Theoretical substitutions between dairy products and all-cause and cause-specific mortality. Results from the Danish diet, cancer and health cohort.

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.

Dietary Fatty Acids, Macronutrient Substitutions, Food Sources and Incidence of Coronary Heart Disease: Findings From the EPIC-CVD Case-Cohort Study Across Nine European Countries.

Background There is controversy about associations between total dietary fatty acids, their classes (saturated fatty acids [SFAs], monounsaturated fatty acids, and polyunsaturated fatty acids), and risk of coronary heart disease (CHD). Specifically, the relevance of food sources of SFAs to CHD associations is uncertain. Methods and Results We conducted a case-cohort study involving 10 529 incident CHD cases and a random subcohort of 16 730 adults selected from a cohort of 385 747 participants in 9 countries of the EPIC (European Prospective Investigation into Cancer and Nutrition) study. We estimated multivariable adjusted country-specific hazard ratios (HRs) and 95% CIs per 5% of energy intake from dietary fatty acids, with and without isocaloric macronutrient substitutions, using Prentice-weighted Cox regression models and pooled results using random-effects meta-analysis. We found no evidence for associations of the consumption of total or fatty acid classes with CHD, regardless of macronutrient substitutions. In analyses considering food sources, CHD incidence was lower per 1% higher energy intake of SFAs from yogurt (HR, 0.93 [95% CI, 0.88-0.99]), cheese (HR, 0.98 [95% CI, 0.96-1.00]), and fish (HR, 0.87 [95% CI, 0.75-1.00]), but higher for SFAs from red meat (HR, 1.07 [95% CI, 1.02-1.12]) and butter (HR, 1.02 [95% CI, 1.00-1.04]). Conclusions This observational study found no strong associations of total fatty acids, SFAs, monounsaturated fatty acids, and polyunsaturated fatty acids, with incident CHD. By contrast, we found associations of SFAs with CHD in opposite directions dependent on the food source. These findings should be further confirmed, but support public health recommendations to consider food sources alongside the macronutrients they contain, and suggest the importance of the overall food matrix.

Changes in intake of dairy product subgroups and risk of type 2 diabetes: modelling specified food substitutions in the Danish Diet, Cancer and Health cohort.

PURPOSE: We investigated the association between an increased intake of one dairy product subgroup at the expense of another within a 5-year period and the subsequent 10-year risk of type 2 diabetes. METHODS: The cohort included 39,393 adults with two measurements of diet assessed using food frequency questionnaires (FFQ) administered in 1993-1997 and 1999-2003. Dairy products were milk (skimmed, semi-skimmed, whole fat), buttermilk, low-fat yogurt, whole-fat yogurt, cheese and butter. Type 2 diabetes cases were ascertained from the Danish National Diabetes Register. The pseudo-observation method was used to calculate risk differences (RD) with 95% confidence intervals (CI). The data were analysed in age strata to fulfil the assumption of independent entry. RESULTS: Among participants aged 56-59 years at completion of the follow-up FFQ, increased intake of whole-fat yogurt in place of skimmed, semi-skimmed or whole-fat milk was associated with a reduced risk (RD% [95% CI]: - 0.8% [- 1.3, - 0.2]; - 0.6% [- 1,1, - 0.1]; - 0.7 [- 1.2, - 0.1]; per 50 g/d, respectively). Among participants aged 60-64 and 65-72, substitution of skimmed milk for semi-skimmed milk was associated with an increased risk of type 2 diabetes (0.5% [0.2, 0.7]; 0.4% [0.1, 0.7]; per 50 g/d, respectively). Similar patterns of associations were found after adjustment for potential mediators. CONCLUSION: Our results suggest that substitution of whole-fat yogurt for milk among those aged 56-59 decreases risk of type 2 diabetes and substitution of skimmed milk for semi-skimmed milk may increase the risk among those aged 60-64 and 65-72.

Replacing Red Meat with Other Nonmeat Food Sources of Protein is Associated with a Reduced Risk of Type 2 Diabetes in a Danish Cohort of Middle-Aged Adults.

