Age-specific Serum Methylmalonic Acid Reference Ranges for More Accurate Interpretation of Vitamin B-12 Status in U.S. Adults (P24-030-19)

Abstract

ObjectivesTo evaluate vitamin B-12 status of U.S. adults. High serum methylmalonic acid (MMA) is a specific functional indicator of low vitamin B-12 status, but it is not sensitive because concentrations also increase with impaired renal function. Our goal was to describe the distribution of serum vitamin B-12 and MMA in U.S. adults, and estimate age-specific reference intervals for serum MMA in a subpopulation with replete vitamin B-12 status and normal renal function. MethodsWe examined cross-sectional data for serum vitamin B-12 and MMA in U.S. adults participating in the National Health and Nutrition Examination Survey from 2011–2014. Vitamin B-12 was assessed by electrochemiluminescence assay and MMA by isotope-dilution LC-MS/MS. ResultsIn both bivariate and multivariate analysis age, race/Hispanic origin, and vitamin B-12 supplementation were generally significantly associated with serum vitamin B-12 and MMA concentrations before and after controlling for additional covariates. We observed higher serum vitamin B-12 and MMA concentrations in persons ≥60 y compared with younger age groups. Non-Hispanic white persons had lower vitamin B-12 and higher MMA concentrations compared with non-Hispanic black persons. Shorter fasting times and impaired renal function were significantly associated with higher serum MMA concentrations, but not with serum vitamin B-12 concentrations after controlling for covariates. The central 95% reference intervals for serum vitamin B-12 and MMA concentrations were wider for persons ≥60 y compared with younger age groups. Compared with the overall population, the central 95% reference interval for serum MMA concentrations was considerably narrower for a vitamin B-12 replete subpopulation with normal renal function, but still age-dependent. Serum vitamin B-12 showed little, while serum MMA showed notable increases with impaired renal function. ConclusionsThe higher serum MMA concentrations throughout the entire distribution in older persons who are vitamin B-12 replete and have normal renal function indicate the need for age-specific MMA reference intervals to better interpret the vitamin B-12 status in clinical and epidemiologic research. Funding SourcesThis work was supported by direct appropriations from U.S. Congress.