955 replies to this topic

[Valijon]

Thank you for your answer. Thats been one of my primary concerns. The other is how Rapamycin may jinder the immune system, more or worsening infections.

[VP.]

Thank you for your answer. Thats been one of my primary concerns. The other is how Rapamycin may jinder the immune system, more or worsening infections.

 

I think my immune system is fine. I had one small cold a few months after I started Rapa but since then no colds or flu. It's still early but I believe it has reduced my seasonal allergies. I don't know why that would happen but I'll confirm that result this spring. My dental hygienist says my gums look great too so that may be due to anti-inflammatory properties of rapa. My wife has had no sickness since she started rapa last April. It will take years to know for sure about the immune response but I see no evidence of weakened response so far. 

[chipw]

I took rapamycin for four months, stopped for 7 and then took it again for 5 months ending 2 weeks ago. I take 3-5mg weekly. I felt i was coming down with a cold or the flu 2 weeks ago but took 5mg rapamycin anyway. I ended up with what i think was the flu. Fever lasted 5 days followed by some upper respiratory crud that im just now getting over. Hard to say if the rapa lowered my immunity or not. Its the first time i have gotten sick while on it. My opinion is that it boosts immunity most of the time but that day or two after dosing, it may lower it a bit.

I plan on starting back next week. Its been mostly beneficial in my opinion. For what its worth, my hygienist commented on the health of my gums last time i was in there. Dont know if its from the rapa or not.

[Valijon]

This is the kind of subjective data we all need. We can read safety studies on dogs, humans, or what have you. To be able to slow aging with minimal to no side effects is the dream. I cant wait to hear more from members of this community.

[QuestforLife]

I took rapamycin at 2mg/week for 2 years. No issues with illness.

 

At 3mg/week with grapefruit juice (a somewhat foolish experiment) I developed nasty cystic acne on my back which immediately (within a week) resolved on discontinuation. I do not attribute this to infection; I believe it was due to reduced skin turnover (and oily skin). I could be wrong about this however.

 

Because I am only 40 I have now discontinued it. I believe that if you have a problem with insulin (pre or full diabetic) or are generally suffering with middle age spread, it is probably extremely beneficial. In me however (without these issues) I think the risk/benefit case is not worth it. I will review this decision when everolimus is off patent (2022?).

Edited by QuestforLife, 30 January 2019 - 09:14 AM.

[PAMPAGUY]

I have been taking rapa for 2 years since Feb. 2017,  6-7 mg. weekly.  No mouth sores.  I believe that Dr. Attia got sores because he is so young.  At 45 years of age his Tor signal is in a low range(normal) and rapa drives it even lower which triggers TOR 2 the immune system.  At 72 yo my Tor signal is quite high, and all I want to do is lower TOR 1 to the normal range.  I believe that 60 yo is about the youngest someone should start Rapa.  Remembering that we all need TOR to live so we don't want to inhibit it too much.  I also take Metformin 2000 mg daily, split between morning and night.  Lithium orotate 5 mg. nightly.  No side effects with any of these medications.  If your looking for results, just follow your blood work.  HbA1c should be lower, my creatinine is at .85 which is very good kidney function, (this is one of the main problems with ageing)

[chipw]

Pampaguy,
I think your probably right on the 60 year starting age. I believe that is what Dr. Green recommends as well. His one exception being carriers of the APOE4 gene. I believe he recommends starting younger for those people of which i am one. I am 49. I think i will drop my dose down to 3mg when i start back though.

By the way, thank you for your many posts on this topic here and on reddit. Your stories were some of the very first posts by an individual actually taking rapamycin. I know you helped me and probably many others.

Edited by chipw, 30 January 2019 - 01:17 PM.

[Valijon]

This is very good information. Again I thank everyone who has shared their experiences. It sounds like Metformin may be the optimal medication for people below 60 or at least 50.

[RWhigham]

Dr Green's fasting BG has crept up to nearly 100 which he considers benign--and not a reason to stop his weekly rapamycin.

