955 replies to this topic

[Rick Flair]

Has anyone seen Dr. Greens new website? https://alzheimer-prevention.com

Also, here is a new interview.http://roguehealthan...ease-rapamycin/

[VP.]

Has anyone else on Rapamycin seen their max heart rate go up? I've noticed about a 3-4% increase in MHR since I started Rapamycin in Jan 2017.  As far as I can tell MHR should go down as you get older. https://www.scienced...31014155744.htm

 

[smithx]

How do you know what your max heart rate is? Did you do a stress echocardiogram test?

 

Has anyone else on Rapamycin seen their max heart rate go up? I've noticed about a 3-4% increase in MHR since I started Rapamycin in Jan 2017.  As far as I can tell MHR should go down as you get older. https://www.scienced...31014155744.htm

 

[PAMPAGUY]

Max heart rate is determined by subtracting your age from 120. 50 yo = 170 MHR.
Resting heart better measure. Take in morning before getting out of bed. This can change due to medication or aerobic conditioning. Strong heart take less beats to move same volume of blood.

[maxwatt]

You mean the subtract age from 220, not 120. There is some genetic variation, but also max heart rate does not follow that formula in conditioned athletes, even amateurs. For them it can be much higher.  I regularly hit 20 beats over my theoretical max when riding a bike outdoors. 

Edited by maxwatt, 23 February 2018 - 02:37 AM.

[VP.]

I’ve seen 190-191 on some of my peak efforts on a bike. Very difficult to reach unless you are chasing someone or being chased. Before dosing low 180’s would be the highest I would see. I have years of data on my computer. Low 180’s more common now. 57 years old so that’s not too bad. I was just wondering if anyone else is seeing something similar.  

[smithx]

My question was how does he know his max heart rate INCREASED after taking rapamycin?
 
Just doing a calculation won't tell you anything about that. It would have to be the result of a stress test.
 

Max heart rate is determined by subtracting your age from 120. 50 yo = 170 MHR.
Resting heart better measure. Take in morning before getting out of bed. This can change due to medication or aerobic conditioning. Strong heart take less beats to move same volume of blood.

 

Commonly held belief would say that you shouldn't try to go that high, for fear of damaging your heart.
 

I’ve seen 190-191 on some of my peak efforts on a bike. Very difficult to reach unless you are chasing someone or being chased. Before dosing low 180’s would be the highest I would see. I have years of data on my computer. Low 180’s more common now. 57 years old so that’s not too bad. I was just wondering if anyone else is seeing something similar.  [/size]

 

Edited by smithx, 23 February 2018 - 08:12 PM.

[VP.]

I don't recommend you go out and try to find out what your max heart rate is because #1, it's painful and hard.  #2, could be dangerous if you are not well trained. I just know what it is because I monitor my HR over years while "racing" with my friends usually over some steep climbs. 

[ryukenden]

Have been on rapa for 1 year. Mycreatine has dropped from 1.2 to .85. That is really good. BPH also improved. Arthritis in right hip has almost disappeared. 71 yo. male

What dose are you taking over past few months? Do you take any breaks?

[PAMPAGUY]

Take 8 mg weekly. Everyone's TOR signal is different. Men stronger than women. Mouth, lip sores are first indication that your using too much. Cut back. 6 mg weekly seems to be safe dose for most people. No breaks. You could do a break like take a month off every 6 months. Good Luck

[ryukenden]

Take 8 mg weekly. Everyone's TOR signal is different. Men stronger than women. Mouth, lip sores are first indication that your using too much. Cut back. 6 mg weekly seems to be safe dose for most people. No breaks. You could do a break like take a month off every 6 months. Good Luck

Thank you

[QuestforLife]

Take 8 mg weekly. Everyone's TOR signal is different. Men stronger than women. Mouth, lip sores are first indication that your using too much. Cut back. 6 mg weekly seems to be safe dose for most people. No breaks. You could do a break like take a month off every 6 months. Good Luck

It isn't (just) that different peoples' TOR levels are different at a given age, though they will be (slightly). It's that TOR seems to go UP with age! No one in their 40s should be on 6mg/week, more like 2mg IMO. I am guessing, but it might be the rise in inflammation, and/or insulin with age that means as you get older you have to block TOR more heavily.

