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Diet, Macro- & Micronutrients, Taste, Whole vs. Processed Food, Obesity & Weight Loss, Evolution

Full auto-generated transcript below. Beware of typos & mistranslations!

Stephen Simpson 7:10

Oh, that's nice to hear, Nick. Thank you.

Nick Jikomes 7:13

Do you guys just want to start off by telling everyone who you guys are and a little bit about your scientific background and what your lab study today?

Stephen Simpson 7:22

Sure. So now, do we want to Dave, do you want to go first? Or do you want

David Raubenheimer 7:29

me to I'm happy to start? Hi, Nick. I'm David Raubenheimer. I'm professor of nutritional ecology at the Charles Perkins centre, University of Sydney. My background is in ecology developed an interest in the role of nutrition in ecology at an early stage. And basically, my interest in nutrition focuses on how animals interact with food environments via nutrition to federal notice nutritional ecology. So it's a branch of nutrition that is informed by ecological and evolutionary sciences. And rather than considering nutrition as an interaction between physiology and biochemistry, as in between nutrients and animal physiology, it considers nutrition as an interaction between the whole organism and its food environment. And that's the perspective that I'll be speaking about today, in relation to our work on animal and human nutrition.

Stephen Simpson 8:36

And Nick, I'm Steve Simpson, and I'm the academic director of the Charles Perkins Center here at the University of Sydney, which is a really major initiative that we established now 11 years ago to bring all of the disciplines of the humanities, social sciences, physical and life sciences and the medical and health sciences all together to try and tackle some of the large health challenges facing the world principally, the burden of chronic disease. And that's something which speaks to both my and David's history as biologists as David just said, we met in the late 1980s at the University of Oxford. I had been working for the previous 10 years or so on understanding appetite and nutritional wisdom in locusts, and also beginning a study of swarming and locus, which is since extended from neuro chemical events within the nervous systems of individuals all the way up to mass migration, collective behavior, global invasion by locusts swarms. And so we started our journey in nutritional biology with that animal With locusts. And over the past three and a half decades, we've extended that work ultimately, to the Charles Perkins Center and the understanding of human obesity, chronic disease and the interaction actually between nutrition and pretty much every aspect of health. So my, my emphasis has been more at the physiological and behavioral end, leading into ecology, and David has really complemented those x bow, that set of expertise and between us the story of eat like the animals is very much our story.

Nick Jikomes 10:44

Yeah, and I, I came across this book last year, and I really liked it. So it's called Eat like the animals. And, you know, one of the sort of overarching reasons that I was attracted to this book is, you know, it's about health and nutrition. But it's not a traditional diet book, it's really sort of a by a biology book in a basic sense. And you guys take, you know, an evolutionary approach, which I think is essential. And we're going to talk about that, you know, just understanding animals as whole organisms and populations inside of environments and how, you know, considering their life history, and having all of that contextual information through which, you know, we think about the specifics of diet metabolism. And I'm hoping we can start at the beginning of the book, because you guys start out with a really fun and illuminating story about a character named Stella. And what's interesting about the story of Stella is you followed Stella's diet dietary habits very carefully. And Stella had no formal education, never went to school, Stella never consulted a nutritionist or a doctor knew anything about the science of metabolism and nutrition. And yet, you tell us that Stella was able to consistently eat a well balanced diet to keep her fit and healthy. So can you guys just summarize the story of Stella for us and why you started the book with that. Yeah, that's

David Raubenheimer 12:09

a pretty remarkable story. Nick Stella ate, over the period of the study, still, at age close to 90 different food types and different we watched, the study was conducted over 30 days. And on each day, she ate different combinations of these collection of about 90 Different foods that were available. So at face value, it looked like things were happening, she was going all over the place from on a day to day basis. But when we did the nutritional analysis, looking at not the food combinations that she ate, but the nutrient combinations that she obtained from eating those combinations of foods, specifically, macronutrients will speak a lot about macronutrients obviously, not the only nutrients. But as we'll show you, they really, really important nutrients. If you looked at the amounts and balance of nutrients that you ate on a day by day basis, the amounts vary quite a lot. But one thing was consistent across those 30 days, regardless of a combination of foods that she ate, she ate a fixed balance of macronutrients. And that told us something is very important about that particular balance of macronutrients was the first conclusion. And the second conclusion was that she has remarkably sophisticated mechanisms for mixing diets in different combinations to achieve target macronutrient balance. And it turned out that, as you said, stellar didn't have reference to die books. She didn't have nutritional calculators, none of that stuff. She did it instinctively. She was a baboon, not a human being. And that got us thinking if baboons in non human species can do this, why do we get it so wrong?

Stephen Simpson 14:02

And we even then stepped to a very much more primitive organism, in fact, something that is not even an animal, a slime mold. And in experiments at the University of Sydney, we challenged little pieces of this since sitio, blob like creature we challenged it to solve nutritional problems. And no matter what problem we threw at it, this little brainless, limbless, slime mold could solve those challenges. It had a level of nutritional wisdom, which was verging on nutritional genius if you gave a different little blobs of food it with mix them precisely to get to the optimal intake of macronutrients to support its growth and development. And this is something as I say, with no brain and With no organs at all, it's just a little chunk of stuff that grows and spreads out across the leaf litter where it normally lives and it to shows remarkable nutritional capabilities. So if a bean can do it, and a slime mold can do it, where have we gone so wrong, so that that really is the opening to eat like the animals.

David Raubenheimer 15:24

And not only that, actually, a really important detail at this is that, of course, slime molds and baboons are very, very different creatures. But the context of those studies was very different as well. slime mold study was done in controlled laboratory conditions, and the study of stellar was done in the wild, she was selecting those food combinations from the foods available in the habitat, she's a free ranging in the wild, free ranging animal.

Nick Jikomes 15:54

Yeah, and so I mean, you give many examples in the book of all different types of organisms, different types of animals, and they, you know, what I took away from it is, you know, all animals, it seems, can naturally and spontaneously balanced their diets, again, without taking courses or talking to nutritionists or knowing anything about, you know, what they're eating in terms of, you know, at the level that a human being can know. And they get their nutritional needs met. And they do this, you know, they do this instinctively, as you say, and so, you know, one of the things we'll talk about is this macronutrient balance, and what that means for a diet to be balanced and to be optimal for what the organism needs. But, you know, one of the things that you point out for animals is that if you eat a high carbohydrate diet, with high carb content, and relatively low protein content, that animals when animals do that, when they have no choice, but to consume a high carb, low protein diet, they tend to eat more calories overall, and become fatter. And so can you talk about, you know, how accurate and how universal is that across the animal kingdom? And what is the general picture here when it comes to fat accumulation and macronutrient composition for animal diets?

