FoundMyFitness - #081 The Anabolic Potential of Omega-3 Fatty Acids | Chris McGlory, PhD

Episode Date: July 3, 2023

Dr. Chris McGlory is an assistant professor at Queen's University in Kingston, Ontario, Canada. Known for his work in the field of muscle physiology and aging, Dr. McGlory's research focuses on elucidating the molecular mechanisms underlying muscle protein synthesis and degradation, with a particular emphasis on the roles that omega-3 fatty acids play in maintaining muscle health in older adults. In this episode, we discuss: (00:00) Introduction (05:50) Start of interview (13:03) Why atrophy is worse for the old than the young (15:23) Can dietary protein prevent atrophy? (17:35) Why reduced movement can insidiously mimic short-term immobilization (22:51) The disability threshold — when atrophy may actually be deadly (24:58) Does high-dose omega-3 hold the key to fighting atrophy? (5g/day) (28:35) Does omega-3 help muscle respond more optimally to low protein? (41:37) Why omega-3 must be preloaded for 4 to 6 weeks (44:20) Why omega-3 trials have conflicting results (50:16) Does omega-3 enhance strength? (52:42) Sex differences in gaining mass and strength (54:46) Improvements in gait speed and balance (muscle performance / physical performance battery) (55:49) How to act on mixed evidence — and should we? (58:17) Why omega-3 may reduce frailty in old age (1:01:59) Why the anabolic mechanisms are counterintuitive (going beyond the canonical anti-inflammatory role of omega-3) (1:07:42) Do omega-3s boost tired, dysfunctional mitochondria? (1:15:16) Why we need an "omega-3 index" for muscle (1:18:52) Why the inflammation from cancer wastes muscle (1:20:38) Does omega-3 reduce atrophy from cancer cachexia? Watch this episode on YouTube Show notes are available by clicking here Join over 300,000 people and get the latest distilled information straight to your inbox several times per month: https://www.foundmyfitness.com/newsletter Become a FoundMyFitness premium member to get access to exclusive episodes, emails, live Q+A's with Rhonda and more: https://www.foundmyfitness.com/premium Learn more about the premium podcast The Aliquot: https://www.foundmyfitness.com/aliquot

Today's episode will cover something profound, something a little unexpected, which is yet another role for omega-3 fatty acids. We are not going to talk about brain function, cardiovascular risk, and surprisingly not even that much about inflammation. Instead, we're going to dive deep into the world of omega-3 fatty acids and their impact on muscle health, and the role of omega-3 for disused atrophy, and perhaps even a role in building muscle. Picture this scenario. You've injured your leg, or you've had a surgery and your leg or legs have been immobilized for weeks. As the cast comes off or as you're able to walk again, you notice a significant loss in muscle mass and strength.

Even if you're otherwise young and healthy, as little as two weeks, could result in nearly 15% loss in the cross-sectional area of your quadricep muscle. This is devastating, but even more so if you're an elderly person. This kind of event can trigger a downward spiral and a crossing of a disability threat. a point at which physical function has become so severely impaired that it now undermines the daily activities that ordinarily would prevent even greater muscle loss. Once this threshold is crossed, it leads to a catabolic crisis. This state perpetuates the body's breakdown of muscle progressing catastrophically towards mortality. But consider if, in that same scenario, you could

cut that disuse muscle atrophy nearly in half. This is where the research of Dr. Chris McClory on omega-3 fatty acids and muscle mass could offer a potential solution. In this episode, we'll explore omega-3's impact on muscle mass, protein synthesis, and mitochondrial function. We'll be exploring the potential benefits of omega-3 fatty acids for enhancing muscle protein synthesis, especially in response to protein consumption. This process can be diminished during periods of disuse and becomes particularly important as we age. We'll discuss if this effect could improve. muscle protein synthesis even when dietary protein intake is less than ideal, a situation

particularly relevant for many older adults. As we age, our protein intake tends to decrease, and our ability to respond to dietary protein and amino acids through muscle protein synthesis weakens. These factors contribute to sarcopenia, which is characterized by the loss of muscle mass in older age. Omega-3's potential to enhance muscle protein synthesis in response to to suboptimal protein intake could be especially beneficial for older adults who often experience both insufficient protein intake and a reduced ability to effectively respond to it, a phenomenon known as anabolic resistance. Dr. McGlory's findings may be applicable to anyone experiencing muscle disuse, but they may hold particular significance for older individuals. His latest research

aims to figure out what the optimal dose and duration of omega-3 supplementation is for muscle health. His new trial will examine muscle protein breakdown and the effects of omega-3s on mitochondria, potentially leading to exciting clinical applications for those experiencing age-related muscle loss or periods of disuse. What is also exciting is the part of this discussion on how omega-3 may improve muscle strength and walking performance in older individuals, especially when combined with resistance training. In other words, it's possible that omega-3, rather than just 5.5,000,

disuse atrophy may actually improve our overall muscle protein synthesis response and thereby enhance our muscle's ability to grow. Yet to be determined, this effect could be general or might better apply to specific situations where dietary protein intake is slightly below ideal, even temporarily. If so, omega-3 might not only be anti-cadabolic, but potentially actively anabolic in these contexts. Now, let's be real. In a world where the the recommended daily allowance for protein intake could be 50% higher and still not fully optimal for hypertrophy, any effect that makes suboptimal protein intake a bit less suboptimal would be appreciated. And what about those days when you're swamped or forget to refuel?

All of these scenarios, whether ongoing or temporary, might be relevant. While we need more evidence to back this exciting possibility, it opens up an intriguing new area of Omega-3 research that Dr. McGlory is exploring. So whether you're an older adult looking to maintain muscle mass, someone recovering from an injury, or anticipating some planned downtime like a surgery, or simply curious about the latest breakthroughs in muscle health, this episode is packed with invaluable insights. Join us as we explore the power of omega-3 fatty acids on a whole new frontier, which is their ability to enhance muscle preservation and recovery.

Before we dive into this conversation, one last thing I want to mention is that the doses used to demonstrate the impressive anti-atrophy effects we discussed today were relatively high. As this is an emerging field, the optimal dose is still under investigation. Just to give you a little context, in Dr. McClory's 2019 study, participants received a total of five grams of omega-3 per day. This dosage is approximately one gram per day higher than prescription omega-3 be used to treat high triglycerides, and roughly three grams per day higher than the amount of omega-3 most people in the United States would need on a daily basis to achieve a high omega-3 index, which is around two grams per day. It is thought that between 80 and 90% of people,

especially in the United States, would benefit from higher omega-3 intake. All right, I'm sure you've had enough preamble, so let's get to this interview with Dr. Chris McClory. Hi, everyone. I'm sitting here with Dr. Chris McGlory, who is an assistant professor at Queens University. He researches the influence of omega-3 fatty acids on muscle mass, protein synthesis, and mitochondrial function. Chris, thank you so much for coming on this show. I have really been looking forward to having this conversation with you. What sort of fires me up about the opportunity to chat with you is the fact that your work brings together to feel in a sort of surprising but exciting, converging way. So I've had the great privilege of having on the show some great minds in muscle biology and exercise physiology, such as Dr. Brad Schoenfeld, Dr. Stuart Phillips, whom you trained with.

I've also talked quite a bit about omega-3 fatty acids on the show. And your work brings together basically these two fields by showing omega-3 fatty acids. They may have a role in both preserving and supporting muscle. So I'm really happy to dig in to that with you. today and I don't know, maybe we can kick things off. You can kind of talk a little bit about how you ended up here and perhaps some of the work that led up to your current investigation looking at omega-3 and its prevention of disuse atrophy. Yeah, sure. And thanks very much for having me on. I've been pretty excited to talk to you about this. It's an area that's obviously very close to my heart and I enjoy talking about it. So really, I kind of started off with my research kind of career, so to speak in Liverpool, John Moore's University, where I worked under the supervision of James Morton and Graham Close, where really we looked at kind of applied sports science and look at

nutritional interventions in that context. But my real interest was in is in muscle protein metabolism. And James was suggesting to me, you know, if you really want to dig into this area, you kind of need to learn how to use stable isotope traces. And at that time, Kevin Tipton, who many of the listeners may know, who's an expert in protein metabolism, he just got a job in Sterling in Scotland and had a PhD advertised to where he was going to train somebody to use stable isotopes in the context of human skeletal muscle. So I applied and I was very lucky I got that position to work with Kevin and somebody called Stuart Galloway. And essentially what I wanted to do is to look at how protein ingestion can affect skeletal muscle and, you know, some of the classic

work that, you know, Stu had done with Dan Moore where they looked at dose responses. And I wanted to kind of expand and learn a little bit more about that. But when I got to Sterling, I, um, I, I had a meeting with Kevin and Stuart, and what they said to me was, you know, we've got the Institute of Aquaculture here, and this is kind of like a European center for the analysis of lipids in fish, basically, in aquaculture. And, you know, are you interested in looking at how, you know, different lipids in omega-3s affect skeletal muscle, and you can use stable isotopes in that context? And I actually thought, you know, I read the proposal that they wrote, and I thought, you know,

this is really interesting. You know, it's a new angle and a new way of looking at skeletal muscle, a different, you know, nutritional intervention. So with a specific focus on omega-3s. So we did a couple of studies. The first one, you know, was a time course change in muscle lipid profiles and then a study using traces to measure muscle-prudencease with omega-3 intake and exercise. And I really enjoyed my time there. We learned a lot. I think we did some good work. But then during the time that I was in, in Sterling, we collaborated with Stu Phillips to do the isotope analysis on his mass specs. And I came to Canada. And whilst I was I was really impressed with the lab and McMaster as a whole.