[XRT doc]

If you are taking rapamycin, it would be great if you could labs, especially Cr  and weight prior to and during treatment. There really needs to be a way of keeping track of users experiences.  

[tintinet]

On rapamycin, mostly 5 mg Q 5 days, for 1 year. No change in weight, blood pressure, blood glucose, triglycerides, cholesterol, etc..

[VP.]

Maybe this belongs in the retailer section but I need to get this out. I bought some TLR rapamycin which came in a very small packet (500 mg). Another poster said the way he took it was to dilute it with alcohol and use an eyedropper to to dose it out. I can say for a fact this did not work for me. My first shipment came from India (the real deal). When that ran out  I thought I would try TLR to save money. With TLR my weight started to rise and I regained half the weight I lost with the real rapamycin within a month. I tried doing doses that I knew in the past would give me mouth ulcers and after repeated tries nothing.That is a big tell. I will get mouth ulcers if I overdose.  One of three things is happening IMO:

   1. The alcohol destroys the activity of rapamycin

   2. It's fake

   3. It's real but very diluted and not really a bargain. 

I have a feeling a lot of the rapamycin that is being sold in bulk powder is fake. That's my opinion anyway. 

[XRT doc]

 

Take 8 mg weekly. Everyone's TOR signal is different. Men stronger than women. Mouth, lip sores are first indication that your using too much. Cut back. 6 mg weekly seems to be safe dose for most people. No breaks. You could do a break like take a month off every 6 months. Good Luck

It isn't (just) that different peoples' TOR levels are different at a given age, though they will be (slightly). It's that TOR seems to go UP with age! No one in their 40s should be on 6mg/week, more like 2mg IMO. I am guessing, but it might be the rise in inflammation, and/or insulin with age that means as you get older you have to block TOR more heavily.

 

 No, i am not sure at all that mtor signalling increases with age, it may decrease in some tissues, but even normal mtor signalling may be harmful in an aged organism

 

http://www.cell.com/...(16)30227-3.pdf

[QuestforLife]

I am almost certain that mTOR signalling rises with age, or atleast the deteriorating health that often comes with age. It makes sense when you consider the whole inflammation-mitochondrial dysfunction-metabolic disregulation that happens with age, but more than that based on the users I know - who vary in age from 40-80, there is a clear trend for older users to take doses that would cause side effects in younger users. Yes the evidence is very sparse at this time, but I believe that is what will be shown.

[XRT doc]

I guess it is symantecs. Review article posted above indicates mtor level are "innappropriate" for advanced age, not elevated (actually decreased in some systems) in absolute terms. Anyway, it would be incredibly helpful and a tremendous service if users at the very least post age, dosage/supplier, weight, creatanine, side effects.     

[Jaris]

I haven't posted here for many months, so I suppose it's time for an update.

 

Age: 60

Pre-condition: Parkinson's Disease

Began taking Rapamycin a year ago (13 months)

Dose: 2 mg Q 3-4 days, so about 4 mg per week. However, I also drink 8-10 oz of grapefruit juice daily, which is expected to effectively increase my dose of Rapa by 3.5 to 4 times.

Note that my dose has changed over the last year, but I've been steady on this dose for about 5 months.

My supplier was a company in India which delivered Biocon Sirolimus blister packs. I have reason to believe that they're legit. DM me if you want to know more.

Other than a few small mouth sores at the beginning, there have been no side effects.

 

When I started, I weighed 168 lb (I'm 5' 7"); Creatine was 1.38.

Now, I weigh 155 lb; creatine as of 2 months ago was .82.

Keep in mind that I have PD, which tends to take the weight off.

Also, I switched from eating chicken almost daily to becoming vegan (though I still have an egg 3x a week).

I'm also very carefully watching my omega6 to omega3 ratio.

 

Really, everything I can think of has improved. I walk/jog 4 miles a day, whereas before I could barely walk (due to PD). Some of that improvement is from better meds for my PD.

