Protein and Muscle Mass. Podcast with Stu Phillips

Proteins exist in every one of your cells, and apart from water, protein probably makes up as much of your body as anything else. Among the vital roles they play, proteins act as building blocks for structures such as hair, skin, and other organs like the liver, and the proteins that you eat provide the raw materials for the proteins in your body.

In a couple of previous blogs (1, 2), I discussed the subject of dietary protein and aging. Today, however, we turn our attention to dietary protein and muscle mass. Whether you want to look great at the beach, perform better at sports, or ward off disease, it’s important to optimize your protein intake. This brings us to the latest episode of humanOS Radio.

In this podcast we concentrate primarily on dietary protein and muscle mass. We explore many subjects though, including:

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Greg Potter - 00:00: Welcome back to humanOS radio. My name is Greg Potter and I'm hosting the show once again today. I'm joined by professor, Stu Phillips from McMaster university. Stu is director of both the fiscal activity center of excellence as well as the McMaster Center for Nutrition, Exercise, and Health Research. While he's probably too humble to admit it, Stu perhaps knows as much about regulation of human skeletal muscle protein as anybody on the planet. Stu, it's great to have you on the show.

Stu Phillips - 00:27: Oh, it's my pleasure to be here. I have to correct you. I think I know, but I'm constantly corrected by people and I'm always learning. So-

Greg Potter - 00:36: There's that humility. We're going to focus mostly on [inaudible 00:00:40] protein. So why should our listeners this be interested in this subject?

Stu Phillips - 00:45: Yeah, I think it's interesting. I call it for a long time the forgotten macronutrient, particularly with respect to sport and sport performance. It was so carbohydrate centric and now we've seen the resurgence of ketogenic and high fat diets. And protein stumbled along and has really come into its heyday recently with probably the recognition that the recommended dietary allowance or the recommended nutrient intake ending depending on which side of the Atlantic you're from a point, .8 kilos per day, isn't actually sufficient for a number of people. And it's really a minimal estimate of what people would require, and not what I would call an optimal estimate.

01:23: Every structure that maintains some sort of integrity in your body including your skeletal muscle being the biggest one, but your bones and your internal organs, your skin and all of your vessels are made up of protein. So there are various pools of protein we call them within your body, but they're constantly turning over. And I think the important point to realize is that you can survive without carbohydrate, I fully admit that. You only need a little bit of fat with the essential fatty acids in it. But you have to have protein. And if you don't, then you're going to break down some pool of protein in your body to maintain those structures that I was talking about.

Greg Potter - 02:02: You mentioned the RDA there Stu. Whereas the RDA is based on body weights, the National Academy of Sciences advises that people should consume tend to 35 percent of the daily energy intake from protein. What do you make of this discrepancy?

Stu Phillips - 02:17: Yeah, it's a good question. It's really confusing. The RDA is actually set by a different organization, The Institute of Medicine. And it relies on the old traditional nitrogen balance method. A lot of people have pointed out flaws. And as you pointed out, the dietary guidance is around somewhere from 10 to 35 percent of energy coming from protein. And again, it comes back to that forgotten macronutrient part because really, the requirements are set for carbohydrates, then for fats, and then what's left over is given to protein. Nonetheless, if you consume 10 to about 12 percent of your energy from protein, you would easily meet the RDA. And then of course you've up to double that and more that according to one organization would be a good thing, or at least okay to consume in terms of overall health. So I could understand why people are confused. And it's really that two different agencies set each number.

Greg Potter -,03:14: Many people listening are probably interested in either building muscle or holding onto it while shedding fat mass. And changes in muscle mass depend on muscle protein balance. Can you explain muscle protein balance is and some fundamentals of how it's regulated?

Stu Phillips - 03:28: The analogy that I'd used that most people can grasp and really understand is when we think about muscle, imagine that it's a brick wall, and you've got bricks going into the end of the wall at one end and bricks being taken out at the other. So there's a constant upkeep or maintenance of the wall or what we call turnover. Then the bricks going in our amino acids and the bricks being taken out also amino acids. You could imagine that if the bricks going in was occurring at a faster rate than the bricks being taken out, you would be gaining size in the wall or your muscle mass would be increasing. Or if the converse is true, then you would be losing muscle mass. So in the two scenarios you painted, gaining muscle mass is really optimized when you are obviously performing resistance exercise of some frequency, which I won't get into. But let's just say you're doing it consistently and you're in a positive energy balance. In other words, you're consuming more energy than your body's expanding and you're getting sufficient protein.

04:27: In our hands, we really come up to a level that's twice the RDA. That's at least 1.6 grams grams of protein per kilo per day, and we think maybe up to as high as 2.2 grams per kilo or one gram per pound if you like the rounding. I'm not sure you can go higher than that and expect to see any more gains in muscle. You can definitely eat more protein, but you certainly can't I don't think use it for muscle gain. In the other situation where you mentioned people are trying to hang onto muscle mass while they're losing fat mass, they've had to put themselves in a little bit of an energy deficit. So in that situation, that's not the most optimal environment for building muscle. But it is a situation where it can happen, albeit on a limited basis. But it relies again on sufficient protein. And the interesting part is that protein is one half of the stimulation of muscle growth or bricks going into the wall, and then resistance exercise is the other. And if you need the analogy than resistance exercise is kind of like employing a new brick layer. It's like putting another person to work at building that wall. So it just proceeds at faster rates and is going to promote muscle growth.

Greg Potter - 05:36: Can you tell us how much protein people need to maximize muscle protein balance on a per meal basis? I know that's been the focus of some of your work.

