PDK inhibitors

[eljefe19]

Thanks guys, yeah I was putting a lot of hope into Rapamycin I even stopped my other mTor supplements. I just sent my doc at OMI to ask about continuing with Rapamycin. I broke it down into immediate effects from Akt and long term effects from B cells. It's pretty clear to me it's not going to have a miraculous effect at this point, but it may if I continue it long enough. Similarly @AdamS I've tried hundreds of meds and supps and nothing has stopped the progression of this illness. Pretty frustrating.

 

[AdamS]

Do you try combinations much? There are almost no supplements that work alone on me except opioids and ALA and it's only to a degree.

I tried Dr Myhill's protocol, think I was taking about 15 pills every morning, also tried quite a lot of other stuff in isolation. Tried Midodrine & Propranolol together and on their own, also tried Ivabradine but noticed no real benefits.

ALA sounds interesting, never tried it personally.

Think i'm going to try antibiotics next. Got some azithromycin, also want to try Ornidazole but don't know if you can get it in the UK. I tried Metronidazole previously but it made me feel pretty awful.

 

[Tunguska]

I tried Dr Myhill's protocol, think I was taking about 15 pills every morning, also tried quite a lot of other stuff in isolation. Tried Midodrine & Propranolol together and on their own, also tried Ivabradine but noticed no real benefits.

ALA sounds interesting, never tried it personally.

Think i'm going to try antibiotics next. Got some azithromycin, also want to try Ornidazole but don't know if you can get it in the UK. I tried Metronidazole previously but it made me feel pretty awful.

I didn't get benefits from antibiotics and wouldn't pin your hopes too high and would proceed carefully - much more carefully than rapamycin - but I can say short course azithromycin was the kindest to my body at the time.

With all due respect I think parts of the MyHill protocol are poor, so don't use that to get any bearings, it would even be counterproductive to some of these things we list. I obviously don't have the miracle combo either (I did make significant progress on brain health with fairly unique things, but I'm working backward from it), but I seriously believe we can do better with the naviaux/fluge-mella and other information. The problem is I only have so much time to put into and it's getting harder. I wonder where @Kimsie went, I think she'd have great input on all this.

 

[adreno]

With all due respect I think parts of the MyHill protocol are poor, so don't use that to get any bearings, it would even be counterproductive to some of these things we list.

What from Myhill's protocol would you consider counterproductive? Q10 perhaps?

 

[Tunguska]

What from Myhill's protocol would you consider counterproductive?

The diet especially (I do pretty much the opposite).

 

[eljefe19]

@Tunguska Why do you think DCA would be dangerous with Rapamycin? I happen to have some DCA that I never really gave much of a trial.

 

[Tunguska]

@Tunguska Why do you think DCA would be dangerous with Rapamycin? I happen to have some DCA that I never really gave much of a trial.

I didn't see any known specific interaction. Maybe my statement was too strong. It's up to you, but DCA alone scared me in the end.

 

[nandixon]

I've posted about it many times, but the supplement/drug that helps me the most is Tagamet (cimetidine) which is available OTC in the US. It took me from going into a severe level of ME/CFS to more moderate, and keeps me there as long as I take it.

It activates both Akt and mTORC1 (reference). Note that this ability has nothing to do with its anti-H2 histamine receptor action.

I take only 1/4 tablet (= 50 mg) about 1 hour after breakfast and at least 2 hours after dinner (i.e., twice a day dosing) to avoid interference with stomach acid secretion. More is not better with this drug.

(Note also that cimetidine can increase the concentrations of various drugs and the amounts of those may need to be adjusted. For example, if you take diphenhydramine you may need to adjust that dose down.)

Like most things we try in ME/CFS, it's likely to work for only a small subset of patients, I'm guessing.

 

[nandixon]

Thanks guys, yeah I was putting a lot of hope into Rapamycin I even stopped my other mTor supplements.

Did you continue with LDN while taking the rapamycin?

 

[AdamS]

I've posted about it many times, but the supplement/drug that helps me the most is Tagamet (cimetidine) which is available OTC in the US. It took me from going into a severe level of ME/CFS to more moderate, and keeps me there as long as I take it.

Thanks for sharing this. I'm sure Tagamet was on Jay Goldstein's list of drugs. I might try it, if it gives me even 10-20% functioning back it will be worth it.

 

[Tunguska]

I've posted about it many times, but the supplement/drug that helps me the most is Tagamet (cimetidine) which is available OTC in the US. It took me from going into a severe level of ME/CFS to more moderate, and keeps me there as long as I take it.

It activates both Akt and mTORC1 (reference). Note that this ability has nothing to do with its anti-H2 histamine receptor action.

I take only 1/4 tablet (= 50 mg) about 1 hour after breakfast and at least 2 hours after dinner (i.e., twice a day dosing) to avoid interference with stomach acid secretion. More is not better with this drug.

(Note also that cimetidine can increase the concentrations of various drugs and the amounts of those may need to be adjusted. For example, if you take diphenhydramine you may need to adjust that dose down.)

