00:00
Hey everybody, it's Mikki here. You're listening to Mikkipedia and this week on the podcast, I speak to Professor Arny Ferrando about his work in protein, essential amino acids, protein timing, aging, anabolic resistance, and how to optimize muscle retention and fat loss. Because of Ani's extensive experience in research and in practice, I think you're going to get a ton from this interview.

00:30
Arny Ferrando is Professor of Geriatrics at the University of Arkansas for Medical Sciences, where he co-directs the Center for Translational Research in Aging and Longevity and holds the position of Wes Smith Distinguished Chair in Geriatrics for Longevity, Health Promotion and Frality Prevention. His research deploys stable isotope techniques to dissect muscle protein metabolism under stress from spaceflight, burn injury,

01:00
renal and heart failure to aging and surgical recovery. He pioneered nutritional, pharmacological and exercise-based strategies to counteract muscle wasting and functional decline. After earning a PhD in nutrition and physiology from Florida State University, he conducted post-doctoral work at NASA's Johnson Space Center. He served as a U.S. Army pilot and armor officer, retiring as Lieutenant Colonel. He's driven by a lifelong athletic spirit.

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from West Point gymnast to powerlifter, bodybuilder, master's track athlete, and now CRAV MAGA instructor. Professor Ferrando also drives multiple research programs funded by NIH, the US Army, and industry. And since 2023, he holds a visiting senior research scientist appointment at IHMC, extending his work to human performance in extreme environments. So, Ani is not so over the socials.

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but we have a link to where you can see his bio at IHMC website. And he mentions multiple times about his colleagues, Abby Smith Ryan and David Church, who you will likely be familiar with if you're interested in this protein space. Before we crack on into the interview though, I would like to remind you that the best way to support this podcast is to hit the subscribe button on your favorite podcast listening platform. That increases the visibility of Micopedia.

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and amongst literally thousands of other podcasts out there. So more people get to learn from the experts that I have on the show, including Professor Ferrando. All right, team, enjoy this conversation.

02:41
Lovely. Well, Dr. Forando, Ani, thank you so much for taking time to speak to me in your afternoon. Super excited to chat to you. I was just saying that I'd been listening to you on another podcast and that I feel like you've just got some, you've got slightly different perspectives to other people in your area, which is always great because it's always good to hear from different experts. But first of all, can we just start with just a bit of context?

03:10
How did you come to focus your research on muscle protein metabolism and then sort of more, I guess, more specifically, essential amino acids? So give us a little bit of your background. Yeah. So I actually, I'm a retired military guy. I don't know if you knew that. I'm actually a pilot. I was a pilot, a helicopter pilot. I flew for about 15 or 16 years, I think it was. And so when I got off...

03:39
active duty and went into the, in our country, you can do a series of things, active duty, meaning you're full time in the military or what we call active reserve. Like, you know, you can still have some sort of civilian life, but you you serve a couple of times a month or whatever. So I was transitioning to that part and I had always been interested in performance. ah I was a, I was a gymnast in college as it was. So I was always interested in athletic performance and then

04:09
going through all the military and seeing how we abused the uh human physiology, I was pretty interested in, you know, how to optimize the physiology for what we had to do task-wise. I, after my PhD, I got a postdoc at NASA uh at the Space Center. And I was fortunate enough, this is way back in, this was 35 years ago now, so.

04:36
At that time, all the things that you've come to understand in terms of protein metabolism were not elucidated yet. One of the things that my mentor at NASA was uh a lady by the name of Helen Lane, was long since retired, but um she was the head of the nutritional uh area there. What she wanted to figure out was like, okay, how do we prevent the muscle loss that accompanies spaceflight?

05:06
She thought amino acids and she went that direction. And at the same time, she elicited the help of Bob Wolfe, who was running his own lab in Galveston, the Shriners Burns Hospital, Galveston. So I had the very unique experience of not only kind of straddling the fence between NASA, but doing the work in Bob Wolfe's lab. And that learning curve was quite steep.

05:32
I might add, but it was just tremendous learning opportunities, you can imagine. Learned from the best. And even when I just came on, Bob was just starting to get into, his lab was just starting to get into the whole amino acid effects. And I had to learn the whole thing about, I had to learn a lot about physiology, obviously, but I had to learn entirely about tracer methodology and clinical medicine. And yeah, it was just a great, it was a great.

05:58
opportunity, it really was. We were at the Burns Hospital, so a lot of my initial investigations were in the stress physiology of burn patients. Tremendous learning opportunity there. But to be honest with you, just learning from Bob, you couldn't have had a better opportunity, laboratory, mentor, colleagues. mean, was like going from... It was kind of like the LeBron James, going from high school to the pros, you know what mean? m

06:24
That's just taking a massive leap in terms of, but uh it stood me quite well. I'm very fortunate and thankful. Yeah. And you know what, Ani, feels like, like listening to you talk about this, like it was a lifetime ago when you started. I mean that with the greatest respect and now protein, feels as sort of having its time in the sun. Like for so many years it was, it was

06:52
ignored, I suppose, in public health recommendations. Almost the last thing that people thought of, were so dialed into ensuring people had 65 % of their calories coming from carbohydrate and less than 10 % of calories coming from saturated fat, but protein wasn't really focused on. But that's shifted, I feel, quite a lot. Is that your perspective as well? Any thoughts on that?

07:17
Yeah, well, I thank you all the generations behind me because there's, as you know, it's still kind of pushing a rock uphill because the DRIs and everything is constructed kind of against protein. And the unfortunate thing is protein has become a very political issue internationally where it really shouldn't. I mean, it should be scientific, it should be physiological, but it's political because of a country's ability to manufacture, make protein and types of protein.

07:46
It was on and on and on. So I think we had to face that and it was so contrived. And obviously there was a lot of misnomers about protein. As a matter of fact, when I was in graduate school, I was surrounded by vegetarians and they just thought I was going to die because I ate all this protein and interestingly they were all overweight. But the point is that, oh, you're going to...