Stu Phillips - 05:44: Yeah. And again, this comes back to a real fundamental understanding around protein. Unlike carbohydrates and unlike fat, we don't have any capacity to store protein. There's not a pool of say liver glycogen in the case of carbohydrate or muscle glycogen or body fat storage adipose tissue in the case of fat. Protein has to be used when it's available. So when you ingest a protein containing meal, amino acids rise. You use them to build the wall, and then subsequently the amino acids decline. You remove the nitrogen, excrete the urea, and you're basically done then with amino acids.

06:20: So on a meal to meal basis, which is what makes sense. If you have to use these amino acids as soon as they are ingested, what we're talking about is at least .3 grams of protein per kilo per meal, and maybe upwards of .5, to .6 at the very most grams of protein per kilogram, per meal. And then if you multiply that out times at most four meals per day, you're getting into the intakes were talking about as high as 2.2 grams per kilo per day

Greg Potter - 06:51: And what might influence what the optimal quantity is? For example, age and exercise training.

Stu Phillips - 06:59: There's probably a number of influencing factors. Age is definitely a factor that negatively influences that number. In other words, you have to consume greater amounts of protein as an older person to get the same protein synthetic response. And at least in meta analyses, we've shown that older people just have a little bit of a harder time gaining muscle with weightlifting. So there's something in the age related program that is preventing older people from from gaining enough muscle. You might be able to overcome it with enough protein and enough work, but it definitely affects it in a negative sense.

07:34: If you're inactive or if you're immobile, so you can imagine hospitalized patients or people who are sick, or if you make your limb a mobile, then you lose muscle because the ability to use those amino acids is severely diminished. And really what we think is that the process of protein synthesis is markedly less sensitive. So you either have to consume more protein, or you have to do some type of physical activity. You can't dial back the clock, at least physical activity and mitigate what happens with aging.

Greg Potter 08:09): You've written persuasively about the need for higher protein intakes and critical illness. And it might be good time to touch on why these patients need more protein.

Stu Phillips - 08:17: Somebody who would be anabolically resistant would be if you gave them the same brand per kilo dose of protein, they would not be able to mount the same muscle protein synthetic response. And In fact, they might not get the same suppression of muscle protein breakdown. We associate with age and immobility.

08:37: So when you think about somebody who's in the intensive care unit in critical care, they're in bed. So they're immobile. Patients in critical care units at least in the province where I live in Canada, are over the age of 60, so they're probably in a category where they're already losing some muscle because of the age related sarcopenia. Due to their sickness, they have high levels of catabolic hormones, particularly cortisol. They have high levels of catabolic cytokines. And that really represents a confluence of factors that come together and really prevent that protein sensitivity idea until they're very anabolic resistance. And data from ICU patients show that they lose muscle mass and they lose it very early and very rapidly. The consequence if you spent a number of days or weeks in the ICU is a syndrome called ICU acquired muscle weakness, and it's definitely related to deconditioning of muscle loss of muscle mass.

Greg Potter - 09:35: Going back to protein needs on a per meal basis, many people consume skewed protein intakes with littler breakfast and lunch, but lots of dinner. Can you speak a little about protein distribution and what studies have different age groups have shown so far?

Stu Phillips - 09:50: I think the preface to answering that question is to point out to people that there's curvilinear relationship between protein dose and muscle protein synthesis that tends to increase fairly rapidly and then plateau and young people. Whereas it tends to remain dampened and then increased with higher doses in older people. So suffice to say that if you think about consuming a small amount of protein, then that's a few bricks that are going to go into the wall. And if you think about consuming a larger amount of protein at least to a point, then that will be more bricks going into the wall. So I think that it then intrinsically makes sense to say well what would be best would be to try and maximize that muscle protein synthetic response at each meal? I'll use the northern hemisphere example.

10:40: Breakfast tends to be the smallest amount of protein. Lunch is somewhere in the middle. And then the dinnertime meal is the largest. And it would probably be a better strategy to say we should get about the same amount at breakfast, lunch, and dinner, so each eating occasion to maximally stimulate muscle protein synthesis. It's not done very often and in other countries where lunch tends to be the bigger protein containing meals.

11:05: Most studies to date, I would be honest in saying have been inconsistent when people have tried to intervene to show this effect. I think the real problem is that all of them have been at least to date, underpowered. They haven't used enough people. But there is observational data to show that people who maintain a more consistent protein meal spacing across the day have higher muscle mass and in some cases actually even have higher muscle strength

Greg Potter - 11:33: And just to consider the other side of the equation Stu. I know that some people have speculated that very high protein intakes could theoretically reduce muscle protein breakdown and thereby increase muscle protein balance. You touched on this earlier. Do you think that any additional gains in lean body mass from very high protein intakes are likely reflective of skeletal muscle specifically, and might that actually be any downside to reducing skeletal muscle protein breakdown?

Stu Phillips - 11:59: The concept you're referring to is one that my former postdoc advisor, Bob Wolf advocated. And what they've done is they use whole body protein measurements and they say, "Look, when we feed people increasingly large doses of protein, protein balance or the difference between synthesis and breakdown improves." But it improves because of a continual suppression of protein breakdown. But that's at the whole body level, and I definitely agree with the data. The question is at the whole body level, how much of that response is really coming from skeletal muscle? So we need to see those data first before I could say to you unequivocally yeah, that makes sense. Protein breakdown goes down with greater protein intakes. Yep. We've hit a plateau in synthesis, but that doesn't matter. If we keep suppressing breakdown, then we're going to get a greater net muscle protein balance. So data is pending on that to whether that is exactly existing muscle or is it something that is in another tissue, is it gut protein, is it liver protein, is blood proteins. Who knows? We need to figure that out.

