Confirmed - CFS Is Hypometabolism Triggered By Environmental Stress

Discussion in 'Scientific Studies' started by haidut, Aug 30, 2016.

  1. haidut

    haidut Member

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    Ray has discussed his views on the so-called "chronic fatigue syndrome" (CFS) in many interviews and some of his articles. His opinion is that CFS is simply hypothyroidism with some specific symptoms depending on individual susceptibility. Many people vehemently disagree with this opinion, but as it has become almost customary over the last few years, the man seems to have been proven right yet again. This study looked at the metabolomics of CFS and found that it is simply a state of hypometabolism. Low levels of FAD (riboflavin), ATP, cholesterol (i.e. steroids) and dopamine were the most important features. This suggests downregulated mitochondrial function. Perhaps most importantly, the study finds CFS is likely triggered by environmental stress. It resembles the well-known "dauer state" in worms (Dauer larva - Wikipedia, the free encyclopedia), which is a hibernation like state that allows them to survive unfavorable conditions. This hibernation-like state suggests a role for serotonin in CFS and indeed the study found that metabolites of tyrosine and phenylalanine, which are reliable biomarkers for dopamine synthesis, are very low in people with CFS. Consequently, serotonin is high. Given that serotonin is a master regulator of metabolism and the primary signal of environmental stress, I wonder if something as simple as a decent dose of a serotonin antagonist or a dopamine agonist would be able to "snap" these people out of hibernation.

    Metabolic features of chronic fatigue syndrome
    "...Chronic fatigue syndrome is a multisystem disease that causes long-term pain and disability. It is difficult to diagnose because of its protean symptoms and the lack of a diagnostic laboratory test. We report that targeted, broad-spectrum metabolomics of plasma not only revealed a characteristic chemical signature but also revealed an unexpected underlying biology. Metabolomics showed that chronic fatigue syndrome is a highly concerted hypometabolic response to environmental stress that traces to mitochondria and was similar to the classically studied developmental state of dauer. This discovery opens a fresh path for the rational development of new therapeutics and identifies metabolomics as a powerful tool to identify the chemical differences that contribute to health and disease."

    "...Our results show that the metabolic features of CFS are consistent with a hypometabolic state. Sphingolipids, glycosphingolipids, phospholipids, purines, microbiome aromatic amino acid and branch chain amino acid metabolites, FAD, and lathosterol were decreased. The decreases in these metabolites correlated with disease severity as measured by Karnofsky scores (SI Appendix, Table S1 A–D). Much research has been done on the hypometabolic phenotype in other biologic systems, including dauer (35), diapause (40), hibernation (41), estivation (42), torpor (43), ischemic preconditioning (44), ER stress (45), the unfolded protein response (46), autophagy (47, 48), and caloric restriction (49). Dauer, which means persistence or long-lived in German, is an example of one well-studied system. The developmental stage of dauer is a hypometabolic state capable of living efficiently by altering a number of basic mitochondrial functions, fuel preferences, behavior, and physical features. Dauer is comprised of an evolutionarily conserved and synergistic suite of metabolic and structural changes that are triggered by exposure to adverse environmental conditions. Entry into dauer confers a survival advantage in harsh conditions (35). When the dauer response is blocked by certain mutations (dauer defectives), animals are short-lived when exposed to environmental stress. These mutations show that the latent ability to enter into a hypometabolic state during times of environmental threat is adaptive, even though it comes at the cost of decreasing the optimal functional capacity. Similar to dauer, CFS appears to represent a hypometabolic survival state that is triggered by environmental stress. The metabolic features of CFS and dauer correspond to the same pathways that characterize the acute CDR and metabolic syndrome (50) but are regulated in the opposite direction. For example, cholesterol, phospholipids, and uric acid are often elevated in the acute CDR and metabolic syndrome, but these metabolites were decreased in CFS patients. A prediction based on these findings is that patients with CFS would be more resistant to the constellation of hypertension, dyslipidemia, central obesity, and insulin resistance that increase all-cause mortality associated with metabolic syndrome (37), but at the cost of significant long-term disability, pain, and suffering."
     
