Vitamin B12 (Cobalamin)

Effects and Benefits

Core Identification

Common Names:
- Vitamin B12
- Cobalamin
- Cyanocobalamin (synthetic form)
- Methylcobalamin (active form)
- Adenosylcobalamin (active form)
- Hydroxocobalamin

Latin Name: N/A (vitamin, not a plant)

Category: Vitamin (B-Complex, Water-Soluble)

Uses

Traditional Uses

• Pernicious anemia treatment - Medical use since the discovery of liver extract therapy in 1926
• "Tonic" injections - Historically given for fatigue and general weakness
• Neurological conditions - Used in various cultures as a nerve tonic

Modern Uses

• Pernicious Anemia and Megaloblastic Anemia - Corrects B12-deficiency anemia characterized by abnormally large red blood cells | Research quality: Strong
• Key findings: Without B12, cells cannot complete DNA synthesis properly during cell division, resulting in large, immature red blood cells; treatment resolves anemia within approximately 6 weeks

• Source citations: Merck Manual Home Health Handbook; TDT Encyclopedia of Vitamins

• Neuropathy and Nerve Function - Maintains healthy nerve sheaths (myelin) and may help treat peripheral neuropathy | Research quality: Strong

• Key findings: B12 is essential for myelin formation; deficiency causes sub-acute combined degeneration of the spinal cord; symptoms include numbness, tingling, difficulty walking, and loss of position sense

• Source citations: Merck Manual Home Health Handbook; TDT Encyclopedia of Vitamins

• Homocysteine Reduction - Works with folate and B6 to lower elevated homocysteine levels | Research quality: Strong

• Key findings: Elevated homocysteine is an independent risk factor for heart disease, stroke, dementia, birth defects, and osteoporosis; B12 supplementation effectively lowers homocysteine levels, especially in older adults

• Source citations: TDT Encyclopedia of Vitamins; The Paleo Answer; Eating Well for Optimum Health

• Cognitive Function in Older Adults - May support memory and mental function | Research quality: Moderate

• Key findings: B12 levels decline with age, contributing to depression and impaired mental function in people over 65; methylcobalamin (1,000 mcg twice daily) recommended as adjunctive treatment for cognitive decline; some cases of B12 deficiency present as dementia

• Source citations: The Natural Remedy Bible; TDT Encyclopedia of Vitamins

• Neural Tube Defect Prevention - Works with folate to prevent birth defects | Research quality: Moderate

• Key findings: Together with folic acid, B12 protects against spina bifida and other neural tube defects; maternal B12 deficiency during pregnancy can cause spontaneous abortions, low birth weight, and developmental problems in infants

• Source citations: TDT Encyclopedia of Vitamins; The Paleo Answer

• Medication-Induced Depletion Correction - Repletes B12 depleted by metformin, PPIs, H2 blockers, and other medications | Research quality: Strong

• Key findings: Multiple drug classes reduce B12 absorption or increase requirements; supplementation prevents deficiency-related complications
• Source citations: A-Z Guide to Drug-Herb-Vitamin Interactions

Active Compounds

Primary Active Ingredients:
- Cobalamin - The vitamin itself; contains a cobalt atom at its center surrounded by a corrin ring structure
- Methylcobalamin - Active coenzyme form used directly by cells; does not require conversion; preferred for neurological conditions
- Adenosylcobalamin - Active coenzyme form involved in energy metabolism in mitochondria
- Cyanocobalamin - Most common supplemental form; stable and inexpensive but requires conversion to active forms
- Hydroxocobalamin - Injectable form; longer retention in the body than cyanocobalamin

Dosage Information

Standard Dosage:
- Form: Tablets, sublingual tablets, lozenges, or capsules
- Amount: 2.4 mcg (RDA); typical supplements contain 100-1,000 mcg
- Frequency: Once daily

Therapeutic Dosage:
- Form: Sublingual methylcobalamin or injections
- Amount: 1,000-2,000 mcg daily (oral) or injections as prescribed
- Purpose: Treating deficiency, neuropathy, cognitive support, medication-induced depletion
- Duration: Injections may be needed indefinitely for pernicious anemia; oral supplementation ongoing for at-risk populations

Maximum Safe Dosage:
- Daily maximum: No established upper limit; B12 has very low toxicity
- Warning threshold: Doses up to 1,000 mcg daily considered safe; high doses generally do not cause adverse effects

Bioavailability Notes:
- Absorption requires intrinsic factor (a protein made in the stomach) for food-bound B12
- Supplemental B12 (especially sublingual) can be absorbed without intrinsic factor
- Only about 1-2% of high-dose oral supplements absorbed through passive diffusion
- Stomach acid is required to release B12 from food but not from supplements
- Methylcobalamin and adenosylcobalamin are directly usable; cyanocobalamin requires conversion
- Conversion ability may decline with age, making methylcobalamin preferred for older adults

How to Take It

Timing:
- Can be taken any time of day
- Take with or without food (supplemental B12 does not require food for absorption)
- Sublingual forms should be held under the tongue until dissolved
- For maximum absorption, take separately from acid-reducing medications

