Folic acid supplements have been considered as safe. A combined analysis from 2009 of two Norwegian randomized controlled clinical trials, with extended post-trial follow-up, demonstrated however, an increased incidence of cancer among patients taking folic acid for homocysteine reduction as secondary prevention of cardiovascular events. In Norway folic acid is among the 10 most sold non-prescription drugs with 17.5 defined daily doses per 1000 inhabitants/day. Norwegian guidelines have since 1998 recommended supplements of folic acid 0.4 mg daily to women periconceptionally in order to reduce the risk of neural tube defects.

The present systematic review explores whether there is an increased cancer risk associated with folic acid supplements given orally. This is done in a systematic review and meta-analysis including controlled studies (randomised and observational) of folic acid supplementation.

Key messages

• Meta-analysis of ten RCTs with mainly elderly men with cardiovascular disease showed a borderline significant increase in incidence of cancer in the folic acid group compared to controls. Overall cancer incidence was not studied in the seven observational studies.When analysing site-specific cancers, prostate cancer was the only cancer type where increased risk was shown for folic acid supplements. No increased incidence of cancer was found in the seven observational studies.
• This review found insufficient documentation to conclude about cancer risk for fertile women that are recommended folic acid periconceptionally in order to reduce the risk of neural tube defects.