What causes vitamin B6 toxicity?

Vitamin B6 Toxicity: Causes and Mechanisms

Vitamin B6 toxicity primarily occurs due to excessive supplementation of pyridoxine, which paradoxically inhibits the active form pyridoxal-5-phosphate, leading to peripheral neuropathy and neurological damage. 1

Mechanisms of Vitamin B6 Toxicity

• Pyridoxine (inactive form) competitively inhibits the active form pyridoxal-5'-phosphate (PLP), causing a functional vitamin B6 deficiency despite high serum levels 1
• Excessive vitamin B6 primarily targets the peripheral nervous system, causing axonal degeneration similar to Wallerian degeneration 2
• Toxicity leads to swelling of axonal mitochondria, disruption of axoplasmic ground substance, and accumulation of dense bodies within neurons 2
• Motor neurons, particularly those feeding distal muscles, are most affected, leading to increasing denervation of muscle fibers 2

Dosage and Toxicity Thresholds

• Acute toxicity can develop with vitamin A intake above 300,000 IU in adults or >60,000 IU in children within a few hours or days 2
• Chronic vitamin B6 toxicity has been associated with prolonged intakes of 300 mg/day, with potential side effects at doses as low as 100 mg/day 3
• Surprisingly, toxicity can occur even at doses below 50 mg/day in some individuals, suggesting significant variability in susceptibility 4
• A recent case report documented toxicity in a patient taking only 6 mg/day of vitamin B6 from a multivitamin, well below the European Food Safety Administration's Tolerable Upper Intake Level of 12 mg/day 5

Clinical Manifestations of Toxicity

• Neurological symptoms include numbness/paresthesia in extremities, loss of distal sensation, motor ataxia, weakness, and loss of deep tendon reflexes 2, 3
• Sensory neuropathy with ataxia or areflexia, impaired cutaneous and deep sensations, and dermatologic lesions may occur 3
• Widespread muscle atrophy, reduction in nerve conduction velocity, and extensive myelin disruption can develop 2
• Non-specific symptoms such as nausea, gastrointestinal disturbances, vomiting, and mood/behavioral changes may also present 2

Risk Factors for Toxicity

• Elderly individuals may be more susceptible to B6 accumulation due to age-related changes in metabolism 3, 6
• Patients with impaired renal function have reduced ability to clear vitamin B6 metabolites, increasing risk of toxicity 3, 6
• Medication interactions, particularly with isoniazid (tuberculosis drug), can alter B6 metabolism 3
• Other medications that can interfere with vitamin B6 metabolism include penicillamine, anti-cancer drugs, corticosteroids, and anticonvulsants 3

Prevention and Management

• Adherence to recommended daily intake of vitamin B6 (1.3-1.7 mg/day for adults) is advised 7, 6
• PLP-based supplements are preferred over pyridoxine supplements due to minimal neurotoxicity 8
• Weekly administration of vitamin B6 (50-100 mg) is preferred over daily use to prevent toxicity due to the long half-life of B6 metabolites 8
• Discontinuation of vitamin B6 supplementation is the primary treatment for toxicity 2
• Recovery from neurological symptoms may take several weeks to months, and some nerve damage may persist even after discontinuation 3

Diagnostic Considerations

• Plasma PLP measurement is recommended, with normal values being 5-50 mg/L (20-200 nmol/L); elevated levels suggest toxicity 3
• In cases of inflammation or serious illness, red cell PLP should be measured instead of plasma levels 3
• No statistical correlation between dosage and vitamin B6 blood levels has been found, indicating individual variability in metabolism 4