Interaction databaseSupplement × PrescriptionReviewed May 2026

Famotidine and Methylcobalamin, a synergy.

Methylcobalamin (a free coenzyme form of B12) does not require gastric acid for absorption, making it a reliable supplemental B12 source for patients on famotidine. Two or more years of H2 blocker use is associated with a 25% higher B12 deficiency risk, which oral methylcobalamin can prevent in most patients.

One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.

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What the row says.

Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.

At a glance

Substances
Famotidine and Methylcobalamin
Pair type
Synergy
Evidence (highest tier)
Moderate
Source citations
2 sources
Stack Score effect
+2 to your Stack Score (per scored synergy row).
Scope
Supplement × Prescription
Last verified
May 30, 2026

Synergy · Moderate evidence

Synergy

What is happening. Methylcobalamin (a free coenzyme form of B12) does not require gastric acid for absorption, making it a reliable supplemental B12 source for patients on famotidine. Two or more years of H2 blocker use is associated with a 25% higher B12 deficiency risk, which oral methylcobalamin can prevent in most patients.

Mechanism. Free B12 supplements bypass the acid-pepsin step needed to release cobalamin from dietary protein. Intrinsic factor binds the free vitamin directly for ileal absorption, which is unaffected by H2-receptor blockade.

Recommendation. If you take famotidine long-term, 500-1000 mcg of oral methylcobalamin daily is a sensible insurance dose. Ask for an annual serum B12 check while on chronic famotidine.

Sources (2)
  1. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-42. PMID 24327038
  2. Miller JW. Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications. Adv Nutr. 2018;9(4):511S-518S. PMID 30032223

Stack Score

How this pair moves the number.

Effect on the composite score

If both Famotidine and Methylcobalamin are in the same stack, this pair applies +2 to your Stack Score (per scored synergy row).

The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.

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