Possible Interaction: Folic Acid and Tetrahydrobiopterin

“Recent studies proposed that folic acid is involved in the regeneration of tetrahydrobiopterin in different disease states.”

“In addition to BH4, studies are also examining the potential role of folic acid therapy, because folic acid can enhance BH4 levels and the NOS coupling state.”

“ Folic acid plays an important role in … (NO) generation; it improves 5,6,7,8-tetrahydrobiopterin (BH4) bioavailability in the vasculature by preventing its oxidation; it increases BH4 regeneration from 7,8-dihydrobiopterin (… stabilizes BH4, which is essential for endothelium-derived nitric oxide to generate NO from L-arginine.”

“…,FA … BH4 (10.56±3.86 and 11.23±2.1919 pmol/g vs 6.32+2.87 nmol/g; P<0.05 vs. control) and ….87±29.67 and 140.87±26.76 nmol/l vs. 165.23±30.56 nmol/l; P<0.05 vs. Hcy group).”

“Besides its well-… effect, folic acid does have a very pronounced direct … it can restore the bioavailability of tetrahydrobiopterin (BH4), an essential cofactor of eNOS, by ameliorating the binding affinity of BH4 to eNOS, … stabilizing BH4 and by enhancing the regeneration of BH4 from the inactive form BH2 (4).”

“ Oral folic acid administration, which has been shown to improve aortic H4B levels to completely prevent or markedly decrease the incidence of AAA, significantly increased tissue and plasma H4B levels in both animal models starting at week 1.”

“Together, … H4B levels decrease … increase with folic acid treatment in two different murine models of AAA and that plasma H4B levels accurately reflect H4B levels in the tissue, suggesting … levels may be used clinically as a novel and powerful biomarker for the development and response to treatment of AAA.”

“This study demonstrates that folic acid reverses the endothelial dysfunction induced by BH4 depletion independently of either the regeneration or stabilization of BH4 or an antioxidant effect.”

“Under diet changes after implementation of BH4 a drop in micronutrient intake (vitamin D, folic acid , iron, calcium, iodine) could be revealed (P = 0.005, P < 0.001, P = 0.004, P = 0.001, P = 0.003, respectively).”