Calcium supplement intake and risk of cardiovascular disease in women.

UNLABELLED: Some recent reports suggest that calcium supplement use may increase risk of cardiovascular disease. In a prospective cohort study of 74,245 women in the Nurses' Health Study with 24 years of follow-up, we found no independent associations between supplemental calcium intake and risk of incident coronary heart disease (CHD) and stroke. INTRODUCTION: Some recent reports suggest that calcium supplements may increase cardiovascular disease (CVD) risk. The objective was to examine the independent associations between calcium supplement use and risk of CVD. METHODS: We conducted a prospective cohort study of supplemental calcium use and incident CVD in 74,245 women in the Nurses' Health Study (1984-2008) free of CVD and cancer at baseline. Calcium supplement intake was assessed every 4 years. Outcomes were incident CHD (nonfatal or fatal MI) and stroke (ischemic or hemorrhagic), confirmed by medical record review. RESULTS: During 24 years of follow-up, 4,565 cardiovascular events occurred (2,709 CHD and 1,856 strokes). At baseline, women who took calcium supplements had higher levels of physical activity, smoked less, and had lower trans fat intake compared with those who did not take calcium supplements. After multivariable adjustment for age, body mass index, dietary calcium, vitamin D intake, and other CVD risk factors, the relative risk of CVD for women taking >1,000 mg/day of calcium supplements compared with none was 0.82 (95% confidence interval [CI] 0.74 to 0.92; p for trend <0.001). For women taking >1,000 mg/day of calcium supplements compared with none, the multivariable-adjusted relative risk for CHD was 0.71 (0.61 to 0.83; p for trend < 0.001) and for stroke was 1.03 (0.87 to 1.21; p for trend = 0.61). The relative risks were similar in analyses limited to non-smokers, women without hypertension, and women who had regular physical exams. CONCLUSIONS: Our findings do not support the hypothesis that calcium supplement intake increases CVD risk in women.

Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study.

BACKGROUND AND AIMS: Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study. METHODS AND RESULTS: The present work is an observational study within the PREDIMED trial. Over an average of 4.3 years of follow-up, there were 273 confirmed cases of CVD among the 7172 participants (96.3%) who completed a validated 137-item food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the Phenol-Explorer database on polyphenol content of each reported food. After multivariate adjustment, a 46% reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake (HR = 0.54; 95% confidence interval [CI] = 0.33-0.91; P-trend = 0.04). The polyphenols with the strongest inverse associations were flavanols (HR = 0.40; CI 0.23-0.72; P-trend = 0.003), lignans (HR = 0.51; CI 0.30-0.86; P-trend = 0.007), and hydroxybenzoic acids (HR = 0.47; CI 0.26-0.86; P-trend 0.02). CONCLUSION: Greater intake of polyphenols, especially from lignans, flavanols, and hydroxybenzoic acids, was associated with decreased CVD risk. Clinical trials are needed to confirm this effect and establish accurate dietary recommendations.

Habitual intake of dietary flavonoids and risk of Parkinson disease.

OBJECTIVE: To prospectively examine whether higher intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, and polymers) were associated with a lower risk of developing Parkinson disease (PD). METHODS: In the current analysis, we included 49,281 men in the Health Professional Follow-up Study and 80,336 women from the Nurses' Health Study. Five major sources of flavonoid-rich foods (tea, berry fruits, apples, red wine, and orange/orange juice) were also examined. Flavonoid intake was assessed using an updated food composition database and a validated food frequency questionnaire. RESULTS: We identified 805 participants (438 men and 367 women) who developed PD during 20-22 years of follow-up. In men, after adjusting for multiple confounders, participants in the highest quintile of total flavonoids had a 40%lower PD risk than those in the lowest quintile (hazard ratio [HR] = 0.60; 95% confidence interval 0.43, 0.83; p trend = 0.001). No significant relationship was observed in women (p trend = 0.62) or in pooled analyses (p trend = 0.23). In the pooled analyses for the subclasses, intakes of anthocyanins and a rich dietary source, berries, were significantly associated with a lower PD risk (HR comparing 2 extreme intake quintiles were 0.76 for anthocyanins and 0.77 for berries, respectively; p trend < 0.02 for both). CONCLUSIONS: Our findings suggest that intake of some flavonoids may reduce PD risk, particularly in men, but a protective effect of other constituents of plant foods cannot be excluded.

