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

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

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Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Electronic address:


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.


Ascorbate; Dihydrobiopterin; Nitric oxide bioavailability; Tetrahydrobiopterin

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