Ascorbic Acid in Cancer Treatment: Let the Phoenix Fly

Cancer Cell. 2018 Nov 12;34(5):700-706. doi: 10.1016/j.ccell.2018.07.014. Epub 2018 Aug 30.


Vitamin C (ascorbic acid, ascorbate), despite controversy, has re-emerged as a promising anti-cancer agent. Recent knowledge of intravenous ascorbate pharmacokinetics and discovery of unexpected mechanisms of ascorbate action have spawned many investigations. Two mechanisms of anti-cancer activity with ascorbate have gained prominence: hydrogen peroxide-induced oxidative stress and DNA demethylation mediated by ten-eleven translocation enzyme activation. Here, we highlight salient aspects of the evolution of ascorbate in cancer treatment, provide insights into the pharmacokinetics of ascorbate, describe mechanisms of its anti-cancer activity in relation to the pharmacokinetics, outline promising preclinical and clinical evidence, and recommend future directions.

Keywords: ascorbic acid; cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / pharmacokinetics*
  • Ascorbic Acid / therapeutic use*
  • DNA Demethylation / drug effects
  • Humans
  • Hydrogen Peroxide / chemistry
  • Mixed Function Oxygenases / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / prevention & control*
  • Oxidative Stress / drug effects
  • Proto-Oncogene Proteins / metabolism


  • Antineoplastic Agents
  • Antioxidants
  • Proto-Oncogene Proteins
  • Hydrogen Peroxide
  • Mixed Function Oxygenases
  • TET1 protein, human
  • Ascorbic Acid