples collected in mainland France to be representative of the population diet and prepared "as consumed". Highest mean concentrations were found in potato chips/crisps (954 μg/kg), French fries and other fried potatoes (724 μg/kg), and salted biscuits other than potato chips (697 μg/kg). Exposure of general adult and child populations was assessed by combining analytical results with national consumption data. Mean acrylamide exposure was assessed to be 0.43±0.33 μg/kg of body weight (bw) per day for adults and 0.69±0.58 μg/kg bw/day for children. Although the exposure assessed is lower than in previous evaluations, the calculated margins of exposure, based on benchmark dose limits defined for carcinogenic effects, remain very low especially for young children (below 100 at the 95th percentile of exposure), indicating a health concern. It is therefore advisable to continue efforts in order to reduce dietary exposure to acrylamide. Copyright Â© 2012 Elsevier Ltd. All rights reserved.
MED-4939
Dieldrin-induced neurotoxicity: relevance to Parkinson's disease pathogenesis.
Parkinson's disease (PD) is increasingly recognized as a neurodegenerative disorder strongly associated with environmental chemical exposures. Recent epidemiological data demonstrate that environmental risk factors may play a dominant role as compared to genetic factors in the etiopathogenesis of idiopathic Parkinson's disease. Identification of key genetic defects such as alpha-synuclein and parkin mutations in PD also underscores the important role of genetic factors in the disease. Thus, understanding the interplay between genes and environment in PD may be critical to unlocking the mysteries of this 200-year-old neurodegenerative disease. Pesticides and metals are the most common classes of environmental chemicals that promote dopaminergic degeneration. The organochlorine pesticide dieldrin has been found in human PD postmortem brain tissues, suggesting that this pesticide has potential to promote nigral cell death. Though dieldrin has been banned, humans continue to be exposed to the pesticide through contaminated dairy products and meats due to the persistent accumulation of the pesticide in the environment. This review summarizes various neurotoxic studies conducted in both cell culture and animals models following dieldrin exposure and discusses their relevance to key pathological mechanisms associated with nigral dopaminergic degeneration including oxidative stress, mitochondrial dysfunction, protein aggregation, and apoptosis.
MED-2042
Position statement. Part one: Immune function and exercise.
An ever-growing volume of peer-reviewed publications speaks to the recent and rapid growth in both scope and understanding of exercise immunology. Indeed, more than 95% of all peer-reviewed publications in exercise immunology (currently >2, 200 publications using search terms "exercise" and "immune") have been published since the formation of the International Society of Exercise and Immunology (ISEI) in 1989 (ISI Web of Knowledge). We recognise the epidemiological distinction between the generic term "physical activity" and the specific category of "exercise", which implies activity for a specific purpose such as improvement of physical condition or competition. Extreme physical activity of any type may have implications for the immune system. However, because of its emotive component, exercise is likely to have a larger effect, and to date the great majority of our knowledge on this subject comes from exercise studies.
MED-4710
Effect of pistachio diet on lipid parameters, endothelial function, inflammation, and oxidative status: a prospective study.
OBJECTIVE: Recent studies have suggested that nuts have favorable effects beyond lipid lowering. We aimed to investigate effect of the Antep pistachio (Pistacia vera L.) on blood glucose, lipid parameters, endothelial function, inflammation, and oxidation in healthy young men living in a controlled environment. METHODS: A Mediterranean diet was administered to normolipidemic 32 healthy young men (mean age 22 y, range 21-24) for 4 wk. After 4 wk, participants continued to receive the Mediterranean diet but pistachio was added for 4 wk by replacing the monounsaturated fat content constituting approximately 20% of daily caloric intake. Fasting blood samples and brachial endothelial function measurements were performed at baseline and after each diet. RESULTS: Compared with the Mediterranean diet, the pistachio diet decreased glucose (P<0.001, -8.8+/-8.5%), low-density lipoprotein (P<0.001, -23.2+/-11.9%), total cholesterol (P<0.001, -21.2+/-9.9%), and triacylglycerol (P=0.008, -13.8+/-33.8%) significantly and high-density lipoprotein (P=0.069, -3.1+/-11.7%) non-significantly. Total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios decreased significantly (P<0.001 for both). The pistachio diet significantly improved endothelium-dependent vasodilation (P=0.002, 30% relative increase), decreased serum interleukin-6, total oxidant status, lipid hydroperoxide, and malondialdehyde and increased superoxide dismutase (P<0.001 for all), whereas there was no significant change in C-reactive protein and tumor necrosis factor-alpha levels. CONCLUSION: In this trial, we demonstrated that a pistachio diet improved blood glucose level, endothelial function, and some indices of inflammation and oxidative status in healthy young men. These findings are in accordance with the idea that nuts, in particular pistachio nuts, have favorable effects beyond lipid lowering that deserve to be evaluated with prospective follow-up studies. Copyright 2010. Published by Elsevier Inc.
MED-4498
Trial of garlic as an adjunct therapy for multidrug resistant Pseudomonas aeruginosa pneumonia in a critically ill infant.
We present a case of a critically ill infant with severe multidrug-resistant Pseudomonas aeruginosa pneumonia and bacteremia who was treated with garlic and antibiotics after in vitro demonstration of a change in the resistance pattern via the disc diffusion method on garlic-treated Mueller Hinton agar. To our knowledge, this is the first report of therapeutic garlic use in a critically ill infant in the literature.
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-4749
Consequence of boar edible tissue consumption on urinary profiles of nandrolone metabolites. I. Mass spectrometric detection and quantification of ...
For the first time in the field of steroid residues in humans, demonstration of 19-norandrosterone (19-NA: 3alpha-hydroxy-5alpha-estran-17-one) and 19-noretiocholanolone (19-NE: 3alpha-hydroxy-5beta-estran-17-one) excretion in urine subsequent to boar consumption is reported. Three male volunteers agreed to consume 310 g of tissues from the edible parts (meat, liver, heart and kidney) of a boar. The three individuals delivered urine samples before and during 24 h after meal intake. After deconjugation of phase II metabolites, purification and specific derivatisation of target metabolites, the urinary extracts were analysed by mass spectrometry. Identification was carried out using measurements obtained by gas chromatography/high resolution mass spectrometry (GC/HRMS) (R = 7000) and liquid chromatography/tandem mass spectrometry (LC/MS/MS) (positive electrospray ionisation (ESI+)). Quantification was realised using a quadrupole mass filter. 19-NA and 19-NE concentrations in urine reached 3.1 to 7.5 microg/L nearby 10 hours after boar tissue consumption. Levels returned to endogenous values 24 hours after. These two steroids are usually exploited to confirm the exogenous administration of 19-nortestosterone (19-NT: 17beta-hydroxyestr-4-en-3-one), especially in the antidoping field. We have thus proved that eating tissues of non-castrated male pork (in which 17beta-nandrolone is present) might induce some false accusations of the abuse of nandrolone in antidoping. Copyright 2000 John Wiley & Sons, Ltd.
MED-3696
Alcohol consumption and breast cancer risk in the Women's Health Study.
The authors assessed the association between moderate alcohol consumption and breast cancer risk in the Women's Health Study (United States, 1992-2004). During an average of 10 years of follow-up, 1,484 cases of total breast cancer (1,190 invasive and 294 in situ) were documented among 38,454 women who, at baseline, were free of cancer and cardiovascular disease and provided detailed dietary information, including alcohol consumption, for the preceding 12 months. Higher alcohol consumption was associated with a modest increase in breast cancer risk; the multivariable relative risks for > or =30 g/day of alcohol vs. none were 1.32 (95% confidence interval (CI): 0.96, 1.82) for total breast cancer and 1.43 (95% CI: 1.02, 2.02) for invasive breast cancer. An increased risk was limited to estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors; the multivariable relative risks for an increment of 10 g/day of alcohol were 1.11 (95% CI: 1.03, 1.20) for ER+PR+ tumors (804 cases), 1.00 (95% CI: 0.81, 1.24) for ER+PR- tumors (125 cases), and 0.99 (95% CI: 0.82, 1.20) for ER-PR- tumors (167 cases). The association also seemed strongest among those taking postmenopausal hormones currently, but the test for interaction was not significant. The findings from this prospective study suggest that moderate alcohol consumption increases breast cancer risk.
MED-2077
Platelet dysfunction in vascular pathologies and how can it be treated.
Cardiovascular diseases are one of the leading causes of morbidity and mortality in industrialized countries, and although many processes play a role in the development of vascular disease, thrombosis is the primary event that precipitates stroke and acute coronary syndromes. The blood platelets are of significant importance in medicine. These cells are involved in many physiological processes, particularly haemostasis through their ability to aggregate and form clots in response to activation. In addition, these dynamic cells display activities that extend beyond thrombosis, including an important role in initiating and sustaining vascular inflammation. The expansion of knowledge from basic and clinical research has highlighted the critical position of platelets in several inflammatory diseases such as arthritis and atherosclerosis. Platelets are emerging as important mediators of inflammation and provide important signals to mediate phenotype of other blood and vascular cells. The important role of platelets in arterial thrombosis and the onset of acute myocardial infarction after atherosclerotic plaque rupture make inhibition of platelet aggregation a critical step in preventing thrombotic events associated with stroke, heart attack, and peripheral arterial thrombosis. However, the use of platelet inhibitors for thrombosis prevention must seek a delicate balance between inhibiting platelet activation and an associated increased bleeding risk. The aim of this review is to up-date the knowledge on platelets physiology and dysfunction in pathologies, such as diabetes mellitus, hypercholesterolemia, and hypertension, emphasizing the link between platelets and the inflammation-related atherosclerosis. The review evaluates the opportunities offered by the novel platelet inhibitors to efficiently alleviate the thrombotic events. Copyright © 2011 Elsevier Ltd. All rights reserved.
MED-2325
Longevity. The allostatic load of dietary restriction.
Restriction of food intake by 10-50% of ad libitum on a per unit of weight or energy content basis can extend the lifespan of a wide variety of species and prevent or delay age-related disease. This review first briefly summarizes the data delineating mortality trajectories of various species' populations maintained on restricted diets to provide insight into the effects of nutrient deprivation on distinct components of the aging process. Next, I discuss a number of important studies that have addressed the question whether it is the lack of calories and/or specific nutrients that determines the longevity response to dietary restriction. Finally, I review the evidence for hormesis as a proximate mechanism underpinning the impact of dietary restriction on lifespan. In aggregate, the currently available demographic data suggest that dietary restriction can both slow the age-related progressive accumulation of cellular damage and also enhance the ability of organisms to cope with irreversible injury. Restriction of essential nutrients as well as calories may affect life expectancy, perhaps in a species specific fashion. Hormesis, i.e. an evolutionary conserved stress response routine providing protection against a wide variety of (other) hazards in response to low levels of stress, is very likely to contribute to the beneficial health effects of dietary restriction. Copyright Â© 2011 Elsevier Inc. All rights reserved.
MED-4706
Regular Consumption of Nuts Is Associated with a Lower Risk of Cardiovascular Disease in Women with Type 2 Diabetes
Higher nut consumption has been associated with lower risk of coronary heart disease (CHD) events in several epidemiologic studies. The study examined the association between intake of nuts and incident cardiovascular disease (CVD) in a cohort of women with type 2 diabetes. For the primary analysis, there were 6309 women with type 2 diabetes who completed a validated FFQ every 2–4 y between 1980 and 2002 and were without CVD or cancer at study entry. Major CVD events included incident myocardial infarction (MI), revascularization, and stroke. During 54,656 person-years of follow-up, there were 452 CHD events (including MI and revascularization) and 182 incident stroke cases. Frequent nut and peanut butter consumption was inversely associated with total CVD risk in age-adjusted analyses. After adjustment for conventional CVD risk factors, consumption of at least 5 servings/wk of nuts or peanut butter [serving size, 28 g (1 ounce) for nuts and 16 g (1 tablespoon) for peanut butter] was significantly associated with a lower risk of CVD (relative risk = 0.56; 95% CI: 0.36–0.89). Furthermore, when we evaluated plasma lipid and inflammatory biomarkers, we observed that increasing nut consumption was significantly associated with a more favorable plasma lipid profile, including lower LDL cholesterol, non-HDL cholesterol, total cholesterol, and apolipoprotein-B-100 concentrations. However, we did not observe significant associations for HDL cholesterol or inflammatory markers. These data suggest that frequent nut and peanut butter consumption is associated with a significantly lower CVD risk in women with type 2 diabetes.
MED-3669
Aromatherapy positively affects mood, EEG patterns of alertness and math computations.
EEG activity, alertness, and mood were assessed in 40 adults given 3 minutes of aromatherapy using two aromas, lavender (considered a relaxing odor) or rosemary (considered a stimulating odor). Participants were also given simple math computations before and after the therapy. The lavender group showed increased beta power, suggesting increased drowsiness, they had less depressed mood (POMS) and reported feeling more relaxed and performed the math computations faster and more accurately following aromatherapy. The rosemary group, on the other hand, showed decreased frontal alpha and beta power, suggesting increased alertness. They also had lower state anxiety scores, reported feeling more relaxed and alert and they were only faster, not more accurate, at completing the math computations after the aromatherapy session.
MED-1416
Faecal urobilinogen levels and pH of stools in population groups with different incidence of cancer of the colon, and their possible role in its aetiology.
Mean faecal urobilinogen levels and the pH of stools were both found to be higher in subjects from a population group at high risk of developing cancer of the colon than in subjects matched for age, sex and socioeconomic status from a low-risk population group. An alkaline reaction of the colon contents seems to have a tumorigenic effect by a direct action on the mucus of the mucous cells. An acidic reaction, on the other hand, appears to be protective. These differences are dependent on the patterns of diet and manner of eating. Proper mastication of food, roughage, cellulose and vegetable fibre, and short-chain fatty acids of milk and fermented milk products in the diet appear to be protective.
MED-5176
Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia.
