The Melanie Avalon Biohacking Podcast Episode #220 - Dr. Gabrielle Lyon

TRANSCRIPT

Melanie Avalon: Hi, friends. Welcome back to the show. I am so incredibly excited about the conversation that I am about to have. I have been looking forward to this for so, so long. So, the backstory on today's conversation a while ago now I'd have to see when it was. I had a fabulous guest on the show, Dr. Gabrielle Lyon. I adore her work because she talks about something that you guys know, I am so passionate about and talk about all the time, which is the role of supporting our muscle and protein intake and all of those things. I mean, I honestly think on The Intermittent Fasting Podcast, we talk about it probably every week, and then I talk about it a lot on this show as well, and I think about it a lot. And so previously, I'd interviewed Gabrielle. We have a lot of mutual friends, and we did a whole episode on protein and it was so incredible. I learned so much, so much amazing feedback. So then when Dr. Lyon was releasing her new book, I was thrilled about the potential of having her on the show again. And friends, okay, so I knew I was going to like the book. I was set up to like it. It blew me away. I cannot recommend enough. Everybody, get this book now. It is a paradigm shift. It will just change the way you view your life, your metabolism, your diet, so many things. It is a game changer. And the name of the book is Forever Strong, which is a brilliant name, by the way, A New Science-Based Strategy for Aging Well, and I [laughs] have so many notes, it's crazy. And I have so many rabbit tangents that I just want to go on and ask Dr. Lyon all of these questions. So, Dr. Lyon, thank you so much for being here. 

Gabrielle Lyon: Thank you so much. I really appreciate you having me back. 

Melanie Avalon: So, I really mean that your book, it's like everything that I could ever want in a book on all of this stuff. So, thank you for what you're doing. I've even gone down the rabbit hole of like-- it took me a long time to read it because I would read something and be so fascinated and then I'd have to go the reference and then I would go on the rabbit hole of the studies and [sigh] it's really good. 

Gabrielle Lyon: There's a lot of references in that book. 

Melanie Avalon: There are, there are. And then once I go on the problem with-- not the problem, but when you go look up a study, it references studies, so then you have to go look up those studies. So, it's hard for me to like stay focused. But in any case, my audience, they are probably super familiar with your work. But for those who are not, could you tell them a little bit about your personal story and what made you so interested in the role of what you call Muscle-Centric Medicine? I know you talk about the epiphany that you had in your career about all of this. So, could you share that with listeners? 

Gabrielle Lyon: Yeah. Let me give you a little bit about the backstory. Now, I graduated high school early, when I was 17, and I moved in with my godmother, whose name is Elizabeth Lipsky. For your listeners, it's important to understand that this was the generation before functional medicine was a thing. Liz Lipsky is a PhD in nutritional sciences and she wrote the book called Digestive Wellness, really a trailblazer in the connection of nutrition and wellness. Before Mark Hyman, before some of these thought leaders really interfaced with the general public, which is incredible to have that information so young. From there, I knew nutrition was going to be the thing. And as fate or serendipity or synchronicity would have it, I ended up going to do my undergraduate in human nutrition, vitamin, mineral metabolism. I landed in the class of the world class expert, Dr. Donald Layman, who has put a lot of the science behind what we now know as protein and muscle and the connection between how much we need to eat. 

I just landed in his classroom and have been mentored by him for the last 20 years. Fast forward through medical school and then into my fellowship. So once a physician finishes residency, they then go on to practice. There is the opportunity to then do additional specialty training, which is exactly what I did. I went back to the Washington University in St. Louis and I did a fellowship in geriatrics and nutritional sciences. Early mornings and later in the evenings, I did research in obesity. And I was looking at the interface between brain function and body composition. I fell in love with one of these participants. And as you can imagine, there's always that one person that is just this big, boisterous energy and captures your heart, and we'll just call her Betsy. She did exactly that for me. She was a mom of three, big brown eyes, robust personality, and I imaged her brain.

Now, Betsy, like a lot of people, had been on the yo-yo dieting train over the course of her lifetime lost hundreds of pounds, lost 20, regained 30, lost another 20, etc. Because the information that the general medical community was providing was go to Weight Watchers, eat less, move more, do cardiovascular activity, and follow somewhat of a food guide pyramid. I imaged Betsy's brain and her brain looked like the beginning of an Alzheimer's brain. Man, and it was at that moment that I had this epiphany. And this epiphany came to me, because I started to think about all the other patients I was seeing, the patients in the nursing home, the patients on the hospital floor, those in the dementia unit, those in the obesity clinic. And the one unifying factor was not that they were overfat, was not that they had obesity. The unifying factor that defined all of their health was the fact that they had unhealthy skeletal muscle. And this is where Muscle-Centric Medicine was born. 

Melanie Avalon: One of the studies I was looking up actually like talking about how I go look at the studies from your book because you mentioned how there's this idea of sarcopenic obesity and so basically, we look at people who are overweight and obese and they can also actually be under-muscled. And I read one of the studies that was talking about this, but with everything that you just said and that because when we look at all of these studies that look at weight loss and obesity and health conditions, and like you mentioned, like Alzheimer's and all these things. If we adjusted for muscle, how much of the actual obesity do you think would be correlated to these conditions? Do you think it's all the muscle or what is the relationship there?

Gabrielle Lyon: That's a wonderful question. The first thing that I want to point out is that we know when individuals there is a threshold for body fat where it becomes a problem for the majority of people, we know over 30% or 30% again it depends on the individual will begin to see metabolic derangements. Whether that's an increase in blood glucose, increase insulin, increase in triglycerides, increase in hs-CRP, other inflammatory markers. There seems to be an issue from a physiological perspective with having excess adipose tissue in and of itself as an inflammatory organ. However, your question was, is it really the skeletal muscle? Where is the interplay between skeletal muscle and obesity? Sarcopenic obesity, sarcopenia is the loss of skeletal muscle mass and function. Sarcopenic obesity is the combination of two and really a changing in body composition. So, we see an increase in body fat with a subsequent loss in skeletal muscle.

When you look at skeletal muscle directly, which by the way, there are very few studies that directly measure skeletal muscle mass. So, Melanie, if you were to go back and look at these studies, the majority of studies examine skeletal muscle through DEXA, which is not a direct measure of skeletal muscle mass. It is an extrapolation. It is directly measuring body fat and it is looking at bone. The rest is extrapolated. When you look at skeletal muscle mass directly and Dr. William Evans has really pioneered this through looking at it, whether it is through a deuterated creatine, which is going to be the way of the future. This is a way of actually tagging skeletal muscle looking at creatine because the majority of creatine is found in skeletal muscle. You will begin to see that the loss of the mass of skeletal muscle mass may have a greater influence on health outcomes than the actual gain of body fat. So, it is the loss of skeletal muscle that is more critical than the gain of body fat.

Melanie Avalon: Is it chicken or the egg with the muscle and the fat gain? Can you have one and not the other. What's all the potential combinations there? 