My neurologist is beginning to notice that I'm doing much better than his other PD patients. At the very least, my PD symptoms haven't gotten worse. Subjectively, they've gotten a lot better.

But, is it mostly taking Rapamycin, improved PD meds, becoming vegan, or improvements from exercise? I've changed too many things to be sure.

I do NOT take Metformin, unlike most others. My reasoning is that Rapamycin as a PD fighter has some clinical studies backing it up, whereas Metformin+Rapamycin doesn't. I'm in this primarily to deal with my PD.

 

Edited by Jaris, 03 March 2018 - 09:09 PM.

[QuestforLife]

You're a really interesting test case Jaris, because of your Parkinson's. What is interesting about rapamycin is that everyone I know who is on it, from age 40-80 ish has experienced athletic improvements. Most intriguingly often an improvement in maximum heart rate is reported. For me these results can't be explained only by reduced cellular senescence, especially as they seem to occur quite quickly. I expect we are seeing an improvement in ATP output of mitochondria, which are very numerous in heart muscle, so changes would be noticed there first. But mitochondria are also dense in neurons, and Parkinson's involves apoptosis of neurons in one important area of the brain. So please keep us posted about your ongoing results.

One other comment - you'd be much better off doing a larger once weekly dose and dropping the grapefruit juice. Otherwise you just don't know what you are getting. Use an excel spreadsheet with a half life of 65 hours to work out how to get a nice high dose at the top but with a nice low level at the nadir. Otherwise you are playing with fire.

[Jaris]

You're a really interesting test case Jaris, because of your Parkinson's. What is interesting about rapamycin is that everyone I know who is on it, from age 40-80 ish has experienced athletic improvements. Most intriguingly often an improvement in maximum heart rate is reported. For me these results can't be explained only by reduced cellular senescence, especially as they seem to occur quite quickly. I expect we are seeing an improvement in ATP output of mitochondria, which are very numerous in heart muscle, so changes would be noticed there first. But mitochondria are also dense in neurons, and Parkinson's involves apoptosis of neurons in one important area of the brain. So please keep us posted about your ongoing results.

One other comment - you'd be much better off doing a larger once weekly dose and dropping the grapefruit juice. Otherwise you just don't know what you are getting. Use an excel spreadsheet with a half life of 65 hours to work out how to get a nice high dose at the top but with a nice low level at the nadir. Otherwise you are playing with fire.

 

I will consider your advice about dosing. I should mention two things:

1) I take every 4th week off completely.

2) Almost always, the day after I take Sirolimus I feel great - as though I could do almost anything physically. On these days, I often push myself a little further than other days.

[PAMPAGUY]

You're a really interesting test case Jaris, because of your Parkinson's. What is interesting about rapamycin is that everyone I know who is on it, from age 40-80 ish has experienced athletic improvements. Most intriguingly often an improvement in maximum heart rate is reported. For me these results can't be explained only by reduced cellular senescence, especially as they seem to occur quite quickly. I expect we are seeing an improvement in ATP output of mitochondria, which are very numerous in heart muscle, so changes would be noticed there first. But mitochondria are also dense in neurons, and Parkinson's involves apoptosis of neurons in one important area of the brain. So please keep us posted about your ongoing results.

One other comment - you'd be much better off doing a larger once weekly dose and dropping the grapefruit juice. Otherwise you just don't know what you are getting. Use an excel spreadsheet with a half life of 65 hours to work out how to get a nice high dose at the top but with a nice low level at the nadir. Otherwise you are playing with fire.

I read an article a few months ago that tested different grapefruit juices on the amount of chemical in them that makes rapa and other drugs more bioavailable.

All brands were different, and the type of grapefruit.  Also, how much you drink.   So this means that you can never tell if your going to get a 10% increase or 300%. Talk about Russian Roulette.  Sorry looked for article, but could not find it.

[VP.]

