Is Vitamin C high dose Safe with Methotrexate?
Free · No account · based on published sources including NIH ODS, FDA drug labels, and peer-reviewed literature
Avoid high-dose Vitamin C supplementation (>2g/day) during high-dose methotrexate therapy. High-dose Vitamin C acidifies urine, which can reduce methotrexate renal clearance and increase toxicity risk. Report any supplement use to your oncology pharmacist.
Why this interaction occurs
High-dose ascorbic acid is excreted renally and can acidify urine pH. Methotrexate and its metabolite 7-hydroxymethotrexate have reduced solubility and tubular secretion in acidic urine, leading to increased renal retention, potential crystalluria, nephrotoxicity, and systemic methotrexate accumulation with enhanced bone marrow and mucosal toxicity.
Evidence
Evidence level: moderate.
Reported safety data
The FDA’s adverse event reporting system (FAERS) has received 499,559 reports mentioning Methotrexate. This reflects reported cases involving the medication in general — not confirmed causation, and not specific to the Methotrexate + supplement combination on this page.
FAERS reports are voluntary and cannot prove that a drug caused an event. Do not use report counts to assess the safety of this specific drug-supplement pair.
Frequently asked questions
Related interactions
All Vitamin C high dose interactions → · All Methotrexate interactions →
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Educational only — not medical advice.
Always confirm with your doctor or pharmacist.