Dr. Gabrielle Lyon – Is Muscle The Organ of Longevity?

Content By: Ari Whitten & Dr. Gabrielle Lyon

In this episode, I am speaking with Dr. Gabrielle Lyon, who is a Washington University fellowship-trained physician in nutritional science and geriatrics and is board-certified in family medicine, and osteopathic manipulation. We will talk about the link between muscle health and longevity and mitochondria.

Table of Contents

In this podcast, Dr. Lyon and I discuss:

  • Why muscle should be considered the “organ of longevity”
  • How lifestyle choices impact mitochondrial health and speed the aging process, similar to muscle loss
  • The effect of excess fat on mitochondrial capacity
  • The role of endurance training, HIIT, AND strength training in optimizing mitochondria
  • Why a sedentary lifestyle inevitably leads to a “disease state”
  • The significance of sufficient protein for retaining skeletal muscle and maintaining mitochondria health

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Ari: Dr. Lyon, my friend. Welcome to the mitochondria summit. It is such a pleasure to have you.

 Dr. Lyon: Yeah, it is really great to see you. I am so sorry that we do not get to sit down in person but who knows? Maybe over the summer, we will get to do it again.

 Ari: For sure. I will see you in San Diego if you are there.

 Dr. Lyon: Yes, I will be there.

The link between muscle tissue and mitochondrial health

 Ari: Cool. Where shall we begin? We need to talk about how all of your work around body composition links to mitochondrial health and energy levels. What is your paradigm around understanding that connection?

 Dr. Lyon: Yeah. Well, the first thing that I want to say is that we know muscle is the organ of longevity and muscle is the largest organ system in the body. It is not the skin, it is not anything else, the heart, you name it, the endocrine system, skeletal muscle in and of itself, it its own organ system. And when you talk about mitochondria, as you can imagine, if skeletal muscle makes up 40% of our body weight, I do not know, are you pretty muscular, so for you maybe it is 50% but the reality is the majority of our mitochondria make skeletal muscle, in within skeletal muscle makes skeletal muscle a perfect way to study mitochondrial health because of just the sheer capacity in the way in which we can leverage skeletal muscle to improve mitochondrial health. And that is really how I think about it is, I was prepping for this summit thinking about, okay, well, how do we focus on mitochondrial health for the individual and what can they do about it? And just from a foundational aspect, what changes, and why does it change?

 Ari: Yeah. Why do you call muscle the organ of longevity? What is the scientific basis of that?

 Dr. Lyon: Well, the idea that muscle is the organ of longevity really focuses on the concept that the healthier our muscle is the more, the more healthy muscle we have. People will say, “Well, body-builders do not live longer,” That may be true, but we are talking about within a physiological norm that the healthier our skeletal muscle system is because of its pinnacle role in longevity, body composition, and energy metabolism the better off that we are. It truly is the organ of longevity.

And when we think about mitochondrial health there are a lot of discussions that as we age there are fundamental changes that have to happen within the mitochondria from a negative aspect. We talk about this increase in free radical formation, this decrease in mitochondria’s ability to clean itself, and mitophagy but the reality is we know that under a microscope if you were to look at a very fit 70-year-old and compared the mitochondria to a very fit 20 year old you would not actually be able to tell the difference, which is crazy. But the reality is we often look at the healthy, sedentary, older population and there is no such thing. Healthy, sedentary, any population is a misnomer, it does not exist. And really, the healthier our skeletal muscle is by default the healthier our mitochondria.

 Ari: We have a number of lines of evidence showing that with each decade of life mitochondrial capacity in skeletal muscle declines by about 10% which may not sound like that much when you phrase it like that but the average 70-year-old has lost 75% of their mitochondrial capacity compared to a young adult, 75%. I often tell people this is like going from a Ferrari engine in your cells when you are 20 to a moped engine when you are 70.

And we also know that if you look at a 70-year-old who is a lifelong exerciser they do not lose 75% of their mitochondrial capacity. They have the same mitochondrial capacity as a young person. We know that this is not actually a normal process of aging per se this is actually the result of the modern lifestyle. What is going on there? Can you add some layers to that story?

 Dr. Lyon: Absolutely. What you are saying is very, very critical. Basically, to sum it up for the listener is that by the time someone gets to 70, they have lost the majority of mitochondrial function and overall mitochondria especially as it relates to skeletal muscle. I will say when we think about the health of mitochondria why it is so important is we can actually feel it and initially the cellular changes we do not feel, right?

From a fundamental process that happens from an individual who is sedentary the ability of the mitochondria to replace itself to go through this process of mitophagy decreases again, an individual who is not exercising. The ability to utilize energy so for beta-oxidation, for fatty acid oxidation so that is really energy utility, utilizing the food that you are eating. The other thing that happens which is so interesting as it relates to mitochondrial health is this decrease in flux within skeletal muscle. This decrease in flux that happens. When we think about healthy skeletal muscle. I talk about it from a way in which we can all picture it.