BACKGROUND: Few cohort studies have modelled replacements of red meat with other sources of protein on subsequent risk of type 2 diabetes using dietary changes. OBJECTIVES: To determine whether replacing red meat with other food sources of protein is associated with a lower risk of type 2 diabetes. METHODS: We used data from the Danish Diet, Cancer, and Health cohort (n = 39,437) of middle-aged (55-72 years old) men and women who underwent 2 dietary assessments roughly 5 years apart to investigate dietary changes. The pseudo-observation method was used to model the average exposure effect of decreasing the intake of red meat while increasing the intake of either poultry, fish, eggs, milk, yogurt, cheese, whole grains, or refined grains on the subsequent 10-year risk of developing type 2 diabetes, compared with no changes in the intakes of these foods. RESULTS: Replacing 1 serving/day (100 g/day) of red meat with 1 serving/day of eggs [risk difference (RD), -2.7%; 95% CI: -4.0 to -1.1%; serving size: 50 g/day], milk (RD, -1.2%; 95% CI: -2.1 to -0.4%; 200 g/day), yogurt (RD, -1.5%; 95% CI: -2.4 to -0.7%; 70 g/day), whole grains (RD, -1.7%; 95% CI: -2.5 to -0.9%; 30 g/day), or refined grains (RD, -1.2%; 95% CI: -2.0 to -0.3%; 30 g/day) was associated with a reduced risk of type 2 diabetes. Analyses of replacements with poultry or cheese, but not fish, also suggested a lower risk, but with wide CIs. After further adjustment for potential mediators (BMI, waist circumference, and history of hypertension or hypercholesterolemia), only the replacement with eggs was associated with a reduced risk (RD, -1.7%; 95% CI: -3.0 to -0.5%; 50 g/day). CONCLUSIONS: Replacing red meat with eggs in middle-aged adults may reduce the risk of type 2 diabetes. In models not adjusted for potential mediators, replacing red meat with milk, yogurt, whole grains, or refined grains was also associated with a reduced risk of type 2 diabetes.

Replacement of potatoes with other vegetables and risk of myocardial infarction in the Danish Diet, Cancer and Health cohort.

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.

Adipose tissue content of alpha-linolenic acid and development of peripheral artery disease: a Danish case-cohort study.

PURPOSE: The aim of this study was to investigate the association between adipose tissue content of the plant-derived n-3 fatty acid, alpha-linolenic acid, and the rate of incident peripheral artery disease (PAD). METHODS: We conducted a case-cohort study nested within the Danish Diet, Cancer and Health cohort (n = 57,053), which was established between 1993 and 1997. Potential PAD cases were identified using linkage with The Danish National Patient Register and all potential cases were validated. Adipose tissue samples from the buttock were collected at baseline and fatty acid composition was determined in cases and in a random sample (n = 3500) from the cohort by gas chromatography. Statistical analyses were performed using weighted Cox regression allowing for different baseline hazards among sexes. RESULTS: During a median of 13.5 years of follow-up, we identified 863 PAD cases with complete information. The median adipose tissue content of ALA in the sub-cohort (n = 3197) was 0.84% (interquartile range 0.73-0.94%) of total fatty acids. In multivariate analyses including adjustment for established risk factors, we observed a U-shaped association between ALA in adipose tissue and rate of PAD, but the association was not statistically significant (P = 0.131). Similar pattern of associations were observed between ALA content in adipose tissue and the rate of PAD among men and women. CONCLUSIONS: We found indications of a U-shaped association between adipose tissue content of ALA and the rate of PAD, but the association was not statistically significant.

Intake of α-linolenic acid is not consistently associated with a lower risk of peripheral artery disease: results from a Danish cohort study.

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.

Substitutions between dairy products and risk of stroke: results from the European Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort.

The association between intake of different dairy products and the risk of stroke remains unclear. We therefore investigated substitutions between dairy product subgroups and risk of stroke. We included 36 886 Dutch men and women. Information about dairy product intake was collected through a FFQ. Dairy products were grouped as low-fat milk, whole-fat milk, buttermilk, low-fat yogurt, whole-fat yogurt, cheese and butter. Incident stroke cases were identified in national registers. We used Cox proportional hazards regression to calculate associations for substitutions between dairy products with the rate of stroke. During a median follow-up of 15·2 years we identified 884 stroke cases (503 ischaemic and 244 haemorrhagic). Median intake of total dairy products was four servings/d. Low-fat yogurt substituted for whole-fat yogurt was associated with a higher rate of ischaemic stroke (hazard ratio (HR) = 2·58 (95 % CI 1·11, 5·97)/serving per d). Whole-fat yogurt as a substitution for any other subgroup was associated with a lower rate of ischaemic stroke (HR between 0·33 and 0·36/serving per d). We did not observe any associations for haemorrhagic stroke. In conclusion, whole-fat yogurt as a substitution for low-fat yogurt, cheese, butter, buttermilk or milk, regardless of fat content, was associated with a lower rate of ischaemic stroke.

