B6 toxicity
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Vitamin B6 Toxicity: 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 well-tolerated, excessive intake can lead to toxicity, manifesting in various symptoms and health issues.
Acute and Chronic Toxicity in Animals
Lethal Doses and Symptoms
Studies on animals have shown that the lethal dose (LD50) of vitamin B6 hydrochloride is 3.7 grams per kilogram for subcutaneous injection and 5.5 grams per kilogram for oral administration in rats. 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 doses1 4.
Long-term Administration
Long-term administration of vitamin B6 at doses of 20 mg/kg in dogs and 25 mg per rat over 80 days did not produce toxic manifestations or pathological changes in organs, indicating that chronic low-dose exposure is generally safe1.
Human Cases of Vitamin B6 Toxicity
Peripheral Neuropathy
Vitamin B6 toxicity in humans is rare but can occur, particularly with supplemental mega-doses. Peripheral neuropathy, characterized by symptoms such as paraesthesia, ataxia, and imbalance, is a common early sign of toxicity. Interestingly, even relatively low doses, such as 6 mg/day, have been associated with toxicity, suggesting a need for further research into safe supplementation levels3 6.
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 vitamin B6 therapy. This case highlights the need for careful monitoring of bleeding symptoms in patients requiring vitamin B6 supplementation2.
Cellular and Molecular Mechanisms
Neurotoxicity
Research indicates that pyridoxine, one form of vitamin B6, can induce cell death in a concentration-dependent manner in SHSY5Y cells. This neurotoxicity is linked to increased expression of Bax and caspase-8, as well as inhibition of pyridoxal-5-phosphate dependent enzymes. These findings suggest that high doses of pyridoxine can mimic symptoms of vitamin B6 deficiency by competitively inhibiting the active form of the vitamin5.
Protective Effects Against Other Toxins
Interestingly, vitamin B6 has shown protective effects against brain damage induced by valproic acid, an antiepileptic drug. In rats, vitamin B6 administration reversed oxidative stress markers and enzyme activity changes caused by valproic acid, indicating its potential therapeutic benefits in specific contexts7.
Conclusion
While vitamin B6 is essential for health, excessive intake can lead to significant toxicity, particularly affecting the nervous system. Both acute and chronic exposures have been studied extensively in animals, and human cases highlight the need for cautious supplementation. Further research is necessary to fully understand the safe upper limits of vitamin B6 intake and its complex interactions within the body.
Sources and full results
Most relevant research papers on this topic
STUDIES ON THE TOXICITY AND PHARMACOLOGY OF VITAMIN B6 (2-METHYL-3-HYDROXY-4,5-BIS-(HYDROXYMETHYL)-PYRIDINE)
Vitamin B6 is toxic at high doses, but its therapeutic use in humans is safe and does not affect metabolism, circulatory, respiratory, or smooth muscle organs.
Non-RCT
Animal StudyB6 and Bleeding: A Case Report of a Novel Vitamin Toxicity
Vitamin B6 therapy can exacerbate bleeding symptoms in patients with pyridox(am)ine-5-phosphate oxidase deficiency and mild hemophilia A, highlighting the need for vigilance in monitoring bleeding symptoms.
Case ReportVitamin B6 Toxicity Secondary to Daily Multivitamin Use: A Case Report
Daily multivitamin use with 6 mg of vitamin B6 can cause toxicity, highlighting the need for further research on the effects of low-dose vitamin B6 supplementation.
Case ReportToxicity of Vitamin B6
Vitamin B6 is toxic at doses up to 1 g per kg, with higher doses causing tonic convulsions in rats, and can cause death within 36 to 72 hours.
Non-RCTAnimal StudyThe vitamin B6 paradox: Supplementation with high concentrations of pyridoxine leads to decreased vitamin B6 function.
High doses of vitamin B6 supplements can cause neuropathy due to pyridoxine, which inhibits the active form of pyridoxal-5'-phosphate, leading to symptoms similar to vitamin B6 deficiency.
In Vitro Study
Highly CitedVitamin B6 Neonatal Toxicity
High doses of vitamin B6 supplements during pregnancy and breastfeeding can cause neonatal tremors, which disappear when the maternal supplement is stopped.
Case ReportEffect of vitamin B6 on brain damage in valproic acid induced toxicity
Vitamin B6 has a protective effect on valproic acid-induced brain damage in rats, reversing oxidative damage and reducing oxidative stress.
RCTAnimal StudyAction and Toxicity of Vitamin B6 Hydrochloride
Vitamin B6 hydrochloride is safe when administered orally or intravenously in doses of 100 to 200 mg, but causes pain when injected intramuscularly.
Influence of vitamin B6 status on aspects of lead poisoning in rats.
Vitamin B6 status influences lead-induced changes in hepatic GSH levels in rats, potentially through its role as a co-factor for enzymes involved in amino acid metabolism.
Non-RCTAnimal StudyPyridoxine Megavitaminosis: An Analysis of the Early Changes Induced with Massive Doses of Vitamin B6 in Rat Primary Sensory Neurons
High toxic doses of vitamin B6 (pyridoxine) in rats cause early changes in primary sensory neurons, leading to axonal reaction and secondary degeneration within 24 hours.
Non-RCTAnimal Study