Experimental studies have reported on the anti-inflammatory properties of polyphenols. However, results from epidemiological investigations have been inconsistent and especially studies using biomarkers for assessment of polyphenol intake have been scant. We aimed to characterise the association between plasma concentrations of thirty-five polyphenol compounds and low-grade systemic inflammation state as measured by high-sensitivity C-reactive protein (hsCRP). A cross-sectional data analysis was performed based on 315 participants in the European Prospective Investigation into Cancer and Nutrition cohort with available measurements of plasma polyphenols and hsCRP. In logistic regression analysis, the OR and 95 % CI of elevated serum hsCRP (>3 mg/l) were calculated within quartiles and per standard deviation higher level of plasma polyphenol concentrations. In a multivariable-adjusted model, the sum of plasma concentrations of all polyphenols measured (per standard deviation) was associated with 29 (95 % CI 50, 1) % lower odds of elevated hsCRP. In the class of flavonoids, daidzein was inversely associated with elevated hsCRP (OR 0·66, 95 % CI 0·46, 0·96). Among phenolic acids, statistically significant associations were observed for 3,5-dihydroxyphenylpropionic acid (OR 0·58, 95 % CI 0·39, 0·86), 3,4-dihydroxyphenylpropionic acid (OR 0·63, 95 % CI 0·46, 0·87), ferulic acid (OR 0·65, 95 % CI 0·44, 0·96) and caffeic acid (OR 0·69, 95 % CI 0·51, 0·93). The odds of elevated hsCRP were significantly reduced for hydroxytyrosol (OR 0·67, 95 % CI 0·48, 0·93). The present study showed that polyphenol biomarkers are associated with lower odds of elevated hsCRP. Whether diet rich in bioactive polyphenol compounds could be an effective strategy to prevent or modulate deleterious health effects of inflammation should be addressed by further well-powered longitudinal studies.

A standardised, national, 160-item FFQ, the FFQ-NL 1.0, was recently developed for Dutch epidemiological studies. The objective was to validate the FFQ-NL 1.0 against multiple 24-h recalls (24hR) and recovery and concentration biomarkers. The FFQ-NL 1.0 was filled out by 383 participants (25–69 years) from the Nutrition Questionnaires plus study. For each participant, one to two urinary and blood samples and one to five (mean 2·7) telephone-based 24hR were available. Group-level bias, correlation coefficients, attenuation factors, de-attenuated correlation coefficients and ranking agreement were assessed. Compared with the 24hR, the FFQ-NL 1.0 estimated the intake of energy and macronutrients well. However, it underestimated intakes of SFA and trans-fatty acids and alcohol and overestimated intakes of most vitamins by >5 %. The median correlation coefficient was 0·39 for energy and macronutrients, 0·30 for micronutrients and 0·30 for food groups. The FFQ underestimated protein intake by an average of 16 % and K by 5 %, relative to their urinary recovery biomarkers. Attenuation factors were 0·44 and 0·46 for protein and K, respectively. Correlation coefficients were 0·43–0·47 between (fatty) fish intake and plasma EPA and DHA and 0·24–0·43 between fruit and vegetable intakes and plasma carotenoids. In conclusion, the overall validity of the newly developed FFQ-NL 1.0 was acceptable to good. The FFQ-NL 1.0 is well suited for future use within Dutch cohort studies among adults.

Improvements in colorectal cancer (CRC) detection and treatment have led to greater numbers of CRC survivors, for whom there is limited evidence on which to provide dietary guidelines to improve survival outcomes. Higher intake of red and processed meat and lower intake of fibre are associated with greater risk of developing CRC, but there is limited evidence regarding associations with survival after CRC diagnosis. Among 3789 CRC cases in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, pre-diagnostic consumption of red meat, processed meat, poultry and dietary fibre was examined in relation to CRC-specific mortality (n 1008) and all-cause mortality (n 1262) using multivariable Cox regression models, adjusted for CRC risk factors. Pre-diagnostic red meat, processed meat or fibre intakes (defined as quartiles and continuous grams per day) were not associated with CRC-specific or all-cause mortality among CRC survivors; however, a marginal trend across quartiles of processed meat in relation to CRC mortality was detected (P 0·053). Pre-diagnostic poultry intake was inversely associated with all-cause mortality among women (hazard ratio (HR)/20 g/d 0·92; 95 % CI 0·84, 1·00), but not among men (HR 1·00; 95 % CI 0·91, 1·09) (Pfor heterogeneity=0·10). Pre-diagnostic intake of red meat or fibre is not associated with CRC survival in the EPIC cohort. There is suggestive evidence of an association between poultry intake and all-cause mortality among female CRC survivors and between processed meat intake and CRC-specific mortality; however, further research using post-diagnostic dietary data is required to confirm this relationship.

