I have a hard time deciphering the language in these studies so I'm not sure if this is relevant to the discussion or not.
http://www.ncbi.nlm.nih.gov/pubmed/12692136
Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase.
Tetrahydrobiopterin (BH4) serves as a critical co-factor for the endothelial nitric-oxide synthase (eNOS). A deficiency of BH4 results in eNOS uncoupling, which is associated with increased superoxide and decreased NO* production. BH4 has been suggested to be a target for oxidation by peroxynitrite (ONOO-), and ascorbate has been shown to preserve BH4 levels and enhance endothelial NO* production; however, the mechanisms underlying these processes remain poorly defined. To gain further insight into these interactions, the reaction of ONOO- with BH4 was studied using electron spin resonance and the spin probe 1-hydroxy-3-carboxy-2,2,5-tetramethyl-pyrrolidine. ONOO- reacted with BH4 6-10 times faster than with ascorbate or thiols. The immediate product of the reaction between ONOO- and BH4 was the trihydrobiopterin radical (BH3.), which was reduced back to BH4 by ascorbate, whereas thiols were not efficient in recycling of BH4. Uncoupling of eNOS caused by peroxynitrite was investigated in cultured bovine aortic endothelial cells (BAECs) by measuring superoxide and NO* using spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine and the NO*-spin trap iron-diethyldithiocarbamate. Bolus ONOO-, the ONOO- donor 3-morpholinosydnonimine, and an inhibitor of BH4 synthesis (2,4-diamino-6-hydroxypyrimidine) uncoupled eNOS, increasing superoxide and decreasing NO* production. Exogenous BH4 supplementation restored endothelial NO* production. Treatment of BAECs with both BH4 and ascorbate prior to ONOO- prevented uncoupling of eNOS by ONOO-. This study demonstrates that endothelial BH4 is a crucial target for oxidation by ONOO- and that the BH4 reaction rate constant exceeds those of thiols or ascorbate. We confirmed that ONOO- uncouples eNOS by oxidation of tetrahydrobiopterin and that ascorbate does not fully protect BH4 from oxidation but recycles BH3. radical back to BH4.
Triffid, you have given a lot to the group, I hope this helps you.
This is basically talking about Nitric Oxide being (NO) produced in the veins, (where it helps blood flow), but the same principle would apply throughout the body. BH4 is used (losslessly) when NO is made in the first place.
Either through oxidation of NO or (according to some theorists faulty production of NO in the first place) you can end up with Peroxynitrite (ONOO) - this is nasty stuff that causes cell death. Again BH4 is the most efficient stuff for converting Peroxynitrite back into Nitric Oxide.
The next best candidate to (BH4) for converting back to NO is Vitamin C - this also helps created Dopamine. I take 5000mg per day and find if helps my health though I am unsure whether that is down to Dopamine or NO, either way I feel better for it.
Be aware that when Nitric Oxide Increases, two things will happen: you will have increased blood flow; your immune system may work better. The former can increase migraines (in the short term), the later can cause a Healing Shock (term your Doctor/Nurse would use) aka a die off reaction.
I find the die off reaction occurs with most things that work for ME and its better to titrate doses (start small and work dose upwards each two weeks) and just put up with minor healing shocks - alternatively when one occurs you can reduce your dose a short while (the usual recommendation).
Urination and Blood Flow
Liquorice extract can be used to stop you peeing too much and increase your blood volume - that in turn helps restore circulation and lowers the demand for NO. My Aunt and I both found that helpful (for the urination).
Do not use if you have high blood pressure, or high Cortisol. You could also add salt and lime to the water you drink, I found both helpful in keeping the water I drink.
To compensate for the lack of NO you could also supplement small amounts of Niacin (Vitamin B3, but NOT the 'flush free' kind). That should help with blood flow to the head and limbs.
Patents (big Pharma)
Sadly though nothing is as good as the BH4 that's missing and you can thank the US Patent office for that. It has permitted the registration of several patents by American, Swiss and German companies for the use of BH4 to increase Catecholamine levels - given that the body makes them from BH4 they have effectively patented the body's own process.
This is NUTS and would not be permitted in most countries (since its both a natural method and a trivial piece of science).
In my personal opinion, the worst culprits for this are the manufacturers of Kuvan.