The epigenetic role of vitamin C in health and disease

Cell Mol Life Sci. 2016 Apr;73(8):1645-58. doi: 10.1007/s00018-016-2145-x. Epub 2016 Feb 4.


Recent advances have uncovered a previously unknown function of vitamin C in epigenetic regulation. Vitamin C exists predominantly as an ascorbate anion under physiological pH conditions. Ascorbate was discovered as a cofactor for methylcytosine dioxygenases that are responsible for DNA demethylation, and also as a likely cofactor for some JmjC domain-containing histone demethylases that catalyze histone demethylation. Variation in ascorbate bioavailability thus can influence the demethylation of both DNA and histone, further leading to different phenotypic presentations. Ascorbate deficiency can be presented systematically, spatially and temporally in different tissues at the different stages of development and aging. Here, we review how ascorbate deficiency could potentially be involved in embryonic and postnatal development, and plays a role in various diseases such as neurodegeneration and cancer through epigenetic dysregulation.

Keywords: DNA methylation; Epigenetics; Histone methylation; JmjC domain-containing histone demethylases; Methylcytosine dioxygenase; Scurvy; Vitamin C.

Publication types

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

MeSH terms

  • Aging
  • Ascorbic Acid / metabolism*
  • Ascorbic Acid Deficiency / genetics
  • Ascorbic Acid Deficiency / metabolism*
  • DNA Methylation / physiology*
  • Dioxygenases / metabolism
  • Embryonic Development / physiology*
  • Epigenesis, Genetic
  • F-Box Proteins / metabolism*
  • Histones / metabolism*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases / metabolism*
  • Neoplasms / pathology
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / pathology
  • Scurvy / pathology


  • F-Box Proteins
  • Histones
  • Dioxygenases
  • Jumonji Domain-Containing Histone Demethylases
  • KDM2A protein, human
  • Ascorbic Acid