13:02: I think the really important point for people to consider is that there is merit in having a high rate of muscle protein turnover. And so the bricks into the wall, out of the wall analogy really talks about then trying to maintain the best quality of wall. So we're taking out the damaged bricks, we're replacing them with new bricks, and we're not allowing damage bricks to accumulate. In that sense then, suppressing breakdown or the bricks out of the wall process really could lead to the accumulation if it is present in muscle, of potentially damaged bricks. And people say, "Well what do you mean by damage bricks?" Well, there are a lot of processes in muscle that damage proteins, oxidation being the one that most people are familiar with, but it could be all kinds of things. It could be nitrosylation, it could be mis-folded proteins, it could be physically damaged proteins. Sometimes we say that's muscle damage.

13:57: So when those things accumulate, it's like the wall isn't as good as if you just keep maintaining a high rate of turnover. So we need to think about those things in and I think the short answer to my long answer is really I haven't seen any data that would support the notion that higher protein intakes leads to an even greater muscle mass accretion, but I stand to be corrected on that and it will be great to get some mechanistic insight into those processes and muscles.

Greg Potter - 14:25: And related to this, there's been some interesting work on pre-bed protein and overnight recovery from exercise. Do you think it might be preferable to consume more protein in that final meal and/or choose protein sources that are more slowly digested?

Stu Phillips - 14:40: Yeah. This is work worked almost exclusively comes out of Luc Van Loon's lab but Mike [Ormsby 00:14:45] at Florida State has done some interesting work in the space as well. The more I read about sleep, actually the more worried I get because I'm not a great sleeper. I can sleep well, but for short periods of time. But needless to say, sleep is aregenerative process. It's when our brain and lots of things to do with our psychology and our mental state tend to recover. But it's also a great physiological repair time. It is also the time when we're not eating, so it's the period where we're in probably the biggest and longest negative muscle protein balance throughout the day. So it does make some sense to think about maybe trying to consume more protein in that later meal, dinner time meal, or think out pre-bedtime, protein containing standard.

15:29: Now I freely admit some people love it. Other people aren't a big fan. There's been a lot of words around things like time restricted feeding, which I read a little bit in, but not enough to really say what it means. But nonetheless, it is a strategy that's shown some benefits in younger men. There was a paper that just came up from a guy named Andy [Huerta 00:15:50] who was working with Luc. And he didn't show any benefit in older individuals. So it's a little bit mixed right now for older folks, but I do see some merit maybe for younger hard training athletes who need to maximize those periods of recovery.

Greg Potter - 16:06: And just to give some background for the listeners, Stu emailed me at about 4:00 AM his time this morning.

Stu Phillips - 16:12: Yeah. And that's not unusual, but as I said to you, try and find an email that comes to you after 9:00. That's pretty rare, so you got to make comfort on one end or another.

Greg Potter - 16:23: Let's turn to protein quality. The digestible indispensable amino acid score is the current gold standard in assessing protein quality. Can you speak a little about the determinants of protein quality, and is it fair to say that there's an inverse relationship between protein quality and how much protein people need at each meal?

Stu Phillips - 16:42: You're using the most current definition, the DIAAS definition. That might surprise some people. Some people might be more familiar with PDCAAS or the protein digestibility-corrected amino acid score. But when you break all of these protein quality measures down, they're really reliant on a number of things.

16:59: First of all, how digestible is the protein? And really what that means is, is there anything in that protein source that is fundamentally anti-nutritional? So by anti-nutritional, I'm going to use the example of plant protein for example, where the plant contains fiber. Fiber is in and of itself no caloric benefit. There's no digestible benefit. It's actually an inert substance and hinders digestion. Now everybody says, "Well hold on a sec." In the presence of too much nutrition period, there's all kinds of benefits. But it fundamentally lowers protein quality. Now animal proteins on the other hand do not have fiber in them and so are more digestible. And then the other part of that score that really is important is what is the compliment of the essential amino acids? And so most people remember vaguely from somewhere in biochemistry or nutrition that there are 20 amino acids, nine of them, or some people argue for more ... Let's use the commonly accepted definition that nine are essential.

18:02: So in other words, those are bricks out of the 20 that we have to put into the machine so that the machine works well. These essential amino acids have to be present in sufficient quantities. I think the best example of understanding where foods might be limiting is the issue of complementary proteins. So in the vegetable, i.e. non animal protein consuming parts of the world, for whatever reasons probably through evolutionary pressure, people have figured out that you need to eat a grain and a legume. So it's red beans and rice in the Caribbean, it's usually some type of bean and corn in Latin America. It's rice and lentils in India. Similarly it's some sort of soy or tofu product and rice either in mainland China or Japan.

18:51: So I think that's intriguing that people have figured out that combination. And really what it speaks to is a limitation of amino acids in one protein that are then compensated for in the other protein. So it's digestibility, essential amino acid content. How would that influence what people are going to eat at a per meal basis? Obviously the more digestible and the higher quality, then the less you would have to consume at each meal.

Greg Potter - 19:19: And just to be clear, according to the DIAAS, which protein sources are the highest quality?

Stu Phillips - 19:25: This is something that before in the past we would have to say well it's a three way tie meal proteins are comprised of whey and casein and soy. Now the DIAAS allows the score to deviate above one, and in that sense then no proteins or casein and soy are at the top of the scoring ladder. Soy is still there. Isolated soy protein, beef and egg are obviously high, but then it goes down which there.