Marine n-3 Polyunsaturated Fatty Acids and the Risk of Ischemic Stroke.

Background and Purpose- We hypothesized that total marine n-3 polyunsaturated fatty acids (PUFA), in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the diet and in adipose tissue (biomarkers of long-term intake and endogenous exposure) were inversely associated with the risk of ischemic stroke and its subtypes. Methods- The Diet, Cancer and Health cohort consisted of 57 053 participants aged 50 to 65 years at enrolment. All participants filled in a food frequency questionnaire and had an adipose tissue biopsy taken at baseline. Information on ischemic stroke during follow-up was obtained from The Danish National Patient Register, and all cases were validated. Cases and a random sample of 3203 subjects from the whole cohort had their fatty acid composition of adipose tissue determined by gas chromatography. Results- During 13.5 years of follow-up 1879 participants developed an ischemic stroke. Adipose tissue content of EPA was inversely associated with total ischemic stroke (hazard ratio [HR], 0.74; 95% CI, 0.62-0.88) when comparing the highest with the lowest quartile. Also, lower rates of large artery atherosclerosis were seen with higher intakes of total marine n-3 PUFA (HR, 0.69; 95% CI, 0.50-0.95), EPA (HR, 0.66; 95% CI, 0.48-0.91) and DHA (HR, 0.72; 95% CI, 0.53-0.99), and higher adipose tissue content of EPA (HR, 0.52; 95% CI, 0.36-0.76). Higher rates of cardioembolism were seen with higher intakes of total marine n-3 PUFA (HR, 2.50; 95% CI, 1.38-4.53) and DHA (HR, 2.12; 95% CI, 1.21-3.69) as well as with higher adipose tissue content of total marine n-3 PUFA (HR, 2.63; 95% CI, 1.33-5.19) and DHA (HR, 2.00; 95% CI, 1.04-3.84). The EPA content in adipose tissue was inversely associated with small-vessel occlusion (HR, 0.69; 95% CI, 0.55-0.88). Conclusions- EPA was associated with lower risks of most types of ischemic stroke, apart from cardioembolism, while inconsistent findings were observed for total marine n-3 PUFA and DHA.

Substitution of Fish for Red Meat or Poultry and Risk of Ischemic Stroke.

We investigated the risk of ischemic stroke and its subtypes when red meat or poultry was substituted with fish. A total of 57,053 participants aged 50⁻65 years at baseline were included in the Danish Diet, Cancer and Health study. All participants filled in a food-frequency questionnaire at recruitment. Potential ischemic stroke cases were identified by linkage to the Danish National Patient Register, and all cases were validated and subclassified. Substitutions were investigated as 150 g/week of fish for 150 g/week of red meat or of poultry using multivariable Cox proportional hazard regression models. During 13.5 years of follow-up, 1879 participants developed an ischemic stroke. Replacing red meat or poultry with fish was not associated with the rate of total ischemic stroke, but there was a statistically significant lower rate of large artery atherosclerosis when fish replaced processed (hazard ratio (HR): 0.78; 95% confidence interval (CI): 0.67; 0.90) and unprocessed (HR: 0.87; 95% CI: 0.75; 0.99) red meat. A statistically significant higher rate of cardioembolism was found when poultry was replaced by total fish (HR: 1.42; 95% CI: 1.04; 1.93). When fatty fish replaced unprocessed red meat, a statistically significant lower rate of small-vessel occlusion was found (HR: 0.88; 95% CI: 0.77; 0.99). In conclusion, replacing red meat with fish was not associated with risk of total ischemic stroke but was associated with a lower risk of subtypes of ischemic stroke.

Dietary Intake of α-Linolenic Acid Is Not Appreciably Associated with Risk of Ischemic Stroke among Middle-Aged Danish Men and Women.

