A daily intake of dairy products is recommended in many countries in order to maintain optimal health throughout life. However, evidence regarding the association between intake of individual dairy products and mortality is limited. We therfore, explored associations between intake of different dairy products and all-cause and cause-specific mortality using specified theoretical substitution analyses. We analysed data from 55 775 Danish men and women aged 50–64 years between 1993 and 1997. Information about dairy product intake at baseline was collected using a validated food frequency questionnaire. Information about vital status and causes of death was obtained through national registers. Measures of associations were calculated using Cox proportional hazards regression. During a median follow-up of 19·0 years, 11 586 participants died. For all-cause mortality, we observed that the intake of low-fat milk, whole-fat milk or low-fat yogurt products in place of cheese was associated with a higher rate of death (hazard ratios between 1·03 and 1·12 per serving/d substituted). The same pattern was present for CVD mortality. For cancer mortality, whole-fat milk and low-fat yogurt products in place of cheese were also associated with a higher rate of death for men while for women, whole-fat milk in place of buttermilk was associated with a higher cancer mortality rate. The results appeared robust in several sensitivity analyses. Our results suggest that intake of low-fat milk, whole-fat milk or low-fat yogurt products in place of cheese is associated with a higher rate of all-cause and cause-specific mortality.

Recent studies found positive associations between intake of red meat and processed meat and total mortality; however, substitution of red meat with poultry and fish has been poorly investigated. We aimed to investigate associations for substitutions of red meat (unprocessed/processed) and total mortality and deaths due to cancer or CVD. We used data from the Danish Diet, Cancer and Health cohort, including 57 053 participants aged 50–64 years at baseline. Information on diet was collected through a validated 192-item FFQ. Information regarding total mortality, deaths due to cancer and deaths due to CVD was obtained by record linkage. Cox proportional hazards models were used to estimate the hazard ratio (HR) of 150 g/week substitutions of red meat with poultry or fish. During a follow-up (mean 16·1 years), 8840 deaths occurred (4567 were due to cancer; 1816 due to CVD). The adjusted HR for total death when substituting 150 g/week total red meat with poultry was 0·96 (95 % CI 0·95, 1·00) and with fish 0·99 (95 % CI 0·97, 1·01). Corresponding HR for cancer death or CVD death were similar. Substitution of processed red meat with fish or poultry was more consistently associated with a lower mortality than substitution of unprocessed red meat. For example, the adjusted HR for total death when substituting 150 g/week processed red meat with poultry was 0·95 (95 % CI 0·92, 0·98). We found that replacing processed red meat with poultry or fish was associated with a lower risk of total mortality and deaths due to cancer, but not deaths due to CVD.

Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29 142 women and 26 029 men aged 50–64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazard ratios (HR) with 95 % CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13·6 years of follow-up, 656 female and 1694 male cases were identified. Among women, the adjusted HR for MI was 1·02 (95 % CI 0·93, 1·13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0·93 (95 % CI 0·77, 1·13) for replacement of potatoes with fruiting vegetables and 0·91 (95 % CI 0·77, 1·07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.

The objective was to investigate the effects of substitution (SUB) dietary guidelines (DG) targeted at the prevention of IHD on dietary intake and IHD risk factors in Danish adults with minimum one self-assessed IHD risk factor. A 6-month single-blinded parallel randomised controlled trial with a follow-up at month 12 included 219 subjects (median age 51 years, 59 % female, 73 % overweight or obese) randomised into an SUB DG, an official (OFF) DG or a control group following their habitual diet (HAB). Participants in the DG intervention groups received bi-weekly reminders of their DG and recipes for dishes and the HAB group received a greeting. Dietary intake and fasting blood, anthropometric and blood pressure measurements were obtained at baseline, month 6 and month 12. Linear regression analyses were applied. At month 6, when compared with the HAB, the SUB had a greater impact on the extent of dietary changes with increased intake of whole grains, dietary fibre and low fibre vegetables compared with the OFF DG, and both DG groups had similar decreased percentage of energy (E%) intake from SFA. The extent of dietary changes was similar at month 12. No overall significant changes from baseline were found in blood pressure, anthropometrics and IHD risk markers. In conclusion, both SUB and OFF DG resulted in cardioprotective dietary changes. However, neither the SUB nor the OFF DG resulted in any overall effects on the selected intermediate risk factors for IHD.

