Welcome to Phoenix Rising!
Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.
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I have a source shipped from India if anyone is interested.Its a strong immunosupressor, I don think its allowed to sell online?
From my dashboard, here on PR, it looks like no one is reading the PM's I had sent. @eljefe19 , @dreampop, @knackers323, check your PM's.
Sudden onset. Relapse remitting, though it's never really "disappeared" for more than a month at one time.Checked. Did you have a sudden/gradual onset and constant or relapse/remitting symptoms?
Argh. I was in bed all day yesterday afternoon and early evening. That day was a total washout. Today my armpit lymph nodes are sore, but I'm back to my new self again. That is a typical "bad" day experience for me (pre Rapamune.) Boo. Hiss. But good news that I rebounded so fast after just one day, and not a week or two months like last time.
One more example of a compound (cordyceps) which seemingly activates both AMPK and Akt/mTOR:If you go back to basics and see AMPK as a primitive intracellular energy sensor, there's logic in thinking its activation should lead to higher Akt, in the context of extracellular nutrients being available, as long as mTorC1 is concurrently inhibited.
In conclusion, we have successfully confirmed that Cordyceps militaris induces fatigue recovery via activating AMPK and AKT/mTOR pathways and regulating serum hormone level. Our data provides experimental evidence in supporting clinical use of Cordyceps militaris as an effective agent against fatigue.
https://www.hindawi.com/journals/ecam/2015/174616/Although our results suggest AKT/mTOR signaling is involved in the antifatigue activities of CM, we fail to explain the relationship between AMPK and AKT/mTOR.
https://www.neuronootropic.com/cordyceps/Aside from increasing dopaminergic and noradrenergic activity, its antidepressant effects are also attributed to a rapid increase in AMPA receptor activity.[30] In both the prefrontal cortex and the hippocampus, an enhancement of AMPA signaling is seen just 45 minutes after treatment. The effect lasts up to 5 days of treatment. Its effects are akin to that of ketamine which acts via the AMPA receptors in the hippocampus and the prefrontal cortex to upregulate mTOR and BDNF.[31][32] Both mTOR and BDNF increase cell growth and proliferation which in turn increases neurogenesis.
They didn't distinguish between mTorC1 and mTorC2, they don't even describe the measurement they used for mTor, so presumably it's one or the other. Some of their statements are strange. If simultaneous I'd think it'd have to be mostly AMPK/mTorC2, which I think might be an under-reported case more than anything. Not impressed by this study.One more example of a compound (cordyceps) which seemingly activates both AMPK and Akt/mTOR:
They do write:
https://www.hindawi.com/journals/ecam/2015/174616/
Would this fit the bill?
Also of interest is that cordyceps enhances AMPA receptor activity, which in turn activates BDNF and mTOR, an effect similar to that of ketamine:
https://www.neuronootropic.com/cordyceps/
In summary, we have identified a mitochondrial mTOR complex that appears to function as a cellular switch regulating glycolytic and respiratory metabolism. Inhibiting mTOR, which is now the basis of treatment of certain cancers, enhances aerobic glycolysis and induces a state of increased dependence on aerobic glycolysis in leukemic cells.
I have a source shipped from India if anyone is interested.
I have a source shipped from India if anyone is interested.
I also had spectacular rapid improvement on high dose azithromycin. Could never figure it out at the time but now I wonder about the mTOR angle.hi XenForo
have you ever taken any other macrolides, did they have an effect?
i had very good improvement on clarithromycin and azithromycin within a day. and back to hell within a day of stopping. so its unlikely it was due to them killing anything.
its known that macrolides have immunomodulatory effects but do you know if they effect mTOR?
I think that info is wrong. Inhibiting mTOR should inhibit glycolysis.I realise that the context is different (Leukemic cells), but isn't this what we want and perhaps why Rapamune/Sirolimus helps?
Argh. I saw my GP and they advise against taking an immunosuppressant. I'm going to go off the Rapamune, and try a few less risky treatments recommended by my GP. No fun, but sounds like it might be the best course for me for now "" I'm not looking forward to the soon-to-come crash. Boo. Hiss.
Risk of cancer. It does make sense to me to exhaust other, less risky, options first. I don't have other obvious autoimmune issues going on, that we know of.Ah bummer. Why did they advise against it? ...
In these cancer cells, aerobic glycolysis is considered to be the process of (1) glycolysis followed by (2) the reduction of pyruvate to lactate.Okay so i'm super confused. I thought mTOR was believed to be under-activated in ME/CFS patients and from memory Davis said in his video NOT to inhibit it...but according to this, inhibiting mTOR does the following:
I realise that the context is different (Leukemic cells), but isn't this what we want and perhaps why Rapamune/Sirolimus helps?
Oxidation of glucose under aerobic conditions results in 32 mol of ATP per mol of glucose but under anaerobic conditions, only 2 mol of ATP can be produced...the difference is huge.
Pyruvate, the end product of glycolysis, can be converted either into acetyl CoA by mitochondrial pyruvate dehydrogenase or into lactate by cytoplasmic lactate dehydrogenase. Inhibition of mTOR by rapamycin increased lactate production in Jurkat cells within 25 min (Fig. 1). We observed no significant changes in glucose consumption at this time point.
In agreement with the hypothesis that inhibition of mTOR shifts glucose metabolism away from mitochondrial respiration, we observed an immediate buildup of intracellular lactic acid.
We found decreased levels of all 6 mitochondrially metabolized organic acids measured following the inhibition of mTOR. Five of these are tri-carboxylic acid (TCA) cycle intermediates; the other, orotic acid, is synthesized in the mitochondria during purine metabolism. This striking decrease in mitochondrial organic acids, in conjunction with diminished oxygen consumption, is indicative of a decrease in mitochondrial metabolism.
Overall, the profile indicates an immediate and profound change in cellular metabolism caused by inhibition of the FKBP12/rapamycin-sensitive functions of mTOR, consistent with enhanced aerobic glycolysis.
The rapamycin-induced increase in lactate production and decrease in uncoupled respiration without detectable change in mitochondrial content led us to hypothesize that inhibiting mTOR diverts the metabolism of pyruvate away from the mitochondria by exerting control over the mitochondrial substrate availability.