Rapamycin for Dogs (part 2)

Dogs

Increasingly people are looking at the research on rapamycin use in dogs and are getting interested in giving it to their own dog, or other pet. I give my dog rapamycin and she’s doing great. I schedule her dosing identical to my own - so when I take my rapamycin, she also gets her rapamycin. I put the 1mg tablet hidden in a small piece of cheese and she takes it with enthusiasm. We work closely with my dog’s vet to make sure she is fully informed about the test we are doing, but my dog’s vet does not yet prescribe rapamycin for dogs in an anti-aging application.

Rapamycin Dosing for Dogs:

In the initial clinical study that the University of Washington did on rapamycin use in dogs, they used a dosing regimen as follows:

Dosing Schedule and Amount:

Schedule: Monday/Wed/Friday

  • The low rapamycin group received 0.05 mg/kg rapamycin (sirolimus) at each dosing.
  • The high rapamycin group received 0.1 mg/kg rapamycin at each dosing.
  • The dogs in the rapamycin treatment groups were dosed to the nearest 0.5 mg based on their body weight at the initial exam.

Note: In this dog study, the dogs were dosed three times per week - M/W/Friday.

I’ve heard that in the new rapamycin dog trial called TRIAD at the University of Washington, they are dosing dogs weekly, at approx. 0.15mg/kg of rapamycin.

In the human applications of rapamycin, most of us are dosing once weekly, and I like to keep it easy by giving my dog its rapamycin at the same time I take mine - but your approach may differ.

Mg. Dosing for representative dog weights:
25lbs/11.3kg, Low Dose Rap: 0.5 mg High Dose Rap: 1.1mg
50lbs/22.6kg, Low Dose Rap: 1.0 mg High Dose Rap: 2.2mg
75lbs/34kg, Low Dose Rap: 1.5 mg High Dose Rap: 3.3mg
100lbs/45.3kg, Low Dose Rap: 2.0 mg High Dose Rap: 4.4mg

Due to the difficulty of pill splitting with these tablets (the rapamycin tablets are very small), other than the very lowest dose (0.5 mg), I suspect that the most people, will just round up or down to the nearest mg in terms of dosing.

Side Effects:

Here are the side effects that they saw in phase 1 of the dog rapamycin study. There were a total of 24 dogs in the trial, 8 were in the placebo group, 5 in the low rapamycin group, and 11 in the high rapamycin group:

Heart Function Improvement
In this 10-week study of rapamycin in middle-aged healthy companion dogs they were looking at heart function as their short-term measure of effectiveness. Just as in the mouse studies, he study saw improvements in heart function in the treated dogs. The dogs that got the biggest benefit with rapamycin are the ones that started with the lowest hear function.

Interestingly, out of that study came a case study of a Doberman and cardiac function. Dobermans as a breed are highly prone (60-65%) to dilated cardiomyopathy. In the study, one owner of a Doberman in the study was giving her dog echocardiograms before coming into the study. That Doberman happened to be randomized into the higher rapamycin group and had one of the best responses in terms of improved cardiac function. The Doberman went from borderline dilated cardiomyopathy to ~10% improvement in EF, which is well into the normal range.

Rapamycin pricing.

The University of Washington now (we believe) uses the Zydus Siromus (sirolimus) version of rapamycin in their Dog Aging Study. This medicine is available from online pharmacies in India for about $0.50 to $1.15 per 1mg tablet. If you give your 30lb dog 1 tablet of 1mg rapamycin (sirolimus) each week, that works out to a cost of about $50 a year.

Veterinarians prescribing rapamycin for dogs.

Please add to this list by commenting below if you find other vets doing this. We recommend you work with a veterinary if you want to give your dog rapamycin, so that the full health history of the dog is taken into consideration prior to prescription.

another company selling rapamycin for dogs:

Dog-related Experiences with Rapamycin

From the recent Tim Ferriss Podcast with Kevin Rose
Tim, there is an absolute difference. Darya and I will tell you that — [my dog “Toast”] he’s having some hip issues as he’s getting older, his hips slip out from underneath him from time to time. And it doesn’t help that we have concrete floors and it makes that a little more slippery for him, but he’s jumping up on people now when they come in the house, including us, and just the level of excitement and energy and everything else that’s come out of him. He’s been on it for about two months now. It is working.