Background: Intake of the plant-derived omega-3 (n-3) fatty acid α-linolenic acid (ALA) may reduce the risk of ischemic stroke. Objective: We have investigated the associations between dietary intake of ALA and the risk of ischemic stroke and ischemic stroke subtypes. Methods: This was a follow-up study. A total of 57,053 participants aged 50-64 y were enrolled into the Danish Diet, Cancer and Health cohort between 1993 and 1997. Intake of ALA was assessed by a validated semiquantitative food frequency questionnaire. Potential incident cases of ischemic stroke were identified in the Danish National Patient Register, validated, and classified into subtypes based on assumed etiology. Statistical analyses were performed via Cox proportional hazard regression with adjustment for established ischemic stroke risk factors. Results: A total of 1859 ischemic stroke cases were identified during a median of 13.5 y of follow-up. In multivariable analyses using restricted cubic splines adjusting for traditional risk factors for ischemic stroke, we observed no clear associations between dietary intake of ALA and the risk of total ischemic stroke or any of its subtypes including ischemic stroke due to large artery atherosclerosis, ischemic stroke due to small-vessel occlusion, and ischemic stroke due to cardio-embolism. Conclusion: Dietary intake of ALA was neither consistently nor appreciably associated with the risk of ischemic stroke or ischemic stroke subtypes among middle-aged Danish men and women. This study was registered at clinicaltrials.gov as NCT03258983.

Substitutions between dairy product subgroups and risk of type 2 diabetes: the Danish Diet, Cancer and Health cohort.

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.

Substitution of Linoleic Acid for Other Macronutrients and the Risk of Ischemic Stroke.

BACKGROUND AND PURPOSE: Ischemic stroke is a major health problem worldwide, but the influence of dietary factors on stroke risk is not well known. This study aimed to investigate the risk of ischemic stroke and its subtypes with a higher intake from linoleic acid and a concomitant lower intake from saturated fatty acids, monounsaturated fatty acids, or glycemic carbohydrates. METHODS: In the Danish prospective Diet, Cancer, and Health Study of 57 053 participants aged 50 to 64 years at baseline, information on diet was collected using a validated semiquantitative food frequency questionnaire. Information on ischemic stroke was obtained from the Danish National Patient Register, and cases were all validated and subclassified according to the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Substitution of linoleic acid for saturated fatty acid, monounsaturated fatty acid, or glycemic carbohydrates was investigated in relation to the risk of ischemic stroke and subtypes. Cox proportional hazards regression was used to estimate the associations with ischemic stroke adjusting for appropriate confounders. RESULTS: During 13.5 years of follow-up 1879 participants developed ischemic stroke. A slightly lower risk of ischemic stroke was found with a 5% higher intake of linoleic acid and a concomitant lower intake of saturated fatty acid (hazard ratio, 0.98; 95% confidence interval, 0.83-1.16), monounsaturated fatty acid (hazard ratio, 0.80; 95% confidence interval, 0.63-1.02), and glycemic carbohydrates (hazard ratio, 0.92; 95% confidence interval, 0.78-1.09), although not statistically significant. Similar patterns of association were found for large-artery atherosclerosis and small-vessel occlusions. CONCLUSIONS: This study suggests that replacing saturated fatty acid, glycemic carbohydrate, or monounsaturated fatty acid with linoleic acid may be associated with a lower risk of ischemic stroke.

Dietary intake and adipose tissue content of long-chain n-3 PUFAs and subsequent 5-y change in body weight and waist circumference.

Background: Adding long-chain n-3 (ω-3) polyunsaturated fatty acids (PUFAs) to a rodent diet reduces fat mass and prevents the development of obesity, but evidence of a similar effect in humans is rather limited.Objectives: We investigated the associations between dietary intake and adipose tissue content of long-chain n-3 PUFAs and subsequent 5-y change in body weight and waist circumference in humans. Effect modification by the carbohydrate:protein ratio and glycemic index was also investigated.Design: A total of 29,152 participants included in the Diet, Cancer, and Health cohort were followed. Dietary intake was assessed with the use of a validated 192-item semiquantitative food-frequency questionnaire. Adipose tissue content of fatty acids was determined by gas chromatography in a random sample of the cohort (n = 1660). Anthropometric measurements were taken at baseline and 5 y later. Associations were investigated with the use of a linear regression model.Results: For high (1.22 g/d) compared with low (0.28 g/d) total n-3 PUFA intake, the difference in 5-y weight change was 147.6 g (95% CI: -42.3, 337.5 g); P-trend = 0.088. No associations between the individual n-3 PUFAs eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid were observed. Intake of n-3 PUFAs was not associated with a 5-y change in waist circumference. For high (0.16%) compared with low (0.06%) adipose tissue content of EPA, the difference in 5-y weight change was -649.6 g (95% CI: -1254.2, -44.9 g); P-trend = 0.027. No associations between total n-3 PUFA, docosapentaenoic acid, and docosahexaenoic acid and 5-y weight change were observed. Adipose tissue content of n-3 PUFAs was not associated with 5-y change in waist circumference. No effect modification by carbohydrate:protein ratio or glycemic index was found.Conclusion: Dietary intake and adipose tissue content of long-chain n-3 PUFAs were neither consistently nor appreciably associated with change in body weight or waist circumference.

