Habitual chocolate consumption and the risk of incident heart failure among healthy men and women.

BACKGROUND: We aimed to examine the association between chocolate intake and the risk of incident heart failure in a UK general population. We conducted a systematic review and meta-analysis to quantify this association. METHODS AND RESULTS: We used data from a prospective population-based study, the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Chocolate intake was quantified based on a food frequency questionnaire obtained at baseline (1993-1997) and incident heart failure was ascertained up to March 2009. We supplemented the primary data with a systematic review and meta-analysis of studies which evaluated risk of incident heart failure with chocolate consumption. A total of 20,922 participants (53% women; mean age 58 ± 9 years) were included of whom 1101 developed heart failure during the follow up (mean 12.5 ± 2.7 years, total person years 262,291 years). After adjusting for lifestyle and dietary factors, we found 19% relative reduction in heart failure incidence in the top (up to 100 g/d) compared to the bottom quintile of chocolate consumption (HR 0.81 95%CI 0.66-0.98) but the results were no longer significant after controlling for comorbidities (HR 0.87 95%CI 0.71-1.06). Additional adjustment for potential mediators did not attenuate the results further. We identified five relevant studies including the current study (N = 75,408). The pooled results showed non-significant 19% relative risk reduction of heart failure incidence with higher chocolate consumption (HR 0.81 95%CI 0.66-1.01). CONCLUSIONS: Our results suggest that higher chocolate intake is not associated with subsequent incident heart failure.

Contribution of cod liver oil-related nutrients (vitamins A, D, E and eicosapentaenoic acid and docosahexaenoic acid) to daily nutrient intake and their associations with plasma concentrations in the EPIC-Norfolk cohort.

BACKGROUND: Total nutrient intake (TNI) is intake from food and supplements. This provides an assessment of nutrient adequacy and the prevalence of excessive intake, as well as the response with respect to biomarkers. Cod liver oil (CLO) is the most frequently consumed supplement in the UK, containing nutrients that might have varying influences on health. We calculated TNI for vitamins A, D and E, as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and assessed associations with the respective blood concentrations. METHODS: Seven-day diet diaries and blood samples were taken from two subsets of the European Prospective Investigation into Cancer (EPIC-Norfolk) cohort (age range 39-79 years; n = 1400 for vitamin D; n = 6656 for remaining nutrients). TNI was calculated for the subgroups: nonsupplement users, those consuming the nutrient in supplement form and those consuming a supplement without this nutrient. RESULTS: CLO-related nutrients were supplemented by 15%-33%, which approximately doubled median intakes. Almost everyone in the supplement + vitamin A group reached the estimated average requirement; however, guideline levels were likely to be exceeded. Partial correlations between intake of vitamins A and D and biomarkers were low and modestly strengthened by the inclusion of supplement sources (correlation = 0.01-0.13). Correlations between biomarker and TNI of vitamin E and EPA+DHA were in the range 0.40-0.46; however, vitamin E exceeding food intake resulted in attenuated coefficients. Linear associations between food or TNI EPA+DHA and plasma were weak but consistent across subgroups. CONCLUSIONS: CLO-related nutrients contribute substantially to nutrient intake, with a risk of over-consumption. Apart from EPA+DHA, biomarker data suggest that CLO-related nutrients in supplements are not linearly associated with vitamin status.

NDRG4, an early detection marker for colorectal cancer, is specifically expressed in enteric neurons.