Gabrielle Lyon: This is another great and critical question and here's how we're going to frame this, Melanie. Early studies out of Yale looked at 18-year-old healthy sedentary college students without any outward sign of obesity. What they found was that when a healthy 18-year-old was sedentary, there was skeletal muscle insulin resistance. Skeletal muscle insulin resistance is really at the focal point of what begins to happen. It is likely the beginning phases of what we begin to see before we see obesity, before we see diabetes. Insulin resistance is really defined or identified as this impaired biological response to insulin. And insulin is a peptide hormone released from the pancreas, which primarily involves liver, muscle, and adipose tissue. Your question is, is it the chicken or the egg that comes first? Is it adipose tissue gain first or is it muscle impairment first? In my opinion and based on the evidence in the literature, it is a muscle issue first. Insulin resistance impairs glucose disposal. 

There is a whole host of other things that happen. There are metabolic consequences that happen with insulin resistance that result in hyperglycemia, hypertension, abnormal lipids, elevated inflammatory markers. And most importantly, as insulin resistance progresses in skeletal muscle, the ability of skeletal muscle to manage glucose as well as manage fatty acids changes. And the way I really like to think about this is, number one, the evidence supports skeletal muscle insulin resistance as a primary site. I'm talking about insulin resistance because it is a precursor for the development of obesity. Skeletal muscle is the primary site for glucose disposal, which means having blood sugar out of the bloodstream into skeletal muscle. 80 some percent of glucose disposal happens there. That is your target tissue. 

Melanie Avalon: Okay, got you. Do you think there's any correlation? Because there's the idea with body weight and body fat gain that the skinny fat paradox. And people who genetically just don't put on as much fat that they get metabolic issues sooner even though it doesn't look like it on the outside, because they just don't basically create that fat storage to create that cushion for that extra energy. Kind of like with the Asian populations, we see that more. Do you think there's any correlation between a person's potential to store excess fat protectively before it becomes an issue and their muscle's ability to dispose the fuel? Okay, and to say it a different way. So, the muscle's ability to deal with glucose and fuel and I guess fatty acids as well compared to the fat tissue's ability to take in excess calories. Do you think there's any correlation between those two? Like, are those two separate systems or are they more connected? 

Gabrielle Lyon: What I'm hearing your question be is what happens to populations that inherently seem to have lower muscle mass.

Melanie Avalon: Like lower body fat, but they become metabolically-- metabolic issues, kind of like an Asian population. 

Gabrielle Lyon: But I would say that in an Asian population, the percent body fat is higher. So, it's not that they have a-- so I believe and we'd have to look at the data, but from what I understand is their actual body fat percentage is high and their muscle mass is low compared to their muscle mass. And so, what happens is and-- we see this in bedrest studies what happens is when you have low muscle mass and I just had Emily Lance on my podcast, and she's part of the Galveston group, and they do a lot of these bedrest studies. Bedrest studies looking at older and younger individuals when they are put on bed rest can lose two pounds of skeletal muscle in their leg in the first five to seven days. That's a lot of skeletal muscle. And what they see is that in those times, they see a significant increase in insulin resistance and a significant impairment in glucose regulation in a very short period of time. So, bringing it back to populations with lower skeletal muscle mass, those populations are inherently at a greater risk already. The question becomes, I think, is there a genetic potential or is it a cultural aspect where maybe the diet is lower in protein or they are potentially not leveraging techniques to increase muscle hypertrophy? You know for that I can't necessarily answer. But the thing that we do know is that lower skeletal muscle mass precedes a lot of the challenges that we see. 

Melanie Avalon: Got you. Okay, I have more on this, but before we get too far away from it, [chuckles] we’re talking about earlier, a second ago, about how none of the, like the majority of the studies don't account for muscle historically, and if they do, it's DEXA scan. Do you think there's any potential because I know with the advent of AI, there's increasingly more an ability to potentially reanalyze studies and relook at data using AI. Do you think there's any potential in the future where we could go back and look at these studies and AI could somehow figure out, like, take into account this muscle factor? Or is it completely lost data because measurements weren't taken away, they needed to be taken, like the creatine stuff. 

Gabrielle Lyon: I think that the only way that we could potentially account for that will be if the studies were done with CT or MRI. But again, these are not a-- when I say direct measure, it's almost like a biological reference. I'm not sure the best way to state it, but again, imaging, is it a direct measure? Not necessarily. For example, measuring blood glucose would be a direct measure. I think it's an interesting thought experiment to see once we correct or utilize AI, will we see differences? Potentially. But this is something that has been completely missed in the data. You know, I don't want to say since the beginning of time, but really for an extended period of time without directly looking at skeletal muscle mass these are issues. What is going to happen now is when we begin to address and look at skeletal muscle mass directly, I believe we are going to see a whole new body of research emerge and that whole new body of research that is going to emerge is going to change. We are at the precipice of changing another paradigm. 

For the longest time, it has been believed that it is only the strength that matters. And from a cognitive perspective, it doesn't make logical sense. It doesn't make logical sense that it is only the strength that matters, not the mass. Because what happens when you have low muscle mass? All the things that we talked about low muscle mass will be a precursor for elevated levels of blood glucose, potentially insulin resistance, potentially elevated levels of triglycerides, etc. What is going to happen when we directly look at skeletal muscle mass? I believe that it is going to change what we have thought about as the importance of actually laying down more of that tissue. 

Melanie Avalon: Wow. I'm just thinking about how much if obesity was partly a proxy for the muscle issue and if that was just left out of all of these studies. It's kind of mind blowing the insinuations there. Okay question about the strength versus the mass when it comes to--because they'll often say that muscle and you talk about it as well, is highly correlated to longevity and mortality. Does that go for both strength and mass equally or is one more than the other? 

Gabrielle Lyon: Right now, people will talk about strength. The majority of the literature just focuses on strength. But there has been a recent few studies that showed that low muscle mass. Again, I believe that these are population-based studies, so not as ideal as we'd like, but that the low muscle mass increases risks of both morbidity and mortality. It really is the loss of tissue, but we just haven't caught up yet. 

Melanie Avalon: Why is grip strength what they normally look at when it comes to strength and longevity? 

Gabrielle Lyon: I believe differently than-- so grip strength is considered just the gold standard for longevity. I'm not exactly sure how they decided or correlated that, but if you really dive into the literature, there're a few things that you may see that grip strength may be determined at birth. So, there is a possibility that grip strength is not going to be the ultimate outcome. But again, the challenge with muscle and the challenge with some of these metrics is oftentimes much of it has been repeated over time. But if you look at some of the younger literature as it relates to younger individuals, there is some evidence to suggest that grip strength is determined at birth. And if that's the case, then it kind of throws out what we think about as it pertains to training for the improvement of grip strength. I'm actually really glad you asked that question because people always talk about grip strength and I'm on the fence. I think that is another potential mistake. 

Melanie Avalon: If you were to hypothesize about why grip strength would be a good indicator of longevity, is there anything special about our hands, our hand muscles, or is it really just that's what they picked and went with?

Gabrielle Lyon: I don't know. I mean, for me, it's not something that I've spent a lot of time addressing or thinking about because on a very fundamental level, I need to be able to answer the question, how is this translatable? For me, I'm much more interested as a geriatrician or someone who trained in geriatrics is how many times and how fast can someone get out of a chair? How fast can they walk? What is their balance like? Do I care about their grip strength? I mean, some people do, but again, I have to be able to answer the question, does this make sense and what am I really looking at? 

