Update on Brad Stanfield's Rapamycin Clinical Study in NZ

#100

First, we can’t ignore the fact that Rapamycin was shown to improve muscle gain in animals. Yes, the mechanism would suggest otherwise and we now finally have proof of that in humans. It makes sense I suppose since animals aren’t strength training the same way that humans are.

You actually bring up something important as far as longevity vs muscles is concerned. It does appear that we must have to choose one or the other when it comes to Rapamycin. I was hopeful that Rapamycin wouldn’t interfere with muscle based on the outcomes of all the animal studies showing that it didn’t.

Since we now know it does in humans (at least for once weekly dosing at 6mg), I personally would rather have big muscles while just continuing all other longevity interventions I’m already doing, even if there is a minor trade off in longevity. Just my personal choice.

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#101

Sounds like cope. Rapamycin, at low to moderate doses, does pretty much nothing even when taken daily. You need full body penetration and saturation at very high doses to have any sort of lifespan extension effect which works even when taken infrequently or only for a ““short”” duration.
Imo 20-100mg taken once every three months while you don’t go outside probably has the best chances of improving your overall health and give you lifespan extension effects.

#102

exactly but that is the point. It implies it by proving that it is not good for muscle building (I’m staying away from the scientific terms and just reading the layman version of it) which is to say that to date most interventions that mimic calorie restriction which is basically mtorc inhibition have shown positive effects on longevity. Even Sglt2i are being argued to provide the longevity benefit via similar mechanics, apart from the glucose impact. I tend to discount this study as anything other than proving the obvious which we knew (or was known) all along which is to say mtorc inhibition is bad for exercise and muscles. Not much new here IMO.
I don’t mean it to say it to be controversial, but I’m a bit more comfortable now (meaning Rapa will help with longevity) than I was last night (pre this study) because as I mentioned above it is exactly what we thought it would do (negatively (mildly) effect exercise) and this study did seem to prove it.

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#103

@John_Hemming and everyone…

If one wants to consider dosing every two weeks vs weekly, how do we begin to figure out the right dose to try?

In the US, it’s easy and cheap ($17) to test rapa blood levels, so it’s an experiment I can easily track.

I’ll think out loud l…

I currently take 8mg each sat

My workout schedule is:

Monday- resistance training (RT)

Wednesday- RT

Friday- pilates

Saturday- rapa day.
I was taking rapa on Saturdays so it was after pilates and 2 days prior to Monday RT.

Until I figure out the pro and con of a two week dosing schedule, would someone recommend I take rapa on Thursday? That is the day after my RT on Wed, and then I have many days before Mon, and I just sacrifice the less important pilates? Or is Friday night a better call?

On pros and cons of dosing schedule:

Every two weeks might be better for muscles… that is good for my puny self.
But, if I’m taking a higher dose, then I’m probably blunting that week’s RT even more, so maybe the extra blunting of one week vs less blunting of one week is a wash?

Rapa cured my insomnia which is the biggest health promoting thing it could ever do for me. I assume skipping one extra week won’t make a difference, but if it did, better I just workout harder.

Does a larger dose make us more vulnerable to negative consequences… greater chances of infection etc… I assume so?

Larger dose might give a boost to some of the health promoting effects… I assume so?

Would just adding one day of RT make all this a moot point… or maybe I should take it every two weeks, and I could add that extra day on my off week and then turn into the @agetron of old ladies

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#104

hope you don’t take this as arguing, but haven’t you been taking RAPA for a while now? And if you are relatively content with your physical appearance (I only wish my body was about 30% as good a shape as yours LOL) then why go for perfection, when we all know that perfection is the enemy of anything and everything. Again, not trying to change your mind, but the marginal effect on muscles I think is compensated by longevity effect of RAPA. Just my opinion.

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#105

I find the results disappointing but actionable.

While weekly dosing of rapamycin seems to blunt exercise. My personal experience is that rapamycin preserves muscle mass and delays sarcopenia. The rat and other mammal studies suggest that this is true even though there are no significant long-term studies in humans.

Exercise is still best.

Since I go to the gym regularly, it looks like I should switch from weekly dosing to biweekly or even monthly dosing.

I am also taking 75 mg of maraviroc daily. “The Chinese University of Hong Kong have repurposed Maraviroc—a well-known antiretroviral drug used to treat HIV—to reverse sarcopenia, the debilitating muscle loss associated with aging.”

Gleaned from Claude Opus 4.7:

“The evidence base for any pharmacological sarcopenia intervention in humans is weak. Maraviroc, rapamycin, urolithin A, MOTS-c, BPC-157 — all have mouse data and thin or absent human efficacy data for muscle mass. The intervention with the most human evidence remains resistance training + adequate protein intake (+ vitamin D if deficient), and the effect size from that is substantially larger than anything pharmacological has demonstrated.”

Multiomics and cellular senescence profiling of aging human skeletal muscle uncovers Maraviroc as a senotherapeutic approach for sarcopenia

Implications of maraviroc and/or rapamycin in a mouse model of fragility

A frailty-model paper co-administered maraviroc and rapamycin (the canonical mTORC1 inhibitor), finding additive benefits on muscle markers: muscle myostatin was reduced in rapamycin and maraviroc+rapamycin groups, and caspase-3 was significantly lower in both MVC and RAPA groups. This suggests overlapping but not identical mechanisms — consistent with maraviroc acting upstream on inflammatory signaling that feeds into mTOR rather than on mTOR itself.