BACKGROUND: Promoter methylation of N-myc Downstream-Regulated Gene 4 (NDRG4) in fecal DNA is an established early detection marker for colorectal cancer (CRC). Despite its connection to CRC, NDRG4 is predominantly studied in brain and heart, with little to no knowledge about its expression or role in other organs. In this study, we aimed to determine the whole-body expression of NDRG4, with a focus on the intestinal tract. METHODS: We investigated NDRG4 expression throughout the body by immunohistochemistry, Western Blotting and in situ mRNA hybridization using tissues from NDRG4 wild-type, heterozygous and knockout mice and humans. In addition, we explored cell-specific expression of NDRG4 in murine whole-mount gut preparations using immunofluorescence and confocal microscopy. KEY RESULTS: NDRG4 is specifically expressed within nervous system structures throughout the body. In the intestinal tract of both mouse and man, NDRG4 immunoreactivity was restricted to the enteric nervous system (ENS), where it labeled cell bodies of the myenteric and submucosal plexuses and interconnecting nerve fibers. More precisely, NDRG4 expression was limited to neurons, as NDRG4 always co-localized with HuC/D (pan-neuronal marker) but never with GFAP (an enteric glial cell marker). Furthermore, NDRG4 was expressed in various neuropeptide Y positive neurons, but was only found in a minority (~10%) of neurons expressing neuronal nitric oxide synthase. CONCLUSIONS AND INFERENCES: NDRG4 is exclusively expressed by central, peripheral and enteric neurons/nerves, suggesting a neuronal-specific role of this protein. Our findings raise the question whether NDRG4, via the ENS, an understudied component of the tumor microenvironment, supports CRC development and/or progression.

Prostate cancer risk related to foods, food groups, macronutrients and micronutrients derived from the UK Dietary Cohort Consortium food diaries.

BACKGROUND/OBJECTIVES: The influence of dietary factors remains controversial for screen-detected prostate cancer and inconclusive for clinically detected disease. We aimed to examine these associations using prospectively collected food diaries. SUBJECTS/METHODS: A total of 1,717 prostate cancer cases in middle-aged and older UK men were pooled from four prospective cohorts with clinically detected disease (n=663), with routine data follow-up (means 6.6-13.3 years) and a case-control study with screen-detected disease (n=1054), nested in a randomised trial of prostate cancer treatments (ISCTRN 20141297). Multiple-day food diaries (records) completed by men prior to diagnosis were used to estimate intakes of 37 selected nutrients, food groups and items, including carbohydrate, fat, protein, dairy products, fish, meat, fruit and vegetables, energy, fibre, alcohol, lycopene and selenium. Cases were matched on age and diary date to at least one control within study (n=3528). Prostate cancer risk was calculated, using conditional logistic regression (adjusted for baseline covariates) and expressed as odds ratios in each quintile of intake (±95% confidence intervals). Prostate cancer risk was also investigated by localised or advanced stage and by cancer detection method. RESULTS: There were no strong associations between prostate cancer risk and 37 dietary factors. CONCLUSIONS: Prostate cancer risk, including by disease stage, was not strongly associated with dietary factors measured by food diaries in middle-aged and older UK men.

Dietary patterns derived with multiple methods from food diaries and breast cancer risk in the UK Dietary Cohort Consortium.

BACKGROUND/OBJECTIVES: In spite of several studies relating dietary patterns to breast cancer risk, evidence so far remains inconsistent. This study aimed to investigate associations of dietary patterns derived with three different methods with breast cancer risk. SUBJECTS/METHODS: The Mediterranean Diet Score (MDS), principal components analyses (PCA) and reduced rank regression (RRR) were used to derive dietary patterns in a case-control study of 610 breast cancer cases and 1891 matched controls within four UK cohort studies. Dietary intakes were collected prospectively using 4- to 7-day food diaries and resulting food consumption data were grouped into 42 food groups. Conditional logistic regression models were used to estimate odds ratios (ORs) for associations between pattern scores and breast cancer risk adjusting for relevant covariates. A separate model was fitted for post-menopausal women only. RESULTS: The MDS was not associated with breast cancer risk (OR comparing first tertile with third 1.20 (95% CI 0.92; 1.56)), nor the first PCA-derived dietary pattern, explaining 2.7% of variation of diet and characterized by cheese, crisps and savoury snacks, legumes, nuts and seeds (OR 1.18 (95% CI 0.91; 1.53)). The first RRR-derived pattern, a 'high-alcohol' pattern, was associated with a higher risk of breast cancer (OR 1.27; 95% CI 1.00; 1.62), which was most pronounced in post-menopausal women (OR 1.46 (95% CI 1.08; 1.98)). CONCLUSIONS: A 'high-alcohol' dietary pattern derived with RRR was associated with an increased breast cancer risk; no evidence of associations of other dietary patterns with breast cancer risk was observed in this study.

Fibre intake in relation to serum total cholesterol levels and CHD risk: a comparison of dietary assessment methods.