08:13
ruin your kidneys. mean, all those rumors that have since long ago been dispelled, but you have to understand that was the mindset at that time. It was just a great evil. And um the problem is, that I didn't tell people this all the time. I don't care if you're vegetarian. I don't care what you do, actually. I really don't care. I just think that number one, the data doesn't really help you in that regard. And

08:41
Number two, and I'm not the only one, or our lab's not the only one, many people have shown that complete protein sources are by far better in the aging process and a number of things. And the other thing I've always said is I could never be a vegetarian because I'm too lazy to do all that, figure all that. That's like, it's too much work. mean, I like chicken. Let me give me chicken breast. You know, it's good. I like beef. I like a burger. mean...

09:10
That's all I need. And since then, and since, as you can tell by looking at me, I've gotten pretty darn old. I have taken a more reductionist viewpoint and started looking at just the effect of the essential amino acids, because as humans, that's what we need. And now there's a lot of benefits to all protein sources. And I'm going to say that right off, like, for example, beef has iron and has, there's a lot of nutrients in-

09:40
beef or our meat sources aside from essential amino acids. But I always bring that up because we as humans are called essential amino acids for a reason. We cannot make them. We're not ruminants. So we have to take them in. And that's my point. That's why I've kind of over the years kind of evolved to a reductionist standpoint like what amino acids are there because that's what I need uh to become.

10:08
to be healthy and remain healthy and functional with aging. I love that, Ani. And I just want to highlight a couple of things that you said, or it's interesting you say that these protein myths are dispelled. I mean, they are not, they are and they aren't, right? Like, always, I still hear, and I see it printed in like digital media as well around the myth around protein in the kidneys or protein in cancer, protein in bone health even, like, which is just seems crazy to me, but it seems like

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once something is out there, it just seems to persist over time, like eggs and cholesterol is another prime example of that. And I'm not sure actually what it would take at this point for people to just sort of have this like, I don't know, come to Jesus moment that actually protein's okay. And I have heard someone say that protein sort of evokes a lot of emotion because it's the only thing that we eat that has a face, you know, and maybe this is part of the challenge with uh getting people to

11:05
to sort of like eat it. But you mentioned, know, we do, obviously we do need these essential amino acids to your point and there is complete protein versus the incomplete protein. But I've had recently heard other protein experts say that, and I've seen papers that say, look, you get your 120 grams of protein from meat or you get 120 grams of protein from tofu.

11:34
doesn't make a difference. Is that what your perspective is? No, not at all. Yeah. Not at all. here's, em in fact, uh my colleague who's actually now uh running the lab was my postdoc at once upon a time named David Church. And DC is now running the lab on a day-to-day basis while I stay engaged scientifically. a number of years ago, we did a study and published it, think, uh

12:04
last year the year before. But we looked at beef versus impossible burger, which is basically tofu. Yeah. Yeah. And so, so, so we looked at equal amounts in of muscle and whole body protein turnover. And then we, looked at beef versus double the impossible burger.

12:31
So it turned out, and it's in the literature, you see it, but beef versus the Impossible Burger gave a much greater response. And you had to do twice the Impossible Burger to get the same response. Now, that speaks to what most people erroneously interpret. And it's true, all the body needs is essential amino acids. And by the way, it doesn't care where it comes from.

12:55
comes from beef, tofu, comes from sigma chemical, comes from Ajinomoto, it doesn't freaking matter. The point is that the body, thankfully, the biology just looks at that chemical structure and knows what to do with it, okay? However, in your country, one of the great leaders in this area, totally the leader, Paul Maughan, who retired from Reddit here recently, if you know Paul, Paul has done a great deal over his career and categorized it.

13:23
what's known as TID, total iliodigestibility. And it's quite clear that the plant sources are, the amino acids from plant sources are not nearly as bioavailable as they are from animal sources, versus complete sources. So why is that important? Again, my colleague DC published a great paper in nutrients that showed a very strong relationship between

13:52
plasma amino acid levels and muscle protein synthesis, muscle and whole body protein synthesis. The take home message is this, the higher you can get the levels and the quicker you can get them there, the greater the protein turnover. So what that means is, this is why I become reductionist, okay, I'm backing into the whole reductionist thing. What that means is the sooner you can get the essential amino acids to the periphery or to the body,

14:21
out of the GI, let's just say out of the GI, the greater the response is. Now, the reason I direct you to DC's paper is it compared everything from free form to whey to combination to uh the protein itself, like uh beef to a mixed meal. And the bottom line is the greater the digestive requirement, the lower the response. Again, the greater the digestive requirement,

14:50
the lower the response. Now you say, okay, for thousands of years, we, we humans have been living off the things we shot, killed, hunted, ate, right? And that's how we live. Okay. And that's still the case. But what I'm talking about and what I want people to understand is I'm not advocating that everybody drops food and goes to just essential amino acids. What my area has been is the optimization of

15:18
protein turnover, proteostasis, muscle, et cetera, with all the circumstances of compromised physiology, aging, recovery from uh surgery, on and on and on and on, space flight. uh mean, just that's where, what I call the stress physiology, uh military, uh the DOD soldiers, that's been the primary focus of my career is looking at

15:46
How do we take the stress physiology and how do we optimize intake to mitigate the losses of protein, whole body proteostasis or protein and function? That's where it all comes in and that's where I become, like I said, reductionist. Realizing we just completed some recent studies with the DOD showing that in those circumstances of like high activity, 30 % caloric deficit,

16:14
You need like 25 grams of EAAs to offset all that. That's high, isn't it? Well, Roger, that, if you had to do that, that's like 50 some grams of whey protein if you had to take it, right? And you still wouldn't get the same response. So that's why the simple form really makes sense in the optimization of the physiology. Now, I tell you, if you're Joe Smith working in the office, your average land squid,

16:42
It doesn't matter. what you want. You know what I mean? So we, you and I, we tend to be in an area that's like a performance based area, right? Like athletes and, you know, like I said, the soldiers, the tactical athletes, things like that. So that's kind of where I've evolved my thinking based on the stress physiology and what is good for stress physiology. Because if it's good for stress physiology, it's good for normal physiology.