A flaxseed lignan extract containing 33% secoisolariciresinol diglucoside (SDG) was evaluated for its ability to alleviate lower urinary tract symptoms (LUTS) in 87 subjects with benign prostatic hyperplasia (BPH). A randomized, double-blind, placebo-controlled clinical trial with repeated measurements was conducted over a 4-month period using treatment dosages of 0 (placebo), 300, or 600 mg/day SDG. After 4 months of treatment, 78 of the 87 subjects completed the study. For the 0, 300, and 600 mg/day SDG groups, respectively, the International Prostate Symptom Score (IPSS) decreased -3.67 +/- 1.56, -7.33 +/- 1.18, and -6.88 +/- 1.43 (mean +/- SE, P = .100, < .001, and < .001 compared to baseline), the Quality of Life score (QOL score) improved by -0.71 +/- 0.23, -1.48 +/- 0.24, and -1.75 +/- 0.25 (mean +/- SE, P = .163 and .012 compared to placebo and P = .103, < .001, and < .001 compared to baseline), and the number of subjects whose LUTS grade changed from "moderate/severe" to "mild" increased by three, six, and 10 (P = .188, .032, and .012 compared to baseline). Maximum urinary flows insignificantly increased 0.43 +/- 1.57, 1.86 +/- 1.08, and 2.7 +/- 1.93 mL/second (mean +/- SE, no statistical significance reached), and postvoiding urine volume decreased insignificantly by -29.4 +/- 20.46, -19.2 +/- 16.91, and -55.62 +/- 36.45 mL (mean +/- SE, no statistical significance reached). Plasma concentrations of secoisolariciresinol (SECO), enterodiol (ED), and enterolactone (EL) were significantly raised after the supplementation. The observed decreases in IPSS and QOL score were correlated with the concentrations of plasma total lignans, SECO, ED, and EL. In conclusion, dietary flaxseed lignan extract appreciably improves LUTS in BPH subjects, and the therapeutic efficacy appeared comparable to that of commonly used intervention agents of alpha1A-adrenoceptor blockers and 5alpha-reductase inhibitors.
MED-3929
Habitual intake of dietary flavonoids and risk of Parkinson disease
Objective: To prospectively examine whether higher intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, and polymers) were associated with a lower risk of developing Parkinson disease (PD). Methods: In the current analysis, we included 49,281 men in the Health Professional Follow-up Study and 80,336 women from the Nurses' Health Study. Five major sources of flavonoid-rich foods (tea, berry fruits, apples, red wine, and orange/orange juice) were also examined. Flavonoid intake was assessed using an updated food composition database and a validated food frequency questionnaire. Results: We identified 805 participants (438 men and 367 women) who developed PD during 20–22 years of follow-up. In men, after adjusting for multiple confounders, participants in the highest quintile of total flavonoids had a 40%lower PD risk than those in the lowest quintile (hazard ratio [HR] = 0.60; 95% confidence interval 0.43, 0.83; p trend = 0.001). No significant relationship was observed in women (p trend = 0.62) or in pooled analyses (p trend = 0.23). In the pooled analyses for the subclasses, intakes of anthocyanins and a rich dietary source, berries, were significantly associated with a lower PD risk (HR comparing 2 extreme intake quintiles were 0.76 for anthocyanins and 0.77 for berries, respectively; p trend < 0.02 for both). Conclusions: Our findings suggest that intake of some flavonoids may reduce PD risk, particularly in men, but a protective effect of other constituents of plant foods cannot be excluded.
MED-1457
A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle.
Obesity and type 2 diabetes have been associated with a high-fat diet (HFD) and reduced mitochondrial mass and function. We hypothesized a HFD may affect expression of genes involved in mitochondrial function and biogenesis. To test this hypothesis, we fed 10 insulin-sensitive males an isoenergetic HFD for 3 days with muscle biopsies before and after intervention. Oligonucleotide microarray analysis revealed 297 genes were differentially regulated by the HFD (Bonferonni adjusted P < 0.001). Six genes involved in oxidative phosphorylation (OXPHOS) decreased. Four were members of mitochondrial complex I: NDUFB3, NDUFB5, NDUFS1, and NDUFV1; one was SDHB in complex II and a mitochondrial carrier protein SLC25A12. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC1) alpha and PGC1beta mRNA were decreased by -20%, P < 0.01, and -25%, P < 0.01, respectively. In a separate experiment, we fed C57Bl/6J mice a HFD for 3 weeks and found that the same OXPHOS and PGC1 mRNAs were downregulated by approximately 90%, cytochrome C and PGC1alpha protein by approximately 40%. Combined, these results suggest a mechanism whereby HFD downregulates genes necessary for OXPHOS and mitochondrial biogenesis. These changes mimic those observed in diabetes and insulin resistance and, if sustained, may result in mitochondrial dysfunction in the prediabetic/insulin-resistant state.
MED-2397
Organochlorine Exposure and Incidence of Diabetes in a Cohort of Great Lakes Sport Fish Consumers
Background Studies have demonstrated ubiquitous human exposure to persistent organic pollutants (POPs) such as p,p′-diphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs). Although there is considerable evidence that POP exposures are associated with prevalent diabetes, these studies do not establish causality because the cross-sectional study design does not allow for assessment of temporality of the exposure–disease association. Prospective studies, however, have been lacking. Objectives This study was designed to determine whether POP body burdens are related to incidence of diabetes in a cohort of Great Lakes sport fish consumers. Methods The cohort was established in the early 1990s and followed through 2005. We tested serum for DDE and PCB congeners and assessed diabetes diagnosis, demographics, and fish consumption. Associations of diabetes with exposures were examined prospectively in participants without diabetes in 1994–1995, followed through 2005. Annual percent changes in DDE and PCB-132/153 from 1994 to 2005 were examined by diabetes status. Results DDE exposure was associated with incident diabetes. Incident diabetes was not associated with mono-ortho PCB-118, total PCBs, or years of sport fish consumption. Annual percent change in DDE and PCB-132/153 did not differ significantly by diabetes status. Conclusions This study demonstrates an association between DDE exposure and incident diabetes. The findings of an association of DDE with incident diabetes and the lack of effect of diabetes on annual percent change in POPs do not support the hypothesis that associations of POPs with diabetes are attributable to reverse causality. Additional studies should address the biological pathways by which DDE could affect glucose homeostasis.
MED-1777
Shedding Light on the Controversy Surrounding the Temporal Decline in Human Sperm Counts: A Systematic Review
We systematically examined the evidence of declining sperm counts and the hypothesis that an increased exposure to environmental pollutants is responsible for such decline. Search engines, including PUBMED, MEDLINE, EMBASE, BIOSIS, and Cochrane library, were used to identify epidemiologic studies published from 1985 to 2013. We concluded that there is no enough evidence to confirm a worldwide decline in sperm counts. Also, there seems to be no scientific truth of a causative role for endocrine disruptors in the temporal decline of sperm production. Such assumptions are based on few meta-analyses and retrospective studies, while other well-conducted researches could not confirm these findings. We acknowledge that difficult-to-control confounding factors in the highly variable nature of semen, selection criteria, and comparability of populations from different time periods in secular-trend studies, the quality of laboratory methods for counting sperm, and apparently geographic variations in semen quality are the main issues that complicate the interpretation of the available evidence. Owing to the importance of this subject and the uncertainties still prevailing, there is a need not only for continuing monitoring of semen quality, reproductive hormones, and xenobiotics, but also for a better definition of fecundity.
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-1526
The effect of inhaling peppermint odor and ethanol in women athletes.
The purpose of this study was to determine whether inhaling peppermint odor has effects on time of running, maximum heart rate (MHR), maximum oxygen consumption (VO2max), oxygen consumption (VO2), minute ventilation (VE) and respiratory exchange ratio (RER) during acute intensive exercise or not. 36 women soccer player were chosen for participating in this research. They were randomly divided in 3 groups (control, inhaling peppermint, inhaling mixture of peppermint and ethanol). In order to be aware of similarity of groups, the subjects' BMI was determined and ANOVA did not show any significant differences (p < 0.05). The subjects of three groups ran on treadmill according to Bruce test. Heart rate, time of running, VO2max, VO2, VE and RER were measured by Gas Analyzer. After collecting the data, ANOVA was done (p < 0.05) and the results showed that in this study the inhaling of fragrant odors did not have any significant effect on the time of running, MHR, VO2max, VO2, VE and RER, which we think is due to the intensity and duration of training. Referring to our results of the present study; we suggest that inhaling peppermint odor during acute intensive exercise has no significant effect on pulmonary indexes and physical performance (Tab. 4, Fig. 1, Ref. 21).
MED-5311
Dinitrophenol and obesity: an early twentieth-century regulatory dilemma.
In the early 1930s, the industrial chemical dinitrophenol found widespread favor as a weight-loss drug, due principally to the work of Maurice Tainter, a clinical pharmacologist from Stanford University. Unfortunately the compound's therapeutic index was razor thin and it was not until thousands of people suffered irreversible harm that mainstream physicians realized that dinitrophenol's risks outweighed its benefits and abandoned its use. Yet, it took passage of the Food, Drug, and Cosmetic Act in 1938 before federal regulators had the ability to stop patent medicine men from selling dinitrophenol to Americans lured by the promise of a drug that would safely melt one's fat away.
MED-4366
The marketing of dietary supplements in North America: the emperor is (almost) naked.
BACKGROUND: Many different dietary supplements are being sold in North America. The quality of the evidence supporting their efficacy covers a wide spectrum: Some are based on solid science (such as vitamin D and fish oil), whereas with most supplements there is little or no supporting evidence. Types of supplements commonly sold include exotic fruit juices (such as goji juice) and single herbs or mixture of herbs. Common claims made in support of particular supplements are that they are rich in antioxidants, induce detoxification, stimulate the immune system, and cause weight loss. Supplements are commonly sold through health food stores and by multilevel marketing. Sales may be promoted using bulk mail ("junk mail"), spam e-mails, and Web sites. A large part of marketing is based on claims that are blatantly dishonest. CONCLUSIONS: Whereas supplements for which good supporting evidence exists generally cost around $3-$4 per month, those that are heavily promoted for which there is little supporting evidence cost about $20-$60 per month. The major cause of this problem in the United States is weakness of the law. There is an urgent need for stricter regulation and for giving better advice to the general public.
MED-5098
A risk-benefit analysis of French high fish consumption: a QALY approach.
The health risk and the nutritional benefit of a food are usually assessed separately. Toxicologists recommend limiting the consumption of certain fish because of methylmercury; while nutritionists recommend eating more oily fish because of omega 3. A common evaluation is imperative to provide coherent recommendations. In order to evaluate the risks along with the benefits related to fish consumption, a common metric based on the quality-adjusted life year (QALY) method has been used. The impact of a theoretical change from a medium n-3 PUFAs intake to a high intake is studied, in terms of the cardiovascular system (CHD mortality, stroke mortality and morbidity) and on fetal neuronal development (IQ loss or gain). This application can be considered as a sensitive analysis of the model used and looks at the impact of changing the dose-response relationships between cardiovascular diseases and n-3 PUFAs intakes. Results show that increasing fish consumption may have a beneficial impact on health. However, the confidence interval of the overall estimation has a negative lower bound, which means that this increase in fish consumption may have a negative impact due to MeHg contamination. Some limits of the QALY approach are identified. The first concerns determination of the dose-response relationships. The second concerns the economic origins of the approach and of individual preferences. Finally, since only one beneficial aspect and one risk element were studied, consideration should be given to how other beneficial and risk components may be integrated in the model.
MED-3856
Hypothesis: is antibiotic use associated with breast cancer?
The hypothesis that antibiotic use may increase cancer risk was first proposed several decades ago and some research suggests an increased risk of breast cancer among women with conditions likely to require long-term antibiotic use (e.g., acne, recurrent urinary-tract infections, UTI). However, this hypothesis has not been verified and the possible biological mechanisms are not entirely clear. A recent cohort study in Finland reported an increased risk of breast-cancer associated with antibiotic use for UTI. The effect of antibiotics on the ability of intestinal microflora to metabolise phytochemicals from edible plants into compounds that may protect against cancer was proposed as a potential mechanism. We extend this hypothesis by proposing that antibiotic use may be associated with breast-cancer risk through effects on immune and inflammatory factors, such as cytokines, T lymphocytes, prostaglandins, and matrix metalloproteinases, as well as disruption of phytochemical and oestrogen metabolism by intestinal microflora. We suggest that some mechanisms may increase breast-cancer risk, while others may decrease risk, depending on the antibiotic classification.
MED-3242
Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition.
Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 3-30%; p(trend) = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 36-7%, p(trend) = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed. Copyright © 2012 UICC.
MED-2894
Two-year randomized, placebo-controlled study of black currant anthocyanins on visual field in glaucoma.
AIM: To examine the influence of the black currant anthocyanins (BCACs) on the disease progression of open-angle glaucoma (OAG), a randomized, placebo-controlled, double-masked trial was made in 38 patients with OAG treated by antiglaucoma drops. METHODS: BCACs (50 mg/day, n = 19) or their placebos (n = 19) were orally administered once daily for a 24-month period. Systemic blood pressure, pulse rates, intraocular pressure (IOP), ocular blood circulation by laser-speckle flowgraphy, and Humphrey visual field mean deviation (MD) were measured during the 24-month period. RESULTS: As a main outcome measurement, we evaluated the difference between the groups in MD deterioration in the eye with a better MD from the trial's baseline through 24 months. A statistically significant difference was observed between the treatment groups in mean change from baseline in MD 24 months after therapy (p = 0.039, unpaired t test). Upon administration of BCACs, the ocular blood flows during the 24-month observational period increased in comparison with placebo-treated patients. However, no significant changes were observed in systemic and ocular conditions including IOP during the 24-month period. CONCLUSIONS: Our results suggest that oral administration of BCACs may be a safe and promising supplement for patients with OAG in addition to antiglaucoma medication. Copyright © 2012 S. Karger AG, Basel.
MED-1483
Empirical evaluation of very large treatment effects of medical interventions.
