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Purpose The Oxford WebQ is a web-based 24-h dietary assessment method which has been used in UK Biobank and other large prospective studies. The food composition table used to calculate nutrient intakes has recently been replaced with the UK Nutrient Databank, which has food composition data closer in time to when participants completed the questionnaire, and new dietary variables were incorporated. Here we describe the updated version of the Oxford WebQ questionnaire nutrient calculation, and compare nutrient intakes with the previous version used. Methods 207,144 UK Biobank participants completed ≥ 1 Oxford WebQs, and means and standard deviations of nutrient intakes were averaged for all completed 24-h dietary assessments. Spearman correlations and weighted kappa statistics were used to compare the re-classification and agreement of nutrient intakes between the two versions. Results 35 new nutrients were incorporated in the updated version. Compared to the previous version, most nutrients were very similar in the updated version except for a few nutrients which showed a difference of > 10%: lower with the new version for trans-fat (− 20%), and vitamin C (− 15%), but higher for retinol (+ 42%), vitamin D (+ 26%) and vitamin E (+ 20%). Most participants were in the same (> 60%) or adjacent (> 90%) quintile of intake for the two versions. Except for trans-fat (r = 0.58, κ = 0.42), very high correlations were found between the nutrients calculated using the two versions (r > 0.79 and κ > 0.60). Conclusion Small absolute differences in nutrient intakes were observed between the two versions, and the ranking of individuals was minimally affected, except for trans-fat.

In a cross-sectional analysis of a population-based cohort (United Kingdom, N = 21,318, 1993–1998), we studied how associations between meal patterns and non-fasting triglyceride and glucose concentrations were influenced by the hour of day at which the blood sample was collected to ascertain face validity of reported meal patterns, as well as the influence of reporting bias (assessed using formula of energy expenditure) on this association. Meal size (i.e., reported energy content), mealtime and meal frequency were reported using pre-structured 7-day diet diaries. In ANCOVA, sex-specific means of biomarker concentrations were calculated by hour of blood sample collection for quartiles of reported energy intake at breakfast, lunch and dinner (meal size). Significant interactions were observed between breakfast size, sampling time and triglyceride concentrations and between lunch size, sampling time and triglyceride, as well as glucose concentrations. Those skipping breakfast had the lowest triglyceride concentrations in the morning and those skipping lunch had the lowest triglyceride and glucose concentrations in the afternoon, especially among acceptable energy reporters. Eating and drinking occasion frequency was weakly associated with glucose concentrations in women and positively associated with triglyceride concentrations in both sexes; stronger associations were observed for larger vs. smaller meals and among acceptable energy reporters. Associations between meal patterns and concentration biomarkers can be observed when accounting for diurnal variation and underreporting. These findings support the use of 7-day diet diaries for studying associations between meal patterns and health.

In Mediterranean countries, adherence to a traditional Mediterranean dietary pattern (MedDiet) is associated with better cognitive function and reduced dementia risk. It is unclear if similar benefits exist in non-Mediterranean regions.The aims of this study were to examine associations between MedDiet adherence and cognitive function in an older UK population and to investigate whether associations differed between individuals with high compared with low cardiovascular disease (CVD) risk.We conducted an analysis in 8009 older individuals with dietary data at Health Check 1 (1993-1997) and cognitive function data at Health Check 3 (2006-2011) of the European Prospective Investigation into Cancer and Nutrition-Norfolk (EPIC-Norfolk). Associations were explored between MedDiet adherence and global and domain-specific cognitive test scores and risk of poor cognitive performance in the entire cohort, and when stratified according to CVD risk status.Higher MedDiet adherence defined by the Pyramid MedDiet score was associated with better global cognition (β ± SE = -0.012 ± 0.002; P 0.001), verbal episodic memory (β ± SE = -0.009 ± 0.002; P 0.001), and simple processing speed (β ± SE = -0.002 ± 0.001; P = 0.013). Lower risk of poor verbal episodic memory (OR: 0.784; 95% CI: 0.641, 0.959; P = 0.018), complex processing speed (OR: 0.739; 95% CI: 0.601, 0.907; P = 0.004), and prospective memory (OR: 0.841; 95% CI: 0.724, 0.977; P = 0.023) was also observed for the highest compared with the lowest Pyramid MedDiet tertiles. The effect of a 1-point increase in Pyramid score on global cognitive function was equivalent to 1.7 fewer years of cognitive aging. MedDiet adherence defined by the Mediterranean Diet Adherence Screener (MEDAS) score (mapped through the use of both binary and continuous scoring) showed similar, albeit less consistent, associations. In stratified analyses, associations were evident in individuals at higher CVD risk only (P 0.05).Higher adherence to the MedDiet is associated with better cognitive function and lower risk of poor cognition in older UK adults. This evidence underpins the development of interventions to enhance MedDiet adherence, particularly in individuals at higher CVD risk, aiming to reduce the risk of age-related cognitive decline in non-Mediterranean populations.

In a cross-sectional analysis of a population-based cohort (United Kingdom, N = 21,318, 1993–1998), we studied how associations between meal patterns and non-fasting triglyceride and glucose concentrations were influenced by the hour of day at which the blood sample was collected to ascertain face validity of reported meal patterns, as well as the influence of reporting bias (assessed using formula of energy expenditure) on this association. Meal size (i.e., reported energy content), mealtime and meal frequency were reported using pre-structured 7-day diet diaries. In ANCOVA, sex-specific means of biomarker concentrations were calculated by hour of blood sample collection for quartiles of reported energy intake at breakfast, lunch and dinner (meal size). Significant interactions were observed between breakfast size, sampling time and triglyceride concentrations and between lunch size, sampling time and triglyceride, as well as glucose concentrations. Those skipping breakfast had the lowest triglyceride concentrations in the morning and those skipping lunch had the lowest triglyceride and glucose concentrations in the afternoon, especially among acceptable energy reporters. Eating and drinking occasion frequency was weakly associated with glucose concentrations in women and positively associated with triglyceride concentrations in both sexes; stronger associations were observed for larger vs. smaller meals and among acceptable energy reporters. Associations between meal patterns and concentration biomarkers can be observed when accounting for diurnal variation and underreporting. These findings support the use of 7-day diet diaries for studying associations between meal patterns and health.

