Great article, thanks. Basically they are saying that breeding for show has ruined another breed. True enough and fair enough, but I think it is possible to breed for longevity. They bring this up toward the end. Whatever the breeder thinks is important is what you get. If you need them to look a certain way, then you will end up losing everything else.
Farm animals bred for show are a different thing altogether than farm animals bred for productivity. With animals you have to decide what you want and go to a breeder that wants the same thing.
Also I still think the dog food could be responsible for the cancer.
My dog has been on rapamycin for 7 months and he has allways had problems with colitis and diarrhea. Once every few weeks. Was really troublesome but since taking rapamycin once weekly he had zero days with diarrhea and his poo has changed tremendously, it is lighter in color, more compact but at the same time seems really lubricated, hard to explain, but looks healthier. So indeed it has some effect on gut.
Id did have the some effect on my gut. I am taking acarbose too, so it is hard to distinguish between what is rapamycin and what is acarbose, but my gut works differently. I have daily bowel movements which were more of an exception than a rule previously.
I still use for myself and my dog “branded” rapamycin, pfizer rapamune. It is the only one available in Europe, but it supposedly have a far better bioavailability comparing to generic versions, that is why generics are not on European market. Compounded rapamycin capsules as much as I have researched can have almost zero bioavailability (some are better, depends on capsule, whether is enteric or not).
I get capsules that he says has a enoteric coating. I have kept the dose the same and seen no changes in behavior and no side effects.
One interesting change is that her stool size is larger that I think could be related to the new pills as I don’t think much else has changed. I would say it was noticeably smaller before and is more the size I would expect from a dog her size now.
Dr Toman now has us trying a few more new things…we added Acarbose, Metformin, Taurine and Fisetin. She has been on these a few months now. She is doing terrific and no side effects. A test of one I know but I will keep folks posted
Case Report: Severe Asymptomatic Hypertriglyceridemia Associated with Long-Term Low-Dose Rapamycin Administration in a Healthy Middle-Aged Labrador Retriever
Rapamycin is an mTOR inhibitor that has been shown to extend the lifespan of laboratory model organisms. In humans, rapamycin is used at higher doses as an immunosuppressive medication to prevent organ rejection. Numerous adverse effects are seen with rapamycin treatment in humans, with one of the most common being dysregulation of lipid metabolism. In humans, this often manifests as mild to moderate serum lipid elevations, with a small subset developing extreme triglyceride elevations. This case report describes an 8-year-old, castrated male, clinically healthy Labrador retriever who developed severe hypertriglyceridemia associated with low-dose rapamycin administration over a six-month period. During this time, the dog was asymptomatic and displayed no other clinical abnormalities, aside from a progressive lipemia. Within 15 days of discontinuing rapamycin treatment, and with no targeted lipemic intervention, the dog’s lipemia and hypertriglyceridemia completely resolved.
I’m not sold on the enteric capsules being any better than non-enteric for absorption; however, Dr. Toman sent out an email recently that California vet laws have changed, which allows him to do tele-vet consults AND prescribe vet medicines out of state. In theory, that means he could now prescribe genuine sirolimus tablets for your dog from your local pharmacy in the USA. Whether or not he’ll do this, I have no idea, since his business model may in part depend on sales of his imported/compounded rapa. Also, of course, even if he would prescribe it, generic sirolimus/rapa isn’t cheap!
Yes - I’d be very wary of any sirolimus from a compounding pharmacy (where they buy powder and put it into capsules themselves). We’ve heard so much from numerous doctors and researchers that the bioavailability of the compounded pharmacy sirolimus has problems with bioavailability. At a minimum I’d ask any doctor that is prescribing compounded pharmacy rapamycin / sirolimus to product some blood tests that validate that the sirolimus is not just being destroyed in the stomach of the dog (or person).
Shared my pharmacy rapamycin/siriolimus with a friend whose dog was 14 years old a year ago… dog had no energy… slept with a warming blanket… hardly moved… today the pup is swimming around the pool.
