955 replies to this topic

[Razor444]

 

I hate to be a wet blanket, but curcumin has been shown to reduce the bioavailability of rapamycin (Everolimus, which is a rapamycin analog - or rapalog). The discussion of this is back about a page, so I'll copy it here:

 

 

 

I believe vit D also increases the metabolism of rapa. So a different dosage may be appropriate for summer/winter.

[to age or not to age]

Jaris: regarding curcumin negatively impacting the bioavailability of everolimus, if we were to not take curcumin 

the day before and the day we take rapamycin, would it get into our systems better? And once it is digested taking

curcumin at that point might not matter. Any ideas?

[Jaris]

Jaris and Valijom,

 

Taking rapa formula before 60 yo.   Just remember what rapa does.  By inhibiting the signal to TORC 1, it is getting rid of bad senescent cells.

https://www.fightagi...enescent-cells/

 

In other words at ages under appx. 60 years you do not have the problem of bad senescent cells which makes you age and all the diseases that go with that.  Your immune system is strong.  In mouse studies they gave young and old mice rapa until death.  They all lived longer, but there was little or no benefit to taking rapa at a earlier age.  A normal person in his 50's can run marathon's and really improve his body and stamina, but once ageing kicks in that is not possible.  Then you want a delaying action by using the rapa formula.  To delay death and ageing and by doing that you are delaying all the diseases that go with it.  If you really want to learn, read Dr. Greens website and all the cites listed there and all your questions will be answered.

 

Rapa is not a fountain of youth.  A young person is not going to get more energy, and get younger.  The best an ageing person can do it delay death for as long as possible until something better comes along, and I believe that will happen in the next 10-20 yrs.

 

If I was under 60, I would not even think of experimenting with rapa, but would concentrate on healthy eating and exercise in order to feel good and strong.  The age of 60 is considered middle age for mice and people when it comes to ageing.  Somewhat different than normal thinking, but if a person is going to live to 90 or above it makes sense.

 

One person's opinion.

Oh, it does a lot more than get rid of senescent cells. As someone has said before: when we are young, "grow, grow, grow" is appropriate and necessary. But as we age, our cells are spending too much time growing and not enough cleaning out garbage and repairing, so by the time we're 50, our cells are already sloppy and leaking, causing inflammation and damaging other cells. If you've never compared a 50 yo's cells to a 30 yo's (human) you really should; the difference is startling. There is (was?) a youtube video on that but now I can't find it.

 

As i said before, I have little to base this on, because very few good studies have been done on humans. Extrapolating from mice to humans is always tricky. For example, a mouse at 20 months might be considered middle-aged, but just before that - at 18 months - he's keeping up with the 12 month old mice. Same can't be said for a 50 yo human keeping up with a 30 yo human. Have you seen many 40 yo NBA stars?

 

So I stand by my previous guess (and that's what we're really doing - don't kid yourself). If I was 45, knowing what I *think* I know now, I would probably be taking a very small dose every 2 weeks or so, with maybe a few months off every year. Just another person's opinion.

Edited by Jaris, 16 May 2017 - 05:36 PM.

[Jaris]

Jaris: regarding curcumin negatively impacting the bioavailability of everolimus, if we were to not take curcumin 

the day before and the day we take rapamycin, would it get into our systems better? And once it is digested taking

curcumin at that point might not matter. Any ideas?

Not too long ago, I would have assumed the same, but now I'm not so sure. It's not just getting something into your system that's important, it's keeping it there. There are various enzymes inside our bodies that bind, over time, with various molecules in order to remove them. Affecting these enzymes can increase or decrease the time a particular type of molecule remains in your system. This amplifies or diminishes the effects of a drug. In this case, curcumin increases the activity of the enzyme that removes rapamycin.

 

So, I think, if you really want to keep taking curcumin, you'd be best off taking it for a day or 2 towards the end of your week. But then, of course, you have to ask: is the curcumin out of my system before the rapamycin gets into it?

The half-life of curcumin is normally very short, and none should still be in your system after 6-8 hours. Some newer formulations have increased the half-life, as you can see here: https://nutritionj.b...1475-2891-13-11

 

Hope this helps!

