Received on April 15, 2009
Accepted on September 21, 2009

Other Areas of Clinical Chemistry

Determinants of Plasma Methylmalonic Acid in a Large Population: Implications for Assessment of Vitamin B₁₂ Status

¹ OPTI, Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK
² Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway
³ Section for Pharmacology, Institute of Medicine, University of Bergen and Haukeland Hospital, Norway
⁴ Department of Public Health and Primary Health Care, University of Bergen, Norway
⁵ OPTI, Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK, and Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway

^* To whom correspondence should be addressed. E-mail: anna.vogiatzoglou{at}dpag.ox.ac.uk.

BACKGROUND: Methylmalonic acid (MMA) in plasma or serum is widely used for assessment of vitamin B₁₂ status. However, data are sparse regarding factors, besides renal function, that may influence MMA concentrations. We searched for important determinants of plasma MMA in the general population.

METHODS: In 6946 middle-aged (47–49 years) and elderly (71–74 years) individuals from the Hordaland Homocysteine Study in Norway, we collected anthropometric measurements, lifestyle data, and plasma MMA, vitamin B₁₂, and creatinine measurements. For 5820 individuals, we also collected dietary data.

RESULTS: Age and plasma creatinine were positively associated with plasma MMA, whereas plasma vitamin B₁₂ was negatively associated. These variables together with sex were the strongest determinants of plasma MMA, accounting for 16% of the variation (R² = 0.16). Addition of anthropometric measures and lifestyle and dietary factors only gave slight improvement (total R² = 0.167). Increased plasma MMA was seen when plasma vitamin B₁₂ was <400 pmol/L. In individuals with vitamin B₁₂ 400 μmol/L (vitamin B₁₂–replete), the 2.5th–97.5th reference limits for MMA were 0.10–0.28 μmol/L (middle-aged) and 0.10–0.36 μmol/L (elderly). When plotted against creatinine (nomograms), the 97.5th percentile of MMA was similar in men and women but approximately 0.15 μmol/L higher in elderly than middle-aged individuals. Vitamin B₁₂–replete participants had MMA upper limits approximately 0.1 μmol/L (elderly) and 0.04 μmol/L (middle-aged) below those of the unselected population at all creatinine concentrations.

CONCLUSIONS: Identified determinants accounted for <17% of the overall variation in plasma MMA. The difference in MMA between middle-aged and elderly individuals is only partly explained by creatinine and vitamin B₁₂ concentrations.