178. Dr. Matt Kaeberlein: The Science, Risk, and Hype Behind Today's Longevity Trends

If you care about longevity, you have probably seen the same pattern over and over again. A new peptide, supplement, biological age test, off-label drug, or protocol starts gaining attention, and suddenly it sounds like the missing piece everyone should be using. The hard part is not wanting to be proactive. The hard part is knowing which claims have real evidence behind them, which ones are still early signals, and which ones may carry risks no one is measuring carefully enough. In this episode, I sit down with Dr. Matt Kaeberlein to talk about how to think about longevity when the answer is rarely a simple yes or no. This conversation helps separate excitement from certainty, and shows why the real question is not only whether something might work, but whether the evidence, safety data, product quality, and risk-reward equation are strong enough to act on. Dr. Matt Kaeberlein is a scientist in the biology of aging and one of the most respected voices bringing scientific discipline to the longevity conversation. He has been involved with the Interventions Testing Program, which rigorously tests aging interventions in mice, and is one of the leaders behind the Dog Aging Project, a large-scale study looking at aging, health, and longevity in companion dogs. His work sits at the intersection of curiosity and caution, which makes him the right person to talk about what is promising, what is overhyped, and what still needs better evidence. What's Discussed: (03:24) Why longevity marketing can move faster than the science. (06:31) The risk-reward question most people skip before trying a new therapy. (09:39) Why years of peptide use does not automatically mean safety is proven. (20:00) The "research use only" peptide problem and why product quality matters. (34:51) How the Interventions Testing Program separates stronger longevity signals from noise. (38:39) Why rapamycin changed the field, and why some popular interventions failed to replicate. (58:43) What the Dog Aging Project may teach us about rapamycin, healthspan, and human aging. Listen to this episode of Extend to understand how to evaluate longevity claims with more clarity. You will hear what deserves excitement, what deserves caution, and what to ask before turning the next promising intervention into your personal health protocol. Thank You to Our Sponsors: Timeline: Timeline powered by Mitopure just dropped the price. Check it out at timeline.com/drshah http://timeline.com/drshah and get an additional 20% off your first month with code DRSHAH. IM8: Try IM8 today with a 30-day money back guarantee. You can get 10% off your first order with code DRSHAH at im8health.com/discount/DRSHAH https://im8health.com/discount/DRSHAH. Learn More About Dr. Darshan Shah: Website: drshah.com http://drshah.com Clinic: next-health.com http://next-health.com Instagram: darshanshahmd https://www.instagram.com/darshanshahmd/ Learn More About Dr. Matt Kaeberlein & the Dog Aging Project: Website: dogagingproject.org/ https://www.dogagingproject.org/ Instagram: @mkaeberlein https://www.instagram.com/mkaeberlein/

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Dr. Darshan Shah?

  Before we get started with this episode, I'd like to invite all of you to the first ever Next Health Longevity Summit, happening in Nashville, Tennessee, at the Conrad Hotel on Saturday, September 12, 2026. This is an all-day summit where you're going to be hearing from some of the best speakers in longevity's medicine, including Dr. Vonda Wright, Dr. Luisa Nicola, many of the podcast guests that you've heard here on the Extend Podcast, and of course, I'm going to be there curating the entire day. We also have incredible vendors coming, so you can try the latest technologies in health, wellness, and longevity. Go to next-health.com/summit and buy your ticket today. We only have 400 spots and

• 0:39Dr. Darshan Shah?

  they're going quickly. That's next-health.com/summit. I look forward to seeing you all there. Welcome to Extend with me, Dr. Darshan Shah, a podcast dedicated to cutting-edge science, research, tools, and protocols designed to help you extend your health span. Having become one of the youngest doctors in the country at the age of 21, and trained and board-certified at the Mayo Clinic, I've accumulated three decades of practice as a board-certified surgeon and longevity expert. Over that time, I've discovered that a mere 20% of health knowledge yields 80% of the results when it comes to your health span. We are living in a new era where we are creating a new healthcare system, no longer focused on disease management, but achieving optimal health and vitality.

• 1:23Dr. Darshan Shah?

  Join me as I interview world-renowned experts, offering you a step-by-step guide to proactively avoid disease, and most importantly, extend your health span. Dr. Matt Kabelin, thank you so much for joining the podcast. Extend, it's been a long time that I've been following your work and watching your Youtubes and listening to you, and it's just such an honor to have you. Thank you for being here.

• 1:47Speaker 01

  Thank you. Yeah, no, it's a pleasure to be able to join you, and I'm just glad we were able to hammer it out here in beautiful Miami.

• 1:53Dr. Darshan Shah?

  I know, we made it happen. I was like, if you're coming, I'm going to make this happen. So thank you for carving a few hours out for me. And, you know, I followed your work for a long time and really appreciate what you're doing to really advance the science, but also bring to this crazy...

• 2:10Dr. Darshan Shah?

  Exploding term longevity.

• 2:12Speaker 01

  Yeah.

• 2:12Dr. Darshan Shah?

  Some sensibility too, you know, and so I really appreciate your, your scientific view of really talking about what is working, what's coming and bringing truth to this.

• 2:22Speaker 01

  Well, well, thank you. And, and, and I, I do try. I mean, I'm a scientist by training, so that's the lens that I look at the world through. And I think, you know, as you alluded to, the space is growing so rapidly. And so much of it feels like marketing has got ahead of the science that, you know, I think it's important for those of us who are scientifically and evidence minded to really try to set expectations. Cause there's a lot of reasons to be really excited about where we're at now and what's coming. And so I think I want to give people a realistic sense of where we're at instead of, you know, some of the, the less evidence based talk that's out there right now. And honestly, some of the less evidence based talk can be dangerous.

• 3:04Speaker 01

  And so also helping people to be able to navigate the space, avoid getting into trouble, separate the signal from the noise.

• 3:11Dr. Darshan Shah?

  Yeah, it's, it's so important right now. And this is where, you know, we've kind of leaned into this podcast of just making sure that we not have the people that talk about this from more of a marketing perspective and really just talk about the science, right? And so I think you're right, the marketing does get way ahead of the science because there's obviously a lot of money to be made. You know, in history, how many people have made money off of selling, you know, the, the longevity cure or the fountain of youth, right?

• 3:38Speaker 01

  Yeah, no, absolutely true. And, uh, you know, I think again, there is a place for that and the consumers demand it, right? The reason there's money to be made is because people want some of this stuff. But I think, you know, there are, there are a lot of people who they want the new solutions, but they also want to know what's real.

• 3:57Dr. Darshan Shah?

  Right.

• 3:57Speaker 01

  And there's a lot of gray area where, you know, this is, I think, something that's, that's hard for maybe people who aren't trained in, in science or statistics to appreciate. There are things that we feel really confident about, right?

• 4:07Dr. Darshan Shah?

  Right.

• 4:08Speaker 01

  And that's kind of where I tend to try to live.

• 4:10Dr. Darshan Shah?

  Yep.

• 4:10Speaker 01

  But then there's this whole gray area of things that, you know, there's some evidence.

• 4:14Dr. Darshan Shah?

  Yes.

• 4:15Speaker 01

  Some reason to believe there's, there's, there's value or, or, or reality there. But you know, our confidence is a lot lower and and you know, maybe maybe it's a 10% chance that's going to work. And so really trying to help people understand that kind of probabilistic thinking about data. Because very little in in science or medicine is 100% rock solid. It's somewhere between, you know, 99% confidence to 1% confidence. And helping people try to figure out where, you know, for this particular supplement. In my situation, where do I fall? Is it a 90% or a 5%? And then you can make your decision. So I think that's just an important framework for maybe people to spend more time thinking about.

• 4:56Dr. Darshan Shah?

  Yeah, absolutely.

• 4:57Speaker 01

  Because the people selling these things will tell you it's all 100%.

• 4:59Dr. Darshan Shah?

  Right, right.

• 5:00Speaker 01

  Right?

• 5:01Dr. Darshan Shah?

  Yeah, the reality is usually it's a bell shaped curve or some sort of like statistical distribution.

• 5:05Speaker 01

  Yeah.

• 5:06Dr. Darshan Shah?

  How anything works for you, right?

• 5:08Speaker 01

  That's right.

• 5:08Dr. Darshan Shah?

  It's you, you have to really understand like your own biology and combine the data. The knowledge of the data with your knowledge of yourself.

• 5:17Speaker 01

  Yeah.

• 5:17Dr. Darshan Shah?

  And see what's going to work for you, right?

• 5:19Speaker 01

  Yeah, I think the other piece there that a lot of people tend to underestimate is the really trying to do an accurate risk assessment, right? So we're talking about the the reward part.

• 5:30Dr. Darshan Shah?

  Right.

• 5:30Speaker 01

  How likely is this to work? And if it does, how big is the benefit going to be? There's that piece. Those, those are two things you should think about on the reward side. On, but then there's the risk side. And and I think, you know, it's kind of interesting to me because a lot of people, when you talk about pharmaceutical drugs, right? Big Pharma, bad word, and nobody likes Big Pharma. Everybody is scared of the risk of the side effects, right? But you get outside of that world, I'll just put peptides out there. And there are peptides is a big category. There are some peptides that are great. There are some peptides that are FDA approved. There are some that aren't. It's all over the place. But in that category, people seem to default to in the absence of evidence of risk or harm, there is no harm.

• 6:10Dr. Darshan Shah?

  Right, right.

