What causes elevated vitamin B6 levels?

Causes of Elevated Vitamin B6 Levels

Elevated vitamin B6 levels are primarily caused by excessive supplementation, which can lead to neurotoxicity even at doses lower than previously thought safe. 1, 2

Common Causes of Elevated Vitamin B6

Excessive Supplementation

• High-dose vitamin B6 supplements are the most common cause of elevated B6 levels, with toxicity traditionally associated with doses of 1000 mg/day or more 3
• Recent evidence suggests toxicity may occur at much lower doses, with reports of neurotoxicity at 100-300 mg/day, and some cases reported at doses as low as 24-40 mg/day 3
• The US authorities have set a safe upper limit at 100 mg/day, but neurotoxicity can potentially occur below this threshold 3

Inappropriate Supplementation Practices

• Inadequate multivitamin formulations, especially those prescribed for bariatric surgery patients, can lead to vitamin B6 overload 4
• Studies show increasing rates of vitamin B6 overdoses, reaching nearly 40% of tested samples in some medical centers 4
• Weekly administration of B6 supplements (50-100 mg) is preferred over daily use due to the long half-life of B6 metabolites, which can help prevent toxicity 1

Renal Disease

• Chronic kidney disease and dialysis patients commonly experience elevated homocysteine levels, which are often treated with B vitamin supplementation including vitamin B6 5
• In dialysis patients, administration of vitamin B6 may lead to higher than normal levels as the kidney's ability to clear vitamin metabolites is compromised 5
• Vitamin B6 supplementation in dialysis patients is recommended despite potential elevation because deficiency contributes to hyperhomocysteinemia 5

Monitoring and Prevention

Plasma Level Monitoring

• A plasma pyridoxal 5'-phosphate (PLP) concentration above 30 nmol/L (7.4 μg/L) indicates adequate vitamin B6 status 1
• Neurotoxicity typically develops at plasma levels exceeding 100 nmol/L (25 μg/L) 1
• Only about 15% of the variability in plasma B6 levels can be explained by the daily dose, suggesting other factors influence B6 metabolism 2

Risk Factors for Elevated Levels

• Bariatric surgery patients are at particular risk due to routine high-dose supplementation protocols 4
• Elderly individuals may be more susceptible to B6 accumulation due to age-related changes in metabolism 5
• Patients with impaired renal function have reduced ability to clear vitamin B6 metabolites 5

Clinical Implications of Elevated B6

Neurotoxicity

• Peripheral neuropathy is the primary manifestation of vitamin B6 toxicity 6, 1
• Symptoms include sensory disturbances, painful neuropathy, and in severe cases, motor neuron damage 4
• PLP-based supplements appear to be less neurotoxic than pyridoxine forms 1

Regulatory Actions

• In the Netherlands, regulatory action in 2018 lowered the maximum daily dose of vitamin B6 in supplements to 21 mg/day 2
• Following this regulation, reports of neuropathy associated with high-dose vitamin B6 decreased significantly 2
• However, some cases of neuropathy continue to be reported even with lower doses, suggesting individual susceptibility varies 2

Prevention Strategies

• Use PLP-based supplements rather than pyridoxine when supplementation is needed 1
• Maintain plasma B6 levels between 30-60 nmol/L (7.4-15 μg/L) for optimal benefit with minimal risk 1
• Consider weekly rather than daily supplementation to prevent accumulation 1
• Exercise caution when prescribing supplements to patients with impaired renal function 5