BACKGROUND/OBJECTIVES: Prospective diet diaries may be more accurate than retrospective food frequency questionnaires (FFQ). The objective of this study was to compare FFQ and 7-day diet diary (7DD) measurements of fibre intake with the incidence of coronary heart disease (CHD). SUBJECTS/METHODS: We compared 7DD and FFQ fibre intake in a nested case-control study in a population of 25639 men and women aged 40-79 years, surveyed in 1993-97 and followed up until 2007. Among 2151 CHD cases and 5354 controls, FFQ and 7DD fibre intake (6 g/day) was examined in relation to serum total cholesterol and CHD using linear and logistic regression adjusted for age and additionally for body mass index, physical activity, smoking status, family history of CHD, social class, diabetes, alcohol, energy, saturated fat and use of lipid lowering medication, antihypertensive medication or aspirin. RESULTS: Age-adjusted serum total cholesterol was inversely associated with 7DD fibre among men and women, but with FFQ fibre among men only. In the multivariate analysis, associations with 7DD fibre were attenuated among men (regression coefficient -0.036 mmol/l, s.e. 0.021, P-value 0.087) and women (regression coefficient -0.069 mmol/l, s.e. 0.036, P-value 0.053), and were non-significant for FFQ fibre. Among men, age-adjusted CHD risk was inversely associated with 7DD fibre (odds ratio (OR) 0.84, 95% confidence interval (CI) 0.79-0.90), but not with FFQ fibre (OR 0.96, 95% CI 0.90-1.12). Among women, age-adjusted CHD risk was inversely associated with 7DD fibre (OR 0.83, 95% CI 0.75-0.93), and had a weaker inverse borderline-significant association with FFQ fibre (OR 0.93, 95% CI 0.87-1.01). Multivariate models yielded similar results. CONCLUSIONS: Inconsistencies in diet-CHD relationships in population studies may be associated with the use of different dietary assessment methods.

Vitamin C intake from diary recordings and risk of breast cancer in the UK Dietary Cohort Consortium.

BACKGROUND/OBJECTIVES: Vitamin C intake has been inversely associated with breast cancer risk in case-control studies, but not in meta-analyses of cohort studies using Food Frequency Questionnaires, which can over-report fruit and vegetable intake, the main source of vitamin C. This is the first study to investigate associations between vitamin C intake and breast cancer risk using food diaries. SUBJECTS/METHODS: Estimated dietary vitamin C intake was derived from 4-7 day food diaries pooled from five prospective studies in the UK Dietary Cohort Consortium. This nested case-control study of 707 incident breast cancer cases and 2144 matched controls examined breast cancer risk in relation to dietary vitamin C intake using conditional logistic regression adjusting for relevant covariates. Additionally, total vitamin C intake from supplements and diet was analysed in three cohorts. RESULTS: No evidence of associations was observed between breast cancer risk and vitamin C intake analysed for dietary vitamin C intake (odds ratios (OR)=0.98 per 60 mg/day, 95% confidence interval (CI): 0.88-1.09, P (trend)=0.7), dietary vitamin C density (OR=0.97 per 60 mg/day, 95% CI: 0.87-1.07, P (trend)=0.5 ) or total vitamin C intake (OR=1.01 per 60 mg/day, 95% CI: 0.99-1.03, P (trend)=0.3). Additionally, there was no significant association for post-menopausal women (OR=1.02 per 60 mg/day, 95% CI: 0.99-1.05, P (trend)=0.3). CONCLUSIONS: This pooled analysis of individual UK women found no evidence of significant associations between breast cancer incidence and dietary or total vitamin C intake derived uniquely from detailed diary recordings.

Variation in intakes of calcium, phosphorus, magnesium, iron and potassium in 10 countries in the European Prospective Investigation into Cancer and Nutrition study.

