Pharmacology of Vitamin C in the Treatment of Cancer: A Comprehensive Review

Vitamin C (ascorbate) has re-emerged as a promising adjunct in oncology due to a clearer understanding of its distinct pharmacology when administered intravenously versus orally. Oral dosing is constrained by saturable intestinal absorption and tight renal regulation, limiting plasma concentrations to low micromolar levels. In contrast, intravenous (IV) administration achieves pharmacologic millimolar plasma concentrations, enabling mechanisms not accessible through dietary or supplemental intake. At these higher levels, ascorbate functions as a pro-drug to generate hydrogen peroxide (H₂O₂) in the extracellular space, selectively inducing oxidative stress and cytotoxicity in cancer cells, which often possess impaired antioxidant defences. Additional proposed mechanisms include modulation of redox signalling, enhancement of sensitivity to chemotherapy and radiotherapy, and regulation of epigenetic enzymes such as TET and HIF hydroxylases. Preclinical studies consistently demonstrate dose-dependent tumour cell killing and synergy with conventional therapies, while early-phase clinical trials report good tolerability, improved quality of life, and signals of therapeutic benefit in malignancies such as pancreatic, ovarian, and glioblastoma. However, definitive efficacy data remain limited due to small sample sizes and heterogeneous protocols. Safety concerns include haemolytic risk in G6PD deficiency and oxalate nephropathy in predisposed patients, underscoring the need for appropriate screening. Overall, current evidence supports the biological plausibility and safety of pharmacologic ascorbate as an adjunct to standard cancer therapy, but well-powered randomized trials and validated biomarkers are required before widespread clinical implementation. Keywords: Vitamin C, Ascorbate, Intravenous Vitamin C, Cancer Therapy, Oxidative stress, Hydrogen Peroxide, Pharmacokinetics, Chemo-radiation Sensitization, Adjunctive oncology