Synergies - What It Works Well With

Complementary Supplements:
1. Folate (Vitamin B9) - Essential partners in DNA synthesis and homocysteine metabolism | Combined effect prevents megaloblastic anemia and neural tube defects; each can mask deficiency of the other
2. Vitamin B6 (Pyridoxine) - Works together in homocysteine pathway | Combined with B12 and folate for optimal cardiovascular protection
3. Iron - Both needed for healthy red blood cell production | Combined effect supports comprehensive anemia prevention
4. B-Complex Vitamins - B vitamins work synergistically in energy metabolism | Complete B-complex supports overall nervous system health
5. Calcium - May improve B12 absorption when taking metformin | Supplementation with calcium reverses metformin-induced B12 malabsorption

Avoidance - What NOT to Combine With

Supplement Interactions:
1. High-dose Vitamin C - Theoretical concern that very high doses may destroy B12 | Take separately by several hours if using megadose vitamin C

Drug Interactions:
1. Metformin - Depletes B12 through calcium-dependent mechanism | Supplement with B12 and calcium; monitor B12 levels | Severity: Moderate
2. Proton Pump Inhibitors (Omeprazole, Lansoprazole, etc.) - Reduces absorption of B12 from food by decreasing stomach acid | Supplement with B12; food B12 absorption impaired but supplement absorption not affected | Severity: Moderate
3. H2 Blockers (Famotidine, Ranitidine, Nizatidine, Cimetidine) - Reduces stomach acid, impairing food B12 absorption | Supplement with B12; consider annual B12 level testing with long-term use | Severity: Moderate
4. Anticonvulsants (Phenobarbital, Valproic Acid, Gabapentin) - May lower B12 levels, particularly in cerebrospinal fluid | Monitor B12 levels; supplementation may prevent nerve and mental problems | Severity: Moderate
5. Nitrous Oxide (Anesthesia) - Inactivates B12, can precipitate acute deficiency | People with borderline B12 status at risk during surgery | Severity: Moderate
6. Oral Contraceptives - May lower B12 levels with long-term use | Monitor levels; consider supplementation | Severity: Mild
7. Antibiotics (long-term) - May reduce gut bacteria that produce small amounts of B12 | Monitor with prolonged antibiotic courses | Severity: Mild
8. Colchicine - Impairs B12 absorption | Supplement if using long-term | Severity: Mild

Food Interactions:
- Alcohol - Chronic alcohol use impairs B12 absorption and depletes body stores
- Cranberry juice may enhance food B12 absorption for people on acid-reducing medications

Safety Information

Contraindications:
- Allergy to cobalamin or cobalt (rare)
- Leber's hereditary optic neuropathy - B12 supplementation may accelerate vision loss
- Caution in polycythemia vera (B12 may stimulate red blood cell production)

Side Effects:
- Generally extremely well-tolerated with minimal side effects
- Rare: Skin rash, itching, or mild diarrhea
- Injectable forms: Injection site reactions possible
- Very rare: Anaphylaxis with injections (more common with hydroxocobalamin)

Long-Term Use:
- Safe for indefinite use
- Required lifelong for pernicious anemia patients
- No cycling needed
- Annual monitoring of B12 levels recommended for high-risk populations

Special Precautions:
- Pregnancy/Breastfeeding: Essential during pregnancy and breastfeeding; vegan mothers must supplement to protect infant neurological development; deficiency can cause serious birth defects and developmental delays
- Older adults: Absorption declines with age due to reduced stomach acid and intrinsic factor; 10-30% of adults over 50 have impaired B12 absorption from food; supplements recommended
- Surgery: Nitrous oxide anesthesia inactivates B12; inform surgeon if B12 status is borderline
- Vegetarians/Vegans: At very high risk of deficiency (studies show 73% of vegans and 24% of lacto-ovo vegetarians are deficient); supplementation essential
- Folic Acid Masking: High folic acid intake can mask B12 deficiency anemia while neurological damage progresses; always supplement B12 when taking high-dose folate

Primary Uses At-a-Glance

Primary: Pernicious anemia, megaloblastic anemia, neuropathy, nerve damage, medication-induced B12 depletion, vegetarian/vegan supplementation

Secondary: Homocysteine reduction, cognitive support in older adults, fatigue (when caused by deficiency), pregnancy support, tinnitus, multiple sclerosis support

Sources

Local Library:
- Gaby, Alan R. - A-Z Guide to Drug-Herb-Vitamin Interactions 2nd Ed (drug interaction data)
- Brewer, Sarah - TDT Encyclopedia of Vitamins (comprehensive vitamin profile)
- Merck - The Merck Manual Home Health Handbook (deficiency, treatment protocols)
- Lust, John - The Natural Remedy Bible (cognitive function, Alzheimer's)
- Lust, John - The Herb Book (vitamin overview)
- Cordain, Loren - The Paleo Answer (vegetarian deficiency data, homocysteine)
- Weil, Andrew - Eating Well for Optimum Health (dietary recommendations)
- Curtis, Susan - Neal's Yard Remedies (dosage chart)
- Behan, Eileen - The Baby Food Bible (infant nutrition)

General Knowledge:
- Clinical studies on B12 forms and bioavailability
- EPIC-Oxford vegetarian study data
- Biochemistry of cobalamin coenzymes