• 6:11Speaker 01

  It's like it's just completely dismiss what could go wrong. And so I think that's where it's also important just to try to get people to understand. What does, what do we know? What do we know? And based on that, what can we really estimate the actual risk is? And then within risk, it's really important to consider there's risk of something minor. Bad happening, then there's the risk of catastrophic side effects where you get a stroke or you get cataracts or you die. So even if the absolute risk of a catastrophic outcome is pretty low, you really should ask yourself, is it worth it to me to maybe lose a little bit of weight? If there's a 0.1% chance that I'm going to have a stroke and be paralyzed for the rest of my life? I think people don't really think about that in a rational way.

• 6:54Speaker 01

  We get very irrational, it seems like, in wellness. So I started, I started referring to this as the wellness blinders. Like, we put blinders on about the risk, some people do, in the wellness space. And I just think it's really important for people to really think hard. You know, what's the best outcome that could happen? How likely is that to happen? And what's the worst outcome that could happen? And how likely is that to happen? And then you can sort of make an informed decision. Now, what I just said, I think, makes sense. And I recognize it's really hard for the average person to be able to do that calculation. Because they don't have access to all the information. They don't necessarily have the ability to dive into the primary literature, understand, okay, there was this one study that was done in mice, but nobody's ever tested this in humans. What does that mean?

• 7:38Speaker 01

  So they need to rely on, hopefully, reliable medical professionals to guide them in that decision.

• 7:43Dr. Darshan Shah?

  Yeah, and the other aspect of risk too is, risk is just really under-reported. Like, if you go looking for, we'll use a Pepto example, right? Complications of BPC157, for example. It takes a lot for someone to see a complication, then write about it as a case report, put it in the literature. That process usually doesn't happen very, very often or frequently. And so, my problem with risk is too, is we really just don't know without the studies as well, where someone's very mindfully documenting the side effects that are happening on a certain group of people, right?

• 8:17Speaker 01

  I think that's super important. And again, this is where, you know, maybe the, the average person doesn't fully appreciate what you just said. Because they're gonna, some people will say, yeah, but BPC157's been used by functional medicine doctors for 20 years, right? If it was really bad, we would know already. What you just said, I think, is really important. That would be true if we got reports for everybody who's using it accurately. About who benefited and who was harmed. This is why we need the randomized placebo-controlled clinical trials where we're going to get both the efficacy signal, if it's there, and the safety signal, if it's there, and be able to say, you know, in this group of, you know, optimally a thousand-plus people,

• 8:58Speaker 01

  this many people had side effects in the BPC157 group, this many people had side effects in the placebo group. It was or wasn't different, right? You're not going to get that from individual doctors who are prescribing it, you know, one-off to their patients. And also, even if the doctors wanted to be honest and report side effects, there's no place for them to really do it Right. in a rigorous way. Right. And that's only if the patients tell them. So again, in the context of a randomized clinical trial, people are going to be surveyed about any side effects that they get. We'll be able to capture that data. Outside of that, we just miss it, right? And so I think that's, maybe most people don't realize this, but it's only a tiny handful of the peptides that are being prescribed

• 9:42Speaker 01

  outside of the FDA-approved peptides, the unapproved peptides. It's only a tiny handful that we have any real human data on. Right. At least randomized clinical trial human data. I think right now there are two clinical trials for BPC157 happening. I don't think any have been published. Right. So, you know, at the highest quality level, we have no data on safety for BPC157. And that's one that's been used, you know, for a long time. You get into the newer shiny object peptides that are out there now. And like, we just have no data at all. Yeah. I've been shocked, and it goes beyond peptides. There are, there are a bunch of doctors using, or you can buy it on the internet, small molecules. They aren't even peptides. They're kind of labeled as peptides. They're not peptides. No. Where there's no human data, and doctors are prescribing it, people are selling it, people are taking it.

• 10:27Speaker 01

  Again, I've actually got an episode coming out on my pod test now. I don't know if you know the story of dinitrophenol, but I think this is a really interesting, you know, It's a great example. Example of what can, can go wrong. And I'm not suggesting anything out there now is as dangerous as dinitrophenol. But it's a really interesting example of a drug that was a metabolic activator. I'm sure you've heard that term, that today would probably Would be called an exercise mimetic, right? Or a mitochondrial activator that kills people. Once you get outside a very narrow range. It's really effective at causing weight loss. Because it uncouples the mitochondria, it causes you to just burn ATP. The problem is when you do that, you give off heat. And if your body temperature gets too high, bad things happen, right? So, you know, I don't, we don't know how many people did.

• 11:12Speaker 01

  It's in the hundreds died from D N P between nineteen twenty and today. It's not really used anymore today. Because it was just prescribed outside of any sort of FDA regulatory oversight. And, and it's actually D N P is actually one of the major catalysts for the current FDA regulations. I think it's nineteen thirty eight Food, Drug and Cosmetic Act. So I think we're starting to see a shift. And, and so this is interesting, right? Because that, that's, that nineteen thirty eight act, I think, was the pendulum swing towards more regulation. Right for drugs. FDA could say a drug's not safe. It had to go through clinical trials and be approved to be allowed to be prescribed. And we're seeing a pendulum swing back the other direction. And look, I personally am very libertarian when it comes to, to health.

• 11:57Speaker 01

  I think if people are fully informed, they should be able to make their own decisions about what they do with their body. It's that fully informed piece that is really hard. But we're seeing this shift back now away from regulation where people and medical professionals some feel much more comfortable prescribing and using therapies that don't have randomized clinical trial data. Hopefully, we won't end up with another situation like binatrophinol where a bunch of people die from this. If we do, I think we'll see the pendulum swing back the other direction. So it would be nice if we could just land somewhere in, in the middle. Somewhere in the middle. I know I've been talking for a while, but I'll. But I've got one thing that I, that really, you know, I feel strongly about.

• 12:38Speaker 01

  And it's quite frustrating to me is that it would be really easy to get the clinical trial data on the top ten prescribed unregulated peptides. Exactly. Right? This is not, this is a solvable problem that actually doesn't cost that much money. Compared to the, what we spend on, you know, what I would call low quality research through NIH. This would be a drop in the bucket. Could actually get answers. We get a committee of experts together, say, these are the 10 things we need to test and go test them.

• 13:06Dr. Darshan Shah?

  Right.

• 13:06Speaker 01

  That's easily doable. And then we would know, do they work? Who do they work for? And what do the risks look like? So somebody ought to just in in leadership in this country or in some other country, just get it together, do these clinical trials. This is easy, it's doable, and we'll know the answer.

• 13:23Dr. Darshan Shah?

  Yeah. And I wonder this all the time myself, like, why are the trials not being done? You know, we always say, like, it's so expensive to do a trial in the United States, right? The FDA makes it extremely expensive to get something through the drug.

• 13:38Speaker 01

  For approval.

• 13:39Dr. Darshan Shah?

  For approval. But we're not talking about getting it approved as a drug. We're talking about doing a clinical trial to, to your point, get to safety and efficacy data, right? And then at least we know that this thing is not harming people, right?

• 13:53Speaker 01

  Right?

• 13:53Dr. Darshan Shah?

  So, yeah, and so I do, I do think, and what would like the sample size be for a trial like that?

• 13:57Speaker 01

  I mean, well, it depends a little bit on the question you want to ask, right? So usually the way you determine the size for a clinical trial is you're going to look at whatever the endpoint is that you're interested in. So if it's, you know, kidney disease or a certain type of cancer, whatever. And there are statistical tools you can use to say, we need this large of a cohort in order to be able to detect this big of a change. So it's going to depend on what's what the indication is. If we're really only interested in safety, like you could, you could make the decision, you know, efficacy is important, but what we're really concerned about is safety. If we were really interested in safety, then I think what you would need to do is say, in the general population, if that's who this the study is going to be done on, let's just say people 55 and older, right?

• 14:42Speaker 01

  What is the likelihood within that population that people are going to develop? And then you have a long list of different conditions and then you do the statistics. Again, I don't know what the answer is. I haven't tried to do the math.

• 14:51Dr. Darshan Shah?

  Yeah.

• 14:52Speaker 01

  I'm guessing 1,000 people would be enough to see at least a strong safety signal. And again, like, I'm not suggesting this is going to be dirt cheap, but I think you could, if you designed this in an efficient way, you could do this at 50 million per intervention. You test 10 interventions, that's 500 million. I mean, that's a lot of money. But again, Compared to what we spend on research that doesn't give us any good information at the end of the day, this would be quite valuable and maybe it would be a lot cheaper, like maybe I'm off by five fold even. But so, so I think it's, it's a matter of what would the, what's the benefit that would accrue from spending that much money? And I think in this case, it's, it's a pretty big benefit and, and I would love to see, I mean, we were chatting briefly before we started filming about the mouse interventions testing program.

• 15:35Speaker 01

  This could be a human version of that, right? Where every year, the government just says, we're going to fund five clinical trials for interesting drugs that pharma isn't gonna, isn't gonna move forward. For whatever reason. We have a, a committee of experts, I would suggest both medical and scientific experts that convene, maybe evaluate a longer list, pick the five that are going to go through testing and then test them. Like that to me would be an amazing program that would provide a lot of really valuable information. And hopefully would help, you know, help people who want access to these new therapies feel more confident. And doctors feel more confident in using them and knowing who is going to benefit from these things.

• 16:20Dr. Darshan Shah?

  When I read about the ITP program, which I heard about through you actually, and your, your work that you put out there. I was like, why are we not doing this for humans? Like this is, this seems like the way forward for these molecules that the, that pharma is not interested in, right? And it really, and like you said, like it's, it might seem like a big number, but we spend so much more money on so many other things that go nowhere, you know?