BACKGROUND/OBJECTIVES: Adequate mineral intake is important for the maintenance of bone health, cellular function and general metabolism, and possibly in the aetiology of cancer and other chronic diseases. This study aimed at investigating variation in intakes of selected minerals across 10 European countries participating in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. METHODS: Nutrient intakes for 36 034 subjects, aged between 35 and 74 years, in 27 centres were obtained using standardized 24-h dietary recall software (EPIC-SOFT). Mean intakes of calcium, phosphorus, magnesium, iron and potassium were calculated by centre and weighted by season and day of the week and were also stratified by age group. The contribution of food groups to total nutrient intake was calculated. RESULTS: There was clear geographical variability in intakes, with differences ranging from 35% for magnesium to 90% for iron in men and 36% for potassium to 75% for calcium in women, and a twofold difference in sources of haem iron (meat and fish). There was a geographical gradient in iron intake, with higher intakes in Southern than in Northern Europe and also around a twofold north-south gradient in the contribution of fruits and vegetables to potassium intake. Compared with reference intakes, the majority of age groups and centres had intakes above the recommended levels. Dairy foods and products contributed the most to calcium and phosphorus intake in almost all centres. Cereals and cereal products contributed the most to magnesium and iron intakes, except in Greece and Germany. CONCLUSIONS: Intakes of minerals vary substantially throughout Europe, with some geographical variability in their food sources.

Dietary glycaemic index and glycaemic load in the European Prospective Investigation into Cancer and Nutrition.

OBJECTIVES: To describe dietary glycaemic index (GI) and glycaemic load (GL) values in the population participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study according to food groups, nutrients and lifestyle characteristics. METHODS: Single 24-h dietary recalls (24-HDRs) from 33 566 subjects were used to calculate dietary GI and GL, and an ad hoc database was created as the main reference source. Mean GI and GL intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall. RESULTS: GI was the lowest in Spain and Germany, and highest in the Netherlands, United Kingdom and Denmark for both genders. In men, GL was the lowest in Spain and Germany and highest in Italy, whereas in women, it was the lowest in Spain and Greece and highest in the UK health-conscious cohort. Bread was the largest contributor to GL in all centres (15-45%), but it also showed the largest inter-individual variation. GL, but not GI, tended to be lower in the highest body mass index category in both genders. GI was positively correlated with starch and intakes of bread and potatoes, whereas it was correlated negatively with intakes of sugar, fruit and dairy products. GL was positively correlated with all carbohydrate components and intakes of cereals, whereas it was negatively correlated with fat and alcohol and with intakes of wine, with large variations across countries. CONCLUSIONS: GI means varied modestly across countries and genders, whereas GL means varied more, but it may possibly act as a surrogate of carbohydrate intake.

Use of dietary supplements in the European Prospective Investigation into Cancer and Nutrition calibration study.

BACKGROUND: Dietary supplement use is increasing, but there are few comparable data on supplement intakes and how they affect the nutrition and health of European consumers. The aim of this study was to describe the use of dietary supplements in subsamples of the 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Specific questions on dietary supplement use were asked as a part of single 24-h recalls performed on 36,034 men and women aged 35-74 years from 1995 to 2000. RESULTS: Between countries, the mean percentage of dietary supplement use varied almost 10-fold among women and even more among men. There was a clear north-south gradient in use, with a higher consumption in northern countries. The lowest crude mean percentage of use was found in Greece (2.0% among men, 6.7% among women), and the highest was in Denmark (51.0% among men, 65.8% among women). Use was higher in women than in men. Vitamins, minerals or combinations of them were the predominant types of supplements reported, but there were striking differences between countries. CONCLUSIONS: This study indicates that there are wide variations in supplement use in Europe, which may affect individual and population nutrient intakes. The results underline the need to monitor consumption of dietary supplements in Europe, as well as to evaluate the risks and benefits.

Meat consumption and K-ras mutations in sporadic colon and rectal cancer in The Netherlands Cohort Study.

Case-cohort analyses were performed on meat and fish consumption in relation to K-ras mutations in 448 colon and 160 rectal cancers that occurred during 7.3 years of follow-up, excluding the first 2.3 years, and 2948 subcohort members of The Netherlands Cohort Study on diet and cancer. Adjusted incidence rate ratios and 95% confidence intervals were computed for colon and rectal cancer and for K-ras mutation status subgroups. Total fresh meat, most types of fresh meat and fish were not associated with colon or rectal cancer, neither overall nor with K-ras mutation status. However, several weak associations were observed for tumours with a wild-type K-ras, including beef and colon tumours, and an inverse association for pork with colon and rectal tumours; for meat products, an increased association was observed with wild-type K-ras tumours in the colon and possibly with G>A transitions in rectal tumours.