Intravenous Vitamin C for Cancer Therapy - Identifying the Current Gaps in Our Knowledge

Abstract

The use of intravenous vitamin C (IVC) for cancer therapy has long been an area of intense controversy. Despite this, high dose IVC has been administered for decades by complementary health care practitioners and physicians, with little evidence base resulting in inconsistent clinical practice. In this review we pose a series of questions of relevance to both researchers and clinicians, and also patients themselves, in order to identify current gaps in our knowledge. These questions include: Do oncology patients have compromised vitamin C status? Is intravenous the optimal route of vitamin C administration? Is IVC safe? Does IVC interfere with chemotherapy or radiotherapy? Does IVC decrease the toxic side effects of chemotherapy and improve quality of life? What are the relevant mechanisms of action of IVC? What are the optimal doses, frequency, and duration of IVC therapy? Researchers have made massive strides over the last 20 years and have addressed many of these important aspects, such as the best route for administration, safety, interactions with chemotherapy, quality of life, and potential mechanisms of action. However, we still do not know the answers to a number of fundamental questions around best clinical practice, such as how much, how often and for how long to administer IVC to oncology patients. These questions point the way forward for both basic research and future clinical trials.

Keywords: ascorbate; cancer; chemotherapy; enzyme cofactor; intravenous vitamin C; pharmacokinetics; quality of life; vitamin C.

FIGURE 1

Proposed mechanisms of action of intravenous vitamin C in cancer cells. (a) Transition metal ion-dependent generation of hydrogen peroxide (H₂O₂) and oxidation of intracellular glutathione (GSH) which causes enhanced oxidative stress and potential cell death. (b) Enhances ten-eleven translocation (TET) DNA hydroxylase activity and jumonji histone demethylase (JHDM) activity which alters gene transcription. (c) Decreases HIF protein levels which decreases gene transcription. (d) Increases collagen synthesis resulting in decreased tumor invasion and metastasis.