• 16:42Speaker 01

  Yeah. And then once you get outside of biomedical research, I mean, we could go down the path of all the stuff we spend money on that goes nowhere. So, um, I, and I, but I do think, you know, what you said is important because, because we're talking here primarily about things that pharma either has abandoned or won't pursue because they don't have patent protection. So when this conversation comes up, a lot of times people will get very upset and they're like, well, why should the government pay for, you know, what pharma should pay for? And I understand that, I understand that perspective. What we're talking about here are therapeutics that pharma is never going to do the clinical trials for. Either because they don't have patent protection or because they're Maybe already FDA approved for something else.

• 17:22Speaker 01

  And so there's no incentive for them to do the very expensive clinical trials for FDA approval or label expansion. So it requires either they don't get done, which is where we've been, you know, for the last 50 years, or the government's going to have to fund these things, or private philanthropy is going to have to fund these things.

• 17:43Dr. Darshan Shah?

  Right. And I think right now with the massive interest in peptide, I mean, there's, there's companies making millions and they're not even FDA approved yet. Like, there needs to be some sort of meeting of the minds here where people are putting money into some sort of research program like this.

• 17:57Speaker 01

  Yeah.

• 17:58Dr. Darshan Shah?

  Where the safety and the efficacy, because that's just going to benefit even those companies that are selling the peptides, right?

• 18:02Speaker 01

  Yeah. Although there is another piece here that's worth mentioning, which is that most of the companies making money off of peptides now are doing it outside of even the quality manufacturing regulatory piece, right? And they label it as research use only or not for human consumption. So that's, that's another, if you're considering using these peptides, that's another safety consideration you need, you need to take into account. Is if you buy it over the internet as opposed to say, getting it from a prescription at a compounding pharmacy. If you buy it off the internet and it says research use only, you really have no idea about the manufacturing quality of that product. Is it even what you think it is? And if it is, what else is in there?

• 18:43Speaker 01

  So that's the other piece, I think, that right now is very problematic because there are a lot of, I'm just going to say, bad actors out there who are selling research grade peptides and other molecules on the internet outside of the regulatory environment. Everybody knows, I mean, they put research grade on there. Everybody knows people are going to put these things in their bodies. And we don't have any insight into product quality.

• 19:07Dr. Darshan Shah?

  Right.

• 19:07Speaker 01

  So now, now what you see now are these secondary markets pop up where people can get their peptide they bought off the internet, tested by somebody else to tell them if it's really what they want it to be.

• 19:18Dr. Darshan Shah?

  Crazy right now. It's such a topsy turvy world. I think in July, you know, when some of these peptides go back on the FDA regulatory list, my hope is that a lot of these research grade things have to go away.

• 19:30Speaker 01

  It'll be interesting to see. So I don't think they'll go away unless there's enforcement because it'll still be cheaper. So, so and, and, and, you know, just for people who may not know exactly what you're referring to, I think it was, I don't know how many years ago it was. It wasn't that long ago. Several of these, these peptides were put onto a, a list and were no longer allowed to be compounded by compounding pharmacies. That I think is going to change. I don't think it has changed yet, but every, every indication is that that will change back to where compounding pharmacies can now compound these peptides when a doctor prescribes them. So that gives, that gives more quality control around the composition of the final product because these compounding pharmacies are required to manufacture and compound at a certain level of, of quality.

• 20:14Speaker 01

  Having said that, I think the research grade market will still be less expensive than the compounded versions and a lot of people will just go to grab, you know, they'll just go to the lowest cost product that's out there, maybe not realizing there is this difference in terms of potential quality of, of the product. So I think that really the only way that's going to go, go away is if there's some sort of enforcement that cracks down on the people who are selling these things on the internet.

• 20:40Dr. Darshan Shah?

  It seems like there's signals that there will be enforcement because, you know, peptide scientists, which is one of the largest of these research grade peptides, closed their doors and they, they just stopped operating because my hypothesis there from people I talked to is because of the signals in the market that things are going towards these becoming more regulated. So my hope is that does happen because, you know, to your point, like some of these research grade peptides that get tested, a lot of them, the testing not only shows that they do not have any of the peptide in there, sometimes it's, it's, because I know some of these people that own these labs and they tell me like sometimes it's a completely different peptide or sometimes it's another compound, like even MDMA in there.

• 21:19Speaker 01

  Wow.

• 21:20Dr. Darshan Shah?

  Yeah. And so people are injecting themselves with compounds that they have no idea that could have severe side effects, right? And so this is where the research grade ones are potentially, or likely, you know, they're just very dangerous, right? And so at least the compounding pharmacy, to your point, not only they're manufacturing guards, like to make sure there's not like infection. Just organisms in there, but there's also quality and also certificate of analysis requirements.

• 21:46Speaker 01

  Right, that's right.

• 21:46Dr. Darshan Shah?

  So, yeah.

• 21:47Speaker 01

  Yeah, yeah. I mean, again, you know, and I want to suggest that everybody who's selling peptides on the internet is a bad actor. I mean, there are people who are trying to do it well. I still think personally, I would not go into that line of business. But, you know, we'll leave that on the table. But the problem is there's so many actors out there. There's just no way for the average consumer to know, like who's really trying hard to manufacture this properly, who's, you know, cutting and who's putting other stuff in there. That's not even the right active ingredient. The other piece, though, that I think, you know, unfortunately, because of sort of the influencer craze around peptides, that a lot of people have been misled into believing that these are going to be life-changing therapies, right?

• 22:28Speaker 01

  So, look, the common peptides, again, the eight or 10 that we're talking about, they're biologically active. They do have biological activity. For some people, they can have beneficial effects. Again, that's a generalization. We could talk about the specific peptides. But none of them are game changers like the GLPs are, right? And I think it's just important for people to appreciate that. None of them are going to move the needle as much as the GLPs. The GLPs are great drugs. They've got some issues, if not used properly with the proper education around lifestyle, but they work. I'm not aware of any of the other peptides that people are excited about where there's any evidence they're anywhere near as effective as the GLPs at what they're supposed to do. So I think it's just important for people to realize when you do this risk reward analysis,

• 23:12Speaker 01

  on the reward side, you know, the reward is lower, I would say, than it's going to be for a GLP. And the risk is way higher when we add on the lack of human safety data, the questions around manufacturing and sourcing. So you really have to consider, you know, what analysis leads you to believe that this is the right thing to do. And it may be, like, again, I'm not going to suggest that if you've done a careful risk reward analysis and you think that this is the right path for you, that you shouldn't do it. But I do think it's, at least for me, it's hard to justify that particular path, especially when we've got other tools like the GLPs or lifestyle. Modifications that can achieve the same goals or hormone therapy, right?

• 23:55Speaker 01

  I think that can be done much more safely than, you know, some of these peptides that are at least in principle are supposed to increase growth hormone or reduce visceral adipose, right?

• 24:05Dr. Darshan Shah?

  Right, right.

• 24:06Speaker 01

  We have, we have better, more tested and more effective strategies to do that.

• 24:11Dr. Darshan Shah?

  And because they are made in pharma, the GLPs, I mean, you, when you get it, it is what it says in the bottle.

• 24:17Speaker 01

  Assuming you don't buy research-grade trisepotide, yeah.

• 24:19Dr. Darshan Shah?

  Exactly, right. Can you break down for us, just to kind of complete this conversation, because it's such a great conversation that we just happened into, and then I'll take us back to the conversation we were gonna have.

• 24:29Speaker 01

  Okay, great.

• 24:29Dr. Darshan Shah?

  But I just want you to break down for the audience here, why, you know, GLP-1s are peptides, they were also used by functional medicine way before the pharma industry were able to patent and sell them.

• 24:40Speaker 01

  Right.

• 24:41Dr. Darshan Shah?

  Why are these patentable versus other peptides?

• 24:44Speaker 01

  So it, it really depends on the peptide. So in order for pharma to be able to get the IP around a peptide that they're gonna want to move it through the FDA clinical trial pipeline, it's gonna have to be a new molecule, right? That, that they have developed or that they buy from someone else that wasn't patented, you know, more than 20 years ago, because there's a certain patent life on a, on a new molecule. So a lot of these peptides that we're talking about now, BPC157 and, and others, some of them actually came up through pharma and they were abandoned. So they were abandoned because they didn't have the efficacy signal, right? So, and so far, no other pharma company's gonna pick up something that a different pharma company got through phase twos, didn't see efficacy and abandoned, right?

• 25:27Speaker 01

  And then some of them have just been around for so long that the, there's no new patent life available.

• 25:33Dr. Darshan Shah?

  Got it.

• 25:34Speaker 01

  To make it worth moving it through the FDA process. And again, you know, that's a different conversation, you know, is the FDA process too slow, too expensive, too burdensome? Yeah, I think everybody would say, yeah, it is. What I don't see are a lot of people coming up with solutions to that. And so I think that's a different conversation around how do we change the way that new therapeutics are evaluated.

