High Folic Acid Intake Unlikely to Worsen B12 Deficiency

Laurie Barclay, MD

June 14, 2011

June 14, 2011 — High intake of folic acid from fortified food and supplements is not likely to worsen the biochemical abnormalities linked to B12 deficiency, according to the results of a cross-sectional study reported online June 8 in the American Journal of Clinical Nutrition.

"In elderly individuals with low serum vitamin B12 (B12), those who have high serum folate have been reported to have greater abnormalities in biomarkers for B12 deficiency: low hemoglobin (Hgb), and elevated total homocysteine (tHcy) and methylmalonic acid (MMA), suggesting that folate exacerbates B12-related metabolic abnormalities," write James L. Mills, MD, MS., senior investigator in the Division of Epidemiology, Statistics and Prevention Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and colleagues. "We determined whether high serum folate in individuals with low serum B12 increases the deleterious effects of low B12 on biomarkers of B12 cellular function."

The study sample consisted of 2507 university students who were questioned about medical history and use of folic acid and B12 supplements and who gave blood samples for testing of serum and red cell folate, hemoglobin, plasma homocysteine, and MMA, holotranscobalamin (holoTC), and ferritin in serum.

Approximately 5% of the students sampled had low levels of B12 (< 148 pM), and these were subdivided based on folate concentration into group 1 (high folate level; > 30 nM) and group 2 (low/normal folate level; ≤ 30 nM). Group 1 had significantly higher mean intakes of folic acid and B12 from supplements and fortified food than did group 2.

Compared with participants in group 2, those in group 1 did not have greater abnormalities in any specific test result of B12 cellular function. In fact, they had significantly higher holoTC and red cell folate levels, significantly lower total homocysteine levels, and nonsignificantly lower (P = .057) MMA concentrations than group 2. Hemoglobin and ferritin levels were not significantly different between the groups.

"Our findings are reassuring for people who have low vitamin B12 levels," Dr. Mills said in a news release. "We found no evidence that folate could worsen their health problems. Consuming higher amounts of folate does not seem to interfere with the body's use of vitamin B12 in otherwise healthy individuals."

Limitations of this study include lack of food intake data and a relatively small number of participants (mostly women) in the low B12-high folate group.

"In our study, we carefully checked for people who had intestinal surgery or disorders that disrupt the absorption of B12, to be sure that they did not bias our analysis," Dr. Mills said. "High folate does not appear to increase the risk of anemia among healthy people with low B12 levels." Dr. Mills said.

This study was funded by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. The study authors have disclosed no relevant financial relationships.

Am J Clin Nutr. Published online June 8, 2011. Abstract

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