Stephen Simpson 17:13

Well, the the capacity, as you said, need to regulate. In other words, to possess separate appetites for key macronutrients that seems to be universal. The key question is if those macronutrient appetites are forced to compete with one another, because the food environment is restricting the organism to a particular balance of macronutrients that perhaps isn't optimal? What does it do? How do those appetites compete with one another, and who wins that competition. And what we found in our very early studies with locusts was that in that animal, the animal would prefer to maintain its intake of protein more consistently, and abandon its regulation of carbohydrates. And hence, in a high carb, low protein environment, it would put on body fat, it would take longer to develop to get enough protein to get to that target level. And on a high protein, lower carb diet, it would eat fewer calories, it would lose body weight and become leaner as a result of that. So in that animal protein is prioritized over carbohydrate in that competition. Now that turns out to be true for a selection of species, but that isn't universal. David, for example, has some really beautiful data from lowland gorillas that show a slightly different pattern. Mondrian mountain gorillas sorry. And we've found that predators generally have a different pattern as well, they tend to prioritize non protein energy over protein. And there are very good trophic ecological and other ecological reasons why that might be the case. So perhaps the gorilla examples worth picking up on their day?

David Raubenheimer 19:20

Yeah, I mean, the the broader point there is that like anything in biology, there's variation and according to the evolutionary circumstances of different species, it's city seems one of the reasons that predators seem not to do that. They do the opposite. What they do is that regulate to, they tend to regulate to a constant fat content in the diet in a book through overland eating protein. One of the reasons they do that is that evolved, it seems they've evolved in a very high protein environment. And this seems to be the pattern and this is what mountain gorillas have in common with, with predators, they show the same pattern of regulation. And what had been common ecologically is that the bubbles in these high land tropical forests with fruits are scarce and intermittently and not abundantly available. So effectively, they've evolved in a habitat where the dinette available most of the time is between 20 and 30% of protein. So that's getting up there. It's close to two domesticated dogs. So it seems that one of the selection forces on these interactions between nutrient specific appetites is the nutritional environment in which they evolve. We've recently shown in another species of monkey, you've learned almost all of the all of the other species of primate that we've studied with one exception and prioritize protein in the way that Steve explained that humans do. The one second exception to the mountain gorillas, the rhesus macaque, what they seem to do, as studies in China shows that they regulate their intake across a wide range of macronutrient compositions, basically, ranging from about 12% energy from protein up to 30% energy from protein, depending on the specific seasonal and ambiguous circumstances they find themselves in, they tend to eat to a constant energy content, and we now understand the environmental factors that have selected for that particular pattern. But as I said, the broad point here is that to understand how, why species regulate in the way that they do, we really need to step back and look at the ecological and evolutionary circumstances.

Nick Jikomes 21:46

Yeah, and, you know, what I want to do in a little bit, is take some of these examples of different species, gorillas, predators, everything and, and talk about those a little bit more, in order to talk about human beings and sort of where we fit into the ecological and evolutionary picture here. But first, I think it would be a good idea at this point to talk about, you know, you mentioned, Stephen, that, you know, there's really just a few appetites out there. And when I read this part of the book, it was really interesting, because, you know, when we think about all of the foods that we eat, and all of the flavors and all of the tastes there, you know, there seems to be an infinite number of tastes out there that we can perceive. And yet, you show us in the book, that, you know, physiologically speaking, when you look at the biology, there's really just a handful of basic nutrients that animals sense. And so can you talk about what the major macronutrients are and how that ties into some of the sensory biology that animals use in order to detect what's actually in their food?

Stephen Simpson 22:46

Yeah, sure. So the the, the three macronutrients as they called and they're, they're called macro because they, they provide the major source of calories in the diet, but not only calories, fat, carbohydrate and protein. And not surprisingly, if you look at the fundamental taste systems, so pretty well anything you'll find taste systems that attuned to each of those, so as well as some of the crucial mineral micronutrients for which there are also separate appetites particularly sodium and calcium. So you'll find taste receptors not only in the in the mouth, but also throughout the gastro intestinal tract, which are responsive to sugars to amino acids, the breakdown products of protein to fatty acids, the breakdown products of fats. And so, what you have is these primary nutrients these macronutrients and their metabolites are sensed there sensed before you ingest a food their sense throughout their their journey through the digestive tract. And then their sense does they enter circulation so there are taste receptors effectively throughout the body, including in the brain. And it's there that this information which comes from nutrients in food, and comes from measures of the state of the animal with respect to its, its state of fat, carbohydrate and protein is store or or levels of bodily, if not necessarily a store in the case of muscle that would be lean tissue. In the case of fat, it would be fat reserves fat deposits, in the case of carbohydrate, this glycogen stores, there are stores there are circulating nutrients there are taste systems that are all tuned such that the the organism is making sense sensible behavioral judgments in relation to food, and then it's extracting, it's digesting, it's utilizing those nutrients appropriately to achieve its nutritional targets. So that's really the foundation of nutritional homeostasis. And the crucial I think the crucial distinction between that view of the world. And the conventional view of appetite, and energy metabolism is that it considers appetite as not a single thing, it's not just the control of energy, it's not just a matter of feeling hungry or feeling full. It's having specific pathways in regards this handful of crucial nutrients that are embodied physiologically, and compete with one another for what is ultimately the behavioral final common path of what you choose to eat, and how much you choose to eat of it. And sitting on top of that, there's, as you say, all manner of other cues that can be learned and associated with nutrition and nutritional quality of foods. Where foods were when you found them there, what they, what what smells and other tastes, cues are associated with them. And those cues are also co opted into the nutritional regulatory, behavioral systems that underpin ultimately eating or not eating a balanced diet.

David Raubenheimer 26:36

And if you think about it, all of this, it sounds complex, and it is complex, but it's immensely sophisticated. And if you think about it, it's not surprising that animals have such sophisticated mechanisms for regulating the precise balance of nutrients that they eat, because it's so damn important for their success. They don't need just energy, they need energy in the form of proteins, fats and carbohydrates in particular ratios. So why not regulate those ratios? And as opposed to just energy overall, it's, it makes, it's pretty obvious from an evolutionary perspective that animals have developed these mechanisms.

Stephen Simpson 27:17

And one of the one of the big innovations, I think, from our work together has been to develop what we've called nutritional geometry, which is a way of actually mapping exactly what David said. So if you if you can measure or estimate, and you can do this, and experiments are in the wild, the intakes of multiple nutrients, particularly these key nutrients that we know, are regulated, you can then develop surface maps or response surfaces to show what's the consequence of being in different places in these nutrient mixture spaces. So if you eat a particular ratio, and a particular amount of nutrients, what's the consequence for everything from gene regulation and nutrients, signaling pathways in your metabolism, all the way through to how long you live, or your risk of dying of some nutrition related illness throughout your life, you can map all of these things, and visualize them as response surfaces. And that's turned out to be an immensely powerful way of showing the imprint of nutrition and nutritional mixtures on every aspect of the biology of organisms, including ourselves.

