mTor Inhibitor Rapamune Helps 5 ME/CFS Patients in Dallas

[Hip]

It is possible that the herbal supplement Garcinia cambogia may be able to reduce the type 2 diabetes risk that occurs when taking rapamycin on a long term basis.

If you look at the proposed mechanism by which rapamycin causes diabetes (see this post), it is thought to be due to insufficient activation of beta oxidation (fat burning) in the mitochondria. Metformin is thought to mitigate the rapamycin diabetes risk by stimulating and up-regulating beta oxidation.

This article says that Garcinia cambogia stimulates fat burning, and may activate beta oxidation. Garcinia cambogia is often sold as a weight loss supplement; its active ingredient is hydroxycitric acid (HCA), and Garcinia supplements will typically contain 50% HCA.

 

[MrTop]

It is possible that the herbal supplement Garcinia cambogia may be able to reduce the type 2 diabetes risk that occurs when taking rapamycin on a long term basis.

If you look at the proposed mechanism by which rapamycin causes diabetes (see this post), it is thought to be due to insufficient activation of beta oxidation (fat burning) in the mitochondria. Metformin is thought to mitigate the rapamycin diabetes risk by stimulating and up-regulating beta oxidation.

This article says that Garcinia cambogia stimulates fat burning, and may activate beta oxidation. Garcinia cambogia is often sold as a weight loss supplement; its active ingredient is hydroxycitric acid (HCA), and Garcinia supplements will typically contain 50% HCA.

Very interseting Hip. I may try along wuth the metformin.

I've spent the last couple of days trying to locate a reliable, cost-effective supplier of rapamycin.

Have you chosen a supplier Hip? Are they India based?

 

[Jesse2233]

From correspondence I've been having with a researcher looking into rapamycin...

"Rapamycin is not a heavy immune suppressant. Far from it. It's a selective immune modulator that increases immunity in populations such as the elderly. It's an atypical drug, with theoretical risk of diabetes but this can be abated with dosing. In a mice trial, long term use of the drug (6 months) was necessary for it to correct PD1+ T cell exhaustion"

YRMV so talk to your doctor / do your research

 

[perovyscus]

I am not past begging anyone who will listen (my wife, this forum, my dog) that this disease in most cases is completely unrelated to the periphery, primarily in fast-onset patients. If you look at the reviews of CFS by neuro-anatomists they explain this in detail. It is repeated cytokine attacks of vulnerable structures in the brain, which are just doing their job --- killing virus.

The reasons the periphery is focused on is because it is low-hanging fruit. Most CFS specialists (not neuroscientists that publish a review of CFS and immediately eject from the field) are systems physiologists and incredibly competent - especially Klimas and Rey. No murine model exists so you cannot prove the aforementioned etiology, nor can you do it for humans, and you especially cannot if literally no one in the field has the training to do so. This is a function of the absence of funding, to an extent.

Rapamycin probably helps people because it quells the microglial inflammation at these structures and (either as a consequence of this or independently) stops the replication of EBV locally.

 

[Jesse2233]

this disease in most cases is completely unrelated to the periphery, primarily in fast-onset patients

Interesting, will you expand on what you mean by periphery?

 

[perovyscus]

Generally speaking, anything outside of the brain.

Rapamycin could function differently in the periphery than it does in the brain, although no models used are applicable to CFS.

Two spikes exist in CFS onset - the first being 18-22 that correlates closely with the age of first sexual partner and EBV infection and would benefit most from that CNS treatment. The second is around 30, that correlates with pregnancy in westernized countries and may indeed be a peripheral issue, given the massive influx of progesterone (heavily anti-inflammatory) that procures. I am not ignorant of the attribution of Lyme disease, chemical sensitivity and allergies to the population, however.

Spinal fluid is a filtrate of the plasma and thus does not precisely correlate to the blood, nor cells taken from the plasma and placed in culture then stimulated (PBMCs). For further reading, here.

This seems like a misplaced post for a semantics issue. It is not semantics. It means when patients are taking the word of five anonymous strangers over the entire breadth of CFS research to date, something in the paradigm needs to change.

 

[MrTop]

I am discontinuing the rapamycin after 14 days; ultimately, it was not the panacea that was described earlier and I did not expect it to be.