Melanie Avalon: Okay. And then actually related to that. So that's really interesting about it potentially being determined at birth. When it does come to strength and mass, what is the role of genetics? What is the role of muscle contraction so mechanical, like the actual mechanical action of the muscle? And then what is the role of the brain, especially going back to what you were talking about earlier about looking at the brains of people with obesity. Does the brain influence the size and strength of our muscles? 

Gabrielle Lyon: Yes. So let me circle back and mention this idea of grip strength. So, people talk about it as this just indispensable biomarker by the way. And looking at it, they believe that it's somewhat of a reliable biomarker for overall quality and strength and that when that is lost, that would essentially show signs of accelerated aging. But again, I'm not so convinced that is the overall metrics. So, I just want to mention that because if we are talking about genetics and changes, I think that there're a lot of other things that potentially could impact grip strength. And again, how do we correlate that all? I just want to make sure that I kind of close that out. I thought that that's important because I have to tell you is your listener at home measuring their grip strength? I hope not. I hope they are at home determining how much they can squat, how fast they can run a mile, how many push-ups can they do? Rather than thinking about grip strength as this indispensable biomarker for a young or middle-aged adult, maybe for an older adult, is that it's easier to measure and easier to test? Again, we have to have enough sense that if we're asking the question and saying that there is a correlation or how is this relating, what is the real answer that we're going for? 

Melanie Avalon: Not grip strength, but just muscles in general and the size and strength of them. What is the role of genetics in that? The role of actually contracting the muscle. So, the physical environment of the muscle and doing that contraction and then the brain or anything else that I'm leaving out. 

Gabrielle Lyon: Yeah, yeah. Let's talk a little bit about contracting skeletal muscle. Skeletal muscle at rest is different than contracting skeletal muscle. Obviously, they're both skeletal muscle. And one of the things that I think is important is we're talking about skeletal muscle but there is also cardiac and smooth muscle. But skeletal muscle makes up 40% of an individual's body, which is interesting because it seems to be retained in that measure. And I've been working on looking at some of this data because is it 40%, is it some people with 30%? But on average it seems to have some consistency of around 40%. There are two broad classes of skeletal muscle and again we're talking in absolutes because I think getting into the weeds of a lot of this of hybrid muscle fiber types and things becomes a bit complicated. But for a broad masterclass overview, there are two general types of skeletal muscle. 

There's slow twitch, which is type one. We think about that with high mitochondrial density. I know Melanie, you and I were at a conference together and I talked about urolithin A. This urolithin A would have the influence on mitochondrial health. This type 1 fiber is metabolically active even at rest. The primary energy fuel source for skeletal muscle is fatty acids. Most people think it's carbohydrates, but it's actually fatty acids at rest. These slow-twitch type 1 fibers are high in myoglobin, so they're red. They typically have low levels of glycogen storage. These are people that are thin and have muscle. They are typically more type 1, smaller cross-sectional areas. Easy way to think about it is kind of like the postural muscles to sitting up straight. They have high endurance, low force production. Endurance training will increase this proportion of type 1 fibers. Again, I think it's important that we lay this out because we're talking generally about skeletal muscles. So, we have to dive a little bit deeper specifically because I'm sure you're going to want to get to what the role of resistance training is and what happens as we age to some of these fiber types. 

The other class we could say is fast-twitch type 2. This is low mitochondrial density, typically lower metabolic activity at rest, high levels of glycogen. I think the type 2 muscle fibers are very important and they're more difficult to maintain as we age. You don't see a lot of really jacked older people. There is a somewhat of a natural transition from type 2 fiber to type 1. Again, is this a training? Is this an aging phenomenon? It's probably a mix of multiple influences. These fiber types have a larger cross-sectional area. This is where creatine would play a role. Also, again, there's glycogen and water that kind of are pulled into this fiber type. These are the fast twitch fibers which have lower endurance and higher force production. The cool thing is that you can train fibers to shift depending on your activity. I believe at birth you are born with more type 2 fibers. 

Again, your training probably influences this more than anything else. And then the next thing that you had mentioned is kind of this contracting skeletal muscle. So, at rest it's the primary site for glucose disposal. At rest it is also a primary site for fatty acid oxidation. When you contract skeletal muscle, the production of force and movement stimulates a different plethora of things that happen within skeletal muscle. And that is when you contract skeletal muscle, skeletal muscle releases myokines. And these myokines are released by myocytes in the muscle cell in response to muscular contractions. And just to put this in perspective, this term was first introduced in 2003. That is not that long ago. 

Melanie Avalon: Wow. [chuckles] Yeah.

Gabrielle Lyon: And they're really implicated in metabolism both locally and systemically. There are over 600 different types of myokines and I would say the majority of them we still probably don't even know. Again, this work is still relatively very, very new. And what is so fascinating is that when you begin to train, let's say the most famous myokine is interleukin-6. And by the way, this was only found 23 years ago, it's not as if we've known about this forever. And it's secreted from muscles into the bloodstream based on a response to muscle contraction. And the amount that reaches the circulation is affected by both the duration and intensity of exercise. So, this means that the way in which you train will have an influence of what kind and the amount of interleukin that is released. So, you're probably thinking, "Well, I don't care about interleukin-6."

Well, you may be not thinking that, but the listener is probably thinking, "Okay, well, why do we care about interleukin-6?" If you were to take a step back during a time where people were discussing this cytokine storm, people were talking about interleukin-6 and all these cytokines. Here is a myokine that is the same structure, but has a different influence because of where it is released on whole body inflammation. So essentially it allows, number one, there seems to be a protective effect against muscle atrophy as well as influencing the immune system, counteracting or balancing interleukin-6 and interleukin-15 from macrophages or other cells of the immune system.

Melanie Avalon: Between like IL-6, IL-8, IL-10. IL-6 is considered anti-inflammatory, right typically?-

Gabrielle Lyon: Yup. 

Melanie Avalon: -and 10 as well, anti-inflammatory.

Gabrielle Lyon: Yes. And it really just depends on the environment because again, when it is released from skeletal muscle, this is a different-- it has a different influence than when it is released from a macrophage. And that is really important to understand. And that this idea that we are leveraging skeletal muscle as an endocrine system and an endocrine organ is pivotable. But the understanding that these myokines really mediate this muscle and brain and adipose and liver, that there is this crosstalk that exercising skeletal muscle has a full body influence and that is a very essential component. So, what I'm saying is it's not just the exercise, it's not just the burning and utilization of calories that is happening with exercise. It is also the implications of the contracting skeletal muscle and what that does. There are myokines that affect lipolysis, that affect the brain, BDNF for hippocampal neurogenesis. These myokines also decrease appetite. All directly released from skeletal muscle, even potentially improves the aging of skin. There is nothing more potent than exercising skeletal muscle when it comes to longevity and having an overall balancing effect in the body. And again, I'm saying this in very black and white terms. None of this exists in black or white terms, but as humans, it becomes very important to be able to put things into frameworks that we can understand and have a conversation around. 

Melanie Avalon: Okay, I'm so fascinated by this. So, the IL-6, when it's released by a macrophage is it called a cytokine, and when it's released by muscle, it's called a myokine, but it's the same compound. 

Gabrielle Lyon: It is the same compound that has different effects. That could because it's tagged differently, but it's essentially the same compound. 