Background Little is known about changes in blood fatty acid compositions over time and the correlates of any changes in a general population. Objective The aim of this study was to estimate changes in 27 individual plasma phospholipid fatty acids and fatty acid groups over time, and to identify potential correlates of these changes. Methods Plasma phospholipid fatty acids were profiled at 3 time-points (1993–1997, 1998–2000, 2004–2011) among 722 participants in the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, UK. Linear regression models were used to estimate both 1) mean changes over time in 27 individual fatty acids and 8 prespecified fatty acid groups and 2) associations of changes in dietary and lifestyle factors with changes in the 8 fatty acid groups, mutually adjusted for dietary/lifestyle factors and other confounders. The prespecified fatty acid groups were odd-chain saturated fatty acids (SFAs), even-chain SFAs, very-long-chain SFAs, marine n–3 polyunsaturated fatty acids (PUFAs), plant n–3 PUFA, n–6 PUFAs, monounsaturated fatty acids (MUFAs), and trans-fatty acids (TFAs). Results Adjusted for confounders, fatty acid concentrations decreased for odd-chain SFAs (annual percentage difference in mol percentage: −0.63%), even-chain SFAs (−0.05%), n–6 PUFAs (−0.25%), and TFAs (−7.84%). In contrast, concentrations increased for marine n–3 PUFAs (1.28%) and MUFAs (0.45%), but there were no changes in very-long-chain SFAs or plant n–3 PUFA. Changes in fatty acid levels were associated with consumption of different food groups. For example, a mean 100 g/d increase in fatty fish intake was associated with a 19.3% greater annual increase in marine n–3 PUFAs. Conclusions Even-chain SFAs and TFAs declined and marine n–3 PUFAs increased over time. These changes were partially explained by changes in dietary habits, and could potentially help interpret associations of baseline fatty acid composition with future disease risk.

BACKGROUND: Maintenance of skeletal muscle in older age is critical to reducing frailty and the risk of falls and fractures. Nutrition has established importance for muscle health in general, but less research has looked at associations of dietary intake of specific micronutrients on skeletal muscle mass in older adults. AIMS: This study aimed to investigate the influence of dietary and circulating magnesium on skeletal muscle mass in a UK population of 14,340 middle to older-aged men and women participating in the EPIC-Norfolk cohort study. METHODS: Dietary nutrient intakes were estimated from 7-day food diaries and fat-free mass (FFM) by bioelectrical impedance analysis. Multivariable regression was used to investigate associations of FFM-based indices of muscle mass with quintiles of dietary magnesium intake or serum magnesium concentration groups. All analyses were stratified by sex, and regression models were adjusted for relevant covariates. RESULTS: Significant positive trends in FFM measures were evident across magnesium dietary intake quintiles for both sexes (all p < 0.001; n = 6350 men; n = 7990 women) and both

The prevalence of sarcopenia, frailty and fractures is increasing. Prevention options are limited, but dietary factors including vitamin E have the potential to confer some protection. This study investigated cross-sectional associations between dietary and plasma concentrations of vitamin E with indices of skeletal muscle mass (SMM) (n = 14,179 and 4283, respectively) and bone density (n = 14,694 and 4457, respectively) and longitudinal fracture risk (n = 25,223 and 7291, respectively) in European Prospective Investigation Into Cancer and Nutrition (EPIC)-Norfolk participants, aged 39&ndash, 79 years at baseline. Participants completed a health and lifestyle questionnaire, a 7-day diet diary (7dDD) and had anthropometric measurements taken. Fat-free mass (as a SMM proxy) was measured using bioimpedance and bone density was measured using calcaneal broadband ultrasound attenuation (BUA) and incident fractures over 18.5 years of follow-up. Associations between indices of SMM, BUA and fracture risk were investigated by quintiles of dietary vitamin E intake or plasma concentrations. Positive trends in SMM indices and BUA were apparent across dietary quintiles for both sexes, with interquintile differences of 0.88&ndash, 1.91% (p &lt, 0.001), and protective trends for total and hip fracture risk. Circulating plasma &alpha, and &gamma, tocopherol results matched the overall dietary findings. Dietary vitamin E may be important for musculoskeletal health but further investigation is required to fully understand the relationships of plasma tocopherols.

Funder: Mars; doi: http://dx.doi.org/10.13039/100007246, Flavan-3-ols are a group of bioactive compounds that have been shown to improve vascular function in intervention studies. They are therefore of great interest for the development of dietary recommendation for the prevention of cardio-vascular diseases. However, there are currently no reliable data from observational studies, as the high variability in the flavan-3-ol content of food makes it difficult to estimate actual intake without nutritional biomarkers. In this study, we investigated cross-sectional associations between biomarker-estimated flavan-3-ol intake and blood pressure and other CVD risk markers, as well as longitudinal associations with CVD risk in 25,618 participants of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort. High flavan-3-ol intake, achievable as part of an habitual diet, was associated with a significantly lower systolic blood pressure (− 1.9 (− 2.7; − 1.1) mmHg in men and − 2.5 (− 3.3; − 1.8) mmHg in women; lowest vs highest decile of biomarker), comparable to adherence to a Mediterranean Diet or moderate salt reduction. Subgroup analyses showed that hypertensive participants had stronger inverse association between flavan-3-ol biomarker and systolic blood pressure when compared to normotensive participants. Flavanol intake could therefore have a role in the maintenance of cardiovascular health on a population scale.

Background: Age-related loss of skeletal muscle mass contributes to poor outcomes including sarcopenia, physical disability, frailty, type 2 diabetes, and mortality. Vitamin C has physiological relevance to skeletal muscle and may protect it during aging, but few studies have investigated its importance in older populations. Objectives: We aimed to investigate cross-sectional associations of dietary and plasma vitamin C with proxy measures of skeletal muscle mass in a large cohort of middle- and older-aged individuals. Methods: We analyzed data from >13,000 men and women in the European Prospective Investigation into Cancer and Nutrition–Norfolk cohort, aged 42–82 y. Fat-free mass (FFM), as a proxy for skeletal muscle mass, was estimated using bioelectrical impedance analysis and expressed as a percentage of total mass (FFM%) or standardized by BMI (FFM BMI). Dietary vitamin C intakes were calculated from 7-d food diary data, and plasma vitamin C was measured in peripheral blood. Multivariable regression models, including relevant lifestyle, dietary, and biological covariates, were used to determine associations between FFM measures and quintiles of dietary vitamin C or insufficient compared with sufficient plasma vitamin C (

