March 14, 2024

From podcast: https://bengreenfieldlife.com/podcast/gabrielle-lyon-podcast/

[00:00:00] Introduction

[00:00:55] Who is Dr. Gabrielle Lyon?

[00:03:34] The concept of muscle-centric medicine

[00:05:02] How did Gabrielle become a weightlifter?

[00:08:06] Gabrielle's strength training routine

[00:09:53] The importance of skeletal muscle mass

[00:17:16] The role of skeletal muscle mass

[00:22:51] Losing and building skeletal muscle mass

[00:27:48] How often should you do resistant training?

[00:32:01] Neural effects of muscle

[00:37:27] How many grams of protein should we take per day?

[00:46:16] Anabolic upper limit

[00:49:48] Muscle-building supplements or additions

[00:58:04] End of Podcast

[00:59:05] Legal Disclaimer

Ben:  My name is Ben Greenfield. And, on this episode of the Ben Greenfield Life podcast.

Gabrielle:  When you directly measure skeletal muscle mass, you do see a correlation between strength and mass, and more importantly, outcomes that we care about: Hypertension, cardiovascular disease, mobility, strength. One layer further is that it's actually the loss of skeletal muscle mass rather than the gain of body fat that is much more detrimental to overall health and longevity.

Ben:  Fitness, nutrition, biohacking, longevity, life optimization, spirituality, and a whole lot more. Welcome to the Ben Greenfield Life show. Are you ready to hack your life? Let's do this.

Well, folks, my guest on today's podcast and I did not coordinate the idea that we were both going to be showing off her guns during today's show but that's the case. Although if you're watching the video version, I think her tattoo is cooler than mine, but I'll leave that up to you to decide. Her name is Dr. Gabrielle Lyon. You've probably heard of her before because she has gotten very popular of late for her entire concept of what she calls Muscle Centric Medicine, and I'm a huge fan. And, Gabrielle just wrote this book, “Forever Strong: A Science-Based Strategy for Aging Well.” It's fantastic. You should read the book. We're going to go into stuff that may or may not be in the book as the discussion evolves, but she is just a fantastic resource for all things strength training, weightlifting, and muscle as medicine in general.

So, Gabrielle, welcome to the show.

Gabrielle:  Hey, friend. So, I think that there is maybe for the hundreds of podcasts that I've done, I don't think I might have worn a tank top one time, by the way.

Ben:  Okay. Well, you picked the right one because we're all into not wearing pants or doing our hair or showing up for podcasts still digging green smoothie shards out of our teeth.

Gabrielle:  Are you walking and podcasting at the same time? By the way, I have never–

Ben:  You know what, I walk for most of my podcasts. I have this whisper-quiet treadmill in my gym called a Walkolution, and it works fantastically. It's got this nice plush foam surface. And, it's one of the best investments I've ever made for my home office aerobic fitness.

Gabrielle:  I'm sold. I'm actually going to get one.

Ben:  Yeah, check it out.

Gabrielle:  I'm going to get it.

Ben:  Yeah, they're pretty cool. They were designed by this dude. He was a Swiss inventor who spent time in Korea and found that when he would walk out in the Korean rice patty shields, he can't make this stuff up by the way, he had less knee and hip pain and his feet got really strong and supple and stretched. And, he came up with this line of mats and shoes. I interviewed him 10 years ago and then found out a couple of years ago that he had advised, I believe, Woodway, owns this company, on the development of a non-motorized walking treadmill that's kind of curved.

Gabrielle:  We have one but it's very loud.

Ben:  Okay. Yeah. No, this is different. You can Google. It's called the Walkolution. This nice plush surface. So, it's incredible. As you know, it's not going to get you strong more about that, but it's great. I probably get, I don't know, 8 to 10,000 steps a day on this thing, so yeah.

Gabrielle:  I love it.

Ben:  There you have it.

Gabrielle:  Well, I'm excited to chat. It's been a long time coming. And, I'm so grateful that you're on board with this concept of muscle-centric medicine, which shockingly, it's this idea that skeletal muscle is the largest organ system in the body. People always talk about the skin.

Ben:  Yeah. I was going to say people say the skin is the biggest organ in the body. What's up with that?

Gabrielle:  It's not, right? So, this idea that skeletal muscle is this organ system. And, what's even more important to understand is that we have medicine and specialists for pulmonology for the lungs, for cardiologist for the heart, endocrinologists for hormones. But, this idea that muscle-centric medicine and muscle as an organ system does not have surrounding it for all of its metabolic properties and all of its potential to counteract diseases of inflammation and autoimmunity. It doesn't have its own form of medicine like what medications negatively impact skeletal muscle. So, that is why I created this concept of muscle-centric medicine.

Ben:  Well, they don't teach weightlifting classes at medical school, right?

Gabrielle:  They don't. But Ben, now if we can speak about it as an organ system, we then have a unifying language. We can now have concrete discussions that unify language that really move the needle for people. And, this is essentially muscle-centric medicine.

Ben:  Well, back to medical school. I mean, I honestly had read your book and you and I have chatted back and forth a few times, but I stalked you a little bit leading up to this podcast, I found some pretty impressive lifting videos on Instagram. You're an explosive kind of CrossFitter-esque weightlifter. I'm just curious about your backstory as far as weight training. Is this something you were doing before medical school, something you've been into all your life? Is it something that's evolved or had you become such a darn good lifter because some of your lifting is actually pretty impressive?

Gabrielle:  Thank you. So, full disclosure, I'm 5'1, maybe a buck 10. On a good day, I might be 110 pounds. My parents are very athletic. My dad was captain of the wrestling team, All-American athlete, very, very athletic growing up. Played soccer for a little bit, ran track, did a little dance and gymnastics, and then very early on, believe it or not, got into bodybuilding. And, this was before–it's not the bodybuilding you see now. Do you remember when there was figure? So, there's figure now, but back in the day I'm talking–

Ben:  Yeah. Well, I was bodybuilding in 2005.