Greg Potter - 19:53: Do you have any advice for people looking to purchase dairy based protein powders?

Stu Phillips - 19:59: I have to be a bit pragmatic here. First of all, my question when people ask that is how much money do you have in your pocket? 'Cause I acknowledge that a lot of athletes live on limited budgets, and students live on limited budgets. That forms a large part of the audience that I talk to. So if budget concerns aren't a limitation, then I would go for whey protein. Whey protein is now evolved from a food science perspective, that they taste really good, in my perspective now. I grew up in an era where the only protein source was Joe Weider. Joe Weider made egg protein, beef protein. And you basically plugged your nose and just slammed it down if you wanted it. So things have gotten way better from a taste standpoint. The other point would be that as I said, it's high quality protein, you don't have to eat a lot of it. And at the same time, I think that it's probably one of the most readily available sources.

20:50: Now people want to compare protein isolates, they want to say which is better on isolate. And to my mind, it absolutely doesn't matter an awful lot as long as they are isolates and they are high quality isolate. So whey is good. Casein is good. It's slower digesting so you get a slightly different amino acid profile, but needless to say I don't know that that makes a huge difference. Soy is fine. Pig protein isolates some people like. And then there are obviously other ones. There's P, now we can talk about insect protein. But from an athlete standpoint I usually recommend a couple of things. First of all, I like whey, I like dairy proteins. Second, I say make sure it's got an informed choice stamp on it. And is it in your budget range, is it something that you can afford? I would probably be the first to admit that protein supplements and isolates are a convenience issue. I think if you're diligent, you can do it with food. But for most people it just provides a convenient form of protein, and in some cases free from the energy of other macronutrients which some athletes desire.

Greg Potter - 21:57: I'm sorry that you had to tolerate those Weider protein powders back in the day.

Stu Phillips - 22:02: They were nasty. I got to be honest with you, talk to anybody my age or older and if they got a hold of them. It was a true sign of dedication to your sport to be able to hand those things down. They tasted pretty bad.

Greg Potter - 22:14: Just thought the perfect combination would be that plus exogenous ketones.

Stu Phillips - 22:18: Yes. Perfect. Rocket fuel poured on top of really nasty tasting.

Greg Potter - 22:23: You mentioned insects there, and dried crickets aren't actually too bad, kind of nutty. Do you have any thoughts on the utility and quality of protein from insects?

Stu Phillips - 22:32: Yeah. This insect protein concept is coming up more and more. I suppose it has to from a sustainability standpoint. I tend not to talk about sustainability because it's not the sort of thing that I study. I learned everything I learned from being on a program where I talk about protein, and then the next person up happens to be a sustainability person. So I've listened to about three or four of them now, but my sense is that there's a sense that things are going to become harder in terms of sustainability. But if you listen to one person it's doom and gloom. If you listen to another person, it's not going to be so bad. But they all acknowledge that by the time 2050 rolls around and we're probably sitting at close to 9 billion people on the planet, we had better find some more sustainable sources of protein than animal proteins.

23:18: So insects make sense. They are a lot of them high in protein relatively speaking, but you need a lot of insects, right? Crickets and roaches or whatever it is that you want to crunch up. They have a nutty flavor. It's a lot like some plant based proteins. It's very similar. Some people like that, and I'm not dismissing it. But just be aware that the outer shell of some of the crunchy insects is made up of titin. And titin is a non-digestible protein source like collagen in some senses, so you just have to appreciate it's a little bit lower protein quality. If insect protein has a future, it's with some type of worm, something that's soft and squishy and doesn't have a hard exoskeleton that's made up of a protein that we can't digest.

Greg Potter - 24:04: Just staying with the subjects of protein sources which are maybe more commonly consumed now than they once were. I think that one of the best ideas that's been popularized by paleo diet proponents is the idea of eating nose to tail. Again, because of sustainability, but also helping people meet their micronutrient needs. Do you know much about the protein quality of organs such as the heart, liver, and kidneys?

Stu Phillips - 24:27: Yeah. That's a great question and it's a point that I've made to a number of people who profess to be paleo. If you look back at our paleo ancestors, if they were animal protein consumers, not necessarily all of them were. But they ate as you said, nose to tail. They had everything in between because it was a long time between meals. So you ate the liver, you ate the intestines, you rate the heart. My sense again is that the only thing that would lower the quality of any organ that you were going to consume from any animal would be the content of any fibrous tissue that it would have. So the more fibrous tissue which is really collagen that would be present in the organ that would lower the quality, but on the whole I would have to think that once you've cooked it and probably broken down some of those proteins, the quality would remain essentially high. But that's an interesting question and something that for anybody who's a budding protein quality researcher, I'm sure that would be interesting data to get.

Greg Potter - 25:25: I know that some people have looked at the effects of consuming collagen and gelatin in the context of post exercise tendon remodeling. So there could be a trade off between its effects on skeletal muscle and some other tissues which are relevant to resistance training.

Stu Phillips - 25:42: Yeah, that's a brilliant point. And Keith [Bars 00:25:45] the guy in that area, it's fantastic work. Different tissue, fundamentally different protein turnover rate, different kinetics of protein turnover the muscle. And as you point out, there's some evidence to suggest that the provision of the amino acids, the collagen protein needs, and that's a different composition than muscle. And the timing of that protein needs to be different. A lot of work to be done there. Whoever can corner the market on some sort of myotendinous or ligamental or joint tissue remodeling protein source, they're going to have a bright future because at my age I can tell you that I don't think your muscles have a problem repairing themselves. But it's your joints that break down, and I think just about any athlete particularly after a long time would tell you that yeah it's my knees, my shoulders, my elbows. And people with osteoarthritis would say a double check that's the degradation that's happening a period of time. So anybody that can invent that supplement, I'm one of your customers absolutely

Greg Potter - 26:49: I'll invest in shares.