The UK Biobank study collected detailed dietary data using a web-based self-administered 24 h assessment tool, the Oxford WebQ. We aimed to describe a comprehensive food grouping system for this questionnaire and to report dietary intakes and key sources of selected nutrients by sex and education. Participants with at least one valid 24-h questionnaire were included (n = 208,200). Dietary data were grouped based on the presence of nutrients as well as culinary use, processing, and plant/animal origin. For each food group, we calculated the contribution to energy intake, key macronutrients, and micronutrients. We also identified the top contributors to energy intake, free sugars and saturated fat by sex and education. From the 93 food groups, the top five contributors to energy intake (in descending order) were: desserts/cakes/pastries; white bread; white pasta/rice; bananas/other fruit; semi-skimmed milk. Wine, beer, and fruit juices were the top beverage contributors to overall energy intake. Biscuits, and desserts/cakes/pastries were the highest contributors to free sugars, total fat, and saturated fat intakes, but also contributed to the calcium and iron intakes. Top contributors to energy, saturated fat, and free sugars were broadly similar by sex and education category, with small differences in average nutrient intakes across the population. This new food classification system will support the growing interest in the associations between food groups and health outcomes and the development of food-based dietary guidelines. Food group variables will be available to all users of the UK Biobank WebQ questionnaire.

Research on Mediterranean diet (MD) adherence and musculoskeletal health is limited. The current study determined if adherence to the alternative MD score (aMED) and MD score (MDS), quantified from 7-d food diaries, was associated with fracture incidence, bone density (calcaneal broadband ultrasound attenuation (BUA)) and fat free mass (expressed over BMI (FFMBMI) using bioelectrical impedance) in 25,450 men and women recruited to the European Prospective Investigation into Cancer study in Norfolk, UK. During 17.4 years of follow up (443,178 total person years) 2195 incident fractures occurred. Higher aMED adherence was associated with 23% reduced total (Q5&ndash, Q1 HR 0.77, 95% CI 0.67, 0.88, p-trend &lt, 0.01) and 21% reduced hip (Q5&ndash, Q1 HR 0.79, 95% CI 0.65, 0.96, p-trend = 0.01) fracture incidence, and significantly higher BUA (Q5&ndash, Q1 1.0 dB/MHz 95% CI 0.2, 1.9, 0.01) and FFMBMI (Q5&ndash, Q1 0.05 kg/(kg/m2) 95% CI 0.04, 0.06, 0.01), comparing extreme adherence quintiles. Higher MDS was also associated with reduced total fractures (Q5&ndash, Q1 HR 0.83, 95% CI 0.71, 0.96, p-trend = 0.03) and significantly higher BUA (Q5&ndash, Q1 1.4 dB/MHz 95% CI 0.5, 2.3, Q1 0.03 kg/(kg/m2) 95% CI 0.01, 0.04, 0.01). This evidence supports the need to develop interventions to enhance MD adherence, particularly in women, where evidence for associations was stronger.

Sarcopenia, characterised by loss of skeletal muscle mass and strength with age, is a significant risk factor for loss of mobility and independence. The combination of low muscle mass and high fat mass in sarcopenic obesity is associated with particularly poor outcomes. Micronutrient deficiencies can occur alongside obesity despite total energy surplus, and older individuals may be at greater risk of deficiency. Research suggests vitamin C is important for musculoskeletal health, but the relationship with obesity is underexplored.This study aimed to investigate associations of plasma vitamin C with obesity status and explore the relationship with the sarcopenic risk factor, low skeletal muscle mass.EPIC-Norfolk cohort study data were analysed. Bioelectrical impedance analysis-estimated fat free mass (FFM; a proxy for skeletal muscle mass) was adjusted for BMI to give a scaled variable, FFMBMI. A ‘low muscle mass’ category was defined as individuals with the lowest 10% FFMBMI, representing those at high risk of sarcopenia. Plasma vitamin C (ascorbic acid) concentrations were categorised as inadequate (< 50micromol/L) or adequate (≥ 50micromol/L), and obesity status as non-obese (< 30kg/m2) or obese (≥ 30kg/m2).Individuals were grouped according to vitamin C and obesity status: 1, non-obese and adequate vitamin C; 2, non-obese and inadequate vitamin C; 3, obese and adequate vitamin C; and 4, obese and inadequate vitamin C. Using logistic regression, the odds ratio (OR) of each vitamin/obesity status group was calculated in relation to membership of the ‘low muscle mass’ category. Analyses were sex-stratified and adjusted for age, smoking status, physical activity, social class, menopausal and HRT status in women, statin use, and corticosteroid use.Data were analysed for 5903 men (mean 62.9 years, SD 9.0) and 7416 women (mean 61.5 years, SD 9.0). Prevalence of vitamin C inadequacy was higher in obese vs non-obese individuals (men 45.8% vs 33.0%; and women 26.0% vs 15.3%). The odds of ‘low muscle mass’ were higher in all vitamin/obesity status groups vs group 1, but the greatest odds were seen for group 4 (combined obesity and inadequate vitamin C) in men (OR 16.5, 95% CI: 12.6–21.6; p < 0.001) and women (OR 30.2, 95% CI: 23.0–39.8; p < 0.001).In this cohort of older individuals higher prevalence of vitamin C inadequacy is associated with obese individuals. Of importance to musculoskeletal health and our understanding of sarcopenia is the observation that while vitamin C inadequacy and obesity are each independently important, their coexistence is a particularly strong predictor of sarcopenic risk.

Background Measures of abdominal adiposity are strongly associated with all-cause mortality and cardiovascular disease (CVD). However, data are limited and conflicting regarding the consequences of changes in body fat distribution. The main aims of this paper are to investigate the association between changes in waist circumference (WC) and all-cause and CVD mortality and to examine these changes in relation to concurrent changes in weight. Methods The European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study recruited 25,639 participants between 1993 and 1997, aged 39–79, a number of whom also attended a second examination (1998–2000), and were followed up to 2016 for mortality. Participants were eligible for inclusion if they had WC, weight and height measurements at both time-points; those with a self-reported history of CVD or cancer, body mass index Results After multivariable adjustment, the HRs (95% CIs) for all-cause mortality for men and women with a WC gain (WCG) > 5 cm were 1.51 (1.29–1.75) and 1.25 (1.06–1.46) respectively. For CVD mortality in men and women with a WCG > 5 cm, the HRs were 1.84 (1.39–2.43) and 1.15 (0.85–1.55) respectively. In analyses of concurrent changes in WC and weight, the greatest risk (HRs) (95% CIs) in men occurred with weight loss and WCG: 1.80 (1.13–2.86) for all-cause and 2.22 (1.03–4.82) for CVD mortality. In women, the greatest risk for both all-cause (HR 1.50 (1.16–1.95)) and CVD mortality (HR 1.81 (1.15–2.85)) was observed in those with weight loss and maintenance of WC (WCM). Conclusions Objectively measured WCG > 5 cm, was associated with subsequent higher total mortality risk and higher CVD mortality risk in men. Interventions focusing on preventing increase in central adiposity rather than lowering weight per se in later life may potentially have greater health benefits.