Nick Jikomes 28:41

So, you know, is it fair to say that, you know, to a first approximation, can we think about, you know, taste basically, as you know, there's there's a nearly infinite amount of flavors that we all experience. And yet you're telling us, there's really only about five key nutrients that were sort of specifically and strongly tuned to detect. So it's almost like color vision, in a sense, where like, all of the colors that we see, are really just different mixtures of a handful of primary colors. And all of the things that we taste perhaps are really just sort of mixtures of these five key nutrients that evolution really wants us to be tracking, so to speak.

Stephen Simpson 29:19

Absolutely. And, and using that same analogy, there is an infinite number of wavelengths of light that we don't detect. Other species do. So you'll have the visual system of a butterfly is seeing the world very differently to the visual system of you and I. But I think in nutrition, the dimensions are rather similar across pretty well everything so sugars, fats, amino acids, and some of the minerals those are really fundamental resources. For any organism, whether that be a slime mold or a person. So that's why you see those dimensions in the physiology of organisms. Now there's more than 100 different nutrients that create a balanced diet, you can't, we think, at least a forward in evolutionary terms to have evolved a regulatory system where every one of those 100 has its own specific appetite, the system would just freeze up, but would be unable to make judgments when it came to what to eat and how much to eat. So what you end up with is simplifying that through evolutionary time, by looking at the associations that are regularly occurring between many of those nutrients and then focusing on just a small number to regulate. So you rely on correlations to get everything else you need for a balanced diet. And as I think we'll probably discuss, if you start breaking those correlations, then you're in for problems.

David Raubenheimer 31:06

Yeah, a good example of that, Nick is, is primates are one of the few groups that is not capable of synthesizing vitamin C, we rely on in our diet for a source of vitamin C, most other animals can synthesize vitamin C. And the reason for that is that primates evolved in a fruit rich environment with bitumen C was abundant so that we're never selected for the biochemical pathways to synthesize vitamin C in the way that other animals were. So the rule of therefore primates is if they just follow their macronutrient appetites and macronutrient tastes responses, and they balance macronutrients in the way that we saw stead of the baboon doing, they don't need to worry about vitamin C, because fruits or some equivalent, or an abundant source of the diet that they use for balancing their macronutrients that vitamin C comes along for the ride, it's a correlation, they don't need a specific mechanism for it.

Nick Jikomes 32:05

I see. So the specific tastes, the nutrients that we can taste as, as a primate, or any animal is really again, you could sort of use a vision analogy. So you're telling us that we don't synthesize vitamin C, because we evolved in a lineage where vitamin C was abundant in the food. So there's no need to detect that it's sort of always there, in a sense in the things that we normally eat, it's almost like, you know, reminds me of like a bumblebee or something like they can see UV light. And they need that to know where we know which flowers to go to. We don't really need to see UV light, specifically. And so we simply don't have the ability.

Stephen Simpson 32:38

Yeah, exactly. Exactly, exactly. And the the one difference, and I think one of the really interesting aspects of the biology of taste, which is slightly different from vision is that the physiological response to taste, so the vigorousness, with which your taste neurons fire when you detect a particular taste compound, that is part of the regulatory system as well. So as you change in your state with respect to carbohydrates, for example, the way in which you detect sweetness changes. So that is itself part of the feedback that controls appetite. And we showed that very early on working in our locus, where in that case, the way in which the taste receptor itself responds, you can manipulate precisely by changing the status of the animal with respect to either carbohydrate or protein. So when the animal is protein deprived, its taste organs responding incredibly vigorously, to being stimulated with a with a mixture of amino acids. And they do so independently of their sweet response. So when they need sugar, or need carbohydrates, they taste sugar much more vigorously. And so what that means is the animal tastes what it needs and eats, what it tastes. And that gives a really simple mechanism for making wise choices as it moves around its nutritional environment.

Nick Jikomes 34:20

And I suppose that's really the explanation for why you know a baboon in the wild with no declarative knowledge of all the facts and the science can spontaneously and naturally come to this bounce diet. They're just literally following their taste buds.

David Raubenheimer 34:36

Not just the taste buds, the taste buds of the rest of the regulatory system, the appetite system, there's learning involved as well, as Steve said earlier to complex sweet, but they're literally following the direction of those biological mechanisms. You're right. Yeah.

Nick Jikomes 34:52

And so even go ahead, go ahead.

Stephen Simpson 34:55

Sorry. No, no, no, it's just gonna pick up on that. If you come back to our locus sis Again, we found that if you render a locus protein deficient for only four hours, so that's not very long. It will subsequently be attracted by smells, or visual cues that it has learned to associate with high protein foods. And it'll only be attracted by those cues. If it's protein deficient, if it's protein replete, it won't. And you can do the same for carbohydrates. So learning is another another way of really sharpening up these fundamental feedbacks that involve taste. And clearly in the, in the world of a foraging primate, there'll be lots of other learners associations that will be linked to the nutritional quality of the foods involved.

Nick Jikomes 35:51

And so is it fair to say that, you know, one of the things I took from the book at least was, you know, we've got these basically five key nutrients that all animals can pick up on, you've got fats, carbohydrates slash sugar, protein, or amino acids, and then calcium and sodium as two key micronutrients? Is it fair to say that our bodies evolved to care, not about how much you're eating, per se, the total sort of volume of all the stuff we're eating, but really the ratios of each of those things. And we, our bodies will motivate us to eat as much as we need to to get sort of a minimum amount of some of those key nutrients or get them in the right ratios.

Stephen Simpson 36:36

Yes, so So, ratios emerge from regulating amounts as well. So it's a bit hard to disentangle the two, but, and hence why we use the geometric metaphor of the target. So you can imagine this point in nutrient space, which is a particular amount of nutrients, A, B, C, D, or what have you, and it's represented as a point. And you need your job is to get to that point, that target. To do that. You could either go around your world and find the food that has the exact same ratio of all those things, and eat that until you hit your target point. Or alternatively, you have to zigzag your way there by selecting complementary foods, which on their own would never allow you to get there. But you could mix them in a way to allow you to get there. And that's very much what stellar the baboon did. The slime mold can do the same thing as well.

David Raubenheimer 37:40

So in in that case, as Steve said, it's ratios emerging from regulatory amounts of different nutrients to meet specific requirements. But nutrition is complex. And there are many cases where it's not the amounts that are primary in the same sense of is the ratio that's primary. So an illustration of that would be the ratio of calcium to phosphorus in the diet. If that ratio is off, you can't absorb into your physiology through the gut. So if, for example, the ratio of prosperous is too high, and calcium is limiting, you can't absorb that limited amount of calcium, because there are high levels of phosphorus prevented. So in that case, in order to meet the specific demands of the two nutrients, physiologically, the animal has to ensure that what it eats has the appropriate balance of calcium to phosphorus

Nick Jikomes 38:37

is see. And so, in order to perform this balancing act, you've got to have the sensory systems that can detect all of these things, which I think all animals do. But it would seem that you also need to have, you know, also need to be in a food environment where you can choose from the appropriate range of things to do this balancing act. And so my question is, how universal is this in the animal kingdom, and in particular, I'm thinking about animals that sort of have no choice as to what they eat. So for example, if I'm a spider and I build a web, I can't choose what type of insect or little creature gets stuck in the web. So is this limited to animals that can just sort of move around and choose from a wide range of food sources? Or is there something that allows all animals even even like a spider to do this?

