Hello Dr. Kaeberlein, physician here and love that you’ve started your own podcast. We would much rather listen to a PhD who studies this, than others. Keep it up and thanks for your work.
Thanks Matt. Your podcasts are invaluable. I'm a 74 year old male, in very good health. I've been taking rapamycin for 12 weeks, 5 mg once per week. No negative side effects except that last week, I got a mouth sore. Not pleasant. Its starting to subside but today is my rapa day and i don't know whether to take it or allow a one week lapse. I'm leaning to take it. I'll come back here to provide an update.
Im 78 and have taken rapa for 7 years straight without more than 1-2 wks vacation. The proper thing to do when you get a mouth sore is to reduce dose 1 mg. This is suppose to be the optimum dose. Go to 4 mg wk., and later can try 5 or more and see if you still get mouth sores. Mouth sores have been my side-effect over the years and is very useful for detecting when you might be getting into the area of inhibiting Tor2 vs Tor1.
@@worldtraveler691 Thank you for that advice. After posting my comment, i decided to skip this week's dose. However, thanks to you, I'm going to take a reduced dose. I'll reduce it by 2 mgs for a dose of 3mgs and see how that goes. As I said, the sore is subsiding and hopefully it will heal very shortly. Fingers crossed for no new sores.
@@juicebox853 Negative to both. But I've only been on it for 12 weeks and have only one post rapamycin blood test (7 weeks after starting). I'm due for another blood test so I'll update this post after I get the results. P.S. I also take metformin (not diabetic nor pre DB) so that may keep my glucose in check.
Very interesting observations and data points. Thanks for making yourself a test subject and reporting all results. I am a type 1 diabetic and use an insulin pump. Recently switched to steel cannulas as the thin plastic tubing on the previous ones, kept bending when I inserted and was receiving zero insulin. Have no clue where it went, but clearly not in my body. I am allergic to various metals so was concerned the steel cannulas might cause inflammation/infection. Thankfully no issues and great insulin delivery. I too can get cavalier about sterilization and after hearing your story, possible rapamycin influence or not, I will be more cautious. Also have a CGM, a dexcom, and have yet to be brave enough to insert in my upper arm. Will eventually overcome my hesitation. Thanks for your podcasts, your channel should grow rapidly. Your delivery of information is detailed yet concise. Also like how you present the human aspect, not grandizing the results. All the best to your dogs skin infection. I had a Boxer girl who would scratch herself raw under her armpits and generally itched everywhere. UF small animal clinic tested her and prescribed weekly injections. I instead took her to a naturopathic vet I also use, and with weekly ozone treatment, a few TCM herbs and weekly acupuncture, her system responded and we never dealt with breakouts again. We also limited her vaccinations (titer tested), put her on raw food diet and added digestive enzymes and probiotics, Quercetin and a few other supplements.
Thanks for the explanation of the infection. Sounds reasonable and not that concerning for rapamycin considering that it had a lot of time to develop an infection..
Anecdotal - I was taking 5mg once per week. Week 5 I ended up with bacterial pneumonia, had to take several different antibiotics...all of which ended up leading to an autoimmune condition called myasthenia gravis. Anecdotal but im not sure its as benign as we think. Does it your immunity substantially?
Your transparency is appreciated. Tacrolimus metabolism pathways must have been reported in the lead-up to the drug being approved. If the pathways of Rapamycin metabolism are known, then it ought to be possible to test the "fast metabolizer" hypothesis with a genome test. Do we even know if cytochrome P450 is involved? There are so many possibilities to explain the rather large discrepancies with the published half-life.
Mice in a trial are kept in very sterile conditions. Could it be that rapamycin makes the immune system less active, and that the longevity of those mice is caused by less collateral damage in the body afflicted by a part of the immune system?
Hi Mat, I have been taking rapamycin since 11 November 23. I am taking 6mg and my weight is 67 (177cm tall). My HDL went from 65 to 81. I have listen Nir Barzilai saying that centenarians have a mutation that makes them have very high HDL (80 plus). Do you think that would be wise to say that rapamycin mimics centenarians phenotype?
