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Numerous studies demonstrated the lack of transferability of polygenic score (PGS) models across populations and the problem arising from unequal presentation of ancestries across genetic studies. However, even within European ancestry there are ethnic groups that are rarely presented in genetic studies. For instance, Russians, being one of the largest, diverse, and yet understudied group in Europe. In this study, we evaluated the reliability of genotype imputation for the Russian cohort by testing several commonly used imputation reference panels (e.g. HRC, 1000G, HGDP). HRC, in comparison with two other panels, showed the most accurate results based on both imputation accuracy and allele frequency concordance between masked and imputed genotypes. We built polygenic score models based on GWAS results from the UK biobank, measured the explained phenotypic variance in the Russian cohort attributed to polygenic scores for 11 phenotypes, collected in the clinic for each participant, and finally explored the role of allele frequency discordance between the UK biobank and the study cohort in the resulting PGS performance.

BACKGROUND: The number of non-Western immigrants with breast cancer in the Netherlands has increased over the past decades and is expected to triple by 2030. Due to insufficient representation in clinical studies, it is unclear what the specific experiences and needs of these women are. Understanding how culture and religion affect these women's experience of breast cancer and how they deal with chemotherapy and treatment-related changes in body weight and lifestyle is crucial for health care professionals to be able to provide effective support. METHODS: A qualitative study was conducted using semi-structured interviews with 28 immigrant women with a history of breast cancer treated with chemotherapy. RESULTS: Women often associated breast cancer with taboo, death or bad luck. Religion offered these women guidance, strength and meaning to the disease, but also limited the women to openly talk about their disease. Women perceived lifestyle factors to have little influence on the development and treatment of cancer. After treatment, however, their thinking changed and these lifestyle factors became of paramount importance to them. They realised that they missed out on information about managing their own diet, exercise and body weight and were eager to share their experiences with other women in their culture with newly diagnosed breast cancer. CONCLUSION: Women became aware during and after breast cancer treatment that it was difficult for them to actively deal with their illness under the influence of their culture and religion. Based on their own experiences and acquired knowledge, they would like to give advice to newly diagnosed women on how to deal with breast cancer within their own culture and religion. Their recommendations could be used by mosques, churches, support groups and health care professionals, to ensure interventions during breast cancer treatment meet their religious and cultural needs and thus improve their quality of life.

Cocoa consumption has beneficial cardiometabolic effects, but underlying mechanisms remain unclear. Epicatechin, the cocoa major monomeric flavan-3-ol, is considered to contribute to these cardio-protective effects. We investigated effects of pure epicatechin supplementation on gene expression profiles of immune cells in humans. In a double blind, placebo-controlled cross-over trial, 32 (pre)hypertensive subjects aged 30 to 80, received two 4-week interventions, i.e. epicatechin (100mg/day) or placebo with a 4-week wash-out between interventions. Gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Epicatechin regulated 1180 genes, of which 234 differed from placebo. Epicatechin upregulated gene sets involved in transcription and tubulin folding and downregulated gene sets involved in inflammation, PPAR signalling and adipogenesis. Several negatively enriched genes within these gene sets were involved in insulin signalling. Most inhibited upstream regulators within the epicatechin intervention were cytokines or involved in inflammation. No upstream regulators were identified compared to placebo. Epicatechin, a cocoa flavan-3-ol, reduces gene expression involved in inflammation, PPAR-signalling and adipogenesis in immune cells. Effects were mild but our findings increase our understanding and provide new leads on how epicatechin rich products like cocoa may affect immune cells and exert cardiometabolic protective effects.

