Folate supplements needed but not allergenic.

To ensure that women of childbearing age receive enough folate-a B vitamin required to head off potentially debilitating fetal defects-the Food and Drug Administration has announced that it will require U.S. food manufacturers to fortify most grain-based products with a synthetic form of the vitamin. That decision preceded by 1 week publication of a British study that concludes such dietary supplementation may be the only way to guarantee that women receive enough folate.

However, the synthetic folate, or folic acid, used to fortify foods and vitamin supplements can provoke an allergic response, notes Mark S. Dykewicz of the St. Louis (Mo.) University School of Medicine. He reported the new finding last week in New Orleans at an American Academy of Allergy, Asthma, and Immunology meeting. Although FDA's new rule "has been made for excellent reasons," he says, the change will make more people likely to develop a life-threatening allergic reaction.

A host of studies has shown that babies born to women who don't consume enough folate early in pregnancy face an increased risk of neural tube defects (SN: 1/28/95, p. 53). Each year in the United States alone, some 2,500 babies are born with these defect s.

Because more than half of all pregnancies are unplanned, and because neural tube defects occur before most women realize they have become pregnant, FDA decided to require manufacturers to add folic acid to enriched breads, flour, corn meal, pasta, rice, a nd other grain-based foods in quantities sufficient to provide most women with the necessary 0.4 milligram of the vitamin daily. That's more than twice the current recommended daily allowance, which most U.S. residents consume.

Until the rule takes effect-slated for Jan. 1, 1998-the Public Health Service recommends that women obtain the vitamin through dietary supplements or foods naturally rich in folate, especially dark green, leafy vegetables, citrus fruits and juices, and le ntils. Women, however, may find it all but impossible to derive what they need from such natural sources, according to a recent, 3-month-long study. Geraldine J. Cuskelly at the University of Ulster in Northern Ireland and her coworkers randomly assigned women to take daily supplements containing 0.4 mg of folic acid, to eat foods fortified with the same amount of the synthetic vitamin, or to eat foods naturally containing 0.4 mg more folate than the average diet. Among the 41 women who completed the tria l, concentrations of the vitamin in the blood rose only in those who consumed the folic acid, Cuskelly's team reports in the March 9 Lancet. The most likely explanation, these researchers say, "lies in the known increased bioavailability of folic acid ove r [natural] food folates."

The subtle chemical differences between food-derived folate and synthetic folic acid may also explain why a woman who could eat folate-rich foods without problems nearly died from an injection of folic acid, says Dykewicz. Though anecdotal reports of such allergies had surfaced now and again, many people discounted them, he says, in part because the vitamin molecule was smaller than those that the immune system typically recognizes.

Dykewicz figured that to trigger an allergic reaction, this chemical must first pump up its size by binding to proteins in the body. As a test, he linked folic acid to a protein in blood and then confirmed that this pairing was recognized by antibodies fr om the allergic woman.

This finding represents the first proof of antibodies to a vitamin, he says. While calling the St. Louis study excellent proof of an allergy to folic acid, Timothy J. Sullivan of the Emory University School of Medicine in Atlanta questions the findings' r elevance to food fortification. He notes that the allergic woman Dykewicz studied received an "astronomical" dose of folic acid as part of cancer therapy and thus may represent an anomaly unsuited for gauging the risks of vitamin quantities in fortified f oods.