We can all picture what a fillet looks like, a fillet steak looks like it is red, it does not have a bunch of fat marbling, it looks unified. As individuals age, not even as they age, as they age and become sedentary as they begin to gain body fat, body fat is not just in the periphery, it is not just visceral body fat, it is not just the body fat that you see but you get ectopic deposits of body fats and you get fat that infiltrates and deposits within skeletal muscle. What ultimately happens, and again, this is a very complex topic. There are all kinds of fat, metabolites that end up affecting skeletal muscle which all increase the risk of insulin resistance and increase in damage to these mitochondria, the mitochondria. And decrease its ability to counterbalance what is happening. This fat infiltrates. And then the other thing that happens is that the infiltration of fat it affects the mitochondria.

 It also affects contractility, an individual’s ability to exercise to full capacity the tissue changes. And one-third of all adults report fatigue, that is one-third. They report some form of fatigue as it relates to muscle strength. If the tissue in and of itself is unhealthy the house that the mitochondria live in is unhealthy. We know that left alone muscle strength declines by 1.5% per year from the ages of 50 to 60. I think that it is more but again, just looking at the literature between 50 and 60 years old you are losing 1.5% of your strength per year. And then, as you mentioned, over the age of 70, or 75, an individual loses 3% per year. Okay. And when we think about that, that actually coincides with an increase in the rise of diabetes, cardiovascular disease, and Alzheimer’s disease. And I always frame it as these are diseases of skeletal muscle but you have provided an opportunity to say why. Why are these diseases that over 80% of individuals over a certain age are getting? And it is because of the health of skeletal muscle. I often talk about it as it relates to muscle mass and strength and its metabolic impact. But on a cellular level, what is it? And it is mitochondria.

Hopefully, that kind of lays out the foundation of the potentiality of what can happen. And then when an individual is not moving that skeletal muscle that we can think of as a suitcase becomes overpacked and it is really this decrease in flux of energy utilization. Whether it is doing resistance exercise or, you know, as it relates to mitochondrial health. I did my fellowship at WashU, Washington University in Saint Louis, and Hallisay. The guy, he was like the godfather of exercise and mitochondrial health. I mean, he was 80 at the time, he was still there. And he is, I think in the 60s began to publish this research about cellular health, mitochondrial health, and exercise. Anyway, that kind of gives the big picture and lays a bit of a foundation as to what happens and hints to what can we actually do to prevent it.

The role of flux

 Ari: You mentioned this word flux. Can you define what that is?

 Dr. Lyon: Yeah. This idea of flux is that when individuals become sedentary there is glycogen which is a storage form of carbohydrates, fatty acids. Skeletal muscle uses a lot of fatty acids. Fatty acid metabolism one primary site is skeletal muscle. Glucose utilization is in part largely done by skeletal muscle.

Flux is the ebb and flow of these substrates, the ebb and flow of the fatty acid metabolism, and the ebb and flow of moving that glycogen out. If you think about it, if you have, I do not know, an item and you leave it around for a long period of time dust accumulates on it, and then things stack up but flux as if you are constantly dusting it off. And that is essentially through exercise, through resistance exercise is through walking, even walking and doing some type of endurance training, and then, of course, you layer on hit high-intensity interval training and sprint interval training, it increases the flux. The skeletal muscle must use these substrates. And that is one of the keys to overall health if we believe the paradigm that skeletal muscle is the organ of longevity and obesity is a consequence of unhealthy muscle.

And ultimately all the other things that we are seeing are really they are anchored in skeletal muscle. It is the only thing that we can leverage. I mean, can you go exercise your liver? Do not say drinking. You can not. You can not exercise your liver. Can you exercise your heart? Yes. But, you could not sit here, I mean, you are kind of a very in-tune person, you might be able to sit here and raise your heart rate, 100, 250 beats per minute but I can not do that, the majority of people can not but I can pick something up and do a bicep curl, I can go and run, do a sprint around the block, not effectively and I look ridiculous but I can still do it. The skeletal muscle is the only organ system that we have direct control over. And that becomes critical to understanding if we want to improve skeletal muscle energetics and we want to improve mitochondrial energetics.

How do we get ahead of these cellular changes that we have been fed happened with aging?

And it is not true if you look at some of Bright Goodpasture’s work and the original work of Holz. And we stand on the shoulders of giants and we look at the evidence. We know that we can impact in a positive way through nutrition through exercise through even supplementation. There are some very interesting nutraceuticals that are very good evidence which is incredible. One is something called urolithin A which I have been very interested in and looking in the research about ways in which we can come in to affect that mitochondrial biogenesis that the health of the mitochondria.

 Ari: Yeah. Beautifully explained. There is an exercise physiologist named Inigo San Milan. I am sure you have probably heard of him. And he studies in his lab, metabolic health. And he studies athletes of various kinds and a particular focus on endurance athletes. And he also studies what he terms are the opposite end of the spectrum of metabolic health which are obese, diabetics, and people with metabolic syndrome. And he has found in his lab that there is about a 400% difference in the number of mitochondria in the mitochondrial capacity between athletes and people with metabolic syndrome. You literally have a 400% bigger engine in the cells of your skeletal muscle if you are an athlete compared to an overweight person with diabetes or metabolic syndrome. Again, Ferrari engine versus moped engine, this is not a small difference, it is not five or 10% difference it is 400% difference. And you made me think of this because you mentioned the word flux. And there is actually a couple of layers that I want to go into this with you on. But one thing that he found that is interesting is this weird paradox where both people with metabolic syndrome and endurance athletes, but actually.