My dog is doing well. I do the 14 year old pug for three weeks and then take one week off and I do the 6 year old pug one week on and one week off. Maybe I’ll experiment. They both have really good blood work but the fourteen-year-old was just sleeping all the time and almost seemed to have dementia and now is doing much better

2mg, 30 lbs dog, ~8 yrs old. I now take 10mg once per week. Started with 5mg once per week. Also take metformin and NR. No side affects noted for the dog, just longer walks, no more back pains, more energy and play.

My senior dog has been on Rapamycin for about a year. Since then, his early stage kidney disease has practically vanished, and he has so much energy!! He’s spunky and doing very well, but his Lipase Levels in blood tests have been steadily rising since on Rapamycin and is now in the hundreds. His Alk. Phos. is rising, too, also very high. This could be a complete coincidence. Anyone else have such an experience? My local vet started him on a very high dose of Rapamycin (3 mg. X 3 weekly), but I have now lowered that to half. Wondering if I should lower it any further. Otherwise, he shows no outward negative side-effects, and Rapamycin has been a completely positive experience for him.

My vet knew nothing about Rapamycin. I asked him for it, as my dog was sick and in early-stage kidney disease. My vet made me sign a waiver, and that was the dose he prescribed. I had to get the Rapamycin elsewhere. So, I gave my 60 pound dog 3 mg. Rapamycin (three times weekly) for two months, with a one month rest period, then for another month. He became a super dog! Running around like he did five years ago. His kidney counts went back to normal, as mentioned, but his Alk.Phos. and Lipase had very slight elevations. After that (even off the Rapamycin) they steadily began to rise and are now in the hundreds. My vet suspected Cushings Disease even before the Rapamycin, so the Rapamycin could just be coincidental. I think you’re right in saying I gave him too aggressive of a dose though. He feels much better now than before, though, despite the lab results. Still, I’m worried that they keep rising. Hope I didn’t damage his pancreas or liver.

From one of the original dog rapamycin studies (see CNN Story here):

See Momo run faster, farther and with far more vigor, energy and youthfulness, his owners say, now that he’s taking a drug meant for humans with cancer. “It’s been remarkable,” Paola Anderson said as she watched Momo, her 13-year-old white Pomsky, run around the backyard, keeping up with dogs a third his age.

5 Year Update on the dogs in the above story:

Sherman passed away last month so he lived 19yr 5 months which is long for a Pom, especially one that had a stroke (15 yr) and acute pancreatitis (8 yr) pre-rapamycin. The average Pom lives 12-16 years and the record is 21 years. Momo is still going strong at 18 yr 9 months. Sherman went on a plane trip/bus tour to France from California in 2019 so I assume he was in fairly good health. All in all a very impressive life/health extension.

News articles on Rapamycin for Dogs:

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I have a 17 year old British shorthair cat with hypertrophic cardiomyopathy. He got a stroke 6 months ago, recovered almost completely ( takes a beta-blocker, an antithrombotic and anticoagulant) and since then I give him a weekly 0,15 mg/ kg dose of rapamycin.

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I have an 8 yr old 80 lb (36kg) male unfixed Rhodesian Ridgeback in good health & I started him on sirolimus a couple months ago. He’s doing great w/ a notable improvement in his activity level & enthusiasm. Dr Green recommended 3mg, 3x/week but I’ve been keeping it at just 2x per week. I’m thinking I’d like to move him to a 1 week dosage or even longer to allow a greater washout plus give him any potential benefit of a higher surge dose. This is the plan followed by Dr. Blagosklonny & others for humans (usually 2 weeks).

Does anyone have any thoughts on a good dose for my dog if applied on a weekly basis? Perhaps 6mg to start? Also, what is a conservative sirolimus half-life for such a dog? My thought is to use that half-life to determine the dosing frequency – perhaps requiring the level to fall below maybe 0.5mg before the next dose. Any thoughts are appreciated!