 

After two years on rapamycin my fasting blood glucose has crept up from low 80's to above 100.

My insulin sensitivity remains very good, so perhaps it is benign.. But I don't like it and am discontinuing rapamycin.

 

[chipw]

Rwigham, did you also take Metformin during your rapamycin use?

[Michael]

Dr Green's fasting BG has crept up to nearly 100 which he considers benign--and not a reason to stop his weekly rapamycin.

 

After two years on rapamycin my fasting blood glucose has crept up from low 80's to above 100.

My insulin sensitivity remains very good, so perhaps it is benign.. But I don't like it and am discontinuing rapamycin.

 

How are you measuring insulin resistance?

[RWhigham]

Rwigham, did you also take Metformin during your rapamycin use?

Yes, but a low dose of 425 mg  once per day.

 

How are you measuring insulin resistance?

 Kraft test - Serum Insulin measured 2hr after start of glucose tolerance test 22 uIU/ml, and blood glucose at 2.5 hr was 78 mg/dL

   Kraft Test.jpg   71.5KB   1 downloads

Edited by RWhigham, 16 February 2019 - 06:32 AM.

[PAMPAGUY]

I have begun another self-experiment with Rapa.  After reading the following 2 articles/trials have decided to take a once a month Rapa dose of 25 mg.  In the Mannick trial, 80 yo's were taking 20 mg weekly, but with side effects.  I will not be taking weekly, but monthly.  The purpose of this is to lose about 5-6 kg. of weight.  As Dr. Green has said, Rapa will help you maintain your weight, but will not help with losing it.  So I needed some help in trying to reset my body weight set point which is controlled by our brains. (Hippocampus)  This requires a large, chronic dose.  The effects in the rat study lasted for at least 10 weeks.   https://journals.plo...al.pone.0093691

 

 Dr. Blagosklonny. stated in the following paper that people should be taking higher doses, and that even a single dose last a long time. (continues to inhibit Tor 1)  https://www.aging-us...cle/101647/text

 

  After reading these 2 excellent papers, I have decided to try the experiment.  It will require at least 3 months, because I feel humans will need multiple doses (in stages) in order to reduce their body weight set point to the weight they want to get to.  The brain will defend that set point once set by reducing your appetite and upping metabolism.  Will report back with results in next 3 months or sooner if successful before then.

 

[chipw]

Interesting and good luck, Pampaguy. Are you planning on returning to once weekly dose after your 3 months of 25mg/monthly?
Do you plan on changing anything else in your routine during this experiment? Like staying away from people for a few days after taking the mega dose to avoid exposure to viruses or bacteria?

[PAMPAGUY]

Interesting and good luck, Pampaguy. Are you planning on returning to once weekly dose after your 3 months of 25mg/monthly?
Do you plan on changing anything else in your routine during this experiment? Like staying away from people for a few days after taking the mega dose to avoid exposure to viruses or bacteria?

Actually Rapa has increased my T-count, and I expect a greater and more robust immune system.  Just like the Mannick trial.  Only when you inhibit Tor 2 will you worry about comprised immunity.  With once monthly dosing, that will never happen.

[smithx]

The first paper you cite doesn't seem to clearly indicate that a high dose resets the body weight set point, and the sample size is too small to draw any strong conclusions.

 

On the other hand, I have successfully reset my body weight set point using the Fasting Mimicking Diet. Despite being fairly strict low carb for a few years, I seemed to be stuck at about 186lbs minimum. 3 monthly courses of FMD lowered my set point to 178 where it has stayed for a year. I am going to start FMD again probably next week.