• 26:00Speaker 01

  Definitely, it can be done more effectively, more efficiently for a lot less money. Again, the incentive structures, though, right now, it's actually pharma kind of likes the system. They complain about it. They kind of like it because they've got a monopoly on it. Huge moat around it, right? Because nobody else can afford to move things through the full FDA approval process in humans. And I'll just throw something out. I haven't really thought this through carefully. So there may be good reasons why, you know, this wouldn't work. But as a template, there is a faster path in companion animals. So a lot of people don't realize this, but there's a Center for Veterinary Medicine that approves drugs for dogs and cats and pets. And they use something called the conditional approval pathway fairly commonly there. If any people are familiar with the company Loyal,

• 26:45Speaker 01

  they're trying to move a drug through this pathway for longevity in dogs, right? Which you could never do in humans for lifespan, for obvious reasons. It takes too long. Right. But this is a pathway where you have to show safety. And if you can show safety and make a case, but it's more of a scientific and bureaucratic case for efficacy than it is doing the pivotal clinical trials, but make a case, there's a pretty good chance this is going to work. And we've already shown it's safe. You can get what's called conditional approval, which allows the company to bring it to market. They've got five years to do the full safe, the full efficacy studies and actually prove efficacy. So this goes a little bit back to what we were talking about before. If we overweight safety in the safety efficacy equation, which I think a lot of people would find reasonable,

• 27:30Speaker 01

  there is a rationale for having a strategy like that in humans, particularly for things that are harder to really show clinical trial signal for. Now, you know, if it's a severe form of cancer and all you have to do is show that people are going to live, you know, a few weeks longer, maybe that's not right for the conditional approval pathway. But if it's an endpoint where, you know, it's going to take a year or two years to actually, in a large population, to see the efficacy signal, maybe there's a reasonable case there for a conditional approval. You show safety, we're confident that it's safe enough. And then you, and then you create some structure where people can have informed consent around this that they know. Okay, it may or may not actually work, but we're pretty confident that it's safe.

• 28:14Speaker 01

  And so it's up to you whether whether you want to try this. Like, I really like that idea.

• 28:18Dr. Darshan Shah?

  That's a great idea.

• 28:19Speaker 01

  And so the question is, how do you actually implement that in humans? But I, again, I think we can look at the companion animals and that could be a template for doing something like this in humans. There is a conditional approval like pathway in humans, but is very rarely used. And I don't really understand the bureaucracy around why it's not more widely used.

• 28:36Dr. Darshan Shah?

  So, I mean, and that's, that's such a great point, by the way, because I thought the conditional approval pathway was something that the FDA could use, but it's only for animals.

• 28:45Speaker 01

  Well, again, there is something like that in humans, but it's very rarely used. And I, I don't know, there's got to be some legislative or bureaucratic reason why it's not more commonly used. I believe, we're going back to peptides, that SS31, the SS31 peptide, the mitochondrial peptide, is alamipretide.

• 29:03Dr. Darshan Shah?

  Yep.

• 29:04Speaker 01

  Got something like a conditional approval for a rare childhood mitochondrial disorder.

• 29:10Dr. Darshan Shah?

  Right, right.

• 29:10Speaker 01

  Where they, they, because they'd done other clinical trials, so they had a pretty good dossier of safety. And they weren't able to show efficacy yet, but FDA gave them this conditional approval. And I don't know, I don't know the, the exact path they took to get there. But again, maybe that can be expanded in some way to make it easier.

• 29:29Dr. Darshan Shah?

  Yeah. I mean, this, this is such a great conversation because in the next five, 10 years, I feel like we're going to figure this all out because the.

• 29:37Speaker 01

  I'm glad you're optimistic.

• 29:39Dr. Darshan Shah?

  There's a massive interest in peptides right now and, and it's almost like this balloon that's about to pop. And so something's gonna have to happen. Either they get completely taken off the market again, or there's going to be some sort of either a conditional approval pathway or some type of ITP-like program or something. And at least the safety data, like, that's such a critical piece of this.

• 29:58Speaker 01

  I, I definitely hope it's, it's the latter and I would love to see both of those things happen. I mean, I think they're both, you know, real steps towards solving problems that, that a lot of people would benefit from. That there's, I don't think there's any good reason to object to doing that. I mean, I suppose you could object to the human ITP program because it costs money. But again, when you look at the benefit that would accrue from spending that money. Compared to other stuff we spend money on like this is a no brainer.

• 30:22Dr. Darshan Shah?

  Right.

• 30:23Speaker 01

  So hopefully that happens. Again, my, my only fear is that if we start to see, you know, a lot of catastrophic negative effects popping up, that there's going to be a, you know, a pushback, pretty severe pushback. Yeah. So hopefully that doesn't happen. And again, I don't really think any of the, the commonly used peptides now are all that dangerous. It's more the manufacturing and impurities piece that I'm concerned about. You're probably familiar with what happened at Rad Fest last year where two women, you know, were getting peptide injections and ended up in the hospital.

• 30:56Dr. Darshan Shah?

  Right.

• 30:57Speaker 01

  And it was in the vendor hall at the conference. Like that kind of behavior, especially when there are outcomes like that, I think puts the entire field at, at risk. I was just at a, my, my first Hollywood longevity party. And, you know, they were giving out intranasal peptides at the party and I'm just like, seriously? Come on, guys. But, you know, the flip side of that is it's probably better than what people were, were snorting in the 1980s in Hollywood. So yeah, it's all relative.

• 31:22Dr. Darshan Shah?

  Oh my gosh. Yeah. This is, it's, you know, when stories like this, it makes it the wild west. It doesn't have to be.

• 31:27Speaker 01

  Yeah.

• 31:27Dr. Darshan Shah?

  Like, you know, the people injecting peptides with no workup or anything in the vendor hall of a conference. Like that did not need to happen.

• 31:34Speaker 01

  Right.

• 31:35Dr. Darshan Shah?

  And it just brought a tremendous spotlight to the potential dangers here, which just sets everything back quite, quite a bit.

• 31:41Speaker 01

  Yep.

• 31:41Dr. Darshan Shah?

  Unfortunately.

• 31:42Speaker 01

  That's why we can't have nice things.

• 31:43Dr. Darshan Shah?

  Yeah.

• 31:46Dr. Darshan Shah?

  Exactly.

• 31:51Dr. Darshan Shah?

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• 32:33Dr. Darshan Shah?

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• 32:55Dr. Darshan Shah?

  You know, going back to this ITP program, which is just so interesting to me. You're in the steering committee and it kind of really addresses this gray gray area of molecules. I think really well, at least as a first step, right?

• 33:10Speaker 01

  Yeah.

• 33:10Dr. Darshan Shah?

  And so I'd love for you just to tell the audience, what is this program? And kind of the structure around it.

• 33:15Speaker 01

  Sure. Yeah. So the ITP or interventions testing program was started, I think, back in like 2005 with the idea that the field needed some way to rigorously test small molecules primarily, but but interventions in general in mice for effects on lifespan. And it was a it was a explicit decision at the time to to really only focus on lifespan. And and the rationale behind that is that, you know, you can improve health in one domain or a couple of domains during aging. But if you're really slowing biological aging, you should be able to increase the population lifespan by some significant amount. So so that's what's measured. And so the idea was, you know, we would nominate or we would allow the community

• 34:00Speaker 01

  to nominate small molecules to be tested. Anybody in the scientific medical community, in fact, anybody in the general public can submit a nomination. This happens every year. And depending on how much funding is available, somewhere between five and seven interventions will be selected. So there are two committees that select these interventions. An access committee, which is a larger committee, more like a traditional NIH review, three reviewers, each give it a score. And then there's the steering committee, which is what I've been on now for for about 15 years. That makes the final decision on which molecules get selected. And so a lot of really interesting stuff has come out of this program over the years. A couple of other things that might just be worth mentioning for people who really want want to understand a little bit more. More is another explicit decision that was made early on was to use what's called a four-way cross.

• 34:45Speaker 01

  It's called UMHET3 as the strain designation. And the reason for this is.

• 34:50Dr. Darshan Shah?

  These are the mice.

• 34:50Speaker 01

  Yeah, these are the mice, the genetic background of the mice. Most mice in laboratory studies are inbred mice. So C57 black sex is the most common strain. And so they, they don't have much genetic diversity. But of course, people and animals in the real world are genetically diverse. So this mouse strain, UMHET3, is designed to have a lot more genetic diversity than the typical mouse strains. I don't know how important that is. It's, it's a reasonable thing to do. I don't know how much it matters, but that's the way all of the studies have been done in this UMHET3 background. So probably the most famous result to come out of the ITP was, was very early on. So in the first set of six or seven drugs that they tested was.

• 35:28Dr. Darshan Shah?

  Matt, I'm so sorry, I'm going to interrupt you one more, one more second. And just so people really understand this ITP process is that there's also two laboratories doing, three laboratories.

• 35:37Speaker 01

  I should have said that, right? So that's another structural feature that's really unique and I think important here. So from the very beginning, there have been three sites where every intervention is tested in replicate. One is at the University of Michigan. Rich Miller has been the director of that site for the entire time of the intervention testing program. Another is at University of Texas Health Science Center, San Antonio. Randy Strong is the director of that site. And then the third is at Jackson Labs in Bar Harbor, Maine. David Harrison was the first director of that site. And so, yeah, so that triplicate replication is important because when they get the data back, they do analyses at each individual site and then also pool all of the data.

• 36:20Speaker 01

  And obviously you feel a lot more confident about a result when it works at each individual site.

• 36:25Dr. Darshan Shah?

  Yeah.

• 36:25Speaker 01

  As opposed to if, if you only see a significant effect when you pool the data.

• 36:29Dr. Darshan Shah?

  Does that answer the question of like, is this study able to be replicated? Well, yes, now you've replicated the same study in three different locations.

• 36:36Speaker 01

  I, I believe it's about as good as you could do in a program like this.

• 36:40Dr. Darshan Shah?

  Yeah, I agree. I, I thought that was important to mention just because the data coming out of the ITP is some of the best signals you can get around this particular type of data.

