The anti-rejection drug rapamycin has been shown in mice and other mammals to reverse cellular damage caused by aging to extend healthy life by up to 20%. This has caused massive off-label prescribing and use of rapamycin in humans as an anti-aging drug.
The GameChanger
What do you tell patients about the evidence-based use of rapamycin for anti-aging?
Host
Geoff Wall, PharmD, BCPS, FCCP, BCGP
Professor of Pharmacy Practice, Drake University
Internal Medicine/Critical Care, UnityPoint Health
Reference
https://www.washingtonpost.com/business/2024/03/15/rapamycin-longevity-drug/
https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext
Pharmacist Members, REDEEM YOUR CPE HERE!
Not a member? Get a Pharmacist Membership & earn CE for GameChangers Podcast episodes! (30 mins/episode)
CPE Information
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Describe the mechanism of action of rapamycin and how it may reverse normal aging.
2. Discuss the current state of evidence of rapamycin for this indication and its safety concerns.
0.05 CEU/0.5 Hr
UAN: 0107-0000-24-129-H01-P
Initial release date: 03/25/2024
Expiration date: 03/25/2025
Additional CPE details can be found here.
The anti-rejection drug rapamycin has been shown in mice and other mammals to reverse cellular damage caused by aging to extend healthy life by up to 20%. This has caused massive off-label prescribing and use of rapamycin in humans as an anti-aging drug.
The GameChanger
What do you tell patients about the evidence-based use of rapamycin for anti-aging?
Host
Geoff Wall, PharmD, BCPS, FCCP, BCGP
Professor of Pharmacy Practice, Drake University
Internal Medicine/Critical Care, UnityPoint Health
Reference
https://www.washingtonpost.com/business/2024/03/15/rapamycin-longevity-drug/
https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(23)00258-1/fulltext
Pharmacist Members, REDEEM YOUR CPE HERE!
Not a member? Get a Pharmacist Membership & earn CE for GameChangers Podcast episodes! (30 mins/episode)
CPE Information
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Describe the mechanism of action of rapamycin and how it may reverse normal aging.
2. Discuss the current state of evidence of rapamycin for this indication and its safety concerns.
0.05 CEU/0.5 Hr
UAN: 0107-0000-24-129-H01-P
Initial release date: 03/25/2024
Expiration date: 03/25/2025
Additional CPE details can be found here.
Hey, ce plan members from CE. Impactus is Game Changers. I'm Jen Moulton, and with me today is our resident game changers contributor, jeff Wall. Hey, jeff, how you doing. Great, how are you?
Speaker 2:You're doing good.
Speaker 1:Good, good, back from spring break. Had a little break last week.
Speaker 2:Yes, we did it was nice. Yeah, absolutely.
Speaker 1:Yeah, it was nice to just unplug for a little bit. We soaked up some sun in Florida, which you never know if there's going to be sun in Florida.
Speaker 2:Yeah, better than you and I in Iowa, that's for sure.
Speaker 1:That's right. That's right. Well, today I am actually super excited about this topic. I just wrote about this in Jed's desk. Actually, I just read the book recently, I guess last fall the book Outlive by Peter Atea, who is a physician and is now in this longevity space. As there are so many of lots of podcasts, lots of Instagram influencers, all these people on longevity, we all want to live longer and more gracefully, so people are capitalizing on that. But he's a physician and does a lot in data and really digs into the studies, and so I find it more interesting than some of the other ones that are a little bit surface. But I've been following his podcast and he talks a lot about Rapamycin, so I was so excited to see that we are going to talk about that on our podcast today too.
Speaker 2:Oh yeah, no, I agree, and we talked about this for recording. I think part of the impetus was this is there's a groundswell of interest, I think, in using this. And then there was a huge article in the Washington Post about a week before this recording and I think, with that kind of media attention, I think physicians and pharmacists are undoubtedly going to get questions about this. Well, hey do you think this is a good idea, sort of thing, yeah, and so I think discussing it is a really good idea.
Speaker 1:So yeah, so we can jump. I'm super interested in your take, so I appreciate that.