CONTEXT: Most medical interventions have modest effects, but occasionally some clinical trials may find very large effects for benefits or harms. OBJECTIVE: To evaluate the frequency and features of very large effects in medicine. DATA SOURCES: Cochrane Database of Systematic Reviews (CDSR, 2010, issue 7). STUDY SELECTION: We separated all binary-outcome CDSR forest plots with comparisons of interventions according to whether the first published trial, a subsequent trial (not the first), or no trial had a nominally statistically significant (P < .05) very large effect (odds ratio [OR], ≥5). We also sampled randomly 250 topics from each group for further in-depth evaluation. DATA EXTRACTION: We assessed the types of treatments and outcomes in trials with very large effects, examined how often large-effect trials were followed up by other trials on the same topic, and how these effects compared against the effects of the respective meta-analyses. RESULTS: Among 85,002 forest plots (from 3082 reviews), 8239 (9.7%) had a significant very large effect in the first published trial, 5158 (6.1%) only after the first published trial, and 71,605 (84.2%) had no trials with significant very large effects. Nominally significant very large effects typically appeared in small trials with median number of events: 18 in first trials and 15 in subsequent trials. Topics with very large effects were less likely than other topics to address mortality (3.6% in first trials, 3.2% in subsequent trials, and 11.6% in no trials with significant very large effects) and were more likely to address laboratory-defined efficacy (10% in first trials,10.8% in subsequent, and 3.2% in no trials with significant very large effects). First trials with very large effects were as likely as trials with no very large effects to have subsequent published trials. Ninety percent and 98% of the very large effects observed in first and subsequently published trials, respectively, became smaller in meta-analyses that included other trials; the median odds ratio decreased from 11.88 to 4.20 for first trials, and from 10.02 to 2.60 for subsequent trials. For 46 of the 500 selected topics (9.2%; first and subsequent trials) with a very large-effect trial, the meta-analysis maintained very large effects with P < .001 when additional trials were included, but none pertained to mortality-related outcomes. Across the whole CDSR, there was only 1 intervention with large beneficial effects on mortality, P < .001, and no major concerns about the quality of the evidence (for a trial on extracorporeal oxygenation for severe respiratory failure in newborns). CONCLUSIONS: Most large treatment effects emerge from small studies, and when additional trials are performed, the effect sizes become typically much smaller. Well-validated large effects are uncommon and pertain to nonfatal outcomes.
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-2183
Impact of cooking and home food preparation interventions among adults: outcomes and implications for future programs
Objective Cooking programs are growing in popularity; however an extensive review has not examined overall impact. Therefore, this study reviewed previous research on cooking/home food preparation interventions and diet and health-related outcomes among adults and identified implications for practice and research. Design Literature review and descriptive summative method. Main outcome measures Dietary intake, knowledge/skills, cooking attitudes and self-efficacy/confidence, health outcomes. Analysis Articles evaluating effectiveness of interventions that included cooking/home food preparation as the primary aim (January 1980 through December 2011) were identified via OVID MEDLINE, Agricola and Web of Science databases. Studies grouped according to design and outcomes were reviewed for validity using an established coding system. Results were summarized for several outcome categories. Results Of 28 studies identified, 12 included a control group with six as non-randomized and six as randomized controlled trials. Evaluation was done post-intervention for five studies, pre- and post-intervention for 23 and beyond post-intervention for 15. Qualitative and quantitative measures suggested a positive influence on main outcomes. However, non-rigorous study designs, varying study populations, and use of non-validated assessment tools limited stronger conclusions. Conclusions and Implications Well-designed studies are needed that rigorously evaluate long-term impact on cooking behavior, dietary intake, obesity and other health outcomes.
MED-4427
Left subclavian arterioesophageal fistula induced by chicken bone with upper gastrointestinal hemorrhage and unexpected death: report of a case.
Left subclavian arterioesophageal fistula resulting from chicken bone ingestion is a rare occurrence. The authors report the death of a 42-year-old Thai female with mental retardation who presented to the hospital with severe hematemesis and arrested Death occurred about 24 hours after laparotomy due to hypovolemic shock Postmortem examination revealed a chicken bone embedded in middle part of esophagus with fistula between the esophagus and the left subclavian artery.
MED-4450
Post-diagnosis dietary factors and survival after invasive breast cancer
Little is known about the effects of diet after breast cancer diagnosis on survival. We prospectively examined the relation between post-diagnosis dietary factors and breast cancer and all-cause survival in women with a history of invasive breast cancer diagnosed between 1987 and 1999 (at ages 20–79 years). Diet after breast cancer diagnosis was measured using a 126-item food frequency questionnaire. Among 4,441 women without a history of breast cancer recurrence prior to completing the questionnaire, 137 subsequently died from breast cancer within 7 years of enrollment. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for intake of macronutrients as well as selected micronutrients and food groups from Cox proportional hazards regression models. After adjustment for factors at diagnosis (age, state of residence, menopausal status, smoking, breast cancer stage, alcohol, history of hormone replacement therapy), interval between diagnosis and diet assessment, and at follow-up (energy intake, breast cancer treatment, body mass index, and physical activity), women in the highest compared to lowest quintile of intake of saturated fat and trans fat had a significantly higher risk of dying from any cause (HR = 1.41, 95% CI = 1.06 to 1.87, P-trend = 0.03) for saturated fat; (HR = 1.78, 95% CI = 1.35 to 2.32, P-trend = 0.01) for trans fat intake. Associations were similar, though did not achieve statistical significance, for breast cancer survival. This study suggests that lower intake of saturated and trans fat in the post-diagnosis diet is associated with improved survival after breast cancer diagnosis.
MED-4757
Comparison of sex hormonal and metabolic profiles between omnivores and vegetarians in pre- and post-menopausal women.
The purpose of the present study was to investigate the sex hormonal and metabolic profiles in vegetarians and compare these with the profiles in omnivores. The design of the present study was cross-sectional. The study sample of pre- and post-menopausal women included forty-one omnivores and twenty-one vegetarians. Thereafter we determined: (1) plasma sex hormones, (2) fasting insulin, NEFA as well as apo-A and apo-B, (3) BMI, (4) a dietary profile (3 d dietary records), (5) physical activity and (6) total faecal excretion per 72 h and total urinary excretion per 72 h. Vegetarians showed higher levels of sex hormone-binding globulin (SHBG), apo-A, total faecal excretion per 72 h and total fibre intake as well as lower levels of apo-B, free oestradiol, free testosterone, dehydroepiandrosterone sulfate (DHEA-s) and BMI. Interestingly, after controlling for BMI, significant differences between groups still persisted except for apo-B. Moreover, stepwise regression analysis showed that total fibre intake explained 15.2 % of the variation in SHBG in our cohort, which accounted for the greatest source of unique variance. Results of the present study indicate that pre- and post-menopausal vegetarians present higher concentrations of SHBG, which could be explained, in part, by higher levels of fibre intake. This may explain, at least in part, the lower risk of developing type 2 diabetes.
MED-4830
Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia.
Muscle pain and weakness are frequent complaints in patients receiving 3-hydroxymethylglutaryl coenzymeA (HMG CoA) reductase inhibitors (statins). Many patients with myalgia have creatine kinase levels that are either normal or only marginally elevated, and no obvious structural defects have been reported in patients with myalgia only. To investigate further the mechanism that mediates statin-induced skeletal muscle damage, skeletal muscle biopsies from statin-treated and non-statin-treated patients were examined using both electron microscopy and biochemical approaches. The present paper reports clear evidence of skeletal muscle damage in statin-treated patients, despite their being asymptomatic. Though the degree of overall damage is slight, it has a characteristic pattern that includes breakdown of the T-tubular system and subsarcolemmal rupture. These characteristic structural abnormalities observed in the statin-treated patients were reproduced by extraction of cholesterol from skeletal muscle fibres in vitro. These findings support the hypothesis that statin-induced cholesterol lowering per se contributes to myocyte damage and suggest further that it is the specific lipid/protein organization of the skeletal muscle cell itself that renders it particularly vulnerable. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
MED-3455
Exercise-induced lipid peroxidation: Implications for deoxyribonucleic acid damage and systemic free radical generation.
Exercise-induced deoxyribonucleic acid (DNA) damage is often associated with an increase in free radicals; however, there is a lack of evidence examining the two in parallel. This study tested the hypothesis that high-intensity exercise has the ability to produce free radicals that may be capable of causing DNA damage. Twelve apparently healthy male subjects (age: 23 ± 4 years; stature: 181 ± 8 cm; body mass: 80 ± 9 kg; and VO(2max) : 49 ± 5 ml/kg/min) performed three 5 min consecutive and incremental stages (40, 70, and 100% of VO(2max) ) of aerobic exercise with a 15-min period separating each stage. Blood was drawn after each bout of exercise for the determination of ex vivo free radicals, DNA damage, protein carbonyls, lipid hydroperoxide (LOOH) concentration, and a range of lipid-soluble antioxidants. Lipid-derived oxygen-centered free radicals (hyperfine coupling constants a(Nitrogen) = 13.7 Gauss (G) and aβ(Hydrogen) = 1.8 G) increased as a result of acute moderate and high-intensity exercise (P < 0.05), while DNA damage was also increased (P < 0.05). Systemic changes were observed in LOOH and for lipid-soluble antioxidants throughout exercise (P < 0.05); however, there was no observed change in protein carbonyl concentration (P > 0.05). These findings identify lipid-derived free radical species as possible contributors to peripheral mononuclear cell DNA damage in the human exercising model. This damage occurs in the presence of lipid oxidation but in the absence of any change to protein carbonyl concentration. The significance of these findings may have relevance in terms of immune function, the aging process, and the pathology of carcinogenesis. Copyright © 2010 Wiley-Liss, Inc.
MED-970
Diet and risk of diverticular disease in Oxford cohort of European Prospective Investigation into Cancer and Nutrition (EPIC): prospective study of British vegetarians and non-vegetarians
Objective To examine the associations of a vegetarian diet and dietary fibre intake with risk of diverticular disease. Design Prospective cohort study. Setting The EPIC-Oxford study, a cohort of mainly health conscious participants recruited from around the United Kingdom. Participants 47 033 men and women living in England or Scotland of whom 15 459 (33%) reported consuming a vegetarian diet. Main outcome measures Diet group was assessed at baseline; intake of dietary fibre was estimated from a 130 item validated food frequency questionnaire. Cases of diverticular disease were identified through linkage with hospital records and death certificates. Hazard ratios and 95% confidence intervals for the risk of diverticular disease by diet group and fifths of intake of dietary fibre were estimated with multivariate Cox proportional hazards regression models. Results After a mean follow-up time of 11.6 years, there were 812 cases of diverticular disease (806 admissions to hospital and six deaths). After adjustment for confounding variables, vegetarians had a 31% lower risk (relative risk 0.69, 95% confidence interval 0.55 to 0.86) of diverticular disease compared with meat eaters. The cumulative probability of admission to hospital or death from diverticular disease between the ages of 50 and 70 for meat eaters was 4.4% compared with 3.0% for vegetarians. There was also an inverse association with dietary fibre intake; participants in the highest fifth (≥25.5 g/day for women and ≥26.1 g/day for men) had a 41% lower risk (0.59, 0.46 to 0.78; P<0.001 trend) compared with those in the lowest fifth (<14 g/day for both women and men). After mutual adjustment, both a vegetarian diet and a higher intake of fibre were significantly associated with a lower risk of diverticular disease. Conclusions Consuming a vegetarian diet and a high intake of dietary fibre were both associated with a lower risk of admission to hospital or death from diverticular disease.
MED-1613
Taiwanese vegetarians have higher insulin sensitivity than omnivores.
The present study was designed to examine the effects of habitual consumption of Taiwanese vegetarian diets on hormonal secretion, and on lipid and glycaemic control. Of the ninety-eight healthy female adults recruited from Hualien, Taiwan (aged 31-45 years), forty-nine were Buddhist lactovegetarians and forty-nine were omnivores. Dietary intakes were measured, and blood levels of nutrients and hormones were analysed. Vegetarians consumed less energy, fat and protein, but more fibre than the omnivores. Compared with the omnivores, the vegetarians had, on average, lower BMI and smaller waist circumference. Except for slightly lower levels of thyroxine (T4) in vegetarians, vegetarians and omnivores both showed similar levels of triiodothyronine (T3), free T4, thyroid-stimulating hormone, T3:T4 ratio and cortisol. Compared with the omnivores, the vegetarians had significantly lower levels of fasting insulin (median: 35.3 v. 50.6 pmol/l) and plasma glucose (mean: 4.7 (se 0.05) v. 4.9 (se 0.05) mmol/l). Insulin resistance, as calculated by the homeostasis model assessment method, was significantly lower in the vegetarians than in the omnivores (median: 1.10 v. 1.56), while beta-cell function was not different between the two groups. BMI and diet were both independent predictors for insulin resistance, and contributed 18 and 15 % of the variation in insulin resistance, respectively. In conclusion, Taiwanese vegetarians had lower glucose and insulin levels and higher insulin sensitivity than did the omnivores. Diet and lower BMI were partially responsible for the high insulin sensitivity observed in young Taiwanese vegetarians.
MED-1487
Patients' Expectations of Screening and Preventive Treatments
PURPOSE An informed decision to accept a health care intervention requires an understanding of its likely benefit. This study assessed participants' estimates of the benefit, as well as minimum acceptable benefit, of screening for breast and bowel cancer and medication to prevent hip fracture and cardiovascular disease. METHODS Three general practitioners sent questionnaires to all registered patients aged 50 to 70 years. Patients agreeing to participate in the study were asked to estimate the number of events (fractures or deaths) prevented in a group of 5,000 patients undergoing each intervention over a period of 10 years, and to indicate the minimum number of events avoided by the intervention that they considered justified its use. The proportions of participants that overestimated each intervention's benefit were calculated, and univariate and multivariable analyses of predictors of response were performed. RESULTS The participation rate was 36%: 977 patients were invited to participate in the study, and 354 returned a completed questionnaire. Participants overestimated the degree of benefit conferred by all interventions: 90% of participants overestimated the effect of breast cancer screening, 94% overestimated the effect of bowel cancer screening, 82% overestimated the effect of hip fracture preventive medication, and 69% overestimated the effect of preventive medication for cardiovascular disease. Estimates of minimum acceptable benefit were more conservative, but other than for cardiovascular disease mortality prevention, most respondents indicated a minimum benefit greater than these interventions achieve. A lower level of education was associated with higher estimates of minimum acceptable benefit for all interventions. CONCLUSION Patients overestimated the risk reduction achieved with 4 examples of screening and preventive medications. A lower level of education was associated with higher minimum benefit to justify intervention use. This tendency to overestimate benefits may affect patients' decisions to use such interventions, and practitioners should be aware of this tendency when discussing these interventions with patients.
