Folates and BH4

This article [Moat et al., 2006: (http://www.ncbi.nlm.nih.gov/pubmed/16387296)] gives some fairly strong evidence that folic acid produces vasodilation and protects against experimental tetrahydrobiopterin (BH4) depletion but does not do so by increasing BH4 regeneration or biosynthesis. Exogenous 5-methyltetrahydrofolate (MTHF, methylfolate) also did not enhance the BH4/BH2 ratio. If MTHF or folic acid had enhanced BH4 regeneration, as exogenous vitamin C was found to in this article, the BH4/BH2 ratio would have been expected to occur. The fact that MTHF does not mimic the effects of vitamin C is actually a good sign, because researchers have talked about the potential downsides of the capacity of vitamin C to facilitate redox cycling reactions with non-transferrin-bound iron, for example. The fact that MTHF does not evidently accelerate the BH4 reductase activity of methylenetetrahydrofolate reductase (CH2THFR) (or reductases other than CH2THFR) is also a property of MTHF that sets it apart from something like riboflavin. Riboflavin has the potential to accelerate clotting factor biosynthesis or enhance the NADPH oxidase activity of NQO1 and other flavin-dependent quinone reductases, as CoQ10 appears to have the capacity to do (http://hardcorephysiologyfun.blogspot.com/2009/01/vitamin-b2-riboflavin-and-vitamin-k.html). This article implies that MTHF does not share that property to a significant extent, and that's consistent with the message that comes out of the literature as a whole.