B12 toxicity
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Vitamin B12 Toxicity: Clinical Insights and Implications
Introduction to Vitamin B12 Toxicity
Vitamin B12, also known as cobalamin, is essential for DNA synthesis, methylation, and mitochondrial metabolism. While deficiency is a well-documented concern, the potential for toxicity from excessive intake is less commonly discussed. This article synthesizes current research on the clinical consequences of vitamin B12 toxicity, particularly focusing on high-dose supplementation and its effects.
Clinical Manifestations of B12 Toxicity
Case Report: High-Dose Cyanocobalamin
A case report highlights the adverse effects of high-dose cyanocobalamin in a young woman treated for pernicious anemia. The patient received multiple daily doses of 1 mg cyanocobalamin, totaling 12 mg. She developed symptoms including acne, palpitations, anxiety, akathisia, facial ruddiness, headache, and insomnia. These symptoms resolved two weeks after discontinuing the supplement, indicating a direct link to the high doses of vitamin B121.
Neurological Implications in Nitrous Oxide Users
Recreational use of nitrous oxide (N2O) can lead to chronic toxicity by oxidizing vitamin B12, rendering it dysfunctional. This dysfunction is a significant factor in the development of neurological disorders among N2O users. Elevated levels of homocysteine (tHcy) and methylmalonic acid (MMA) are prevalent in these individuals, suggesting that these biomarkers are more reliable indicators of B12 status than total circulating vitamin B12 or holotranscobalamin (holoTC)2.
Vitamin B12 and Chemotherapy-Induced Toxicity
Impact on Neutropenia in Lung Cancer Treatment
A study investigated the role of vitamin B12 and folic acid supplementation in reducing chemotherapy-induced toxicity in lung cancer patients. The results showed no significant difference in the rates of severe neutropenia or overall survival between the supplemented and non-supplemented groups. However, a subset of patients who successfully reduced homocysteine levels with supplementation experienced less neutropenic toxicity, suggesting a potential benefit in specific cases3.
Vitamin B12 Deficiency and Toxicity Interplay
Effects on Amyloid-β Toxicity
Research using the C. elegans model demonstrated that vitamin B12 deficiency exacerbates amyloid-β (Aβ) toxicity, leading to faster and more severe paralysis. Supplementation with B12 alleviated these effects, indicating that elevated homocysteine levels due to B12 deficiency contribute to oxidative stress and Aβ toxicity4.
Selenium Methylation and Toxicity
Vitamin B12 plays a crucial role in the methylation of selenium, a process that detoxifies selenium compounds. B12-deficient rats showed impaired selenium methylation, leading to higher tissue selenium levels and increased toxicity. This finding underscores the importance of adequate B12 levels in mitigating selenium toxicity8.
Conclusion
While vitamin B12 is essential for numerous metabolic processes, excessive intake can lead to adverse effects, particularly when administered in high doses. Clinical manifestations of B12 toxicity can include dermatological, neurological, and systemic symptoms. Additionally, the interplay between B12 deficiency and toxicity highlights the complex role of this vitamin in various metabolic pathways. Careful monitoring and appropriate dosing are crucial to avoid potential toxicity, especially in clinical settings involving high-dose supplementation.
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Most relevant research papers on this topic
Toxicity induced by multiple high doses of vitamin B12 during pernicious anemia treatment: a case report
Multiple high doses of vitamin B12 during pernicious anemia treatment can cause unexpected and unusual side effects, such as acne, palpitations, anxiety, and insomnia.
Case ReportVitamin B12 Status in Recreational Users of Nitrous Oxide: A Systematic Review Focusing on the Prevalence of Laboratory Abnormalities
Increases in tHcy and MMA levels are the most prevalent abnormalities in recreational nitrous oxide users, and should be measured alone or in combination for proper assessment.
Systematic ReviewAn unblinded, randomised phase II study of platinum-based chemotherapy with vitamin B12 and folic acid supplementation in the treatment of lung cancer with plasma homocysteine blood levels as a biomarker of severe neutropenic toxicity
Vitamin B12 and folic acid supplementation in platinum-based lung cancer chemotherapy did not improve toxicity, quality of life, or overall survival rates.
RCT
Rigorous JournalEffects of Vitamin B12 Deficiency on Amyloid-β Toxicity in Caenorhabditis elegans
B12 supplementation lowers homocysteine levels and alleviates amyloid- toxicity in C. elegans, suggesting oxidative stress is an important factor in A toxicity.
In Vitro StudyRigorous JournalStudy of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine
Vitamin B12 and folinic acid supplementation does not appear to prevent or reduce zidovudine-induced myelotoxicity in the overall treated population, but may have a beneficial effect in certain subgroups of patients.
RCTVitamin B12 deficiency
Vitamin B12 deficiency affects individuals of all ages, particularly the elderly, and is caused by inadequate intake, bioavailability, or malabsorption, with management relying on B12 supplementation.
Highly CitedVitamin B12 deficiency
Vitamin B12 deficiency can lead to serious clinical consequences, and diagnosis and management require careful consideration of individual factors and dietary habits.
Systematic Review
Very Rigorous JournalHighly CitedEffect of vitamin B12 status on selenium methylation and toxicity in rats: in vivo and in vitro studies.
Vitamin B12 deficiency significantly decreases the ability of rats to methylate selenium, leading to increased selenium toxicity and decreased resistance to selenite toxicity.
Non-RCT
Animal StudySevere but Not Moderate Vitamin B12 Deficiency Impairs Lipid Profile, Induces Adiposity, and Leads to Adverse Gestational Outcome in Female C57BL/6 Mice
Severe vitamin B12 deficiency leads to increased body fat, altered lipid profile, and adverse gestational outcomes in female C57BL/6 mice, with stress markers and inflammation as potential underlying mechanisms.
Non-RCTAnimal StudyHighly CitedRelationship between Vitamin B12 and Cobalt Metabolism in Domestic Ruminant: An Update
A minimum requirement for cobalt in ruminants is 0.11 ppm dry matter, with current recommendations advising supplementation up to 0.20 mg Co/kg DM, which may increase animal production, particularly in dairy cattle.
Rigorous JournalHighly Cited