MED-2222
Effect of cocoa/chocolate ingestion on brachial artery flow-mediated dilation and its relevance to cardiovascular health and disease in humans.
Prospective studies indicate that high intake of dietary flavanols, such as those contained in cocoa/chocolate, are associated with reduced rates of cardiovascular-related morbidity and mortality in humans. Numerous mechanisms may underlie these associations such as favorable effects of flavanols on blood pressure, platelet aggregation, thrombosis, inflammation, and the vascular endothelium. The brachial artery flow-mediated dilation (FMD) technique has emerged as a robust method to quantify endothelial function in humans. Collectively, the preponderance of evidence indicates that FMD is a powerful surrogate measure for firm cardiovascular endpoints, such as cardiovascular-related mortality, in humans. Thus, literally thousands of studies have utilized this technique to document group differences in FMD, as well as to assess the effects of various interventions on FMD. In regards to the latter, numerous studies indicate that both acute and chronic ingestion of cocoa/chocolate increases FMD in humans. Increases in FMD after cocoa/chocolate ingestion appear to be dose-dependent such that greater increases in FMD are observed after ingestion of larger quantities. The mechanisms underlying these responses are likely diverse, however most data suggest an effect of increased nitric oxide bioavailability. Thus, positive vascular effects of cocoa/chocolate on the endothelium may underlie (i.e., be linked mechanistically to) reductions in cardiovascular risk in humans. Copyright © 2012 Elsevier Inc. All rights reserved.
MED-4662
Iodine-induced neonatal hypothyroidism secondary to maternal seaweed consumption: a common practice in some Asian cultures to promote breast milk s...
Mild iodine deficiency is a recognised problem in Australia and New Zealand. However, iodine excess can cause hypothyroidism in some infants. We highlight two cases which illustrate the risks of excess dietary iodine intake during pregnancy and breastfeeding. They also describe a cultural practice of consuming seaweed soup to promote breast milk supply. Although most attention recently has been on the inadequacy of iodine in Australian diets, the reverse situation should not be overlooked. Neither feast nor famine is desirable. © 2011 The Authors. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
MED-2121
Dietary intervention in acne
The purpose of this paper is to highlight the endocrine signaling of Western diet, a fundamental environmental factor involved in the pathogenesis of epidemic acne. Western nutrition is characterized by high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of insulin- and IGF-1-level elevating dairy proteins. Metabolic signals of Western diet are sensed by the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), which integrates signals of cellular energy, growth factors (insulin, IGF-1) and protein-derived signals, predominantly leucine, provided in high amounts by milk proteins and meat. mTORC1 activates SREBP, the master transcription factor of lipogenesis. Leucine stimulates mTORC1-SREBP signaling and leucine is directly converted by sebocytes into fatty acids and sterols for sebaceous lipid synthesis. Over-activated mTORC1 increases androgen hormone secretion and most likely amplifies androgen-driven mTORC1 signaling of sebaceous follicles. Testosterone directly activates mTORC1. Future research should investigate the effects of isotretinoin on sebocyte mTORC1 activity. It is conceivable that isotretinoin may downregulate mTORC1 in sebocytes by upregulation of nuclear levels of FoxO1. The role of Western diet in acne can only be fully appreciated when all stimulatory inputs for maximal mTORC1 activation, i.e., glucose, insulin, IGF-1 and leucine, are adequately considered. Epidemic acne has to be recognized as an mTORC1-driven disease of civilization like obesity, type 2 diabetes, cancer and neurodegenerative diseases. These new insights into Western diet-mediated mTORC1-hyperactivity provide a rational basis for dietary intervention in acne by attenuating mTORC1 signaling by reducing (1) total energy intake, (2) hyperglycemic carbohydrates, (3) insulinotropic dairy proteins and (4) leucine-rich meat and dairy proteins. The necessary dietary changes are opposed to the evolution of industrialized food and fast food distribution of Westernized countries. An attenuation of mTORC1 signaling is only possible by increasing the consumption of vegetables and fruit, the major components of vegan or Paleolithic diets. The dermatologist bears a tremendous responsibility for his young acne patients who should be advised to modify their dietary habits in order to reduce activating stimuli of mTORC1, not only to improve acne but to prevent the harmful and expensive march to other mTORC1-related chronic diseases later in life.
MED-1577
Treatment-related progressive multifocal leukoencephalopathy: current understanding and future steps
Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder of the brain caused by a ubiquitous polyomavirus, JC virus. PML is almost always associated with some underlying immunosuppression and acquired immune deficiency syndrome has been the most common predisposing disorder. Recently, different pharmacological agents have been demonstrated to increase the risk of PML. Therapies that predispose people to PML can be classified into three categories: therapies that uniquely increase the risk for the disorder, such as the monoclonal antibodies natalizumab and efalizumab; therapies that appear to increase the risk in individuals already at risk of PML due to pre-existing conditions, such as rituximab and mycophenolate mofetil; and therapies with a mechanism of action that might suggest a potential for increased PML risk and/or with which rare cases of PML have been observed. Unlike the latter two classes, therapeutic agents uniquely increasing the risk of PML are associated with a much greater prevalence of the disorder and a latent interval from the time of drug initiation to the development of PML. PML development with pharmacological agents has provided new insight into the pathogenesis of this devastating disorder. This review focuses on the risks of PML with multiple pharmacological agents, the proposed pathogenesis with these agents, and potential risk mitigation strategies.
MED-3319
Epidemiologic Investigation of Immune-Mediated Polyradiculoneuropathy among Abattoir Workers Exposed to Porcine Brain
Background In October 2007, a cluster of patients experiencing a novel polyradiculoneuropathy was identified at a pork abattoir (Plant A). Patients worked in the primary carcass processing area (warm room); the majority processed severed heads (head-table). An investigation was initiated to determine risk factors for illness. Methods and Results Symptoms of the reported patients were unlike previously described occupational associated illnesses. A case-control study was conducted at Plant A. A case was defined as evidence of symptoms of peripheral neuropathy and compatible electrodiagnostic testing in a pork abattoir worker. Two control groups were used - randomly selected non-ill warm-room workers (n = 49), and all non-ill head-table workers (n = 56). Consenting cases and controls were interviewed and blood and throat swabs were collected. The 26 largest U.S. pork abattoirs were surveyed to identify additional cases. Fifteen cases were identified at Plant A; illness onsets occurred during May 2004–November 2007. Median age was 32 years (range, 21–55 years). Cases were more likely than warm-room controls to have ever worked at the head-table (adjusted odds ratio [AOR], 6.6; 95% confidence interval [CI], 1.6–26.7), removed brains or removed muscle from the backs of heads (AOR, 10.3; 95% CI, 1.5–68.5), and worked within 0–10 feet of the brain removal operation (AOR, 9.9; 95% CI, 1.2–80.0). Associations remained when comparing head-table cases and head-table controls. Workers removed brains by using compressed air that liquefied brain and generated aerosolized droplets, exposing themselves and nearby workers. Eight additional cases were identified in the only two other abattoirs using this technique. The three abattoirs that used this technique have stopped brain removal, and no new cases have been reported after 24 months of follow up. Cases compared to controls had higher median interferon-gamma (IFNγ) levels (21.7 pg/ml; vs 14.8 pg/ml, P<0.001). Discussion This novel polyradiculoneuropathy was associated with removing porcine brains with compressed air. An autoimmune mechanism is supported by higher levels of IFNγ in cases than in controls consistent with other immune mediated illnesses occurring in association with neural tissue exposure. Abattoirs should not use compressed air to remove brains and should avoid procedures that aerosolize CNS tissue. This outbreak highlights the potential for respiratory or mucosal exposure to cause an immune-mediated illness in an occupational setting.
MED-4929
Vitamins E and C in the Prevention of Cardiovascular Disease in Men: The Physicians’ Health Study II Randomized Trial
Context Basic and observational studies suggest vitamins E or C may reduce risk of cardiovascular disease (CVD). However, few long-term trials have evaluated men at initially low risk of CVD, and no previous trial in men has examined vitamin C alone in the prevention of CVD. Objective To test whether long-term vitamin E or C supplementation decreases risk of major cardiovascular events among men. Design, Setting, and Participants The Physicians’ Health Study II (PHS II) is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. We enrolled 14,641 U.S. male physicians initially aged ≥50 years, including 754 (5.1%) men with prevalent CVD at randomization. Intervention Individual supplements of 400 IU vitamin E every other day and 500 mg vitamin C daily. Main Outcome Measures A composite endpoint of major cardiovascular events (nonfatal myocardial infarction (MI), nonfatal stroke, and CVD death). Results During a mean follow-up of 8.0 years, there were 1,245 confirmed major cardiovascular events. Compared with placebo, vitamin E had no effect on the incidence of major cardiovascular events (both active and placebo vitamin E groups, 10.9 events per 1,000 person-years; hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.90–1.13; P=0.86), as well as total MI (HR, 0.90; 95% CI, 0.75–1.07; P=0.22), total stroke (HR, 1.07; 95% CI, 0.89–1.29; P=0.45), and cardiovascular mortality (HR, 1.07; 95% CI, 0.90–1.29; P=0.43). There was also no significant effect of vitamin C on major cardiovascular events (active and placebo vitamin E groups, 10.8 and 10.9 events per 1,000 person-years, respectively; HR, 0.99; 95% CI, 0.89–1.11; P=0.91), as well as total MI (HR, 1.04; 95% CI, 0.87–1.24; P=0.65), total stroke (HR, 0.89; 95% CI, 0.74–1.07; P=0.21), and cardiovascular mortality (HR, 1.02; 95% CI, 0.85–1.21; P=0.86). Neither vitamin E (HR, 1.07; 95% CI, 0.97–1.18; P=0.15) nor vitamin C (HR, 1.07; 95% CI, 0.97–1.18; P=0.16) had a significant effect on total mortality, but vitamin E was associated with an increased risk of hemorrhagic stroke (HR, 1.74; 95% CI, 1.04–2.91; P=0.036). Conclusions In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of major cardiovascular events. These data provide no support for the use of these supplements for the prevention of CVD in middle-aged and older men.
MED-5154
Whole-grain intake is associated with body mass index in college students.
OBJECTIVE: To measure whole-grain intake in college students and determine the association with body mass index (BMI). DESIGN: Cross-sectional convenience sample of college students enrolled in an introductory nutrition course. SETTING: Large state university. PARTICIPANTS: 159 college students, mean age: 19.9. MAIN OUTCOME MEASURES: Intake of whole grains, refined grains, calories, and fiber from food records; BMI determined from height and weight measurements. ANALYSIS: Analysis of variance with linear contrasts; participants grouped by BMI category (P<.05). RESULTS: Average intake of cereal grains was 5.4 servings per day, of which whole-grain intake accounted for an average of 0.7 servings per day. Whole-grain intake was significantly higher in normal weight students than in overweight and obese students (based on BMI). CONCLUSIONS AND IMPLICATIONS: The low intake of whole grains in this population of college students indicates the need for interventions aiming to increase whole-grain intake to the recommended minimum of 3 servings per day. College students who are concerned about their body weight may be motivated to increase their intake of whole-grain foods; however, their intake of whole grains is likely to be influenced by the availability of these food items in campus dining halls and other locations around the college campus.
MED-1350
A Pill for the Ill? Patients’ Reports of Their Experience of the Medical Encounter in the Treatment of Depression
Background Starting in the 1960s, a broad-based patients’ rights movement began to question doctors’ paternalism and to demand disclosure of medical information, informed consent, and active participation by the individual in personal health care. According to scholars, these changes contributed to downplay the biomedical approach in favor of a more patient-oriented perspective. The Swedish non-profit organization Consumer Association for Medicines and Health (KILEN) has offered the possibility for consumers to report their perceptions and experiences from their use of medicines in order to strengthen consumer rights within the health care sector. Methodology In this paper, qualitative content analysis was used to analyze 181 KILEN consumer reports of adverse events from antidepressant medications in order to explore patients’ views of mental ill health symptoms and the doctor-patient interaction. Principal Findings Overall, the KILEN stories contained negative experiences of the patients’ medical encounters. Some reports indicated intense emotional outrage and strong feelings of abuse by the health care system. Many reports suggested that doctors and patients had very different accounts of the nature of the problems for which the patient was seeking help. Although patients sought help for problems like tiredness and sleeplessness (often with a personal crisis of some sort as a described cause), the treating doctor in most cases was exceptionally quick in both diagnosing depression and prescribing antidepressant treatment. When patients felt they were not being listened to, trust in the doctor was compromised. This was evident in the cases when the doctor tried to convince them to take part in medical treatment, sometimes by threatening to withdraw their sick-listing. Conclusions Overall, this study suggests that the dynamics happening in the medical encounter may still be highly affected by a medical dominance, instead of a patient-oriented perspective. This may contribute to a questionable medicalization and/or pharmaceuticalization of depression.
MED-919
Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.
OBJECTIVE: The objective was to provide guidelines to clinicians for the evaluation, treatment, and prevention of vitamin D deficiency with an emphasis on the care of patients who are at risk for deficiency. PARTICIPANTS: The Task Force was composed of a Chair, six additional experts, and a methodologist. The Task Force received no corporate funding or remuneration. CONSENSUS PROCESS: Consensus was guided by systematic reviews of evidence and discussions during several conference calls and e-mail communications. The draft prepared by the Task Force was reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Core Committee, and cosponsoring associations, and it was posted on The Endocrine Society web site for member review. At each stage of review, the Task Force received written comments and incorporated needed changes. CONCLUSIONS: Considering that vitamin D deficiency is very common in all age groups and that few foods contain vitamin D, the Task Force recommended supplementation at suggested daily intake and tolerable upper limit levels, depending on age and clinical circumstances. The Task Force also suggested the measurement of serum 25-hydroxyvitamin D level by a reliable assay as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D(2) or vitamin D(3) was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection.
