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Background: High intakes of saturated fat have been associated with cardiovascular disease, and milk fat is rich in saturated fat. Objective: The objective of this study was to investigate the association between the serum milk fat biomarkers pentadecanoic acid (15:0), heptadecanoic acid (17:0), and their sum (15:0+17:0) and a first myocardial infarction (MI). Design: The study design was a prospective case-control study nested within a large population-based cohort in Sweden. Included in the study were 444 cases (307 men) and 556 controls (308 men) matched on sex, age, date of examination, and geographic region. Clinical, anthropometric, biomarker fatty acid, physical activity, and dietary data were collected. The odds of a first MI were investigated by using conditional logistic regression. Results: In women, proportions of milk fat biomarkers in plasma phospholipids were significantly higher (P < 0.05) in controls than in cases and were, in general, negatively, albeit weakly, correlated with risk factors for metabolic syndrome. The crude standardized odds ratios of becoming an MI case were 0.74 (95% CI: 0.58, 0.94) in women and 0.91 (95% CI: 0.77, 1.1) in men. After multivariable adjustment for confounders, the inverse association remained in both sexes and was significant in women. In agreement with biomarker data, quartiles of reported intake of cheese (men and women) and fermented milk products (men) were inversely related to a first MI (P for trend < 0.05 for all). Conclusions: Milk fat biomarkers were associated with a lower risk of developing a first MI, especially in women. This was partly confirmed in analysis of fermented milk and cheese intake. Components of metabolic syndrome were observed as potential intermediates for the risk relations. Am J Clin Nutr 2010;92:194-202. doi: 10.3945/ajcn.2009.29054.

Background: A high consumption of fruit and vegetables is possibly associated with a decreased risk of colorectal cancer (CRC). However, the findings to date are inconsistent. Objective: We examined the relation between self-reported usual consumption of fruit and vegetables and the incidence of CRC. Design: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 452,755 subjects (131,985 men and 320,770 women) completed a dietary questionnaire in 1992-2000 and were followed up for cancer incidence and mortality until 2006. A multivariate Cox proportional hazard model was used to estimate adjusted hazard ratios (HRs) and 95% CIs. Results: After an average follow-up of 8.8 y, 2,819 incident CRC cases were reported. Consumption of fruit and vegetables was inversely associated with CRC in a comparison of the highest with the lowest EPIC-wide quintile of consumption (HR: 0.86; 95% CI: 0.75, 1.00; P for trend = 0.04), particularly with colon cancer risk (HR: 0.76; 95% CI: 0.63, 0.91; P for trend < 0.0l). Only after exclusion of the first 2 y of follow-up were these findings corroborated by calibrated continuous analyses for a 100-g increase in consumption: HRs of 0.95 (95% CI: 0.91, 1.00; P = 0.04) and 0.94 (95% CI: 0.89, 0.99; P = 0.02), respectively. The association between fruit and vegetable consumption and CRC risk was inverse in never and former smokers, but positive in current smokers. This modifying effect was found for fruit and vegetables combined and for vegetables alone (P for interaction < 0.01 for both). Conclusions: These findings suggest that a high consumption of fruit and vegetables is associated with a reduced risk of CRC, especially of colon cancer. This effect may depend on smoking status.

Background: Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, require substitution of other macronutrients to maintain energy balance. Objective: We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age. Using substitution models, our aim was to clarify whether energy from unsaturated fatty acids or carbohydrates should replace energy from SFAs to prevent CHD. Design: This was a follow-up study in which data from 11 American and European cohort studies were pooled. The outcome measure was incident CHD. Results: During 4-10 y of follow-up, 5249 coronary events and 2155 coronary deaths occurred among 344,696 persons. For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from carbohydrates, there was a modest significant direct association between carbohydrates and coronary events (hazard ratio: 1.07; 95% CI: 1.01, 1.14); the hazard ratio for coronary deaths was 0.96 (95% CI: 0.82, 1.13). MUFA intake was not associated with CHD. No effect modification by sex or age was found. Conclusion: The associations suggest that replacing SFAs with PUFAs rather than MUFAs or carbohydrates prevents CHD over a wide range of intakes.