To assess the relationship between dietary intake of antioxidants (vitamin C, vitamin E, β-carotene, lutein, flavonoids and lignans) and cognitive decline at middle age, analyses were performed on data from the population based Doetinchem Cohort Study. Habitual diet and cognitive function were assessed twice with a 5-year interval in 2613 persons aged 43–70 year at baseline (1995–2002). Diet was assessed with a validated 178-item semi-quantitative FFQ. Cognitive function was assessed with a neuropsychological test battery, consisting of the 15 Words Learning Test, the Stroop Test, the Word Fluency test, and the Letter Digit Substitution Test. Scores on global cognitive function, memory, processing speed, and cognitive flexibility were calculated. In regression analyses, quintiles of antioxidant intake were associated with change in cognitive domain scores. Results showed that higher lignan intake was linearly associated with less decline in global cognitive function (P= 0·01), memory (P< 0·01) and processing speed (P= 0·04), with about two times less declines in the highest v. the lowest quintile. In the lowest quintile of vitamin E intake, decline in memory was twice as fast as in all higher quintiles (P< 0·01). Global cognitive decline in the highest lutein intake group was greater than in the lowest intake group (P< 0·05). Higher flavonoid intake was associated with greater decline in cognitive flexibility (P for trend = 0·04). Intakes of other antioxidants were not associated with cognitive decline. We conclude that within the range of a habitual dietary intake, higher intake of lignans is associated with less cognitive decline at middle age.

The objective of the present study was to investigate the relationship between total and subtypes of bacterial fermented food intake (dairy products, cheese, vegetables and meat) and mortality due to all causes, total cancer and CVD. From the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort, 34 409 Dutch men and women, aged 20–70 years who were free from CVD or cancer at baseline, were included. Baseline intakes of total and subtypes of fermented foods were measured with a validated FFQ. Data on the incidence and causes of death were obtained from the national mortality register. Cox proportional hazards models were used to analyse mortality in relation to the quartiles of fermented food intake. After a mean follow-up of 15 (sd 2·5) years, 2436 deaths occurred (1216 from cancer and 727 from CVD). After adjustment for age, sex, total energy intake, physical activity, education level, hypertension, smoking habit, BMI, and intakes of fruit, vegetables and alcohol, total fermented food intake was not found to be associated with mortality due to all causes (hazard ratio upper v. lowest quartile (HRQ4 v. Q1) 1·00, 95 % CI 0·88, 1·13), cancer (HRQ4 v. Q1 1·02, 95 % CI 0·86, 1·21) or CVD (HRQ4 v. Q1 1·04, 95 % CI 0·83, 1·30). Bacterial fermented foods mainly consisted of fermented dairy foods (78 %) and cheese (16 %). None of the subtypes of fermented foods was consistently related to mortality, except for cheese which was moderately inversely associated with CVD mortality, and particularly stroke mortality (HRQ4 v. Q1 0·59, 95 % CI 0·38, 0·92, Ptrend= 0·046). In conclusion, the present study provides no strong evidence that intake of fermented foods, particularly fermented dairy foods, is associated with mortality.

Accelerated cognitive decline increases the risk of dementia. Slowing down the rate of cognitive decline leads to the preservation of cognitive functioning in the elderly, who can live independently for a longer time. Alcohol consumption may influence the rate of cognitive decline. The aim of the present study was to evaluate the associations between the total consumption of alcoholic beverages and different types of alcoholic beverages and cognitive decline at middle age. In 2613 men and women of the Doetinchem Cohort Study, aged 43–70 years at baseline (1995–2002), cognitive function (global cognitive function and the domains memory, speed and flexibility) was assessed twice, with a 5-year time interval. In linear regression analyses, the consumption of different types of alcoholic beverages was analysed in relation to cognitive decline, adjusting for confounders. We observed that, in women, the total consumption of alcoholic beverages was inversely associated with the decline in global cognitive function over a 5-year period (P for trend = 0·02), while no association was observed in men. Regarding the consumption of different types of alcoholic beverages in men and women together, red wine consumption was inversely associated with the decline in global cognitive function (P for trend < 0·01) as well as memory (P for trend < 0·01) and flexibility (P for trend = 0·03). Smallest declines were observed at a consumption of about 1·5 glasses of red wine per d. No other types of alcoholic beverages were associated with cognitive decline. In conclusion, only (moderate) red wine consumption was consistently associated with less strong cognitive decline. Therefore, it is most likely that non-alcoholic substances in red wine are responsible for any cognition-preserving effects.

Phenolic acids are secondary plant metabolites that may have protective effects against oxidative stress, inflammation and cancer in experimental studies. To date, limited data exist on the quantitative intake of phenolic acids. We estimated the intake of phenolic acids and their food sources and associated lifestyle factors in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Phenolic acid intakes were estimated for 36 037 subjects aged 35–74 years and recruited between 1992 and 2000 in ten European countries using a standardised 24 h recall software (EPIC-Soft), and their food sources were identified. Dietary data were linked to the Phenol-Explorer database, which contains data on forty-five aglycones of phenolic acids in 452 foods. The total phenolic acid intake was highest in Aarhus, Denmark (1265·5 and 980·7 mg/d in men and women, respectively), while the intake was lowest in Greece (213·2 and 158·6 mg/d in men and women, respectively). The hydroxycinnamic acid subclass was the main contributor to the total phenolic acid intake, accounting for 84·6–95·3 % of intake depending on the region. Hydroxybenzoic acids accounted for 4·6–14·4 %, hydroxyphenylacetic acids 0·1–0·8 % and hydroxyphenylpropanoic acids ≤ 0·1 % for all regions. An increasing south–north gradient of consumption was also found. Coffee was the main food source of phenolic acids and accounted for 55·3–80·7 % of the total phenolic acid intake, followed by fruits, vegetables and nuts. A high heterogeneity in phenolic acid intake was observed across the European countries in the EPIC cohort, which will allow further exploration of the associations with the risk of diseases.