MED-2803
Dietary polyphenols and mechanisms of osteoarthritis.
Osteoarthritis is a condition caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and anti-inflammatory pathways. It primarily affects the articular cartilage and subchondral bone of synovial joints and results in joint failure, leading to pain upon weight bearing including walking and standing. There is no cure for osteoarthritis, as it is very difficult to restore the cartilage once it is destroyed. The goals of treatment are to relieve pain, maintain or improve joint mobility, increase the strength of the joints and minimize the disabling effects of the disease. Recent studies have shown an association between dietary polyphenols and the prevention of osteoarthritis-related musculoskeletal inflammation. This review discusses the effects of commonly consumed polyphenols, including curcumin, epigallocatechin gallate and green tea extract, resveratrol, nobiletin and citrus fruits, pomegranate, as well as genistein and soy protein, on osteoarthritis with an emphasis on molecular antiosteoarthritic mechanisms. Copyright © 2012 Elsevier Inc. All rights reserved.
MED-2116
Turning acne on/off via mTORC1
Over the past 10 years, the increase in comprehension of the mechanisms behind acne has been truly exponential. Starting with the ethnological work of Cordain, accelerated by the epidemiological work of Adebamowo, supported by the clinical trials of Smith and Mann, Kwon, DiLandro and others, the interface of diet and acne is coming into focus. Melnik now presents an exceptional pair of papers that illustrate for dermatologists what translational research is all about. The Western diet, the role of dairy, FoxO1 and mTORC1, the interplay of agonists and antagonists, therapeutics present and future – the jigsaw puzzle is coming together.
MED-4629
Vegetarian diet for patients with rheumatoid arthritis: can the clinical effects be explained by the psychological characteristics of the patients?
In a controlled, single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA. In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters. The patients who participated in the clinical trial differed significantly from other RA patients. Firstly, they had a higher internal score and a lower chance score on the Multi-dimensional Health Locus of Control Scale (MHLCS). Secondly, their belief in the effect of ordinary medical treatment, evaluated by a 10-cm visual analogue scale, was lower, and their belief in the effect of 'alternative', unconventional forms of treatment was higher. Of the patients who were randomized to a vegetarian diet, there was no significant difference between diet responders and diet non-responders with regard to the MHLCS scores. But, diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders. The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Questionnaire. Throughout the clinical trial, this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders. We conclude, firstly, that patients with certain psychological characteristics were selected to the clinical trial; secondly, that the MHLCS scores could not explain the clinical improvement, but it may have been influenced by the patients' beliefs in ordinary and 'alternative' forms of treatment; and thirdly, that dietary treatment decreased psychological distress.
MED-4642
Diets and hormonal levels in postmenopausal women with or without breast cancer.
The role of diet in breast cancer (BC) risk is unclear. Fiber could reduce BC risk, through the enterohepatic circulation of estrogens. We examined the relationship between diet and sex hormones in postmenopausal women with or without BC. Thirty-one postmenopausal women (10 omnivores, 11 vegetarians, and 10 BC omnivores) were recruited. Dietary records (5 days) and hormone levels (3 days) were evaluated on 4 occasions over 1 yr. Vegetarians showed a lower fat/fiber ratio, a higher intake of total and cereal fiber (g/d)/body weight (kg), a significantly lower level of plasma estrone-sulfate, estradiol, free-estradiol, free-testosterone, and ring D oxygenated estrogens, and a significantly higher level of sex-hormone-binding-globulin than BC subjects. Fiber was consumed in slightly larger amounts by omnivores than by BC subjects. Omnivores had significantly lower plasma testosterone and estrone-sulfate but higher sex-hormone-binding-globulin than BC subjects. No difference was found for the urinary 16-oxygenated estrogens. However, the 2-MeO-E1/2-OH-E1 ratio was significantly lower in omnivores than in BC group. This ratio is positively associated with the fat/fiber ratio. In conclusion, testosterone may contribute to causing alterations in the levels of catechol estrogens and 16-oxygenated estrogens. The fat/fiber ratio appears to be useful in evaluating dietary effects on estrogen metabolism.
MED-4896
Acne vulgaris: a disease of Western civilization.
BACKGROUND: In westernized societies, acne vulgaris is a nearly universal skin disease afflicting 79% to 95% of the adolescent population. In men and women older than 25 years, 40% to 54% have some degree of facial acne, and clinical facial acne persists into middle age in 12% of women and 3% of men. Epidemiological evidence suggests that acne incidence rates are considerably lower in nonwesternized societies. Herein we report the prevalence of acne in 2 nonwesternized populations: the Kitavan Islanders of Papua New Guinea and the Aché hunter-gatherers of Paraguay. Additionally, we analyze how elements in nonwesternized environments may influence the development of acne. OBSERVATIONS: Of 1200 Kitavan subjects examined (including 300 aged 15-25 years), no case of acne (grade 1 with multiple comedones or grades 2-4) was observed. Of 115 Aché subjects examined (including 15 aged 15-25 years) over 843 days, no case of active acne (grades 1-4) was observed. CONCLUSIONS: The astonishing difference in acne incidence rates between nonwesternized and fully modernized societies cannot be solely attributed to genetic differences among populations but likely results from differing environmental factors. Identification of these factors may be useful in the treatment of acne in Western populations.
MED-2945
Chinese lacto-vegetarian diet exerts favorable effects on metabolic parameters, intima-media thickness, and cardiovascular risks in healthy men.
BACKGROUND: To investigate whether the Chinese lacto-vegetarian diet has protective effects on metabolic and cardiovascular disease (CVD). METHODS: One hundred sixty-nine healthy Chinese lacto-vegetarians and 126 healthy omnivore men aged 21-76 years were enrolled. Anthropometric indexes, lipid profile, insulin sensitivity, pancreatic β cell function, and intima-media thickness (IMT) of carotid arteries were assessed and compared. Cardiovascular risk points and probability of developing CVD in 5-10 years in participants aged 24-55 years were calculated. RESULTS: Compared with omnivores, lacto-vegetarians had remarkably lower body mass index, systolic and diastolic blood pressure, and serum levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, γ-glutamyl transferase, serum creatinine, uric acid, fasting blood glucose, as well as lower total cholesterol/high-density lipoprotein cholesterol ratio. Vegetarians also had higher homeostasis model assessment β cell function and insulin secretion index and thinner carotid IMT than the omnivores did. These results corresponded with lower cardiovascular risk points and probability of developing CVD in 5-10 years in vegetarians 24-55 years old. CONCLUSIONS: In healthy Chinese men, the lacto-vegetarian diet seems to exert protective effects on blood pressure, lipid profiles, and metabolic parameters and results in significantly lower carotid IMT. Lower CVD risks found in vegetarians also reflect the beneficial effect of the Chinese lacto-vegetarian diet.
MED-2105
Recent Perspectives on the Relations between Fecal Mutagenicity, Genotoxicity, and Diet
DNA damage is an essential component of the genesis of colonic cancer. Gut microbial products and food components are thought to be principally responsible for the damage that initiates disease progression. Modified Ames tests and Comet assays have been developed for measuring mutagenicity and genotoxicity. Their relevance to oncogenesis remains to be confirmed, as does the relative importance of different mutagenic and genotoxic compounds present in fecal water and the bacteria involved in their metabolism. Dietary intervention studies provide clues to the likely risks of oncogenesis. High-protein diets lead to increases in N-nitroso compounds in fecal water and greater DNA damage as measured by the Comet assay, for example. Other dietary interventions, such as non-digestible carbohydrates and probiotics, may lead to lower fecal genotoxicity. In order to make recommendations to the general public, we must develop a better understanding of how genotoxic compounds are formed in the colon, how accurate the Ames and Comet assays are, and how diet affects genotoxicity.
MED-2676
Mutagenicity testing in the Salmonella typhimurium assay of phenolic compounds and phenolic fractions obtained from smokehouse smoke condensates.
Smokehouse smoke, which is used for flavouring meat products, was investigated for its mutagenic activity in the Salmonella typhimurium assay. We were chiefly concerned with the fractions free of polycyclic aromatic hydrocarbons but containing phenol compounds, which are responsible for the preservative and aromatizing properties of the smoke. The most abundantly occurring phenol compounds (phenol, cresols, 2,4-dimethylphenol, brenzcatechine, syringol, eugenol, vanilline and guaiacol) gave negative results when they were tested for mutagenicity at five concentrations up to 5000 micrograms/plate, with and without S-9 mix, using five strains of S. typhimurium. Even when phenol was further investigated in a variety of test conditions, no induction of his+ revertants was observed. When smokehouse smoke was condensed and fractionated the majority of the various phenolic fractions also gave negative results when tested at five concentrations using five strains of S. typhimurium. However there was a slight increase in the number of revertants in a few cases. The presence in the phenolic fractions of very small amounts of mutagenic impurities, the nature of which needs further investigation, cannot be excluded. These results support the further development of non-hazardous smoke-aroma preparations, based on the phenolic components of smokehouse smoke.
MED-946
Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome.
BACKGROUND: Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder. The role of pharmacotherapy for IBS is limited and focused mainly on symptom control. OBJECTIVES: The objective of this systematic review was to evaluate the efficacy of bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. SEARCH STRATEGY: Computer assisted structured searches of MEDLINE, EMBASE, The Cochrane library, CINAHL and PsychInfo were conducted for the years 1966-2009. An updated search in April 2011 identified 10 studies which will be considered for inclusion in a future update of this review. SELECTION CRITERIA: Randomized controlled trials comparing bulking agents, antispasmodics or antidepressants with a placebo treatment in patients with irritable bowel syndrome aged over 12 years were considered for inclusion. Only studies published as full papers were included. Studies were not excluded on the basis of language. The primary outcome had to include improvement of abdominal pain, global assessment or symptom score. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from the selected studies. Risk Ratios (RR) and Standardized Mean Differences (SMD) with 95% confidence intervals (CI) were calculated. A proof of practice analysis was conducted including sub-group analyses for different types of  bulking agents, spasmolytic agents or antidepressant medication. This was followed by a proof of principle analysis where only the studies with adequate allocation concealment were included. MAIN RESULTS: A total of 56 studies (3725 patients) were included in this review. These included 12 studies of bulking agents (621 patients), 29 of antispasmodics (2333 patients), and 15 of antidepressants (922 patients). The risk of bias was low for most items. However, selection bias is unclear for many of the included studies because the methods used for randomization and allocation concealment were not described. No beneficial effect for bulking agents over placebo was found for improvement of abdominal pain (4 studies; 186 patients; SMD 0.03; 95% CI -0.34 to 0.40; P = 0.87), global assessment (11 studies; 565 patients; RR 1.10; 95% CI 0.91 to 1.33; P = 0.32) or symptom score (3 studies; 126 patients SMD -0.00; 95% CI -0.43 to 0.43; P = 1.00). Subgroup analyses for insoluble and soluble fibres also showed no statistically significant benefit. Separate analysis of the studies with adequate concealment of allocation did not change these results. There was a beneficial effect for antispasmodics over placebo for improvement of abdominal pain (58% of antispasmodic patients improved compared to 46% of placebo; 13 studies; 1392 patients; RR 1.32; 95% CI 1.12 to 1.55; P < 0.001; NNT = 7), global assessment (57% of antispasmodic patients improved compared to 39% of placebo; 22 studies; 1983 patients; RR 1.49; 95% CI 1.25 to 1.77; P < 0.0001; NNT = 5) and symptom score (37% of antispasmodic patients improved compared to 22% of placebo; 4 studies; 586 patients; RR 1.86; 95% CI 1.26 to 2.76; P < 0.01; NNT = 3). Subgroup analyses for different types of antispasmodics found statistically significant benefits for cimteropium/ dicyclomine, peppermint oil, pinaverium and trimebutine. Separate analysis of the studies with adequate allocation concealment found a significant benefit for improvement of abdominal pain. There was a beneficial effect for antidepressants over placebo for improvement of abdominal pain (54% of antidepressants patients improved compared to 37% of placebo; 8 studies; 517 patients; RR 1.49; 95% CI 1.05 to 2.12; P = 0.03; NNT = 5), global assessment (59% of antidepressants patients improved compared to 39% of placebo; 11 studies; 750 patients; RR 1.57; 95% CI 1.23 to 2.00; P < 0.001; NNT = 4) and symptom score (53% of antidepressants patients improved compared to 26% of placebo; 3 studies; 159 patients; RR 1.99; 95% CI 1.32 to 2.99; P = 0.001; NNT = 4). Subgroup analyses showed a statistically significant benefit for selective serotonin releasing inhibitors (SSRIs) for improvement of  global assessment and for tricyclic antidepressants (TCAs) for improvement of abdominal pain and symptom score. Separate analysis of studies with adequate allocation concealment found a significant benefit for improvement of symptom score and global assessment. Adverse events were not assessed as an outcome in this review. AUTHORS' CONCLUSIONS: There is no evidence that bulking agents are effective for treating IBS.  There is evidence that antispasmodics are effective for the treatment of IBS. The individual subgroups which are effective include: cimetropium/dicyclomine, peppermint oil, pinaverium and trimebutine. There is good evidence that antidepressants are effective for the treatment of IBS. The subgroup analyses for SSRIs and TCAs are unequivocal and their effectiveness may depend on the individual patient. Future research should use rigorous methodology and valid outcome measures.
MED-2967
Atherogenesis: a postprandial phenomenon.
