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Am J Clin Nutr. 2011 Aug;94(2):552-61. doi: 10.3945/ajcn.111.015222. Epub 2011 Jun 15.

Monitoring of vitamin B-12 nutritional status in the United States by using plasma methylmalonic acid and serum vitamin B-12.

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Office of Dietary Supplements, National Institutes of Health, Bethesda, MD 20892-7517, USA.



Various definitions, criteria, tests, and cutoffs have been used to define vitamin B-12 status; however, a need exists for the systematic study of vitamin B-12 status in the United States because of concerns about high folic acid intakes and the potential for associated adverse effects.


The objective was to determine the effect of different cutoff choices on outcomes and of the different degrees of serum vitamin B-12 status, definable by the concurrent use of a functional and circulating marker as the first steps to developing a data-based consensus on the biochemical diagnosis of vitamin B-12 deficiency.


Data from NHANES, a nationally representative cross-sectional survey, were examined for adults aged >19 y (mean ± SD age: 45 ± 1 y) from 1999 to 2004 (n = 12,612).


Commonly used cutoffs had a greater effect on prevalence estimates of low vitamin B-12 status with the use of vitamin B-12 than with the use of methylmalonic acid (MMA; 3-26% and 2-6%, respectively). A cutoff of >148 pmol/L for vitamin B-12 and of ≤210 nmol/L for MMA resulted in significant misclassifications. Approximately 1% of adults had a clear vitamin B-12 deficiency (low vitamin B-12 and elevated MMA); 92% of adults had adequate vitamin B-12 status. A high percentage of younger women characterized the group with low vitamin B-12 and normal MMA (2% of adults) and may have falsely reflected low vitamin B-12. Adults with elevated MMA (5%) only were demographically similar (ie, by age and race) to the deficient group and may have included some individuals with early vitamin B-12 deficiency.


These analyses indicate the challenges of assessing vitamin B-12 status when uncertainties exist about the appropriate cutoffs. Future studies should determine definable endpoints to achieve this goal.

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