Researchers affiliated with the Health Professional Follow-Up Study and the Nurses’ Health Study have reported that folic acid supplementation in patients with recurrent colorectal adenoma was not protective or harmful in most patients. However, patients who were folate deficient had a significant 39% decrease in adenoma recurrence. The details of this study appeared in an early online publication on October 28, 2009 in the American Journal of Clinical Nutrition.[1]

The role of micronutrients in relationship to cancer incidence has become a major focus among researchers. Some dietary choices have been shown to reduce the risk of developing certain types of cancers; however, newer research has also shown exogenous vitamins do not lower the incidence of cancer and, in some instances, they may increase cancer risks. Thus, there is evolving evidence that exogenous vitamin supplementation is no substitute for micronutrients in food.

Retrospective and randomized trials have shown that colorectal cancer is increased in persons with the lowest dietary intake of folic acid compared with persons with a high intake of dietary folic acid. In one study the risk of colon cancer was reduced by 27% in persons with the highest folic acid intake compared with the lowest intake. This study also found that men who consume higher amounts of alcohol combined with inadequate intakes of folate and methionine are at a higher risk of developing rectal carcinoma.

Recently, researchers involved in a multicenter U.S. trial have reported that folic acid supplementation in patients did not prevent, and may have increased, the incidence of recurrent colorectal adenomas. Researchers affiliated with the Aspirin/Folate Polyp Prevention Study have also reported that supplementation with folic acid significantly increases the risk of prostate cancer.

Researchers from Norway have also shown that that folic acid and B12 supplements in patients with ischemic heart disease increase the risk of cancer and all-cause mortality in a population that does not fortify food with folic acid.

The current study involved 338 patients with recurrent colorectal adenoma who received folic acid supplementation and 334 patients who received a placebo. For the entire cohort, the incidence of recurrent adenomas was not affected by folic acid supplementation. However, persons who had a baseline folate level of 7.5 ug/mL or less and received folic acid supplementation had a 39% decreased risk of recurrent colorectal adenoma. In persons with a folate level over 7.5 ug/ml, folic acid supplementation had no effect on recurrent colorectal adenomas. These authors concluded: “Our results do not support an overall protective effect of folic acid supplementation on adenoma recurrence. Folic acid supplementation may be beneficial among those with lower folate concentrations at base line.”

Comments: Understanding the role of folic acid in carcinogenesis is made even more complex by the fact that genetic factors may modify the way the body metabolizes folate. In one recent study, researchers from Sweden reported that postmenopausal women with high plasma folate levels associated with the 677T allele of the folate-metabolizing enzyme methylenetetrahydrofolate reductase [MTHFR] gene had an increased risk of developing breast cancer.[2] It’s possible that genetic variation of the MTHFR gene could influence the results of the various clinical trials being carried out to determine the effect of supplemental folate in cancer prevention.

References:

[1] A randomized trial of folic acid supplementation and risk of recurrent colorectal adenoma. American Journal of Clinical Nutrition [early online publication]. October 28, 2009.