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A downside to preventing birth defects?

By one measure, the addition of folic acid to most breads, pastas, rice, and other grain-based foods has been a spectacular success, saving more than 1,000 babies born in the United States and Canada each year from spina bifida, anencephaly, and other neural tube birth defects that can cause lifelong pain, disability, or death.

But the fortification of foods with folic acid, a B vitamin, may have also led to an unintended consequence: an estimated 15,000 more cases of colon and rectal cancer each year than there otherwise might have been.

It's well documented that more folic acid in young women's diets has prevented neural tube defects. This month, for example, Canadian researchers published a study in The New England Journal of Medicine showing that since 1998, the year that it became mandatory to add folic acid to certain foods, the prevalence of neural tube defects in seven Canadian provinces decreased from 1.58 per 1,000 births to 0.86 per 1,000 births -- a reduction of almost 50 percent.

The story is similar in the United States, which began requiring folic acid fortification the same year.

But the timetable of the downward trend in neural tube defects exactly corresponds to a significant, sustained upward tick in the rate of cases of colorectal cancer, according to new data from researchers at Tufts University.

The study, published in Cancer Epidemiology Biomarkers & Prevention, shows that before the late 1990s, the incidence of colon cancer was decreasing on a steady, predictable curve, presumably because of increased screening with colonoscopies, during which precancerous polyps and early cancers are removed. However, the curve has shifted.

Colon cancer cases continue to decline, but since the advent of folic acid fortification, there have been four to six more cases of colon cancer per 100,000 people in the United States and Canada each year than the original curve would have projected -- translating to an estimated extra 15,000 people diagnosed per year in this country and another 1,500 in Canada.

Joel Mason, the leader of the study and director of the Vitamins and Carcinogenesis Laboratory at the USDA Human Nutrition Research Center at Tufts, acknowledged that he and his colleagues observed an association between more folic acid and more colon cancer rather than proved a cause and effect. But, he said, the folic acid-cancer connection has "a pretty robust degree of biologic plausibility."

There is evidence that folic acid helps protect noncancerous cells from becoming cancerous.

The hitch, Mason said, is that an estimated 35 percent to 50 percent of people over 50 already have precancerous polyps -- and for them, the extra folic acid may be dangerous. The precancerous cells replicate more rapidly than normal ones, and folic acid seems to put that process into overdrive.

Exacerbating the problem is that the lining of the intestine is one of the most rapidly proliferating tissues of the body; normal cells there turn over extremely quickly, creating a completely new lining every 72 to 96 hours. Add too much folic acid to that environment, and whatever precancerous cells are present might divide even more rapidly and potentially lead to a more aggressive cancer.

It's "not just a theoretical concern," Mason said. In the 1940s, Sidney Farber, after whom the Dana-Farber Cancer Institute was named, started giving large doses of folic acid to children with leukemia -- a condition in which white blood cells crowd out red ones -- in the hope that the nutrient would contribute to the formation of more red blood cells. But their cancer worsened more quickly. Farber called it "the acceleration phenomenon." That prompted him to switch to an anti folic acid, methotrexate, which blocked the cancer cells' ability to divide. The children got better, and modern chemotherapy was born.

So, should folic acid be taken out of the food supply? Researchers say no.

Philippe de Wals of Laval University in Quebec, lead author of the recent Canadian study, says the benefits of folic acid are well documented, backed by a number of studies, while the risk for colon cancer is less well supported.

Mason agrees. "I am in no way saying that we should be doing away with folic acid fortification at the present time," he said. "It is highly unlikely that women in their 20s and 30s, childbearing age, harbor any precancerous or cancerous cells, and there is incontrovertible evidence now that supplemental quantities of folic acid are going to help prevent really devastating birth defects. "

His concern is for people over 40, when colon cancer incidence begins to rise, he said. "The single biggest risk factor for colon cancer is older age."

As a result of his research, Mason thinks people middle-aged and older ought to be more circumspect about taking supplemental folic acid in multivitamin pills. Perhaps, he said, multivitamin manufacturers targeting supplements to older people will consider using lower concentrations of folic acid.

Taking multivitamins in addition to eating foods that contain folic acid plus foods that are voluntarily fortified "might be putting us over the top," he said. "How we do folic acid fortification should be a matter of open debate in the immediate future."

But people shouldn't be concerned about the vitamin where it occurs naturally -- in green leafy vegetables, beans, and fruits. That form of the nutrient, called folate, has been shown to be helpful in the prevention of both neural tube defects and various forms of cancer, Mason said.