Alcohol consumption and risk of coronary heart disease among men with type 2 diabetes mellitus.

OBJECTIVES: The goal of this study was to examine the relationship between alcohol intake and risk of coronary heart disease (CHD) among men with type 2 diabetes. BACKGROUND: Type 2 diabetes is associated with an increased risk of CHD. Emerging evidence suggests that moderate alcohol intake is associated with an important reduction in risk of CHD in individuals with type 2 diabetes. METHODS: We studied 2,419 men who reported a diagnosis of diabetes at age 30 or older in the Health Professionals' Follow-up study (HPFS). During 11,411 person-years of follow-up after diagnosis, we documented 150 new cases of CHD (81 nonfatal myocardial infarction [MI] and 69 fatal CHD). Relative risks (RR) were estimated from pooled logistic regression adjusting for potential confounders. RESULTS: Alcohol use was inversely associated with risk of CHD in men with type 2 diabetes. The age-adjusted RRs corresponding to intakes of < or =0.5 drinks/day, 0.5 to 2 drinks/day and >2 drinks/day were 0.76 (95% confidence interval: [CI]: 0.52 to 1.12), 0.64 (95% CI: 0.40 to 1.02) and 0.59 (95% CI: 0.32 to 1.09), respectively, as compared with nondrinkers (p for trend = 0.06). When we controlled for body mass index, smoking, family history of MI, hypertension, hypercholesterolemia, duration of diabetes, physical activity level, vitamin E supplements and intake of trans fat, polyunsaturated fat, fiber and folate, RRs were 0.78 (95% CI: 0.52 to 1.15), 0.62 (95% CI: 0.40 to 1.00) and 0.48 (95% CI: 0.25 to 0.94) (p for trend = 0.03). The benefits of moderate consumption did not statistically differ by beverage type. CONCLUSIONS: Moderate alcohol consumption is associated with lower risk of CHD in men with type 2 diabetes.

Vitamin supplement use and the risk of non-Hodgkin's lymphoma among women and men.

The authors examined use of individual supplements of vitamins A, C, and E only and multivitamins in relation to risk of non-Hodgkin's lymphoma in prospective cohorts of 88,410 women in the Nurses' Health Study (1980-1996), with 261 incident cases during 16 years of follow-up, and of 47,336 men in the Health Professionals Follow-Up Study (1986-1996), with 111 incident cases during 10 years of follow-up. Multivitamin use was associated with a higher risk of non-Hodgkin's lymphoma among women but not among men; the multivariate relative risks for long-term duration (10 or more years) were 1.48 (95% confidence interval (CI): 1.01, 2.16) for women and 0.85 (95% CI: 0.45, 1.58) for men. The pooled multivariate relative risk from the two cohorts was 1.18 (95% CI: 0.70, 2.02). Use of individual supplements of vitamins A, C, and E only was not associated with risk among men. An increased risk associated with the use of individual supplements of vitamins A, C, and E only among women appeared to be secondary to the use of multivitamins by the same persons. Because an elevated risk among multivitamin users was not observed consistently in the two cohorts and the pooled data were not significant, the elevated risk among women may be the result of chance.

Prospective study of zinc intake and the risk of age-related macular degeneration.

PURPOSE: Zinc is found in high concentrations in the retina and is hypothesized to reduce the risk of age-related macular degeneration (AMD). Any long-term benefit associated with dietary zinc intake has not been evaluated. METHODS: We followed 66,572 women and 37,636 men who were > or = 50 years old and had no diagnosis of AMD or cancer. Zinc intake from food, multivitamins, and supplements was assessed with a semiquantitative food-frequency questionnaire at baseline (in 1984 for women and in 1986 for men) and repeated during follow-up (twice for women, once for men). RESULTS: During 10 years of follow-up for women and 8 years of follow-up for men, we confirmed 384 incident cases of AMD (195 cases of the early form and 189 cases of the late form) associated with a visual acuity loss of 20/30 or worse. After multivariate adjustment for potential risk factors, the pooled relative risk was 1.13 (95% confidence interval [CI], 0.82 to 1.57; p-value, test for trend, 0.74) among participants in the highest quintile of total zinc intake (energy-adjusted median; 25.5 mg/day for women and 40.1 mg/day for men) compared with those in the lowest quintile (energy-adjusted median; 8.5 mg/day for women and 9.9 mg/day for men). The relative risk for highest compared with lowest quintile was 1.04 (95% CI, 0.59 to 1.83; p-value, test for trend, 0.54) for zinc intake from food. Subjects who took zinc supplements had a pooled multivariate relative risk of 1.04 (95% CI, 0.75 to 1.45). CONCLUSIONS: In these two large prospective studies, moderate zinc intake, either in food or in supplements, was not associated with a reduced risk of AMD.

