Vitamin b6 toxicity
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Vitamin B6 Toxicity: Causes and Risk Factors
Vitamin B6 (pyridoxine) is a water-soluble vitamin essential for many metabolic processes. While it is generally considered safe, toxicity can occur, especially from excessive intake through supplements rather than food sources 168. Most cases of vitamin B6 toxicity are linked to high doses found in over-the-counter (OTC) supplements, with many multivitamins containing amounts above the recommended daily intake of 1.7–2 mg . Notably, toxicity has been reported even at doses lower than previously established upper limits, such as 6 mg per day, which is below the European Food Safety Administration’s tolerable upper intake level of 12 mg/day .
Clinical Manifestations of Vitamin B6 Toxicity
Peripheral Neuropathy and Neurological Symptoms
The most common and well-documented symptom of vitamin B6 toxicity is peripheral neuropathy, which typically presents as sensory disturbances like tingling, numbness, ataxia, and imbalance 135679. These symptoms can paradoxically mimic those of vitamin B6 deficiency 56. Neuropathy is usually sensory and axonal in nature, and symptoms often improve after discontinuing the supplement 169. In rare cases, acute toxicity can cause convulsions and severe neurological impairment, as observed in animal studies at extremely high doses .
Other Toxic Effects
Although rare, vitamin B6 toxicity can also present with unusual symptoms. For example, a pediatric case reported excessive bleeding associated with high-dose pyridoxal-5-phosphate supplementation in a child with a metabolic disorder and mild hemophilia A, suggesting that vitamin B6 toxicity may exacerbate bleeding tendencies in susceptible individuals .
Mechanisms of Vitamin B6 Toxicity
Research indicates that the neurotoxic effects of vitamin B6 are primarily due to the inactive form, pyridoxine, which can competitively inhibit the active form, pyridoxal-5-phosphate, leading to impaired enzyme function and neuronal damage 57. High circulating levels of pyridoxine may inhibit pyridoxal kinase (PDXK), an enzyme necessary for converting pyridoxine to its active form, potentially disrupting neurotransmitter synthesis (such as GABA) and causing excitotoxicity and neurodegeneration in sensory neurons . This mechanism helps explain why symptoms of toxicity resemble those of deficiency.
Prevalence and Public Health Considerations
A significant proportion of multivitamins on the market contain vitamin B6 in amounts exceeding recommended daily values, especially those targeted at older adults . This widespread availability increases the risk of unintentional chronic overconsumption and subsequent toxicity. Awareness among healthcare providers and the public about the potential for toxicity, even at relatively low supplemental doses, is important for prevention 13.
Severity and Prognosis
Most cases of vitamin B6 toxicity are reversible, with symptoms improving after stopping the supplement and normalizing vitamin B6 levels 169. However, the severity of neuropathy does not always correlate with moderately elevated plasma B6 levels, suggesting that only very high levels or prolonged exposure are likely to cause significant harm . Screening for vitamin B6 toxicity should be considered in patients with unexplained neuropathy, especially if they are taking supplements .
Conclusion
Vitamin B6 toxicity is primarily associated with excessive supplement use and can cause peripheral neuropathy and, in rare cases, other symptoms such as bleeding. Toxicity can occur at lower doses than previously thought, and the risk is heightened by the prevalence of high-dose vitamin B6 in OTC supplements. Most symptoms are reversible upon discontinuation, but awareness and monitoring are essential to prevent and manage toxicity effectively 13567910.
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