Speaker 2:So yeah, we'll jump into it. You know, one of the things that I've read other longevity experts talk about is that if you take a look at our Pharmacopeia at this point you know basically our 50,000 foot view of developing drugs. It's usually been anti something right. You know somebody has disease, it's causing something, you know there's some molecular or receptor, you know site problem and we're going to try and block that or stop that. So really kind of anti antibiotic, anti hyperlipidemia, anti hypertensive, anti hyperglycemic, I mean you can go on and on and on. But the vast majority of our pharmacotherapy is there's something wrong going on that leads to a disease state and we're going to try and block what's wrong, to basically amirilate the disease state or slowest progression or whatever. There is very little on. You know, are there medications we could give to patients before they develop chronic disease that would either prevent the development of chronic disease or significantly lessen its impact? And you know there was a paper that came out a few years ago that suggested and this was pre COVID, so these numbers have probably been, I think, somewhat blunted by COVID, but you know they estimated that.
Speaker 2:You know since the dawn of the 20th century that the average Western European and American has gained 11 to 12 years lifespan, right. So you know we are living, you know, 11 to 12 years longer than our ancestors did in the early 20th century. But unfortunately that those aren't good years, right, those are. Those are, in many patients, unfortunately, years where they just are living longer with with more and more comorbid diseases.
Speaker 2:The comedian Dennis Lyrie talked about this. He kind of joked about you know, you know he had at the time he was a heavy smoker and he said one of the things that irritated him about people who told him about smoking is that said, well, you know, smoking takes 10 years off your life and his argument was those are the 10 worst years there that you know, the years where you're in pain and and and you know, and all this other stuff. So I mean he is being deceased, of course, but I think I think that that that's a real issue is that, yes, where our lifespans are increasing, but unfortunately our middle and early lifespans aren't increasing, right, so people aren't spending more time, you know, without disease. They're spending more time with disease or alive with disease. So there's a lot of interest in, as Jen points out, there's the whole industry.
Speaker 2:Maybe a good word of longevity medicine. In other words, what can we do to help extend the lifespan of people in young or middle age who largely don't have disease, and prevent those diseases from occurring and allowing them to live a longer healthy life without disease? And so again there's there's been a lot of notice about this and the one of the
Speaker 2:drugs that has been purported to do this has been the anti rejection drug, rapamycin, and rapamycin is kind of a backup drug, I think, to most solid organ transplant protocols. I mean, nowadays, you know you get a kidney transplant, liver transplant, you're going to get, you know, tachyrolimus and and mycophenolate, usually those. There's some variation there with certain types of organ transplants. Adding on drugs like rapamycin or serolimus or everolimus is used just to help prevent the possible development of acute rejection, especially with organs that you basically can't afford to have fail, like the heart of the lung. So that's where the drug kind of has FDA approved and kind of looked at.
Speaker 2:But now there's this kind of grounds, well, from, as you know, you know from physicians and, unfortunately, influencers on social media and etc. Etc. And hey, this is a drug that you know may in fact do what we're talking about. It may, if you take it before you have disease. You can have an extended lifespan where you're healthy, you know. And so that's kind of the the idea of the high rapamycin, and we'll explain why the thought that is here kind of coming up here.
Speaker 2:Now, remember that the FDA, you know it, does not approve any drug for longevity, to my knowledge, and the only indication really for this medication is organ transplants. And so you know, basically there will probably never be a randomized control trial on this, for two reasons one, rapamycin is long been generic and two, I don't even know how you design a study like that. I mean, would you literally just, you know, randomize you know 30 year olds and who are healthy, and give half of them rapamycin, half of them know, and then follow them for 10 years? I mean, I'm not sure that that you could ever probably do a proper randomized control trial, because you literally have to have this trial going on for a decade plus.
