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.


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.
Hvas
A M
AM
Department of Hematology, Aarhus University Hospital, Aarhus Amtssygehus, Tage Hansens Gade 2, 8000 Aarhus C, Denmark. Anne_Mette.Hvas@aas.auh.dk
Ellegaard
J
J
Nexø
E
E
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
D015415:Biomarkers; D008764:Methylmalonic Acid; D014805:Vitamin B 12