Decreased Coronary Artery Disease in Women with Increased Folate and Vitamin B6 Intake


Synopsis: During 14 years of follow-up, those women with low intakes of folate and B6 had higher cardiovascular risk. The opposite was also true; those with high intakes of folate and B6 had lower risk of coronary heart disease.

Source: Rimm EB, et al. JAMA 1998;279:359-364.

Rimm and colleagues conducted a prospective cohort study in 80,082 women from the Nurses' Health Study who had no previous history of cardiovascular disease, cancer, hypercholesterolemia, or diabetes. They analyzed their food frequency questionnaires, and they were able to derive their usual intake of folate and B6.

By then following these nurses' health over a 14-year period, they were able to calculate the incidence of nonfatal MIs and fatal coronary heart disease. With the 658 cases of nonfatal MI and the 281 cases of fatal coronary heart disease compared to folate and B6 intake, the authors were able to develop relative risk of quintiles of B6 and folate intake compared to incidence of coronary heart disease. They found that, at the lowest level of folate and B6 intake, there was significant coronary artery disease. At the highest level of intake (almost 4 times higher than the lowest quintile), they found half as much coronary heart disease.

Then, by further analyzing the data, they found that moderate amounts of alcohol intake strongly decreased the cardiovascular risk among the women with the highest folate and B6 intakes.

Rimm et al conclude that the current recommended dietary allowances of folate and B6 need to be raised to increase a primary prevention of coronary heart disease among women.


As a primary care physician reading the medical literature, I was always interested in why there was so much excitement about homocystinuria and its relation to coronary disease. After all, how often does anybody see homocystinuria? Drawing a blood homocysteine level was not exactly a common test either.

Rimm et al have done a great service to primary care by pointing out that folate and B6 are important cofactors for the homocysteine metabolism. By looking at patients or nurses in the Nurses' Health Study who took different amounts of folate and B6 , they found that high amounts had reduced the incidence of coronary heart disease. We are already recommending higher amounts in primary care preconception counseling because of its reduction of neural tube defects in pregnant women.

What is most fascinating about Rimm et al's study is that the protective effect with folate and B6 intake holds true for all ages at all levels after correcting for the other significant risk factors such as smoking or diabetes.

By comparing alcohol consumption in nondrinkers, mild drinkers, and moderate drinkers, the authors found that the relative risk of coronary heart disease was also reduced across all folate and B6 intake levels. (It should be noted that extreme amounts of ETOH were not analyzed.)

In a related editorial by McCully, animal and bench data regarding the homocysteine theory of arteriosclerosis is discussed. Also mentioned are dietary data showing reduction of folate and B6 because of the increase of white flower, white rice, sugar, fats, and oils in our diet.

McCully also discusses that moderate alcohol intake decreases cardiovascular risk among women, reflecting other studies that have been done about alcohol intake, and theorizes why this might be so.

As primary care physicians, recommending a multivitamin with folate and B6 intake above the recommended dietary allowance may, in fact, reduce coronary heart disease among women. This would be additive to mild-to-moderate alcohol consumption.