955 replies to this topic

[malbecman]

 There is True Life Research which is selling it as a research chemical.  You can get 1000 mgs (yes, 1 gram) for $339.  500mg is $199

 

https://teamtlr.com/...53123-88-9.html

 

I was able to verify its ID using HRMS, eg, it is the molecule its supposed to be but no idea of metals or possibly other contaminants.   I used it on my dog (the one in my profile) starting ~1.5 yrs ago and she lived to 16. Seemed to help.

[ceridwen]

I think Dr Green would write a prescription for less

[poonja]

The price for 500 mg is very good but I assume this is in powder form and one would need a very precise scale to implement a dosing strategy unless volumetric dosing was an option.  Is this seller reliable as they have a large list of interesting products.  

[Nate-2004]

I would have expected your dog to live quite a bit longer actually. 16 is kind of normal. I guess dosing matters.

[RWhigham]

The price for 500 mg is very good but I assume this is in powder form and one would need a very precise scale to implement a dosing strategy unless volumetric dosing was an option.  Is this seller reliable as they have a large list of interesting products.  

 

Dissolving 500mg of rapamycin powder in EverClear  which does not freeze in the freezer where it keeps quite well in a dropper bottle wrapped in tin foil to keep the light out.  With 1/2 mg per drop, a typical dose is 10 or 12 drops added to some water.

Edited by RWhigham, 13 April 2018 - 03:46 AM.

[malbecman]

I would have expected your dog to live quite a bit longer actually. 16 is kind of normal. I guess dosing matters.

 

 The expected life span for a lab is 10-14 years (this is the generally accepted average) so she did outlive the average.   I also didnt start her until ~14 because I was not familiar with the rapamycin story.

[Nate-2004]

Dissolving 500mg of rapamycin powder in EverClear  which does not freeze in the freezer where it keeps quite well in a dropper bottle wrapped in tin foil to keep the light out.  With 1/2 mg per drop, a typical dose is 10 or 12 drops added to some water.

 

Hey can you pm me with where you're getting 500mg powder?

[VP.]

As I've said previously I'm not so sure rapamycin mixed with alcohol keeps it potency. I went back to Indian suppliers after getting disappointing results with TLR rap + alcohol.  

[RWhigham]

As I've said previously I'm not so sure rapamycin mixed with alcohol keeps it potency. I went back to Indian suppliers after getting disappointing results with TLR rap + alcohol.  

Did you keep it in the freezer and in the dark?

[VP.]

Did you keep it in the freezer and in the dark?

I kept it in the refrigerator in the dark. 

[smithx]

Everyone who is considering taking rapamycin more frequently than once every 5-7 days should read this carefully:
https://www.ncbi.nlm...pubmed/26463117

The full article is available on sci-hub.

[MikeDC]

Everyone who is considering taking rapamycin more frequently than once every 5-7 days should read this carefully:
https://www.ncbi.nlm...pubmed/26463117

The full article is available on sci-hub.

A well‐known side effect of rapamycin treatment in humans and mice is testicular degeneration (Wilkinson et al., 2012), and we observed that both the intermittent rapamycin and daily rapamycin treatment regimens significantly decreased testes mass (Fig. 3C). Daily rapamycin decreased testes weight by approximately 75%, while the intermittent (1×/5 days) rapamycin regimen decreased testes weight by almost 60%.“
“

[MikeDC]

A well‐known side effect of rapamycin treatment in humans and mice is testicular degeneration (Wilkinson et al., 2012), and we observed that both the intermittent rapamycin and daily rapamycin treatment regimens significantly decreased testes mass (Fig. 3C). Daily rapamycin decreased testes weight by approximately 75%, while the intermittent (1×/5 days) rapamycin regimen decreased testes weight by almost 60%.“
“

“All three rapalogs significantly reduced testes weight, although the testes of everolimus‐treated mice were slightly heavier than those from rapamycin‐treated mice (Fig. 5E), and were equivalent in weight to testes from mice treated 1×/5 days with rapamycin (Fig. 3C).”

