Some so-called observational studies have suggested people who get more of the vitamins in their diet, or have higher levels in their blood, are less likely to get colon cancer (see Reuters Health story of September 2, 2011). But that type of analysis can be influenced by other diet and lifestyle differences between participants.

In the new study, Dr. Yiqing Song from Brigham and Women's Hospital in Boston and colleagues randomly assigned women to take daily folic acid and vitamins B6 and B12 or a vitamin-free placebo pill - then followed them to see who developed colon polyps. That's known as a randomized controlled trial, considered the gold standard for medical studies.

The 1,470 women in the trial, with an average initial age of 62, were part of a larger study of antioxidants and heart disease and took their assigned daily vitamins between 1998 and 2005.

Women in the "active" treatment group took 2.5 milligrams of folic acid (a synthetic form of folate), 50 mg of vitamin B6 and 1 mg of vitamin B12 each day.

All participants had a colonoscopy or sigmoidoscopy to check for colon polyps - which can develop into cancer if not removed - sometime before mid-2007. And according to their medical records, 355 had a confirmed polyp.

Polyp risk was not related to treatment group: 24.3 percent of women taking the vitamins developed polyps, compared to 24.0 percent of those on placebo pills. The lack of benefit remained after the researchers accounted for women's weight as well as smoking, alcohol and exercise.

"Where we are is really kind of an interesting impasse," said Dr. John Baron, an epidemiologist from the Geisel School of Medicine at Dartmouth in Lebanon, New Hampshire.

"The observational data continually show an inverse association between measures of folic acid, that is diet or blood level, and the risk of colorectal cancer. The clinical trial data such as we have… suggest no benefit overall."

The U.S. government requires grain products such as cereal and rice be fortified with folic acid in order to prevent some birth defects that have been linked to low folate levels in pregnant women. As a result, very few women taking placebos were deficient in folate when they were assessed at the end of the study, Song's team reported Friday in the Journal of the National Cancer Institute.

The Institute of Medicine recommends that adults and teens get 400 micrograms of folate daily. Women who could become pregnant are advised to take a folic acid supplement as well.

One hypothesis is that folic acid can help ensure DNA replicates correctly, which in theory could decrease the risk of cancer. But there's also been some concern that high doses of folic acid can feed the growth of pre-cancerous polyps in people who already have them.

Baron, who wasn't involved in the new study, told Reuters Health those worries are "largely theoretical," but they are a reason not to go overboard with folic acid, nonetheless.

According to the American Cancer Society, the lifetime risk of developing colon or rectal cancer is 1 in 20.

The United States Preventive Services Task Force, a government-backed panel, recommends people age 50 to 75 get screened for colon cancer using colonoscopy, sigmoidoscopy or fecal occult blood testing at regular intervals.

Baron said the combined data, though conflicting, don't support the protective effects of B vitamins, over and above what's in a normal diet, on the colon.

"Most people in the U.S. are reasonably well nourished, and with folic acid supplementation now there's not serious concern about folate deficiency," Baron said.

"For general health, a usual diet for most people is sufficient. Taking large doses (of folic acid) is, at a minimum, wasteful."

SOURCE: bit.ly/AoyC3I Journal of the National Cancer Institute, online October 12, 2012.

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