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The Risk of Colorectal Tumor is Not Reduced With Folic Acid Supplements

According to a study in the June 6 issue of JAMA, folic acid supplements do not appear to reduce risk of colorectal tumors. Some previous studies have suggested that folate supplementation may help to prevent colorectal tumors.

Bernard F. Cole, Ph.D., of Dartmouth Medical School, Hanover, N.H., and colleagues evaluated the effect of folate for the prevention of new colorectal adenomas in persons with a history of these types of lesions. The trial was conducted at nine clinical centers in the U.S. and Canada between July 1994 and October 2004 and included 1,021 men and women with a recent history of colorectal adenomas but no previous large intestine cancerous tumor.

Participants were randomly assigned to receive 1 mg/day of folic acid (n = 516) or placebo (n = 505), and were separately randomized to receive aspirin (81 or 325 mg/day) or placebo. Follow-up consisted of two colonoscopic examination cycles (the first interval was at 3 years and the second at 3 or 5 years later).

Contrary to what the researchers expected, more adenomas were seen in people who received folic acid. In the first follow-up interval, adenomas occurred in 42.4 percent of the participants in the placebo group and 44.1 percent of the participants in the folic acid group. In the second follow-up interval, adenomas occurred in 37.2 percent of the participants in the placebo group and 41.9 percent of the participants in the folic acid group.

In both follow-up intervals, participants in the folic acid group tended to have higher rates of advanced adenomas and multiple adenomas. Advanced adenomas have features, such as larger size, that increase the risk that they will develop into colorectal cancer. In the first follow-up interval, advanced adenomas occurred in 8.6 percent of the participants in the placebo group and 11.4 percent of the participants in the folic acid group.

The respective numbers in the second follow-up interva l were 6.9 percent and 11.6 percent for both groups, a 67 percent (but non-statistically significant) 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 those in the placebo group (13 individuals, 4.3 percent).

"In conclusion, our study indicates that folate, when administered as folic acid for up to 6 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. In view of the fortification of the U.S. food supply with folate, and some suggestions that folate could conceivably increase the risk of neoplasia even outside the colorectum, this line of investigation should have a high priority," the authors write.


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