Vitamin C may reduce risk of hypertension, either in itself or by marking a healthy diet pattern. We assessed whether plasma ascorbic acid and the a priori diet quality score relate to incident hypertension and whether they explain each other's predictive abilities. Data were from 2884 black and white adults (43% black, mean age 35 years) initially hypertensionfree in the Coronary Artery Risk Development in Young Adults Study (study year 10, 1995- 1996). Plasma ascorbic acid was assessed at year 10 and the diet quality score at year 7. Eight-hundred-And-forty cases of hypertension were documented between years 10 and 25. After multiple adjustments, each 12-point (1 SD) higher diet quality score at year 7 related to mean 3.7 μmol/L (95% CI 2.9 to 4.6) higher plasma ascorbic acid at year 10. In separate multiple-Adjusted Cox regression models, the hazard ratio of hypertension per 19.6-μmol/L (1 SD) higher ascorbic acid was 0.85 (95% CI 0.79-0.92) and per 12-points higher diet score 0.86 (95% CI 0.79-0.94). These hazard ratios changed little with mutual adjustment of ascorbic acid and diet quality score for each other, or when adjusted for anthropometric variables, diabetes, and systolic blood pressure at year 10. Intake of dietary vitamin C and several food groups high in vitamin C content were inversely related to hypertension, whereas supplemental vitamin C was not. In conclusion, plasma ascorbic acid and the a priori diet quality score independently predict hypertension. This suggests that hypertension risk is reduced by improving overall diet quality and/or vitamin C status. The inverse association seen for dietary but not for supplemental vitamin C suggests that vitamin C status is preferably improved by eating foods rich in vitamin C, in addition to not smoking and other dietary habits that prevent ascorbic acid from depletion.

Background: Diet has been associated with better mental health in general populations, but less is known on this association in patients with a history of coronary heart disease.The objective of this study is to examine the cross-sectional associations between dietary patterns and mental health in elderly patients with a history of myocardial infarction.Methods: Data were drawn from the final assessment of the Alpha Omega cohort that monitored patients with a history of myocardial infarction (age range 60-80 years). 2171 patients with complete data for diet and mental health were included in this study. Diet was assessed with the 203-item Food Frequency Questionnaire, and subsequently categorized into two scores: the Dutch Healthy Nutrient and Food Score (DHNaFS) and the Dutch Undesirable Nutrient and Food Score (DUNaFS). Depressive symptoms, assessed with the Geriatric Depression Scale (GDS-15), and dispositional optimism, assessed with the 4-item questionnaire (4Q), were cross-sectionally analyzed in relation to dietary patterns using linear regression analysis.Results: Patients were on average 72.2 years old and 79.5% were male. The DHNaFS score was associated with less depressive symptoms and higher dispositional optimism (β = -0.108; PConclusions: A healthy dietary pattern, in particular a higher consumption of vegetables, fruit, whole grains, fish and low-fat dairy, was associated with less depressive symptoms and higher optimism. However, given the cross-sectional nature of our analyses, our findings may also be explained by more optimistic participants making healthier food choices. Therefore, future prospective or interventions studies are needed to establish the direction of causality of this association.

INTRODUCTION: The development of metabolic syndrome (MetS) is influenced by environmental factors such as smoking and alcohol consumption. We determined the combined effects of smoking and alcohol on MetS and its individual components.METHODS: 64,046 participants aged 18-80 years from the LifeLines Cohort study were categorized into three body mass index (BMI) classes (BMIRESULTS: Prevalence of MetS varied greatly between the different smoking-alcohol subgroups (1.7-71.1%). HDL cholesterol levels in all alcohol drinkers were higher than in non-drinkers (0.02 to 0.29 mmol/L, P values1 drink/day) and tobacco showed higher triglycerides levels. Up to 2 drinks/day was associated with a smaller waist circumference in overweight and obese individuals. Consumption of >2 drinks/day increased blood pressure, with the strongest associations found for heavy smokers. The overall metabolic profile of wine drinkers was better than that of non-drinkers or drinkers of beer or spirits/mixed drinks.CONCLUSION: Light alcohol consumption may moderate the negative associations of smoking with MetS. Our results suggest that the lifestyle advice that emphasizes smoking cessation and the restriction of alcohol consumption to a maximum of 1 drink/day, is a good approach to reduce the prevalence of MetS.