And Dr. Phillips at the time was moving towards a more clinical setting with muscle loss, muscle disheuse and aging. And I thought to myself, you know, I'd be really interested to see how Omega-3s, you know, are influencing the response in that clinical setting, not necessarily in just healthy younger people. So I was lucky enough to be afforded the opportunity to be mentored by Stu. And he invited me over and was like, yeah, let's, you know, I'm willing to support you in your Amiga-3 work. and, you know, we can look at some studies and designing some studies with specific focus on, you know, omega-3s and muscle loss. And at the, coincidentally, at the same time, Graham Holloway, who was at Guelph, who was an expert in mitochondrial biology, had done some work in omega-3s as well. And at the time, and this was around 2014, it was a growing literature that mitochondria, which I, at the time, not much about at all, was regulating some of the processes and muscles. So I thought, you know, well, why don't we team up with Graham as well?

So essentially that kind of led to the study where we did the Amiga 3 feeding with immobilization in young women and teamed up with Graham and his student, Paula Mayotte, where they took the mitochondrial angle and we published those two papers. So that's a very long-winded answer to your short question, but hopefully that gives you some insight into how I ended up here. And then when I finished my postdoc, a job came up at Queens, and I applied for it and luckily got it. And now we've set up the lab to really take the work forward and to expand on what we've already done. with omega-3s and human skeletal muscle. No, that's a really interesting story. And I wonder if you hadn't had that aquaculture, sort of that little exposure there where, you know,

that was part of the story. Like, would you have come across Omega-3? Like, was it even being studied in the literature? I remember way back when I, gosh, I mean, it was, maybe I was a post-doc, maybe I was finishing graduate school. I don't remember, but it was a study I'd read. and I think it was like horses in muscle mass or something, an old study. Yeah.

Yeah, is that ringing about? So basically I'm wondering, would you, like, would you have come across Omega 3, like studying Omega 3 in its role in muscle? Do you think that's something you would have just come across just by reading, you know, the literature? I may have come across it, but I didn't think it would have picked my interest like it did because Kevin and Stuart were very, Stuart Galloway at the time as it's done. They're very passionate about the topic.

you know, it was a natural link with aquaculture. And I think the study, it may not be horses, it may be horses, but the one I can think of is in growing stairs. And it was out of LaValle where they, they fed growing stairs, the omega threes, the infused them and, and shown how it affected a whole body protein balance. And that was the first study. And then the second one was by Bettina Mittenolfes group in humans. And they were the two key studies that were in the proposal, like Kevin and Stuart, had her put together and got funding for with aquaculture. So whether I'd have gone in that direction, I don't think so. I think it's thanks to those guys in Sterling that I really started to jump on this bandwagon and just become fascinated. I think the other element was when I was

training at John Moore's and doing sports science. It was hammered home to learn metabolism as an integrated approach, not just protein by itself or carbohydrates. It's how lipids, carbohydrates and proteins interact in performance. And against that backdrop, I really was very interested in understanding think how lipids specifically omega-3 fatty acids interact and alter protein metabolism in human muscle. Well, I'm certainly glad you ended up where you are today. I agree with you 100%. It is extremely fascinating. And as I think we both agree, also quite important from a public health standpoint. So leading up to the muscle disuse atrophy, can you talk about what that is, what are some of the mechanisms underlying it, you know, in what circumstances can it be actually life-threatening?

Sure. So I think, you know, most people who've had a cast or a brace on their arm, you know, you apply it, and then after six weeks you get it cut off and, you know, if you're like me, afterwards you've got a skinny, hairy arm and you've got quite an obvious loss of muscle there and also muscle strength. And it's a point of, well, maybe not as a point in contention anymore, but, you know, one of the reasons that we think that occurs is because there's a reduction in the rate at which we create new muscle proteins in the form of muscle protein synthesis. So when you reduce muscle protein synthesis in both the fast and in response to amino acids, it leads to a negative balance of skeletal muscle over time.

That kind of reduces the size of muscle that you have. So, you know, for younger folks, it's probably, you know, it's not nice to have a cast or to have an injury, but we can recover from, I say we, but generally the younger folks can recover from that relatively quickly with some, you know, rehabilitation of exercise and adequate nutrition. I think it becomes a little bit more of a problem as you get older, particularly for older adults and particularly for older adults who are going into surgery or who have had surgery. Because, you know, that rapid loss of muscle may not always come back to baseline in the older folks. And I think, you know, I've heard this before on one of the old podcast, I believe with

Stu is that, you know, when it's called the catabolic crisis model that was coined by the late Doug Patton Jones and Kirk English. But essentially, the more insults that all the people have with those periods of inactivity and immobilization, they lose the muscle. It may not come back and then they lose a little bit more. And all of a sudden, you reach a threshold beyond which, you know, you can't perform activities of daily living. You know, you just don't have that muscle or that muscle mass or muscle strength

to be able to perform things like going for a walk or going to the shops or being able to, you know, go to the bathroom independently. And essentially, you lose those activities. of independent living, which is not really good for older people. And we also know that, you know, muscle strength in and of itself. And to some degree, muscle size is a predictor of or cause mortality and disability. So losing muscle in those situations is not necessarily a good thing at all. So you mentioned something really important. And, you know, in case of, you know, for me, it was quite educational that the loss of muscle protein or the decrease in muscle protein,

synthesis seems to be the major driver of this, you know, disuse, muscle disuse atrophy. Why is, or is, let's say you could take in an optimal amount of essential amino acids that are required to stimulate muscle protein synthesis. Is that enough to prevent protein, prevent muscle disuse atrophy? And if not, like, why? No, it's not. I think the main message here is that you really can't out nutrition, physical, inactivity or mobilization. It can mitigate the decline, so it could take the edge off. So increasing the overall dose and quality of protein nutrition, particularly the essential amino acids may protect against the declines to some degree, but it's never going to completely, you know, abate the decline. It's only going to be partially

protective. And one of those, we still don't really know the reasons as to what we know that there's a decline in protein synthesis, but we don't know what the molecular level. level exactly why it is that the body can't mount that adequate protein synthetic response to feeding. And it's also down in the fasted state as well. So simply consuming higher amounts of essential amino acids may be partially protective and there's particularly lucine and the branch chain amino acid, lucine and essentials, it may be partially protective against the declines in muscle mass, but it's not entirely

effective. And it certainly isn't entirely effective protect against declines and strength, which is oftentimes what we really care about. So it's, you know, but the issue there is, you know, you can, if you can certainly perform some kinds of contraction or activity, if you're sick or you're unwell to some degree. But if you're going through surgery and you're lying in a hostel bed and you're really sick or you're in ICU, for example, you know, you're not going to be performing contraction there. The nutrition is the only real way that we can target, um, protecting that decline in muscle mass. But again, to answer your question, it's only partially protective. It doesn't completely

block a or block the declines in mass. Well, you kind of brought up another interesting point, and that is, so you're talking about this muscle disuse in response to basically maybe a surgery, perhaps illness, bed rest. I mean, this is like a prolonged type of immobilization, right? What's the difference with respect to disuse atrophy when you're having a prolonged type of immobilization like you've described? Maybe you have a cast or bed rest or surgery. illness perhaps, but or just like reduced physical activity. I mean, there, people go through these

periods where life, you know, workload, you know, children, like things happen where your exercise routine, your physical activity goes down. And I mean, the pandemic would be obviously the biggest example of that. Obviously, we're not in the pandemic anymore, but it's a good, I think, example of reduced physical activity. How does, what's the difference between like the disused atrophy, how it's, you know, affected basically between those types of immobilization periods. Yeah, that's a great question. So we've recently just published the meta-analysis. Nick Peribresensky led that in. We looked at the decline in muscle, mass and size and healthy people. And what Nick did is he looked at, you know, differentiate between naught to seven days, seven to 14 and 14 onwards.

And this isn't generally healthy people. And what we found out, there was a rapid decline after seven days, a greater decline or a further decline from 7 to 14, then it tapered out. Now, this is in healthy people. And then in people who are compromised or, you know, are actually going through surgery, these declines can even be greater. But what we do know is that declines with complete inactivity or muscle issues, they occur very, very rapidly. Within the first seven days, you can see upwards of, you know, sometimes up towards a seven to maybe even 10% loss in size and mass. But something that is not as often studied. Like you just said, those periods of inactivity in which you're not completely immobile, but you are reducing your, say, daily step count. And as you said, the pandemic is a great example of

that. And we've done a couple of studies. I did the study as a postdoc with Tanner Stokes when we were in Stu Phillips's lab where we subjected all the people to reduce daily step count. I believe it was below a thousand steps per day. And that kind of mimicked what people would experience during, say, the pandemic, when they were being quarantined for two weeks or, you know, influenza or the step count typically experienced in hospital. And what we found was that there was a downregulation of protein synthesis. And this was in older pre-diabetic populations. And it wasn't fully recovered after two weeks to return to activities. So, you know, we had a baseline period for around five days. And then it was a two-week reduction to below a thousand steps per day. And then, you know,

back to normal recovery levels of step count. And the point. And the point, creating synthetic response hadn't managed to recover to its baseline. And we also noticed that indices of insulin sensitivity and insular resistance have been compromised and weren't coming back. And this paper was published in 2017. So it's kind of prescient that we then have, you know, the pandemic coming in which rightly so is, you know, we're being told you've got to quarantine for two weeks to mitigate the spread. But I think one thing that's being missed there is that there may well have been some negative effects that they might not be as great in magnitude as bed rest or complete immobilization, but they're certainly pernicious in nature in that they are

imposing a negative, certainly metabolic effect and a downregulation of protein synthesis. Now, certainly they would recover if you extend the measurement out to six weeks, but if you go back to what I said at the start about that catabolic crisis model, maybe the decline in it is not as great, but it's still another insult, it's still another contribution to that kind of staircase, downward staircase pattern. And then if you think, you know, I moved to Canada nine years ago in the winter's here, are certainly not as warm, is not as mild as they are at home. And, you know, when you're in minus 20 and all the people are a little bit scared to go outside, they don't go walking outside.

