Sports Science Dudes

Episode 94 - Optimizing Muscle Health: Dr. Arny Ferrando on Protein, Aging, and Performance

• Jose Antonio PhD

Share episode

Dr. Arny Ferrando shares groundbreaking research on essential amino acids, muscle protein synthesis, and emerging cognitive benefits of targeted amino acid supplementation.

• Essential amino acids (EAAs) produce greater anabolic response than whole proteins due to requiring no digestion and producing higher blood concentrations
• Free-form EAAs need only 15 grams for maximal response compared to 40 grams of whey protein
• Taking EAAs one hour before exercise provides optimal muscle protein synthesis due to increased blood flow during workouts
• Physiological aging matters more than chronological age when determining nutritional interventions
• New research shows EAAs may enhance cognitive function by modulating dopamine/serotonin balance
• EAA supplementation helps mitigate muscle loss during bed rest or recovery from injury
• The mTOR pathway's connection to cancer is often misinterpreted and shouldn't discourage proper protein intake
• Testosterone replacement therapy should be based on symptoms rather than numbers alone
• Higher protein turnover is energetically expensive, potentially helping with weight management

Try combining essential amino acids, protein, and creatine supplementation for optimal results, especially when recovering from injury or dealing with age-related muscle loss.


Speaker 1:

Welcome to the Sports Science News. I'm your host, Dr Jose Antonio, and today my special guest is Dr Arne Ferrando. He's a professor Department of Geriatrics at University of Arkansas for Medical Sciences. Great background he has. He graduated West Point in 1978. That was during the Carter administration, which apparently, to Arne, was one of his favorite administrations. He got his PhD from Florida State in 1991, did a postdoc at NASA Johnson Space Center. He finished that in 1994, right at the start of the Clinton administration, which, by the way, wasn't so bad looking back.

Speaker 2:

Correct.

Speaker 1:

Anyway, he served as active duty US Army officer, retired lieutenant colonel from the Army Reserve in 2003. And you've done a boatload of work basically on amino acid, muscle protein metabolism, etc. Etc. So, wanted to pick your brain with probably five of the most common questions I get, and I figured you'd probably be best at addressing these.

Speaker 1:

Number one this is one I get all the time Essential amino acids versus whole protein and I know most of the data is on whey, but could you address that EAAs versus whole protein, whether it's milk-based protein, soy or a plant-based protein what happens acutely and what happens maybe over the long haul?

Speaker 2:

Yeah, so thanks for bringing that up. So I think that you've seen me over the years and I tell people this I've become, because of the data and the research, I've become pretty reductionist in my thinking, and what I mean is the human body needs the nine essential amino acids, so termed because the body can't make them, and, with all the work that we've done now I want to say up front this is in terms of optimization. Okay, so, like you know, joe ten peg out there living his life. You know we, we've been eating protein for thousands of years. Obviously, you know we live on, it's all good, but you and I are in the field. When we think about optimization optimization for performance, optimization for aging, optimization for some sort of pathology, whatever it is. That's been my background and so, in that regard, it become very reductionist in my thinking.

Speaker 2:

Again, the free form essential amino acids by themselves, um are much greater in their anabolic effect, and I point everybody to the paper that my colleague, david Church, did in Nutrients in 2020, which nicely looked at all that the effect of peripheral amino acid concentrations from various protein sources and the effect on whole body and muscle protein synthesis. It's quite clear that the free forms themselves produce a much greater anabolic response because they require no digestion, so there's no gi load or any problem with that. They they produce a greater c-max, in other words maximal concentration of the blood, and time to c-max, which. I say that because that is the signal for muscle to start its metabolic machinery, start turning over. So in that regard it's a more optimal approach. Now, would I recommend somebody do nothing but essential amino acids their whole life and no protein? Of course not, but I think that you have to understand that optimally utilize them, because I think your next question was timing and I can kind of move right into that.

Speaker 1:

Before you get to that, do a dose by dose comparison. Let's say it's 20 grams away versus what would be the equivalent EAAs.