Background The effect of individual saturated fatty acids (SFAs) on serum cholesterol levels depends on their carbon-chain length. Whether the association with myocardial infarction (MI) also differs across individual SFAs is unclear. We examined the association between consumption of individual SFAs, differing in chain lengths ranging from 4 through 18 carbons, and risk of MI. Methods We used data from 22,050 and 53,375 participants from EPIC-Norfolk (UK) and EPIC-Denmark, respectively. Baseline SFA intakes were assessed through validated, country-specific food frequency questionnaires. Cox regression analysis was used to estimate associations between intakes of individual SFAs and MI risk, for each cohort separately. Results During median follow-up times of 18.8 years in EPIC-Norfolk and 13.6 years in Denmark, respectively, 1204 and 2260 MI events occurred. Mean (±SD) total SFA intake was 13.3 (±3.5) en% in EPIC-Norfolk, and 12.5 (±2.6) en% in EPIC-Denmark. After multivariable adjustment, intakes of C12:0 (lauric acid) and C14:0 (myristic acid) inversely associated with MI risk in EPIC-Denmark (HR upper versus lowest quintile: 0.80 (95%CI: 0.66, 0.96) for both SFAs). Intakes in the third and fourth quintiles of C4:0–C10:0 also associated with lower MI risk in EPIC-Denmark. Moreover, substitution of C16:0 (palmitic acid) and C18:0 (stearic acid) with plant proteins resulted in a reduction of MI risk in EPIC-Denmark (HR per 1 energy%: 0.86 (95%CI: 0.78, 0.95) and 0.87 (95%CI: 0.79, 0.96) respectively). No such associations were found in EPIC-Norfolk. Conclusion The results from the present study suggest that the association between SFA and MI risk depends on the carbon chain-length of the SFA.

Studies have reported a higher mortality risk associated with weight loss, particularly in middle-aged and older adults, although some of these studies did find that gaining weight was also associated with an increased mortality risk. We examined changes in weight in relation to mortality in a prospective population-based cohort study of men and women, resident in Norfolk, UK. Participants were assessed at baseline (1993–1997) and at a second examination (1998–2000), as part of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study, and followed up to 2015 for mortality. Participants with a self-reported history of cancer or cardiovascular disease, body mass index 5 kg. Similar associations were observed after excluding deaths in the first 5 years of follow-up. Results for weight gain were inconclusive. We conclude that objectively measured weight loss, but not weight gain, was associated with subsequent higher mortality risk in this population-based study of middle-aged and elderly men and women. However, undiagnosed, pre-existing disease and the inability to account for weight cycling need to be remembered when interpreting these results. Unravelling the causal pathways underlying this association will require more detailed studies, including that of changes in body composition. Electronic supplementary material The online version of this article (10.1007/s10654-017-0343-y) contains supplementary material, which is available to authorized users.

Objectives Assess the association between marine omega-3 polyunsaturated fatty acid (n-3 PUFA) intake from supplements, mainly cod liver oil, and coronary heart disease (CHD) mortality. Design Prospective cohort study, with three exposure measurements over 22 years. Setting Norfolk-based European Prospective Investigation into Cancer (EPIC-Norfolk, UK). Participants 22 035 men and women from the general population, 39–79 years at recruitment. Exposure Supplement use was assessed in three questionnaires (1993–1998; 2002–2004; 2004–2011). Participants were grouped into non-supplement users (NSU), n-3 PUFA supplement users (SU+n3) and non–n-3 PUFA supplement users (SU-n3). Cox regression adjusted for time-point specific variables: age, smoking, prevalent illnesses, body mass index, alcohol consumption, physical activity and season and baseline assessments of sex, social class, education and dietary intake (7-day diet diary). Primary and secondary outcome measures During a median of 19-year follow-up, 1562 CHD deaths were registered for 22 035 included participants. Results Baseline supplement use was not associated with CHD mortality, but baseline food and supplement intake of n-3 PUFA was inversely associated with CHD mortality after adjustment for fish consumption. Using time-varying covariate analysis, significant associations were observed for SU+n3 (HR: 0.74, 95% CI 0.66 to 0.84), but not for SU-n3 versus NSU. In further analyses, the association for SU+n3 persisted in those who did not take other supplements (HR: 0.83, 95% CI 0.71 to 0.97). Those who became SU+n3 over time or were consistent SU+n3 versus consistent NSU had a lower hazard of CHD mortality; no association with CHD was observed in those who stopped using n-3 PUFA-containing supplements. Conclusions Recent use of n-3 PUFA supplements was associated with a lower hazard of CHD mortality in this general population with low fish consumption. Residual confounding cannot be excluded, but the findings observed may be explained by postulated biological mechanisms and the results were specific to SU+n3.

