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

Abstract

Background: 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. Objective: 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. Design: Data from NHANES, a nationally representative crosssectional survey, were examined for adults aged .19 y (mean 6 SD age: 45 6 1 y) from 1999 to 2004 (n = 12,612). Results: 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. Conclusions: 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.Am J Clin Nutr 2011;94:552-61.

Laboratory Evaluation for Vitamin B12 Deficiency: The Case for Cascade Testing

“…These experts questioned the value of further hypothesis generating epidemiologic studies and stated that prospective clinical trials are urgently needed. 8,25,26 From a cost-effective public health standpoint, some might advocate widespread oral vitamin B 12 supplementation without laboratory testing to provide insurance against subclinical B 12 deficiency. 27 Although the general public and commercial health food suppliers have a seemingly insatiable appetite for "fountain of youth" dietary supplements, it seems premature to recommend mandatory fortification of the food supply without well-conducted, randomized clinical trials.…”

Potential Links between Impaired One-Carbon Metabolism Due to Polymorphisms, Inadequate B-Vitamin Status, and the Development of Alzheimer’s Disease

“…A relatively recent analysis of data from the National Health and Nutrition Examination Survey reported elevated Hcy levels in ~6% of the U.S. population aged ≥19 years, with levels ranging from >3% in 19–39 year-olds to ~18% in those ≥60 years old [186]. Despite mandatory folic acid fortification, around 5% and 15% of men and women, respectively, in the age range of ≥19years have folate intakes below the Estimated Average Requirement (EAR) in the United States [187].…”

Highly sensitive and selective measurement of underivatized methylmalonic acid in serum and plasma by liquid chromatography-tandem mass spectrometry

“…Plasma methylmalonic acid (MMA; reference interval, 60-360 nM [2]) is widely accepted as a functional biomarker of vitamin B12 deficiency [3,4].…”