My 15-17 y/o rescue chihuahua is doing great on rapa. We started him on it in January 2023 as a last ditch effort after he rapidly declined and had a ruptured CCL in the fall of 2022. The vet was supposed to give us an orthopedic referral for him and sadly never got back to us even with after repeated requests from my husband. We were seriously expecting the worst and I didn’t think my rapa order was going to arrive in time to help him because he was so pitiful. I gave him a dose immediately after getting it in the mail on the evening of 1/6/23 and he was acting different by the next morning. His energy and excitement returned rapidly and his mobility improved dramatically over the next few weeks. He’s only had one time where his leg seemed to be bothering him in the last 11 months and I just gave him an extra dose that week. He runs and plays like he did when he was around 8 now. I fortunately haven’t needed to take him to the vet since he’s been on rapa but I would like to find him someone who is rapa friendly in case of future need.
This is a loooong thread. I started at the beginning but gave up… So, it’s probably been mentioned already but dogs have a much more acidic stomach acid than humans. Like 10x more. And, around 100x more the volume of stomach acid. Also, dogs have a much shorter digestive tract than humans. Therefore the food and drugs consumed by humans have more time to digest and absorb. The more acidic digestive system and short digestive tract of dogs are a couple of the reasons why they can easily digest bones and avoid becoming ill from eating a dead animal that has been rotting in the dirt. Probably has something to do why they might be using special capsules for rapamycin in the trials.
The enteric coating on some human medications may not break down in dogs, causing pills to pass undigested. There are different enteric coatings. Whatever is often used to coat human aspirin may cause it to pass undigested in dogs, apparently. I haven’t researched this to know which coating in particular, or whether any sirolimus manufacturers use it.
I’ve been using Zydus rapamycin mostly for myself and my dog and have not seen any tablets passing entirely through my dogs system undigested. Of course, its much harder to know if the pill is getting destroyed in the gut prior to getting to the intestine… and I’ve done no dog blood sirolimus level testing (are these even available) to check.
Are they actually using specially developed capsules for the dogs in the Dog Aging Project as opposed to generic sirolimus tablets? If so, I imagine there must be a reason to believe the human-formulated tablets wouldn’t work for dogs. All this time I’ve been thinking rapa in standard gelcaps wouldn’t work but that human rapa tablets would. Has anyone specifically asked Matt Kaeberlein about this?
They are using using the trium vet version of rapamycin. I’m not sure why they are using. It. Would be best to talk to trium vet about their product to get details.
In a recent interview with Peter Attia who asked what keeps him up at night about the study, Kaeberlein responded he worried the dose was not large enough.
Pharmacokinetic assessment of sirolimus-treated dogs
A validated method for extraction of a sirolimus analog was used as described to extract sirolimus from 100 μL of each blood sample by means of protein precipitation with 0.2M zinc sulfate followed by liquid-liquid extraction with 1 mL of ethyl acetate.26 The sirolimus concentration in each sample was determined by use of liquid chromatography-tandem mass spectrometry with tacrolimus as an internal standard as previously described.18
Further, the majority of dogs demonstrate measured sirolimus blood levels below 10 ng/mL. The AUC/dose equivalents for cycle 1-Day 11 and cycle 1-Day 25 timepoints were 1499 ± 1446 [nghr/ml]/[mg/kg] and 1357 ± 1475 [nghr/ml]/[mg/kg], respectively. To assess sirolimus pharmacokinetic variability across treatment duration (cycles 1-4), sirolimus levels were measured at 2- and 8- hours post dosing (Figure 3b). ANOVA showed that 2- and 8- hour timepoints were significantly different (p < 0.0001), but none of these average values were significantly different across cycles of treatment (p = 0.4825). Within this dataset, intra-patient variability was relatively small compared to inter-patient variability, suggesting that PK differences were largely patient-dependent. The magnitude of inter-patient PK variability was underscored by the wide range trough concentrations calculated from a subset of dogs (n=78) receiving sirolimus being 0.53 to 30.98 ng/mL, which span across predicted sub-therapeutic (< 10 ng/mL) and therapeutic (> 10 ng/mL) concentrations.