Folic Acid Did Not Prevent Adenomas

HANOVER, N.H.Folate, when administered as folic acid (for up to six years), did not decrease risk of adenoma formation in the large intestine among individuals with previously removed adenomas; in fact, it could possibly increase the risk for some types of colorectal tumors, according to researchers from Dartmouth Medical School.

In the study (JAMA, 297:2408-2409, 2007), Bernard F. Cole, Ph.D., and colleagues evaluated the effect of folate for the prevention of new colorectal adenomas (benign tumors, precursors of most colorectal cancers) in persons with a history of these lesions.

The trial, conducted at nine clinical centers in the United States and Canada between July 1994 and October 2004, included 1,021 men and women with recent history of colorectal adenomas, but no previous large intestine cancerous tumors. Participants were randomly assigned to receive 1 mg/d folic acid (n = 516) or placebo (n = 505), and then separately randomized to receive aspirin (81 or 325 mg/d) or placebo.

Follow-up consisted of two colonoscopic examination cycles, the first at three years, the second three or five years later. First follow-up results showed adenomas occurred in 42.4 percent of participants in the placebo group, and 44.1 percent of participants in the folic acid group. Second interval results showed adenomas occurred in 37.2 percent and 41.9 percent, respectively. Numbers in the second follow-up interval were 6.9 percent and 11.6 percent for both groupsa 67 percent increased risk of advanced adenomas. Participants in the folic acid group (30 individuals, 9.9 percent) had more than twice the risk of having three or more adenomas than the placebo group (13 individuals, 4.3 percent).

Over all, folic acid was associated with higher risks of having three or more adenomas, and of non-colorectal cancers; there was no significant effect modification by sex, age, smoking, alcohol use, body mass index, baseline plasma folate or aspirin allocation.

The researchers concluded: "Our study indicates folate, when administered as folic acid for up to six years, does not decrease the risk of adenoma formation in the large intestine among individuals with previously removed adenomas. The evidence for an increased risk of adenomas is equivocal and requires further research.

Following the studys release, the Council for Responsible Nutrition (CRN) issued a statement noting the lack of an observed benefit in this study may have resulted because folic acid was used like a drug to treat pre-existing disease, rather than as a nutrient. Its not surprising that folic acid alone may not prevent the recurrence of adenomas, said Andrew Shao, Ph.D., CRNs vice president, scientific and regulatory affairs. CRN also noted most multivitamins contain between 200 and 400 mcg/d folate per serving, while food fortification is estimated to provide up to 120 mcg/d folic acid in the United States, which still comes short of the 1,000 mcg UL for folic acid.