Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function

Annu Rev Nutr. 2013;33:45-70. doi: 10.1146/annurev-nutr-071812-161246. Epub 2013 Apr 29.


New evidence for the regulation of vitamin C homeostasis has emerged from several studies of human genetic variation. Polymorphisms in the genes encoding sodium-dependent vitamin C transport proteins are strongly associated with plasma ascorbate levels and likely impact tissue cellular vitamin C status. Furthermore, genetic variants of proteins that suppress oxidative stress or detoxify oxidatively damaged biomolecules, i.e., haptoglobin, glutathione-S-transferases, and possibly manganese superoxide dismutase, affect ascorbate levels in the human body. There also is limited evidence for a role of glucose transport proteins. In this review, we examine the extent of the variation in these genes, their impact on vitamin C status, and their potential role in altering chronic disease risk. We conclude that future epidemiological studies should take into account genetic variation in order to successfully determine the role of vitamin C nutriture or supplementation in human vitamin C status and chronic disease risk.

Publication types

  • Review

MeSH terms

  • Animals
  • Ascorbic Acid / metabolism*
  • Biological Transport
  • Genetic Variation*
  • Homeostasis*
  • Humans
  • Oxidoreductases / metabolism*
  • Sodium-Coupled Vitamin C Transporters / genetics*
  • Sodium-Coupled Vitamin C Transporters / metabolism


  • Sodium-Coupled Vitamin C Transporters
  • Oxidoreductases
  • Ascorbic Acid