title: Increased plasma methylmalonic acid level does not predict clinical manifestations of vitamin B12 deficiency.
abstract: 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.
  
  
  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 micromol/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 total 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.
authors: Department of Hematology, Aarhus University Hospital, Aarhus Amtssygehus, Tage Hansens Gade 2, 8000 Aarhus C, Denmark. Anne_Mette.Hvas@aas.auh.dk
authors: A M
authors: AM
authors: Hvas
authors: J
authors: J
authors: Ellegaard
authors: E
authors: E
authors: Nexø
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003718:Denmark; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011336:Probability; D012042:Registries; D012680:Sensitivity and Specificity; D014805:Vitamin B 12 / Q000008:administration & dosage; D014806:Vitamin B 12 Deficiency / Q000097:blood* / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D015415:Biomarkers; D008764:Methylmalonic Acid; D014805:Vitamin B 12