Speaker 2:So we will probably never know with high level of certainty whether drugs like rapamycin do in fact extend lifespan. Now, you know, shorter studies might be able to say, ok, well, look, we can't say for sure you're going to live longer compared to controls, but all these biomarkers and looking at muscle mass and also other stuff may show that, you know, hey, compared to normal aging, this doesn't prove. But the problem is that we're probably not going to to get some high level of that on this. And so, unfortunately, you know, I think we do kind of fall into two camps. Or you've got people like a genus pointing out who I think are really trying to get data driven approach to this and saying, ok, you know, this is what the level of evidence shows in in animals, is what the level of human's? Let's take a look at the pros and cons. And then you've got kind of the celebrity doctor approach to doctor Oz, like approach of you know, hey, why not? You know can't hurt you, sort of stuff. And oh, by the way, I've got this on my website and etc. Etc. So, you know, I think that you know, those who are getting asked questions about this really should probably know what the latest data shows.
Speaker 2:There have been more and more physicians who are prescribing this as an anti-ageant treatment. The Washington Post, in their article, note that they kind of did a review and found that there are multiple, multiple anti-aging or longevity health practitioners prescribers for our prescribing Rafa Mayasin and that probably thousands of patients across the United States were using it. And it's cheap, it's generic. So I mean, unlike a lot of the stuff we talk about, you can get it for about 10 bucks a week, so I mean, it's actually fairly inexpensive. They actually interview a physician in the Washington Post article who says he's treated 1500 patients with Rafa Mayasin's 2017 and he calls it the most important drug in the history of medicine.
Speaker 2:I'll be honest, whenever I hear stuff like that, I hear ducks quacking in the background, but that's just me. So I think that that's obviously a way kind of semi-crazy take, but I think that we shouldn't let we shouldn't let that kind of hyperbole basically keep us from taking a look at the evidence surrounding this. Now, this all stems from studies that were done in the early 2000s, particularly with mice, that found that mice who were given Rafa Mayasin their lifespan was extended anywhere from 20 to 60%, and so the mice who received Rafa Mayasin lived longer and, importantly, did not develop a lot of the disease associated with aging compared to their controls, and so there are a number of those studies that kind of came out. Now, another person they interview in this Washington Post article, a physician named Alana Bulby who's a longevity expert of the University of Texas. They quoted her saying mice might be a little bit different from humans when it comes to the drug, and I completely agree with that assessment that mice are not humans. So I think that, like all things there's been, the history of medicine is replete of stuff that looked really good in the lab, looked really good in animal studies and then just never took off in humans because it either wasn't well tolerated or didn't do what it did in humans that it did in animals. So I think taking the evidence that, okay, well, mice are mammals, humans are mammals, so if it increases the longevity of mice, it probably increases the longevity of humans, is a gigantic leap. That I don't think is evidence-based and probably not the way to go. But that hasn't stopped several companies from trying to either figure this out or make money off it, or both. For example, there's a company called Altos Labs which is now looking at derivatives of a rapamyus and that might be more targeted and maybe safer and will undoubtedly be more expensive. There's another company called the Hevolution Foundation that is pledging to spend a billion dollars a year to look at drugs that are anti-aging, and again, a lot of these influencers and social media have a mass, pretty large followings and are really promoting the benefits of rapamyus.
Speaker 2:So now, how rapamyusin was discovered is kind of interesting. Like most anti-rejection drugs, it was completely serendipitous. Rapamyusin was collected by a scientific expedition in the 1960s when they were examining the soil of Easter Island, which is not really what we should be calling it. We should be calling it Rapa Nui, because that's what the natives call it. It's one of the most remote inhabited places on earth, and they looked at the soil and found that this drug basically not necessarily blocks the immune system and does have immunosuppressive properties, but it also seems to regulate the immune system, and so because of that it was looked at in organ rejection and was approved to clean back in 1999 for that. That's why it's generic now and it's why it's relatively easy to get.