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#106

There are mammalian studies showing rapamycin shortens lifespan, but they’re in specific, non-normal contexts. Mammalian studies with normal genetics have improved lifspan. We are waiting on Matt Kaeberlein’s dog project results. I hope we have some preliminary observations soon.

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#107

Definitely not an argument. I always like your insight so anytime somebody like you can challenge me on something, I appreciate it more because it enables me to reconsider… “I’d rather get it right than be right.” To steal a quote from Huberman (regardless of what we think of him, that was a good quote).

Thanks for the compliment about my physical appearance. I do wonder if I might have made even more gains if I wasn’t taking Rapamycin the whole time. I am still on a big list of other longevity drugs/supplements so it’s not like I am flying “naked” without Rapamycin.

I just read Matt Kaeberlain’s statement above and now think I will do a 10mg Rapamycin every 1-2 months approach. He is right that there is still valuable positive data I shouldn’t dismiss. This is all new so I’m still deciding.

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#109

This sound interesting. I might give this a try myself at some point.

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#110

I’ve just been taking 6mg every 3 months or so. Treating it like doing a week long FMD or something like that. That plus increased infection risk has made my wary of more frequency

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#111

Stanfield mysteriously said prior to the results being released that if someone were to use Rapamycin, every 6 week dosing might make the most sense. Now I understand why he made that suggestion.

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#112

That’s two people on every 6 weeks.

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#113

John, on your higher (but unspecified) dose, do you encounter any noticeable side effects? Any un-noticed side effects (like lipid or glucose disregulation)?

#114

It is not that much different to the dose where i published the results on this forum.

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#115

I never added it back after I logged how it impacted my strength. My wife had the same experience - she also had to drop it. When I reach my hypertrophy goal and enter maintenance, at most I might take it once a month or maybe every 6 weeks during a deload week.

This result doesn’t surprise me at all.

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#116

The marmoset study (daily 1mg/kg dosing) has resulted in a 15% lifespan improvement without noticeable frailty compared to the controls. It may be that a minor limit on muscle growth may be the price to pay for 10% or 15% life extension.

I’ve been communicating with Adam Salmon and he will give me an update this summer. There is still at least one of the marmosets still alive… so they haven’t wrapped up the study yet.

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#117

I must re-examine my approach to longevity. Unfortunately, all longevity theories have major hurdles to overcome, as exemplified by the Hayflick Limit. This has the major gotcha of trying to increase telomere length will increase your chances of getting cancer and exacerbating any existing cancer.

I asked Claude Opus 4.7 (spending some of my tokens)
Aging Theories.pdf (99.1 KB)

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#118

I am getting more bullish on rapamycin. The result from this clinical trial shows that it’s having an effect… it’s inhibiting mTOR. Of course that’s the point but it’s inhibiting it in the way we kind of expect.

I learned long ago that mTOR is important for exercise physiology. They tested some hyperactive mTOR effect hypothesis in this trial, and that couldn’t be compensated during the study duration. Short term gains were affected. Who knows about long term gains and sarcopenia that takes decades, and more than muscles age which mTOR inhibition would affect.

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#119

As I previously mentioned, I do think rapamycin delays sarcopenia. Because of my n=1 experiment, I can only go by the observation of my contemporaries and myself. Not to mention that every single one of my coworkers that were my age or older are dead, and I’m not (yet).

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#120

After reading everything said… I can see what is the concern… and maybe not surprising.

I began my medical prescription intervention with Testosterone…TRT. Had crazy muscle and weight gain… hit a new weight high of 200+ pounds… that was a full year of weekly testosterone prior to starting rapamycin.

Read that rapamycin at 3 months … excess weight would topple… and it did… concerning me at first. That 200 pounds dropped a few pounds a week and was closer to 180.

Then, the weight loss… the visceral fat loss stopped… it cleared all the excess. And… just likecthat stopped… preserving all the needed stuff.

So true, I didn’t grow bigger on rapamycin… but on my shredded muscle frame… it did not stop me from getting stronger. Like the Bubble Bee that shouldn’t be able to fly… I, without gaining muscle size… I continued to gain strength :muscle: raising weights every 3-4 months. Almost doubling my ability… and I can still equally lift …if not out lift most of the younger gym bros.

So like Matt Kaeberlein says… it is one study… don’t read too much into it… I am leaner… and stronger… maybe more like the tough sinewy cro-magnon hunter’s build. No fat, nothing extra.

Weekly 6 mg dosing pretty much non-stop almost 5 years… only break was this year to let thymus grow for my CT Scan. And, I felt the absence of rapamycin at 2 months… body started feeling out of sync. Pushed to skip 3 months. Wanted to get back on and feel good again.

I did overdose… higher amounts weekly…for 7 months… no MTOR 1 recovery…I did feel more tired then more lean… bio-markers showed faster aging too.

Dose is important. My N=1 is 6mg weekly rapamycin and 200 mg TRT. I think they have a synergistic balance… shredded, strong… low inflammation… great DNA Methylation.

Not growing … but not losing either… maintaining and no loss of strength. To look the same 5 years out. For me it is working :100:.

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