The hypothesis that plasma chylomicrons in persons who ingest a cholesterol-rich diet are atherogenic is evaluated. Evidence is presented that in humans, and experimental animals, chylomicron remnants as well as low-density lipoproteins are taken up by arterial cells. In persons who do not have familial hyperlipoproteinemia, atherogenesis may occur during the postprandial period. Research directions that may contribute to the evaluation of chylomicron remnants as a risk factor for atherogenesis are discussed. Lipoprotein studies after administration of a test meal containing fat and cholesterol are urgently needed.
MED-4919
Long-term health and quality-of-life consequences of mass screening for childhood celiac disease: a 10-year follow-up study.
OBJECTIVE: Mass screening for celiac disease is controversial. The objective of this study was to determine whether detection of childhood celiac disease by mass screening improves long-term health status and health-related quality of life. METHODS: We conducted a prospective 10-year follow-up study of 32 children who were aged 2 to 4 years, had celiac disease identified by mass screening, and had a gluten-free diet (19) or a normal gluten-containing diet (13). The follow-up included assessments of general health status, celiac disease-associated symptoms, celiac disease-associated serum antibodies, and health-related quality of life. RESULTS: Ten years after mass screening, 81% of the children were adhering to a gluten-free diet. The health status improved in 66% of the treated children: in 41% by early treatment and in 25% by prevention of the gluten-dependent symptoms that they developed after diagnosis. For 19% of the children, treatment after screening would not have improved their health status, because they had no symptoms at screening and have remained symptom-free while consuming gluten. The health-related quality of life of the children with symptoms improved significantly after 1 year of gluten-free diet. Ten years after screening, the health-related quality of life of the children with celiac disease was similar to that of the reference population. CONCLUSION: Identification by mass screening led 10 years later to health improvement in 66% of children without deterioration of generic health-related quality of life. There is a good compliance after mass screening. In a research setting, delaying treatment for children without symptoms seems to be an option after a positive screening test. Long-term follow-up studies are needed to assess possible long-term complications in untreated, nonsymptomatic celiac disease.
MED-3649
Food-borne origins of Escherichia coli causing extraintestinal infections.
Most human extraintestinal Escherichia coli infections, including those involving antimicrobial resistant strains, are caused by the members of a limited number of distinctive E. coli lineages, termed extraintestinal pathogenic E. coli (ExPEC), that have a special ability to cause disease at extraintestinal sites when they exit their usual reservoir in the host's intestinal tract. Multiple lines of evidence suggest that many of the ExPEC strains encountered in humans with urinary tract infection, sepsis, and other extraintestinal infections, especially the most extensively antimicrobial-resistant strains, may have a food animal source, and may be transmitted to humans via the food supply. This review summarizes the evidence that food-borne organisms are a significant cause of extraintestinal E. coli infections in humans.
MED-5246
The effect of caffeine on intraocular pressure: a systematic review and meta-analysis.
BACKGROUND: Caffeine is widely consumed, and its effect on intraocular pressure (IOP) has been reported in conflicting data. The aim of this meta-analysis was to quantitatively summarize the effect of caffeine on IOP in normal individuals and in patients with glaucoma or ocular hypertension (OHT). METHODS: A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify pertinent randomized controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and EMBASE. A systematic review and meta-analysis was performed. IOP at 0.5 hour (h), 1 h and 1.5 h after caffeine ingestion was the main outcome measurement. RESULTS: Six RCTs (two parallel-designed and four crossover-designed) evaluating 144 participants fulfilled inclusion criteria. The risk of bias for these studies was uncertain. Among the participants, 103 were normal individuals and 41 were patients with glaucoma or OHT. In normal individuals, the IOPs measured at 0.5 h, 1 h and 1.5 h post-intervention were not affected by ingestion of caffeine. The weighted mean difference (WMD) with 95% confidence intervals (95%CI) for each measurement point were -0.740 (-2.454, 0.974), 0.522 (-0.568, 1.613) and 0.580 (-1.524, 2.684). However, in patients with glaucoma or OHT, IOP increased at each measurement point, with the WMD and 95%CI being 0.347 (0.078, 0.616), 2.395 (1.741,3.049) and 1.998 (1.522,2.474) respectively. No publication bias was detected by either Begg's or Egger's test. CONCLUSION: Available evidences showed that caffeine had different effects on IOP in different groups of individuals. For normal individuals, IOP was not changed by ingestion of caffeine, while for patients with glaucoma or OHT, IOP increased significantly. More high-quality RCTs are warranted to confirm this. The mechanisms underlying this phenomenon and the clinical significance are to be explored.
MED-1315
Primary and acquired resistance of colorectal cancer cells to anti-EGFR antibodies converge on MEK/ERK pathway activation and can be overcome by co...
PURPOSE: The EGFR-independent activation of the RAS/RAF/MEK/MAPK pathway is one of the resistance mechanisms to cetuximab. EXPERIMENTAL DESIGN: We have evaluated, in vitro and in vivo, the effects of BAY 86-9766, a selective MEK1/2 inhibitor, in a panel of human colorectal cancer cell lines with primary or acquired resistance to cetuximab. RESULTS: Among the colorectal cancer cell lines, five with a KRAS mutation (LOVO, HCT116, HCT15, SW620, and SW480) and one with a BRAF mutation (HT29) were resistant to the antiproliferative effects of cetuximab, whereas two cells (GEO and SW48) were highly sensitive. Treatment with BAY 86-9766 determined dose-dependent growth inhibition in all cancer cells, including two human colorectal cancer cells with acquired resistance to cetuximab (GEO-CR and SW48-CR), with the exception of HCT15 cells. Combined treatment with cetuximab and BAY 86-9766 induced a synergistic antiproliferative and apoptotic effects with blockade in the MAPK and AKT pathway in cells with either primary or acquired resistance to cetuximab. The synergistic antiproliferative effects were confirmed using other two selective MEK1/2 inhibitors, selumetinib and pimasertib, in combination with cetuximab. Moreover, inhibition of MEK expression by siRNA restored cetuximab sensitivity in resistant cells. In nude mice bearing established human HCT15, HCT116, SW48-CR, and GEO-CR xenografts, the combined treatment with cetuximab and BAY 86-9766 caused significant tumor growth inhibition and increased mice survival. CONCLUSION: These results suggest that activation of MEK is involved in both primary and acquired resistance to cetuximab and the inhibition of EGFR and MEK could be a strategy for overcoming anti-EGFR resistance in patients with colorectal cancer. ©2014 American Association for Cancer Research.
MED-4393
Phytonutrient intake by adults in the United States in relation to fruit and vegetable consumption.
BACKGROUND: Individuals consuming diets dense in fruits and vegetables consume an array of phytonutrients as well as recognized nutritional components, including vitamins, minerals, and fiber. There is a growing body of evidence that phytonutrients may play positive roles in health. OBJECTIVE: The purpose of this research was to estimate usual intakes of nine individual phytonutrients by Americans consuming recommended levels of fruits and vegetables compared to intakes by adults not meeting these recommendations, and to identify contributions of food sources to total phytonutrient intakes. The phytonutrients examined in this study are found predominantly in fruits and vegetables. DESIGN: Food consumption data from the National Health and Nutrition Examination Surveys 2003-2006 and phytonutrient concentration data from US Department of Agriculture databases and the published literature were used to estimate energy-adjusted usual intakes. Student's t tests were used to compare mean energy-adjusted phytonutrient intakes between subpopulations who consumed recommended amounts of fruits and vegetables vs those who did not. Percentage contributions of each phytonutrient by food source were estimated for all adults. RESULTS: Energy-adjusted intakes of all phytonutrients other than ellagic acid were considerably higher among both men and women meeting dietary recommendations for fruit and vegetable intakes compared to those not meeting the recommendations; energy-adjusted intakes of ellagic acid were higher only among women meeting vs not meeting the recommendations. For five of the nine phytonutrients (α-carotene, β-cryptoxanthin, lycopene, hesperetin, and ellagic acid), a single food accounted for 64% or more of the total intake of the phytonutrient. CONCLUSIONS: Energy-adjusted intakes of carotenoids and flavonoids are higher among men and women whose diets conform to dietary guidance for fruits and vegetables. A limited number of foods provide the majority of these phytonutrients. Findings from this research provide important reference information on the phytonutrient contributions of a diet rich in fruits and vegetables.
MED-5287
Candy consumption was not associated with body weight measures, risk factors for cardiovascular disease, or metabolic syndrome in US adults: NHANES...
There is limited research examining the relationship of candy consumption by adults on diet and health. The purpose of this study was to determine total, chocolate, or sugar candy consumption and their effect on energy, saturated fatty acid and added sugar intake, weight, risk factors for cardiovascular disease, metabolic syndrome (MetS), and diet quality in adults 19 years and older (n = 15,023) participating in the 1999-2004 National Health and Nutrition Examination Survey. Twenty-four-hour dietary recalls were used to determine intake. Covariate-adjusted means ± SE and prevalence rates were determined for candy consumption groups. Odds ratios were used to determine the likelihood of cardiovascular risk factors and MetS. A total of 21.8%, 12.9%, and 10.9% of adults consumed total, chocolate, and sugar candy, respectively. Mean daily per capita intake of total, chocolate, and sugar candy was 9.0 ± 0.3, 5.7 ± 0.2, and 3.3 ± 0.2 g, respectively; intake in consumers was 38.3 ± 1.0, 39.9 ± 1.1, and 28.9 ± 1.3 g, respectively. Energy (9973 ± 92 vs 9027 ± 50 kJ; P < .0001), saturated fatty acid (27.9 ± 0.26 vs 26.9 ± 0.18 g; P = .0058), and added sugar (25.7 ± 0.42 vs 21.1 ± 0.41 g; P < .0001) intake were higher in candy consumers than nonconsumers. Body mass index (27.7 ± 0.15 vs 28.2 ± 0.12 kg/m(2); P = .0092), waist circumference (92.3 ± 0.34 vs 96.5 ± 0.29 cm; P = .0051), and C-reactive protein (0.40 ± 0.01 vs 0.43 ± 0.01 mg/dL; P = .0487) levels were lower in candy consumers than nonconsumers. Candy consumers had a 14% decreased risk of elevated diastolic blood pressure (P = .0466); chocolate consumers had a 19% decreased risk of lower high-density lipoprotein cholesterol (P = .0364) and a 15% reduced risk of MetS (P = .0453). Results suggest that the current level of candy consumption was not associated with health risks. Copyright © 2011 Elsevier Inc. All rights reserved.
MED-1678
Combined effect of low-risk dietary and lifestyle behaviors in primary prevention of myocardial infarction in women.
BACKGROUND: Limited data are available on the benefit of combining healthy dietary and lifestyle behaviors in the prevention of myocardial infarction (MI) in women. METHODS: We used factor analysis to identify a low-risk behavior-based dietary pattern in 24 444 postmenopausal women from the population-based prospective Swedish Mammography Cohort who were free of diagnosed cancer, cardiovascular disease, and diabetes mellitus at baseline (September 15, 1997). We also defined 3 low-risk lifestyle factors: nonsmoking, waist-hip ratio less than the 75th percentile (< 0.85), and being physically active (at least 40 minutes of daily walking or bicycling and 1 hour of weekly exercise). RESULTS: During 6.2 years (151 434 person-years) of follow-up, we ascertained 308 cases of primary MI. Two major identified dietary patterns, "healthy" and "alcohol," were significantly associated with decreased risk of MI. The low-risk diet (high scores for the healthy dietary pattern) characterized by a high intake of vegetables, fruit, whole grains, fish, and legumes, in combination with moderate alcohol consumption (>/= 5 g of alcohol per day), along with the 3 low-risk lifestyle behaviors, was associated with 92% decreased risk (95% confidence interval, 72%-98%) compared with findings in women without any low-risk diet and lifestyle factors. This combination of healthy behaviors, present in 5%, may prevent 77% of MIs in the study population. CONCLUSION: Most MIs in women may be preventable by consuming a healthy diet and moderate amounts of alcohol, being physically active, not smoking, and maintaining a healthy weight.
MED-940
An open label, randomized, fixed-dose, crossover study comparing efficacy and safety of sildenafil citrate and saffron (Crocus sativus Linn.) for t...
Saffron (Crocus sativus Linn.) have been perceived by the public as a strong aphrodisiac herbal product. However, studies addressing the potential beneficial effects of saffron on erectile function (EF) in men with ED are lacking. Our aim was to evaluate the efficacy and safety of saffron administration on EF in men with ED. After a 4-week baseline assessment, 346 men with ED (mean age 46.6+/-8.4 years) were randomized to receive on-demand sildenafil for 12 weeks followed by 30 mg saffron twice daily for another 12 weeks or vice versa, separated by a 2-week washout period. To determine the type of ED, penile color duplex Doppler ultrasonography before and after intracavernosal injection with 20 microg prostaglandin E(1), pudendal nerve conduction tests and impaired sensory-evoked potential studies were performed. Subjects were assessed with an International Index of Erectile Function (IIEF) questionnaire, Sexual Encounter Profile (SEP) diary questions, patient and partner versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire and the Global Efficacy Question (GEQ) 'Has the medication you have been taking improved your erections?' No significant improvements were observed with regard to the IIEF sexual function domains, SEP questions and EDITS scores with saffron administration. The mean changes from baseline values in IIEF-EF domain were +87.6% and +9.8% in sildenafil and placebo groups, respectively (P=0.08). We did not observe any improvement in 15 individual IIEF questions in patients while taking saffron. Treatment satisfaction as assessed by partner versions of EDITS was found to be very low in saffron patients (72.4 vs 25.4, P=0.001). Mean per patient 'yes' responses to GEQ was 91.2 and 4.2% for sildenafil and saffron, respectively (P=0.0001). These findings do not support a beneficial effect of saffron administration in men with ED.
MED-3046
Changes in brain activation associated with reward processing in smokers and nonsmokers. A positron emission tomography study.
Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [H2(15O)] positron emission tomography (PET), we measured regional cerebral blood flow (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded.
MED-1663
MR aortography and serum cholesterol levels in patients with long-term nonspecific lower back pain.
