Vitamins

Methylcobalamin (B12)

Evidence: strong_human

Mechanism of Action

Methylcobalamin serves as a cofactor for methionine synthase, transferring a methyl group from 5-MTHF to homocysteine to regenerate methionine and subsequently SAMe. Adenosylcobalamin (the other active B12 form) is a cofactor for methylmalonyl-CoA mutase in mitochondrial energy production and odd-chain fatty acid metabolism. B12 is essential for myelin synthesis, DNA synthesis (thymidylate synthase pathway), red blood cell maturation, and neurological function. Deficiency causes megaloblastic anemia and irreversible subacute combined degeneration of the spinal cord.

Dosing Protocol

Standard: 1000-5000 mcg methylcobalamin daily (sublingual preferred)

Loading: 5000 mcg/day sublingual or IM injections (1000 mcg weekly x8) for deficiency

Maintenance: 1000 mcg/day sublingual

Administration: oralsublingualintramuscular injection

Timing: Morning, sublingual for best absorption (bypasses intrinsic factor requirement). Can combine with methylfolate.

Duration: ongoing

Notes

B12 deficiency is epidemic among: vegans/vegetarians, elderly (reduced intrinsic factor), metformin users, PPI users, and post-bariatric surgery patients. Serum B12 is a poor marker — methylmalonic acid (MMA) and homocysteine are more sensitive. Functional B12 deficiency can exist with 'normal' serum levels. Neurological damage from B12 deficiency can be irreversible — screen aggressively. Some individuals do better with hydroxocobalamin or adenosylcobalamin than methylcobalamin (COMT slow metabolizers).

Stacking

  • Methylfolate
  • P5P (B6)
  • Iron (if also deficient)
  • TMG

Interactions

  • Metformin [MEDIUM] — Metformin reduces B12 absorption by 10-30% — supplementation recommended for all long-term metformin users
  • Proton pump inhibitors (PPIs) [MEDIUM] — PPIs reduce gastric acid needed for B12 release from food proteins
  • Colchicine [LOW] — Reduces B12 absorption
  • Chloramphenicol [LOW] — May reduce B12 hematologic response

Contraindications

  • Leber's hereditary optic neuropathy (cyanocobalamin specifically; methylcobalamin is generally safer)
  • Polycythemia vera

Side Effects

  • Acne/skin breakouts (common)
  • Anxiety (overmethylation in susceptible individuals)
  • Diarrhea
  • Headache
  • Hypokalemia (during rapid repletion of severe deficiency)

Key Papers

  • 10.1056/NEJMcp1113996
  • 10.3390/nu12061796
  • 10.1001/jamainternmed.2013.6288

Source Quality

Methylcobalamin and adenosylcobalamin are the active coenzyme forms. Hydroxocobalamin (long-acting, used in Europe for injection) is also excellent. AVOID cyanocobalamin (requires decyanation, produces cyanide). Sublingual lozenges or liquid for best absorption without relying on intrinsic factor. Brands: Jarrow Methyl B-12, Pure Encapsulations Adenosyl/Hydroxy B12, Seeking Health.

Disclaimer: This information is for educational purposes only and is not medical advice. BioAccelera Labs does not diagnose, treat, or prescribe. Consult a licensed healthcare provider before using any compound.

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