Vitamin B6
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"vitamin B6"[MeSH Terms] AND deficiency
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Here is a thorough overview of Vitamin B6 drawn from Harrison's, Bradley & Daroff's Neurology, and Guyton & Hall:
Vitamin B6 (Pyridoxine)
What It Is
Vitamin B6 is a family of compounds - pyridoxine, pyridoxal, and pyridoxamine - along with their 5'-phosphate derivatives. All three are converted in the body to the active coenzyme form, pyridoxal 5'-phosphate (PLP).
Functions
PLP is a cofactor for more than 100 enzymes, primarily involved in:
- Amino acid metabolism - transamination reactions (synthesis of non-essential amino acids); the conversion of homocysteine to cystathionine
- Neurotransmitter synthesis - synthesis of serotonin, dopamine, GABA, and norepinephrine
- Heme biosynthesis - aminolevulinate synthase (the first enzyme in heme synthesis) requires PLP; this is why deficiency causes anemia
- Glycogen and lipid metabolism
- Niacin synthesis - conversion of tryptophan to niacin
- Sphingoid base metabolism and steroid hormone receptor modulation
(Guyton & Hall; Harrison's, p. 2652)
Dietary Sources
| Source | Form |
|---|---|
| Plant foods (legumes, wheat bran, nuts) | Pyridoxine (less bioavailable) |
| Animal tissues (meat, fish, poultry) | PLP and pyridoxamine phosphate (more bioavailable) |
Vitamin B6 is present across all food groups, but bioavailability is higher from animal sources.
Recommended Daily Allowance
~2 mg/day in adults (Bradley & Daroff's, p. 1801)
Deficiency
Causes
- Dietary insufficiency (malnutrition, breastfeeding by malnourished mothers)
- Medications: isoniazid, hydralazine, penicillamine, L-dopa, cycloserine - these react with PLP's carbonyl groups, inactivating it
- Malabsorptive states: bariatric surgery, inflammatory bowel disease
- Renal failure (loss via dialysis)
- Alcoholism (increased metabolic demand + poor nutrition)
- Women and elderly have a high prevalence of low serum levels
Clinical Features
| System | Manifestation |
|---|---|
| Skin | Dermatitis (seborrhoeic-like), glossitis, stomatitis, cheilosis |
| Nervous system | Peripheral sensorimotor neuropathy; depression, confusion, personality changes |
| Infants | Seizures (refractory to anticonvulsants), hyperirritability, exaggerated startle |
| Blood | Microcytic hypochromic anemia (reduced heme synthesis) |
| Metabolic | Hyperhomocysteinemia (impaired homocysteine-to-cystathionine conversion) - linked to cardiovascular risk |
| Inflammatory | Elevated C-reactive protein, increased inflammation |
Isoniazid neuropathy: sensory symptoms start in the distal feet; burning pain, impaired sensation, distal weakness, depressed tendon reflexes. Pyridoxine 50 mg/day prevents this. In acute isoniazid overdose (coma, metabolic acidosis, seizures), pyridoxine is the specific antidote.
(Harrison's, p. 2652; Bradley & Daroff's, p. 1801)
Pyridoxine-Dependency Syndromes (rare)
These require pharmacologic doses (100-200 mg/day):
- Cystathionine β-synthase deficiency (homocystinuria)
- Pyridoxine-responsive sideroblastic anemia
- Gyrate atrophy with chorioretinal degeneration (ornithine aminotransferase deficiency)
- Neonatal seizures due to inborn errors in PLP metabolism (mutations in ALDH7A1, PNPO, TNSALP, PLPBP, and others) - require long-term high-dose pyridoxine or PLP
Diagnosis
- Low plasma PLP < 20 nmol/L confirms deficiency
Treatment
| Indication | Dose |
|---|---|
| Simple dietary deficiency | 50 mg/day |
| Medication-induced deficiency (e.g., isoniazid) | 100-200 mg/day |
| Dependency syndromes | 100-200 mg/day |
| Nausea/vomiting in pregnancy (+ doxylamine) | Standard therapeutic dose |
Note: Vitamin B6 must NOT be given with L-dopa, as PLP accelerates peripheral conversion of L-dopa to dopamine, reducing CNS availability.
Toxicity
- Safe upper limit: 100 mg/day
- High doses (>1000 mg/day): reliable sensory neuropathy within months - sensory ataxia, areflexia, impaired sensation, positive Romberg sign
- Chronic lower doses (~200 mg/day for many years): mild sensory polyneuropathy
- The neuropathy is reversible on cessation in most cases
- Prudent limit for therapeutic use: 50 mg/day or less
(Bradley & Daroff's, p. 1801; Harrison's, p. 2652)
Key Drug Interactions Summary
| Drug | Mechanism of Interaction |
|---|---|
| Isoniazid, hydralazine, penicillamine, cycloserine | React with PLP's carbonyl group - cause deficiency |
| L-dopa | PLP enhances peripheral decarboxylation of L-dopa - reduces drug efficacy; B6 should be avoided |
Quick Clinical Pearls
- The AST/ALT ratio in alcoholic liver disease is elevated partly because ALT is more dependent on vitamin B6 than AST - deficiency preferentially lowers ALT
- Pyridoxine + doxylamine is effective for severe nausea and vomiting of pregnancy
- Despite theoretical benefit from lowering homocysteine, randomized trial evidence for cardiovascular benefit is limited
- High-dose B6 has been tried for carpal tunnel syndrome, PMS, schizophrenia, autism, and diabetic neuropathy - none have shown consistent benefit
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