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Folic acid and colon cancer: Some benefits and no harm

By Stephen Daniells , 30-Oct-2009

Supplements of folic acid may reduce the recurrence of colorectal cancer in people with low levels of the nutrient, but not people who already have adequate amounts, says a new study from Harvard.

And contrary to other studies, the Harvard researchers found “no evidence for an increased risk of advanced or multiple adenomas”, according to findings of a double-blind, randomized trial published in the American Journal of Clinical Nutrition.

The study may go some way to weakening the arguments of opponents of folic acid fortification who cite studies that reported potential increases in colorectal cancer risk associated with folic acid. Epidemiological evidence suggests a slight increase in colorectal cancer rates following the introduction of fortification. Such associations have been noted in the US, Canada, and Chile.

However, over 30 case-control and prospective cohort studies have reported colorectal cancer risk reduction associated with folate.

Folate is found in foods such as green leafy vegetables, chick peas and lentils, while folic acid is the synthetic, bioavailable form of the vitamin used in fortification programmes worldwide, as well as in supplements and other fortified foods.

Folic acid versus folate

A possible explanation for the contradictory results of studies with the vitamin and colorectal cancer may be the difference between the synthetic and natural forms of the vitamin. “The fact that folic acid, which is not a naturally occurring form of the vitamin, is used by food and pharmaceutical industries for fortification and supplementation is potentially of importance,” wrote Tufts University’s Joel Mason in Nutrition Reviews.

On passage through the intestinal wall, folic acid is converted to 5-methyltetrahydrofolate, the naturally circulating form of folate. However, some studies have suggested that oral doses of folic acid in high doses may overwhelm this conversion pathway, leading to measurable levels of folic acid in the blood.

According to Joel Mason from USDA Human Nutrition Research Center on Aging at Tufts University, high folate levels in certain people who harbour pre-cancerous or cancerous tumours may actually promote cancer.

The new study represents randomised clinical trial evidence of no risk for folic acid. Furthermore, the researchers, led by Kana Wu, found a protective effect of supplements in people with low levels of the B vitamin at the start of the study.

Wu and co-workers conducted a double-blind, randomised trial of the effects of folic acid supplementation (1 milligram per day) or placebo on recurrent colorectal tumours over three to six and a half years.

Overall, no beneficial or detrimental effects were observed as a result of folic acid supplementation. However, among participants with plasma folate levels below 7.5 nanograms per millilitre, folic acid was found to decrease the risk of tumour recurrence by 39 per cent.

“Our results do not support an overall protective effect of folic acid supplementation on adenoma recurrence,” wrote the researchers. “Folic acid supplementation may be beneficial among those with lower folate concentrations at baseline,” they concluded.

Source: American Journal of Clinical Nutrition
Published online ahead of print, doi:10.3945/ajcn.2009.28319
“A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma”
Authors: K. Wu, E.A. Platz, W.C. Willett, C.S. Fuchs, J. Selhub, B.A. Rosner, D.J. Hunter, E. Giovannucci

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