17:12
Now, 100%. So, this is super interesting because just to your point on the beef burger versus the impossible burger, if you have to double the amount of the impossible burger to have the same response, it's double the amount of calories and we already live in this calorie-laden environment anyway. No one needs that. Roger that. That's exactly right. And also, mean, because I've seen studies that people report to illustrate

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no difference, same amount of protein, over 12 weeks, these young college athletes did a resistance-based training, no difference here. I just wonder whether it's to do with the population studied, the young population, or maybe the length of time as well. 12 weeks for a study is a reasonable length of time, but in real life, is it long enough to assess

18:10
know, whether or not it's optimal, I guess. Yeah, no, your point is valid. the problem is, that here's what I found in all these years. It's hard to talk to people about nutritional effects because nutritional effects take time and must be consistently done to have effects. Okay. Whereas drugs,

18:40
hormones or whatever, the effects are much more acute. So that's why, at least in American society, they're so geared towards give me a pill doc, give me a shot doc, you know what mean? They're looking for that hormonal effect. However, the basic science and research that we've long done shows a tremendous effect of the EAs, for example, especially when combined with activity, exercise. There's an interactive effect that's much greater than either alone.

19:10
And that's because you get the freeform out quickly, as I discussed with you. But also, the exercise results in an increase of blood flow. So you're getting what we call an increased delivery to the tissue. So delivery is blood flow times concentration. So you see you have an increase in concentration, and then you have this big increase in blood flow. So all the tissues that need these amino acids in the body get to see a great deal of it.

19:39
And that's the signal for protein turnover, whether it be the liver or the muscle. Yeah. And it's interesting because right now as well, and then I don't think you have a presence on social media, Annie, do you? Like, I'm pretty sure you've said, no, I'm, yeah, yeah. So you will miss all of the- happen, Nikki. Not gonna happen. Yeah, yeah, no. You're missing nothing. I I spend all my time looking at it, but- I say that my tombstone's gonna say he was never on social media. So-

20:05
I don't care. You found me. You found me. See what I said. You found me. I didn't talk to you. I have no desire to even learn any of that. anyhow, go ahead. Yeah, which is great. so then I can just report to you then that, you know, the other thing that I see a lot is that, you know, branch chain amino acids are useless. you know, we, no one needs to take a branch chain amino acid supplement if they're meeting their total protein requirements.

20:35
And I understand and appreciate that. Let me stop you there because I don't think they're not useless. They're not effective in stimulating protein turnover, despite a couple of studies, including one of my best friends, Kevin Tipton, may rest in peace showed, you know, before he passed. But the bottom line is, in fact, I did a study when I was one of my first studies, as a matter of fact, published a long time ago.

21:03
with pretty elegant methods and showed no effects of branched chain amino acid. However, in terms of with exercise, higher intensity exercise, they are efficacious, you know, because the muscle will use those endogenous ones for oxidation when you provide them that mitigates that. That's been shown a number of years ago. So in terms of like intense exercise, they're not...

21:29
They're beneficial, but in terms of stimulating whole body oh anabolism or protein turnover, no, you need all these essential amino acids for the most part. Yeah, no, that's great. I'm pretty sure I've seen a couple of things using BCAAs and showing some usefulness. one has been in, like I'm a runner. And so I look at that sort of athletic population as well.

21:58
And I see that during exercise, they can be helpful with recovery actually, like the most recent study maybe even a year ago. And then I saw another, someone talks about them in the context of helping reduce delayed onset muscle soreness for endurance athletes as well. to your point, probably providing that amino acid sort of amino acids to help, guess, I don't know.

22:28
I guess. But I think what the point is, is that, you'd much rather have a whey protein, which probably has all of the essential amino acids, rather than just rely on those BCAAs. Roger that. Yeah, cool. And in fact, um there are essential amino acid powders out there that have not just the BCAAs, they have that sort of complete um profile of essential amino acids.

22:55
question, like people always talk about the leucine threshold, which is obviously important, but you're referring to the idea that in fact, all of these amino acids are important for that muscle protein turnover. It's not, have we focused too much on leucine? Well, I don't know if it's, you know, it's certainly shown to be a key uh aspect important. And in fact, you know, a number of years ago, we had a

23:24
postdoc, he's now a full professor out in Arizona, his name's Christos Casanos. And he did a very nice study in young and old subjects with seven grams of amino EAAs and showed that when there was... So we had 26 % leucine in one formula and 41 % leucine in the other formula. And when we raised the leucine, the older responded like the younger.

23:52
when we had a low leucine, there was a blunt response in the elderly. So it does speak to the importance of some sort of threshold of leucine. I think you have to be careful because, you know, there's been, in fact, we did it ourselves. We never published it because it was a, it was, was no, there was no finding. And Luke Van Loon did it as a matter of fact, where he gave just supplemental leucine throughout the day with their meals, et cetera, et cetera.

24:22
found no effect. So the bottom, the way I read that is that in order to get the stimulation I was telling you about, that DC has in his papers, um you need the entirety of the amino acids because you can start stimulation maybe with the leucine, but in order for that chain to promulgate, in order to build protein, you need all the building blocks available. It's just like going to construction site and mixing cement.

24:51
but you only have so many bricks to cement together. You know what saying? Yeah, hear you. And you mentioned before about, you don't care what anyone eats. If you're a land squid, it doesn't matter. Hilarious, by the way, land squid. But I also think that land squids probably want to be a bit more than land squids as well, and they're not intentionally so. And sometimes it is that, you know, they think foods are high in protein, like legumes and things like that and nuts, but they're really not.