• 36:49Speaker 01

  It's definitely the gold. Standard for longevity data and by longevity, I mean lifespan data in mice. And it's important to say, you know, the field has been led astray multiple times by one-off studies where somebody reported, you know, that a drug increased lifespan in mice. And then when people tried to replicate it, it didn't work. In fact, the ITP has failed to replicate, you know, a few of the more popular drugs that are out there. And just to name names. Let's name some. Resveratrol, nicotinamide riboside are two of the big ones. NR, of course, is an NAD booster that lots of people are still really excited about. Sorry, didn't replicate even in mice.

• 37:29Speaker 01

  And if you look at those studies, the NR study is sort of, I think, illustrative of what can often go wrong. So in these one-off studies where somebody reports a lifespan extension, you will often, if you look at the actual data, you will see that the control animals in that study were short-lived. And what the, what the intervention did was it just brought them back towards more where their lifespan should have been. That's a classic sign of a poorly conducted mouse lifespan study. I am very skeptical of any one-off study that has short control lifespans and somebody claims a lifespan extension because they almost never reproduce. So I know we're getting in the weeds a little bit, but, but this is, I mean, this, it's important to understand that one paper is not something that you want to hang your

• 38:12Speaker 01

  hat on, especially when we're talking about something in the longevity space. That's why replication is so important. So yeah, that, that triplicate, built-in triplicate replication, well, not perfect. Again, if, if you see a signal at all three sites, that gives you a high degree of confidence. This is, this is a real signal. And I will say, it's been frustrating at times for, I know, for the ITP investigators and for those of us who, you know, who have a vested interest in the ITP, sometimes it doesn't work at all three sites. And so then you're kind of left with, hmm, what does that mean? And so it is, it is a bit challenging, but that's the nature of science. That's why we repeat experiments. So anyways, I think the, you know, the ITP showed its value very early on because in that first set of, of drugs, there were, there were five or six.

• 38:56Speaker 01

  They were started in either 2004 or 2005 was rapamycin. Yep. And there's an interesting story here about how sometimes, you know, you can have really, really happy accidents in science. So because of the way the ITP works, they got to have a really large group of mice. I mean, we're talking, you know, a hundred, 100 mice in each group at each site times five to seven drugs. So it's a large cohort of animals you've got to breed up, right? They don't just magically appear. So when they were starting this first set of drugs, they realized that the rapamycin wasn't bioavailable in the formulation that they had. And this is well known in human medicine. Rapamycin is unstable at gastric pH, so you have to do something to it. You have to put a coating on it to get it to the small intestine where it's absorbed.

• 39:40Speaker 01

  So, but they had to start the experiment because they had thousands of mice ready to go. So they were like, well, crap.

• 39:48Speaker 01

  We'll just work on an enteric coating and we'll start the mice on the rapamycin when we get it done. It probably only take a couple of months. So they started all the mice on the other drugs at either six or nine months of age, which is, you know, maybe 30 years old for a human, maybe, maybe less. And it ended up taking them, I don't know, 12 months to figure out the enteric coating. So the, the rapamycin mice didn't actually start getting the drug until they were 20 months old. But it was an accident. That wasn't designed. And nobody thought it was going to work. Like, like at that time, the field believed you could only get big effects on lifespan if you started the treatment at young age because nobody had found anything that, that, that broke that pattern. And, you know, fortunately, what they found was that rapamycin gave a pretty large effect.

• 40:29Speaker 01

  I mean, again, in mice, a 15% increase in lifespan, that's, there aren't that many things that reproducibly have that magnitude of effect on lifespan. So rapamycin had a 15% increase in lifespan in females, a 9% increase in males, starting at 20 months of age. And that really, I think, was a paradigm shift that got people, and that, and again, that's important because if you're thinking that we might want to try Rapamycin or whatever drug comes out of ITP in people. You don't want something you got to start giving to teenagers.

• 40:56Dr. Darshan Shah?

  Yeah.

• 40:56Speaker 01

  You want something you can start giving to people in their 50s, 60s, 70s, 80s, right?

• 41:00Dr. Darshan Shah?

  Right.

• 41:01Speaker 01

  So it was a paradigm shift in the way the field thought about longevity therapeutics. That it was actually possible to have meaningful effects on aging trajectories, starting an intervention in middle age. And now people have gone back, rapamycin now is the most robust and reproducible intervention in mice for longevity and health span. Dozens of labs have shown the same thing. The interventions testing program has shown at higher doses, you get bigger effects. So.

• 41:30Dr. Darshan Shah?

  And what about a young, has anyone tested at a younger age as well?

• 41:33Speaker 01

  It doesn't seem to really make much difference. So this is another thing that's been surprising. Dose has a bigger effect on magnitude of lifespan extension than when you start, it seems. Now, again, I have to be a little careful and say, nobody has done all the different possible, you know, combinations, right? And you have to appreciate, we're always going to be working with insufficient data when it comes to lifespan experiments. Cause they're so long, so expensive. But with what we've got, I think we can say with some degree of confidence that you get a much, much bigger range of lifespan extension by changing the dose than changing whether you start at six months or nine months. The thing that's interesting about rapamycin is people have even gone back now and done even short intermittent treatments early in life.

• 42:14Speaker 01

  And you still get a lifespan benefit. So we don't really understand all of the, all of the, the, the, the things that go into the biology of aging. That's another, I mean, this, we could spend a whole episode on this, but that's a whole nother myth. This idea that we're close to solving aging. Like, I'm sorry, guys, we are not close to solving aging. But we don't really understand what the optimal regimen for rapamycin is, just that it always seems to work.

• 42:36Dr. Darshan Shah?

  Yeah.

• 42:36Speaker 01

  And, and you can get up to about a 30% increase in lifespan and you can slow functional declines and diseases of aging across most, if not all, organs and tissues in the body. So it really seems to be slowing biological aging at some root level as opposed to just impacting cancer or just impacting heart function. The other thing that's I find most compelling is with rapamycin in particular, there are now multiple examples. Where you can look at functional declines that have already happened in the heart or the ovaries or the immune system or the oral cavity. And in just eight, six to, six to 10 weeks with rapamycin, you can actually reverse those functional declines. And you can partially reverse molecular features of aging. So again, I don't like the, the phrase reversing aging

• 43:20Speaker 01

  because nobody's, nobody's reversed all aspects of biological aging. That's another lie that people tell. Nobody has reversed aging, but we can reverse features of aging. We can reverse some functional declines associated with aging. And rapamycin seems to be able to do that in mice. And there's interesting evidence in people directionally for some of these things as well. So rapamycin was really the first hit to come out of the ITP. It's been going every year, you know, like I said, since, since 2005. I think 2009 was the first paper published because it takes a while. And other interesting things have come out. So some of the things that, that, that I find most intriguing, acarbose was the next big hit from the ITP. That's an anti diabetic drug. So that kind of makes sense. We know metabolic health is really important,

• 44:05Speaker 01

  but it's probably doing stuff other than just metabolic health to have a big impact on, on lifespan in mice. Most mice will certainly die with cancer. And I think most people are comfortable saying mice in the lab typically die from cancer. So it's got to be impacting cancer. Estrogens have come out multiple times. So 17 alpha estradiol was the first. And then there's another estriol that also has been shown to increase lifespan in mice.

• 44:30Dr. Darshan Shah?

  Men and male and female mice.

• 44:31Speaker 01

  It's larger in males than in females, which is, which is interesting. One of the reasons why I find, and then the other one that I find really compelling are the SGLT2 inhibitors. That's probably my, if somebody is like, what's your favorite drug to do? That's probably the one I would pick. Most people would be like, not rapamycin. But no, the SGLT2 inhibitors and the, the, the estrogens are particularly interesting to me because there was a study from UK Biobank in people that looked at all prescription medications that had, they had to have more than a thousand prescriptions or something like that, but all widely prescribed prescription medications. And they asked, you know, if we, if we do our best to match the health status for the people getting this particular drug, which ones affect mortality? Interesting things didn't affect mortality.

• 45:13Speaker 01

  More Metformin did not reduce mortality in that in that study. Metformin is a great diabetes drug, but it I don't think it does anything to aging biology. Or I shouldn't say that it's not effective at really modulating aging biology in a way that leads to big effects on lifespan and health spend. But what did come out were multiple types of estrogens, primarily in women, which, you know, that's where that's where it's going to be prescribed. So that's where the male female thing in the mice isn't completely clear. And SGLT2 inhibitors as a class. So that doesn't prove these things are slowing aging in people, but it's certainly intriguing and directionally correct. So I think there's a lot of a lot of rationale now for really trying to dive into the molecular mechanisms in mice. So we can start to tease out, how is this working?

• 45:58Speaker 01

  And then see if the same thing is true in people.

• 46:00Dr. Darshan Shah?

  Yeah. So what you're talking about there is we're finding the signals in mice around these four particular compounds that you had mentioned.

• 46:06Speaker 01

  And there are a few others. So there's probably 10. There's 10 or 12 that reach statistical significance, but a lot of them are on the lower side, like very small percentage effects. And a couple of them haven't replicated in subsequent studies by the ITP.

• 46:19Dr. Darshan Shah?

  Right, right.

• 46:20Speaker 01

  So I kind of, I mean, my philosophy throughout my entire scientific career is focus on the things that have big effect sizes. And so that's, those are the, those are the ones that I'm most intrigued by because they seem like they're, they're almost certainly a real effect and they're pretty reasonably sized effects.

• 46:35Dr. Darshan Shah?

