Noting that some countries have been hesitant to fortify flour with folic acid due to concerns about cancer incidence, Stein Emil Vollset, M.D., from the Norwegian Institute of Public Health in Bergen, and colleagues conducted a meta-analysis of data from 49,621 participants in 13 trials that compared folic acid with placebo and recorded data on cancer incidence. The authors sought to examine any effects of site-specific cancer rates with folic acid supplementation.

The researchers found that, during a weighted average scheduled treatment duration of 5.2 years, participants randomized to receive folic acid versus placebo had a four-fold increase in the plasma concentration of folic acid (57.3 versus 13.5 nmol/L). However, no significant effect was observed on overall cancer incidence, and there was no indication of a greater effect with longer duration of treatment. The results of the individual trials were not marked by significant heterogeneity. Folic acid supplementation also had no significant effect on the incidence of cancer of the large intestine, prostate, breast, lung, or any other specific site.

"The present meta-analysis rules out moderate increases in overall cancer incidence from folic acid supplementation during the trials," the authors write. "Nationwide dietary fortification involves doses of folic acid that are an order of magnitude lower than the doses studied in these trials."

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