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BH4 and the Genetics of ME/CFS

Discussion in 'Genetic Testing and SNPs' started by Mimi, Jan 23, 2015.

  1. nandixon

    nandixon Senior Member

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    I'm going to try to make a post later today, probably on @Mimi's other thread (http://forums.phoenixrising.me/index.php?threads/bh4-gch1-question.35140/), showing the major and minor alleles for all 38* SNPs that 23andMe gives data for on the GCH1 gene, and how to research them. (It'll be at least several hours before I can do this, and possibly tomorrow.)

    *The newest testing platform may have fewer than 38.

    Edit: I made the post here:
    http://forums.phoenixrising.me/index.php?threads/bh4-gch1-question.35140/#post-550201
     
    Last edited: Jan 25, 2015
  2. Mimi

    Mimi Senior Member

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    Medford, OR
  3. nandixon

    nandixon Senior Member

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    Yes, I remember reading that one, and I believe that I thought it looked pretty valid. So if a person is homozygous (AA = +/+) for rs841, they may possibly have the anomalies described in that paper.
     
  4. Mimi

    Mimi Senior Member

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    Hi kell88 - I sent you a message. Look in your Inbox and you should find it.

    @nandixon - thanks for the link to the MTHFR study. I don't know if you noticed this, but in the end, they determined that MTHFR was a weak peroxynitrite scavenger, but it was highly effective at lowering peroxynitrite because it boosted BH4.

    the peroxynitrite scavengers i've seen mentioned most often are vitamin C (which also recharges BH4), gamma tocopheral e and glutathione. inosine was mentioned in a parkinson's study as being very effective, and it's also supposed to be an immune modulator. idebenone is supposed to be 30-100x more powerful than vitamin E (alpha tocopherols) and i'm a big fan of idebenone personally because it brought back my memory.

    i am thinking that a BH4 study should include Kuvan and L-5MTHF plus at least one antioxidant. vitamin c is cheapest but my vote would probably go to idebenone for best effect. or maybe s-acetyl glutathione.
     
  5. Mimi

    Mimi Senior Member

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    forgot to mention agmatine. body builders take it for a huge NO boost since it's more bioavailable than arginine. it's decarboxylated arginine, which is one step closer to NO. my sense is that combining agmatine with BH4 could be a real kick in the pants. moreover, agmatine is supposed to be a great antidepressant, as well as a strong analgesic, an LH and GH booster and a few other cool things. it's an interesting profile, and it's cheap - $10.99 on SmartPowders.com.

    if i get good results i'll post them here. if i get great results, i'll start a new thread and post the link.
     
  6. nandixon

    nandixon Senior Member

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    They were saying it's a weak superoxide scavenger.
     
  7. Mimi

    Mimi Senior Member

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    oh, you're quite right! that's excellent.
     
    nandixon likes this.
  8. marywatson1003

    marywatson1003

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    Hi,
    Please excuse my shaky genetics knowledge, but I wanted to ask anyone who could chime in-- I know from Promeathease that I have the "double CAT" mutations. I have severe cfs and am planning to make an appointment with the genetic center at the nearby Cleveland Clinic. I'm not sure if it will be worth while and if I will be taken seriously... If they'll test my BH4 levels or not. Has anyone worked with a Dr. on this issue? Nevertheless, in the meantime I'm considering trying to supplementation on my own.
     
    Critterina likes this.
  9. mariovitali

    mariovitali Senior Member

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    @Mimi

    Congrats for the post. Supporting BH4 was a major component of my recovery i believe. Just wanted to ask about another mutation for TH (Tyrosine Hydroxylase) Gene aka Rs10840491. Promethease tells me i am (A;G). I also have the GCH-1 Mutation (One Copy) and Homozygous MTHFR Mutation (C677T).
     
  10. Mimi

    Mimi Senior Member

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    Hi mariovitali,

    So glad to hear of your recovery! Yay!! Glad to hear supporting BH4 was so helpful to you. And thanks for sharing your Regimen. Did you take resveratrol because it's an estrogen receptor stimulator and BH4 synthesis inducer? Also, what brand did you take? How cool that you have the same genetic signature. I feel that these snps are just so critical. But I don't know anything about the tyrosine snp. If it's causing a deficiency, of course that would impact your dopamine and all the NTs that follow. I tried to surf it up but my connection speed is abysmally slow today. But your Regimen just loaded so I see why you took the resveratrol. I wanted to see if you took Longevinex which is made in a vacuum. And wow, TUDCA looks like it's exactly what I need. I think my bile got thick after 8 months on Valcyte. Thanks a lot!!