You should be prepared to sacrifice your teste even with intermittent dosing and rapalogs.

[Benko]

Mike,

Does that go along with effects on test level?

[smithx]

I wouldn't draw that conclusion from this study.

 

The mice in this study were dosed at 2mg/kg. After correcting for mouse metabolism by dividing by 6 (please correct me if there's a better quick formula), we get 0.333mg/kg human equivalent.

 

So for a 170lb person that would be equivalent to about 26mg per dose, or 13x what I've been taking and over 4x what anyone here says they've been taking.

 

Also, I have been taking rapamycin every 10 days, which should further reduce the undesirable side-effects of daily dosing.

 

It's not guaranteed to be safe, but "sacrifice your testes" is very much overstating based on what's in the article.

 

 

You should be prepared to sacrifice your teste even with intermittent dosing and rapalogs.

 

[PAMPAGUY]

71 yo male.  Been taking rapamycin 6 mg. weekly for 15 months and my sex life is great.

 

Enough said period.

[Nate-2004]

Back to the only human mTORC1 inhibition study on everolimus, I got a quote from Alibaba stating everolimus is $516 per gram. Considering it, but I don't know if the source is trusted or not.

[VP.]

Alibaba is a den of thieves IMHO. 

[Heisok]

I had remembered that Blagosklonny had recommended a PDE5 inhibitor , but for non ED reasons. Anybody using one?

 

Dr. Green updated his current usage in March, 2018.

 

"UPDATE: MARCH 2018.

Now on weekly rapamycin, 6 mg a week for just over 2 years.

Weight 156 pounds. No dieting.

Glucose metabolism seems excellent with Insulin 4.6. Insulin lower August 4.1 probably reflects high level physical activity in Summer and very little physical activity in winter.

Only meds: Rapamycin, Lisinopril.

Lipids good: HDL 60, LDL 74.

(Low Lipids August 2016 on Lipitor stopped due to side-effect from Lipitor.)

Initial mild anemia at 1 year now returned to baseline.

WBC 5.0 low normal associated with longevity.

Creatinine at 2 years at normal level, was initially elevated. Jump creatinine August 2017 probably due to hypotension and dehydration from blood pressure meds. 

 

The above laboratory results suggest that all the "experts" who say can't take rapamycin long-term to prevent diseases of aging are MISINFORMED.  There is extreme difference between DAILY VERSUS WEEKLY. 

 

My experience is that weekly rapamycin has an acceptable safety profile in contrast to daily rapamycin which I consider toxic."

 

https://rapamycintherapy.com/

 

I am sure this has been posted before, but here is a link to Blagosklonny's May 2017 "From rapalogs to anti-aging formula"

 

https://www.ncbi.nlm...les/PMC5482593/

 

[tintinet]

I'm not taking an pharmaceutical PDE5 in hibitors, but I am on a few of the "natural" ones listed on this website:

 

 

 

https://morningsteel...de5-inhibitors/

[MikeDC]

I wouldn't draw that conclusion from this study.

The mice in this study were dosed at 2mg/kg. After correcting for mouse metabolism by dividing by 6 (please correct me if there's a better quick formula), we get 0.333mg/kg human equivalent.

So for a 170lb person that would be equivalent to about 26mg per dose, or 13x what I've been taking and over 4x what anyone here says they've been taking.

Also, I have been taking rapamycin every 10 days, which should further reduce the undesirable side-effects of daily dosing.

It's not guaranteed to be safe, but "sacrifice your testes" is very much overstating based on what's in the article.

Typically mice data needs to be divided by 12. You then divide that by another 10 for safety.

This study is a follow up on humans and it shows Rapamycin reduces testosterone and reduce sperm production.

https://www.ncbi.nlm...ubmed/17326771/

mTORC1 is a central regulator of male fertility.
mTORC1 May be regulated differently in different types of cells. So far we know mTORC1 inhibition is bad for intestine cells and testis cells. The bad effect on testis is not a side effect. It is on-target effect. This means mTORC1 inhibition is not the holy grail of anti aging.

https://www.tandfonl...rnalCode=ibmg20

Edited by MikeDC, 20 April 2018 - 01:37 PM.

