Rapamaycin and HMB (hydroxymethylbutyrate)

I currently take Rapamycin and am considering adding the supplement HMB to offset sarcopenia. I’m 51 and have definitely noticed some loss of muscle mass (or difficulty in maintain or gaining muscle mass) despite my dedicated efforts in the gym.

My concern is, it appears that HMB is an activator of mTORC1. If so, isn’t that at odds with what Rapamycin is doing? My fear is that taking it could counter the effects of longevity I am striving for with Rapamycin.

Looking for any insight into using HMB and Rapamycin concurrently, both pros and cons.

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HMB is an activator of mTORC1. If so, isn’t that at odds with what Rapamycin is doing?

I don’t know anything about HMB in particular, but couldn’t one say the same thing about dietary protein? I’ve never heard anyone say “don’t consume protein when taking rapamycin.”

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HMB can be beneficial if you are not consuming enough protein to match your resistance training output. If you are not seeing results, your workout programming may need adjusting, or you need to increase calories through protein and fat sources, whether taking HMB or not. I take HMB as a backup as I know I don’t always meet my protein requirements.
As far as your concern goes, rapa’s mechanisms for longevity thru mtor work basically the same as caloric restriction. It’s similar to the age old question of how do i build muscle while losing body fat, for which a perfect answer doesnt exist, other than having the best diet and enough protein while in a calroic deficit. What Im saying is there are always competing mechanisms when trying to balance the two with or without rapa/HMB. If you NEED to significantly increase muscle, taking rapa and/or being calorie deficient would not be ideal…but I think a balance can be found. 1.6 grams of protein per kg of body weight per day should be your minimum intake.

Thank you for the thoughtful post and providing the PubMed article.

I read the summary page of the article. I’m intrigued by the findings, though I am not sure the dosing protocol recommended here for longevity will yield the muscle loss prevention documented in this study. Again, I did not read the entire research product, but did notice this statement on that summary page…

“2) Developing optimal protocols for rapamycin treatment. Optimized dose, dosing frequency, and dosing intervals may help achieve maximum beneficial effect. As shown in recent reports, long-term (~21 month) rapamycin treatment at 14ppm failed to prevent age-related decline of muscle fiber size, whereas a short-term (6 week) rapamycin treatment at 0.15mg/kg succeeded.”

I am 170lbs, so 77kg. I would need to take 11.5mg of Rapamycin for this short-term 6 week cycle. I’m an every week taker of Rapamycin, but maybe it is a situation where I take my normal dose (6mg/week) and then bump up to 11.5mg for the 6 week cycle. That seems like a high dose but I have no idea what some people have taken and how they tolerated those higher doses. The study summary doesn’t clarify if Rapamycin is taken daily, weekly, or some other frequency.

Also, I’m not sure what “14ppm” translates to for milligrams of Rapamycin. That was the dosage administered for the “long-term” treatment that did not prevent muscle loss.

Thanks again for your reply.

Jeff and Everyone,

Thank you for this most interesting discussion.

I am 66, taking 5 mgr of Rapamycin once a week, working out with weights and running, taking whey protein and HMB pretty much every other day. Looks like muscle building is going well.

One thing I can add to the discussion, in the hope that it doesn’t complicate things:

Recent research re building lean muscle has determined that at ‘our age’, meaning to say after 50, there’s something going on called "anabolic resistance”. Means, I can lift weights. eat all the protein, and still see only slow build-up of muscle mass. Frustrating indeed !!

What the ‘gurus’ say about this is, that we need to shift our intake of amino acids towards Lycine and a couple others to be successful. I recommend looking into that research. It’s pretty convincing to me.

Thanks again,


If you haven’t already considered Testosterone and DHEA that has been a game changer for both men and women for longevity and maintaining muscle. My husband hasn’t lost any mass despite not lifting as heavy into his late 50s. Stay well!

Hi Tara,
I have definitely been considering TRT. I have just heard some pretty bad things regarding side effects as well as shady “medical” clinics administering the treatment. Though I would go to an actual physician to ensure that I am getting the proper diagnosis and treatment with adequate follow-up. Still though, it does seem to be something not to take lightly, but like in your husband’s case, I have also heard plenty of success stories. I have always measured on the low end of the testosterone spectrum so I am pretty sure I could benefit from the treatment.

Thanks for your advice.