European Prospective Investigation Into Cancer And Nutrition-Netherlands Research Articles

Adherence to the EAT-Lancet Healthy Reference Diet in Relation to Risk of Cardiovascular Events and Environmental Impact: Results From the EPIC-NL Cohort.

Background The Healthy Reference Diet (HRD) was created to formulate dietary guidelines that would be healthy and sustainable. We aimed to construct a diet score measuring adherence to the HRD and to explore its association with cardiovascular events and environmental impact. Methods and Results We included 35 496 participants from the population-based EPIC-NL (European Prospective Investigation into Cancer and Nutrition-Netherlands) study. HRD scores were calculated using data from food frequency questionnaires (0-140). Data on morbidity and mortality were retrieved through linkage with national and death registries. Data on environmental impact indicators were obtained from life cycle assessments. Associations between adherence to the HRD and cardiovascular events were estimated with Cox proportional hazard models. Linear regression analysis was conducted for the adherence to the HRD and each environmental indicator. High adherence to the HRD was associated with 14%, 12%, and 11% lower risks of cardiovascular disease (hazard ratio [HR]Q4vsQ1, 0.86 [95% CI, 0.78-0.94]), coronary heart disease (HRQ4vsQ1, 0.88 [95% CI, 0.78-1.00]), and total stroke (HRQ4vsQ1, 0.89 [95% CI, 0.72-1.10]), respectively. High HRD adherence was associated with 2.4% (95% CI, -5.0 to 0.2) lower greenhouse gas emissions, 3.9% (95% CI, -5.2 to -2.6) less land use, 0.5% (95% CI, -2.6 to 1.6), less freshwater eutrophication, 3.3% (95% CI, -5.8 to -0.8), less marine eutrophication, 7.7% (95% CI, -10.8 to -4.6), less terrestrial acidification, and 32.1 % (95% CI, 28.5-35.7) higher blue water use. Conclusions High adherence to the HRD was associated with lower risk of cardiovascular disease, coronary heart disease, and modestly lower levels of most environmental indicators but a higher level of blue water use.

Milk intake and incident stroke and CHD in populations of European descent: a Mendelian randomisation study.

Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777024 participants (50804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483966 participants (61612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk.

Pure Fruit Juice and Fruit Consumption Are Not Associated with Incidence of Type 2Diabetes after Adjustment for Overall DietaryQuality in the European ProspectiveInvestigation into Cancer andNutrition–Netherlands (EPIC-NL) Study

Background:Dietary guidelines on pure fruit juice consumption vary from country to country regarding the inclusion of pure fruit juice in the recommendations as an acceptable alternative for fruit. Current epidemiological evidence on the association between pure fruit juice consumption and diabetes risk is scarce. Objectives:We studied the association of both pure fruit juice and fruit consumption with diabetes risk and investigated the differences between low and high fruit consumers in the association of pure fruit juice consumption with diabetes risk. Methods:This prospective cohort study included 36,147 participants in the European Prospective Investigation into Cancer and Nutrition–Netherlands (EPIC-NL) Study aged 20–69 y at baseline. Fruit juice and fruit consumption were assessed using a validated food-frequency questionnaire; amounts of consumption were divided into 5 categories and quintiles, respectively. Incident type 2 diabetes cases were mainly self-reported and verified against medical records. Cox regression was used to estimate adjusted HRs and 95% CIs. Results:After an average follow-up of 14.6 y, 1477 verified incident cases of type 2 diabetes were documented. Compared with no consumption, pure fruit juice consumption was not significantly associated with type 2 diabetes, with adjusted HRs ranging from 0.92 (95% CI: 0.79, 1.09) to 1.03 (95% CI: 0.83, 1.26). The associations did not differ between participants with low and high fruit consumption. None of the categories of fruit consumption were associated with type 2 diabetes (lowest quintile as reference). Adjusted HRs ranged between 0.93 (95% CI: 0.78, 1.10) and 1.00 (95% CI: 0.84, 1.19). Adjustment for the Dutch Healthy Diet Index, as an overall measure of dietary quality, strongly attenuated the observed associations of type 2 diabetes with both fruit juice and fruit consumption. Conclusions:We found no evidence for associations between pure fruit juice and fruit consumption and diabetesrisk after adjustment for overall dietary quality for participants in the EPIC-NL study. This trial was registered at https://www.trialregister.nl/trial/6939 as NL6939.

