What are the risks of excessive vitamin B6 (Vitamin B6) levels?

Risks of Excessive Vitamin B6 Levels

Excessive vitamin B6 levels can cause sensory neuropathy with ataxia or areflexia, impaired cutaneous and deep sensations, and dermatologic lesions. 1

Neurological Toxicity

• Peripheral neuropathy is the primary manifestation of vitamin B6 toxicity, typically presenting with numbness/paresthesia in extremities, loss of distal sensation, motor ataxia, weakness, and loss of deep tendon reflexes 2
• Neurotoxicity can occur at various dosage levels:
  • Established toxicity at doses ≥1000 mg/day (approximately 800 times the daily intake from foods) 3
  • Reports of toxicity at intakes of 100-300 mg/day 3
  • Recent evidence suggests toxicity may occur at much lower doses in some individuals, even with daily multivitamin use containing only 6 mg of vitamin B6 4

Muscle and Nerve Damage

• Elevated B6 levels can contribute to muscle atrophy through effects on peripheral nerves 2
• Animal studies show that vitamin B6 deficiency (and by extension, toxicity from B6 antagonists) can cause:
  • Significant loss of neural tissue
  • Reduction in nerve conduction velocity
  • Widespread muscle atrophy
  • Extensive myelin disruption
  • Fragmentation of intramuscular nerve fibers 1

Safe Levels and Recommendations

• The US authorities have established:
  • No-observed-adverse-effect-level at 200 mg/day
  • Safe upper limit at 100 mg/day 3
• ESPEN guidelines indicate that negative effects have been related to prolonged intakes of 300 mg/day, with potential side effects at doses as low as 100 mg/day 1
• Long-term doses of 100 mg/day have been associated with Lhermitte signs (indicating spinal cord effects) 1

Monitoring and Prevention

• Plasma pyridoxal phosphate (PLP) levels should be used to determine vitamin B6 status:
  • Adequate status: >30 nmol/L (7.4 μg/L)
  • Risk of toxicity: >100 nmol/L (25 μg/L) 5
• In cases of inflammation or serious illness, red cell PLP should be measured instead of plasma levels 1
• PLP-based supplements are preferred over pyridoxine supplements due to minimal neurotoxicity observed in neuronal cell viability tests 5
• Weekly administration (50-100 mg) is preferred over daily use to prevent toxicity due to the long half-life of B6 metabolites 5

Special Populations at Risk

• Patients with impaired renal function have reduced ability to clear vitamin B6 metabolites, leading to potential elevation 2
• Bariatric surgery patients are at particular risk due to routine supplementation practices:
  • Up to 40% of patients may experience vitamin B6 overdose due to inadequate formulation of supplements 6
  • Regular monitoring is essential in this population 6
• Elderly individuals may be more susceptible to B6 accumulation due to age-related changes in metabolism 2

Recovery from Toxicity

• A washout period of 20-40 days is typically required for complete clearance of vitamin B6 7
• Some nerve damage may persist even after discontinuation of excessive vitamin B6 intake, as demonstrated in animal studies 1

Clinical Approach to Suspected B6 Toxicity

• Review all medications and supplements for potential vitamin B6 content or interactions 2
• Measure plasma PLP levels to confirm elevated B6 status 1
• Discontinue all sources of supplemental vitamin B6 if levels are elevated 7
• Monitor for improvement in neurological symptoms, which may take several weeks to months to resolve 1