 Dr. Lyon: I know exactly where you are going.

 Ari: Interestingly not the general population of the typical average person who is not an athlete and is not very overweight and with metabolic syndrome, that does not apply to them. But both of the extremes, the endurance athlete and the overweight people have large fat drop deposits in their muscle cells. And it seemed to them a weird paradox that the athletes would have the fat droplets the same as the overweight person. But they found that the difference is flux. The difference is. Since you know where I am going with it, you describe it.

 Dr. Lyon:  Yeah. I am not surprised at how well-read you are on this topic. And what you are describing is this, it is called exactly what you are saying, the athlete’s paradox. There is all different ways in which fat can be stored in skeletal muscle. There is intermediate cellular fat, there is intramuscular fat, and there is interfat tissue. It can be in the tissue, around the tissue, or in all the different places. And one of the things that is so important to understand is fat is a good fuel source. And those endurance athletes rely on the fuel source above and beyond glycogen, muscle glycogen which, by the way, is one way in which muscles get energy. It is not actually directly available in the bloodstream. People will say, “Well, my muscles will help stabilize my blood sugar,” well, it does not directly and these amino acids have to go to the or these substrates have to go to the liver to then help maintain blood sugar. But the flux is what keeps these athletes healthy. They have designed their body and as we think about mitochondria on muscle it is adaptable which is very interesting. It is adaptable. And the fat droplets within the muscle are adapted for the athlete to be able to execute any span of endurance-type activities.

 And it is healthy because of the flux. It is not just sitting there with sedentary behavior with decreased flux comes increase in reactive oxygen species, increase in these what is called dice or glycerols, increase in these ceramides. These are byproducts that build up and there is a whole bunch.

And listen, if you were to go on PubMed, you were to Google mitochondrial dysfunction you will see probably a thousand different theories and a thousand different reasons why is it, endoplasmic reticulum stress, is it decrease in NAD, is it a decreasing glutathione, you name it. And the reason I point that out is it really highlights the complexity of the scientific literature out there. And what we can do is, is we can simplify it in a way that we understand that the body is adaptable. And we can train our muscles directly and subsequently train our mitochondria. And it is probably the biggest mover that we have individuals with metabolic syndrome. And when I think about for the listener what they would do and they would say, “Well, how do I know if I have metabolic syndrome?”

It is a collection of symptoms or not symptoms, it is a collection of signs. And some of those signs would be looking at blood work and seeing an increase in triglyceride levels or an increase in fasting glucose and an increase in fasting insulin and potentially elevated levels of body fat and hypertension, these kinds of things. If you have those things you can say that in some area, on some degree, your mitochondria is likely, not healthy. certainly, your muscle is not healthy.

And again, it is not a black or white picture, it is just like flux happens and does not. This spectrum of change is not linear and this spectrum of change is what we call the catabolic crisis of aging which we can, of course, discuss if you want. When we are doing activities like endurance-type activities and high-intensity interval training and getting out and moving, and let us say. I would say three to four days a week someone should be involved in resistance-type activities that really pushes their body.

I am not calling Ari on the phone doing a bicep curl and not fatiguing my muscle because again, we can not say, okay, mitochondrial turnover but I can say, well, I am going to work hard enough so that my muscles are fatigued over the week if we break it down into a week. And then doing some kind of high-intensity interval training and some kind of longer endurance to improve that flux. This was a long-winded way of saying that there is a paradox of what we see if someone were to look in the literature that, yes, it is a fuel source for those that are highly active and it is something that is deadly for individuals over a lifetime.

 Ari: And the difference is that the fat that is in the muscles of those athletes is moving constantly.

 Dr. Lyon: All the time. All the time.

 Ari: The fat that is there is temporarily there only for a few hours before it gets used up whereas the fat in the overweight people is just stuck there producing all these toxic byproducts.

 Dr. Lyon: Exactly. And what are these toxic byproducts that leverage and what do they do? Well, again, if we believe muscle is this organ of longevity and muscle is the home to mitochondria and we know that as it relates to glucose disposal, utilizing of glucose from the diet it has to go to muscle. And if that muscle is already overpacked we are going to start seeing an increase in blood sugar, we are going to start seeing an increase in triglycerides, we are going to see an increase in fasting levels of insulin. We can directly see the impact from skeletal muscle as the primary site of our metabolism, essentially.

The important role of endurance training in healthy individuals

 Ari: Another thing that came out of my listening to the work of Inigo San Milan. This exercise physiologist researcher that I mentioned. He said something that struck me in a bad way. He said that when he tests the metabolic health of athletes who just lift weights and do high-intensity interval training they do not have nearly as ideal metabolic health as the ones who are endurance athletes and as someone who had just spent at that time 20-plus years only doing resistance exercise in high-intensity interval training and not doing any endurance training. I went, well, damn, that really sucks.

 Dr. Lyon: There is still hope for you.

