Lowered levels of tetrahydrobiopterin (BH4), a cofactor necessary for eNOS to function, can result from hyperglycemia and failure of NO production.

Therapeutic Efforts Pharmaceutical
#1

I stumbled this across a few sites…could it be that we’re deficient in Tetrahydrobiopterin(BH4) which is a cofactor necessary for eNOS?

Supplementation with BH4 has been shown to improve endothelial dysfunction in diabetics.

High blood sugar (hyperglycemia) activates oxidative stress, producing free radicals and changing eNOS acivity. This results in the production of harmful reactive oxygen species (ROS) rather than beneficial NO. This oxidative stress can cause damage to the inner lining of blood vessels (endothelial dysfunction) leading to arteriosclerosis. Did propecia cause a deficiency in this enzyme?

rainbowgrocery.coop/nutritio … es/lithium

Here is another site guys…you can test for this deficiency, it just MAYBE worth looking into…

bh4.org/BH4_Deficiency_History.asp

#2

Interesting enough anonn1 is that alot of those articles were about lithium effecting brain fuction.
In my recently returned hair test lithium was the lowest of everything .005 (.007-.020)LOW

In regards to the bh4 it is something that is worth looking into, but if no one does its wasted information. We need individuals to step up and take random tests like this and if we get a strange result…someone else has a test, then we know we are onto something. Guys the endos dont know…we are going to have to work this out ourselves.
Im not having a shot at anyone, but i want to get better and im sure as hell anonn1 does.

#3

Going Further…GENE MUTATIONS can cause TETRAHYDROBIOPTERIN Deficiency
ghr.nlm.nih.gov/condition/tetrah … deficiency

What genes are related to tetrahydrobiopterin deficiency?
Tetrahydrobiopterin deficiency can be caused by mutations in one of several genes, including GCH1, PCBD1, PTS, and QDPR. These genes provide instructions for making enzymes that help produce and recycle tetrahydrobiopterin in the body. Tetrahydrobiopterin (also known as BH4) is a molecule that helps process several amino acids, including phenylalanine. It is also involved in the production of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain.If one of the enzymes fails to function correctly because of a gene mutation, little or no tetrahydrobiopterin is available to help process phenylalanine. As a result, phenylalanine can build up in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage. Tetrahydrobiopterin deficiency can also alter the levels of certain neurotransmitters, which disrupts normal brain function.

Read more about the GCH1, PCBD1, PTS, and QDPR genes.

#4

schircks.com/tablets/sys/ins … frame1.htm

This is the supplier. There aren’t too many suppliers, this one is in Switzerland. Guys, please look further into this…

They come in 10mg to 50 mg pills. that you can cut up into quarts.

#5

en.wikipedia.org/wiki/Tetrahydrobiopterin

Tetrahydrobiopterin (THB, BH4; Kuvan) or sapropterin, is a naturally occurring essential cofactor of the three aromatic amino acid hydroxylase enzymes, used in in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin (5-hydroxytryptamine (5-HT)), melatonin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and nitric oxide (NO).

I’m curious to see if this drug could also help out people in the SSRI community who haven’t recovered from sexual side effects as well

Contents [hide]
1 History
2 Biosynthesis
3 Functions
4 Significance
5 See also
6 References
7 External links

[edit] History
THB was discovered to play a role as an enzymatic cofactor. The first enzyme found to use THB is phenylalanine hydroxylase (PAH).[1]

[edit] Biosynthesis
[b]THB is biosynthesized from guanosine triphosphate /b by three chemical reactions mediated by the enzymes (GTP cyclohydrolase I (GTPCH), 6-pyruvoyltetrahydropterin synthase (PTPS), and sepiapterin reductase (SR).[2]

[edit] Functions
THB has the following responsibilities as a cofactor:

Tryptophan hydroxylase (TPH) for the conversion of L-tryptophan (TRP) to 5-hydroxytryptophan (5-HTP)

Phenylalanine hydroxylase (PAH) for conversion of L-phenylalanine (PHE) to L-tyrosine (TYR)

Tyrosine hydroxylase (TH) for the conversion of L-tyrosine to L-DOPA (DOPA)

Nitric oxide synthase (NOS) for conversion of a guanidino nitrogen of L-arginine (L-Arg) to nitric oxide (NO)

Glyceryl ether monooxygenase (GEMO) for the conversion of 1-alkyl-sn-glycerol to 1-hydroxyalkyl-sn-glycerol

Significance
A deficit in THB biosynthesis and/or regeneration results in phenylketonuria (PKU) from excess L-phenylalanine concentrations or hyperphenylalaninemia (HPA), as well as monoamine and nitric oxide neurotransmitter deficiency or chemical imbalance. The chronic presence of PKU can result in severe brain damage, including symptoms of mental retardation, microcephaly, speech impediments such as stuttering, slurring, and lisps, seizures or convulsions, and behavioral abnormalities, among other effects.
THB, developed by BioMarin under the brand name Kuvan and approved by the United States (U.S.) Food and Drug Administration (FDA) on December 13, 2007, is a synthetic preparation of the dihydrochloride salt of the substance, used in the treatment of PKU.[3] HPA due to THB deficiency-mediated PKU. Sapropterin is the first non-dietary treatment for patients with PKU that has been shown in randomized, double-blind trials to be effective in lowering blood phenylalanine levels. [4]

According to researchers at the University of Illinois at Chicago, THB may be of benefit in the management and treatment of intractable systolic heart failure, based on research in mice. This is especially significant, given that THB has already been tested and determined to be safe in human patients using it in the management of phenylketonuria, and also because there are far fewer ways to manage systolic heart failure than for diastolic heart failure.

#6

Looks like its quite hard to get hold of, that you may have to be diagnosed with the condition before you can get it.
Have you found anywhere that offers the test?

Thanks

#7

I would to get my hands on this and try it…It looks very promising my friend…As for testing for the deficiency, I’ll look into it…I’m sure it’s very expensive…

#8

It is a FDA approved medication too in the U.S.(This is GOOD! Doctors can prescribe it).

It’s marketed under the brand name “Kuvan” at

bmrn.com/products/kuvan.php

#9

Good find. To get a presciption you would have to be tested?
Are there any doctors around that are into this stream of illness and what kind of doctor would it be? endo?
Sorry for the dumb questions man.

#10

Read the information on it…PHE levels need to be checked…

Kuvan is a medicine for people with Phenylketonuria (PKU). An enzyme in your body PAH (phenylalanine hydroxylase) helps break down phenylalanine (Phe), an amino acid found in food. In patients with PKU this enzyme does not work right. PKU leads to high blood Phe levels. High blood Phe levels are toxic to the brain and can lead to lower intelligence and decrease in the ability to focus, remember, and organize information.

#11

??? i did.

My angle is to find out what the next step for us would be :slight_smile:

#12

Has anyone taken any action with this or further found out anything about this? Or does anyone know natural sources of where to find Tetrahydrobiopterin like in food?

I find this very intersting since it’s required for your body to create nitric oxide. I randomly stumbled on this thread: prohealth.com/me-cfs/blog/boardDetail.cfm?id=1257636 and people with chronic fatigue syndrome are looking into this same problem as well.

Although, it seems information is scarce on it.

#13

Found this on wiki, it’s a variation of carnitine that’s supposed to increase nitric oxide. Has anyone tried it?

en.wikipedia.org/wiki/Glycocarn