You're Eating More Protein Than You Need | Prof. Leigh Breen

0:00Dr Karan: Building muscle is so much more than getting stronger and looking better. Your muscle is an organ that creates changes throughout your whole body, and that's what we're digging into with Prof. Leigh Breen. I'm Dr Karan, and in this podcast, I speak to the world's foremost experts in science and medicine to cut through the BS of modern health advice. Thanks as always to Throne Science, the world's first continuous, hands-free, smart toilet device that can track your gut health with Every Flush for sponsoring the show, as well as Loam Science, the world's first clinically backed invisible fiber blend.

0:33Dr Karan: Professor Libreen, thank you so much for taking the trip down to London to join me today. Pleasure. Thanks for the invite. You spent most of your career studying protein metabolism, longevity, muscle. A lot of people think about muscle as just something that is the building blocks of our body that we use to pick up heavy stuff and get us around you know, everyday life, but actually it's tied to brain health, immune health, gut health, liver health, so many different things. What do people need to understand about muscle beyond just lifting heavy things? Yeah, and that's a great point. And one of the most common misconceptions.

1:07So, you know, without doubt, muscle helps with locomotion, helps us complete everyday activities of living. So you use the example of moving stuff and moving ourselves and moving stuff. But we also come to understand over the last couple of decades that exercise can be thought it was an endocrine organ so in response to physical activity and exercise muscle can release factors called called myokines that can exert broader physiological health benefits across a number of different tissues and organs as well so these myokines effectively small molecules that are able to communicate messages to other tissues so for example with exercise and physical activity that muscle response can communicate to the cardiovascular system to promote health benefits also the brain and a whole range of other systems as well that we'll maybe we'll talk about today.

1:50Dr Karan: So these myokines, they are presumably just anti-inflammatory compounds, but also in addition to producing an anti-inflammatory effect, which is likely beneficial in multiple organ systems, there are also chemical messengers, neurochemicals. And you mentioned the brain as well, which we'll talk about. So based on what you said, this release of hormones and chemicals that the muscle produces, would you say that the muscle could be thought of as an endocrine organ based on that yeah I think we're shifting our perspective and our understanding of muscle and most muscle physiologists now will refer to it also as an endocrine organ as well as a a tissue that supports function and strength yeah absolutely and what happens in the hours after exercise say I go to the gym nine o 'clock in the morning lift some weights do some resistance exercise you know go on a treadmill for 20 minutes what's happening in the minutes and then hours And then for the rest of the day after that session, is there like a halo effect for the rest of the day and perhaps even longer from that just one session?

2:52Yeah, it's a great question. And the short answer would be yes, but then the more nuanced answer would be it depends. So if we think about muscle health, first of all, we've come to understand that the response to exercise training or a workout seems to be more long lived than just a very, very short window after exercise in terms of the release of factors that exert health benefits. and that probably also extends to a range of other different tissues as well but in response to exercise there if we move away from perhaps myokines and more to other hormones it was conventionally thought that the release of things like testosterone growth hormone and IGF-1 was really what exerted muscle adaptive remodeling effects so was the stimulus that supported muscle growth we've come to understand over the decades that that process appears to be managed at a local level so within the within the muscle fiber itself so as muscle fibers are activated when they're put into tension during during our training that sets off a process of signals that are linked to muscle protein turnover and increased muscle protein synthesis and that's that's ultimately what drives an increase in in protein and expansion of muscle fibers that we commonly characterize at the gross level as an increase in muscle mass and those are the hormonal responses i mentioned testosterone igf growth hormone without doubt they exert some biological effect.

4:09There are very few instances in human biology where there are redundant responses to a given stimulus that don't exert any effects. We think those hormonal responses may be linked more to remodeling of the extracellular matrix. So effectively the collagenous tissue that surrounds and supports muscle, potentially also our tendons and ligaments, and perhaps also other tissues such as the heart.

4:30Dr Karan: We were spoken about the effects on the brain. A lot of people typically say that exercise is good for the brain. There's a lot of, you know, consequential reasons that maybe obviously if someone is joining a running club community aspect, doing running with other people, which is going to be, you know, good for your mental health and good for your brain. The simple act of exercising, releasing endorphins, blood flow, maybe fresh air, all those things are good for the brain. But independent of those factors, is there something driven by the hormone release from the muscle and the myokines that we spoke about that neurochemically from that point of view is good for the brain you said there's that crosstalk but yeah I'm not a brain guy but I've worked with and published with enough enough brain guys and girls to have picked up a few a few bits along the way so yeah without doubt physical activity and exercises is great for brain health so I think this occurs seems to occur through a number of different pathways so first of all we think about neuroplasticity so effectively the remodeling of the structure and the function of the brain that that seems to well supported you mentioned blood flow we know that exercise increases brain blood flow and of course also mental health well-being and a number of different aspects of cognition as well the mechanism through which that seems to be driven does appear to be neuroendocrine so there's a release of a factor called bdnf brain derived neurotrophic factor that is a muscle but also the level of the brain as well so this this hormone seems to promote neural function as well So yeah, BDNF seems to be particularly important.

