Comparing Bryan Johnson's RAPAMYCIN DATA: INTERESTING RESULTS | 31 - R-Files #5
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- čas přidán 12. 06. 2024
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The R-Files is a series of episodes about rapamycin, a naturally occurring compound originally discovered in soil samples from Easter Island, also known as Rapa Nui (hence the drug's name). Rapamycin belongs to a class of drugs called macrolides and has potent immunosuppressive and anti-proliferative effects. The drug has garnered attention for its potential anti-aging properties and has attracted research interest for its ability to extend lifespan and delay age-related diseases in various model organisms, including yeast and mice.
In our fifth episode of the R-Files, Matt shares insights from his recent course of off-label rapamycin use, which he started in January 2024 and plans to continue for at least the next month or two. He describes improvements in joint pain and body fat loss as well as an unexpected bacterial infection, and speculates about whether rapamycin may have contributed to any of these effects. He also discusses rapamycin's half-life in his blood, which is significantly lower than that reported in the published literature.
0:00 Trailer
0:44 Introduction
3:47 Aches and pains
4:29 Effects on weight and body fat loss
9:24 Matt's rapamycin half-life
14:19 Bryan Johnson's rapamycin half-life
17:06 Matt's bacterial infection
21:57 Wrapping up
Producers: Tara Mei, Nicholas Arapis
Video Editor: Jacob Keliikoa
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Hi, I'm Matt Kaeberlein. I spent the first few decades of my career doing scientific research into the biology of aging, trying to understand the finer details of how humans age in order to facilitate translational interventions that promote healthspan and improve quality of life. Now I want to take some of that knowledge out of the lab and into the hands of people who can really use it.
On this channel I talk about all things aging and healthspan, from supplements and nutrition to the latest discoveries in longevity research. My goal is to lift the veil on the geroscience and longevity world and help you apply what we know to your own personal health trajectory. I care about quality science and will always be honest about what I don't know. I hope you'll find these videos helpful! - Věda a technologie
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.
Thank you for your support @epigeneticnerd4244! - Tara
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.
@@worldtraveler691 How do you know that mouth sores = mTORc2 inhibition?
@@bill9989 Have either of you had a significant increase in cholesterol or blood sugar from rapamycin?
@@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.
Excellent episode. Commenting on Bryan, sharing your detailed data, acknowledging possibility of side effects… please keep this up 🙌
I’ve been impressed with your discipline when it comes to nutrition and exercise! 9.9% 🚀
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.
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.
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 ...
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.
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..
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?
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?
Does the dog get the rapamycin ?
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.
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?
Interesting. I am concerned about the possible LDL increase.
@@juicebox853 I don’t think you need to worry about that. I am tracking other friends with rapa and we all reduce our LDL.
Could your dog’s skin infection issues be related to rapamycin use?
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 took one dose and could tell its effects persisted for at least 6 weeks. It is POTENT, as least for me.
Is it good for treating Dupuytren's?
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” 🤔
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?
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.
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.
78 taking Rap once a week. Should it be taken daily instead to smooth out the decline in potency?
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
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.
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.
🔥🔥
Did MATT say his dosage?
8 mg wk
@@worldtraveler691 thanks
Is a shorter half life beneficial?
We don't know at this point. - Tara
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.
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
Why blame rapamycin for infection when you stuck yourself without sterilization of the area?
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.
Well, when you do something, share your results.
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.
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.
Bryan probably is taking berberine, peperine both block that P??? pathway. Something to look into Bryans stack. Good luck. Libre 3 is great, better.
Not seeing the value of these n of 1 stories?
I think a few grams of taurine would get at least similar benefits without the downsides, cost or hassle.
OK. I'll take your word for it
Brian looks like the Alien on Star Treck original series
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.
i dont see that its making you look younger matt. perhaps try a course of petides instead.
Yeah, I am sure some underground non fda approved peptides from some unknown Chinese manufacturer would be best for health.
@@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 better than anyone ive seen taking rapamycin my friend. proof is in the pudding
@@juicebox853 clueless. proof is in the look. and he doesnt look like hes aging backwards. so rapamycin cant be effective fanboy
@@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.
Then don’t watch the channel if you can’t comprehend how this is valuable, dummy
Do not try to learn, you are a lost cause.