Association of folate intake and serum homocysteine in elderly persons according to vitamin supplementation and alcohol use.

BACKGROUND: The serum total homocysteine concentration (tHcy), an indicator of folate status and a possible risk factor for vascular disease, is elevated with impaired renal function and poor vitamin B-12 status, which are common in the elderly. OBJECTIVE: Our objective was to determine the association between tHcy, folate intake, alcohol consumption, and other lifestyle factors in elderly persons. DESIGN: This cross-sectional study used linear regression to model changes in tHcy. Subjects were 278 men and women aged 66-94 y studied in 1993. RESULTS: Total folate intake was negatively associated with tHcy in models adjusted for age, sex, serum creatinine, and serum albumin. We found an interaction between food folate intake and supplement use. Food folate intake had an inverse dose-response relation with tHcy that was limited to nonusers of supplements. Predicted tHcy was 1.5 micromol/L lower in users of supplements containing folate and vitamin B-12 than in nonusers and was independent of food folate intake. We found a positive dose-response relation of coffee and tea intake with tHcy, a positive association for alcohol intake of > or = 60 drinks/mo compared with low intake, and an interaction of alcohol use with folate intake and supplement use. Compared with alcohol users, nonusers had higher predicted tHcy and a lower inverse dose-response relation of food folate intake with tHcy. CONCLUSIONS: The inverse association between folate intake and tHcy was strongest among nonusers of supplements and among alcohol drinkers. Identifying modifiable factors related to tHcy, a possible risk factor for vascular disease, is especially important in elderly persons.

Blood donations and risk of coronary heart disease in men.

BACKGROUND: In experimental animals, iron overload appears to promote atherosclerosis and ischemic myocardial damage, but the results of epidemiological studies that relate iron stores to risk of coronary heart disease (CHD) have been inconsistent. METHODS AND RESULTS: We prospectively studied blood donations, which effectively reduce body iron stores, in relation to the risk of CHD among participants in the Health Professionals Follow-up Study. The lifetime history of blood donation was assessed with a questionnaire in 1992. The 38 244 men who were free of diagnosed cardiovascular disease at that time were included in the analyses. During 4 years of follow-up, we documented 328 nonfatal myocardial infarctions and 131 coronary deaths. Although the number of lifetime blood donations was strongly associated with lower plasma ferritin levels in a subsample, the blood donation was not associated with risk of myocardial infarction or fatal CHD. The age-adjusted relative risk (RR) of myocardial infarction for men in the highest category of blood donations (>/=30) compared with never donors was 1.2 (95% CI 0. 8 to 1.8), and this RR was not materially changed after adjustment for several coronary risk factors. No significant associations were found between blood donation and the risk of myocardial infarction in analyses restricted to men with hypercholesterolemia or those who never used antioxidant supplements or aspirin. CONCLUSIONS: The study results do not support the hypothesis that reduced body iron stores lower CHD risk.

Prospective study of dietary supplements, macronutrients, micronutrients, and risk of bladder cancer in US men.

Data derived from laboratory investigations suggest that a number of dietary variables may contribute to bladder carcinogenesis. Although bladder cancer is the fourth leading cause of cancer in men in the United States, dietary studies are few. The authors examined the relations between intakes of macro- and micronutrients and the risk of bladder cancer among men in the prospective Health Professionals Follow-Up Study. Each participant completed a 131-item food frequency questionnaire in 1986 and in 1990, from which nutrient intakes were calculated. During 12 years of follow-up, 320 cases of bladder cancer were diagnosed. No association was observed for total caloric or macronutrient intake and bladder cancer risk. Similarly, we found no relation for dietary intake of potassium, sodium, calcium, magnesium, phosphorus, iron, or water-soluble vitamins and bladder cancer risk. Total vitamin E intake and vitamin E supplements were inversely associated with risk. In addition, a dose-response relation was observed for duration of vitamin E supplement use. A suggestive inverse association was seen with dose of vitamin C supplement use. More studies are needed to determine the role of vitamins E and C supplement intake in bladder carcinogenesis.