STUDY DESIGN: A cross-sectional analysis of the feeding arteries of the lumbar spine and cholesterol levels on patients with long-term nonspecific lower back pain. OBJECTIVES: To evaluate whether occlusion of lumbar and middle sacral arteries or serum cholesterol levels are associated with lower back pain and/or with disc degeneration. SUMMARY OF BACKGROUND DATA: Atherosclerosis in the wall of the abdominal aorta usually develops at the ostia of branching arteries and the bifurcation, and may obliterate orifices of lumbar and middle sacral arteries. Obstruction of these arteries causes ischemia in the lumbar spine and may result in back symptoms and disc degeneration. METHODS: MR aortography and cholesterol blood tests were performed on 51 patients with long-term lower back pain without specific findings (i.e., spinal or nerve root compression) in regular lumbar MR images. The patients ranged from 35 to 70 years of age (mean age, 56 years). Serum cholesterol and low-density lipoprotein (LDL) cholesterol levels were measured. To assess symptoms and disability NASS low back Outcome Instrument was used. RESULTS: Twenty-nine (78%) of 37 men and 11 (77%) of 14 women showed occluded lumbar and/or middle sacral arteries. The prevalence of occluded arteries was 2.5 times more than in subjects of corresponding age group in a Finnish necropsy material. Twenty-three (62%) men and seven (50%) women had significant disc degeneration. Disc degeneration was associated with occluded lumbar/middle sacral arteries (P = 0.035). Patients with occluded arteries or significant disc degeneration did not complain more severe symptoms than those without, whereas patients with above normal serum LDL cholesterol scored higher in neurogenic symptoms (P = 0.031) and complained more often severe pain (P = 0.049) than those with normal LDL cholesterol. CONCLUSIONS: The study indicates that lumbar and middle sacral arteries are often occluded in patients with nonspecific long-term lower back pain. Occlusion of these arteries may also be associated with disc degeneration.
MED-757
Turning back the clock: adopting a healthy lifestyle in middle age.
PURPOSE: To determine the frequency of adopting a healthy lifestyle (5 or more fruits and vegetables daily, regular exercise, BMI 18.5-29.9 kg/m2, no current smoking) in a middle-aged cohort, and determine the subsequent rates of cardiovascular disease (CVD) and mortality among those who adopt a healthy lifestyle. METHODS: We conducted a cohort study in a diverse sample of adults age 45-64 in the Atherosclerosis Risk in Communities survey. Outcomes are all-cause mortality and fatal or non-fatal cardiovascular disease. RESULTS: Of 15,708 participants, 1344 (8.5%) had 4 healthy lifestyle habits at the first visit, and 970 (8.4%) of the remainder had newly adopted a healthy lifestyle 6 years later. Men, African Americans, individuals with lower socioeconomic status, or a history of hypertension or diabetes were less likely to newly adopt a healthy lifestyle (all P <.05). During the following 4 years, total mortality and cardiovascular disease events were lower for new adopters (2.5% vs 4.2%, chi2P <.01, and 11.7% vs 16.5%, chi2P <.01 respectively) compared to individuals who did not adopt a healthy lifestyle. After adjustment, new adopters had lower all-cause mortality (OR 0.60, 95% Confidence Interval [CI], 0.39-0.92) and fewer cardiovascular disease events (OR 0.65, 95% CI, 0.39-0.92) in the next 4 years. CONCLUSIONS: People who newly adopt a healthy lifestyle in middle-age experience a prompt benefit of lower rates of cardiovascular disease and mortality. Strategies to encourage adopting healthy lifestyles should be implemented, especially among people with hypertension, diabetes, or low socioeconomic status.
MED-2046
Efficacy and safety of Chlorella supplementation in adults with chronic hepatitis C virus infection
AIM: To evaluate the safety and efficacy of Chlorella in 18 patients chronically infected with hepatitis C virus (HCV) genotype 1. METHODS: Eighteen adults with chronic infection by HCV genotype 1 received daily oral supplementation of Chlorella for 12 wk. Changes in the RNA levels of HCV, as well as those of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were evaluated following this treatment period. Paired t tests were conducted to compare the means of the different variables at the beginning and end of the study. Side effects and quality of life aspects were also compared between weeks 0 and 12 of the study period. RESULTS: A majority 84.61% of the patients had a significant decrease in their ALT levels from week 0 to week 12. Evaluation of side effects showed that Chlorella was well tolerated. Quality of life assessment showed that 76.9 of the participants reported an improvement in their energy levels and 46.1% reported an improvement in their perception of general health. Although 69.23% also showed a decrease in their AST levels, this was not statistically significant. Most patients that exhibited an improvement in their ALT and AST levels also showed a tendency toward a decreased HCV viral load. The HCV RNA levels showed a decrease in 69.23% of the patients, which along with changes in AST/ALT ratios from week 0 to week 12, these results were not statistically significant. CONCLUSION: Chlorella supplementation was well tolerated in patients with chronic HCV and associated with a significant decrease in ALT liver enzyme levels.
MED-1316
Colloidal oatmeal: history, chemistry and clinical properties.
Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses. In 1945, a ready to use colloidal oatmeal, produced by finely grinding the oat and boiling it to extract the colloidal material, became available. Today, colloidal oatmeal is available in various dosage forms from powders for the bath to shampoos, shaving gels, and moisturizing creams. Currently, the use of colloidal oatmeal as a skin protectant is regulated by the U.S. Food and Drug Administration (FDA) according to the Over-The-Counter Final Monograph for Skin Protectant Drug Products issued in June 2003. Its preparation is also standardized by the United States Pharmacopeia. The many clinical properties of colloidal oatmeal derive from its chemical polymorphism. The high concentration in starches and beta-glucan is responsible for the protective and water-holding functions of oat. The presence of different types of phenols confers antioxidant and anti-inflammatory activity. Some of the oat phenols are also strong ultraviolet absorbers. The cleansing activity of oat is mostly due to saponins. Its many functional properties make colloidal oatmeal a cleanser, moisturizer, buffer, as well as a soothing and protective anti-inflammatory agent.
MED-4463
Phenethyl isothiocyanate sensitizes human cervical cancer cells to apoptosis induced by cisplatin
Naturally-occurring chemopreventive agent phenethyl isothiocyanate (PEITC), derived primarily from watercress, has been shown to inhibit cell growth and induce apoptosis in cancer cells. In this study, we examined the potential of PEITC in enhancing cisplatin-induced apoptosis in cervical cancer cells. HeLa cells were exposed to PEITC, cisplatin or both. Pretreatment of cells with PEITC strongly enhanced cisplatin-induced cytotoxicity. PEITC activated the mitogen-activated protein kinases, including JNK, ERK, and p38. The synergistic induction of apoptosis was significantly attenuated by MEK1/2 inhibitor U0126, but not by JNK or p38 inhibitor, suggesting that ERK activation is responsible for the synergistic effect. We found that NF-κB signaling pathway is not involved in the synergistic effect. Sulforaphane and benzyl isothiocyanate, two other members of the isothiocyanate family, also sensitize HeLa cells to apoptosis induced by cisplatin. Furthermore, we found that the synergistic effect was not seen in normal cells. Finally, we demonstrated that Noxa induction was associated with apoptosis induced by PEITC plus cisplatin. Taken together, this study shows that PEITC can sensitize cancer cells to apoptosis induced by cisplatin and this effect is mediated through ERK activation, suggesting the potential of PEITC to be used as an adjuvant with cisplatin in combination therapeutic treatments.
MED-3493
Acute hepatotoxicity after ingestion of Morinda citrifolia (Noni Berry) juice in a 14-year-old boy.
We present a case of a 14-year-old previously healthy boy with acute hepatotoxicity after noni berry juice consumption. As the popularity of noni berry consumption continues to increase, heightened awareness of the relation between noni berry consumption and acute hepatotoxicity is important.
MED-3148
Sympathetic nervous system activity and resting metabolic rate in vegetarians.
We examined the resting metabolic rate (RMR) and sympathetic nervous system activity of young male vegetarians (n = 17) and nonvegetarians (n = 40). Subjects were characterized for RMR by indirect calorimetry, norepinephrine kinetics from infusions of tritiated norepinephrine, energy and macronutrient intake from a 3-day food diary, and body composition by underwater weighing. Vegetarians reported a greater relative intake of carbohydrates (62% +/- 5% v 51% +/- 6%, P < .01) and a lower relative intake of fat (25% +/- 5% v 33% +/- 6%, P < .01) than nonvegetarians, whereas no differences were observed in daily energy intake, body composition, or maximal aerobic capacity (VO2max) between groups. Vegetarians exhibited an 11% higher absolute RMR (1.29 +/- 0.15 v 1.16 +/- 0.13 kcal/min, P < .01), a higher plasma concentration of norepinephrine (216 +/- 33 v 165 +/- 18 pg/mL, P < .01), and a greater norepinephrine appearance rate (0.50 +/- 0.08 v 0.36 +/- 0.09 micrograms/min, P < .01) than nonvegetarians. After statistically controlling for differences in relative amounts of carbohydrate and fat in the diet and for norepinephrine concentrations, no significant differences in adjusted RMR between vegetarians and nonvegetarians were noted. These results suggest that the higher RMR observed in young male vegetarians is partially mediated by differences in dietary macronutrient composition and increased sympathetic nervous system activity.
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-5276
8:45-90:00. The Influence of a High Fat Meal Compared to an Olestra Meal on Coronary Artery Endothelial Dysfunction by Rubidium (Rb)-82 Positron Em...
Background: Cellular changes lead to coronary artery endothelial dysfunction (ED) and precede plaque formation. Clinical events, such as unstable angina and acute coronary syndromes, are common consequences of ED. Coronary artery ED, as characterized by Rb-82 PE, is a perfusion abnormality at rest, which improves following stress. In risk factor modification studies, particularly in cholesterol-lowering trials, coronary artery ED has been demonstrated to be reversible. Other studies have correlated low fat diet modification with improvement in coronary artery disease.Purpose: This study evaluates changes in myocardial perfusion following meals with low versus high TG content, and its influence on post prandial serum TG.Methods: With a randomized, double blind placebo controlled, cross over design, we investigated 19 patients (10 with ED and 9 with normal perfusion) with Rb-82 PET for myocardial blood flow at rest and with adenosine stress. PET images and serum triglycerides were obtained before and after an olestra (OA) meal (2.7g TG, 44g olestra) and a high-fat meal (46.7g TG). Meals were matched for carbohydrate, protein, and cholesterol content.Results: Myocardial perfusion (uCi/cc) increased 11 - 12% following the OA meal compared to the high-fat meal in patients with ED. For all patients combined, serum TG increased significantly (p < 0.01) in the non-OA group with the median change from baseline to 170.0 mg/dl, compared to 21.5 mg/dl in the OA group during the 6 hours following the meal.Conclusions: A single olestra meal significantly diminishes post prandial serum TG levels and improves myocardial perfusion in patients with endothelial disease.
MED-1123
Systematic literature review on economic implications and pharmacoeconomic issues of rheumatoid arthritis.
OBJECTIVES: To provide a state of the art of economic analyses applied to rheumatoid arthritis (RA). METHODS: A systematic literature review on economic consequences and pharmacoeconomic issues of RA was performed. RESULTS: 127 valid articles were examined in this review. Generally, the financial impact of RA is substantial for health-care systems and society worldwide, although differences exist among national economies. Both direct and indirect (i.e. loss of productivity) costs contribute to economic burden of RA and must be taken into account when estimating overall impact to society. Disease severity, disease activity, age and socioeconomic status have been found to be the most relevant predictors of cost increase in RA. Moreover, introduction of biological anti-rheumatic agents has significantly raised direct medical costs in certain patients, but has also led to marked improvements in reducing disease activity, joint damage, and productivity loss in many of these patients. RA has also a significant impact on all aspects of quality of life; recent publications on health utility scores showed RA to be one of the diseases associated with poorest quality of life. CONCLUSIONS: RA represents a clinical and economic burden for healthcare systems. Although attributable RA costs have been extensively evaluated over the last decades, several issues, especially concerning the use of expensive therapies, must be addressed and frequently updated. Future research should also provide health economic evidence from usual practice settings, and on the economic impact of different therapeutic approaches to pursue specific clinical targets in individual patients.
MED-4332
Potent antimutagenic activity of white tea in comparison with green tea in the Salmonella assay.
There is growing interest in the potential health benefits of tea, including the antimutagenic properties. Four varieties of white tea, which represent the least processed form of tea, were shown to have marked antimutagenic activity in the Salmonella assay, particularly in the presence of S9. The most active of these teas, Exotica China white tea, was significantly more effective than Premium green tea (Dragonwell special grade) against 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and four other heterocyclic amine mutagens, namely 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). Mechanism studies were performed using rat liver S9 in assays for methoxyresorufin O-demethylase (MROD), a marker for the enzyme cytochrome P4501A2 that activates heterocyclic amines, as well as Salmonella assays with the direct-acting mutagen 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-hydroxy-IQ). White tea at low concentrations in the assay inhibited MROD activity, and attenuated the mutagenic activity of N-hydroxy-IQ in the absence of S9. Nine of the major constituents found in green tea also were detected in white tea, including high levels of epigallocatechin-3-gallate (EGCG) and several other polyphenols. When these major constituents were mixed to produce "artificial" teas, according to their relative levels in white and green teas, the complete tea exhibited higher antimutagenic potency compared with the corresponding artificial tea. The results suggest that the greater inhibitory potency of white versus green tea in the Salmonella assay might be related to the relative levels of the nine major constituents, perhaps acting synergistically with other (minor) constituents, to inhibit mutagen activation as well as "scavenging" the reactive intermediate(s).
MED-5219
The antiaging approach for the treatment of dry eye.
