Question 1

Why does the calculator refuse to dose a healthy omnivore?

Accepted Answer

The largest Mendelian-randomization study to date (PMID 40739033) found null effect on cognitive performance and 8 psychiatric outcomes from raising serum B12 in genetically replete adults. A mixed omnivore diet meets the 2.4 µg/day RDA without supplementation. The calculator surfaces a no-benefit refusal and redirects to lab work (serum B12 + MMA) before recommending dose. If labs show deficiency or context changes (vegan, metformin ≥4 y, post-bariatric, atrophic gastritis), pick a different goal.

Question 2

Why do I need annual B12 screening on metformin?

Accepted Answer

ADA 2026 standards recommend annual B12 + MMA + CBC after 4 years on metformin. The 2026 Diabetologia GWAS (PMID 41537778) identified CUBN rs1801222 — AA homozygotes hit 12.84% deficiency on long-term metformin vs 6.02% in GG, and reach the 10% deficiency threshold in 11 years vs 21. If you know your genotype and you're AA, screen every 6 months and supplement prophylactically at 500–1000 µg/day.

Question 3

Oral or intramuscular B12 for pernicious anemia?

Accepted Answer

Oral 1000 µg/day cyanocobalamin reverses pernicious anemia in 88.5% of patients at 1 month and 100% by 12 months (Lacombe 2024, PMID 38797248) — and the Cochrane review (PMID 29543316) found low-quality but consistent evidence that oral and IM are equivalent for serum B12 normalization. The historical IM-by-default reflex is outdated. IM is still appropriate for inability to swallow, refractory malabsorption, or patient preference.

Question 4

Cyanocobalamin, methylcobalamin, or hydroxocobalamin?

Accepted Answer

Cyanocobalamin is first-line for repletion and gap-filling — equal efficacy to methylcobalamin per Cochrane, longest shelf life, cheapest. Methylcobalamin (mecobalamin) is the form with peripheral-neuropathy meta-analysis evidence (PMID 32716261) — the calculator forces methyl on the DPN goal. Hydroxocobalamin is appropriate for chronic kidney disease, Leber's hereditary optic neuropathy (where cyanocobalamin is contraindicated due to theoretical cyanide load on the optic nerve), and as a longer-half-life IM option in clinical settings.

Question 5

What about transdermal patches and sublingual lozenges?

Accepted Answer

Avoid transdermal patches — the cobalamin molecule is too large for meaningful skin absorption, and severe deficiency on patch reliance is documented in the literature. Sublingual / lozenge B12 is fine but offers no confirmed advantage over swallowed tablets at equivalent doses; the alleged sublingual mucosal absorption advantage is not supported by head-to-head pharmacokinetic studies.

Question 6

Can supplementing cause acne or rosacea?

Accepted Answer

Yes — high-dose oral or IM cyanocobalamin and methylcobalamin can trigger acneiform eruptions on the face, shoulders, and chest, and aggravate papulopustular rosacea (especially with B6 stacks). The calculator flags this for ≥1000 µg/day methylcobalamin specifically. If a flare develops, discontinue and switch to hydroxocobalamin.