Like they normally do, they stay inside in their home. So, you know, their step count is reduced done. So anyway, to cut all a kind of long story short there is they're negative. They're not as bad necessarily as complete disuse, but they may actually occur with more frequency than complete immobilization, which I think is an important point as well. Yeah, and you brought up a really good point there with the seasonal effect because I think it's probably, people are probably, you know, at least experiencing some, to some degree of this disuse atrophy without even really realizing it because, you know, you think of muscle disused atrophy. You think of it as being like severely immobilized, at least, you know, typically I think that's what most people are thinking

about where they're just in a cast or they're injured, you know, bed rest. But they're not thinking of, oh, wintertime when I'm not going out and doing my outside. activities as much. And that is actually a really good point because I think it's common, even in places that do have more mild winters, people get, you know, they basically just don't go outside, even when it's, you know, not quite as cold, but just a little bit colder. You know, I know myself included. Fortunately, I have got indoor cycles and stuff that I, like, you know, think are just, I think they're life-changing and life-saving, honestly. But you talked about this catabolic crisis and it kind of leads into the disability threshold. What is that and how many

periods of this inactivity or mobilization does it typically take for a person to get there? Yeah. I think it's difficult to provide like a quantitative number on this of like, you know, new to meter strength or, you know, size of muscle or volume of muscle. I think it's a kind of a theoretical constructive. We all know there's probably a threshold of muscle mass and strength that I would require to get out of this chair or to, you know, walk from here to the end of the road, unassisted. And, you know, when I require assistance or somebody would require assistance, I would say that that is that threshold where you require help to get around. Now, you know, you could start off with a fair bit of muscle, but over time, you know, with those repeated insults,

that is when, you know, an inadequate recovery, the more that they occur within a space of time, the quicker the trajectory is going to be to breach that time at which you are not able to perform activities of daily living. Like I said, in younger folks, it's not too much of an issue, but, you know, you can imagine as you get older, we have sarcopenia, which is, you know, the loss of muscle mass and strength or function,

and when you superimpose physical inactivity onto the biological decline in muscle mass and strength, Socopena, you can see how it can really accelerate, you know, the negative effects of muscle loss and strength as we age. So I think putting a number on it will be very difficult. I think the message will be very much, you know, try to stay as physically active as possible throughout life. And, you know, we really can't avoid. Sometimes you go out your play sport, you get injured. If somebody goes out and they walk, they slip, they fall. They may need a knee replacement. I think it's just about, you know, preparing as best as you can for that insult. You know, like a surgery is essentially an insult. your body, you know. So, you know, it's, it's a challenge and to prepare yourself for that, not just recovery, but also going into that situation to make sure you're in the best possible shape that you can be in to help you recover when you come out. Well, there's obviously a need for investigating, you know, additional nutritional interventions to perhaps, you know, help mitigate some of this disuse atrophy, which leads to the omega-3, the role of omega-3

in this. And you've investigated the... effects of high dose omega-3 fatty acid supplementation on muscle disuse atrophy in young women. This is a, I mean, this study was extremely interesting to me, but I'd love if you could share a little bit about the study that you did, maybe the protocol used, and described some of the key findings of that study. Sure, yeah. So kind of maybe just a little bit of brief background is, you know, as we knew at the time that, you know, the decline in muscle mass with inactivity was due to the desensitization of muscle to

the provision of amino acids so that, you know, the normal protein synthetic responses declined and therefore leading to a loss of muscle mass. A paper being published by Bettina Mittenorf's group showing that if you feed omega-3 fatty acids to older people and then infuse amino acids, it can enhance the sensitivity of muscle tissue to the provision of those amino acids. So somehow, you know, omega-3s were being incorporated into muscle and rendering muscle more anabolically sensitive to the provision of amino acids. So we thought, well, you know what, if that's what's happening in that situation, maybe in a period of disuse in which there's desensitization of the muscle, we could restore that, feed a normal protein diet and see if we can mitigate the decline.

So using a protocol that we'd worked on in Scotland where we knew it took around four weeks of high-dose omega-3s to see a substantial increase in the omega-3 profile of the muscle, we loaded young women up in either control or the omega-3s for four weeks, and then, we subjected them to a single-leg immobilization. So basically one leg was put in a brace. And then after two weeks, we allowed them just to, you know, go and recover, do what they normally did. So it was, it was no active rehabilitation. It was just passive recovery. And throughout the protocol, we took measurements of muscle size by MRI, you know, before after immobilization and then two weeks after recovery. We took biopsies to measure changes in protein synthesis,

the expression of genes and also some of that muscle went to Graham Holloway's lab with Paula where they did some mitochondrial analysis to see whether there's any kind of link. And what we really found was it was very surprising to us. You know, it was seem that the omega-3s were completely protective, at least from a mass point of view, and they took the edge of the decline in muscle size as measured by MRI. So those omega-3s have been incorporated into the muscle of the participants. There was no change in the omega-3.

content and the control group, as you would expect, because there was no real omega-3 fatty acids in that supplement. And, you know, there was that protection. And then the important thing, I think, when we look at it, is that actually it helped the people in the omega-3 group recover their muscle earlier than the people in the control group. So if you kind of think about that catabolic crisis model where we've got that decline and then failed recovery, and this is in all the people, maybe we could actually increase that trajectory back to recovery. And this is kind of where I think the omega-3s may be very important. And from a mechanistic point of view, we use Deuterium to assess rates of muscle protein

synthesis. And consistent with the previous work by Patina Mitendulfus Group and Gordon-Smith, we found that in the omega-3 group, there was higher rates of protein synthesis, which would kind of, again, corroborate the mechanisms of action of omega-3s, which is to enhance the prate synthetic response to daily protein-feeding. This is like such important research in my opinion. I think so my question, I have multiple questions, but one is if omega-3 is sort of lessening the decrease in muscle protein synthesis during disuse. In other words, like you said, I guess sensitizing in a way the muscle tissue to the amino acids

for muscle protein synthesis. Do you think that could be extended to conditions perhaps that are not just, you know, full-out immobilization, but just where people are taking in, you know, lower amounts of protein. So do you think that perhaps you could get more bang for your buck with your protein intake by potentially also taking in higher dose omega-3 fatty acids? Yeah, and again, that's a great point. It's something that was, so we, I think me and you've talked about this, you know, our fair is that we did a paper in younger people in Scotland where we had fed them with omega-3 fatty acids.

and then gave them a dose of protein. And we didn't really see too much of effect. There was a bit of a trend, but it was statistically non-significant. It was a proof of concept study more than 18 now, so we may have been underpowered with the design. But looking back, we actually gave the participants a saturating dose of protein. We gave them 30 grams of protein, which we know maximally saturates the response. And something we thought about was maybe if we'd given less protein

and given, you know, and allowed that or provided an opportunity or, you know, we didn't hit the ceiling with the proteosynthetic response to protein ingestion, we dropped it down and gave an opportunity for the omega-3 fatty acids to work. Maybe we would have seen an effect. Now, the question then becomes, so why don't you just take protein, which is a legitimate and good question, we don't need to take omega-3s, but if you are somebody who's elderly and you don't want to consume or you can't consume large amounts of protein, or if in fact you're in hospital, and we know in hospital, they are, you know, typically protein malnourished. It's not, you know, you don't go to hospital for a dinner, you know, it's, it's a place where, you know, the quality of the food is not

necessarily as good as it could be. Maybe in that particular situation is where we could see the effectiveness of the omega-3s is just to potentiate the normal response to low-dose protein intake. But to my knowledge, there's no studies that have actually addressed that particular question. I mean, hopefully, you know, that'll change in the future, you know, like if you were to give the, you know, essential amino acids or protein, you know, in the form of protein, you know, with the mega-3s, like, would there be even a more robust effect, perhaps at a, you know, not the saturating effect, like the 30 grams, but maybe, you know, 20 or 15 grams. Like, would you, it'd be interesting to see how the muscle protein synthesis response in

skeletal muscle is affected by that. So, you also mentioned that your, your study examined, you know, the expression of genes associated with the skeletal muscle protein turnover in amino acid transport. I think it's a very interesting area when we dive into mechanism. I'd love to dive a little bit further. But what were your observations in that study? Yeah, so the first thing I want to say as well is that, you know, the study we did in the FASMJ paper, you know, it's the, I think the first one in humans with complete immobilization.

So, you know, the jury's still out. We'd like to see it corroborated in different laboratories in different populations. But in and of itself, it's still exciting. I think that when it comes to the amino acid transport mechanism, you know, we see these effects of the protein census. And all of a sudden we're going, wow, how is this happening? Like, what's going on? And I did notice a paper in actual pigs where they'd seen omega-3-fite acids

had altered the gene expression of an amino acid transport of Coddlach 1. And we thought maybe actually this could be one of the mechanisms that we saw in explaining the enhanced protein synthesis and protection of muscle loss in our paper. It was a secondary analysis, so it wasn't a primary outcome, but we probed for changes in lap 1 gene expression. So that's an amino acid transporter for branched chain amino acid lucene. And we found a trend for a treatment effect, which essentially was that there was a trend for an increase in the omega 3. But again, there's some caveats there. One, we're underpowered.

Secondly, it's the gene, not the protein. And also, you know, you can have an increase in protein content, but is the protein functional? you know, is it working more efficiently? So we don't know the answers to those questions. I'm not too sure the amino acid transport is the mechanism. I'm at first I did, but I've become less convinced of that as time's gone on. But it's something that we did see a trend of a treatment effect yet. And I think there's a little bit of a tangent I'm going to go on, but because the part of the mechanic, like I know we've talked about this, you know, the accumulation of omega-3 fatty acids in the cell membranes, the lipid membranes.