Dietary intervention studies suggest that flavan-3-ol intake can improve vascular function and reduce the risk of cardiovascular diseases (CVD). However, results from prospective studies failed to show a consistent beneficial effect. Associations between flavan-3-ol intake and CVD risk in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) were investigated. Data were available from 24,885 (11,252 men; 13,633 women) participants, recruited between 1993 and 1997 into the EPIC-Norfolk study. Flavan-3-ol intake was assessed using 7-day food diaries and the FLAVIOLA Flavanol Food Composition database. Missing data for plasma cholesterol and vitamin C were imputed using multiple imputation. Associations between flavan-3-ol intake and blood pressure at baseline were determined using linear regression models. Associations with CVD risk were estimated using Cox regression analyses. Median intake of total flavan-3-ols was 1034 mg/d (range: 0–8531 mg/d) for men and 970 mg/d (0–6695 mg/d) for women, median intake of flavan-3-ol monomers was 233 mg/d (0–3248 mg/d) for men and 217 (0–2712 mg/d) for women. There were no consistent associations between flavan-3-ol monomer intake and baseline systolic and diastolic blood pressure (BP). After 286,147 person-years of follow-up, there were 8463 cardiovascular events and 1987 CVD related deaths; no consistent association between flavan-3-ol intake and CVD risk (HR 0.93, 95% CI: 0.87; 1.00; Q1 vs Q5) or mortality was observed (HR 0.93, 95% CI: 0.84; 1.04). Flavan-3-ol intake in EPIC-Norfolk is not sufficient to achieve a statistically significant reduction in CVD risk., Graphical abstract, Highlights • Median intake of total flavan-3-ol monomers in EPIC Norfolk was 233 mg/d for men and 217 mg/d for women. • There were no consistent associations between flavan-3-ol monomer intake and baseline systolic and diastolic blood pressure in EPIC Norfolk. • There were no consistent association between flavan-3-ol intake and CVD risk in EPIC Norfolk. • Flavan-3-ol intake in EPIC-Norfolk is not sufficient to achieve a statistically significant reduction in CVD risk.

Carotenoids are found in abundance in fruit and vegetables, and may be involved in the positive association of these foods with bone health. This study aimed to explore the associations of dietary carotenoid intakes and plasma concentrations with bone density status and osteoporotic fracture risk in a European population. Cross-sectional analyses (n 14 803) of bone density status, using calcaneal broadband ultrasound attenuation (BUA) and longitudinal analyses (n 25 439) of fracture cases were conducted on data from the prospective European Prospective Investigation into Cancer and Nutrition-Norfolk cohort of middle-aged and older men and women. Health and lifestyle questionnaires were completed, and dietary nutrient intakes were derived from 7-d food diaries. Multiple regression demonstrated significant positive trends in BUA for women across quintiles of dietary α-carotene intake (P=0·029), β-carotene intake (P=0·003), β-cryptoxanthin intake (P=0·031), combined lutein and zeaxanthin intake (P=0·010) and lycopene intake (P=0·005). No significant trends across plasma carotenoid concentration quintiles were apparent (n 4570). The Prentice-weighted Cox regression showed no trends in fracture risk across dietary carotenoid intake quintiles (mean follow-up time 12·5 years), except for a lower risk for wrist fracture in women with higher lutein and zeaxanthin intake (P=0·022); nevertheless, inter-quintile differences in fracture risk were found for both sexes. Analysis of plasma carotenoid data (mean follow-up time 11·9 years) showed lower hip fracture risk in men across higher plasma α-carotene (P=0·026) and β-carotene (P=0·027) quintiles. This study provides novel evidence that dietary carotenoid intake is relevant to bone health in men and women, demonstrating that associations with bone density status and fracture risk exist for dietary intake of specific carotenoids and their plasma concentrations.

DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed.

Objective:To describe the average consumption of carbohydrate-providing food groups among study centres of the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods:Of the 27 redefined EPIC study centres, 19 contributed subjects of both genders and eight centres female participants only (men,n=13 031; women,n=22924, after exclusion of subjects under 35 and over 74 years of age from the original 36 900 total). Dietary data were obtained using the 24-hour recall methodology using the EPIC-SOFT software. The major sources of dietary carbohydrate were identified, and 16 food groups were examined.Results:The 10 food groups contributing most carbohydrate were bread; fruit; milk and milk products; sweet buns, cakes and pies; potato; sugar and jam; pasta and rice; vegetables and legumes; crispbread; and fruit and vegetable juices. Consumption of fruits as well as vegetables and legumes was higher in southern compared with northern centres, while soft drinks consumption was higher in the north. Italian centres had high pasta and rice consumption, but breakfast cereal, potato, and sweet buns, cakes and pies were higher in northern centres. In Sweden, lower bread consumption was balanced with a higher consumption of crispbread, and with sweet buns, cakes and pies. Overall, men consumed higher amounts of vegetables and legumes, bread, soft drinks, potatoes, pasta and rice, breakfast cereal and sugar and jam than women, but fruit consumption appeared more frequent in women.Conclusion:The study supports the established idea that carbohydrate-rich foods chosen in northern Europe are different from those in the Mediterranean region. When comparing and interpreting diet–disease relationships across populations, researchers need to consider all types of foods.

BACKGROUND: The American Heart Association has prioritised seven cardiovascular health metrics to reduce the cardiovascular burden, including: body mass index, healthy diet, physical activity, smoking status, blood pressure, glycated haemoglobin A1c and total cholesterol. The aim of the current study was to assess the association between the American Heart Association-defined health metrics and the risk of cardiovascular events in the EPIC-Norfolk prospective study. DESIGN: Prospective cohort study. METHODS: An overall cardiovascular health score was calculated based on the number of health metrics including ideal, intermediate or poor. Cox proportional hazards models were used to describe the association of the seven metrics separately and the overall health score with risk of coronary heart disease, stroke and cardiovascular disease. A total of 10,043 participants was included in the analysis (follow-up 1993-2008). For all individual health metrics a more ideal status was associated with a lower risk of cardiovascular events. RESULTS AND CONCLUSION: As for the overall cardiovascular health score, those in the highest (i.e. healthiest) category (score 12-14) had an adjusted hazard ratio for coronary heart disease of 0.07 (95% confidence interval (CI) 0.02-0.29, P

ObjectiveA diet rich in phyto-oestrogens has been suggested to protect against a variety of common diseases but UK intake data on phyto-oestrogens or their food sources are sparse. The present study estimates the average intakes of isoflavones, lignans, enterolignans and coumestrol from 7 d food diaries and provides data on total isoflavone, lignan and phyto-oestrogen consumption by food group.DesignDevelopment of a food composition database for twelve phyto-oestrogens and analysis of soya food and phyto-oestrogen consumption in a population-based study.SettingMen and women, aged 40–79 years, from the general population participating in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) between 1993 and 1997, with nutrient and food data from 7 d food diaries.SubjectsA subset of 20 437 participants.ResultsThe median daily phyto-oestrogen intake for all men was 1199 μg (interquartile range 934–1537 μg; mean 1504 μg,sd1502 μg) and 888 μg for all women (interquartile range 710–1135 μg; mean 1205 μg,sd1701 μg). In soya consumers, median daily intakes were higher: 2861 μg in men (interquartile range 1304–7269 μg; mean 5051 μg,sd5031 μg) and 3142 μg in women (interquartile range 1089–7327 μg; mean 5396 μg,sd6092 μg). In both men and women, bread made the greatest contribution to phyto-oestrogen intake – 40·8 % and 35·6 %, respectively. In soya consumers, vegetable dishes and soya/goat's/sheep's milks were the main contributors – 45·7 % and 21·3 % in men and 38·4 % and 33·7 % in women, respectively.ConclusionsThe ability to estimate phyto-oestrogen intake in Western populations more accurately will aid investigations into their suggested effects on health.