Stephen Simpson 39:26

Well, this spider example actually speaks to one of our experiments where we asked that very question of insects or predatory insects and arthropods, including spiders. Can you regulate your intake of macronutrients? Because at the time people felt that predators didn't need to because you are what you eat. Why would you bother measuring your relative intakes of fat and protein for example, when all you need to do is eat pray and We showed in different sorts of predator that they had different responses. And in the case of the web spin spinning spider, it kind of has to deal with what it catches. So you get some things that stuck in your web? How do you actually deal with that, to get over to extract a particular ratio of nutrients that might be your optimal? And what we found there was, the answer is by spitting in different ratios of digestive enzyme. So they spit their enzyme into their prey, they turn it into a nutrient soup, and they suck it. And if you put different amounts of proteases lipases, into your prey, you can suck out different ratios of protein, and fat. And that's exactly what the spiders did. In other cases, if you're a free ranging predator, a beetle or, or another sort of free ranging spider, then you, you can catch things and reject them, if you if they don't meet what you need. Or you can selectively catch them. So it depends where you are and how you go about finding your food. But in every single case, they're regulating either pre or post ingested Lee, what they're acquiring from their food environment.

Nick Jikomes 41:24

I see. So this is

David Raubenheimer 41:25

why I was emphasizing the complexity that the full suite of regulatory mechanisms is that in different cases, depending on for example, the complexity of the food environment and the range of foods that are available, different stages, in that process, we'll be doing the homeostatic regulation was gave a good example in relation to vitamin C and primates. A species where they can't obtain vitamin C from the foods have evolved physiological mechanisms for synthesizing vitamin C, and that enables them to live in environments where fruits aren't an abundant part of the diet. Exactly right in different species, different components of the regulatory mechanisms adapt to the specific ecological circumstances. But same goal, balanced diet.

Stephen Simpson 42:20

And there'll be circumstances where the environment for whatever reason, makes it hard to achieve that balance. So you can't easily select between alternatives to get to where you need to be. And it's there that you see the expression of these competitive interactions between different appetites. So David has some really lovely examples in Arang attends and we work together with a fabby Anika Felton fabulous primatologist looking at free ranging spider monkeys in in South America, same system. At different times of the year, they have availability of different sorts of foods. So, Dave, you you should tell that story?

David Raubenheimer 43:07

Well, it's a very, again, a very complex interplay between what's available, what they eat, and how they're processed what they've eaten physiologically. In the case of orangutangs, and many other species. As we said earlier, the priority is to ensure that on a daily basis, they get the correct amount of protein. For the reason that Steve mentioned earlier, we can't really store protein in the same way so we can store fats and excess carbohydrates in the form of fats, so that the rank terms are much looser in terms of the regulation of fat and carbohydrate, and that go through periods in which they because of the lack of vailable fruit day, they've been drawn fat reserves. In other periods, fruits are abundantly available, then they eat fats and carbohydrates, and they're stored as fat so that they can draw on those reserves at a later period. So you can see their regulation taking place via two mechanisms and across different timescales. On a daily basis, the question of selecting which foods are eaten proteins prioritized at that level. In the longer term, it's a question of storing and retrieving from storage nutrients that vary in the environment at a much longer over a much longer time scale, such as fats and carbohydrates fruits, provides a very clear illustration of the the interplay between natural ecological cycles in food availability is food selection, using the mechanisms such as specific appetites and tastes, responses and other mechanisms and the physiology, how it mediates those relationships. I think Ranga chimes in example, where I collaborate with a wonderful orangutan biologist in the United States, Aaron Vogel is probably ie the example that we know in most detail from primates in the wild showing how physiology interacts with behavior and ecology in this way. And highly relevant, as noted after we will speak about shortly to the human situation.

Nick Jikomes 45:16

And so, we we've talked about this a little bit, but we haven't named it. Can you tell everyone? What is this thing called the protein leverage hypothesis? And how does this tie into? What are some of the key groups of organisms that are sort of primarily concerned with hitting their minimum amino acid requirements? And then maybe we can go into after that talking about like other types of organisms that you mentioned earlier that think about think or behave as if they want to hit minimum fat requirements and things like this? So protein leverage hypothesis, what what is this? And how widespread is it in the animal kingdom?

Stephen Simpson 45:53

Well, protein leverage is essentially where the protein appetite is prioritized. So protein intake is prioritized in food environments where you can't get to your target. So in other words, if a protein is diluted relative to the optimal concentration in the diet, then protein leverage is the phenomenon whereby the animal will increase its food intake, to get closer to its protein target, thereby, largely abandoning its regulation of non protein energy intake. So if you dilute protein, with fats and carbohydrates, and it doesn't matter, which then the animal will over consume total energy to get to its same intake, or at least to approach that intake of protein at the target. And vice versa. If you put the animal on to a higher protein to non protein ratio than is optimal at the target, then it will under consume total energy, because it hits its protein targets sooner before it's met. Its its total caloric intake, even thereby losing weight as a result. So protein leverage is essentially the expression of the competitive interactions between different appetite systems where protein is prioritized. So the protein leverage hypothesis was our positing that this mechanism is perhaps an explanation for the human obesity epidemic. It is our protein appetite system interacting in a food environment where there has been a consistent dilution of protein in the food environment by incorporation of large quantities of industrially processed fats and carbohydrates.

Nick Jikomes 48:05

I see. So if you're in an environment where you're relatively low in protein abundance, you need proteins just to run, you know, we're made out of proteins, right? So every animal needs a minimum amount of amino acids to build its proteins to just do Cellular Physiology, generally speaking, yes. So you need to have a minimum amount of amino acids. If you're in a food environment, where there's maybe more carbohydrates and fats and other things compared to protein, your body's basically going to motivate you to keep eating any number of calories it takes for you to hit that minimum amount of amino acids to just run the stuff of your body. That's the basic idea.

David Raubenheimer 48:47

That is the basic idea. And getting back to the Ranga tangs, you can see why that would have evolved because they're wrong at times, there's a benefit to overheating fat and carbohydrate in in situations where it's abundantly available, because predictably, within their Recology they're going to be periods when there's a fat and carbohydrate shortage. So this energy that their store can then be drawn upon, in other circumstances to be adaptive. But of course, in our changed environment, that's very different because if we dilute protein in the food supply, we don't go through go through in modern industrialized food environments, periods where, where there's the complementary imbalance to higher protein, relatively fat and carb hydrate, in which case we'll be drawing the fat reserves.

