 So, most of us have an aha moment that got us started. What was your aha moment that guided your book? Yeah, actually, I did have an aha moment and this was during my geriatric fellowship. So I did a fellowship in geriatrics and nutritional sciences in Washington University. So part of the deal was in order for me to do advanced nutritional sciences, I had to do a fellowship, a medical fellowship, and the medical fellowship that I had to do was in geriatrics. For those listeners or viewers who don't know what that is, that is specializing in individuals over the age of 65. And geriatrics, they deal with falls, musculature, memory, Alzheimer's, diabetes, etc. You name it, Dr. Gundry, you're very well aware of the conditions that a geriatrician would be challenged with. In the mornings and in the evenings, I was doing metabolic research. Muscle biopsies, fat biopsies, and cardiovascular testing, as well as brain imaging. And this one participant changed everything for me. Will just call her Betty. She was a mom of three in her mid 50s and always cycled with the same 20 pounds. She did exactly what the medical community was telling her to do, which was exercise more and eat less. And in the process, she lost weight. But over the years, she destroyed her metabolism, she destroyed her skeletal muscle, and really impacted her brain because of her metabolic dysregulation. So when we imaged her brain, her brain looked like the beginning of an Alzheimer's brain, I felt really responsible. Even though, again, she hadn't been my patient, she was a study participant, but it was at that moment that I realized that we had been chasing the wrong tissue. It's not about fat. It wasn't about obesity. And I started to think, what were some of the things that all my patients had in common? Whether they were in the nursing home, whether they were in the dementia unit, and it wasn't that they were over fat. It was the unifying factor was that they all had unhealthy skeletal muscle. And that was where muscle centric medicine was born. So take us through that. Sarcopenia is the fancy word for a loss of muscle as we get older. And certainly, we see that extensively in not only our older patients, but certainly many, quote, seemingly healthy people who are over fat or obese are struck. When, for instance, we get a CAT scan for some other reason, and they have thighs that were just as big as they were when they were in high school, but their thighs now are mostly fat rather than muscle, whereas when they were in high school, the odds are that it was mostly muscle and not much fat. But their circumference was the same. So they're oblivious to the fact that their external size may be the same, but it's totally different internally. Yeah. That's what we think about sarcopenic obesity, and it really is that the weight remains the same, but the body composition changes. And one of the things that we have to recognize is that although sarcopenia, which is exactly what you said, it's the loss of skeletal muscle mass, which is size and function and or strength, is typically thought about as a disease of aging, whether you are in your 50s or 60s, 70s, this is when skeletal muscle would decline. I would argue that sarcopenia and obesogenic sarcopenia also begin in your 30s, just as Alzheimer's cardiovascular disease, insulin resistance, which probably begins well beyond your 30s, that the diseases that we think about with aging and metabolic dysfunction are in fact related, if not in part due to skeletal muscle, changes in your 30s. All right. I think you and I both agree that muscle health is absolutely essential for longevity and that it has everything to do with metabolic health. So as I've written and you've written, muscles are metabolic organs. So tell us about your research on this metabolic organ, the muscle that we've neglected. Yeah. Skeletal muscle is quite fascinating and, you know, I was so fortunate to train with one of the world leading experts in protein and skeletal muscle metabolism. He's an individual by the name of Dr. Donald Lehman, professor emeritus at the University of Illinois. And all of the protein and muscle research that we see now really stemmed in part from much of his work that was in the 80s. He really started to understand that the amount of protein that we have really stimulates the health of skeletal muscle. And we have to ask ourselves, why skeletal muscle? Why is skeletal muscle so important? Number one, based on the percentage of body weight, it makes up 40% of our body weight. Shear mass alone, it is the largest endocrine organ, yes, endocrine organ in the body. Skeletal muscle is also the primary site for glucose disposal, meaning the carbohydrates that you eat. Skeletal muscle is the primary place that it goes. Skeletal muscle is also an amino acid reservoir for when someone, not if, but when they get injured because the reality is injured or sick, whether it's the flu, et cetera, something at some point is going to happen where you will be in a highly catabolic state where your metabolism is kicked up due to infection or inflammation. Skeletal muscle is the primary reservoir for the body protective compounds. Skeletal muscle is also critical for fatty acid oxidation. People care about cholesterol, but skeletal muscle at rest is the primary site for fatty acid oxidation, making it important as it relates to, again, fats and lipids and cholesterol in your body. Another important point about skeletal muscle is that it's an immune regulator. The organ system, when you contract skeletal muscle, skeletal muscle secretes myokines and myokines influence and interface with the immune system