It seems as though for every study in support of a dietary supplement there is a contradictory study that demotes the supplement. Researchers at St. Michael’s Hospital in Canada published an article this month in PLoS ONE describing a possible link between folic acid–the synthetic form of folate, a B vitamin–and an increased risk of developing breast cancer. Folate intake has increased in the last 15 years due to mandatory fortification of white flour, enriched pasta, and cornmeal products; natural folate is found in leafy green vegetables, broccoli, egg yolks, lentils, and oranges. The recommended daily intake for men and women over 19 years of age is 400 micrograms (mcg), but for women who are trying to conceive, the recommendation is four times that amount in order to reduce incidence of neural tube defects in their newborn child. Another population who often supplements with folic acid is cancer patients; cancer survivors use vitamin supplementation more than the general population. This is why at first glance the study by Dr. Young-In Kim may be alarming–after all, why use a supplement that promotes cancer if you just survived cancer?
Before any recommendations are made for or against folic acid supplementation, it is important to understand the experiments conducted and the interpretation of the results. The study used rats as subjects; newborn rats were given a normal diet with 2 mg folic acid/kg food (the basal dietary requirement in rats) until seven weeks of age, at which point the mammary carcinogen DMBA was administered. Normal diet was continued until a single mammary tumor (the sentinel tumor) developed (6-21 weeks), and then the rats were split into groups of 44 rats each: 2, 5, 8, or 10 mg folic acid/kg food. For 12 weeks, the sentinel and any new tumors were evaluated for size and location. Upon sacrifice, mammary tumors were counted, measured with calipers, and weighed.
Final analysis revealed that sentinel tumor weight, volume, and area were significantly increased in the groups receiving more than the control 2 mg folic acid/kg food, but there was not a significant dose-response relationship. Interestingly, the 5 mg group trended toward the highest final sentinel tumor measurements, and tumor progression was significantly more rapid. The authors gave no indication why this level of supplementation, which was chosen to mimic “the likely total folate intake (~0.8-1.0 mg folic acid/day or 2-2.5x RDA) from fortified foods and multivitamin containing 0.4 mg folic acid in North American populations in the post-fortification era,” elicited the greatest effect on tumor measurements, but they stated that folate accumulation in tissue is limited by enzyme activity and may have plateaued beyond 5 mg/kg. It was suggested that the mechanism by which folic acid promoted tumorigenesis is an increase in nucleotide precursors available for replicating neoplastic cells, which grow uncontrollably to form tumors; also, HER2 receptor expression on tumors was increased.
The question now may be: should we throw out our vitamins and stop eating supplemented food? The answer is definitely not. First, DMBA-induced mammary tumorigenesis does not replicate human breast cancer, although it is a widely used model due to similarities in genetic markers and hormonal dependence. Second, the effect was seen in rats with pre-established mammary tumors; the majority of the population does not have breast cancer. Third, the metabolism of folic acid in rats is different from the folate metabolism in humans, meaning that the results cannot–as of now–be used to draw conclusions on folic acid use in humans. Finally, other researchers have shown that folic acid may actually prevent tumor establishment in normal tissue.
Future work should certainly evaluate a correlation between folic acid supplementation and breast cancer progression in women, given the fact that women with breast cancer are exposed to folic acid supplementation in their food.