Stephen Simpson 49:37

So one in six. Yeah. The one very special thing as you said, Nick about protein of the three macronutrients that not only yields energy, but it has nitrogen, and you need nitrogen to build tissues to reproduce to maintain tissues, and therefore protein has a rather special place amongst the three macronutrients. And then the human diet, it's the, it's the smallest of the three in terms of its contribution, the standard human percent protein in the diet, give or take is around 15% of total calories. But those are really important calories because of the nitrogen. So unless we're able, and we're not to fix atmospheric nitrogen, like a legume, because we can't do that we need nitrogen in protein in food.

David Raubenheimer 50:40

So another way of thinking about it is, protein is a dual purpose nutrient in the sense that it provides that nitrogen, as Steve said, whereas fat and carbohydrate don't, but in circumstances where fat and carbohydrate are scarce, many species humans included can to some extent, derive carbohydrate in the form of glucose from the surplus amino acids that they've eaten, so that it's a source of energy as well as a source of building blocks, you can see them why it's a special nutrient can't be stored, and it's a dual purpose nutrient.

Nick Jikomes 51:19

So, you know, you've mentioned so far, so certain animals seem to be tuned, you know, in the competition, so to speak, among all of the appetites. A protein can for some organisms take priority. And this is the protein leverage hypothesis, keep eating stuff until you get the mean minimum amino acid requirements your body needs. But you also mentioned earlier that other organisms seem to use like a different macronutrient as the one that gets prioritized. Can you maybe reiterate some of that a little bit, and what are sort of the key differences between these different groups of organisms that are, you know, protein leveraged versus fat leveraged, and so forth.

David Raubenheimer 51:56

One of the key differences with predators and we think, mountain gorillas, we haven't done that measurements yet. And we've got a good idea that it happens also, in the reasons macaques that I mentioned is that they have a very well developed physiological ability to D emanate excess amino acids to go through a process known as gluconeogenesis. The same process, I just referred to previously, where amino acids are physiologically processed to give rise to excrete re nitrogen plus a source of glucose that forms that that is channeled into energy metabolism. So they've developed physiological means of overeating, sir surplus amino acids and channeling them into energy metabolism. And that physiological means of doing that means that they're able to overheat protein to a much greater extent, in circumstances where they're fat and carbohydrate limited because that overeating of protein provides a glucose to partly compensate for the low carbohydrate and fat availability. So it seems the key issue is a physiological adaptation, enabling those species to more effectively channel amino acids into a surplus amino acid change energy metabolism.

Nick Jikomes 53:22

Yeah, so it's very interesting, because there's something almost a little counterintuitive to a lot of people here, I think, which is, you're saying gorillas and predators like a lion or a tiger or something, because they're dieters, naturally, so high in protein, they have physiological mechanisms that allow them to effectively deal with that protein and use it for energy and so on and so forth. Right? Naively, you would think, well, gorillas are basically vegetarians, they're not going to have a lot in common physiologically with predators. And yet they do because in fact, both types of organisms, despite this completely different diet, on the surface, at least, they're actually both very high in protein. And that's what really matters is the macronutrient composition, not the fact that you're eating vegetation per se, or animal meat per se.

David Raubenheimer 54:06

Exactly. So foods on other than an end in their own right, that means to an end, and that end, as we say, is obtaining a balanced diet. In the case of gorillas, the food that contains very high protein 30%, in some cases, up to 50% of energy from protein, or leaves, particularly young growing leaves that are relatively low in fiber, very high levels of protein. So it's very interesting to see how in those circumstances as you say, species that are seemingly worlds apart in terms of the foods that they eat, they have underlying commonality, and that is very high protein diet and they adapt in the same way through what's known as triple convergent evolution to dealing with those high levels of protein in similar ways.

Stephen Simpson 54:55

They both think your panda example is another beautiful one of exactly that you should tell that story naked love it.

David Raubenheimer 55:03

Yeah, exactly. So giant panda has ever studied with a group of colleagues in China. Looking at the case of the giant panda where it, as you will probably know, it's, it has this reputation of being an extreme herbivore. Its extreme herbivore because it feeds exclusively on plant material exclusively on one group of plants, which is the bamboos. And that particular group has a very low nutrient content, partly because it's, it's heavily diluted by fiber. So the macronutrient content of that book is very, very low, complete opposite to seemingly what you see in predators. And the paradox is that pandas belongs to a group known as the con Libera, that are largely carnivorous or omnivorous, the bears and the lions and dogs and so forth. So when we did is we thought, well, let's not think about the absolute levels of macronutrients. But from the work that we've been doing more generally showing the importance of a balance of nutrients, let's have a look at what the balance of macronutrients in that bamboo is. And it turns out balance of nutrients is right up there in terms of percentage energy contributed by protein with what an exclusive predator like a wolf or a lion would be eating between 50 and 60% of energy in the diet of pandas comes from protein. So what that shows is that, in fact, at some level, at the physiological level, at least, John and pandas aren't at all an extreme example of a herbivore, their diet is very similar to the diets of the ancestors, which is a carnivorous diet. And that in potentially explains the evolutionary conundrum of how it is that a carnivorous group can evolve into such an extreme Herbert risk group. It's not extreme middle, there's a bridge there and the bridge that very, very short bridge actually is the one of macronutrients.

Nick Jikomes 57:05

Interesting. Yeah. So. So in a sense, this, I mean, it's a sort of a weird way of putting it, I guess. Pandas are almost like predators that prey on bamboo, in a sense.

David Raubenheimer 57:17

We've called them macro nutritional carnivores is the level of food they're not at the level of macronutrients, they certainly are

Nick Jikomes 57:26

good. So I mean, this is all interesting. But now we're coming to something which I think is especially interesting. It'll take me a minute to unpack this, but just for listeners, that we've all I think, had the experience, you know, plugged into the Internet, and we all care about, we hear a lot of stuff from a lot of people about diet, nutrition, because it's a topic everyone cares about. Everyone cares about how they look and how they feel. And we want to eat what we want to eat. But we also know what happens if you just indulge in different things too much. And, you know, there's every opinion under the son out there about diet and nutrition and what's best and why. But I think you guys are sort of really giving us a method here for maybe cutting through some of the noise. And so what I mean by that is this, you've got some people out there who say, Well, I mean, humans are omnivores, right, we eat we animal material, we plant material, it's about a healthy mix of both other peoples, you know, on one extreme will say things like, you should really be eating, almost exclusive plant based diet, you know, vegans would be the more extreme example of this animal protein and things like this are not good for you and should be eating only plant based things. You've then you've got the opposite. You've got people who are the so called carnivores, saying no, no, humans evolved to be mostly carnivorous. And therefore we shouldn't be eating all that much plant based food, and it should be mostly meat. And based on what you've told us so far, if you just look at the physiological adaptations that an organism has, you can sort of tell what kind of food environment is involved in. So for example, you know, whether it's wolves eating animal meat, whether it's the panda eating baboon, or the mountain gorilla, they have physiological mechanisms that allow them to deal with a very high protein diet. And so if we start to use this sort of evolutionary lens and think about the type of diet we you know, should be eating quote, unquote, or that we evolved to deal with most optimally, what kind of organism are humans? Are we biased towards? Never as omnivores? Are we biased towards being plant based omnivores? How do you guys think about that?