Gabrielle:  Okay.

Ben:  And, there was figure then. How do you differentiate between modern figure and old figure?

Gabrielle:  Well, I think that modern older figure was the women were smaller. Right now, I think that the figure women, again, I haven't really looked into the sport so much lately, but it seems to have moved more towards this bodybuilding-esque look. But, before that, there used to be, back in the day, obstacle courses. That was the first iteration kind of a women's fitness movement. They did these obstacle courses. I was really interested in the obstacle courses and I spent time at the University of Limerick. I spent a year at the University of Limerick looking at exercise physiology and nutritional sciences. And, while I was there, I became obsessed with this idea that I was going to do an obstacle course. Started training while I was there.

Ben:  I don't want make you sound old, this is before Spartan and Tough Mudder and all that?

Gabrielle:  Yeah. I think it was. I graduated med school 2006, so 1990, 2000.

Ben:  Yeah, probably. Yeah, I don't think Spartan took off till maybe 2000, maybe '08, '09, something like that.

Gabrielle:  Right. So, this was before that. And then, I decided, well, I couldn't really find a ton of obstacle courses so I was going to do Fitness America. And, Fitness America was a combination of bikini. You have to go on your bikini. I've never do this nowadays. Now, bikini and some kind of dance with athletic moves that you had to do, and that's really what started my interest in skeletal muscle, specifically. And, yeah. So, I've been training my entire life and I still train, train through both pregnancies. I do mix of CrossFit style. I enjoy that a lot. I always try to challenge myself do something different.

Ben:  So, what's it look for you on a typical week? What's your actual strength training routine look like?

Gabrielle:  Yeah. My actual strength training routine is three days a week of something explosive depending on my recovery. So, I actually work with a coach. I live here in Houston. So, I train Port Carlos. It gets inundated with questions, but I train a place called Sigma Training. And, what we do is three days a week, we do a mix. Sometimes we'll do heavier lifts whether it's a heavier squat or a deadlift, but we'll always do something explosive in nature. Do a lot of sled pushes.

And, my training, so we'll do sled pushes, we'll do kettlebell swings, we'll try to add in something rotational, always thinking about why do people get injured, what are the planes of motion that they're moving in. We always incorporate some functional training because my goal isn't necessarily to get bigger, but it is to continue to improve. And, we will just pick a target and we'll work that target for 12 weeks or more. Right now, it's more explosivity and rehabbing a hamstring that I tore. I was training for a 50-hour event and I tore my hamstring, which has taken years to recover.

Ben:  Wait, a 50-hour what event, like a running?

Gabrielle:  You actually did it with Kokoro. 

Ben:  Oh, that? Yeah, okay. Yeah, a lot of people get injured training for that. That's a beast.

Gabrielle:  Yeah. And, it doesn't help that I'm married to a SEAL. So, his idea was just do 100 push-ups a day, just do this, but my volume was too high. It was probably four hours a day. and, I avulsed my hamstring. I ripped my hamstring off the bone. I was a little over 80% avulsion. Actually went through two and a half years of PRP and stem cell and regeneration for my hamstring, but it still can flare up now, still can flare up.

Ben:  Yeah. Wow.

So, the explosive training that you're doing, is this based on some of the–I guess there's actual studies. I think the majority of them were done like rodent models and guinea pigs associating, I believe, it's a decreased rate of telomere shortening with explosive wiry powerlifter type of muscle versus bodybuilding-esque mass. Are you familiar with those studies?

Gabrielle:  I'm not. Telomere length, I don't think so much about that from an aging perspective. Perhaps I should.

Ben:  Yeah. Well, it's not the most cutting-edge measure. I mean, even the Horvath clocks and methylation data, it's based on some pretty small sample sizes and small cell numbers. But yeah, the idea basically is that powerful muscle is more associated with longevity than muscle mass or overall strength.

Gabrielle:  We are at the precipice of change for that, for that belief. So, for the last 30-plus years, when we think about how do we study muscle, it's really two populations. We've studied muscle with athletes, right? That's really kind of the traditional model, we study athletes. And, that is the interest with muscle biopsies and how do we make our athletes better. And then, the other overarching body of literature is aging; geriatrics, sarcopenia, even though sarcopenia actually only became a diagnosis in 2016, which got an ICD-10 code or an ICD whatever. At that time, it was not 10 but an International Classification Of Disease 2016. And, the traditional belief because we use DEXA to measure body composition, there is not a huge correlation. There's a very minimal correlation between body, muscle mass, and strength, and these outcomes. That is incorrect.

Ben:  An inverse correlation between body muscle mass and strength.

Gabrielle:  Yeah. People will say that muscle mass doesn't matter. People will say that it really is just strength that matters and the amount of mass that one has does not correlate to outcomes that we care about.

Ben:  Okay, got it.

Gabrielle:  And, there's about 30 years of literature. And, you will always hear people say that it's really the strength that matters. We care about strength, we don't care about mass. That's not true.

Ben:  Yeah, because that is what you hear a lot is you don't got to be a bodybuilder, you don't need a ton of hypertrophy. And, not to derail you too much, but I think part of that might be to a lot of these studies that have been done in untrained individuals where you see a neuromuscular responsive training that occurs before you see almost a musculoskeletal hypertrophic response. Meaning that people get strong more quickly than they put on size, for example. So, in an untrained individual when they first start training, they see some improvements in strength, et cetera, that come prior to the actual development of appreciable muscle mass thus leading, I think, a lot of researchers to say, “Well, see, you could get strong and get the benefits of strength training unit if you're not putting on muscle.”

Gabrielle:  That is a very good point. And, I do believe that that is part of it. And, the other part of it is that we haven't been measuring skeletal muscle mass directly. The incremental changes that can be detected from a DEXA is not enough. You will require say a 10% change in muscle mask before you have a detectable change. And, exactly what you're saying is someone might get strong before they put on mass. Again, whether it's untrained/trained, trained individual like yourself, it's going to take a lot more work for you to put on mass than say an average individual.

