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Recruitment procedure and flow of participants through the study. MMA indicates methylmalonic acid. Proportional effects of different doses of cyanocobalamin on mean methylmalonic acid MMA A , total homocysteine tHcy B , holotranscobalamin holoTC C , and vitamin B 12 D concentrations after 16 weeks of supplementation.

Error bars represent SD. Arch Intern Med. Background Supplementation with high doses of oral cobalamin is as effective as cobalamin administered by intramuscular injection to correct plasma markers of vitamin B 12 deficiency, but the effects of lower oral doses of cobalamin on such markers are uncertain.

We assessed the effects of daily oral doses of 2. Results Supplementation with cyanocobalamin in daily oral doses of 2. Vitamin B 12 deficiency, due to intrinsic factor deficiency, hypochlorhydria, or food-bound malabsorption, affects mainly older people. In the setting of vitamin B 12 deficiency, methylmalonyl—coenzyme A is hydrolyzed to methylmalonic acid MMA.

Thus, elevated plasma concentrations of MMA and total Hcy tHcy can be used as biochemical markers to aid in the diagnosis of vitamin B 12 deficiency and to monitor the response to cobalamin supplementation. A major knowledge gap concerns the lowest dose of oral cobalamin supplementation that will normalize elevated MMA concentrations. The aim of the present trial is to determine the lowest dose of cyanocobalamin that is required for a maximal reduction in MMA concentrations in a randomized, parallel-group, double-blind, controlled, dose-finding study in older people with mild vitamin B 12 deficiency.