Looking Ahead to Change: Little by Little
I don't make New Year's Resolutions. I don't think I ever really did, but the last decade or two would have been enough to stifle that impulse. I've just been too aware that I don't have that much control over what happens in my life.
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Beta-3 Receptor Involvement

Discussion in 'General Treatment' started by dreampop, Mar 14, 2017.

  1. dreampop

    dreampop Senior Member

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    I'm writing this about an idea I had about the beta-3 receptor in CFS.
    Per wikipedia: Actions of the β3 receptor include
    Which doesn't seem particularly important at first. Let me start with OI, many patients with CFS have it. Frequent Urination is a common symptom and led me to Mirabergon, a new drug that acts as a beta3 agonist. It relaxes the bladder basically. But in addition, it was found to raise blood pressure, basal heart rate and metabolic rate which are signs of cardiac stimulation.

    I also read that beta3 agonist that pass the blood brain barrier can have anti-anxiety and anti-depressive activities. This brought me back to Leptin, which was found to have an inverse relationship with CFS symptoms. It was assumed this was because it primed microglia activity. However, Leptin also attenuates the HPA axis, "leptin was found to dampen the HPA axis response to many kinds of stress" (http://www.nature.com/nrendo/journal/v11/n5/full/nrendo.2015.34.html, https://www.ncbi.nlm.nih.gov/pubmed/17725965).

    I have seen many people fail, including myself, for any noticeable benefits from microglia inhibition, despite trying many supplements and acknowledging that supplements are only so strong (but should be strong enough based on my research). However, I have also seen many people express improvements from sleep inhibition or food inhibition - which inhibit leptin expression or secretion (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC535701/).

    In addition to doing the above, Beta3 activation suppresses Leptin expression (https://www.ncbi.nlm.nih.gov/pubmed/8666142) and Leptin secretion (https://www.ncbi.nlm.nih.gov/pubmed/12080443, https://www.ncbi.nlm.nih.gov/pubmed/8756584).

    It got me thinking if beta 3 tolerance or under activation might contribute to CFS. So, what about the metabolism? In @Hip 's review of Myhills research is noted "in ME/CFS patients, during physical exercise, there is an acute shortage of energy and the mitochondria cannot recycle ADP back to ATP fast enough, so there is a build up of ADP molecules." Myhill notes in her own paper "ECT...regenerates ATP from ADP by the process of oxidative phosphorylation".

    It just happens, that the thermogenesis activated by the beta 3 receptor is via activation of mitochondrial uncoupling factor 1 - "which mediates a proton conductance pathway that uncouples oxidative phosphorylation," (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC508828/, https://www.ncbi.nlm.nih.gov/pubmed/9530130) in fat and slow twitch muscle fibers.

    I'm far from an expert on the metabolism and mitochondria, and I can't seem to find the specific blocks that Fluge and Mella and Davis identified (2 different ones if anyone remembers feel free to post them), other wise I would try to see if there is a link there.

    Anyway, I just thought it was interesting.

    Edit: I did find Fluge and Mella identified pyruvate dehydrogenase inhibition. I couldn't find a link so far, but its possible that some of the activities of b3 act on the kinases which inhibit or activate PD downstream.

    Also found this w/ regards to calcium ions "Calcium ion has a role in regulation of PDC in muscle tissue, because it activates PDP". PDP activates PD, so maybe the Australian's research can be linked to Fluge & Mellas.
     
    Last edited: Mar 14, 2017
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  2. dreampop

    dreampop Senior Member

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    Also interesting is, "A Phase II study for irritable bowel syndrome (IBS) evaluated 102 patients with IBS. Solabegron demonstrated significant reduction in pain associated with the disorder and a trend for greater improvement in the quality of life, compared to placebo." Solabebegron is an unreleased beta 3 agonist.
     
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  3. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Clenbuterol is an asthma drug bodybuilders use to burn fat through increasing their metabolism. Its said to be a beta 2 agonist but from memory yrs back they showed it had beta 3 agonist qualities. I dont think u can get pure beta agonists as they all seem to effect the receptors to certain degrees.

    Many asthma medications when inhaled to work effectively for fat burning but when taking orally as a pill they have more pronounced effects.

    I recall beta 3 agonists stimulate brown adipose tissue which is said to be the mechanism to which it increase metabolism.
     
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  4. eljefe19

    eljefe19

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    I take Clenbuterol for MCAS and haven't noticed any improvements in ME/CFS symptoms from it. Just my two cents.
     
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  5. eljefe19

    eljefe19

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    @dreampop Supplementing with microglial inhibitors (many of which also happen to inhibit mTOR) also did not do me any good and may have made me worse. If I take anything now I make sure to check all it's mechanisms in case it's contraindicated for some other reason. I think mTOR activation and a few other routes are more promising than microglial activation inhibition.
     
  6. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Ive used salbutamol tablets which are similar but with much shorter half life. Their stimulant effects give me abit of pep.
     
  7. Mohawk1995

    Mohawk1995 Senior Member

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    Our experience with our son was that any stimulant might give him an initial boost, but had no ability to sustain a true improvement. If the mechanism that drives energy is shut down as it appears is the case according to the research at Stanford, then you can "put all the gas in the world in the engine, but it won't run because there is no spark". Maybe the shorter half life of the salbutamol keeps from overwhelming the energy producers (mitochondria) and creating an adverse affect? Really strong stimulants just shut his system down.
     
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