Toxicity of b6
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Toxicity of Vitamin B6: An Overview
Introduction to Vitamin B6 Toxicity
Vitamin B6, also known as pyridoxine, is a water-soluble vitamin essential for various metabolic processes, including amino acid, carbohydrate, and lipid metabolism. While it is generally considered safe, excessive intake can lead to toxicity, manifesting primarily as neurological symptoms.
Acute and Chronic Toxicity Levels
Lethal and Toxic Doses in Animals
Studies have shown that the lethal dose (LD50) of vitamin B6 hydrochloride in rats is 3.7 grams per kilogram when administered subcutaneously and 5.5 grams per kilogram when given orally. Doses above 1 gram per kilogram can cause toxic symptoms such as impaired coordination and tonic convulsions in dogs, rabbits, and rats, which are significantly higher than therapeutic doses 15. Chronic administration of lower doses (20 mg/kg in dogs and 25 mg/rat) over 80 days did not produce toxic effects or pathological changes .
Human Toxicity and Safe Upper Limits
In humans, vitamin B6 toxicity is rare but can occur, especially with high-dose supplements. The US authorities have set the no-observed-adverse-effect-level at 200 mg per day and the safe upper limit at 100 mg per day. However, there have been reports of neurotoxicity at intakes as low as 24 mg and 40 mg per day, suggesting that even relatively low doses can sometimes be harmful .
Neurological Effects and Peripheral Neuropathy
Mechanisms of Neurotoxicity
High doses of pyridoxine can lead to sensory neuronal pain and peripheral neuropathy. This is due to pyridoxine's competitive inhibition of the active form, pyridoxal-5'-phosphate, which is essential for enzyme function. This inhibition can cause symptoms similar to those of vitamin B6 deficiency, such as cell death and increased expression of pro-apoptotic markers like Bax and caspase-8 27.
Case Reports and Clinical Observations
Several case reports highlight the neurotoxic effects of vitamin B6. For instance, a 73-year-old male developed progressive peripheral neuropathy with a serum vitamin B6 level of 259.9 nmol/L, despite only taking a daily multivitamin containing 6 mg of vitamin B6. This case underscores the need for further research into the effects of even low-dose supplementation . Another report described a newborn with tremors due to the mother's high intake of vitamin B6 supplements during pregnancy, which resolved after discontinuation of the supplement .
Other Toxic Effects
Bleeding Disorders
A unique case reported excessive bleeding in a pediatric patient with pyridox(am)ine-5-phosphate oxidase deficiency and mild hemophilia A, exacerbated by essential vitamin B6 therapy. This case expands the spectrum of known vitamin B6 toxicity and highlights the need for vigilance in monitoring for bleeding symptoms in patients requiring supplementation .
General Toxicity in Animals
In animal studies, high doses of vitamin B6 caused peculiar toxic symptoms such as tonic convulsions and impaired righting reflexes. These symptoms persisted for several days to weeks, depending on the dose . Mice tolerated repeated doses of 100 mg/kg intravenously without pathological changes, but pain occurred with intramuscular injections .
Conclusion
While vitamin B6 is essential for health, excessive intake can lead to significant toxicity, primarily affecting the nervous system. Both acute and chronic high doses can cause severe neurological symptoms, and even relatively low doses have been associated with adverse effects in some cases. Therefore, it is crucial to monitor vitamin B6 intake, especially when using supplements, to avoid potential toxicity. Further research is needed to better understand the mechanisms and safe upper limits of vitamin B6 supplementation.
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