David Raubenheimer 59:32

So the first thing is that humans what characterizes humans, what's the most distinctive thing about our diet? Historically, and evolution really is the extreme diversity. So that, as you've just said, the humans that subsist on largely plant based diet living in tropical forests, and there are humans like the traditional Inuit that run a largely animal based diet and and all that Intermediate, so we're exceptionally generalist at the level of foods. But if you think about the problem as we do not so much the level of foods but at the level of nutrients, and there's a very strong signal in everything, we see that humans are a typical primate in the sense of being adapted, principally adapted to a diet that has approximately 15 to 20% of energy from protein. And you can see the if you look at the central tendency, what human populations across the globe and prosper, possibly, probably throughout history have tended towards is that ratio of macronutrients and protein from from energy. There are some exceptions, but as we've seen in ecology, we can also explain those exceptions because species like be the mountain gorilla that evolved from a group that largely is rigorous. The lowland gorillas have evolved specific adaptations to cope with that environment, in the same way as human populations, such as the traditional Inuit have evolved specific adaptations to cope with a very high protein diet. But the the strongest signal of all is given the option, humans will choose a diet of approximately 15% of protein of energy from protein, regardless of the foods that is combined from.

Stephen Simpson 1:01:25

And you'll see if you look across the globe, no human population with food sufficiency, exists on less than a 10% protein diet, nor above 25 to 30%. So there is a range, which is highly typical of humans in their natural environments. But as David said, were the cockroach of the primate world, we can make use of just about any latitude and any food environment that is thrown at us. And we'll turn it into an appropriate food culture,

Nick Jikomes 1:02:06

I say, so we're protein leveraged. So we will keep eating to get at least a certain amount of amino acids. And when you say when you cite this 15% Number, that less sort of the average person will typically get approximately 15% of its calories from protein. Is that a modern human like us living right now? Or is that like a hunter gatherer or living in a traditional human ecology that we evolved from?

David Raubenheimer 1:02:34

It's kind of both. We know from randomized controlled trials, that that is what a human a modern human will select in an appropriate experimental environment controlling out all compounds. So there's something fundamental just signal of regulatory biology. The Sorry, what is your your previous question?

Nick Jikomes 1:02:56

Oh, yes, I was just asking, is that 15% number? Is that a measurement that comes from like modern humans today in the modern food environment? Or is it you know, what we think the ancestral situation was?

David Raubenheimer 1:03:07

Yep. So So up until recently, it was believed that in the ancestral Paleolithic situation, diets were high in protein, then that in some cases substantially higher. And it's true in relation to extremely temperate environments. But, but both those examples are humans making the most of a bad situation. Most hunter gatherer populations, new information indicates at relatively low protein diet ballpark within within that that region subsisting to a large extent on a plant based diet. Not exclusively, of course, hunting played an important role. We are omnivores to animal foods fed into the diet, but most populations at a relatively low carbohydrate diet. But there's one key difference between the 15% of protein that we get in modern food environments and the 15% of protein in hunter gatherer diets. And that is another dietary component that's critically important for health and for appetite regulation. And that is fiber. We live in an environment that we're protein is diluted by processed foods that not only is protein stripped out of it, but fiber is stripped out of it and also micronutrients, the range of things that in our hunter gatherer diet, we would obtain through the correlate through correlation, as we discussed previously, that is also stripped out. So that combination of low fiber, relatively low per diluted protein, and also palatability, you've sort of flavor in some things that make these foods super attractive, that's the killer. So in an environment where 15% protein exists in a complex real food based food environment, it's very different if if 10% protein in, in a processed food environment.

Nick Jikomes 1:05:04

And this is this is really where I wanted to go next to this, you know why? Why can still have the baboon effortlessly and naturally balanced her diet. And yet human, we can't, you know, but we know about nutrition and we're smart, and we have big brains. And yet, were completely going off the rails, it seems that sort of sounds like your hypothesis for this has to do with this protein leverage phenomenon, we, our bodies are going to motivate us to eat as much as we can to get at least a certain amount of amino acids. And so if the modern food environment is sort of dilute for protein, and higher in carbohydrates, and lower in fiber, and these things, that the reason we keep eating is to get that minimum amino acid requirement. And having that high carb, low protein, low fiber combination is literally going to cause us to be fat,

Stephen Simpson 1:05:51

and high fat as well. It's not just carbs, yep. Now, exactly. And that it comes back to what we said earlier, the protein leverage protein leverages food intake, and if that translates into high energy intake, them will have a problem. So in a plant based diet, or a diet, which is low, and its energy density, and low and protein, protein leverage just ensures that you eat enough food to gain enough protein. And in doing so you don't over consume calories. But if you strip out the fiber, and you replace some of the protein and all of the fiber with easily digested non protein energy in the form of particularly industrially processed fats and carbs, then protein leverage is going to leverage energy intake, not just food intake. It's

David Raubenheimer 1:06:53

really important to emphasize that we haven't lost our ability to regulate macronutrient, or dietary intake in the way that we see other species included, including stellar doing. And we've shown that as I said, we've done randomized control trials in controlled environments where we can show that humans regulate to 15%, roughly 15% of energy from protein. And if you drop it experimentally, below that they over eat energy. In fact, in our experiment, they put on weight. And if you go above that, they're under heat, energy and lose weight, so haven't lost the ability. But what's happened is that our environment has been subverted in a way that those evolved biological mechanisms backfire on us via that protein leverage mechanism.

Stephen Simpson 1:07:43

So there's a wonderful example make when, when you're starting to become low in protein, there's a particular hormone that's released largely from your liver called FGF 21. And in our experiments, and others around the world, we've found that what that does is it turns on your protein seeking appetite. And that means apart from anything else, that the taste of protein becomes highly salient, it becomes very attractive. And if it happens that the taste of protein, which is umami, and savoriness, is coupled with fats and carbohydrates, then we're going to be led astray. And that's exactly what's happening in the savory snack food industry, for example. And we showed this in a in one of our clinical trials in Sydney, where we found that people on a lower protein, a 10% protein diet, ate more calories. They did so principally by increasing snacking between meals, on snacks that had savory flavor characteristics, even though we'd controlled everything and we're fooling them, essentially, we'd created protein decoys, and that's what is happening out there in the environment at the moment. And it's remarkable how little, we get it wrong. So if you look over the last 50 years, total protein intake as a proportion of calories, has only fallen by, you know, one or one and a half percent. But that has been enough to drive more than 10% increase in calorie intake because of this leverage effect. And that's a pretty good regulatory response, but not good enough.

David Raubenheimer 1:09:43

And because it's cumulative, so those mechanisms, as we said, with the orangutangs as an example, they evolved in an environment where that's a good thing you eat fats and carbs, but we no longer have a period of, you know, Durang equivalent of food shortage. So as cumulative that small amounts crew belong times to give rise to the problem.