 Ari: Yeah. There is still hope. I have since dramatically upped my endurance activity because of that. But what is interesting about this is I just want to impose the cultural narrative, the dominant narratives, and popular narratives within the evidence-based fitness nutrition movements. For the last 20-plus years, it was very focused on, hey, endurance training is kind of a waste of time. It is silly cardio, it is not really effective for fat loss, and it is kind of worthless. If you want to waste your time doing that stuff, that is fine but it is not really needed. What you really need to do is lift weights and control your diet to look good. And now you have this very smart exercise physiologist saying, actually, it is pretty important to overall metabolic health. I am wondering if you have any thoughts on that. And maybe like me, you have.

 Dr. Lyon: Yes. I have.

 Ari:  Maybe change your relationship with endurance exercise.

 Dr. Lyon: I love that you are bringing this up. It is interesting the narrative swing. Initially, it is Jane Fonda. Let us just do cardio, you got to get a great bandanna and amazing leg warmers and that is all you need to do. And for the longest time that was what everybody did. You and I were not doing that. But you understand the picture. Everyone was eating the food guy pyramid and doing lots of cardio and no weights. And now over the last, I do not know what would you say, but maybe the last ten years or so, maybe not quite that long, it is been do not do any zone two cardio, do not do any endurance training. All of that is an absolute waste of time which is not the case at all. And that is not what the evidence would suggest, especially as it relates to mitochondrial health. Resistance exercise and high-intensity interval training are great for flux utilization. It is great for strength and hypertrophy. But as it relates to overall mitochondrial health, mitochondrial health, and say VO2 max which is a way in which individuals are measuring output like this respiratory quotient.

And this output is all about endurance training. Endurance training is a critical component of overall health and wellness. And actually, the combination of endurance training with resistance is key. And it is interesting if you go back and you look into the literature, the majority of literature when it talks about input into input and outcome in about and around mitochondrial health it is all about endurance training. You are absolutely correct in saying it is super important.

In fact, my husband just ran the Boston Marathon speaking of endurance training. And this was a former Navy SEAL who is kind of a tank-ish dude who, for him, it was always about weight training. And as we all think about longevity and what is it going to take to not just have longevity but also to have energy. But increase in energy and a decrease in fatigue we have to think about endurance training. And I am curious as to how much endurance training you are doing nowadays.

 Ari: I started actually riding a bike. I started using a friction trainer. I set up a bike with a friction trainer. And then measuring my heart rate. I started measuring my heart rate for the first time so that I could be in zone two and do 45-minute sessions on the bike. But the problem was right now I am doing so much surfing almost every morning for two plus hours.

 Dr. Lyon: So rough.

 Ari: And I started playing tennis. And I am doing jujitsu. And I am doing capoeira. I realized I am doing so much endurance and high-intensity interval training, plus I am doing weight training like four days a week. I realized I just do not have the bandwidth to fit in the dedicated zone two sessions. I am doing many hours, sometimes three or four hours a day of a combination of endurance and high-intensity interval training but it is not perfectly zoned too. But I just do not have the bandwidth to fit in extra zone to work beyond all the stuff I am doing. And I figure I probably got it covered at this point.

 Dr. Lyon:  Yes. Very active. I think you bring up a good point. I mean, when we think about the current recommendations and what do we know, we know that only 24% of adults are meeting the daily activity requirements, 24% are meeting both exercise aerobic activity and resistance training, 24% of adults, that is insane. Why is that? I think part of it is cultural, part of it is time. And then the question is, is knowing what to do? There is a lot of distraction that happens when individuals are distracted, then they do not execute. What can we do to mitigate some distractions and execute in a way that is meaningful? And to me, if the current recommendation is 150 minutes of moderate to vigorous activity a week plus two days of resistance-type training you are doing way more than that, you have met your needs, right?

 Ari:  I would say I probably get that per day, not per week.

 Dr. Lyon: Which is incredible. And if we know that baseline recommendations which is the minimum to prevent and eliminate active disease process then you are probably right on the money. And I would encourage everybody to do something where their heart rate goes up a bit over a period of time, it does not have to be something crazy, even if it is speed walking you are still getting some kind of activity, it does not have to be this running a marathon or running long distances but doing some kind of endurance type activity which could easily be also riding a bike. You can do it 30 minutes a day.

 Ari: What do you do personally for endurance?

 Dr. Lyon: Well, right now, for me, I am adding in one longer endurance session, a zone two session a week and that is 45 minutes on a Saturday or Sunday. And I have had to really work to do that because my normal proclivity would be to do some kind of resistance training which Ari and I, you and I have been friends for many years. You know exactly how I train. I do some kind of resistance and I will do some kind of high-intensity interval.

But I will not be spending a long time doing this endurance-type training. But because of the literature, it is so serendipitous that I have also been thinking about and reading. I have added in that one day as well as starting to add two other days where I am just doing it. We have an Airdyne bike. And instead of doing all-out sprints just doing a pacing, maybe it is 120 beats per minute, nothing crazy where I can have a nice conversation. Yeah.

 Ari:  Yeah. The Airdyne bike to do all out is pure torture. You got to be a serious masochist to do all-out intervals on that thing.

 Dr. Lyon: Yes. All of which I think is really critical but what I love about what you are saying is that it is all free. These are free ways in which people can move the needle if they understand the science. And they are motivated by the idea that people often think about fatigue as I am not sleeping well enough or maybe I eat too big of a meal and all of those things are true.

