High Dose Vitamin C for cancer – ask and learn

Dr. Weeks’ Comment:  Here is an article alerting conventional oncologists to the fact that high dose vitamin C  (50-100 grams) is in common use.



Vitamin C: Intravenous Use by Complementary and Alternative Medicine Practitioners and Adverse Effects
Sebastian J. Padayatty,#1 Andrew Y. Sun,#1 Qi Chen,2 Michael Graham Espey,1 Jeanne Drisko,2 and Mark Levine1*
1Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, United States of America
2Program in Integrative Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States of America
Joel Joseph Gagnier, Editor
University of Michigan, Canada
#Contributed equally.
Anecdotal information and case reports suggest that intravenously administered vitamin C is used by Complementary and Alternate Medicine (CAM) practitioners. The scale of such use in the U.S. and associated side effects are unknown.
Methods and Findings
We surveyed attendees at annual CAM Conferences in 2006 and 2008, and determined sales of intravenous vitamin C by major U.S. manufacturers/distributors. We also queried practitioners for side effects, compiled published cases, and analyzed FDA’s Adverse Events Database. Of 199 survey respondents (out of 550), 172 practitioners administered IV vitamin C to 11,233 patients in 2006 and 8876 patients in 2008. Average dose was 28 grams every 4 days, with 22 total treatments per patient. Estimated yearly doses used (as 25g/50ml vials) were 318,539 in 2006 and 354,647 in 2008. Manufacturers’ yearly sales were 750,000 and 855,000 vials, respectively. Common reasons for treatment included infection, cancer, and fatigue. Of 9,328 patients for whom data is available, 101 had side effects, mostly minor, including lethargy/fatigue in 59 patients, change in mental status in 21 patients and vein irritation/phlebitis in 6 patients. Publications documented serious adverse events, including 2 deaths in patients known to be at risk for IV vitamin C. Due to confounding causes, the FDA Adverse Events Database was uninformative. Total numbers of patients treated in the US with high dose vitamin C cannot be accurately estimated from this study.
High dose IV vitamin C is in unexpectedly wide use by CAM practitioners. Other than the known complications of IV vitamin C in those with renal impairment or glucose 6 phosphate dehydrogenase deficiency, high dose intravenous vitamin C appears to be remarkably safe. Physicians should inquire about IV vitamin C use in patients with cancer, chronic, untreatable, or intractable conditions and be observant of unexpected harm, drug interactions, or benefit.
Among the most enduring of alternative medical treatments, vitamin C (ascorbic acid, ascorbate) is also one of the most popular. In 2007, it was the most widely sold single vitamin, with sales of 884 million dollars in the US1 [1]. Independent of its use to treat the deficiency disease scurvy, vitamin C has been used by non-mainstream physicians orally and parenterally for more than 60 years as a therapeutic agent [2][7]. Oral vitamin C is widely used by the public to prevent or treat infections, especially the common cold [8]. In one of its more controversial applications, gram doses of vitamin C were promoted by the two-time Nobel Laureate Linus Pauling as a cancer treatment agent [9], [10]. Anecdotal evidence led us to posit that intravenous (IV) vitamin C is still used by Complementary and Alternative Medicine (CAM) practitioners to treat diverse conditions including infections, autoimmune diseases, cancer and illnesses of uncertain origin [11][13].
Despite its purported popularity, the extent of use of IV vitamin C is unknown. Its use in CAM has not been well publicized by practitioners and their patients, and is likely to be unrecognized by mainstream physicians. Benefits if any and especially side effects of such use may be unreported or under-reported. It is useful to know if high dose IV vitamin C therapy is widely used, and if so how and for what, so that conventional physicians can improve patient care by identifying any ill effects or drug interactions, and reporting benefit if any.
New knowledge has elucidated possible mechanisms of action of IV vitamin C and for the first time made therapeutic effects biologically plausible [14]. It is now known that IV but not oral administration of vitamin C produces pharmacologic plasma concentrations of the vitamin [15], [16]. Past studies used oral and/or IV routes inconsistently, making such studies, in retrospect, flawed and difficult to interpret [17]. Recent in vitro experiments indicated that vitamin C only in pharmacologic concentrations killed cancer cells but not normal cells, and that the mechanism was via hydrogen peroxide formation [18]. In vivo animal data indicated that hydrogen peroxide was produced selectively in extracellular fluid around normal and tumor tissues by pharmacologic vitamin C concentrations [19], [20]. At these concentrations, vitamin C slowed tumor growth [20], [21]. Pharmacologic vitamin C concentrations produced in animals by parenteral administration were reproduced in patients in a recent phase I clinical trial [16].
Because of the new interest in IV vitamin C, coupled to need to characterize use and uncover side effects, we surveyed CAM practitioners anonymously. We also searched for side effects of IV vitamin C administration in the published medical literature and in the Food and Drug Administration (FDA) adverse events database, and estimated sales volumes of IV vitamin C preparations.
Our study obtained quantitative information that substantiated previous anecdotal reports. Despite unexpected wide use, we found side effects of vitamin C were surprisingly few when patients were properly screened. The findings in this paper will alert conventional practitioners about unrecognized wide use of IV vitamin C, will remind them to query patients about such use, and may help to uncover either unexpected adverse events or benefit and spur further research in this area.

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