 

See:

https://joshmitteldo...ake-it-a-habit/

 

And the original paper:

https://www.cell.com...(15)00224-7.pdf

 

 

 

I have begun another self-experiment with Rapa.  After reading the following 2 articles/trials have decided to take a once a month Rapa dose of 25 mg.  In the Mannick trial, 80 yo's were taking 20 mg weekly, but with side effects.  I will not be taking weekly, but monthly.  The purpose of this is to lose about 5-6 kg. of weight.  As Dr. Green has said, Rapa will help you maintain your weight, but will not help with losing it.  So I needed some help in trying to reset my body weight set point which is controlled by our brains. (Hippocampus)  This requires a large, chronic dose.  The effects in the rat study lasted for at least 10 weeks.   https://journals.plo...al.pone.0093691

 

 Dr. Blagosklonny. stated in the following paper that people should be taking higher doses, and that even a single dose last a long time. (continues to inhibit Tor 1)  https://www.aging-us...cle/101647/text

 

  After reading these 2 excellent papers, I have decided to try the experiment.  It will require at least 3 months, because I feel humans will need multiple doses (in stages) in order to reduce their body weight set point to the weight they want to get to.  The brain will defend that set point once set by reducing your appetite and upping metabolism.  Will report back with results in next 3 months or sooner if successful before then.

 

 

[VP.]

Rapamycin and fasting work though different pathways and may be synergistic: 

 

Since the initial suggestion that rapamycin, an inhibitor of TOR nutrient signaling, increased lifespan comparable to dietary restriction, investigators have viewed rapamycin as a potential dietary restriction mimetic. Both dietary restriction and rapamycin increase lifespan across a wide range of evolutionarily diverse species (including yeast, C. elegans,Drosophila, and mice) as well as reducing pathology and improving physiological functions that decline with age in mice. The purpose of this article is to review the research comparing the effect of dietary restriction and rapamycin in mice. The current data show that dietary restriction and rapamycin have different effects on many pathways and molecular processes. In addition, these interventions affect the lifespan of many genetically manipulated mouse models differently. In other words, while dietary restriction and rapamycin may have similar effects on some pathways and processes; overall, they affect many pathways/processes quite differently. Therefore, rapamycin is likely not a true dietary restriction mimetic. Rather dietary restriction and rapamycin appear to be increasing lifespan and retarding aging largely through different mechanisms/pathways, suggesting that a combination of dietary restriction and rapamycin will have a greater effect on lifespan than either manipulation alone.

https://academic.oup.../glz060/5373089

[QuestforLife]

 

I have begun another self-experiment with Rapa.  After reading the following 2 articles/trials have decided to take a once a month Rapa dose of 25 mg. 

 

 

Hi Pampaguy

 

I too have considered much higher, but less frequent doses.

 

Did you experience any side effects from taking 25mg in one go?

 

Thanks

Edited by QuestforLife, 12 March 2019 - 04:45 PM.

[PAMPAGUY]

Zero side effects. Take with a lot of water.

[Zisos]

I've corresponded with Dr Green many times and he has stated to me that taking low dose rapamycin  in your 40s (2mg per week), is very smart. So its not just for people 60+. Even at 40 (actually I'm 39) I've seen athletic benefits, so I theorize that it isn't just about suppressing geroconversion (arrested cells converted to full senescence). It is clearly also having a beneficial effect on the mitochondria of the heart, based on what I and others I correspond with have experienced. 

 

I got about 3 years supply from dropshipmd. It was a complete arse to do as I had to get my bank to do a wire transfer to India. They kept coming back with more questions, sent the wrong amount etc,. but it eventually got sorted. At least I won't have to do it again for a few years.

 

Any company in India selling at dropshipmd prices and smart enough to set up a PayPal or Bitcoin account is going to make a lot of money!

 

Well, it turns out that there is an Indian company that offers everolimus 

 

Name of Company: Vea Impex

Website: http://veaimpex.co.in/

Product: Everbliss  Tablets 10 mg  

Generic Name: Everolimus

Price: $120 per pack of 10 tablets

Shipping: $20-$30 (depending on the method of shipment)

Payment Method: Paypal 

Prescription: Not Required (No questions were asked)

Delivery Time: Received in 2 weeks after payment

 

 

 

I have also contacted dropshipmd. They offered 10 tablets of 10mg Everolimus at $220.