But what about doing that activity that truly moves the needle? I will give you an example. An individual could sleep all they want like sleep great and eat well and if they are not moving and if they are not actively recruiting skeletal muscle and focusing on what they need to do for strength, resilience, mobility, and mitochondrial health they will still feel terrible, they will still feel tired.

I do not care if you were eating perfectly and laying out. Have you gone on a vacation where you have totally relaxed and you are in Costa Rica, on the beach doing nothing? The more you do nothing the more tired you get even if you are sleeping, getting massaged, and eating well. I think that the way that the body is designed is we have these homeostatic processes which homeostasis is really just being in balance. And the homeostatic process which we normally go to is how do we influence the things that are easy. It is easy to eat well and people argue with me, no, It is, I mean, I think so. It is easy to get sleep even if you are not disciplined to do it does not mean that it is a difficult thing.

We are not talking about. The barrier to entry is, for example, I just came back from Special Operations Week in Florida and flew home, I could have easily gone to bed at an appropriate time because I had to wake up at frigging five in the morning to go train but I did not. I woke up at five to go train but I did not do the easy thing which is get sleep. The difficult thing is actually leveraging the physicality to be working hard enough and putting the effort into actually move the needle. The hard thing actually is exercise, especially as it relates to if you were to think about the body,

The body is designed for challenge. Nothing is more powerful than exercise, no medication. And the reason is, is because exercising skeletal muscle not only impacts the mitochondria but exercising skeletal muscle secretes these myokines there are peptides that travel throughout the body that interface with the immune system. We know that as individuals have healthy skeletal muscle they also have a healthier immune system. Skeletal muscle leveraging this house of the mitochondria does everything else. Challenges the homeostatic balance and that challenges are what is necessary.

Protein requirements for optimal health

 Ari: In the same vein of the example that you gave of sitting on the beach doing nothing and that not being energizing, it is also the case that if you provide more fuel to your mitochondria. Your mitochondria depend on mostly carbs and fats for fuel. And if you say, hey, maybe the reason I am not energetic enough is my mitochondria do not have enough fuel, maybe I will provide more carbs and fats. And of course, that not only does not energize you it actually is the opposite when you have a chronic excess of those fuels, it is actually toxic to your mitochondria. To your point, the body likes balance and I would add the body likes flux. Going back to the earlier point, the body likes to be in movement with these ebbs and flows with things flowing through it. It likes to be in movement with nutrients flowing in and out not in a static state. When the nutrients is stuck your body is stuck.

 Dr. Lyon: We have to because that static state would essentially be a disease state. I know that your community is very astute and they are very interested in the research and you do such a good job at providing that. If they go back and they look at the literature they will see populations of people defined as healthy, sedentary individuals. I would argue that that in and of itself is a disease model. It is a disease model. And as we begin to think, what does health mean? It does go back to muscle, It does go back to mitochondria because these are the things that we can leverage.

And especially from a nutritional aspect excess calories regardless of where you are getting it is very challenging. It is very challenging if you are not utilizing it and whether it is in the form of carbohydrates or fats, protein is very difficult to store as energy. But a fatty protein meal would be challenging for the body because now you are talking about it overconsumption of calories and those kinds of things. But lean proteins alone, those amino acids are very difficult to store. If we were to think about how would one eat for mitochondrial health, there is the bigger input which is movement and exercise.

That is probably 75% of the equation but 24% of people are doing it yet 100% of people are eating. How do we get the low-hanging fruit which is really nutritious? How do we get the thing right that 100% of people are doing? And we have to think about how do we fuel for mitochondria. And how do we fuel for mitochondria is how we fuel for muscle health. And I have often talked about dietary protein to help maintain muscle health and this is very suiting for the conversation of mitochondria because inactivity and as we age, again, could you overcome quote the aging process through activity? You could.

And the evidence you quoted is there. Aging is not a thing that happens. Are there normal things that potentially could happen? Yes. Do we know what an amazing healthy 80-year-old looks like? Now that is probably 1% of the population. As it relates to nutrition there are certain things. And I say this cautiously because I have always talked about this concept of anabolic resistance. And anabolic resistance is the inefficiency of skeletal muscle to sense dietary protein.

And why is that important? And just to take a step back to lay the foundation for the listener is skeletal muscle as an organ system is a nutrient-sensing system and it is exquisitely sensitive to dietary protein in particular amino acids. And one of the things in the literature that we see that happens with the quote aging population which now I have to rethink the way in which I speak about it, is the aging population is that we see a decreased ability for skeletal muscle to recognize these amino acids.

 The efficiency of utilization goes down and this is called anabolic resistance. We have seen people that we love that are older get sarcopenic and small. And that is often why people come to the clinic because they say, “Oh, my gosh, I do not want to age like my parent’s age,” but this idea of antibiotic resistance can be overcome by dosing dietary protein correctly. And, Ari, I have always talked about this even distribution of dietary protein and what does that mean? I often recommend one gram per pound ideal body weight for dietary protein as it relates to muscle health which then relates to mitochondrial health.