[PAMPAGUY]

Drug Half Life Calculator = determines rapa in system before next dose.  Rapa half life 60 hours.

 

http://www.drugsdb.c...ife-calculator/

 

 

 

http://www.miniwebto...=9&n3=168&n4=60

 

another which you can fill in the hours.  Last 3 values for me would be 9 mg, 168 hours (7 days), 60 half life. = 

1.29228564937

 

 

Edited by PAMPAGUY, 16 May 2017 - 10:03 PM.

[Skyguy2005]

Jaris: regarding curcumin negatively impacting the bioavailability of everolimus, if we were to not take curcumin 

the day before and the day we take rapamycin, would it get into our systems better? And once it is digested taking

curcumin at that point might not matter. Any ideas?

 

If you start rapping about all the bad things you've done, that's how you'd know it's working.
 

[DareDevil]

I dissolved the 500mg of Rapamycin in 10ml of 90% alcohol. I took my first weekly dose of 9mg associated with 1000mg aspirin, 5mg roacutane (isotretinoine), and 20mg of a cholesterol lowering statin.

 

The Metformin from TLR is in salt cristals. Taking 1000mg mixed into a yoghurt made me almost lose my cookies. It tastes like heavy duty large rock salt making the yoghurt extremely nauseating. It must be somehow dissolved prior to ingestion it is so very salty!  Any ideas on how to reduce the discomfort of its ingestion? I will reduce the daily dosage to 50mg if it tastes this awful and produces nausea.

 

DareDevil

Edited by DareDevil, 17 May 2017 - 10:47 PM.

[tintinet]

I started with 250 mg. Took me a while to increase the dose.

[malbecman]

 Put it in gelatin capsules?  You can get them off Amazon and the size O will hold 250-500mgs, depending on your crystals.

[DareDevil]

I can't say if it's a placebo effect, as I didn't expect much of anything knowing that Rapamycin has effects over a long period of intake and no sudden results. However, I've noticed better energy levels and also generally feeling in better physical shape a mere twelve hours after my first intake of the above outlined protocol. I didn't take my usual supplements to not cloud the results. This substance will remain on my bucket list for some time to come. I think that dissolving the powder in 90% alcohol works quite well. I only need to find a way to absorb the metformin without getting ill from the salt crystals it's blended into. FWIW

 

DD

[DareDevil]

One thing I wonder, and obviously this has to do with a very different half life to each substance taken together, is whether a protocol can be simplified even if slightly less effective?

 

- weekly intake of Rapamycin / Metformin / Aspirin / Tretinoine / Statin / (hope to add Candesartan)

 

While it may be better to always keep higher levels of each of the above in the bloodstream while Rapamycin is slowly dwinding, it might still provide 60 or 70% of the benefits with a far simpler weekly intake protocol?

 

I am trying out many protocols and wanting to simplify my daily intakes. Thanks for your ideas.

 

DareDevil

[VP.]

How well did it dissolve? How did you measure out for 9mg?

I dissolved the 500mg of Rapamycin in 10ml of 90% alcohol. I took my first weekly dose of 9mg associated with 1000mg aspirin, 5mg roacutane (isotretinoine), and 20mg of a cholesterol lowering statin.

 

The Metformin from TLR is in salt cristals. Taking 1000mg mixed into a yoghurt made me almost lose my cookies. It tastes like heavy duty large rock salt making the yoghurt extremely nauseating. It must be somehow dissolved prior to ingestion it is so very salty!  Any ideas on how to reduce the discomfort of its ingestion? I will reduce the daily dosage to 50mg if it tastes this awful and produces nausea.

 

DareDevil

 

[longévité]

 

Jaris and Valijom,

 

Taking rapa formula before 60 yo.   Just remember what rapa does.  By inhibiting the signal to TORC 1, it is getting rid of bad senescent cells.

https://www.fightagi...enescent-cells/

 

In other words at ages under appx. 60 years you do not have the problem of bad senescent cells which makes you age and all the diseases that go with that.  Your immune system is strong.  In mouse studies they gave young and old mice rapa until death.  They all lived longer, but there was little or no benefit to taking rapa at a earlier age.  A normal person in his 50's can run marathon's and really improve his body and stamina, but once ageing kicks in that is not possible.  Then you want a delaying action by using the rapa formula.  To delay death and ageing and by doing that you are delaying all the diseases that go with it.  If you really want to learn, read Dr. Greens website and all the cites listed there and all your questions will be answered.

