Glycemic load and coronary heart disease in a Mediterranean population: the EPIC Greek cohort study.

BACKGROUND AND AIMS: High glycemic load (GL) has been associated with increased coronary heart disease (CHD) risk. We evaluated whether preference of low-GL foods conveys incremental benefits with respect to CHD, especially to people adhering to the traditional Mediterranean diet (MD). METHODS AND RESULTS: We analyzed data from the Greek European Prospective Investigation into Cancer and Nutrition, including 20,275 participants free of cardiovascular diseases, cancer, or diabetes at baseline and without incident diabetes. Subjects completed a validated, semi-quantitative food frequency questionnaire at enrollment. We calculated a 10-point MD adherence score and the dietary GL, and estimated hazard ratios (HRs) for CHD incidence and mortality through Cox proportional hazard regression. After a median follow-up of 10.4 years, 417 participants developed CHD, and 162 died from the disease. A significant positive association of GL with CHD incidence emerged (HR for the highest versus the lowest tertile = 1.41, 95% confidence interval, CI: 1.05-1.90). HRs for CHD mortality exceeded unity but were not statistically significant. The association with GL was stronger among subjects with higher body mass index. High adherence to MD with low/moderate GL was associated with lower risk of CHD incidence (HR = 0.61, CI: 0.39-0.95) and mortality (HR = 0.47, 95% CI: 0.23-96). CONCLUSION: High dietary GL increases the risk of CHD. Compared to a high GL diet with suboptimal adherence to the traditional Mediterranean pattern, a low/moderate GL diet that also conforms to the traditional MD principles could lead to a 40% reduced risk for CHD, and over 50% reduced risk for death from CHD.

Impact of thearubigins on the estimation of total dietary flavonoids in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Thearubigins (TR) are polymeric flavanol-derived compounds formed during the fermentation of tea leaves. Comprising ∼70% of total polyphenols in black tea, TR may contribute majorly to its beneficial effects on health. To date, there is no appropriate food composition data on TR, although several studies have used data from the US Department of Agriculture (USDA) database to estimate TR intakes. We aimed to estimate dietary TR in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and assess the impact of including TR or not in the calculation of the total dietary flavonoid intake. Dietary data were collected using a single standardized 24-h dietary recall interviewer-administered to 36 037 subjects aged 35-74 years. TR intakes were calculated using the USDA database. TR intakes ranged from 0.9 mg/day in men from Navarra and San Sebastian in Spain to 532.5 mg/day in men from UK general population. TR contributed <5% to the total flavonoid intake in Greece, Spain and Italy, whereas in the UK general population, TR comprised 48% of the total flavonoids. High heterogeneity in TR intake across the EPIC countries was observed. This study shows that total flavonoid intake may be greatly influenced by TR, particularly in high black tea-consuming countries. Further research on identification and quantification of TR is needed to get more accurate dietary TR estimations.

Dietary intakes and food sources of phytoestrogens in the European Prospective Investigation into Cancer and Nutrition (EPIC) 24-hour dietary recall cohort.

BACKGROUND/OBJECTIVES: Phytoestrogens are estradiol-like natural compounds found in plants that have been associated with protective effects against chronic diseases, including some cancers, cardiovascular diseases and osteoporosis. The purpose of this study was to estimate the dietary intake of phytoestrogens, identify their food sources and their association with lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. SUBJECTS/METHODS: Single 24-hour dietary recalls were collected from 36,037 individuals from 10 European countries, aged 35-74 years using a standardized computerized interview programe (EPIC-Soft). An ad hoc food composition database on phytoestrogens (isoflavones, lignans, coumestans, enterolignans and equol) was compiled using data from available databases, in order to obtain and describe phytoestrogen intakes and their food sources across 27 redefined EPIC centres. RESULTS: Mean total phytoestrogen intake was the highest in the UK health-conscious group (24.9 mg/day in men and 21.1 mg/day in women) whereas lowest in Greece (1.3 mg/day) in men and Spain-Granada (1.0 mg/day) in women. Northern European countries had higher intakes than southern countries. The main phytoestrogen contributors were isoflavones in both UK centres and lignans in the other EPIC cohorts. Age, body mass index, educational level, smoking status and physical activity were related to increased intakes of lignans, enterolignans and equol, but not to total phytoestrogen, isoflavone or coumestan intakes. In the UK cohorts, the major food sources of phytoestrogens were soy products. In the other EPIC cohorts the dietary sources were more distributed, among fruits, vegetables, soy products, cereal products, non-alcoholic and alcoholic beverages. CONCLUSIONS: There was a high variability in the dietary intake of total and phytoestrogen subclasses and their food sources across European regions.

Genetic predisposition to coronary heart disease and stroke using an additive genetic risk score: a population-based study in Greece.