Bryan's rapa blood level is almost exactly what male mice levels were on the 42 ppm in one study which had over 20% life extension in mice. Based on everything I've read, I think the effect of rapamycin on life extension is going to depend heavily on dose and frequency, and I suspect the off label crowd converging on 6 mg once weekly most likely is too little and may have near-zero effect. Only one or two mice studies had weekly dosing, most were daily chow. I'm starting with 5mg twice a week and plan to increase.
Hi Matt.Good and honest information.Regarding your skin infection it has nothing to do with rapamycin.the infection was localized due to introduction of bacteria through the application process either from fingers contamination or the bacteria was already present on the skin.your immunity kept the infection localized without penetration into the deep tissue, or dissemination into the blood stream causing bacteremia.The bacteria likely to have been MRSA which causes local painful abscess.Clindamycin was the appropriate drug for this though I prefer TMP /Sulfa witch has less microbiome disturbing effect, C Diff etc. If your dog has recurrent skin infection with MRSA it will be difficult to eliminate from the house including furniture items etc . Culture of one of the infected areas on the dog can help identify the bacteria. If any household get skin infections again it is important to culture it and treat it with TMP/ sulfa asap before culture results. It is important to wash hands good before cleansing the skin during Libre 3 application.
Matt, Bryan took the Rapamycin with olive oil which has been shown to flatten the peak and extend half life. Could you please share your protocol? Empty stomach?
Matt, three comments/questions. First in the iTP experiments, or in Joan Mannick’s work, did those activities track half lives of Rapa? If so those numbers would seem to be more realistic in describing the half life of a low dose pulsed usage. Second, your CGM issue had to be the source of your infection. Did Rapa make it worse? Who knows, but I bet not. Third, I think the comment below about whether a blood marker is really the way to see if Rapa is being non-active may point to the issue - maybe Rapa is taken up by the cells where it does its real work in inhibiting MTor1, and there’s no way i would think to come up with a measurable number there.
Thanks Dr. Kaeberlein for sharing your experience. Not medical advice, but what are your thoughts about hair transplant while taking weekly Rapamycin? Could it inhibit survival of transplanted hair follicles or help their survival rate? It becomes a challenge deciding on things like vaccines, dental implants and other medical procedures; should one continue or take a pause ...
Your half life assay is for blood clearance. Is Labcorp assessing all the main blood components, RBC, plasma and serum for rapa content? Are the published 63 hour half life values using the same assay? Body clearance is going to take longer than blood clearance because rapa goes intracellular. With a small dose shouldn't we expect rapa to disappear from the blood into cells rather quickly? The full picture on rapa half life with low doses still feels fuzzy without knowing specifics on some of these details.
I did exactly the same thing with my pet ferret - “ Hairy Plopper” had a staph-aureus skin infection, & I transferred it during an Omnipod & Dexcom CGM change. …. (I am type 1)… 😬 🤦🏻♂️ 🤷♂️ ~~~> Tis Life! Shit happens, & quite often! 👍🏻
@optispan Hi Matt, I would love to know what you are doing dietarily to reduce your body fat? Also, curious if your dog is on Rapamycin and if during your infection treatment if you stopped the Rapamycin? Great epidode! Thanks!
Matt, you are not measuring the terminal half life of rapamycin correctly. You can see from the points on your graph in the video that you are actually measuring the initial transient spike at the very beginning. The dynamics of that initial spike characterize the initial half life of the drug, not the terminal half life. The 63 hours quoted in the literature is the terminal half life, not the initial half life. Rapamycin has a short initial half life. You need to wait for that transient to settle and reach a steady state. Then you can start measuring the terminal half life. Please also see my previous comment below.
Some drugs like rapamycin follow a *biphasic elimination*. First a short steep spike, and then a slow steady decline. This is fairly common in pharmacology. The relevant half life for dosing is the slow steady decline. Not the spike. Please consult a standard pharmacology textbook on biphasic elimination.