25:20
Can I share, like, Dr. Ani, I tell my dad to have an essential amino acid powder with his porridge for breakfast, because I know he loves porridge, and I don't want to tell him to stop eating porridge. I mean, I try, he will ignore me anyway. Is that a good thing to do? What do you call porridge? I'm sorry. Oh, oatmeal, oatmeal. Okay, okay, okay. That's I thought you meant. Yeah, no, I think you got a good idea there. And, you know, uh

25:49
Let me be transparent too. Like uh Bob and I have like three patents through the University of Essential Amino Acids in their license that can give you the product names here. Yeah. And Bob has more. He has another company called AminoCo with his son, and they have other formulas for other directed usage, the patent did. um but yeah, to your point, you have to be careful with those formulas because uh there are

26:19
A lot of people claim they have an essential amino acid formula and they use our research as evidence, which is true in terms of a general sense of amino acid formulas. the problem is that we're the ones that did the testing. The only ones I tell the people is the ones I can speak to. Because I spent 25 years and whatever, know, 25 clinical trials and millions of dollars in our laboratory.

26:49
developing research, I could tell you that this one works. I can't tell you whether it works because there's no data. That's the way the industry is. They use our data showing how essential amino acids improve this and that, increase muscle protein synthesis, et cetera, but that's not exactly a test of their formula. So it's licensed now throughout the world in Korea and Japan, here in the United States.

27:18
MyoHealth from Triveda, uh Zymogen. There's another recent one, Muscle Rescue is another one, and uh a company called Sissel, S-I-S-E-L has it also. uh But I was blanking on, oh, Idea Village, Idea Village is the name of the copper, Copperfit, yeah. Yeah, yeah, yeah. So yeah, if you could put that in your notes and people can look at it. Yeah.

27:46
But yeah, 100 % well, is it a certain amount of leucine to isoleucine or valine or is that what the people need to be looking out for like a two to one or a three to one or a? Well, I get this question a lot and I think people kind of have a misunderstanding about how this whole area evolved. Okay. um

28:12
It evolved over, like I said, a great number of years and a great amount of money and a great number of RCTs and studies. um we started off, um you know, again, like I said, it was over 25 years ago. We started off. So let me give the credit where credit's due. So again, this was all Bob had an NIH grant for 30 years. OK, which is unheard of today. And it was called Substrate Cycling.

28:42
was the name of the grant. And he started off like in burn patients looking at glucose utilization, characterized all that, then fatty acid utilization, characterized all that, long before Arnie came along. Then when Arnie came along, was just coincident that he was starting to look at the amino acid aspect of metabolism. And so the idea was, well, we know, you know, proteins made of amino acids and muscles. like, how do we stimulate? How's this thing done? How's it work?

29:12
So we started off, believe it or not, by taking human muscle, hydrolyzing it, and looking at the components. Made sense, didn't it? You'd think, well, okay, let's start off by giving what's in the human muscle. Well, that only got you part of the way there, okay? We had some pretty elegant methods. I'm not gonna bore you or your listeners with, but we had some pretty elegant methods.

29:36
Both was tracer methodology and we did oh what we call cross limb balance models where we cannulated the femoral artery in vain took muscle biopsies characterized the kinetics, but we learned a lot from those studies we learned about Transport into the cell and we learned a lot about delivery and so I just wanted you to appreciate that every step of the way we made tweaks based on the studies that we did okay, and you have to understand in our

30:04
area, these were all part of studies that were designed to look at other aspects, like for example, burns, rehabilitation from burns, exercise, mean, all these things. So it's not like Bob pulled us aside and said, we're going to develop an amino acid formula, here we go. We just came about as a result of all the work we did, all the work that he directed in those years, again, to his credit.

30:33
So that's what I was saying. So we tweaked it here when we did this. We tweaked the leucine here. You know what mean? So it evolved into this formula we now have. Does that mean that that's the only amino acid formula that works for humans? I doubt it. I'm just saying that we have the data to say that this is the one we tested and worked. Okay? So again, I want to be fair to everybody. I don't want to make it sound like this is the only formula in the world that has any chance of efficacy.

31:02
I'm just saying it's the one that we tested. No, I love that. And I guess if anyone listening to this is like, huh, what shall I use? Well, of course, we're going to put the links to the ones that you've mentioned, which have your data. And I also just think looking more broadly at an essential amino acid powder rather than just a branched chain amino acid powder might actually be worthwhile if someone feels like there's a place for their, that EAA is in their, like in their diet.

31:32
Yes. In fact, let's say what? While we're talking here, you go ahead and ask and I'm going to send you these links and my response to the email. Amazing. That'll be great. I mean, yeah, another area, obviously, we talk a lot about muscle protein synthesis, but muscle protein breakdown is clearly, you know, the other side of the coin and equally as important. And as we age and to your point with your work, looking at NASA and and

32:00
wound patients and things like that. Can we just have a general conversation around anabolic resistance, recovery from sort of trauma? And what are some important, I guess, things that people should be aware of or know of, particularly as we age, I suppose? Yeah. So it seems that as we age, there's a physiology, you know, is cruel.

32:28
cruel mistress as I say. I'm probably more than twice your age, Mickey, and I can tell you, I'm gonna brace you, all those lies they tell about getting older, they're just that, they're lies. There's nothing good about getting older, okay? Nothing gets better, there's no fine wine and lalegies, that's all bullshit, all right? The physiology is designed to, I mean, it's programmed cell death, right? I mean, everybody knows this. This has an expiration date, it doesn't live forever.

32:58
And so because of that, you have to understand that the physiology predisposes you to uh less than optimal responses as you age. And so that's where you hear the term anabolic resistance. But what we have dealt with is kind of ways to overcome that. And again, there are a number of hormonal and nutritional ways, but that's kind of really where...

33:25
VEAs, I think, have stood above most things, aspects in their ability to overcome anabolic resistance with aging. So anytime the physiology is stressed, there's an anabolic resistance, okay, whether it's epichloric, uh no sleep, like I go back to the soldier stuff, no sleep, uh high activity. uh

33:52
recovery from surgery, major stressor like that, oh whatever it is, there's an anabolic resistance induced because what you have to understand, and I just gave a lecture at ISSN, International Society for Sports Nutrition, um a month or so ago. uh what people don't get, because we're athletes and we're active and all that stuff. everybody tends to be what I call myocentric, right? We focus on muscle.

