Vitamin B₁₂ and homocysteine

In examining the relationship of serum vitamin B12 levels to homocysteine levels,1 Julie Robertson and colleagues highlight the utility of homocysteine in the clinical investigation of vitamin B12 deficiency.

Both methylmalonic acid and homocysteine are elevated in vitamin B₁₂ deficiency. The measurement of methylmalonic acid requires not readily available methods involving mass spectrometry, whereas homocysteine is readily measured in the clinical laboratory by fluorescent polarization, enzymatic assays and high-pressure liquid chromatography. There is a strong correlation between methylmalonic acid and homocysteine levels, and the sensitivity of homocysteine levels for identifying vitamin B12 deficiency is greater than 95%.2^,3^,4 Measurement of creatinine, folate and vitamin B₁₂ levels and the patient's response to treatment will clarify the cause of the elevated homocysteine levels. At my institution we no longer routinely offer methylmalonic acid measurement as the diagnostic efficiencies of methylmalonic acid and homocysteine seem similar for the identification of a functional vitamin B₁₂ deficiency.

Robertson and associates state that 17.3% of their population (73/421 cases) had a vitamin B₁₂ deficiency. Of the 50 patients in whom methylmalonic acid was measured, 59% had elevated methylmalonic acid levels, confirming a functional vitamin B12 deficiency. It would have been interesting to know what the homocysteine levels were in these 73 subjects and to conduct a receiver–operator curve analysis to determine the efficiency of methylmalonic acid and homocysteine for identifying vitamin B12 deficiency. If all the patients with elevated methylmalonic acid levels also had elevated homocysteine levels, this would support the idea that homocysteine alone (without methylmalonic acid) can be used to assess vitamin B12deficiency and its response to treatment.