A randomized, double-blind, placebo-controlled study of oral vitamin B12 supplementation in older patients with subnormal or borderline serum vitamin B12 concentrations. Oral versus intramuscular cobalamin treatment in megaloblastic anemia: a single-center, prospective, randomized, open-label study.
To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia (PA).
                Randomized, double-blind, placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month.
                Two geriatric hospitals in the North Western Health Care Network, Melbourne, Australia.
                Thirty-one inpatients with serum vitamin B12 levels between 100 and 150 pmol/L, without PA, other malabsorption disorders, or progressive neurological or terminal illness. The mean age was 81.4 years.
                After informed consent, a medical and drug history was taken and the Mini-Mental State Examination (MMSE) completed. A dietitian made assessment of oral cobalamin intake. Blood was taken for serum vitamin B12, serum and red cell folate assay, full blood examination, fasting serum gastrin, parietal and intrinsic factor antibodies, fasting serum homocysteine, and creatinine. Patients were then randomized to receive 10 microg oral cyanocobalamin, 50 microg oral cyanocobalamin, or placebo treatment for 1 month, after which the investigations and clinical examinations were repeated.
                Percentage change in the level of vitamin B12, homocysteine, folate, and red cell parameters and absolute changes in MMSE were calculated and compared between groups. The groups were compared on the number of responders who improved their level of B12 by 20%. Chi-square calculations on changes in serum vitamin B12 concentration were also performed.
                Mean serum vitamin B12 +/- standard deviation improved by 51.7 +/- 47.1% in the 50-microg group, 40.2 +/- 34.4% in the 10-microg group, and 11.7 +/- 24.5% in the placebo group. The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group (P=.044). The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group (P=.186). Eight of 10 subjects in each treatment group were classified as responders, compared with two of 11 in the placebo group (P=.004). Homocysteine levels fell in patients receiving cyanocobalamin, but this fall failed to reach statistical significance. There were no significant changes in the other parameters measured.
                Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12. This result has implications for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12. Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administration and lower cost.
                This study assessed the effects and cost of p.o. versus i.m. cobalamin treatment in patients with megaloblastic anemia due to cobalamin deficiency.
                This was a 90-day, prospective, randomized, open-label study conducted at the Division of Hematology, Department of Internal Medicine, Adnan Menderes University Research and Practice Hospital (Aydin, Turkey). Patients aged > or =16 years with megaloblastic anemia due to cobalamin deficiency were randomized to receive 1000-microg cobalamin p.o. once daily for 10 days (p.o. group) or 1000-microg cobalamin i.m. once daily for 10 days (i.m. group). After 10 days, both treatments were administered once a week for 4 weeks, and after that, once a month for life. Patients were assessed for the presence of reticulocytosis between treatment days 5 and 10 until it was detected. Therapeutic effectiveness was assessed by measuring hematologic parameters on days 0, 10, 30, and 90 and serum vitamin B12 concentration on days 0 and 90. The Mini-Mental State Examination was used before and after the B12 therapy for cognitive function assessment and 125-Hz diapozone was used for vibration threshold testing. Neurologic sensory assessment, including soft-touch and pinprick examinations, was used to identify neuropathy at baseline and study end. Tolerability was assessed using laboratory tests and patient interview. Cost was assessed using the cost of the study drug and of the injection.
                Sixty patients completed the study 26 in the p.o. group (16 men, 10 women; mean [SD] age, 60 [15] years) and 34 in the i.m. group (17 men, 17 women; mean [SD] age, 64 [10] years). Reticulocytosis was observed in all patients. In the p.o. group, at days 30 and 90, all hematologic parameters changed significantly versus day 0 (mean hemoglobin levels increased [both P<0.001]; mean corpuscular volume decreased [both P<0.001]; mean white blood cell count increased [day 30, P<0.01; day 90, P<0.001]; and mean platelet count increased [both P<0.001]). The mean serum vitamin B12 concentration increased significantly from day 0 to 90 (P<0.001). These hematologic parameters and the recovery patterns were similar between the 2 groups. Neurologic findings included sensitive peripheral neuropathy in 9 patients (15.0%), alteration of cognitive function (loss of memory, impaired concentration) in 7 patients (11.7%), and loss of sense of vibration in 5 patients (8.3%). Neurologic improvement was detected in 7 of 9 patients (77.8%) in the p.o. group and 9 of 12 patients (75.0%) in the i.m. group at day 30.
                In this study of patients with megaloblastic anemia due to cobalamin deficiency, p.o. cobalamin treatment was as effective as i.m. cobalamin treatment. P.o. treatment also was better tolerated and less expensive compared with IM treatment. However, because of the small sample size and the short term of this study, further long-term studies are needed to determine the efficacy of p.o. cobalamin treatment.
The evidence derived from these limited studies suggests that 2000 mcg doses of oral vitamin B12 daily and 1000 mcg doses initially daily and thereafter weekly and then monthly may be as effective as intramuscular administration in obtaining short term haematological and neurological responses in vitamin B12 deficient patients.