Background: Some evidence indicates that a low selenium intake may be associated with an increased risk of prostate cancer. Objective: The aim of this study was to investigate the association of plasma selenium concentration with subsequent prostate cancer risk and to examine this association by stage and grade of disease and other factors. Design: A nested case-control study was performed among men in the European Prospective Investigation into Cancer and Nutrition (EPIC). The association between plasma selenium concentration and prostate cancer risk was assessed in 959 men with incident prostate cancer and 1059 matched controls. Results: Overall, plasma selenium concentration was not associated with prostate cancer risk; the multivariate relative risk for men in the highest fifth of selenium concentration compared with the lowest fifth was 0.96 (95% CI: 0.70, 1.31; P for trend = 0.25). There were no significant differences in the association of plasma selenium with risk when analyzed by stage or grade of disease. Similarly, the association of selenium with risk did not differ by smoking status or by plasma [alpha]- or [gamma]-tocopherol concentration. Conclusion: Plasma selenium concentration was not associated with prostate cancer risk in this large cohort of European men.

Background: Plausible biological mechanisms underlie possible associations between fatty acids in blood and risk of prostate cancer; epidemiologic evidence for an association, however, is inconsistent. Objective: The objectives were to assess the association between plasma phospholipid fatty acids and risk of total prostate cancer by stage and grade. Design: This was a nested case-control analysis of 962 men with a diagnosis of prostate cancer after a median follow-up time of 4.2 y and 1061 matched controls who were taking part in the European Prospective Investigation into Cancer and Nutrition. The fatty acid composition of plasma phospholipids was measured by gas chromatography, and the risk of prostate cancer was estimated by using conditional logistic regression with adjustment for lifestyle variables. Results: We found a positive association between palmitic acid and risk of total, localized, and low-grade prostate cancer. The risk of prostate cancer for men in the highest quintile compared with the lowest quintile of palmitic acid was 1.47 (95% CI: 0.97, 2.23; P for trend = 0.032). We found an inverse association between stearic acid and the risk of total, localized, and low-grade prostate cancer; men in the highest quintile of stearic acid had a relative risk of 0.77 (95% CI: 0.56, 1.06; P for trend = 0.03). There were significant positive associations between myristic, [alpha]-linolenic, and eicosapentaenoic acids and risk of high-grade prostate cancer. Conclusion: The associations between palmitic, stearic, myristic, [alpha]-linolenic, and eicosapentaenoic acids and prostate cancer risk may reflect differences in intake or metabolism of these fatty acids between the precancer cases and controls and should be explored further.

Background: Epidemiologic studies have produced conflicting results with respect to an association of dietary fat with breast cancer. Objective: We aimed to investigate the association between fat consumption and breast cancer. Design: We prospectively investigated fat consumption in a large (n = 319 826), geographically and culturally heterogeneous cohort of European women enrolled in the European Prospective Investigation into Cancer and Nutrition who completed a dietary questionnaire. After a mean of 8.8 y of follow-up, 7119 women developed breast cancer. Cox proportional hazard models, stratified by age and center and adjusted for energy intake and confounders, were used to estimate hazard ratios (HRs) for breast cancer. Results: An association between high saturated fat intake and greater breast cancer risk was found [HR = 1.13 (95% CI: 1.00, 1.27; P for trend = 0.038) for the highest quintile of saturated fat intake compared with the lowest quintile: 1.02 (1.00, 1.04) for a 20% increase in saturated fat consumption (continuous variable)]. No significant association of breast cancer with total, monounsaturated, or polyunsaturated fat was found, although trends were for a direct association of risk with monounsaturated fat and an inverse association with polyunsaturated fat. In menopausal women, the positive association with saturated fat was confined to nonusers of hormone therapy at baseline [1.21 (0.99, 1.48) for the highest quintile compared with the lowest quintile; P for trend = 0.044; and 1.03 (1.00, 1.07) for a 20% increase in saturated fat as a continuous variable]. Conclusions: Evidence indicates a weak positive association between saturated fat intake and breast cancer risk. This association was more pronounced for postmenopausal women who never used hormone therapy.