Stu Phillips - 26:51: Yeah. Well, like you said. If anybody's got any bright ideas, the latest analyses on dietary supplements to improve knee osteoarthritis [inaudible 00:27:01] bright area. Most of the trials out there are small, they're short term. There's been some that show benefits, but the vast majority show inconsistent results. So I know a lot of people are fans of bone broth and a lot of other collagenous supporting therapies, but in my estimation at least in the science that I've read, there's really not a consistent message there. But definitely more work to be done. Keith Bar is the guy, he's going to come out with something I get the feeling.

Greg Potter - 27:27: And can you speak about using leucine to bolster the anabolic effects of lower quality proteins? Do you think this is a good strategy for Vegans, for example?

Stu Phillips - 27:36: Yeah. Interesting question. So the whole bricks in bricks out analogy. The one brick that is the thing that gets the whole process going is leucine. It really is not just a substrate for being a brick in the wall, but it's also if you like the golden brick when it shows up, the whole process of brick lane get started. So the concept from a muscle standpoint is that if you had a lower quality protein so that it didn't have all of the bricks, or if you had a smaller dose of protein, could you make it appear larger by giving people more leucine? And we've done some work in that area, and I think that there's some legs to the whole concept.

28:12: How much leucine? Hard to say. We've done proof of concept studies where we've gone above what we think is reasonable, but it does show effects. Could it bolster vegetable source proteins? I'm sure it could. There's been some work from Luc van Loon's lab again that a protein like wheat protein, which is not a particularly high quality protein. But when you add leucine from a muscle standpoint, it begins to look almost milk protein like. So you can make lower quality proteins better by adding leucine.

Greg Potter - 28:44: Just thinking about other populations, on a per gram basis protein seems to be more satiating than carbs or fat. This is great when you're trying to get a six pack, but it can be a problem for elderly people with poor appetites. So what do you think about spiking smaller amounts of protein with leucine in this instance?

Stu Phillips - 29:00: Yeah, as you point out it's the double edged sword. I'm not satiety person. I know what I know about satiety again from hearing from a lot of good satiety people speaking on similar programs, when we talk about protein. My sense is that yes, it sits top of the heap in terms of suppressing appetite and for longer than either fat or carbohydrate. So in young people can be great, can be an adjunct in weight loss. I think there's a lot of reasons for that. In older people, the suppression of appetite, particularly frailer, older people would not be the thing that you want.

29:33: So as you point out, maybe these smaller protein meals with a little bit more leucine is the way to go. It requires though an engineered product. It's not an actual food source strategy. Not that that's a bad thing. What I do worry when people begin to over rely on supplemental sources of protein and not food sources, only because particularly older people, they're missing out on the nutrients then that are contained in food that they need to get. So any beverage that did that would probably be a good idea if they were to substitute back in some of the micronutrients, etc. that were missing from not eating food for example.

Greg Potter - 30:13: My understanding is that leucine metabolites the HMB have some effects that are distinct from leucine, but do you think there's good evidence that leucine and HMB have different effects on muscle protein balance? And can you comment briefly on the steroid light gains that have been reported in some HMB free acid papers?

Stu Phillips - 30:29: Yeah. The normal metabolism of leucine as soon as it enters a lot of cells, we'll use muscle as the example, is to deaminate the amino acid. So the first thing that gets formed is the keto acid, [inaudible 00:30:41] acid or a lot of people call it alpha hydroxy isocaproic acid or alpha HICA is the name that a lot of people use on supplements. And people have said, "You can give alpha HICA and it's just as potent as leucine." My answer is well, actually that's what the majority of leucine becomes in skeletal muscle is ketoisocaproic acid anyway. So why would it surprise anybody that that metabolite is similar to leucine? Beta-hydroxy beta-methylbutyrate, or beta HMB is a scarcely made metabolite of leucine in humans. Mainly because we have a very low activity of the enzyme that makes it. But nonetheless people have isolated this leucine metabolite, given it back to people, and they do show that it has anabolic properties like leucine.

31:27: Again, not surprising. It's structurally similar. It has a longer half-life than leucine. The amino acid would mainly because it's not metabolized as quickly. So you can get away with small doses of it. From that standpoint then, those metabolites have been used. Alpha-HICA quite sparingly, but beta HMB has got a long and rich history. Started out with experimental applied sciences. Bill Phillips, not a relation I hasten to add it. Was part of EAS out of Golden, Colorado. They were acquired subsequently by Abbott Pharmaceuticals. Abbott trimmed the product line down from about 80 products to about 10 to 15 basically because they said a lot of them didn't work, but they've held on beta HMB and it's present in a lot of formulations for older people, etc. Most of the trials would compare beta HMB to nothing, so that's the traditional active to placebo trial.

32:22: Some people, when you give them the free acid form of beta HMB which is supposed to have a longer half life and it does, its availability is greater, would then potentially confer some anabolic advantage. All of the studies that I'm aware of, and they all come out or Phil Atherton's lab. Dan Wilkinson is the lead author on these papers, have never shown that the free acid form of beta HMB is any more effective than the calcium form, which was the early form of the salt that was available. And neither of them are any more effective than leucine. And that's work that we collaborated with Phil and Dan. So I find it hard to believe if the mechanism isn't there to show that it's more potent that it would lead to the types of games that have been reported in some studies. And we're talking about gains of muscle between seven to nine kilos in 12 weeks. So that rate of growth is comparabLe to at least some of the better data out there.