Excessive salt intake is associated with hypertension and cardiovascular diseases. Salt intake exceeds the World Health Organization population nutrition goal of 5 grams per day in the European region. We assessed the health impact of salt reduction in nine European countries (Finland, France, Ireland, Italy, Netherlands, Poland, Spain, Sweden and United Kingdom). Through literature research we obtained current salt intake and systolic blood pressure levels of the nine countries. The population health modeling tool DYNAMO-HIA including country-specific disease data was used to predict the changes in prevalence of ischemic heart disease and stroke for each country estimating the effect of salt reduction through its effect on blood pressure levels. A 30% salt reduction would reduce the prevalence of stroke by 6.4% in Finland to 13.5% in Poland. Ischemic heart disease would be decreased by 4.1% in Finland to 8.9% in Poland. When salt intake is reduced to the WHO population nutrient goal, it would reduce the prevalence of stroke from 10.1% in Finland to 23.1% in Poland. Ischemic heart disease would decrease by 6.6% in Finland to 15.5% in Poland. The number of postponed deaths would be 102,100 (0.9%) in France, and 191,300 (2.3%) in Poland. A reduction of salt intake to 5 grams per day is expected to substantially reduce the burden of cardiovascular disease and mortality in several European countries.

BACKGROUND: Pulmonary tuberculosis (TB) patients often suffer from anorexia and poor nutrition, causing weight loss. The peptide hormones leptin and its counterpart ghrelin, acting in the regulation of food intake and fat utilization, play an important role in nutritional balance. This study aimed to investigate the association of blood concentrations of leptin, ghrelin and inflammatory cytokines with body mass index (BMI) in TB patients with and without type 2 diabetes mellitus (T2DM). METHODS: BMI, biochemical parameters and plasma levels of leptin, ghrelin and inflammatory cytokines were measured before the start of treatment in 27 incident TB patients with T2DM, 21 TB patients and 23 healthy subjects enrolled in this study. RESULTS: The levels of leptin were significantly higher in TB patients (35.2 ± 19.1 ng/ml) than TB+T2DM (12.6 ± 6.1 ng/ml) and control (16.1 ± 11.1 ng/ml) groups. The level of ghrelin was significantly lower in TB (119.9 ± 46.1 pg/ml) and non-significantly lower in TB+T2DM (127.7 ± 38.6 pg/ml) groups than control (191.6 ± 86.5 pg/ml) group. The levels of TNF-α were higher, while IFN-γ and IL-6 levels were lower in patients than in the control group. Leptin showed a negative correlation with BMI in TB (r=-0.622, p0.05) groups, but negative correlation with BMI in the control (r=-0.693, p

Background Prevalence of type 2 diabetes (T2D) is increasing worldwide. T2D prevention by lifestyle intervention is effective. Pragmatic scalable interventions are needed, with evidence to efficiently target and monitor such interventions. We report pooled analyses of data from three European trial cohorts: to analyse T2D incidence, sustained weight loss and utility of risk predictors. Methods We analysed data on 749 adults with impaired glucose tolerance (278 men and 471 women, mean age 56 years, mean BMI 31 kgm−2) recruited between 1993 and 2003, and randomised to intensive lifestyle intervention (I) or lifestyle advice control (C). The intervention aimed to increase physical activity, modify diet, and promote weight loss≥5%. Using Cox-regression survival analysis, we assessed T2D incidence and the impact on T2D incidence of sustained weight loss, and of baseline cut-point values of FINDRISC score, fasting plasma glucose (FPG), and HbA1c. Results Mean follow-up duration was 3.1 years. T2D was diagnosed in 139 participants (I = 45/379, C = 94/370). Cumulative T2D incidence was 57% lower in the intervention compared with the control group (HR 0.42 (95% CI 0.29 to 0.60) P

The purpose of this cross-sectional study was to investigate the joint associations of physical activity level (PAL) and dietary patterns in relation to cardiovascular disease (CVD) risk factors among Chinese men. The study population consisted of 13 511 Chinese males aged 18-59 years from the 2002 China National Nutrition and Health Survey. Based on dietary data collected by a food frequency questionnaire, four dietary patterns were identified and labeled as "Green Water'' (high consumption of rice, vegetables, seafood, pork, and poultry), "Yellow Earth'' (high consumption of wheat flour products and starchy tubers), "New Affluent'' (high consumption of animal sourced foods and soybean products), and "Western Adopter'' (high consumption of animal sourced foods, cakes, and soft drinks). From the information collected by a 1-year physical activity questionnaire, PAL was calculated and classified into 4 categories: sedentary, low active, active, and very active. As compared with their counterparts from the New Affluent pattern, participants who followed the Green Water pattern had a lower likelihood of abdominal obesity (AO; 50.2%), hypertension (HT; 37.9%), hyperglycemia (HG; 41.5%), elevated triglyceride (ETG; 14.5%), low HDL (LHDL; 39.8%), and metabolic syndrome (MS; 51.9%). When compared to sedentary participants, the odds ratio of participants with very active PAL was 0.62 for AO, 0.85 for HT, 0.71 for HG, 0.76 for ETG, 0.74 for LHDL, and 0.58 for MS. Individuals who followed both very active PAL and the Green Water pattern had a lower likelihood of CVD risk factors (AO: 65.8%, HT: 39.1%, HG: 57.4%, ETG: 35.4%, LHDL: 56.1%, and MS: 75.0%), compared to their counterparts who followed both sedentary PAL and the New Affluent pattern. In addition, adherence to both healthy dietary pattern and very active PAL presented a remarkable potential for CVD risk factor prevention.

