Methylcobalamin — the bioactive B12.

Vitamin B12 exists in several forms. Cyanocobalamin — the cheapest, most stable, most widely sold form — must be converted by the body into methylcobalamin or adenosylcobalamin before it's actually usable. That conversion is inefficient in some patients (genetics, age, certain medications), which is why serum B12 levels can look normal while functional B12 is low.

Methylcobalamin skips the conversion step. It's the coenzyme form directly involved in methionine synthase activity — the enzyme that drives the methylation cycle, recycles homocysteine, and supports myelin synthesis in the nervous system.

Methionine synthase requires methylcobalamin as a cofactor to convert homocysteine into methionine. Methionine is then converted to S-adenosylmethionine (SAMe), the universal methyl donor for hundreds of reactions: DNA methylation, neurotransmitter synthesis, myelin maintenance, phospholipid turnover.

When that pathway is under-supplied, the downstream signals are fatigue, brain fog, mild cognitive slowing, sometimes elevated homocysteine (a vascular risk marker). Restoring the methyl-B12 input is one of the cheapest, safest interventions in functional medicine.

Methylcobalamin injections tend to fit:

• Patients with low or low-normal serum B12 + symptoms (fatigue, cognitive complaints)
• Patients with elevated homocysteine on labs
• Patients on metformin, PPIs, or other medications known to lower B12
• Patients with MTHFR variants who convert cyanocobalamin inefficiently
• Vegan/vegetarian patients without consistent supplementation

Patients with normal labs and no symptoms don't need it. Excess B12 is excreted, so there's no toxicity risk — just no benefit either.

Typical clinical protocol: 1mg (1,000mcg) subcutaneous injection, once weekly. Some patients with malabsorption start with a 2–4 week loading phase (1mg twice weekly) before settling into maintenance.

Lab follow-up at 3 months — serum B12, homocysteine, and a methylmalonic acid (MMA) check to confirm functional B12 status, not just the easy serum number.

Patients who start with truly low B12 often notice energy and mental-clarity changes within 2–4 weeks. Patients already in range typically don't feel anything — and don't need it. Homocysteine drops are usually visible at the 3-month lab recheck.

Methylcobalamin specifically — not cyanocobalamin. Sourced through our U.S. 503A compounding pharmacy. We don't prescribe B12 reflexively for “fatigue” without labs confirming the deficiency — there's no benefit to a patient who's already replete, and we'd rather find the actual cause.