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Rapamycin Personal Experience Thread

rapamycin mtor rapamune sirolimus emcure everolimus

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#1 resveratrol_guy

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Posted 22 November 2019 - 02:39 PM


I think it's time that someone created this thread. We have lots of discussion of the other aspects of this drug, but nothing dedicated to personal experience. A lot of informative anecdotes are mixed in with threads concentrating on other aspects of rapamycin. For example:

https://www.longecit...opinion-article
https://www.longecit...ave-you-noticed
https://www.longecit...pamycin-therapy
https://www.longecit...lantoin-synergy

I don't log in often, but the changes I've noticed from this drug have been profound enough to warrant a public report.

First of all, we have Rapamune, Sirolimus, and Emcure, sorted descending by price. I've taken all of them. On the latter 2, I experienced a noticeable boost in appetite, and gained weight, mostly as visceral fat. I stopped all rapamycin for several months before starting Rapamune a month ago. The only difference is that I had been taking 3 mg/week of the latter 2, as compared to 4 mg/week of the former. I suspect that Sirolimus is real, and perhaps Emcure as well, but somehow Rapamune is less contaminated in a way which matters.

At 45, I now have the body composition of a mouse in a calorie restriction study. My weight is down to 67 kg at 186 cm. This has been through no effort whatsoever on my part. I drink a liter of juice (typically, orange) for breakfast, munch through an all-you-can-eat salad bar until I'm full, and have the odd banana, dark chocolate bar, or pack of nuts or seeds every day. I studied the ketogenic Bredesen protocol for Alzheimer's prevention, prior to throwing the book out the window and heading down to the salad bar. I don't particularly watch my intake of sugar or sodium, and the only thing I actively police is my protein intake, and above all my intake of animal protein (read: methionine). In a nutshell, I'm trying to fake out the epigenetic profile of an individual with Laron syndrome. (If I were really hardcore, or had cancer, I might take pegvisomant, but I'm not there yet.) In other words, minimize IGF1. Quite the opposite of a ketogenic diet with ample protein allowance.

I do take berberine (which according to one study is superior, gram-for-gram, to metformin), fish oil (because alpha linoleic acid is hard to convert to DHA and EPA), zinc (for unrelated reasons involving synaptic glutamate suppression), vitamin D, taurine (thanks, Turnbuckle), K2 (to prevent atherosclerosis), carbon 60 olive oil (with a few weeks skipped here and there), moringa oleifera and cat's claw (sporadically, for killing cancer cells, especially after pollution exposure), shiitake-maitake pills (sporadically, for visual memory maintenance), and random bursts of Longvida lipidated curcumin. I also take Candesartan to lower blood pressure by suppressing angiotensin 2, and have done so since 2018. But, for all that, it's only after taking rapamycin, and Rapamune in particular, that my body weight collapsed and my episodic memory went into high gear.

I could go on and on about my history of blood tests, but there are really only 2 things that stand out, post-rapamycin. One is that my blood sugar has increased from the 70s during keto to 85. This is consistent with type 0 diabetes (courtesy of mTORC2). If I have to become diabetic in order to live like this, so be it. To each his own. (Everolimus, a rapamycin analog, might fix this, if it ever gets cheap enough.)

The other thing is a collapse in red cell distribution width (RDW), which I mentioned previously but has now persisted for 15 months:

1/9/2015 13.3
1/15/2015 13.5
3/6/2015 14.0
11/18/2015 14.9
12/31/2015 14.9
2/19/2016 13.6
3/15/2016 14.9

Staye on a low-protein ("lowpro") diet for a month.

6/11/2018 14.2

Stayed on Sirolimus for 10 weeks, 3 mg/week.

8/20/2018 12.7

Stayed on Rapamune for 4 weeks, 4 mg/week.

11/19/2019 12.8

This is despite the first 7 measurements representing various different dietary modalities; nothing mattered until I started rapamycin.

RDW, by the way, isn't a measure of the width one's red cells. It's a measure of the width of (the distribution of (the widths of one's red cells)). In my view, this value repesents the strictness with which one's marrow is sticking to the red cell manufacturing specification. Just like with a tire manufacturer, the less deviation in the size that there is from one sample to the next, the better. It's thus a measure of quality control. Low RDW may also imply that red cells are receiving less damage due to fewer interactions with pathological aggregates in the blood. Reducing protein intake had essentially no effect, after accounting for the existing noise level in the data. It was only rapamycin which precipitated the collapse within a matter of weeks. I suppose one could also interpret these numbers as red cells surviving for shorter periods of time due to accerlated release from the marrow, but if that were the case, then I would expect to see reduced lifespans in animals due to excessive replication stress in the hematopoietic niche.

But only Rapamune -- neither Sirolimus nor Emcure -- caused the rapid weight loss and very noticeable improvement in visual episodic memory. My only source of animal protein is eggs, of which I consume 2 or 3 per week. My memory, and certainly my sleep quality, was distinctly inferior on a ketogenic diet without rapamycin -- a diet which was rich in the very nutrients that neurons need. Part of this is no doubt attributable to my inability to sleep when eating foods rich in glutamic acid (long story, probably due to a problem with zinc transporter 3). And for the record, I eat no processed food whatsoever except for olive oil, dark chocolate, and occasionally butter. (I also consume yoghurt, but only for purposes of restoring gut bacteria after a course of antibiotics or a bout of digestive issues, both of which being rare.) And no grain products except for those composed of buckwheat, barley, quinoa, or rice, and even then, in handful-per-day quantities on average. I nonetheless have no fear of potatoes, sweet potatoes, fruit, or beans of any variety. But pasta? Forget it.

But surely all this fructose is causing my cholesterol level to explode! Let's see: LDL is 90 and HDL is 70. Meh. (Let me emphasize that my olive oil habit knows no restraint!)