Background: Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA), a biomarker for prostate cancer. Methods: The Alpha Omega Trial (ClinicalTrials.gov Identifier: NCT00127452) was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a 2x2 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60-80 years with an initial PSA concentration 4 ng/mL). Findings: Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a difference of 0.10 (95% confidence interval: -0.02 to 0.22) ng/mL (P = 0.12). The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84-1.58). Interpretation: An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from -0.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer. Trial registration information: ClinicalTrials.gov; Identifier: NCT00127452. URL: http://www.clinicaltrials.gov/ct2/show/NCT00127452. © 2013 Brouwer et al.

Regular physical activity positively influences whole body energy metabolism and substrate handling in exercising muscle. While it is recognized that the effects of exercise extend beyond exercising muscle, it is unclear to what extent exercise impacts non-exercising muscles. Here we investigated the effects of an acute endurance exercise bouts on gene expression in exercising and non-exercising human muscle. To that end, 12 male subjects aged 44-56 performed one hour of one-legged cycling at 50% W(max). Muscle biopsies were taken from the exercising and non-exercising leg before and immediately after exercise and analyzed by microarray. One-legged cycling raised plasma lactate, free fatty acids, cortisol, noradrenalin, and adrenalin levels. Surprisingly, acute endurance exercise not only caused pronounced gene expression changes in exercising muscle but also in non-exercising muscle. In the exercising leg the three most highly induced genes were all part of the NR4A family. Remarkably, many genes induced in non-exercising muscle were PPAR targets or related to PPAR signalling, including PDK4, ANGPTL4 and SLC22A5. Pathway analysis confirmed this finding. In conclusion, our data indicate that acute endurance exercise elicits pronounced changes in gene expression in non-exercising muscle, which are likely mediated by changes in circulating factors such as free fatty acids. The study points to a major influence of exercise beyond the contracting muscle.

BACKGROUND: There is some evidence that the association of fish and marine fatty acids with stroke risk differs between men and women. We investigated the gender-specific associations of habitual intake of the marine fatty acids eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) and fish on incident stroke in a population-based study in the Netherlands. METHODS: We prospectively followed 20,069 men and women, aged 20-65 years, without cardiovascular diseases at baseline. Habitual diet was assessed with a validated 178-item food frequency questionnaire. Incidence of stroke was assessed through linkage with mortality and morbidity registers. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (95%CI). RESULTS: During 8-13 years of follow-up, 221 strokes occurred. In women, an inverse dose-response relation (P-trend = 0.02) was observed between EPA-DHA intake and incident stroke, with an HR of 0.49 (95% CI: 0.27-0.91) in the top quartile of EPA-DHA (median 225 mg/d) as compared to the bottom quartile (median 36 mg/d). In men, the HR (95%CI) for the top quartile of EPA-DHA intake was 0.87 (0.51-1.48) (P-trend = 0.36). Similar results were observed for fish consumption and stroke incidence. CONCLUSION: A higher EPA-DHA and fish intake is related to a lower stroke risk in women, while for men an inverse association could not be demonstrated.