It does change transporter receptors that are embedded in those cell membranes. It changes their structure and function. So I'm a lot more familiar with research in rodents looking at transports more in the brain, you know, and if you, for example, like cause DHA deficiency. in rodents, you will significantly alter at the protein level, the gluten-1 transporters that are responsible for transporting glucose across the blood-brain barrier. And so it's interesting, you looked at the gene and not protein, because I would think the protein level would be more important if you're thinking of a sort of cell membrane fluidity where, you know, the effects have to do with, you know, the transporters, you know, the transporters,

function and human structure and levels in the actual cell membrane. So it's kind of interesting. Yeah, I'd be honest, at the time, I think we did, I cast about my mind, we did measure the protein, but the antibody for human skelet muscle at the time was terrible. So, you know, I think actually myself and Dan Moore worked on this when I first came to Canada using like positive and negative controls to try to, you know, look at that one protein expression in human skeletal muscle. and it's certainly improved recently.

They've certainly improved the antibody. I know that, but at the time, it was a bit of a nightmare to tease out. So the antibody for human muscle was very, very difficult to get working. So I think it's certainly improved now, the ones that are out there. But we looked at the blotts when we were working with the protein, and it was just something that is you couldn't really hang your hat on at that stage. But maybe in the future, you know, with some more work, we could probe that in muscle for sure. Yeah, that would be interesting.

I mean, obviously you're only as, it's only as good as the same. sensitivity of the techniques and tools you're using. Do you think that, so has anyone else looked at whether or not omega-3s have an effect on disuse atrophy in males or in older adults, where disuse atrophy can be more catastrophic, as you mentioned? Not by knowledge in terms of disuse atrophy. There was one study with intermittent armor mobilization and a mixed cohort, but with intermittent armor mobilization, I don't know really what you can draw from a conclusion. In terms of older people with immobilization, omega-3s, not to my knowledge.

The only other study that I'm aware of with this is in rodents where they fed with a high-fish oil diet and they protected against disuse atrophy in that context, and that was one of the reasons that we decided to pursue it in humans. But certainly in men know, and one of the reasons we chose women is, firstly, there's not a lot of research out there in general and women. Secondly, they're more susceptible to ACL injuries. So it's a, it's a, it's at risk population. And thirdly, there was some evidence that the omega-3s were more effective in women than in men. And instead of jumping straight into a study in older women where, you know, it is a bit risky, right? We've said they don't

recover. We thought we'd start in younger women. So the next logical extension is, again, to follow this up in potentially older women and older men who are actually going through surgery, not just we're putting a brace on them. I have another question that's kind of related to one of my previous questions about, you know, the sensitization of, you know, how omega-3 may be sensitizing skeletal muscle to essential amino acids throughout, whatever, whatever combined mechanisms. Do you think that, you know, with respect to older adults and the anabolic-resistant, that they, you know, they basically have, so they become less sensitive to the amino acids.

Do you think that there may be a role for omega-3 in perhaps even anabolic resistance by enhancing the response to amino acids and skeletal muscle, too, in older adults? I think the jury still out, very much so in this regard. There are a couple of papers that have shown, you know, if you feed omega-3s, it improves muscle mass. there's meta-analysis supporting this, but the exact mechanism I'm not exactly convinced of yet. In terms of, you know, the effect of the omega-3s, I think it depends upon the omega-3 status as well of people.

So if you've got people who are already got a high omega-3 status, say, you know, their EPA plus DHA composition of the blood is around, you know, 8% or more or something like that, you know, is the effectiveness of feeding amygia-3s really? going to be detectable, but compared to people who have, like, less than 4% in the blood, you know, so I think in my mind, it's, you know, with the designs and things we've talked about is, is it's context specific? I would suggest that you would have more of a chance of detecting an effect of omega-3s if they had a low omega-3 status, and they also had a generally lower protein

diet. So the synergistic effect of increasing omega-3, phospholipid membrane content or muscle content or composition in combination with the increased protein intake would potentially be additive or have a synergistic effect more so compared to people who have already have a high omega-3 status. It might be the same as, you know, if you're already consuming around 1.6 grams per kG of body protein is really increasing that to two going to have that much more of an effect when you're training, probably not. So I think, you know, but if you're in the lower amount or you're deficient, that's when you're likely to see the effect. I think, and most people, um, most people are not getting an F-Omega-3, like that's pretty well-known.

And also, most people are, you know, with the protein intake, too, I mean, I think, I think especially older adults, as you mentioned, it just becomes more difficult to, like, chew and, you know, they're just not as hungry, and there's lots of reasons why they're not consuming as much protein. What do you think, what do you think it's going to take to get more studies on omega-3's role in disuse atrophy in, you know, different, you know, men, women across the lifespan. But, you know, getting this into clinical practice, like, what do you think it's going to take? Like, is there, is there more research on it?

The short answer is money. Like, and, you know, these studies cost money. And at the end of the day, like, you know, to do the high quality RCTs in these populations, you know, requires, you know, obviously good research team. But also we need, we need obviously to support them with the funding. We've been very lucky in that we've, you know, been quite successful. with a few grants recently. But I think what we would need is a higher quality of evidence where we're starting to produce the real strong, well-designed RCTs that then, you know, will feed into good, high-quality meta-analyses. And then when we start to see the, you know, the changes or the potential benefits that have derived from metronautical data, then maybe that will alter

prescription or how we approach, you know, nutrition in those particular settings. But in terms of, you know, doing the studies, obviously it's just, it's just money, isn't it, you know, to be able to conduct them and making sure you've got the appropriate techniques and research personnel. So to kind of shift gears a little bit more into looking at omega-3 in skeletal muscle, skeletal muscle mass and strength, also maybe function, I'm very interested in that as well. You talked a little bit earlier about looking at omega-3, you know, changing the skeletal muscle lipid profile. How long does it take for those changes to occur? And do you think that's important for designing a protocol, for example,

like if it's taking a certain amount of time and you're looking for an effect that you need to at least, you want the skeletal muscle lipid profile to change before looking at the effect? Yeah, that's an excellent question. So, you know, I don't think the omega-3s impart their efficacy via the acute ingestion. I think the way in which they impart their effects is through, you know, modification of the composition or the lipid composition of the target tissue. And in skeletal muscle, we know, say, after five, if you take around five grams of amoeka threes, three grams of EPA, two grams of DHA, say, as a combination, you'll probably see a small change after about two weeks in the muscle.

You see a rapid change in the blood. But it takes around four weeks before you start to see that kind of big difference. And, you know, a third. that dose, it typically will level off. We've seen this in the FASA paper we did with tissue satrophy. It wasn't, you know, the primary aim of the paper, but between six and eight weeks, it seemed to level off. And this is in the muscle phospholipid profile. And we did a time course study in Scotland in Sterling where, you know, that was whole muscle. But it seemed to track the phospholipid diffraction relatively well is essentially four weeks before, you know, you see that kind of significant change. And then it plateaus off between six and eight weeks.

So, you know, it does take time. And I believe the mechanism of action is the modulation of the lipid profile. And at least, you know, certainly the phospholipid membrane, but also potentially inside the cell itself. So it's not something that happens in hours. It takes time for it to be incorporated into the phospholipid membrane of muscle. So that seems really important if you're looking at the potentially anabolic effects of omega-3 on skeletal muscle protein synthesis, because if it's taking four weeks and you

you think the mechanism is more based on the phospholipid, you know, content in the membranes, cell membranes, mitochondrial membranes, both, that seems like, you know, people that are doing trials. So I noticed in, I think it was in your facet paper, the trial, didn't you do like a preloading, they were taking omega-3 before the immobilization? Yeah, four weeks, four-week lead. And so we used, we did a time custody in younger men when I was in Sterling, where we just basically fed young men, omega-3s, and did biopsy that, you know, zero well minus two zero so the act of their own internal control and then I believe it was one

two and four weeks and we didn't see anything at one week but we did it too but the the gc that we used to measure the lipids is a very precise instrument so whilst you may see a statistical increase the change is probably clinically insignificant but then you know after four weeks is when we start to see a substantial change so you know we use that information to say you know what like let's not hedge our bets with a two-week loading period. Let's make sure we see a substantial change in the muscle. So we'll do a four-week load, and then they'll go through a two-week period of mobilization. I think this is really important because, you know, notoriously in clinical trials, particularly nutrition, how you design the trial is so important for the outcome, right?

And it makes all the difference. So do you think that people that are going to be repeating these studies are repeating these studies or doing similar studies. Do you think they're aware of the effects, you know, how the, basically how long it takes for the omega-3 fatty acids to be incorporating the cell membranes and how that is important in terms of designing their clinical trials? Because the last thing you want is all these different protocols and then you have different conflicting results and then everyone's confused, right? Yeah. And I think that's, it's a question to get a lot. It's like, is there a dose response? could you give more in a short period?

