Taking folic acid supplements does not reduce the risk of developing precancerous tumors in the colon and may even increase the risk, a new study has found.
"We had great hope that folic acid would be a very cheap and effective agent to prevent large bowel adenomas. We expected that folic acid would decrease the risk for colorectal cancers, perhaps as much as 40 percent. So these results are disappointing," said Robert Sandler, M.D., a study co-author and chief of the division of gastroenterology and hepatology in the University of North Carolina at Chapel Hill School of Medicine.
In addition, the government-mandated addition of folic acid to common grain-based foods such as bread, flour and pasta may be a contributing factor to increased risk and thus research into this possibility should have a high priority, the study authors concluded.
Sandler said there is no reason for people to think that fortified foods are risky and should be avoided. At the same time, he said, there is now reason to doubt that folic acid fortification will prevent colorectal cancer, which is one of the more common cancers.
"Women who are contemplating pregnancy or in early pregnancy should continue to seek out folic acid-fortified foods and take supplements," Sandler said. "The rest of us should await more data before we change our eating patterns or before policymakers revisit food supplementation."
The study appears in the June 6, 2007, issue of the Journal of the American Medical Association. The lead author is Bernard F. Cole, Ph.D., of Dartmouth Medical School. The research took place at nine clinical centers, including UNC, between 1996 and 2004. Partial funding for the study was provided by the National Institutes of Health. Folic acid supplements provided to patients during the study were provided by Wyeth Consumer Health Care.
Previous research has shown that taking folic acid supplements significantly reduce the incidence of neural tube defects, such as spina bifida, in newborns. For this reason, the Food and Drug Administration required the addition of folic acid to many grain-based foods starting in 1998. Earlier studies also suggested that folic acid might play a role in preventing colorectal cancer.
To investigate folic acid supplements effects on colorectal cancer, Cole and his colleagues recruited 1,021 men and women who had previously been treated for adenomas (precancerous colon tumors) to take part in the clinical trial. The patients were randomly assigned to take one milligram of folic acid a day or a placebo. They were also separately randomized to receive aspirin, in doses of either 81 or 325 milligrams a day, or placebo. Study participants had two follow-up colonoscopies to check for tumors. The first colonoscopy was three years after the participant joined the trial. The second interval was three to five years later.
The results showed little difference between the number of tumors found in the folic acid and placebo groups. In the first follow-up interval, tumors were found in 42.4 percent of the placebo group and 44.1 percent of the folic acid group. In the second follow-up interval, 37.2 percent in the placebo group had precancerous tumors compared to 41.9 percent in the folic acid group.
However, people in the folic acid group had higher rates of advanced tumors and multiple tumors. They were more than twice as likely as those in the placebo group to have three or more precancerous tumors. A higher rate of non-colorectal cancers, primarily prostate cancer, was also found in the folic acid group.
"We found no clear evidence that folic acid supplementation provided any health benefits," the researchers wrote. They also noted that fortification of the food supply with folic acid may have affected their results, and that the evidence of increased risk was equivocal and thus 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 bowel, this line of investigation should have a high priority," the study concluded.