A prospective study of folate and vitamin B6 and risk of myocardial infarction in US physicians

J Am Coll Nutr. 1996 Apr;15(2):136-43. doi: 10.1080/07315724.1996.10718578.


Objective: To assess prospectively the risk of myocardial infarction (MI) associated with decreased plasma levels of folate and pyridoxal phosphate (PLP, a form of vitamin B6) in relation to elevated levels of total homocysteine (tHcy).

Design: Nested case-control study using prospectively collected blood samples.

Setting: Participants in the Physicians' Health Study.

Subjects: 14,916 male physicians, aged 40-84 years, with no prior MI or stroke provided plasma samples at baseline and were followed for 7.5 years. Samples from 333 men who subsequently developed MI, and their paired controls matched by age and smoking, were analyzed for folate and PLP levels.

Measures of outcome: Acute MI or death due to coronary disease.

Results: In a model controlling for diabetes, angina, hypertension, Quetelet's index, and total/high-density lipoprotein cholesterol, men with the lowest 20% of folate levels (< 2.0 ng/mL) had a relative risk of 1.4 (95% confidence interval 0.9-2.3) compared with those in the top 80%. For the lowest 20% of vitamin B6 values, the relative risk was 1.5 (95% CI: 1.0-2.2). When we included both folate and B6 in a model with cardiovascular risk factors, the relative risk of MI for low as compared to high levels of folate was 1.3 (95% CI: 0.8-2.1) and for PLP, 1.3 (95% CI: 0.9-2.1). Adding tHcy to this model did not add significant predictive value (chi sq = 2.0, p > 0.05), except in the first half of the follow-up interval when men with the top 5% of tHcy values had an almost three-fold increase in risk of MI.

Conclusions: Although not statistically significant, these prospective data are compatible with the hypothesis that low dietary intake of folate and/or vitamin B6 contribute to risk of MI.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cohort Studies
  • Diet
  • Folic Acid / blood*
  • Homocysteine / blood
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / etiology*
  • Myocardial Infarction / prevention & control
  • Prospective Studies
  • Pyridoxal Phosphate / blood
  • Pyridoxine / blood*
  • Risk Factors


  • Homocysteine
  • Pyridoxal Phosphate
  • Folic Acid
  • Pyridoxine