Summary:
Intravenous vitamin C is used by some health care providers in supportive cancer care. Pharmacological levels of plasma ascorbate (>0.3mM) are achievable only through IV administration. Cytotoxicity of vitamin C to cancer cells in vitro occurs at plasma levels ranging from 1mM to >20mM, depending on cancer cell type. Plasma levels of 20mM are commonly targeted to achieve potentially cytotoxic effects in vivo, although several cancer cell lines exhibit cytotoxic responses at much lower concentrations. The dose required to achieve plasma ascorbate levels of 20mM typically ranges between 1-1.5g/kg of body weight per infusion. This monograph focuses on IVC at doses of ≥15g which we have defined as high dose, although some data on low dose IVC is provided. Proposed mechanisms of action of high dose IVC include generation of hydrogen peroxide creating oxidative stress, enzyme cofactor activities, anti-angiogenic and anti-inflammatory actions, and immune effects. Twenty-five clinical trials have been published using IVC in cancer populations. These 25 studies include seven randomized controlled trials (RCTs) and 18 single-arm trials. Most published studies have been relatively small, and many have been uncontrolled. Results from these clinical trials, as well as from observational studies demonstrate that IVC is generally safe and well tolerated, with minimal and mild side effects. Some but not all studies have found benefits for quality of life and symptom management alongside cancer treatments or as monotherapy. There is promising preliminary research for IVC administered in addition to standard treatments for tumour response and/or survival outcomes in advanced pancreatic cancer, non-small cell lung cancer, and RAS-mutant colorectal cancers. More research is needed, particularly from larger, randomized and placebo-controlled trials to confirm these findings and study its impact in other cancers.