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.

Intake of the plant-derived n-3 fatty acid α-linolenic acid (ALA) has been associated with anti-atherosclerotic properties. However, information on the association between ALA intake and development of peripheral artery disease (PAD) is lacking. In this follow-up study, we investigated the association between dietary intake of ALA and the rate of PAD among middle-aged Danish men and women enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Incident PAD cases were identified through the Danish National Patient Register. Intake of ALA was assessed using a validated FFQ. Statistical analyses were performed using Cox proportional hazard regression allowing for separate baseline hazards among sexes and adjusted for established risk factors for PAD. During a median of 13·6 years of follow-up, we identified 950 valid cases of PAD with complete information on covariates. The median energy-adjusted ALA intake within the cohort was 1·76 g/d (95 % central range: 0·94–3·28). In multivariable analyses, we found no statistically significant association between intake of ALA and the rate of PAD (P = 0·339). Also, no statistically significant associations were observed in analyses including additional adjustment for co-morbidities and in sex-specific analyses. In supplemental analyses with additional adjustment for potential dietary risk factors, we found a weak inverse association of PAD with ALA intake above the median, but the association was not statistically significant (P = 0·314). In conclusion, dietary intake of ALA was not consistently associated with decreased risk of PAD.

The association between lifestyle and survival after colorectal cancer has received limited attention. The female sex hormone, oestrogen, has been associated with lower colorectal cancer risk and mortality after colorectal cancer. Phyto-oestrogens are plant compounds with structure similar to oestrogen, and the main sources in Western populations are plant lignans. We investigated the association between the main lignan metabolite, enterolactone and survival after colorectal cancer among participants in the Danish Diet, Cancer and Health cohort. Prediagnosis plasma samples and lifestyle data, and clinical data from time of diagnosis from 416 women and 537 men diagnosed with colorectal cancer were used. Enterolactone was measured in plasma using a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. Participants were followed from date of diagnosis until death or end of follow-up. During this time, 210 women and 325 men died (170 women and 215 men died due to colorectal cancer). The Cox proportional hazards model was used to estimate hazard ratios (HR) and 95 % CI. Enterolactone concentrations were associated with lower colorectal cancer-specific mortality among women (HRper doubling: 0·88, 95 % CI 0·80, 0·97, P=0·0123). For men, on the contrary, enterolactone concentrations were associated with higher colorectal cancer-specific mortality (HRper doubling: 1·10, 95 % CI 1·01, 1·21, P=0·0379). The use of antibiotics affects enterolactone production, and the associations between higher enterolactone and lower colorectal cancer-specific mortality were more pronounced among women who did not use antibiotics (analysis on a subset). Our results suggest that enterolactone is associated with lower risk of mortality among women, but the opposite association was found among men.

Potatoes have been a staple food in many countries throughout the years. Potatoes have a high glycaemic index (GI) score, and high GI has been associated with several chronic diseases and cancers. Still, the research on potatoes and health is scarce and contradictive, and we identified no prospective studies that had investigated the association between potatoes as a single food and the risk of pancreatic cancer. The aim of this study was to prospectively investigate the association between potato consumption and pancreatic cancer among 114 240 men and women in the prospective HELGA cohort, using Cox proportional hazard models. Information on diet (validated FFQ’s), lifestyle and health was collected by means of a questionnaire, and 221 pancreatic cancer cases were identified through cancer registries. The mean follow-up time was 11·4 (95 % CI 0·3, 16·9) years. High consumption of potatoes showed a non-significantly higher risk of pancreatic cancer in the adjusted model (hazard ratio (HR) 1·44; 95 % CI 0·93, 2·22, Pfor trend 0·030) when comparing the highest v. the lowest quartile of potato consumption. In the sex-specific analyses, significant associations were found for females (HR 2·00; 95 % CI 1·07, 3·72, Pfor trend 0·020), but not for males (HR 1·01; 95 % CI 0·56, 1·84, Pfor trend 0·34). In addition, we explored the associations by spline regression, and the absence of dose–response effects was confirmed. In this study, high potato consumption was not consistently associated with a higher risk of pancreatic cancer. Further studies with larger populations are needed to explore the possible sex difference.