5:58And actually thinking beyond those short-term acute effects in response to exercise, that hormone response in the longer term, chronic exposure to this factor and potentially other hormonal factors as well, seems to support longer-term brain health outcomes. So when we think about dementia and Alzheimer's disease risk, this seems to be lower in people who've been able to engage in lifelong physical activity or perhaps structured exercise as well. So yeah, a number of different benefits. you know it's really really wide ranging in terms of brain health so i guess that's one of those

6:29Dr Karan: halo effects we're talking about longer term brain protective effects from exercise and even in the shorter term so you know i've got a you know a 13 week old child now so my sleep is in the bin completely but i found i can somewhat mitigate the negative effects on my physical and mental health from this sleep deprivation i've been experiencing over the last few months by doing exercise first thing in the morning. And, you know, I'm not completely back to 100%, but maybe the BDNF release, the myocardial release, just doing some motion is helping to, you know, offset some of those harmful effects of just getting four hours of sleep a night for the last few weeks.

7:08Yeah, absolutely. I think you're right. It extends beyond cognition, learning and memory and brain remodeling effects to mental health as well. We're still really trying to understand, I think, what factors drive that positive mental health response to exercise at the brain level. But I share your pain in a sense that I also have a 13-week-old as well as two others. So sleep, stress, all of those things that can circulate as part of my daily life, the 45, 60 minutes a day I get to exercise, yeah, as untold beneficial health effects for me.

7:44Dr Karan: I want to talk about something that's quite personal to me and about some medical conditions that I suffered from. I used to have high cholesterol and fatty liver disease and that primarily stemmed from a severe lack of fibre in my diet. And on my quest for finding the perfect fibre supplement over the last few years that could help me add more fibre into my diet, I couldn't find one. That ticked all the boxes that I wanted and the high bar that I set for myself. So it built Loam Science. What I'm most proud of is not the product. I know that's great, but it's the fact that we've run two clinical trials on it, two randomized controlled trials, which is far more than the vast majority of supplements on the market will ever do.

8:20Dr Karan: And we've got even more coming because I'm a doctor first and foremost and a scientist. And I wanted to build something that I could actually stand behind with data and not just rely on good branding. So if you want to understand what's inside Loam Science and why, the science is all on the website and the link is in the show notes. There's something which is less well understood by a lot of people, but I'm very interested in gut health and I've been seeing some research. It's not maybe the highest quality research, some mechanistic data and observational data, looking at the role and the connection between the muscle and the guts.

8:56Dr Karan: There was interesting biobank cohort study looking at older women and older men specifically, and looking at proxies of longevity, like, you know, grip strength. And they found actually in older women and older men, and it was more pronounced in older women that the higher fiber intake cohorts had higher grip strength and other proxies of longevity, which suggests there may be this underpinning between the gut and muscle, the gut muscle axis. What do we know about it so far and what is the link? Yeah, well, what we know so far is that the gut and muscle appear to be in close communication. Now, these two tissues systems don't necessarily dictate the function and the health of the other but they communicate.

9:38So if we think about the link from muscle to gut, first of all, and we go back to myokine release, we know that regular exercise can improve gut health. So gut motility, first of all, but also in terms of the production of healthy bacteria in the gut as well, so a healthy gut microbiome. We know there are clear links there that may be driven by myokines. So exercise and that muscle response creates an environment in which the gut can thrive, but it's a bi-directional relationship as well so a gut that's thriving in response to exercise in this muscle response also creates an environment in which muscle can survive as well they can thrive as well so cyclical and bi-directional healthy gut microbiota seems to reduce systemic inflammation and we know that's great for muscle protein turnover and can support help us support muscle mass and strength with advancing age so that appears to be the link so they don't directly control one another but optimizing these two these two systems creates an environment where the other one can thrive.

10:35Dr Karan: Yeah, it's fascinating because as you mentioned, there's a lot of data which suggests that if you do exercise more, then the composition and diversity of your gut microbiome may be positively influenced. And we also know that obesity states are associated with a more dysbiotic or abnormal microbiome composition. So it stands to reason that if you optimize your gut, you optimize your microbiome and the, you healthier microbiome composition will produce more of those anti-inflammatory short chain fatty acids, which have that anti-inflammatory effect towards the muscle, prevent any breakdown of muscle fibers.

11:09Dr Karan: But also there's a connection with the guts and liver and the muscle as well. So, you know, that's probably like an interesting triangulation point to the muscle as well. Yeah, absolutely. So the gut muscle liver axis seems to be an interesting relationship. So So, yeah, I mean, the health of each of these systems, the independent health of each of these systems seems to influence the other one as well. So we've done some work over the recent years on muscle health in patients with chronic liver disease. And I guess most relevant to this conversation today are those with metabolic associated steatotics or muscle patients.

11:46And we found that those that are able to engage in exercise and support higher levels of muscle mass strength and function seem to be able to reverse some of those harmful impacts on the liver. So in terms of the fatty depositions on the liver that we know are going to ultimately become really, really harmful if left to progress, some of those harmful effects can be reversed or seem to be less severe in those patients who enter disease with healthy levels of muscle mass strength and function.

12:13Dr Karan: So when people think about the paradigm of building muscle, we know the number one stimulus is resistance training. And people often, you know, rightly educate protein, adequate protein intake to, you know, ensuring that you can maximize and optimize muscle protein synthesis. But based on the available data, UK Biobank data, and, you know, other data that, you know, is coming out there, maybe also as part of that kind of protocol or paradigm, we should be thinking about gut health optimization, optimizing fiber intake, fermented foods, plant diversity could also support muscle protein synthesis or at the very least limit the pace of sarcopenia as we age.

12:53Yeah, no, I absolutely agree. I mean, I think the focus until this point, until relatively recently, has been around optimizing protein intake as a way to squeeze more of an adaptive response out of the training you get. So you mentioned, and rightly so, that the most important thing you can do is the resistance training, right? It's the analogy of the ice cream sundae, right? It's the ice cream, the whipped cream and the majority of the sundae and the protein nutrition gives you the added small benefit, maybe the sprinkles and the cherry on the top, but it's not much of the sundae really. So yeah, I think we're starting to explore how other micronutrients and components of our diet can support muscle health.