And, you know, I mean, it would be interesting if someone gave an acute, you know, we start the omega-3 supplement, you know, and you see, like, and then you see an effect quite immediately, you know, that would suggest the mechanism of action is not what I'm proposing it is. So, you know, I'd be relatively surprised if that was the case. But I think if we are going to, if we are agreeable that it is the modulation of the lipid profile that is driving the effects, well, the modulation of that profile takes weeks at the doses that we typically use. So I think from my perspective is if you really, if people

are going to try to look at the effect, it's better off to maybe do that loading phase and then titrate back. It's like white people you do, you know, you do the cell culture or the rodents where you knock it out, knock it in the gene out. And then you start, you've got this effect. You've got the biggest potential chance to see the effect. And then you bring it in into a more realistic situation. Is it a case where we, you know, we do these studies where we do longer, longer feeding, where we tried to induce a big change in the omega-3 profile, and then, you know, once we've established that that is the driver mechanism, how low can we do? You know, can we drop the change in the muscle composition lower? And if so, could we do a short feeding period or at least loading

period? You know, these are questions that still need to be asked, or answered, sorry. I think a lot of, you know, because when most people think of omega-3, there's the anti-inflammatory component, you know, where the metabolites, the resolvins, the marisans, you know, all the SPMs, protectants, these are involved in resolving inflammation. And that can be quite quick. So, I mean, there's some clinical study showing that, you know, these SPMs are, you know, they're in the bloodstream pretty immediately after taking them and they can last like 24 hours. So, you know, people might be looking more at the anti-inflammatory, I hate calling it anti-inflammatory because it doesn't work the same way as like the typical n-sades do, right? But more of the inflammatory role,

you know, anti-inflammatory role of omega-3, which obviously there's there's a role in, you know, muscle mass with respect to inflammatory conditions, right? So that also is one reason why I was thinking, well, people might just, you know, be doing the, you know, short, like they give the, they start the immobilization and then they give the omega-3 at the same time because they're thinking more of the inflammatory effect, right, versus the change in the composition of the actual, you know, skeletal muscle lipid profile. So it's very important to bring up. Do you think that, so I kind of want to get into the differences between, you know, gaining muscle mass and gaining muscle strength. And why, you know, it's, why is it so difficult for older people to gain

muscle mass, whereas they can really gain more strength from resistance training. So, for example, like they resistance train, right? They can get big increases in muscle strength, but not as big in mass. Why is that? Yeah, I actually, to be honest, you don't really know the answer to that question. I think my guess would be that all the people typically don't engage in exercise, that are resistance exercise that often. So when they initially begin training, they do see those initial quite quick gains and strength. But what we do know is that all the folks tend to believe not just resistant to the anabolic influence of protein or amino acid ingestion or essential amino acid ingestion, they seem to be anabolicly resistant to resistance exercise or an acute barrel

resistance exercise across like a wide range of loading spectrums. So there is one paper out there that has looked at the prontestynthetic response across that and all the people and seen it's somewhat diminished. But you can, you know, people up to the age of 90 can certainly gain strength when engaging with resistance exercise. And I think, you know, as you get to that age, you probably care more about your strength and your functional abilities than, you know, having a lot of muscle, so to speak. So I think why that happens, I think it's maybe just because that they don't engage in exercise as much resistance exercise. So it's detectable earlier. And when you combine that with the fact that there's anabolic resistance, potential anabolic resistance

to training in and of itself, that may explain why you can detect these bigger effects of strength or gains in strength compared to mass in those populations. But again, it's really not my, I would say, I'm not an expert in that area, but it would just be a more of an educated guess. Is there any role for nutrition in gains and strength, like amino acids? That's an interesting question, yeah. So I think from amino acid perspective, I'd say the gains and strength that would be afforded through amino acid, ingestion, and may well be just fed through increases of muscle mass or the small increases of muscle mass that occur. And, you know, I know that there's like a little bit of disconnect between, you know,

changes in mass and strength per se, but the gains and strength in that role may be because of the change in mass. But I think if you think about omega-3s, there's been a couple of papers out there where Stuart Gray's paper that comes to mind from Glasgow where they fed omega-3s to all the people during resistance training and found only in women that it enhanced the strength response to a period of resistance training in women and that was omega-3s. There's been all the papers as well, one from a group in Brazil, again, looking at the effect of omega-3s with resistance training in all the women showing that it potentially, it potentially, it potentially, the strength gains. Exactly how that works or how that happens,

that we're not too sure. I think it may be related to incorporation of DHA into the myelin sheath or to the neural networks that can enhance that strength adaptation. But I think that's one of the exciting things about omega-3s is that we see this phenotype change, but when you look under the hood, we don't really know what's going on. So I think from an omega-3 perspective, that is something that I think is a very interesting. Were these studies mostly in older women? Yep. Older men and women from, yeah, so both were in older people.

And there wasn't, the strength wasn't, you didn't see the strength increases in men, older men? not in no well once there was a study in brazil that was believed by redaki and colleagues and that was in a jcn and that that was a female only cohort um so there's no real sex differences there but the study by i think it was the boy and as stuart gray was the senior author in stuarton some excellent work in this area he's in glasgow um they found that the effect was more pronounced in women compared to men but you know after talking to stuery it's a case of you know is it you know is it is it a real effect you know, is it because the women may not have been, they may have been less trained than the male cohort so that when they engaged, there was a bigger response.

If that was the case, then you'd expect it in both the control in the omega-3, so you wouldn't see an effect of Omega-3. So it would suggest that the Omega-3s are having an effect there. And I know Stuart has followed a little bit of that workup with krill oil. So it's not just like, you know, Omega-3 is, or fish oil. Stuart's done some work, Stuart Gray, with krill oil that is replicated some findings from Bettina Mittenolfers group with increases in strength with omega-3 supplementation or size. So I think there's some exciting work there, and it does seem to be that at least the omega-3s themselves may be affording or conferring some strength benefits, whether it's

alone in the absence of resistance training or with resistance training, particularly in women. Are there, so the sex differences with respect to gaining muscle mass and gaining muscle strength, just generally speaking, are, like, what are the sex differences? Well, in general? In general. And then the next question is about omega-3. And, like, I mean, I know there is a sex difference with respect to converting the plant, omega-3, the plant, what you get from plants, ALA into EPA and DHA.

So estrogen really plays a big role in increasing the conversion of ALA into EPA and DHA. But I don't know if there's, I don't, I'm not aware of literature showing specifically if you start with, a marine source if, you know, converting, for example, EPA into DHA, like if there's a role for estrogen in that. Yeah, off the top of my head, I really don't know. I do know that there's SNPs on particular genes in women that may actually enhance the conversion of EPA to DHA. There's a group in Toronto that I've done some excellent work there.

But I'm not off the top of my head too familiar. I know that, you know, women or females can convert them more efficiently than men, but that would feed into, you know, an improvement in muscle mass or muscle function, I'm not too sure. And in terms of the general trading adaptations between all, younger, there's no difference, really, from my knowledge in terms of younger men and younger women with the gains, despite some dogma out there is that the gains are pretty much quite similar. When it comes to all the folks, I think that to me it doesn't seem like there is either

in that particular, and again, I'm not a particular expert in that. I don't believe there's too much of a difference between women and men. I think a lot of it may well be driven by, you know, who typically trains or who typically is engaging in those types of exercises versus who is not. So if you get somebody who's never really, you know, engaged in resistance exercise and then starts in that regimen, they may gain a little bit more than people who don't. And I think that may explain some of the sex differences if they do exist in older folks, but I think the differences are very minimal generally.

What about muscle performance? So, you know, does omega-3... Or do you know if Omega 3 plays a role in, like, performance? Maybe older adults? Yeah, I think one of the issues, those types of measurements is that, you know, with the SPPB is they generally secondary outcomes. And, you know, the reliability of them is, you typically need to lodge a number of people to detect an effect. But there was a meta-analysis recently published suggesting that I think it was either gate speed or walking speed was improved in all the people with an omega-3 supplementation suggestion, that suggesting that there may be an enhanced effect in terms of function. It's a great question because,

you know, sitting on a dynamometer or a leg press and improving your strength, that may be great, but is it going to help improve those activities of daily living? And I think that's the key question for older people. And the meta-analysis that I think, you know, you shared with me and we've talked about before, it does seem to suggest that omega-3s in that population could, you know, enhance either gate speed or walking performance. And I think that's kind of important for that population. Yeah. So I think we're in agreement that we just, just, you know, we really need, you know, larger well-designed trials and studies to repeat and confirm what has been shown in a variety of, you know, other smaller studies. Although there

are some meta-analyses out there. Again, it's like you said, well, the quality of data. I mean, we just, there's always, there's always a need for more, especially if you want to get this into clinical practice. I'll just, I'll share an anecdote with you. So a couple days ago, I was in an elevator in a doctor's office. And a guy came in the elevator. His wife pushed him in a wheelchair and he had just had surgery. He actually just had a knee replacement. And I told, I said, oh, well, you should, you know, you should go home and make sure you have some omega-3 fatty acids in the form of like fish oil because there's some evidence that may play a role in helping you maintain muscle mass. You know, it's called disuse atrophy. And the older gentleman said,

those don't do anything. And I said, well, I, you know, I'm a PhD scientist and I'm actually, you know, you know, been reading some literature and going to talk to an expert. And he goes, well, I'm an MD. I'm a rheumatologist. And I'm going to tell you, we could have a conversation about it. But, and so, you know, I think the take home for me was, you know, how do we get this into clinical practice? It seems like, you know, yeah, I guess there are smaller studies that we're talking about here. And so more work needs to be done. But I truly believe that omega-3s are playing a role, especially in the disuse atrophy. And as we're going to talk about in a minute, sarcopenia.

