955 replies to this topic

[Zisos]

So with the admittedly low 2.5mg (1/4 of 10mg) dose and shorter half-life of everolimus how do you plan to achieve any significant effects?

If anything, one needs to take bigger, not smaller, dose than sirolimus (whose "typical" dose is 6mg) to achieve similar results.

 

I have no idea which is the most appropriate dose. It might even be person specific.  I just feel safer taking a small dose, to begin with. Depending on the effects (positive or negative), I might increase it.  Most likely I will keep it at 2.5mg per week for 3-6 months. After that, I will decide if there is merit in increasing or decreasing it.

[aribadabar]

I have no idea which is the most appropriate dose. It might even be person specific.  I just feel safer taking a small dose, to begin with. Depending on the effects (positive or negative), I might increase it.  Most likely I will keep it at 2.5mg per week for 3-6 months. After that, I will decide if there is merit in increasing or decreasing it.

 

 At 2.5mg once a week I expect zero effects as it is too low a dose to exert anything perceptible, positive or negative. Keeping this for months, it would be a waste of time and money IMO.

[QuestforLife]

Would you mind sharing your age? 15mg of sirolimus seems pretty high in my opinion.

Sorry for the slow reply.

I'm 40 and my usual weekly dose is 2mg. I hadn't taken rapamycin in around a year however, and there may be some benefit in larger, more occasional doses.

[Chris Pollyanna]

A new study in pre-print shows that a rapalog RAD001, which I believe is Everolimus, administered at the human equivalent dose of 0.5mg, counteracts muscle loss in ageing:

 

Inhibition of mTORC1 signaling in aged rats counteracts the decline in muscle mass and reverses multiple parameters of muscle signaling associated with sarcopenia

https://www.biorxiv....1/591891v1.full

 

Quote:

 

"To determine if we were able to ameliorate age-related muscle loss with rapalog treatment, we measured the wet weights of the tibialis anterior (TA), plantaris, gastrocnemius, and soleus muscles. Consistent with previous data, all muscles, except for the soleus muscle from 24-month old vehicle treated rats had considerably reduced mass compared to 9-month old rats (Fig. 2A). RAD001 treatment did not lead to further atrophy in any of these muscles. On the contrary, rapalog appeared to be protective for aged animals, and reduced extensive muscle mass loss. Plantaris and TA muscles showed a surprising increase in mass, with the TA muscle being significantly increased compared to vehicle treated animals (Fig. 2A). Our data provide strong evidence that when administered to sarcopenic rats, low dose rapalog treatment is not detrimental to muscle mass. Rather, it allows for animals to maintain or gain muscle."

Edited by Chris Pollyanna, 26 April 2019 - 03:46 PM.

[koschei]

Hey , I’m also interested in Rapamycin.
The most interesting article I found was this one:

https://www.research...lication_detail

[VP.]

New Rapamycin anti aging pathway independent of mTOR. 

https://www.medicaln..._medium=twitter

 

For many years, scientists have believed that rapamycin exerts most of its effect by blocking the appropriately-named mechanistic target of rapamycin (mTOR). However, they also suspected that the drug might work through more than just this cell signaling pathway.

Now, by uncovering a second cell target for rapamycin, a recent study offers valuable insights into the drug's potential as a neuroprotective, anti-aging agent.

The second target is a protein called transient receptor potential mucolipin 1 (TRPML1). Targeting TRPML1 appears to spur a recycling process that stops cells clogging up with waste material and faulty proteins.

Accumulation of faulty proteins in cells is a characteristic of aging. It is also a hallmark of Alzheimer's, Parkinson's, and other neurodegenerative diseases.

 

The study is the work of researchers at the University of Michigan in Ann Arbor and the Zhejiang University of Technology in China. They report their findings in a recent PLOS Biology paper.

[VP.]

