Too much folate: a risk factor for cancer and cardiovascular disease?

Curr Opin Clin Nutr Metab Care. 2009 Jan;12(1):30-6. doi: 10.1097/MCO.0b013e32831cec62.


Purpose of review: The intent of this evidence-based review is to analyze the role of folate in chronic diseases, focusing on cancer and cardiovascular disease.

Recent findings: Low folate status has been shown to be a risk factor for cancer and cardiovascular disease. Although epidemiological data suggest an inverse association between folate status and disease risk, intervention studies give equivocal results, suggesting the response to folate intake does not follow a linear continuum. Moreover, recent folate intervention trials raise concern about possible adverse effects of folate supplementation and suggest that too much folate in inopportune settings may be potentially harmful in individuals at higher risk for cardiovascular disease and cancer.

Summary: Although folate intake at sufficient levels appears to be an effective cancer chemopreventive strategy, high-dose supplementation of folate has generally not been effective in reducing recurrence of cardiovascular events or colorectal adenomas in clinical intervention trials. Although controversial, high folate status achieved through folate fortification or supplementation may increase the risk of certain chronic diseases among certain individuals, possibly by interfering with the homeostasis of one-carbon metabolism. Further research is urgently needed to accurately define the relationship between supraphysiological intake of folate and chronic diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Adenoma / chemically induced
  • Adenoma / prevention & control
  • Cardiovascular Diseases / chemically induced*
  • Chronic Disease
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / prevention & control
  • Dietary Supplements
  • Dose-Response Relationship, Drug
  • Epigenesis, Genetic
  • Folic Acid / administration & dosage
  • Folic Acid / adverse effects*
  • Folic Acid / metabolism
  • Homocysteine / blood
  • Humans
  • Neoplasms / chemically induced*
  • Neoplasms / prevention & control
  • Risk Factors


  • Homocysteine
  • Folic Acid