People will say, well, what is my ideal body weight? I will say, I have no idea. Ari does not know his ideal body weight and I do not know my ideal body weight but I could say I am 110 pounds. I am happy with that weight. I am what? A very low body fat percentage because that is just the place that I live. I am good with 110 grams of protein. If you know where you are happy, you can say it is one gram per pound of your ideal body weight make up that number, the last time you felt amazing you do that now.

Now for the longest time, I have said, okay, well you need to have a minimum of 30 grams of protein per meal to get enough of those amino acids to hit this mechanism within the skeletal muscle to create this muscle protein synthesis. I am sure the listener is going, “What is she talking about?” Well, 30 grams of protein that would be four ounces of a steak or four ounces of chicken, that would be the minimum requirement to stimulate this tissue. Well, turns out that it is actually the first meal and the last meal that is most critical. Or overcoming this anabolic resistance which simply means you are improving the efficiency of dietary protein to be recognized by skeletal muscle, to protect skeletal muscle.

Again, you are eating dietary protein because skeletal muscle is made up of protein. You have to eat that to lay down to do tissue turnover. We turn over 250 grams of proteins a day. We are only eating a hundred grams and maybe a bigger person is 350 grams of protein. If someone is thinking and listening and they want a tangible takeaway and their thinking, well, how do I protect my mitochondria by protecting my skeletal muscle? And I would say that the first and last meal of the day is most important.

And your protein target can be between, if you really want to get crazy with it, 40 and 50 grams of dietary protein which would equal a five-ounce or six-ounce protein serving or some kind of protein shake. First and last meal you will protect your tissue.

Ari:  And it is probably worth pointing out to people that this protein intake is not just important for building muscle but a huge portion of our body is made of proteins.

 Dr. Lyon: Yeah, nearly all of it. Exactly right.

 Ari:  Including much of what is in mitochondria as well?

 Dr. Lyon: Yes, absolutely. And when you eat with a protein-forward perspective in mind you support skeletal muscle and subsequently support mitochondrial health. And by really keeping calories in check, we know obviously gaining weight, decreasing blocks, excess calories really become toxic to just the overall metabolism and mitochondria in and of itself. Because you are now increasing free fatty acids and you are increasing glucose and all these things that really destroy mitochondria.

How do we design a diet that optimizes for mitochondrial health? And the way that you design a diet that optimizes for mitochondrial health is really twofold from my perspective. Number one, the foundation, and that foundation is dietary protein, and dosing that correctly, quite simply 40 to 50 grams, probably closer to 50 if everyone was thinking about doing it at that first and last meal, I do not really care about that middle meal. And it allows individuals to eat within a restricted window which is very big for people.

There is a lot of talk about autophagy. And there are many ways to get there which is really this body’s renewal process. But I do not care about that middle meal. And the reason I do not care about that middle meal is because the mechanisms of the input of the amino acids are still going. And I think that this might be a part two conversation but quite simply, the middle meal does not matter. That middle meal does not likely need to meet a threshold.

 Ari:  It is interesting that you say that. I have never heard somebody say that before. And I have noticed this through my own self-experimentation. And partly this results from living in a warm climate like I do in Costa Rica, during the time of year that I am here, I eat less. And there is some research suggesting that when you are in a hotter climate it tends to reduce appetite which is what I found.

I get super lean super easily when I combine, doing a lot of exercises, I am very active here and I combine that with eating two meals a day and I do not focus on eating a third meal in the middle of the day, I just focus on my first meal, maybe it comes after surfing, I get home at 10 or something like that, 10:30, and then I eat a second meal at 6:30. I can get super lean like that within a couple of weeks of doing that. I can lose multiple percentages of body fat doing that. And I find actually that if I incorporate a third meal in the middle of the day it does not really do anything significant as far as muscle mass but it does seem to prevent me from losing body fat.

Dr. Lyon:  Is not that amazing? You are already doing it, you are very tuned in. And you are actually by mistake or by design doing the things that we have now started to teach and move forward for practitioners which is exactly that. I just gave a lecture at obesity medicine and we talk about this.

Everyone’s thinking about it, and for the longest time, it was all about this even distribution. Well, it is kind of about the even distribution in some regards protect skeletal muscle but do we need that middle meal, you do not. And there is only two ways to stimulate muscle, exercise, and diet. You are already hitting that balance. I would encourage everybody to try what you were doing and what you are talking about, those two big meals, and then spacing it within an eight to nine-hour window. I would suggest everybody try that. I want to add.

 Ari: I will have 60 or 70 grams of protein in each meal.

 Dr. Lyon: I would love to point out something people will say, well, you can only absorb X, Y, and Z, 30 grams of protein. That is not true. You are utilizing all of that protein. From a muscle perspective at about 55 grams, you are probably no longer gaining muscle benefits but you are gaining benefits from everything else. All those other tissues that you talked about which include the liver, gut, skin, all the other tissues, all the other hormones, and all the other cellular processes are now getting benefits.

Urolithin A

Once something caps out for skeletal muscle. The reason I talk about eating for skeletal muscle is because that is our foundation but we need all of it. Now to the second part of how do we eat for mitochondrial health? I like to think about phytonutrients and I like to think about antioxidant capacity. And I will throw in there gut microbiome which is this compound urolithin A.