Ben:  Right.

Gabrielle:  And, because of that, that has created a lot of what I, and I hate to use the word “wrong thinking” but really an incorrect hypothesis that we have now layered decades of research. There's a new validated way to look at body composition and specifically muscle mass, and that is something called a D3-creatine. And, it directly measures muscle mass.

Ben:  What's it called? A D3-creatine?

Gabrielle:  A D3 creatine dilution. And, what this is is it's a dilution method and it uses this assumption of a 24-hour creatine excretion, this is a lot of words, assessment of muscle mass. So, basically, 90% of total body creatine pool exists in skeletal muscle. And so, what happens is that creatine that turns over in muscle, and through that conversion of creatine to creatinine, they can directly measure skeletal muscle mass. And, when that is utilized, and it's been validated in neonates and children and adults, when you directly measure skeletal muscle mass, then you do see a correlation between strength and mass, and more importantly, outcomes that we care about.

And, one more thing. And, when I say outcomes, I mean hypertension, cardiovascular disease, mobility, strength. And, one layer further is that it's actually the loss of skeletal muscle mass rather than the gain of body fat that is much more detrimental to overall health and longevity.

Ben:  Really? That's super interesting. People say, well, fat turns out inflammatory cytokines, is a storehouse for toxins, and blah, blah, blah. But, what we saying is the loss of muscle mass is actually more deleterious than the gain in fat cell size or number.

Gabrielle:  Exactly.

Ben:   Interesting.

Gabrielle:  And, in this literature, the guy who pioneered this is a guy named William Evans. And, here's one of the analogies that he uses. It's kind of when you lose your keys and there's a street lamp in an alley and you lose your keys and the only light is underneath the street lamp, even if you lost your keys 15 feet away, you don't look over there because you don't have a light. So, it's like the streetlight effect. You're looking where there's light, but it could just be totally wrong. And, that has colored our perspective, number one, on the importance of hypertrophy training, the importance of the amount of mass. We talk about skeletal muscle mass from a functional perspective, meaning strength and endurance and all of the physical metrics, but it's really the metabolic metrics that we have to understand relate not just to strength but the health of skeletal muscle. You cannot be healthy without a robust amount of healthy skeletal muscle. It does not exist.

So, for all the literature in PubMed or some of these large databases, if you pull out a study and the study says healthy sedentary adult, that is a disease state.

Ben:   Yeah, yeah.

Well, I want to get into some of the metabolic effects of muscle, but surely there must be, I guess, a law of diminishing returns. If you get to the point where you can't wear skinny jeans or put your hands in your pockets, and I've even said this before, I wonder if some of the reasons that bodybuilders tend to, painting with a broad brush it seems, die a little bit earlier. Part of it might be due to the cardiomegaly and the athlete's heart phenomenon and the stress in the heart. But, don't muscles at a certain point become very demanding as far as endogenous antioxidant production or what you have to carry or cool? Have you ever thought about a Goldilocks Zone of muscle mass?

Gabrielle:  So, I have and I want to mention a few things. So, number one, we do not know anyone's optimal skeletal muscle mass. I cannot say, Ben, you should be 115 pounds of skeletal muscle mass. It does not exist. We have defining charts for sarcopenia and cachexia, but we do not have a optimal muscle mass. Contrary to say body fat percentage, we might say greater than 30% is a problem. And, let's say an ideal body fat percentage for a woman would be anywhere from, and I'm just making up this number because I don't actually to see women greater than 24%, but again, it depends on where she is naturally, if she's looking to get pregnant, et cetera, et cetera.

Ben:  And, by the way, the most recent study on all-cause mortality related to fat was about 11 to 22% for men and about 22 to–no, it was lower than that. I think it was low 20s, late teens up to around 34% for women. And, I suppose you could come close to estimating ideal muscle mass by saying, looking at epidemiological data, here's about how much someone your height and weight should weigh. And then, in a man, multiply that by you what would it be, so 11 to 22%, 0.89 to 0.78, and that'd give you a rough approximation of what a good muscle mass would be for you. Kind of like reverse engineering.

Gabrielle:  Yeah. That's very smart. And, we did some of that in my book. We put together a table. So, we took athletic populations and then we took sarcopenic populations and we put together, it's an appendicular lean mass chart to see where someone is that they could use say an inbody and utilize those numbers, plug it in, and see. But, even that, it's not foolproof because again, we haven't been measuring skeletal muscle mass directly. And, I'm going to actually, I have a great question for you because I cannot wrap my head around this. 

So, we say 11 to 22% of body fat would not be great for a guy. But, the standard for a human is 40% muscle mass. So, there's cardiac muscle, there's smooth muscle, and then there's skeletal muscle. 40% of the body would be skeletal muscle, but how could that be true and how can that be unchanging?

Ben:  That accounts for 51 to, what, 62 % of overall mass and you would then have to say that 30-plus percent of the entire mass is bone and water.

Gabrielle:  So, I think that we probably haven't been questioning that enough quite frankly in terms of just what we are thinking. But, beyond the importance of skeletal muscle mass in relation to physical activity, it is an organ system. And, there's the metabolic role that your listeners are all very accustomed to. They know that healthy skeletal muscle is the primary site for glucose disposal. We know that the carbohydrates that you eat must be disposed of somewhere.

Ben:  Right. I think it was you. You call it the metabolic sink.

Gabrielle:  Yeah, yeah. And, I think that we have a good framework for understanding this. And again, it's a primary site for fatty acid oxidation. People always talk about how metabolically active skeletal muscle is at rest. It's not quite frankly and it typically uses fatty acid.

Ben:  Unless you're doing that soleus push-ups.

Gabrielle:  Right. Not a not a very metabolically active tissue compared to the brain or these other kidney or these other organ systems or individual organs, but again, site for glucose disposal. The more healthy muscle mass you have, the more you are going to have glucose tolerance outside of training.

