Review of high‐dose intravenous vitamin C as an anticancer agent

@article{Wilson2014ReviewOH,
  title={Review of high‐dose intravenous vitamin C as an anticancer agent},
  author={Michelle K Wilson and Bruce C. Baguley and Clare Rosemary Wall and Michael B. Jameson and Michael P Findlay},
  journal={Asia‐Pacific Journal of Clinical Oncology},
  year={2014},
  volume={10}
}
In the 1970s, Pauling and Cameron reported increased survival of patients with advanced cancer treated with high‐dose intravenous (IV) vitamin C (L‐ascorbate, ascorbic acid). These studies were criticized for their retrospective nature and lack of standardization of key prognostic factors including performance status. Subsequently, several well‐designed randomized controlled trials failed to demonstrate a significant survival benefit, although these trials used high‐dose oral vitamin C. Marked… 
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TLDR
There is no high-quality evidence to suggest that ascorbate supplementation in cancer patients either enhances the antitumor effects of chemotherapy or reduces its toxicity.
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TLDR
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TLDR
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Efficacy and Interaction of Antioxidant Supplements as Adjuvant Therapy in Cancer Treatment
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It was difficult to determine whether antioxidants affect treatment outcomes or whether antioxidants ameliorate adverse effects induced by chemotherapy and radiotherapy, and the harm caused by antioxidant supplementation remains unclear for patients during cancer therapy, except for smokers undergoing radiotherapy.
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References

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TLDR
It is reported here that intravenous doses can produce plasma concentrations 30- to 70-fold higher than the maximum tolerated oral doses, and the role of vitamin C in cancer treatment should be reexamined, and insights from vitamin C pharmacokinetics can guide its clinical use.
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TLDR
The hypothesis that vitamin C supplementation during cancer treatment may detrimentally affect therapeutic response is supported, as vitamin C given before mechanistically dissimilar antineoplastic agents antagonizes therapeutic efficacy in a model of human hematopoietic cancers by preserving mitochondrial membrane potential.
A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients.
TLDR
Intravenous vitamin C therapy for cancer patients given continuous infusions of 150 to 710 mg/kg/day for up to eight weeks suggests that ascorbate infusions did not adversely affect renal function.
Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice
TLDR
It is shown that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogen-peroxide-dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells, and this action may have benefits in cancers with poor prognosis and limited therapeutic options.
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TLDR
The range of vitamin C concentrations possible in humans, pharmacokinetics studies were conducted and showed that when vitamin C is ingested by mouth, plasma and tissue concentrations are tightly controlled by at least 3 mechanisms in healthy humans: absorption, tissue accumulation, and renal re absorption.
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  • Medicine
    Proceedings of the National Academy of Sciences of the United States of America
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TLDR
Analysis of the survival-time curves indicates that deaths occur for about 90% of the ascorbate-treated patients at one-third the rate for the controls and that the other 10% have a much greater survival time, averaging more than 20 times that for the Controls.
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TLDR
The ingestion of large doses of ascorbic acid is contraindicated in cases of renal insufficiency, chronic hemodialysis patients, unusual forms of iron overload, and oxalate stoneformers.
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    Proceedings of the National Academy of Sciences of the United States of America
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TLDR
Human pharmacokinetics data indicate that ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H(2)O(2), and that blood can be a delivery system of the pro- drug to tissues.
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TLDR
The effect of ascorbate on doxorubicin efficacy was concentration dependent; low doses were protective while high doses increased cell killing, suggesting tumoricidal concentrations may be achievable in vivo.
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