Does folic acid supplementation reduce the risk of colorectal cancer in adults?

Folic acid supplementation (1 mg/d) does not reduce the risk of colorectal adenoma. Interestingly, daily folic acid actually increased the risk of advanced colorectal lesions, suggesting supplementation might actually increase the risk of cancer. (LOE = 1b)

Cole BF, Baron JA, Sandler RS, et al, for the Polyp Prevention Study Group. Folic acid for the prevention of colorectal adenomas. A randomized clinical trial. JAMA 2007;297:2351-2359.  [PMID:17551129]

Randomized controlled trial (double-blinded)

Industry + govt

Concealed

Outpatient (specialty)

Recent evidence suggests that folic acid may have an antineoplastic effect in the large intestine. These investigators enrolled 1021 adults, aged 21 years to 80 years, with a recent history of colorectal adenoma without known colon cancer. Eligible subjects randomly received, in double-blind fashion, with concealed allocation assignment, aspirin plus 1 mg folic acid per day, aspirin alone, 1 mg folic acid per day alone, or placebo. Findings associated with aspirin were reported separately (Baron JA, et al. N Eng J Med 2003;348:891-899). Individuals assessing outcomes remained masked to treatment group assignment. Follow-up occurred for 91% of subjects for up to 8 years. Using intention-to-treat analysis, there was no significant difference at 3 years or at 6 to 8 years in the incidence of colorectal adenoma detected by colonoscopy between the group taking folic acid and those taking placebo (44.1% vs 42.4%; 41.9% vs 37.2%, respectively). The incidence of at least one advanced colorectal lesion was, however, significantly higher among patients assigned to the folic acid supplementation group (11.6% vs 6.9%; number needed to treat to harm = 38). The study was 94% powered to detect a 40% reduction in the risk of adenoma with folic acid supplementation.