So, let's assume that you are an individual who is training, you are depleting muscle glycogen, which you do need to be doing. There is a component of unhealthy skeletal muscle that is weak, that is a swamp pool, right? A pond where you are not utilizing these substrates. That is all what I would consider unhealthy muscle.

As you think about the health of skeletal muscle and its importance, again, muscle for glucose, fatty acid oxidation, and then another really interesting aspect of skeletal muscle, which it comes as no surprise, is this storage of–it's the amino acid reservoir for any kind of highly catabolic state, for any time of bed rest, which is the number one treatment of choice when people get sick is people go to bed, people go into the hospital, they get put on bed rest. This is very deleterious to skeletal muscle.

Ben:  Yeah. And, by the way, I should interject that I heard that the mortality that occurs with age is typically due to frailty induced by injuries or illness that keep you bedridden for certain periods of time as life progresses and you gradually lose muscle. Is there something to that idea?

Gabrielle:  Actually, yes. And, the evidence will support within one week. Let's say an individual is 65 years old, and again, we're speaking in absolutes. There is variation. And, I do want to circle back to some of these diminishing returns of exercise. You could put a older adult on bed rest and in one week they might lose 2 pounds, if not more, of skeletal muscle mass from their legs in seven days. Protein might have a sparing effect for the first seven days. But, after that, if you are not moving, you will lose tissue, versus a younger individual will lose, I don't know, in 30 days might lose–again, there's really two camps, but let's just say a younger individual will also lose skeletal muscle mass but at a fraction of the rate. If I was going to throw out a number, I would say that a older individual will lose skeletal muscle mass three times faster.

Ben:  Are you saying that's because of a diminished amino acid pool with age?

Gabrielle:  No. That's a really good question. There's a couple things that happen to muscle is the young muscle, and this called a catabolic crises model and Doug Paddon-Jones developed this model. And, he was in Galveston. The catabolic crisis model is that up until age 40 or 50, and again you got to think, these are probably untrained individuals, our ability to recover from a skeletal muscle mass perspective seems to be more robust. But, as an individual ages, they never get up to baseline functioning. They lose skeletal muscle mass quickly. And, in that quick loss of skeletal muscle mass comes a whole host of metabolic problems. For example, when you lose skeletal muscle mass, one of the things that we see in blood work is we start to see an increase in blood glucose, fasting blood glucose. We see an increase in insulin. These things in insulin resistance can happen very quickly in skeletal muscle.

So now, you've taken an older individual, you've put them on bed rest, they're losing skeletal muscle. And, let's say they're trying to recover from something, you put them in an insulin-resistant state and you begin to create low-grade inflammation and metabolic derangement, then you'll see an increase in triglycerides. All of these things that the cascade is, again, so detrimental. And, a lot of these people don't recover versus a younger individual, although I have to say we say older and younger. There are a handful of things that potentially change, but we're a sedentary society. 50% of individuals are not working out. So, these diseases of aging that we think about like cardiovascular disease, hypertension, Alzheimer's disease, these diseases don't begin later on in life, they begin in our 30s. And, I would argue that the changes in skeletal muscle mass also begin in our 30s. They begin much earlier.

Ben:  Yeah. Perhaps this is a good time to come back to this idea of the law of diminishing returns that you wanted to address because if you're going into old age with a lower amount of muscle mass due to neglecting strength training, I think that this aggravates that issue all the more. I mean, the latest evidence I saw was you can be 85 plus and actually not just maintain muscle but build muscle. So, it's kind of like the Chinese problem, “The best time to plant a tree is 20 years ago or today.” But, I encourage a lot of young people to start strength training early so they build muscle mass reservoirs going into old age, going into injury, going into illness. You talk to runners and endurance athletes. 

In short, you've probably seen some of this, Gabrielle. There's pretty good evidence that increased capillary density such as you would get from aerobic training or even concurrent training mixing up strength and cardio can accelerate your ability to be able to gain muscle due to better blood flow and metabolite feeding to the muscle. But, when I see people doing yoga, running, swimming, and I don't know, sauna and cold plunge, and this is very common in the biohacker community, neglecting just, pardon the expression, lifting heavy shit or making yourself harder to kill with weights. I get very concerned especially when people say, “I'm going to start strengthening when I'm 40, when I'm 50.” I think you got to get it on early.

Gabrielle:  I totally agree with you.

And, the law of diminishing returns, I think that epidemiology data, which is obviously we know poor quality data, a whole host or a handful of people were saying you shouldn't train, what was it, resistant train more than 60 minutes a week or something like that.

Ben:   Oh, my gosh, you're going to open up a can of worms here.

Gabrielle:  No, no, I'm not trying to, I just want to mention.

Ben:  Yeah. But, mention it. Dr. Mercola, he was probably the most popular guy championing this idea that if you lift more than three times a week or exceed as little as 30 minutes of strength training a week, you see increased all-cause risk of mortality. I don't know about you. I dug into the studies. I couldn't find the actual protocol being used, but the only population for which I could imagine that to be the case would be the extreme competitive weightlifter who's, whatever, 30 to 60 weeks or hours a week of weight training consists of max deadlifts and extremely soul crushing movements.

Gabrielle:  Right. But also, these studies had a ton of confounders. And, a lot of it was epidemiology. These are not high-quality studies.

Ben:  I agree.

Gabrielle:  And, on the flip side of that, we know that skeletal muscle mass increases your survivability. We know that training, resistance training with–I mean, the body of evidence to support more than 60 minutes is, I mean I was just looking at a paper earlier today, because believe it or not I'm working on my next two books and it's all protocol-based, that there are so many protocols that show improvements in biomarkers related to metabolic dysfunction, strength, mobility that are all longer than 60 minutes. 