13:29It's becoming quite clear when you look at components of the whole food matrix that we think beyond the protein, there are other components that seem to be associated with good muscle health outcomes as well. you mentioned fiber there as well so i would i would urge people you know for focusing on increasing protein intake is probably a prudent strategy or increasing protein intake beyond current guidelines that are set in place to avoid deficiency i think a little bit more protein than that is probably beneficial for the vast majority of the population but that shouldn't come at the expense of neglecting other key nutrients as well and we know that fiber intake is problematic for for a lot of individuals.

14:05And if the focus on getting very, very high protein means taking away fiber from the diverse range of plant sources, that would be a bad way to go. I would recommend somebody steer away from that. We don't all need bodybuilding, high levels of protein intake to support and maintain good muscle health across the life course.

14:24Dr Karan: So I guess for most people, you know, correct me if I'm wrong, but the literature suggests 1.2 to 1.6 grams per kilo per day would be an optimal range to, you know, get most of the gains to just, in addition to training, optimizing muscle protein synthesis. And if you're like an elite level athlete and very well trained, you know, there is case for going above towards 1.82 grams and maybe in specific populations, post-surgery, pregnancy, very elderly again, or like, you know, post-cancer treatment, again, pushing towards that higher end towards two. but you know apart from that there's no real need for the average person to go two grams per day per kilo and above no no I don't think so the vast majority of our population are consuming between 1.0 and 1.2 grams yeah the ground body massive protein a day anyway so already above the recommendations in FAO and the WHL to avoid deficiency so most of us are consuming enough protein but then when we think about how much rather than a scenario where we're trying to avoid deficiency if we think about trying to improve or support the health of certain tissues like muscle then going beyond that might be beneficial so if people are able to hit somewhere in the range of 1.2 to 1.6 grams per kilogram body mass a day of protein the chances are they're getting more than enough to support the and and maintain muscle tissue especially if they're exercising alongside that that protein intake as well so that that would be the recommended range and i think whether you're young middle-aged or older it's a great range to try and hit and 1.2 to 1.6 can be problematic and challenging it does require a little bit of additional thought to get there and also this idea that protein intake should be spread distributed evenly across the day as well so as opposed to a really a protein heavy dinner meal in the evening actually thinking about am i getting enough protein at breakfast am i getting enough at lunch but potentially with a mid-afternoon snack as well is that protein present to support that muscle remodeling process um when you go beyond 1.6 and you the return you get in terms of the support for muscle mass or muscle building becomes diminishing so with those increments beyond 1.6 the return you get is smaller and smaller as well um i mean we often hear about the sort of figure that's touted around of one gram per pound of body weight which is over two grams per kilo body mass a day right so So, I mean, I think there's a status scenario really where we're talking about bodybuilders, potentially, you know, elite strength powerlifter, strong men, strong women, competitors.

16:570.1 % of the population. Yeah, I think, you know, and only in those populations would you be able to discern some benefit, functional or muscle mass benefit from going to those extremely high levels. I mean, I think those levels, they appear to be relatively safe. They don't appear to be health complications from going that high. But in the general population, mere mortals like you and I, the amount of effort required to get to those levels, we would spend most of our day thinking about how we can squeeze more protein in, which doesn't seem worth it.

17:25Dr Karan: I guess, yeah, to your point earlier, my concern would be for the average person who is going above the thresholds that we outlined, not only could you risk cutting out other nutrients like fiber and other essential micronutrients as well, vitamins and minerals, but also just based on the anatomy of our body, all that protein is primarily absorbed in the small intestine. And if you're going consistently above the capacity of the small intestine to absorb protein, it leaks into the colon where your gut bacteria start fermenting that protein and those amino acids into pro-inflammatory compounds.

18:00Dr Karan: You know, that proteolytic fermentation you get, they switch from fiber fermentation, which is their native state to proteolytic fermentation. and you get these pro-inflammatory compounds, which can cause low-grade inflammation to the colon. So over a long period of time, if someone is consistently eating well above what they need, 200, 240 grams a day, which is not unusual for, you know, young men trying to train in the gym and, you know, like do that sort of thing. And then they get chronic gut problems. It may be in part because of lactose intolerance, because of high whey protein consumption, but also it just could be because of an imbalance between their protein fiber ratio.

18:37Yeah, I think so. So I think in, in, in scenarios where protein intake is very high, the, the, the, the colonic, um, inflammatory effects you, you mentioned there aren't necessarily problematic if, if other components of the diet and micronutrients are adequate. So I think it's only when there's an inadequacy and this is practiced over a very, very long time. Could it, could it become problematic and, um, and cause some of those issues now into how that manifests in terms of very serious health complications? I don't think we're there yet in understanding that um yeah without doubt i think if you're consuming very very high protein with a view to optimizing muscle mass some aspects of performance and strength it will be prudent to consider the other key nutrients in the diet that are adequate as well absolutely

19:17Dr Karan: now something with regards to protein that's had a lot of hype recently is collagen protein i have somewhat softened my stance as we discussed uh previously off air first of all to set the seen collagen powders are you know very viral right now everywhere everyone seems to be using collagen powders mainly seems to be touted for benefits of skin and joint health there also seems to be a lot of data out there randomized control trials meta-analyses systematic reviews a large proportion of those are industry funded which is not inherently a bad thing i mean they're just you know funded by people but you know that's a inherent bias there but doesn't mean the data is wrong just on that alone there is some non-industry funded research also some recent reviews of that and my initial take on collagen powders was that you know they're a total scam and they're not needed because they're an incomplete amino acid profile i mean it's got glycine proline hydroxy proline which are a unique combination this triple helical structure which you don't really find in other things.