Diet is recognised as one modifiable lifestyle factor for ischaemic heart disease (IHD). We aimed at investigating the associations between adherence to the Danish Food-Based Dietary Guidelines (FBDG) indicated by a Dietary Quality Index (DQI) and selected cardiometabolic risk factors in a cross-sectional study with 219 Danish adult participants (59 %women; age 31–65years) with a minimum of one self-rated risk marker of IHD. Information regarding diet was obtained using web-based dietary assessment software and adherence to the Danish FBDG was expressed by a DQI calculated from 5 food and nutrient indicators (whole grain, fish, fruit and vegetables, energy from saturated fat and from added sugar). Background information, blood samples and anthropometrics were collected and blood pressure was measured. Linear regression analyses were used to evaluate the association between DQI and cardiometabolic risk factors. DQI was inversely associated with LDL:HDL ratio and TAG (−0·089 per unit; 95 % CI −0·177, −0·002 and −5 % per unit; 95 % CI −9, 0, respectively) and positively associated with HDL-cholesterol (0·047 mmol/l per unit; 95 % CI 0·007, 0·088). For men, DQI was inversely associated with BMI (−3 %per unit; 95 % CI −5, −1), trunk fat (−1 % per unit; 95 % CI −2, −1), high-sensitivity C-reactive protein (−30 % per unit; 95 % CI −41, −16 %), HbA1c (−0·09 % per unit; 95 % CI −0·14, −0·04), insulin (−13 % per unit; 95 % CI −19, −7) and homoeostatic model assessment-insulin resistance (−14 % per unit; 95 % CI −21, −7). In women, DQI was positively associated with systolic blood pressure (2·6 mmHg per unit; 95 % CI 0·6, 4·6). In conclusion, higher adherence to the current Danish FBDG was associated with a more beneficial cardiometabolic risk profile in a Danish adult population with a minimum of one self-rated risk factor for IHD.

The aim of this study was to investigate the associations for specified substitutions between different subgroups of dairy products and the risk of type 2 diabetes. We used data from the Danish Diet, Cancer and Health cohort including 54 277 men and women aged 50–64 years at baseline. Information regarding intake of dairy products was obtained from a validated FFQ, and cases of type 2 diabetes were identified through the Danish National Diabetes Register. Cox proportional hazards regressions were used to estimate associations. During a median follow-up of 15·3 years, 7137 cases were identified. Low-fat yogurt products in place of whole-fat yogurt products were associated with a higher rate of type 2 diabetes (hazard ratio (HR) 1·17; 95 % CI 1·06, 1·29) per serving/d substituted. Whole-fat yogurt products in place of low-fat milk, whole-fat milk or buttermilk were associated with a lower rate of type 2 diabetes (HR 0·89; 95 % CI 0·83, 0·96; HR 0·89; 95 % CI 0·82, 0·96; HR 0·89; 95 % CI 0·81, 0·97; per serving/d substituted, respectively). The pattern of associations was similar when intake was expressed as kJ/d (kcal/d). These findings suggest that intake of whole-fat yogurt products in place of low-fat yogurt products, low-fat milk, whole-fat milk and buttermilk are associated with a lower rate of type 2 diabetes.