And it's a shame that it's going to take such a long time to get that into the clinical practice, you know. Yeah. And I think, you know, the jury still, to some degree, is very much out. you know, we need more work and to really, to study how it may be working and also in the larger populations, whether it's working. But I think the first thing is do no harm. And, you know, if, in my understanding, as long as the supplements are good quality supplements, or especially if you get it from food sources, you know, oily fish and there's good quality proteins in there, if you're going to increase your omega-3 content of your diet, you know, I don't really see too much harm in it. If you're

using a quality supplements or you're taking it, particularly from a food-first approach with oily fisher, I think that would be a good idea all around, you know, especially if you're coming or you're recovering from surgery. So, sarcopenia. As we age, we lose muscle mass, we lose strength. This is called sarcopenia. And there's all sorts of problems. It's associated with a two to threefold increased risk of falls, frailty, disability. I mean, on and on, as you mentioned, mortality. Obviously, protein intake, resistance training, most important here, as you've, you've already mentioned, but there seems to be emerging evidence that omega-3 fatty acids, again, EPA and DHA being the major players here, are playing important role. So in the context

of sarcopenia, you know, there's a, there's a disequilibrium. It's my understanding there's a disequilibrium between muscle catabolism and muscle animalism. So is there evidence that it can shift it towards animalism in the context of sarcopenia? Yeah, so there's certainly evidence, it's definitely by no means a short case. So essentially the reality is that the older folks as they, you know, as we age, there is that anabolic resistance to protein ingestion that will contribute towards the negative protein balance that may lead to that decline. That's independent from physical inactivity, which would accelerate that natural biological decline. So the first thing is I would always say that exercise, particularly resistance exercise, like I said, at the very start,

you can't out nutrition, physical, in activity. You've really got to make sure that you perform an exercise and stick into the guidelines and especially resistance exercises, as we know, a very potent means to enhance or maintain skeletal muscle mass and strength. But in terms of Omega 3 is to supplement that approach, I think there is emerging evidence. And I think the series of papers in Bettina-Mittorf's group, I think were the landmark papers in this field where, you know,

they were the ones that did the showing the, an enhanced protein synthetic response to amino acid infusion with omega-3s and they replicated that in younger people and older people and that's like the landmark study that really got me interested when I was in Scotland and studying this and that was published in AJCN with Gordon Smith as the lead author and then you know you're looking at those data and if you look at the difference that the omega-3s had on a protein synthetic response you're thinking there's no way like that is that is huge and then they followed it up with a another study in younger people that kind of led a lot of credence to it. And then they followed up with a longitudinal

feed. And I think it was six months of two grams per day of EPA and DHA. And the changes there were quite significant, I believe it was in, I believe it was mass, I'm not too short strength. And at that point, you're like, wow, okay, well, now I need to see, that's one lab. It's a really strong lab, very well respected, a high quality work. But, you know, just to, you know, confirm you'd like to see other people doing a group. Well, Stuart Gray then published a paper with krillol, similar participant cohort, similar duration, and replicated what had been shown by Bettina Mittenorphus group. So then you're thinking, okay, there's something really going on here. And then, you know, we've seen the protection against tissue atrophy in young women.

So there's now this growing body of evidence that suggests that amygote3 is anabolic. And they seem to be anabolic, particularly in older adults, not just from a protein synthetic point of view, but also from the perspective of kind of mitigating the declines in muscle mass and size. And I would encourage anyone really interested in the Sarkapini element of this is to look up Gordon-Smith's paper in AJCN and also Stuart Gray's work with krill oil because the results are from two independent labs across the Atlantic, different supplements, but still delivering EPA and DHA, and the results are very, very interesting and quite encouraging. Do you think that because sarcopenia has also has more of an inflammatory component to it, at least my understanding is there's a little more of an inflammatory component to sarcopenia, perhaps also because inflammation goes up as you age and people have more inflammation?

Do you think there's like a sort of dual role, like in addition to this anabolic effect you've been talking about with sensitizing skeletal muscle to amino acids, perhaps an anti-inflammatory role as well? Yeah, and that is a great question and an important talk and point in the field as well, because the studies that I just talked about from Bettina Mittenoffers group with Gordon Smith as the lead author, they saw these changes in the absence of any real change in circulating inflammatory markers. So, you know, people were thinking, well, actually, this is, and normally when you think of omega-3 fatty acid, you think of heart health and then anti-inflammatory effects. So that's a natural mechanism, and especially because low-grade inflammation or inflammation, is it inflammation or is it inflammation or is the concept?

and older people is there's a bit of a difference between what's circulating in the blood and what's going on inside the muscle. And you kind of low-grade inflammation can actually impinge on proteins that regulate protein synthesis. So one, for example, the ZIF2 alpha. So when that's phosphorylated, it can impinge on the ability to mount a protein synthetic response. So by resolving the inflammation, particularly inside of the muscle, potentially this is one way in which omega-3 fatty acids and all the populations may be working. Very, very interesting. Let's dive a little more into the mechanisms.

Like, I think, you know, we already talked a little bit about, you know, the cell membrane, incorporating EDHA into the cell membrane, the membrane fluidity. Perhaps, you know, I brought up the transport, you know, the transporter's function structure and how that could be potentially linked to lucene. And perhaps, I guess it's called the lat transporter, you mentioned. Yeah, that one, yeah. Can you actually measure intracellular? amino acid concentration from a muscle biopsy? So you can. You can measure intracellular amino acid concentrations.

The difficulty there is there is some evidence that with muscle disuse, there may be an increase or a change at least in intracellular amino acid concentrations. If they're not being used to build muscle, they may build up inside the intercellular space. Now, that's very limited evidence. But there is some there. Elisa Glover, when she was working with Stu Phillips, Dr. Philipson, they published the paper, I think it's in J-Fiz.

And if you look at the branch chain concentrations in the intracellular space in one of the tables there would suggest there may be an increase. So I think in the context of amino acid transporter, one of the reasons I kind of changed my mind a little bit on whether Omega-3s were working via transport mechanism is because Luke Van Loon's group with Ben Wall as the lead author did a paper where they labeled with a stable isotube, they labelled the drink that people were consuming before and after immobilization. And what they found was that the enrichment, which is basically the ratio of the tracer compared to the tracy, so it's a carbon tracer, which is labeled. The ratio actually wasn't

altered too much. In fact, it was higher after remobilization in intracellular space, which would suggest that there's actually not an impairment in transport across the membrane and that the impairment in protein synthesis with disuse is actually intracellular. So that doesn't mean that omega-3s may work by improving transport across and potentially enhancing the protein-synthetic response. But to me, it would suggest that the mechanisms that are resulting in a decline in protein-synthesis with disuse are intracellular, not a lack of or an impingement on transport across the memory. So I mentioned a little bit about the glucose transfer, Glute 1

transporters at the brain. Do you know anything about whether or not omega-3 has any sort of acute or long-term effects of exercise on glucose transport into muscle? And is glucose transport into muscle also anabolic? Is that, I don't know. No, not to my knowledge. I don't think it is. I mean, above basal levels of insulin concentration, it's pretty much from it's permissive for pretty census. But in terms of the literature is really mixed. So if you look at the rodent literature, it seems to have quite a positive effect

on insulin sensitivity and glucose regulation. The work in humans is not as convincing. So that's where, like I said, the lack of high quality RCTs in the field of the omega-3s with the primary outcome of glucose to sum, but the literature is very mixed. And I also sometimes thinking,

would it work in people who were compromised with the lower omega-3 status, versus people who are already healthy, you know, I don't know how effective it would be in those particular contexts. You know, if you've already got a relatively high omega-3 content in the membrane, is giving more going to be efficacious

in respect of transport for glucose across the membrane. I'm not too sure, but my understanding is that the literature in humans is very mixed when it comes to the management of, you know, say type 2 diabetes or glucose handling with omega-3s in those populations. I see. Again, then it also comes down to was there preloading? Did they, you know, was it four weeks? Did they have four weeks of omega-3 before studying anything?

If these effects are, you know, being regulated at least through the changes in the cell membrane fluidity, then you would assume that you'd have to at least have four weeks of omega-3 loading in there, right? Down to protocol yet again. But cells are not the only, you know, structure that. have membranes, phospholipid membranes. So mitochondrial membranes, both EPA and DHA accumulate in mitochondrial membranes. You alluded to mitochondria earlier. Is there a possibility that omega-3 modulates mitochondria in human skeletal muscle? Yeah, there is. And, you know, the mitochondria is something that I've just started to really get into in terms of in my lab and set up. I learned, you know,

some of the techniques from Graham Holloway when I was at Guelph as a postdoc. And that's like a norm that I'm trying to develop in my lab now to address some of these questions. And I do think that's probably the most exciting area for me right now with omega-3s and how it links to the regulation of protein synthesis. So, for example, Graham had shown a number of years ago that feeding omega-3s in younger people can affect, you know, ADP sensitivity or ADP-stimulated respiration in the mitochondria in human skeletal muscle. And then in our disuse atrophy study, again, it seemed to affect ADPTN.

respiration, but then, you know, that's nice in terms of a concept. So what, how does that then feed into skeletal muscle? Well, there's now emerging evidence, sorry, into protein synthesis. Now, there is emerging evidence that there seems to be some kind of mitochondrial systolic cross-talk whereby, you know, if you think about the mitochondria, that's the primary site of, you know, where we produce energy and muscle protein synthesis is a very energetically expensive process. So if the mitochondria are not working properly, then there may not be the energy. And you know, to, you know, mount a protein-synthetic response and, you know, vice versa. Another caveat with the mitochondrial analysis is it depends on the time, you know,

what substrates you're using to stimulate respiration, you know, if you're using a carbohydrate or a fat-based substrate. But nevertheless, is what we're trying to investigate now is whether, you know, there is this cross-talk between the translation or the initiation and translation factors that regulate protein synthesis and, you know, mitochondrial protein synthesis and mitochondrial protein synthesis and mitochondrial respiration and there's been some papers in worms and preclinical models showing that you know mitochondrial translation or the translation of mitochondrial proteins in and of itself will feed in as a signal to whether we uh to the systolic factors that regulate protein synthesis in an

ATF4 dependent fashion so again this is preclinical it's very early but what we're studying here is is whether that occurs um in humans we've got a so studies and surgery in the hospital going on now with amygothrase, and we're doing the biopsies, and we've got the respiration measures, and we're going to try and tease that out. So I do think the mitochondria are a very, very interesting area of research when it comes to omega-3s and protein turnover, and it's something that we're really looking to explore a little bit more, but exactly what that link is. I'm not too sure at this stage.

Well, that's very exciting. I think I would be interested also just seeing what, not necessarily in skeletal muscle, but, like, you know, looking at the broader scientific literature, like, what's known about how omega-3 DHA EPA affect the mitochondrial function, mitochondria structure, their dynamics. All those things would be, you know, obviously interesting to kind of be able to see, well, if that's going on other tissues, perhaps something similar also in skeletal muscle. And so that's all, that's really exciting.

