Folic acid continues in the news

In 1931, in Bombay, Lucy Wills conducted an experiment in which she fed monkeys a diet of white rice and white bread and induced a megaloblastic anemia similar to that commonly seen in India in pregnant women. Neither administration of the then-known vitamins nor liver extract reversed the anemia. Subsequently, she showed that the anemia could be prevented by ingestion of brewer’s yeast. During the next 10 years, vitamin researchers in various parts of the world, using different animal and bacterial models, identified curative factors that were each named as vitamins or other factors, including vitamin M, vitamin Bc, U factor, and L. casei factor. Also during that time, the substance in brewer’s yeast was identified. Researchers at the University of Texas then isolated from spinach a concentrate of L. casei factor that turned out to be identical to the Lucy Wills factor. Since they extracted it from spinach leaves, the vitamin was named folacin from the Latin folium or leaf. This early history of folate filled with aliases seems a fitting prelude to the often-confusing role of folic acid in human nutrition and health today. For some of its functions, its role in the prevention of many conditions has been documented. For example, Canada, the United States, and Hungary have recognized folate’s importance in the prevention of neural tube defects and have mandated the fortification of grain products. Other birth defects also appear to be lessened with adequate folic acid. Yet, some countries have taken a more cautious view and are worried that elevated levels in the population can put segments of the population, such as the elderly, at risk. Further, its importance in protecting against other diseases is still the subject of much study and is nearly as confusing as some of its early history. The following segment highlights reports from recent months on the reduction of birth defects, the improvement of memory and hearing, and the reduction of cardiovascular disease and cancers. Finally, it takes a look at problems of excess. Recent reports in the literature from France (6) and Norway (22), countries where the incidence of cleft palate is high, and from a meta-analysis (1) strongly suggest that incidence of cleft lip and cleft palate is inversely associated with folate intake in the mothers’ diets. U.S. data on the incidence of cleft lip and palate show that the mandatory fortification of flour with folic acid is also associated with a small decrease in these disfiguring and problematic birth defects (25). Data show that the timing of the decline is consistent with the introduction of fortification. These data from the various countries in aggregate strongly suggest that folate fortification reduces yet another birth defect. Despite the truly beneficial effects of folate on pregnancy outcome, there is great concern that folate intake is decreasing. In a report issued in January 2007 (5), the U.S. Centers for Disease Control found that, among women in their childbearing years, blood folate levels in 2004 had declined by16% from the levels recorded in 2000. At least two dietary trends may be partly responsible for this drop. First, there was the overall diet craze to eliminate carbohydrates. Second, a shift occurred from fortified, refined products to whole-grain foods. While whole-grain products have some natural folate, many of them are not and cannot by regulation (Standard of Identity) be fortified. Supplements also have not been very successful. According to the March of Dimes, the taking of supplements is limited by cost, lack of awareness, and a widespread belief among Hispanic women that a vitamin supplement could cause weight gain. Thus, the new data indicate that only 33% of women of childbearing age (down from 40%) take a vitamin supplement with folate. The March of Dimes predicts that, if folate intake continues to decrease, the gains in reduced neural-tube defects may be erased. As a result, the March of Dimes expects to join a coalition petitioning the Food and Drug Administration to double the levels of folate in enriched grains. Data on folate intake in Canada show similar trends. According to a recent study in Toronto, the average dietary folate of 61 university-educated women was 562 μg per day during pregnancy and 498 μg per day during lactation (17). From these data, Sherwood and her colleagues estimated that one-third of the highly educated women in her sample were getting inadequate folate during pregnancy and lactation. Folate intake by other socioeconomic groups, she suggested, may be even less. While these results may suggest to some that folate fortification is ineffectual, it is nevertheless true that, without fortification, 98% of the women would have failed to meet their requirements. Health Canada is asking for comments about folate and vitamin B12 in the diet (10). In addition to its role in reducing birth defects, folate is reported to positively influence the health of other population segments. However, as in its confusing history, not all the studies agree. Some data suggest that folate may be helpful in reducing the cognitive decline associated with aging. Previous research suggests that high serum concentrations of homocysteine are associated with poor cognitive performance and Alzheimer’s disease. Since folate is involved in keeping homocysteine levels low, there is thought that this B vitamin might be involved in memory issues associated with aging. Recent articles do little to add clarity about folate’s overall role, as various studies both refute and support such a relationship. For example, the overall outcome of a study on more than 1,000 multiethnic elderly people showed no relationship between Alzheimer’s and any B vitamin studied, nutrition