When I think about what are some things in the evidence that we know can improve mitophagy. And I would encourage everybody to go back and look at the literature on urolithin A. It is a post-biotic. And 30 to 40% of individuals do not even make it. And basically, we think about urolithin A there are these ellagic tannins that they come from pomegranates and other kinds of foods that are high polyphenol foods and the gut microbiome converts it to urolithin A. But not everybody can convert it which is so fascinating. And you are probably thinking, well, why do I care about urolithin A? Because in the literature there is 20 years of data that would support its impact on mitophagy which is the capacity of the body to regenerate and renew mitochondria. It is incredible. I am taking it Shayne’s taking it.

And I think it is going to be the next biggest thing after fish oil. You know how fish oil came out in these omega threes and we were seeing all of its effects. There is some very good evidence that improves strength and it improves endurance and VO2 max, things that are incredible. I think that combining dietary protein, understanding that there is a phytonutrient component which would be reds and greens, and if individuals are not interested in eating high volume which I am not, that you can do a red or green powder. That is easy. Again, how are you going to eat your fiber?

One should consider that. And then this post-biotic addition which would be urolithin A. Another supplement that I think is valuable is glutathione whether you are eating it or getting a shot. I think there is evidence to support the utilization of kind of that triad.

Ari: This is a big thing I have been debating for the last few minutes in my head whether we should open this up. But I think it is important. I know it is something you could talk about for 2 hours.

 Dr. Lyon:  But I might not know the answer.

The downside of dietary religions

Ari:  You do because we have talked about it in person before. The world is filled with lots of competing dietary cults, dietary religions, and dietary ideologies and they really are like cults, unfortunately. And there is also a lot of shady stuff that goes on, a lot of cherry-picking to support particular dietary narratives where an ignoring of evidence that conflicts with that.

And a lot of people wanting, strong financial incentives for people to have the next big secret diet, Hey, everybody else is stupid, keto and paleo and veganism and they all got it wrong, and really this is the greatest new thing. We have now got virtually I think everything other than water has been demonized at this point. And we have everything from the carnivore.

People who are convinced that broccoli and lentils and blueberries are trying to kill us and the vegan people who are convinced that your protein recommendations are deadly. Let us just speak to that component, this idea that high protein consumption is harmful to health is going to lead to increases in mTOR and is going to promote IGF-1 and cancer. Just summarize kind of the latest thinking on that.

 Dr. Lyon: Well, the first thing that I would want everyone to think critically about is what is actually considered high protein, what number would that be? We know that high protein is what? In the literature is not defined. But we do know that the bare minimum to prevent deficiencies is point eight grams per kg. Point eight grams per kg. I do not know what that comes out to be a pound, I do not know, you are good at math, but point eight grams per kg is a minimum to prevent deficiencies.

 Ari: Saying around point four.

 Dr. Lyon: Point four grams per pound is the bare minimum to prevent a deficiency would a high protein diet. And that is basically how that is set up. It is two standard deviations between what would be deficient. It is two standard deviations above what would be considered deficient. If that is the bare minimum and we were to double that number and we would get 1.6 grams per Kg. would that be considered a high protein diet?

No, that would be considered from a definition standpoint. If we double the minimum then that is moderate. We now double them. Now we know that one point six grams per kg may be more in line with optimal health yet people would say, well, then that would be considered high protein, it is not. High protein would likely be considered above two point two grams per KG.

 Ari: Or one gram of protein per pound.

 Dr. Lyon: Yeah. That would be considered more of a high-protein diet in terms of evidence to support dietary protein. Every study out there would suggest that if you look at body composition changes and body composition would be a decrease in body fat and an increase in skeletal muscle mass or at least the maintenance of lean body mass which I wish we had more time, we would talk about that. But Lean body mass is all tissues outside of adipose tissue. That every single one of those studies people do better above the RDA, above the minimum.

And in fact, they have landed on the general recommendation is between one point two to one point six grams per KG. Okay. This is now in a more optimal range. If someone were to say, okay, what is the issue with a higher protein diet, I would say, well, you are now at one point six grams per KG. Is it really that much higher? Not terribly. And at what point do we see any detrimental effects in the literature? And we have never seen detrimental effects even above three point three to three point four grams per kg Now, I am not saying people should eat that. But if we were really to say what is the evidence support and the evidence does not support any known issue with a high protein diet. And people need to take a step back and realize that the way in which these recommendations and these definitions came out were really to prevent bare minimum disease states. There is no evidence to support that.

And in fact, the lower your protein intake towards the RDA the more animal-based products that you need because you have to be able to compensate for the nutritional value. Meaning you have to be able to reach your bioavailable zinc, B12, multiple kinds of B vitamins, and iron. The lower an individual’s protein intake is the more it should actually be high-quality sources, animal-based sources. If an individual is choosing to just eat a plant-based diet they are going to require more total calories if they are eating whole foods and a higher amount of dietary protein which goes against if the protein is bad you are now needing to consume a higher amount of protein above and beyond that minimum amount of point eight grams per Kg. just to cover the amino acid need.