 

Rapa is not a fountain of youth.  A young person is not going to get more energy, and get younger.  The best an ageing person can do it delay death for as long as possible until something better comes along, and I believe that will happen in the next 10-20 yrs.

 

If I was under 60, I would not even think of experimenting with rapa, but would concentrate on healthy eating and exercise in order to feel good and strong.  The age of 60 is considered middle age for mice and people when it comes to ageing.  Somewhat different than normal thinking, but if a person is going to live to 90 or above it makes sense.

 

One person's opinion.

Oh, it does a lot more than get rid of senescent cells. As someone has said before: when we are young, "grow, grow, grow" is appropriate and necessary. But as we age, our cells are spending too much time growing and not enough cleaning out garbage and repairing, so by the time we're 50, our cells are already sloppy and leaking, causing inflammation and damaging other cells. If you've never compared a 50 yo's cells to a 30 yo's (human) you really should; the difference is startling. There is (was?) a youtube video on that but now I can't find it.

 

As i said before, I have little to base this on, because very few good studies have been done on humans. Extrapolating from mice to humans is always tricky. For example, a mouse at 20 months might be considered middle-aged, but just before that - at 18 months - he's keeping up with the 12 month old mice. Same can't be said for a 50 yo human keeping up with a 30 yo human. Have you seen many 40 yo NBA stars?

 

So I stand by my previous guess (and that's what we're really doing - don't kid yourself). If I was 45, knowing what I *think* I know now, I would probably be taking a very small dose every 2 weeks or so, with maybe a few months off every year. Just another person's opinion.

 

 

According to his interview for Spring Chicken: Stay Young Forever or Die Trying (https://tinyurl.com/kubwqpf), Mikhail Blagosklonny had been taking Rapamycin continuously for 5 years as of 2014.

 

As Dr. Blagosklonny was born in 1961, it is determinable he began taking Rapamycin at age 48 or age 49.  Personally, I believe Blagosklonny knows better than the retired Pathologist Green who keeps getting mentioned here as to whether Rapamycin is efficacious in middle age.

 

Also cited earlier in the thread: Tim Ferriss (age 39) and Peter Attia, MD (age 43) both vaguely self-reported trying Rapamycin and are on the forefront of the longevity movement. Check out their interview together at http://tim.blog/2016...aster-island/. 

 

Dr. Attia also has an interesting interview with Chris Kessler about Rapamycin here where he notes "rapamycin is the only drug that has ever enhanced the lifespan in all four model species—yeast, worms, flies, and mammals.": https://chriskresser...th-peter-attia/

Edited by longévité, 20 May 2017 - 07:50 AM.

[VP.]

Alex Zhavoronkov takes Rapamune. He is 38 years old.

 

https://en.wikipedia...lex_Zhavoronkov

 

 

https://www.facebook...&type=3

 

 

[tintinet]

Alex Zhavoronkov takes Rapamune. He is 38 years old.

https://en.wikipedia...lex_Zhavoronkov


https://www.facebook...&type=3

I'd like to know his dose and schedule and whether he also takes Metformin, etc..

[sthira]

Alex Zhavoronkov takes Rapamune. He is 38 years old.

https://en.wikipedia...lex_Zhavoronkov


https://www.facebook...&type=3

Is it interesting that he's using the Ageless Cell supplement? It is the stuff formulated by LEF and Insilico. NAC, myricetin, EGCG, and gamma-tocotrienol.

Anyone take it? Why would he?

[Heisok]

He is the CEO of InSilico, but that does not answer the question. I am also curious,

Edited by Heisok, 22 May 2017 - 02:49 AM.

[tintinet]

Alex Zhavoronkov takes Rapamune. He is 38 years old.

https://en.wikipedia...lex_Zhavoronkov


https://www.facebook...&type=3

Is it interesting that he's using the Ageless Cell supplement? It is the stuff formulated by LEF and Insilico. NAC, myricetin, EGCG, and gamma-tocotrienol.

Anyone take it? Why would he?

I'm wondering about this also- looks like a typical overpriced LEF melange to me.

