What Is Vitamin B12?
Vitamin B12 (cobalamin) is a water-soluble vitamin synthesised exclusively by micro-organisms. In the human diet it is found only in animal products (meat, fish, eggs, dairy). It is an essential cofactor for two key enzymes:
- Methionine synthase: converts homocysteine to methionine — critical for methylation reactions, DNA synthesis, and nerve myelination
- Methylmalonyl-CoA mutase: important for fatty acid metabolism and myelin synthesis (the nerve’s protective sheath)
Notably: the body maintains B12 stores for 3–5 years (mainly in the liver). Deficiency therefore develops gradually — by the time neurological symptoms appear, damage may already be advanced.
Who Is at Risk?
B12 deficiency is one of the most common yet most frequently overlooked nutritional deficiencies:
| At-risk group | Cause | Comment |
|---|---|---|
| Vegans | No B12 in plant foods | Supplementation essential |
| Vegetarians | Limited amounts via dairy/eggs | Risk depends on intake |
| Adults aged 60+ | Atrophic gastritis → less intrinsic factor | Up to 20% affected (Green 2017) |
| Metformin users | Metformin impairs intestinal B12 absorption | 4.3× higher deficiency risk after >3 years |
| PPI users | Reduces gastric acid → worse B12 release from food | Long-term risk |
| Gastric bypass patients | No intrinsic factor | Lifelong supplementation required |
Symptoms and Diagnosis
Early symptoms are non-specific: fatigue, difficulty concentrating, tingling in hands and feet (paraesthesia), burning tongue. These are often ignored for months.
Severe deficiency leads to:
- Polyneuropathy (nerve damage, potentially irreversible if not treated early)
- Megaloblastic anaemia (large, immature red blood cells)
- Cognitive impairment, dementia-like symptoms
Diagnosis: Serum B12 alone is unreliable (false-normal results possible). More sensitive markers: holotranscobalamin (active B12) and methylmalonic acid (MMA) — elevated MMA is the most reliable deficiency marker per Herrmann & Obeid (2008).
What Do the Studies Show?
Clearly established
- B12 deficiency causes severe, potentially reversible conditions if treated early (clear causal evidence)
- Supplementation reliably raises blood levels
- High-dose oral B12 (1,000–2,000 µg/day) is as effective as injections in most patients — even without intrinsic factor, passive diffusion absorbs ~1% of the dose, meaning 10 µg from 1,000 µg
- EFSA-approved claims for energy, nervous system, red blood cells, and fatigue reduction
Interesting but limited
Cognition and brain atrophy: The VITACOG study (Smith 2010, n=168) showed that B vitamins (including B12) slowed brain atrophy in mild cognitive impairment with elevated homocysteine by 53%. Important: this effect occurred only in those with high baseline homocysteine — not in people with normal values.
Contested
Homocysteine and heart disease: B vitamins significantly lower homocysteine, but a meta-analysis (Clarke 2010) shows that homocysteine reduction does not consistently translate into fewer heart attacks. The assumed mechanism (homocysteine → cardiac risk) is weaker than long believed.
Not established
- Energy boost in people with normal B12 levels (despite widespread belief)
- Longevity effects in adequately nourished individuals
- Cognitive improvement without actual deficiency or elevated homocysteine
Which Form?
| Form | Properties | Recommendation |
|---|---|---|
| Cyanocobalamin | Cheapest standard form; must be converted in the body | Sufficient for most people |
| Methylcobalamin | Active form, directly usable; preferred for nerve issues | Useful for neurological complaints |
| Adenosylcobalamin | Mitochondrial active form | Complementary to methylcobalamin |
| Hydroxocobalamin | Depot form for injections | Clinical use only |
For most people, cyanocobalamin at standard doses is sufficient — inexpensive, stable, well studied. People with MTHFR polymorphism (methylation impairment) may benefit from methylcobalamin, though clinical evidence for this is limited.
Dosage
- Vegans: At least 250 µg/day orally, or 2,000 µg twice weekly (passive diffusion)
- Deficiency correction: 1,000–2,000 µg/day orally over several weeks until normalisation
- Prevention in at-risk groups: 500–1,000 µg/day
- Maintenance dose after deficiency: 100–500 µg/day
Vitamin B12 is safe — no known toxicity at high oral doses. Excess is renally excreted. No relevant drug interactions.
Limitations
- B12 deficiency is frequently missed because serum B12 is a poor marker and symptoms are non-specific
- Cognitive studies (VITACOG) are small and limited to subgroups with elevated homocysteine — not generalisable to the healthy general population
- The metformin association is well established, but whether B12 supplementation in these patients improves clinical outcomes (beyond just levels) is less well studied
EFSA Status
EFSA has approved multiple health claims for vitamin B12, including:
- Contributes to normal nervous system function
- Contributes to formation of red blood cells (together with folate)
- Normal energy metabolism
- Reduction of tiredness and fatigue
- Normal psychological function
Recommendation: Who Should Test and Supplement?
Annual B12 check (holotranscobalamin + MMA) is sensible for:
- Vegans and strict vegetarians
- Adults aged 65+
- Long-term metformin or PPI users
- People with unexplained fatigue or tingling in the extremities
In confirmed deficiency: 1,000 µg/day orally — sufficient even without intrinsic factor via passive diffusion (~1% absorbed, i.e. 10 µg from 1,000 µg).