Melanie Avalon: Okay. Oh, it's tagged different. Okay. My second question was which felt a little esoteric by hearing what you just said, maybe it's not so esoteric. I was wondering if the IL-6 knew if it came from a muscle. 

Gabrielle Lyon: Yes.

Melanie Avalon: So, it does know because it's tagged. 

Gabrielle Lyon: Yeah. There's some kind, yes. 

Melanie Avalon: Okay. That tells it what to do or how to act.

Gabrielle Lyon: How it has somewhat of a pleiotropic effect. Yes. 

Melanie Avalon: Okay, good. I was haunted by this. I was like, how does it know where it came from and what it's doing? [laughs] 

Gabrielle Lyon: Again, incredibly fascinating because typically when we think about exercise, so Melanie, the biggest thing here is the goal. My ultimate goal is to change the conversation of what muscle is about. Five years ago, if you talk about muscle, everybody is thinking about muscle for performance. Can we agree upon that? For performance, for looking good naked, for being able to do and run a certain distance or lift a certain thing? My goal with Muscle-Centric Medicine is to make it the pinnacle of health and wellness. To understand that muscle-centric medicine is a whole new approach that acknowledges the health of one's skeletal muscle tissue and how this significantly impacts the health of all other organ systems within the body. And most critical is the perspective that it is rooted in actionable behavioral recommendations that we have direct control over. And I know that's a little bit of a mouthful, but it's essential to move the perception of skeletal muscle as purely performance to the multitude of other roles it has within inflammation, within even lipolysis, within exercising skeletal muscle stimulates GLP-1 from the intestine, I mean, from both intestinal L-cells and pancreatic B cells. I mean, this is incredible to think that contracting skeletal muscle leads to improved insulin secretion and action but also has implications on gut function. 

Melanie Avalon: To that point, because you mentioned in the book how it's our well, I don't know if it's our largest-- Is that our largest organ system? 

Gabrielle Lyon: It is our largest organ.

Melanie Avalon: And on top of that, it's our only one with voluntary control, which, I mean, so there're just so many paradigm shifts because one, it's affecting literally everything, like you're saying. And it's the one thing we can actually really voluntarily control. So, it's huge.

Gabrielle Lyon: My friend, it is the only thing. It is the only thing that we can control. Can we think about our liver and exercise our liver? I mean, maybe drinking, but how much? Right, there is no when you can actually think about do we contract our bicep? Do we do a leg extension? Do we do a squat? Again, the only organ that we have biological control.

Melanie Avalon: Not the smooth muscle though, that would be the exception. 

Gabrielle Lyon: Smooth muscle would be uterus. We don't have direct control over that. And then cardiac muscle, we don't have direct control over that.

Melanie Avalon: Is smooth muscle also what lines our blood vessels throughout our body. 

Gabrielle Lyon: Right.

Melanie Avalon: Okay, got you. Although with a cardiac, like doing cardio using our heart, does that strengthen our heart muscle? 

Gabrielle Lyon: Totally. But you're not able to sit here and if I said, "Melanie, I'm going to pay you a million dollars. Please bring your heart rate up to 150 beats a minute. Could you do it? Could you do it?"

Melanie Avalon: Oh, yeah.

Gabrielle Lyon: No, nobody could do it. Even if I said I'm going to give you $5 million, I need you to hit 220 beats a minute. Could you do it? But if I said I need you to do 150-pound squat, at least you could try.

Melanie Avalon: Yeah. Oh, actually related to that because that's a question I've always had. They say, whoever they is, they say that we don't fully contract to our full potential because our brain stops us. Is that true? 

Gabrielle Lyon: Maybe, I'm not totally sure. But yes, typically there would be some kind of central fatigue. There may be-- I haven't really looked at the data, but it would make sense.

Melanie Avalon: Okay, got you. 

Gabrielle Lyon: But the question is, does it have to be to full potential or what are we looking for? Ultimately the question is what we're looking for is an adaptation. When we are contracting skeletal muscle, we're looking for an adaptation. We're looking for the adaptation of either muscle strength, size or local endurance. Also, now everybody listening is thinking I'm going to contract skeletal muscle because I also want to release myokines. I'm going to throw something else out there that is not commonly discussed about skeletal muscle. And I had to take it out of my book, because my book was already 400 pages. Before I did this book, it was probably 600 pages and they had to cut it back. Exercising skeletal muscle releases glutamine, which is a semi essential amino acid and glutamine is a fuel source for cells of the immune system, for lymphocytes. This is a direct relationship between exercising skeletal muscle and cells of the immune system. That is profound. 

Melanie Avalon: I think that was in the version I read. 

Gabrielle Lyon: Well, you're VIP, so you got a very early version. 

Melanie Avalon: I think I got the early version. 

Gabrielle Lyon: Not everybody got that version. In fact, it didn't even make it in the book, I don't think.

Melanie Avalon: Because it was talking about glutamine being released from muscle. And I was like, "Oh, that's really fascinating." Wow, okay. Another question about this, because you were just talking about the adaptation and the stimulus and the growth and such. So, they'll often say when people have not been exercising and have not been doing strength training that they can make gains pretty fast because they're coming from a baseline of not already having done that. On the flipside, you talk about this role of muscle memory in the book and how you can reactivate. So, if you have muscle, maybe you can say this more eloquently and correct me where I'm wrong, but if you have muscle that you've been training and then you lose it, it sounds like you have a sort of muscle memory that you can reactivate it. So, what do we do with that seeming paradox of coming from a baseline of nothing makes it seem, "easier to make gains," but also this muscle memory idea would make it, "easier to make gains." So, what's happening? [chuckles] 

Gabrielle Lyon: I like what you're saying. One of the things that we have to understand is that it is really important that we prioritize the health of our skeletal muscle system early on. In the context of skeletal muscle memory, it's really the capacity of skeletal muscle to respond to different environmental stimuli that in a manner as if it had already been there before. For example, for me, I have been well trained my entire life. I am very interested in this. If I were to stop training, then for me to reinitiate and gain back that tissue would be much easier than for someone who has never built a certain threshold in the way that it may be easier for someone to put on muscle if they haven't. They are not necessarily going from a healthy state to a more healthy state. They're probably going from a deficit state to a baseline state. 

Muscle memory, the way I would think about it, is going from a healthy state or at least having been at a healthy state, to again gaining back a healthier body composition, if that makes sense. So again, low muscle mass is not a healthy state. An untrained individual, arguably, I would say is unhealthy. There's no such thing as a healthy sedentary person. And I don't mean that derogatory in any way. We just have to appreciate that if we're talking about this metabolically and medically that we believe skeletal muscle as an endocrine organ, then having less-- going from a less to a baseline is not necessarily going from baseline to more. Does that make sense? 

Melanie Avalon: It does, yes, completely. 

Gabrielle Lyon: Such good questions. I'm taking notes because I just love these questions. 

Melanie Avalon: Thank you. You should see my little chart. 

Gabrielle Lyon: We need a part two. These are just really good questions. 

Melanie Avalon: Oh, no. Yes, I would love that. And another question about the actual fueling of the muscle. What is the effect because you've mentioned-- glucose and glycogen throughout here, you've mentioned fatty acids. What are the different effects on the muscle of using those two different potential fuel sources? Oh, and amino acids as well. 