And again, it is kind of complex but just to simply understand there is no evidence to support that a quote high protein diet is detrimental. In fact, it is used for modalities, for individuals that have to undergo surgery, it is used for individuals that have to undergo healing, and a higher protein diet is used for those who have been injured or burned. In the academic arena, there is a whole host of reasons why a higher protein diet is better.

Okay, there is that piece. Then there was this whole big thing about red meat and cancer which has largely been retracted. And then the Annals of Internal Medicine examined this body of literature. The lead individual was named Johnston. And for those people that are not aware, the Annals of Internal Medicine is like the Super Bowl of journals. There were multiple studies done with multiple individuals for checks and balances. They had no investment into the outcome. There were vegans, there were vegetarians.

They all examined this evidence. It was run through a process called the grade process in which evidence is evaluated. And they found no high-quality evidence with the addition of Red meat, not processed but whole red meat, and cancer yet it is pervasive. And I will just leave them with one more thing is that people will say, well, you should reduce red meat because you should reduce cholesterol, you should reduce your eggs because of cholesterol. That cholesterol recommendation was taken out of the dietary guidelines in 2015. We do not have a cholesterol recommendation. If something is repeated over and over enough people believe it to be true and these myths die hard.

 Ari: Yeah, 100%. Dr. Lyon, are there any, I mean, I could talk to you for another five hours but we are pretty much at the end of our time here. Are there any final words that you want to leave people with or do you want to maybe provide a quick summary of your key recommendations that you have gone over here?

 Dr. Lyon: Yes, certainly. Number one muscle is the organ of longevity and it is the only organ system that you can directly impact. The way in which you are going to do it is the obvious physical exercise and nutrition as it when it comes to physical exercise, resistance exercise is key. Also endurance-type exercise and just sprinkle in one day of doing something that you really do not want to whether it is high-intensity interval training that could be different for everybody.

But really doing the difficult thing is exercise. 24% of the population is meeting the recommendations. Now moving to dietary interventions for healthy mitochondrial and mitochondrial health and muscle health. 100% of people are eating in order to leverage food for muscle mitochondrial health. I like to intertwine them because, again, skeletal muscle is the home of mitochondria, for the most part, is optimized for dietary protein separated into the first and the last meal as your primary targets, the middle meal, I do not really care.

Really thinking about that, I strongly recommend high-quality proteins because of the nutrient density, especially when you are keeping calories controlled. You do not need a ton of calories but you do need a ton of quality. And then sprinkling the adjunct things on, if you have a beautiful home and now you are going to add drapes, you will add in some kind of phytonutrient whether it is a red or green powder or even a purple powder, and my favorite Mitopure or urolithin A, this compound.

And potentially if you wanted to get crazy with it you could even also add in omega threes but thinking about those things. It is the exercise piece of the recommendation, it is the dietary piece of the recommendation. And I will say leaving individuals without confusion, do not be distracted. There are core fundamental principles that are evidence-based that you can execute on. It does not have to be confusing. Remember that confusion is a distraction. And as you age the window of time in which you can get better closes. And that is intense to think about yet true. Do not be distracted by the shiny objects, focus on evidence-based information, and move that needle forward. And may I recommend two resources?

 Ari: Please. And tell people where they can learn more from you and follow your work.

 Dr. Lyon: I had a TEDTalk come out recently where I explain muscle as the organ of longevity and really as a key component. Maybe you would be so generous to link it. They can find it in TEDTalk. I have a book coming out called “Forever Strong”. Where it takes these core fundamental principles and it breaks it out into very easy pathways. And there are pages and pages and pages of high-quality references there.

So that if individuals are interested in evidence-based information I have done what I feel is a very good job in doing that and providing that. People can find me on Instagram. Dr. Gabrielle Lyon. My YouTube, my podcast. I am hoping, Ari, you will come on my podcast which is Gabrielle Lyon Show. We have a great newsletter. And we are going to be doing 30 Gs which is recipes, weekly recipes which is going to be cool.

 Ari: Nice. Awesome. When is your book come out?

 Dr. Lyon: October 17th. It is available for preorder right now. And what took two years and two babies to do.

 Ari:  Awesome. Dr. Lyon, thank you so much for coming on, sharing your brilliance. I really appreciate it. It is always amazing to chat with you. And to everybody listening you should feel very blessed to get this information because this was an hour talk but the methods that she is outlined, she is given you very explicit advice on practical things to do each day and each week.

And implementing this advice versus not implementing it literally can add years and decades to your life and certainly massively increase your health span, the length of time that you have a functional brain and body. And this is not an exaggeration. When I say decades, I mean, this advice may be the difference between dying at age 63 from a heart attack versus living to age 93 in pretty good health. The tools that she is giving you here are truly foundational to good health, to great energy, and to a long life and a long health span. I hope you will implement it. Thank you so much, Dr. Lyon. As always, I look forward to our next conversation.

Show Notes

00:00 – Intro
00:40 – Guest Intro Gabrielle Lyon
01:58 – The link between muscle tissue and mitochondrial health
10:55 – The role of flux
22:00 – The important role of endurance training in healthy individuals
33:28 – Protein requirements for optimal health
45:20 – Urolithin A
47:57 – The downside of dietary “religions”


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