20:21Dr Karan: And we obviously need collagen for skin health, bone health, muscle health, but it's not a muscle building protein source as opposed to whey protein, for example, or other plant proteins. But there is data on skin and joint health, and there is non-industry funded research suggesting independent of whey protein in resistance trained individuals, there is some incremental benefit of things like collagen. And especially given most of us don't really get collagen from dietary sources from cartilage or connective tissue and eating nose to tail animal sources is there some potential benefit from collagen powders for some for some people and actually is it right that i'm softening my stance in going from it's totally useless to actually there may be some benefit for some people and overall it could be a net positive because i I can't see it causing any major side effects or harm apart from just being expensive.

21:20Yeah, you make some great points. And I'd agree with you in terms of softening my stance and being a little bit more open-minded to the huge amount of evidence that's been generating in the last four or five years in this area around collagen supplementation. I think in terms of muscle, first of all, so we, seminal studies in the field decades ago demonstrated that it appeared to be the essential amino acids that are required to drive muscle protein synthesis and seem to be really key for helping us to develop muscle mass and so you mentioned some of the amino acids the non-essentials and incomplete amino acids that are present in collagen that we don't think or expect would promote a huge protein synthesis response and so would be kind of you know invaluable in terms of supporting muscle health in the post-exercise recovery period compared to something like, you know, most animal-derived proteins like whey that are really enriched in essential amino acids and the branched-chain amino acids like leucine.

22:17But actually, there have been a number of studies that demonstrate some potential effects of collagen on muscles. So if you take a large dose of whey protein and you switch some of that whey out and replace it with collagen, the muscle protein synthesis response after exercise seems to be sustained. really um so what it suggests to us is the the theory here really is then that perhaps there's something about that essential amino acids in the whey protein that kick-stars this this muscle protein synthesis remodeling response and the non-essential amino acids in the collagen might through some mechanism be able to sustain this response in a way that doesn't look too different from say 30 or 40 grams of whey protein i'm not i can't think why people would want to switch the whey protein dose out but if you're trying to potentially target other tissues so if you're thinking about joint health, potentially skin as well, then potentially removing some of that whey protein or consuming a combination of whey and collagen gives you the best of both worlds.

23:13So you're supporting your muscle adaptive remodeling response. There's potentially also a benefit being delivered to tendons and ligaments. And I mentioned those collagen structures that surround and support muscle as well and help to transmit force. And so that force is recognized by the muscle. So that's potentially a dual benefit there. I think we're still fully understanding that. With regards to skin, there's, I don't know if this is published or not yet, but I see there's emerging evidence to suggest that the intake of collagen over either acutely or over an extended period of time doesn't seem to upregulate or increase the synthesis of skin.

23:49Doesn't. Doesn't seem to at the moment. Now, that's obviously a response to a very specific collagen supplement. We then need to consider dosing, timing, frequency, and all these things. And maybe if we do that, there's a benefit to skin health as well. But at the moment, when we look beyond the tissue responses even and look at functional or performance outcomes, aspects of recovery after damaging exercise seem to be quite well supported when people consume collagen. So in terms of jump height or the ability to reproduce high levels of force output, the intake of collagen seems to, as has been shown, to play a role there in a number of studies.

24:26So the, the weight of evidence is suggesting that there's some benefit here. Um, I think it's now about drilling down what that is and then also how collagen forms part of our kind of sensible dietary habits.

24:39Dr Karan: So I guess, you know, there are so many different types of collagen. Uh, you know, the, I guess the most useful for human health is type one, type three collagen, you know, in terms of the subtypes. So if, you know, to be very clear, I don't have any financial incentive for collagen. I'm not involved in any way or incentivized for that, but if someone were choosing a collagen supplement, are there specific things that you'd look at in terms of it's hydrolyzed, you know, X, Y, Z, what would someone be looking at? Yeah. I don't think we're that far advanced yet that we would recommend one supplement over another for muscle, tendon, ligament, or skin.

25:16I think really you're looking at the, I think the relative dose of some of those non-essential amino acids you mentioned before. also the glycine the proline the hydroxyproline you're looking at the content of those three primarily and effectively if in in in a given in a given number of grams of a serving how much of the protein is present in there now if those numbers closely match what that tells you is that there's not a lot of other stuff in there as well beyond that so i i think you're looking for those those figures to match as closely as you can so what i mean by that is when you take a scoop of your collagen powder out the weight of that of that dose should hopefully it should it should roughly correspond with the amount of the essential amino acids that the product tells you are in there you don't want that to be too discrepant does collagen on the i don't know if

25:59Dr Karan: you'd be able to answer this but on the back of nutritional labels does collagen count as a dietary protein source because it's incomplete i don't think it does at the moment yeah so if you were if something on the back of the pack said it's a 20 gram scoop and it said you know the percentage of dietary intake from that is 50 % or, you know, it's 12 grams of protein. Am I to assume that out of the 20 gram scoop, only 12 grams can be counted as, as a non-collagen protein source. And then the other eight grams could be collagen or something else. Yeah. I think in, in, in, in, in, in products that are, I guess aren't marketed as, as collagen based then.

26:38Yeah. Yeah. I think you're right to assume that. Yeah.