I, so there's a few studies, like limited, I'd say limited evidence showing that DHA and EPA can increase the metabolic rate of both resting and during exercise in older women. Yeah. And these effects were even more profound in like fat oxidation. So it was like a 19% increase in resting metabolic rate and 27% increase in during exercise for fat oxidation. Do you think this could be attributed to a mitochondrial related mechanism? Yeah. Potentially incorporation into the into the in and outicondrial, you know, membranes of the mitochondria

could potentially alter, you know, ADP handling and oxygen utilization. And again, this is not exactly my particular area of expertise, but I've seen some work of like, you know, from Australia where they've shown like, you know, feeding Amiga-3s can, I think it was particularly DHA can reduce the oxygen cost of exercise and reduce heart rate. Again, this is, this is something, you know, where you kind of read one piece of literature that is slightly related but not related and you try to use it to feed in to generate these hypotheses with, you know, how it affects muscle mass regulation as well as the mitochondria. But from my understanding is I really wouldn't know how that actually works in terms of, you know,

changes in substrate oxidation with omega-3s. One kind of natural thought is when you're giving people high doses of omega-3s, five grams per day, which is a lot more than typically what we would consume, maybe it switches the, you know, the substrates that are being oxidized or it may induce a very small shift towards the oxidation of fatty acids as opposed to carbohydrates. And there is a little bit of evidence that, you know, that might not, in the context of, you know, glucose homeostasis, that might not necessarily be a great thing because if you're shifting from, you know, oxidizing glucose to fats, then in diabetic patients or people

with high levels of circulating glucose, it may actually even bump those levels. So kind of going back to what we talked about before in terms of substrate utilization with these feeding protocols. But I wonder if just the sheer effects on increasing glute three transporters in skeletal muscle would you'd at least be getting the glucose transporting the muscle and out of circulation if that would just in and of itself be somewhat beneficial. Yeah. Yeah, and I'm not aware of any evidence that, you know, there is increasing glute four transporters in skeletal muscle with omega-3s. And maybe there is, I'm just not aware of it. And sometimes I think with the transporters, it makes me think about the, the last.

that one work is you may have more of protein content, but is that protein content functional? You know, is it actually more effective and more efficient? You know, I don't know. You mentioned something about the dose as well, and I think it kind of, to go back to the importance of protocols, you know, how long does it take omega-3s to accumulate in mitochondrial membrane? So you mentioned four weeks, you know, for, you know, the change in the skeletal muscle, like, lipid membranes. But like what if it's something similar for the mitochondrial membranes and, you know, the dose as well. You also mentioned sort of food first approach and, you know, eating fatty fish, of course, salmon and sardines, macaroni, mackerel being sort of the best sources

of omega-3. But you're not going to get, you know, four to five grams a day. And first of all, people aren't going to eat fatty fish every day. Like they're just not. They don't. They don't even eat it weekly. Like, that's, that's like, we have. We have N. Haines studies on that. They're not, they're not eating fish, a lot of, a lot of, especially in America, in the United States. But, you know, so the question is, is like, the 45 or even perhaps, what if it's even higher dose? Like, what if we don't even, like, there's not, there's been no dose response studies, right, to even know. No. So do you, like, how feasible, obviously it's good to get omega-3 from food sources, like, for many reasons. But if we're looking at the accumulation, like, you know, some of these effects. in the mitochondrial membranes, in the cell membranes and skeletal muscle, how feasible do you think it is to only get it from food? Again, it just... So I think this kind of leads me to a slightly separate kind of answer, if you don't mind,

is, you know, the Omega 3 index, which has been established in blood and is related to the CVD risks. We haven't really got something similar in skeletal muscle, so we don't know what is the level of Omega 3s or EPA DHA and there's even now evidence that the two may have opposing effects, but what is the amount or relative contribution or composition in the muscle membrane that has then linked to a clinically meaningful cutoff or outcome? And I think that's kind of something that, you know,

will take a long time for us to establish. And this is where it comes to getting it into the clinics. It's a case of like, well, how much do I need to take? What is the clinical cutoff in terms of the muscle or the blood? And how is that going to help the patient? And I think the, you know, thinking back of, well, it would, the answer is it would depend upon what is the level in the muscle that we need to get to to see these effects. So then we can work back through a dose response. So you might be able to take a large amount in a five day period and then just top it off with like one gram a day.

So do you take five grams a day and then just top it off with one gram a day and it stays in that range? I know Stuart Galloway is doing looking at some work like that at the moment. Or is it a case if you just take one a day or two a day? and you just do that all year round, and then you're going to see a level of change in the muscle phospholipid membrane. I just don't know the answer to that question, and I think the next steps for us to really start convincing people of,

you know, omega-3s are important, is to link the mechanism, firstly, and then what is the change in the composition of the membrane and how does that relate to important clinical outcomes? Right. With the mechanism, you know, when most people think about, so we talked about mitochondria and mitochondrial membranes, When you think about muscle mass, you think about the anabolic signaling pathways, like

mTOR, the P70S6, Kines 1. Does omega-3 affect those anabolic pathways in humans? Well, it's a complex question. So, you know, I think this field is evolving more and more, you know, like when I was, you know, really into this with the molecular work, which I've kind of moved away from a little bit now, is mTOR was the B-all and Endor, and its target S6K1, or, on. on the 389 residue. I think we now know there's a little bit more going on,

well, a lot more going on in terms of the regulation of muscle mass, muscle protein synthesis at least. But in the studies in which there was the potentiation of protein synthesis, both in Bettina-Mittenden Dover's work in humans, but also going back to, you know, the steers that we talked about, the cows at the very start of the podcasters, it seemed to be affecting the M-Tor P-70 pathway. Now, is that an independent effect of EP&DHA directly targeting

those proteins, or is it the fact that it's potentiated the amino acid response and it's the amino acids so that are enhancing EMTO? We know EMTO is very sensitive to changes in losing concentration, so is it an indirect or is it a direct effect? And again, we don't really know. There is some work in cell culture suggested that EPA may have a direct effect, but exactly how that works, I'm not too sure. But my guess would be actually that it's just the general modification of the lipid or the lipidome or lipid profile of the muscle that then enhances the effectiveness of amino acids. So the potentiation is driven largely by the amino acids, which is influenced by the lipid profile of the muscle. Yeah, that's a really good. I think that's a really good point. And it makes

a lot of sense as well. I mean, obviously more work to be done. Yeah. Kind of going back just to the inflammatory, because omega-3s are so well known in that, in that world, how does high inflammation affect protein turnover in skeletal muscle? Well, I think that the highest state of inflammation can trigger some of the, you know, some breakdown pathways. But we know that from the perspective of muscle protein synthesis, which is the predominant arm that we generally focus on in humans, one reason is it is largely that the arm that dictates the size of muscle mass, but also measuring breakdown in vivo is very difficult. But essentially the inflammation or, you know, low, low grade inflammation in the muscle can somewhat put the brakes on protein synthesis as maybe the better. way to put it and like I said some of the the initiation factors one of them is the IF2 alpha can be can be affected or at least phosphory by by inflammatory state or the inflammatory state of the cell which would

impinge upon protein synthetic pathways so you know there's a little it's not too clear the literature to me at this moment but it seems like if having a higher state of inflammation inside of the muscle cell can negatively impact some of the initiation factors so you know you've got you know protein initiation elongation to, you know, for pretenesis, and some of the initiation factors can certainly be affected by higher levels of inflammation inside of the muscle. That's interesting. I didn't know that before this discussion with you. We talked a little bit about sarcopenia, which has an inflammatory component, cancer caccia being probably one of the big ones that there's definitely a really, I think, major role of inflammation in cancer cacacia, where a muscle, you know, atrophy, if you

call it breakdown. I don't know what, you know, is just pretty devastating, predicts poor survival. Do you see a role for omega-3 in cancer cacacia? Is there any evidence? There is, I think it's slightly mixed, but there certainly is evidence that EPA treatment may protect against cancer cacchia, or the loss of muscle with cancer. And again, I do know that the evidence is a little bit of mixed, and it's obviously very difficult in those populations to get those high-quality RCTs. But, you know, there is some evidence there that, you know, the omega-3s can kind of mitigate against the decline in mass. And there's Avera Mazarek in Alberta, in Canada,

has doing some really excellent work about looking at how amygia threes can actually protect against the negative impact of chemotherapy. So we know that chemotherapy in and of itself is toxic and can have a negative effect on muscle. And in pre-clinical models, in rodents, what Veer is showing is that actually feeding amygia threes and those animals may actually protect against the negative impacts of chemotherapy on muscle. and we're currently collaborating with a area to see whether that might be occurring in a mitochondrial-dependent fashion.

They're in animals and, you know, she's in Alberta, so we're only really, we can't do the in vivo respiration measures of mitochondria, but we are looking at some of the new mitochondrial factors and mitochondrial translation factors that, like I talked about before, that may actually be feeding into the protective effect with omega-3s against, you know, chemotherapy-induced atrophy. Very cool. Well, we've covered a lot of grandkids. with respect to the role of omega-3 in muscle, skeletal muscle, before I kind of shift gears and ask you one other question. Can you, you're doing, you have an ongoing trial right now. Can you describe a little bit about what the trial is and what the sort of hypothesis is and

the goal? We have a number of ongoing omega-3 trials. We have for sex differences in muscle with omega-3 feeding, and that's led by a master student, Sydney Smart. And then we've got a large bed rest study in the hospital. That's led by Emily Ferguson, who's a PhD student with me. And she's going to be looking at the effects of high-dose omega-3s in combination with essential amino acid ingestion to kind of mitigate the loss of muscle mass and strength in people going through a period of bed rest.

