Relationship between methylmalonic acid and cobalamin in uremia

Background. To evaluate the requirement for routine supplementation with vitamin B-12 and to study the effect of a change from injection to oral B-12 supplementation, we examined the relationship between cobalamin and methylmalonic acid in plasma from 67 patients on chronic hemodialysis, all in regular therapy with intramuscular cobalamin injections (1 mg) every third month. Methods. Starting just before one cobalamin injection, blood samples were collected once a month during a nine-month withdrawal from regular cobalamin substitution to a final three-month period with cyanocobalamin tablets (1 mg) administered once daily. Results. Plasma cobalamin was above the lower reference limit in all subjects, and from a peak value one month after the regular injection, the cobalamin concentration during the withdrawal period decreased to a level below the point of origin, followed by a significant rise after cyanocobalamin tablets. The methylmalonic acid concentrations were above the reference interval. In the withdrawal period, the concentrations significantly increased further, followed by a significant decrease after oral cyanocobalamin substitution. Conclusion. We demonstrated a within-patient inverse relationship between the concentrations of methylmalonic acid and cobalamin in plasma from these uremic patients. Despite the fact that only two of the patients developed subnormal plasma cobalamin values, we demonstrated a B-12 depletion during the withdrawal period. Treatment with cyanocobalamin tablets once daily was found efficient, but the oral doses should possibly be increased.