BACKGROUND: A positive parental history of myocardial infarction (MI) is an independent risk factor for cardiovascular diseases (CVD). However, different definitions of parental history have been used. We evaluated the impact of parental gender and age of onset of MI on CVD incidence. METHODS: Baseline data were collected between 1993 and 1997 in 10,524 respondents aged 40-65 years. CVD events were obtained from the National Hospital Discharge Register and Statistics Netherlands. We used proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for CVD incidence and adjusted for lifestyle and biological risk factors. RESULTS: At baseline, 36% had a parental history of MI. During 10-year follow-up, 914 CVD events occurred. The age and gender adjusted HR was 1.3 (95% CI 1.1-1.5) for those with a paternal MI, 1.5 (1.2-1.8) for those with a maternal MI and 1.6 (1.2-2.2) for those with both parents with an MI. With decreasing parental age of MI, HR increased from 1.2 (1.0-1.6) for age ≥70 years to 1.5 (1.2-1.8) for age

Contains fulltext : 98290.pdf (Publisher’s version ) (Open Access) BACKGROUND: The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from prospective studies and explore whether there is a non-linear association of red and processed meats with colorectal cancer risk. METHODS AND FINDINGS: Relevant prospective studies were identified in PubMed until March 2011. For each study, relative risks and 95% confidence intervals (CI) were extracted and pooled with a random-effects model, weighting for the inverse of the variance, in highest versus lowest intake comparison, and dose-response meta-analyses. Red and processed meats intake was associated with increased colorectal cancer risk. The summary relative risk (RR) of colorectal cancer for the highest versus the lowest intake was 1.22 (95% CI = 1.11-1.34) and the RR for every 100 g/day increase was 1.14 (95% CI = 1.04-1.24). Non-linear dose-response meta-analyses revealed that colorectal cancer risk increases approximately linearly with increasing intake of red and processed meats up to approximately 140 g/day, where the curve approaches its plateau. The associations were similar for colon and rectal cancer risk. When analyzed separately, colorectal cancer risk was related to intake of fresh red meat (RR(for 100 g/day increase) = 1.17, 95% CI = 1.05-1.31) and processed meat (RR (for 50 g/day increase) = 1.18, 95% CI = 1.10-1.28). Similar results were observed for colon cancer, but for rectal cancer, no significant associations were observed. CONCLUSIONS: High intake of red and processed meat is associated with significant increased risk of colorectal, colon and rectal cancers. The overall evidence of prospective studies supports limiting red and processed meat consumption as one of the dietary recommendations for the prevention of colorectal cancer.

Background: Elevated blood pressure (BP), which is a major risk factor for cardiovascular disease, is highly prevalent worldwide. Recently, interest has grown in the role of dietary protein in human BP. We performed a systematic review of all published scientific literature on dietary protein, including protein from various sources, in relation to human BP.Methodology/Principal Findings: We performed a MEDLINE search and a manual search to identify English language studies on the association between protein and blood pressure, published before June 2010. A total of 46 papers met the inclusion criteria. Most observational studies showed no association or an inverse association between total dietary protein and BP or incident hypertension. Results of biomarker studies and randomized controlled trials indicated a beneficial effect of protein on BP. This beneficial effect may be mainly driven by plant protein, according to results in observational studies. Data on protein from specific sources (e.g. from fish, dairy, grain, soy, and nut) were scarce. There was some evidence that BP in people with elevated BP and/or older age could be more sensitive to dietary protein.Conclusions/Significance: In conclusion, evidence suggests a small beneficial effect of protein on BP, especially for plant protein. A blood pressure lowering effect of protein may have important public health implications. However, this warrants further investigation in randomized controlled trials. Furthermore, more data are needed on protein from specific sources in relation to BP, and on the protein-BP relation in population subgroups.

