Featured article | December 2025
High-dose vitamin C: A promising anti-tumor agent, insight from mechanisms, clinical research, and challenges
Hanzheng Zhao, et al., Genes & Diseases (2026) 13, 101742
This review examines how very high doses of vitamin C may support cancer treatment by exploiting metabolic vulnerabilities in cancer cells, influencing gene regulation, modulating immune responses, and complementing standard therapies. The mechanistic rationale is supported by consistent preclinical evidence and an expanding body of human clinical research.
Discussed in this article:
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Cancer-selective metabolic stress
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Many cancer cells rely on unusually high sugar uptake to sustain rapid growth and stress tolerance.
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Upregulated sugar transporters allow both glucose and oxidized vitamin C to enter the cell.
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At pharmacologic levels, vitamin C generates hydrogen peroxide that diffuses into cancer cells, where it induces lethal oxidative stress.
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Inside the cell, oxidized vitamin C further depletes antioxidant reserves and disrupts energy metabolism, leaving cancer cells vulnerable to oxidative damage.
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Gene regulation
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Vitamin C supports enzymes involved in restoring normal gene activity, including reactivation of tumour-suppressor genes that are commonly silenced in cancer.
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These effects appear particularly relevant in certain blood cancers and selected solid tumours.
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Tumour–immune interactions
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By countering tumour-driven immune suppression, vitamin C may enhance immune cell infiltration and function within the tumour microenvironment.
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These effects may improve responsiveness to immunotherapy.
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Combination therapy
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Clinical outcomes are often more favourable when vitamin C is used alongside chemotherapy, radiation, or immunotherapy rather than as a standalone treatment.
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Reported benefits include improved treatment tolerance and, in some studies, longer survival.
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Intraveneous (IV) vitamin C
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IV vitamin C bypasses intestinal absorption limits and achieves plasma concentrations required for pharmacologic effects.
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Clinical studies commonly use doses ranging from 0.6 to 1.5 g/kg, administered 2–3 times per week, with some protocols using daily infusions during active treatment.
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When patients are appropriately screened, IV vitamin C is generally well tolerated, with mostly mild and transient adverse effects.
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Oral and liposomal vitamin C
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Standard oral vitamin C achieves plasma levels of approximately 0.1–0.2 mM, with higher doses producing little additional increase.
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Liposomal formulations modestly improve absorption, reaching ~0.3–0.4 mM, but do not replicate pharmacologic plasma concentrations.
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As a result, oral and liposomal vitamin C are best viewed as supportive or adjunctive rather than therapeutic in oncology settings.
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Plasma vitamin C levels by route:
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Oral: ≤ 0.1–0.2 mM
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Liposomal: up to ~0.3–0.4 mM
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Intravenous: ~10–20 mM or higher, where vitamin C shifts from antioxidant to pro-oxidant activity relevant to cancer biology
“With deeper exploration of its mechanisms, vitamin C shows great promise as an economical and non-toxic anti-tumor agent.”