Prospective study of major dietary patterns and risk of coronary heart disease in men.

BACKGROUND: Previous studies on diet and coronary heart disease (CHD) focused primarily on individual nutrients or foods. OBJECTIVE: We examined whether overall dietary patterns derived from a food-frequency questionnaire (FFQ) predict risk of CHD in men. DESIGN: This was a prospective cohort study of 44875 men aged 40-75 y without diagnosed cardiovascular disease or cancer at baseline in 1986. RESULTS: During 8 y of follow-up, we documented 1089 cases of CHD (nonfatal myocardial infarction and fatal CHD). Using factor analysis, we identified 2 major dietary patterns using dietary data collected through a 131-item FFQ. The first factor, which we labeled the "prudent pattern," was characterized by higher intake of vegetables, fruit, legumes, whole grains, fish, and poultry, whereas the second factor, the "Western pattern," was characterized by higher intake of red meat, processed meat, refined grains, sweets and dessert, French fries, and high-fat dairy products. After adjustment for age and CHD risk factors, the relative risks from the lowest to highest quintiles of the prudent pattern score were 1.0, 0. 87, 0.79, 0.75, and 0.70 (95% CI: 0.56, 0.86; P: for trend = 0.0009). In contrast, the relative risks across increasing quintiles of the Western pattern score were 1.0, 1.21, 1.36, 1.40, and 1.64 (95% CI: 1.24, 2.17; P: for trend < 0.0001). These associations persisted in subgroup analyses according to cigarette smoking, body mass index, and parental history of myocardial infarction. CONCLUSIONS: These data suggest that major dietary patterns derived from the FFQ predict risk of CHD, independent of other lifestyle variables.

Proportion of colon cancer risk that might be preventable in a cohort of middle-aged US men.

OBJECTIVE: Diet and lifestyle likely play major roles in colon cancer incidence; however, the proportion of colon cancer risk that might be preventable is unknown. Thus, we estimated the proportion of colon cancer risk among men in the prospective Health Professionals Follow-up Study that might be attributable to a constellation of modifiable risk factors, and thus might be preventable. METHODS: We included 47,927 men aged 40-75 years in 1986, among whom we confirmed 411 colon cancer cases from 1986 to 1996. Risk factors considered were obesity, physical inactivity, alcohol consumption, early adulthood cigarette smoking, red meat consumption, and low intake of folic acid from supplements. We calculated a risk score that was the sum across the six risk factors of the values of 1 (better exposure) to 5 (worse exposure) corresponding to the exposure category. We entered the risk score into a logistic regression model and estimated the population attributable risk percent (PAR%) using the method of Bruzzi et al. RESULTS: After adjusting for age and family history of colorectal cancer and comparing the risk score for the combined six modifiable colon cancer risk factors at or above the approximate 20th, 10th, or 5th percentiles vs. below, the PAR% increased from 39% (95% confidence interval (CI) = 23-58%), to 48% (95% CI = 25-71%), to 55% (95% CI = 27-80%), respectively. Using a second method in which we used cut-points consistent with general-good health behaviors for each risk factor, comparing men with at least one risk factor to men without any risk factors (3.1% of the men), the PAR% was 71% (95% CI = 33-92%). CONCLUSION: The findings from this analysis suggest that, if all the members of this cohort of middle-aged US men had a modifiable exposure distribution comparable to the men with low risk scores, a large proportion of colon cancer risk might be avoidable. Additional study is required to determine whether making changes in these six risk factors now would reduce the risk of colorectal neoplasia, or whether the proportion of colon neoplasia that might be avoidable would be similar in populations with different characteristics.

Antioxidants for vascular disease.

The epidemiologic data do not support a strong role for vitamin C in reducing risk of coronary disease. The evidence supporting a protective effect for the family of dietary carotenoids is stronger, but any important protective effect attributable to the specific supplementation of beta-carotene can be excluded. Conversely, results from observational and experimental studies consistently support an effect of vitamin E supplementation on reducing risk of coronary heart disease. The evidence suggests that the major effect, if any, is found at supplemental intake levels at or greater than 100 IU/d. If confirmed in further trials, the net benefit of vitamin E supplementation among populations with existing coronary disease may be substantial, although the current available evidence is insufficient to warrant a change in public policy recommendations.

Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States.

A clinical trial of vitamin E and beta-carotene supplementation for lung cancer prevention among male smokers in Finland recently reported an unexpected, strong protective effect of vitamin E against prostate cancer incidence and mortality. Our objective was to prospectively examine supplemental vitamin E intake and prostate cancer risk in a distinct U.S. population. In 1986, we identified 47,780 U.S. male health professionals, free from diagnosed cancer, who completed a dietary and lifestyle questionnaire; supplemental vitamin E and prostate cancer incidence were updated biennially through 1996. We estimated relative risks (RRs) from multivariate pooled logistic regression models. There were 1896 total (non-stage A1), 522 extraprostatic, and 232 metastatic or fatal incident prostate cancer cases diagnosed between 1986-1996. Men consuming at least 100 IU of supplemental vitamin E daily had multivariate RRs of 1.07 (95% confidence interval [CI], 0.95-1.20) for total and 1.14 (95% CI, 0.82-1.59) for metastatic or fatal prostate cancer compared with those consuming none. Current use, dosage, and total duration of use of specific vitamin E supplements or multivitamins were not associated with risk. However, among current smokers and recent quitters, those who consumed at least 100 IU of supplemental vitamin E per day had a RR of 0.44 (95% CI, 0.18-1.07) for metastatic or fatal prostate cancer compared with nonusers. Thus, supplemental vitamin E was not associated with prostate cancer risk generally, but a suggestive inverse association between supplemental vitamin E and risk of metastatic or fatal prostate cancer among current smokers and recent quitters was consistent with the Finnish trial among smokers and warrants further investigation.

A prospective study of coffee consumption and the risk of symptomatic gallstone disease in men.

CONTEXT: Coffee has several metabolic effects that could reduce the risk of gallstone formation. OBJECTIVE: To examine the association between coffee consumption and the risk of symptomatic gallstone disease in men. DESIGN AND SETTING: The Health Professionals Follow-up Study, a prospective cohort study, in which the consumption of coffee and other caffeinated drinks was assessed starting in 1986 as part of the 131-item food frequency questionnaire given to US male health professionals with follow-up through 1996. PARTICIPANTS: A total of 46008 men, aged 40 to 75 years in 1986, without history of gallstone disease. MAIN OUTCOME MEASURES: Newly symptomatic gallstone disease (diagnosed by ultrasonography or x-ray) or a cholecystectomy. RESULTS: During 404 166 person-years of follow-up, 1081 subjects reported symptomatic gallstone disease, of whom 885 required cholecystectomy. After adjusting for other known or suspected risk factors, compared with men who did not consume regular coffee in 1986 and 1990, the adjusted relative risk (RR) for those who consistently drank 2 to 3 cups of regular coffee per day was 0.60 (95% confidence interval [CI], 0.42-0.86) and for those who drank 4 or more cups per day the RR was 0.55 (95% CI, 0.33-0.92). All coffee brewing methods showed a decreased risk. The risk of symptomatic gallstone disease also declined with increasing caffeine intake (P for trend = .005). After controlling for known or suspected risk factors, the RR for men in the highest category of caffeine intake (>800 mg/d) compared with men in the lowest category (< or =25 mg/d) was 0.55 (95% CI, 0.35-0.87). In contrast, decaffeinated coffee was not associated with a decreased risk. CONCLUSIONS: In this cohort of US men, coffee consumption may have helped to prevent symptomatic gallstone disease.

Relation of consumption of vitamin E, vitamin C, and carotenoids to risk for stroke among men in the United States.