Speaker 2:

Yeah, that's the problem, because whey protein, which is an outstanding protein, obviously an outstanding complete protein, but only has about 40 to 45% essential amino acids, Okay so. So that's a problem in and of itself. So a 20 gram dose let's say a 40 gram dose of whey, is about 15 to 20 grams of essential amino acids, Whereas when you take 15 grams of free form EA you get a maximal response. We've shown that in others pretty clearly you get a maximal response. So that's part of the issue number one. Number two is there's no GI load, and why I keep bringing up the GI load is because with older people, if it discomforts their stomach or distends their stomach, they're not doing it.

Speaker 1:

They're done, they're just not doing it.

Speaker 2:

You can tell them until you're blue in the face, but they're just not doing it. Okay. So that's another reason why over the years kind of became more reductionist in nature, because there's one thing, to come up with something that works, but if people don't do it, then you've got a problem. Oh, by the way, diet and exercise works well. Why is Zympic and Glips and everything so popular? You get my drift.

Speaker 2:

It's like nobody does it. Nobody does diet, exercise. So you know, I think that's part of the problem. And then the other aspect of that is is that protein is ureogenic and so, again, that's a could be a little more problematic in older age, when, when the kidneys aren't operating as efficiently, etc. Whereas the essential amino acids, free form, are non-ureogenic.

Speaker 1:

Do me a favor and define older age, because I throw the term around a lot. When does old become old?

Speaker 2:

Yeah, now that's a good question, by the way, because again I'm quick to remind everybody, you and I are in a very small percentage of our society, like ISSN, for example, like how many zeros are after the decimal point you know what I'm saying so. In other words, these are people who are lifelong exercisers, understand nutrition, understand exercises. If you know, at our conference there's nobody obese in our conference right, I mean, it's just not there.

Speaker 2:

It's very hard to find somebody overweight, to be honest with you, even who qualifies overweight? So I think when I define aging, I define physiological aging. I think that's the best way to look at it, not a number, because I'm 68. You know, I still have a 16% body fat. You know I am still, despite two joints and a third coming on, you know, still quite functional, et cetera, et cetera. So you can actually be old I do air quotes at 40 years of age because your physiology has deteriorated, because you're overweight, and then you have, you know, tissue inflammation, diabetes. I mean you get this whole sequelae of events. So everybody likes to. In science, we like to quantify old as, like you said, somebody picked 60. Well, now that we're both over 60, I'm kind of bristle at that.

Speaker 1:

Well, what's interesting is, when I submit these IRB applications and the term older adult is put in there, we are always asked to operationally define it chronologically, like when does older become older, and I just sort of default. I've used the typical age of retirement, which I think is no longer 65. I think it's 67 now or something that keeps creeping.

Speaker 2:

Social security. You're right, yeah, you're right, yeah, so it's just arbitrarily, that's what I use.

Speaker 1:

But you're right, there are people in their forties or fifties who are not quite functional, who would classify as wow, they're not aging well at all. So but yeah, the people at ISSN are fairly unique. Now address you had started to address the timing issue of essential amino acid supplementation as it relates to exercise, so comment on that.

Speaker 2:

Yeah. So the reason I was kind of sliding right into it because I think the GI requirement has a lot to do with that. From our work back in Galveston, we clearly showed that the combination of the EA and exercise is interactive, ok, much more anabolic than either alone. In fact, resistance exercise by I always show this slide off, you remember like fasting, like net balance across the muscle tissue, fasting, resistive exercise is just as still a negative. And then amino acids alone, but then the two of them together is is more than additive, it's interactive.

Speaker 2:

So again, I explained this to somebody recently is that's because of once you have, it's all about delivery to the muscle system, and delivery is concentration times blood flow. So think about it. In that case you got both of them working for you, right? You take them before the exercise and then you exercise and blood flow. So now the muscle sees a great deal of the amino acids and what can't be actively transported is often mass action into the muscle. Okay, so so the ideal timing in that regard is like one hour before, and we found that after one hour after it's also effective, not as effective as one hour before, but still anabolic. So let's compare again the free form with the protein. Um, you're probably one of those guys. Since you've been taking whey protein your whole life, you can take it before exercise and it's fine, okay, and um, I couldn't that. In fairness, in fairness, joey, in the early days of the whey protein, you really had to be hardy to take that stuff, I mean.

