Tetrahydrobiopterin generate BH4 or BH3 radical and BH2, respectively. Research shows that ascorbic acid (also known as ascorbate or vitamin C) can reduce BH3 radical into BH4, preventing the BH3 radical from reacting with other free radicals (superoxide and peroxynitrite specifically). Without this recycling process, uncoupling of the endothelial nitric oxide synthase (eNOS) enzyme and reduced bioavailability of the vasodilator nitric oxide occur, creating a form of endothelial dysfunction. Ascorbic acid is oxidized to dehydroascorbic acid during this process, although it can be recycled back to ascorbic acid. Other than PKU studies, tetrahydrobiopterin has participated in clinical trials studying other approaches
Vitamin C an article by Linus Pauling. Briefly, his position was that for optimal health, humans should be consuming at least 2,300 mg/day to compensate for the inability to synthesize vitamin C. The recommendation also fell into the consumption range for gorillas - a non-synthesizing near-relative to humans. A second argument for high intake is that serum ascorbic acid concentrations increase as intake increases until it plateaus at about 190 to 200 micromoles per liter (µmol/L) once consumption exceeds 1,250 milligrams. As noted, government recommendations are a range of 40 to 110 mg/day and normal plasma is approximately 50 µmol/L, so 'normal'