Different lifestyle patterns across Europe may influence plasma concentrations of B-vitamins and one-carbon metabolites and their relation to chronic disease. Comparison of published data on one-carbon metabolites in Western European regions is difficult due to differences in sampling procedures and analytical methods between studies. The present study aimed, to compare plasma concentrations of one-carbon metabolites in Western European regions with one laboratory performing all biochemical analyses. We performed the present study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort among 5446 presumptively healthy individuals. Quantile regression was used to compare sex-specific median concentrations between Northern (Denmark and Sweden), Central (France, Germany, The Netherlands and United Kingdom) and Southern (Greece, Spain and Italy) European regions. The lowest folate concentrations were observed in Northern Europe (men, 10·4 nmol/l; women, 10·7 nmol/l) and highest concentrations in Central Europe. Cobalamin concentrations were slightly higher in Northern Europe (men, 330 pmol/l; women, 352 pmol/l) compared with Central and Southern Europe, but did not show a clear north–south gradient. Vitamin B2 concentrations were highest in Northern Europe (men, 22·2 nmol/l; women, 26·0 nmol/l) and decreased towards Southern Europe (Ptrend< 0·001). Vitamin B6 concentrations were highest in Central Europe in men (77·3 nmol/l) and highest in the North among women (70·4 nmol/l), with decreasing concentrations towards Southern Europe in women (Ptrend< 0·001). In men, concentrations of serine, glycine and sarcosine increased from the north to south. In women, sarcosine increased from Northern to Southern Europe. These findings may provide relevant information for the study of regional differences of chronic disease incidence in association with lifestyle.

A greater adherence to the traditional Mediterranean (MED) diet is associated with a reduced risk of developing chronic diseases. This dietary pattern is based on higher consumption of plant products that are rich in flavonoids. We compared the total flavonoid dietary intakes, their food sources and various lifestyle factors between MED and non-MED countries participating in the EPIC study. Flavonoid intakes and their food sources for 35 628 subjects, aged 35–74 years and recruited between 1992 and 2000, in twenty-six study centres were estimated using standardised 24 h dietary recall software (EPIC-Soft®). An ad hoc food composition database on flavonoids was compiled using analytical data from the United States Department of Agriculture and Phenol-Explorer databases. Moreover, it was expanded to include using recipes, estimations of missing values and flavonoid retention factors. No significant differences in total flavonoid mean intake between non-MED countries (373·7 mg/d) and MED countries (370·2 mg/d) were observed. In the non-MED region, the main contributors were proanthocyanidins (48·2 %) and flavan-3-ol monomers (24·9 %) and the principal food sources were tea (25·7 %) and fruits (32·8 %). In the MED region, proanthocyanidins (59·0 %) were by far the most abundant contributor and fruits (55·1 %), wines (16·7 %) and tea (6·8 %) were the main food sources. The present study shows similar results for total dietary flavonoid intakes, but significant differences in flavonoid class intakes, food sources and some characteristics between MED and non-MED countries. These differences should be considered in studies about the relationships between flavonoid intake and chronic diseases.

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.

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.

To postpone cognitive decline and dementia in old age, primary prevention is required earlier in life during middle age. Dietary components may be modifiable determinants of mental performance. In the present study, habitual fruit and vegetable intake was studied in association with cognitive function and cognitive decline during middle age. In the Doetinchem Cohort Study, 2613 men and women aged 43–70 years at baseline (1995–2002) were examined for cognitive function twice, with a 5-year time interval. Global cognitive function and the domains memory, information processing speed and cognitive flexibility were assessed. Dietary intake was assessed with a semi-quantitative FFQ. In multivariate linear regression analyses, habitual fruit and vegetable intake was studied in association with baseline and change in cognitive function. Higher reported vegetable intake was associated with lower information processing speed (P = 0·02) and worse cognitive flexibility (P = 0·03) at baseline, but with smaller decline in information processing speed (P < 0·01) and global cognitive function (P = 0·02) at follow-up. Total intakes of fruits, legumes and juices were not associated with baseline or change in cognitive function. High intakes of some subgroups of fruits and vegetables (i.e. nuts, cabbage and root vegetables) were associated with better cognitive function at baseline and/or smaller decline in cognitive domains. In conclusion, total intake of fruits and vegetables was not or inconsistently associated with cognitive function and cognitive decline. A high habitual consumption of some specific fruits and vegetables may diminish age-related cognitive decline in middle-aged individuals. Further research is needed to verify these findings before recommendations can be made.

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.