to help balance out other kinds of inflammatory processes. Then, of course, the other side to skeletal muscle is how it responds to dietary protein, which I'm sure that we're going to talk about the thermic effect of feeding and the actual influence that skeletal muscle mass has on our baseline metabolic rate. This actually is a good spot to talk about what do you think about the current GLP-1 agonists that are sweeping the country and your thoughts on skeletal muscle and these compounds? It's a great topic of conversation, and I'm sure that you've spoken about this quite frequently about GLP-1 agonists and GIP-1 agonists. So ozempic has gotten quite a lot of press, which is somaglotide. Quite recently, people have been talking about how the use ozempic or somaglotide or these GLP-1s have been negatively impacting skeletal muscle. I've actually looked into this data to see what is the mechanism of action. I have not found any. I believe that the use of these agents with the decrease in overall food intake and the decrease in protein intake without sufficient training is actually what is leading to skeletal muscle mass loss, because I'll tell you this, Dr. Gundry. We use these agents all the time in our clinical practice. So I have a clinical practice. We use the combination agents, and we track their body composition and muscle mass. With a protein forward diet and sufficient resistance training, all of our patients are able to maintain skeletal muscle mass. That would seem to be the exception to the rule, and thank you for maximizing exercise and protein consumption in these folks. What I see, unfortunately, in my patients, and I've actually never willingly prescribed these drugs, but my patients who have been placed on them by well-meaning physicians, their insulin levels go up, which is one of the actions of the drug, which to me is a bad thing, but their skeletal muscle mass, their weakness is impressive, and my patients notice the loss of their muscles, and literally to a person. And they bring it up to me, not the other way around. And certainly there are some studies, not all of them, that muscle mass is a consequence of long-term use. Yeah, the unfortunate part about some of those studies is they haven't controlled for diet or exercise. Correct. And as I can see in clinical practice, I do see the maintenance, and I've seen all their blood markers improve, including insulin, as well as skeletal muscle mass maintenance. So I think, in part, is it the dosing that is being used? Is it the dosing? Is it the training? Is it the nutrition plan? And I'll tell you something else that I think is also surprising is these medications are spoken about as if someone can never come off of them. In my clinical practice, we are able to help really make metabolic change and then take individuals off these medications. It is not something that we foresee individuals having to stay on indefinitely. That's encouraging, because as you know, a paper just came out this week, placebo controlled trial, with using these medications for six months and then changing over with a diet and exercise program, one group continued on the active drug. The other group got a placebo shot. The placebo group unfortunately gained 50% of their weight back in three months, despite a diet and exercise program. And that's hot off the press this week, so it worries me to say the least. Okay, let's get down to the brass tacks. Obviously, protein is necessary to build muscle mass. But I think probably thanks to Dr. Adkins way back when, people were under, I think, the mistaken impression that the more protein I eat, the more muscles I will grow. What say you? We know that that's not true. The only time that you're going to put on muscle mass with consuming more protein would be if you were actually under consuming protein in the first place. You cannot, and I think that you make a really good point, you cannot simply eat protein and put on muscle mass. Skeletal muscle is a very dynamic tissue. It requires adaptation. It requires stimulus. And of course, it requires dietary protein. But I will also say that from my understanding, the Atkins diet was not considered a high protein diet, which I think we should define. I think it was more of a higher fat diet, where a protein percentage from a percentage of calories may have been 20, was it maybe 20%? Well, the original Atkins diet was a high fat diet, but he got into so much trouble with the American Medical Association that he morphed into a high protein doctor. And I've argued in my books because I knew his co-author very well. When he morphed to a high protein doctor, that's when his weight began going up. Now, he was, I think the last person to say he was into fitness and exercise. So I think that's a big part. But one of the things that I think you and I would agree on is that we have no storage system for excess protein, but we do not waste calories. And so we will convert protein via gluconeogenesis into sugar. And we have a storage system for sugar. It's called fat. I've argued in my books that that's one of the reasons Atkins did die a fat man. So but tell us about your protocol to prevent that from happening, the lion protocol. Yeah. I think that metabolism is very complicated. And when we think about dietary protein, we have to think about, in the overall picture, what would be considered high protein? So the current recommendation is 0.6 grams per kg, I'm sorry, 0.8 grams per kilogram, which is the minimum to prevent deficiencies. And for those that use pounds, that's 0.37 grams per pound of body weight. So for example, if you're a 115 pound female, then the