A New Study Links Folic Acid and Vitamin-B12 to Increased Cancer Risk

Folate and vitamin-B12 are B-vitamins used by the body to produce DNA within cells. These vitamins are of particular importance for red blood cells and deficiency leads to eventual anemia. Multivitamins, supplements, and fortified foods contain folic acid, which is the synthetic form of folate. The folate pathway is the target of methotrexate, a drug used to curb inflammation in chronic conditions such as Crohn's disease, rheumatoid arthritis, and psoriasis.

Folate deficiency during pregnancy has been linked with the neuronal birth defect known as spina bifida. For this reason, flour and grain products are fortified in the United States with folic acid. A new study published in the journal JAMA suggests that folic acid and vitamin-B12 supplementation may increase the risk of cancer development. This raises public policy questions about the use of folic acid in the United States to fortify foods.

The study was conducted in Norway, a country that does not fortify its food with folic acid. The study was a follow up to two studies where the original goal was to assess the use of folic acid and vitamin-B12 together to improve health outcomes for patients with heart disease. However, folic acid and vitamin-B12 supplementation provided no additional benefit for heart disease patients. Unexpectedly, folic acid and vitamin-B12 increased the risk for cancer development in comparison to placebo or vitamin-B6 alone treated groups. Approximately 10% of individuals receiving folic acid plus vitamin-B12 developed cancer in comparison to 8.4% of those receiving either placebo or vitamin-B6. Deaths from cancer or from any cause were increased in the folic acid plus vitamin-B12 treated groups compared to the other groups, with statistically significant hazard ratios of 1.38 and 1.18 respectively.

Although the data is alarming, the authors did point out limitations to their study. Family history and exposure to environmental risk factors for cancer were not accounted for. The authors also pointed out that their data needs to be confirmed by other long term trials before concrete conclusions can be made regarding the overall safety of folic acid and vitamin-B12 in relation to cancer. The dose of folic acid given was 4 to 6 times higher than what would be expected from fortified foods in the United States, making a correlation to consuming supplemented foods alone difficult.

Which characteristics may leave one individual more susceptible to carcinogenesis while ingesting folic acid over another remains unclear. The level of folic acid that may promote oncogenesis is another area in question, as low level supplementation in animals may be protective against cancer. Interestingly, mean plasma levels of folic acid in the United States are lower than those reported in the folic acid treated groups in the study.

Although the contribution of folic acid and vitamin-B12 supplementation to cancer development remains unclear, it does raise several safety questions that should be addressed. Does the fortification of foods in United States represent a significant modifiable risk factor for cancer development? Does additional folic acid intake in multivitamins and supplements, in addition to fortified food, provide any long term health benefit that is offset by the possible induction of cancer?

References:

Drake, BF; Colditz, GA. Assessing Cancer Prevention Studies - A Matter of Time. JAMA. 2009; 302 (19): 2152-2153

Ebbing M, Bonaa KH, Nygard O, et al. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA. 2009;302(19):2119-2126

Katzung B, Masters S, Trevor A. Basic and Clinical Pharmacology. 2009. McGraw-Hill Medical; 11 edition