Ultimate Longevity Bible

Biomarker

Vitamin B12 (Cobalamin)

Last updated Sat May 30 2026 00:00:00 GMT+0000 (Coordinated Universal Time)

ObservationalStandard nutritional biomarker

Why serum B12 alone misleads

Serum B12 (total cobalamin) includes inactive bound forms. ~5–10% of older adults with "normal" serum B12 have functional deficiency. Better indicators:

  • Methylmalonic acid (MMA) — rises before serum B12 falls.
  • Holotranscobalamin — the active fraction.
  • Homocysteine — less specific but easier to measure.

If serum B12 is in the 200–400 zone and symptoms or risk factors are present, get MMA.

Clinical consequences of deficiency

  • Megaloblastic anaemia (late).
  • Peripheral neuropathy (often irreversible if prolonged).
  • Subacute combined degeneration of the spinal cord.
  • Cognitive impairment / dementia symptoms.
  • Glossitis, mood disturbance.

Causes

  • Inadequate intake (vegans, restricted diets).
  • Pernicious anaemia (autoimmune loss of intrinsic factor).
  • Atrophic gastritis (very common over age 60).
  • Metformin (~20% of long-term users).
  • PPIs (chronic use).
  • Gastric or ileal resection / bypass.
  • Crohn's disease.

Treatment

  • Oral 1,000–2,000 μg/day is often sufficient even in pernicious anaemia (high-dose passive absorption).
  • IM 1,000 μg weekly × 8 then monthly for severe deficiency or neurological involvement.
  • Sublingual formulations may help in atrophic gastritis.

Related entries

Homocysteine, Methylmalonic acid, Metformin, Plant-based diet.

References

  • Stabler, S. P. Vitamin B12 deficiency. N. Engl. J. Med. 368, 149–160 (2013).

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