Written by Luc Geeraert and the CAM-Cancer Consortium.
Updated July 9, 2014

Intravenous high-dose vitamin C

What is it?

Description / Names

Vitamin C is also known as L-ascorbic acid or as sodium L-ascorbate.

Ingredients / Components

The richest natural sources of vitamin C are fruits and vegetables, and a balanced diet usually meets the daily requirements. Vitamin C is sold as a nutritional supplement in a variety of forms.

Application and dosage

Vitamin C can be administered via several routes including orally. This article only discusses the intravenous administration of high doses of vitamin C (> 0.5 g per kg body weight).

Phase I dose-finding studies in cancer patients recommend the use of 1.5 g to 2 g intravenous vitamin C per kg body weight three to four times per week.1,2 In further clinical research it is advised to start treatment with a lower dose, and, if no adverse events are observed, to gradually increase doses to their final level.1,3

Ascorbic acid solutions for clinical infusion might be unstable over time.4-6

There is no consistent information available as to which clinical dose would be needed to yield an anti-cancer effect.7 The above-mentioned dose of 1.5 g per kg body weight was only found to be safe and to be capable to achieve plasma ascorbic acid concentrations of more than 10 mM for several hours in patients with normal renal function.1

History / Claims of efficacy

Vitamin C was isolated by Szent-Györgyi in 1928.8 The vitamin plays a key role in several biological functions including the biosynthesis of collagen. It is a major water-soluble reducing agent and anti-oxidant, quenching potentially damaging free radicals resulting from metabolic respiration. Acute lack of vitamin C leads to scurvy, a disease marked by connective tissue damage and blood vessel fragility eventually resulting in death.9

Soon after its isolation, methods for vitamin C synthesis were developed and the molecule became widely available. Over the years, a wealth of case reports, anecdotal accounts and pilot studies, all reporting some degree of clinical benefit conferred by supplemental vitamin C in cancer, were published.10 Two controlled retrospective studies (using 10 g vitamin C per day, intravenous and oral) by Cameron and Pauling further substantiated these claims.11,12 As the latter studies lacked randomization and were retrospective, the US National Cancer Institute (NCI) sponsored two randomized, placebo-controlled, double-blind trials to evaluate the effect of high-dose vitamin C on symptoms and survival of patients with advanced cancer;13,14 but Creagan and Moertel, who used 10 g oral (not intravenous) vitamin C per day, did not find a therapeutic benefit in the treatment of cancer. Hence, the use of vitamin C in cancer therapy was abandoned by mainstream oncologists in the 1980s.15,16

In the late 1990s, it was found that vitamin C concentrations in plasma and tissues were tightly controlled through intestinal absorption, tissue accumulation, and renal reabsorption and excretion.17-20 As a result, it was impossible to increase plasma and tissue concentrations once oral intake of vitamin C exceeded 200 mg per day. However, intravenous administration bypassed this tight control until equilibrium was restored through renal excretion. In healthy volunteers, oral administration of the maximum tolerated dose of 3 g every 4 hours resulted in peak plasma concentrations of 0.22 mM, while an intravenous vitamin C dose of 50 g produced a peak plasma concentration of 13.4 mM.21 Comparable results were found in cancer patients.1,22,23

Hence, the route of administration is critical in achieving pharmacologic concentrations of vitamin C, urging the reevaluation of vitamin C in cancer treatment.9,24

Mechanisms of action / Alleged indications

At the normal low physiological concentrations (0.1 mM), vitamin C is an anti-oxidant that inactivates reactive oxygen species.25 However, at high pharmacologic concentrations (up to 20 mM) it was found to become a pro-oxidant generating oxidative species, i.e. extracellular hydrogen peroxide, which is lethal to cancer cells.26,27 Normal cells were unaffected by both concentrations of vitamin C. In vitro findings were confirmed in rats and mice, where virtually the same cancer-killing hydrogen peroxide concentrations were found in extracellular fluid, but not in blood, after intravenous administration of high-dose vitamin C; oral doses did not result in generation of hydrogen peroxide.28-30 It was proposed that extracellular hydrogen peroxide diffuses into cancer cells and mediates toxicity by ATP depletion, thereby causing cell death. Moreover, hydrogen peroxide toxicity compromises membranes, glucose metabolism, and DNA integrity. In normal cells hydrogen peroxide is readily neutralized by antioxidant enzymes like catalase, glutathione peroxidase, and superoxide dismutase, while levels of these antioxidant enzymes are low or imbalanced in most human cancers.31

Daily high-dose intravenous vitamin C significantly decreased the volume of tumours in mice by 41-53% for diverse aggressive cancer types.29 Inhibition of tumour growth was also found in other mouse models of human cancers and in human cancer cell lines.9,30,32-34.

Prevalence of use / providers

Although use of high-dose intravenous vitamin C was abandoned by mainstream oncologists, the compound is in wide use by complementary and alternative medicine practitioners.35

Legal issues

None.

Cost and expenditure

Vitamin C infusions, to be applied by a medical practitioner, are widely available at moderate cost (around $150.00 per infusion in a clinic). 

Citation Luc Geeraert, CAM-Cancer Consortium. Intravenous high-dose vitamin C [online document]. http://ws.cam-cancer.org/The-Summaries/Other-CAM/Intravenous-high-dose-vitamin-C. July 9, 2014.

References

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