Cancer risk independent of folic acid supplementation

By Lynda Williams, Senior medwireNews Reporter

Folic acid supplementation does not increase or decrease the risk for cancer, suggests research published in The Lancet.

The scientists collated data for 49,621 patients participating in 10 clinical trials of folic acid for the prevention of cardiovascular disease and three for the prevention of colorectal cancer in patients with adenomas.

Over an average of 5.2 years of supplementation, plasma concentrations of folic acid quadrupled in the patients given the vitamin versus those given placebo (57.3 vs 13.5 nmol/L), but there was no significant difference in the overall incidence of cancer excluding non-melanoma skin cancers (7.7 vs 7.3%, relative risk =1.06).

There was also no significant relationship between cancer incidence and duration of folic acid supplementation. Nor was there significant heterogeneity across the 13 trials or between the cardiovascular and colorectal adenoma studies, say Robert Clarke (University of Oxford, UK) and co-authors.

In addition, the team found no evidence for a link between folic acid supplementation and the risk for site-specific malignancy, such as cancers of the breast, prostate, lung, or large intestine.

Clarke et al comment: "The median daily dose of folic acid in the trials was 2.0 mg, which is greater than in most widely used vitamin supplements (0.1-0.8 mg) and an order of magnitude greater than the dose typically delivered by flour fortification programmes (0.1-0.4 mg)."

However, Joshua Miller (Rutgers University in New Brunswick, New Jersey, USA) and Cornelia Ulrich (Fred Hutchinson Cancer Research Center, Seattle, Washington, USA) write in an accompanying commentary that the findings should be "viewed with caution."

They note that the 6% increase in overall cancer risk and the 15% increase in prostate cancer risk were both close to statistical significance, and that although these risks are small, they could place individuals receiving excessive folic acid from use of both supplements and fortified foods at risk.

"The complexity of the biological relation between folate and cancer requires cautious interpretation," Miller and Ulrich conclude. "Additional epidemiological and statistical analyses are warranted to address population-based hypotheses that are consistent with our current understanding of the biochemistry and biology of folate and cancer."

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