Background: Findings from early observational studies have suggested that the intake of dietary fat might be a contributing factor in the etiology of prostate cancer. However, the results from more recent prospective studies do not support this hypothesis, and the possible association between different food sources of fat and prostate cancer risk also remains unclear. Objective: The objectives were to assess whether intakes of dietary fat, subtypes of fat, and fat from animal products were associated with prostate cancer risk. Design: This was a multicenter prospective study of 142 520 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary fat intake was estimated with the use of country-specific validated food questionnaires. The association between dietary fat and risk of prostate cancer was assessed by using Cox regression, stratified by recruitment center and adjusted for height, weight, smoking, education, marital status, and energy intake. Results: After a median follow-up time of 8.7 y, prostate cancer was diagnosed in 2727 men. There was no significant association between dietary fat (total, saturated, monounsaturated, and polyunsaturated fat and the ratio of polyunsaturated to saturated fat) and risk of prostate cancer. The hazard ratio for prostate cancer for the highest versus the lowest quintile of total fat intake was 0.96 (95% CI: 0.84, 1.09; P for trend = 0.155). There were no significant associations between prostate cancer risk and fat from red meat, dairy products, and fish. Conclusion: The results from this large multicenter study suggest that there is no association between dietary fat and prostate cancer risk.

Background: Plant sterols are bioactive compounds, found in all vegetable foods, which inhibit cholesterol absorption. Little is known about the effect of habitual natural dietary intake of plant sterols. Objective: We investigated the relation between plant sterol density (in mg/MJ) and serum concentrations of cholesterol in men and women in northern Sweden. Design: The analysis included 37 150 men and 40 502 women aged 29-61 y, all participants in the Vasterbotten Intervention Program. Results: Higher plant sterol density was associated with lower serum total cholesterol in both sexes and with lower LDL cholesterol in women. After adjustment for age, body mass index (in kg/[m.sup.2]), and (in women) menopausal status, men with high plant sterol density (quintile 5) had 0.15 mmol/L (2.6%) lower total serum cholesterol (P for trend = 0.001) and 0.13 mmol/L (3.1%) lower LDL cholesterol (P = 0.062) than did men with low plant sterol density (quintile 1). The corresponding figures for women were 0.20 mmol/L (3.5%) lower total serum cholesterol (P for trend < 0.001) and 0.13 mmol/L (3.2%) lower LDL cholesterol (P for trend = 0.001). Conclusions: The present study is the second epidemiologic study to show a significant inverse relation between naturally occurring dietary plant sterols and serum cholesterol. To the extent that the associations found truly mirror plant sterol intake and not merely a diet high in vegetable fat and fiber, it highlights the importance of considering the plant sterol content of foods both in primary prevention of cardiovascular disease and in the dietary advice incorporated into nutritional treatment of patients with hyperlipidemia.

Background: Previous studies suggest that high plasma concentrations of carotenoids, retinol, or tocopherols may reduce the risk of prostate cancer. Objective: We aimed to examine the associations between plasma concentrations of 7 carotenoids, retinol, [alpha]-tocopherol, and [gamma]-tocopherol and prostate cancer risk. Design: A total of 137 001 men in 8 European countries participated. After a mean of 6 y, 966 incident cases of prostate cancer with plasma were available. A total of 1064 control subjects were selected and were matched for study center, age, and date of recruitment. The relative risk of prostate cancer was estimated by conditional logistic regression, which was adjusted for smoking status, alcohol intake, body mass index, marital status, physical activity, and education level. Results: Overall, none of the micronutrients examined were significantly associated with prostate cancer risk. For lycopene and the sum of carotenoids, there was evidence of heterogeneity between the associations with risks of localized and advanced disease. These carotenoids were not associated with the risk of localized disease but were inversely associated with the risk of advanced disease. The risk of advanced disease for men in the highest fifth of plasma concentrations compared with men in the lowest fifth was 0.40 (95% CI: 0.19, 0.88) for lycopene and 0.35 (95% CI: 0.17, 0.78) for the sum of carotenoids. Conclusions: We observed no associations between plasma concentrations of carotenoids, retinol, or tocopherols and overall prostate cancer risk. The inverse associations of lycopene and the sum of carotenoids with the risk of advanced disease may involve a protective effect, an association of dietary choice with delayed detection of prostate cancer, reverse causality, or other factors. KEY WORDS Carotenoids, retinol, tocopherols, lycopene, prostate cancer, nested case-control study