34:23
But I want you to understand that focusing on muscle is a luxury because if the whole body isn't satisfied, isn't happy, all the muscle does is serve as a reservoir for the body's amino acids. Okay? So there are more important proteins in the body to keep you alive than are in the muscle. Like all the liver proteins, all the tissue proteins that have to be made, they are

34:51
of primary concern to the body. And so if they're not made, then the body suffers from that. And it's only when you have the luxury of that being satisfied that you can pay attention to the muscle. I always say, this is before your time, long before your time, but um there used to be a whole issue with Northern England, Ireland area where they had the Belfast. There was a issue between Protestants and Catholics.

35:20
if you knew your history, and people were starving themselves to death as a form of protest. Well, somebody was pressing enough to collect blood from these people who were starving themselves to death. the blood amino acid levels were main constant right up to the time that they died. Meaning that the muscle can provide what the body needs until it just runs out. Okay.

35:48
So again, I say that because like in a fasted state, that's why the body or the muscle efflux is amino acids. skeletal muscle serves as the body's reservoir for amino acids in stress, in fasting, in chlorectal deficit, all those things. So in one sense, you're robbing Peter to pay Paul as the saying goes in that regard. So you just have to understand

36:18
when you talk about anabolic resistance, stress physiology, et cetera, you've got to keep, because like hematocrit, transthyretin, um hemoglobin, and all these proteins are much more important than um what do call, myofibrillar proteins to the body, okay? I get their functional aspect, but to the body's survival, this is much more important. And in fact, when you look back in our early studies,

36:47
The turnover rate of muscle protein for somebody like you, young and active, is probably about one and half to 2 % per day. Well, the turnover of those main liver proteins is like 10 times that, five to 10 times that. So what does that tell you the body's priority is? It's not turning your muscle, it's turning over liver proteins. I hope that helped.

37:12
You know, it does. so I want to get back to the anabolic resistance and resistance training and protein. But first of all, like if someone's not eating protein and they're active, if they are like just they're having some proteins in the form of, know, dare I say it, bread and chickpeas and lentils and things like that, and they're active, their body essentially will be drawing on

37:39
their own reservoir, their muscle to supply these other proteins across the course of the day. Yeah. But again, that's not, think you have to understand that that's only in the stress physiology as I defined it, either increased stress or low intake or too much activity. mean, the stress physiology, usually, most of us in a

38:08
you know, we're well fed, et cetera. Nobody's starving in New Zealand or Australia or, you know, United States for the most part. So, em you know, the anabolic resistance that you speak of then comes with like the aging process and em which I call the aging process. It is a stress physiology, by the way. It's not what you think of stress like clinical stress or, you know, stress that soldiers go through, but

38:37
It's a compromised physiology with aging. another prime demarcation point, we just completed a study on this, is the menopause transition for women. There is really a profound demarcation point in human physiology for women with a menopause transition. And uh we have found that there's an anabolic resistance to that.

39:07
and resistance to the effects of amino acids. think I don't have data to show this yet, but I think that's what leads to the weight gain and all that sequelae of issues and problems that postmenopausal women often face, especially if they're inactive. Well, that's super interesting because so many people are out there saying there's no difference in protein requirements around menopause for women and no need for any

39:36
differential sort of guidelines. So Annie, and that was, I was wanting to talk to you about that because I thought that you might have a different perspective based on other, podcasts I've listened to you on. So can you just sort of detail out where the anabolic resistance comes from and why that would contribute to the weight gain? Is it menopause? Is it perimenopause? Like, what, like, do you have an idea of- It starts at perimenopause. So-

40:03
once you start having those irregular cycles, the whole process is already in gear. We did a very nice study with Abby Smith Ryan at North Carolina and published that Abby Abby's kind of, you know, one of the leaders in this area has done a great job with it, but looking at, you know, tracer and protein homeostasis in the body and all that stuff. And I think protein turnover is energetically expensive in the body. Okay. It takes

40:33
a lot of energy to do that. So let's just say somebody, you know, let's just say somebody has a, uh I'm going to make it easy for demonstration purposes. Let's say it costs 500 kilocalories a day to turn over skeletal muscle protein on protein in the body. Okay. Yeah. All right. So let's say that you now transition into perimenopause and on into menopause. And so that whole

41:01
process becomes much less efficient. So we're unable to turn over muscle because of the aging process. That's exactly right. You're not able to do it as well. So now you're not expending those calories to do that. it's still like a rheostat switch. I'm going give you the example like it's an on-off switch. Instead of doing 500 calories a day, you now don't use those 500 calories to turn over protein.

41:29
In seven days, seven times five is 3,500 calories. That's a pound. Now, it's not that brutal, but that's why, I mean, all I've trained many years, martial arts and all this stuff, many women who have gone through the menopause transition, and every one of them bitch to me. They're working their butt off. They're training like hell, but they're still complaining about, I'm gaining this weight. So the physiological demarcation is very real.

42:00
So you really have to, that's why at that point, exercise is still a must, but then you really have to start thinking about, how am gonna amend this system? And number one is, you need more essential amino acids. It's just that simple. I favor the free form for the reasons I told you, but back to your original point is that again is a lie. And Bob wrote a paper a number of years ago saying optimal protein intake for aging elderly and said then 1.5,

42:29
uh grams per kilogram and all the work that we and others have done since then showed you that older people need closer to 1.5 grams per kilogram, not the NHANES 1.1 or the RDA 0.8. You need a much higher amount. so the problem is, is this is why, again, Mickey, I've become very reductionist. The problem is, that, okay, you can tell your mother, I'm assuming your mother's postmenopausal, may not be, so I apologize if she isn't, but

42:59
And say your mother's postmenopause and, you know, she's like, okay, she has the same problem, same complaints. And you say, mom, you need to eat more protein. Well, the problem is, that with other forms of protein come calories, right? And calories ultimately become a problem, right? Because either you got to work them off or compensate for them. That's why I think the EAAs and the free forms have great potential

43:29
postmenopausal because 10 grams of EAAs, which will give you pretty much close to the maximal, is 40 calories. Yeah, it's nothing. Yeah. That's right. That's exactly right. Or 15 grams. It's 60 calories. So that's my point. Not only that, but as DC showed in his paper, you get a much more robust response. So it's a win-win in that regard. What happens is there seems to be...