  Absolutely. And those four too are the ones that, you know, all the longevity enthusiasts, if you look search Reddit, those are the four things that people are mostly talking about. Right? Those, and I would say hormone replacement therapy is a favorite of the longevity world, but that already has a long history.

• 46:49Speaker 01

  Right.

• 46:50Dr. Darshan Shah?

  As far as what's coming up, those are the four I see a lot of. And what's really interesting is some of the ones you mentioned that did not have an effect are also not proving out in human studies like Metformin, Resveratrol.

• 47:02Speaker 01

  Right.

• 47:03Dr. Darshan Shah?

  What was the third one you mentioned? Metformin, Resveratrol?

• 47:05Speaker 01

  Oh, Nicotinamide riboside.

• 47:06Dr. Darshan Shah?

  NR, right? And so now we have this, we have a signal that is more than just noise. It's actually a signal that we can apply to humans when we're looking at drugs for extending human lifespan.

• 47:20Speaker 01

  Yeah.

• 47:21Dr. Darshan Shah?

  And so. Like, I want to make a big distinction between lifespan and health span on these as well. What you're also saying is there's health span effects to rapamycin in the mice.

• 47:30Speaker 01

  Right.

• 47:30Dr. Darshan Shah?

  Is that correct?

• 47:31Speaker 01

  That's right.

• 47:31Dr. Darshan Shah?

  Is that also true for SGLT2 inhibitors?

• 47:33Speaker 01

  Yes.

• 47:33Dr. Darshan Shah?

  The estrogen metabolites?

• 47:35Speaker 01

  Yeah, all of these, I mean, again, none of the others have been studied as extensively as rapamycin for broad health span effects. All of them have shown, when people have looked, benefits in different health span metrics and also molecular signatures consistent with partial reversion back to a more youthful state. So I think with all of them, there's reason to believe that they're not only going to be lifespan modifiers. And actually, let me add to that because I think there is, it's an important distinction, right? Health span versus lifespan. But I think there's a misperception around the idea that that we have been able to dramatically increase lifespan without improving health span.

• 48:14Dr. Darshan Shah?

  Yeah.

• 48:15Speaker 01

  There are a couple of papers in C. elegans that honestly, I don't think they're very good papers. I don't think we can really measure health span in C. elegans. I worked on C. elegans for many years, so I know what I'm talking about here. I would not draw any conclusions from those papers. Outside of those, I'm not aware of any evidence that we can robustly increase lifespan without also increasing health span. So I think it's a non-issue. We don't want to do that. We all agree to that. I think it's a non-issue. I do think there are interventions that can improve health span metrics without increasing lifespan. I don't know of any that improve health span across the entire system without also increasing lifespan. But certainly, there are ways to improve health without increasing lifespan.

• 48:52Dr. Darshan Shah?

  Yeah, for sure.

• 48:53Speaker 01

  And that may be where some of these other drugs, metformin in certain populations, nicotinamide riboside in certain populations, can improve health span metrics in a subset of people without necessarily significantly increasing population lifespan.

• 49:06Dr. Darshan Shah?

  And that was my point. Like, we don't know if NR is great for health span and not lifespan. It could be, we just don't know.

• 49:12Speaker 01

  It could be. Again, I'm, it is possible that we will find drugs that at the population level will generally improve health span without increasing lifespan. I don't know of anything yet. There are a couple, what I, I guess, maybe the way I would think about this, or the way I think about it is some of these drugs that have had sort of modest effects on lifespan. Maybe haven't been reproducible. Maybe they are able to improve health span with a larger effect size than they are lifespan. I would put alpha-ketoglutarate in that bucket. So AKG is an interesting drug. It's sort of on my, you know, intermediate between tier one and tier two. If I was gonna, if I was gonna, you know, rank supplements. Pretty consistently gives health span benefits in mice. The lifespan effect is small in one study, not there in the next study.

• 49:56Speaker 01

  So, you know, I don't, I don't know what that means. NR maybe in that category as well. The issue with all of the NAD precursors is that the studies that have shown effects on lifespan are just really bad studies. They're just not, not quality lifespan experiments. And they haven't been reproducible. And that seems to be a feature of the NAD biology literature. For whatever reason, just a lot of irreproducible science. And so when I see that in a subfield, it just makes it really hard for me to evaluate. You know, there's a lot of smoke. I just don't know what's fire. And I would say the same thing's true. Although there's a lot less data in the human literature on the NAD precursors. The clinical trials that have been done are mixed. Sometimes there's a efficacy signal, sometimes there's not.

• 50:40Speaker 01

  It depends on what you're actually claiming you're, you're measuring. But none of them are really high-quality clinical trials. And so you just have to kind of be like, maybe. And the idea that NAD generally declines in people is sort of a myth. Maybe it's not a myth, but it's not demonstrated. Like it is, people speak with a lot more certainty about that than the data actually justify. I actually don't think it's true. NAD declines in some people.

• 51:02Dr. Darshan Shah?

  There's a big paper that just came out, um, just recently about a big study on the total organism NAD levels. Actually, for humans, what they found did not decline as we age.

• 51:12Speaker 01

  Yeah. No, I mean, that's what I think the answer is. But all of this, you know, you have to recognize one study never tells the whole story. There are technical challenges around measuring NAD. So, so I'm not, I'm not saying NAD boosters don't have any value. But I certainly don't, don't feel confident in saying that they do or in really being able to predict who's going to benefit and who's not.

• 51:33Dr. Darshan Shah?

  Yeah.

• 51:37Dr. Darshan Shah?

  Hi, Dr. Shaw here. I want to take a minute to talk to you about cellular health. So in my clinics, I've actually seen 30-year-old people with cells that look like they're pushing retirement. And I've also seen 60-year-olds with cells that look like they're 40 years old. So what's the difference? It's really about how fast their telomeres are breaking down. Your cells, you see, are like phones, and they have limited cellphone battery. Poor sleep, stress, processed foods, all of these things can drain that battery way faster than it should. So this is the reason why I partnered with IM-8. IM-8 powers that cellular battery. It's not just another multivitamin. It's a comprehensive 92-ingredient formula designed specifically for cellular health and longevity.

• 52:22Dr. Darshan Shah?

  I'm talking 900mg of vitamin C. That's like 20 oranges worth of DNA protection. The clinical dose of CoQ10 that you need to power your cellular engine. You also get zinc, selenium, vitamin E, alpha lipoic acid. All of these work synergistically for cellular repair and protecting your telomeres. So instead of taking a handful of pills every day and all these supplements, IM-8 actually gives you everything that you need in one scientifically formulated system. And this isn't just a theory anymore. IM-8 had partnered with Oxford University, the International Space Station, San Francisco Research Institute, and they've done studies, and they've gotten this NSF certified to truly power your health.

• 53:05Dr. Darshan Shah?

  Most people are aging twice as fast as they should, unfortunately. You don't have to be one of them. Try IM-8. I actually have a discount secured for you if you go to drshah.com/ima or go to im8health.com/discount/drsah and you can get 20% off with my discount code, DrShah. You can also find the link below.

• 53:30Dr. Darshan Shah?

  Can I ask you an important question about the lifespan extension definition? When you're measuring lifespan extension in these mice, are you saying the average ages which these mice die is at the older end of their lifespan than mice usually die? Or are we pushing mice past their theoretical maximum age?

• 53:47Speaker 01

  Yeah, good question. So it can be either. It would have to be a large effect. So we're talking like 30% and up to really move the entire survival curve past the maximum of the of the control animals. There are two interventions. I would put rapamycin in the maybe it does that bucket. Maybe on the best of days. The only other intervention that clearly moves you, the animals outside of the normal lifespan range, I would say, is caloric restriction. And so there was a study done, it was published in the early 90s now, where they got a 60% increase in lifespan. But these were in mice that were, the controls were long-lived. And this is why I think that percent increase can be really misleading. Because you'll read garbage papers where the mice lived, you know, half as long as

• 54:31Speaker 01

  they were supposed to, and then the intervention brought them to their, where their lifespan should have been. That's 100% increase in lifespan. It just means nothing, right? So this was a 60% increase over a long-lived control. And in that case, you know, pretty much all of the animals in the caloric restriction group died after all of the animals in the control group. Or sorry, yeah, they started dying when all of the animals in the control group had already died. I think the way, the way though, that this is done in practice is when we say an increase in lifespan, what we're usually talking about is median lifespan. So the where, what, at what day or month or week, depending on the unit you want to use, are 50% of the animals dead?

• 55:09Dr. Darshan Shah?

  Yeah.

• 55:10Speaker 01

  And then is that statistically different between the two groups? There are tools you can use to also look at maximum lifespan. And so often what you'll see reported is the statistical outcome for median and maximum lifespan across the cohort.

• 55:23Dr. Darshan Shah?

  Makes sense.

• 55:24Speaker 01

  One important thing to appreciate, if this is going to translate to people, which again, we don't know for sure yet, there is going to be an individual component to this. And, and that's, that, that is why I think paired with, you know, doing the studies to understand, does rapamycin or acarbose or SGLT2 inhibitors slow aging in people? Also, understanding which biomarkers can we use to predict which individuals are going to benefit?

• 55:46Dr. Darshan Shah?

  That would be.

• 55:47Speaker 01

  And by how much?

• 55:47Dr. Darshan Shah?

  Right. Is there a biomarker signal that you're aware of right now?

• 55:51Speaker 01

  I mean, the one most people would point to are the epigenetic clocks.

• 55:54Dr. Darshan Shah?

  Yes.

