Does vitamin C enhance nitric oxide bioavailability in a tetrahydrobiopterin-dependent manner? In vitro, in vivo and clinical studies

Nitric Oxide. 2014 Jan 30;36:51-7. doi: 10.1016/j.niox.2013.12.001. Epub 2013 Dec 9.


Ascorbate (Asc) has been shown to increase nitric oxide (NO) bioavailability and thereby improve endothelial function in patients showing signs of endothelial dysfunction. Tetrahydrobiopterin (BH₄) is a co-factor of endothelial nitric oxide synthase (eNOS) which may easily become oxidized to the inactive form dihydrobiopterin (BH₂). Asc may increase NO bioavailability by a number of mechanisms involving BH₄ and eNOS. Asc increases BH₄ bioavailability by either reducing oxidized BH₄ or preventing BH₄ from becoming oxidized in the first place. Asc could also increase NO bioavailability in a BH₄-independent manner by increasing eNOS activity by changing its phosphorylation and S-nitrosylation status or by upregulating eNOS expression. In this review, we discuss the putative mechanisms by which Asc may increase NO bioavailability through its interactions with BH₄ and eNOS.

Keywords: Ascorbate; Dihydrobiopterin; Nitric oxide bioavailability; Tetrahydrobiopterin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Ascorbic Acid / metabolism*
  • Biomarkers / metabolism
  • Biopterin / analogs & derivatives*
  • Biopterin / chemistry
  • Cardiovascular Diseases / metabolism
  • Guinea Pigs
  • Humans
  • Mice
  • Nitric Oxide / pharmacokinetics*
  • Nitric Oxide Synthase Type III / metabolism
  • Nitrogen / metabolism
  • Oxygen / metabolism
  • Phosphorylation
  • Rats
  • Reactive Oxygen Species / metabolism
  • Risk
  • Vasodilation


  • Biomarkers
  • Reactive Oxygen Species
  • Biopterin
  • Nitric Oxide
  • 7,8-dihydrobiopterin
  • Nitric Oxide Synthase Type III
  • sapropterin
  • Nitrogen
  • Ascorbic Acid
  • Oxygen