Folic-Acid Effects Depend on B12 Levels

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FORTIFICATION OF FOODS with folic acid, credited with reducing one type of birth defect by more than 25% since 1998, may be a two-edged sword for older people. New research at Tufts' Jean Mayer USDA Human Nutrition Research Center on Aging suggests that increased folic acid intake can be harmful as well as beneficial, depending on a person's vitamin B12 levels.

"In this study of older Americans in the age of folic-acid fortification, we found direct associations between high serum folate and both anemia and cognitive impairment in subjects with low vitamin B12 status," wrote lead author Martha Savaria Morris, PhD, in the American Journal of Clinical Nutrition. "Among subjects with normal vitamin B12 status, on the other hand, high serum folate was associated with protection from cognitive impairment."

In the 1990s, trials indicated that increased intake of folic acid in women before pregnancy and during early pregnancy clearly lowered the risk of neural tube defect (NTD), also known as spina bifida. That led the US Food and Drug Administration (FOA) to require folic-acid fortification in breads, cereals, flours, pastas and other grain products, beginning in 1998. Although the NTO rate has fallen sharply in the US and Canada, other countries have held off on similar mandates, in part because of concerns about folic acid's relationship with vitamin B12. According to the National Institutes of Health, up to 30% of adults age 50 and older may have atrophic gastritis, an increased growth of intestinal bacteria that impairs their ability to absorb vitamin B12 from food.

"Historic reports on the treatment of pernicious anemia with folic acid suggest that high levels of folic acid could delay the diagnosis of or exacerbate the effects of vitamin B12 deficiency, which affects many seniors," Morris explains. "This idea is controversial, however, because observational data are few and inconclusive."

So Morris and her Tufts colleagues set out to compare the effects of folic acid on anemia and cognitive impairment in two groups divided by their B12 levels in the blood. The study used data on 1,459 participants in the US National Health and Nutrition Examination Survey (NHANES), all over age 59. One-quarter of the subjects had low vitamin B12 levels.

After adjusting for other factors, the researchers found significant links between low B12 and increased risk of anemia (170%) and cognitive impairment (150%). Among the subjects with low vitamin B12 status, high levels of folate were associated with both anemia (210%) and cognitive impairment (160%). Those findings suggest a possible harmful effect from excess folic acid when paired with B12 deficiency.

For subjects with normal B12 levels, however, folic acid seemed to have a beneficial effect on cognitive impairment. High folate levels in this group were associated with a 60% lower risk of cognitive impairment. No significant association was seen for other conditions.

The findings imply that the benefits of folic-acid fortification must be weighed against possible increased risk for seniors with low B12, wrote A. David Smith, PhD, of the University of Oxford in an accompanying editorial.

"We encourage further study of these relations and their underlying mechanisms," the Tufts researchers concluded. They expressed the hope that their findings would both inform the continuing debate about proper levels of folic-acid fortification and influence efforts to detect and treat low vitamin B12 status in seniors.

TO LEARN MORE: American Journal of Clinical Nutrition, January 2007; abstract at .