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We describe a novel dietary assessment strategy to estimate usual food intake in the ongoing large-scale multi-center German National Cohort (GNC). The dietary assessment is based on three 24 h food lists (24h-FL) and a food frequency questionnaire (FFQ) enriched by information from the representative German National Nutrition Survey II (NVS II). The novelty of this dietary assessment strategy is based on separating the probability of food intake from daily consumption amounts. The probability of consumption is estimated from 24h-FLs used in the GNC. To estimate daily consumption amounts, the already collected data of the NVS II are used. The 24h-FL simplifies the question on food consumption for all foods asked to consumption or not and so the questionnaire can be completed in about 10 minutes, reducing the burden on study participants. As proof of concept, we applied the assessment strategy to pretest data collected in 2012 to 2013 to assess the feasibility of the instruments. In brief, the novel dietary assessment strategy comprises three steps. First, the individuals’ consumption probability is estimated by three 24h-FLs and one FFQ applying a logistic linear mixed model adjusted for characteristics of the participants. Second, person-specific daily consumption amounts are estimated from the NVS II applying a linear mixed model taking the characteristics of the participants into account. Third, usual food intake is estimated by the consumption probability multiplied by person-specific daily amounts. Usual intake of 41 food groups in 318 men and 377 women were estimated. Of those participants who completed the first 24h-FL, 84.4, and 68.5% completed the second and third 24h-FL, respectively. No associations were observed between probability to participate and lifestyle factors. The estimated usual food intake distributions were in a plausible range as shown by comparing the estimated energy intake to the energy needs approximated by estimated total energy expenditure. Total energy was estimated to be 2,707 kcal/day for men and 2,103 kcal/day for women. With a few exceptions, the estimated food-based consumption probabilities did not differ considerably between men and women. The differences in energy intake between men and women were mainly due to their differences in the estimated person-specific daily amounts. As a conclusion, plausible but not validated values for usual food intake were derived in the pretest study, so that the combination of three repeated 24h-FLs, an FFQ and person-specific daily amounts from an external source is a feasible strategy for dietary assessment.
Pattern analysis has emerged as a tool to depict the role of multiple nutrients/foods in relation to health outcomes. The present study aimed at extracting nutrient patterns with respect to breast cancer (BC) aetiology.
Nutrient patterns were derived with treelet transform (TT) and related to BC risk. TT was applied to twenty-three log-transformed nutrient densities from dietary questionnaires. Hazard ratios (HR) and 95 % confidence intervals computed using Cox proportional hazards models quantified the association between quintiles of nutrient pattern scores and risk of overall BC, and by hormonal receptor and menopausal status. Principal component analysis was applied for comparison.
The European Prospective Investigation into Cancer and Nutrition (EPIC).
Women (n 334 850) from the EPIC study.
The first TT component (TC1) highlighted a pattern rich in nutrients found in animal foods loading on cholesterol, protein, retinol, vitamins B12 and D, while the second TT component (TC2) reflected a diet rich in β-carotene, riboflavin, thiamin, vitamins C and B6, fibre, Fe, Ca, K, Mg, P and folate. While TC1 was not associated with BC risk, TC2 was inversely associated with BC risk overall (HRQ5 v. Q1=0·89, 95 % CI 0·83, 0·95, Ptrend<0·01) and showed a significantly lower risk in oestrogen receptor-positive (HRQ5 v. Q1=0·89, 95 % CI 0·81, 0·98, Ptrend=0·02) and progesterone receptor-positive tumours (HRQ5 v. Q1=0·87, 95 % CI 0·77, 0·98, Ptrend<0·01).
TT produces readily interpretable sparse components explaining similar amounts of variation as principal component analysis. Our results suggest that participants with a nutrient pattern high in micronutrients found in vegetables, fruits and cereals had a lower risk of BC.
Health-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.
Cross-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.
Multi-centre, European study.
Persons (n 36 970) aged 35–74 years, constituting a random sample of 519 978 EPIC participants.
The 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.
Dark 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.