Substitution among milk and yogurt products and the risk of incident type 2 diabetes in the EPIC-NL cohort.

BackgroundHigher dairy consumption has been associated with lower type 2 diabetes (T2D) risk, whereas dairy product subtypes appear to differ in their T2D risk association. We investigated whether replacing one type of milk or yogurt product with another is associated with T2D incidence.MethodsParticipants of the European Prospective Investigation into Cancer and Nutrition‐Netherlands (EPIC‐NL) cohort (n = 35 982) were included in the present study. Information on milk and yogurt consumption at baseline was obtained by a validated food frequency questionnaire. T2D cases were identified by self‐report or linkage to the hospital discharge registry, and validated by consulting the general practitioner. Multivariable Cox proportional hazard models were used to estimate associations.ResultsDuring a mean of 15 years of follow‐up, 1467 indecent T2D cases were validated. Median total milk and yogurt intake was 1.5 servings (25th percentile to 75th percentile: 0.8–2.4). After adjustment for demographic and cardiovascular risk factors, replacement of one serving (200 g) of whole‐fat milk [hazard ratio (HR) = 0.93, 95% confidence interval (CI) = 0.60–1.44], buttermilk (HR = 0.88, 95% CI = 0.58‐1.34), skimmed milk (HR = 0.87, 95% CI = 0.57–1.32) or skimmed fermented milk (HR = 0.99, 95% CI = 0.63–1.54) with whole‐fat yogurt was not associated with T2D risk. Substitutions among other milk and yogurt products were also not associated with T2D risk. Sensitivity analysis investigating T2D risk halfway follow‐up suggested a lower risk for substitutions with whole‐fat yogurt.ConclusionsNo evidence was found for the association between substitutions among milk and yogurt products and the risk of incident T2D, although we cannot exclude possible attenuation of results as a result of dietary changes over time. This analysis should be repeated in a population with a wider consumption range of whole‐fat yogurt.

Age at menarche and heart failure risk: The EPIC-NL study

AimsEarly age at menarche has been reported to be associated with increased risks of developing type 2 diabetes (T2D) and coronary heart disease (CHD) in adulthood, but a late menarche has also been found to be associated with an increased risk of CHD. Both T2D and CHD are important risk factors for developing heart failure (HF). We examined the relationship between age at menarche (AAM) and HF incidence in women from the European Prospective Investigation into Cancer and Nutrition – Netherlands (EPIC-NL) cohort study. Methods and resultsThe EPIC-NL cohort comprised 28,504 women aged 20–70 years at baseline (1993–1997). Mean age at menarche was 13.3 (standard deviation 1.6) years. During a median follow-up of 15.2 years HF occurred in 631 women. Cox proportional hazard regression models, stratified by cohort and adjusted for potential confounders, were used to investigate the associations between AAM and HF incidence. After confounder adjustment, each year of older age at menarche was associated with a 5% lower risk of HF (hazard ratio 0.95 (95% CI, 0.91–1.00), p-value 0.048). Further adjusting for body mass index (BMI), prevalent CHD, hypertension, or prevalent T2D as potential mediators between early menarche and risk of HF attenuated the associations between AAM and risk of HF to non-significance. ConclusionOlder AAM reduced the risk of HF in this study. BMI, prevalent CHD, hypertension and prevalent T2D seemed to mediate this association. Future research with a longer follow-up should establish whether there is an independent effect of AAM on HF risk. Also, further phenotyping of HF cases is necessary to enable whether the associations differ for the various subtypes of HF.

Are our diets getting healthier and more sustainable? Insights from the European Prospective Investigation into Cancer and Nutrition - Netherlands (EPIC-NL) cohort.

