High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer

Abstract

Open Access

Mounting evidence indicates that vitamin C has the potential to be a potent anti‐cancer agent when administered intravenously and in high doses (high‐dose IVC). Early phase clinical trials have confirmed safety and indicated effi‐ cacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi‐targeting effects of vitamin C were unravelled, demonstrating a role as cancer‐specific, pro‐oxidative cytotoxic agent, anti‐cancer epigenetic regulator and immune modulator, reversing epithelial‐to‐mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and boosting immune response. Moreover, high‐dose IVC is powerful as an adjuvant treatment for cancer, acting synergistically with many standard (chemo‐) therapies, as well as a method for mitigating the toxic side‐effects of chemotherapy. Despite the rationale and ample evidence, strong clinical data and phase III studies are lacking. Therefore, there is a need for more extensive awareness of the use of this highly promising, non‐toxic cancer treatment in the clinical setting. In this review, we provide an elaborate overview of pre‐clinical and clinical studies using high‐dose IVC as anti‐cancer agent, as well as a detailed evaluation of the main known molecular mechanisms involved. A special focus is put on global molecular profiling studies in this respect. In addition, an outlook on future implications of high‐dose vitamin C in cancer treatment is presented and recommendations for further research are discussed.