Vitamin B12 (Cobalamin)
B12· also: Cobalamin, Vit B12, Cyanocobalamin
Clinical Overview
Vitamin B12 (cobalamin) is a water-soluble vitamin essential for DNA synthesis, nerve myelin sheath maintenance, and red blood cell formation. It is found only in animal products, making strict vegans at high risk of deficiency. B12 absorption requires intrinsic factor — a protein produced by stomach parietal cells — making gastric disorders another major risk factor.
Why This Test Matters
Vitamin B12 deficiency causes megaloblastic anemia (large, dysfunctional red blood cells) and subacute combined degeneration of the spinal cord — a neurological condition causing progressive weakness, balance problems, and cognitive decline. The neurological damage can be irreversible if not treated promptly. Importantly, folate supplementation can mask the hematological manifestations while allowing the neurological damage to progress — making B12 testing essential alongside folate.
Reference RangesWHO/IFCC standards
| Reference Range | Unit | Notes |
|---|---|---|
| 200 – 900 | pg/mL | — |
Also reported in: pmol/L.
Critical (Panic) Values
Critical Low: < 100 pg/mL. Values outside these limits require immediate clinical attention.
What Causes Abnormal Results?
High B12 Causes
- B12 supplements or injections
- Liver disease (release of stored B12)
- Myeloproliferative disorders (elevated B12-binding proteins)
- Solid organ cancers (paraneoplastic)
Low B12 Causes
- Vegan and strict vegetarian diet (most common in young adults)
- Pernicious anemia (autoimmune destruction of intrinsic factor producing cells)
- Atrophic gastritis (reduced intrinsic factor and gastric acid)
- Post-gastric surgery (gastrectomy, bariatric surgery)
- Crohn's disease (terminal ileum is the absorption site for B12)
- Long-term metformin use (reduces B12 absorption)
- Long-term proton pump inhibitor (PPI) use
- Alcohol excess
- Tapeworm (Diphyllobothrium latum) — competes for B12
Signs & Symptoms to Watch For
How to Prepare for This Test
No fasting required. B12 supplements should ideally be stopped for a few days before testing (if assessing status, not monitoring supplementation) for the most accurate result. Note that even a single B12 injection can normalize serum B12 for weeks.
Factors That Can Affect Results
- Recent B12 injection or high-dose oral B12 (raises level acutely)
- Folate deficiency (can co-occur with B12 deficiency)
- High-dose folate supplementation (may mask B12 deficiency anemia)
- Methotrexate (depletes folate and affects B12 metabolism)
Related Topics
Frequently Asked Questions
Can B12 deficiency cause permanent nerve damage?
Yes. Prolonged B12 deficiency causes subacute combined degeneration (SCD) of the spinal cord — damage to the dorsal and lateral columns. Early symptoms (tingling, balance problems) are reversible with B12 treatment. However, if deficiency persists for months to years, the demyelination becomes permanent and the neurological deficits may not fully resolve. Early diagnosis and treatment are critical.
Can I rely on serum B12 alone to diagnose deficiency?
Serum B12 has significant limitations — levels can be in the "normal" range despite cellular deficiency (especially in elderly patients). More functional markers include methylmalonic acid (MMA) and homocysteine, which accumulate when B12-dependent enzymes are impaired. Elevated MMA (with normal folate) is the most specific marker of cellular B12 deficiency and should be measured when B12 is borderline low (200–300 pg/mL) with clinical symptoms.
Do vegans need B12 supplements?
Yes. B12 is found only in animal products — meat, fish, dairy, and eggs. Strict vegans who do not supplement invariably develop B12 deficiency over time (often within 2–5 years of starting a vegan diet, depending on body stores). All vegans should take a daily B12 supplement (at least 25–250 µg/day for cyanocobalamin) or consume B12-fortified foods (plant milks, nutritional yeast).