955 replies to this topic

[LOOKINGFORTIME]

The International  Anti-Aging Site, is preparing to sell Rapamycin.

 

https://www.antiaging-systems.com/

[PAMPAGUY]

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/

 

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.

 

[PAMPAGUY]

DOB:  7-26-46  Male, 177 lbs., 71", Rapamycin 6 mg. once weekly for 16 months, (no side effects) Metformin 1000 mg. daily, N+R 1.5 gm of each + 15 gm Stearic Acid twice weekly, 5 mg Statin, Crestor daily. (will stop statin in 3 more months and get another lipid profile) BP 110-120/65-75. (measure daily)  Resting heart rate (52-56).  B/P and Cholesterol have dropped as I have lost weight.  No longer take B/P medication.  Have lost 20 lbs last 12 months.  Believe the combination of Rapa and Metformin helped.  Took 2000 mg  Metformin split into 2 daily doses until I lost 20 lbs, then back to 1000 mg daily.  Really lowered blood sugar and urge to eat also.

 

Lab results 4-23-18: TC 130, LDL 74, HDL 43, Trigliceride 85,  Creatinine .5, GFR 108,(reduced kidney function is a major hallmark of ageing) Glucose 100, HbA1c 5.5 from 6.4 9 months ago. CBC within normal limits.

 

Had an arthritic rt. hip, no longer.  Can walk for many miles without any pain. Believe the rapa stops or slows down the arthritis deterioration. 

[Jaris]

Interesting. Thanks for your post, Pampaguy. Your lab results look good to me, though I'm not trained to understand it all.

 

I'm 60, take 5mg a week ,(no metformin) with a week off every 5th week. I've taken it for 18 months. I too lost weight from 165 to 152. I'm 5'7", so my BMI is 23.8 now. I too can now walk many miles with few problems other than muscle soreness. I regularly walk 3 miles a day, some days more like 4 or 5. One thing I've begun to do is sprint up hills. It gets my heart and breathing going well - my heart is not racing dangerously. There are 2 factors that set me apart and might be affecting my condition: I have Parkinson's (symptoms mostly controlled for now by Rytary) and I've been eating a vegan diet for about 4 months. I see improvements in everything, but I haven't had my bloodwork done Lately. I'll do that and post the results.

[geo12the]

The International  Anti-Aging Site, is preparing to sell Rapamycin.

 

https://www.antiaging-systems.com/

 

Have people successful gotten Rapamycin here? The site seems very convoluted. The terms you check off are vague about requiring a prescription.

[PAMPAGUY]

Compare to dropshipmd.com. 300 1 mg Sirolimus x $1.60mg + $8 shipping. My 3rd order. 1 yr supply

[APBT]

Have people successful gotten Rapamycin here? The site seems very convoluted. The terms you check off are vague about requiring a prescription.

 

I've not purchased rapa, but I have purchased from IAS several times with no issues.

Compare to dropshipmd.com. 300 1 mg Sirolimus x $1.60mg + $8 shipping. My 3rd order. 1 yr supply

 

The RapaPRO product https://theantiaging...-rapamycin.html is slightly less expensive at $1.50 per mg: 60 mg for $90 (sans shipping).

[Nate-2004]

Compare to dropshipmd.com. 300 1 mg Sirolimus x $1.60mg + $8 shipping. My 3rd order. 1 yr supply

 

Results so far?

[QuestforLife]

Don't bother unless you have a prescription. It's required through https://www.antiaging-systems.com

[Iporuru]

Don't bother unless you have a prescription. It's required through https://www.antiaging-systems.com

 

Yes, I've just tried to order, but they asked for a valid prescription - not older than 6 months
 

[APBT]

Hmm, maybe the Rx is necessary for European orders.  I added the RapaPRO to my cart and went up to the point of making payment, without being prompted for a Rx.

Edited by APBT, 06 June 2018 - 10:37 PM.

[tintinet]

Hmm, maybe the Rx is necessary for European orders. I added the RapaPRO to my cart and went up to the point of making payment, without being prompted for a Rx.