Ben:  All the ones I saw that you're probably referring to also were up to 140 minutes a week, right? We're talking four times that, which was cited recently by people who are not completely shoving strength training under the bus but I think not doing people a favor when it comes to maintaining the metabolic and beneficial aspects of strength training you've been talking about.

Gabrielle:  Yeah. And then, the other thing that we have to understand is 50% of Americans are not training, 50% of Americans are not fully sedentary.

Ben:  Right. The same type of people who don't need to hear from, bless their hearts, Sean Baker or Paul Saladino that vegetables are going to kill you because they're already eating a standard American diet or the same type of people who do not need to hear that strength training is going to kill you because they're sedentary.

Gabrielle:  No. And, when I started to see that, I was quite frankly really surprised. We can't look for hacks for hard work because it requires discipline, which is something you're really good at. It requires discipline. It requires being able to push through any barriers. You become stronger. You build confidence. And again, exercise is going to change the body's homeostasis more effectively than anything. There is no pill that is nearly as effective as changing metabolic parameters, as changing the influence on our overall health than training.

We're just catching up. Again, skeletal muscle as an organ system, it secretes myokines. I don't know if you've seen some of the literature out of Copenhagen, but Bente Pederson, she's a physician who also studies exercise immunology and she coined the term myokines. And, what this is is as skeletal muscle contracts, and it's typically related to the amount of input. So, if someone is doing a certain kind of endurance training or a certain kind of resistance training, they will release in a somewhat linear fashion. I mean, there's hundreds of different myokines that are released, these molecules, these peptides from exercising skeletal muscle that have anti-inflammatory effects that regulate something like interleukin 6. So, there's interleukin 6 that comes from skeletal muscle that has a very different effect than interleukin 6 coming from macrophages.

Ben:  Yeah, yeah. It's a good reason, by the way, to not take high-dose vitamin C or vitamin E or do a 10-minute cold soak after workout because you actually don't want to quell that myokine response.

Yeah, the idea though, I think, a lot of people are thinking is well, typical meat head, doesn't muscle just kind of make you a big old lunk. Talk to me about the neural effects of muscle.

Gabrielle:  Yeah. I think that when you say the neural effects of muscle, I will tell you that the brain-muscle connection as you know is highly correlated. We know that exercise improves cognitive performance. We know that, again, is it a myokine release? Is this an increase in BDNF? It's typically there's increase in irisin and cathepsin b, these myokines that actually then influence BDNF release in the brain. It is believed that this is neuroregenerative. That might be a very bold statement, but kind of have some counter and protective effects from our day-to-day insult from aging, from metabolic dysfunction in the brain, which when we think about metabolic dysfunction, we think about Alzheimer's type 3 diabetes of the brain. A large portion of Alzheimer's disease is a metabolic disease, insulin resistance in the brain. Exercise can improve these things and I think it's really twofold. It improves the overall metabolic health of the individual and it also improves the functioning and the firing of the brain and the myokine BDNF. I think it is a very complicated system.

Ben:  Yeah, yeah. Well, I mean, all the more so, I don't know if you mess around with blood flow restriction or Kaatsu training at all, but you get a huge dump of VEGF, vascular endothelial growth factor, and vasoactive intestinal polypeptide into the brain. So, it's literally you're getting these crossing the blood-brain barrier and the spark in neurogenesis is significant. There was a while where people were saying, well, whatever, the typical nerdy cross country athlete and stupid football player and aerobic exercise makes you smarter. And, I think Jonathan Ratey talked about this in his book, “Spark.” But, the idea that aerobic training is more associated with cognitive improvements than strength training. But, if you are strength training using a method that specifically builds up some amount of lactic acid and muscle tissue, you see a surge in BDNF and VEGF that's similar to what you get from aerobic or high-intensity interval training.

Gabrielle:  You also bring up another really good point is that the modality seems to have different metabolic adaptations. It seems that they turn on different genes. It seems as if things are not replaceable. For example, if someone is going to do endurance-type exercise, you can't just do endurance. If you really want to think about the totality of health, I mean listen, there should be some kind of endurance type activity. But, that can't be instead of high-intensity interval training and that can't be instead of lifting heavier weights. There's some data out of McMaster Austin University that show that older individuals as long as they go to failure and they're creating enough of a stimulus, their rep range could be 40 reps that they will still have a skeletal muscle benefit, they'll still be able to put on muscle, they'll still be able to maintain muscle.

Ben:  Yeah. You're correct. Is it 90 seconds to 120 seconds of time under tension? And, this is why I like working a little bit of super slow training is enough of a continuous increase in peripheral blood pressure or driving a little bit more resistance against the heart to where you get a cardiovascular training effect from resistance training.

Gabrielle:  And, this brings up a good point that it can't be replaceable. So, for example, if we tell an individual who's afraid of lifting heavier weights, well, you can just do a bazillion reps, will you make improvements? Yes, but at the same point in time, when we think about this strength training continuum, you do have to stress your body in different ways. Again, I'm going against the data would support, you can lift lighter weights for a period of time and that that would be sufficient, but I don't know if they know the difference has yet to be determined in the metabolic adaptations within skeletal muscle.

Ben:  Yeah. That's kind of like Brad Schoenfeld's research. And, if you look at the low load high rep, high load low rep argument is that you can achieve similar gains with both. But, if you actually look at the volume equity between the two, you need a ton more volume and significant increases in volume from the body weight approach. And, if you have the time during the day to work yourself up to 500 push-ups instead of doing a few heavy reps of chest press for a few sets, great, but it's definitely not the most efficient way and you got to increase volume significantly over time with low load.

Gabrielle:  That is exactly the paper that I'm referring to which Brad Schoenfeld is the lead author. And, the paper is loading recommendations for muscle strength, hypertrophy, local endurance, a reexamination of the repetition continuum. And, you're exactly correct.

Ben:  I do want to make sure that I talk with you about nutrition because this is a big piece, the idea of protein and other things that you can do. So, obviously, the question that everybody ask, probably the second most commonly asked question beside “Is this going to break my fast, bro?” is “How many grams of protein should I eat per day?” What's your take on that?