Speaker 2:

So it was nasty, it was that yeah right, right before all the food science got a hold of it, you know, and all different forms, and we come a long way.

Speaker 1:

Let's face it I think the issue I had is the like dairy. Dairy protein just tastes better than free-form amino acids, and that's the only reason like I'll drink a 40 gram shake of whey. I don't know if I want to drink a 20 gram shake of essential amino acid just because of the taste.

Speaker 2:

Is it too sweet for you? The?

Speaker 1:

essentials? Yeah, no, I think I like the sort of the mouthfeel of the milky, mouthfeel of whey.

Speaker 2:

They call it in food science the organoleptic properties.

Speaker 1:

Oh, I like the organoleptic properties.

Speaker 2:

Yeah, yeah yeah, You're right, but just for myself and others. In the old days when I'd take whey protein before a workout, I would see it again in like five minutes. I couldn't keep it down. So that's the advantage again of the essential amino acids you can drink them before, all, throughout, et cetera. They don't require digestion. They result in no GI load. Some people can handle it, Some people can't.

Speaker 1:

Ok so let's experiment. You'll have to send me some, and maybe my wife will experiment with it as well, so see if she likes it.

Speaker 2:

Yeah, yeah, we'll do. Actually, we'll do so. So I think you know, give it a shot, because I think that the higher intensity, especially for your wife, when you get up to higher intensities, you're diverting blood flow from away from the gi to the exercising muscle, right? I mean, we got a bike, basically six liters of blood to do something within the body. It's a closed loop. So it's you know it's going to go to where the need is. So once you take it away from the gut now you start developing some of those gi issues in terms of now tell a little bit about.

Speaker 1:

You know people, athletes get injured. Maybe they break a bone so they become inactive, or just maybe the elderly or the older adult they tend to be sick. There's late, late, uh, you know. Bed rest is prolonged essential amino acid supplementation, maybe versus whole protein, maybe versus creatine? Do any of those, are any of those effective in at least lessening the atrophy or the loss of muscle protein?

Speaker 2:

Yeah, I think they all are to various degrees. I think they all are.

Speaker 1:

And how would you compare the three?

Speaker 2:

I'm sorry.

Speaker 1:

How would you compare the three creatine, whole protein and essential?

Speaker 2:

I think the data clearly shows that they're all efficacious. Creatine seems to be more long-acting in its effects. You know, we're looking at the data, although I like the fact that you know I had a long talk with Darren Kandow and Scott Forbes down there because I'm getting ready to submit a protocol with creatine and EAAs combined or a grant, and so I was kind of picking their brains on a lot of things. As you know, they've kind of set themselves up as the experts in that area and what I like is there's so many other benefits that are surfacing with creatine.

Speaker 2:

Everybody thought muscle, you know whole body proteostasis, but now there's benefits to sleep, there's benefits to bone, there's benefits to cognition, even acutely cognizant benefits in alzheimer's disease, I mean so, so obviously, um, there's a lot of important aspects of that in the brain. I think it's the brain energetics of creatine that really help with cognition etc. But in terms of their acute effects on uh, muscle protein or let me say, whole body protein, turnover proteostasis, the free form, are what I would put first. They're by far and away the greater effect. Okay, then I would put the whey protein, for example, and again this is covered in DC's paper quite nicely. Of course we didn't look at creatine. But again, creatine, I think, as you know, has a longitudinal effect. So if it was my aunt or mom or dad, I'd do all three. If they were recovering from hip arthroplasty, I'd do all three. And in fact we've published data on the EAs and hip and knee arthroplasty.

Speaker 1:

So yeah, yeah, like you, you know I take a pragmatic approach. Do it all, you know, sort of it's kind of a shotgun approach, but do it all because they all should help to some extent.

Speaker 2:

Well, that's right. And the first rule of medicine, I'm quick to remind people, right, do no harm. So obviously, amino acids, protein and creatineine, all of them have been shown to do no harm whatsoever in you know everything.

Speaker 1:

So now, going back earlier conversation we had because this is something I was I wasn't aware of and it was a conversation that stemmed from you speaking with tony reachy about some of this extraocular muscle stuff we wanted to do with creatine, but you had mentioned that essential amino acids do have a cognitive effect, which I was not familiar with. That literature Could you explain to the audience?

