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Vitamin B12 Deficiency: Symptoms, Causes, Diagnosis, and Treatment

Signs and Symptoms of Vitamin B12 Deficiency

Vitamin B12 (cobalamin) is essential for DNA synthesis, red blood cell formation, neurological function, and homocysteine metabolism. Deficiency affects multiple systems:

Neurological (often earliest, can be irreversible)

  • Paresthesias (numbness/tingling) in hands/feet — "stocking-glove" distribution
  • Gait disturbance, balance problems, falls
  • Memory impairment, concentration difficulty, brain fog
  • Mood changes: depression, irritability, apathy
  • Severe: confusion, psychosis, dementia-like picture
  • Optic neuropathy (vision loss)

Hematologic

  • Megaloblastic anemia: fatigue, weakness, pallor, shortness of breath, palpitations
  • Macrocytosis (high MCV) on CBC — often precedes anemia

Other Manifestations

  • Glossitis (beefy, sore, smooth tongue), angular cheilitis
  • GI: nausea, appetite loss, constipation/diarrhea, weight loss
  • Skin hyperpigmentation (knuckles, palmar creases)
  • Infertility, recurrent miscarriage (elevated homocysteine)
  • Elevated homocysteine → cardiovascular/thrombotic risk

Causes and Risk Factors

  • Malabsorption (most common in adults): Pernicious anemia (autoimmune anti-intrinsic factor/parietal cell antibodies), atrophic gastritis, H. pylori, bariatric surgery (especially RYGB), celiac, Crohn's, pancreatic insufficiency, SIBO.
  • Dietary insufficiency: Vegans/vegetarians (no animal products), elderly (reduced intake + absorption).
  • Medications: Metformin (↓ absorption), PPIs/H2 blockers (↓ acid → ↓ B12 release from food), colchicine, cholestyramine.
  • Genetic: TCN2, FUT2, MTRR variants affect transport/metabolism.

Diagnosis

  • Serum B12: <200 pg/mL = deficient; 200–300 = borderline. Limited sensitivity/specificity.
  • Methylmalonic acid (MMA): Gold standard functional marker; elevated in B12 deficiency (even with normal serum B12).
  • Homocysteine: Elevated in B12 and folate deficiency.
  • Holotranscobalamin (active B12): Earlier marker; not widely available.
  • Antibodies: Anti-intrinsic factor, anti-parietal cell (pernicious anemia).

Treatment

  • Intramuscular B12: 1,000 mcg weekly × 4–8 weeks, then monthly (standard for malabsorption/pernicious anemia).
  • High-dose oral: 1,000–2,000 mcg/day (1% passive absorption bypasses IF); effective for many, including pernicious anemia.
  • Sublingual/nasal: Alternatives.
  • Monitor: Reticulocyte count (7–10 days), MMA normalization, neurologic recovery (may be incomplete if delayed).

Vitamin B12 deficiency can cause permanent neurologic damage if untreated. If you have symptoms or risk factors, request MMA + serum B12 testing. Early treatment is highly effective.

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