Speaker 2:There are numerous telehealth companies. There's one called AgelessRx that I'm sure. You basically give them some money, they give you a two-minute review and send a prescription of rapamyusin to your local pharmacy. Not only is oral rapamyusin being looked at, but compounded topical is being looked at as an anti-aging skin cream. And again, it's worth noting that again, there's not a lot of evidence that looks at whether topical rapamyusin in fact does anything. How does it do this? Well, rapamyusin is an inhibitor of mTOR, and mTOR is one of the major regulators of the aging process. So as we get older, all ourselves start to develop some sayings where, basically, they start to die more rapidly, they start to show signs of stress and stop working like they should, and one of the big propagators of that is this cytokine called mTOR. And rapamyusin and its derivatives and there's several other rapamyusin-like drugs out there all block mTOR, so they block this major regulator of the aging process, and so that's kind of the theory. We've got some animal studies, so what do?
Speaker 2:human studies look like and that is the point of a systematic review and we'll have a link to that and the Washington Post article in our show notes that the systematic review was just published two years ago, where they aimed to basically take a look at the effects of rapamyusin in humans. What has been studied up to this point in humans? As you might imagine, there are almost no randomized controlled trial data out there, so this is largely case series or retrospective controlled studies or things along those lines. There's been a couple of small RCTs but on the whole it's pretty poor data, to be honest, with you taking a look at rapamyusin in a variety of disease states, trying to determine whether it has a benefit in aging in the immune system, the cardiovascular system, the pulmonary system, et cetera, et cetera, et cetera.
Speaker 2:So that's what the results of this systematic review is. The introduction of the systematic review notes that, again, the mTOR pathway has been linked to multiple chronic disease processes. It causes declined immune function, it causes deteriorating pulmonary function, it helps accelerate bone loss. It helps, it probably has some role in the loss of tumor process factor cells and surveillance cells looking for cancer. So, again, you're more likely to build cancer as you age, et cetera, et cetera, et cetera. They also note, and they do quite a bit of talk about how it may have a lot to do with the loss of sight as we all age, basically. So in this study, again, it's a systematic review.
Speaker 2:So, like most systematic reviews, they did a extensive review of PubMed, mbass, scopus, the Cochrane database, et cetera, et cetera, and they basically just used the terms of all the rapamycin or rapamycin derivatives, like rapamycin, serolimus, everolimus, et cetera, et cetera. They wanted to look at patients who were over age 18. They wanted to look at outcomes that were either aging-related physiological changes or on disease and almost all of them are on disease, unfortunately and that they were interventional studies with either rapamycin or serivatives. Basically, they did exclude obviously animal and in vitro other type studies. They looked at cancer or obviously organ rejections, because that's what it's approved for.
Speaker 2:And if the studies had fewer than five participants in the study, they were excluded. That's a good idea. We'll probably not include those either. Basically, once that was done, they did what most systematic reviews do the studies were then pulled. They then reviewed the studies. They used the standard Cochran bias tool that takes a look at that level of bias in studies. They had two independent reviewers then go through all the studies taking a look at that and if there were conflicts they had a third reviewer to kind of break the tie. As always, they look at things like the randomization process, the intervention, and even see outcome data. Again, that's pretty standard.
Speaker 2:When it was all said and done, they reviewed a ton of articles. That came up with 35 articles undergoing full screening and 19 articles included in this review. The vast, vast majority of these, again, were either retrospective control studies or very small randomized control studies or essentially large case series. So you know, again, not strong data, and they mentioned that in the systematic review several times. So, 19 articles 10 of them were in healthy individuals, nine of them were in patients with aging related diseases and six of the nine ones focused on neurodegenerative disorders, one on pulmonary disorders and two on rheumatologic disorders.
Speaker 2:When you added it all up, they had only 401 patients in this 19 studies, a accumulation of 19 trials. So again, that tells you right there how small the number of patients in each trial was. Meeting age was 50 years, though the spread was incredibly wide, up to 85 years in some of these groups, and the core size raised from six patients to 121 patients. So, again, if even one study had 121 patients, that tells you again, the 18 studies were just incredibly small. Right, the vast majority of them used rapamycin, though there were a few studies that looked at everolimus and serolimus, which, again, are our derivatives of rapamycin, basically.