[MikeDC]

mTORC1 is critical for intestinal immunity.

https://www.nature.c...icles/srep34939

[bobolander]

I received the results from the Horvath clock test yesterday.  My epigenetic age is 70 and my chronological age is 83.  Two years ago telomeres were age appropriate.  I'm in great health, play tennis daily - and really feel even younger than 70.

 

I have been taking 2mg of Rapamycin weekly together with grapefruit juice for a little over two years.  I also take Metformin, Desatanib + Q, Melatonin, Creatine, Curcumin, J147, Resveratrol, DHEA, NR, D3, Statin, Reishi, ALT711, Thyroxin, Green tea, C60 in the past) - and many vitamins from LEF.

 

I'm hoping that as more members are tested, Longecity will create a spreadsheet that includes age spread and current or past use of anti-aging meds.  We could in just a few months notice tantalizing trends or correlations.

 

I hope I'm posting this in the right place - Rapamycin being only one of many drugs taken.

[Razor444]

I had remembered that Blagosklonny had recommended a PDE5 inhibitor , but for non ED reasons. Anybody using one?

 

 

I'm using tadalafil in the morning, and sildenafil in the evening, for non-ED reasons.

 

I prefer tadalafil due to its longer half-life and since it doesn't make my vision go blue (which sildenafil does do).

[aribadabar]

Alibaba is a den of thieves IMHO. 

 

As opposed to Big Pharma being a pack of robbers?

[Razor444]

Table 2, from the following link, has fruit juices which inhibit CYP3A4 (the enzyme which metabolizes rapamycin):

 

http://www.bioline.org.br/pdf?pr15252

 

Lemon juice is included in the list.

[Razor444]

From the Wikipedia sidebar (on bioavailability):

18% (tablet), higher with high-fat meals.

 

So high-fat meals probably increase the dose of any given tablet.

 

 

 

[Razor444]

Another list which enumerates substances which increase/decrease CYP3A4:

 

https://www.selfhack...om/blog/cyp3a4/

 

Notably: Resveratrol decreases CYP3A4.

[bladedmind]

I rarely comment; please forgive me if this is too off-topic.  I worked through all the rapamycin threads and the Alan Green website, secured rapamycin from dropshipmd, and tried it in cautious doses( 2mg week 1, 5 week 2, 6 week 3).  I took a break because I was trying some other substances for peripheral vascular disease and did not want to mix speculative treatments with low documentation.  I didn’t notice any bad effects from rapamycin, nor any good effects (which take time of course).  I’ll probably return to rapamycin, but again with caution about mixing treatments.

 

I’m 68, APOE 4/4, metabolic syndrome, diabetic 2 controlled by metformin, high blood pressure controlled by telmisartan.  I’ve recently been somewhat fatigued (maybe hay fever? but including easy physical fatiguability but no shortness of breath or heart burden) and renewed experimentation with nootropics.  I tried out a 10:1 cordyceps product from an esteemed nootropics vendor (not saying name because not shilling) that offers a 1:1 extract and 10:1 extract (the 10:1 standardized to a higher 0.3% cordycepin content).  Recommended dosage per internet sources for 1:1 extract runs around 1 g (1-3g according to examine.com) to 9 g maximum.  I wasn’t paying close attention and did 1.5 g of the 10:1 extract on day 1.  Physical fatigue was half-relieved, mental clarity improved, mood was excellent. I had the week before reduced from 40 mg to 20 mg of telmisartan because my blood pressure was moving too low (diastolic below 60, maybe causing fatigue?) but it was beginning to edge a bit high (140 systolic).  The morning after my first cordyceps dose my blood sugar was 100 (usually 120 from dawn phenomenon). Blood glucose unusually perfect for remainder of day and since then.  My blood pressure is running around 125/75. After more research the morning of day 2 I concluded that 1.5 g was far too high for this 10:1 extract, so reduced to 500 mg on day 2; then 250 on day 3; and now to 150 on day 4. Why reduce dosage?  Because positive results are stable at reduced dosage.  I’ve skipped telmisartan for two days because my blood pressure is perfect, maybe a little low, without it (I frequently monitor when experimenting and will be careful). 