Udgivelsesdato: 2010-null BACKGROUND: Given the recognized health effects of visceral fat, the understanding of how diet can modulate changes in the phenotype "waist circumference for a given body mass index (WC(BMI))", a proxy measure of visceral adiposity, is deemed necessary. Hence, the objective of the present study was to assess the association between dietary factors and prospective changes in visceral adiposity as measured by changes in the phenotype WC(BMI). METHODS AND FINDINGS: We analyzed data from 48,631 men and women from 5 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthropometric measurements were obtained at baseline and after a median follow-up time of 5.5 years. WC(BMI) was defined as the residuals of waist circumference regressed on body mass index, and annual change in WC(BMI) (DeltaWC(BMI), cm/y) was defined as the difference between residuals at follow-up and baseline, divided by follow-up time. The association between energy, energy density (ED), macronutrients, alcohol, glycemic index (GI), glycemic load (GL), fibre and DeltaWC(BMI) was modelled using centre-specific adjusted linear regression, and random-effects meta-analyses to obtain pooled estimates. Men and women with higher ED and GI diets showed significant increases in their WC(BMI), compared to those with lower ED and GI [1 kcal/g greater ED predicted a DeltaWC(BMI) of 0.09 cm (95% CI 0.05 to 0.13) in men and 0.15 cm (95% CI 0.09 to 0.21) in women; 10 units greater GI predicted a DeltaWC(BMI) of 0.07 cm (95% CI 0.03 to 0.12) in men and 0.06 cm (95% CI 0.03 to 0.10) in women]. Among women, lower fibre intake, higher GL, and higher alcohol consumption also predicted a higher DeltaWC(BMI). CONCLUSIONS: Results of this study suggest that a diet with low GI and ED may prevent visceral adiposity, defined as the prospective changes in WC(BMI). Additional effects may be obtained among women of low alcohol, low GL, and high fibre intake.

Background - Biomarkers that allow detection of the onset of disease are of high interest since early detection would allow intervening with lifestyle and nutritional changes before the disease is manifested and pharmacological therapy is required. Our study aimed to improve the phenotypic characterization of overweight but apparently healthy subjects and to identify new candidate profiles for early biomarkers of obesity-related diseases such as cardiovascular disease and type 2 diabetes. Methodology/Principal Findings - In a population of 56 healthy, middle-aged overweight subjects Body Mass Index (BMI), fasting concentration of 124 plasma proteins and insulin were determined. The plasma proteins are implicated in chronic diseases, inflammation, endothelial function and metabolic signaling. Random Forest was applied to select proteins associated with BMI and plasma insulin. Subsequently, the selected proteins were analyzed by clustering methods to identify protein clusters associated with BMI and plasma insulin. Similar analyses were performed for a second population of 20 healthy, overweight older subjects to verify associations found in population I. In both populations similar clusters of proteins associated with BMI or insulin were identified. Leptin and a number of pro-inflammatory proteins, previously identified as possible biomarkers for obesity-related disease, e.g. Complement 3, C Reactive Protein, Serum Amyloid P, Vascular Endothelial Growth Factor clustered together and were positively associated with BMI and insulin. IL-3 and IL-13 clustered together with Apolipoprotein A1 and were inversely associated with BMI and might be potential new biomarkers. Conclusion/ Significance - We identified clusters of plasma proteins associated with BMI and insulin in healthy populations. These clusters included previously reported biomarkers for obesity-related disease and potential new biomarkers such as IL-3 and IL-13. These plasma protein clusters could have potential applications for improved phenotypic characterization of volunteers in nutritional intervention studies or as biomarkers in the early detection of obesity-linked disease development and progression

Udgivelsesdato: 2009-null BACKGROUND: Experimental studies show that a reduction in dietary energy density (ED) is associated with reduced energy intake and body weight. However, few observational studies have investigated the role of ED on long-term weight and waist circumference change. METHODS AND PRINCIPAL FINDINGS: This population-based prospective cohort study included 89,432 participants from five European countries with mean age 53 years (range: 20-78 years) at baseline and were followed for an average of 6.5 years (range: 1.9-12.5 years). Participants were free of cancer, cardiovascular diseases and diabetes at baseline. ED was calculated as the energy intake (kcal) from foods divided by the weight (g) of foods. Multiple linear regression analyses were performed to investigate the associations of ED with annual weight and waist circumference change. Mean ED was 1.7 kcal/g and differed across study centers. After adjusting for baseline anthropometrics, demographic and lifestyle factors, follow-up duration and energy from beverages, ED was not associated with weight change, but significantly associated with waist circumference change overall. For 1 kcal/g ED, the annual weight change was -42 g/year [95% confidence interval (CI): -112, 28] and annual waist circumference change was 0.09 cm/year [95% CI: 0.01, 0.18]. In participants with baseline BMI

