Abstract

BackgroundSerum methylmalonic acid (MMA) is regarded as a sensitive marker of vitamin B-12 status. Elevated circulating MMA is linked to neurological abnormalities. Contribution of age, supplement use, kidney dysfunction, and vitamin B-12 deficiency to high serum MMA in post-folic acid fortification period is unknown.MethodsWe investigated prevalence, population attributable risk (PAR), and PAR% for high MMA concentrations in the US. Data from 3 cross-sectional National Health and Nutrition Examination Surveys conducted in post-folic acid fortification period were used (n = 18569).ResultsLikelihood of having high serum MMA for white relative to black was 2.5 (P < 0.0001), ≥ 60 y old persons relative to < 60 y old persons was 4.0 (P < 0.0001), non-supplement users relative to supplement users was 1.8 (P < 0.0001), persons with serum creatinine ≥ 130 μmol/L relative to those with < 130 μmol/L was 12.6 (P < 0.0001), and persons with serum vitamin B-12 < 148 pmol/L relative to those with ≥ 148 pmol/L was 13.5 (P < 0.0001). PAR% for high MMA for old age, vitamin B-12 deficiency, kidney dysfunction, and non-supplement use were 40.5, 16.2, 13.3, and 11.8, respectively. By improving serum vitamin B-12 (≥ 148 pmol/L), prevalence of high MMA would be reduced by 16-18% regardless of kidney dysfunction.ConclusionsOld age is the strongest determinant of PAR for high MMA. About 5 cases of high serum MMA/1000 people would be reduced if vitamin B-12 deficiency (< 148 pmol/L) is eliminated. Large portion of high MMA cases are not attributable to serum vitamin B-12. Thus, caution should be used in attributing high serum MMA to vitamin B-12 deficiency.

Highlights

  • Elevated circulating methylmalonic acid (MMA) is an emerging potential risk factor for neurodegenerative diseases and may be neurotoxic [1,2]

  • Caution should be used in attributing high serum MMA to vitamin B-12 deficiency

  • After excluding persons with kidney dysfunction, population attributable risk (PAR)% for high MMA for vitamin B-12 deficiency is marginally increased which further strengthens our notion that even in the absence of renal dysfunction a large portion of high MMA cases might not be affected with the improvement in vitamin B-12 status

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Summary

Introduction

Elevated circulating methylmalonic acid (MMA) is an emerging potential risk factor for neurodegenerative diseases and may be neurotoxic [1,2]. Epidemiological studies have linked high circulating MMA with declined cognitive function [5,6]. Serum MMA is considered as a sensitive marker of tissue vitamin B-12 deficiency [7,8]. In vitamin B-12 deficiency, serum MMA is derived from L-methylmalonyl CoA due to impaired function of methylmalonyl CoA mutase [11]. Serum methylmalonic acid (MMA) is regarded as a sensitive marker of vitamin B-12 status. Elevated circulating MMA is linked to neurological abnormalities. Contribution of age, supplement use, kidney dysfunction, and vitamin B-12 deficiency to high serum MMA in post-folic acid fortification period is unknown

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