Red meat has been suggested to be adversely associated with risk of myocardial infarction (MI), whereas vegetable consumption has been found to be protective. The aim of this study was to investigate substitutions of red meat, poultry and fish with vegetables or potatoes for MI prevention. We followed up 29 142 women and 26 029 men in the Danish Diet, Cancer and Health study aged 50–64 years with no known history of MI at baseline. Diet was assessed by a validated 192-item FFQ at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95 % CI for MI associated with specified food substitutions of 150 g/week. During a median follow-up of 13·6 years, we identified 656 female and 1694 male cases. Among women, the HR for MI when replacing red meat with vegetables was 0·94 (95 % CI 0·90, 0·98). Replacing fatty fish with vegetables was associated with a higher risk of MI (HR 1·23; 95 % CI 1·05, 1·45), whereas an inverse, statistically non-significant association was found for lean fish (HR 0·93; 95 % CI 0·83, 1·05). Substituting poultry with vegetables was not associated with risk of MI (HR 1·00; 95 % CI 0·90, 1·11). Findings for substitution with potatoes were similar to findings for vegetables. Among men, a similar pattern was observed, but the associations were weak and mostly statistically non-significant. This study suggests that replacing red meat with vegetables or potatoes is associated with a lower risk of MI, whereas replacing fatty fish with vegetables or potatoes is associated with a higher risk of MI.

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.

Several studies have investigated the potential benefits of marine n-3 PUFA in CVD, generally suggesting a lower risk of CHD. However, recent trials have questioned these results. This study investigated the association of fish consumption with dietary intake of marine n-3 PUFA with incident myocardial infarction (MI). In a Danish cohort study, 57 053 subjects between 50 and 64 years of age were enrolled from 1993 to 1997. From national registries, we identified all cases of incident MI. Dietary fish consumption was assessed using a semi-quantitative food questionnaire, including twenty-six questions regarding fish intake. In addition, we calculated the intake of total and individual marine n-3 PUFA. During a median follow-up of 17·0 years, we identified 3089 cases of incident MI. For both men and women, a high intake of fatty fish was inversely related to incident MI. Thus, when comparing the highest and the lowest quintile of fatty fish intake, we found a 12 % lower relative risk of MI in men (hazard ratio (HR) 0·88; 95 % CI 0·77, 1·00) and a 22 % lower relative risk in women (HR 0·78; 95 % CI 0·63, 0·96) after adjustments. For women, similar associations were observed for individual and total marine n-3 PUFA. In contrast, intake of lean fish was not associated with MI. In conclusion, incident MI was inversely related to a high intake of fatty fish, but not lean fish. However, test for trends across quintiles was not statistically significant. In general, this study supports the view that consumption of fatty fish may protect against MI.

Low-Se status may be associated with a higher risk of notably advanced prostate cancer. In a Danish population with a relatively low Se intake, we investigated the association between pre-diagnostic Se status and (1) the risk of total, advanced and high-grade prostate cancer and (2) all-cause and prostate cancer-specific mortality among men with prostate cancer. Within the Danish ‘Diet, Cancer and Health’ cohort, including 27 179 men, we identified 784 cases with incident prostate cancer through 2007. Each case was risk set-matched to one control. Two-thirds (n 525) of the cases had advanced disease at the time of diagnosis, and among these 170 had high-grade disease; 305 cases died (n 212 from prostate cancer) during follow-up through 2012. Plasma Se was not associated with total or advanced prostate cancer risk, but higher Se levels were associated with a lower risk of high-grade disease (HR 0·77; 95 % CI 0·64, 0·94; P=0·009). In survival analyses, a higher level of plasma Se was associated with a lower risk of all-cause (HR 0·92; 95 % CI 0·85, 1·00; P=0·04), but not prostate cancer-specific mortality. Higher levels of selenoprotein P were associated with a lower risk of high-grade disease (HR 0·85; 95 % CI 0·74, 0·97; P=0·01), but not with the risk of or mortality from advanced prostate cancer. In conclusion, levels of plasma Se and selenoprotein P were not associated with the risk of total and advanced prostate cancer, but higher levels of these two biomarkers were associated with a lower risk of high-grade disease.