33:20: The same that's seen with weekly supplementation with very good anabolic steroid testosterone enanthate. When I see gains with a supplement that are on par with what are seeing when people are taking steroids, I begin to wonder about the veracity of the data. I'm not saying it's untrue, but you wonder whether some of the subjects on there were maybe dabbling in steroids or something was going on methodologically, but we just can't account for. Again, we've compared it recently, it being beta HMB in the calcium form to a protein containing supplement with a relatively high dose of leucine and the same protocols as these steroid-like gains. And we see no difference between the protein leucine versus the protein HMB scenario. So HMB, there's no magic around it. It's definitely no more potent, at least in my estimation than leucine. And it's an expensive dietary ingredient controlled by one company. So you I think need to think about that when you see studies that are reporting on it because it's really distributed and tightly regulated by metabolic technologies incorporated, which is the research arm of the patent holders of the University of Iowa, so everybody needs to be aware of that.

Greg Potter - 34:35: And are there any relatively novel nutraceuticals that you think are promising for the anabolic actions and skeletal muscle? And do you think anything as safe as creatine might be around the corner?

Stu Phillips - 34:46: Creatine is our golden child in terms of supplements, mainly because it's been around for so long. It is effective, it's safe. Everything, it checks a lot of the boxes. And so if that's the gold standard in terms of anabolic supplements, and I would definitely agree with you on that, the only thing that I see evidence for that's coming close and it's not novel by any sense, is just the application of high dose omega three polyunsaturated fatty acids, particularly enriched obviously in the very long chains which are eicosapentaenoic acid or EPA, docosahexaenoic acid or DHA. So these really concentrated forms of fish oil. In that sense there does seem to be some good data around enhancing anabolic sensitivity, and maybe even reducing catabolism works well in older people. Works better for reasons I'm not 100 percent familiar with, but in women. But it works in both sexes. It shows some promise. It's an interesting nutrient. There's probably some other benefits maybe on the cardiovascular side that would force me to conclude it's probably not a bad choice.

Greg Potter - 35:53: And I'm going to use anabolic sensitivity to segue to fat loss. It seems that relative protein needs go up when people are in calorie deficits. Can you speak a little about this, including effects of protein on preservation of skeletal muscle and anabolic sensitivity?

Stu Phillips - 36:08: So I think anybody who's messed around with putting themselves in a caloric deficit would know that you lose body weight. Weight on a scale is great, the numbers go down, assuming you're adherent of course. And the real trick then is to figure out what it is that you're losing. So let's put water aside for now because most of the studies that we've done in the good studies that are done out there have been able to account for shifts in body water content. So we'll talk about the two main compartments then that are lost, and the majority of which is going to be body fat, which is what a lot of people want to lose. But then you're going to lose some muscle, and it depends then on the relative balance of energy intake. So how deep is the energy deficit? Are you really restricting food, or are you in a complete starvation state. Are you just drinking water, so a prolonged fast to starvation?

36:58: In those situations, the work that we've done and a lot of other people have done really shows that increasing the content of dietary protein helps. If you like, it's delivering more of the substrate, so there's probably feedback mechanisms that are feeding back to the protein synthetic and protein degradation machinery saying, we don't need to break down as much of this body protein that we have here because we're getting a lot in from the diet. So that's one strategy.

37:24: The other one is obviously the practice resistance exercise, but it does appear in that situation that you need more protein on a per kilogram body weight basis than you would obviously if you're in either a neutral energy balance or a positive energy balance. And I think some of the best work that's been done out there was a really good review by a fella named Eric Helms. And it's in the International Journal of Sport nutrition Exercise Metabolism. And he estimates that protein needs could probably be as high as three grams per kilogram now of lean body mass. So it's obviously a little bit lower for total body mass per kilo per day. I would agree with some of those estimates. I think at least two grams per kilo if you're in a deep energy deficit and you're working out very hard would be a good strategy to hang on to muscle mass.

Greg Potter - 38:13: Moving on to other macronutrients, can you speak a little about the effects of co ingestion of protein with the other macronutrients, including alcohol or muscle protein balance?

Stu Phillips - 38:23: Yeah. Anything that's consumed with protein is going to slow its digesting down. How much content exiting into the small intestine are slower. For the most part, it appears that when you co-ingest carbohydrate, that's true. Fat contrary to what some people might believe, it doesn't slow things down to a huge extent and it may be because, and again this is going to some work from Luc van Loon's lab, the fat rises to the top in your stomach, and so it puts that body layer, that floats to the top of the stomach content. And the protein tends to get into the small intestine.

38:57: Alcohol is a little bit different for the main reason that the ethanol and alcohol has a lot of effects at the level of the liver, and even at the level of the muscle, I would add. It tends to lessen the effectiveness of protein. We've done one study in collaboration with the [Louiseb Berk 00:39:14] and John Holly, [Donny Camara 00:39:15] down at the Australian Institute of Sport and in conjunction with [inaudible 00:39:21] at RMIT. And all I can say is that when you consume fairly large quantity of alcohol, I believe in the end it averages out to about 20 units.

39:29: Remember, unit's not an ounce. It's still a good amount, but it was modeled on what some Australian rules players and rugby league players would consume on a good night out. We showed that had a very detrimental effect on muscle protein synthesis. The question I always get asked then is, so is one glass of wine or a couple of beers, is that going to affect things? The short answer is, I don't know. If you gave me a list of best practices for athletes, I would tell them that alcohol is something that if you can manage it in a period of very high intensity training, you should try and avoid drinking it if you can, and be prepared that the more you drink, the more you're undoing some of the positive effects that you've had. So I'm never going to begrudge anybody that drinks if they would like one, but where are you on the scale? You want to climb on the podium on the next Olympics? If you do, then maybe it's time to think about your intake of alcohol.