BOOM! Strait from Steve Horvath: 

Rapamycin retards epigenetic ageing of keratinocytes independently of its effects on replicative senescence, proliferation and differentiation

 

The advent of epigenetic clocks has prompted questions about the place of epigenetic ageing within the current understanding of ageing biology. It was hitherto unclear whether epigenetic ageing represents a distinct mode of ageing or a manifestation of a known characteristic of ageing. We report here that epigenetic ageing is not affected by replicative senescence, telomere length, somatic cell differentiation, cellular proliferation rate or frequency. It is instead retarded by rapamycin, the potent inhibitor of the mTOR complex which governs many pathways relating to cellular metabolism. Rapamycin, however, is also an effective inhibitor of cellular senescence. Hence cellular metabolism underlies two independent arms of ageing – cellular senescence and epigenetic ageing. The demonstration that a compound that targets metabolism can slow epigenetic ageing provides a long-awaited point-of-entry into elucidating the molecular pathways that underpin the latter. Lastly, we report here an in vitro assay, validated in humans, that recapitulates human epigenetic ageing that can be used to investigate and identify potential interventions that can inhibit or retard it.

In summary, the observations above represent the first biological connection between epigenetic ageing and rapamycin. These results for human cells add to the evidence that extension of life, at least by rapamycin, is indeed accompanied by retardation of ageing. These observations also suggest that the life-extending property of rapamycin may be a resultant of its multiple actions which include, but not necessarily limited to suppression of cellular senescence [36–38,48] and epigenetic aging, with the possibility of augmentation of cellular proliferative potential.

 

https://www.aging-us...cle/101976/text

 

Edited by VP., 05 June 2019 - 03:46 AM.

[QuestforLife]

BOOM! Strait from Steve Horvath: 

Rapamycin retards epigenetic ageing of keratinocytes independently of its effects on replicative senescence, proliferation and differentiation

 

The advent of epigenetic clocks has prompted questions about the place of epigenetic ageing within the current understanding of ageing biology. It was hitherto unclear whether epigenetic ageing represents a distinct mode of ageing or a manifestation of a known characteristic of ageing. We report here that epigenetic ageing is not affected by replicative senescence, telomere length, somatic cell differentiation, cellular proliferation rate or frequency. It is instead retarded by rapamycin, the potent inhibitor of the mTOR complex which governs many pathways relating to cellular metabolism. Rapamycin, however, is also an effective inhibitor of cellular senescence. Hence cellular metabolism underlies two independent arms of ageing – cellular senescence and epigenetic ageing. The demonstration that a compound that targets metabolism can slow epigenetic ageing provides a long-awaited point-of-entry into elucidating the molecular pathways that underpin the latter. Lastly, we report here an in vitro assay, validated in humans, that recapitulates human epigenetic ageing that can be used to investigate and identify potential interventions that can inhibit or retard it.

In summary, the observations above represent the first biological connection between epigenetic ageing and rapamycin. These results for human cells add to the evidence that extension of life, at least by rapamycin, is indeed accompanied by retardation of ageing. These observations also suggest that the life-extending property of rapamycin may be a resultant of its multiple actions which include, but not necessarily limited to suppression of cellular senescence [36–38,48] and epigenetic aging, with the possibility of augmentation of cellular proliferative potential.

 

https://www.aging-us...cle/101976/text

 

 

Far be it for me to correct the great Steve Hovath, but 'the observations above represent the first biological connection between epigenetic ageing and rapamycin' is not correct.

 

Rapamycin was shown to slow methylation back in 2017. See: 'Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment.'

 

https://genomebiolog...3059-017-1186-2

[Guest]

I have to opportunity to buy rapamycin (or better everolimus) for an affordable price, but appreciate some feedback.

 

 

Due to unrelated reasons I'm visiting India at the moment and figured, that I could try out everolimus. Every pharmacy will accept orders for it, no question asked (even though legally most drugs require prescriptions even in India). The price is about 1 US-Dollar per 1 mg. I'm well aware that studies in mice administer rapa daily - a dosing scheme, that is possibly going to be detrimental in humans. Though even intermittent dosing of 5 mg might have a positive effect proportional to efforts (time/money) invested.

 

 

2 Questions.

 

 

1. Study bias

 

All studies on everolimus that I found about its major advantages - shorter half time, better bioavailability, better tissues distribution - are done by people directly financially connected to Novartis. So I'm a little skeptical if it's really a better drug than original rapamycin. Are there studies about it's positive effects, that are not done by people with massive conflicts of interest? Is it used in animal studies?