recommended dietary allowance would be 45 grams of dietary protein. Now what we do know is that that is not sufficient to protect against aging. There's many things that happen with skeletal muscle as it relates to being able to maintain protein turnover. The body turns over around 250 to 300 grams of protein a day. And that system and that process becomes more challenged as we get older. That is why increasing dietary protein above the RDA has been shown in nearly every study that 0.8 grams per kg. For those individuals that increase to 1.2 grams per kg, fair significantly better from a blood sugar regulation, from triglycerides, from blood pressure, from insulin, the dietary protein as we increase it can have really important benefits. And you mentioned about gluconeogenesis, I agree with you, it is a substrate-driven process is what you were saying is that for every 100 grams of dietary protein, you might convert 60 grams to glucose. The question becomes is how fast is that conversion and the process and time that it were to take for that to happen. And then the other thought process behind it is when you improve dietary protein and you get the numbers right, you actually stimulate the health of skeletal muscle. And that becomes really important, especially as you age. I didn't know Atkins, but I would fair to say that his total calorie consumption was probably way too high. Yeah, I think we would both agree with that. He actually was one of the first people to talk about and recognize that one of the benefits, and I wrote about this actually in my first book years ago, that protein is very thermogenic in that we literally, we can argue about how much waste 30% of the calories in protein in the process of digesting protein into absorbable amino acids. And it clearly does have a thermogenic effect. And he was one of the first to propose that if you were going to choose a macronutrient, that you might as well choose the thermogenic effect of protein for that benefit, controversial subject in its own right, in that mTOR is a sensing molecule of protein availability and that there are a class of drugs like rapamycin that suppresses mTOR. And I certainly come from the field of, I think, expressing mTOR as a wonderful thing, the older we get. And you would probably argue that mTOR would be a really great thing, the older we get. And yet, when I look at my super old patients, 95 and above, and I have a big practice in the super old, these people run insulin-like growth factor levels, IGF-1s, quite low, in fact, remarkably low. And most of us use insulin-like growth factor 1 as a stand-in, as a measurable stand-in for mTOR activation. So one of the things that I keep coming back to is the Italian cyclist study, which you're probably aware of, where they took Italian cyclists, put them on a training table for three months, where everyone had the exact same amount of calories and had the exact same training program, and one group ate in a 12-hour window. They had breakfast at 8 o'clock, lunch at 1, and they had to finish dinner at 8 o'clock. The other group had to eat the same number of calories, but had breakfast at 1 o'clock in the afternoon, lunch at 4 o'clock, and then had to finish dinner at 8. And the people, they both had the same muscle mass at the end of the period. The cyclists who had the 7-hour eating window lost weight, the other group didn't, and the cyclists in the 7-hour eating window plummeted their IGF-1, whereas the other group was the same. And I use that to justify time-restricted eating and the benefits of that. So they're eating the same amount of protein, and they both have the same muscle mass, but one has a lot lower IGF than the other. Yeah, I think you bring up a great point. When we think about mTOR, which is mechanistic target of rapamycin, we have to recognize that it's in all tissues. It's in the brain, it's in the pancreas, it's in the kidneys, it's in the liver. And mTOR is sensitive to different influences depending on where it is in the tissue. So for example, mTOR in liver may be exquisitely more sensitive to insulin or overall calorie burden from carbohydrates, same with the pancreas, versus mTOR in skeletal muscle is exquisitely sensitive to protein, losing, in fact, that's nearly the only place. So while I think that we can both agree that mTOR stimulation over a period of time is not ideal, right? The worst of all worlds would be to eat a high carbohydrate diet, small amounts over the entire day and continuously stimulate mTOR. I think that that is a terrible idea, quite frankly, probably one of the worst. Where I think mTOR is very beneficial and necessary is in skeletal muscle and in very discrete ways of stimulating it and then allowing it to reset. So for example, exercise and resistance training also stimulates mTOR. It stimulates mTOR in skeletal muscle, so we can't say, well, stimulating mTOR in all tissues is bad because that would be the same as saying exercise is bad. And we clearly know that that's not true. So I think we can frame the conversation that mTOR is stimulated by various different mechanisms and various different tissues. And the worst of all worlds is to continuously stimulate this mechanistic target of rapamycin because it is a growth promoter over time, where stimulating mTOR is very necessary is through skeletal muscle, through dietary protein, which has an on and off switch and exercise. So I think that we can think about it in this kind of whole picture, which leads me to time-restricted feeding. I think that there is great benefit for that. I do not think that we should be feeding at all times continuously. Time-restricted feeding, we initiate that in our practice. I think that it is very beneficial for gut rest, for calorie control, and quite frankly, for some of the mechanisms that you're talking about turning on mTOR and then allowing it to reset and turn off. So surprisingly, we're not in disagreement in that at all. Now, you mentioned something I think just now that I think is really important that in my new book, Gut Check, I make a strong case and it's good to hear you say it. The gut needs periods of rest to repair itself. And we in our current American diet, like Sasha Panda has shown Americans eat 16 hours a day nearly continuously. And that repair process is really important. I suspect, although I think we'll talk about this, I'm a big fan of Volter Longo's work from the USC Longevity Center. And as you probably know, Volter is a low-protein proponent. 