Substitution of meat and fish with vegetables or potatoes and risk of myocardial infarction.

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.

Dietary intake and adipose tissue content of α-linolenic acid and risk of myocardial infarction: a Danish cohort study.

BACKGROUND: Intake of the plant-derived ω-3 (n-3) fatty acid α-linolenic acid (ALA, 18:3; n-3) may reduce coronary heart disease (CHD) risk, but the results of previous studies have been inconsistent. OBJECTIVE: We aimed to investigate the association between dietary intake of ALA, adipose tissue content of ALA, and risk of incident myocardial infarction (MI). DESIGN: A total of 57,053 participants, aged 50-64 y, were enrolled in the prospective Danish cohort study Diet, Cancer and Health between 1993 and 1997. Dietary intake of ALA was assessed with the use of a validated semiquantitative food-frequency questionnaire in the full cohort, whereas the adipose tissue content of ALA was determined with the use of gas chromatography in all incident MI cases and in a random sex-stratified sample of the total cohort (n = 3500). RESULTS: During a median of 17 y of follow-up, we identified 2177 male and 912 female cases of MI. After appropriate exclusions, we included 2124 men and 854 women for analyses of dietary intake of ALA, whereas 1994 men and 770 women were included in the analysis of the adipose tissue content of ALA. In multivariate analyses that were conducted with the use of restricted cubic splines and adjusted for established CHD risk factors, weak positive associations in men and weak U-shaped associations in women were shown between both dietary intake and the adipose tissue content of ALA and risk of MI, but these associations were not statistically significant. Additional adjustments for dietary factors did not influence the observed associations numerically. CONCLUSION: This study suggests that ALA has no appreciable association with risk of incident MI in either men or women.

Dietary n-6 PUFA, carbohydrate:protein ratio and change in body weight and waist circumference: a follow-up study.

OBJECTIVE: To investigate the association between the intake of n-6 PUFA and subsequent change in body weight and waist circumference at different levels of the carbohydrate:protein ratio. DESIGN: Follow-up study with anthropometric measurements at recruitment and on average 5·3 years later. Dietary intake was determined at recruitment by using an FFQ that was designed for the study and validated. We applied linear regression models with 5-year change in weight or waist circumference as outcome and including a two-way interaction term between n-6 PUFA and carbohydrate intakes, lower-order terms, protein intake, long-chain n-3 PUFA intake and other potential confounders. Due to adjustment for intake of protein, levels of carbohydrate indirectly reflect levels of the carbohydrate:protein ratio. SETTING: Diet, Cancer and Health follow-up study, Denmark. SUBJECTS: Women and men (n 29 152) aged 55 years. RESULTS: For a high intake of n-6 PUFA (6·9 % of energy) v. a low intake of n-6 PUFA (3·4 % of energy), the difference in 5-year weight change was -189·7 g (95 % CI -636·8, 257·4 g) at a low carbohydrate:protein ratio and -86·7 g (95 % CI -502·9, 329·6 g) at a high carbohydrate:protein ratio; the differences in 5-year waist circumference change were 0·26 cm (95 % CI -0·47, 0·98 cm) and -0·52 cm (95 % CI -1·19, 0·15 cm), respectively. Inclusion of the dietary glycaemic index did not change the results. CONCLUSIONS: No consistent associations between the intake of n-6 PUFA and change in body weight or waist circumference at different levels of the carbohydrate:protein ratio were observed.

Body characteristics, [corrected] dietary protein and body weight regulation. Reconciling conflicting results from intervention and observational studies?