Speaker 2:The doses were literally all over the place, anywhere from one milligram a day orally to higher doses where they actually did therapeutic drug monitoring and targeted levels in kind of the six to eight range, which is what we do when we're looking at at organ rejection. So doses were all over the place. Trial periods were all over the place. Some of these studies literally gave one or two doses of the drug. Others looked at multiple week studies. So again all over the place when it comes to dosing and duration and things along those lines.
Speaker 2:So, keeping all that in mind, what do we kind of find when we take a look at the studies, looking at neurologic stuff and again, the vast majority of these were people who already had some sort of neurologic disease and see if rapamycin was beneficial.
Speaker 2:And the bottom line was no, rapamycin did not seem to improve neurologic disease in patients.
Speaker 2:And when they did do, looked at one study that looked at rapamycin one milligram a day for eight weeks in relative and healthy individuals to see if it would affect cognitive dysfunction, and it had no benefit in cognitive dysfunction. So from a neurologic standpoint, at least with the poor evidence we have today, that does not look like rapamycin either stabilizes, improves or treats neurologic dysfunction, either in healthy individuals or individuals with disease. They did do in some of these studies taking a look at MRIs to see if there was you know again any difference in blood flow or nerve fiber thickness, and again they didn't really find anything in those patients they took a look at. Apparently there's been several studies that have looked at vision changes, especially in patients with macular degeneration and giving rapamycin, and actually found there was a couple studies that did find that patients who already had macular degeneration rapamycin may be beneficial. But they also found that in healthy patients who just have normal degeneration of eyesight with aging, that doses of rapamycin may actually lead to retinal thinning, which is not a good thing.
Speaker 2:So maybe a benefit in patients with existing, especially diabetic, macular retinopathy problems, but not in patients with essentially just normal decline of vision with health. In the world of pulmonary medicine, patients with pulmonary hypertension low doses of everolimus did statistically significantly increase baseline measurements of cardiac output and lung function and actually found that patients had increased ability to exercise and things like that. Now, of course pulmonary hypertension has some inflammatory components, so it's certainly possible that just its anti-inflammatory effects may be the reason why. But for whatever reason, it seems with pulmonary hypertension rapamycin may have a benefit. Again, all in small studies they looked at the endocrine effects of rapamycin pretty significantly. Unlike the calcium urin inhibitors, these drugs do not seem to increase blood sugars. One of the big problems with tecralimus and cyclosporin is that they very commonly increase blood sugars.
Speaker 2:The mTOR inhibitors don't do that. There's some thought that maybe they would actually delay the progression of diabetes or prevent the development of diabetes. The data here is a little bit more mixed. Some studies did show that it caused patients who were pre-diabetic or were healthy that it actually allowed them to use insulin more efficiently. That uptake of insulin into tissues was better in patients who were on rapamycin. But again, those were poorly done studies with either one or two doses. Again, hard to extrapolate that. But when they took a look at patients who had diabetes, rapamycin did not seem to have a significant effect on plasma concentration of fasting glucose random glucose or hemoglobin A1c.
Speaker 2:Unfortunately, while it may have some small effect in poorly done studies in healthy patients to perhaps have them use insulin more efficiently, it does not seem that in patients who are pre-diabetic or diabetic that rapamycin currently has data to support its use in treating diabetes. Probably one of the things they studied that the mTOR inhibitors seem to have the best data in again unsurprisingly is rheumatoid arthritis. There's been several 12-week studies that have looked at either everolimus or serolimus with rheumatoid arthritis and have found that, yeah, it improves symptoms, decrease joint swelling, decrease markers of inflammation Again not surprising, knowing that's an anti-inflammatory drug. Unfortunately, in those studies they also found an increase in total cholesterol, ldl cholesterol and triglyceride, so that may not be a very good thing as well. And then they looked at muscle development.
Speaker 2:There's several small studies that have looked at healthy individuals and have put them on several weeks of mTOR inhibitors to see if it improves exercise tolerance or muscle development and it seemed to have, at least in these studies, no real effect. So it didn't seem to improve exercise tolerance. When they looked at muscle development markers, it didn't seem to improve either. Also, there was a small study looking at physical function and just healthy individuals age 70 to 95. And this if we're really kind of trying to take a look at the use in elders to see if it would actually work as an anti-aging agent. They unfortunately found in this study, at one milligram a day, or really for eight weeks, that there was no significant increase in exercise, walking, speed, grip, strength, muscles, anything along those lines.