And finally, at the same appointment at which the latest blood work was done, the nurse took my blood pressure. I hadn't taken my Candesartan that morning just to see what would happen. It ended up at 104/65, which I saw for myself on the hospital's digital meter. A month after my stroke in 2013, at precisely the same hospital, it had been in the 160s.

Today, life is pretty much like it was prior to the stroke. Even my tinnitus, which resulted from it, is rather quiet, although it's still present. Maybe this is all due to something else, but in fact the past few weeks have been stressful with travel and, in the past few days, a low-grade virus of some sort. And yet, my visual memory is as good as it was many years ago. I'm profoundly thankful for all the help I've received, from so many people, over several years, which, against all odds, has brought me to this point.
 


Edited by resveratrol_guy, 22 November 2019 - 03:15 PM.

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#2 adamh

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Posted 23 November 2019 - 03:21 PM

Interesting. I have been on it only about 10 weeks. No weight loss at all and appetite seemed up. I started on berberine and it may have helped with the appetite possibly but still no weight loss. Had a mouth sore and a rash the first few weeks. Rash went away after pausing a couple weeks. I've been taking 1/4 tab of aas 5m tabs per week.

 

On the positive side my arthritis does not bother me as much. The discomfort came back when I paused the rapa but went away again after I got back on it. Seems like a real benefit. Also my muscles seem firmer, I might be slightly stronger but I have not taken measurements to verify so its just subjective. 

 

Its hard to say if my cognition is better, certainly not worse. Sleep does not seem better but maybe a little, I don't wake during the night and not be able to go back to sleep as happened occasionally before. So it might be a bit better but still equally hard to fall asleep, my main sleep problem. 

 

I recently bought a gram of rapamycin from china. It might be bunk but the company had good reviews. I just started on it this week. Its hard to say if it has done anything, my appetite might be a little lower since then but too soon to say. It might be better than what I got from aas which they admit was underdosed. Odd that I got the side effects if it was only about 0.8 mg like they say. Even 1.25 mg a week is a low dose so I'm surprised I had as much results as I did. This new stuff might be better than the aas and was much cheaper. If it knocks out my appetite and drops some pounds I will be very satisfied. I will know in a week or two if its real and how it affects me

 

So very preliminary results and mostly subjective. I have had no lab tests but subjectively I feel better. The pain reduction on arthritis alone is worth it and more benefits may come with longer use. I thought my report might add a bit particularly for those who have not tried it and wonder about how fast it works etc.


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#3 resveratrol_guy

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Posted 24 November 2019 - 03:57 PM

Well now that you mention it, I've previously noticed that what little joint pain I tend to have gets erased by my weekly dose of Rapamune. It happens within an hour or so -- many times faster than the longterm effects. The pain stays gone for most of the week.

Physical strength is an interesting question. I haven't measured it, unfortunately. For what little it's worth, it does surprise me how much heavy luggage I can carry with my wimpy teenage physique. Maybe this has to do with mitobiogenesis. Hopefully someone will study this properly.

AAS what? Is that a brand? If you can afford it, I would suggest starting with the known-good stuff (Rapamune), then perhaps working your way down over several months to progressively dodgier brands, until you find the cheapest source that performs as expected. I probably would never have received all these benefits, had I stayed on Sirolimus. By the way, it's from Dr. Reddy, and Indian company with some history of FDA sanctions.

The other issue is dosage. To be fair, I don't recall ever having taken 4 mg of Sirolimus in one go, so perhaps the effects would have been similar to those of Rapamune, had I done so. I doubt that, but on the other hand, we have compounds such as resveratrol, where the nature of the effects, and not merely the magnitude, varies with dose.

I was due for another 4 mg today, but haven't bothered because I seem to be getting over a cold, so I need to have some vigorous immune activity. I'm looking forward to getting back on it, particularly since I noticed that I was slightly more forgetful today.

Speaking of which, I've had to compose a lot of emails recently, and it's objectively clear that I'm leaving out fewer words. For example, I would write "I will go the park" when I meant "I will go to the park" just because my brain is working ahead of the text, and I guess the language pipeline drops words here and there because it forgets what I'm currently typing. (I know this because I always proofread before sending, so I'm quite used to my historical performance in this regard. Turnbuckle mentioned the same sort of issue in his Dissolve and Detoxify Alzheimer's discussion, which does not include rapamycin.) Granted, the problem isn't completely gone, as you can see above: "the width one's red cells".

The other objective measure that sticks out in my experience is parentheses matching. I do a lot of math work, so I might need to type something like:

   z = (x + 4 * (3 + log (y + 1)) + 7) * 5

but I'll often end up with something like:

   z = (x + 4 * (3 + log (y + 1) + 7) * 5

because I just forgot which parentheses nesting level I was working in. This never escapes my notice, because such malformed expressions trigger compilation errors. It seems to me that I have trouble at deeper levels now, than previously, on account of encountering fewer such errors. The working memory requirements for this skill are similar to those needed to avoid dropping words.

1.25 mg/week is a very low dose. It's hard to imagine that even being worth the trouble and expense. Granted, dose calibration is a very protracted process indeed, as the effects are so latent. Small changes can precipitate large effects, as you found with your rash. Potentially, one could even end up dying prematurely due to an overly restrained immune system.

And, finally, I'm thinking of breaking up my 4 mg into 2 x 2 mg or 4 x 1 mg, more or less equally spaced in time. I think there are as many theories in favor of doing so, as against it, and I just need to find out. Ideally, I just want stable effects over time, but I'm leery of developing tolerance, if such a thing exists with rapamycin.
 


Edited by resveratrol_guy, 24 November 2019 - 04:07 PM.


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