Researchers have established that short-term use of folic acid supplements is unlikely to substantially increase or decrease overall cancer risk and has little effect on the risk of developing any specific cancer including cancer of the colon, prostate, lung and breast.
The findings of a meta-analysis involving almost 50 000 individuals were published online first in The Lancet.
"The study provides reassurance about the safety of folic acid intake, either from supplements or through fortification, when taken for up to five years," said Robert Clarke, MD, University of Oxford, Oxford, United Kingdom.
"The nationwide fortification of foods involves much lower doses of folic acid than studied in these trials, which is reassuring not only for the U.S., who have been enriching flour with folic acid to prevent neural tube birth defects since 1998, but also for over 50 other countries where fortification is mandatory (i.e., Australia, South Africa, Chile, Argentina, and Brazil)."
Dr. Clarke and colleagues from the B-Vitamin Treatment Trialists' Collaboration conducted a meta-analysis of all large randomised trials of folic acid supplementation (alone or in combination with other B vitamins) up to the end of 2010.
They found that those who took daily folic acid for five years or less were not significantly more likely to develop cancer than those who took placebo, with 1,904 (7.7 percent) new cases of cancer reported in the folic acid groups and 1,809 (7.3 percent) in the placebo groups.
Even among those with the highest average intake of folic acid (40 mg/day) no significant increase in overall cancer incidence was noted.
In addition, there was no significant difference between folic acid and placebo groups in the number of participants experiencing colorectal, lung, breast, prostate, or any other type of cancer. Importantly, there was also no evidence that the risk of developing cancer increased with longer folic acid treatment.
"Both the hopes for rapid cancer prevention and the fears about rapidly increased cancer risk from folic acid supplementation were not confirmed by this meta-analysis," said Dr. Clarke.
However, he cautioned that "it remains to be seen whether any beneficial or harmful effects on cancer incidence will eventually emerge with even longer treatment or follow-up."
In an accompanying commentary, Cornelia M. Ulrich, National Center for Tumor Diseases, and German Cancer Research Center, Heidelberg, Germany, and Joshua W. Miller, Rutgers University, New Brunswick, New Jersey, discuss the importance of taking into account the dual relationship of folate with cancer—how it may cause existing cancer cells to grow, but protects against initiation—when interpreting the results. They noted that this relationship has potentially significant ramifications for "those who consume excess folic acid from fortification and supplements combined," they wrote. "Notably, 1 percent to 4 percent of the U.S. population, depending on age, sex and ethnic origin, exceed the tolerable upper limit (1 mg/day) for total consumption of folic acid."