Dry eye is one of the most common eye disorders affecting millions of people. It causes ocular irritation or discomfort, and decreases functional vision, causing a dramatic deterioration in the quality of life. Although new treatments such as the P2Y2 agonist or cyclosporine eye drops have been developed and a certain level of patient satisfaction can now be obtained, no fundamental treatment has been developed. Currently, there is no therapy available to recover lacrimal function to its normal status. Recent progress in the understanding of aging has laid the foundations for a new way of thinking about intervention of the aging process. Because dry eye is accelerated by aging, a useful approach for the prevention or treatment of dry eye may be to interfere with the aging process. In the scientific community, there is a global consensus that calorie restriction can extend the life span of various kinds of animals, establishing an intervention to aging. Another important hypothesis believed to be involved in aging is the free radical theory. According to these theories, the aging process may be managed by controlling levels of calories or reactive oxygen species. In this review, these 2 important aging theories, calorie restriction and free radical aging, are examined, and we discuss how to apply these theories to the prevention and treatment of dry eye.
MED-976
Prevalence of diverticular disease, hiatus hernia, and pelvic phleboliths in black and white Americans.
Phleboliths, and especially diverticular disease and hiatus hernia, are rarer in developing countries than in economically more developed communities, but all three conditions were as common in Black as in White Americans. This finding suggests that they are due to environmental rather than to genetic causes. A deficient intake of dietary fibre may be the common factor predisposing to these three conditions.
MED-1696
Gender, Race, and Diet Affect Platelet Function Tests in Normal Subjects Contributing to a High Rate of Abnormal Results
Summary To assess sources of variability in platelet function tests in normal subjects, 64 healthy young adults were tested on 2–6 occasions at 2 week intervals using 4 methods: platelet aggregation (AGG) in platelet-rich plasma (PRP) in the Bio/Data PAP-4 Aggregometer (BD) and Chrono-Log Lumi-Aggregometer (CL); and AGG in whole blood (WB) in the CL and Multiplate Platelet Function Analyzer (MP), with ATP release (REL) in CL-PRP and CL-WB. Food and medication exposures were recorded prospectively for 2 weeks prior to each blood draw. At least one AGG abnormality was seen in 21% of 81 drug-free specimens with CL-PRP, 15% with CL-WB, 13% with BD-PRP, and 6% with MP-WB, increasing with inclusion of REL to 28% for CL-PRP and 30% for CL-WB. Epinephrine AGG and REL were significantly reduced in males (P<0.0001). Ristocetin AGG and collagen and thrombin REL were significantly reduced in Blacks (P<0.0001). One-third of specimens drawn following flavonoid-rich food exposures had aberrant results, compared to 8.5% of specimens without such exposures (P=0.0035). PRP tests had less intra-individual variation than WB tests. Gender, race, diet, and test system affected results of platelet function testing in healthy subjects, suggesting caution when interpreting the results of platelet function testing in patients.
MED-1340
Milk Consumption During Teenage Years and Risk of Hip Fractures in Older Adults
Importance Milk consumption during adolescence is recommended to promote peak bone mass and thereby reduce fracture risk in later life. However, its role in hip fracture prevention is not established and high consumption may adversely influence risk by increasing height. Objective To determine whether milk consumption during teenage years influences risk of hip fracture in older adults and to investigate the role of attained height in this association. Design Prospective cohort study over 22 years of follow-up Setting United States Participants Over 96,000 Caucasian postmenopausal women from the Nurses’ Health Study and men age 50 and older from the Health Professionals Follow-up Study Exposures Frequency of consumption of milk and other foods during ages 13–18 and attained height were reported at baseline. Current diet, weight, smoking, physical activity, medication use, and other risk factors for hip fractures were reported on biennial questionnaires. Main Outcome Measures Cox proportional hazards models were used to calculate relative risks (RR) of first incident hip fracture from low-trauma events per glass (8 fl oz or 240 mL) of milk consumed per day during teenage years. Results Over follow-up, 1226 hip fractures were identified in women and 490 in men. After controlling for known risk factors and current milk consumption, each additional glass of milk per day during teenage years was associated with a significant 9% higher risk of hip fracture in men (RR=1.09, 95% CI 1.01–1.17). The association was attenuated when height was added to the model (RR=1.06, 95% CI 0.98–1.14). Teenage milk consumption was not associated with hip fractures in women (RR=1.00, 95% CI 0.95–1.05 per glass per day). Conclusion and Relevance Greater milk consumption during teenage years was not associated with a lower risk of hip fracture in older adults. The positive association observed in men was partially mediated through attained height.
MED-762
The Ethiopian Field Epidemiology and Laboratory Training Program: strengthening public health systems and building human resource capacity.
The Ethiopian Field Epidemiology and Laboratory Training Program (EFELTP) is a comprehensive two-year competency-based training and service program designed to build sustainable public health expertise and capacity. Established in 2009, the program is a partnership between the Ethiopian Federal Ministry of Health, the Ethiopian Health and Nutrition Research Institute, Addis Ababa University School of Public Health, the Ethiopian Public Health Association and the US Centers of Disease Control and Prevention. Residents of the program spend about 25% of their time undergoing didactic training and the 75% in the field working at program field bases established with the MOH and Regional Health Bureaus investigating disease outbreaks, improving disease surveillance, responding to public health emergencies, using health data to make recommendations and undertaking other field Epidemiology related activities on setting health policy. Residents from the first 2 cohorts of the program have conducted more than 42 outbreaks investigations, 27analyses of surveillance data, evaluations of 11 surveillance systems, had28oral and poster presentation abstracts accepted at 10 scientific conferences and submitted 8 manuscripts of which 2are already published. The EFELTP has provided valuable opportunities to improve epidemiology and laboratory capacity building in Ethiopia. While the program is relatively young, positive and significant impacts are assisting the country better detect and respond to epidemics and address diseases of major public health significance.
MED-1010
Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis.
BACKGROUND: Sexual dysfunction (SD) is an important underestimated adverse effect of antidepressant drugs. Patients, in fact, if not directly questioned, tend to scarcely report them. The aim of the present meta-analysis was to quantify SD caused by antidepressants on the basis of studies where sexual functioning was purposely investigated through direct inquiry and specific questionnaires. METHODS: A literature search was conducted using MEDLINE, ISI Web of Knowledge, and references of selected articles. Selected studies performed on patients without previous SD were entered in the Cochrane Collaboration Review Manager (RevMan version 4.2). Our primary outcome measure was the rate of total treatment-emergent SD. Our secondary outcome measures were the rates of treatment-emergent desire, arousal, and orgasm dysfunction. RESULTS: Our analyses indicated a significantly higher rate of total and specific treatment-emergent SD and specific phases of dysfunction compared with placebo for the following drugs in decreasing order of impact: sertraline, venlafaxine, citalopram, paroxetine, fluoxetine, imipramine, phenelzine, duloxetine, escitalopram, and fluvoxamine, with SD ranging from 25.8% to 80.3% of patients. No significant difference with placebo was found for the following antidepressants: agomelatine, amineptine, bupropion, moclobemide, mirtazapine, and nefazodone. DISCUSSION: Treatment-emergent SD caused by antidepressants is a considerable issue with a large variation across compounds. Some assumptions, such as the inclusion of open-label studies or differences in scales used to assess SD, could reduce the significance of our findings. However, treatment-emergent SD is a frequent adverse effect that should be considered in clinical activity for the choice of the prescribed drug.
MED-1683
Platelets and atherogenesis: Platelet anti-aggregation activity and endothelial protection from tomatoes (Solanum lycopersicum L.)
In recent years, it has been shown that platelets are not only involved in the arterial thrombotic process, but also that they play an active role in the inflammatory process of atherogenesis from the beginning. The interaction between platelets and endothelial cells occurs in two manners: activated platelets unite with intact endothelial cells, or platelets in resting adhere to activated endothelium. In this context, inhibition of the platelet function (adhesion/aggregation) could contribute to the prevention of atherothrombosis, the leading cause of cardiovascular morbidity. This can be achieved with antiplatelet agents. However, at the public health level, the level of primary prevention, a healthy diet has also been shown to exert beneficial effects. Among those elements of a healthy diet, the consumption of tomatoes (Solanum lycopersicum L.) stands out for its effect on platelet anti-aggregation activity and endothelial protection, which may be beneficial for cardiovascular health. This article briefly discusses the involvement of platelets in atherogenesis and the possible mechanisms of action provided by tomatoes for platelet anti-aggregation activity and endothelial protection.
MED-4098
Dietary intakes of mushrooms and green tea combine to reduce the risk of breast cancer in Chinese women.
To investigate effects of dietary mushrooms and joint effects of mushrooms and green tea on breast cancer, a case-control study was conducted in southeast China in 2004-2005. The incident cases were 1,009 female patients aged 20-87 years with histologically confirmed breast cancer. The 1,009 age-matched controls were healthy women randomly recruited from outpatient breast clinics. Information on frequency and quantity of dietary intake of mushrooms and tea consumption, usual diet, and lifestyle were collected by face-to-face interview using a validated and reliable questionnaire. Compared with nonconsumers, the Odds ratios (Ors) were 0.36 (95% CI = 0.25-0.51) and 0.53 (0.38-0.73) for daily intake of >or=10 g fresh mushrooms and >or=4 g dried mushrooms, based on multivariate logistic regression analysis adjusting for established and potential confounders. There were dose-response relationships with significant tests for trend (p < 0.001). The inverse association was found in both pre- and postmenopausal women. Compared with those who consumed neither mushrooms nor green tea, the ORs were 0.11 (0.06-0.20) and 0.18 (0.11-0.29) for daily high intake of fresh and dried mushrooms combined with consuming beverages made from >or=1.05 g dried green tea leaves per day. The corresponding linear trends were statistically significant for joint effect (p < 0.001). We conclude that higher dietary intake of mushrooms decreased breast cancer risk in pre- and postmenopausal Chinese women and an additional decreased risk of breast cancer from joint effect of mushrooms and green tea was observed. More research is warranted to examine the effects of dietary mushrooms and mechanism of joint effects of phytochemicals on breast cancer.
MED-1636
Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials.
Coffee drinking has been associated with increased serum cholesterol levels in some, but not all, studies. A Medline search of the English-language literature published prior to December 1998, a bibliography review, and consultations with experts were performed to identify 14 published trials of coffee consumption. Information was abstracted independently by two reviewers using a standardized protocol. With a random-effects model, treatment effects were estimated by pooling results from individual trials after weighting the results by the inverse of total variance. A dose-response relation between coffee consumption and both total cholesterol and LDL cholesterol was identified (p < 0.01). Increases in serum lipids were greater in studies of patients with hyperlipidemia and in trials of caffeinated or boiled coffee. Trials using filtered coffee demonstrated very little increase in serum cholesterol. Consumption of unfiltered, but not filtered, coffee increases serum levels of total and LDL cholesterol.
MED-4855
Does the hip powder of Rosa canina (rosehip) reduce pain in osteoarthritis patients?--a meta-analysis of randomized controlled trials.
OBJECTIVE: Meta-analysis of randomized controlled trials (RCTs)--of a hip powder of Rosa canina (rosehip) preparation for symptomatic treatment of osteoarthritis (OA), in order to estimate the empirical efficacy as a pain reducing compound. METHOD: RCTs from systematic searches were included if they explicitly stated that OA patients were randomized to either rosehip or placebo. The primary outcome was reduction in pain calculated as effect size (ES), defined as the standardized mean difference (SMD). As secondary analysis the number of responders to therapy was analyzed as Odds Ratios (OR), and expressed as the Number Needed to Treat (NNT). Restricted Maximum Likelihood (REML) methods were applied for the meta-analyses using mixed effects models. RESULTS: The three studies (287 patients and a median trial-duration of 3 months)--all supported by the manufacturer (Hyben-Vital International)--showed a reduction in pain scores by rosehip powder (145 patients) compared to placebo (142 patients): ES of 0.37 [95% confidence interval (CI): 0.13-0.60], P=0.002. Test for homogeneity seemed to support that the efficacy was consistent across trials (I(2)=0%). Thus it seems reasonable to assume that the three studies were measuring the same overall effect. It seemed twice as likely that a patient allocated to rosehip powder would respond to therapy, compared to placebo (OR=2.19; P=0.0009); corresponding to a NNT of six (95% CI: 4-13) patients. CONCLUSIONS: Although based on a sparse amount of data, the results of the present meta-analysis indicate that rosehip powder does reduce pain; accordingly it may be of interest as a nutraceutical, although its efficacy and safety need evaluation and independent replication in a future large-scale/long-term trial.
MED-4988
Type of Vegetarian Diet, Body Weight, and Prevalence of Type 2 Diabetes
OBJECTIVE We assessed the prevalence of type 2 diabetes in people following different types of vegetarian diets compared with that in nonvegetarians. RESEARCH DESIGN AND METHODS The study population comprised 22,434 men and 38,469 women who participated in the Adventist Health Study-2 conducted in 2002–2006. We collected self-reported demographic, anthropometric, medical history, and lifestyle data from Seventh-Day Adventist church members across North America. The type of vegetarian diet was categorized based on a food-frequency questionnaire. We calculated odds ratios (ORs) and 95% CIs using multivariate-adjusted logistic regression. RESULTS Mean BMI was lowest in vegans (23.6 kg/m2) and incrementally higher in lacto-ovo vegetarians (25.7 kg/m2), pesco-vegetarians (26.3 kg/m2), semi-vegetarians (27.3 kg/m2), and nonvegetarians (28.8 kg/m2). Prevalence of type 2 diabetes increased from 2.9% in vegans to 7.6% in nonvegetarians; the prevalence was intermediate in participants consuming lacto-ovo (3.2%), pesco (4.8%), or semi-vegetarian (6.1%) diets. After adjustment for age, sex, ethnicity, education, income, physical activity, television watching, sleep habits, alcohol use, and BMI, vegans (OR 0.51 [95% CI 0.40–0.66]), lacto-ovo vegetarians (0.54 [0.49–0.60]), pesco-vegetarians (0.70 [0.61–0.80]), and semi-vegetarians (0.76 [0.65–0.90]) had a lower risk of type 2 diabetes than nonvegetarians. CONCLUSIONS The 5-unit BMI difference between vegans and nonvegetarians indicates a substantial potential of vegetarianism to protect against obesity. Increased conformity to vegetarian diets protected against risk of type 2 diabetes after lifestyle characteristics and BMI were taken into account. Pesco- and semi-vegetarian diets afforded intermediate protection.