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Epidemiologic data and findings from animal studies suggest a beneficial effect of folic acid in primary prevention of colorectal cancer. In an international multisite study, investigators assessed whether folic acid supplementation prevents colorectal adenomas by enrolling 1021 adults (mean age, 57) with at least one recently removed adenoma. All known polyps were removed within 3 months of enrollment. Subjects were randomized to supplementation with folic acid (1 mg/day) or placebo and underwent colonoscopy roughly 3 years after randomization; 607 participants continued to a second colonoscopy at roughly 6 years.
Risk for adenoma formation did not differ significantly between the folic acid and placebo groups (44% vs. 42% at 3 years, 42% vs. 37% at 6 years). A trend toward more high-grade adenomas was observed in the folic acid group (11% vs. 9% at 3 years, 12% vs. 7% at 6 years). The incidence of noncolorectal cancers was significantly higher in the folic acid group (11% vs. 6%), mostly because of an increase in prostate cancer.
Cole BF et al. Folic acid for the prevention of colorectal adenomas: A randomized clinical trial. JAMA 2007 Jun 6; 297:2351-9.
Ulrich CM and Potter JD. Folate and cancer — Timing is everything. JAMA 2007 Jun 6; 297:2408-9.
Comment
These results show no benefit from folic acid supplementation in secondary prevention of colorectal adenomas, with a possible increased risk for higher-grade adenomas. As editorialists note, the findings raise questions about possible differential effects of timing: Early folic acid supplementation may prevent adenoma formation, but supplementation after the earliest stages of adenoma development may promote carcinogenesis. This possibility urgently requires further study, because the U.S. food supply has been fortified with folic acid since 1998.