A correct discussion of half life has to separate initial half life from terminal half life. Rapamycin is known to have a fast initial half life and a long terminal half life. The *terminal* half life is reported in the literature as 63 hours. The initial half life is much shorter than this. It is not correct to calculate the terminal half life from the initial peak at 2 hours. You must wait for the initial transient spike to settle and reach a steady state first. The dynamics of that initial transient spike give the initial half life, not the terminal half life.
I had a heart transplant 24 years ago and rely wanted to go on Rapaa but heard cuts take forever to heal my original cut also took very long to heal. Original I was also on steroid for 6 months. For your dog healing problem maybe try medical honey and quality Kiefer Also check d3 levels zinc and Thyroid problems also Parathyroid disease
Does anyone know of research or studies that monitor a continuous low dose like I do at 1mg 2x /week ? I always wonder if it’s doing any good at a consistent intake without any rest periods or “pulsing” 🤔
Is the difference in half life just a result of differences between off-label vs organ transplant-specific dosage? Pharmacokinetics are not always dose-linear.
Looking at the rapamycin decay figure its possible the decay of serum levels are biphasic. In the case of Bryan Johnson it could decay quickly and then more slowly and could be very similar to yours Matt, just shifted with the higher dose. Increased temporal sampling would resolve.
It would be interesting to hear if before you started the course of rapamycin you were gaining muscle between DEXA scans. If you were gaining muscle and that slowed when starting the rapamycin that could mean it was still having an impact on lean mass.
Metformin makes it easier to lose weight, too, at least for someone with metabolic dysfunction, which I'm sure I had as a very overweight, out of shape, post-menopausal woman. Metformin was like flipping a switch on my metabolism.
Sirolimus lowers the immune system so transplant pts do not go through organ rejection. The combo of not cleaning the CGM site and skin bacteria in addition to lowered immune system response, led to your bacterial infection.
😂 guy, you do realize he’s one of the main scientists studying rapamycin right? You thinking it doesn’t know what it’s used for and its effect on the immune system?? You’re also repeating what he already said in the video
I think it usually means that they are cleared quicker out of the blood via kidney or liver. But I am thinking could it also mean that they are absorbed into the cells better in some cases. The only way to find it out is to have an intracellular rapa test.
Not using the ‘sterile’ wipe not related to infection. There was a UK study on childhood IM vaccinations alternating sterile isopropyl alcohol wipes with no wipe in 50000i kids and the local infection rate for both groups was the same …zero.
Thanks for sharing. That's really interesting. Upon further investigation I read this "However, the study was insufficiently powered to detect a difference in the primary outcome of skin infection. Due to the limitations of the study it is difficult to draw sound conclusions of whether alcohol swabbing reduces infection rates compared to no swabbing." Also, this is different, he kept the cgm on the wound which could act as an ideal environment for bacteria to grow. I'm also fairly sure those kids in the study were not expired to dogs with skin infections during the vaccination.
@@juicebox853 well the fda approved compounding pharmacies in your country purchase from these so called chinese manufacturers. because its cheap and they make big $$ Besides dont make unfounded comments you know nothing about. look into it. people who do those things look aND FEEL super healthy, young and vibrant. you know; a true testament of anti aging not someone looking haggard and making claims of stuff that dont work. Sorry fan boy. you have to look young and healthy to make any claim of antiaging. im sorry your hero does not. Ask brian johnson, he knows about peps
@@juicebox853 erm rapa isnt approved by fda for antiaging smarty pants. and the poster boy for rap isnt showing signs it works. so stop kidding yourself.
I click on this channel’s videos because the thumbnails are engineered to exploit the algorithm but never learn anything watching the videos because they are so dry. Talking head boring, more cowbell needed.
The problem is humans still die in rheir sixties or seventies. God shortened our lifespans so much over the past 2023 years due to sin and just Generationional offspring. Each generations lifespan got shorter and shorter. Noah actually lived over 900 years. Our lifespans are very short.
@@vickybiagini8623 God has nothing to do with anything. Realize mankind has created 18000 gods over time, many before xian beliefs. In fact the story of jesus was stolen from horus, an egyptian god predating xianity by thousands of years! Educate yourself.