 

 

2. More generally - I'm uncertain about the delivery

 

according to this review study:

"Inhibition of the Mechanistic Target of Rapamycin (mTOR)–Rapamycin and Beyond"

http://perspectivesi.../5/a025924.full

 

The oral administration of rapa in mice studies faced problems, that could be solved by coating rapa in a polymer, quote:

"The ITP was able to solve the technical challenges of delivering rapamycin to mice in chow by microencapsulating it in an enteric polymer to protect rapamycin from the acidic environment of the stomach. In 2009, the ITP published the first of several manuscripts on the effects of rapamycin on mice, showing that rapamycin could extend the life span of genetically heterogeneous HET3 mice when treatment began at 20 mo of age."

 

and the original study noted:

 

"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice"

https://www.ncbi.nlm...les/PMC2786175/

Quote: "Rapamycin was microencapsulated by Southwest Research Institute, using a spinning disk atomization coating process with the enteric coating material Eudragit S100. This coating increased the fraction of rapamycin that survived the food preparation process by 3- to 4-fold, and protected the agent from digestion in the stomach." 

 

As far as I can tell, the pills destined to be consumed by humans lack the coating. Obviously they are still effective, give that they are effectively employed in organ-transplant patients. But is this daily dosing of 5mg to 50mg really on the same level (scaled for different metabolism) - especially blood level - as is achieved in the mice studies driving all the hype about rapamycin? And can I just "bite a pill in half" if I only require 50% of the doses without compromising delivery? Could just 5 mg of uncoated rapamycin every monday even remotely get the same life extension effect as the equivalent of 50mg daily in mice?

[PAMPAGUY]

The first thing you want to do is state your age and sex because without that there is no way to tell how strong of a TOR signal you have.  Women have lower TOR and as such such require less rapa.  I have been taking rapa for 2 1/2 years at 6 mg weekly with metformin daily.  I am 73 yo.   No side effects, so dont over think this.  I have a strong TOR signal that goes up as you age.  60 is considered the minimum age to start although some people start in there 40's or 50's at low dose 2-3 mg weekly.  Up to age 60 your TOR signal is relative low.  High TOR = bad ageing.  I believe rapamycin is as good everolimus, and so do the docs.

No problem ever having sirolimus delivered to US from India.  I believe that 4 mg at 60, 5 mg at 65, 6 mg at 70+ is an educated estimate to start.

 

Check out rapamycintherapy.com for lots of info and cites from Dr. Green.  Also, the best human study which talks about the % of inhibition of TOR on dosage is Mannick study.     Google:  mTOR inhibition improves immune function in the elderly

                             Joan B. Mannick, 1 * Giuseppe Del Giudice, 2 Maria Lattanzi, 2 Nicholas M. Valiante, 3

                             Jens Praestgaard, 4 Baisong Huang, 1 Michael A. Lonetto, 1 Holden T. Maecker, 5 John Kovarik, 6

                             Simon Carson, 7 David J. Glass, 1 Lloyd B. Klickstein 

[Guest]

The Mannick-paper is really interesting - though it should be noted, that it's still paid for by Novartis.

 

 

To make sense of the pathway outlined in that study, I found this paper rather helpful:

 

"Protein Phosphorylation as a Key Mechanism of mTORC1/2 Signaling Pathways"

https://www.intechop...naling-pathways

 

 

If the numbers hold true, even small amounts of 0,5 mg of Rapamycin can inhibit mTORC1 activity by (up to) 38%. 5 mg up to 50%. Is this enough - particularly given that people for life extension take it once every 5-7 days?

 

 

Here I'm referencing the Kaeberlein paper:

"Rapamycin and aging: When, for how long, and how much?"

https://www.ncbi.nlm...les/PMC4401992/

 

and the 2009 lifespan study. To give a better picture of the required amount, let's look into the 2009 lifespan paper linked in my previous post. Quote:

"To document biochemical effects of rapamycin at the dose used for the lifespan studies, we evaluated the phosphorylation status of ribosomal protein subunit S6 (rpS6), a target substrate of S6 kinase 1 in the mTOR signalling pathway20, in visceral white adipose tissue (a sensitive indicator of mTOR inhibition by rapamycin treatment in vivo). Figure 3B shows that rapamycin reduced phosphorylated rpS6 4–5 fold when fed from 270 to about 800 days of age. Blood levels of rapamycin in the treated mice were equivalent in males and females, between 60 and 70 ng/ml."