Gabrielle:  Well, I'm going to tell you what the evidence supports and then I'm going to tell you what I believe to be the right target.

Ben:  Okay.

Gabrielle:  The evidence right now supports, well, first, you've talked about this, I think a lot in the past, is we know that the minimum is the RDA. The minimum to prevent deficiencies would be 0.8 grams per kg, which turns out to be what, 0.47 grams per pound, right?

Ben:  Yeah, yeah, a little below 0.5. Yeah.

Gabrielle:  Really, really low. For example, if a woman is 150 pounds, her minimum would be 45 grams of protein to prevent a deficiency. Albeit a deficiency from protein doesn't happen overnight, it is typically a trend over time because of challenges with protein turnover in the body. There's all kinds of things. It's not an immediate, immediate deficiency, which I think is a problem. And, that's why people get a little confused. But, that's a minimum to prevent a deficiency. And then, on the same hand, and I'm going to get your question, just from a framework of thinking about it, if you got sick and you know that the minimum vitamin C to prevent scurvy is 60 milligrams a day, would you shoot for a higher amount of vitamin C? Probably. Nobody thinks about protein in that way, but the RDAs are still set that way. The evidence supports at least 1.2 to 1.6 grams per kg. So, essentially double the RDA would be a more optimal range.

Now, to put in perspective, I would consider the RDA 0.8 gram per kg a lower protein diet. And, by definition, if we have semantics right, that's the minimum to prevent a deficiency. So, that would be a lower protein diet. If you were to double that, 1.6 grams per kg, evidence definitely supports that. That would be a moderate protein diet. That would be enough to be able to manage appropriately muscle turnover, potentially body composition. Is that optimal? I would say that that is not optimal.

Ben:  Yeah, yeah, I agree.

Gabrielle:  Optimal would be 1 gram per pound ideal body weight.

Ben:  1 gram per pound.

Gabrielle:  Ideal body weight.

Ben:  Ideal body weight. Okay, got it. Yeah.

Gabrielle:  Of ideal body weight. But, the question and I think also we have to recognize that the RDA was based on animal-based foods. It was based on high-quality proteins. So, the minimum to prevent a deficiency would be 45 grams of higher quality protein. And, I do think that that's an important differentiation to make because there's a lot of confusion in the space about the kinds of protein, the sourcing, et cetera.

Ben:  Yeah.

Gabrielle:  The other component to this conversation, so if I were to go on record and say 1 gram per pound ideal body weight, you can go lower than that and you certainly can go higher than that without deleterious effects. But, if someone is doing a lot of endurance, maybe you do better with additional carbohydrates and how are you going to get your fiber and your fruits and vegetables, et cetera. The distribution question is having a resurgence. It's having a moment, the protein distribution.

Ben:  I know, that recent 100-gram post-workout protein feeding study.

Gabrielle:  And, by the way, we should mention that this group is probably the finest group. So, it's van Loon's group, and they are probably one of the finest groups in the protein space. That paper was not necessarily reflective of many of the papers within that group. Does protein distribution matter for a younger person? It doesn't.

Ben:  And, we should explain, by the way, before we get too far down this road, that means how many times your protein feedings are split up throughout the day, right? Protein distribution.

Gabrielle:  Yeah. So, originally, I've been studying protein metabolism for 20 years and I started in Donald Layman‘s lab. And, Don Layman is one of the grandfathers of protein. It'd be so cringeworthy that he's hearing me say that because he's in his 70s, birthday's coming up. And, the idea of protein distribution started out with this idea that leucine, which is one of the essential amino acids, is required to stimulate muscle protein synthesis. And, they were really looking at early body composition studies, and Layman and Doug Paddon-Jones, they really put out a handful of papers in which they did an even distribution. Meaning, for example, 30 grams of dietary protein three times a day as a way to manage body composition. And, I really think that that did the world of disservice because people took that and ran with it and said, well, this is what is required for optimizing body composition. It's 30 grams three times a day. And, there's actually not evidence to support that.

So now, we have a new paper that has come out talking about how there's no anabolic upper limit to protein. So, the whole idea of eating a protein bolus, the amount of protein per meal is really you have to understand or one has to understand, it's for the health of skeletal muscle. If you do not hit a particular leucine threshold, which is one of those branched-chain amino acids, you do not stimulate mTOR, you do not stimulate this muscle protein synthetic response. You are subthreshold and it's one reason potentially why I think we see a lot more sarcopenia than we should, which is a decrease in muscle mass and function. But, we have to recognize that that first meal of the day, hitting between 30 and 50 grams of dietary protein, that's where nearly all of the research is on that first meal of the day.

Ben:  Okay. 

Gabrielle:  Some could argue that because it's coming out of an overnight fast, there's no confounders, et cetera, et cetera, et cetera. But regardless, the first meal of the day whenever you're going to take it is where you are going to get the most anabolic response to your meal.

Ben:  Also fantastic for circadian rhythmicity and jumpstarting sleep drive as well. You could probably do the leptin signaling.

Gabrielle:  I think that I am certainly not a leptin expert, but there's certainly evidence for circadian entrainment with food. People always think about it with light, but it is absolutely with food.

Ben:  That's why I don't skip breakfast when I travel. I'll do the intermittent fasting thing for the first few days. And, even though I'm not a huge egg-bacon guy at home, usually if the hotel has a restaurant, I'll go down and just order six eggs and olive oil or ghee or something like that.

