I have been following your channel for a while. I am 65. My father died from ALS. It was so painful to witness this. There is a study published in Nature last year. Double blind study with rapamycin for ALS patients….very promising: “Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis” I decided to take rapamycin. Started last week! Thank you for your effort and work. Great channel!
Women should test their estradiol and other hormones too, not just men. After about two months of weekly rapa while using HRT (patch), my estradiol plumetted. The only reason I knew was because I had significant symptoms (tenderness) and asked for a test, which was then compared to one I had months earlier. When I stopped taking the rapamycin, my estradiol returned to normal and symptoms resolved. Was surprised it could have this effect.
I'm surprised that many people have forward-thinking physicians who prescribe rapamycin. My Primary Care doctor turned me down flat. He had just looked up rapamycin on his laptop and saw that it was used for organ transplants. He said, "That is a powerful medicine that you don't need, and I cannot prescribe it." I'm 67, with osteoporosis and neuropathy. I explained to my doctor that rapamycin was being called an age-related anti-inflammatory. Still, so many doctors, like my doctor, have never heard of rapamycin and think it should only be used for organ transplants. More doctors everywhere need to watch the Optispan podcast.
I sent a message to my doc prior to visit him. I called the desk to mention that I sent a message to my doc and requested him to read. I attached several links of TH-cam videos and explained why I like to try this therapy. In his office when I visited him, he said nothing and just asked me how much I like to take. I told him 6mg per week. I started last week!😂
Rapamycin should not be prescribed by your every day doctor... It has a very limited evidence base in humans. It should only be available to those wanting to experiment with themselves! Needs so much more data, long term safety, efficacy in specific conditions, before it hits guidelines
100% should not be prescribed by every day family doctors. This is a specialist medication with little human evidence and thus does not have these indications or appear in guidelines. It's off label. It should only be prescribed by specialists and also at a cost.
New subscriber here. I discovered the channel from the video "Ageing scientist critiques..". This is already my fav podcast now and I cant get enough of Dr. Matt Kaeberlein. He is such a well articulated and level headed science communicator.
I've taken (and still am) many longevity supplements including rapamycin (I stopped) and metformin (still) and astaxanthin, Taurine, glynac and others. I've never "felt" anything with them and don't think I should. If anything slows aging, you're still aging; just not as fast. So tomorrow, you'll still be older. Should that have a positive feel? I don't think so.
Agreed completely about the NYTimes article. I found the article glib but, then again, the content of the NYT is not what it used to be. Your conversation with Jon Berner re. lithium and possibly lithium+rapa was wildly interesting. Thanks.
I have been taking weekly 6mg Sirolimus for 3 years now. I do have a single APOE4 allele. Feel great Have a GlycanAge of 41, Function Health age 50...I am 61. Can't tell anything from the Rapa as far as noticeable factors, as I eat whole food mainly meat and exercise daily.
Saturated animal fats will cause significant cardiovascular risk long term. Heart disease happens on an S curve so expect statins soon, if you are not on already.
Great talk. Thanks for doing it. As a healthy 65 year old who has been thinking about taking Rapamycin off label for a while now, this video was greatly informative and gives me additional comfort in how to proceed.
After about two months of 4-6 mg/weekly rapamycin, it spiked my CRP and caused flares of my recurrent myocarditis (first triggered by covid vax). The flares were initially mild and short-lived. Around weeks 10-11, I began experimenting with taking 1 mg every other day, then had a serious, unusual flare that continued for almost two weeks. I think rapamycin might trigger a cytokine imbalance and new inflammation in certain people with a pre-existing immune dysfunction. There are a couple of studies and papers on it (involving people who dose daily). On the upside, the chronic, searing shoulder pain I had before starting rapamycin was completely resolved after an 11-week course and has not returned, even after a 6 month break. So I'm hoping it made some beneficial changes to my immune system. Thank you for all of the great info you and your team make available.
It'd be great if you guys made a video about Glycine. Specifically about an aspect nobody talks about: the link between glycine and cancer. It seems it is, like serine, used a lot by cancer cells.
