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The NAD+ Deficiency is a contributing factor in the CFS/ME progression?

Discussion in 'General ME/CFS News' started by Radio, Jan 6, 2014.

  1. Radio

    Radio *****

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    Viral Connection, NAD synthesis: Kynurenine Pathway
    Viruses can affect the NAD Synthesis in the Kynurenine pathway. We know quinolinic and interferon gamma are elevated in the majority CFS/ME subgroups. The NAD+ deficiency is a contributing factor in the CFS/ME progression. The main critical concern is the NADH recycling anaerobic metabolism (ADP to ATP) imbalance. This is the reason why it's import to supplement to bypass the weak NAD synthesis. Nicotinamide, NAD, NADH, R- lipoic acid can compensate for the NAD+ deficiency. Riboflavin is needed for the monoamine oxidase enzyme, which functions in this metabolism.

    [​IMG]
    Kynurenine Pathway Metabolites in Humans: Disease and Healthy States
    http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CDgQFjAB&url=http://www.la-press.com/redirect_file.php?fileId=1868&filename=IJTR-2-Guillemin-et-al&fileType=pdf&ei=M3HLUtauJobfsASmpoLQDQ&usg=AFQjCNFEpPCWbRBqRfKZX3PYzI2IcmtFlg&sig2=BdUNdAknPb76k-zC9PLmzQ&bvm=bv.58187178,d.cWc

    NAD Synthesis

    http://en.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide
    THE FATE OF PYRUVATE
    http://www.hippocampus.org/homework-help/Biology/Central Catabolic Pathways_The Fate of
    Pyruvate and NADH.html
    Last edited: Jan 8, 2014
    anne_likes_red, helen1 and Emootje like this.
  2. Radio

    Radio *****

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    Several metabolic routes allow NAD+ synthesis from four different precursors (blue box). In the de novo pathway, NAD+ is synthesized from L-tryptophan, which is converted to quinolinic acid (not shown) and then to nicotinic acid mononucleotide (NaMN). An import pathway originates with nicotinic acid (Na), which is converted to NaMN (through the Preiss–Handler pathway), nicotinic acid adenine dinucleotide and then NAD+. A salvage pathway uses nicotinamide (Nam) to regenerate NAD+(Refs 1, 2). Na and Nam are collectively referred to as niacin, or vitamin B3. A fourth, recently discovered route incorporates nicotinamide riboside in the salvage pathway106. NAD+ and its phosphorylated relative NADP (not shown) are used as cofactors in several different redox reactions that are catalysed by NAD+ dehydrogenases (yellow box). These reactions are not accompanied by any net consumption of the nucleotides. Conversely, a net loss of NAD+ is associated with ADP-ribose-transfer reactions that take place during ADP-ribose cyclization (orange box), mono- or poly(ADP-ribosyl)ation and the deacetylation of proteins (green boxes). All these ADP-ribose-transfer reactions link NAD+ metabolism and the energy status of the cell to various aspects of cellular signalling for different cellular functions. Free ADP-ribose or derivative molecules can result from poly(ADP-ribose) degradation, which is catalysed by PARG isoforms and hydrolases (ARHs; ADP-ribosylarginine hydrolases), or from O-acetyl-ADP-ribose hydrolysis by Nudix O-acetyl-ADP-ribose hydrolase. These molecules might participate in the activation of TRPM2 channels (which are involved in calcium entry)107 and might react with proteins (resulting in glycation), which can lead to severe endothelial dysfunction, as in the case of diabetes-mellitus-associated atherosclerosis and other cardiovascular diseases.

    [​IMG]

    NaDS, NAD+ synthase; NaMNAT, nicotinic acid mononucleotide adenylyltransferase; Nampt, nicotinamide phosphoribosyl transferase; NaPRTase, nicotinic acid phosphoribosyltranferase; NMNAT, nicotinamide mononucleotide adenylyltransferase; Nrk1, nicotinamide riboside kinase-1; PARG, poly(ADP-ribose) glycohydrolase; PARP, poly(ADP-ribose) polymerase.
    anne_likes_red and alex3619 like this.
  3. knackers323

    knackers323 Senior Member

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    Is there any reason why NADH wouldn't work? It has no effect on me
  4. alex3619

    alex3619 Senior Member

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    Logan, Queensland, Australia
    NADH is not very effective by itself. It needs to be converted to NAD. Under conditions of oxidative stress, or low lipoic acid, for example, then NADH might even make someone feel worse.

    I find this model interesting, but to go anywhere we need to be discussing how to transition it from a collection of interlocking hypotheses into a testable hypothesis/model that might get enough attention for a small clinical trial. Models come and go, very few make that transition.

    For example, can we identify symptoms specific to various problems in this area that are suitable for a questionnaire? Then use those to create a basis for asking patients who have taken these various treatments and if they have helped, and what symptoms on the list they had or didn't have. Then see if there are key symptom clusters that give a higher chance of indicating a responder. Then use that to promote a pilot study, simultaneously testing treatments and responder markers?
    Radio likes this.
  5. Hanna

    Hanna Senior Member

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    Jerusalem, Israel
    I would like to give a try and supplement with NAD+. As I live in Israel, I order from iHerbs. NAD+ from Now food has been discontinued. And The one from Source Naturals hasn't been available... What would be a fairly good replacement (if NADH is pretty innefficient...) ? Or do you know some source of NAD+ that ships abroad?
  6. alex3619

    alex3619 Senior Member

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    Logan, Queensland, Australia
    Given our circadian issues, I think these two are interesting:

    http://www.ncbi.nlm.nih.gov/pubmed/19286518
    Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1.

    This paper is on Research Gate. http://www.researchgate.net/publica...rol_of_the_NAD_salvage_pathway_by_CLOCK-SIRT1


    http://symposium.cshlp.org/content/76/31.full
    The Time of Metabolism: NAD+, SIRT1, and the Circadian Clock

    I think a failure of our circadian mechanism might underlie many of our sleep, liver and glucose tolerance issues.
    anne_likes_red likes this.
  7. adreno

    adreno 3% neanderthal

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    Tundras of Europa
    I didn't get much positive out of supplementing NAD. Niacinamide doesn't help me either.
  8. Radio

    Radio *****

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    The first step would be to create a data base of lab testing from other CFS/ME members. I develop my hypotheses based off of studying labs and oat testing posted in this forum. We need to find the next RichVank disciple to take these hypothesis to the next level. Also, Orthomolecular medicine could be a possible treatment option for CFS down the road.
    Last edited: Jan 17, 2014
  9. Radio

    Radio *****

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    I would like to give a try and supplement with NAD+. As I live in Israel, I order from iHerbs. NAD+ from Now food has been discontinued. And The one from Source Naturals hasn't been available... What would be a fairly good replacement (if NADH is pretty innefficient...) ? Or do you know some source of NAD+ that ships abroad?

    I've had good results with Niacinamide 500mg 3-6xday...The information on this thread is not intended to be medical advice. The information is meant to inspire and motivate you to make your own decisions surrounding your health care and dietary needs.
    Hanna likes this.

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