How to acquire Kuvan (sapropterin, tetrahydrobiopterin, BH4) for raising neurotransmitters & treating nitrosative stress

[junkcrap50]

I am making a new thread based on post by @Learner1 in the Bhupesh Prusty thread about tetrahydrobiopterin (BH4) or Kuvan. It seemed there was some interest in Kuvan from others besides me: @Learner1 , @stefanosstef , @raghav , @ScottTriGuy , @Badpack

I've been wanting to get my hands on it for a long time to help raise neurotransmitter like dopamine. Learner1 has been able to get her hands on some in the US and has had some great results with it. So I have several questions.

Learner’s Posts:

Another patient had bought some outright and have me a couple packets to try.

I've been trying to get my hands on it for 4 years, since I read Martin Pall's ONOO- Cure and Pauling was Right papers as well as Morris and Maes' paper on oxidative and nitrosative stress creating peroxynitrites which damage mitochondrial membranes and impairs complex I. My testing showed impaired complex I -31% of normal at one point and I had high nitrotyrosine, which is a marker of peroxynitrites. Additionally, Ron Tomkins ADDED oxidative and nitrosative stress as known features of ME/CFS in his conclusion at last year's NIH conference, eben though none of the presenters had mentioned it that week.

So, knowing I had a peroxynitrite problem, and having gotten some improvement by intensive focus on using nutrients called out in Pall's 2 papers, I was very interested in the one ingredient I hadn't been able to get my hands on, tetrahydrobiopterin (BH4), which was a cheap supplement until about 12 years ago, but BioMarin bought and made into an orphan drug for children with PKU, phenylketonuria, a rare genetic problem involving the PAH gene. I saw their Australian drug application - they predicted 34 kids in Australia would need it as its such a rare genetic disease... Thus justifying the high price.

However, BH4/Kuvan can benefit a large number of other patients as well. Pity its not more available...only 7 mail order-only "specialty" pharmacies in the US carry it.

My friend gave me 2 100mg packets along with a covered test tube and pipette. Knowing neither of us has PKU, it didn't seem like the full dose might be required. As he had more experience, I asked him how much he thought I should try. He said 5-10mg.

So, I dumped the 100mg into the test tube with 10ml water, shook it up and used 1 ml sublingually, holding it under my tongue gor about 5 minutes. Within 10 minutes, I felt a rush of mental energy, felt clear headed, and when I went to the gym, I eas able to raise my normal resistance of 6 on the elliptical I normslly use to 11, a level I haven't hit in over 5 years, and normal for normal women my age. This was repeatable daily for 10 days, at 1ml or 10mg a day of Kuvan. I have found a case in early afternoon, with sleepiness, but found if I divided it into 6mg/4mg or 7mg/3mg, it gave me almost normal functiin, aling with my daily NMN.

Given this success, I approached my prescription drug insurance who is used to my weird requests (LDN, ketotifen, compounded meds, getting an exception to take a brand name as generic due to my allergies) and made a case for getting it approved, providing the Pall, Maes and Morris articles, my labs showing peroxynitrites, and explaining the benefits. When they asked for additional info, I sent them info on Kuvan in 3 clinical trials, including for exercise intoletance which was the indication I wanted it for.

Kuvan comes in cartons of 30 100mg packets, a months supply for PKU patients. I figuted out all I needed was 3 packets for a month, or only 9 for a 90 day supply. Tge retail price I was quoted by a pharmacy was $50 a packet, or $150 for a 1 month supply, and not outrageously expensive. So, my insurance approved it for a year. The other 2 ways of getting it are to but the research chemical, but its MORE and illegal, or to buy the usually out of stock, ship on ice Ecological Formulas 2.5mg pills, also more expensive for my dose. Neither is as effective, apparently the Kuvan formulation, with vitamin C, is more effective.

As long as a doctor will prescribe it, you cssn get it from a specialty pharmacy.

I told my ME/CFS specialist and my neurologist about it. Both are amazed and pleased - they'd tried getting it before for patients, but at the full, super expensive dose - they didn't realize so little could do so much. They'll try with other patients... BioMarin also has a special "Kuvan department" who will help walk us through the insurance approval process. I have no idea how helpfultheyd be - most of their clients are PKU patients for on-label use.