Ya- just ordered from Anti-aging store. No prescrption requested yet.

[MikeDC]

More evidence that mTORC1 is regulated differently in different tissues. We have known high mTORC1 is good for intestinal stem cells and testosterone and testis health. This one shows low mTORC1 causes depression and they are activating mTORC1 to treat depression.

http://www.navitorpharma.com

[QuestforLife]

More evidence that mTORC1 is regulated differently in different tissues. We have known high mTORC1 is good for intestinal stem cells and testosterone and testis health. This one shows low mTORC1 causes depression and they are activating mTORC1 to treat depression.

http://www.navitorpharma.com

 

Oh yes, because we all need a pharmaceutical grade mTOR activator which hasn't  passed through clinical trials LOL!

 

There is a great deal of evidence that depression is linked to inflammation, see for example:

 

www.ncbi.nlm.nih.gov/pmc/articles/PMC5542678

www.ncbi.nlm.nih.gov/pubmed/23995180

www.ncbi.nlm.nih.gov/pmc/articles/PMC3846682

www.ncbi.nlm.nih.gov/pmc/articles/PMC5050394

 

 

And rapamycin has been shown to reduce inflammation, for example after a coronary stent:

 

www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2010000800012

 

And for my own part, in 2015 my C reactive protein was a low 1 mg/L; I was using lots of fish oil at the time, resveratrol, and some bioavailable curcumin.

 

In 2018 on rapamycin my C reactive protein had fallen further to 0.5, despite discontinuing fish oil, resveratrol and curcumin.

 

We all know gut and intestine lining turns over quickly - that's the reason you get mouth sores if you take too high a dose of rapamycin (as the mouth lining is similar). That is why we are following an INTERMITTENT protocol.

 

As for testes health, I haven't noticed a reduction in teste size or ejaculate volume in the > 1 year I've been taking weekly rapamycin. I have noticed improved sexual function, probably due to improvements in vascular health.

Edited by QuestforLife, 07 June 2018 - 07:53 AM.

[Jesuisfort]

Hello, Can rapamycin totally prevent cancer ?  

[geo12the]

Has anyone thought about taking Everolimus instead of Rapamycin? This is the derivative of Rapamycin that has fewer metabolic side effects. It's available on dropshipmd in 10 mg tablets. 

[PAMPAGUY]

Has anyone thought about taking Everolimus instead of Rapamycin? This is the derivative of Rapamycin that has fewer metabolic side effects. It's available on dropshipmd in 10 mg tablets. 

 

 

There are no side effects when taking 1-6 mg once. weekly.  Have talked with many people taking rapa weekly for anti ageing purposes and none of them have had any metabolic side effects you mentioned.  If mouth sores, just reduce dosage.  You want to inhibit TOR 1, not shut it down.  Need it to live.  Take enough to inhibit TOR 1, without affecting TOR 2.  Been taking 6 mg once week for 18 months.  Remember the drug companies that ran those trials, used there own rapalog instead the generic rapa.  Costco Pharmacy selling it for $10 mg.  I agree that Everolimus affects TOR 2 less than rapa.  So you could take more of the Everolimus without any side effects.  It was developed for kidney transplant patients who are taking 1-3 mg daily, where it really builds up in the blood.  They want to inhibit TOR 2, shut down immune system so kidney will not be rejected.

 

That said, Rapa works great for ageing and I see no reasons for Everolimus.  You left off the cost per mg. of Everolimus.  Bet it is 2-3 times more expensive at least.  Thousands per yr., vs appx. $500 yr. Sirolimus. $1.60 mg.

[Jesuisfort]

There are no side effects when taking 1-6 mg once. weekly.  Have talked with many people taking rapa weekly for anti ageing purposes and none of them have had any metabolic side effects you mentioned.  If mouth sores, just reduce dosage.  You want to inhibit TOR 1, not shut it down.  Need it to live.  Take enough to inhibit TOR 1, without affecting TOR 2.  Been taking 6 mg once week for 18 months.  Remember the drug companies that ran those trials, used there own rapalog instead the generic rapa.  Costco Pharmacy selling it for $10 mg.  I agree that Everolimus affects TOR 2 less than rapa.  So you could take more of the Everolimus without any side effects.  It was developed for kidney transplant patients who are taking 1-3 mg daily, where it really builds up in the blood.  They want to inhibit TOR 2, shut down immune system so kidney will not be rejected.