 

 

There are 3 measures for rapamycin intake and effect in the paper:

 

1. food intake: 14 ppm concentration in food (2.24 mg/kg/day)

 

2. blood level: 60-70 ng/ml

 

3. phosphorylation: "reduced 4-5 fold"

 

 

Some illustrative numbers humans for comparison:

 

1. 2,24 mg/kg is - for a 70 kg person and allometric scaling - about 20-25 mg of Rapa per day. The best effects on longevity in mice in a later study even used the people-equivalent of about 70 mg of Rapa per day.

 

 

2. according to this study for effectiv blood level in transplant patients:

 

"Sirolimus: the evidence for clinical pharmacokinetic monitoring."

https://www.ncbi.nlm...pubmed/16029064

 

the desired level is 12-20 microg/liter (that is 12-20 ng/ml). Desired refers to minimizing side effects and still achieving immuno-supression; not maximising the immune effect.

 

 

3. Decrease "4-5 fold" is an imprecise expression. I'm assuming, that activity is reduced to 20%-25% of it's original activity - so 75%-80% reduction in mice. 5 mg according to Mannick can lead up to about 50% reduction.

 

 

 

By food-intake and blood-level, taking 5 mg every couple of days clearly is very far apart from anything used in mice to obtain life extension effects. Even in transplant patients blood levels are far short of levels seen in life extension mice. The phosphorylation numbers aren't quite as bleak. 50% remaining activity in man vs. 20% remaining in mice doesn't sound all too bad. If this is the main driver. But again - 5 mg aren't taken daily, so suppression to 50% is not 24/7 (the 20% in mice is).

 

I still wonder, that the mice didn't complain about side effects - ulcers/sores and rashes at all places - given that many humans tend to experience these at just 5 mg every 5-7 days. Let alone 25 mg every day. It might be, that mTOR is simply heavily upregulated in mice (i.e. fast development, many kids and die soon) compared to humans... so mTOR can be suppressed to a larger extend and not cause side effects. This of course could mean, that the life extension as seen in mice is not translatable, as humans have less mTOR activity as a baseline.

 

 

Given these numbers - especially if Rapa just corrects an overactive mTOR in mice (so humans are already good to go) - a 5 mg regime every monday of course likely falls (far?) short of the life extension benefits seen in mice. Taking it daily is not an option either.

 

 

Still undecided if it's reasonable to take it. But if everolimus got indeed less side effects I guess I give it the benefit of the doubt.

 

 

Damn.... just imagine that Rapa really just "corrects" overactivity in mice.... and in addition humans only obtain reduction to 50% for 1-2 days instead of 20% for 24/7... we really need those SENS-interventions.

Edited by Guest, 01 July 2019 - 12:15 PM.

[PAMPAGUY]

Remember:  .5 mg dose was "daily" =38%.  5 mg(once weekly) = more than 50%.  20 mg(once weekly) = complete inhibition.  20 mg = many side effects.  None on other doses.  It is all about the 1/2 life.  You must give the rapa with a 60-70 hour 1/2 life enough time to get to the nadir.  (almost all out of your system before next dose)  If not, then it builds up in system and causes a lot of troubles. (want that in kidney rejection - daily doses)  In order to not trigger TOR 2 you must walk a tight rope between enough TOR 1 inhibition without triggering TOR 2 side effects.

 

At 5-7 mg once weekly, it is a good medium in my personal experience and also in others.  6 mg. = appx. 65-75% inhibition.  Slows down SENS substantially. (zombie mitochondria) until a true SENS treatment is ready.  

[Guest]

I don't doubt you personal experience.

 

Still: mice seem to tolerate a manifold higher intake/blood level of Rapa than humans are able to - and it's those doses that lead to the headline-life-span results reported. Moreover those insane doses in mice don't even lead to complete inhibition of mTor.

 

 

What is your take on this?

 

 

Do mice just not respond well to Rapa and need a massively higher dose? That would be at odds with the mTor-Rapa-connection being evolutionary highly preserved and certainly among mammals.