To identify differences in dietary quality, dietary greenhouse gas (GHG) emissions and food consumption over 20 years in a Dutch cohort. Participants (n8932) filled out an FFQ in 1993-1997 and in 2015. The Dutch Healthy Diet index 2015 (DHD15-index) score, GHG emissions and consumption of food groups (g/4184kJ (1000kcal)) were compared between the time points with paired t tests. The Netherlands. European Prospective Investigation into Cancer and Nutrition - Netherlands (EPIC-NL) cohort, aged 18-65 years at baseline. Total energy intake decreased by -678 (95 % CI -4908, 3377)kJ/d (-162 (95 % CI -1173, 807)kcal/d) for men and -372 (95 % CI -3820, 3130)kJ/d (-89 (95 % CI -913, 748)kcal/d) for women. DHD15-index scores increased by 11 % (from 64·8 to 71·9points) and 13 % (from 65·2 to 73·6points) in men and women, respectively (P<0·0001), mainly due to an increased (shell)fish and nuts/seeds/nut paste consumption. After energy intake adjustment, dietary-related GHG emissions increased by 5 % in men (2·48-2·61kgCO2-eq/4184kJ (1000kcal), P<0·0001) and were similar in women (0·4 %, 2·70-2·71kgCO2-eq/4184kJ (1000kcal), P=0·3930) due to the increased consumption of (shell)fish, nuts/seeds/nut paste, poultry and higher GHG-intensive red meats such as beef. This Dutch cohort analyses showed more healthy diets without mitigated GHG emissions over a 20-year period, at similar energy intakes. Higher consumption of (shell)fish and poultry was not yet at the expense of red and processed meat. Lower consumption of animal-based foods is needed to achieve healthier as well as environmentally friendly diets.

Risk for Heart Failure: The Opportunity for Prevention With the American Heart Association’s Life’s Simple 7

ObjectivesThe aim of this study is to determine whether combinations of specific Life’s Simple 7 (LS7) components are associated with reduced risk for heart failure (HF). BackgroundThe American Heart Association recommends the concept of LS7: healthy behaviors that have been shown to reduce cardiovascular disease. MethodsA total of 37,803 participants from the EPIC-NL (European Prospective Investigation Into Cancer and Nutrition–Netherlands) cohort were included (mean age: 49.4 ± 11.9 years, 74.7% women). The LS7 score ranged from 0 to 14 and was calculated by assigning 0, 1, or 2 points for smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose. An overall ideal score (11 to 14 points) was present in 23.2% of participants, an intermediate score (9 or 10 points) in 35.3%, and an inadequate score (0 to 8 points) in 41.5%. ResultsOver a median follow-up period of 15.2 years (interquartile range: 14.1 to 16.5 years), 690 participants (1.8%) developed HF. In Cox proportional hazards models, ideal and intermediate LS7 scores were associated with reduced risk for HF compared with the inadequate category (hazard ratio: 0.45 [95% confidence interval (CI): 0.34 to 0.60] and hazard ratio: 0.53 [95% CI: 0.44 to 0.64], respectively). Our analyses show that combinations with specific LS7 components, notably glucose, body mass index, smoking, and blood pressure, are associated with a lower incidence of HF. ConclusionsA healthy lifestyle, as reflected in an ideal LS7 score, was associated with a 55% lower risk for HF compared with an inadequate LS7 score. Preventive strategies that target combinations of specific LS7 components could have a significant impact on decreasing incident HF in the population at large.

Intake of dietary saturated fatty acids and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort: associations by types, sources of fatty acids and substitution by macronutrients

PurposeThe association between dietary saturated fatty acids (SFA) intake and type 2 diabetes (T2D) remains unclear. This study aimed at investigating the association between SFA intake and T2D risk based on (1) individual SFA (differing in carbon chain length), (2) food sources of SFA and (3) the substituting macronutrients.Methods37,421 participants from the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort were included in this study. Baseline dietary intake was assessed by a validated food frequency questionnaire. T2D risks were estimated by Cox regression models adjusted for non-dietary and dietary covariates.Results893 incident T2D cases were documented during 10.1-year follow-up. We observed no association between total SFA and T2D risk. Marginally inverse associations were found for lauric acid (HR per 1 SD of energy%, 95% CI 0.92, 0.85–0.99), myristic acid (0.89, 0.79–0.99), margaric acid (0.84, 0.73–0.97), odd-chain SFA (pentadecylic plus margaric acids; 0.88, 0.79–0.99), and cheese derived SFA (0.90, 0.83–0.98). Soft and liquid fats derived SFA was found related to higher T2D risk (1.08, 1.01–1.17). When substituting SFA by proteins, carbohydrates and polyunsaturated fatty acids, significantly higher risks of T2D were observed (HRs per 1 energy% ranging from 1.05 to 1.15).ConclusionIn this Dutch population, total SFA does not relate to T2D risk. Rather, the association may depend on the types and food sources of SFA. Cheese-derived SFA and individual SFA that are commonly found in cheese, were significantly related to lower T2D risks. We cannot exclude the higher T2D risks found for soft and liquid fats derived SFA and for substituting SFA with other macronutrients are influenced by residual confounding by trans fatty acids or limited intake variation in polyunsaturated fatty acids and vegetable protein.