I have had this condition severe since I was 14 after contracting chicken-pox and glandular almost simultaneosly. Requiring a long spell in hospital.

I certainly couldnt judge rapamycin in a fortnight after having a condition for 36 years.

 

[MrTop]

Pero

I do not understand what you are trying to say.

Are you saying rapamycin cannot and will not work?

It is my understsnding that science is only at the tip if tge iceberg in understanding the effects of this drug.

 

[nandixon]

@nandixon much luck to you! looking forward to hearing your results

I've taken 1 mg of rapamycin/sirolimus 4 days in a row now (after breakfast with a fat source). The first day I took it with not-from-concentrate grapefruit juice (8 oz or about a quarter of a liter) to effectively obtain a loading dose (by inhibition of the CYP3A4 enzyme; I also take the sirolimus with my usual morning dose of cimetidine, 50 mg, which is also a CYP3A4 inhibitor but much weaker than grapefruit juice).

No negative side effects so far. Perhaps a small increase in energy beginning day 1, but it's too early to tell anything really.

 

[MrTop]

I've taken 1 mg of rapamycin/sirolimus 4 days in a row now (after breakfast with a fat source). The first day I took it with not-from-concentrate grapefruit juice (8 oz or about a quarter of a liter) to effectively obtain a loading dose (by inhibition of the CYP3A4 enzyme; I also take the sirolimus with my usual morning dose of cimetidine, 50 mg, which is also a CYP3A4 inhibitor but much weaker than grapefruit juice).

No negative side effects so far. Perhaps a small increase in energy beginning day 1, but it's too early to tell anything really.

Good luck. Keep us all informed please.

 

[MrTop]

Nandixon

Can you pleaee give some idea of level od cfs you endure, onset, timeframe etc?

Are you planning to slowly increase dosage?

Thanks

 

[Hip]

I also took rapamycin for the first time a few days ago: I took just a single 1 mg dose of rapamycin with my main meal, but because I also happen to be taking the potent CYP3A4 inhibitor drug itraconazole at the moment (as well as drinking grapefruit juice), I think this will effectively multiply my dose by a factor of 5, making the dose I took equivalent to 5 mg (see this post for why).

I plan to take 1 mg (which is equivalent to 5 mg) once every 5 days, which follows the intermittent rapamycin protocol detailed in this post. The intermittent rapamycin protocol was designed to lower the diabetes risk.

I did not notice anything on the day I took the rapamycin, but on the two days that followed, I experienced a sort of slight mental numbness to the reality around me, like a sort of apathy or ennui. I was also a little more tired.

Today is now the third day after the day I took my single rapamycin dose, and I feel better today (the slight mental numbness has disappeared). Apart from that, I have not noticed much else so far.

 

[Tunguska]

Rapamycin could function differently in the periphery than it does in the brain, although no models used are applicable to CFS.

That is a good point but I think it's several layers more complicated. For example the M1 vs M2 is a generalization, M2 is split into m2a/m2b/m2c and some studies show m2b has inflammatory properties and implicated in model of Lupus. In one of the more technical papers they characterize M2-dominant diseases (might be m2b) and possible "endotoxin tolerance" states, such that the shift to M1 itself normally thought of as inflammatory could be the benefit. Doxycycline is the other agent identified as M1 polarizer (http://www.jbc.org/content/early/2014/02/06/jbc.M113.535765) and it's usually characterized as an "anti-inflammatory" substance. So the very idea of "anti-inflammatory" is highly contextual and mix of overlapping effects, brain or not. Then there's dosage (in that first study was 0.1mg/kg Rap) and course duration. Then the timing of the macrophage/microglia activation/resolution during acute immune triggers (the resolution-time macrophages are a state between M1 and M2). Then all those effects on macrophages which may have nothing to do with the polarization state (e.g. the other thread). It's impossibly hard to try to map this into a single functional idea.

 

[XenForo]

Have any of you guys who have access to Rapamycin tried combining it with Arginine (several-gram doses/day)?

I tried Now Foods Arginine 500mg and Citrulline 250mg, Capsules for at least a week. Actually, it may have made me more tired, if anything. It's always hard to tell whether something is having an effect, or if it's just regular CFS ups and downs, but I did feel more tired on Citruline and Arginine for what that's worth.

 

[Jesse2233]

any updates on your rapamycin experience @XenForo?