 Gabrielle Lyon: Yeah. Yeah, yeah. 

Melanie Avalon: Yeah. What are the implications of all those? And then I have a second part question. 

Gabrielle Lyon: One important part I think to recognize is that skeletal muscle is somewhat self-containing in the way that exercising skeletal muscle will use what it has. And I was just talking to Don Layman about this. We were kind of going back and forth because I got a very interesting question. I got this question about Intralipid. 

Melanie Avalon: That was my second question. 

Gabrielle Lyon: Yeah, intramuscular lipids. And when somebody would use that, the reality is exercising the only way to use substrates through muscle is exercise versus utilizing stored body fat or even having to pull from amino acids. But substrates like fatty acids or fat and glycogen are used by exercising skeletal muscle. Glycogen does not directly buffer or contribute to blood sugar regulation when you are exercising, that's the liver. When you are exercising skeletal muscle, first of all, at rest, it uses mostly fatty acids. Exercising skeletal muscle, the longer that you go, the more you are going to use. You're going to shift into using carbohydrates and using glycogen. The next component to that question is that you asked about this or you're going to ask about it, which I think is a really good question is this idea of, so what happens when skeletal muscle is unhealthy? 

Unhealthy skeletal muscle looks like a marbled steak. And that is fat infiltration whether it's  myositis, whether it is intramuscular lipids, or even in the athlete's paradox where the athlete has stores of triglycerides that uses it for energy. But when skeletal muscle becomes unhealthy, this fat can infiltrate around skeletal muscle tissue. It can infiltrate within the tissue, it can ultimately become-- There may be an increase in fibrosis and connective tissue which ultimately changes the body's ability to respond both strength, mobility and energy metabolism. And I think that that's important to understand. Now, you asked another question. Most amino acids are metabolized in the liver, the branched-chain amino acids are metabolized largely in skeletal muscle. That just goes to show that there is an unbalanced proportion of what actually gets into the bloodstream. Majority is metabolized by the liver, but the branched-chain amino acids are largely metabolized by skeletal muscle. 

Melanie Avalon: Do they go through the liver on the way to the muscle or do they go directly to the muscle? 

Gabrielle Lyon: Well, they have to get into the bloodstream, but the majority of branched-chain amino acids are left untouched and go to skeletal muscle. And that is just an interesting, it just-- what this highlights for me is the importance of branched-chain amino acids for skeletal muscle. That's really what that highlights to me. 

Melanie Avalon: And can we get those completely from food? Is there a benefit to taking BCAA supplements? 

Gabrielle Lyon: Not necessarily. 

Melanie Avalon: Not necessarily a benefit or not necessarily. 

Gabrielle Lyon: Not necessarily a benefit? Again, when we talk about protein, we typically talk about it as a generic term. We say protein as if it's one thing, but dietary protein is 20 different amino acids or 20 different nutrients, but yet we still talk about dietary protein as if it is one thing, and it's not. So, leucine, isoleucine, threonine, phenylalanine, tryptophan, they all have unique biologically different roles in the body. Primarily for the health of skeletal muscle is you need all of the dietary protein, you need all the full complex of proteins to put down new tissue. But in order to even trigger this process of muscle protein synthesis, which is this incorporation of different amino acids, what you require is you require leucine. And leucine is one of the branched-chain amino acids and skeletal muscle is exquisitely sensitive to leucine concentrations in a meal and in the bloodstream. So, I'm not sure exactly where I was going with that. Oh, you were asking about branched-chain amino acids. 

What would happen if I just gave branched-chain amino acids? If I just gave you branched-chain amino acids, it would be the equivalent of putting the key into a car and turning the ignition, and that engine would turn over, but the car wouldn't have any gas. The gas would be the full complex of amino acids. For that reason, I don't recommend branched-chain amino acids as a standalone, because what is the goal? We have to be able to provide the answer to any question. What is the goal? What is my goal of grip strength? What is my goal of ingesting these branched-chain amino acids? What is my goal of doing this kind of exercise? What is the outcome that I'm looking for? And the outcome that we're looking for is not just stimulating muscle protein synthesis, but what we're looking for is the sparing of muscle tissue, the health of overall lean body mass, which includes liver and bone and intestine and skin. And the way in which we are going to do that is we're going to hit the threshold of skeletal muscle first. So, no, that's a very long-winded way of saying do we just need branched-chain amino acids? No. What I'd much rather have someone do is add in an essential amino acid mix with a lower protein meal or one could potentially add in branched-chain amino acids with a lower protein meal.

Melanie Avalon: Okay. I do have some questions about the leucine before that because before leaving the fueling of the muscles with the intramuscular lipid droplets, because I have been so haunted by this athlete's paradox concept for so long. Because I was thinking, you talk about it in the book and we hear about the issues of having these fat droplet buildups in our body, and yet athletes seem to have a lot of intramuscular triglycerides and fat droplets, but they're healthy and what's going on there. And so, in my head, I was like, "Well, maybe it's just because they're using them more, like maybe they're burning through it so it's not as much of an issue." That was just my hypothesis. Then last night I went down the rabbit hole. Are you familiar with the two different types of lipid droplets in the muscle? 

Gabrielle Lyon: There's a lot. So, tell me what--

Melanie Avalon: So, it was talking about literally a paper about what was happening with the athlete's paradox. I got so excited when I found it. It was talking about lipid droplets and skeletal muscle, saying that there's intermyofibrillar lipid droplets, which are really metabolically active, and they serve as an energy reservoir during acute exercise. And then there's subsarcolemmal lipid droplets that are fewer in number, less active, they're higher in patients with type 2 diabetes. And it was saying that they're, like, closer to the surface. And so maybe it was talking about how when we look at these lipid droplets, we just look at one number, kind of like with the protein, and we just look at it like a protein, but we don't look at the type. I thought it was so fascinating. I was like, "Oh, this explains so much."

Gabrielle Lyon: Yeah. One thing that we could agree upon is that a trained individual is going to have healthier skeletal muscle than a sedentary individual. So yes, the athlete's paradox got the name because it was unusual that these triglycerides would be within skeletal muscle but it is actually used for energy system and developed because of the need for energy versus looking at a diabetic or an older individual that has skeletal muscle fat infiltration not because they are using it for energy, but because in fact, that they weren't. And some of these studies will look at CT, but again, a CT is not going to be a great way to identify that. But, yeah, I think it's incredibly fascinating. 

Melanie Avalon: Yeah. Because the question I was haunted by, and there's actually a correlated question with high lipid levels on keto diets, because I was thinking, if these athletes have these really high levels of intramuscular lipid droplets and then they stop being an athlete, does that mean now they just have all this fat there? And then the similarity would be like people on keto diets who have really high, like, LDL and cholesterol, but they say it's all fine because of their high HDL or their inflammatory status or their lack of plaque. But then I think, what if they do make a dietary shift and now they're just awash in LDL and cholesterol? What if they stop doing what they're doing to keep maintaining that anti-inflammatory state? This is more contemplating. 

