Vitamin B6, B9 & B12

Approved Uses:

• Vitamin B₆ (Pyridoxine):
• Prevention and treatment of pyridoxine deficiency (e.g., due to poor diet, malabsorption, long-term isoniazid therapy).
• Adjunct in pyridoxine-dependent epilepsy (rare inherited metabolic disorder).
• Vitamin B₉ (Folic Acid):
• Treatment and prevention of folate-deficiency anemia and megaloblastic anemia.
• Prevention of neural tube defects in pregnancy (e.g., spina bifida, anencephaly).
• Vitamin B₁₂ (Cobalamin):
• Treatment and maintenance of vitamin B₁₂ deficiency (e.g., pernicious anemia, atrophic gastritis, malabsorption syndromes).
• Macrocytic anemia due to B₁₂ deficiency.

Off‑label (Clinically Accepted) Uses:

• Combined supplementation to reduce elevated homocysteine in cardiovascular risk management.
• Adjunctive use in peripheral neuropathy (e.g., diabetic, idiopathic).
• Management of pregnancy-related nausea (with high-dose B₆ formulations).
• Adjunct in depression or mood disorders alongside antidepressants.

Adults:

• Vitamin B₆: 1.3–2 mg daily for maintenance; therapeutic doses (e.g., neuropathy): 25–100 mg/day.
• Folic Acid: 400–800 µg daily; in pregnancy or deficiency up to 1,000 µg (1 mg) per day.
• Vitamin B₁₂: Oral: 500–1,000 µg once daily; Intramuscular (IM): 1,000 µg every 1–3 months per deficiency regimen.

Combination Tablet (typical once‑daily):

• B₆ 50 mg | Folic Acid 400 µg | B₁₂ 500 µg.

Elderly:

• Same dosing; attention to absorption—prefer IM B₁₂ if malabsorption detected.

Pediatrics:

• B₆: 0.5–1 mg/day maintenance; deficiency treatment: up to 10–25 mg/day under medical supervision.
• Folic Acid: 150–300 µg/day baseline, up to 1 mg/day in deficiency.
• B₁₂: Age-appropriate oral or IM dosing per pediatric guidelines; combination formulas less common.

Renal Impairment:

• No routine adjustment required; water-soluble and cleared renally.
• ESRD or dialysis patients may need higher doses, especially B₁₂.

Hepatic Impairment:

• Generally no dose adjustment; monitor in severe hepatic failure due to altered metabolism/storage.

Administration Route & Duration:

• Oral doses with or without food.
• IM injections for B₁₂ deficiency follow loading and maintenance schedule.
• Duration varies: until biochemical/clinical correction, then maintenance or preventive dosing.

• Vitamin B₆ (Pyridoxine): Converted to pyridoxal 5′-phosphate (PLP), a coenzyme essential in transamination, decarboxylation, neurotransmitter synthesis (serotonin, dopamine, GABA), and hemoglobin formation.
• Folic Acid (B₉): Converted to tetrahydrofolate derivatives, vital for one-carbon metabolism in DNA/RNA synthesis, methylation reactions, and red blood cell maturation.
• Vitamin B₁₂ (Cobalamin): Coenzyme for methionine synthase (homocysteine to methionine conversion) and methylmalonyl-CoA mutase (fatty acid and energy metabolism), critical for DNA synthesis and neurologic myelination.
• Collectively, they support hematopoiesis, neurologic function, and metabolic equilibrium, particularly by lowering homocysteine levels and promoting red blood cell and nerve health.

• Absorption:
• B₆: Readily absorbed in jejunum, peak plasma ~1–2 h.
• Folic Acid: Absorbed in proximal small intestine, with peak ~1 h.
• B₁₂: Requires intrinsic factor–mediated absorption; passive diffusion (~1%) at high oral doses; peak ~6–8 h; IM route bypasses absorption.
• Distribution:
• B₆: Widely distributed; stored in liver and muscle.
• Folic Acid: Circulates as folate derivatives; distributed into red blood cells and tissues.
• B₁₂: Bound to transcobalamin II; stored in liver for long-term reserves.
• Metabolism:
• B₆: Intracellular conversion to PLP.
• Folic Acid: Converted to dihydrofolate and tetrahydrofolate coenzymes.
• B₁₂: Converted to methylcobalamin and adenosylcobalamin in tissues.
• Half-life:
• B₆: ~25 days (PLP form).
• Folic Acid: ~85 hours (~3.5 days).
• B₁₂: ~6 days in circulation; liver stores last months to years.
• Elimination:
• B₆ & Folic Acid: Excreted in urine, mainly inactive metabolites.
• B₁₂: Excreted via bile and urine; enterohepatic recirculation recycles B₁₂, excess excreted in urine.