Almost double. And they did not accept Paypal

 

So, the choice is obvious.

[poonja]

Is everolimus equal to rapamycin?  Is it your intention to split in half for dosing at 5mg/wk?

[Andey]

I take Rolimus, Cipla`s Everolimus brand that is also manufactured by BDR that makes Everbliss. Tablet is not coated and I take half of it each week.

That way 1 pack lasts for 20 weeks.

Slightly moldy taste when I dissolve it sublingually(I expect it to increase bioavailability two-fold as it is true for tacrolimus).

Haven't noticed anything, positive or negative. No significant mouth ulcers, if anything I notice them less frequently and its always after I accidentally bit my cheek.

I don't get cold much, but that was before too. No significant changes in blood tests too.

[Valijon]

We need to find out if everolimus and sirolimus are the same milligram per milligram. If so, you could use a pill cutter to get 4 2.5mg doses. In your 40s, one a week would do it.

[Andey]

We need to find out if everolimus and sirolimus are the same milligram per milligram. If so, you could use a pill cutter to get 4 2.5mg doses. In your 40s, one a week would do it.

 

 Interesting question

 at least for the immunosupresive effect, their conversion is 1:1. (I don't quite get how they compared them though)

 https://www.ncbi.nlm...pubmed/21457330

 Also I recall that Everolimus was claimed to inhibit MTORC2 less so less `side effects` like ulcers should occur.

[QuestforLife]

Well, it turns out that there is an Indian company that offers everolimus

Name of Company: Vea Impex
Website: http://veaimpex.co.in/
Product:

Everbliss

Tablets

10 mg

Generic Name: Everolimus

Price: $120 per pack of 10 tablets

Shipping: $20-$30 (depending on the method of shipment)

Payment Method: Paypal

Prescription: Not Required (No questions were asked)

Delivery Time: Received in 2 weeks after payment

I have also contacted dropshipmd. They offered 10 tablets of 10mg Everolimus at $220.

Almost double. And they did not accept Paypal

So, the choice is obvious.

This is a great find. Do you have to contact them to get prices?

Interesting question
at least for the immunosupresive effect, their conversion is 1:1. (I don't quite get how they compared them though)
https://www.ncbi.nlm...pubmed/21457330
Also I recall that Everolimus was claimed to inhibit MTORC2 less so less `side effects` like ulcers should occur.

Although this may not suit your wallet, you can take more everolimus because with weaker mTOR2 inhibition you can inhibit mTOR1 more with a higher dose without the side effects.

[Valijon]

Fewer side effects is a real boon. I could go 5mg a week. Thanks for letting us all know.

[Zisos]

@QuestforLife

 

Regarding Pricing:

I first found them @ indiamart, where they advertise the price in  Indian currency. When I converted it to US$,

I contacted them, and asked them for price in US$, and method of payment. They responded pretty quickly.

 

 

Regarding effects of everolimus

I have no background in biology. However, from what I have read, everolimus has a much shorter  halflife than serolimus. So there is less risk of influencing mTor2. That means you could either take it more frequently, or bigger dose than serolimus, hopefully with better results.

 

 

I have not started treatment yet. I want to do some basic blood tests before I start. I plan to  take 1/4 of the pill per weak.

 

 

 

[aribadabar]

 everolimus has a much shorter  halflife than serolimus. So there is less risk of influencing mTor2. That means you could either take it more frequently, or bigger dose than serolimus, hopefully with better results.

 

I plan to  take 1/4 of the pill per weak.

 

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.

[QuestforLife]

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 would expect and equal dose of everolimus and sirolimus to have the same beneficial effects, but everolimus to have less side effects. Therefore it is safer to go for a bigger dose and see if you can increase the benefits.

I'd try half a pill a week (5mg).

I recently tried 15mg of sirolimus (Rapamycin). I don't take it regularly anymore so didn't have any in my system already. Aside from feeling rather sleepy the next day I have no side effects to report.

[Valijon]

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