Possible Interaction: Vitamin C and Tetrahydrobiopterin

“Preclinical studies show that high-dose vitamin C can prevent or restore microcirculatory flow impairment by inhibiting activation of nicotinamide adenine dinucleotide phosphate-oxidase and inducible nitric oxide synthase, augmenting tetrahydrobiopterin , preventing uncoupling of oxidative phosphorylation, and decreasing the formation of superoxide and peroxynitrite, and by directly scavenging superoxide.”

“ Vitamin C , folate, and other antioxidants enhance endothelial BH4 bioavailability through chemical stabilization or scavenging of reactive oxygen species, thereby contributing to the maintenance of physiological homeostasis in the endothelium.”

“In addition, folic acid and infusions of vitamin C are able to restore eNOS functionality, most probably by enhancing BH4 levels as well.”

“Furthermore, it appears that beneficial effects of some antioxidants (e.g., vitamin C ) on vascular function could be mediated via increased intracellular concentration of tetrahydrobiopterin.”

“… AA resulted in …% decrease in BH4 levels (0.49 ± 0.08 to 0.04 ± 0.01 pmol/10⁶ cells, p⟨0.001) at 20 kPa oxygen (O2), and … (0.24 ± 0.03 to 0.03 ± 0.01 pmol/10⁶ cells, p=0.01) after exposure to 60 kPa O2.”

“Treatment with vitamin C for 24 h significantly increased levels of the eNOS co-factor tetrahydrobiopterin (BH4), whereas MnTBAP did not affect its levels.”

“Our data demonstrate that ascorbic acid leads to a chemical stabilization of tetrahydrobiopterin.”

“Pretreatment with vitamin C abolished BH4 effects on ACh-dependent vasodilation.”

“However, when the cofactor tetrahydrobiopterin was omitted from the assay, a similar potentiating effect of ascorbate pretreatment as seen in intact cells was demonstrated, suggesting that ascorbic acid may either enhance the availability of tetrahydrobiopterin or increase its affinity for the endothelial NOS.”

“As ascorbic acid (AsA) is an antioxidant that is rich in the brain, alteration in the AsA concentration in the brain may affect the proper metabolism of BH4.”