• Pregnancy: Considered safe and essential. Folic acid is recommended to prevent neural tube defects; B₆ aids in reducing nausea and vomiting; B₁₂ deficiency prevention vital for maternal and fetal health.
• Lactation: All three are excreted into breast milk. Standard supplementation levels are safe. High-dose B₆ (>100 mg/day) may cause reversible infant neuropathy; caution with high dosing.
• Recommendation: Prenatal supplementation is standard; ensure doses remain within recommended safe ranges unless deficiency present.

• Vitamin B₆: Water-soluble B-vitamin (coenzyme).
• Folic Acid (B₉): Water-soluble B-vitamin (folate).
• Vitamin B₁₂: Water-soluble B-vitamin (cobalamin).

• Hypersensitivity to any component.
• Pernicious anemia treated with folate alone (risk of masking B₁₂ deficiency).
• High-dose pyridoxine (>200 mg/day) in patients with pre-existing sensory neuropathy.

• Vitamin B₆ neuropathy: High doses (≥200 mg/day) may lead to sensory neuropathy; discontinue if symptoms occur.
• Folate masking B₁₂ deficiency: High-dose folic acid can mask hematologic signs while neurologic damage progresses; always evaluate B₁₂ before folic acid alone.
• Allergic reactions: Rare, but possible with injectable forms—monitor for rash, anaphylaxis.
• Chronic liver or kidney disease: Monitor levels and adjust dose if necessary.
• Chemotherapy interactions: Folate may interfere with antifolate-based cancer treatments; follow oncology guidance.

Common (physiologic dosing):

• GI discomfort, mild nausea, rare allergic rash.

High-dose or prolonged use:

• Pyridoxine: Sensory neuropathy, ataxia.
• Folic Acid: Rare GI upset, allergic skin reactions.
• B₁₂ (IM): Injection-site pain, mild diarrhea.

Rare / Serious:

• Hypersensitivity (especially injectable), anaphylaxis.
• Masking of B₁₂ deficiency neurologic signs.

Timing & Dose Dependence:

• GI symptoms may appear early; neuropathy develops over weeks–months of high-dose pyridoxine.

• Vitamin B₆: Deficiency risk with isoniazid (co-supplement recommended); may reduce levodopa efficacy.
• Folic Acid: Antagonizes methotrexate; anticonvulsants (phenytoin, carbamazepine) decrease folate; trimethoprim reduces folate absorption.
• Vitamin B₁₂: Long-term metformin or proton-pump inhibitors may impair absorption; chloramphenicol may interfere with utilization.
• Alcohol: Chronic heavy intake impairs metabolism of all B‑vitamins; increased requirement common.

• Neural tube defect prevention: Universal folic acid (400 µg/day) preconception and early pregnancy per WHO and national guidelines.
• Cardiovascular: Homocysteine-lowering via B-vitamins found not convincingly reduces CV events; supplemental use limited to deficiency or specific indications.
• Neuropathy management: Emerging evidence supports combined B₆/B₁₂ formulas for improved symptom relief in diabetic neuropathy; formal guidelines note modest benefit.
• No strong new contraindications; advisory updates continue regarding high-dose pyridoxine neuropathy risk.

• Temperature: 15 °C–30 °C (59 °F–86 °F).
• Humidity & Light: Protect from moisture and direct sunlight; store in tightly closed container.
• Handling: Do not freeze. Tablets/caps sealed until use.
• Reconstitution/Refrigeration: Not applicable.
• Safety: Keep out of reach of children. Label doses carefully to prevent accidental overdose.