Greg Potter - 40:26: Ketogenic diets and exogenous ketones all the rage right now. What do we know about their effects on muscle protein balance?

Stu Phillips - 40:33: Not a lot, in short. I think again that there is some evidence, John Holly's lab is doing a really nice job in this area showing that if you keep levels of fatty acids high, you tend to negatively affect muscle protein synthesis. However, exercise can overcome that effect quite robustly. In other words, you'd probably don't have to do a lot to overcome it. But I think it's fair to say that if you're in a state of ketosis in a negative energy balance, you're looking to use a ketotic diet to lose weight, then you're going to lose some muscle mass. And for the main reason, there's a lot of them. But insuLin is ridiculously low, which is a desired consequences to get rid of body fat.

41:16: But insulin if it has a very potent effect on muscle and on anybody protein, is it's highly effective at suppressing protein breakdown. So the brakes on protein breakdown are removed in a ketotic [inaudible 00:41:29]. At the same time, if your ketotic, a lot of people subscribe to the lower protein version of a ketotic diet. Not everybody's doing that, I will admit. And in that sense now you're reducing the bricks or the supply for muscle. So I would guess if people have data on this, I'm sure it's out there, you're going to lose muscle protein probably I would think at least a quarter of the body weight that you will lose is lean mass and the majority of that would be muscle. So it's something to think about. For some people that's not an issue, but the way to obviously counter that is to be physically active and performed resistance exercise, but for people who don't, you just know that you're going to lose muscle as well as you're going to lose pounds.

Greg Potter - 42:13: I remember speaking to you about a particularly interesting study that Kevin Tipton published 12 years ago. It basically showed that a suboptimal dose of protein from whole milk increased thigh muscle amino acid uptake as much as isoenergetic skim milk, despite the whole milk containing substantially less protein. And in the last few years there's been some cool work on the anabolic effects of whole foods such as eggs. Can you tell us a little about these findings?

Stu Phillips - 42:37: Good friend of mine Kevin Tipton did that [inaudible 00:42:40]. Interestingly enough, there's a third condition in that paper where they took the calories that were in the skim milk and they actually increased the dose of skim milk so you got more protein and it wasn't even as effective as the whole milk. And Nick Berge lab has got some really interesting data an the eggs, so eat the yolk, not just the egg whites. Showing that there's something that we don't fully appreciate in the food matrix. And a lot of people have argued fat and calories, and I won't dismiss that. But I think that what we're seeing is there's some complex bioactive maybe or food matrix effects that are influencing skeletal muscle protein synthesis. What it is, is going to take some serious unraveling. And in short, I don't know what it is. I think it could be a bioactive, it could be a whole food matrix in fact, it could be calories.

43:30: There's a lot of things. Somebody needs to do a good job unraveling that whole thing. Very, very interesting. And again I think goes back to the sentiment I expressed earlier on, which is the whole foods. There's a rich nutrient package in a lot of these things that it's doing things that we just don't understand.

43:47: And so there's some benefit to thinking about whole food, protein based hyper or protein diets that are very, very nutrient rich. And in particular if you think about dairy proteins and meat based proteins and egg based proteins, very nutrient rich. So you're hitting a lot of nutrient targets when you increase those, when you increase protein content.

Greg Potter - 44:09: I'd like to finish by addressing some controversies. First, do high protein diets leech calcium from bones?

Stu Phillips - 44:16: Yeah. So again, old theory based on observational data that people consuming higher protein had more calcium in their urine, and then the circular logic was therefore they're leeching calcium from your bones because the protein makes your blood more acidic, it's called the acid-ash hypothesis. Subsequently shown with very good metabolic balance studies, and lots of observational data that the converse is true. Protein does not leech calcium from your bones. If anything, protein is a bone supportive nutrient. But, you need to have calcium and vitamin D or on your side of the atlantic vitamin D dialed into the right level, so at least 1,000 milligrams of calcium, probably 1,200 if you're a woman. And vitamin D, arguably 600 to 1,000 international units per day. And those need to be at sufficient levels, but no detrimental effects on bone whatsoever.

Greg Potter - 45:12: Next. In people without existing kidney dysfunction, are high protein diets bad for renal health?

Stu Phillips - 45:19: Another common misconception, so here's where this comes from, at least in my estimation. People with chronic kidney disease, the vast majority of which are people who have either full blown or prediabetes or have hypertension or put on lower protein containing diets. And that's to reduce the renal solute load so the work that the kidney has to do to excrete things like urea, which is the primary excretory product of protein metabolism is reduced. And when we do that, people with kidney disease live for longer. So again, the incorrect circular logic that is made and it really goes back to an old hypothesis by a guy named Brenner in the 1950s, said that the protein contributes to the renal filterable solute load, and not effectively exhausts are tires out kidneys and results in damage to the functional unit of the kidney which is nephron.

46:18: When you go to human data, when you look, and obviously this is observational data. Or even interventional data, there's no evidence for this. I know that absence of evidence isn't evidence for absence, but my point is show me some data that does show that, and when you systematically review this, Mary Van Elswyk published a review this year. No evidence whatsoever. We have a paper in press at the journal of nutrition on intervention studies, and no effect on kidney function. So a lot of people say it. A lot of dietitians seem to remember it, and I hate to pick on dieticians, but they're the ones that bring it up mainly because I think they can remember their time on a renal unit. It's circular logic to apply one to the other, and we really need to do a better job of just educating people about the association or lack there of between those two things.