26:41Dr Karan: Cause I, cause I think that's one of the issues with the industry where we've had the nuanced discussion about collagen, what it can do, what it can't do, emerging evidence. But a lot of people, brands, manufacturers use collagen as an all-encompassing protein source to say that it's going to, they imply that it's going to help with everything, muscle, whatever. Because collagen, to manufacture and produce and source, it is a cheap protein source, arguably cheaper than whey protein, which actually the price isn't. So actually people use that to just bulk up the product right and actually they're doing a disservice and not being fair in their marketing by saying this is collagen it may support x y and z but it's not going to help with muscle protein synthesis as much as yeah i think we see this a lot with with again a huge kind of emerging range of products on the supermarket shelves marketed as high protein and contains 20 grams of protein and you've got kind of snack confectionery bars that contain huge amounts of protein now but what we don't know is often is the source of protein that's in there that that often isn't described and there's a good chance as you as you mentioned that it may be protein that is not necessarily of the quality that our muscles need or would respond best to and it's very unlikely that 20 grams of protein in your chocolate bar is going to be way very very unlikely as well so yeah not all proteins that i don't think are created equal in terms of their benefits to muscle and other tissues so i i think it's it's it's prevalent everywhere right even in bread i think there's always been um in the manufacture of bread there's always been a kind of high proportion of protein there used for kind of a emulsifying um and kind of a taste and consistency properties of the of the bread but now all of a sudden people have recognized that the protein that's in that bread that's been in that bread for decades can be confused as a marketing tool so all of a sudden we're hearing you know five grams of protein per kind of slice of bread and um but but yeah i think the protein that's in there isn't necessarily an amount or a source that is particularly beneficial to to especially when you consider the other things that are in there beyond the protein as well right so um you know it doesn't seem like the protein hype is showing any signs of slowing down in fact it's getting faster and harder as evidenced by you know the prices per kilo of whey protein i I mean, there's a whey shortage in the world because so many products and brands are using protein in their products for this supplying the kind of protein economy.

29:06Dr Karan: And I think the protein economy is likely being driven now by the GLP-1 economy. More people are on GLP-1s and concerns about muscle loss and muscle wastage and needing to increase protein amounts and provide that satiety for weight loss. So I'd love to talk about that. First of all, just regards to protein, classic industry protein has been things like whey protein, which we have known about for decades. people glugging their whey protein shakes. Is there some benefit to diversifying your protein source similar to, you know, we harp on about diversifying your fiber sources, not just focusing on inulin, but other fiber sources, because they provide different benefits to impacts on health, different gut bacteria.

29:44Dr Karan: Is there also a similar case to be made for protein where say someone had 120 grams per day from whey protein, I'm sure that will be absolutely fine to some degree, depending on their gut sensitivity but is it better physiologically to have 120 grams of protein from plant animal way a mix of different things yeah i i the phrase we've often used and borrow this from from colleagues we've worked with in the past is um food first but not food always so i think supplements have a place in helping us get to higher protein intakes so convenient accessible easy to to you know to have on the go but without doubt i think if people can achieve their protein intake goals through the consumption of animal or plant-based foods that's without doubt the best way to go we used to think that something about a supplement so this rapid digestion and absorption and this this this quick and high peak of amino acids in the bloodstream was what was necessary to optimize the the muscle remodeling response after a workout hence people kind of chugging shakes in the dressing room straight after straight after the gym we've come to understand that that isn't necessarily the case or that that there's no anabolic there's no anabolic window as such it's more of a kind of open barn door so if the workout has been of sufficient intensity and demand kind of high degree of effort has been has been elicited then that muscle is sensitive for 24 hours afterwards potentially even 48 hours so what that tells you is that it's not just the protein you consume in the first hour after your workout but the protein that you consume with every meal and snack for the next day or two that is going to support that muscle adaptive remodeling response so yeah i think food first but not food always foods when you compare them to supplements in terms of how they support muscle protein synthesis and longer term adaptive remodeling they don't appear to be inferior compared to things like whey protein or casein we think that even though the absorption kinetics how the amino acids appear in circulation may be a bit slower with food because of all of the other the other micronutrients as as well kind of complex food matrix there are other components in there as we we touched on earlier that may support muscle health yeah micronutrients i guess a lot of people historically have prioritized and almost glorified animal protein over plant protein because of this you know previously outdated assumption that you get an amino acid spike in the bloodstream earlier in a animal protein rich meal versus plant protein but actually over several days, you know, there's the same impact on muscle protein synthesis between animal and plant protein.

32:15Dr Karan: And actually the reason you don't get an amino acid spike with plant protein is because of probably the fiber delaying the gut absorption. And actually that's a benefit longer term because it has a probably a more favorable, um, impact on your cardiovascular system on your gut. And I guess we've got an abundance of data now suggesting that in terms of muscle protein synthesis animal and plant are probably equivalent and you could probably give the extra tick to plant because of the other impacts it may have on weight loss on just general gut and cardiovascular health yeah i i mean they they seem to perform comparably so um whether it's animal based or plant based i think as long as the dose is sufficient as you provide enough of of the source this seems to be um support equivalent muscle anabolic responses so you're right in thinking that the the fact that animal proteins generally were more enriched in essentially you know as compared to plant and that they also didn't have these so-called anti-nutritional factors that slowed their digestion absorption you know it's kind of great theory to support why an animal protein may be preferential for muscle remodeling especially if you're your exercise training we've come to understand that's that's not necessarily the case and and most high quality plant proteins do the job just as well as animal proteins like like way whether and that and that seems to translate to whether you're young middle-aged or older as well there doesn't seem to be heaps of difference we did some some work was published a year or so ago where we were um we thought that the role of protein quality and the importance of these essential amino acid spikes would potentially becoming more important the older you got and and effectively the less sensitive your muscles are to the protein you provide so we we've thought that was a scenario where protein from animal sources might play a kind of pivotal role but we found that wasn't the case so in middle-aged and older adults consuming a diet containing typical amounts of daily proteins so it was clamped at about 1.0 grams of protein per kilogram body mass a day whether that came mostly from plant or mostly from animal didn't alter how much new muscle protein these middle-aged and older older adults built over the course of this this short-term intervention so basically don't get in the weeds too much make sure number one your resistance training that's with number one lever for muscle building.