 

Or do mice have a much higher baseline-Tor activity? Think of an anabolic life cycle: grow fast (sexual maturity at about six weeks of age), pump out 100 kids and die after 2 years. In that case the mice results might not be translatable - certainly not using 5 mg every 7 days - as human Tor1 is already at a very inactive level comparatively.

 

 

 

You could compare it with caloric restriction: mice are able to tolerate a much higher level of CR than people (or monkeys) are able to - and get their best life extension effects on that.

 

 

 

 

I'll probably still try it out... though it likely isn't 20% life extension, but maybe 5%.

Edited by Guest, 02 July 2019 - 08:35 PM.

[PAMPAGUY]

I have taken 25 mg. once monthly also without side effects. (Chronic dose required)  It is the 2nd dose that gives you trouble if you have not waited for rapa to clear out of your system.  Many believe that the mTor inhibition lasts a long time after stopping rapa.  Tried this for weight reduction. (to reset weight set point in brain).  I have gone back to 6 mg. weekly, because my weight is where I want to be.  Lost 5 kg.  71 in,  165 lbs

73 yo male

 

Single Rapamycin Administration Induces Prolonged Downward Shift in Defended Body Weight in Rats

https://www.ncbi.nlm...les/PMC4008417/

[Valijon]

I took 1mg rapamycin every Saturday night for 3 weeks. I didnt alter anything else. By the third week I was getting fatigue and muscle pain. This wasnt from working out. This was pain that would just start up out of the blue. In my very early 40s and a healthy male that works out 5 days per week. I discontinued therapy after I got bruised at work. The bruise was slow to heal and this normally never happens. I am considering 0.5mg once per week in the future. It seems MTORC1 is less active than I originally believed in younger people.

[PAMPAGUY]

From Fighting Aging:  Newletter July 29,  2019.

 

https://www.fightagi...or-of-lifespan/

Edited by PAMPAGUY, 28 July 2019 - 05:12 PM.

[Andey]

Mikhail Blagosklonny wrote an article in Nature on connection between rapalogs, fasting and insulin resistance. I think it could be of interest here.

He thinks of rapamycin in terms of starvation mimetic.

https://www.nature.c...1419-019-1822-8

[PAMPAGUY]

First human study proving that Rapamycin reverses ageing via epigenetic clocks.  Major break-though.              https://www.ncbi.nlm...les/PMC6555449/

 

Rapamycin retards epigenetic ageing of keratinocytes independently of its effects on replicative senescence, proliferation and differentiation

 

In summary, the observations above represent the first

biological connection between epigenetic ageing and

rapamycin. These results for human cells add to the

evidence that extension of life, at least by rapamycin, is

indeed accompanied by retardation of ageing. These

observations also suggest that the life-extending

property of rapamycin may be a resultant of its multiple

actions which include, but not necessarily limited to

suppression of cellular senescence [36-38, 48] and

epigenetic aging, with the possibility of augmentation of

cellular proliferative potential.

Edited by PAMPAGUY, 08 September 2019 - 05:51 AM.

[Michael]

 

First human study proving that Rapamycin reverses ageing via epigenetic clocks.  Major break-though.              https://www.ncbi.nlm...les/PMC6555449/

 

 

First, this is not a "human study:" it's a study of human skin cells in a dish. Second, nothing that happens in cells in a dish constitutes a "breakthrough," let alone a "major breakthrough." (The exception would be the derivation of induced pluripotent stem cells). It's a "breakthrough" if it happens in (at the very least) a living, breathing mammal, and if nothing similar has happened before.

 

Third, this study did not show even in keratinocytes that rapa "reverses ageing via epigenetic clock:" it showed that it slowed the ongoing advancement of one particular epigenetic clock. Of course, we already know that rapa slows aging in rodents; it would be interesting if it slowed an epigenetic aging clock, but since we don't yet have any evidence that slowing the advancement of such clocks in humans actually slows aging, even that would only suggest a breakthrough has occurred. On this front, cff. the TRIIM study, which found a tailored combination of hGH, DHEA, and metformin slowed the epigenetic aging clock — but I'm not at all convinced that this means aging was actually slowed in these people (a couple of whom I know), and wouldn't yet call it a 'breakthrough.'