 

I thought that was pretty dramatic, so started doing more research on cordyceps, which is not much discussed on longecity or reddit.  It reduces AMPK and is a mtorc inhibitor.

 

I don’t have biochemistry training and so am hoping that a more informed person might offer interpretation.

 

https://www.ncbi.nlm...ubmed/19940154/

Cordycepin inhibits protein synthesis and cell adhesion through effects on signal transduction.

Wong YY, et al. J Biol Chem. 2010.

Abstract

 

3'-Deoxyadenosine, also known as cordycepin, is a known polyadenylation inhibitor with a large spectrum of biological activities, including anti-proliferative, pro-apoptotic and anti-inflammatory effects. In this study we confirm that cordycepin reduces the length of poly(A) tails, with some mRNAs being much more sensitive than others. The low doses of cordycepin that cause poly(A) changes also reduce the proliferation of NIH3T3 fibroblasts. At higher doses of the drug we observed inhibition of cell attachment and a reduction of focal adhesions. Furthermore, we observed a strong inhibition of total protein synthesis that correlates with an inhibition of mammalian target of rapamycin (mTOR) signaling, as observed by reductions in Akt kinase and 4E-binding protein (4EBP) phosphorylation. In 4EBP knock-out cells, the effect of cordycepin on translation is strongly reduced, confirming the role of this modification. In addition, the AMP-activated kinase (AMPK) was shown to be activated. Inhibition of AMPK prevented translation repression by cordycepin and abolished 4EBP1 dephosphorylation, indicating that the effect of cordycepin on mTOR signaling and protein synthesis is mediated by AMPK activation. We conclude that many of the reported biological effects of cordycepin are likely to be due to its effects on mTOR and AMPK signaling….

 

….In contrast to rapamycin, cordycepin inhibits the activities of both the mTORC1 and the mTORC2 complexes, affecting the activity of the protein kinase Akt.

 

 

Wong et al say that rapamycin reduces mTORC1 but not mTORC2.  According to Alan Green’s summary, “Use of rapamycin once a day is harmful because it knocks out mTOR1 and mTOR2; but use once a week is safe because it only lowers mTOR1.”  If cordycepin lowers both mTORC1 and mTORC2 then there should be same problem using it every day as there is with rapamycin; if mTORC2 inhibition is bad for anti-aging purposes, and inhibition of mTORC2 is immediate with cordycepin but cumulative with rapamycin, then daily cordycepin could be more of a hazard than daily rapamycin?  In my 5 days of experiment I’ve see more dramatic subjective and objective response than any noninebriant I have toyed with – especially the perfect blood sugar and blood pressure readings.  It’s so powerful I want to continue yet am also worried about using it too much, or at all. I’m ignorant of biochemistry and don’t understand scientific journals’ discussions of mechanisms of action (there a good number of cordyceps review articles the last 10 years), and am unable to reason about whether cordycepin is worse, the same, or better than rapamycin for anti-aging purposes.  There is ambiguity in the cordyceps informal and formal literature about whether it is immuno suppressant, immuno modulating, or immuno stimulating. 

 

I experimented with a much weaker formulation of cordyceps daily for six months in 2012.  I noticably had more energy but also that year atypically had four respiratory infections and gave it up  (although temporarily living in a snow climate at exactly the same period so causation unsure); at the same time I developed a new and quite strong allergy to chemical exposures (resolved after a year).   I realize that those are anecdotes and that they point in different directions, but just adding FWIW. 

 

I thought it useful to include this information in this thread because of user interest in mTORC inhibition and in alternatives given the inconveniences involved in securing rapamycin.

 

 

[MikeDC]

https://www.ncbi.nlm...rapamycin liver