Recent meta-analyses have confirmed that fish consumption is related to decreased risks of ischaemic stroke and fatal CHD, while there seem to be no clear associations between fish consumption and the risks of haemorrhagic stroke and non-fatal CHD. As no studies in German populations have been reported to date, we assessed whether fish consumption as recorded by FFQ between 1994 and 1998 was related to incident myocardial infarction (MI) and stroke within the German arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards regression analyses were conducted based on the data of 48 315 participants aged 35–65 years at baseline. The median fish intake was 16·4 g/d (25th–75th percentile 8·2–28·8 g/d). During a mean follow-up of 8·1 years, 605 incident MI and 525 incident strokes have been documented. After multiple adjustment, fish consumption was not related to incident MI (hazard ratio (HR) 0·84, 95 % CI 0·66, 1·08, Ptrend= 0·21) or stroke (HR 0·96, 95 % CI 0·73, 1·26, Ptrend= 0·67). Separate analyses for fatal MI, ischaemic stroke and haemorrhagic stroke did not show significant associations, either. With regard to non-fatal MI, there was a non-significant trend for an inverse association (HR 0·78, 95 % CI 0·59, 1·03, Ptrend= 0·07). Overall, fish consumption was not related to the risks of MI and stroke in the EPIC-Germany study.
Epidemiological studies suggest health-protective effects of flavan-3-ols and their derived compounds on chronic diseases. The present study aimed to estimate dietary flavan-3-ol, proanthocyanidin (PA) and theaflavin intakes, their food sources and potential determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration cohort. Dietary data were collected using a standardised 24 h dietary recall software administered to 36 037 subjects aged 35–74 years. Dietary data were linked with a flavanoid food composition database compiled from the latest US Department of Agriculture and Phenol-Explorer databases and expanded to include recipes, estimations and retention factors. Total flavan-3-ol intake was the highest in UK Health-conscious men (453·6 mg/d) and women of UK General population (377·6 mg/d), while the intake was the lowest in Greece (men: 160·5 mg/d; women: 124·8 mg/d). Monomer intake was the highest in UK General population (men: 213·5 mg/d; women: 178·6 mg/d) and the lowest in Greece (men: 26·6 mg/d in men; women: 20·7 mg/d). Theaflavin intake was the highest in UK General population (men: 29·3 mg/d; women: 25·3 mg/d) and close to zero in Greece and Spain. PA intake was the highest in Asturias (men: 455·2 mg/d) and San Sebastian (women: 253 mg/d), while being the lowest in Greece (men: 134·6 mg/d; women: 101·0 mg/d). Except for the UK, non-citrus fruits (apples/pears) were the highest contributors to the total flavan-3-ol intake. Tea was the main contributor of total flavan-3-ols in the UK. Flavan-3-ol, PA and theaflavin intakes were significantly different among all assessed groups. This study showed heterogeneity in flavan-3-ol, PA and theaflavin intake throughout the EPIC countries.
Studies have suggested that moderate alcohol consumption is associated with a reduced risk of CVD and premature mortality in individuals with diabetes mellitus. However, history of alcohol consumption has hardly been taken into account. We investigated the association between current alcohol consumption and mortality in men and women with diabetes mellitus accounting for past alcohol consumption. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort was defined of 4797 participants with a confirmed diagnosis of diabetes mellitus. Men and women were assigned to categories of baseline and past alcohol consumption. Hazard ratios (HR) and 95 % CI for total mortality were estimated with multivariable Cox regression models, using light alcohol consumption (>0–6 g/d) as the reference category. Compared with light alcohol consumption, no relationship was observed between consumption of 6 g/d or more and total mortality. HR for >6–12 g/d was 0·89 (95 % CI 0·61, 1·30) in men and 0·86 (95 % CI 0·46, 1·60) in women. Adjustment for past alcohol consumption did not change the estimates substantially. In individuals who at baseline reported abstaining from alcohol, mortality rates were increased relative to light consumers: HR was 1·52 (95 % CI 0·99, 2·35) in men and 1·81 (95 % CI 1·04, 3·17) in women. The present study in diabetic individuals showed no association between current alcohol consumption >6 g/d and mortality risk compared with light consumption. The increased mortality risk among non-consumers appeared to be affected by their past alcohol consumption rather than their current abstinence.
