Methylcobalamin (B12) vs Vitamin K2 (MK-7)

Mechanism

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.

Standard Dosing

1000-5000 mcg methylcobalamin daily (sublingual preferred)

Timing

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

Cycle Duration

ongoing

Side Effects

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

Contraindications

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

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Mechanism

Vitamin K2 (menaquinone-7) activates vitamin K-dependent proteins via gamma-carboxylation of glutamic acid residues. Key targets: osteocalcin (directs calcium into bone matrix), matrix Gla protein (MGP, inhibits arterial calcification), Gas6 (cell signaling, neuroprotection), and protein S (anticoagulant). MK-7 has a long half-life (~72 hours vs 1-2 hours for K1) enabling consistent carboxylation activity with once-daily dosing. It works synergistically with Vitamin D3 to regulate calcium metabolism — D3 increases calcium absorption while K2 directs its deposition.

Standard Dosing

100-200 mcg MK-7 daily

Timing

With fat-containing meal alongside Vitamin D3.

Cycle Duration

ongoing (mandatory co-supplement with Vitamin D3)

Side Effects

• Generally very well tolerated
• Rare: mild GI discomfort
• Theoretical thrombotic risk in deficiency-rebound scenario (unproven)

Contraindications

• Warfarin/coumarin anticoagulant therapy (unless specifically directed by physician with INR monitoring)

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