Is there BH4 supplement/medicine?

[GlassCannonLife]

As an update, I have been on a 20mg dose. I was able to provide by insurance with amino acid results that showed high phenylalanine which convinced them I should get it. BioMarin also had a group who can help you get it approved.

Do you have to take it ongoingly to maintain the benefits?

 

[Alvin2]

Any updates on this?
I'm also in Canada. Not sure i can get the doc to prescribe it and its not covered by my drug plan unless i have PKU (which afaik i do not).

 

[Consul]

https://www.omfcanada.ngo/genetic-and-metabolic-markers-of-bh4-deficiency-in-long-covid/

STUDY HYPOTHESIS AND DESCRIPTION
Tetrahydrobiopterin (BH4) is a vitamin-like cofactor that is made in the body by a series of enzymatic steps. However, there are common mutations in the biosynthesis pathway that are associated with cofactor deficiency. BH4 is needed for metabolism of a small number of amino acids that are precursors to neurotransmitters, and deficiency leads to cognitive impairment and a wide variety of other symptoms associated with neurotransmitter imbalance. BH4 is also needed for the enzyme nitric oxide synthase, which is a major regulator of blood flow dynamics and immune cell function.

We have determined that individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome are more likely to have pathogenic variants in BH4 synthesis genes compared to the general population, and we have also identified a corroborating metabolic signature that predicts BH4 deficiency. Oxidative stress during infection can also lead to BH4 deficiency, so there are many potential routes to the same problem. We propose to test whether these genetic markers and other indicators of BH4 deficiency are also present in subjects with Long Covid. If we are successful, we will show that ME/CFS and Long Covid have a common underlying disease mechanism that includes deficiency of BH4.

Ron Davis study

 

[Alvin2]

https://www.omfcanada.ngo/genetic-and-metabolic-markers-of-bh4-deficiency-in-long-covid/



Ron Davis study

Is this new?
I would totally sign up for this if i knew how.

On my own front i tried to find out what pharmacy stocks BH4 it and the price (assuming i can get a prescription), its about $50/tablet and my local pharmacy can't get it.
My drug plan does not cover the cost except for PKU and even then its by application/approval only.

Though apparently there is a generic on the market since 2020ish in Canada, the pharmacy never looked for the generic so i have to call again and get them to look into it.

 

[Consul]

Is this new?
.

Not sure. But they apparently found more dysfunctional mutations in the relevant genes in pwme than controls, that sounds like news to me. Big news i would say.

 

[Alvin2]

Not sure. But they apparently found more dysfunctional mutations in the relevant genes in pwme than controls, that sounds like news to me. Big news i would say.

I hope its big news but tragically genetic deviations are a dime a dozen and most of them mean very little.
On the plus side if we can compensate by taking BH4 thats good news.
And hopefully they investigate it and either figure out it is a big deal or label it as noise.

 

[pattismith]

https://www.omfcanada.ngo/genetic-and-metabolic-markers-of-bh4-deficiency-in-long-covid/



Ron Davis study

I wish I could read the full paper!

 

[Consul]

New pilot study from Simmaron research finds high levels of BH4 instead of low levels.

https://www.mdpi.com/1422-0067/24/10/8713

 

[Violeta]

New pilot study from Simmaron research finds high levels of BH4 instead of low levels.

https://www.mdpi.com/1422-0067/24/10/8713

They should measure the neurotransmitters because maybe Bh4 isn't being used to form neurotransmitters and is just floating around in the blood stream.

"BH4 is an important cofactor of amino acid metabolism [8]. Amino acids, such as phenylalanine, tyrosine, and tryptophan, are converted into important cellular intermediates by the action of hydroxylase enzymes. BH4 serves as an essential cofactor of all these hydroxylase enzymes [9,10,11]. Accordingly, the bioavailability of BH4 is critical for the synthesis of neurotransmitters, such as dopamine and serotonin [10]. Apart from these hydroxylase enzymes, BH4 also regulates the function of nitric oxide synthase enzymes and controls the production of nitric oxide (NO) in endothelium."