BACKGROUND/OBJECTIVES: Physiological evidence indicates that high-protein diets reduce caloric intake and increase thermogenic response, which may prevent weight gain and regain after weight loss. Clinical trials have shown such effects, whereas observational cohort studies suggest an association between greater protein intake and weight gain. In both types of studies the results are based on average weight changes, and show considerable diversity in both directions. This study investigates whether the discrepancy in the evidence could be due to recruitment of overweight and obese individuals into clinical trials. SUBJECTS/METHODS: Data were available from the European Diet, Obesity and Genes (DiOGenes) post-weight-loss weight-maintenance trial and the Danish Diet, Cancer and Health (DCH) cohort. Participants of the DCH cohort were matched with participants from the DiOGenes trial on gender, diet, and body characteristics. Different subsets of the DCH-participants, comparable with the trial participants, were analyzed for weight maintenance according to the randomization status (high or low protein) of the matched trial participants. RESULTS: Trial participants were generally heavier, had larger waist circumference and larger fat mass than the participants in the entire DCH cohort. A better weight maintenance in the high-protein group compared to the low protein group was observed in the subgroups of the DCH cohort matching body characteristics of the trial participants. CONCLUSION: This modified observational study, minimized the differences between the RCT and observational data with regard to dietary intake, participant characteristics and statistical analysis. Compared with low protein diet the high protein diet was associated with better weight maintenance when individuals with greater body mass index and waist circumference were analyzed. Selecting subsets of large-scale observational cohort studies with similar characteristics as participants in clinical trials may reconcile the otherwise conflicting results.

Adipose tissue trans-fatty acids and changes in body weight and waist circumference.

Previous studies have suggested that the intake of trans-fatty acids (TFA) plays a role in the development of obesity. The proportions of adipose tissue fatty acids not synthesised endogenously in humans, such as TFA, usually correlate well with the dietary intake. Hence, the use of these biomarkers may provide a more accurate measure of habitual TFA intake than that obtained with dietary questionnaires. The objective of the present study was to investigate the associations between the proportions of specific TFA in adipose tissue and subsequent changes in weight and waist circumference (WC). The relative content of fatty acids in adipose tissue biopsies from a random sample of 996 men and women aged 50-64 years drawn from a Danish cohort study was determined by GC. Baseline data on weight, WC and potential confounders were available together with information on weight and WC 5 years after enrolment. The exposure measures were total trans-octadecenoic acids (18:1t), 18:1 Δ6-10t, vaccenic acid (18:1 Δ11t) and rumenic acid (18:2 Δ9c, 11t). Data were analysed using multiple regression with cubic spline modelling. The median proportion of total adipose tissue 18:1t was 1.52% (90% central range 0.98, 2.19) in men and 1.47% (1.01, 2.19) in women. No significant associations were observed between the proportions of total 18:1t, 18:1 Δ6-10t, vaccenic acid or rumenic acid and changes in weight or WC. The present study suggests that the proportions of specific TFA in adipose tissue are not associated with subsequent changes in weight or WC within the exposure range observed in this population.

Meat consumption and mortality--results from the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Recently, some US cohorts have shown a moderate association between red and processed meat consumption and mortality supporting the results of previous studies among vegetarians. The aim of this study was to examine the association of red meat, processed meat, and poultry consumption with the risk of early death in the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Included in the analysis were 448,568 men and women without prevalent cancer, stroke, or myocardial infarction, and with complete information on diet, smoking, physical activity and body mass index, who were between 35 and 69 years old at baseline. Cox proportional hazards regression was used to examine the association of meat consumption with all-cause and cause-specific mortality. RESULTS: As of June 2009, 26,344 deaths were observed. After multivariate adjustment, a high consumption of red meat was related to higher all-cause mortality (hazard ratio (HR) = 1.14, 95% confidence interval (CI) 1.01 to 1.28, 160+ versus 10 to 19.9 g/day), and the association was stronger for processed meat (HR = 1.44, 95% CI 1.24 to 1.66, 160+ versus 10 to 19.9 g/day). After correction for measurement error, higher all-cause mortality remained significant only for processed meat (HR = 1.18, 95% CI 1.11 to 1.25, per 50 g/d). We estimated that 3.3% (95% CI 1.5% to 5.0%) of deaths could be prevented if all participants had a processed meat consumption of less than 20 g/day. Significant associations with processed meat intake were observed for cardiovascular diseases, cancer, and 'other causes of death'. The consumption of poultry was not related to all-cause mortality. CONCLUSIONS: The results of our analysis support a moderate positive association between processed meat consumption and mortality, in particular due to cardiovascular diseases, but also to cancer.