Speaker 2:So unfortunately, in this small study they actually did not see a benefit in an older, healthy patients to actually improve quality of life sort of stuff or aging issues and stuff like that.
Speaker 2:The other thing they looked at pretty significantly was the immune response to vaccines, and this is probably one of the areas where these drugs have been studied the best.
Speaker 2:Again, while these drugs are probably described as anti-inflammatories, a better way some of these longevity experts are talking about the drug is that it's an immune regulator, so it isn't necessarily an anti-inflammatory or pro-inflammatory drug.
Speaker 2:It basically helps regulate the immune system so that the body can can make a response to foreign invaders, like you know, bacteria, viruses, stuff like that but can regulate the immune system so that there isn't a pro-inflammatory spike with with with a lot of pro-inflammatory diseases. So when we take a look at the immune response to vaccines, there's actually pretty good data on this. There's now been several fairly decent randomized control trials, mostly with the everolimus, that have found that if you take these drugs around the time that you receive vaccines, you see a significant, significantly higher spike in antibody titers, especially the influence, and that's probably the one that's been studied the most. Even in patients who are relatively older, who usually don't have a very good response because of, as we get older, immune system just doesn't work as well, they actually found that even in older patients they saw a significant increase in antibody titers, but again, particularly the influenza in patients who received rapamycin around the same time that they received the vaccine.
Speaker 2:So that's kind of interesting, I think. Certainly, again, not something I'm probably going to recommend routinely, but it is interesting and may give us a clue to kind of what we can use these medications for Now rapamycin is an anti-rejection agent, so it does have again some issues when it comes to infection and things like that.
Speaker 2:And so, you know, I think the other piece that we have to kind of really seriously consider is the safety of these medications, and the systematic review, I think, does a really good job of taking a look at safety and saying, ok, you know what did?
Speaker 2:they find in these 19 studies In general, surprisingly, they found that there were very few significantly serious side effects with the mTOR inhibitors and that they were almost always reversible upon discontinuation of treatment. And really the big side effect they found with most patients was canker mouth sores that were difficult to heal and that's actually long been known as a big side effect of the mTOR inhibitor, so that's not particularly surprising. However, they do note that in the study that looked at rheumatoid arthritis that they found that there was a higher number of patients who had serious infections and in fact they had two deaths due to septic shock in the rapamycin group compared to the placebo group in rheumatoid arthritis. So you know again, I think it's worth noting that these drugs do have the potential to be immunosuppressive and probably do increase the risk of infection.
Speaker 2:Now, the low doses that a lot of the longevity experts are recommending, which is largely one milligram a day, you know, is probably, for the purposes of organ rejection, some therapeutic in most patients. So I think what a lot of longevity experts are arguing is that at these low doses you're still going to get the effect on the cells of mTOR inhibition, but you're not going to get to the level of immunosuppression that would increase the risk of serious infection. I think that remains to be seen, and I do think that it's something that you know. If your patients are asking you about this, I think you really need to think about, especially if they are at risk of having other infections. So if you had a diabetic or if you had a patient who had other you know issues associated with immune response I'd be a little nervous about recommending it just based on safety, to say nothing of efficacy, and I think that the mouth ulcers are going to be the other thing you're probably going to want to warn your patients about.
Speaker 2:So the authors of the systematic review. Basically, you know, their summary was that if you take a look at some very, very poor studies, there are signals that the drugs may improve some immune responses and may improve some pulmonary responses and may have, you know, some small effects and some other disease states, but at this point it does not seem to improve neurologic function and a contruction muscular function. And the one study that tried to take a look at just basically giving it to older, healthy patients did not seem to find a benefit in quality of life, muscle strength, things along those lines. So the evidence to date has not been very strong. Now again that it doesn't answer the central question If I take rapamycin when I'm 45 years old and I'm relatively healthy, will that add on to my healthy lifespan? Again, I'm not sure how we're ever going to really figure that out, just you know, based on the difficulty of doing studies on that.
Speaker 2:So I mean you know, does the systematic review answer the question that? I think a lot of longevity experts are arguing that you know, taking the struggle when you're younger and healthy will prevent the development of disease. We don't know, but I think that the evidence you know in humans does suggest that there are some improvements in several people who already have disease.
Speaker 2:But one could argue that a lot of that is just due to its anti-inflammatory effect and that there's that it in and of itself probably doesn't, in those patients, improve the healthy cells, if you will, that are going on in patients basically. So you know, they know that that safety was better than I think they expected, that in these small studies they did not find a significant increase in infections, though again they point out that there's that rheumatoid arthritis study and that most people tolerated the drug pretty recently.
Speaker 2:So as far as the studies themselves they know that very small sample sizes, that they you know were kind of poorly conducted studies, the doses were all over the place, et cetera, et cetera, et cetera.
Speaker 2:And they also noted that the one study that showed an increase in lipids was pretty concerning as well. So they kind of walk away from the study, suggesting that the data right now to suggest that rapamycin either improves longevity in healthy patients or helps, you know, blunt or stop age-related diseases is pretty minimal. And they also note that that don't know the right dose, we don't know how long, et cetera, et cetera, et cetera. So there's a ton of questions and not very much answers. So you know what do you, as a prescriber or a pharmacist, you know, when a patient inevitably comes to you and says hey, I saw in the Washington Post there's this paper that you know that they're using this drug and many people live longer and I'm 45 and I work out and I'm real healthy and I, you know, want to live as long as I can and I want to be healthy. I think I should take this drug. What do you tell them? Well, I think that the bulk of the evidence in humans right now does not support its use in just extending healthy life in humans, again, acknowledging that you know we're probably never going to get strong data that it does seem to improve health in animals, particularly mammals that have been studied. But, as was pointed out earlier, you know, mice are not men or humans, and so I think that you take a big leap when you make that assumption. It is cheap, it seems to be fairly well tolerated, but I again, you know, I'm not really sure if you were to start somebody on Rapa Myas and how you could prove that it in fact is improving, is keeping them youthful or keeping them healthy as they go on. So, you know, in the end I probably not recommend that based on the evidence that we have now. If some of these Rapa Myas and derivatives come out that are being studied and I'm sure will be much, much more expensive if they were defined that you know, that might be something else. But I, at this point I would be hard-pressed to recommend this drug based essentially on animal data.
Speaker 2:But you know, I think you're going to run into patients and I think a lot of the patients that come to you with this are going to be. Well, I studied on the internet or I follow this guy, you know, on Instagram or whatever that you know says that it works really good and he's a doctor and he's a longevity guy and blah, blah, blah, blah, blah. I think that you know, those are the people who are often going to come to you, and if you don't prescribe it and I'm not saying you should prescribe it they're probably going to get it from somebody else anyway. And so I think that if that's the case, then if you're like, well, you know, if you are going to do this, then here's what I want to want you to watch out for, and I think the two big things are, you know, again, mouth ulcers development, infection, stopping the drug If you start to develop a serious infection with a fever. I think it's a good idea.
Speaker 2:And for the pharmacists out there, like many of these medications, there are some drug interactions and we could have probably done an entire podcast just on that. So, again, watching closely for drug interactions and people on medications is going to be important. So I think the role of most prescribers, who aren't going to be interested in prescribing this medication based on the evidence for longevity, are going to have to deal with these patients on these medications from another source, and what we need to know about safety and drug interactions is going to be pretty important.
Speaker 1:So that's going to origin.
Speaker 2:What do you think?
Speaker 1:Yeah, well, super interesting. And I think to your last point, you know, just making sure that people tell you if they're on it from somewhere else, so that you can, you know, identify those drug interactions. You know, we're always on the search for the you know magic bullet.
Speaker 2:Yeah, without the views.