Like most things we try in ME/CFS, it's likely to work for only a small subset of patients, I'm guessing.

(I actually bought the Tagamet but I'm still waiting for a good period to try it to give it a good run... because of the specific dosing you said was crucial)

 

[AdamS]

I've just popped a Rantidine (Zantac) actually, not sure if Tagamet is available in the UK...let's see what happens!

 

[Jesse2233]

I've posted about it many times, but the supplement/drug that helps me the most is Tagamet (cimetidine) which is available OTC in the US. It took me from going into a severe level of ME/CFS to more moderate, and keeps me there as long as I take it.

What sort of symptomatic benefits did you notice with Tagamet?

 

[junkcrap50]

I think the best results have been from super high-dose thiamine, a few posters, Lynn, Sidereal, etc. had great experiences with that, albeit temporary. But there are just as many if not more failures including me.
http://forums.phoenixrising.me/inde...ent-story-focus-on-thiamine-deficiency.24059/
The thread is titled "thiamine deficiency" but they were taking 1500mg+ so more than likely it's just the therapeutic effect(s), betting on PDH/PDK or something in glycolysis anyway. I'm not sure if it did anything for people's PEM though (this plays into my belief it might be more useful during activity although it should help a little anytime [but also that it may be better in combinations]).

I've come across that small paper/case study too after researching PDH and have been meaning to try high dose thiamine. I believe that it has a good chance of helping some people with their low PDH enzyme. Super high dose thiamine has been able to help genetic deficiencies in PDH in some children. I was going to try this myself but then got side tracked with other theories and supplements to try. So I'll have to come back to it.

I've posted about it many times, but the supplement/drug that helps me the most is Tagamet (cimetidine) which is available OTC in the US. It took me from going into a severe level of ME/CFS to more moderate, and keeps me there as long as I take it.

It activates both Akt and mTORC1 (reference). Note that this ability has nothing to do with its anti-H2 histamine receptor action.

I take only 1/4 tablet (= 50 mg) about 1 hour after breakfast and at least 2 hours after dinner (i.e., twice a day dosing) to avoid interference with stomach acid secretion. More is not better with this drug.

(Note also that cimetidine can increase the concentrations of various drugs and the amounts of those may need to be adjusted. For example, if you take diphenhydramine you may need to adjust that dose down.)

Like most things we try in ME/CFS, it's likely to work for only a small subset of patients, I'm guessing.

Yes I've heard Tagamet (cimetidine) work in a subset of CFS patients. It's listed in one doctor's list of CFS drugs, which when I read it looked like a list of hit or miss things for specific subset of patients. I'm beginning to think that there is a large component of MCAS in CFS patients that is going unrecognized because it doesn't present in the typical MCAS way. So, perhaps the cimetidine is controlling part of your MCAS and the cytokine cascade that comes from MCAS.

 

[nandixon]

So, perhaps the cimetidine is controlling part of your MCAS and the cytokine cascade that comes from MCAS.

I can rule that possibility out because neither famotidine (Pepcid) nor ranitidine (Zantac) - two other anti-H2 histamine drugs - are in the slightest bit helpful for me. (One has no effect at all, the other makes me worse.)

 

[nandixon]

What sort of symptomatic benefits did you notice with Tagamet?

Mostly increased energy and decreased PEM (less post-exertional fatigue that happens in a delayed manner).

 

[AdamS]

I can rule that possibility out because neither famotidine (Pepcid) nor ranitidine (Zantac) - two other anti-H2 histamine drugs - are in the slightest bit helpful for me. (One has no effect at all, the other makes me worse.)

Yeah i'm not having fun on Ranitidine, regretting taking it

 

[junkcrap50]

I can rule that possibility out because neither famotidine (Pepcid) nor ranitidine (Zantac) - two other anti-H2 histamine drugs - are in the slightest bit helpful for me. (One has no effect at all, the other makes me worse.)

Well, you know youself best obviously. In Dr. Afrin's book Never Bet Against Occam: Mast Cell Activation Disease and the Modern Epidemics of Chronic Illness and Medical Complexity, which I'm reading right now, has many cases of MCAS that did not respond to the typical H1 and H2 blockers. One reason is that it's not just histamine which is released by mast cells. Many cytokines and inflammatory signals are released as well. He's also had to use some biologics to control their MCAS. I'm still learning all about it.

 

[Jesse2233]

Yeah i'm not having fun on Ranitidine, regretting taking it

Ugh side effects?

 

[kangaSue]

I don't know if any of these are commercially available yet but pyruvate kinase M2 PKM2 activators also activates mTOR signaling.

https://www.nature.com/articles/srep21524
[Activation of mTOR signaling usually requires nutritional and hormonal signals7. However, PKM2 overexpression alone activated mTOR signaling under serum starvation (Fig. 5H), amino acids starvation (Fig. 5I) or both (Fig. 5J). These results showed that PKM2 overexpression is sufficient to activate mTOR signaling, regardless the existence of growth factors and amino acids signals.]