Antioxidant intake and pancreatic cancer risk: the Vitamins and Lifestyle (VITAL) Study.

BACKGROUND: Oxidative stress causes damage to many components of human cells (ie, proteins, lipids, and DNA) and is involved in carcinogenesis. Nutrients with antioxidant properties may protect against oxidative stress. In this study, the authors examined the intake of antioxidants from diet and supplements in relation to pancreatic cancer risk among participants of the Vitamins and Lifestyle (VITAL) Study. METHODS: The participants included 77,446 men and women ages 50 to 76 years who were residents of western Washington State and who completed a baseline questionnaire between 2000 and 2002. Participants reported usual diet over the past year and use of supplements over the past 10 years in addition to demographic and lifestyle factors. During a median follow-up of 7.1 years, 184 participants developed pancreatic adenocarcinoma. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for 7 antioxidants: ß-carotene, lutein plus zeaxanthin, lycopene, vitamin C, vitamin E, selenium, and zinc. RESULTS: An inverse association was observed between dietary selenium and the risk of pancreatic cancer (medium vs low intake: HR, 0.58; 95% CI, 0.35-0.94; high vs low intake: HR, 0.44; 95% CI, 0.23-0.85; Ptrend = .01); however, when supplemental and dietary exposures were combined, the association was no longer statistically significant. CONCLUSIONS: Dietary selenium intake was inversely associated with the risk of pancreatic cancer, and the observed association was attenuated by selenium supplementation.

Types of fish consumed and fish preparation methods in relation to pancreatic cancer incidence: the VITAL Cohort Study.

The associations of types of fish and fish preparation methods with pancreatic cancer risk remain unknown. The authors conducted a prospective cohort study in western Washington State among 66,616 adults, aged 50-76 years, who participated in the VITamins And Lifestyle cohort study. Diet was assessed by a food frequency questionnaire. Pancreatic cancer cases were identified by linkage to the Surveillance, Epidemiology, and End Results cancer registry. During an average follow-up of 6.8 years, 151 participants developed pancreatic cancer (adenocarcinoma). Long-chain (n-3) polyunsaturated fatty acids (LC-PUFAs) and nonfried fish intake were inversely associated with pancreatic cancer incidence. When the highest and lowest tertiles of exposure were compared, the multivariable-adjusted hazard ratio of pancreatic cancer was 0.62 (95% confidence interval: 0.40, 0.98) (P(trend) = 0.08) for LC-PUFAs and 0.55 (95% confidence interval: 0.34, 0.88) (P(trend) = 0.045) for nonfried fish. Docosahexaenoic acid showed a greater inverse association with pancreatic cancer than eicosapentaenoic acid. No statistically significant associations were observed with fried fish and shellfish consumption. The potential health impact of fish consumption may depend on the types of fish consumed and fish preparation methods. LC-PUFAs, particularly docosahexaenoic acid, and nonfried fish, but not shellfish or fried fish, may be beneficial in the primary prevention of pancreatic cancer.

Antioxidant and DNA methylation-related nutrients and risk of distal colorectal cancer.

OBJECTIVE: To investigate the relationship between antioxidant nutrients (vitamins C and E, beta-carotene, selenium) and DNA methylation-related nutrients (folate, vitamins B6 and B12) and distal colorectal cancer risk in whites and African Americans and to examine intakes from food only versus total (food plus dietary supplements) intakes. METHODS: Data are from the North Carolina Colon Cancer Study-Phase II, a case-control study of 945 distal colorectal cancer (including sigmoid, rectosigmoid, and rectum) cases and 959 controls. In-person interviews captured usual dietary intake and various covariates. Multivariate logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: High intakes of each antioxidant and DNA methylation-related nutrient were significantly associated with lower risk in whites. In African Americans, the highest category of selenium from food only had a marginally significant inverse association with distal colorectal cancer risk (Q4 vs. Q1 OR: 0.55, 95% CI 0.29-1.02). Supplements did not provide additional risk reduction beyond intakes from food. CONCLUSIONS: Our findings provide evidence that antioxidant and DNA methylation-related nutrients may lower the risk of distal colorectal cancer in whites, and selenium may lower risk in African Americans. Optimal micronutrient intakes from food alone may be more beneficial than supplementation.

Associations of toenail selenium levels with inflammatory biomarkers of fibrinogen, high-sensitivity c-reactive protein, and interleukin-6: The CARDIA Trace Element Study.

The authors examined the associations of toenail selenium levels with blood concentrations of fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) in an 18-year follow-up study comprising 4,032 Americans aged 20-32 years at baseline (1987) from the Coronary Artery Risk Development in Young Adults (CARDIA) Trace Element Study. Toenail samples were collected in 1987, and selenium concentrations were measured by means of instrumental neutron-activation analysis. Fibrinogen level was analyzed in 1990, 1992, and 2005; hs-CRP was assessed in 1992, 2000, and 2005; and IL-6 was measured in 2005. After adjustment for potential confounders, no statistically significant associations between toenail selenium levels and any of the 3 inflammatory biomarkers were documented. Comparing the highest quintile of toenail selenium level with the lowest, odds ratios for elevated levels of fibrinogen (>460 mg/mL), hs-CRP (>3 microg/mL), and IL-6 (>3.395 pg/mL, 80th percentile) were 1.03 (95% confidence interval (CI): 0.77, 1.38; P for trend = 0.76), 1.02 (95% CI: 0.83, 1.27; P for trend = 0.92), and 0.98 (95% CI: 0.71, 1.36; P for trend = 0.82), respectively. Gender, race/ethnicity, smoking status, and selenium supplementation did not appreciably modify these results. This study found no associations between toenail selenium and inflammation as measured by fibrinogen, hs-CRP, and IL-6.

Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies.

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.

Antioxidant vitamins and coronary heart disease risk: a pooled analysis of 9 cohorts.

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 free 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.

Relation between intake of vitamins C and E and risk of diabetic retinopathy in the Atherosclerosis Risk in Communities Study.

BACKGROUND: The potential protective effect of vitamins C and E against the development of diabetic retinopathy has not been thoroughly evaluated in epidemiologic studies. OBJECTIVE: The objective was to study the association between prevalent diabetic retinopathy and intake of vitamins C and E in participants of the Atherosclerosis Risk in Communities Study. DESIGN: A total of 1353 subjects with type 2 diabetes diagnosed between 1993 and 1995 or before were included. Nutrient intake was assessed with a food-frequency and supplement questionnaire administered between 1987-1989 and 1993-1995. Prevalent retinopathy (n = 224) was determined in 1993-1995 from graded fundus photographs. RESULTS: No association of retinopathy with intake of vitamin C or E from food alone or from food and supplements combined was observed. The odds ratios and 95% CIs for retinopathy for quartile 4 compared with quartile 1 of vitamins C and E intakes from food and supplements combined were 1.1 (0.7, 1.9) and 1.3 (0.8, 2.2), respectively, after adjustment for diabetes treatment and serum glucose. There was a significant interaction of the observed relations with serum glucose concentration (P < 0.05). Additionally, a decreased odds of retinopathy was found among users (reported use > or =3 y before 1993-1995) of vitamin C or E supplements or multisupplements compared with reported use of no supplements: 0.5 (0.3, 0.8), 0.5 (0.2, 0.8), and 0.4 (0.2, 0.9), respectively. CONCLUSION: No significant overall associations were observed between risk of retinopathy and intake of major dietary antioxidants. The observed association between risk of retinopathy and supplement use may reflect nondietary factors or a possible benefit of supplementation.