0.3 grams per kg. So he recommends below the RDA. Correct. He believes in the data support him that as we get older, let's say, across 65 years of age as a threshold, our protein needs increase. And I think even he will admit that. Now, I've argued with him, I'll show you where I'm going, that the reason our protein needs increase is because we have damaged the absorptive surface of our gut wall. And in my patient population, most of the people that I operate on for heart disease back in the day had low albumins and low total proteins. And this was a view, this was, these people were old, they were sarcopenic, blah, blah, blah, makes sense. Interestingly enough, when I put them on my program of removing major dietary lectins and actually reducing animal protein, their albumins and their total proteins rose almost, you wouldn't believe it. But I have come to the belief, and I've been doing this for 25 years now, that much of our problem with protein is we have damaged the wall of our gut. So that a lot of the protein we eat is not available for proper absorption. Any thoughts on that? Yeah, first of all, we can't discount your decades of experience in practice. I know I certainly see things that seem amazing in my own practice. So I think that that's, it's just very fascinating. And we do know that there is changes in gastrointestinal health and splenchnic extraction of nutrients. So again, could it be somewhere or something that could be used cyclically? If you are certainly seeing this kind of improvement with somewhat of a protein restriction, I mean, I think it's unusual, but again, it sounds as if there are things related to gut lining and gut integrity. The one thing that I think about is that, for example, threonine is an essential amino acid that we have to get from the diet that is important from use in production. And without it, and when protein is low, we don't utilize protein to rebuild and repair gut lining, et cetera. So, you know, from a mechanistic standpoint, I don't necessarily understand why, but I certainly can appreciate that dietary protein absorption as we age becomes much more challenging. So would it be a way in which it would be cyclical that if you are removing something that is irritating to the gut lining, allowing it to heal, I think it's very interesting. Yeah, and the reason I bring it up is I think your concept of gut rest is a really good idea because it does allow for repair. You know, all the longevity studies with C. elegans has certainly convinced me that death begins as the gut wall becomes porous. And the more porous it becomes, the more death approaches more rapidly. And these are newer studies, maybe a few years old. And what they found that there are a certain percentage of the population that may potentially be able to use the gut microbiome to extract essential amino acids. Oh, yeah. This was out of Don Lehmann and Suzanne Devkota at Cedar Sinai worked on some of these studies where they saw that certain populations may be able to their own gut microbiome may be able to generate essential amino acids, which would somewhat go to your your concept of if we remove dietary protein or is there a possibility of a cyclical protein ingestion, then perhaps the body has mechanisms to make up for this in a, you know, a window of time, whether it's four or six weeks. I think I think it's very fascinating. Yeah, and to complete that circle, I've written in previous books and in gut check that exercise actually promotes a different gut microbiome that becomes efficient at producing amino acids and extracting amino acids. So there's another good reason to exercise. Yeah. I have to tell you, my book Forever Strong, which hit the New York Times, it was an instant New York Times bestseller as a first time author, which is congratulations, which is a pretty big deal. Outsold Atomic Habits and Arnold Schwarzenegger, it's first week, which is just extraordinary. I hadn't anticipated that. And really, the concept is that muscle is the organ of longevity and that skeletal muscle has really been underserved. We've always focused on obesity and we've always focused on fat, but we've gotten the tissue wrong. We've gotten the question wrong. It's really a midlife muscle crisis. And if you talk about aging and you talk about gut health, like you do in your book, gut check, and if that is, in fact, the beginning of illness and disease, then the things that we can do early on, like taking care of the health and well-being of our skeletal muscle, can change the trajectory of our aging. Because if skeletal muscle is at the focal point of metabolism, of gut health, of immune health, of our body armor, of our mobility, then it truly stands to reason that muscle is at the pinnacle of health and wellness. And not just as it relates to looking