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Folic Acid Supplements Don't Seem to Reduce Polyp Risk

June 5, 2007

In an unexpected about face, folic acid supplementation does not decrease the risk of benign colorectal tumors, and may possibly increase risk for some types of these lesions, also called polyps, Dartmouth Medical School and Norris Cotton Cancer Center researchers have found.

The findings, reported in the June 6 issue of JAMA, are contrary to some previous studies that suggested folate supplementation may help prevent colorectal adenomas, the benign tumors that are often precursors to colorectal cancers.

Folic acid and its derivative, folate, are essential nutrients for humans and help make new cells. Studies have indicated that supplementation can help prevent neural tube defects in newborns, and in the last decade certain foods have been fortified with folate. Low-folate diets also appeared to be associated with increased colorectal cancer risk.

Lead author Dr. Bernard F. Cole, associate professor of community and family medicine, and colleagues evaluated the effect of folate in preventing new colorectal adenomas in patients with a history of such lesions. Contrary to what the researchers expected, they saw more adenomas in people who received folic acid compared to those who did not.

"We were surprised that folic acid did not decrease adenoma risk. We were even more surprised that the folic acid group did worse in some ways," noted Cole. He added that the results should be interpreted with caution because the suggestion of a higher risk with folate was strongest when looking at secondary measures of size and number of adenomas. "We typically assign lower weight to such findings," he said.

"The potential importance of the finding is that there were suggestions of harm for something that is in all multivitamins and breakfast cereals," said co-author Dr. John Baron, professor of medicine and of community and family medicine. "This is far from definitive, so I don't think people should worry at this point, but it's something that should be looked into."

The trial, conducted at nine clinical centers in the US and Canada over a decade (July 1994- Oct 2004), 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 and were separately randomized to receive aspirin (81 or 325 mg/day) or placebo. Follow-up consisted of two colonoscopic examination cycles, the first at three years and a second three or five years later).

More adenomas occurred in the folic acid groups: 44.1 percent of the participants in the folic acid group compared to 42.4 percent in the placebo group at the first interval, and 41.9 percent of those in the folic acid group versus 37.2 percent of the placebo group at the second interval.

At both follow-up intervals, those in the folic acid group tended to have higher rates of advanced 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 11.4 percent of those in the folic acid group compared to 8.6 percent of the placebo group, while at the second follow-up interval they were 11.6 percent versus 6.9 percent respectively. Participants in the folic acid group (9.9 percent) had more than twice the risk of having three or more adenomas than those in the placebo group (4.3 percent).

The possibility that folate raises the cancer risk requires more research, according to the investigators, but given its prevalence in foods, they urged rapid action. "In view of the fortification of the US 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, " they concluded.

Other Dartmouth authors are: Drs. Richard I. Rothstein, Douglas J. Robertson, Loretta H. Pearson, Elizabeth L. Barry, Judy R. Rees, E. Robert Greenberg, and Leila A. Mott.