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I’m not sure what the dosing /week is going to be in the new TRIAD rapamycin dog trial but if you extrapolate from the preliminary dog study they did where they dosed three times at week (mentioned at the top of this post) - it should total somewhere between 4.5mg and 9mg (which would be high for an 80lb human).

In the dog studies they don’t do any peak or trough sirolimus blood testing - and I’m not sure if the half life of sirolimus in dogs is the same as humans. its probably pretty close given that the researchers in this area think that dogs tested with rapamycin are a pretty good proxy for human testing.

As far as dosing mg/kg per week for the dogs in the main TRIAD clinical trial starting this year (I think) - if Matt Kaeberlein @mkaeberlein has time, perhaps he can comment…

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Also - I did note this about the TRIAD clinical trial which I found interesting… not sure of the rationale for using this type of rapamycin in the trial - would be interesting to understand:

The drug will be given once a week based on the human data from clinical trials with everolimus, which is a rapamycin derivative. It seems that an equivalent total dose given once a week rather than daily has better efficacy with reduced side effects. We are using a form of rapamycin that is coated for enteric release. It’s not the eRapa (encapsulated rapamycin) that’s used in mice, that’s a different formulation, but it is also not exactly the same as generic rapamycin (sirolimus) tablets that organ transplant patients take

From here:

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Yes, I saw that. I wonder if there Is there any dog specific reason for encapsulation and also what the conversion factor to sirolimus would be. It seems to make total sense to think a 1 week dose is better. I know we’re all in uncharted territory.

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0.15mg/kg once weekly is what they’re using in the TRIAD study (per Dr. Kaeberlein in recent Peter Attia podcast).

I’m about to start my dog on rapamycin and will be using the three times weekly dose (total of 9mg per week for my 67 pound dog) but will also be doing regular blood work to monitor him.

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Sirolimus or everolimus?

They are using sirolimus in the TRIAD dog/rapamycin clinical trial.

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OK that’s good to know and fits w my plan to go to a 6mg regimen with my dog w the timing of the next dose based on levels declining to <0.5 mg based on a 60 hour half-life. Assuming this goes well, I’m thinking of slowly increasing the dose level in line with what us humans are doing. He’s half my weight though so maybe always half my dose. Any thoughts greatly appreciated.

Isn’t the half life of sirolimus a lot shorter in dogs? I thought I’d seen that somewhere, or maybe it was in one of the Kaeberlein/Attia podcasts.

38 hours per this study: Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs: A pilot study - PMC

“The terminal half-life of rapamycin in dogs was greater than 60 hours.”

It seems that there is some variance in the literature :grinning_face_with_smiling_eyes: :smiley:

Looks like they gave the drug by IM injection in the osteosarcoma study, which would extend the half life.

My thought is to use 60 based on some internet searches. I want to be conservatively realistic so I’d like to hear if anyone thinks I should use a different period.

I have a dog too - and have been giving her approx. the same dose/kg that I’m taking. But I’m also thinking that going forward I may slowly increase her dose to the level I’m considering going to in the future, so I get an early look at any possibly side effects that I may get as I also ramp up dosing.

Our dogs can give us an early and accelerated look at the results of rapamycin since they age much faster than we do. And since we are acting as Guinea pigs as far as rapamycin goes, why not recruit our dogs too in the test of higher doses?

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That’s great feedback, thanks. Am I right that you’re on a 2 week regimen? If so, then your dog is as well? Can I ask what dose you’re considering for the future?

Yes - right now 20mg every two weeks. It seems reasonable to consider slowly, over the next year, work up to 30mg or 40mg - given the Everolimus clinical study on dosing I posted last week.

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Hello
I am about to start my 140lb, 6 year old, leonberger/st.Bernard mix on rapamycin and just had a couple questions before I officially started with my dog.
I planned on doing 3mg/week for him.
I was wondering to those who gave their dog rapamycin, did you get blood work done with your vet before hand? If so, what did you look for? Then after giving rapamycin, how often did you get blood work done for you dog?
In regards to timing of giving rapamycin, what time of day

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