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Rimm EB, Willett WC, Hu FB, et al. Folate and Vitamin B6 From Diet and Supplements in Relation to Risk of Coronary Heart Disease Among Women. JAMA. 1998;279(5):359–364. doi:10.1001/jama.279.5.359
From the Departments of Epidemiology (Drs Rimm, Willett, Colditz, Manson, Hennekens, and Stampfer) and Nutrition (Drs Rimm, Willett, Hu, and Stampfer and Ms Sampson), Harvard School of Public Health, Boston, Mass; the Channing Laboratory (Drs Rimm, Willett, Colditz, Manson, Hennekens, and Stampfer) and the Division of Preventive Medicine (Drs Manson and Hennekens), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; and the Department of Ambulatory Care and Prevention (Dr Hennekens) Harvard Medical School, Boston, Mass.
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 µg/d vs 158
µg/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,
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.
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