 

[XenForo]

I've been back on 1/2 mg of Rapamune for about a month. It has been a huge help. Although I probably need to start lowering my level of activity so I'm not trying to work 7 hour days because that will make me crash again eventually, even on Rapamune.

After reading through the past few pages of posts, I wanted to mention a couple other things about my situation - they may or may not be relevant. I'm on a ketogenic diet and very very very good about not eating supplemental sugar, meaning table sugar or cane sugar, added fructose, syrup, or even processed foods (except when I eat at restaurants.) I try to grow my own food or buy at farmers' markets. So I have a high fat, low sugar diet. Again, I have no idea if that is relevant. Also, my dose of Rapamune is very small; I don't weigh very much - I'm around 11 stone / 68 kg and take only 1/2 mg Rapamune per day (mornings). The other thing I wanted to mention is that I think my me/cfs started with viral onset, a very long time ago, when I was 2 or 3 years old, with raging stiff neck followed by delirious fever. Whatever the case, I've had me/cfs for many many decades. Oh and also, I see the Stanford CFS clinic, and they prescribe antiviral meds for me, and Sulfasalazine, which I think helps me lots as well. I think it's an anti-inflammatory drug. Last thing I wanted to mention is I have poor short term memory, and have had major me/cfs brain fog that has finally lessened with the rapamune.

 

[Jesse2233]

@XenForo wow glad it's still helping, never heard of an onset that early in life, quite interesting

what are your major symptoms? and does your condition wax / wane over time w/o treatment or more or less remain stable? has a primary mitochondrial disorder been ruled out?

 

[XenForo]

@XenForo...never heard of an onset that early in life
what are your major symptoms? and does your condition wax / wane over time w/o treatment or more or less remain stable? has a primary mitochondrial disorder been ruled out?

I still suffer from fatigue - that is now my major issue. My short term memory has always been poor, and it still is, though I'd say less so. My crashes now last a day, two days, not months and months like they used to. Although I have to remind myself about how much better I'm doing now, when I do crash. I can always expect to be exhausted after working 4, 5 hours, but of course that's just the nature of me/cfs I guess. Nowadays my symptoms seem to come after I push myself and don't seem to come out of nowhere like they used to. I just need to get through the tail end of a difficult part of my life, then I think I can relax more and work on a more "cfs-friendly" workload / schedule. Sorry, not sure what primary mito disorder is - probably haven't been tested for that. I'll ask the Stanford doc about that when I talk to them next.

EDIT: oh, um, another symptom is my intelligence waxes and wanes. I built a robot and then it stopped working and now I'm like, wait, how in the world was I ever smart enough to pull that off? How did I build that thing in the first place? I have no idea how to try to fix it. I have to wait until I'm feeling energized and "smart" to try to tackle that one. That happens a lot to me, and school was a total nightmare for me since I was never consistent intellectually. I think it maybe depends on my energy level. It's just frustrating, as you can imagine. It's so much harder to be "dumb" as a smart person than someone who is always not so smart and used to not being intelligent.

 

[Jesse2233]

I still suffer from fatigue - that is now my major issue. My short term memory has always been poor, and it still is, though I'd say less so. My crashes now last a day, two days, not months and months like they used to. Although I have to remind myself about how much better I'm doing now, when I do crash. I can always expect to be exhausted after working 4, 5 hours, but of course that's just the nature of me/cfs I guess. Nowadays my symptoms seem to come after I push myself and don't seem to come out of nowhere like they used to. I just need to get through the tail end of a difficult part of my life, then I think I can relax more and work on a more "cfs-friendly" workload / schedule. Sorry, not sure what primary mito disorder is - probably haven't been tested for that. I'll ask the Stanford doc about that when I talk to them next.

Thanks for elaborating. It's great that rapamycin has allowed such an increase in what you can do.

Mitochondrial disease is a genetic defect that causes key metabolic enzymes to underperform. It usually shows up early in childhood and has extremely severe symptoms

 

[XenForo]

...Mitochondrial disease is a genetic defect that causes key metabolic enzymes to underperform. It usually shows up early in childhood and has extremely severe symptoms

Well if they're consistent symptoms, then that's not what I have, but I'll ask the doc anyway. I used to be pretty good at sports, except of course when I wasn't.