Speaker 2:

Well, that's because there is no literature yet. We're working on the paper. As we speak. It's just again data from our laboratory and again I'll give Kyle Byer or scientist Dr Kyle Byer credit because he's the one that actually conducted the research. But so we did two studies and they both were highly efficacious. We tried to tweak the formula. The second time didn't seem to matter. So that data hopefully will be coming out you know soon, because you know he's on summer break now and we're gonna wrap the paper.

Speaker 2:

But the bottom line is this is that our hypothesis was when you look at um cognition, joey, you know you have dopamine and serotonin, and it's they're not the only neurotransmitters, as you know, but they're prime players. And dopamine is formed from tyrosine, phenylalanine, tyrosine, dopamine, ok, tyrosine, it crosses the blood brain barrier with the lat one transporter and forms neuronally into dopamine, whereas serotonin, which counteracts the effects of dopamine, is the tryptophan to serotonin. Now, the way we approach the formula was since, unlike muscle that has a number of active transporters of amino acids, the brain only has one primary one, which is called LAT1. So the idea was now there's competition for that LAT1. And we kind of viewed it as a rheostat switch, like most things are in physiology right. In other words, let's change the ratio such that there's a, there's a, an emphasis towards phenylalanine, tyrosine dopamine and less of an emphasis towards tryptophan serotonin, and that that is exactly what happens, because we measured the blood amino acids and we measured surrogates for uh dopamine, like hva, homovenolic acid in the blood, things of that nature.

Speaker 2:

So everything kind of fit together the cognitive resilience after the psychological stress test, and that that was a um, a panel of like. It's a computer, just like. You remember the old like touch dot things that we had when we were young. Oh yeah, well, this is much more uh, elegant than that. So there was four panels, uh, and they were. They were given like and this panel would be tracking. So if you track in that little red dot with the mouse in this panel, they would show you a number of numbers and then you had to recall them. In this panel it was the Stroop test. You know what that is.

Speaker 2:

Like it says find the red number six, but it's written in blue, so you really have to kind of think it through. And then I'm trying to remember what this other one is. But so there's four panels and so it's like a good 30 minutes of that. It's pretty, you know, psychologically that'll wear you out totally, totally, totally so.

Speaker 2:

so they took uh, 20 grams, uh, uh, before two and one hour before the test, and again, uh, the amino acids were able to mitigate all the decreases, the decreases. Complex and simple reaction time, the the it was able to mitigate the increases of frustration. You know all those cognitive measures motivation, frustration, concentration, I mean all those things.

Speaker 1:

So again, Could you pare it down to any of the single amino acids, primarily?

Speaker 2:

Well, we use the complete amino acid formula, and so that's a very good question Would it be just good enough to give tyrosine? So, out of Eucerium what's his name man, I apologize to him, I'm blanking on his name Long time Eucerium researcher gave a lot of tyrosine like six, seven grams of tyrosine, and during cold weather or he found a benefit, but that's a hell of a lot of tyrosine which isn't soluble, and so that's another reason why we took this approach. It's it's just like okay, we have a complete amino acid formula and, in fairness, don't know like the effects of, like the bcaa in the brain. You know we haven't gotten far down. I don't know if we ever have to or need to. The good news is is we have an essential amino acid form. The way I approach this, joe is a twofer. From the DOD standpoint, a pilot standpoint, it's a twofer. I have a formula that maintains proteostasis and, by the way now, it enhances cognition.

Speaker 1:

That's a win-win right. Yeah, that's true. That would be the best way to sell it.

Speaker 2:

So it's a twofer. It's exactly right. You get a twofer because you know, with sustained operations, you know proteostasis is a big deal and the lack of proteostasis leads to cognitive decline. That's been clearly shown in military operations. So so again, I have something here that can solve both your problems.

Speaker 1:

I would imagine it would also help under conditions of sleep deprivation right.

