junkcrap50
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How on earth were you able to get Kuvan (BH4)? What effects did you notice from? Any cognitive benefits? I've been interest and wanting to try it to help raise my dopamine and neurotransmitters.
Bhupesh Prusty: "we are on a perfect path for identifying potential transferable factors in ME/CFS blood that can cause mito dysfunction..." GoFundMe
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stefanosstef
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How do you achieve 2?
MonkeyMan
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https://mitochondrialdiseasenews.co...33-therapy-for-primary-mitochondrial-disease/
KL1333 is a modulator of the cellular levels of NAD+, a central co-enzyme in the cell’s energy metabolism. It has been shown to increase mitochondrial energy output, reduce lactate accumulation, lower the formation of harmful free radicals, and have long-term benefits on energy metabolism, such as the formation of new mitochondria. So far, no safety issues have been reported.
KL1333 is a modulator of the cellular levels of NAD+, a central co-enzyme in the cell’s energy metabolism. It has been shown to increase mitochondrial energy output, reduce lactate accumulation, lower the formation of harmful free radicals, and have long-term benefits on energy metabolism, such as the formation of new mitochondria. So far, no safety issues have been reported.
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Do you mind telling us or asking Prusty what those pre-approved drugs are?
I asked him exactly that and from then on he stopped replying to my mails.
Hope this isnt going to off topic now, but some time ago Ron said that MS has a lot of similarities to Cfs and that ppl with MS and Fatigue maybe have MS and Cfs but it just doesnt get diagnosed that way. Here is a study about mitochondrial fusion inhibition and an altered immune system. Maybe there is something to it. https://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1201&context=neurologyfp
Learner1
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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
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Learner1
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I don't have MS, and the 3 neurologists I've seen don't think so either, and MRI looked clean.
In 1995 when I started getting light sensitivity my neurologist did a VEP test(Visually Evoked Potential) in one eye the latency was 120 ms and 100 in the other. They suspected a demyelinating disorder. I also started getting vitreous float around that time.(I dont think that is a coincidence). Six months later the results came 120 in both eyes and the MRI was normal. But I still had light sensitivity. They could not understand it. Later in 2007 I was diagnosed with left hippocampal sclerosis. The MRI and MRS came clear on Multiple sclerosis. But my immune system had gone hyper way back in 1995 itself. I have not consulted a rheumatologist yet.
Lets see if Prusty is able to put together the jigsaw puzzle (with Naviaux) and Carmen Scheibenbogen with whom Prusty is also collaborating. So I have high hopes on them. Lets wait for Prusty's first paper. Hope they dont shut down the lab in Bavaria. Anybody from Prusty's place of work here ? How is the corona threat perception there ? Hope he gets sufficient time to push the results of his experiments through to the publisher and the reviewers.
Lets see if Prusty is able to put together the jigsaw puzzle (with Naviaux) and Carmen Scheibenbogen with whom Prusty is also collaborating. So I have high hopes on them. Lets wait for Prusty's first paper. Hope they dont shut down the lab in Bavaria. Anybody from Prusty's place of work here ? How is the corona threat perception there ? Hope he gets sufficient time to push the results of his experiments through to the publisher and the reviewers.
ScottTriGuy
Stop the harm. Start the research and treatment.
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Thanks for sharing @Learner1 -- your research and results are very interesting.
My 'ME' doctor just started me on phospatidyl choline a few days ago.
He's very open minded and I'm thinking of asking him to prescribe Kuvan, but I need to wrap my head around it - and bring him the research.
I had previously purchased - but have not yet started - nicotinamide riboside (NR) (Tru Niagen).
Tru Niagen has this page 'NMN vs NR' - https://www.truniagen.co.nz/blogs/news/8-key-differences-between-nmn-nr
3 questions if I may:
Your thoughts on NMN vs NR.
Do you follow a phenylalanine restricted diet?
Is there other research, beyond what you've cited above, that I should consider for my doctor?
By coincidence, I'm friendly with the president of PKU Canada (who is also president of Best Medicines Coalition).
junkcrap50
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Thank sos much @Learner1 I will definitely look into it. I might make a new thread to discuss this topic too if you don't mind, as @ScottTriGuy has some interest/questions too.
@Learner1 I googled on BH4 and it says it inhibits Mito complex I and IV. So how does that help in your case ? Is there some other mechanism by which BH4 exerts its effects.
Tetrahydrobiopterin Causes Mitochondrial Dysfunction in Dopaminergic Cells: Implications for Parkinson's Disease
In the present study, we show that BH4 leads to inhibition of activities of complexes I and IV of the electron transport chain (ETC) and reduction of mitochondrial membrane potential.
Tetrahydrobiopterin Causes Mitochondrial Dysfunction in Dopaminergic Cells: Implications for Parkinson's Disease
In the present study, we show that BH4 leads to inhibition of activities of complexes I and IV of the electron transport chain (ETC) and reduction of mitochondrial membrane potential.
New Fluorescent Marker Allows Detailed Study of Mitochondria in Live Cells, Study Reports
https://mitochondrialdiseasenews.co...led-study-of-live-mitochondria-study-reports/
Researchers at Nagoya University’s Institute of Transformative Bio-Molecules have developed a new marker molecule, called MitoPB Yellow, which has a much longer lifespan under the microscope. This marker is specific for the inner mitochondrial membrane, making the mitochondria visible for longer periods of time.
Furthermore, the new marker allows researchers to detect structural changes of the mitochondrial inner membrane in live cells. Before, these structural changes could only be seen in dead cells.