34:27Dr Karan: Number two, make sure you have just sufficient protein cumulatively in total. And if you were looking for cutting down the amount of saturated fats or helping with cholesterol, you're obviously gonna get those benefits with plant versus animal, but you shouldn't worry about the difference between the two. No, absolutely not. No, I don't think so. Quick one before we continue and something I've been genuinely nerding out on in my chief of science role at Throne Science is poop and pee. You see, most of us are completely blind to what's happening in our guts and urinary health day to day. We often wait until something is wrong.

35:01Dr Karan: But your body's actually constantly churning out data in your urine, in your bowel habits, in those patterns that most people never track. I'm proud to say that at Throne Science, we're building technology that captures exactly that. Passive, consistent biomarker monitoring of your gut health, your hydration status, your prostate health markers, without you even having to think about it. From a clinical standpoint, the shift from reactive to continuous monitoring is really important because that is where the early signal detection happens and that's when you can change your habits and hopefully outcomes as well.

35:33Dr Karan: I've been deeply involved from the science side because I think the research here is serious and with rising rates of colon cancer, poop talk is no laughing matter. So if you're curious about what that data could tell you, the links in the show notes. We talk about, you know, we've mentioned about this GLP-1 rise. A lot of people have this, I guess, unwarranted concern about GLP-1 and GIP medications specifically causing a breakdown of muscle. The data doesn't seem to suggest any direct causation between these weight loss medications and muscle breakdown directly. There's obviously an indirect effect, which you see with any degree of weight loss, especially rapid weight loss that we see in studies, whether it's bariatric surgery or anything else, you know, if someone's got cancer, if you lose a lot of weight, a proportion of that weight loss is lean mass.

36:22Dr Karan: So bone density and skeletal muscle. But correct me if I'm wrong, there is no established physiological biochemical pathway in which GLP-1 medications are upregulating the degradation of muscle fibers or anything like that, that we can say right now. You're not wrong. There isn't yet. But what I would say is that the more these medications evolve and we start to see dual and triple agonists, so they're GLP-1 based. We're now seeing GIPs and, you know, retatricide, and we're seeing amylin inhibitors kind of factored into the mix as well. Glucagon agonists also. So we're seeing these cocktail of, they're GLP-1 based, but there's a cocktail of, and obviously the intention there is to promote more rapid, more pronounced weight loss, right?

37:09it's to be the best, most effective product out there. But what we don't understand yet is how these combinations of medications that instigate this weight loss impact muscle. So there's emerging preclinical data to suggest that these isolated and combined effects of the different compounds may have a direct impact on the processes that regulate muscle tissue. It's not been confirmed yet in humans, but we hope to get there in time. but i think your your general position on this is is is correct at the moment we we're still understanding the i guess firstly the extent to which muscle mass deteriorates on these drugs because people generally haven't done a great job in prioritizing muscle mass and assessing it in a way that is is reliable and robust and also the the knock-on impact of that muscle mass loss on health and function as well as being it's been characterized in a number of ways but it's difficult to draw firm conclusions from that as well so we're still trying to get to the heart of that and some of the work we're doing in leicester actually is to to try and drill drill down on that what appears to be the case for the majority of glp1 users at the moment is that they appear to be able to withstand any muscle mass loss that may occur on these drugs because as you rightly point out the body weight loss is so great yeah that ultimately functions seem to be improved so the ability to rise from a chair, climb the stairs to, to, to, to perform a shuttle walk test.

38:34You can do these things because you're lighter, even though you've got a little bit less muscle, you've still got enough muscle and much less body weight that you can perform these functions better. Well, also if someone's on a GLP one, I think studies have suggested when they've done

38:47Dr Karan: MRI scans, the actual efficiency and function of the muscle is better because the intramuscular fat content is also reduced. So it's a more efficient, healthier muscle environment. Yeah, potentially. And I think I spoke about some of the preclinical work in this space that will emerge in the next year or two that shows that when you look at mitochondrial biology within the muscle as well, some of these compounds seem to have beneficial effects on the mitochondria. It's very, very clear in animals and it's potentially going to become apparent in humans as well. So yeah, I think for the vast majority of users entering these medications with type 2 diabetes, obesity, levels of muscle mass are so high and the quality of that mass is generally quite poor.

39:24that losing a bit of that mass and losing some of the the intramyel cellular lipid as well results in improved measures of function i i don't think we should be completely unconcerned about the loss of muscle mass though because i think there are scenarios we need to carefully consider before we make kind of blanket guidance or we brush over this so i think for the older adult where levels of muscle mass may be relatively low even in obesity that the presence of obesity as you know can potentially mask sarcopenia or low levels of muscle mass. It's a sort of hidden danger with obesity in older age.

