Taking folic acid supplements neither increases nor decreases the incidence of cancer during the treatment period, according to a meta-analysis of 13 large randomized controlled trials that examined this issue, which was reported online Jan. 25 in the Lancet.
Folic acid fortification of flour to prevent neural tube defects has been mandatory in several countries beginning in the late 1990s, and since then further supplementation has been touted as a possible cancer preventive. But several other countries do not allow folic acid fortification and discourage supplementation, partly because of fear that it could promote cancer incidence or progression.
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Folic acid supplements did not increase or decrease incidence of cancer according to a meta-analysis with nearly 50,000 subjects.
The investigators reviewed all the randomized trials published in the medical literature through 2010 that assessed the effects of folic acid supplements. Trials were included in the meta-analysis if they contained at least 500 subjects, assessed cancer incidence as an outcome, and randomized subjects to either supplements or placebo for at least 1 year. The researchers included 13 trials with 49,621 subjects in their meta-analysis.Neither the hope that folic acid supplements might prevent cancer nor the fear that they might promote it were borne out by this meta-analysis, said Dr. Stein Emil Vollset of the Norwegian Institute of Public Health and the University of Bergen (Norway), and his associates.
Two-thirds of the participants were men, and the mean age at baseline was 64 years. Daily doses of folic acid ranged from 0.5 mg to 5 mg in 12 of the studies, and another study assessed a high dose of 40 mg daily. The duration of treatment was 1.8-7.4 years (mean, 5.2 years).
Taking the supplements was associated with a quadrupling of plasma levels of folate and a 25% reduction in plasma homocysteine levels. In the single trial of high-dose folic acid, supplements raised plasma levels of folate 100-fold but produced little further effect on plasma homocysteine levels.
Folic acid supplementation had no significant effect on the incidence of cancer overall. The rate of all types of cancer was 7.7% in subjects who took the supplements and 7.3% in subjects who took placebo, a nonsignificant difference, Dr. Vollset and his colleagues reported (Lancet 2013 [doi: 10.1016/S0140-6736(12)62001-7]).
The overall cancer incidence did not change with increasing duration of treatment or increasing dose of the supplements, nor did it vary by patient age, sex, baseline folate levels, baseline homocysteine levels, or the use of flour fortification in the country of residence.
Even in the trial of high-dose supplements that raised plasma levels of folate 100-fold, there was no significant difference in overall cancer incidence between the supplement group (65 cancers) and the placebo group (72 cancers).
Folic acid supplementation also had no effect on the incidence of site-specific cancers, including colorectal, lung, breast, and prostate cancers. Thus, these trials "provide no significant evidence of short-term effects of folic acid supplementation on overall cancer incidence or on the incidence of any particular type of cancer," the researchers said.
Neither this meta-analysis nor the randomized controlled trials it was based on addressed whether there are longer-term beneficial or harmful effects of folic acid supplementation, they added.
This study was supported by the British Heart Foundation, the UK Medical Research Council, Cancer Research UK, and the UK Food Standards Agency.