Gabrielle Lyon: Yeah. I think these are really interesting and thought-provoking questions. I'm going to see if I can find something. My guess is that the only way to really leverage any of that fuel would be through training. So, the question would be, what happens if an athlete all of a sudden becomes sedentary? What happens with that triglyceride store? And I think that the next level to that question would be, well, I suppose the best way to think about that would be how much fat is infiltrated into the tissue in a sedentary human? And again, it's likely a spectrum and a continuum, but really fascinating. I'm fully expecting you to send me some papers, Melanie now.

Melanie Avalon: [chuckles] Well, like, a similar thing would be like, say you have a lot of muscle as an athlete and you stop, well, that's not good, but losing the muscle presumably wouldn't be toxic compared to stopping and having all this fat might be toxic. So, I'm just really interested.

Gabrielle Lyon: Yeah. Really, really good thoughts. 

Melanie Avalon: Back to the leucine [chuckles] like you were talking about. So, you mentioned it now. You mentioned it all throughout the book. And it's the importance of leucine to properly activate muscle protein synthesis and how we need a certain amount at a meal to do that. So why leucine? How does it interact with mTOR? And how does it literally interact? Does it connect with mTOR? What's actually happening there? And why does it have to be a certain amount to do that? 

Gabrielle Lyon: Yeah. So, I'm going to really kind of put this out in a way that, again, will provide a framework for understanding. First of all, leucine is one of the branched-chain amino acids. And again, it is specifically related to muscle protein synthesis, and it is required in a threshold amount. And I think that part of the belief when I say threshold, typically when you're younger, you don't require this leucine threshold. So, this goes back to not just the idea of the threshold, but it has to do with also the changing in skeletal muscle tissue as we age. And leucine is one of these essential amino acids and one of the amino acids that's necessary for the stimulation of this pathway known as mTOR. So, it's actually mTORC1. And basically, the discovery of kind of this mTOR pathway, the regulation of this signal transduction pathway didn't even come about till the 90s.

So basically, what ended up being discovered is that the ability of leucine alone to stimulate skeletal muscle led to a whole host of new papers and just an exploration of the science which ultimately recognized that leucine stimulated mTORC1, which is activated by other enzymes and there're numerous different pathways. But ultimately this pathway then goes on to stimulate muscle protein synthesis and the activation of messenger RNA which ends up being this initiation factor. And it's very sensitive to this and I'm going to also highlight something else. It's very sensitive to the intracellular leucine concentration. Right now, when you do a test and you look at leucine levels in the bloodstream, this is not an indication of you know if you are looking at just fasting levels of leucine in the blood or fasting levels of amino acids, this is not a reflection of intracellular leucine and it's this intracellular leucine content. 

And in fact, I'll say that leucine will never be determined to be, "a limiting amino acid" based on some of these blood levels because the blood maintains a certain amount of leucine in the bloodstream. So, I guess this is for the providers that are listening to your show. You guys should not be measuring amino acids in the bloodstream because that is not where the impact is. It is really the intracellular concentrations. So anyway, mTOR signaling then has this whole host of effects and then it produces muscle protein synthesis. Again, this is critical for the regulatory system or the regulatory signal to even happen and it requires when you are younger, it could be 0.5 g of leucine, it could be not much. It doesn't really matter when you are young and driven largely by hormones, doesn't have the same influence. However, as you age and there’re multiple studies that look at the amounts of leucine, let's say we want to say that in a 30 g high quality protein meal, there's 2.5 g of leucine. That is the minimum threshold for a more mature adult to stimulate mTORC1 for initiation of muscle protein synthesis. 

Again, we don't also know how long that stays active, but it is required for synthesis to even happen. And maybe this rate of synthesis declines after two to three hours. Again, maybe there's this refractory period, not totally sure, but that first meal of 30 g of protein is essential to stimulate this process when you are below that threshold and you are maturing, you will not stimulate this mechanistic target of rapamycin because of the change in skeletal muscle. Skeletal muscle has a decrease in efficiency of sensing the leucine threshold. So, I know that that is kind of a little deep into the weeds. But to bring it all back, one must understand that this-- and I talk about this in my book, so in my book, Forever Strong, which obviously we're talking about, is built on some of these premises of understanding this meal distribution because it's important, especially as we age. 

Melanie Avalon: Do you know, with that reduced capacity to sense leucine, if it's just like a mechanical breakdown byproduct of aging or is it no longer being prioritized by the body because of aging, which might be the same thing? Basically, is the body purposely not caring as much anymore because we've reached a certain timeline and it's not important to have muscle as much or is it a defect from aging? 

Gabrielle Lyon: It may be a biological process, this anabolic resistance. And again, it's really just the efficiency of utilization. And arguably there's efficiency of a lot of things that go down as we age, whether it's mitochondria, a protein turnover, just the efficiency of our body over time. And one could look at, there's the hallmarks of aging, that paper that originally came out in 2013 that highlights this. But whether it is and it's interesting you asked this question because you're asking a direct question. And my answer would be I don't know what a very active older individual if their efficiency would go down at the same rate. But I would say for the majority of the population, we can assume that anabolic resistance happens.

And also, anabolic resistance can happen with obesity. And it could just be a reflection of the health of skeletal muscle. And that's why understanding that it is this 24-hour amount of dietary protein, which I recommend it 0.7 to 1 gram per pound, ideal body weight. But typically, the way in which it is distributed is important for an aging individual, but not necessarily for an athlete. So according to the ISSN, if you look at their protein timing and recommendations for athletes, they care more about a 24-hour period. But if you believe in the data of so much of this work, looking at meal distribution and muscle protein synthesis threshold, then you would have to infer that the protein dosing is important and the way in which it's dosed is critical. 

Melanie Avalon: Well, actually to that point, and that was the question I had, is that potential of the elongated 24-hour window for the athletes because the resistance training and exercise has primed their system to be more receptive and so they have more leeway? Is that a potential? I know you talked in the book about how you might actually need less protein when you are resistance training because you become so much more and I'm using such casual terminology, but it becomes more receptive, essentially. 

Gabrielle Lyon: Well, an athlete has a highly trained muscle, and also, they're younger. They probably have more hormones, a better hormonal status. And the balance between diet and exercise and hormones shifts. With shifting when you are young, you have good capillary perfusion, you have great blood flow, good splanchnic extraction. You're able to absorb the foods that you're eating. As you age capillary perfusion decreases, IGF-1 decreases, testosterone decreases, all of which impact skeletal muscle over time. 

Melanie Avalon: Okay, got you. I want to know if the body is doing this completely on purpose or if it's-- 

Gabrielle Lyon: No, no. It's kind of like if you don't start a car for a long well, think about it. I've had actually been asked this question before and I thought about this a lot, is think about a car that you don't start, you might drain the battery. It's not because the car is trying to drain the battery, it's because it hasn't been used. And this is where use becomes to be critical. The body was designed to move. If you don't use it, you lose it. This is no different. It's not that it becomes we are aging and there is a reality to aging. And I know some people say aging is a disease. I don't know. I mean, ultimately there is an end of life and in the US, we try to forget that that is a thing. We can talk about longevity. And to me it's not all about longevity. It's at some point we all die. How do we want to live while we have the time to do so? 

Melanie Avalon: Yeah. Our health span compared to our lifespan as well. The actual leucine, when it activates mTORC1, how long does it stay activated? And is it binary? So is it basically-- because you said younger population, it doesn't require that threshold to activate, whereas when you're older it does. So how much of it is a spectrum versus being binary on and off? 

