A randomized placebo controlled trial of vitamin B₁₂ supplementation to prevent cognitive decline in older diabetic people with borderline low serum vitamin B₁₂

Background & aims Older diabetic people are at risk of cognitive decline. Vitamin B₁₂ deficiency in older people is associated with cognitive impairment and Alzheimer's disease. Vitamin B₁₂ deficiency may therefore contribute to cognitive decline in older diabetic people. We therefore performed a randomized placebo-controlled trial of vitamin B₁₂ supplementation to prevent cognitive decline in older diabetic people with mild vitamin B₁₂ deficiency. Methods 271 diabetic non-demented outpatients aged 70 years or older with plasma vitamin B₁₂ 150–300 pmol/L in outpatient clinics were randomly assigned to take either methylcobalamin 1000 μg or two similar looking placebo tablets once daily for 27 months. All subjects were followed up at 9 monthly intervals. The primary outcome is cognitive decline as defined by an increase in clinical dementia rating scale (CDR) global score. The secondary outcomes included Neuropsychological Test Battery (NTB) z-scores, serum methymalonic acid (MMA) and homocysteine. Results The subjects in the trial groups were well matched in clinical characteristics, except that active intervention group had more smokers. 46.5% and 74.1% had elevated serum methymalonic acid (≥0.21 μmol/L) and homocysteine (≥13 μmol/L) respectively. 44% of the subjects had CDR score of 0.5 suggesting questionable dementia. At month 9 and 27, serum MMA and homocysteine was significantly reduced in the active treatment group, when compared with placebo group. (P < 0.0001, student t test) At month 27, there was no significant group difference in changes in CDR or NTB z-scores. Exclusion of smokers did not alter the results. Subgroup analysis of high MMSE and serum MMA showed similar results. Conclusion Vitamin B₁₂ supplementation did not prevent cognitive decline in older diabetic patients with borderline vitamin B₁₂ status. Clinical trial registration ClinicalTrials.gov: NCT02457507.