Are they going to go anywhere with the oxidative stress mentioned in the article?

"Finally, a ROS production assay in cultured microglial cells followed by Pearson correlation statistics indicated that the elevated BH4 in serum samples of CFS + OI patients might be associated with the oxidative stress response."

 

[CristianSerious]

Where can you find BH4 in Europe to buy ?

 

[datadragon]

Under inflammation a number of changes happen to put your body into an inflammatory state similar to a see saw. One of those changes is the lowering of Tetrahydrobiopterin (BH4). Under conditions of oxidative stress, BH4 availability is diminished due to its oxidation, which subsequently leads to NOS uncoupling and generation of highly oxidative free radicals including superoxide and peroxynitrite. This is mainly due to the reduced uptake and availability of zinc during inflammation/infection.

Guanosine 5′-triphosphate cyclohydrolase-I(GTPCH-I), encoded by the GCH-I gene, is the rate-limiting enzyme in BH4 synthesis. Continuing along the de novo BH4 synthesis pathway, H2NTP is next converted to 6-pyruvoyl tetrahydropterin by the zinc-dependent enzyme, PTPS. Although GTPCH is rate limiting to BH4 synthesis in most cells, PTPS has been suggested to be rate limiting in some, most notably human hepatocytes. PTPS may become rate limiting in other tissues and cells, after stimulation with cytokines and other immunological stimuli that induce BH4 synthesis by up-regulation of GTPCH expression https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038990/

The PPAR-α agonist Fenofibrate upregulates Tetrahydrobiopterin (BH4) level through increasing the expression of Guanosine 5′-Triphosphate Cyclohydrolase-I (GTPCH) in human Umbilical Vein Endothelial Cells. Guanosine 5′-triphosphate cyclohydrolase-I(GTPCH-I), encoded by the GCH-I gene, is the rate-limiting enzyme in BH4 synthesis. https://www.hindawi.com/journals/ppar/2011/523520/

All PPAR agonists tested lost their potency to downregulate the TNF-α–induced inflammatory response in zinc-deficient cells. However, if zinc was added back, all PPAR agonists significantly downregulated the TNF-α–mediated induction of inflammatory transcription factors NF-κB and AP-1 and significantly reduced the expression of their target genes, VCAM-1 and IL-6 https://www.sciencedirect.com/science/article/pii/S0022316623029346?via=ihub

Our previous study demonstrated that homocysteine impairs coronary artery endothelial function by decreasing the level of BH4 in patients with hyperhomocysteinemia. Our previous study also showed that plasma level of BH4 was significantly increased by PPARα agonist fenofibrate in patients with hypertriglyceridemia https://journals.physiology.org/doi/full/10.1152/ajpendo.00367.2010

Homocysteine has recently been found to be a competitive inhibitor of the nuclear transcription factors: Peroxisome proliferator activated receptors (PPARs) alpha and gamma https://link.springer.com/article/10.1186/1475-2891-3-4 Homocysteine that rises from that not only increases ER Stress but also NLRP3 inflammasome activation as well from the studies mentioned before in other posts of mine so it seems its all part of the shift to an inflammatory state.

Tetrahydrobiopterin (BH4) is a critical cofactor for the rate limiting enzymes in the synthesis of the monoamine neurotransmitters. BH4 is necessary for the conversion of phenylalanine to tyrosine by PAH, tyrosine to L-DOPA by tyrosine hydroxylase (TH) leading to the production of dopamine and norepinephrine, and tryptophan to 5-HTP leading to the production of serotonin.

Zinc regulates iNOS-derived nitric oxide formation in endothelial cells. Zinc inhibits iNOS-dependent nitrite accumulation in endothelial cells. Zinc decreases cytokine-induced iNOS expression in endothelial cells. Zinc inhibits iNOS promoter activity. NF-kB silencing abolishes cytokine-induced iNOS expression. Zinc inhibits the transactivation activity of NF-κB. https://www.sciencedirect.com/science/article/pii/S2213231714000834