Edited by tintinet, 22 May 2017 - 07:55 AM.

[PAMPAGUY]

Started rapa experiment on Feb 04, 2017.  Got labs from May 03, 2017 when I got my physical.  I will be 71 in July.  

Weight 188 lbs., 71" tall, lost 12 lbs most fat.  Easy to say no to food with Rapa + Metformin.  I expect to be below 180 by my next labs in 3 months.  It is not a lose weight pill, but it helps.  I'm taking 2000 mg Metformin SR daily, split between morning and late afternoon.  I feel that I have control over my eating which I have never had before.  No side effects so far.  Had a sore on my tongue from Rapa, but went away in 1 day.  Rapa is suppose to increase Lipids, and Glucose.  With Metformin and Crestor my Lipids and Glucose have actually improved.

 

Lipids, Total-129, LDL-57, HDL-49, Triglyceride-116  My creatinine(kidney function) went from 135 to 1.04 which was amazing. This usually goes up with age.  Expect this to drop even further next time.  Fasting Glucose-99. A1C-6.2.  Expect both the numbers to drop as I still have 20 more lbs to lose.  CBC, WBC 7.50, RBC-4.92, HGB-14.2, HGT-42.9.  I have more energy and I feel that goes along with a higher RBC and the other oxygen carrying blood cells.  I was borderline anemic which is caused by low RBC counts.  If you can carry more oxygen then you will have more stamina and energy.  Feeling better for me on this formula is a slow, but steady improvement.

 

My goal is to have the same smile of happiness as my white dog moniker from the Dog Project.

 

Will post my labs, side effects, etc. to this post every 3 months.  This way it will be easy to compare.  If anyone wants to know more blood results just ask.

 

[Mind]

First let me compliment LongeCity forum posters with continuing to lead the web in high quality life extension and supplement discussions.

 

That being said, a poster did report the off-topic nature of a few posts in this thread (a couple pages back), and many of you appropriately "junked" these posts as well.

 

I am not going to separate those out (too much work) however, please try to stay on the topic of rapamycin. This is a substance with potential and this thread contains some very useful information.

 

If you would like to discuss the rationale of using rapamycin in combination with other supplementation, please start a new discussion.

 

I additional off-topic posts are reported in this thread, they will be deleted.

[VP.]

Short-term rapamycin treatment increases ovarian lifespan in young and middle-aged female mice

Although age-related ovarian failure in female mammals cannot be reversed, recent strategies have focused on improving reproductive capacity with age, and rapamycin is one such intervention that has shown a potential for preserving the ovarian follicle pool and preventing premature ovarian failure. However, the application is limited because of its detrimental effects on follicular development and ovulation during long-term treatment. Herein, we shortened the rapamycin administration to 2 weeks and applied the protocol to both young (8 weeks) and middle-aged (8 months) mouse models. Results showed disturbances in ovarian function during and shortly after treatment; however, all the treated animals returned to normal fertility 2 months later. Following natural mating, we observed prolongation of ovarian lifespan in both mouse models, with the most prominent effect occurring in mice older than 12 months. The effects of transient rapamycin treatment on ovarian lifespan were reflected in the preservation of primordial follicles, increases in oocyte quality, and improvement in the ovarian microenvironment. These data indicate that short-term rapamycin treatment exhibits persistent effects on prolonging ovarian lifespan no matter the age at initiation of treatment. In order not to disturb fertility in young adults, investigators should in the future consider applying the protocol later in life so as to delay menopause in women, and at the same time increase ovarian lifespan.

http://onlinelibrary...acel.12617/full

[PAMPAGUY]

Brand new published article by  Mikhail V. Blagosklonny, Phd, MD.  "From rapalogs to anti-aging formula"  In my view one of the most important papers ever published on delaying ageing.

 

  From article, "Given that rapamycin consistently extends maximal lifespan in mice, rapamycin will likely allow mankind to beat the current record of human longevity, which is 122 years. Yet, rapamycin will not extend life span as much as we might wish to. Now is the time for anti-aging drug combinations. For example, metformin is currently undergoing repurposing as an anti-aging agent. Several other existing drugs can be re-purposed. Now we can design an antiaging formula, using drugs available for human use. However, we must first discuss the link between growth, aging and age-related diseases."

