Daily folic acid supplements may double the risk of prostate cancer amongst men, according to a new US study that raises questions about fortification with the vitamin.
According to findings published in the Journal of the National Cancer Institute, daily folic acid supplements of one milligram were associated with a doubling had more than twice the risk of prostate cancer compared with men who took a placebo.
The study, led by Jane Figueiredo, PhD, an assistant professor of preventive medicine at the University of Southern California (USC) also suggested that high folate levels at the start of the study were associated with a protective effect against prostate cancer.
“This clinical trial provides evidence that daily supplementation with 1 mg of folic acid was associated with an increased risk of prostate cancer,” wrote Figueiredo. “It is unclear why dietary and plasma levels among non-multivitamin users may be inversely associated with risk.
“These findings highlight the potentially complex role of folate in prostate carcinogenesis,” she added.
Commenting on the study, the editors of the journal wrote: “Given the small number of prostate cancers in this study, the estimates of prostate cancer risk in the placebo and folic acid groups should be interpreted with caution.”
Andrew Shao, PhD, vice president, scientific and regulatory affairs, from the Council for Responsible Nutrition (CRN), a trade association, said that the results of the study are “intriguing and warrant further research”.
“It is important to point out that the amount of folic acid given to participants in this study (1 milligram daily) was well above the recommended intake levels and the amount found in daily multivitamins, which typically contain 200-400 micrograms.
“It would be inappropriate at this point to reach firm conclusions based on such limited data, especially in the face of vast evidence showing benefit for folic acid supplementation,” said Dr Shao.
“To their credit, the investigators acknowledge the limitations of the study, suggesting it is premature to issue any specific safety recommendations,” he added.
The folate-folic acid story
Folate is found in foods such as green leafy vegetables, chick peas and lentils, and an overwhelming body of evidence links has linked folate deficiency in early pregnancy to increased risk of neural tube defects (NTD) - most commonly spina bifida and anencephaly - in infants.
This connection led to the 1998 introduction of public health measures in the US and Canada, where all grain products are fortified with folic acid - the synthetic, bioavailable form of folate.
While preliminary evidence indicates that the measure is having an effect with a reported 15 to 50 per cent reduction in NTD incidence, parallel measures in European countries, including the UK and Ireland, are still on the table.
The researchers performed a secondary analysis of data from the Aspirin/Folate Polyp Prevention Study (AFPP), a placebo-controlled randomised trial to investigate the role of aspirin and folic acid on colon health in men and women at high risk of the disease.
Of the 643 men who were randomly assigned to one milligram of folic acid per day or placebo, the researchers estimated the risk of prostate cancer to be 9.7 per cent at 10 years in men in the folic acid group, and 3.3 per cent in men in the placebo group.
On the other hand, dietary folate intake and plasma folate levels showed a trend toward reduced risk of prostate cancer, although the difference did not reach statistical significance.
"The synthetic form of folate, folic acid, found in supplements, is more bioavailable compared to folate from dietary sources and we know the amount of folate available is critical," said Figueiredo. "Adequate levels of folate may be beneficial, but too much folate is unlikely to be beneficial."
Alternatively, these results may be due to chance, and replication by other studies is needed, she noted.
The study was supported by the National Cancer Institute and the National Institutes of Health.
Commenting on the study, Dr Shao added: “We must not lose sight of the safe, well-established benefits of folic acid supplementation/fortification for women of childbearing age to prevent neural tube defects, as well as other potential benefits of folic acid supplementation, such for cardiovascular health and cognitive function in the general population.
“The most important message for the scientific community is that research on the cancer preventative effects of diet and micronutrients, including folic acid, should continue.
“For consumers, the most important message is that they should continue to feel confident in the safety and efficacy of consuming the recommended amounts of folic acid as part of an overall healthy lifestyle,” added Dr Shao.
Source: Journal of the National Cancer Institute
Published online ahead of print, doi: 10.1093/jnci/djp019
“Folic Acid and Risk of Prostate Cancer: Results From a Randomized Clinical Trial”
Authors: J.C. Figueiredo, M.V. Grau, R.W. Haile, R.S. Sandler, R.W. Summers, R.S. Bresalier, C.A. Burke, G.E. McKeown-Eyssen, J.A. Baron.