Speaker 1:We just want. We want to take something and live forever. I think the other one, the other drug that has had some longevity discussions, is metformin, and there is a little bit more evidence about that, so I wondered if you could just briefly touch on that as well.
Speaker 2:Absolutely. And metformin I mean again, I'm not suggesting that everybody and the dogs are taking metformin, but I think that yeah, there is some pretty good evidence, both in animals and a little bit in humans again, about just general anti-aging properties and some of the things, but primarily in patients who are starting to develop the metabolic syndrome. So people who are starting to their blood sugar is starting to creep up, their LELs starting to creep up, their blood pressure starting to creep up. But again, it happens to many, if not most especially Americans, as we get older, that there are some randomized, controlled trials that are relatively well done, that actually go out six months or a year that shows that metformin can seem to help stabilize or even reverse the beginnings of the metabolic syndrome in these patients.
Speaker 2:So while again, I'm not sure I started taking metformin when I was 20 years old, I think at your 40, 50, 55, 60, and you're seeing your family medicine doc or your internist, then they're like, yeah, you're human, global, and A1C is 6.2, we got to watch that. Or G, your blood pressure is starting to creep up. Or, wow, your LEL is starting to get a little bit higher. I mean, again, definitely use the medications that are indicated for that. But there is some evidence suggesting again, especially in that kind of young to middle middle age. At my age I'm starting to think that there's young middle age and middle middle age and then high middle age.
Speaker 2:Younger and younger every day, exactly Like almost all healthcare professionals. The older you get, you see a patient you're like that's not that old, they're not that old, but in any event, yeah, I think metformin is something to consider in patients, particularly as they kind of reach that middle middle age, young middle age sort of thing, 40s, 50s where they are starting to see the development of the metabolic center.
Speaker 2:Now, of course, a lot of that's related to obesity. So obviously they should do lifestyle changes, try and get their diet under better control, try and get their weight under better control, certainly, but yes, I think there's an evidence there. I have no doubt that somebody somewhere in patients in their 40s and 50s is going to do a study with the GOP1 drugs about this? Because why not? We use GOP1 drugs now for everything else, so I wouldn't do that, we'll start to put it in the water?
Speaker 2:Yeah, exactly.
Speaker 2:Well, I think one of the things you could argue is that and I think there's evidence that suggests this too is that there is kind of a Goldilocks area of weight for most humans that you don't want to be too thin either, right?
Speaker 2:I mean that being too thin associated with its own issues, right? And so I mean I think kind of being having kind of a BMI in actually the high end of normal is what I've read is so if you're, the normal BMI is kind of 18 to 25, if you can run a BMI in the 23, 24, 25 range, that seems to be the sweet spot as far as the development of disease that they've seen so far, that there actually is a spike in other diseases, as you're doing, If your weight goes down too much, right. So there's kind of this Goldilocks target that so far is really what we should be trying to do. And so I think, yeah, who knows, Will they end up using GOP1 drugs, that kind of target, this high normal BMI, and will that end up having some benefit in longevity and healthy longevity? As time goes on? It'll be very interesting to see.
Speaker 1:Yeah well, we're all looking for the easy road and we know it's not an easy road. I mean, a lot of what Dr Atia talks about in that book is actually doing the hard work for a long Japanese, and I'm guilty of it too, so no judgment here, but it's. I think those are the questions that we ask patients is how, and the fact that it is inexpensive it's probably going to lead a lot of people to it.
Speaker 1:I mean, we're seeing, obviously GOP1s are not inexpensive for people who insurance doesn't pay for it, and they're still doing it. So you know whether that cost is a barrier or not. But with RAPA, MySEN, it's not because it is so inexpensive. So I think we're going to start to see it a lot. So I think it's important just to know what the risks are. And thanks for doing a great job of that.
Speaker 2:No problem.
Speaker 1:All right, so fun topic this week. That's it for this week. So if you're a CE plan member, be sure to claim your CE credit for this episode by logging in at ceimpactcom. And, as always, have a great week and keep learning. We'll talk to you soon, jeff, thanks, thank you.