Nick Jikomes 1:10:07

So another thing I want to ask you guys about that ties into all of this. And this is something that not all people, but many people, many non scientists, and even some scientists, when they think about diet, and we talk about what is the best diet, or what is an optimal diet, the piece that's crucial that people often leave off, as the next part of the sentence is, for what, and I want to talk about trade offs here. And in particular, something that's very basic in biology. I remember learning about this stuff. You know, in grade school, when I learned about ecology and things. There are trade offs between sort of reproductive output and volume, and longevity. So So for example, we could talk about the best diet for reproductive purposes, we could talk about the best diet for living the longest life possible, we could talk about the best diet for, you know, getting jacked and building muscle or becoming like an elite athlete. And there's not one diet, I think that fits all of those, I think there's going to be trade offs between each of those things. Can you talk a little bit about some of the core trade offs and how those types of macronutrient ratios for things like longevity versus athletic performance and things like this?

Stephen Simpson 1:11:17

Yeah, you're exactly right. And you can add to that there are different optimal diets at different stages of life. So the optimal diet for an infant is 7%, protein, high and fat, and carbs. That is certainly not the optimal diet for somebody in their 20s. But it's breast milk. And that's perfect for an infant. Similarly, as you get into, as we've shown recently, women around the menopause have a higher protein requirement because of the hormonal changes that accompany that transition, leading to the loss of lean mass that you have to replenish in a higher protein diet. Likewise, when you get in either six to an advanced age, your efficiency of retaining bodily protein starts to decline, and therefore you need to eat more protein. If you're metabolically challenged, if you have insulin resistance, then you start to lose body protein as well. And that's as a result of insulin not inhibiting protein breakdown as it normally would. That means your protein requirements have gone up. And unless you change the composition of your diet, you're going to be in trouble because protein leverage will drive increased intake of non protein energy. But you're right, these trade offs are fundamental features of the life history of all organisms. And the most fundamental of all, is between reproduction and longevity. These these are two outcomes, which require two different nutritional strategies. If you're going to live longer, or reproduce maximum Li, you can't do so on exactly the same diet, you need to trade off one against the other. And traditionally, it was figured that there were there were sort of built in trade offs. If you used energy for one, you couldn't use it for the other. Now, what we've gone on to show is, it's actually more in some ways simpler than that. These are just different things, different life history outcomes that do best on different nutrient mixtures. So across the life course, a lower protein, higher complex carbohydrate intake, will support longevity, particularly during midlife and into early late life. Whereas reproduction is maximized in a whole series of different organisms on a higher protein intake. So you, you can depending on what you're trying to achieve, a different diet will suit those different purposes. And then these are embedded deeply in the evolution of our life history strategies. And it translates all the way through to the clinic. So if you're metabolically dysregulated, if you've got type two diabetes, for example, the optimal diet to intervene in that circumstance is not the same as somebody who was healthy, and let's say lean at a similar age, we need to think of diet in a more sophisticated way. And then you add on top of that, genetic variants, different populations, different individuals have different genetic substrates, different genetic predispositions, and even epigenetics, where you carry the imprint of even your parents and grandparents life lifestyle in your regulatory physiology and the way your genes are expressed. All of this ultimately will influence what's the precisely optimal diet for you in a given circumstance. I think you can simplify If, however, without having to get right down to precise individual nutritional determination if you listen to your appetites and put them in the appropriate food environment.

Nick Jikomes 1:15:27

And, you know, that's the key thing.

David Raubenheimer 1:15:29

We've shown in several species now that as nutrient requirements change in that way, to align the nutritional intake with the optimal life history that evolved in specific ecological circumstances, then nutrient selection changes accordingly to track those changing requirements. And from what we've seen of human regulatory systems, there's no reason why the same shouldn't be true for us. In fact, there's every reason that it almost certainly is. So we don't need to do complex calculations, what we need to do is we need to decide three things we need to decide what do we want out of a diet. And I think it's true to say that in modern environments, the goal is a healthy, long life. Because we're not reproducing to level two, most of us who are fortunate enough to live in medical environments are not reproducing to levels where we need insurance numbers of children to be born, because almost certainly some of those are going to be died at childbirth and beyond. We basically reproducing to replacement values. So we don't need a high protein diet for that. But the goal is to assemble a diet that gives us a long healthy lifespan, which is a relatively lower protein diet. The other thing to remember is that we don't need to calculate that, as we said, our biological mechanisms will lead us to that outcome, if that's what you want, you just need to ensure that it's in the correct food environment.

Nick Jikomes 1:16:58

So let's think about this. Maybe even more concretely. So when we say the correct food environment, let's imagine a human being today, living in America, Australia, the so called Western world. Let's imagine a middle aged person 30s 40s Let's say they their goal is to lead a long, non obese life. Where were in food space, what is their diet look like in terms of macronutrient composition?

Stephen Simpson 1:17:35

That would, we we would guess from the experimental data, comparative data from across species, and also looking at human natural human populations and age specific mortality estimates. And we've done that and others have done a lot of this work in particularly in recent years. But that would be a modest low to moderate protein diet probably around 15%, perhaps even slightly lower than that, coupled with high levels of fiber and complex carbohydrates and healthy fats. To do that, you would need you could do that in many different combinations, of course, that so you can you can achieve a given nutritional outcome endlessly in terms of foods and food likes and dislikes and ideologies and cultures. But you would require quite a reasonable plant based company components of your diet to do that. Animal based proteins or plant based proteins could allow you to do it as well, of course, but it would be a whole food, low junk food diet, which is full of healthy plant derived fiber, relatively low in protein, or balanced amino acid complement. So that requires you to mix protein types, particularly if you're eating largely plant based proteins, or to incorporate really healthy proteins from animal sources.

Nick Jikomes 1:19:17

And is what you're getting at there with the protein that the amino acid distributions are going to tend to be different for animal versus plant based proteins. And if so, can you kind of describe that for people?

Stephen Simpson 1:19:29

Yes, so So there are certain amino acids that are particularly prominent in certain foods and certain animal based foods. The branched chain amino acids, for example, tend to be higher in animal and in plant based foods, but that's not entirely true. You can find. You can find plant based foods and animal based foods that allow you quite simply to to get some somewhere near a balanced amino acid complex that. So amongst those amino acids, there's 20 that are common protein amino acids, there's about nine of them give or take that are required in the diet. And if you get their ratio wrong, you can end up with outcomes that are undesirable. So too high a branched chain amino acid intake is known to have bad outcomes in all sorts of different ways. But it's also necessary. If you want to build lean tissue, if you want to grow muscle, you need branched chain amino acids. So you need as much as you need, not more.

Nick Jikomes 1:20:40

I see. And I suppose that that's where sort of lifestyle comes into the situation. So the amino acid content by volume and and its composition, would be different for two identical people, with the exception that maybe one of them is lifting weights a lot, and the other one is not doing that so much.

