From the Guidelines
Pyridoxine can cause significant side effects, particularly at high doses, with the most notable being sensory neuropathy, which can occur with prolonged intake of doses as low as 100 mg/day. The side effects of pyridoxine are primarily dose-dependent and can include sensory neuropathy with ataxia or areflexia, impaired cutaneous and deep sensations, and dermatologic lesions, as noted in the espen micronutrient guideline 1. Other potential side effects, though less commonly associated directly with pyridoxine in the provided evidence, can include headache, nausea, and stomach pain. It's crucial to recognize that while pyridoxine is essential for normal nerve function, excessive intake can lead to neuronal damage.
Key Considerations for Pyridoxine Supplementation
- Dose: The recommended dose for supplementation to minimize the risk of side effects, particularly neuropathy, is generally considered to be between 25-100 mg daily for most adults, with the understanding that doses above 100 mg/day can increase the risk of neuropathy 1.
- Duration: Prolonged intake of high doses increases the risk of side effects.
- Individual Sensitivity: Some individuals may experience side effects at lower doses, emphasizing the need for personalized supplementation plans.
- Monitoring: Patients should be monitored for signs of neuropathy or other side effects, and supplementation should be adjusted or discontinued if symptoms arise.
Clinical Implications
The evidence from the espen micronutrient guideline 1 highlights the importance of careful consideration of the dose and duration of pyridoxine supplementation to minimize the risk of adverse effects, particularly sensory neuropathy. While other studies, such as the American Thoracic Society guidelines 1, discuss various side effects of different medications, the focus on pyridoxine supplementation underscores the need for a cautious approach to vitamin B6 intake to preserve nerve function and overall health. Therefore, it is recommended to keep pyridoxine supplementation at or below 100 mg/day to minimize the risk of neuropathy and other side effects, as supported by the most recent and highest quality evidence available 1.
From the Research
Pyridoxine Side Effects
- Pyridoxine deficiency and excess have been implicated as a cause for peripheral neuropathy 2
- Supplementation with pyridoxine at doses greater than 50 mg/d for extended duration may be harmful and should be discouraged 2
- Higher vitamin B6 levels, which usually occur following the taking of nutritional supplements, may lead to the development of a predominantly, if not exclusively, sensory neuropathy of the axonal type 3
- Current scientific evidence supports a neurotoxic role of B6 at high levels 3
- Excessive pyridoxine intake induces neuropathy through the preferential injury of sensory neurons 4
- Pyridoxine toxicity is a well-known cause of primary sensory, length-dependent, axonal polyneuropathy, and can also cause autonomic symptoms 5
Mechanism of Pyridoxine Toxicity
- The mechanism behind pyridoxine-induced neuropathy is unknown, but it may be related to γ-aminobutyric acid (GABA) neurotransmission 4
- High circulating concentrations of pyridoxine may lead to a similar condition via the inhibition of pyridoxal kinase (PDXK) 4
- PDXK inhibition and consequently disrupted GABA neurotransmission is the most plausible mechanism of toxicity 4
Treatment and Prevention
- There is inadequate evidence to support routine pyridoxine supplementation in patients with disorders of peripheral nervous system 2
- Supplementation with vitamin B6, even as part of a nutritional multivitamin supplement, has not been proven harmful at permitted daily doses in patients who already suffer from peripheral neuropathy 3
- Treating diabetic peripheral neuropathy with high dose vitamin B6 or placebo results in a similar frequency of symptomatic improvement 6