Red meat has been suggested to be adversely associated with risk of myocardial infarction (MI), but previous studies have rarely taken replacement foods into consideration. We aimed to investigate optimal substitutions between and within the food groups of red meat, poultry and fish for MI prevention. We followed up 55 171 women and men aged 50–64 years with no known history of MI at recruitment. Diet was assessed by a validated 192-item FFQ at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95 % CI for specified food substitutions of 150 g/week. During a median follow-up time of 13·6 years, we identified 656 female and 1694 male cases. Among women, the HR for replacing red meat with fatty fish was 0·76 (95 % CI 0·64, 0·89), whereas the HR for replacing red meat with lean fish was 1·00 (95 % CI 0·89, 1·14). Similarly, replacing poultry with fatty but not lean fish was inversely associated with MI: the HR was 0·81 (95 % CI 0·67, 0·98) for fatty fish and was 1·08 (95 % CI 0·92, 1·27) for lean fish. The HR for replacing lean with fatty fish was 0·75 (95 % CI 0·60, 0·94). Replacing processed with unprocessed red meat was not associated with MI. Among men, a similar pattern was found, although the associations were not statistically significant. This study suggests that replacing red meat, poultry or lean fish with fatty fish is associated with a lower risk of MI.

No study has yet investigated the intake of different types of whole grain (WG) in relation to all-cause and cause-specific mortality in a healthy population. The aim of the present study was to investigate the intake of WG products and WG types in relation to all-cause and cause-specific mortality in a large Scandinavian HELGA cohort that, in 1992–8, included 120 010 cohort members aged 30–64 years from the Norwegian Women and Cancer Study, the Northern Sweden Health and Disease Study, and the Danish Diet Cancer and Health Study. Participants filled in a FFQ from which data on the intake of WG products were extracted. The estimation of daily intake of WG cereal types was based on country-specific products and recipes. Mortality rate ratios (MRR) and 95 % CI were estimated using the Cox proportional hazards model. A total of 3658 women and 4181 men died during the follow-up (end of follow-up was 15 April 2008 in the Danish sub-cohort, 15 December 2009 in the Norwegian sub-cohort and 15 February 2009 in the Swedish sub-cohort). In the analyses of continuous WG variables, we found lower all-cause mortality with higher intake of total WG products (women: MRR 0·89 (95 % CI 0·86, 0·91); men: MRR 0·89 (95 % CI 0·86, 0·91) for a doubling of intake). In particular, intake of breakfast cereals and non-white bread was associated with lower mortality. We also found lower all-cause mortality with total intake of different WG types (women: MRR 0·88 (95 % CI 0·86, 0·92); men: MRR 0·88 (95 % CI 0·86, 0·91) for a doubling of intake). In particular, WG oat, rye and wheat were associated with lower mortality. The associations were found in both women and men and for different causes of deaths. In the analyses of quartiles of WG intake in relation to all-cause mortality, we found lower mortality in the highest quartile compared with the lowest for breakfast cereals, non-white bread, total WG products, oat, rye (only men), wheat and total WG types. The MRR for highest v. lowest quartile of intake of total WG products was 0·68 (95 % CI 0·62, 0·75, Ptrend over quartiles< 0·0001) for women and 0·75 (95 % CI 0·68, 0·81, Ptrend over quartiles< 0·0001) for men. The MRR for highest v. lowest quartile of intake of total WG types was 0·74 (95 % CI 0·67, 0·81, Ptrend over quartiles< 0·0001) for women and 0·75 (95 % CI 0·68, 0·82, Ptrend over quartiles< 0·0001) for men. Despite lower statistical power, the analyses of cause-specific mortality according to quartiles of WG intake supported these results. In conclusion, higher intake of WG products and WG types was associated with lower mortality among participants in the HELGA cohort. The study indicates that intake of WG is an important aspect of diet in preventing early death in Scandinavia.