Vitamin B12
Vitamin B12
Generic Name
Vitamin B12
Mechanism
Vitamin B12 (cobalamin) is an essential cofactor for two critical enzymatic reactions in humans:
• Methionine synthase (MTR): Transfers a methyl group from 5‑methyltetrahydrofolate to homocysteine, generating methionine and tetrahydrofolate.
• Methylmalonyl‑CoA mutase: Converts methylmalonyl‑CoA to succinyl‑CoA in the mitochondrial matrix, a key step in odd‑chain fatty‑acid and choline catabolism.
By maintaining normal *homocysteine* and *methylmalonic acid* metabolism, cobalamin preserves DNA synthesis, myelin maintenance, and overall cellular proliferation. Deficiency leads to ineffective erythropoiesis, macrocytic anemia, and neurodegeneration.
Pharmacokinetics
| Parameter | Typical Value |
| Absorption | Requires intrinsic factor (IF) for active intestinal uptake; passive absorption ≈ 1–2 % at oral doses > 100 µg. |
| Distribution | Widely distributed in intracellular compartments, concentrated in liver, bone marrow, and nervous tissue. |
| Half‑life | 6–12 months (storeable in hepatic tissue). |
| Metabolism | Degradation intracellularly into adenosyl‑ and methyl‑cobalamin forms; no significant hepatic metabolism. |
| Excretion | Renal excretion of unbound B12; negligible hepatic clearance. |
Key point: Large oral doses (> 1 mg) bypass IF–mediated transport via passive absorption.
Indications
- Macrocytic (megaloblastic) anemia – pernicious anemia, atrophic gastritis, gastric surgery, chronic alcohol use.
- Early‑stage subacute combined degeneration of the spinal cord (to relieve neuropathic pain, gait disturbance).
- Sperm quality improvement – especially in men with idiopathic infertility.
- Prevention of neural tube defects (NTDs) in pregnancy (≥ 400–500 µg daily).
- PCA (pre‑CNS) in Alzheimer’s disease – adjunctive, limited evidence.
- Mitigation of heterocyclic amine‑induced oxidative stress in certain oncology protocols.
Contraindications
- Allergy to cyanocobalamin or other B12 analogs.
- Severe renal impairment – not contraindicated, but dose adjustment is rarely required; monitor serum B12 if chronic kidney disease (CKD) Stage 3+.
- History of paradoxical thromboses – rare; B12 can transiently raise homocysteine levels; use cautiously in patients on antiplatelet therapy.
Warnings: Monitor for neuropsychiatric changes in patients with baseline euphoria or mania; rare risk of anaphylaxis in individuals with severe IgE‑mediated allergies.
Dosing
- Intramuscular (IM):
- *Initial/maintenance:* 1 mg *cobalamin* (cyanocobalamin or hydroxocobalamin) IM daily for 1–2 weeks.
- *Maintenance:* 1 mg IM once weekly, tapering to 1 mg IM monthly once levels normalize.
- Oral:
- *Deficiency:* 1000–2000 µg *cobalamin* orally daily (usually 1000 µg is sufficient for most).
- *Supplementation / pregnancy:* 1000–2000 µg orally daily.
- *Sublingual:* 1000 µg daily as an add‑on.
- Dermal: Regressive; rarely used today.
Note: Oral high‑dose therapy is effective for pernicious anemia in most patients, eliminating the need for lifelong IM injections.
Monitoring
| Parameter | Target Range | Frequency |
| Serum B12 | ≥ 200 pg/mL (≥ 148 pmol/L) | Baseline → Every 3–6 months |
| Metabolic markers |
• Methylmalonic acid (MMA) < 0.4 µmol/L • Homocysteine < 15 µmol/L | After 3‑4 weeks of therapy |
| Complete Blood Count (CBC) | Normal MCV (< 95 fL) – improvement within 2–3 weeks | After 2–3 weeks |
| Neurologic exam | Normal gait, reflexes | At each clinic visit |
| Renal function | eGFR ≥ 30 mL/min/1.73 m² | Every 6 months for CKD patients |
Tip: Negative feedback on homocysteine may be masked by folate supplementation; consider folate‑independent B12 assessment.
Clinical Pearls
- “Red‑water” injection: Use *hydroxocobalamin* (injectable, 1 mg IM) when rapid correction is needed; it is visible as a persistent intramuscular stain for a few months.
- High‑dose oral is generally safe: Even in pernicious anemia, 1 mg oral daily yields absorption of ~1 % by paracellular diffusion – adequate for most patients.
- Stop folate‑only therapy if B12 deficiency suspected – Folate alone can mask anemia and worsen neurotoxicity.
- Sublingual dose of 1000 µg daily is as effective as IM 1 mg, but watch for patient compliance.
- Vulnerable populations: Pregnant women, vegan/vegetarian diets, chronic GI disorders, and hemochromatosis patients – screen early.
- Neuropathy Assessment: Use the Swan–Greenland milestone scale; B12 supplementation improves subjective and objective measures within 8 weeks.
- Check MMA in “gray zone” B12 < 400 pg/mL – helps differentiate true deficiency from B12 resistance.
By mastering these fundamentals, medical students and clinicians can confidently diagnose, treat, and monitor patients affected by Vitamin B12 deficiency or those requiring preventive supplementation.