    Mimi
     
    mariovitali and Gondwanaland like this.
  11. Gondwanaland

    Gondwanaland Senior Member

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    Ha, no wonder my estrogen levels are undetectable. And perhaps this is why I can't tolerate resveratrol/grape seed extract. Thanks for putting the things this way!
     
    Last edited: May 20, 2015
    Mimi likes this.
  12. mariovitali

    mariovitali Senior Member

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    Hi @Mimi

    I really don't know what happens with Resveratrol (RSV). I feel great when i take it but 3 days later i am not sure. I believe i read that RSV downregulates E2. And low E2 could also affect BH4 in a negative way. However, i also saw PubMed articles stating that RSV boosts BH4...!

    Go figure ;-)
     
    Gondwanaland likes this.
  13. kel88

    kel88 Senior Member

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    *** offtopic if someone will try BH4/Kuvan, i have it for sale. It did nothing for me ... (Its a shame).
    But i have to pay my own risk at insurance! I have used 6 tablets of it. The rest i have it at home so if someone is looking for buying it... You can contact me :)
     
  14. JPV

    JPV ɹǝqɯǝɯ ɹoıuǝs

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    It still may be a few more years before we see a generic Kuvan, thanks to convoluted generic drug laws. And even once the generic is approved and tested, the new manufacturers will have a period of exclusivity that keeps prices inflated...
    If I read this correctly, it may not be until 2020, or later, before we see an expensive generic version of Kuvan available.
     
    Last edited: Jun 23, 2015
  15. Hip

    Hip Senior Member

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    I have not been able to find any clear statements about when BH4 (Kuvan) orphan drug status is due to end.

    BH4 was given orphan drug status in 2002. Biomarin and Merck Serono are the only companies that can sell BH4 under this orphan drug marketing exclusivity deal. I understand that in the US, orphan drug market exclusivity is given for 7 years, and in the EU it is given for 10 years.


    I read about the FDA giving an extension to BH4's orphan drug marketing exclusivity until June 2015 here:
    So from that statement, I thought that BH4 orphan drug status would end in June 2015, but I can find no clear written indication that this is the case.
     
    leokitten likes this.
  16. JPV

    JPV ɹǝqɯǝɯ ɹoıuǝs

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    Yeah but laws such as The Hatch-Waxman Act seem to create some sort of stumbling block in the timeline for competitors to able to make generics versions. Like I said in my original post, it all seems very convoluted and a bit hard to understand.

    In addition to what I quoted above, I found a BioMarin press release saying that 2017 may be the earliest date that they expect a generic version to appear on the market...
     
  17. Hip

    Hip Senior Member

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    Oh well, so that's another two year's wait for (hopefully) cheaper BH4.

    Still, it might be that some small-scale companies like the Swiss lab (Schircks Laboratories) start selling BH4 prescription-free after June 2015.
     
    leokitten likes this.
  18. JPV

    JPV ɹǝqɯǝɯ ɹoıuǝs

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    I hope you're right. It's certainly something on my list of things to try but not at the current prices.

    From what I understand, Kuvan is a synthetic form of Tetrahydrobiopterin. I'm not quite sure but it seems that they somehow managed to block other forms of Tetrahydrobiopterin, that have nothing to do with their synthetic version, from distribution. The pharmaceutical industry and governments are so corrupt that it doesn't surprise me to see how laws are set up to stifle competition.
     
  19. Hip

    Hip Senior Member

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    I don't think we can necessarily assume it's corrupt or stifles competition, unless you know specifically otherwise. The idea of an orphan drug is a good one:
     
    Last edited: Jun 23, 2015
  20. JPV

    JPV ɹǝqɯǝɯ ɹoıuǝs

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    Maybe I don't fully understand it but Didn't the Orphan Drug Law allow BioMarin to take something that should be an affordable OTC supplement and to turn it into a prescription pharmaceutical costing $40 a tablet? Maybe the idea is a good one but the real world implementation leaves much to be desired...
     

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