Background: Epidemiologic studies of dietary fat and breast cancer risk are inconsistent, and it has been suggested that a true relation may have been obscured by the imprecise measurement of fat intake. Objective: We examined associations of fat with breast cancer risk by using estimates of fat intake from food diaries and food-frequency questionnaires (FFQs) pooled from 4 prospective studies in the United Kingdom. Design: A total of 657 cases of breast cancer in premenopausal and postmenopausal women were matched on study, age, and recruitment date with 1911 control subjects. Nutrient intakes were estimated from food diaries and FFQs. Conditional logistic regression was used to estimate ORs for breast cancer associated with total, saturated, monounsaturated, and polyunsaturated fat intakes with adjustment for relevant covariates. Results: Neither the food diaries nor the FFQs showed any positive associations between fat intake and overall breast cancer risk. ORs (95% CIs) for the highest compared with lowest quintiles of percentage of energy from total fat were 0.90 (0.66, 1.23) for food diaries and 0.80 (0.59, 1.09) for FFQs. Conclusion: In this study, breast cancer risk was not associated with fat intake in middle-aged women in the United Kingdom, irrespective of whether diet was measured by food diaries or by FFQs.

Phyto-oestrogens have been associated with a decreased risk for osteoporosis, but results from intervention and observational studies in Western countries have been inconsistent. In the present study, we investigated the association between habitual phyto-oestrogen intake and broadband ultrasound attenuation (BUA) of the calcanaeum as a marker of bone density. We collected 7 d records of diet, medical history and demographic and anthropometric data from participants (aged 45–75 years) in the European Prospective Investigation into Cancer-Norfolk study. Phyto-oestrogen (biochanin A, daidzein, formononetin; genistein, glycitein; matairesinol; secoisolariciresinol; enterolactone; equol) intake was determined using a newly developed food composition database. Bone density was assessed using BUA of the calcanaeum. Associations between bone density and phyto-oestrogen intake were investigated in 2580 postmenopausal women who were not on hormone replacement therapy and 4973 men. Median intake of total phyto-oestrogens was 876 (interquartile range 412) μg/d in postmenopausal women and 1212 (interquartile range 604) μg/d in men. The non-soya isoflavones formononetin and biochanin A were marginally significant or significantly associated with BUA in postmenopausal women (β = 1·2; P P P

Objective: Supplements are an important source of micronutrient intake, which, unless taken into account, can misclassify individuals with regard to levels of nutrient exposure. A label-based vitamin and mineral supplements (ViMiS) database was developed to contain manufacturers’ information and to enter supplement use by participants in the European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk). The ViMiS database contains information on all ingredients, broken down into nutrient information in order to be combined with nutrient intake derived from food consumption. Design: Development of the ViMiS database and cross-sectional analysis of supplement use in a population-based study. Setting: Men and women aged 40–79 years from the general population participating in the EPIC-Norfolk study between 1993 and 1997, with data available from 7 d diet diaries (7dDD).Subjects A subset of 19 330 participants with available 7dDD and known supplement status. Results: To date, the ViMiS database includes 2066 supplements, which altogether contain 16 586 ingredients, with a median of eleven nutrient/ingredients per supplement. Forty per cent of the cohort took a supplement, of which cod liver oil was the most common (24·5 %). Conclusions: The ViMiS database provides a flexible tool for estimating total nutrient intake. The high prevalence of supplement use in the general population indicates that supplement use needs to be taken into account when examining the relationship of intake of particular nutrients to health outcomes.

Phytoestrogens are a group of non-steroidal secondary plant metabolites with structural and functional similarity to 17β-oestradiol. Urinary and plasma phytoestrogens have been used as biomarkers for dietary intake, however, this is often not possible in large epidemiological studies or to assess general exposure in free-living individuals. Accurate information about dietary phytoestrogens is therefore important but there is very limited data concerning food contents. In this study, we analysed the phytoestrogen (isoflavone, lignan and coumestrol) content in more than 240 different foods based on fresh and processed fruits and vegetables using a newly developed sensitive method based on LC–MS incorporating 13C3-labelled standards. Phytoestrogens were detected in all foods analysed with a median content of 20 μg/100 g wet weight (isoflavones: 2 μg/100 g; lignans 12 μg/100 g). Most foods contained less than 100 μg/100 g, however, 5% of foods analysed contained more than 400 μg/100 g, in particular soya-based foods and other legumes. The results published here will contribute to databases of dietary phytoestrogen content and allow the more accurate determination of phytoestrogen exposure in free-living individuals.

Dietary phytoestrogens may be involved in the occurrence of chronic diseases. Reliable information on the phytoestrogen content in foods is required to assess dietary exposure and disease risk in epidemiological studies. However, there is little information on isoflavone, lignan, and coumestrol content of cereals and cereal-based foods, leading to an underestimation of intake. This is the first study of phytoestrogens (isoflavones: biochanin A, daidzein, formononetin, genistein, glycitein; lignans: matairesinol, secoisplariciresinol; coumestrol) in a comprehensive selection of 101 cereals and cereal-based foods-including breads, breakfast cereals, biscuits, pasta and rice-consumed in the UK using a sensitive LCMS technique with 13C-labelled internal standards. Phytoestrogens were detected in all foods analyzed; bread contained the highest amount of phytoestrogens-many as isoflavones-with an average content of 375 +/- 67 microg/100 g wet weight (excluding soya-linseed bread with 12,000 microg/100 g). Most other foods contained less than 100 microg/100 g, many as lignans. Our study shows that all foods analyzed contained phytoestrogens, with the highest amount found in breads, making them one of the main sources of dietary phytoestrogens in the UK. These results will allow a more accurate estimation of exposure to dietary phytoestrogens.

