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New biomarker test for ME/CFS: NADPH measurement at Riordan Clinic

Discussion in 'Latest ME/CFS Research' started by richvank, Apr 11, 2012.

  1. richvank

    richvank Senior Member

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    Hi, all.

    Here's a press release about a newly patented diagnostic for ME/CFS:

    http://www.marketwatch.com/story/ri...ents-with-chronic-fatigue-syndrome-2012-04-11

    Note that low NADPH has a lot of ramifications: NADPH is normally used to convert folic acid to THF. It is also used to reduce oxidized glutathione. It also supports Phase I detox by the CYP450 enzymes. It does other good things, also.

    I think that the reason it is low in ME/CFS is that the main source of it is the pentose phosphate shunt on the glycolysis pathway. When the mitochondria become dysfunctional in ME/CFS, the cells are forced to ramp up glycolysis to try to make up the shortfall in ATP production. This is done primarily by the enzyme phosphofructokinase, which is upregulated by low ATP and high AMP. When this occurs, more of the flow goes through the main glycolysis chain, and less is available to enter the pentose phosphate shunt, so less NADP+ gets reduced to NADPH, and therefore, NADPH goes down.

    Best regards,

    Rich
  2. Ember

    Ember Senior Member

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    roxie60 likes this.
  3. Esther12

    Esther12 Senior Member

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    It's in 'Alternative Therapies'... anyone know this journal?

    All the authors are from 'Riordan Clinic'.

    I've not read the paper, but I feel instinctively sceptical about the likelihood of this being a breakthrough. Thanks for pointing it out though.
    Waverunner likes this.
  4. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Hi Rich,

    Dr. Ayodhya (sp?) tested that on me at the same time the first methylation panel was done, and it was indeed very low. Thanks for posting this.

    Sushi
  5. alex3619

    alex3619 Senior Member

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    Thanks Rich, this looks like a very important link. Bye, Alex
    anne_likes_red likes this.
  6. Ember

    Ember Senior Member

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    Unfortunately, they've removed from their site the full text of the study.
  7. alex3619

    alex3619 Senior Member

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    This study is not a critical study for ME or CFS. Its importance is that they offer a potential test, which requires more validation, of mitochondrial function - a way to measure fatigue. It appears to be valid for possibly loosely defined CFS and for cancer patients. If it can be broadly validated then it may serve as an objective test of fatigue levels in patients - including ME patients. As its a blood test even severe patients could be tested. This may also serve as a biomarker for treatment - you could then track progress via the fatigue severity. It may also serve to put another boot into the hypothesis that our fatigue is all in the mind.

    However, as I said, it needs further testing. In particular I would be very interested to see if what it measures in something like the test-retest protocol. Can it pick up the decrease aerobic capacity the second day? If it can it will indeed be a big step forward. If it can't it will be just another test of no great consequence to us.

    Bye, Alex
    roxie60, ahimsa, Adster and 3 others like this.
  8. lnester7

    lnester7 Seven

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    Sushi: did they give you supplement to increase?
    Sorry but way out of me league here. So my question is: if one is low, then what supplement can increase? Have anybody tried that? results??



    Also, I am confused. I saw this posted, are they trying to lower NADPH??

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234599/

    However, it is possible to decrease the production of brain proinflammatory cytokines by down-regulating brain macrophage-like cells and microglia. This can be achieved by using the tetracycline derivative minocycline (e.g., (Fan et al., 2007)) or by blockers of NADPH oxidase activation...
  9. alex3619

    alex3619 Senior Member

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    Hi lnester7, wow, long paper you linked to. They are looking at blocking NADPH oxidase which is a mechanism some immune cells use to produce dangerous free radicals to kill pathogens. It uses up NADPH. If they can block this pathway then they reduce inflammation and increase NADPH availability. However, they also decrease the immune capacity to fight infection. Bye, Alex
    taniaaust1 likes this.
  10. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Hi Inester,

    I am not sure there is a supplement to increase NADPH, but others may know more. I was told that this was typical for low mitochondrial function (if I remember correctly).

    As to the quote, not sure what the relation of NADPH oxidase activation is in relation to levels of NADPH. We need someone with more knowledge here! Also decreasing the level of proinflammatory cytokines by down regulating brain macrophage-like cells sounds like a trade off. We don't want the inflammation but we do need the action of macrophages (not sure what macrophage-like cells are) in order to go after pathogens.

    This is one of the balances doctors try to achieve when giving GcMAF--it activates macrophages and this produces inflammation, so they try to give a low enough dose to activate enough macrophages to do the work, but not to activate too many which can make inflammation worse. They also give other things to lower inflammation.

    Best,
    Sushi

    Best,
    Sushi
  11. kaffiend

    kaffiend Senior Member

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    I believe this is why d-ribose supplementation was so effective for me. d-ribose is formed from the pentose phosphate pathway.

    High doses of lipothiamine (50mg X times/day) has allowed me to stop taking d-ribose (lipothiamine is much cheaper).
  12. adreno

    adreno 3% neanderthal

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    So I guess supplementing NAD wouldn't help? The problem is later in the chain?
  13. panthere

    panthere

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    Is test available to general public?
    roxie60 likes this.
  14. biophile

    biophile Places I'd rather be.

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    US Patent filed in 1996? : "NADH and NADPH pharmaceuticals for treating chronic fatigue syndrome".

    Abstract: A method for treating Chronic Fatigue Syndrome or alleviating symptoms thereof wherein the reduced form of nicotinamide adenine dinucleotide (NADH) or the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) or physiologically compatible salts or derivatives of NADH and/or NADPH are administered to a person suffering from the syndrome or its symptoms. Patients so treated exhibit greatly improved physical strength and performance over time, and their symptoms including fatigue, muscle pain and weakness, and headaches are greatly alleviated.

    http://www.freepatentsonline.com/5712259.html
  15. Snow Leopard

    Snow Leopard Senior Member

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  16. lnester7

    lnester7 Seven

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  17. adreno

    adreno 3% neanderthal

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  18. lnester7

    lnester7 Seven

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    Adreno: why NAD Vs NADH?

    I tried to find the difference between supplementing NAD Vs NADH I didn't find any data on which one is best.
    Does anybody know which one is better and why?
    MeSci likes this.
  19. adreno

    adreno 3% neanderthal

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    We want to make NADP(H), not NADH.
  20. kaffiend

    kaffiend Senior Member

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    For anyone interested in reading a journal article, this is a nice review of the pentose phosphate pathway and the importance of NADPH in maintaining the pool of reduced glutathione.

    http://www.ncbi.nlm.nih.gov/pubmed/18987987

    "NADPH is used for the reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH). GSH is important for the detoxification of reactive oxygen species (ROS) and converts reactive hydrogen peroxide into H2O. NADPH is also used in many anabolic pathways, such as lipid synthesis, cholesterol synthesis and fatty acid chain elongation. The NADPH/NADP+ couple is essential in maintaining GSH in its reduced form and for maintaining the production of certain hormones (e.g. estradiol, testosterone)."

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