Low dietary folate intake is associated with an excess incidence of acute coronary events: The Kuopio Ischemic Heart Disease Risk Factor Study

Circulation. 2001 Jun 5;103(22):2674-80. doi: 10.1161/01.cir.103.22.2674.


Background: Although several prospective studies have shown that low folate intake and low circulating folate are associated with increased risk of coronary heart disease (CHD), the findings are inconsistent.

Methods and results: We studied the associations of dietary intake of folate, vitamin B(6), and vitamin B(12) with the risk of acute coronary events in a prospective cohort study of 1980 Finnish men 42 to 60 years old examined in 1984 to 1989 in the Kuopio Ischemic Heart Disease Risk Factor Study. Nutrient intakes were assessed by 4-day food record. During an average follow-up time of 10 years, 199 acute coronary events occurred. In a Cox proportional hazards model adjusted for 21 conventional and nutritional CHD risk factors, men in the highest fifth of folate intake had a relative risk of acute coronary events of 0.45 (95% CI 0.25 to 0.81, P=0.008) compared with men in the lowest fifth. This association was stronger in nonsmokers and light alcohol users than in smokers and alcohol users. A high dietary intake of vitamin B(6) had no significant association and that of vitamin B(12) a weak association with a reduced risk of acute coronary events.

Conclusions: The present work in CHD-free middle-aged men is the first prospective cohort study to observe a significant inverse association between quantitatively assessed moderate-to-high folate intakes and incidence of acute coronary events in men. Our findings provide further support in favor of a role of folate in the promotion of good cardiovascular health.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Analysis of Variance
  • Clinical Trials as Topic
  • Cohort Studies
  • Coronary Disease / blood
  • Coronary Disease / epidemiology
  • Coronary Disease / prevention & control*
  • Diet
  • Dose-Response Relationship, Drug
  • Finland / epidemiology
  • Folic Acid / administration & dosage*
  • Folic Acid / blood
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prospective Studies
  • Pyridoxine / administration & dosage
  • Risk Factors
  • Vitamin B 12 / administration & dosage


  • Folic Acid
  • Pyridoxine
  • Vitamin B 12