Non-occupational physical activity levels of shift workers compared with non-shift workers

ObjectivesLack of physical activity (PA) has been hypothesised as an underlying mechanism in the adverse health effects of shift work. Therefore, our aim was to compare non-occupational PA levels between...

Shift workers have a similar diet quality but higher energy intake than day workers.

Shift work is associated with adverse health outcomes, and an unhealthy diet may be a contributing factor. We compared diet quantity and quality between day and shift workers, and studied exposure-response relationships regarding frequency of night shifts and years of shift work. Cross-sectional general population data from the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort was used. Dietary intake was assessed in 1993-1997 among adults aged 20-70 years using a food frequency questionnaire. We calculated energy intake, the Mediterranean Diet Score (MDS) and WHO-based Healthy Diet Indicator (HDI). In 2011-2014, we retrospectively identified 683 shift workers and 7173 day workers in 1993-1997. Using multivariable-adjusted linear regression analysis, we estimated regression coefficients (β) and 95% confidence intervals (95% CI) of the differences in dietary intake between day and shift workers. Shift workers had a higher energy intake than day workers (β:56 kcal/d, 95% CI 10-101), and a higher consumption of grains, dairy products, meat and fish (P<0.05). The difference in energy intake was largest for shift workers with ≥5 night shifts/month. They consumed 103 kcal/d (95% CI 29-176) more than day workers. No associations were found with MDS and HDI. Shift workers and particularly those with a high frequency of night shifts had a higher energy intake than day workers. Regardless of number of night shifts and years of shift work, shift workers had similar diet quality as day workers. This suggests that increased energy intake among shift workers may contribute to shift work-induced adverse health outcomes.

Adherence to the Dutch Guidelines for a Healthy Diet and cancer risk in the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort.

To examine the association between adherence to the Dutch Guidelines for a Healthy Diet created by the Dutch Health Council in 2006 and overall and smoking-related cancer incidence. Prospective cohort study. Adherence to the guidelines, which includes one recommendation on physical activity and nine on diet, was measured using an adapted version of the Dutch Healthy Diet (DHD) index. The score ranged from 0 to 90 with a higher score indicating greater adherence to the guidelines. We estimated the hazard ratios (HR) and 95 % confidence intervals for the association between the DHD index (in tertiles and per 20-point increment) at baseline and cancer incidence at follow-up. We studied 35 608 men and women aged 20-70 years recruited into the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) study during 1993-1997. After an average follow-up of 12·7 years, 3027 cancer cases were documented. We found no significant association between the DHD index (tertile 3 v. tertile 1) and overall (HR = 0·97; 95 % CI 0·88, 1·07) and smoking-related cancer incidence (HR = 0·89; 95 % CI 0·76, 1·06) after adjustment for relevant confounders. Excluding the components physical activity or alcohol from the score did not change the results. None of the individual components of the DHD index was significantly associated with cancer incidence. In the present study, participants with a high adherence to the Dutch Guidelines for a Healthy Diet were not at lower risk of overall or smoking-related cancer. This does not exclude that other components not included in the DHD index may be associated with overall cancer risk.