39:57In those scenarios, the loss of muscle mass on GLP-1s can potentially be debilitating. We're still trying to understand how, even though body mass loss may be greater, so we're still trying to understand how these medications impact measures of function in older adults. And I also think about weight cycling as well. So all the patients on GLP-1s will eventually come off the medications. It may be one year, maybe two years. these aren't lifelong treatments and a couple of really interesting articles have recently demonstrated that the majority of glp1 uses is in the year or 18 months after the medications regain an awful lot of the weight again now we're trying to understand what that weight regain looks like but there's there's a lot of theoretical evidence to suggest that it may predominantly be fat mass so even if you lose some muscle mass on the glp1s and you only regain the fat mass from a body composition perspective after starting the medications three or four years down the line you may be worse off in terms of function metabolic health so uh you're seeing um cycling where if

41:00Dr Karan: you're on the medication for a year you lose fat and some muscle and then you stop the medication and you regain some weight some regain the fats with less muscle yeah and you keep going down on a stepwise degradation where maybe the body composition continues to deteriorate because there's increasingly more muscle loss than the fat reduced. So when you think about body tissue compartments, overall, the ratio of fat to muscle mass is becoming poorer with every year that this occurs. And it's interesting to speak to patients who are on these medications. And we've kind of done a lot of focus group work and had these conversations.

41:34A lot of people who, well, those who are unable to positively engage in the lifestyle and behavior change as well as the medications, which we know are key for long-term kind of successful health outcomes see these medications as something that they will cycle on and off for the rest of their lives yeah this is where people are going now so we're seeing people with obesity and you know maybe in their 30s and 40s taking the medications for a period of time achieve great health benefits regain the weight and then they're fully open to the idea that in two years time they'll be back on the medication again and this is going to be a lifelong a lifelong practice effectively cycling on and off um i mean we really don't know much about the long-term safety implications yeah of doing that um but it's almost certainly going to be harmful for body composition

42:20Dr Karan: i i'm interested though of the kind of like non-weight loss or weight loss independent effects because in a lot of people who are on glp1s who would be classified as non-responders so they lose less than five percent of their total body weight in some of these people you still see reversal of fatty liver, reductions in blood pressure, improvements in heart outcomes, you know, complete reversal of sleep apnea, cardiovascular health benefits, mental health benefits, all these things present. And maybe that's part of that general anti-inflammatory effect because we know there's GLP-1 receptors on the bone.

42:52Dr Karan: And so some anti-inflammatory effect providing that independent of the weight loss. So I think there's something interesting there. And to your point, as we evolve in the paradigm of treating people with GLP-1s, it's about establishing some degree of personalization to that person. You know, because once we get triple and quadruple receptor agonists, certain populations and cohorts might respond better to those different receptors and different cocktails of drugs. But also equally important is that different people respond completely differently in terms of weight loss, in terms of side effects.

43:28Dr Karan: And I think there was a recent study out of the Mayo Clinic, which suggested that actually there was a certain subtype of obesity, which they just found called the hungry gut phenotype, where actually it's not the fact that they're just more hungry, it's that they're less full. Their guts produce and their brains produce fewer fullness signals. And there's also changes anatomically to their gastric emptying, their gut motility, which just makes them less satiated. And they respond even better to tizepatide, the dual receptor agonist, because now you're providing the fullness, which is actually not so much of a problem in the, you know, other phenotypes where actually there is some baseline production.

44:06Dr Karan: And so I think looking at maybe some genetic phenotyping and genotyping where you figure out like who would benefit the most and who would lose the least muscle. I don't know. I think there's something there potentially. Yeah, no, I agree. I think, I think, you know, the only way to get there is large scale studies, patients on a given intervention and then understanding the broad biological effects across different tissues of systems of the medication. trying to understand from those biological factors what may or may not determine somebody's responsiveness and you're right in saying you know even if body mass doesn't alter an awful lot people you know we do see people who don't lose more than five percent there are in in the broader sense of the way there are no non-responders really there are there are there are always health benefits somewhere down the chain some of these things are hidden most people go are on the medications for body weight uh body weight loss but even if that isn't achieved there's improvement in a number of other areas as well i think so what determines that is really interesting and i think if we can understand that then we it gives us a great framework from which we can actually um we can actually kind of base subsequent um interventions as well so we might know that somebody's not responding to a kind of conventional glp1 okay so is it is it to zepatide or do they need a do they need an amylin inhibitor as well or a glucoanagonist on there as well to optimize their response yeah i constantly see every few months these viral videos and images online showing someone in their 30s who trains and showing a cross-section like an mri cross-section or a ct cross-section of their thigh and showing the muscle mass and then you see someone who's untrained and doesn't do any exercise in their 30s showing less muscle and then you compare it to someone in their 80s who is training all their life and the 80 year old who is training has the same amount of muscle mass as someone in their 30s who's untrained.

45:54Dr Karan: Now, I don't know the background of whether that's actually true. Is that real case reports that someone's followed or is it just like a viral image? But it does stand to reason that, you know, the more you train throughout your life, you'll preserve some muscle. But I think that is fascinating about like, you know, the requirement, well, we lose muscle as we age, that's impossible to get rid of, but we can slow it down. What is your take on that? Because, you know, it's a viral image. I might be responsible for some of those images. I think we've published one or two reviews where we've, we may have, I think we've added these images in.

46:27So, and so, so then they're not purely viral, they are real.

