Increased plasma methylmalonic acid level does not predict clinical manifestations of vitamin B12 deficiency

Background: The prevalence of vitamin B-12 deficiency, defined as an elevated concentration of plasma methylmalonic acid (P-MMA), has been estimated to be 15% to 44% in the elderly. However, we do not know whether an increased P-MMA level actually indicates or predicts a clinical condition in need of treatment. Participants and Methods: In a follow-up study, 432 individuals not treated with vitamin B-12 were examined 1.0 to 3.9 years after initial observation of an increased P-MMA concentration (>0.28 mu mol/L). The examination included laboratory tests, a structured interview to disclose symptoms, a food frequency questionnaire, and a clinical examination including a Neurological Disability Score. Results: Variation in P-MMA levels over time was high (coefficient of variation, 34%). In only 16% of participants, P-MMA levels increased substantially, whereas 44% showed a decrease. Level of P-MMA was significantly but not strongly associated with levels of plasma cobalamins (r = -0.22, P < .001) and plasma total homocysteine (r = 0.37, P < .001), After adjustment for age and sex, we found no associations between P-MMA concentration and the to tal symptom score (P = .61), the total Neurological Disability Score (P = .64), or other clinical manifestations related to vitamin B-12 deficiency. Conclusions: An increased level of P-MMA did not predict a further increase with time and clinical manifestations related to vitamin B-12 deficiency. We therefore challenge the use of an increased P-MMA concentration as the only marker for diagnosis of vitamin B-12 deficiency.