  2. charlie

    charlie The Law & Order Admin

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    Boom. There it is.

    :rightagain
     
  3. DaveFoster

    DaveFoster Member

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    That explains my reduced symptoms after taking a week off.
    I would say absolutely; paired with rest, I've been taking cyproheptadine and mirtazapine, along with Pansterone, thyroid, and antibiotics. They've all helped, especially the antibiotics.
     
  4. PeatThemAll

    PeatThemAll Member

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    Although his theory has been challenged, Dr. St-Amand's book mentions an interesting hypothesis: cell metabolism is slowed down because of a bottleneck in phosphate clearance at the kidney level.

    Stress and insulin further complicate clearance.

    Just mentioning regarding the final state (CFS symptoms): it just might be an adaptation to a bigger underlying, remote problem.
     
  5. haidut

    haidut Member

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    If it is indeed phosphate build up then it would be very easy to remediate - niacinamide is very good at lowering phosphate, especially in kidney patients.
    THE EFFECT OF ORAL NIACINAMIDE ON PLASMA PHOSPHORUS LEVELS IN PERITONEAL DIALYSIS PATIENTS
    Use of nicotinamide to treat hyperphosphatemia in dialysis patients. - PubMed - NCBI
    Medscape: Medscape Access
     
  6. PeatThemAll

    PeatThemAll Member

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  7. nullredvector

    nullredvector Member

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    Well the can of worms is open now... I guess I'l have to try something
     
  8. SQu

    SQu Member

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    Does it sound plausible for these things to worsen ..
    ... As one raises energy levels to combat CFS symptoms and recover? It would explain so much! I function much much better now but the above got worse and now I'm working on those.
     
  9. Blossom

    Blossom Member

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    That's what happened to me. It has been like a pendulum swinging in the opposite direction that is just recently starting to stabilize. I never imagined how much time it would take. @aguilaroja described it once in a thread a long time ago that I'd love to find again because it helped me understand what I have been experiencing as just part of the healing process.
     
  10. Emstar1892

    Emstar1892 Member

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    Which antibiotics have been effective, @DaveFoster, and how long have you been on them? I'm glad you've found some success.
     
  11. nullredvector

    nullredvector Member

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    Me three!
     
  12. DaveFoster

    DaveFoster Member

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    I'm on metronidazole (Flagyl) and cephalexin (Keflex). This is one of the proposed treatments for small-intestinal bacteria overgrowth (SIBO). Not just the antibiotics, but ample amount of rest is important.

    After lowering my adrenaline, my resting pulse is around 60-70, so this underscores the hypometabolic activity, although it's anecdotal.
     
  13. Emstar1892

    Emstar1892 Member

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    Intriguing! Have you tested for SIBO/infections or are you treating by symptoms?

    Ah, you're doing better than me. Still on 45bpm.
     
  14. Blossom

    Blossom Member

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    And we are the lucky ones!
     
  15. DaveFoster

    DaveFoster Member

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    SIBO confirmed by a hydrogen breath test; I had an incremental increase of 70, where the confirmed score would be a rise of 3. In other words, I was 23-fold higher in hydrogen concentration, which indicates a severe overgrowth. The combination of antibiotic, antifungal (with S. Boulardii), and anti-adrenaline, anti-serotonin has been tremendously powerful for mood.

    Mirtazapine is a weird drug; it makes you feel better than you should in a hypometabolic state (as it inhibits noradrenaline reuptake, so stress makes you feel extra high), so you can't trust your feelings with these kinds of drugs: only your pulse and temp.
     
  16. DesertRat

    DesertRat Member

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    The crucial piece in this study for me, was that the hypometabolic state is protective, and doing things to speed up the mitochondria tend to make it worse. Niacinamide definitely helps; I'm experimenting with ritanserin and Vit D (to raise dopamine) and notice a slight increase in energy but, at the same time, a decrease in the ability to fall asleep and sleep soundly. Consequently, after a few days, it evens out. One of these days I'll get ahold of cryto --I can't find out where to get it in Italy.