OBJECTIVE: To determine the extent to which the risk for incident coronary heart disease (CHD) increases in relation to a genetic risk score (GRS) that additively integrates the influence of high-risk alleles in nine documented single nucleotide polymorphisms (SNPs) for CHD, and to examine whether this GRS also predicts incident stroke. METHODS: Genotypes at nine CHD-relevant SNPs were determined in 494 cases of incident CHD, 320 cases of incident stroke and 1345 unaffected controls drawn from the population-based Greek component of the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. An additive GRS was calculated for each study participant by adding one unit for the presence of each high-risk allele multiplied by the estimated effect size of that allele in the discovery samples. Statistical analysis was performed using logistic regression. RESULTS: The GRS was significantly associated with the incidence of CHD where the odds of CHD incidence in the highest quintile of the GRS were 1.74 times higher (95% confidence interval [CI]=1.25-2.43, p for trend=0.0004), compared to the lowest quintile. With respect to stroke, a weaker and non-significant positive association with GRS was apparent as the odds of stroke incidence in the highest quintile of the GRS were 1.36 times higher (95% CI=0.90-2.06, p for trend=0.188), compared to the lowest quintile. CONCLUSION: A GRS relying on nine documented "CHD-specific" SNPs is significantly predictive of CHD but it was not found to be statistically significantly associated with incident stroke.

Concentrations of IGF-I and IGFBP-3 and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Insulin-like growth factors (IGFs) and their binding proteins (BPs) regulate cell differentiation, proliferation and apoptosis, and may have a role in the aetiology of various cancers. Information on their role in pancreatic cancer is limited and was examined here in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. METHODS: Serum concentrations of IGF-I and IGFBP-3 were measured using enzyme-linked immunosorbent assays in 422 cases and 422 controls matched on age, sex, study centre, recruitment date, and time since last meal. Conditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounding variables. RESULTS: Neither circulating levels of IGF-I (OR=1.21, 95% CI 0.75-1.93 for top vs bottom quartile, P-trend 0.301), IGFBP-3 (OR=1.00, 95% CI 0.66-1.51, P-trend 0.79), nor the molar IGF-I/IGFBP-3 ratio, an indicator of free IGF-I level (OR=1.22, 95% CI 0.75-1.97, P-trend 0.27), were statistically significantly associated with the risk of pancreatic cancer. In a cross-classification, however, a high concentration of IGF-I with concurrently low levels of IGFBP-3 was related to an increased risk of pancreatic cancer (OR=1.72, 95% CI 1.05-2.83; P-interaction=0.154). CONCLUSION: On the basis of these results, circulating levels of components of the IGF axis do not appear to be the risk factors for pancreatic cancer. However, on the basis of the results of a subanalysis, it cannot be excluded that a relatively large amount of IGF-1 together with very low levels of IGFBP-3 might still be associated with an increase in pancreatic cancer risk.

Eating out, weight and weight gain. A cross-sectional and prospective analysis in the context of the EPIC-PANACEA study.

OBJECTIVE: The aim of this study was to examine the association of body mass index (BMI) and weight gain with eating at restaurants and similar establishments or eating at work among 10 European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. SUBJECTS: This study included a representative sample of 24,310 randomly selected EPIC participants. METHODS: Single 24-h dietary recalls with information on the place of consumption were collected using standardized procedures between 1995 and 2000. Eating at restaurants was defined to include all eating and drinking occasions at restaurants, cafeterias, bars and fast food outlets. Eating at work included all eating and drinking occasions at the workplace. Associations between eating at restaurants or eating at work and BMI or annual weight changes were assessed using sex-specific linear mixed-effects models, controlling for potential confounders. RESULTS: In southern Europe energy intake at restaurants was higher than intake at work, whereas in northern Europe eating at work appeared to contribute more to the mean daily intake than eating at restaurants. Cross-sectionally, eating at restaurants was found to be positively associated with BMI only among men (ß=+0.24, P=0.003). Essentially no association was found between BMI and eating at work among both genders. In a prospective analysis among men, eating at restaurants was found to be positively, albeit nonsignificantly, associated with weight gain (ß=+0.05, P=0.368). No association was detected between energy intake at restaurants and weight changes, controlling for total energy intake. CONCLUSION: Among men, eating at restaurants and similar establishments was associated with higher BMI and possibly weight gain.

Fruits and vegetables consumption and the risk of histological subtypes of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: To examine the association between fruit and vegetable consumption and risk of different histological subtypes of lung cancer among participants of the European Prospective Investigation into Cancer and Nutrition study. METHODS: Multivariable Cox proportional hazard models were used to analyze the data. A calibration study in a subsample was used to reduce dietary measurement errors. RESULTS: During a mean follow-up of 8.7 years, 1,830 incident cases of lung cancer (574 adenocarcinoma, 286 small cell, 137 large cell, 363 squamous cell, 470 other histologies) were identified. In line with our previous conclusions, we found that after calibration a 100 g/day increase in fruit and vegetables consumption was associated with a reduced lung cancer risk (HR 0.94; 95% CI 0.89-0.99). This was also seen among current smokers (HR 0.93; 95% CI 0.90-0.97). Risks of squamous cell carcinomas in current smokers were reduced for an increase of 100 g/day of fruit and vegetables combined (HR 0.85; 95% CI 0.76-0.94), while no clear effects were seen for the other histological subtypes. CONCLUSION: We observed inverse associations between the consumption of vegetables and fruits and risk of lung cancer without a clear effect on specific histological subtypes of lung cancer. In current smokers, consumption of vegetables and fruits may reduce lung cancer risk, in particular the risk of squamous cell carcinomas.

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 intakes of retinol, beta-carotene, vitamin D and vitamin E in the European Prospective Investigation into Cancer and Nutrition cohort.

OBJECTIVES: To describe the intake of the fat-soluble nutrients retinol, beta-carotene, vitamin E and vitamin D and their food sources among 27 redefined centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. METHODS: Between 1995 and 2000, 36,034 subjects (age range: 35-74 years) completed a single standardized 24-h dietary recall using a computerized interview software program (EPIC-SOFT). Intakes of the fat-soluble nutrients were estimated using the standardized EPIC Nutrient Database. RESULTS: For all the nutrients, in most centres, men had a higher level of intake than did women, even after adjustments for total energy intake and anthropometric confounders. Distinct regional gradients from northern to southern European countries were observed for all nutrients. The level intake of beta-carotene and vitamin E also showed some differences by level of education, smoking status and physical activity. No meaningful differences in the nutrient intake were observed by age range. CONCLUSIONS: These results show differences by study centre, gender, age and various lifestyle variables in the intake of retinol, beta-carotene, vitamin E and vitamin D between 10 European countries.

Alcohol consumption patterns, diet and body weight in 10 European countries.

BACKGROUND/OBJECTIVES: Europe has the highest level of alcohol consumption in the world. As drinking patterns are important determinants of the beneficial and harmful effects of alcohol consumption, we investigated alcohol consumption in relation to nutrient intake, place of consumption, education and body weight in a sample of adults from 10 European countries. METHODS: A 24-h dietary recall interview was conducted on 13 025 men and 23 009 women, aged 35-74 years, from 27 centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Means and standard errors of alcohol consumption, adjusted for age, were calculated, stratified by gender and centre. RESULTS: In many centres, higher level drinkers (males consuming >24 g of ethanol/day, equivalent to >2 standard drinks and females consuming >12 g of ethanol/day equivalent to >1 standard drink) obtained more energy from fat and protein and less from sugar than did abstainers. The proportion of energy from starch tended to be higher for male and lower for female higher level drinkers than for abstainers. Female higher level drinkers had a lower body mass index than did abstainers, whereas male higher level drinkers generally weighed more. Male higher level drinkers were less educated than abstainers in Mediterranean countries, but were more educated elsewhere. Female higher level drinkers were usually more educated than were abstainers. Outside the home, consumption (both genders) tended to be at friends' homes, particularly among men in Northern and Central Europe, and in bars in Spain. CONCLUSIONS: This study reveals clear geographical differences in drinking habits across Europe, and shows that the characteristics of different alcohol consumption categories also vary.

Plasma phyto-oestrogens and prostate cancer in the European Prospective Investigation into Cancer and Nutrition.

We examined plasma concentrations of phyto-oestrogens in relation to risk for subsequent prostate cancer in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition. Concentrations of isoflavones genistein, daidzein and equol, and that of lignans enterolactone and enterodiol, were measured in plasma samples for 950 prostate cancer cases and 1042 matched control participants. Relative risks (RRs) for prostate cancer in relation to plasma concentrations of these phyto-oestrogens were estimated by conditional logistic regression. Higher plasma concentrations of genistein were associated with lower risk of prostate cancer: RR among men in the highest vs the lowest fifth, 0.71 (95% confidence interval (CI) 0.53-0.96, P trend=0.03). After adjustment for potential confounders this RR was 0.74 (95% CI 0.54-1.00, P trend=0.05). No statistically significant associations were observed for circulating concentrations of daidzein, equol, enterolactone or enterodiol in relation to overall risk for prostate cancer. There was no evidence of heterogeneity in these results by age at blood collection or country of recruitment, nor by cancer stage or grade. These results suggest that higher concentrations of circulating genistein may reduce the risk of prostate cancer but do not support an association with plasma lignans.