43:57
a transition to like simple carbohydrate things. And it's the worst way to go. Right. Because you stimulate insulin and you stimulate storage of that. And now you're working against yourself. So, you know, that's what I keep telling everybody. As you get older, you really got to stay away from the carbohydrates. Tough to do because I just went up to our local supermarket this morning to do some shopping and and take a look at it. I mean, you know this yourself, because you're a nutritionist. Just look how much

44:27
how many shells and shells of useless carbohydrate garbage we got there. Everything from two whole rows of cereal. No, I hear you. also a lot of those now have a label high protein because they've managed to pop in some soy protein isolate in there, some poor quality and people just get like a little bit confused. Like, well, this must be good for me. Yeah, you nailed that. Yeah. You got that. I hope you talk about that a good bit because I think it takes some education.

44:56
on the parts of people like you to educate the public as to that. And you're right, it's the... We have the Federal Trade Commission that does the labeling here and all this. I don't know what you all have in New Zealand, something similar. But in order to make those claims, there's a very low bar. Like you said, it doesn't talk about quality protein versus non-quality. It's just, here's a protein. Well, it is a protein, like you said. And you add it, you spray it in here, you pulverize it. They have...

45:23
pretty interesting ways of doing that from a food science perspective, but it doesn't get the physiology any further ahead. That's what your visitors have to understand. And Ani, to your point, if I go back to the menopause, it's, I mean, a woman becomes more insulin resistant at that time as well because of lower estrogen. So you've got that coupled with this anabolic resistance, which means they're not turning over as much muscle. So

45:51
they've got that elevated blood sugar plus their eating similarly, but not burning the same number of calories. I mean, it's not all doom and gloom because hopefully a lot of women listening to this are like me, close to 50, in that sort of phase, but we are strength training and we are focusing on protein. But actually we are, to your point earlier, a little bubble compared to the general population, probably.

46:18
Yeah, that's right. I mean, that's exactly right. That's why I came and gave that an ISSN, because I said we're all Meyer-centric, we're all performance oriented, you know what mean? But you have to realize, like, what are we, like, pointing and how many zeros there are after that decimal point in terms of our occupation of the population, you know what mean? It's a very small, I mean, we tend to hang in those circles, we tend to look at those videos and all that stuff, but in reality, you know, like in a population of 350 million United States, it's a... uh

46:47
relatively small number of people that, you know, exercises on a regular basis. So, you know, you're right. What happens is most people just go through life and like I said, there's a whole sequelae of events that come after that. you know, because of this, you know, the tissue becomes more hyperinflammatory and because it becomes more hyperinflammatory, it becomes uh more uh exposed to the disease process like diabetes, etc.

47:15
which is the worst disease to have, as you know. So all these things, they're insidious. Like you said, women go through menopause, what, 45 to 50 some years of age normally. But the problem is, is now you've another 30 to 40 years to live, right, after that, in this state. And so I said it's insidious and it gets worse. And if you don't do something about it upfront, which is what I've kind of been trying to beat the drum about, is like,

47:44
Once they start getting to that point where like they're looking at menopause or starting to transition, you really need to do something now. Yeah. Yeah. Because the longer you wait, the worse off it becomes. Yeah. And nothing is worse. This is why, this is why pharma loves this whole thing. Right. Um, the, glip, jip, RRA, agonist, right? I mean, this is like, this is, this is it. This is the multi-billion dollar industry now. You know I mean? Just.

48:12
Abuse yourself, doc, give me a shot, doc, give me a shot. and, you know, we're starting to study those with many others, I'm sure. I don't think it's that simple. Again, I think that there's obviously a lot of muscle loss. And, you know, I think there's more to it than just the chlorectal deficit that goes with it, to be honest with you. So I think it's like typical of human aging and also pharma. You solve one problem,

48:42
but you've created one or two others. Yeah. And Ani, when I talk to people about protein and resistance training, often they're like, well, what is the most important for protecting and preserving muscle? I mean, is that just asking a dumb question because they're equally as important, like eating enough protein and doing the resistance training? I don't know if I got the question in there. I'm sorry. But you're right. uh

49:10
Yeah, so can you offset a lower protein diet with resistance training? Yeah, no. No, because here's the fallacy with that. The more you stimulate turnover, the more substrate you need to do that turnover. So again, if you have a lower substrate availability, IEAA availability, because of the digestion requirement or the poor quality of protein, you're really not getting anywhere with that. You see what I'm saying? uh

49:39
What you and I keep discussing is why I become a reductionist. You see what saying? tell everybody this is why I developed into what I keep saying. I'm a reductionist. It's like to me the simplest answer here is the provision of the EAs pre-formed. And again, I'm not suggesting nobody's protein anymore. I'm just saying for optimization of the physiology, it should be a consideration. Yeah, no, totally. What are your thoughts on fasting, Annie?

50:08
And in protein timing, actually, because this is, you won't see this, but I see it all of the time. People have these full-on debates as to how important timing of protein is across a day. What are your thoughts on that? um So that doesn't seem to be the case. We had a postdoc who now is a professor in Korea in Seoul named Il-young Kim, who we call Neil. eh

50:38
Neil did a very nice study over the day where we looked at provision of protein, I think it was beef protein, in the normal American pattern, like mostly at dinner, I think 65 % at dinner and rest, or equal distribution throughout the three meals. We did a 24 hour study, did not make any difference. It's the total amount that makes a difference. amount of protein, nitrogen intake, the body seems to utilize it as it needs.