To investigate the intake of plant sterols and identify major dietary sources of plant sterols in the British diet. A total of 24 798 men and women recruited during 1993–1997, participating in the European Prospective Investigation into Cancer (EPIC-Norfolk). A database of the plant sterol (campesterol, β-sitosterol, stigmasterol, campestanol and β-sitostanol) content in foods, based on gas-liquid chromatography (GLC) analyses, was linked to nutritional intake data from food frequency questionnaires in the EPIC-Norfolk population. The mean (s.d.) intake of total plant sterols was 300 (108) mg/d for men and 293 (100) mg/d for women. Bread and other cereals, vegetables and added fats were the three major food sources of plant sterols representing 18.6 (8.9), 18.4 (8.5) and 17.3 (10.4)% of the total plant sterol intake respectively. Women had a higher plant sterol density than men (36.4 vs 32.8 mg/1000 kJ, P

Background\ud \ud Flavonoids are a group of phenolic secondary plant metabolites that are ubiquitous in plant-based diets. Data from anthropological, observational and intervention studies have shown that many flavonoids are bioactive. For this reason, there is an increasing interest in investigating the potential health effects of these compounds. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations.\ud \ud Objective\ud \ud The objective of this study is to determine the habitual intake and main sources of anthocyanidins, flavanols, flavanones, flavones, flavonols, proanthocyanidins, theaflavins and thearubigins in the European Union.\ud \ud Design\ud \ud We use food consumption data from the European Food Safety Authority (EFSA) and the FLAVIOLA Food Composition Database to estimate intake of flavonoids.\ud \ud Results\ud \ud Mean (±SEM) intake of total flavonoids in Europe was 428±49 mg/d, of which 136±14 mg/d were monomeric compounds. Gallated flavan-3-ols (53±12 mg/d) were the main contributor. The lowest flavonoid intake was observed in Mediterranean countries (monomeric compounds: 95±11 mg/d). The distribution of intake was skewed in many countries, especially in Germany (monomeric flavonoids; mean intake: 181 mg/d; median intake: 3 mg/d).\ud \ud Conclusions\ud \ud The habitual intake of flavonoids in Europe is below the amounts found to have a significant health effect.

Biomarkers of individual susceptibility: field studiesBiomarker: single-nucleotide polymorphisms in COMT, CYP19, ESR1, and SHBG genesEffect studied: cancer riskTissue/biological material/sample size: urine, bloodMethod of analysis: genotypingStudy design: nested case-control studyStudy size: 89 cases and 178 controlsImpact on outcome (including dose-response): Odds ratios for phytoestrogen exposure, as assessed using the four methods, were not significantly associated with prostate cancer risk (P = 0.15-0.94). Men with the CC genotype for the ESRI PvuII polymorphism had significantly higher risk for prostate cancer compared with men with the TT genotype [adjusted odds ratio = 4.65 (1.60-13.49); P = 0.005]. Prospective phytoestrogen exposure was assessed using both biomarkers and estimates of intake in 89 British men recruited into the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition study, men who subsequently developed prostate cancer. Results were compared with those from 178 healthy men matched by age and date of recruitment. Levels of seven phytoestrogens (daidzein, genistein, glycitein, O-desmethylangolensin, equol, enterodiol, and enterolactone) were measured in spot urine and serum samples. Five single-nucleotide polymorphisms in COMT, CYP19, ESR1, and SHBG genes were genotyped. Urinary levels of all phytoestrogens correlated strongly with serum levels. Correlation coefficients ranged from 0.63 (glycitein) to 0.88 (daidzein) (P < 0.001). Urinary and serum levels correlated significantly with isoflavone intake assessed from food diaries (R = 0.15-0.20; P < 0.05) but not with that from a food-frequency questionnaire. Odds ratios for phytoestrogen exposure, as assessed using the four methods, were not significantly associated with prostate cancer risk (P = 0.15-0.94). Men with the CC genotype for the ESRI PvuII polymorphism had significantly higher risk for prostate cancer compared with men with the TT genotype [adjusted odds ratio = 4.65 (1.60-13.49); P = 0.005]. Our results utilizing a combined prospective exposure provide no evidence that phytoestrogens alter prostate cancer risk in British men, whereas the C allele for the PvuII polymorphism may be associated with increased risk.

It has been suggested that the consumption of a diet rich in phytoestrogens might protect against a variety of diseases common in Western societies. However, there are little available data on the food sources or distribution of intake in the UK diet. To estimate the average intake and range of soya foods and isoflavones in a population-based cohort and to provide data on isoflavone consumption by food group. Men and women (11 843) from the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary daidzein and genistein intakes were obtained from 7-day food diaries, completed by participants between 1993 and 1998 and calculated from an in-house food composition database. Energy and anthropometric measurements were also carried out. Average daily isoflavone intakes for both men and women were less than 1 mg (interquartile range (IQR) men: 0.39–0.82 mg; women: 0.30–0.64 mg). However, in soya-consumers, average daily intakes were higher: 8.6 mg in women (IQR: 2.28–10.72 mg) and 7.5 mg in men (IQR: 2.22–9.17 mg). In both men and women, bread and bread rolls made the highest contribution to isoflavone intake – 62.5 and 53.0%, respectively. In soya-consuming men and women, vegetable dishes and milks were the main contributors – 25.0 and 38.5% in men and 38.5% and 26.0% in women, respectively. Isoflavone intake is low in the UK but may be an underestimate due to soya added to commercial products. Future analyses of the isoflavone and lignan content of basic ingredient foods and commercial items commonly consumed in the UK diet will enable more accurate estimates of phytoestrogen intake to be made. The ability to estimate isoflavone intake in Western populations more accurately will enable investigations to be conducted into the suggested beneficial effects of phytoestrogens on health.

ObjectiveHealth-beneficial effects of adhering to a healthy Nordic diet index have been suggested. However, it has not been examined to what extent the included dietary components are exclusively related to the Nordic countries or if they are part of other European diets as well, suggesting a broader preventive potential. The present study describes the intake of seven a priori defined healthy food items (apples/pears, berries, cabbages, dark bread, shellfish, fish and root vegetables) across ten countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) and examines their consumption across Europe.DesignCross-sectional study. A 24 h dietary recall was administered through a software program containing country-specific recipes. Sex-specific mean food intake was calculated for each centre/country, as well as percentage of overall food groups consumed as healthy Nordic food items. All analyses were weighted by day and season of data collection.SettingMulti-centre, European study.SubjectsPersons (n 36 970) aged 35–74 years, constituting a random sample of 519 978 EPIC participants.ResultsThe highest intakes of the included diet components were: cabbages and berries in Central Europe; apples/pears in Southern Europe; dark bread in Norway, Denmark and Greece; fish in Southern and Northern countries; shellfish in Spain; and root vegetables in Northern and Central Europe. Large inter-centre variation, however, existed in some countries.ConclusionsDark bread, root vegetables and fish are strongly related to a Nordic dietary tradition. Apples/pears, berries, cabbages, fish, shellfish and root vegetables are broadly consumed in Europe, and may thus be included in regional public health campaigns.