Gabrielle Lyon: Great, great question. I think that it is always on and off. I say that. But is that true? We also know that mTOR, again, mechanistic target of rapamycin mTOR is in every cell and it's in the pancreas and it's in the brain and it's activated and can remain more of a low-level hum as you age. But specifically, when we're talking about skeletal muscle, it is an on or off thing. It doesn't kind of happen or kind of not. But when you're young, the sensitivity and the threshold is likely substantially lower. And also, other things that activate mTORC1 in skeletal muscle are insulin, are exercise, there're other influences and I would say that the relationship between that changes. So, when you're younger, it's insulin and growth hormones. And when you're older, the way to stimulate that tissue is going to be through diet and exercise. So, the balance between the two. 

Melanie Avalon: What about mTORC2? Is it involved with this at all? 

Gabrielle Lyon: No, it's not. That is involved in other tissues. I actually haven't spent a lot of time studying that protein complex. But yes, I would say that it is not. 

Melanie Avalon: Whenever I hear them thrown around like the C1, C2, it's usually the vibe that's given is they're pretty similar. Like there's not usually much distinction that I receive. So, this is a big distinction if the C1 is the primary one with the muscle. So, speaking of these different-- because you just mentioned all these different ways that you can stimulate like the role of exercise, diet, all these things. Does just eating protein or just eating leucine, can it stimulate muscle growth or do you also have to have physical stimulus. 

Gabrielle Lyon: Another genius question. If you are potentially low or deficient in skeletal muscle, I think there is a degree of laying down tissue that will happen. If you are healthy and not, "deficient in protein or deficient in muscle," you do require stimulation. You do require that stimulus, but one is not going to happen necessarily without the other. If you are on 100% high carbohydrate diet and you're not getting these amino acids, it's not going to happen. You do require amino acids. Great questions. 

Melanie Avalon: Thank you. [chuckles] I've just been thinking about all this for so long. Okay, here's a question for you. When you are eating, and maybe we should tell the listeners and listeners, you've got to get Forever Strong, because I know we're going way in the nuance of all these things, but there's so much information in this book and there's very applicable implementable, easy to do, [chuckles] easy to understand protocols. So definitely get the book because it's a very valuable resource and there's a lot of mindset as well at the end of every chapter, which is super encouraging and motivating and really important as well in this whole journey. So, the RDAs, how did you formulate your Lyon RDAs for protein amounts compared to the official ones? Which was kind of shocking to learn the history behind that and especially like, the similarities between the Great Depression amounts of protein. 

Gabrielle Lyon: Yeah. I'm so glad you liked this book, Melanie, because I know how many books that you read. 

Melanie Avalon: Oh, I love it. I love it. 

Gabrielle Lyon: There's just so much history behind this. So, the dietary protein recommendations really came from initially out of need, out of the Great Depression, when they drafted about a million soldiers and everybody was unfit for war, it was somewhat of an emergency. And after that happened, they started to say, "Well, listen, we got to fix this." How are we going to get people strong? And the way we're going to get people strong is that we're going to feed them high quality proteins. They need to eat liver, they need to eat beef, they need to eat fruits and vegetables, and they need to be vital. And then they highlighted the importance of dietary protein.

Again, they didn't actually know in detail what that was going to be, that number per se they then-- And I will also mention that they said either you're helping Uncle Sam or you're helping Hitler. And in order to help Hitler, it was a very high processed carbohydrate diet and low-protein diet. And by the way, we are seeing a push for a lower protein diet. Just to kind of mention that you guys have to get the book to read a little bit about the history, but you know we are seeing narratives reemerging in that way. In 1968, they issued the first dietary guidelines for protein, and that was 0.37 grams per pound, which is if I'm 115 pounds then that's 45 g of protein and that's the minimum to prevent deficiencies. That number has not been changed to this day. 

Melanie Avalon: I would be starving. [laughs] I'm so hungry just thinking about that. Also, just really quick sidenote, something that blew my-- it was a mind-blown moment reading your book when you talked about the role of regulation and the health claims or the education that can happen from commodities versus non-commodity products. It basically explained about how plant-based processed foods can make a lot of health claims and your steak can't blew my mind.

Gabrielle Lyon: Yeah. And we'll just highlight for the listener. So basically, you have whole foods which are commodities, beef, chicken, soy, corn, whatever, a whole food commodity under the USDA. Then you have processed foods that are under FTC and conglomerate like that and the USDA collectively. All the farmers put together their money and their collective marketing budget of 750 million. One company like PepsiCo is almost a $2 billion budget. And we know that whoever controls the money, controls the narrative. And what you are hearing, not only that one can be disparaging against the other. Processed foods can largely say whatever they want until they're shut down versus a commodity has much more strict guidelines and they can't say anything. They can't say beef is better than X, Y and Z or beef is a better source of protein than a fake plant burger, whereas a plant burger can say whatever they want. 

Melanie Avalon: It's so upsetting. I never thought about it before, but you talk about how the gut milk thing, that's not any one brand, it's just like milk. I was like, "You're right." It never occurred to me [chuckles] that there's not like-- the "education comes from the collective of the meat or the milk or the egg industry." But then when you're talking about how they can't actually even really educate or make claims, it was really frustrating. Going back to that 14-gram recommendation. So compared to your recommendation, how intuitive-- because there's this whole world of intuitive eating. How intuitive is getting this adequate protein? Can a person just-- will their body tell them they need more protein and they can be intuitive if they really listen? Or do they really have to weigh and measure to make sure they're getting enough protein? 

Gabrielle Lyon: Well, there is this concept called the protein leverage hypothesis when basically your body will be driven to eat a certain percentage of calories from protein. The issue with intuitive eating is you don't do intuitive banking; you don't do intuitive driving. You measure things. Once you get a sense of what it is that you are eating, then you can become more intuitive when you have a baseline understanding. But going right to intuitive eating, I think is a mistake because again, nutrition is a science. And if we dose it correctly and you have a sense of where you are when you're feeling great and how you're eating, when you're feeling great. Then it's a non-negotiable. 

Melanie Avalon: And then how about the actual protein type that you're eating? So, plant versus animal, and then I'm really interested in within the animal world, land versus sea, because I go down the rabbit hole of, like, "inflammatory amino acid profiles." So, I'm curious if you have thoughts on that. 

Gabrielle Lyon: Well, they are not interchangeable. Animal and plant protein are not interchangeable. You cannot say, for example, a fake meat burger is the same as a beef burger even if the fake meat burger has more phytonutrients per se. There are different metabolomics and different metabolites that just, again are completely different. Animal-based products, gravity-bearing products are going to be the highest quality. But then again, whey is the gold standard. So, whey-- as a percentage of leucine, whey is the gold standard for an amino acid profile that is robust closest to ours. Fish has about 5 g of protein per 1 ounce, whereas beef, say, has 8 g of protein per 1 ounce. But the difference isn't just in the amino acids. It's also in the food matrix. So, beef would have anserine, carnitine, creatine, more iron, potentially B12, etc., whereas fish may have more omega-3s or other kinds of other nutrient values. Therefore, in my mind, there is a place for both, but they are not interchangeable. Hopefully that answered your question. 