    A paper that came out April 2015 found decreased AMPK and glucose uptake in cultured skeletal muscle cells from individuals with CFS/ME and with fibromyalgia -- no increased uptake after several hours of electrical stimulation, increased myogenin expression, and diminished release of IL-6. AMPK is 5'-adenosine monophospate-activated protein kinase. This makes sense to me in terms of my own experience with this illness for 30 years, where exercise intolerance and inability to condition the muscles seems paramount. I'd definitely like to see how this connects with the metabolomics research.

    So far 3 years of doing thyroid, niacinamide, sugar, with excellent temps and pulse, has helped me sleep better but made absolutely no difference whatsoever in exercise tolerance; indeed, it has gotten worse.
     
  17. Sheila

    Sheila Member

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    Dear Mr DesertRat
    You appear to be a high temperature version of Rattus Experimentus that is to be found extensively on this forum. Greetings to you and welcome.
    I am interested in your 3 years of doing thyroid...excellent temps and pulse and the 'absolutely no difference whatsoever in exercise tolerance; indeed it has gotten worse" because I have found similar in some afflicted by CFS and am ever am focused on what might be 'missing'.
    This really is a punt, but I wonder if exercise triggers hypoglycaemia more readily for some reason in these people and from there symptoms seem to recur as a protective mechanism against endotoxin ingress and mitochondrial poisoning thereupon. Is cellular memory involved and how do you program the body not to panic and shut down?
    Once again I don't have a very clear question here, I have just seen an improvement in some CFS people with metabolic strategies but if they go anywhere near 'overdoing' things, they're suddenly shot. Many of them have long periods without food and much physical/mental strain in their past history which would suggest considerable endotoxin damage and that there has been a strong use of cortisol to cope - as I always say, I have not met a CFS who was a 'slacker', usually quite the opposite. And their frustration with themselves at suddenly falling in a hole again is very real and tragic to observe.
    If you have any thoughts, and indeed data on what your temps and pulse do on exercise, I would be pleased to hear them, thank you.
    Sincerely
    SheilaOceaniaRattus
     
  18. SQu

    SQu Member

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    I don't have data, but what I call 'bad patches' were a keynote for me, absolutely typical, but I never got the sense I shared this pattern with many people. They wiped me out for weeks and even trying hard not to overdo things, even in a good patch doing a bit more and feeling fine for it, would sink me quickly. I no longer consider myself to have CFS, yet I still get them, just milder. I'm in one now. All progress unravels during them. Nothing works and you hit a ceiling on raising levels of everything that should help. Eg t3, sugar, supps. It's like nothing will get through. At one point I thought I had it narrowed down to estrogen, and, though not easy to pinpoint, to the PMS phase and symptoms, vaguely. Focusing on anti PMS measures did seem to help, somewhat. Not sure anymore, but might be worth considering. For some.
     
  19. jyb

    jyb Member

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    Mind sharing what CFS symptoms you have with exercise and how your muscles feel? I have no CFS but I do know what hypo metabolic states do to my muscles so I am wondering if it is the same to some degree. For me, a hypometabolic state makes muscles usable but more tediously and more likely to jitter. Notice how jitterness seems common in old age. They basically feel weak, almost ticklish. However, my muscles remain intact even without exercise - no matter what, I remain lean and toned - the muscle mass is surprisingly robust. I say surprising because I know people with metabolism I would consider absolutely perfect (in every way equal to what Ray considers healthy in his articles) but who would struggle to acquire and maintain the muscles I have. That is why I sometimes wonder if this muscle hypometabolic feeling is not just something to do with the brain - that it couldn't be overturned fast with some kind of switch. It's probably not as easy, but on the outside it looks like that.
     
  20. kiran

    kiran Member

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    Hmm, how do you tolerate fat? How much of it do you eat? Exercise tolerance may depend on fat.
     
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