 

You're a really interesting test case Jaris, because of your Parkinson's. What is interesting about rapamycin is that everyone I know who is on it, from age 40-80 ish has experienced athletic improvements. Most intriguingly often an improvement in maximum heart rate is reported. For me these results can't be explained only by reduced cellular senescence, especially as they seem to occur quite quickly. I expect we are seeing an improvement in ATP output of mitochondria, which are very numerous in heart muscle, so changes would be noticed there first. But mitochondria are also dense in neurons, and Parkinson's involves apoptosis of neurons in one important area of the brain. So please keep us posted about your ongoing results.

One other comment - you'd be much better off doing a larger once weekly dose and dropping the grapefruit juice. Otherwise you just don't know what you are getting. Use an excel spreadsheet with a half life of 65 hours to work out how to get a nice high dose at the top but with a nice low level at the nadir. Otherwise you are playing with fire.

I read an article a few months ago that tested different grapefruit juices on the amount of chemical in them that makes rapa and other drugs more bioavailable.

All brands were different, and the type of grapefruit.  Also, how much you drink.   So this means that you can never tell if your going to get a 10% increase or 300%. Talk about Russian Roulette.  Sorry looked for article, but could not find it.

 

I agree about grape fruit juice but for some money and access to rapamycin is an issue. The randomness of grape fruit/drug interactions can be ameliorated by using a set about (1.5 cups) of the same brand in a consistent manner. The more bitter the juice the greater the effect.

Edited by VP., 04 March 2018 - 08:13 PM.

[poonja]

I  squeeze one fresh grapefruit and drink and then take my raps 3-4 hours later.

[QuestforLife]

The whole point of using intermittent rapamycin dosing is to get a high Maximum to knock down mTORC1, but a nice low Minimum to avoid knocking down mTORC2. So, for example my dose of 2mg a week assuming a 65 hour half life gives you a Maximum (after repeated dosing) of 2.4mg and a Minimum of 0.4mg. Alan Green takes 6mg a week, so that gives you a Maximum of 7.2mg and a Minimum of 1.2mg.

 

Grapefruit juice will not improve the Maximum, but will raise the Minimum by some unknown amount, increasing the chance of side effects. It's even worse if you dose more than once per week. I initially trialled rapamycin with grapefruit juice, and after the initial acclimatisation suffered no, or very rare mouth sores. But after a while (around 5 or 6 months) I started suffering painful, deep acne on my back.  I eventually worked out it was the rapamycin, and missing a week or two completely resolved the symptoms. I'd probably reduced the turnover of cells in my skin, and on my back that resulted in cystic acne. Since I've restarted treatment without grapefruit juice there have been no re-occurrence of the symptoms.

 

https://www.ncbi.nlm...pubmed/16781309

[XRT doc]

I haven't posted here for many months, so I suppose it's time for an update.

 

Age: 60

Pre-condition: Parkinson's Disease

Began taking Rapamycin a year ago (13 months)

Dose: 2 mg Q 3-4 days, so about 4 mg per week. However, I also drink 8-10 oz of grapefruit juice daily, which is expected to effectively increase my dose of Rapa by 3.5 to 4 times.

Note that my dose has changed over the last year, but I've been steady on this dose for about 5 months.

My supplier was a company in India which delivered Biocon Sirolimus blister packs. I have reason to believe that they're legit. DM me if you want to know more.

Other than a few small mouth sores at the beginning, there have been no side effects.

 

When I started, I weighed 168 lb (I'm 5' 7"); Creatine was 1.38.

Now, I weigh 155 lb; creatine as of 2 months ago was .82.

Keep in mind that I have PD, which tends to take the weight off.

Also, I switched from eating chicken almost daily to becoming vegan (though I still have an egg 3x a week).

I'm also very carefully watching my omega6 to omega3 ratio.

 

Really, everything I can think of has improved. I walk/jog 4 miles a day, whereas before I could barely walk (due to PD). Some of that improvement is from better meds for my PD.

My neurologist is beginning to notice that I'm doing much better than his other PD patients. At the very least, my PD symptoms haven't gotten worse. Subjectively, they've gotten a lot better.

But, is it mostly taking Rapamycin, improved PD meds, becoming vegan, or improvements from exercise? I've changed too many things to be sure.

I do NOT take Metformin, unlike most others. My reasoning is that Rapamycin as a PD fighter has some clinical studies backing it up, whereas Metformin+Rapamycin doesn't. I'm in this primarily to deal with my PD.