Phytoestrogens have been hypothesized to protect against prostate cancer via modulation of circulating androgen concentrations. We conducted a cross-sectional study of 267 men in the Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with 2 aims: first, to investigate the association between phytoestrogen exposure (measured from diet, urine, and serum) and plasma concentrations of sex hormone-binding globulin (SHBG), androstanediol glucuronide, testosterone and Free Androgen Index (FAI); and second, whether the association may be modified by polymorphisms in CYP19 and SHBG genes. Dietary daidzein and genistein intakes were obtained from food diaries and computed using an in-house food composition database. Urinary and serum concentrations of 3 isoflavones (daidzein, genistein, glycitein), 2 daidzein metabolites O-desmethylangolensin (O-DMA) and 2 lignan metabolites (enterodiol and enterolactone) were measured using mass spectrometry. There was no association between dietary, urinary, and serum phytoestrogens and plasma SHBG concentrations. Enterolactone was positively associated with plasma androstanediol glucuronide concentrations (urinary enterolactone: r = 0.127, P = 0.043; serum enterolactone: r = 0.172, P = 0.006) and FAI (urinary enterolactone: r = 0.115, P = 0.067; serum enterolactone: r = 0.158, P = 0.011). Both urinary and serum equol were associated with plasma testosterone (urinary equol: r = 0.332, P = 0.013; serum equol: r = 0.318, P = 0.018) and FAI (urinary equol: r = 0.297, P = 0.027; serum equol: r = 0.380, P = 0.004) among men with the TT genotype but not the CC or CT genotypes (r = -0.029 to -0.134, P = 0.091-0.717) for the CYP19 3'untranslated region (UTR) T-C polymorphism. Urinary and serum enterolactone showed similar genotype-dependent associations with testosterone but not with FAI. In this first study on phytoestrogen-gene associations in men, we conclude that enterolactone and equol are positively associated with plasma androgen concentrations, and interactions with CYP19 gene may be involved.

Cross-sectional studies investigating the relationship between phytoestrogens in diet, urine, or blood with plasma estradiol and sex hormone binding globulin (SHBG) have been inconclusive. We investigated the relationship among phytoestrogen exposure, polymorphisms in the ESR1, COMT, CYP19, and SHBG genes, and plasma estradiol and SHBG levels in 125 free-living postmenopausal women taking part in a cohort study (European Prospective Investigation of Cancer and Nutrition-Norfolk) using three different markers: dietary, urinary, and serum phytoestrogens. Phytoestrogen levels (daidzein, genistein, glycitein, O-desmethylangolensin, equol, enterodiol, and enterolactone) in spot urine and serum were analyzed by gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry, respectively. Plasma estradiol and SHBG were measured by immunoassays. Adjusting for age and body mass index, urinary daidzein, genistein, glycitein, and serum daidzein and glycitein were negatively correlated with plasma estradiol (R = −0.199 to −0.277, P

Subjects of this study consisted of 333 women (aged 45–75 years) drawn from a large United Kingdom prospective study of diet and cancer, the European Prospective Investigation of Cancer and Nutrition-Norfolk study. Using newly developed gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry methods incorporating triply 13C-labeled standards, seven phytoestrogens (daidzein, genistein, glycitein, O-desmethylangolensin, equol, enterodiol, and enterolactone) were measured in 114 spot urines and 97 available serum samples from women who later developed breast cancer. Results were compared with those from 219 urines and 187 serum samples from healthy controls matched by age and date of recruitment. Dietary levels were low, but even so, mean serum levels of phytoestrogens were up to 600 times greater than postmenopausal estradiol levels. Phytoestrogen concentrations in spot urine (adjusted for urinary creatinine) correlated strongly with that in serum, with Pearson correlation coefficients > 0.8. There were significant relationships (P < 0.02) between both urinary and serum concentrations of isoflavones across increasing tertiles of dietary intakes. Urinary enterodiol and enterolactone and serum enterolactone were significantly correlated with dietary fiber intake (r = 0.13–0.29). Exposure to all isoflavones was associated with increased breast cancer risk, significantly so for equol and daidzein. For a doubling of levels, odds ratios increased by 20–45% [log2 odds ratio = 1.34 (1.06–1.70; P = 0.013) for urine equol, 1.46 (1.05–2.02; P = 0.024) for serum equol, and 1.22 (1.01–1.48; P = 0.044) for serum daidzein]. These estimates of risk are similar to those established for estrogens and androgens in postmenopausal breast cancer but need confirmation in larger studies.

Objective: We examined the relation between intake of natural dietary plant sterols and serum lipid concentrations in a free-living population. Design, setting and participants: Cross-sectional population-based study of 22 256 men and women aged 39–79 y resident in Norfolk, UK, participating in the European Prospective Investigation into Cancer (EPIC-Norfolk). Main exposure and outcome measures: Plant sterol intake from foods and concentrations of blood lipids. Results: Mean concentrations of total cholesterol and low-density lipoprotein cholesterol, adjusted for age, body mass index and total energy intake, decreased with increasing plant sterol intake in men and women. Mean total serum cholesterol concentration for men in the highest fifth of plant sterol intake (mean intake 463 mg daily) was 0.25 mmol/l lower and for low-density lipoprotein cholesterol 0.14 mmol/l lower than those in the lowest fifth of plant sterol consumption (mean intake 178 mg daily); the corresponding figures in women were 0.15 and 0.13 mmol/l. After adjusting for saturated fat and fibre intakes, the results for total cholesterol and low-density lipoprotein cholesterol were similar, although the strength of the association was slightly reduced. Conclusions: In a free-living population, a high intake of plant sterols is inversely associated with lower concentrations of total and low-density lipoprotein serum cholesterol. The plant sterol content of foods may partly explain diet-related effects on serum cholesterol concentration.