Contains fulltext : 118282.pdf (Publisher’s version ) (Open Access) BACKGROUND AND AIMS: Individuals with Lynch syndrome have a high lifetime risk of developing colorectal tumors. In this prospective cohort study of individuals with Lynch syndrome, we examined associations between use of dietary supplements and occurrence of colorectal adenomas. MATERIALS AND METHODS: Using data of 470 individuals with Lynch syndrome in a prospective cohort study, associations between dietary supplement use and colorectal adenoma risk were evaluated by calculating hazard ratios (HR) and 95% confidence intervals (CI) using cox regression models adjusted for age, sex, and number of colonoscopies during person time. Robust sandwich covariance estimation was used to account for dependency within families. RESULTS: Of the 470 mismatch repair gene mutation carriers, 122 (26.0%) developed a colorectal adenoma during an overall median person time of 39.1 months. 40% of the study population used a dietary supplement. Use of any dietary supplement was not statistically significantly associated with colorectal adenoma risk (HR = 1.18; 95%CI 0.80-1.73). Multivitamin supplement use (HR = 1.15; 95%CI 0.72-1.84), vitamin C supplement use (HR = 1.57; 95%CI 0.93-2.63), calcium supplement use (HR = 0.69; 95%CI 0.25-1.92), and supplements containing fish oil (HR = 1.60; 95%CI 0.79-3.23) were also not associated with occurrence of colorectal adenomas. CONCLUSION: This prospective cohort study does not show inverse associations between dietary supplement use and occurrence of colorectal adenomas among individuals with Lynch syndrome. Further research is warranted to determine whether or not dietary supplement use is associated to colorectal adenoma and colorectal cancer risk in MMR gene mutation carriers.

Background: Dietary polyunsaturated fatty acids (PUFA) are inversely related to coronary heart disease (CHD) in epidemiological studies. We examined the associations of plasma n-6 and n-3 PUFA in cholesteryl esters with fatal CHD in a nested case-control study. Additionally, we performed a dose-response meta-analysis of similar prospective studies on cholesteryl ester PUFA. Methods: We used data from two population-based cohort studies in Dutch adults aged 20-65y. Blood and data collection took place from 1987-1997 and subjects were followed for 8-19y. We identified 279 incident cases of fatal CHD and randomly selected 279 controls, matched on age, gender, and enrollment date. Odds ratios (OR) were calculated per standard deviation (SD) increase of cholesteryl ester PUFA. Results: After adjustment for confounders, the OR (95% CI) for fatal CHD per SD increase in plasma linoleic acid was 0.89 (0.74-1.06). Additional adjustment for plasma total cholesterol and systolic blood pressure attenuated this association (OR:0.95; 95% CI: 0.78-1.15). Arachidonic acid was not associated with fatal CHD (OR per SD:1.11; 95% CI: 0.92-1.35). The ORs (95% CI) for fatal CHD for an SD increase in n-3 PUFA were 0.92 (0.74-1.15) for alpha-linolenic acid and 1.06 (0.88-1.27) for EPA-DHA. In the meta-analysis, a 5% higher linoleic acid level was associated with a 9% lower risk (relative risk: 0.91; 95% CI: 0.84-0.98) of CHD. The other fatty acids were not associated with CHD. Conclusion: In this Dutch population, n-6 and n-3 PUFA in cholesteryl esters were not significantly related to fatal CHD. Our data, together with findings from previous prospective studies, support that linoleic acid in plasma cholesteryl is inversely associated with CHD.

Background The ability of subjects to respond to nutritional challenges can reflect the flexibility of their biological system. Nutritional challenge tests could be used as an indicator of health status but more knowledge on metabolic and immune responses of different subjects to nutritional challenges is needed. The aim of this study was to compare the responses to high-fat challenges varying in fat type in subjects with different metabolic risk phenotypes. Methodology/Principal Findings In a cross-over design 42 men (age 50–70 y) consumed three high-fat shakes containing saturated fat (SFA), monounsaturated fat (MUFA) or n-3 polyunsaturated (PUFA). Men were selected on BMI and health status (lean, obese or obese diabetic) and phenotyped with MRI for adipose tissue distribution. Before and 2 and 4 h after shake consumption blood was drawn for measurement of expression of metabolic and inflammation-related genes in peripheral blood mononuclear cells (PBMCs), plasma triglycerides (TAG), glucose, insulin, cytokines and ex vivo PBMC immune response capacity. The MUFA and n-3 PUFA challenge, compared to the SFA challenge, induced higher changes in expression of inflammation genes MCP1 and IL1β in PBMCs. Obese and obese diabetic subjects had different PBMC gene expression and metabolic responses to high-fat challenges compared to lean subjects. The MUFA challenge induced the most pronounced TAG response, mainly in obese and obese diabetic subjects. Conclusion/Significance The PBMC gene expression response and metabolic response to high-fat challenges were affected by fat type and metabolic risk phenotype. Based on our results we suggest using a MUFA challenge to reveal differences in response capacity of subjects. Trial Registration ClinicalTrials.gov NCT00977262

