Evidence summary for clinicians

Vitamin B12 absorption is largely dependent on intrinsic factor. Food-cobalamin malabsorption is common, particularly with advancing age, reduced gastric acid, atrophic gastritis, or medications such as metformin. Passive diffusion accounts for only a small fraction of absorption.

Network meta-analysis of B12 administration routes shows that while high-dose oral, sublingual and intramuscular routes can all raise serum levels, intramuscular administration ranked highest for increasing B12 concentrations in the included studies.

Broader micronutrient bioavailability is influenced by host factors (age, gut health, medications), dietary antagonists and the food matrix. Fat-soluble vitamins such as vitamin D are particularly dependent on bile acids and micelle formation.

Intravenous administration bypasses gastrointestinal absorption and first-pass metabolism, achieving essentially complete bioavailability. Classic pharmacokinetic work on vitamin C demonstrated that oral dosing is tightly controlled, while intravenous dosing produces substantially higher plasma concentrations.

Dissolving microneedle arrays have been shown to penetrate the stratum corneum with high insertion efficiency and to deliver vitamin B12 transdermally.

Additional dissolving microneedle formulations (PVP/trehalose) demonstrated measurable permeation of vitamin B12 through skin and subsequent biological activity in endothelial cell models.

Pharmacokinetic evaluation of cyanocobalamin-loaded dissolving microneedles in animal models showed systemic exposure with a more sustained profile compared with injection in the reported study.