Whether there are differences between countries in the validity of self-reported diet in relation to BMI, as evaluated using recovery biomarkers, is not well understood. We aimed to evaluate BMI-related reporting errors on 24 h dietary recalls (24-HDR) and on dietary questionnaires (DQ) using biomarkers for protein and K intake and whether the BMI effect differs between six European countries. Between 1995 and 1999, 1086 men and women participating in the European Prospective Investigation into Cancer and Nutrition completed a single 24-HDR, a DQ and one 24 h urine collection. In regression analysis, controlling for age, sex, education and country, each unit (1 kg/m2) increase in BMI predicted an approximately 1·7 and 1·3 % increase in protein under-reporting on 24-HDR and DQ, respectively (both P < 0·0001). Exclusion of individuals who probably misreported energy intake attenuated BMI-related bias on both instruments. The BMI effect on protein under-reporting did not differ for men and women and neither between countries on both instruments as tested by interaction (all P>0·15). In women, but not in men, the DQ yielded higher mean intakes of protein that were closer to the biomarker-based measurements across BMI groups when compared with 24-HDR. Results for K were similar to those of protein, although BMI-related under-reporting of K was of a smaller magnitude, suggesting differential misreporting of foods. Under-reporting of protein and K appears to be predicted by BMI, but this effect may be driven by ‘low-energy reporters’. The BMI effect on under-reporting seems to be the same across countries.
Flavonols, flavanones and flavones (FLAV) are sub-classes of flavonoids that exert cardioprotective and anti-carcinogenic properties in vitro and in vivo. We aimed to estimate the FLAV dietary intake, their food sources and associated lifestyle factors in ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. FLAV intake and their food sources for 36 037 subjects, aged between 35 and 74 years, in twenty-seven study centres were obtained using standardised 24 h dietary recall software (EPIC-SOFT). An ad hoc food composition database on FLAV was compiled using data from US Department of Agriculture and Phenol-Explorer databases and was expanded using recipes, estimations and flavonoid retention factors in order to increase its correspondence with the 24 h dietary recall. Our results showed that the highest FLAV-consuming centre was the UK health-conscious group, with 130·9 and 97·0 mg/d for men and women, respectively. The lowest FLAV intakes were 36·8 mg/d in men from Umeå and 37·2 mg/d in women from Malmö (Sweden). The flavanone sub-class was the main contributor to the total FLAV intake ranging from 46·6 to 52·9 % depending on the region. Flavonols ranged from 38·5 to 47·3 % and flavones from 5·8 to 8·6 %. FLAV intake was higher in women, non-smokers, increased with level of education and physical activity. The major food sources were citrus fruits and citrus-based juices (especially for flavanones), tea, wine, other fruits and some vegetables. We concluded that the present study shows heterogeneity in intake of these three sub-classes of flavonoids across European regions and highlights differences by sex and other sociodemographic and lifestyle factors.
Anthocyanidins are bioactive flavonoids with potential health-promoting effects. These may vary among single anthocyanidins considering differences in their bioavailability and some of the mechanisms involved. The aim of the present study was to estimate the dietary intake of anthocyanidins, their food sources and the lifestyle factors (sex, age, BMI, smoking status, educational level and physisical activity) involved among twenty-seven centres in ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthocyanidin intake and their food sources for 36 037 subjects, aged between 35 and 74 years, in twenty-seven redefined centres were obtained using standardised 24 h dietary recall software (EPIC-SOFT). An ad hoc food composition database on anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin) was compiled using data from the US Department of Agriculture and Phenol-Explorer databases and was expanded by adding recipes, estimated values and cooking factors. For men, the total anthocyanidin mean intake ranged from 19·83 (se 1·53) mg/d (Bilthoven, The Netherlands) to 64·88 (se 1·86) mg/d (Turin, Italy), whereas for women the range was 18·73 (se 2·80) mg/d (Granada, Spain) to 44·08 (se 2·45) mg/d (Turin, Italy). A clear south to north gradient intake was observed. Cyanidins and malvidins were the main anthocynidin contributors depending on the region and sex. Anthocyanidin intake was higher in non-obese older females, non-smokers, and increased with educational level and physical activity. The major food sources were fruits, wine, non-alcoholic beverages and some vegetables. The present study shows differences in both total and individual anthocyanidin intakes and various lifestyle factors throughout Europe, with some geographical variability in their food sources.
