Oral vitamin B12 for patients suspected of subtle cobalamin deficiency: a multicentre pragmatic randomised controlled trial

Multicentre pragmatic randomized controlled trial in western Switzerland. Adults in primary care and nursing homes with borderline serum vitamin B12 levels (125-200 pM/l) and suspected subtle cobalamin deficiency were enrolled; the active intervention arm included 26 participants, with mean age 69.6 years and 53.8% female.

The active intervention was oral cobalamin (vitamin B12) 1000 μg daily for 4 weeks, compared with placebo. The effect was assessed again after treatment cessation to determine whether metabolic changes persisted.

One month of oral vitamin B12 improved the primary metabolic marker: serum methylmalonic acid fell by 0.13 μmol/l (95% CI 0.06-0.19) more than in the placebo group. Serum vitamin B12 increased significantly, but homocysteine, hematocrit, mean corpuscular volume, and clinical symptom/sign improvement did not show meaningful benefit. After three months off treatment, the methylmalonic acid difference was no longer detectable. The authors concluded that short-term oral vitamin B12 normalizes methylmalonic acid, but the clinical significance of correcting metabolic markers alone remains uncertain.

The trial was small and short, with only 26 participants in the active arm and limited follow-up after stopping treatment. Benefits were mainly biochemical rather than clinical, and the metabolic effect did not persist four months after treatment initiation. Generalizability is limited to older adults with borderline B12 levels and suspected subtle deficiency in primary care settings.