Background: Epidemiologic studies have suggested a lower risk of coronary heart disease (CHD) at higher intakes of fruit, vegetables, and whole grain. Whether this association is due to antioxidant vitamins or some other factors remains unclear. Objective: We studied the relation between the intake of antioxidant vitamins and CHD risk. Design: A cohort study pooling 9 prospective studies that included information on intakes of vitamin E, carotenoids, and vitamin C and that met specific criteria was carried out. During a 10-y follow-up, 4647 major incident CHD events occurred in 293 172 subjects who were tree of CHD at baseline. Results: Dietary intake of antioxidant vitamins was only weakly related to a reduced CHD risk after adjustment for potential nondietary and dietary confounding factors. Compared with subjects in the lowest dietary intake quintiles for vitamins E and C, those in the highest intake quintiles had relative risks of CHD incidence of 0.84 (95% CI: 0.71, 1.00; P = 0.17) and 1.23 (1.04, 1.45; P = 0.07), respectively, and the relative risks for subjects in the highest intake quintiles for the various carotenoids varied from 0.90 to 0.99. Subjects with higher supplemental vitamin C intake had a lower CHD incidence. Compared with subjects who did not take supplemental vitamin C, those who took >700 mg supplemental vitamin C/d had a relative risk of CHD incidence of 0.75 (0.60, 0.93; P for trend < 0.001). Supplemental vitamin E intake was not significantly related to reduced CHD risk. Conclusions: The results suggest a reduced incidence of major CHD events at high supplemental vitamin C intakes. The risk reductions at high vitamin E or carotenoid intakes appear small. KEY WORDS Antioxidant, carotenoids, cohort, coronary heart disease, diet, Pooling Project of Cohort Studies on Diet and Coronary Disease, vitamin C, vitamin E

The purpose of this investigation was to study the degradation of [beta]-glucan in the small intestine and the molecular weight of [beta]-glucan in the excrete of nine ileostomy subjects after consumption of different diets based on bread made with oat bran (oat bread), a fiber-rich barley fraction (barley bread), or wheat flour (wheat bread) as the main ingredients. Oat bread with enzymatically degraded [beta]-glucan was also used (oat + enzyme bread). The [beta]-glucan intake from the four diets was 12.5, 12.9, 1.1, and 4.0 g/d, respectively. On the basis of dry matter, the night effluents accounted for [nearly equal to] 15% of the total amount of the excrete, with the highest proportion (22%) being for the wheat-bread diet. A notable loss of [beta]-glucan (0.7-2.4 g/d, or 13-64%) was found when intake was compared with excretion. In vitro, a higher viscosity development with time for dispersions of oat bread compared with barley bread was noted, which could be related to the higher molecular weight of the [beta]-glucan in this bread. There seemed to be a depolymerization of the [beta]-glucan both during bread making and transit through the upper gastrointestinal tract.

The excretion of bile acids, cholesterol, dry matter, nitrogen, fat, and energy in ileostomy effluent, and plasma lipid concentrations were studied in eight subjects with ileostomies. The subjects consumed a wheat bread-based, low-fiber diet (LFD) for 3 wk and a rye bran bread-based, high-fiber diet (HFD) for 3 wk. The ileal excretion of dry matter, nitrogen, fat, and energy was higher during the HFD period. The daily excretion and the percentage of conjugated bile acids were significantly higher and the percentage of free bile acids lower in the ileostomy effluents during the HFD as compared with the LFD period. No significant difference in the excretion of cholesterol, net cholesterol, sterol, or net sterol was noted between the HFD and LFD periods. No significant differences in plasma concentrations of HDL-, LDL-, and total cholesterol, and apolipoprotein A-I and B were observed between the two 3-wk dietary periods.

A higher excretion of dry matter, fat, nitrogen, energy, and total bile acids in ileal effluents; a lower plasma low-density-lipoprotein (LDL) and total cholesterols (12.1% and 9.0% lower respectively); but no change in plasma high-density-lipoprotein (HDL) cholesterol or apolipoproteins A-I and B were observed in nine subjects with ileostomies when they consumed an oat-bran, bread-based, high-fiber diet (HFD) as compared with a wheat-flour, bread-based, low-fiber diet (LFD) for 3 wk with a crossover design. Of the nine subjects only the subjects with a low daily excretion of bile acids had an elevated excretion of total bile acids during the HFD compared with the LFD. Total cholesterol, LDL cholesterol, and apolipoprotein B in plasma also decreased by 11.3%, 15.3%, and 10.7%, respectively, after consumption of the HFD for 3 wk. Am J Clin Nutr 1992;56:99-105.