Cross-sectional studies suggest that dietary supplement use is associated with favourable demographic and lifestyle factors and certain health conditions. However, factors that affect the consistency of supplement use have not been investigated in prospective cohort studies. The aim of the present study was to seek baseline demographic, lifestyle and health-status predictors of subsequent consistent vitamin and/or mineral supplement use. A total of 8968 men and 10 672 women of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort, who answered the supplement-use questions in the baseline survey and two follow-up surveys, were categorised into three groups: consistent, inconsistent and never users. At baseline, 28·5 % of men and 38·6 % of women reported vitamin and/or mineral supplement use. After a median follow-up of 8·5 years, 14·6 % of men and 22·9 % of women were consistent users. During follow-up, 36·0 % of male and 26·6 % of female initial users stopped supplement use, whereas 27·8 % of male and 39·4 % of female initial non-users started supplement use. Women were more likely to be consistent users than men. Older age ( ≥ 50 years), lower BMI ( < 25 kg/m2) and self-reported hyperlipidaemia were common predictors of consistent use for both sexes. Additional predictors included higher educational level for men, and being more physically active and higher lifetime alcohol consumption for women. Consistent users had the highest intake of dairy products, fish, fruits and vegetables, and wine but the lowest intake of total meat. We concluded that supplement use is a fairly unstable behaviour in free-living individuals. Individuals with a favourable lifestyle and healthier diet are more likely to show consistent supplementation.
In contrast to some extensively examined food mutagens, for example, aflatoxins, N-nitrosamines and heterocyclic amines, some other food contaminants, in particular polycyclic aromatic hydrocarbons (PAH) and other aromatic compounds, have received less attention. Therefore, exploring the relationships between dietary habits and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. We have investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts. Both types of adducts are biomarkers of carcinogen exposure and possibly of cancer risk, and were measured, respectively, in leucocytes and erythrocytes of 1086 (DNA adducts) and 190 (Hb adducts) non-smokers. An inverse, statistically significant, association has been found between DNA adduct levels and dietary fibre intake (P = 0·02), vitamin E (P = 0·04) and alcohol (P = 0·03) but not with other nutrients or food groups. Also, an inverse association between fibre and fruit intake, and BMI and 4-aminobiphenyl-Hb adducts (P = 0·03, 0·04, and 0·03 respectively) was observed. After multivariate regression analysis these inverse correlations remained statistically significant, except for the correlation adducts v. fruit intake. The present study suggests that fibre intake in the usual range can modify the level of DNA or Hb aromatic adducts, but such role seems to be quantitatively modest. Fibres could reduce the formation of DNA adducts in different manners, by diluting potential food mutagens and carcinogens in the gastrointestinal tract, by speeding their transit through the colon and by binding carcinogenic substances.
In addition to their possible direct biological effects, plasma carotenoids can be used as biochemical markers of fruit and vegetable consumption for identifying diet–disease associations in epidemiological studies. Few studies have compared levels of these carotenoids between countries in Europe.
Our aim was to assess the variability of plasma carotenoid levels within the cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).
Plasma levels of six carotenoids – α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin – were measured cross-sectionally in 3043 study subjects from 16 regions in nine European countries. We investigated the relative influence of gender, season, age, body mass index (BMI), alcohol intake and smoking status on plasma levels of the carotenoids.
Mean plasma level of the sum of the six carotenoids varied twofold between regions (1.35μmoll−1 for men in Malmö, Sweden vs. 2.79μmoll−1 for men in Ragusa/Naples, Italy; 1.61μmoll−1 for women in The Netherlands vs. 3.52μmoll−1 in Ragusa/Naples, Italy). Mean levels of individual carotenoids varied up to fourfold (α-carotene: 0.06μmoll−1 for men in Murcia, Spain vs. 0.25μmoll−1 for vegetarian men living in the UK). In multivariate regression analyses, region was the most important predictor of total plasma carotenoid level (partial R2=27.3%), followed by BMI (partial R2=5.2%), gender (partial R2=2.7%) and smoking status (partial R2=2.8%). Females had higher total carotenoid levels than males across Europe.
