New research suggests pros and cons of folic acid

by Eric Schroeder
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WASHINGTON — A new study published in the June 6 issue of the Journal of the American Medical Association suggests high doses of folic acid do not prevent precancerous colon polyps in people prone to them and may actually increase the risk of developing the growths.

The study follows earlier research that has shown diets low in folic acid led to a higher risk of colon cancer.

Researchers now speculate that some folic acid helps — as long as the colon is free of microscopic cancer cells. But once cancer starts, folic acid may feed its growth.

As part of the study, researchers conducted a double-blind, placebo-controlled randomized trial between 1994 and 2004 on 1,021 men and women with a recent history of colorectal adenomas and no previous invasive large intestine carcinoma. They then examined data from 987 adults who underwent colonoscopic follow-up. According to the study, 44.1% of those who took 1 milligram of folic acid per day (more than double the recommended daily allowance for folic acid) developed precancerous polyps, which compared with 42.4% of the placebo pill group.

"You really should not take folic acid to prevent colorectal adenomas," said co-author Bernard Cole of Dartmouth-Hitchcock Medical Center. "It’s ineffective for that purpose."

While the difference in the first round of screenings was not statistically significant, the results of a second round of colonoscopies a few years later were. Among the folic-acid takers, 11.6% had advanced adenomas while 6.9% of the placebo-pill group did. And folic acid more than doubled the risk of having three or more precancerous polyps, the study found.

Researchers did not see any real difference in rates of colon cancer, just in the precancerous colon growths.

Responding to the study, though, the Grain Foods Foundation (G.F.F.) pointed out that even the authors said evidence for an increased risk of adenomas is equivocal and requires further research.

"It is important to note that this study involves a relatively small number of subjects with a pre-existing cancerous colon and therefore it is difficult to apply the study results to a generally healthy population," the G.F.F. said. "Additionally, this is a secondary prevention study. Primary research has demonstrated folic acid’s role in protecting against the development of cancer. Even the authors state that ‘overall, epidemiological data from cohort and case-control studies have tended to find folate intake to be inversely associated with risks of colorectal cancer and adenomas.’ The benefits of folic acid in these primary studies were evident through both diet and supplemental forms.

"Overall, the benefits of folic acid are well-documented, particularly in the area of reducing the risk of neural tube birth defects. Additionally, there is scientific evidence for folic acid in reducing the risk of congenital cardiovascular defects, stroke, and Alzheimer’s disease. If you are a healthy individual, it is important not to eliminate any nutrient in the diet (such as folic acid in enriched grains) because of the research that has demonstrated its primary disease prevention benefits."

Daniel Fabricant, Ph.D., vice-president of scientific regulatory affairs for the Natural Products Association, also urged caution in reviewing the study’s findings.

"This study is not about prevention at all, because every one of the subjects in this study already had this condition," Dr. Fabricant said. "What this study might address is a prevention of a reoccurence, which is a distinction with an enormous difference. It would be grossly inaccurate to suggest or report that folic acid is therefore ineffective for primary prevention of colorectal adenomas based on this study.

"Secondly, the study failed to account for other basis factors that may be at work here, including calcium and vitamin D intake from diet, for instance. Without this essential knowledge, it is impossible to draw clear conclusions about the effects of folic acid on this particular condition.

"This might explain why the authors themselves seem confused. They initially state that ‘on the whole, the biological and epidemiological evidence supports the potential for folate supplementation to prevent colorectal neoplasia in humans.’ Then, they do an about face in their conclusion and speculate regarding an increased risk for colorectal neoplasia, despite stating that ‘evidence for an increased risk is equivocal."

Grants from the National Institutes of Health funded the study. Some of the researchers reported financial ties to drug companies, such as consulting work and research support.

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