Using RAPA for AD prevention

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Re: Using RAPA for AD prevention

Postby slacker » Sun Feb 09, 2020 4:56 am

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Re: Using RAPA for AD prevention

Postby bosco » Mon Mar 02, 2020 5:06 pm

Hi Newtothis,
I see you posted this about a year ago. I'm very interested in rapa but want to find out more before traveling to NY. I live in California a would like to get a Rx for rapa closer to home. What has been your experience, ie. side effects, positive effects. Anything you can share would be appreciated. Are you also taking Metformin. Any thoughts about Dr. Green and does he do any follow ups? Thanks in advance for any information you can share.
Very best,
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Re: Using RAPA for AD prevention

Postby bosco » Tue Mar 03, 2020 4:40 pm

I see that most of these posts are from almost a year ago. I would love to know if anyone has followed through and started taking rapamycin and or metformin. If not why? If so, any comments or thoughts. Seem like the only place to get a Rx is from Dr. Green. Are there other sources.
Thanks,
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Re: Using RAPA for AD prevention

Postby Newtothis3/4 » Wed Mar 18, 2020 9:39 pm

I’ve been taking Rapamycin, metformin and NAD+ for 8 months now. Yes, Rapa works. It’s incredible. All of my labs have improved or stayed the same. My memory is the best it has ever been. My skin, nails, gums, energy and cardiovascular ability or all like they were when I was 25. The visible changes are indicative of Rapamycin being able to completely stop AD from ever forming. I am confident that anyone who takes Rapamycin intermittently before AD symptoms appear will never get AD (or cancer, diabetes, etc). In fact, Dr. Green recently told me that a woman who works in Southern California whose one of the countries leading scientists working on the E4 gene (she is E3/4) just became a patient of his. She also brought a few other doctors to become patients for the longevity aspect. If her conclusion is that taking Rapa is the best way to stop AD, than I’d say I’m in good company:)

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Re: Using RAPA for AD prevention

Postby karelena » Thu Jul 09, 2020 4:44 am

Newtothis3/4 wrote:I am confident that anyone who takes Rapamycin intermittently before AD symptoms appear will never get AD (or cancer, diabetes, etc).


I am not so confident that it will 100% prevent AD, but I started taking it too a couple of weeks ago. It just seems that the mechanism of action would be helpful in particular for APOE 4/4. My prescription also came from Dr. Green. Thankfully sirolimus is now available as a generic in the US, a 3 month supply was $330 at Costco with a GoodRx coupon. It is very off label so insurance is likely to deny coverage.

Dr. Green also recommends senolytics, in particular dasatinib and fisetin once every 2-6 months. Are you doing this also?

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Re: Using RAPA for AD prevention

Postby Brian4 » Thu Jul 09, 2020 5:43 am

bosco wrote:I see that most of these posts are from almost a year ago. I would love to know if anyone has followed through and started taking rapamycin and or metformin. If not why?

Hi Bosco,

I decided not to take rapamycin, partly for reasons cited earlier (dosage needed for effect is probably huge), but mainly because I'd rather wait until an mTOR inhibitor is developed with a very short half-life, so that one could take it late in the evening and it would reinforce the natural mTOR rhythms of the body (lower – though not in all tissues – at night; higher during the day).

Also, evolution gave us a program of longevity and health based on restricted eating, a program that includes a simple way to alter mTOR levels (eat less). Until we have more research, I feel more comfortable lowering mTOR signaling through diet.

A reminder of what Tincup noted:
Tincup wrote:Prior discussion of Rapamycin here.
There are some good tidbits in other threads.

bosco wrote: Seem like the only place to get a Rx is from Dr. Green. Are there other sources.
Any doctor can prescribe it, and antiaging doctors in particular are likely to be very willing to prescribe it. Here's one list of doctors with at least some experience prescribing rapamycin:
https://age-reversal.net/physician-directory/

Dr. Green has more experience with rapamycin than most doctors, however. But there are others who have been prescribing rapamycin off-label for several years.