BACKGROUND: Antioxidants increase the resistance of low-density lipoprotein to oxidation and may thereby reduce risk for atherosclerosis. OBJECTIVE: To determine whether intake of vitamin E, vitamin C, or carotenoids predict risk for total or ischemic stroke. DESIGN: Prospective observational study. SETTING: The Health Professionals Follow-up Study. PARTICIPANTS: 43,738 men 40 to 75 years of age who did not have cardiovascular disease or diabetes. MEASUREMENTS: Repeated and validated dietary assessments were done by using a self-administered 131-item food-frequency questionnaire, which included questions on dose and duration of vitamin supplement use. The follow-up period was 8 years. RESULTS: A total of 328 strokes occurred: 210 ischemic, 70 hemorrhagic, and 48 unclassified. After adjustment for age, smoking, hypertension, hypercholesterolemia, body mass index, physical activity, parental history of myocardial infarction, alcohol consumption, and total energy intake, the relative risk for ischemic stroke in the top quintile of vitamin E intake (median, 411 IU/d) compared with the bottom quintile (5.4 IU/d) was 1.18 (95% CI, 0.77 to 1.82). The relative risk for ischemic stroke in the top quintile of vitamin C intake (1167 mg/d) compared with the bottom quintile (95 mg/d) was 1.03 (CI, 0.66 to 1.59). Results for total stroke were similar. Associations of vitamin intake with hemorrhagic stroke were also nonsignificant, but the CIs were wide. Neither dose nor duration of vitamin E or vitamin C supplement use was related to risk for total or ischemic stroke. The relative risk for ischemic stroke was 1.16 (CI, 0.81 to 1.67) in men using 250 IU or more of vitamin E supplementation per day compared with men who used no vitamin E supplements and was 0.93 (CI, 0.60 to 1.45) in men using 700 mg or more of vitamin C supplementation per day compared with men who used no vitamin C supplements. A significant inverse relation between lutein intake and risk for ischemic stroke was seen but was not independent of other dietary factors. CONCLUSIONS: Vitamin E and vitamin C supplements and specific carotenoids did not seem to substantially reduce risk for stroke in this cohort. Modest effects, however, cannot be excluded.

Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study.

OBJECTIVE: To examine the relation between nut consumption and risk of coronary heart disease in a cohort of women from the Nurses' Health Study. DESIGN: Prospective cohort study. SETTING: Nurses' Health Study. SUBJECTS: 86 016 women from 34 to 59 years of age without previously diagnosed coronary heart disease, stroke, or cancer at baseline in 1980. MAIN OUTCOME MEASURES: Major coronary heart disease including non-fatal myocardial infarction and fatal coronary heart disease. RESULTS: 1255 major coronary disease events (861 cases of non-fatal myocardial infarction and 394 cases of fatal coronary heart disease) occurred during 14 years of follow up. After adjusting for age, smoking, and other known risk factors for coronary heart disease, women who ate more than five units of nuts (one unit equivalent to 1 oz of nuts) a week (frequent consumption) had a significantly lower risk of total coronary heart disease (relative risk 0.65, 95% confidence interval 0.47 to 0.89, P for trend=0.0009) than women who never ate nuts or who ate less than one unit a month (rare consumption). The magnitude of risk reduction was similar for both fatal coronary heart disease (0.61, 0.35 to 1.05, P for trend=0.007) and non-fatal myocardial infarction (0.68, 0.47 to 1.00, P for trend=0.04). Further adjustment for intakes of dietary fats, fibre, vegetables, and fruits did not alter these results. The inverse association persisted in subgroups stratified by levels of smoking,use of alcohol, use of multivitamin and vitamin E supplements, body mass index, exercise, and intake of vegetables or fruits. CONCLUSIONS: Frequent nut consumption was associated with a reduced risk of both fatal coronary heart disease and non-fatal myocardial infarction. These data, and those from other epidemiological and clinical studies, support a role for nuts in reducing the risk of coronary heart disease.

Intake of potassium, magnesium, calcium, and fiber and risk of stroke among US men.

BACKGROUND: Animal experiments and epidemiological studies have suggested that high potassium intake may reduce the risk of stroke, but the evidence is inconclusive, and the role of other nutrients in potassium-rich foods remains unknown. METHODS AND RESULTS: We examined the association of potassium and related nutrients with risk of stroke among 43 738 US men, 40 to 75 years old, without diagnosed cardiovascular diseases or diabetes, who completed a semiquantitative food frequency questionnaire in 1986. During 8 years of follow-up, 328 strokes (210 ischemic, 70 hemorrhagic, 48 unspecified) were documented. The multivariate relative risk of stroke of any type for men in the top fifth of potassium intake (median intake, 4.3 g/d) versus those in the bottom (median, 2.4 g/d) was 0.62 (95% CI, 0.43, 0.88; P for trend=0.007). Results for ischemic stroke alone were similar. Intakes of cereal fiber and magnesium, but not of calcium, were also inversely associated with risk of total stroke. These inverse associations were all stronger in hypertensive than normotensive men and were not materially altered by adjustment for blood pressure levels. Use of potassium supplements was also inversely related to risk of stroke, particularly among men taking diuretics (relative risk, 0.36; 95% CI, 0.18, 0.72). CONCLUSIONS: Although these data do not prove a causal relationship, they are consistent with the hypothesis that diets rich in potassium, magnesium, and cereal fiber reduce the risk of stroke, particularly among hypertensive men. Potassium supplements may also be beneficial, but because of potential risks, use should be carefully monitored and restricted to men taking potassium-losing diuretics.

Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer.

BACKGROUND: In a recent randomized intervention trial, the risk of prostate cancer for men receiving a daily supplement of 200 microg selenium was one third of that for men receiving placebo. By use of a nested case-control design within a prospective study, i.e., the Health Professionals Follow-Up Study, we investigated the association between risk of prostate cancer and prediagnostic level of selenium in toenails, a measure of long-term selenium intake. METHODS: In 1986, 51,529 male health professionals aged 40-75 years responded to a mailed questionnaire to form the prospective study. In 1987, 33,737 cohort members provided toenail clippings. In 1988, 1990, 1992, and 1994, follow-up questionnaires were mailed. From 1989 through 1994, 181 new cases of advanced prostate cancer were reported. Case and control subjects were matched by age, smoking status, and month of toenail return. Selenium levels were determined by neutron activation. All P values are two-sided. RESULTS: The selenium level in toenails varied substantially among men, with quintile medians ranging from 0.66 to 1.14 microg/g for control subjects. When matched case-control data were analyzed, higher selenium levels were associated with a reduced risk of advanced prostate cancer (odds ratio [OR] for comparison of highest to lowest quintile = 0.49; 95% confidence interval [CI] = 0.25-0.96; P for trend = .11). After additionally controlling for family history of prostate cancer, body mass index, calcium intake, lycopene intake, saturated fat intake, vasectomy, and geographical region, the OR was 0.35 (95% CI = 0.16-0.78; P for trend = .03). CONCLUSIONS: Our results support earlier findings that higher selenium intakes may reduce the risk of prostate cancer. Further prospective studies and randomized trials of this relationship should be conducted.

Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women.

CONTEXT: Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B6. However, prospective data relating intake of these vitamins to risk of coronary heart disease (CHD) are not available. OBJECTIVE: To examine intakes of folate and vitamin B6 in relation to the incidence of nonfatal myocardial infarction (MI) and fatal CHD. DESIGN: Prospective cohort study. SETTING AND PATIENTS: In 1980, a total of 80082 women from the Nurses' Health Study with no previous history of cardiovascular disease, cancer, hypercholesterolemia, or diabetes completed a detailed food frequency questionnaire from which we derived usual intake of folate and vitamin B6. MAIN OUTCOME MEASURE: Nonfatal MI and fatal CHD confirmed by World Health Organization criteria. RESULTS: During 14 years of follow-up, we documented 658 incident cases of nonfatal MI and 281 cases of fatal CHD. After controlling for cardiovascular risk factors, including smoking and hypertension and intake of alcohol, fiber, vitamin E, and saturated, polyunsaturated, and trans fat, the relative risks (RRs) of CHD between extreme quintiles were 0.69 (95% confidence interval [CI], 0.55-0.87) for folate (median intake, 696 microg/d vs 158 microg/d) and 0.67 (95% CI, 0.53-0.85) for vitamin B6 (median intake, 4.6 mg/d vs 1.1 mg/d). Controlling for the same variables, the RR was 0.55 (95% CI, 0.41-0.74) among women in the highest quintile of both folate and vitamin B6 intake compared with the opposite extreme. Risk of CHD was reduced among women who regularly used multiple vitamins (RR=0.76; 95% CI, 0.65-0.90), the major source of folate and vitamin B6, and after excluding multiple vitamin users, among those with higher dietary intakes of folate and vitamin B6. In a subgroup analysis, compared with nondrinkers, the inverse association between a high-folate diet and CHD was strongest among women who consumed up to 1 alcoholic beverage per day (RR =0.69; 95% CI, 0.49-0.97) or more than 1 drink per day (RR=0.27; 95% CI, 0.13-0.58). CONCLUSION: These results suggest that intake of folate and vitamin B6 above the current recommended dietary allowance may be important in the primary prevention of CHD among women.