Gabrielle:  And, that is a good strategy. So, the first meal of the day really getting that anabolic response again is where the literature–I feel comfortable saying that we could look at the literature and there's a large body of evidence that that first meal of the day is very important for that anabolic response of, again, why do we care about it? Because we care about protecting muscle. If you believe that you cannot be a healthy individual without healthy muscle, you must take action to really think about what are the habitual things that one must do for optimizing muscle mass. That being said, people will say, well, that middle meal is important, a lunch meal. It's not. So, these initiation factors like EIF4 and these other initiation factors, once muscle protein synthesis is started, we don't know actually how long it lasts. Maybe mTOR resets at five or six hours later. We don't really know. But, what we do know is that those initiation factors are still going. And so, if you add in a middle meal, you're not going to necessarily get a more robust muscle protein synthetic response, which is different than what everyone has been talking about.

Ben:  Yeah. So, what I'm hearing then is that you start off your day with 30 to 50 grams, and then just get in the rest of it during the day up to the amount of, I'm going talk to my American listeners now, go with grams per pound, around like 0.7 to 0.8 grams per pound or 1 pound per desired mass goal just however you get it the rest of the day as long as you're starting off with 30 to 50 grams at the beginning of the day.

Gabrielle:  I think that that is absolutely reasonable. I will also say that that last meal, one could argue for that last meal of hitting another 30 to 50 or more. It doesn't really matter before you're going into an overnight fast.

Ben:  Okay.

Gabrielle:  And then, I will say if you're younger and you're training and you're healthy, the distribution doesn't necessarily matter. But, for other components of health that you're talking about like circadian entrainment and things of that nature, and you might not want a huge bolus of food, et cetera. So, we can't just be myopic and say, okay, well, it's just about protein. It's not. It's about protein. It's about how are we layering this in a cycle in a 24-hour feeding period or a 24-hour period.

And then, that last meal of the day is important, but this paper that came out talked about how there was no anabolic upper limit. The evidence doesn't support that.

Ben:  Yeah. And, by the way, you're referring to the paper where they gave people 100 grams.

Gabrielle:  Correct.

Ben:  Yeah.

Gabrielle:  Correct. There were a lot of challenges with that paper that I think are not necessarily being mentioned. By the way, I have to say these are extraordinary researchers, but they chose casein, which we know is four times slower in absorption. They chose 25 of casein, which is not enough to really elicit a major response. And then, they chose a 100 but there was no gradation. So, if they had chosen 45 grams of casein, there wouldn't be a difference from a anabolic response from 45 to 100 because we've already initiated muscle protein synthesis. We've already initiated all these factors and mTOR. So, the idea that there's no upper limit to an anabolic response would mean that you could put on, I don't know, 1 pound of lean body mass in 12 hours. There is an upper threshold of an anabolic response. That is in the literature and including the literature in that group.

Ben:  Okay.

Gabrielle:  So, I think the point is that that paper shows, one, what is the idea of that paper is that you can absorb all the protein, perhaps.

Ben:  Yeah, because that's, I don't know what you tell your gastroenterologist friends who say, well, the body can't absorb than 40 grams at a time or floating around the internet you'll see people even say 30 grams at a time. You're saying that's not true and maybe what this paper at least shows is that that's not true.

Gabrielle:  And, I think that the paper was incredible. It used exhaustive exercise and it seemed as if there was a very unusual kind of recovery response that we might not account for. I mean, that was really unusual. There's a lot of really good things to the paper, but I think the idea that we extrapolate that there's no upper limit to an anabolic response and that people could just eat 200 grams of protein potentially in a day. And, maybe that's better than eating twice a day. I think that that would be really taking it out of context.

And, here's where I think it matters. It doesn't matter if you're young, but where it does matter it matters if you're older. So, for example, let's say we talked earlier about this catabolic crisis. So, somebody goes, falls, breaks the hip, I don't know, gets sick, is on bed rest, and they're believing that they should have one meal a day and that's sufficient. That would not be an ideal strategy for someone who is challenged with a catabolic insult, whether it's an infection or a bed rest state, et cetera. And, we just have to be careful. I don't think that this paper changes any current strategy quite frankly,

Ben:  Yeah. Okay, that makes sense.

Now, when it comes to muscle building, talk about protein. I know you and I are both huge fans of essential amino acids, especially those rich and adequate leucine for the muscle protein synthesis reasons that you described earlier. So, I think protein and essential amino acids, in my opinion, those are a no-brainer. I've already had 15 grams of essential amino acids today. It's only, what, 11:30 a.m. So, what else though as far as muscle building supplements or additions would you add in or recommend based on what you know?

Gabrielle:  Well, there's a couple things. I don't know if you've heard of. I do want mention the essential amino acids. We talk a lot about amino acids as it relates to, well, number one we talk about protein is if it's one thing, which we know, it's not it's 20 different amino acids. And then, we talk about the idea that these amino acids are interchangeable. And, I think that that is really doing the complexity of protein research and information a disservice.

Ben:  And, what do you mean interchangeable?

Gabrielle:  Is that people will say, well, this has 10 grams of dietary protein and that must be equivalent to this other 10-gram of dietary protein.

Ben:  Oh, I see. Yeah, yeah.

Gabrielle:  And, the reality is these essential amino acids, and I just want to highlight this because I do think that it's important to recognize that, for example, leucine we spoke about that plays a role in the activation of mTOR. But, what about threonine, which is an essential amino acid that is important for mucin production, or tryptophan which is important for serotonin production, or lysine which is important for carnitine and fatty acid oxidation? And, these amino acids and these foods they're not interchangeable. And, I think that when we talk about how are we optimizing human health that it's not the same to say, okay, well, you can have this peanut butter and that peanut butter is the same as this 4-ounce steak. The amino acids are different. The micronutrients are different. And, we do have to do a better job. And, the next frontier, I think is going to be understanding the limiting amino acids. And, I won't go off into a rabbit hole about methionine, lysine, and leucine, but those are the three key limiting amino acids that I think are going to get a lot more play coming up in the literature.

Ben:  And, when you say limiting amino acids, you mean limiting for muscle protein synthesis or something else?