In this study, researchers compared the MitoPB Yellow to other mitochondrial fluorescent markers. MitoPB Yellow showed greater stability — even after 50 images had been taken using the microscopy, researchers saw no significant decrease in the fluorescence intensity. Moreover, the intensity of MitoPB Yellow was maintained above 70%, the highest rating among the different mitochondrial markers.
To demonstrate the usefulness of MitoPB Yellow for imaging live cells, researchers placed mitochondria under conditions that are known to induce structural changes, which became visible using MitoPB Yellow.
Changes in mitochondria in response to deprivation of nutrients were also observed in great detail (high-resolution).
In this stressful environment, the inner mitochondrial membranes fused together both within a single mitochondrion and between neighboring mitochondria. This process may increase energy production while protecting these cellular structures from degradation.
By allowing for a more detailed study of live mitochondria, MitoPB Yellow may aid in understanding, diagnosing and developing therapies for mitochondrial disease.
“In summary, MitoPB Yellow surpasses currently used fluorescent mitochondrial markers,” the researchers wrote.
This marker may enable analysis of “the mitochondrial inner-membrane structures in living cells at unprecedented resolution,” their study concluded.
https://mitochondrialdiseasenews.co...led-study-of-live-mitochondria-study-reports/
Researchers at Nagoya University’s Institute of Transformative Bio-Molecules have developed a new marker molecule, called MitoPB Yellow, which has a much longer lifespan under the microscope. This marker is specific for the inner mitochondrial membrane, making the mitochondria visible for longer periods of time.
Furthermore, the new marker allows researchers to detect structural changes of the mitochondrial inner membrane in live cells. Before, these structural changes could only be seen in dead cells.
In this study, researchers compared the MitoPB Yellow to other mitochondrial fluorescent markers. MitoPB Yellow showed greater stability — even after 50 images had been taken using the microscopy, researchers saw no significant decrease in the fluorescence intensity. Moreover, the intensity of MitoPB Yellow was maintained above 70%, the highest rating among the different mitochondrial markers.
To demonstrate the usefulness of MitoPB Yellow for imaging live cells, researchers placed mitochondria under conditions that are known to induce structural changes, which became visible using MitoPB Yellow.
Changes in mitochondria in response to deprivation of nutrients were also observed in great detail (high-resolution).
In this stressful environment, the inner mitochondrial membranes fused together both within a single mitochondrion and between neighboring mitochondria. This process may increase energy production while protecting these cellular structures from degradation.
By allowing for a more detailed study of live mitochondria, MitoPB Yellow may aid in understanding, diagnosing and developing therapies for mitochondrial disease.
“In summary, MitoPB Yellow surpasses currently used fluorescent mitochondrial markers,” the researchers wrote.
This marker may enable analysis of “the mitochondrial inner-membrane structures in living cells at unprecedented resolution,” their study concluded.
Learner1
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Did you read the papers I posted? I do not think its inhibiting complex I any more than it already was but will test soon to see.
BH4 is a natural substance that everyone needs. Your paper says BH4 toxicity can lead to oxidative stress that can impair mito complexes. My BH4 is LOWER tgan most people's so I don't think adding a tiny dose of Kuvan will make me toxic with it. What is toxic is the peroxynitrites that damage mito membranes and impair complex I. Which can itself lead to Parkinson's.
But, please read the papers.
Learner1
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Here are the papers I referred to.
Learner1
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You're welcome. I've just been following breadcrumbs left by the researchers and have been fortunate to have naturopathic doctors who knew some about this and were curious to help me explore.
My ME/CFS specialist is very supportive about PC. I was getting it IV but the US supply has dried up lately. The FDA has been making it very difficult. I've also been on Garth Nicolson's formulation, NT Factor for 2 years.
I've tried NADH, NAD+, NMN, and NR. I tried NR twice at 1g doses for 2 months as the literature looked good. It did absolutely nothing for me. All the other variants helped. Could be because I have rare SNPs for NMRK1 and 2. NR gets broken apart in the digrstivecsystem and has to be. reassembled.
My doctor just shared this paper with me:
https://neurohacker.com/nad-introduction-to-an-important-healthspan-molecule
It concludes that stacking different NAD substances so the body can used the 4 different pathways to make it is best, which is pretty much what I'd settled on anyway. And knowing that de novo synthesis isn't my best choice due to Phair's trap, I just use NAD+ for that one, not tryptophan or 5-HTP. I get NAD+ IV every week or two, injectable high potency B complex 3 times a week, and take sublingual NMN daily...
No. My phenylalanine is higher than normal range but my neuro and I think it's because I take tyrosine or I run out of dopamine and its backing up a little. (I need a lot of a minor or I run short of several.)
NADH may help some, but having a high NAD+/NADH ratio is desirable.
I've read a lot of articles on NAD, etc. All the benefits of the highly touted NR are the same with NMN.. If NR works for you great, but I think it's more expensive
There are biohackers who "stack" NAD or precursors with huge amounts of NAD. This can potentially promote cancer growth if you hsve any around.
Also, none of these are likely to cure anyone without beating any infections back and replenishing any other depleted nutrients. Repairing membranes with phospholipids is wise, too, as you're doing. But, if you put more gas in a broken system, not only may it not help as much, but it could damage the system, which needs to be repaired befire it can perform.
Woukd be interested in his view. I'm irritated tgat Kuvan is such a super special, super expensive drug only for PKU, when it's a substance that can benefit a lot more people lol PWME. There are 2 cl8nical trials going on for exercise intolerance...
bthompsonjr1993
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Yes, I don't doubt that he has great idea like that. I just think it will be years before we have anything that is widely accepted and readily available for patients at doctor's offices