51:08
So that is the most important thing. Now, in terms of timing, timing with exercise is the important issue in terms of supplementation. We found out that given the uh EAA within an hour before exercise has a substantial stimulatory effect. And even in effect, given taking one hour after exercise, but though before is the most. And it's what I had mentioned to you before, Mickey, you had this

51:37
Huge concentration increase in the blood and you have blood flow increase at the same time. So delivery to the tissue is dramatically higher. And that's the signal at the cell interface, whether it's a muscle cell or liver cell, that's the signal to say, hey, we got what we need. We got the bricks, let's get the mortar going and let's build a wall. Yeah, nice one. And one of the final thing that I would love to check to you about, is

52:06
um We've obviously talked a lot about muscle protein turnover, but to your point, essential amino acids do far more than just uh focus in on the muscle. And you've talked a little bit about essential amino acids in the brain. Can we unpack this relationship a little bit further and why they're so essential for neurotransmitter production, um which I think is an often overlooked piece of

52:35
why protein is so important or to your point, essential amino acids. Yeah, thank you. So we now have uh a couple studies with substantial uh information on this. um the idea again, just like that whole thing 25, 30 years ago, starts off with kind of a teleological argument. You know what I mean? Like, well, this should, and then you test it and lo and behold, it does. So

53:05
The idea was, and I'm hoping we get a chance, we have two and three coming, what we call pre-applications to our Department of Defense. And the idea is to look at the essential amino acid formulas in pilots. I told you I was a pilot, but right across the river here, we have the world's training center for C-130 planes here, so cargo planes.

53:33
This is the World Training Center for this. And there's a number of problems in these larger aircraft because they have to fly long periods of time. And so, and they do what we call turns. They land mission again, just keep doing what we call turns. So it's very fatiguing as you can imagine. And so the military is looking for ways to keep the pilot sharp through this whole thing.

54:03
uh Up until this point, was speed. It was go-pill. They called it the go-pill. Well, caffeine, speed, it all works the first time fine. But when you have to do a turn and you have to sleep in between, now you got a problem because you're amped up, you can't sleep, you get up, the second mission is disastrous. And everybody's, you know...

54:28
got a tight asshole trying to kind of make sure they're not killing themselves in a cockpit, right? Because, you know, it's a high stress environment. There's a lot happens in the cockpit, especially on a military mission. People just think you're flying, but flying is just like one of the last things you think of on a military mission. have to fly and it's like you drive in a car. You're driving a car. You're talking to a phone. You don't think it's a secondary skills set. You know, the primary skill set is all the mission oriented stuff you have to do in that cockpit.

54:58
Okay, so um what we found when we did what we call a psychological stress test in younger folks actually, and we gave them the essential amino acids is we were able to mitigate the decreases with psychological stress testing. So you put them through, very much analogous to the cockpit with pilots. In a cockpit, there's a lot going on at the same time. I'm checking this instrument on this phone call.

55:25
planning this mission, I'm looking at that target, I'm looking at my GPA, you know what mean? I have to do all these things. I have to get to that place, have to fire the target or drop the things I need to, I have to do all these things at the same time. So it's just constant, you know, high stress mission requirements. so we gave him a stress test where we had this four panels and we asked him to do like, they're adding numbers in this panel.

55:53
Stroop test is, you know what the Stroop test is? Yeah. Stroop test is where you say find the red, find the word labeled red seven, but it's written in blue. You know what mean? Yeah. have to think about it. Oh, okay. And then down here, you're using tracking. In other words, you're doing what we call coordination or simple reaction time. You're tracking a dot and touching it. And this other one, you're remembering

56:23
series of things. So they'll flash ABGF and then they'll do other things. What were those numbers, letters again? Oh, it was ABGF. You see what saying? Now that's totally like being a pilot, be honest with you. That's totally like what a pilot's like. So anyhow, we did that test and then we gave them the essential amino acids and the essential amino acids were able to mitigate the decline and all that stuff.

56:47
it mitigated decline in simple reaction time, complex reaction time, anxiety. You know, they got anxious, they got frustrated. I mean, all those psychological parameters, the EAs were pretty much able to mitigate that. And we just completed a, we, I didn't, my colleague in Israel, a guy by the name of Jay Hoffman finished a study in mice where he overtrained mice.

57:17
And then he gave some EAAs and he measured a number of things in the brain, uh receptors and all this other stuff, as well as their ability to uh behaviorally function. And again, the EAAs were beneficial. So here's the thought process behind it. I'm sorry to drag that out on you. No, please. uh The thought process was this. uh There's only like one receptor in the brain. It's called LAT1 where it takes up amino acids.

57:46
Whereas in a muscle, there's a number of different receptors, but in our brain, there's primarily one called LAT1. so, filoning, tyrosine, dopamine, okay? Tyrosine gets taken up and then converted to dopamine as needed. On the other side of things, like I said, you got to think of this as a rheostat switch. Dopamine is the excitatory uh neurotransmitter. One of the primary uh non-excitatory is serotonin, right? That's tryptophan.

58:16
serotonin. That's why you see these supplements trip the rest and all this stuff. It's basically a trip to vein, make serotonin. So the idea is, in physiology, you don't ever want to shut anything off. It's a rheostat switch. Like I said, it's a ratio. It's like you walking into your den and you're turning on the lights, you turn on brighter or dimmer depending on what you and your husband want to do with that. this is the same thing. The idea is provision of the essential amino acids

58:46
tweaks the rheostat switch in favor of dopamine so that the ratio of dopamine to serotonin is much greater. And as a result, you maintain that psychological performance. And that alertness and the things like that. Exactly. Exactly. And so that's why I said, certainly have enough preliminary data, both with psychological tests and in mice, to warrant, I hope, testing this in pilot populations. So that's kind of...

59:15
where we are right now with that. And the mice model, I assume, is a good model for a human brain? There's a certain, I guess there's a certain number of things that are conserved. I am not an animal researcher, mice person. I'm learning with Jay as we go and I ask a lot of the same questions. But obviously the advantage is that they're very controlled, same genetics.