Greg Potter - 47:08: You contributed to a terrific unpublished rebuttal to a cross sectional study published in Cell Metabolism a few years ago. Can you comment on whether people should be concerned about the effects of protein on signaling through mTORC1 and the insulin growth hormone IGF-1 Axis?

Stu Phillips - 47:25: Well, in the short time we have left, here's kind of the Reader's Digest version. The theory is protein results in IGF-1 release. And it's true, it does. That's an attributable positive effect of [inaudible 00:47:38] protein. Bone supported because IGF-1 is anabolic for bone. The negative or downside is the IGF-1 is a cancer promoting hormone, and higher levels of it are associated underscore with development of cancers. There are experimental models in which IGF-1 has been knocked down or increased, and growth hormone and growth hormone receptors have been either knocked out or amplified.

48:08: Let's just say that in all of those experimental models, the rates of cancer in lots of different types of animals goes up. The observational study that you're referring to is a paper in cell metabolism. Levine is the first author, Longo is the last author. And it's really Walter Longo who's a big proponent of this thesis, and he's got a lot of really cool experimental model data and he talks about models of dwarfism, how a certain type of dwarfism results in longer life.

48:38: And my point is it's eitHer one or the other. It's a knockout situAtion or it's an excess situation, or it's a lack in the case of dwarfism. And then enter the Levine analyzed and Hanes data. And the short answer is I have some serious reservations about the way that that data has been analyzed. I think it would be fair to say that the reviewing expertise at Cell Metabolism wasn't there to the sufficient degree to look at the cross sectional data and the way it was analyzed. So somebody needs to just redo that analysis. And probably with a bigger cohort size, because there are bigger databases that are out there. And if it's an observational trend that keeps coming up, then I'll bow and acquiesce and say, "Okay, maybe there's something there." But to date, that paper's it. And I think the analysis that was done was pretty poor.

Greg Potter - 49:32: Next restricting intake of the amino acid methionine has been shown to sometimes prolong lifespan in other organisms. Do you think it makes sense for humans to restrict methionine or tryptophan intake in the pursuit of greater longevity?

Stu Phillips - 49:47: A lot of amino acid restriction just like caloric restriction and time restricted [inaudible 00:49:51], they look great in animal systems. They look great in human short term, and you can say, "Some people have done this for a year," and I'm like, "If you live for 80, one year is not much." But the subclinical phenotype of somebody who does these things looks good. I think it's probably safe to say that it's not a viable strategy in the longterm. I don't see that we're going to go through a period of either methionine or protein restriction. One of the things that is, even out of the Levine and Longo paper showing that when you get a little bit older, and it's not quite clear when this happens, is that actually lower protein intakes are associated with adverse outcomes. Things like reduced immune function, reduce muscle protein, and probably a functional deficit.

50:36: So I think we have to be careful about blanket advice to restrict protein, restrict methionine, restrict branch chains for example, from the standpoint of human metabolism. And what we really need are some good longterm intervention trials to bolster up so this observational data, or to bolster some of the very strong data in animal models, which in fairness is quite convincing. But we need to appreciate the increased level of complexity wHen we scale it up to humans. Just really, really difficult to do. So I don't want to jump the gun on my conclusion, but I'm still skeptical about a lot of those effects, to be honest with you.

Greg Potter - 51:14: Final one, do you think that consuming isolated amino acids to support synthesis of specific neuromodulators or neurotransmitters is likely to have meaningful effects on brain chemistry?

Stu Phillips - 51:26: That's a good question. I'm not a neurotransmitter guy. I'm [inaudible 00:51:30] aware of the research in this area. I would think in certain individuals you could find that if you consumed for example tryptophan as a precursor to serotonin, that some people would respond to that. The problem, I think for a lot of people is that neurotransmitter biosynthesis is not a delivery responsive process. In other words, just providing the substrate is not enough in most circumstances, unless you're deficient to increase the level of that neurotransmitter. I know when I say this, I'm going to get emails from somebody going, "I have," and I fully agree. I think there are probably some people out there the same as there are people who have a very adverse reaction to high doses of monosodium glutamate, for example.

52:19: So there are probabLy people on the high non-response or response spectrum that would argue for this being a viable alternative. I think for most people, you're going to be hard pushed to show something there. But it's not something I read a lot in. I've done a little bit of reading because of the teaching that. I have yet to be overly impressed by individual amino acid supplementation trials to boost neurochemical content. But there's probably a lot of animal literature that I'm glossing over it to be fair.

Greg Potter - 52:53: Where can people find your work online Stu?

Stu Phillips - 52:55: I'm on twitter at @Mackinprof. That's M-A-C-K-I-N-P-RO-F. I'm on Facebook, searchable as Stuart Phillips. I also have Stuart M. Phillips PhD as a page that I maintain on Facebook. I do have an Instagram account. It's also Mackinprof. But I tend not to take a lot of pictures of myself doing stuff because that's just not what my generation does. But I'm trying in that area to put more stuff on Instagram. Those are the three main social media platforms I dabble in.

Greg Potter - 53:27: And your twitter feed is one of a handful that I've routinely read over time, so thank you for it.

Stu Phillips - 53:32: Thanks. And I apologize if I'm offending anybody on that one, and that's just what Canadians do. We just apologizes.

Greg Potter - 53:39: Stu thanks very much for your time and keep up the great work.

Stu Phillips - 53:42: Absolutely. Yeah, my pleasure. Thanks for having me on the show.