I seem to have a severe side effect from rapamycin: dizziness and the loss of coordination. I started at 2 mg/week and started feeling it soon. I had to pause after 4 weeks to see if it would go away. It did after 3 weeks, so I resumed with 4 mg for 4 weeks. The symptoms were bad for a day or two after taking a dose, with dizziness and a kind of "about passing out" episodes, but were going away in a week. Then I started 6 mg, and it caused a severe loss of coordination and dizziness. I skipped an extra week and tried 6 mg again, and this time it was the worst. Now it's over 4 weeks since my second (and the last) 6 mg dose, and I still feel dizzy and unbalanced. At 2 mg and 4 mg, I was checking my sirolimus levels after a week, and they were minimal (0.5). Also, even at 2 mg, my HbA1c in a month went up to 5.8 and have stayed there through three months since. I've had a good dozen of HbA1c tests in the last two years, and it has been 5.4-5.6 and never 5.8 in my records.
Those are potentially very serious side effects of rapamycin and you should stop taking it and see your doctor, see PML section at the mayoclinic site for Sirolimus. The HbA1c -- if rapa is reducing production of red blood cells, then HbA1c could go up. The only way to know is test HBA1c, RDW, reticulocytes and wear as CGM pre and post. An involved design, not often done for obvious reasons.
@jamesgilmore8192 in fact I did wear CGM and tested RDW, glucose spikes were really high on rapa, and RDW went up, but especially MCV went up to the new highs in my records. My MCV was always stable 91-93, now it's 97.
How is dose effected bioavailability? Does the discussion of e.g. 5mg dose take into account the low bioavailability in pill form, referring to the Pearl trial?
would like to hear how to reason about the increased risk of skin cancer, something that no one seems to want to address. the risk is even stated in the package insert
Agree strongly with Matt and as always he's very diplomatic. Dillon is an idiot at least in this instance, and I have so much experience unfortunately with similarly ignorant Physicians who have not read the literature and don't know anything about mtor Networks telling my patients that rapamycin is a dangerous drug and cannot be prescribed except for Organ transplants and rare cancers. Unfortunately, the level of ignorance about aging and, for that matter, so many other areas of biology in those trained (brainwashed?) in the paradigms of the medical industrial complex is widespread. We don't really have a Healthcare System we have a 'boxology' disease care system in which people are told that the diseases of Aging are all separate problems. That is biologically false and scientifically falsified to a major degree, and yet the Healthcare System doesn't know that.
I'd recommend lifestyle stuff - sauna, weight training, Vo2 max training, zone 2 👍🏽 sauna has got data for other proteinopathies like Alzheimer's. Best of luck 🤞🏽
In several episodes, Matt trivializes or otherwise does not present methylation tests positively. And he really has not given any compelling reason why. I would like him to really make a compelling case. Please show how "actual" aging is different. Yes, there are probably 50 other things that change that could be measured. The thing is in many of those it becomes reflected in the methylation results. Probably not all, but enough to make it a very good proxy. Now, which test, averaging them and such, that is more complex.
Nate -- The main criticism is the number of degrees of freedom in the epigenome far outweighs the constraints you can put on them currently, and one needs to resort to various statistical approaches to resolve the problems. Many of the newer generation clocks are being tied to measured biomarkers (proteomics etc), but these epigenome biomarker proxies are poorly correlated with the actual biomarkers. This means the clocks are capturing the mean responses of a collection of biomarkers and the epidemiological epigenome variance related to the proxies (which can be large). Attaching meaning to the clocks, in particular for changes at the individual level or within a small exploratory trial say, is extremely difficult. They are really designed to work on an epidemiological level, not withstanding the other problems.
I think Matt has given at least one compelling reason: methylation clocks are too sensitive to manipulation by environmental factors, eg you stay awake for 72 hours and "age" 20 years. As far as I can see, he thinks they certainly measure something, but they aren't validated on long-term clinical outcomes and are just too stochastic to be really useful at present.
@@askingwhy123 But who is to say those environmental factors are not real? It probably would take at least 20 years off your life to give up sleep for the rest of your life. If you carry on with any health destroying process, it should not be a shock that you will age faster and die sooner. And it sounds like that would be of high utility. It is a wake-up call to quit smoking, or whatever. You don't really need long term data, taking many decades. It is like dendrochronology. Just like with tree rings, you can put together a picture of the past by matching up tree rings of multiple trees. With humans, you just need 5-10 years of change from many people of different ages to put together a picture of change patterns that would be in full lives.
@@askingwhy123 Other biomarkers behave in similar ways for large changes like staying awake and fasting. That represents aging and adaptive complexity rather than a failing of the biomarkers themselves. Some of the newer epigentic clocks are tied to clinical outcomes so that is starting to be resolved. The big question is whether improving the epigentic clocks through interventions actually translates to outcomes in humans...
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I have been following your channel for a while. I am 65. My father died from ALS. It was so painful to witness this. There is a study published in Nature last year. Double blind study with rapamycin for ALS patients….very promising: “Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis”
I decided to take rapamycin. Started last week! Thank you for your effort and work. Great channel!
Women should test their estradiol and other hormones too, not just men. After about two months of weekly rapa while using HRT (patch), my estradiol plumetted. The only reason I knew was because I had significant symptoms (tenderness) and asked for a test, which was then compared to one I had months earlier. When I stopped taking the rapamycin, my estradiol returned to normal and symptoms resolved. Was surprised it could have this effect.
I love the new intro. Straight to the point.
I'm surprised that many people have forward-thinking physicians who prescribe rapamycin. My Primary Care doctor turned me down flat. He had just looked up rapamycin on his laptop and saw that it was used for organ transplants. He said, "That is a powerful medicine that you don't need, and I cannot prescribe it." I'm 67, with osteoporosis and neuropathy. I explained to my doctor that rapamycin was being called an age-related anti-inflammatory. Still, so many doctors, like my doctor, have never heard of rapamycin and think it should only be used for organ transplants. More doctors everywhere need to watch the Optispan podcast.
LOL, I am taking it too. 6mg 1x a week. My Primary care doctor called it an immune suppressor.
@@patrickmcguinness1363 Wow, very cool doc. You're lucky. Is he a young doctor?
I sent a message to my doc prior to visit him. I called the desk to mention that I sent a message to my doc and requested him to read. I attached several links of TH-cam videos and explained why I like to try this therapy. In his office when I visited him, he said nothing and just asked me how much I like to take. I told him 6mg per week. I started last week!😂
Rapamycin should not be prescribed by your every day doctor... It has a very limited evidence base in humans. It should only be available to those wanting to experiment with themselves! Needs so much more data, long term safety, efficacy in specific conditions, before it hits guidelines
100% should not be prescribed by every day family doctors. This is a specialist medication with little human evidence and thus does not have these indications or appear in guidelines. It's off label. It should only be prescribed by specialists and also at a cost.
After searching a lot, I found Dr Matt's rapa protocol is to take it for 12 weeks and then take a break of 6-8 months before another round.
New subscriber here. I discovered the channel from the video "Ageing scientist critiques..". This is already my fav podcast now and I cant get enough of Dr. Matt Kaeberlein. He is such a well articulated and level headed science communicator.
I've taken (and still am) many longevity supplements including rapamycin (I stopped) and metformin (still) and astaxanthin, Taurine, glynac and others.
I've never "felt" anything with them and don't think I should. If anything slows aging, you're still aging; just not as fast. So tomorrow, you'll still be older. Should that have a positive feel? I don't think so.
This is a great conversation. Love the format.
Appreciate the support and feedback!
- Nick
Agreed completely about the NYTimes article. I found the article glib but, then again, the content of the NYT is not what it used to be. Your conversation with Jon Berner re. lithium and possibly lithium+rapa was wildly interesting. Thanks.
The PEARL study had people taking compounded rapa and it wasn’t very bioavailable, so they really need to redo that whole study in my opinion
I am in PEARL and I agree with you. They have raised it to 15mg to try to get more into us.
So is that not the same rapa as the one sold by Pfizer?
Would love to hear your take on Glycine as well
I have been taking weekly 6mg Sirolimus for 3 years now. I do have a single APOE4 allele. Feel great Have a GlycanAge of 41, Function Health age 50...I am 61. Can't tell anything from the Rapa as far as noticeable factors, as I eat whole food mainly meat and exercise daily.
Saturated animal fats will cause significant cardiovascular risk long term. Heart disease happens on an S curve so expect statins soon, if you are not on already.
Great talk. Thanks for doing it. As a healthy 65 year old who has been thinking about taking Rapamycin off label for a while now, this video was greatly informative and gives me additional comfort in how to proceed.
Now we want to hear Dr. Kaeberlein's take on Omega-3 (fish oil) pills.
I’ve been on it for a week and I love it
After about two months of 4-6 mg/weekly rapamycin, it spiked my CRP and caused flares of my recurrent myocarditis (first triggered by covid vax). The flares were initially mild and short-lived. Around weeks 10-11, I began experimenting with taking 1 mg every other day, then had a serious, unusual flare that continued for almost two weeks. I think rapamycin might trigger a cytokine imbalance and new inflammation in certain people with a pre-existing immune dysfunction. There are a couple of studies and papers on it (involving people who dose daily). On the upside, the chronic, searing shoulder pain I had before starting rapamycin was completely resolved after an 11-week course and has not returned, even after a 6 month break. So I'm hoping it made some beneficial changes to my immune system. Thank you for all of the great info you and your team make available.
It'd be great if you guys made a video about Glycine. Specifically about an aspect nobody talks about: the link between glycine and cancer. It seems it is, like serine, used a lot by cancer cells.
Thanks for the suggestion! - Tara
I seem to have a severe side effect from rapamycin: dizziness and the loss of coordination. I started at 2 mg/week and started feeling it soon. I had to pause after 4 weeks to see if it would go away. It did after 3 weeks, so I resumed with 4 mg for 4 weeks. The symptoms were bad for a day or two after taking a dose, with dizziness and a kind of "about passing out" episodes, but were going away in a week.
Then I started 6 mg, and it caused a severe loss of coordination and dizziness. I skipped an extra week and tried 6 mg again, and this time it was the worst. Now it's over 4 weeks since my second (and the last) 6 mg dose, and I still feel dizzy and unbalanced.
At 2 mg and 4 mg, I was checking my sirolimus levels after a week, and they were minimal (0.5).
Also, even at 2 mg, my HbA1c in a month went up to 5.8 and have stayed there through three months since. I've had a good dozen of HbA1c tests in the last two years, and it has been 5.4-5.6 and never 5.8 in my records.
Those are potentially very serious side effects of rapamycin and you should stop taking it and see your doctor, see PML section at the mayoclinic site for Sirolimus. The HbA1c -- if rapa is reducing production of red blood cells, then HbA1c could go up. The only way to know is test HBA1c, RDW, reticulocytes and wear as CGM pre and post. An involved design, not often done for obvious reasons.
@jamesgilmore8192 in fact I did wear CGM and tested RDW, glucose spikes were really high on rapa, and RDW went up, but especially MCV went up to the new highs in my records. My MCV was always stable 91-93, now it's 97.
@@maestroharmony343 All negative changes it seems so far.
@@maestroharmony343 What happens when you fast? Similar things as above?
@jamesgilmore8192 no, fasting is good for me and very positive for blood work. Also, I fasting the days I was taking rapamycin.
Those Rapa nui statuses behind are a nice touch
Would be interesting to hear your comments on Dario Amodei's claims about AI & longevity in his essay Machines of Loving Grace.
How is dose effected bioavailability? Does the discussion of e.g. 5mg dose take into account the low bioavailability in pill form, referring to the Pearl trial?
I’ve been taking 5mg every Monday since June 2021 😃
Did you have mouth sores. If so what medicine did you use .
@@zakkiuddin5551 Fortunately, I did not 😀
@@zakkiuddin5551maybe that only happens if you have herpes
would like to hear how to reason about the increased risk of skin cancer, something that no one seems to want to address. the risk is even stated in the package insert
Agree strongly with Matt and as always he's very diplomatic. Dillon is an idiot at least in this instance, and I have so much experience unfortunately with similarly ignorant Physicians who have not read the literature and don't know anything about mtor Networks telling my patients that rapamycin is a dangerous drug and cannot be prescribed except for Organ transplants and rare cancers.
Unfortunately, the level of ignorance about aging and, for that matter, so many other areas of biology in those trained (brainwashed?) in the paradigms of the medical industrial complex is widespread.
We don't really have a Healthcare System we have a 'boxology' disease care system in which people are told that the diseases of Aging are all separate problems. That is biologically false and scientifically falsified to a major degree, and yet the Healthcare System doesn't know that.
What is your take on the potential of rapamycin for Parkinson's Disease?I wounder if my father should take it
I'd recommend lifestyle stuff - sauna, weight training, Vo2 max training, zone 2 👍🏽 sauna has got data for other proteinopathies like Alzheimer's. Best of luck 🤞🏽
Matt, I have heard of people taking rapamycin with olive oil. They say it gives them better bioavailability. What do you think of that?
I’ll add this to the next Q&A
- Nick
How safe is the genric version of rapa? It seems all of it is made in India.
If I decide to try rapamycin which biomarkers should I monitor before and after
Would love the berberine/metformin comparison
Thanks! This is on our list of future episode ideas.
Bizzarre why clinical trials aren't being conducted for neurodegenerative disorders?
There is study published in Nature last year. Double blind study with rapamycin for ALS patients….very promising..
Why do you guys never talk how physics interacts with bio chemistry?
In several episodes, Matt trivializes or otherwise does not present methylation tests positively. And he really has not given any compelling reason why. I would like him to really make a compelling case. Please show how "actual" aging is different. Yes, there are probably 50 other things that change that could be measured. The thing is in many of those it becomes reflected in the methylation results. Probably not all, but enough to make it a very good proxy.
Now, which test, averaging them and such, that is more complex.
Nate -- The main criticism is the number of degrees of freedom in the epigenome far outweighs the constraints you can put on them currently, and one needs to resort to various statistical approaches to resolve the problems. Many of the newer generation clocks are being tied to measured biomarkers (proteomics etc), but these epigenome biomarker proxies are poorly correlated with the actual biomarkers. This means the clocks are capturing the mean responses of a collection of biomarkers and the epidemiological epigenome variance related to the proxies (which can be large). Attaching meaning to the clocks, in particular for changes at the individual level or within a small exploratory trial say, is extremely difficult. They are really designed to work on an epidemiological level, not withstanding the other problems.
I think Matt has given at least one compelling reason: methylation clocks are too sensitive to manipulation by environmental factors, eg you stay awake for 72 hours and "age" 20 years. As far as I can see, he thinks they certainly measure something, but they aren't validated on long-term clinical outcomes and are just too stochastic to be really useful at present.
@@askingwhy123 But who is to say those environmental factors are not real? It probably would take at least 20 years off your life to give up sleep for the rest of your life. If you carry on with any health destroying process, it should not be a shock that you will age faster and die sooner.
And it sounds like that would be of high utility. It is a wake-up call to quit smoking, or whatever.
You don't really need long term data, taking many decades. It is like dendrochronology. Just like with tree rings, you can put together a picture of the past by matching up tree rings of multiple trees. With humans, you just need 5-10 years of change from many people of different ages to put together a picture of change patterns that would be in full lives.
@@askingwhy123 Other biomarkers behave in similar ways for large changes like staying awake and fasting. That represents aging and adaptive complexity rather than a failing of the biomarkers themselves. Some of the newer epigentic clocks are tied to clinical outcomes so that is starting to be resolved. The big question is whether improving the epigentic clocks through interventions actually translates to outcomes in humans...
Experiments of dogs? Lab dogs? I hope not because such casual abuse of dogs is immoral and would make you a POS.
Don't take it and thankfully do not need it
One trick pony 😅