[chipw]

First, this is not a "human study:" it's a study of human skin cells in a dish. Second, nothing that happens in cells in a dish constitutes a "breakthrough," let alone a "major breakthrough." (The exception would be the derivation of induced pluripotent stem cells). It's a "breakthrough" if it happens in (at the very least) a living, breathing mammal, and if nothing similar has happened before.

 

Third, this study did not show even in keratinocytes that rapa "reverses ageing via epigenetic clock:" it showed that it slowed the ongoing advancement of one particular epigenetic clock. Of course, we already know that rapa slows aging in rodents; it would be interesting if it slowed an epigenetic aging clock, but since we don't yet have any evidence that slowing the advancement of such clocks in humans actually slows aging, even that would only suggest a breakthrough has occurred. On this front, cff. the TRIIM study, which found a tailored combination of hGH, DHEA, and metformin slowed the epigenetic aging clock — but I'm not at all convinced that this means aging was actually slowed in these people (a couple of whom I know), and wouldn't yet call it a 'breakthrough.'

The triim study is interesting.  I notice they used a HGH dose of .015mg/kg.  Thats about 4iu for a 200 pound man.  Thats a large dose compared to the 1-2iu usually recommended for a replacement dose assuming the HGH was taken daily 

[ta5]

On his Rogue Health and Fitness blog, P. D. Mangan interviewed Dr. Green (for the 2nd time), posted today:

Rapamycin Anti-Aging Medicine: An Update with Alan S. Green, M.D.

 

Q 1. How have your patients fared? What have you learned from clinical practice with rapamycin (and other drugs) that you didn’t know when you started?

 

Dr. Alan S. Green: My first anti-aging patient drove from Ontario, Canada to my NYC office on 4/22/17. Your first interview which posted on 6/5/17 was of huge importance in increasing patient awareness. The second patient was seen on 6/16/17. At that point in time, the only person in the public domain who had taken weekly rapamycin for a year or more was me.

 

Now approximately 2 years later, this office has seen over 360 patients. In my opinion, the results have been spectacular. No patient has died and nobody has had a serious complication. It is still my opinion that rapamycin is the greatest new drug since the dawn of the age of antibiotics some ninety years ago.

 

 

And more on the site.

[sub7]

I have taken 25 mg. once monthly also without side effects. (Chronic dose required)  It is the 2nd dose that gives you trouble if you have not waited for rapa to clear out of your system.  Many believe that the mTor inhibition lasts a long time after stopping rapa.  Tried this for weight reduction. (to reset weight set point in brain).  I have gone back to 6 mg. weekly, because my weight is where I want to be.  Lost 5 kg.  71 in,  165 lbs

73 yo male

 

Single Rapamycin Administration Induces Prolonged Downward Shift in Defended Body Weight in Rats

https://www.ncbi.nlm...les/PMC4008417/

25 mg is a very large dose,

After a while I started to have issues with 1 mg taken every 3rd day (after like the 5th dose). It was an extremely anti-androgen like effect I had. Crash in libido and anhedonia.

 

For context, would you say that even someone like me, could potentially tolerate a large dose taken at once? The above study seems to show that even a single dose is extremely potent and has lasting effects. 

 

Just for context, what would you say are the doses you yourself can tolerate taken weekly? 
As you may have guessed, I am trying estimate how much of a single dose I can experiment with without running into the issues I had when taking twice-weekly doses of 1 mg.

[PAMPAGUY]

25 mg is a very large dose,

After a while I started to have issues with 1 mg taken every 3rd day (after like the 5th dose). It was an extremely anti-androgen like effect I had. Crash in libido and anhedonia.

 

For context, would you say that even someone like me, could potentially tolerate a large dose taken at once? The above study seems to show that even a single dose is extremely potent and has lasting effects. 

 

Just for context, what would you say are the doses you yourself can tolerate taken weekly? 
As you may have guessed, I am trying estimate how much of a single dose I can experiment with without running into the issues I had when taking twice-weekly doses of 1 mg.