 

That said, Rapa works great for ageing and I see no reasons for Everolimus.  You left off the cost per mg. of Everolimus.  Bet it is 2-3 times more expensive at least.  Thousands per yr., vs appx. $500 yr. Sirolimus. $1.60 mg.

 

Hello, do you have any source that support this dosage ? I'm 22 and just want to avoid cancer

[PAMPAGUY]

Hello, Can rapamycin totally prevent cancer ?  

 

 

Cancer is caused by basically 3 things.

1,  Genetic predisposition for certain kinds of cancer.   You can get your DNA tested for many types of cancer. appx. $200. This is the type that most kids get and very few adults.

2.  Environmental causes.  Smoking which changes your DNA, toxic chemicals, etc.

3.  Old age, as you age your immune system can no longer protect you and your mitochondria gets all messed up leaving you vulnerable to cancer.  Most cancers are in older people.  Very few people get cancer that are not elderly unless they smoke or in there families DNA.

Rapa delays many of ageing cancers.  The Number 1 cause of cancer is ageing.  Most will still die of cancer, heart disease or stroke, but if taking Rapa it will hopefully delay it 20-30 yrs.

 

A young person like yourself should get DNA tested and if predisposition for a certain cancer, then act upon it.  If you smoke, stop.  Start taking Rapa around 50.  In the meantime, just relax for the next 30 years.

[Madfern]

Have people successful gotten Rapamycin here? The site seems very convoluted. The terms you check off are vague about requiring a prescription.

 

I have bought 2 lots of 2g rapamycin from 2 different chinese suppliers via Alibaba.  About $200 / lot.

 

Then I got a friend who is a chemist to verify the identity of the 2 lots using LC-MS/MS. Both lots checked out ok.

 

Using a mg resolution scale, I measured 7mg doses and packaged them up in veggie-caps.  The caps remain mostly empty because 7mg is only about half a match head in volume.  You might ask why 7mg -- well, that was kind of the minimum I could repeatably measure with the scales I have...

 

I have now taken 7mg rapamycin once per week, for 4 weeks.  No noticable side effects so far.  No quantifyable, positive effects either.

 

Anybody doing these kinds of self experiments should find a sympathetic GP and discuss this with her/him.

My GP orders LFTs (Liver Function Test) on a regular basis, my next LFT results are due in about 2 weeks.

There are other tests which might be useful, e.g. CRP, ask your GP.

 

I also have a baseline DNA methylation test (MyDNAge) and plan to get another one after about 8 weeks on rapamycin.

[BioHacker=Life]

Have people successful gotten Rapamycin here? The site seems very convoluted. The terms you check off are vague about requiring a prescription.

 

I ordered it from one of their us sites and subjectively after a month I do feel like it had an effect. 

[Andey]

What could be an adequate dosage of Everolimus to take once a week? Is there any coefficient to calculate analogous Rapamycin to Everolimus dosage? 

[Andey]

Compare to dropshipmd.com. 300 1 mg Sirolimus x $1.60mg + $8 shipping. My 3rd order. 1 yr supply

 

They ve charged me with $370 for 120*1mg tablets+shipping.

[PAMPAGUY]

They ve charged me with $370 for 120*1mg tablets+shipping.

That is over $3.00 mg. plus shipping is more expensive.  Did they ask for Rx?  Dropshipmd.com  charges $8 shipping.  No Rx. You have to use MoneyGram ($10), bank wire, or Western Union which is more of a hassle, but saving hundreds of dollars is worth it.  I order once a year.

 

$3 x 300 = $900 plus shipping vs $1.60 x 300 = $480 plus $8 shipping.