46:30Dr Karan: Real images, yeah. It's possible if you are, I mean, we've done a lot of work over the years. I worked with a great PhD student a few years ago in a population of master athletes. So older adults who've engaged in generally in very long-term physical activity and structured exercise training and are still competitive, you know, well beyond their 60s. and in some cases into their 80s. And in terms of their physiology, it more closely reflects a much younger person. So they buy back many, many years of physiological function and good health through these lifelong exercises. So yeah, I think sarcopenia, this progressive loss of muscle mass, strength and function, to some degree is an inherent age-related process that no one can truly avoid, not completely.

47:14But I think I've changed my stance over the years And I think most of it is driven by this.

47:19Dr Karan: Most of this deterioration is driven by lifestyle factors, I think, inactivity, poor or undernutrition. And, you know, there are other factors that are somewhat unavoidable. So I think the presence of chronic disease, illness or injury, which we know we have an increased risk of as we age, the presence of those factors can also speed up this muscle loss process. So I think it's very difficult to avoid all of those factors and get to the age of 80 years old. But when we compare athletes, an older athlete is still not the same as a younger athlete, right? So their world record times will slow down and their peak performance will drop off, even if they're able to stay free of disease and maintain consistent training habits.

47:59So that tells us that some aspects of this deterioration is unavoidable. But actually, I think a large majority of it is reversible with structured exercise training.

48:08Dr Karan: You know, so obviously there's some unavoidable things, such as you mentioned illness or someone having surgery. if someone is having surgery or a period of illness where they just can't train for several weeks or several months what degree of muscle loss do we see and what can someone do about that to build them back up to baseline or get close to it's a great question we've you know we're now sitting on 20 or 30 years worth of work that's characterized this so we're unsure whether these things differ between younger and older people as well so in terms of the the amount of muscle you lose whether you're male female young or old it's pretty rapid so as soon as you unload somebody you unload the muscle and you make somebody still for a period of time you you put them in bed or you they're in a cast on crutches that deterioration starts almost immediately appears to be comparable comparable as i mentioned across the populations uh in our own studies we demonstrated that the the loss of muscle mass in just five days of quite strict bed rest in older people is roughly the equivalent of what you would see with somewhere between three and five years of longitudinal aging so these are the year by year the age-related muscle losses is relatively subtle these figures it's you know 0.5 to 1 % of your muscle mass will be lost a year which which is relatively 30 roughly is that the I think the face it's been reported from the fourth decade of life so I think 40 and onwards obviously it seems to the steepness of that curve seems to increase the only yeah as well so yeah in our own work we generally demonstrated that and you know that others out there have reported a figure of you know with with 10 days of bed rest or immobilization the equivalent of 10 years of aging of longitudinal aging in terms of muscle mass loss so it's pretty serious how quickly can you get that back then well this is so this is where age may come into it because when you're younger we appear to be quite resilient to this in terms of how we bounce back and respond so even without aggressive retraining and form resistance and strength training it appears that younger muscle is it's going to rejuvenate and regenerate quite well certainly people don't notice any long-term functional deficit when they're younger if they've had a period of injury and generally get back to performance and competition quite quickly in older age we know that response isn't as efficient and even with quite aggressive structured rehabilitation training even after um eight twelve weeks older muscle in some cases still hasn't got back to where it was pre pre-dissues we were understanding why that may be so older muscle seems to be a little bit a little bit more resistant to the anabolic effects of protein nutrition and exercise so all the muscles respond well you can get you can get great effects it's just those responses aren't necessarily youthful responses um and so yeah it's possible to get it back but you know i think older adults you know really need to focus on um on rehabilitation afterwards as well i think but there are also a lot of things people can do to um to slow or prevent that in the first place so this is why a focus on maintaining healthy levels of muscle mass and strength earlier in adulthood is a key a key strategies because if you if you enter some point later in your life if you enter a period of ill health where you are bed bound um sick and can't can't exercise if you enter that with healthy levels of muscle mass and strength it's a physiological reserve that allows you to better withstand the the insult that that illness throws at you so it's easier to slow down the loss of muscle than it is to gain muscle in older age well yeah i think it's yeah i would say it's both really so i think if if we've got older people who are yeah i think if you're 50 60 years old you suffer a fall or a fracture if you go into that with relatively healthy levels of muscle mass and strength the chances are that you will um you'll be out of the cast sooner the chances of any kind of long-term follow-on injury or mobility limitation are reduced and in terms of independence and um return to high quality uh high levels of quality of life all of those things are better supported if you enter with higher levels of muscle now i'm not talking here about bodybuilder levels of muscle mass which i think is sometimes misconstrued i think i'm talking about at a younger age taking the muscle you have performing some form of structured resistance exercise to potentially improve and increase the muscle mass but actually it's more about its strength and function as well that's really all you need i think moving beyond that to bodybuilder levels of yeah super high levels of muscle mass is is not necessarily a requirement and i don't know that would be a good thing in in in very older age anyway so it's making the most of what you've got um in kind of sensible terms not being super muscular and yeah yeah super heavy and yeah so so we know that if you do that then you stand a pretty good chance of of of um you know you'll be your length of stay in hospital will be will be reduced and we know that's going to have great knock-on benefits for the health services law in terms of the cost of treating people we can free up bed space yeah we're less likely to get back there in a few years time because we have these healthy levels of muscle mass and strength i think Yeah, a lot of people probably in their younger decades think about muscle as this locomotion lifting.

53:17Dr Karan: Yeah. And there's a, maybe people don't really think about the functional quality of muscle to prevent, you know, accelerated age and other comorbidities as well. And Lee, thank you so much for joining me today and just shedding light on protein and muscle, which a lot of people talk about, but actually I think there's a lot of hyperbole and not enough nuance. So thank you so much. Welcome. Pleasure.