• 55:54Speaker 01

  That's very, again, those are useful research tools. They're useful at the population level right now in research. They're not useful clinically, in my opinion, both because none have been validated for clinical use. And most of the tests that people are using in the clinics are provided by these direct to consumer companies where we have no information about error rates. So I just think it's important for people who use the epigenetic tests right now to recognize there is no difference that's big enough between two measurements that you can statistically be confident it's a real difference.

• 56:24Dr. Darshan Shah?

  Yeah, and I know you did an interesting experiment with.

• 56:27Speaker 01

  I did, yeah.

• 56:28Dr. Darshan Shah?

  Epigenetic clocks.

• 56:29Speaker 01

  Well, and all that experiment showed was there's a lot of noise, right? But understanding that there's a lot of noise is only useful if you can then put error bounds on that noise. And what I'm saying is, we have no error bounds right now. So that's, to me, the biggest deficit in the companies that are marketing the test. I do think they could one day be useful clinically. The other limitation to the epigenetic test right now is we don't have a mechanistic connection to why they're correlating with mortality or with disease risk. In other words, we know what we're measuring are methylation marks at specific places in the genome, which are going to influence gene expression at those locations. What we don't have is a connection between the specific gene that this epigenetic mark is regulating and longevity or mortality or disease risk.

• 57:14Speaker 01

  So we don't have that mechanistic connection.

• 57:15Dr. Darshan Shah?

  Right.

• 57:16Speaker 01

  So it's just a, it's a pattern. We don't really know what it means. We don't know which populations or individuals it's going to work for. I still like traditional blood-based biomarkers and functional measures as the go-to when you're thinking about biomarkers that we can be pretty confident are telling us something about health.

• 57:34Dr. Darshan Shah?

  Yeah.

• 57:35Speaker 01

  I would love to have a really gold standard, you know, biology of aging biomarker. We just don't have it.

• 57:40Dr. Darshan Shah?

  We just don't have it right now. So that brings me to your canine experiment that we're doing. And if you can talk a little bit about that and the.

• 57:49Speaker 01

  Sure.

• 57:49Dr. Darshan Shah?

  You're testing rapamycin on dogs, right? And I'd love to know what you're measuring, kind of how you set this experiment up and tell us all about it.

• 57:56Speaker 01

  Sure.

• 57:56Dr. Darshan Shah?

  Dog aging project.

• 57:57Speaker 01

  Yeah, so we have a clinical trial of rapamycin in. Companion dogs. So first thing to say, these are all companion dogs living with their owners. We don't do anything in dogs in the laboratory. The Rappamycin clinical trial is really only a small part, at least in terms of number of dogs, of the overall dog aging project. So the dog aging project was really started with two goals. One is to understand aging biology in dogs. And what I mean by that is what are the most important genetic and environmental factors that influence health and longevity in companion dogs living with their owners? The second goal was to do something about it, and that's where the clinical trial comes in. So there are 50, probably almost 55,000 dogs and owners now all around the US participating in the dog aging project.

• 58:40Speaker 01

  The vast majority of those dogs are observational. So we're collecting data from the owners. From a subset of dogs, we get whole genome sequencing, metabolism, microbiome, epigenome, veterinary records, things like that. That's all with the goal of correlating health outcomes to factors that might influence health. So genetic factors, diet, exercise, other animals being around.

• 59:04Dr. Darshan Shah?

  So you're kind of running this like the UK BioBank for dogs?

• 59:07Speaker 01

  Yep, exactly. Yeah, and one of the reasons why I think this makes so much sense, aside from the fact that many people consider their dogs to be part of their family, right? So if we're successful at improving health and longevity of people's dogs, there's intrinsic value to that. Dogs also age very much like people do from a biological perspective, but they do it seven to 10 times faster. Meaning that what would take 30 years from a human observational study, we can do in three or four years in dogs. And so the rate at which you can accumulate data and generate hypotheses from the sort of an observational study is much more rapid.

• 59:40Dr. Darshan Shah?

  Right.

• 59:40Speaker 01

  So that's most of the dog aging project. Having said that, what really got me excited and led me to really push to create the dog aging project? I should say, Dog Aging Project is a joint project that three of us, myself, Daniel Promislo, who's now at Tufts, and Kate Creavy, who's at Texas A&M, started 2014 or so. Daniel and Katie had been thinking about observational studies of aging in dogs well before this. What really motivated me to push it forward and create the Dog Aging Project? Was the idea of frankly, making my dog live longer.

• 1:00:15Speaker 01

  What kind of dog do you have? I had a German shepherd. His name was Dobby. I lost him. It's been a year and a half now. Yeah, thank you. It was brutally difficult. But he was the inspiration for the dog aging project. And you know, it was through a series of conversations with Daniel that, you know, I had this light bulb moment where I was like, you know, in my lab, we were studying rapamycin, we were studying caloric restriction. It was like, you know, we're studying these things in mice. The field, we have probably eight or nine or 10. Some of them are going to work in dogs. And then I was like, oh my God, we could slow aging in dogs. And so from that moment, I felt like I had to really do this. And so first question was, what do we test? Right? And for all the reasons we've sort of already talked about, it was either rapamycin or caloric restriction.

• 1:00:59Speaker 01

  Those were the two that had the best data. Getting owners to calorically restrict their dogs would be a real heavy lift. So rapamycin was sort of the obvious choice. So then the question was, you know, could I get money to do it? And could we do it safely? Again, people consider their dogs to be like their children. So I approached this very much like a pediatric clinical trial. You want to absolutely make sure you're not going to hurt anybody's dog. So we were fortunate that at the time, there were some studies of hemangiobarcoma and osteosarcoma in dogs going on with rapamycin. So we were able to talk to those investigators, get some dosing information, understand, you know, where we could be confident there wouldn't be side effects. And then, you know, with a lot of sweat equity, I scraped together enough money to do a short 10 week clinical trial.

• 1:01:42Speaker 01

  And so that was our first foray. It was my first foray into doing clinical trials at all. And oh my God, I have learned so much over the last, you know, 10 years now, about all the, all the things that make clinical trials difficult. But you know, it was, it was, it's been a great experience. So in that first clinical trial, we designed it as a 10 week study. Again, safety was the primary thing we were interested in, right? But we thought, because people in mice at that time had shown that by echocardiogram, which is ultrasound for the heart, you could see improvements in age-related changes in heart function. So we thought, we're going to do this trial. Let's go ahead and give the dogs echocardiograms before and after. So we did the study. Relatively small. I think we had 24 dogs. All of our studies are randomized placebo-controlled,

• 1:02:26Speaker 01

  double-blind or triple-blind, if you want to include the dogs. Clinical trials. So the vets don't know, the owners don't know, dogs presumably don't know if they're getting rapamycin or the placebo. So a couple of things came out of that study. One was no safety signals, which was great. Owner reported, so every week the owners got surveys. They didn't know if their dog was getting rapamycin or placebo. So owner reported improvements in activity and quality of life. And then by echocardiogram, two of the three endpoints, which were all left ventricular function endpoints. So how well is that left ventricle contracting? That goes down with age. We saw statistically significant improvements. And the third, it was directionally going towards improvement as well from rapamycin.

• 1:03:04Dr. Darshan Shah?

  In just 10 weeks.

• 1:03:04Speaker 01

  In just 10 weeks. But that fits really well with the mouse study. And again, in mice, six to 10 weeks is enough to reverse functional changes in the heart, the immune system, the ovary, and the oral cavity. So the interesting thing is there's a hint in people. So there have been studies with a derivative of rapamycin called everolimus that six weeks of treatment with everolimus is enough to boost immune function as measured by a vaccine response in healthy older people. That fits pretty well. I mean, this would be a deep dive into mTOR biology, but that fits pretty well with the idea that one of the things that mTOR does, when you turn it down, which is what rapamycin does, is it blunts chronic sterile inflammation. Pretty rapidly. And I think when you do that, then you see these functional improvements show up.

• 1:03:48Dr. Darshan Shah?

  So interesting.

• 1:03:49Speaker 01

  So anyways, that was the first study. Then we started again, went back to raising money, got a fortunate to get a philanthropic grant from a foundation called the Donner Foundation that funded the second clinical trial, which was a six-month clinical trial. That was done at Texas A&M University. That trial also showed owner-reported improvements in quality of life and activity. And again, no safety signal. One dog got high triglycerides, which is a known side effect of rapamycin in organ transplant patients. There's probably a genetic component, but the nice thing is all of these, all of the side effects in the organ transplant patients and in this dog that got high triglycerides went away as soon as the dog came off rapamycin. So as long as you monitor, not a big deal. Dogs don't get vascular disease, really. So it's not a huge issue there either. That's the only dog we've ever seen that in.

• 1:04:33Speaker 01

  And then we finally, after six years, got the first NIH grant to fund the project. And that allowed us to start on what is the ongoing clinical trial now. So we have a clinical trial called TRIAD, test of rapamycin in aging dogs, 580 dogs. It's about half enrolled with lifespan as the primary endpoint. So that 580, we believe, gives us the statistical power to detect a 9% change in lifespan. And so I mentioned early on, the very first study with rapamycin in mice, 9% in males. So that's the lowest I'm aware of that's ever been reported. And so that's what we powered our clinical trial to hopefully be able to detect. So lifespan is the primary endpoint, but we're looking, of course, at a variety of health span metrics as well. So half the dogs get echocardiograms at every visit.

• 1:05:18Speaker 01

  Half the dogs get neurological exams at every visit. All of the dogs get get full veterinary exams, genomes, sequenced metabolome, microbiome, epigenome, and clinical chemistry.