Parental history of type 2 diabetes and cardiometabolic biomarkers in offspring

Parental history of type 2 diabetes (T2D) is associated with cardiometabolic risk. We aimed to investigate the associations of parental history of T2D with cardiometabolic biomarkers and to subsequently investigate to what extent these putative associations were explained by modifiable factors. Cross-sectionally, we analysed a random sample of 2001 participants without T2D (20-70 years) from the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL). Plasma levels of 12 biomarkers - total, HDL and LDL-cholesterol, triglycerides, HbA1c, gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), asparate aminotransferase (AST), albumin, uric acid, creatinine and high-sensitivity CRP (hs-CRP) - were assessed according to categories of parental history of T2D. In age and sex-adjusted analyses, offspring with parental history of T2D had significantly higher ALT [β = 0·074; 95% confidence interval (95%CI), 0·023-0·126] and AST levels (β = 0·033; 95%CI, 0·001 to 0·066) and a trend towards higher HbA1c (β = 0·011; 95%CI, -0·001 to 0·024) and GGT (β = 0·049; 95%CI, -0·015 to 0·112) levels. Adjustment for diet, smoking, alcohol intake, physical activity and educational level modestly attenuated the magnitude of these associations, but they remained significant for ALT and borderline significant for AST. After further adjustment for adiposity, additional attenuation was observed, but the association remained significant for ALT. Only maternal history of T2D was associated with higher ALT levels. T2D in both parents was associated with increased levels of all liver enzymes, but the association remained significant for GGT after adjustment for adiposity. Overall, the modifiable factors explained 21·2-45·4% of these associations. The contribution of adiposity was 18·2-38·9%. We conclude that parental history of T2D was associated with higher non-fasting levels of liver enzymes in a general population without T2D. Adiposity substantially contributed to these associations. The contribution of diet and lifestyle factors was modest.

Abstract P219: Plasma Uric Acid and Risk of Type 2 Diabetes: The Influence of a Uric Acid Related Dietary Pattern and Metabolic Risk Factors

Background: Current evidence suggests a positive relation of uric acid with diabetes risk, but it is still unclear whether this association is independent of other risk factors such as obesity and diet. Objective: To investigate whether plasma uric acid concentrations are independently associated with incident type 2 diabetes, and to investigate the role of a uric acid related dietary pattern in this association. Methods: We used a case-cohort study, nested in the European Prospective Investigation into Cancer and Nutrition - Netherlands (EPIC-NL) study. The study included 2318 subcohort members and 845 incident diabetes cases, with a mean follow-up of 10 years. At baseline, blood samples were taken and diet was assessed using a validated food frequency questionnaire. A dietary pattern was obtained with reduced rank regression. Diabetes was mainly self-reported, and verified against general practitioner records. Results: Mean plasma uric acid concentrations were 275 and 217 µmol/L for males and females respectively. After adjustment for age, sex, measures of adiposity, hypertension, biochemical markers and other confounders, uric acid related to a statistically significant higher risk of diabetes (HR 1.59 [95%CI: 1.06, 2.40]). A uric acid related dietary pattern (high: alcohol, meat , French fries, sugared soft drinks, snacks, low-fibre bread, low: soy products, tea) did not influence the relation. Conclusions: This study supports that high uric acid concentrations increase risk of diabetes, independent of risk factors such as obesity and diet.

Carbohydrate quantity and quality and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition–Netherlands (EPIC-NL) study

Carbohydrate quantity and quality may play an important role in the development of type 2 diabetes. We investigated the associations of dietary glycemic load (GL), glycemic index (GI), carbohydrate, and fiber intake with the incidence of type 2 diabetes. A prospective cohort study was conducted in 37,846 participants of the EPIC-NL (European Prospective Investigation into Cancer and Nutrition-Netherlands) study, aged 21-70 y at baseline and free of diabetes. Dietary intake was assessed with the use of a validated food-frequency questionnaire. Incident diabetes cases were mainly self-reported and verified against general practitioner records. During a mean follow-up of 10 y, 915 incident diabetes cases were documented. Dietary GL was associated with an increased diabetes risk after adjustment for age, sex, established diabetes risk factors, and dietary factors [hazard ratio (HR) per SD increase: 1.27; 95% CI: 1.11, 1.44; P < 0.001] [corrected]. GI tended to increase diabetes risk (HR: 1.08; 95% CI: 1.00, 1.17; P = 0.05). Dietary fiber was inversely associated with diabetes risk (HR: 0.92; 95% CI: 0.85, 0.99; P < 0.05), whereas carbohydrate intake was associated with increased diabetes risk (HR: 1.15; 95% CI: 1.01, 1.32; P < 0.05). Of the carbohydrate subtypes, only starch was related to increased diabetes risk [HR: 1.25 (1.07, 1.46), P < 0.05]. All associations became slightly stronger after exclusion of energy misreporters. Diets high in GL, GI, and starch and low in fiber were associated with an increased diabetes risk. Both carbohydrate quantity and quality seem to be important factors in diabetes prevention. Energy misreporting contributed to a slight attenuation of associations.