And that's in healthy people, but it's going to generate us a lot of important tissue. Well, we're going to do the, we're going to do measurements of muscle size with MRI, muscle strength of dynamometry and the, you know, the respiration measures with mitochondria, but also using the tracer approaches and proteomic and lipidomic approaches to try to really get a mechanistic insight into how omega-3 is affecting the muscle in, in that setting. But, you know, a common criticism of those types of studies is it's not actually reflecting

what's happening in a surgical setting. So we've also teamed up with the hospital here in my PhD student, Danny Nyman's leading a study where, you know, we've got people going through ACL surgeries. So this is young and middle-aged people who are going through ACL, and we're going to provide them with high-dose amygia threes and see whether, you know, in that particular setting, there's likely going to be hyper-inflammation. So are omega-3 is more efficacious in that situation

in which they can, you know, take the edge off the inflammatory response and have those independent actions on protein synthesis as well? So we have a number of trials going on, but we're obviously really trying to dig into this area and make headroads over the next few headway. sorry, over the next few years, but primarily we've got the sex different study, the bed rest study and then also a surgery study going on as well with ACL injuries or surgeries. Is there any reason to not do, I mean, I guess the immobilization studies, it seems like

they're mostly done in young people because you know of how devastating they can be in an older population. But what if you find people that are older and getting a surgery? Like, is it like you're doing with your middle-aged, you know, a younger ACL type of? study. Yeah, and that's certainly something that. So that's the next step that we're looking to do is to certainly is to do this with older people, either, you know, with surgery or some ICU patients. But like we talked about at the start, you know, I need to write the grants for that. So it costs a bit of money for a lot of the analysis. So we're looking to, you know, write some grants and try and follow up

and some of that work. So that'll be the next phase after we've completed this work to, you know, try to tease. So we tried to take like a mechanisms based clinical approach to studying and of three-fight acids and muscle. Like, we know that patients and we know that physicians care about clinical outcomes, right? So we're not going to go to them and say, oh, improves their mitochondrial respiration. They're like, I don't care. Does it help my patient recover? And does it affect their ability to move? So we've got those primary outcomes. And then, you know, to kind of, you know, keep us, you know, really interested in the mechanisms and how it's working and keep the biochemist savvy. We really try to tease into what are the mechanisms in muscle. And

that's what the muscle biopsies afford us in allowing us to do that. Well, it's very important work. It would be very interesting to see if these effects are even more robust in an older population. So, you know, lots to do. I did want to kind of just shift gears, and I had one sort of area of interest that sort of has been on my radar recently. And it's this idea because I've always been sort of more of an endurance, you know, training kind of person. I'm certainly not an athlete, but I've always. you know, been a runner and I like to do more endurance training types of activities. Although since last summer, when I started to really get into the muscle biology and had,

you know, stew on and on Brad Schoenfeld yourself, I, you know, I'm a lot, I see how important resistance training is and I've really tried hard to incorporate a lot more of that into my routine. However, often I do do aerobic, you know, training in the same session as resistance training. And so there was a recent study you contributed to you. You were a co-author on about the role of aerobic conditioning in muscle hypertrophy. And I think there's been, I mean, I've just heard from, you know, the echo chamber that there's this prevailing belief that aerobic exercise might actually impede gains from resistance training.

So I was wondering if you could clarify how aerobic exercise could actually even potentially promote. muscle growth and maybe discuss some of the potential mechanisms behind this phenomenon. That was identified in the study you were part of. Yeah, sure. And as a disclaimer, this is certainly not my area of expertise. But my understanding, at least, is, you know, the classic work by Hickson a while ago was suggesting that there may be an interference effect between performing both, particularly with strength gains.

And since that work, you know, people were asking the question and it followed up with some of the molecular work in cells and animals, suggesting A&P may inhibit MTOR. and you activate AMPK, sorry, with endurance exercise, it stops then to all being activated with resistance. And I think whilst that may be the case in cells and rodents, the human work really hasn't, that's not, but it's not washed out in the human work at all. It doesn't seem to be an interference effect, at least when it comes to muscle hypertrophy. And there's been some good work by some Scandinavian groups there, Tommy Lundberg being one of them, and William Apropos done some molecular work as well. And in fact, as you've suggested, it may actually have an opposite effect

where you pre-condition or you perform aerobic exercise, and that may enhance capilleliorization, so facilitating blood delivery to the muscle cell. And then when you perform resistance exercise, the muscle is primed to receive more nutritional, you know, insulin and amino acids to enhance the response, the pretingsynthesic response to resistance exercise.

So essentially, it's potentially promoting greater nutrient delivery to the muscle so that I can build. And another factor is, is satellite cells. So satellite cells will, you know, donate their nuclear material, you know, the transcription factors and to enhance the ability to grow. So there's some evidence that satellite cells, and it's growing now, stronger evidence that satellite cells play a really important role in the remodeling of muscle and the contributions towards hypertrophy with resistance training and in the endurance exercise may not only enhance nutrient delivery, but also activate

satellite cells where they can donate their nuclear material to support the growth response to resistance training. So essentially, you know, I think that there is some evidence. It certainly doesn't seem to be even, you know, especially if you're not doing high levels, really high levels of exercise, it seems that the average everyday person, it's not going to do harm at all to do some aerobic exercise with resistance. And if anything, you know, we know that, you know, VO2 max in and in and of itself. And exercise capacity is very, is a predictive of, mortality and it's also important to maintain cardiovascular health and function. So I never really think it's a bad idea to incorporate endurance and resistance. But I will say and echo what other people

have said is the majority of the research out there in terms of health is on endurance and there's not as much on resistance. But I do think that, you know, there's certainly a role for both and I would like a little bit more resistance out there than endurance. Maybe that's just my biases. But I do think a combination of both of them really are beneficial and they may even be synergistic as you. you've just suggested. Do you think doing the aerobic exercise or training after the resistance training could also be similar because you're also still, I mean, you're still increasing, you know, capillary and basalilation and, you know, stuff? Yeah, you think so. Okay. So, I mean, I obviously, if you're like going out and running 10 miles, you're not going to be able to, like, you're going to be

too tired, but I'm talking about a 10 or 15 minute Tabata, which is typically like what I'll do when when I'm doing the resistance training as well. But these days I do, I do it. My, my tibadas will be in the morning and then I'll do resistance training later on in the evening actually. So, but it's still like in the same, the same day. Yeah. I don't see much of a problem with that at all. I mean, at the end of the day, it's, it's, I mean, people like yourself are very reactive. It's, it's maybe a consideration, but I think the majority of people just need to get out there and do, do exercise and of itself. And the, the, the slight, you know, small chance that there may be an interference effect between the two, which I don't think

really does exist, is certainly outweighed by the benefits of engaging in the exercise in and of itself, you know, so I think that's just kind of a bit of a red herring thing with the interference effect. I think it's more likely that it has a beneficial effect than anything else, engaging in both resistance and endurance, and endurance is going to confer its independent effects, sort of central, you know, you do a lot of endurance exercise, the central adaptations, you know, there's cardiovascular adaptations, and then the peripheral adaptations also occur and then they may feed into enhancing the the synthetic response or at least the hypertrophic response to resistance training. And there is a meta-analysis out there by, I think Tommy Lundberg suggesting that, you know, like certainly at least with cycling,

it doesn't seem to have that much of an effect. You know, it also kind of raises this, opens the door of like when you look at protocols for these trials that are being done, looking at muscle hypertrophy and fill in the blank, whatever they're looking at. In many cases, the control, quote-unquote control group will be like passive recovery, but the passive recovery is them on a stationary cycle doing some low wattage, but then you're going, wait a minute, maybe that's not so inert. Maybe that's actually promoting more hypertrophy in a way, right? I mean, potentially. Maybe. Maybe. I think the other thing is, and you said it before about precision, and sometimes when I see the word hypertrophy,

I like look into the devils and the details. When people say hypertrophy, it's like, did you use an MRI? Did you put a tape measure around the lake? Did you use Dexia? Did you do immunohistochemistry to look at type 1, type 2 fibers, which very variable? So I think a lot of the times, you know, like I said, the devil's in the details and the paper just beyond the abstract is, how did you measure hypertrophy? And I think that's also a key question because, you know, I wouldn't just hang my hat on, on cross-sectional area of individual fibers alone. I'd like to see, you know, maybe some MRI data and complemented with some other actual

measures of hypertrophy. So, yeah, I think reading the papers in a little bit more detail can reveal more. That's good to know. Do you mind if I send you some papers sometime to ask you a question or two? You're definitely much more poised to look at that stuff than I am. And there's like, when you see the conflicting data, like, if I had more of a handle on what you just mentioned, like the types of procedures and stuff being used, it would probably bring more clarity to why there's a, you know, conflicting data, for example. But really amazing work

that you're doing, Chris, with respect to the omega-3 and its role in, you know, potentially being anabolic, as you said, and how this may be, you know, very relevant, obviously, for muscle disuse atrophy and perhaps circropenia, but maybe just in general, like low amino acid intake or optimizing, sensitizing us to our amino acids. So all of it, very exciting, much more work to be done. I'm very thankful that you're out there doing it. And hopefully others are as well and more studies to come, high quality studies. If people want to learn more about your research, if they want to read more, ask you questions, where can they find you? Well, we've got a lab website just in the building right now, but I think the best way is

gate where I put all the papers and I'm not on Twitter. I've done my best to stay off Twitter for as long as I can, but people can email me at Chris, C-H-R-I-S dot McGlory at Queens-U.C-A. So it's not Queens.com. It's queens-u.com. So I am happy to answer emails and engage with people if they've got any questions. And yeah, I'd just like to thank you for the opportunity to talk all things, Amiga-3. I think, you know, very rarely I get to talk for an hour and a half about Amiga-3 is to anyone. I put a glass eye to sleep with this sometimes. So it would be a, it's good to chat and to engage. Well, thank you so much, Chris.

I look forward to your ongoing trials and keeping up with the research that you're doing. I hope you enjoyed this episode with Dr. Chris McClory. If you're looking to quickly learn more or dive deeper into the science on Omega 3, you will probably enjoy my premium members podcast, the Aliquot, and my monthly Q&A sessions where you get to ask me anything

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