Plasma levels of carotenoids vary substantially between 16 different regions in Italy, Greece, Spain, France, Germany, the UK, Sweden, Denmark and The Netherlands. Compared with region of residence, the other demographic and lifestyle factors and laboratory measurements have limited predictive value for plasma carotenoid levels in Europe.
To evaluate the reproducibility of, and to compare and calibrate, diet measures by the Northern Sweden 84-item food-frequency questionnaire (FFQ) with measures from 24-hour diet recalls (24-HDR).
Randomly selected respondents (n=246) from the EPIC (diet-cancer) and MONICA (diet-cardiovascular disease) study cohort in Northern Sweden were invited to answer the FFQ twice over a one-year interval (FFQ1 and FFQ2), and to complete ten 24-hour recalls (reference method) in the months between. Plasma β-carotene concentrations were determined from a subset of 47 participants.
Vasterbotten and Norrbotten, Northern Sweden.
Ninety-six men and 99 women, who completed the study.
The reproducibility of the FFQ was high in terms of both mean energy and nutrient intakes and relative ranking of participants by intake levels (median Pearson correlation of 0.68). Moderately higher food intake frequencies were recorded by FFQ1 compared with 24-hour recalls for dairy products, bread/cereals, vegetables, fruits and potato/rice/pasta, whereas meat, fish, sweet snacks and alcoholic beverage intakes were lower. The median Spearman coefficient of correlation between FFQ1 and the average of ten 24-HDR measurements was 0.50. Daily energy and nutrient intakes were similar for FFQ1 and 24-HDR measurements, except for fibre, vitamin C, β-carotene and retinol (FFQ1<24-HDR) and sucrose and cholesterol (FFQ1>4-HDR). Pearson coefficients of correlation between FFQ1 and 24-HDR corrected for attenuation due to residual day-to-day variation in the 24-HDR measurements ranged from 0.36 to 0.79 (median 0.54). Adjustment for energy had only very moderate effects on the correlation estimates. Calibration coefficients estimated by linear regression of the 24-HDR on the FFQ1 measurements varied between 0.30 and 0.59 for all nutrients except alcohol, which had calibration coefficients close to 1.0. These low calibration coefficients indicate that relative risk estimates corresponding to an absolute difference in dietary intake levels measured by the FFQ will generally be biased towards 1.0. Plasma β-carotene levels had a Pearson coefficient of correlation of 0.47 with the 24-HDR measurements, and of 0.23 with FFQ1 measurements.
The Northern Sweden FFQ measurements have good reproducibility and an estimated level of validity similar to that of FFQ measurements in other prospective cohort studies. The results from this study will form the basis for the correction of attenuation and regression dilution biases in relative risk estimates, in future studies relating FFQ measurements to disease outcomes.
To examine statistical models that account for correlation between random errors of different dietary assessment methods, in dietary validation studies.
In nutritional epidemiology, sub-studies on the accuracy of the dietary questionnaire measurements are used to correct for biases in relative risk estimates induced by dietary assessment errors. Generally, such validation studies are based on the comparison of questionnaire measurements (Q) with food consumption records or 24-hour diet recalls (R). In recent years, the statistical analysis of such studies has been formalised more in terms of statistical models. This made the need of crucial model assumptions more explicit. One key assumption is that random errors must be uncorrelated between measurements Q and R, as well as between replicate measurements R1 and R2 within the same individual. These assumptions may not hold in practice, however. Therefore, more complex statistical models have been proposed to validate measurements Q by simultaneous comparisons with measurements R plus a biomarker M, accounting for correlations between the random errors of Q and R.
The more complex models accounting for random error correlations may work only for validation studies that include markers of diet based on physiological knowledge about the quantitative recovery, e.g. in urine, of specific elements such as nitrogen or potassium, or stable isotopes administered to the study subjects (e.g. the doubly labelled water method for assessment of energy expenditure). This type of marker, however, eliminates the problem of correlation of random errors between Q and R by simply taking the place of R, thus rendering complex statistical models unnecessary.
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