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Re: Using RAPA for AD prevention

Postby Tincup » Thu Jul 09, 2020 7:01 am

There is a recent Peter Attia podcast with Lloyd Klickstein M.D., Ph.D on the topic. I've only listened to the intro.
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Re: Using RAPA for AD prevention

Postby karelena » Fri Jul 10, 2020 3:53 am

Brian4 wrote:
bosco wrote:I

I decided not to take rapamycin, partly for reasons cited earlier (dosage needed for effect is probably huge), but mainly because I'd rather wait until an mTOR inhibitor is developed with a very short half-life, so that one could take it late in the evening and it would reinforce the natural mTOR rhythms of the body (lower – though not in all tissues – at night; higher during the day).


Brian



I think that some do not realize that mouse dosages in mg/kg do not equate to human dosages in mg/kg. The mouse surface area/kg and basal metabolic rate are very different. For example mouse heart rate is 310-840 and resp rate is 80-230. Typically the mouse dose is reduced by a factor of 12 to arrive at an equivalent human dose. 10 mg/kg for a mouse would be 0.8 mg/kg for a human.

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Re: Using RAPA for AD prevention

Postby Brian4 » Fri Jul 10, 2020 5:19 am

karelena wrote:
Brian4 wrote:
I decided not to take rapamycin, partly for reasons cited earlier (dosage needed for effect is probably huge), but mainly because I'd rather wait until an mTOR inhibitor is developed with a very short half-life, so that one could take it late in the evening and it would reinforce the natural mTOR rhythms of the body (lower – though not in all tissues – at night; higher during the day).

Brian

I think that some do not realize that mouse dosages in mg/kg do not equate to human dosages in mg/kg. The mouse surface area/kg and basal metabolic rate are very different. For example mouse heart rate is 310-840 and resp rate is 80-230. Typically the mouse dose is reduced by a factor of 12 to arrive at an equivalent human dose. 10 mg/kg for a mouse would be 0.8 mg/kg for a human.
Allometric scaling is more of an art than a science. A nice explanation is here:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737649/
I'm not an expert in rapamycin metabolism, but people who are tell me that the conversion from the mice studies to a human equivalent dosage is complicated because of rapamycin's unique pharmacodynamics. They said the human equivalent dose (per bodyweight) would likely be much higher than MED/12. I'll try to get more info. Regardless, I'd love to see a clinical trial looking into this.

But note that even with the factor of 12 scaling, the dose would still be vastly higher than what Green and others are recommending.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996648/

We initially used a treatment regimen consisting of intraperitoneal (i.p.) injections of 8 mg/kg rapamycin daily for 90 days.
Even with 12:1 scaling, that's a massive dose.

Brian

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Re: Using RAPA for AD prevention

Postby karelena » Fri Jul 10, 2020 6:00 pm

Brian4 wrote:
karelena wrote:
Brian4 wrote:

But note that even with the factor of 12 scaling, the dose would still be vastly higher than what Green and others are recommending.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996648/

Even with 12:1 scaling, that's a massive dose.

Brian


I have read some newer articles with "low dose rapamycin," as low as 0.5 mg/kg in mice, as well as intermittent dosing (3 times a week, then a week off or once a week). Also, a typical human dose for transplant patients is 1-2 mg/day, much lower than the human equivalent of 8mg/kg (human dose equivalent would be 0.66 mg/kg or 47 mg/day for a 70 kg human!)

I'm going to look and see if anyone has measured the mouse blood levels as we do in humans (target level for transplant patients is 6-20 ng/ml); I wonder if the mice have a much higher level, or if their phamacokinetics are just very very different from us. If the mice have high drug levels then that is something that we should NOT replicate, as high levels in humans cause a whole host of nasty side effects such as hyperlipidemia, insulin resistance, bone marrow depression and renal and hepatic dysfunction. Also "neuropathy," which I definitely don't need! Maybe the mice are much more tolerant to side effects of high doses than humans are, so while it is a great drug for the mice, not so much for humans if high doses are needed.


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