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Folic acid supplementation did not affect cancer incidence
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Folic acid supplementation showed no significant effect on the incidence of overall or site-specific cancer during the first 5 years of treatment, according to results of a meta-analysis.
The fortification of flour with folic acid for the prevention of neural defects has been mandatory in the United States since 1998. The practice is mandatory in several other countries, yet New Zealand and western European countries do not follow it due to concerns about increased cancer risks, according to background information in the study.
In the current study, Stein E. Vollset, MD, a professor in the department of public health and primary health care for the Norwegian Institute of Public Health at the University of Bergen in Bergen, Norway, and colleagues examined the effects of folic acid supplementation on site-specific cancer rates in randomized trials completed before 2011. The researchers identified trials that compared folic acid vs. placebo, had scheduled treatment durations of at least 1 year, included at least 500 participants and produced data on cancer incidence.
Vollset and colleagues included data from 13 randomized trials in their analysis. The trials included a combined 49,621 patients.
The weighted average scheduled treatment duration was 5.2 years.
Study results showed that supplementation quadrupled plasma concentrations of folic acid but had no significant effect on overall cancer incidence. The researchers reported 1,904 cancers among patients assigned to folic acid and 1,809 cancers among patients assigned to placebo (RR=1.06; 95% CI, 0.99-1.13).
Researchers did not observe a trend toward greater effect with longer treatment, nor did they find significant heterogeneity in the results of the 13 trials (P=.23).
The results also did not demonstrate a significant association between folic acid supplementation and incidence of cancer of the large intestine, prostate, lung, breast or any other specific site.
“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,” Vollset and colleagues wrote.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Ralph Green, MD, PhD, FRCPath
The relationship between folate and cancer is complex. There is a yin yang effect of folate on cancer incidence. Folate is required for synthesis of thymidine and purines that play a role in both DNA repair and cell proliferation. Cancer cells require folate for proliferation, and one of the most powerful anticancer agents is the antifol methotrexate. However, in the precancerous state, folate may play an anticancer role by also assisting with DNA repair. Also, folate plays a role in providing methyl groups for gene silencing, which may influence expression of either oncogenes or tumor suppressor genes. Considering this complex matrix of possible effects of folate on cancer initiation and progression, it is possible that the study by Vollset and colleagues, as well as others that showed no discernible effect of folic acid intake on cancer incidence, conceals the underlying anticancer effects of folate in some individuals being balanced by the cancer-promoting effects of folate in others.
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