[PAMPAGUY]

What could be an adequate dosage of Everolimus to take once a week? Is there any coefficient to calculate analogous Rapamycin to Everolimus dosage? 

Here is the clinical study where they used 5 mg. Everolimus  weekly on elderly patients with very few side effects.  Many others have correct rapa dosage for most people at 6 mg week.

 

https://sci-hub.tw/h...anslmed.3009892

[Andey]

That is over $3.00 mg. plus shipping is more expensive.  Did they ask for Rx?  Dropshipmd.com  charges $8 shipping.  No Rx. You have to use MoneyGram ($10), bank wire, or Western Union which is more of a hassle, but saving hundreds of dollars is worth it.  I order once a year.

 

$3 x 300 = $900 plus shipping vs $1.60 x 300 = $480 plus $8 shipping.

Nope, they haven't asked for Rx. Surprisingly they responded in Russian to my inquiry though. They proposed wire transfer. Which is an unnecessary hassle for me.

Its kinda hard sell for me because I see people selling india`s generic Everolimus 180$ for 10*10mg(from Cipla and they are one of the top quality India manufacturers) and original rapamycin from Pfiser $370 for 100*1mg (haven't called them so it could be a bogus though)

 

Next choice is antiagingsystem. I am trying to contact them to pay them somehow via card, so far no response.

Edited by Andey, 08 June 2018 - 09:50 AM.

[VP.]

What could be an adequate dosage of Everolimus to take once a week? Is there any coefficient to calculate analogous Rapamycin to Everolimus dosage? 

 

I would start at 2 mg a week and slowly work up. I'm 57 and I'm fine with 3 mg a week but soon after going to 4 mg I got a mouth sore (stomatitis).I believe that to be an indication of mTOR C-2 inhibition. I think the older you are, or maybe just less healthy you are, the more rapamycin you can tolerate before you get sores. 

[QuestforLife]

I would start at 2 mg a week and slowly work up. I'm 57 and I'm fine with 3 mg a week but soon after going to 4 mg I got a mouth sore (stomatitis).I believe that to be an indication of mTOR C-2 inhibition. I think the older you are, or maybe just less healthy you are, the more rapamycin you can tolerate before you get sores.

I've done some research into this; I originally though mTOR must be going up with age - and in some limited case like insulin resistance it does - but I think what is primarily happening with mitotic cells is that as they get old with shorter telomeres they divide more slowly (and process proteins and recycle mitochondria more slowly). They do this to preserve themselves. So this means a blockade on slowly dividing cells takes longer (or a greater dose) to do harm than on faster dividing cells.

Blagosklonny has a lot to say on this subject.

https://www.ncbi.nlm...les/PMC3615154/

As for everolimus it has a half life of 30 hours compared to ~ 60 hours for sirolimus (rapamycin). So you can either double your dose and make the mTOR inhibition deeper without having to worry about side effects, or take it twice as often and inhibit for twice as long. I would strongly recommend doing the first not the latter.

Of course everolimus is on patent for 4 more years, I think, so it will be very expensive in comparison with rapamycin.

Edited by QuestforLife, 08 June 2018 - 01:02 PM.

[Nate-2004]

Maintaining telomere length is the big issue with inducing autophagy I think. Not sure why it works well on mice but in humans it may not be so good. I really hate the patent system by the way. It only serves to produce the opposite outcome of the reasoning used to justify the kind of protectionism it entails. I guess we can wait 4 years for it, or by then we'll see dramatic progress on other fronts, making it obsolete.

[Andey]

What is the current consensus on insulin resistance induced by rapamycin?

 

Ive actually took my first 5mg Everolimus this week.  Nothing to write about, the only thing that I noticed is an increased lymphatic load in the neck region for 2 days post-pill like I was having some flu. 

I check my BG quite often because I am trying to get max number of summer fruits without falling out of ketosis for too long and my BG spikes became way higher than usual. I could just cut out carbs more but dont like the thought that my insulin is probably way higher now because of induced resistance.

Is it a best practice to take something like metformin while taking rapamycin like drugs or just don't bother with it?