Finally Found a Treatment...Can Anyone Please Explain This?

Swim15

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I’ve had several longer breaks in symptoms the past 10 months (2x 7-10 days) and thought it was due to something I was taking but couldn’t replicate it.

I finally did replicate it however and have been pouring over literature trying to decide what exactly is happening and the most likely mechanism.

ITPP - I posted a thread a few days ago about ITPP (myo inositol trispyrophosphate) which is an almost Eric effector of hemoglobin that can increase oxygen release up to around 50%. Incredible performance enhancer. By itself this helps with physical fatigue a fair amount 40-50% and mental fatigue

Cabergoline - this is a dopamine (primarily selective D2) agonist. Also has some affinity at other DA receptors and Alpha receptors. By itself this drug doesn’t seem to do a whole lot...maybe a very tiny mood elevation.


Neither of these drugs make an enormous difference by themselves is the weird thing (ITPP much more so than the caber but still not a lot). COMBINING them, however, makes an enormous difference and I had almost all my symptoms fade over the course of 12 hours after taking them both.

Energy is back, sense of humor is back, brain fog is gone, mental clock speed is much faster, sex drive and function is back strong, and an overall general feeling of wellbeing is back.

Can anyone try and help postulate why? Been looking at every angle non stop to try and figure out what about this combination is elliciting 100% improvement, and in such a short time period
 

Hip

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COMBINING them, however, makes an enormous difference and I had almost all my symptoms fade over the course of 12 hours after taking them both.
So you find ITPP plus cabergoline greatly improve your ME/CFS symptoms, but these drugs do not do a great deal on their own. Interesting.

Can you quantify that improvement by stating where you are on ME/CFS scale of very severe, severe, moderate, mild, remission before you take this treatment, and where you end up on the scale as a result of this treatment?


How long have you been experiencing this improvement, by the way? Because unfortunately lots of ME/CFS treatments end up just being a flash in the pan, and they stop providing benefit after some weeks or months.
 

Swim15

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So you find ITPP plus cabergoline greatly improve your ME/CFS symptoms, but these drugs do not do a great deal on their own. Interesting.

Can you quantify that improvement by stating where you are on ME/CFS scale of very severe, severe, moderate, mild, remission before you take this treatment, and where you end up on the scale as a result of this treatment?


How long have you been experiencing this improvement, by the way? Because unfortunately lots of ME/CFS treatments end up just being a flash in the pan, and they stop providing benefit after some weeks or months.
Yeah it’s incredibly interesting. With no treatment at all I would put myself as severe or on the severe end of moderate. With them I’d say I’m mild and 85-90% of symptoms are gone. As far as things go, I’m generally back to my pre-CFS self. I can tell my energy is still off some but nowhere near the usual.

I didn’t realize it until I connected the two and looked back at logs but I was actually inadvertently using this combination last summer and it got me through the MCAT. So it’s been working on and off (through my accidental combinations) for a year and consistently relieves symptoms within 24 hours or less of dosing.
 

Hip

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@Swim15, when you take the ITPP + cabergoline combo as a single dose, how long do the benefits last before wearing off?

I believe the the effects of a single dose of ITPP last for about a week. And the half-life of cabergoline is pretty long too, around 63–69 hours (nearly 3 days). So you might expect the benefits of a dose of ITPP + cabergoline to last for a few days.

Is that what you observe, a tail off of beneficial effect after a few days? Or have you just been dosing daily, so that you have not noticed the tail off?



I just did some random Googling, and found this study which reports that cabergoline can occasionally cause drug-induced hemolytic anemia (destruction of red blood cells by autoimmune attack on these cells).

That suggests cabergoline might be having some effect on red blood cells, and maybe that effect is somehow synergistic with ITPP's action on these blood cells?

I'll see what else I can find by more random Googling.



By the way, where did you buy your ITPP? I am interested in trying this.
 

gbells

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I’ve had several longer breaks in symptoms the past 10 months (2x 7-10 days) and thought it was due to something I was taking but couldn’t replicate it.

I finally did replicate it however and have been pouring over literature trying to decide what exactly is happening and the most likely mechanism.

ITPP - I posted a thread a few days ago about ITPP (myo inositol trispyrophosphate) which is an almost Eric effector of hemoglobin that can increase oxygen release up to around 50%. Incredible performance enhancer. By itself this helps with physical fatigue a fair amount 40-50% and mental fatigue

Cabergoline - this is a dopamine (primarily selective D2) agonist. Also has some affinity at other DA receptors and Alpha receptors. By itself this drug doesn’t seem to do a whole lot...maybe a very tiny mood elevation.


Neither of these drugs make an enormous difference by themselves is the weird thing (ITPP much more so than the caber but still not a lot). COMBINING them, however, makes an enormous difference and I had almost all my symptoms fade over the course of 12 hours after taking them both.

Energy is back, sense of humor is back, brain fog is gone, mental clock speed is much faster, sex drive and function is back strong, and an overall general feeling of wellbeing is back.