Melanie Avalon: It does. And you mentioned in the book that if people are doing, like, getting it all from plants that they likely need I had it written down, like, 34%. 

Gabrielle Lyon: So basically, it's also really important to understand that, again, we're just talking about protein. We're talking about amino acids. What about all the other low molecular weight bioactive compounds like creatine? You're not going to get that from plants. You're not going to get taurine, which is really important for aging and potentially energy for eyes. You're not going to get that, they're not interchangeable, and we shouldn't be eliminating food groups. There should be an interface between the two. 

Melanie Avalon: And when it comes to creatine, because people are talking about creatine all the time. And so, I'm often thinking, like, "Should I be taking creatine?" Do you need to add any specific amino acids if you are eating a shockingly high-protein diet? Like, I eat a shockingly high-protein diet? 

Gabrielle Lyon: No, you would not be someone who needs creatine then. 

Melanie Avalon: Okay. I eat like pounds and pounds [chuckles] of meat every night. Okay. And this is a very random question, but the thermic effect potential of protein. I'm curious because you talk in the book about how the amino acids from when we eat a meal, they're used structurally, but then they can also be used as fuel and then they can also be converted into essentially glucose. Do you know if the thermic effect of protein differs based on how you're using those amino acids? 

Gabrielle Lyon: It does. And that's why you see variations in the literature from 15% to potentially 20% of this thermic effect of food. So, if you were eating 100 grams of just pure protein, your net caloric cite the body might recognize 80 calories of protein. Or if you're eating 100 calories of protein, if you are eating it in a particular meal threshold, again, this is my thoughts as well as Don's, that it's that muscle protein synthetic response that generates the variations in thermic effect of feeding. So, if it's lower, maybe you're influencing thermic effect of feeding at 15%, maybe a little bit lower. But when you're hitting this threshold and challenging the machinery, that is what makes a difference. 

Melanie Avalon: Oh, wow. I'm so excited that you had answer to that. I was like, "This is going to be too nuanced of a question," or not nuanced, but too, like, random. What you just said to clarify your theory is that thermic effect ramps up when you're going past the limit.

Gabrielle Lyon: Yep.

Melanie Avalon: Okay. Oh, wow. Okay, that's so fascinating. Oh, and then we talked about this on The Intermittent Fasting Podcast. Vanessa Spina was talking about what she learned from you and Dr. Layman. And we talked about this and we got so much kickback on this, which is protein turning to glucose. So, what are your thoughts on how much glucose from a given meal can potentially or does turn into glucose? 

Gabrielle Lyon: Yeah. I think it just depends. Is it substrate driven? So, there're various influences, but a good rule of thumb is 100 g of dietary protein may generate 60 g of glucose, potentially. But again, I think that it depends on the state of the person and it depends on and it's through gluconeogenesis. So, it's not like you're eating 100 g of protein and then it's just converting to sugar. It's not this immediate process. It really depends, I think, on other influences and how much you have and the state of, again, how much glucose that you have in a bloodstream. I think that there're multiple influences, but the rule of thumb is for every 100 g of dietary protein you will generate through gluconeogenesis, around 60 g. 

Melanie Avalon: Oh, and then with that, because you talk in the book about seeing potentially slightly higher resting blood sugar and/or HbA1c-- probably and HbA1c in people on high-protein diets. Are you concerned about that at all or how do you feel about that? 

Gabrielle Lyon: No, because insulin is good. Insulin, triglycerides are typically all good.

Melanie Avalon: Okay. And what about the liver enzyme elevations temporarily in women? What do you think is happening there? 

Gabrielle Lyon: I don't necessarily see that. What I will say is that when individuals eat larger one huge protein meal, as opposed to potentially a more distributed amount, you may see a bigger liver versus bigger skeletal muscle. But again, the changes may be so slight. I don't see a ton of increase in liver enzymes. I do see increase in liver enzymes when people are training, but again, it's transient. 

Melanie Avalon: Okay. So, at the end of the book, you do provide these three different tracks. How did you come up with these tracks? And how can people know which track to go on? And is there one track that does all of them? 

Gabrielle Lyon: These tracks are developed through again clinical practice. I saw what needed to happen, and I've been a physician since 2006. So over time, you see the impact and the influence of these things. A great place to start for everybody would be, again, if they have weight to lose, then I would do a weight loss track. If they don't have weight to lose, like, for someone like you, I would stick to a longevity track. Individuals would just feel great. But again, this book is for everybody. And Melanie, if we can get this book out there, it will change the conversation completely. 

Melanie Avalon: I agree. I agree so much. It's one of those books where and I said this at the beginning and I'm saying it again, it's just this massive huge paradigm shift that has implications about literally everything in medicine. And I'm really, really shocked that this is not out there more. And maybe that's like a good question to sort of end with. Why do you think this hasn't been realized yet? Why do we end up here? 

Gabrielle Lyon: Because as humans, we continue to ask the same question over and over again and we are not necessarily thinking outside the box. And again, I coined the term Muscle Centric Medicine from decades of experience. In order to have flashes of insight, you have to be in the weeds doing the work for decades, and you just wait for that moment of insight to come. The other aspect is that when we continue to ask the same question over and over again and want a different answer, we have to wake up to the fact that if we're not getting a different answer, maybe it's because we're asking the wrong question. 

Melanie Avalon: Yeah. Actually, another book I'm reading right now, it's called What's Gotten Into You. But it's about the history of the discovery of all the particles of the universe and atoms and electrons and everything, and the personal story of everybody making those discoveries and the takeaway-- And I'm having it again, talking to you right now, is that so much of this is just like chance. It's just like, what researcher happened to discover something at some point and then that became like the thing that we focused on, and then it's so hard to change. So, I feel like I will be so excited to see a few decades from now, hopefully there's maybe hopefully before, a complete shift, and it'll be like, Dr. Gabrielle Lyon was first talking about this, [laughs] and then here we are. Hopefully it'll become the new norm. I really hope so. 

Gabrielle Lyon: It's going to happen. It's going to happen. Well, thank you so much for having me. And again, depending on when this comes out, they can go to my website drgabriellelyon.com. I'm giving away $200 worth of just free stuff with one purchase of the book. They can also get it on Amazon. And let's see. I have a great podcast called The Dr. Gabrielle Lyon Show. Great newsletter. I'm on Instagram, I'm on Twitter now called X, YouTube, you name it, you can find me. 

Melanie Avalon: Well, thank you so much, Dr. Lyon. We will put all of this in the show notes. Those will be at melanieavalon.com/foreverstrong. Last question, I promise it's super easy, super-fast, and it's just because I realize more and more each day the importance of mindset, which, like I said, listeners, is also all throughout the book. So, what is something that you're grateful for? 

Gabrielle Lyon: I'm grateful for the opportunity to share this message and I'm grateful for the opportunity to show my children how one message can change the world. 

Melanie Avalon: I love it. Well, thank you so much. I am so, so grateful, words cannot even describe how grateful I am for what you're doing. And I'm so excited for everybody to read this book and bring on the paradigm shift. Thank you for what you're doing. I'll talk to you very soon. 

Gabrielle Lyon: Thanks, Melanie. 

Melanie Avalon: Bye.

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