Vitamin B12 replacement strategies: a Brazilian delphi consensus.

Abstract

Background: Vitamin B12 deficiency is common in older adults, atrophic gastritis, and after bariatric surgery, and can cause irreversible neurological injury. Oral, sublingual, and intramuscular routes all correct serum concentrations, yet whether any route is superior for clinically meaningful outcomes is unclear, and international guidelines diverge. This consensus was convened to define where evidence is adequate, where it is lacking, and the priority research questions.

Methods: This was a modified Delphi consensus study. The RAND/UCLA Appropriateness Method was applied through a two-stage process of 2 electronic rounds and an in-person meeting in São Paulo, Brazil. Panellists were recruited between 1 July 2025 and 15 July 2025. Thirty statements were voted on, presented as 31 graded items, using a binary (agree or disagree) format with a priori percentage-agreement grades (A+, 100%; A, 90%-99.9%; B, 80%-89.9%; C, 70%-79.9%; and D, 66%-69.9%). Draft statements, informed by a systematic review, were rated anonymously by a Brazilian multidisciplinary panel of 20 experts across haematology, gastroenterology, endocrinology, bariatric surgery, and geriatric medicine/neurology. Of 20 experts invited, all 20 agreed to participate and completed the electronic rounds (100%); 16 (80%) attended the in-person meeting. Patient representatives (n = 2) participated as non-voting observers. Grade A (at least 90% agreement) was the stopping rule. This consensus was not registered.

Findings: In total, 30 statements across 6 modules were agreed, comprising 31 separately graded items as statement 1 was presented in two parts (1a and 1b); 22 of 31 items (71%) reached grade A+ (100% agreement) and 9 of 31 (29%) reached grade A (90%-99.9%). All routes were judged capable of normalising serum vitamin B12, but none showed proven superiority for symptom resolution, neurological recovery, functional status, or quality of life. Evidence gaps were greatest after bariatric surgery, in older adults with cognitive impairment or frailty, and in pernicious anaemia. Dosing, monitoring, and response definitions varied substantially.

Interpretation: Vitamin B12 replacement across all routes remains guided primarily by biochemical rather than clinical evidence. Treatment should be individualised by aetiology, patient preference, feasibility, and access, with functional biomarkers and clinical assessment complementing serum levels. Adequately powered, long-term comparative trials using standardised, patient-centred outcomes are the priority.

Funding: This work was funded by Myralis Indústria Farmacêutica Ltda, São Paulo, Brazil.