Can anyone try and help postulate why? Been looking at every angle non stop to try and figure out what about this combination is elliciting 100% improvement, and in such a short time period
This article says ITPP increases exercise capacity through allowing more oxygen binding. Some people here use hyperbolic oxygen chambers as treatment. Maybe more oxygen inhibits the viruses so they aren't as active.
 

Swim15

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hypoxia is a main driver of me/cfs.
Agreed. Only thing I can’t figure out is why they do so little on their own. The ITPP definitely does more for energy but my mood, personality, sex drive/function and positive head space all come back with the addition of Cabergoline in addition to more energy.

Been pouring over literature lol
 

Swim15

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@Swim15, when you take the ITPP + cabergoline combo as a single dose, how long do the benefits last before wearing off?

I believe the the effects of a single dose of ITPP last for about a week. And the half-life of cabergoline is pretty long too, around 63–69 hours (nearly 3 days). So you might expect the benefits of a dose of ITPP + cabergoline to last for a few days.

Is that what you observe, a tail off of beneficial effect after a few days? Or have you just been dosing daily, so that you have not noticed the tail off?



I just did some random Googling, and found this study which reports that cabergoline can occasionally cause drug-induced hemolytic anemia (destruction of red blood cells by autoimmune attack on these cells).

That suggests cabergoline might be having some effect on red blood cells, and maybe that effect is somehow synergistic with ITPP's action on these blood cells?

I'll see what else I can find by more random Googling.



By the way, where did you buy your ITPP? I am interested in trying this.
Effects last around 5-7 days in line with the half life.

I’m actually out of ITPP - had a few doses left and went back to retry this combo this week after looking at some past notes. I figure I’ve got 4-5 days left until I feel like shit again.

My source for the ITPP was an equine and animal pharmacy or sorts but they’ve picked up on ITPP in animal doping so places have stopped carrying it. Science bio and some peptide places did for a bit but everyone is out of stock right now. I’ve contacted some labs about custom synthesis so hopefully I can get more made ASAP.

While they’re clearly very synergistic and do both overlap, ITPP seems to be better at improving physical energy and metabolism which is expected and caber improves mood and psychological symptoms more. Fucked my girlfriend like a champ last night after having almost no sex drive or function for months
 

Hip

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Science bio and some peptide places did for a bit but everyone is out of stock right now.
I found some places which appear to be in stock for ITPP — see this post.

And someone on a Reddit thread suggested synthesis of ITPP by using the cheap supplement inositol hexaphosphate (IP6) as the starting point should be possible, though I was not able to find any home synthesis instructions.
 

Swim15

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@Swim15 when you get some more ITPP, you could experiment with other dopamine D2 agonist drugs, like memantine, bromocriptine or ropinirole, and see if you get the same benefits. If you get the same benefits, it suggests that the effect of cabergoline on the D2 receptor is critical. If you do not, it suggests some other mechanism of cabergoline is responsible.
I may cautiously experiment but I’m relatively careful about what I take so it’ll probably be slow. Have weird reactions to meds a lot.

I think pramipexole does work as well from looking back through notes but the mech of all DA agonists is so similar that I’d expect some crossover.

I think there’s a lot of other potential mechs but I tend not to think it’s specifically D2 agonism because rasagiline and selegiline (MAO-B inhibitors) didn’t have the same effect even when taken in the MAO-A and MAO-B ranges. Neither L-Dopa not adderall has had the same effect either so dopamine agonism isn’t my first thought - granted a selective agonist isn’t quite the same.

I’m still wondering about interactions with alpha receptors and/or effects on microglia or other cells. Really baffled by this one but I’ve also been trying to possibly tie it into the hypothesis behind CT-38.

Besides that I haven’t totally ruled out some impacts of DA agonists on the gastrointestinal tract.
 

Swim15

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I found some places which appear to be in stock for ITPP — see this post.

And someone on a Reddit thread suggested synthesis of ITPP by using the cheap supplement inositol hexaphosphate (IP6) as the starting point should be possible, though I was not able to find any home synthesis instructions.
I looked at the synthesis and thought about attempting it but honestly I don’t think it’s something most people could do at home unless they are have access to an organic lab.
 

mitoMAN

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Did you have your prolactin levels checked ?
I know that bodybuilders use cabergolin for prolactin suppression.
Maybe it has something to do with your case?
Should explain the sex drive and positive erection at least.
 

Swim15

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Did you have your prolactin levels checked ?
I know that bodybuilders use cabergolin for prolactin suppression.
Maybe it has something to do with your case?
Should explain the sex drive and positive erection at least.
Yep I’ve had them pulled several times (along with many other labs) in the past year and have been totally normal.
 

Swim15

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One of my theories at this point is that Cabergoline acts as an alpha 2 antagonist which would cause a decrease in vascular resistance and increase dilation.

Gonna see if my doc will let me try an alpha blocker to see if any effects are the same.

There are a few small holes in that one but just trying to think through them all.