No Link Between Folic Acid Supplements and Colorectal Cancer

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A new American Cancer Society study concludes that theres no evidence folic acid from fortified foods or supplements increases the risk of colorectal cancer. Earlier research, including a 2007 Tufts study, had suggested that an excess of folic acid-such as that contributed by the 1998 federal mandate to fortify flour and cereals-might increase colorectal-cancer incidence. Folic-acid fortification has helped reduce spina bifida birth defects, but some experts wondered whether the body might react differently to folic acid, a synthetic form, than to natural folate.

Victoria Stevens, PhD, and colleagues looked at data on 56,011 women and 43,512 men, ages 50-74, participating in the Cancer Prevention Study II Nutrition Cohort. Over eight years, 1,023 cases of colorectal cancer were diagnosed. Neither high intake of folic acid nor of natural folate was associated with a greater risk, and high total folate was actually associated with a 19% lower risk.

Publishing their results in Gastroenterology, researchers concluded, Our findings are consistent with… results from the only trial to assess colorectal cancer, rather than adenoma [benign tumors that may progress to cancer], as the endpoint, suggesting that folate intakes in the range of 800 micrograms [mcg] per day should not be expected to increase risk of colorectal cancer.

Joel B. Mason, MD, director of Tufts HNRCA Vitamins and Carcinogenesis Laboratory, comments, I think the study does provide us with some genuine reassurance that the potential cancer-promoting effect is not a widespread phenomenon among people who take supplements. I would not go so far, however, to state that this study eliminates all concern over a possible cancer-promoting effect of excess folic acid intake.

Dr. Mason points out that that the group ingesting the most folic acid in this study averaged only 660 mcg per day and that only 2.0-2.1% of participants exceeded a daily intake of 1,000 mcg. I have felt all along that if a cancer-promoting effect exists in the general population it probably is only present among those taking exceptionally high levels of folic acid. A person who is taking one multivitamin each morning, a bowl of fortified cold cereal, and a B-complex pill each evening is reaching an intake of 1,300-1,400 mcg of folic acid each day-which is far greater than what has been examined in this study.

On the other hand, a new analysis of data from three large randomized trials will dampen enthusiasm that folic-acid supplements might actually protect against colorectal cancer, researchers said. John A. Baron, MD, of Dartmouth Medical School, and colleagues pooled data on a total of 2,632 men and women with a history of colorectal adenomas over 3.5 years. Doses of extra folic acid ranged from 500 to 1,000 micrograms daily.

Writing in the International Journal of Cancer, Dr. Baron and colleagues concluded, Daily use of folic acid supplements… does not prevent the occurrence of new colorectal adenomas in the large bowel among men and women with a previous history of adenomas.

TO LEARN MORE: Gastroenterology, online before print; abstract at dx.doi.org/10.1053/j.gastro.2011.04.004. International Journal of Cancer, July 1, 2011; abstract at dx.doi.org/10.1002/ijc.25872.

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