good in a bikini or having power and strength. All of that is wonderful, but certainly a byproduct of a much more important conversation, which is focusing on resistance training and dietary protein, because food is something that 100% of people do and really dialing it in. It's interesting, because I think that we have different approaches on nutrition. And I bet you both of them could be used in conjunction in a cyclical manner. My protein recommendation is 1 gram per pound ideal body weight, which is on the higher end. Again, it would be considered a higher protein diet. And that is to protect skeletal muscle as we age, and of course, body composition, et cetera. And I bet you there is a way in which both of our programs and plans work in conjunction, because of what is the target at any one point in time. Let me ask you, since a couple of weeks ago, I got to debate a vegan cardiologist. I only know one. I know who it is. It's very sweet, I'm sure. Well, you may not know her. She's from the West Coast. Anyhow, do you care in your book, or do you care where your patients get their dietary protein from? Yes, I've been studying this for 20 years. I've studied under one of the world leading protein experts. I have trained seven years in nutritional sciences and done a fellowship at Washington University in nutritional sciences. Which is a great place, by the way. Yes, and the evidence supports that it does matter where your protein comes from. And I think that when we look at plant versus animal proteins, the profile of amino acids defines whether something is considered a high protein, a high quality protein versus a low quality protein. It is hard fast biological numbers that are not up for debate. A high quality protein is something that has a robust profile of the essential amino acids that mimic what is needed in a human. For example, a lean cut of beef or fish or chicken has an amino acid profile that matches the needs of a human. A plant-based protein has the amino acid profile necessary for plants or matches plants. If we were to take it one step further, we don't eat for protein. We eat for the essential amino acids. And it is a much bigger conversation than just the dietary protein, but we'll start there. So if someone were to say, I am going to get all of my protein from plant sources, Dr. Gundry, you and I both could agree that we would look at a chicken breast and we would look at a plate of broccoli or peanut butter and say these two are not the same. They are not the same in structure. They are not the same in nutrient value. They are clearly not the same. And when you look at the amount of chicken, so for one ounce of a chicken breast in order to get those same amino acids, which what we talked about was leucine. We talked earlier in this conversation that you require two and a half grams of leucine to stimulate muscle. In order to get the appropriate amount of amino acids to equal that one small chicken breast, you would require six cups of quinoa and over a thousand calories and hundreds of grams of carbohydrates. If you were to do it from edamame, you might require an entire cup or two of edamame. You would be required to eat 35% more calories from that plant-based protein source to meet the amino acid needs. That is metabolically devastating for people. And that's just the dietary protein. The point that we talk about these equivalents, this one ounce equivalent. So for example, a one ounce equivalent of dietary beef, so a one beef ounce equivalent and you take a one ounce equivalent of a peanut butter, peanut butter might have 1.5% of the essential amino acids, whereas the one ounce equivalent of dietary meat has an exponential amount of these essential amino acids. So these proteins are clearly not equal and there's a digestibility aspect. A recent paper out of Luke Van Loon's, one of the first papers of its kind came out and Luke Van Loon, who's a protein researcher, muscle guy, one of the best in the business, looked at two meals that were isocaloric and had the same amount of protein. One was a beef-based meal that had carbohydrates, et cetera. Everything was equal. Each had around 40 grams of protein. The other was a chickpea vegan meal. And what they found was the plant-based meal never reached the peak amino acids in the blood to stimulate muscle. And this was looking at women in the 75 and they did a crossover design study. So each group did both the same. It was a very well-designed study. And I caution individuals who think that they can get all of their protein from plant-based sources because they're not the same. They're not the same in digestibility. They don't trigger muscle protein synthesis the same, especially as you age, especially Dr. Gundry, if you have gut issues, we're exactly what you were saying where you're not absorbing it. And I think that it's a real problem when we tell our aging population to go more plant-based. Now, we also have to think about what about iron, zinc, selenium, creatine, and serine. The amount of nutrients in an animal-based source is really, really important. It has essential nutrients that you cannot get from plants. And as a trained geriatrician, I can't think of a worse advice to give someone. Well, as my audience knows, the good news is I would never recommend a human being eating peanut butter, chickpeas, quinoa, or edamame. So we agree on that completely. I hope you enjoyed this episode of the Dr. Gundry podcast. Make sure to check out the next one here. One packet of Splenda kills off 50% of your microbiome. One packet. Imagine doing that several times a day, like I used to do. No wonder I was sick all the time.