By using an HDRI nitrotyrosine test, paired with a Genova Diagnostics NutrEval and dosing the nutrients mentioned in Pall's papers. And the nutrients in the Correction of Mitochondria paper, by Thomas Seyfried, Dom D'Agostino, and Garth Nicolson. A lot of 5-MTHF, MB12, HB12 and NT Factor/phosphatidyl choline. Plus NAD+ or NMN.

This seems to be in Phase 1 clinical trials for primary mitochondrial diseases, which will eventually make it expensive and for limited on-label use. It does not seem to be for acquired mito dysfunction. But maybe it will work. I want to get well now and have found a path, though complicated thst has worked for me. I think that going after my multiple infections, including HHV6, with Valcyte, was a key part of what's worked well

Just thought I'd update this thread. A fellow patient gave me a couple 100mg packets of Kuvan, and they have proven to be a lifesaver!

He provided them with a test tube with a lid and a pipette, advising me to try 5-10mg a day. My brain felt exceptionally clear within 15 minutes and I was able to increase exercise intensity. Two months on it, the effect has not pooped out and I've increased overall activity level by 30% sustained. My days do vary and I have good days and bad days, but it's been great.

I think it helps in several ways. I have MTHFR A1298C and CBS 699T SNPs. I've had low serotonin, low dopamine, low epinepherine. And low acetylcholine. And I think I have chronically too little NO, but a tendency toward high peroxynitrites, for which I take high dose folate, B12, C, and other Bs. I think Kuvan helps all of this.

I looked into all methods of getting it - research chemical, pteridin, and Kuvan, from a specialty pharmacy. Kuvan is cheaper by the milligram, running about US$150 for a 90 day supply of about 900mg, about 10mg a day. The biggest issue I have had is with the pharmacy, who is upset about breaking the packet apart over several days. The only way they'll fill it is to take a packet every nth day. So, every nth day, one can dump the packet into a dropper bottle with 10ml water, then dropper out however much is needed per day, done sublingually.

Great stuff - hope others are using it. I've had no side effects.

I don’t have much knowledge to add or contribute, but have a ton of questions, mostly directed at @Learner1 . But hopefully the answers will be helpful for others too. Sorry there’s so many, but I would appreciate if you answered.

QUESTIONS:
Testing:

1. What are all the ways to test for and track nitrosative stress or peroxynitrate levels?
   1. Is it only: Nitrotyrosine, Biopterin & Neopterin, Nitric Oxide (NO), MitoSwab test (for Complex I)? Are there any other ways?
2. Is there anyway to test for iNOS?
3. Learner, what tests did you use to evaluate nitrostative stress?
4. Did you do followup testing after having been on BH4? What were the results like?

Cost/Pricing of Kuvan:

1. The price you listed in your two posts above are different. What's the correct price? $50/100mg packet = $150/mo or $150 for 900mg / 9 months?
2. Is the price what you pay personally or what it costs insurance? How much does it cost you personally?
3. Or are you saying that insurance paid and approved for the whole cost of Kuvan? So you get it free with insurance? Because it was such a low dose, thus very cheap?
4. What did you send to insurance to get authorization? A formal letter with references or just papers with an explanation of their links?
5. What was most convincing for insurance, the Complex 1 research and your MitoSwab test?

Getting Kuvan/BH4:

1. What are the specialty pharmacies that sell it? You can PM me if that’s preferable.
2. Which had the lowest price?
3. I assume insurance had a preferred pharmacy, right?
4. The price you got was $150/mo for about 10mg/day? Correct? From my math this is just the full, regular price of Kuvan per mg but at a lower dosage. Basically, 100 mg is around $1,164 for a supply of 30 powder for reconstitution, so 10mg $116 for 30 day supply. Right? So no discount for paying cash?
5. @raghav , you mentioned that Kuvan is available as generic in India? What is it’s price in India? What is the drug name for it there? Would it be hard for a local running a online mail order pharmacy to get a prescription? I've had some luck with them for other drugs

* Note, Kuvan will be available as generic in the US October 1, 2020.

Other:

1. Do you have any other relevant papers or articles that I have not uploaded?
2. Does reconstituting BH4 in water inactivate it after several days? You say you add 100mg in 10ml & use 1ml sublingually. Is it still effective days 9 & 10?
3. Is there a dose dependent effect with Kuvan? Do you feel more of it's effect with a higher dose.
4. Do you have any MAO or COMT SNPs? I wonder how these snps and the slow breakdown of neurotransmitters would have on taking BH4.

I’ve attached several relevant papers on ON/ONOO. I will add links to more BH4 research in relation to neurotransmitters later.

 

[raghav]

My city is still under complete lockdown. I had made some enquiries on Indiamart with some dealers but lockdown struck. So I am waiting for relaxation of lockdown. Will update when I have more info.

 

[Hip]

And alternative to Kuvan which is easier to obtain is the BH4 supplement by Ecological Formulas called Pteridin-4. The cost of 60 x 2.5 mg capsules (a total of 150 mg of BH4) is around $100.

Whereas on https://goldpharma.cn the cost of 30 x 100 mg of Kuvan BH4 is about $1000, which works out to about $50 for 150 mg.

 

[junkcrap50]

And alternative to Kuvan which is easier to obtain is the BH4 supplement by Ecological Formulas called Pteridin-4. The cost of 60 x 2.5 mg capsules (a total of 150 mg of BH4) is around $100.

Thanks. I'm aware of Pteridin-4. I've taken it before, but never sublingually. I didn't notice anything taking it orally. I'm considering ordering 1 bottle of it, which would last 15 days, to do a trial of various sublingual dosages. It's still very difficult to acquire as it's rare in stock. I wonder, is it as potent as Kuvan? I wonder, if @Learner1 has tried the pteridin and can compare it to the real deal Kuvan.

Also, for a 30 days of 10mg dose, Pteridin is actually more expensive, from prices I can find online.

 

[Hip]

I've taken it before, but never sublingually.

Sublingual seems to have better bioavailability: this study says sublingual BH4 is up to 76% more bioavailable than oral.

By the way, whenever I take something sublingually, I actually massage the substance into all my oral mucous membranes: gums and cheeks, as well as under the tongue.

 

[junkcrap50]

Sublingual seems to have better bioavailability: this study says sublingual BH4 is up to 76% more bioavailability than oral.

By the way, whenever I take something sublingually, I actually massage the substance into all my oral mucous membranes: gums and cheeks, as well as under the tongue.

Thanks Hip!

 

[Learner1]

@junkcrap50 Given what people have said on PR, the specific formulation of Kuvan makes it more bioavailable and for longer than pteridin. And, yes, Kuvan is actually cheaper if you just buy it, running about US$15.50-17 retail per 100g packet at the 2 pharmacies I checked.

I'm using a brown glass dropper bottle and keep it refrigerated when I'm not using it to retain potency just in case. I've noticed it changed from colorless to yellow over a 10 day period, but have not noticed a drop in effectiveness.

I've learned that in addition to being an ingredient in the Pall protocol to reduce peroxynitrites, which was my original sim, it gets burned in converting arginine to nitric oxide and am investigating nitric oxide deficiency and inadequate NADPH as possible issues as well.

Thinking of running some experiments with higher finding as NO strips have me low in NO. I think the bump in NO is what's given me the 25% increase in energy since I started it.

 

[Learner1]

Sorry, reading my tags in reverse order. Let me try to answer your questions. Thanks for starting this thread! As you can see, though I'd been doing well before, Kuvan, since the beginning of March, has made a big difference in what I can do.

QUESTIONS:
Testing:

1. What are all the ways to test for and track nitrosative stress or peroxynitrate levels?
   1. Is it only: Nitrotyrosine, Biopterin & Neopterin, Nitric Oxide (NO), MitoSwab test (for Complex I)? Are there any other ways?
2. Is there anyway to test for iNOS?
3. Learner, what tests did you use to evaluate nitrostative stress?
4. Did you do followup testing after having been on BH4? What were the results like?

I've done a MitoSwab with mito content and complexes I-IV, along with an HDRI NO and nitrotyrosine and a Genova Diagnostics NutrEval. I've done MitoSwab 3 times and NutrEval 3 times over the past 28 months and HDRI nitrotyrosine twice (waiting on my latest kit from them - they are a pain to deal with, but I don't think anyone else does their tests in the US - their European sister lab does Europe . That will tell me peroxynitrite change after starting BH4.

I don't know how to test iNOS. I'd also like to be able to test SOD and catalase. I'm also trying to get to the bottom of an extraordinary oxidative stress problem as evidenced by high lipid peroxides and depleted antioxidants in the NutrEval, do an interested in more ways to figure out the cause,which might possibly be hydroxyl radicals or lack of MnSOD

Cost/Pricing of Kuvan:

1. The price you listed in your two posts above are different. What's the correct price? $50/100mg packet = $150/mo or $150 for 900mg / 9 months?
2. Is the price what you pay personally or what it costs insurance? How much does it cost you personally?
3. Or are you saying that insurance paid and approved for the whole cost of Kuvan? So you get it free with insurance? Because it was such a low dose, thus very cheap?
4. What did you send to insurance to get authorization? A formal letter with references or just papers with an explanation of their links?
5. What was most convincing for insurance, the Complex 1 research and your MitoSwab test?

It's free for me as I met my out of pocket max for the year. Before that, I'd pay the copay for the prescription according to my plan. The generic would help greatly.

In making my case, I provided my ME/CFS diagnosis, the Maes/Morris paper and both Pall papers. And my MitoSwab and nitrotyrosine results and an amino panel showing my phenylalanine above range (I'd been taking tyrosine.. ) When asked for more info, I provided other BH4 research NOT related to PKU, and the info on the current clinical trials for exercise intolerance using Kuvan in renal and cardiomyopathy patients.

Getting Kuvan/BH4:

1. What are the specialty pharmacies that sell it? You can PM me if that’s preferable.
2. Which had the lowest price?
3. I assume insurance had a preferred pharmacy, right?
4. The price you got was $150/mo for about 10mg/day? Correct? From my math this is just the full, regular price of Kuvan per mg but at a lower dosage. Basically, 100 mg is around $1,164 for a supply of 30 powder for reconstitution, so 10mg $116 for 30 day supply. Right? So no discount for paying cash?
5. @raghav , you mentioned that Kuvan is available as generic in India? What is it’s price in India? What is the drug name for it there? Would it be hard for a local running a online mail order pharmacy to get a prescription? I've had some luck with them for other drugs

The price I was quoted by Walgreens specialty pharmacy was about $154 for 900mg and Accredo, ExpressScripts' specialty formula quoted $145 for 900mg, which was a 90 day supply. So around $50 a month. I don't know who the other 5 specialty pharmacies are, but BioMarin told me there were only 7 and they were all mail order.

Both were cheaper than pteridin or the research chemical.

Kuvan us stabilized and doesn't need to be shipped on ice, so no risk of it going bad - it's in sealed foil packets.

Other:

1. Do you have any other relevant papers or articles that I have not uploaded?
2. Does reconstituting BH4 in water inactivate it after several days? You say you add 100mg in 10ml & use 1ml sublingually. Is it still effective days 9 & 10?
3. Is there a dose dependent effect with Kuvan? Do you feel more of it's effect with a higher dose.
4. Do you have any MAO or COMT SNPs? I wonder how these snps and the slow breakdown of neurotransmitters would have on taking BH4.

I have MTHFR A1298C, and the relevant CBS and COMT SNPs. And 2 homozygous SID2 SNPs. And PEMT. No MAO. All predisposing me to lousy BH4 and shredded mito membranes. My serotonin, dopamine, and epinepherine are all below range but I have absolutely no mood issues. I am having a low pyruvate issue which may be related to low epinepherine, which may possibly be a side effect of my POTS beta blocker.

More Kuvan helps. In afternoons when I've overdone it in the morning, I've gotten a lift out of 5 more mg.

As I mentioned above, I've been looking into nutic oxide and it seems mine is very low I suspect that Kuvan is increasing it and on addition to improved exercise, I think my autoimmune high blood pressure POTS has improved slightly with the Kuvan for that reason, so I've been able to reduce the beta blocker.

When I started, I was able yo side the intensity on the sane elliptical machine I've used throughout this illness from a plodding 6 to 11, which is more normal and I was able yo keep it up at 15 minutes out, my max time. I haven't been able to do it in the past month due to our stay at home order, but I did have a 10.9 mile walking day, in 2 walks. It did trigger the first PEM I've had in 3 months which lasted a day, but I hadn't had that much activity in 5.5 years.

I haven't found it dissipates much on Day 9 it. 10. Maybe s tiny bit, but I'm usually dumping down every last drop in the bottle on Day 10 so maybe that compensated. Nit much, though. Like I said, the color changes from clear to yellow over time .

I do want to run some experiments regarding the BO, now that I realized NO is made from arginine by using BH4. I think I'm trying to solve a NOS uncoupling problem that's why my oxidative stress is out of control and not having enough MnSOD isn't helping. Also wondering if I need catalase

Yes, I have a bunch of other articles. It's late now, but remind me and I'll post them in my opinion BH4 is useful stuff and BioMarin has done a great number of patients a bug disservice by restricting the indication to PKU

Both my NE)CFS specialist and neurologist knew about it and said they'd tried getting it for patients in the past but couldn't, but I think they tried for $1500 a month worth, nit the $50 a month I wanted. And, I think more science may be available now ...

And alternative to Kuvan which is easier to obtain is the BH4 supplement by Ecological Formulas called Pteridin-4. The cost of 60 x 2.5 mg capsules (a total of 150 mg of BH4) is around $100.

Whereas on https://goldpharma.cn the cost of 30 x 100 mg of Kuvan BH4 is about $1000, which works out to about $50 for 150 mg.

Pteridin is not as stable, it's expensive, and I'd be taking 4-6 capsules a day, maybe more. Kuvan (or the generic) are better formulations and cheaper.

 

[Hip]

Pteridin is not as stable, it's expensive, and I'd be taking 4-6 capsules a day, maybe more. Kuvan (or the generic) are better formulations and cheaper.

Yes, I read that BioMarin BH4 is stable for 2 years at room temperature, whereas normally BH4 requires refrigeration, and even then, is only stable for 4 months (at least according to the Schircks Lab literature).

But the Ecological Formulas Pteridin-4 supplement is useful if someone just wants to try BH4, without spending $1000 on a packet of Kuvan.

Another cheap source of BH4 is nootropicsource.com, who sell 50 mg for $40.


I recently bought some Ecological Formulas Pteridin-4, but did not notice much from daily doses up to 5 mg, except maybe a slight mood boost. But I do not have the MTHFR A1298C mutation which affects BH4.


If anyone takes BH4, note that it is sensitive to being oxidized to BH2 by reactive oxygen species and peroxynitrite, so it might be an idea to take some antioxidants with your BH4, such as vitamin C and vitamin E. This sensitivity to oxidation applies to both your naturally-made BH4, and any BH4 you supplement with.

This study found that a regimen of L-arginine, vitamin C, and vitamin E increased natural BH4 levels by 32%.


An another thread on BH4 can be found here.

 

[junkcrap50]

Thank you so much @Learner1 ! Lots of great info and answered a ton of my questions. It's even cheaper than I thought $150/3months. Fantastic.

 

[Learner1]

But the Ecological Formulas Pteridin-4 supplement is useful if someone just wants to try BH4, without spending $1000 on a packet of Kuvan.

A packet of Kuvan is about US$15-17.

This study found that a regimen of L-arginine, vitamin C, and vitamin E increased natural BH4 levels by 32%.

Arginine used BH4 to make nitric oxide. Not a good idea if one is short of BH4. Or if one has a history of herpes viruses. The antioxidants work in a network and increasing them will help the others recycle. Increasing BH4 can help oxidative and nitrosative stress. They all interrelate.

An another thread on BH4 can be found here.

All good info.

 

[Hip]

A packet of Kuvan is about US$15-17.

Is that the right figure? Goldpharma.cn are selling Kuvan for just over $1000 for 30 x 100 mg.

 

[kangaSue]

Another cheap source of BH4 is nootropicsource.com, who sell 50 mg for $40.

@kyzcreig said in another thread that nootropics' BH4 is improperly stored at room temperature so it will degrade in a matter of days even if sealed air tight.
https://forums.phoenixrising.me/threads/is-there-bh4-supplement-medicine.22480/page-9#post-939002

 

[Hip]

@kyzcreig said in another thread that nootropics' BH4 is improperly stored at room temperature so it will degrade in a matter of days even if sealed air tight.
https://forums.phoenixrising.me/threads/is-there-bh4-supplement-medicine.22480/page-9#post-939002

It depends on the formulation: the Kuvan formulation made by Biomarin is room temp stable for 2 years, I believe.

 

[Learner1]

Kuvan comes in 100mg or 500mg packets of powder, I'm assuming, to keep it fresh. The formulation is aimed to keep it stable, though, which is superior to any other version that must be kept cold or it disintegrates.

I've had no degradation of effect when I mixed 2 100mg packets with 20ml water and kept it refrigerator in a brown dropper bottle and used it sublingually over 12 days. It started out clear and gradually turned yellow.

 

[kangaSue]

Being a registered and approved med, I have no doubt that Kuvan should be and would be shelf stable. I gather there is no guarantee of that being the case with alternative sources of BH4 though, such as the Nootropics offering.

I was interested in Kuvan as a possible treatment for gastroparesis after seeing a pharma company was looking into re-purposing Kuvan for this condition.
https://btbjapan.com/ETX PHARMA PRESENTATION JULY2016.pdf

 

[Learner1]

Being a registered and approved med, I have no doubt that Kuvan should be and would be shelf stable. I gather there is no guarantee of that being the case with alternative sources of BH4 though, such as the Nootropics offering.

Exactly. And if the alternative sources aren't shipped cold, they'd be pretty useless - I've seen many complaints of this.

I was interested in Kuvan as a possible treatment for gastroparesis after seeing a pharma company was looking into re-purposing Kuvan for this condition.
https://btbjapan.com/ETX PHARMA PRESENTATION JULY2016.pdf

Aargh! Apparently, Kuvan went off patent a couple of years ago. I'm not aware of any generics, and it's only sold through 7 mail order specialty pharmacies in the US, since it's such a special orphan drug, even though it could potentially benefit a few million people.

Kuvan is in clinical trials for exercise intolerance in renal patients and cardio patients, too.

I think increasing NO us the key. I think it's why my high blood pressure, resistant to 9 BP drugs, has finally lowered, so I've been able to drop the dose of the one I'm on to 1/6th of what I was on. These explain what's going on - I've been deficienct in citrulline in the past and had to supplement...

https://www.berkeleylife.com/wellness/science-of-heart-health/causes-low-nitric-oxide-levels/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953417/

 

[kangaSue]

Being a registered and approved med, I have no doubt that Kuvan should be and would be shelf stable.

Sounds like even Kuvan (sapropterin dihydrochloride) isn't the best BH4 med. Apparently, sapropterin being a synthetic form of BH4 is rapidly oxidized once taken orally, does not penetrate cells or the blood–brain barrier efficiently, delivers suboptimal clinical benefits.

Sepiapterin is a natural precursor of BH4 and is converted to BH4 intracellularly so has substantial pharmacological advantages over sapropterin that include better plasma stability, preferential transport across cell membranes leading to rapid increase in intracellular BH4 levels, penetration of the blood-brain barrier, and possible direct effect on enzymatic function. Censa Pharmaceuticals is deveoping a sepiapterin drug (CNSA-001) that will also target gastroparesis.
https://www.pharmasalmanac.com/arti...ociated-with-bh4-dependent-enzymatic-pathways
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072796/

I'm not aware of any generics

Release of a generic had been held up by a court case between Biomarin and PAN Pharmaceuticals I think it was, but that has now been settled so paves the way for a generic release in the near future.

Personally, I can only eat without getting, nausea, vomiting and abdominal pain in taking an NO donor med more typically used for angina, nicorandil. Still have a very restricted diet and intake though so not ideal. Other nitrates also work but can't be continually dosed without developing tolerance to them. I tried supplements of arginine and citrulline first but couldn't tolerate either of them even at low dose.

I think most doctors I've seen for (idiopathic) gastroparesis think I'm a bit nutty in believing that the NO donor drug is the most effective med for my condition even though it's speculated by their peers that it may be the case
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170494/

 

[Learner1]

Sounds like even Kuvan (sapropterin dihydrochloride) isn't the best BH4 med. Apparently, sapropterin being a synthetic form of BH4 is rapidly oxidized once taken orally, does not penetrate cells or the blood–brain barrier efficiently, delivers suboptimal clinical benefits.

Sepiapterin is a natural precursor of BH4 and is converted to BH4 intracellularly so has substantial pharmacological advantages over sapropterin that include better plasma stability, preferential transport across cell membranes leading to rapid increase in intracellular BH4 levels, penetration of the blood-brain barrier, and possible direct effect on enzymatic function.

Did you mean to quote your own post?

The blood brain barrier is leaky in most of us, it's not an impermeable a barrier as one would think.

From my first 10mg sample dose of Kuvan in February, I've felt a clearer brain within 5 minutes.

Once I started on it, I had a little problem with it wearing off on some days when I was more active. After experimenting, I found that I do best with a 20mg dose, energy is steady and no crashing, and it's as good as when I started. It greatly helps my brain function and energy, as well as significantly lowering my blood pressure. I also did nitrotyrosine testing and my level was normal, not high, indicating that the BH4 is helping me avoid overproduction of peroxynitrites.

So, I'm not exactly convinced of the criticism of it

Sepiapterin is not on the market to buy, so it's not superior if one can't take it.

Censa Pharmaceuticals is deveoping a sepiapterin drug (CNSA-001) that will also target gastroparesis.
https://www.pharmasalmanac.com/arti...ociated-with-bh4-dependent-enzymatic-pathways
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072796/

Glad there's more development in this area, expanding the indications that BH4 can be used for. But again, I'm all for taking things that are for sale now, rather than waiting.

Release of a generic had been held up by a court case between Biomarin and PAN Pharmaceuticals I think it was, but that has now been settled so paves the way for a generic release in the near future.

Thanks for the info!

Personally, I can only eat without getting, nausea, vomiting and abdominal pain in taking an NO donor med more typically used for angina, nicorandil. Still have a very restricted diet and intake though so not ideal. Other nitrates also work but can't be continually dosed without developing tolerance to them.

The Berkeley Life product has been helpful in raising my NO. Have you tried it?

I tried supplements of arginine and citrulline first but couldn't tolerate either of them even at low dose.

Arginine uses up BH4 to make NO. Citrulline recycles back to arginine. So, without enough BH4, could be problematic?

I think most doctors I've seen for (idiopathic) gastroparesis think I'm a bit nutty in believing that the NO donor drug is the most effective med for my condition even though it's speculated by their peers that it may be the case
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3170494/

I don't! I haven't had any luck with GI docs, much better luck with functional medicine doctors... But, you see one, don't you?

 

[cph13]

@Learner1 I haven't read this entire thread. So forgive me, i dont have the brain power to spare with a pending telemed appt @9:30am. Impreparing for.
but.... this "caught my eye"
QUOTE: Arginine uses up BH4 to make NO. Citrulline recycles back to arginine. So, without enough BH4, could be problematic?END QUOTE
Here's my issues....my arginine is below normal limits does that mean my bh4 is stable? Or do I not have arginine to have bh4. Sorry if I'm confusing things. I'm onerwhelmed.
( I have terrible feet, ankle leg swelling....no heart issues)
BTW. I've been supp. Citrulline 3-5g a day and slowly its raising arginine.