59:41
Okay, you have the same genetic strain in mice, so usually your variability is not like human variability. And obviously you sacrifice them at the end and you could do things with the tissue that you can only do by indirect measures in humans. Like you take blood, but you're not taking cerebral spinal fluid, it's so dangerous in a human. You can do all those things in an animal. you can get, the two of them we call preclinical, which is the animal, and then these RCTs that we're doing now.

01:00:10
you put the two of those together, the data is very consistent throughout the different species. No, that's good. And then Ani, I mean, you were talking about the essential amino acids in sort of performance and that requirement to be alert and on task. And then in general population, a lot of people struggle with depression and anxiety and things like that. Like, is there a role for amino acids? And maybe it's

01:00:39
the provision of a different ratio of them to help with these neurotransmitters? Do you see any of that in any of your work or research or just the thought of it? I think it's a very good question. We haven't gotten there yet. In fact, DC was talking about em looking at the kids who are ADHD. Oh, very good. I guess he himself was ADHD when he was younger. And so he kind of has a soft spot for that. But I think it's a

01:01:06
It's a very good hypothesis. It's a very good aim is looking at the exact of that issue because that's what the ADHD drugs do is increase dopamine production. So if you can increase dopamine productions by a simple nutritional formula, why not? So I think, you know, he has the desires and designed to head that direction. uh Bob is also getting ready to test that with Parkinson's disease. Oh, that sounds really oh

01:01:35
point, we're heading that direction, but we're embryonic in those. Yeah, no, I love it. And for what it's worth, I've just worked with so many clients who say that once they bump their protein up, they just feel calmer. It just so much calmer and their brain is clearer. I mean, yeah, like amino acids get, we always have that muscle centric. I think your point's valid because I think that based on a day we filed,

01:02:03
the anxiety level is greatly reduced. know, stress of a cockpit or the demands of a cockpit are very anxiety provoking, right? It's high anxiety, you know what mean? So I think that if you can alleviate that anxiety, helps you, you know, focus is maintained and it helps you perform without a decrement. Yeah.

01:02:32
Yeah, no, makes perfect sense. Finally, Annie, like you're a guy that's active, you're a guy, obviously you eat. Do you want to share a little bit about what you do personally? Like, like I'm super interested, like, what do you do from a health perspective at your advanced age? Just kidding on the advanced age. Yeah, no, you're right. You're right. I don't know if I get the...

01:02:57
Yeah, people are always interested to know what the experts do personally to help with their age optimization. mean, you talk about it all of the time. So, do you practice what you preach? Yes, I do. I definitely do. um I really do a lot of the essential amino acids. By the way, last November I got my left shoulder replaced and this November I'm getting my right shoulder replaced. um

01:03:24
I could tell you, and I got my hip replaced 15 years ago. So I'm like the $85 man now. I got all new parts. m But they're all working great. I a new lease on you. I told you I was a gymnast in college. so that was where most of these injuries were derived. um And I've maintained activity throughout my lifetime, uh martial arts to a great extent and other things.

01:03:52
um I believe in moderation and all things controlled. So I pretty much eat a higher protein diet, as you can imagine. That's either between foods and or the EAAs. I very much limit um what I call garbage carbohydrates. It's not like I don't eat a cookie, but I eat one, not six. You know what mean?

01:04:20
So I think that's a problem you got to learn to control. It's not like I won't eat a fudge sickle or something, but I eat one every couple of days instead it's four. That's just the way I do things. I've always been good at controlling those things. You're not having them around. You know what I mean? I tell my wife, don't buy those cookies, don't bring them in the house. Because I know that if you bring them in the house, I'm eating them. So that's why I said just don't bring them in the house.

01:04:48
Yeah, and then the activity. I've just always my whole life been just active. And now, as I've gotten older, my activity has evolved like everything else, I'm sure. Were you a runner in college, Mickey? Yeah, I've been running for forever, I think. Okay. But you can tell me that at 47 years of age, you're running as much as you did when you were 19 or 20.

01:05:13
It's certainly not as fast either. I've slowed down and now I hit the long events. Yeah. No, it's just, mean, it's dealing with getting over. So I'm the same way. uh I do lift and I do martial arts and still, I mean, I do combat. I get together and train with guys at least twice a week, do some sparring, do some boxing, do some weights. But usually I can't.

01:05:38
I don't have it in me to spend time in the gym anymore. I'm like a 30 minute gym guy. I'm a hit guy. I have one hit. I go in, I do my five or six exercises, four or five rounds, and I'm out in 30 minutes. People ask me, Jesus, yes I am. I'm out of here. So I found that to be beneficial for a whole number of ways because it doesn't require, it doesn't get me sore. It doesn't require a great deal of recovery, number one.

01:06:06
Number two, I get the cardiovascular component as long as the musculoskeletal component. Yeah. So that's kind of how I've evolved to be honest with awesome. No, that's awesome, Ani. And I love chatting to people who practice what they preach, but who's also, and to your point, like just constantly evolving what you do and also a lifelong learner actually, like super curious, just want to know more. And then also just really generous with your time.

01:06:34
to share it as well because there is a lot of misinformation out there and then we hear it from someone who's literally doing the research and is still involved now. I just think it's really valuable for everyone. So thank you so much for your time. I really enjoyed the conversation. Well, thank you for having me, Mickey. It was delightful. I'm glad you reached out to me. I'm glad we had a chance to talk. I'll be glad to do it again in the future. That sounds great. Thanks, Annie. Have a nice day. Thank you very much.

01:07:13
Alrighty, hopefully you just really enjoyed geeking out on protein as I did and I found him so insightful and just really fun to chat to. So let me know what you think of that interview. Next week on the podcast team, I speak to Paul Booth who is sports nutritionist, exercise physiologist who helped lead Ruth Groff and Tom Evans to their respective wins at the UTMB which just happened a couple of weeks ago. Stoked to bring that to you. That's next week.

01:07:43
Until then though you can catch me over on Instagram threads and X @mikkiwilliden, Facebook @mikkiwillidennutrition or head to my website mikkiwilliden.com and book a one-on-one call with me. All right team you have the best week. See you later.