Speaker 2:

Totally. That's actually the second objective or specific aim of the thing is during four hours of sleep. Being a pilot myself, I can tell you how dramatically your performance is affected by lack of optimal sleep 's. It's just very stressful during a military mission. In the cockpit it's not everybody thinks well, you're flying. Flying is the last thing you get a chance to think about. That has to be secondary nature. It's like you driving a car and talk. You know what I mean. It's driving the car is a very secondary nature at this point. You know you have to handle all the radios and the operations and the fires and the guns, and you know other helicopters. But it's very, it's very difficult.

Speaker 1:

So yeah and uh. Well, long-haul truckers, I mean, those guys are driving for hours and hours?

Speaker 2:

yeah, exactly, I can see it would help them as well. To your earlier point, by the way, most people rely on um, uh, most people rely on even the military relies on stimulants like modafinil and stuff like that, and while they get you through the acute aspect of the mission, you can't sleep thereafter. So that's where the problems are right. So when you need to sleep, you're still hopped up, you can't sleep, and so you're sleep deprived the second day, no matter how you cut it.

Speaker 1:

Interesting.

Speaker 2:

Okay, I got one final question for you.

Speaker 1:

This is one that's asked commonly. It deals with mTOR and it's activated, obviously by amino acids, with, with leucine as the primary driver, right, but also it's it's elevated, you know, under conditions of various tumor cell growth or cancer. So reconcile the two because it's it's a fairly common question.

Speaker 2:

Yeah, I think people actually don't know the intricacies of that when it's associated with protein turnover. In fact, bob has given a number of talks on this and clearly showed that movements in the mTOR pathway have very little to do with the muscle protein synthesis, and I think that's because it's a timing thing. Right, there's signals, so signal doesn't last forever, and the people who got dirty with this will tell you if you're going to try to catch a signal mTOR, you need to do it X amount of time after this intervention. So I think that's where people go wrong is like. Oftentimes you've missed that light and so you end up misinterpreting the the aspect of that. I think it's part of the signaling process and anytime there's protein turnover, that signaling process is inherent in it. So, but I think the misinterpretation comes because the timing is so fleeting you know what I mean, whereas muscle protein synthesis when you think about it, joey, methodologically is discerned over a number of hours yeah the whole signaling pathway is like 30 minutes here or an hour here.

Speaker 2:

You see, I'm saying so, if you're not catching that window right, you're not getting that data to interpret. So I think that's where a lot of the misinterpretation comes from.

Speaker 1:

I think, yeah, and I think also there's a pragmatic aspect of protein intake that deals with just preventing or alleviating sarcopenia, you know, in combination with resistance training. So so I think there's that aspect that people seem to forget when they're talking about mTOR.

Speaker 2:

Sometimes Bob often says this, but sometimes I think it's counting angels on the head of a pin. I mean, obviously it has biological significance because it's part of our system, but I think it's one of those areas that we went to in science and through hundreds of millions of dollars after, and I think we over-interpreted what we have there because, in all fairness, the gross measures of muscle protein synthesis, breakdown, balance still hold right. They still hold per given intervention. A we know what the protein balance is, both across the muscle and the whole body. That's all that matters. So the rest of it becomes granular. The rest of it, in my opinion, becomes more like a pharma issue, right for targets of drug therapy, etc. From you and I standpoint in terms of nutrition and exercise. That's why it just hasn't really not an area we grossly endeavored into.

Speaker 1:

Right. One last question unrelated to this, about testosterone. And you know there's an age-related drop in testosterone and testosterone. Some of the work by Bessine back in 96 showed that you can increase muscle cross-sectional area with testosterone without training. In fact testosterone and anthate by itself increase muscle cross-sectional area, I think, better than training without testosterone. So what are your thoughts on that vis-a-vis aging? Because I know in Florida you know testosterone replacement therapy is something that's fairly common with older men and women, believe it or not.

Speaker 2:

Yeah, so I don't know if I agree with what you said, because training by far and away has a greater effect on trisectional area.

Speaker 1:

Well, I was just referring to that one study.

Speaker 2:

Yeah, you are right in that, taking that over a period of time. As you know, the great thing Shelly's done a lot of great work, has gotten funded by the NIH a number of times and done longitudinal studies. So, clinically, while we did all the initial work in terms of testosterone is affected on metabolism, protein metabolism. Shelly did some really awesome work over the years on the clinical outcomes and use of older men, characterizing the side effects and cardiovascular risks, all the above. She's just done outstanding work on that.