My personal feeling is that every person is different as far as dosages are concerned.  Some of the elderly people in the Mannick study, (quoted above) were over 85 years old and taking 20 mg. weekly for 4 weeks.  The group that took that high dose had many side effects, but none serious.  So I do not believe that 20 mg is too much.  I believe Dr. Green is taking 14 mg weekly and he is 78 yo. (believe he is treating his heart condition, besides ageing) I think a dose of up to 10 mg weekly should be OK, but a dose of 6-7 mg will also give you around a 75% Tor inhibition.  Just remember to not take too often.  If you get mouth sores, which is common, just skip a week. My feeling is that your are not getting any Tor inhibition taking 1 mg twice weekly.  Waste of money at that dose and schedule.  Minimum would seem to be 5 mg weekly which would give you around 50% inhibition.

[Valijon]

Two of the most important factors are age and genetics. At first, half a mg per week was too much. I got severe muscle pain like you don't get from working out. I didn't want to give up on this wonder drug. I'm 43 and very healthy. I was able to get to 1mg per week but I still got mouth sores the first 2 or 3 weeks. One reason I returned to it is that it helps me with my kidneys. My eGFR is half what it needs to be. Sirolimus is supposed to help with that and do something good for teeth. Recalcification? Finally 1% topical Rapamycin cream is available in Australia and New Zealand since 2014. It's in clinical trials in the U.S. From what I could discern, rapa cream makes retinol look like a joke. I've been searching for a supplier of rapa cream but, no luck so far.

[Andey]

Two of the most important factors are age and genetics. At first, half a mg per week was too much. I got severe muscle pain like you don't get from working out. I didn't want to give up on this wonder drug. I'm 43 and very healthy. I was able to get to 1mg per week but I still got mouth sores the first 2 or 3 weeks. One reason I returned to it is that it helps me with my kidneys. My eGFR is half what it needs to be. Sirolimus is supposed to help with that and do something good for teeth. Recalcification? Finally 1% topical Rapamycin cream is available in Australia and New Zealand since 2014. It's in clinical trials in the U.S. From what I could discern, rapa cream makes retinol look like a joke. I've been searching for a supplier of rapa cream but, no luck so far.

 

  Do you supplement with Creatinine?  eGFR formula is based on Creatinine value(its basically a Creatinine clearance rate) so if you supplementing it(or just eating too much meat) than it could skew result.

[Andey]

My personal feeling is that every person is different as far as dosages are concerned.  Some of the elderly people in the Mannick study, (quoted above) were over 85 years old and taking 20 mg. weekly for 4 weeks.  The group that took that high dose had many side effects, but none serious.  So I do not believe that 20 mg is too much.  I believe Dr. Green is taking 14 mg weekly and he is 78 yo. (believe he is treating his heart condition, besides ageing) I think a dose of up to 10 mg weekly should be OK, but a dose of 6-7 mg will also give you around a 75% Tor inhibition.  Just remember to not take too often.  If you get mouth sores, which is common, just skip a week. My feeling is that your are not getting any Tor inhibition taking 1 mg twice weekly.  Waste of money at that dose and schedule.  Minimum would seem to be 5 mg weekly which would give you around 50% inhibition.

 

 To be fair, Mannick study used Everolimus which is arguably less potent than Rapamycin and has a shorter half life, therefor 20mg is not directly applicable to Rapamycin.

I agree on other arguments but as many drug side effects its an individual thing. reportedly body get accustomed to rapa in few months and those ulcers disappear.

[Valijon]

Creatine and no. My creatinine levels were a little out of the high range at about 1.7. Established baseline is 0.6-1.2 but, this is for people who do not lift weights. We have a much higher protien turnover. I'm guilty of not staying hydrated from coffee consumption. It's my one value that was off and it freaked my doctor out. It's been way up some years and back to 50 other years. It could be an overabundance of red meat or processed foods. I'm making dietary changes right now.

[Valijon]

For anyone looking to create their own topical rapamycin cream: http://www.osuderm.org/Compounds

[smithx]

For anyone looking to create their own topical rapamycin cream: http://www.osuderm.org/Compounds

 

Used ointment mills seem to be $2K +

https://www.ebay.com...sacat=0&_sop=15

 

 

This compounding pharmacy has it available at 0.2%:

https://www.wedgewoo...in-topical.html

Edited by smithx, 12 January 2020 - 07:22 PM.

[Valijon]

It looks like you'll need a prescription for this. I'm very surprised that I cant locate Indian or Chinese pharmacies with this. Seems the word hasn't gotten around hardly at all about this. We all know the Billions of dollars people spend on skin care and anti-aging each year.