 

Best part is that Viagra is part of antiaging formula.

                                         

http://www.impactjou...33&path[]=57761

Edited by PAMPAGUY, 31 May 2017 - 07:57 AM.

[PAMPAGUY]

Now, the time is for the anti-aging formula, which combines around 7 drugs with diet and physical exercise. The anti-aging formula is ready for human use. If one will wait until the life-extending effect will be shown in others, this individual will not be alive by the time of the result. Human clinical trials are needed to optimize the doses and schedules. However, unless we participate in clinical trials ourselves, we will not know how long participants will live because they are expected to outlive non-participants. If we want to live longer we should be participants in clinical trials. In the best scenario, this might allow us to live long enough to benefit from future discoveries of anti-aging remedies. Experimental anti-aging drugs such as pan-mTOR inhibitors might be approved for future anti-aging formulas. Finally, if mTOR-driven aging will be abolished, anti-oxidants may become useful to treat post-aging syndrome [245]. And step-by-step, humanity will extend life span.

[Chris Pollyanna]

Hi,

 

A heads up to some up and coming research on rapa:

 

resTORbio a subsidiary of PureTech, has taken up Novartis' work on Everolimus (a rapalog), which demonstrated a 20% improvement in immunity among elderly subjects in a paper published in 2014. They have just initiated a Phase 2b study on it and another rapalog.

 

However, even more exciting, is the fact that it appears that Novartis has already conducted a successful follow up to that first study, which when released should provide us with more information regarding dosing and potential side effects! (and hopefully a bit of efficacy!) 

 

"The Phase 2b study builds on two successful Phase 2a studies conducted by Novartis that assessed the immune-enhancing potential of these mTORC1 inhibitors in hundreds of elderly patients. The unpublished results from one of those studies, which form the foundation for further clinical development of RTB101 alone or in combination with RAD001 (Everolimus) for immunosenescence and other aging-related diseases, will be detailed in an upcoming peer-reviewed publication."

http://www.businessw...Phase-2b-mTORC1

[Decimus]

I am beginning rapamycin today. I am a 40 year old male. I will be taking 3mg every 10 days. This was the dose and frequency recommended to me by Alan Green. I will let people know if I get any effects, positive or negative.

[PAMPAGUY]

Good luck. Are you taking anything else? Did you see Dr Green at his office? Only 40 yo very low dose.
Again, Good Luck

[VP.]

Good luck. Are you taking anything else? Did you see Dr Green at his office? Only 40 yo very low dose.
Again, Good Luck

I understand Dr. Green will not see anyone under 60. Is that still true?

[APBT]

Since we now have more than a few folks experimenting with Rapamycin, I thought it might be useful to have a central location to discuss places to purchase, vendors etc...  I've started a thread for those who care to share.
http://www.longecity...amycin-vendors/

 

[Decimus]

Only 40 yo

 

 

I don't consider 40 to be that young. I've been a member here since I was 29 and I'm a big believer that it is, unfortunately, unlikely that anything will come out in the next 10-15 years that will do anything to meaningfully reverse aging so, everyone over 35ish should be taking measured risks to slow down aging as much as possible now.

 

 

Are you taking anything else?

 

I take: 

 

glycine which has increased lifespan in mice between 30-40%

 

spermidine which increases lifespan 10% in mice 

 

and glucosamine which increase lifespan in mice upwards of 10%

 

 

Did you see Dr Green at his office? 

 

I did.  He won't accept phone consultations.  He's a knowedgeble fellow and it was very difficult to accurately measure out 2-3mg on a scale of the rapamycin I received from LTR.  Very glad I took the time to get a legitimate prescription.  This is not a drug you want to guesstimate the dose on.  

 

 

Good Luck

 

 

Thank you.

[Decimus]

 

Good luck. Are you taking anything else? Did you see Dr Green at his office? Only 40 yo very low dose.
Again, Good Luck

I understand Dr. Green will not see anyone under 60. Is that still true?

 

 

I've been in contact with Alan for about a year.  We agreed the risks for a 40 years person on rapamycin is low if the dose is lower and slightly less frequent than the "standard protocol."  He will see people under 60.