What are the symptoms of Vitamin B6 toxicity?

Vitamin B6 Toxicity Symptoms

Vitamin B6 toxicity primarily manifests as peripheral sensory neuropathy affecting the extremities, with numbness, paresthesia, loss of distal sensation, motor ataxia, weakness, and loss of deep tendon reflexes being the hallmark clinical features. 1

Primary Neurological Manifestations

The dominant clinical presentation involves the peripheral nervous system, with motor neurons—particularly those innervating distal muscles—being most vulnerable:

• Sensory symptoms: Numbness and paresthesia (tingling) in the extremities that can progress to complete loss of distal sensation 2, 1
• Motor dysfunction: Motor ataxia, muscle weakness, and loss of deep tendon reflexes 2, 1
• Sensory ataxia: Impaired coordination due to sensory nerve damage 3
• Painful neuropathy: Some patients experience painful tingling sensations in the legs rather than just numbness 3

Non-Neurological Symptoms

Beyond the characteristic neuropathy, vitamin B6 toxicity can produce systemic symptoms:

• Gastrointestinal disturbances: Nausea, vomiting, and general GI upset 2
• Mood and behavioral changes: Apathy, depression, and fatigue 2
• Dermatologic lesions: Skin manifestations can occur with excessive levels 1

Underlying Pathophysiology

The mechanism of toxicity involves direct damage to peripheral nerves:

• Axonal degeneration: Similar to Wallerian degeneration, with swelling of axonal mitochondria and disruption of axoplasmic ground substance 1
• Myelin disruption: Extensive myelin breakdown and fragmentation of intramuscular nerve fibers 1
• Denervation: Progressive denervation of muscle fibers leading to muscle atrophy 1
• Reduced nerve conduction: Decreased conduction velocity in affected nerves 1

Critical Dosing Context

A crucial caveat: While toxicity was historically associated with mega-doses exceeding 300 mg/day 1, more recent evidence demonstrates that toxicity can occur at surprisingly low doses:

• Negative effects have been documented with prolonged intakes of 300 mg/day, with potential side effects at doses as low as 100 mg/day 1
• Case reports document toxicity with daily intakes of only 24-40 mg 3 and even 6 mg from a standard multivitamin 4
• The European Food Safety Administration established a Tolerable Upper Intake Level of 12 mg/day, yet toxicity has been reported below this threshold 4

The Pyridoxine Paradox

An important mechanistic insight: The inactive form pyridoxine (the most common supplemental form) competitively inhibits the active form pyridoxal-5'-phosphate 5. This means that symptoms of vitamin B6 toxicity paradoxically mimic vitamin B6 deficiency because high doses of pyridoxine block the function of the active coenzyme 5. This explains why supplementation intended to help can actually cause harm.

Recovery Considerations

• Discontinuation of vitamin B6 supplementation is the primary treatment 1
• Recovery from neurological symptoms may take several weeks to months 1
• Important warning: Some nerve damage may persist even after discontinuation, as demonstrated in animal studies showing that a significant proportion of peripheral nerve damage remained 37 days after stopping the intervention 2

Clinical Vigilance

Physicians must maintain high suspicion for vitamin B6 toxicity in any patient presenting with unexplained peripheral neuropathy, particularly sensory neuropathy 6. A detailed supplement history is essential, as patients may not consider over-the-counter multivitamins as relevant medications 4, 3.