• 1:05:32Dr. Darshan Shah?

  580 dogs?

• 1:05:33Speaker 01

  Yep.

• 1:05:33Dr. Darshan Shah?

  That's fantastic data.

• 1:05:34Speaker 01

  And it's a three-year, three-year study period. So every dog gets treated for one year. Again, half placebo, half rapamycin, one-year treatment, two-year follow-up. We've got about 20 clinical sites, so it's block randomized at every site. I mean, we really tried to do this to the very highest standards. We're not going for FDA approval or FDA label expansion, but we really tried to build the clinical trial to the very highest standards so that we can have confidence in whatever we see. So, you know, I wish I could tell you that, that, you know, we're going to know the answer next year, but given the way that the trial, you know, is going, it's probably a year from full enrollment. And then the dogs have to treat the, have to finish the, the study period.

• 1:06:12Dr. Darshan Shah?

  Yeah.

• 1:06:12Speaker 01

  Once all of the dogs have completed the one-year treatment, we will do an interim analysis. We may be able to say something about some of the endpoints, but I don't think we're going to know for lifespan until all of the dogs have gone through the full three years.

• 1:06:24Dr. Darshan Shah?

  Sure, sure. And how does, let's assume that the signal turns out that it's the same signal you've seen before with echoes and with lifespan improvement. And this is incredible, like rigorous, good research on this. And now we've gone from mice to dogs, right? And so we already know rapamycin's FDA approved.

• 1:06:43Speaker 01

  Yeah.

• 1:06:44Dr. Darshan Shah?

  We already know there's a high safety signal. How do humans or people then look at the results of this study? And then make a determination about like whether they should be trying rapamycin or not?

• 1:06:55Speaker 01

  Yeah, well, this is, it's actually interesting because there's a lot of concern around safety with rapamycin in humans, primarily because of the way it was clinically developed and approved. It's an organ transplant drug at high doses in people taking strong immunosuppressants. There are side effects there. I'm not going to try to say there aren't. They're not life threatening, but they're not fantastic. So now there have been probably tens of thousands of people by this point who've used rapamycin off label. And we actually have a pretty good feel for what the safety signal looks like. It's pretty nonexistent. 15% of people will get mouth sores. Outside of that, I haven't seen anything that's statistically significant. Maybe a little signal for, you know, glucose perturbations or bacterial risk, but it never reaches statistical significance.

• 1:07:40Speaker 01

  So I think we know how to use it safely. I think rapamycin is one of the few cases for off-label use of an FDA-approved drug where we have reasonable evidence across multiple age-related domains that we can look at and make an informed risk reward calculation. I'm not suggesting everybody should be taking rapamycin. I'm not convinced it slows biological aging in people. I would say if, if you forced me to like make a guess, I'd say, yeah, rapamycin, SGLT2 inhibitors, probably slow biological aging in people. GLP-1s, maybe. But I'm not confident enough to say like, yeah, we have a lot of good data there.

• 1:08:14Dr. Darshan Shah?

  Yeah.

• 1:08:14Speaker 01

  I do think there are use cases where rapamycin makes sense in people.

• 1:08:18Dr. Darshan Shah?

  Right.

• 1:08:18Speaker 01

  But if you ask me as well, like between SGLT2 inhibitors and rapamycin, what would I feel most confident suggesting that, that people could use safely off-label broadly speaking? I'd say the SGLT2 inhibitors.

• 1:08:31Dr. Darshan Shah?

  Yeah.

• 1:08:32Speaker 01

  So that's kind of where I'm at. But and again, we could spend a whole episode talking about the different human data on rapamycin. There are a lot of signals for different conditions. I would put any chronic inflammatory disease, likely. Chronic fatigue syndrome following viral infection, very likely, really good data there. If you're an APOE4 homozygote, there's Not a lot, but I would say pretty compelling data for rapamycin in that context, both for cerebral blood flow and volume changes in the brain, both of which we can measure. The nice thing is we've got biomarkers there we could measure. So those are places where I think, you know,

• 1:09:04Dr. Darshan Shah?

  Fertility?

• 1:09:05Speaker 01

  There's a use case. Yeah, there's one study out of China looking at in vitro fertilization in women and showed an effect of rapamycin there. There's another clinical trial out of Columbia that has completed. They haven't released the results yet. That's Yu Shinsu and Zev Williams, looking at premature ovarian failure in women. So, early signal. That's where I feel like there's maybe not quite, I mean, again, it depends on your personal situation, right? Maybe not quite as much evidence, but again, if you've sort of evaluated the entire equation and you feel like it's right for you in that context, yeah. I will say, and again, a lot of this is just anecdote. You talk to a lot of people. Rapamycin definitely does stuff to the ovaries. I think we just don't really know exactly what it's doing at this point. So, so there is a signal there for sure.

• 1:09:50Dr. Darshan Shah?

  Right, right. And so it's an exciting time, I think. You know, we have, we have a lot going on. We talked about peptides, we talked about rapamycin, STL2 inhibitors, which we didn't even get to, but people can do some research there. I'm on even kind of myself. Are those going to come off patent soon? They're so expensive.

• 1:10:05Speaker 01

  Which ones?

• 1:10:06Dr. Darshan Shah?

  Evo Kana, the STL2 inhibitors?

• 1:10:08Speaker 01

  I don't know which ones are on patent and which ones aren't, actually, to be honest with you.

• 1:10:13Dr. Darshan Shah?

  There's, they're all very expensive right now.

• 1:10:15Speaker 01

  Yeah, I'm on Giardiance and, but you know, with insurance, it's not bad. It's like,

• 1:10:19Dr. Darshan Shah?

  Yeah.

• 1:10:20Speaker 01

  Not $36 a month, I think is what I think.

• 1:10:22Dr. Darshan Shah?

  Maybe I need to switch over to that one then.

• 1:10:25Speaker 01

  I mean, this is a whole nother thing. Like the expense of these pharmaceuticals, you know, it's such a game. Like, you can, you can submit your pharmaceutical drug prescription, you know, and it'll, it'll be $500 and then you go get a coupon and it's $40, but you need to know the coupons there to get it. It's like, can we just fix the system?

• 1:10:43Dr. Darshan Shah?

  Yeah.

• 1:10:43Speaker 01

  It's ridiculous.

• 1:10:45Dr. Darshan Shah?

  It's kind of ridiculous. But I mean, I really feel like this is an exciting time because there's, there's a lot of new research coming out. There's old research. There's research that you're putting out there that really does kind of give you signals, right? And so I'm hoping that we can just accelerate the research to your point and find a way to really accelerate this because, and maybe that solution will come with AI, will come with data crunching.

• 1:11:08Speaker 01

  It'll help. I think AI will help. Yeah. I think what I would say is the thing I'm most excited about is this, there does seem to be a shift in mentality. And again, you know, For as much as I get frustrated sometimes with the big name people who are getting a lot of attention because they aren't very scientific, I think they have helped the discussion.

• 1:11:26Dr. Darshan Shah?

  They have.

• 1:11:27Speaker 01

  And there is a shift in mentality, both among medical providers and among the general population, towards recognizing that proactive health is what we should be doing. Keeping people healthy is way better than keeping people sick. And so that's very encouraging, but along with that comes, you know, this rush for shiny object, latest experimental therapy. So what I think will happen is we'll get more and more mainstream medical community taking rigorous approaches to proactive healthcare. And so we're gradually going to get this type of quality healthcare available to more people. And really, that's, I think, what we need to do.

• 1:12:04Dr. Darshan Shah?

  Absolutely.

• 1:12:05Speaker 01

  There's always going to be the people who want to try the experimental stuff, and that's fine. If you want to do that, great, go do it. But I think for the average person, creating a system where they can get access to evidence-based proactive healthcare will give everybody, I think, the opportunity for between 10 and 20 more years of healthy life. So this is a big deal.

• 1:12:22Dr. Darshan Shah?

  It's a big deal.

• 1:12:23Speaker 01

  And so there is a lot of reason to be excited about that and also to continue to try to push forward this science and the evidence-based approaches.

• 1:12:31Dr. Darshan Shah?

  To match it, right. And for the first time ever, I'm seeing many physicians getting involved in the conversation. Whereas before, there was no, it was just like a hard stop on conversations around these types of health span promoting therapeutics. And now people are talking about it.

• 1:12:45Speaker 01

  And even the people who are particularly critical of the field are at least having the conversation. So that's good.

• 1:12:51Dr. Darshan Shah?

  Exactly. And I credit you for a lot of this. So thank you so much for putting this work out there and doing the hard work. And it was such a pleasure having you on the podcast. Thank you.

• 1:13:00Speaker 01

  Thank you. It's been a pleasure.

• 1:13:01Dr. Darshan Shah?

  Where can people learn more from you?

• 1:13:03Speaker 01

  Yeah, so I'm on Instagram and X and LinkedIn, @MKBerline. And I've got my own podcast on YouTube, also @MKBerline.

• 1:13:12Dr. Darshan Shah?

  Thank you so much.

• 1:13:13Speaker 01

  Thanks.

• 1:13:17Dr. Darshan Shah?

  Thank you so much for listening to the podcast today. Please remember to subscribe if you liked this episode and give us a good review and share a link with your friends. It really helps to support all of our efforts. I also want to remind you that the information shared on this podcast is for educational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. Please consult with your healthcare provider or physician before making any decisions or taking any action based on what you hear today, especially if you have any underlying health conditions or on any medications. Your doctor knows your personal health situation the best and it's always important to seek their guidance.