Gabrielle:  Great question. For everything. That's a wonderful question. Leucine particularly for muscle protein synthesis, and then methionine that creates this integrated stress response if that is limiting or restricted, and then lysine, lysine is really important again for fatty acid oxidation and growth. And, those pools last a lot longer. So, that would not be a meal-to-meal amino acid that we care about, it would be more of the overall strategy of eating versus leucine would be a meal-to-meal type of amino acid that we care about.

Ben:  Okay, interesting.

Gabrielle:  So, that's where the future is going.

Ben:  What else other than amino acids then would you look at like your go-to stack for muscle building or maintenance?

Gabrielle:  One of the things I'm very interested in and I'm curious as to your thoughts, but there's a compound called urolithin A.

Ben:  Yeah.

Gabrielle:  30 to 40% of individuals, some people make it, some people don't, and it's a postbiotic. It is made in the gut microbiome. It's an ellagitannin from things like pomegranate or walnut. And, I think that there's some pretty good evidence for the urolithin A's impact on mitochondrial health and function, strength and endurance, primarily in older individuals through the process of mitophagy, which is obviously cleaning out these old mitochondria and helping with the regeneration of mitochondria, keeping it “youthful.” I don't know however you want to say it. I really, really like urolithin A. If I could have made a supplement and brought it to market, I probably would have developed something like that.

Ben:  Yeah, I agree. I mean, most of the resistance training studies been done in mice or rodent models, but it's still impressive. And, I've been taking a probiotic for a while that has pomegranate seed extract in it and then have used the Timeline Nutrition stuff as well. And, I think there's enough evidence in absence of harm and side effects to where if you can afford to add it into your protocol, I wouldn't rank it above amino acids and definitely wouldn't rank it above creatine, but I think it's good for that.

Gabrielle:  I absolutely agree with you. I do think it's phenomenal. I think creatine is also hugely impactful and we're going to start to see more greater impacts of creatine on cognition. I know that we're seeing it right now in older individuals. But, it's going to be interesting as we kind of switch the focus from ATP and performance-based creatine's influence to brain function. So, creatine would definitely be on there if someone is eating a lot of red meat.

Ben:  I agree. We should mention that. Well, that and sleep deprivation, but it's at least double, triple or even quadruple the dose recommended typically for performance. And, considering once you exceed 5 grams and some people 2.5 grams you get.

Gabrielle:  Yeah.

Ben:  Yeah, you paint in the back of the toilet seat so to speak. You got to kind of break it up during the day. But, if you're willing to do 4, let's say 2.5-gram portions of creatine throughout the day–and it's dirt cheap compared to a nootropic.

Gabrielle:  I would agree with that. I definitely think that that's important. And then, there's some foundational ones like omega-3 fatty acids. They're seeing some evidence to support that it might affect women differently. I don't know if they have nailed down the mechanism of action, but I do think that it has something to do with the ribosomes, the impact on the ribosomes for women and that would be omega-3 fatty acids. We know that it can be helpful for a whole host of things, brain health, mood, et cetera, vitamin D unless you're out there in the sun all the time.

Ben:  Yeah, that's a good stack. So, we have fish oil, vitamin D, creatine, amino acids, maybe some urolithin A. Yeah, I think that's fantastic. I mean, I can't say I can name. There's all sorts of other things out there like ATP precursors or blood flow-enhancing agents, but what you just named is a pretty good stack. One other I would throw would be colostrum. I really like the effects of colostrum and growth hormone, particularly.

Gabrielle:  So, gut health, the gut muscle access is going to be the next frontier. The gut muscle access is going to be the next frontier.

Ben:  Yeah. Well, I should ask you actually. When you say gut muscle access, what do you mean?

Gabrielle:  For example, urolithin A is a postbiotic that directly affects mitochondrial function.

Ben:  Okay, yeah.

Gabrielle:  There is the ingestion or the creation of this postbiotic that actually has skeletal muscle effects. I think that it's probably bidirectional. You're talking about colostrum. I had mentioned before that my husband's a SEAL in my clinical practice a whole portion of the practice is all special operations. And, one of the things that we always, always do is we treat gastrointestinal infections, we treat parasites, we treat all kinds of things. And again, this is anecdotal, but the better their gastrointestinal health is, the better their physical performance, the better their nutrient absorption, everything. And, of course, there's butyrate production. There's a whole host of things. But, I do think that there is a gut muscle access that is going to be just there's going to be a lot more attention on that because we've all talked about the gut microbiome.

Ben:  Yeah, yeah. If for no better reason that it's hard to do a deep barbell squat when you have diarrhea, right?

Gabrielle:  True. Also true.

Ben:  Yeah. Yeah, okay. Gabrielle's great laying everything out. I'm going to link to everything that we talked about, except maybe the Morpheus laser because I don't know if I can hunt that down. You go to BenGreenfieldLife.com/Lyon, Gabrielle's last name, L-Y-O-N, BenGreenfieldLife.com/Lyon. Gabrielle, thank you so much.

Gabrielle:  Thank you so much for having me, Ben.

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Having trouble mustering the motivation for a muscle-building gym session?

With a background that includes a combined research and clinical fellowship in geriatrics and nutritional sciences at Washington University in St. Louis and undergraduate training in nutritional sciences at the University of Illinois, she is a subject-matter expert and educator in the practical application of protein types and levels for health, performance, aging, and disease prevention. Dr. Lyon's book, Forever Strong: A New, Science-Based Strategy for Aging Well, outlines her whole-body, whole-person protocol for muscle health optimization.

Through her private practice, popular YouTube channel, influential podcast, and new book, she asks a fundamental question: How can you build strength, not just in the weight room, but in your daily life? Dr. Lyon's mission is to help you uncover the secrets to building consistent dietary and lifestyle habits, so you can show up for yourself and your loved ones, making the world a stronger place, one step at a time.

Join Dr. Gabrielle Lyon and me as we delve into the science behind building and maintaining skeletal muscle mass, the benefits of resistance training for brain health, the optimal daily protein intake for muscle synthesis, and much more!

During this discussion, you'll discover: