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

[Learner1]

@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.

First of all, I'm not a doctor, so anything I say is just a guess. My arginine runs a little low, and I've supplemented both citrulline and ornithine further on in the urea cycle in the past, to bring my levels up, which had the good side effect of helping me sleep better.

There are a number of reasons why arginine could be low. First is that you're using more than you're eating - many patients have low amino acid levels, so eating adequate protein is a first step, along with digesting what you're eating, so digestive enzymes might be helpful if this is not happening.

In my case, I believe my arginine is low because I've been frantically using it trying to make nitric oxide. BH4 is needed to make nitric oxide from arginine, which then converts to citrulline. I have shied away from supplementing arginine because I have a history of multiple herpes viruses, and arginine tends to promote their activity.

So, because I have other reasons for needing BH4, I'm taking it, and also working on increasing my nitric oxide which is chronically low. I've used humann brand nitric oxide test strips, which show whether I'm high medium or low. And after finding I was low in nitric oxide, I've been using a supplement from Berkeley life to successfully raise my nitric oxide levels.

Citrulline can recycle back to arginine, so that's a way of getting more arginine. But having more arginine isn't the big goal, it's what the things that arginine can do and convert into that are most useful, and most people find that it's nitric oxide that's deficient. NO deficiency is related to several diseases.

I hope this isn't too overwhelming an answer, but try reading and rereading it and looking up a diagram of the urea cycle and BH4, and look at the Berkeley life website which discusses nitric oxide deficiency And hopefully you will get the answers you're looking for. If not, let me know what your questions are and I'll try to do a better job at the answering.

Good luck!

 

[kangaSue]

Did you mean to quote your own post?

I did, yes.

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

That wasn't meant as a criticism, more just to point out that if there was a choice, sepiapterin sounds like it would be the better thing to take.

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

Yeah, fair comment. It is available as a pharmaceutical chemical for research purposes though.

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

Haven't tried it, no. I tolerate very little in the way of any supplements (or vitamins, minerals, herbs etc) and was floored when the NO donor worked without causing any side effects other than an initial headache.

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?

I had one GI who was worth his weight in gold and believed an NO donor could have good benefit but he retired a year ago. I don't see a functional medicine doctor either, just do my own thing in trying to find solutions.

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

That makes sense to me, but I'm not the sharpest tool in the shed for figuring these things out.

 

[Treeman]

Is kuvan only available on prescription?

This is the situation in the UK trying to get Kuvan, the company want £70,000 ($88,386.55) per patient per year In the USA annually at the above prices its about $700! https://www.bbc.co.uk/news/health-48218737

 

[junkcrap50]

Is kuvan only available on prescription?

This is the situation in the UK trying to get Kuvan, the company want £70,000 ($88,386.55) per patient per year In the USA annually at the above prices its about $700! https://www.bbc.co.uk/news/health-48218737

Yes. Pretty much. But you can buy it in a homeopathic dosage from Ecological Formulas or from a nootropic bulk powder website, as mentioned further up in this tread. But in October 2020, the patent for Kuvan will expire, at least in the US. So it will be cheaper, but probably still very expensive.

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.

@raghav , I was wondering if you had any chance to follow up your inquiries for BH4 in India? How is the pandemic and lockdowns fairing over there?

 

[knackers323]

Has anyone found any online pharmacy that sells kuvan without prescription ?

 

[Treeman]

Any updates from anyone?
Have you sourced any?
Is it still working for you @Learner1?
Anyone tried the alternatives written about with any success?
Thanks.

 

[Learner1]

20mg Kuvan daily is still working great for me, 6 months on it.

I did communicate with the author of this paper who thinks it'll wear off in most people and it's better to go at it in the ways suggested in the paper. However, I'd tried all of those prior to the Kuvan and Kuvan is far more effective.

We agreed it probably depends on one's QPDR, GCH1, PTS, and PCDB1 genes.

 

[J.G]

I don't know that BH4 will "wear off". To the extent that BH4 supplementation eases the consequences of the hypothesized metabolic trap by allowing better synthesis of dopamine and serotonin where this is impaired, I would expect to see structural improvement like @Learner1 has experienced.

Par Pharmeutical have begun shipment of their generic tetrahydrobiopterin in the US starting Oct 1. Hopefully prices of "homeopathic" BH4 formulations will fall, making it a bit more affordable to experiment for efficacy. Maybe it'll make getting an off-label prescription easier too. I suppose time will tell.

https://uk.finance.yahoo.com/news/endo-begins-shipment-generic-kuvan-213800029.html

 

[bread.]

First of all, I'm not a doctor, so anything I say is just a guess. My arginine runs a little low, and I've supplemented both citrulline and ornithine further on in the urea cycle in the past, to bring my levels up, which had the good side effect of helping me sleep better.

There are a number of reasons why arginine could be low. First is that you're using more than you're eating - many patients have low amino acid levels, so eating adequate protein is a first step, along with digesting what you're eating, so digestive enzymes might be helpful if this is not happening.

In my case, I believe my arginine is low because I've been frantically using it trying to make nitric oxide. BH4 is needed to make nitric oxide from arginine, which then converts to citrulline. I have shied away from supplementing arginine because I have a history of multiple herpes viruses, and arginine tends to promote their activity.

So, because I have other reasons for needing BH4, I'm taking it, and also working on increasing my nitric oxide which is chronically low. I've used humann brand nitric oxide test strips, which show whether I'm high medium or low. And after finding I was low in nitric oxide, I've been using a supplement from Berkeley life to successfully raise my nitric oxide levels.

Citrulline can recycle back to arginine, so that's a way of getting more arginine. But having more arginine isn't the big goal, it's what the things that arginine can do and convert into that are most useful, and most people find that it's nitric oxide that's deficient. NO deficiency is related to several diseases.

I hope this isn't too overwhelming an answer, but try reading and rereading it and looking up a diagram of the urea cycle and BH4, and look at the Berkeley life website which discusses nitric oxide deficiency And hopefully you will get the answers you're looking for. If not, let me know what your questions are and I'll try to do a better job at the answering.

Good luck!

how do you test your NO? could you please link the the product? ty

 

[Learner1]

Either Humann or Berkeley Life saliva test strips.

https://shop.humann.com/products/ni...MRlJFQZqRoC85MQAvD_BwE&variant=19861378072687

https://www.amazon.com/dp/B01M74FOXH/ref=cm_sw_r_cp_apa_i_EIXEFbAWGDQWA

Par Pharmeutical have begun shipment of their generic tetrahydrobiopterin in the US starting Oct 1. Hopefully prices of "homeopathic" BH4 formulations will fall, making it a bit more affordable to experiment for efficacy. Maybe it'll make getting an off-label prescription easier too.

Dr. Reddy's also has a generic approved, which should hit the US market soon. Hoping the price goes down. And that it won't have to be a "specialty drug" anymore, with only 7 US mail order specialty pharmacies carrying it.

Is the "homeopathic" formulation you're talking about the Ecological Formulas Pteridin? It is limited to 2.5 mg due to BioMarin's patent. It is not shelf stable and must be kept refrigerated, where the Kuvan, PR, and Dr. Reddy's versions are shelf stable, and they come in 100 mg and 500 mg doses. I'm finding the 20 mg of Kuvan Is the right test for me, although I would bet that 10 mg might be plenty for others. The Ecological Formulas product is slightly more expensive than Kuvan, if you do the math.

 

[J.G]

Is the "homeopathic" formulation you're talking about the Ecological Formulas Pteridin? It is limited to 2.5 mg due to BioMarin's patent. It is not shelf stable and must be kept refrigerated, where the Kuvan, PR, and Dr. Reddy's versions are shelf stable, and they come in 100 mg and 500 mg doses. I'm finding the 20 mg of Kuvan Is the right test for me, although I would bet that 10 mg might be plenty for others. The Ecological Formulas product is slightly more expensive than Kuvan, if you do the math.

Yes, I'm aware of the limitations of Pteridin-4. The issue is that in Europe, it's impossible to get Kuvan for ME. Unlike in the US, there are no tools to work with, no strings to pull. We don't have true ME clinics and/or centers of expertise like Stanford's or the Bateman Horne Center, nor do there exist independent cutting-edge ME specialists, because the medical climate does not permit them to exist. Even if you somehow found an amenable physician, they cannot possibly prescribe an expensive $20.000+/year patented medicine like Kuvan for off-label use. The system will not permit it. And say you somehow cleared that hurdle, insurance will not cover it. Not in a million years. It's difficult to put into words just how "stuck" the average European patient is. There are no options.

Anyway, all this is a long way of saying that trying Kuvan is entirely out of reach for most Europeans. A much cheaper generic may, in time, slightly boost our chances. Better yet to run an extended trial with an OTC formulation.

Ah, neat. I hadn't heard about Dr. Reddy's generic BH4. News report:
https://in.finance.yahoo.com/news/dr-reddys-laboratories-announces-us-061600199.html

 

[Learner1]

My Kuvan dose would be $300 per month, if I had to pay for it, and insurance didn't cover it, not $20,000. And, believe me, in the US, we pay for a lot of things out of pocket, on top of hefty health insurance premium payments, unlike in countries where you have government paid healthcare

There are no approved drugs for ME/CFS here in the US, so no insurance company would pay for one, as everything is experimental for ME/CFS.

However, if you happen to have an indication that is not ME/CFS, it is quite possible to get things covered.

Think of it this way, if you had a broken arm would your system pay to have a cast put on it? If you got cancer or diabetes, would they give you chemotherapy or insulin? If you had an war infection would they pay for antibiotics?

Same here. I had an amino acids panel done showing high phenylalanine, and I try to sample which worked, and I was able to get it covered. It is also useful to dig through your genes, there are different genes that are associated with phenylketonuria, GCH1, QDPR, PTD, PCBD1, and PAH genes - you might see if you have mutations on any of them, leading to a mild form, which might benefit from Kuvan.

 

[J.G]

I had an amino acids panel done showing high phenylalanine, and I try to sample which worked, and I was able to get it covered. It is also useful to dig through your genes, there are different genes that are associated with phenylketonuria, GCH1, QDPR, PTD, PCBD1, and PAH genes - you might see if you have mutations on any of them, leading to a mild form, which might benefit from Kuvan.

Hmm. That's an ingenious approach. I'm happy that worked for you So you in fact have mild congenital phenylketonuria? Or is your Phe elevated as a consequence of ME? Did the first induce the second? It's noteworthy that Dr. Phair hypothesizes a second metabolic trap involving Phe / Tyr (in addition to the published one centred on Trp).

My understanding of those theories, however, is that *intracellular* Trp is elevated in ME, not circulating Trp, which is what an amino acid panel would pick up on. The Phe / Tyr second trap is suspected intracellular too. Again, an animo acid panel does not accurately reflect what's going inside the cells. ME patient amino acid panels usually come back normal. (They're also not especially reliable.) So if your Phe was elevated on them, it really does suggest a form of PKU.

From a biochem standpoint, I believe that pwME may benefit from supplemental BH4 / sapropterin dihydrochloride (Kuvan). But folks who have textbook ME without a genetic predisposition to PKU will struggle to follow in your footsteps and obtain Kuvan in the manner you did.

Thank you for sharing your story!

Edit: wording

 

[Treeman]

unlike in countries where you have government paid healthcare

I think I've spoke about this before. In the UK this is NOT a benefit. We do not have compassionate medicine and if there are no recommended drugs there are no drugs given under any circumstances. We can't get anti virals, we cant get LDN we cant get anything not even melatonin to help sleep. The UK NHS systems has no compassion, empathy for ME/CFS sufferers and treats us with contempt. Last year the NHS spent £8.5 billion on obesity related illnesses, most they say caused by over eating and nothing on trying to discover what causes ME/CFS. Severely messed up!

 

[Treeman]

Has anyone tried any of the written about products? Thanks.

 

[Learner1]

I think I've spoke about this before. In the UK this is NOT a benefit. We do not have compassionate medicine and if there are no recommended drugs there are no drugs given under any circumstances. We can't get anti virals, we cant get LDN we cant get anything not even melatonin to help sleep. The UK NHS systems has no compassion, empathy for ME/CFS sufferers and treats us with contempt. Last year the NHS spent £8.5 billion on obesity related illnesses, most they say caused by over eating and nothing on trying to discover what causes ME/CFS. Severely messed up!

Well, you do have private healthcare, just as we do. I've paid for a fair amount of my care and treatment myself, which unfortunately many here cannot afford to do. Here's hiw people in the US acquire melatonin:

https://www.amazon.com/dp/B00O37VH9O/ref=cm_sw_r_cp_apa_fabc_ETr0FbM7ZHG2P?_encoding=UTF8&psc=1

This is a UK facing site that you can order if from:

https://uk.iherb.com/c/Melatonin?gc...snP_h8h55cA3LUnZpdxoCw30QAvD_BwE&gclsrc=aw.ds

 

[Treeman]

Well, you do have private healthcare, just as we do.

Yes, but we have already paid for the NHS, I don't think it's acceptable to pay in to a system that refuses to help me when I'm sick, does anyone?

You can only get medicines with a prescription from a legitimate prescriber in the UK, Yes you can buy as above, but its not legal.

 

[junkcrap50]

You can only get medicines with a prescription from a legitimate prescriber in the UK, Yes you can buy as above, but its not legal.

That's what it takes to get quality care nowadays, even in the US.

 

[Treeman]

That's what it takes to get quality care nowadays, even in the US.

There are millions of sick people in the UK who get quality care from the NHS, just not ME/CFS sufferers