Speaker 2:

So I think that what you have to understand with testosterone I have these conversations almost daily with people. Joey, it's interesting you bring that up Because friends of mine you know have been, you know, are at that age now. So the interesting aspect about testosterone clinically is that if you go to the doctor and you do blood work and your testosterone, total testosterone is 250 or 300, he's not going to say, joey, we need to put you on trt until you start complaining. Doc, I have abc, the issues okay, and and. So if it's not, if you're non-symptomatic, like many other things, if you're non-symptomatic, okay. Well, I'll give you a perfect example. I spiked a high PSA, he was telling you know, and my dad had prostate cancer. So I wanted to follow it through. Oh, you know the doc was talking oh, the cancer, cancer cancer, and this, the range and that range. I get the image nothing at all clean. So it's prostatitis, right, it's old guy swallowing prostate, but I have no symptoms, so there's nothing to do. It's just like at this point you treat the symptoms. So you know it's the same thing in terms of testosterone.

Speaker 2:

If you don't go to the doc and say, doc, and here's the thing, like guys like you and I would notice that because you're training every day, you're doing something every day, you're out there paddling. You know you're pushing yourself. The average land squid would not know that. I mean, they're not their. Their bar is so low that they're you know they're not pushing the system. You and I push the physiology. So now we will notice when something's amiss and that's when you know that tr is directed and in the final statement, it's quite efficacious and it can be done quite safely too. And keep in mind I tell everybody this because you and I hung around the gym in our early years we saw how testosterone can go awry.

Speaker 2:

Yeah, but it's testosterone. The R stands for replacement therapy. Ok, so you're just putting in exogenously what your body cannot produce endogenously for whatever reason. For me it was an injury, uh, aging, whatever, okay. So that's another thing. I I always tell people that you know and you do need to work with a physician and you can get the levels ironed out and you can live on it for many, many, many happy years. So did I help you? I, I went, I meandered a bit on that, but sorry no, the meandering helped, so I appreciate it.

Speaker 1:

Um, and that's all I have today. I mean, I appreciate you coming on the show. Uh, you're a wealth of information when it comes to amino acids and, uh, maybe I should give it another shot. It's um, um, it's about time I try, because I pretty much will try anything. I use my body as well.

Speaker 2:

Well, the other thing too is, um, I don't know where you stand with your, like, ideal weight, competitive, you know, performance weight and all, because you know that has something to do with always get old, even my me, I'm still doing combatives and all. It's amazing to me how, like, a couple pounds did take speed and everything else for me, I mean, and I'm not exactly competing at a high level, I'm not, you know, chris Algieri, you know what I mean, or Tony Ricci, so, but I can tell. So I say that because when you take the protein, you're taking in more calories, and you got to think about that, whereas the free form amino acids are only four, four calories per gram. So in 15 grams, for maximal response, you got 60 calories well, that's why I'm thinking it's, it's worth trying.

Speaker 1:

I feel better at about 180. I'm about 185 now, um, and I probably feel even better at 170 to 175. The problem is, it's hard for me to get down to 170, 175.

Speaker 2:

Now, unless I really cut back on calories so or exercise a lot more, which all right so let me let me propose something else to you which we did not talk about is that protein turnover is energetically an expensive proposition. So the more you again adjust that rheostat switch to higher protein turnover, the more energy you're utilizing. The flip side of that coin is we found with the menopause transition. That's why women gain weight in the menopause transition because the muscle becomes resistant to to affect as amino acids and protein turnover. So let's say it takes. Let's say protein turnover costs you 500 calories a day, joey, good general amount.

Speaker 2:

If the muscle becomes resistant and you're longer spending that, it takes. Let's say protein turnover costs you 500 calories a day, joey, right, good general amount. If the muscle becomes resistant and you're no longer spending that 500 calories, where do you think that 500 calories is going? Okay, and after seven days, seven times 500 is 3,500 calories, which is one pound. So you see what I'm saying. It's like this is the way that you adjust the rheostat in that system. So the more you can tweak that system to turnover, the more calories you're using, and over time. It's not gonna happen in one or two days, but consistency will help you lose and maintain that weight.