BACKGROUND: Little is known about the relation of different dietary protein types with blood pressure (BP). We examined whether intake of total, plant, animal, dairy, meat, and grain protein was related to BP in a cross sectional cohort of 20,820 Dutch adults, aged 20-65 y and not using antihypertensive medication. DESIGN: Mean BP levels were calculated in quintiles of energy-adjusted protein with adjustment for age, sex, BMI, education, smoking, and intake of energy, alcohol, and other nutrients including protein from other sources. In addition, mean BP difference after substitution of 3 en% carbohydrates or MUFA with protein was calculated. RESULTS: Total protein and animal protein were not associated with BP (p(trend) = 0.62 and 0.71 respectively), both at the expense of carbohydrates and MUFA. Systolic BP was 1.8 mmHg lower (p(trend)36 g/d) than in the lowest (

Vitamin K is essential for activation of γ-carboxyglutamate (Gla)-proteins including the vascular calcification inhibitor matrix Gla-protein (MGP). Insufficient vitamin K intake leads to production of uncarboxylated, mostly inactive proteins and contributes to an increased cardiovascular risk. In kidney transplant recipients, cardiovascular risk is high but vitamin K intake and status have not been defined. We investigated dietary vitamin K intake, vascular vitamin K status and its determinants in kidney transplant recipients. We estimated vitamin K intake in a cohort of kidney transplant recipients (n = 60) with stable renal function (creatinine clearance 61 [42–77] (median [interquartile range]) ml/min), who were 75 [35–188] months after transplantation, using three-day food records and food frequency questionnaires. Vascular vitamin K status was assessed by measuring plasma desphospho-uncarboxylated MGP (dp-ucMGP). Total vitamin K intake was below the recommended level in 50% of patients. Lower vitamin K intake was associated with less consumption of green vegetables (33 vs 40 g/d, p = 0.06) and increased dp-ucMGP levels (621 vs 852 pmol/L, p500 pmol/L) in 80% of patients. Multivariate regression identified creatinine clearance, coumarin use, body mass index, high sensitivity-CRP and sodium excretion as independent determinants of dp-ucMGP levels. In a considerable part of the kidney transplant population, vitamin K intake is too low for maximal carboxylation of vascular MGP. The high dp-ucMGP levels may result in an increased risk for arterial calcification. Whether increasing vitamin K intake may have health benefits for kidney transplant recipients should be addressed by future studies.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects.\ud \ud AIM: We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake.\ud \ud METHODS AND FINDINGS: Participants, aged 20-60 years at baseline, came from five European countries. Cases ('weight gainers') were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a 'weight gainer' (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2 x 10⁻⁷).\ud \ud CONCLUSIONS: We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.

Background Trans fatty acids are produced either by industrial hydrogenation or by biohydrogenation in the rumens of cows and sheep. Industrial trans fatty acids lower high-density lipoprotein (HDL) cholesterol, raise low-density lipoprotein (LDL) cholesterol, and increase the risk of coronary heart disease. The effects of trans fatty acids from ruminants are less clear. We investigated the effect on blood lipids of cis-9, trans-11 conjugated linoleic acid (CLA), a trans fatty acid largely restricted to ruminant fats. Methodology/Principal Findings Sixty-one healthy women and men were sequentially fed each of three diets for three weeks, in random order, for a total of nine weeks. Diets were identical except for 7% of energy (approximately 20 g/day), which was provided either by oleic acid, by industrial trans fatty acids, or by a mixture of 80% cis-9, trans-11 and 20% trans-10, cis-12 CLA. After the oleic acid diet, mean (± SD) serum LDL cholesterol was 2.68±0.62 mmol/L compared to 3.00±0.66 mmol/L after industrial trans fatty acids (p