 

Thanks for sharing info. Welcome others to share their numbers. Regarding doses of rapamycin. In the Mannick study, they used weekly doses of affinitor whose half life is around 37 hours.  Weekly dose,of rapamycin is more aggressive, given that rapamycin has double the half life.. I would think twice about doing anything to effectively prolong half life of rapamycin. The whole point of intermittent dosing is to achieve a low nadir to lessen the potentially harmful affects of rapamycin on mtor2. It may not be a bad idea to take one week off a month to clear it.

 

Edited by XRT doc, 05 March 2018 - 05:56 PM.

[Nate-2004]

The whole point of using intermittent rapamycin dosing is to get a high Maximum to knock down mTORC1, but a nice low Minimum to avoid knocking down mTORC2. So, for example my dose of 2mg a week assuming a 65 hour half life gives you a Maximum (after repeated dosing) of 2.4mg and a Minimum of 0.4mg. Alan Green takes 6mg a week, so that gives you a Maximum of 7.2mg and a Minimum of 1.2mg.

 

Grapefruit juice will not improve the Maximum, but will raise the Minimum by some unknown amount, increasing the chance of side effects. It's even worse if you dose more than once per week. I initially trialled rapamycin with grapefruit juice, and after the initial acclimatisation suffered no, or very rare mouth sores. But after a while (around 5 or 6 months) I started suffering painful, deep acne on my back.  I eventually worked out it was the rapamycin, and missing a week or two completely resolved the symptoms. I'd probably reduced the turnover of cells in my skin, and on my back that resulted in cystic acne. Since I've restarted treatment without grapefruit juice there have been no re-occurrence of the symptoms.

 

https://www.ncbi.nlm...pubmed/16781309

 

I could swear that in one of these Rapamycin threads someone posted a link to a study that determined intermittent rapamycin for the purpose of avoiding mTORC2 inhibition was not enough to inhibit mTORC1 to any effective degree but now after scouring all the posts and using the search tool I can't find where that was or recall who posted it. It was *the* post that turned me off of rapamycin.

 

Can someone point me to a good Rapa vendor on Alibaba or wherever?

Edited by Nate-2004, 05 March 2018 - 06:32 PM.

[XRT doc]

The best evidence for this is the mannick study: 219 pts in australia randomized to different dosing of rapamycin

https://www.ncbi.nlm...pubmed/25540326

[Michael]

 

The whole point of using intermittent rapamycin dosing is to get a high Maximum to knock down mTORC1, but a nice low Minimum to avoid knocking down mTORC2. So, for example my dose of 2mg a week assuming a 65 hour half life gives you a Maximum (after repeated dosing) of 2.4mg and a Minimum of 0.4mg. Alan Green takes 6mg a week, so that gives you a Maximum of 7.2mg and a Minimum of 1.2mg.

 
I could swear that in one of these Rapamycin threads someone posted a link to a study that determined intermittent rapamycin for the purpose of avoiding mTORC2 inhibition was not enough to inhibit mTORC1 to any effective degree but now after scouring all the posts and using the search tool I can't find where that was or recall who posted it. It was *the* post that turned me off of rapamycin.

 

 
I expect that you're thinking of a series of posts from me, most notably this one (followed up here and here; but I'd suggest looking at this first, to understand the evidence base behind those).

 

At absolute, bare minimum, people should be investing in therapeutic drug monitoring: between genetic variability and other factors, even getting to levels that might plausibly work without overshooting is a crapshoot.
 

The best evidence for this is the mannick study: 219 pts in australia randomized to different dosing of rapamycin
https://www.ncbi.nlm...pubmed/25540326

As already pointed out by others, that study used everolimus, not rapamycin — a different drug with different pharmacokinetics. It's useful, but the best evidence on using it as an anti-aging drug is still the rodent data, plus human PK data.

[XRT doc]

Everolimus is a very very similar drug to rapamycin, except for the half life. I do this for a living. Rodent studies in medicine often dont tanslate  into human beings - they are not as compelling as randomized data on 200+ humans.