Stephen Simpson 1:20:58

Right, your target is different as the way we would construe it.

Nick Jikomes 1:21:05

And so, so one of the things I want to talk about a little bit more is, so on the one hand, in the book, you talk a lot about how basically, for a protein leverage species like our own, if you have a high carb, low protein diet, relatively speaking, that will tend to give you more longevity and help you have a longer lifespan. But it's not good for sort of your reproductive progress. And then the other direction, right, it goes in the other direction, a higher protein, lower carb diet is going to make you perform better on the reproductive access. But it's going to come at the expense of lifespan. And the thing that so that made sense to me based on everything you presented in the book. But it also confused me with respect to a long lived species, like humans in particular. And I'm hoping you guys can unconfuse me here, because on the one hand, the idea is, as we just said, high carb, low protein means longer lifespan, but at the same time, that's also the diet that tends to promote things like obesity and metabolic disease, and that those things should should not promote long lifespans. So is there something I'm missing there?

Stephen Simpson 1:22:13

No, no. We call this the protein paradox. So so everything you said about a low protein, high carbohydrate diet is true. And we are a low protein species we have our diet is relatively, as we already said, low in protein, exceptionally low in protein as an infant. So that fits with our being a long lived species for sure. No, the problem, the answer to the paradox comes in two things. One is that our protein requirements change across the life course. So a low protein diet, as we just said earlier, later in life very late in life sort of 6065. Well, that's not very late, I'm already there. But when you get beyond 65, your requirements for protein do go up. Because naturally, you're less efficient at maintaining the protein that you eat. For useful purposes. It's like there's a hole in our protein bucket. So so it does change across the life course. But the really significant solution to that paradox is that the quality of macronutrients matters a lot, in particular, the quality of carbohydrates. So we, for example, published just a couple of years ago, really extensive study in mice, the standard sort of pre clinical model for this sort of stuff, where we traded protein against the type of carbohydrate in the in the diet. And we showed that, as many others have done around the world now that if you're on a relatively as a mouse on a lower protein 10% Protein diet, you will be longer lived and healthier. Except when the carbohydrate is in the form of in particular, we found the high fructose corn syrup mixture, which is a front as glucose equally molar mixture.

Nick Jikomes 1:24:22

So exactly the thing that many people are, right?

Stephen Simpson 1:24:25

Yeah, so what what it means is that protein leverage in a normal healthy human food environment will maintain a relatively low protein intake. So it'll get you to your target, but not require you to eat excess calories to do so because of the complexity of the carbohydrate and the matrix of fiber within which it resides. But if you put that low protein with junk carbohydrate, then you're in trouble. So the very worst diet under those circumstances was a 10%, high fructose corn syrup diet. And to offset the costs of that you had to, in this mouse experiment, we had to increase the percent protein to limit calorie intake. So if you're on a rubbish carbohydrate diet as a mouse, at least higher protein is helpful. But that's the only circumstance where higher protein is helpful, both and it's, it's only helpful because it's restricting calorie intake because of the protein leverage effect, which happens to be pretty weak in mice, actually, they show it less strongly than humans. They do show it but not nearly as strongly as us. So it's probably an underestimate of the human circumstance.

Nick Jikomes 1:25:48

Yeah. And I want to, well, here's what I want to discuss. And then I think there's something we want to unpack before that. So I want to talk about what what an obese person should think about in terms of their macronutrient balance to lose weight. But before we get there, I want to explicitly address a couple things that we've mentioned, but haven't really dove into. So you've talked about complex carbs versus simple carbs. I want to talk about that and what exactly that means. And then I also want to talk about something else you said, which is healthy fats, unhealthy fats. So taking those one at a time. What's the difference between complex carbohydrates and simple carbohydrates?

Stephen Simpson 1:26:28

Yes, so carbohydrates are a, they are on a continuum from mono saccharides, very simple. sugar molecule molecules to long polymers have stuck together, typically glucose. And those, as they get stuck together in longer and longer chains, they become harder and harder to digest, putting it very simply to the point where the most abundant carbohydrate on the planet is the one that we can't, as a human digest, rather few animals can and that cellulose, every single plant cell is surrounded by a little box of carbohydrate, cellulose, which to us is inaccessible carbohydrate. So you have either totally inaccessible carbs, carbs that are hard for us to digest, but our microbiome can do the job for us. So they're the so called resistant starches, the hard to digest starches. And then you've got the easier to digest starches that, you know, for example, found in many grains and potatoes all the way down to the dye saccharides, such as sucrose all the way back to the individual glucose and fructose molecules. So carbohydrates are a kind of complex macronutrients, they come in various different forms. And what we know is that if you provide sufficient resistant starch, that you give your microbiome something to do, that's a really significant part of our regulatory physiology, the training of our immune system, and so on. It's a really important part of our biology. Similarly, if you have enough a lot of largely unable to be digested start starch and cellulose in the diet that gives the bulk that allows you to maintain a reasonable gut passage rate. So you slow the rate at which food moves moves through your gut and you remain satiated longer, you absorb water, so you end up with softer feces, and so forth. So carbs of all different sorts are really important to us. And fundamentally, glucose is the fuel that all of our cells will use as their fuel of first resort. You don't have to have too much carbs in your diet before your brain will go back to burning glucose as its preferred fuel. But it can burn ketone bodies as well, but it doesn't really like doing that. You 20 grams of carbs is enough, and it'll flip back into using glucose as its principal fuel. So that's the spectrum of carbohydrates, fats, likewise, there are endless sorts of you know, they're classified according to their degree of saturation. And, and the Amiga threes and sixes and so on and so forth. It's a complex macronutrient dimension, in which as David said earlier, probably ratios are important. So the Omega three to omega six ratio seems to be something that needs needs to be within a particular bound for it to be most helpful for, for human physiology.

Nick Jikomes 1:30:08

And so this is

David Raubenheimer 1:30:09

all very complex and most people, well, you know, myself included, when I'm choosing a diet, I can't do those calculations, I don't want to diet, so about something different than doing calculations, they're about the joy of eating and nourishing your body. But we have stressed, this is where food environments come in. Because if you have a diet, as we said, that consists largely of whole plant derived foods, you don't need to worry about those things and carbohydrates that you get automatically will align with the healthy side of the spectrum that Steve has spoken about. It's when you start subverting those diets through introducing excessive amounts of highly processed industrialized carbohydrates that you get the problem. So one thing I'm trying to emphasize is you can really simplify the high dimensionality of these issues at the level of foods and think about which foods to minimize in a diet, which category of foods and it's industrialized process to do all the calculating, you need to get a healthy diet.

Nick Jikomes 1:31:17

Yeah, one of the things, you know, I've tried to think about as I have conversations like this, and I just learned about diet metabolism is there's so much signal and and so much noise out there. You know, as you said, David, how do we reduce the dimensionality and think about what are the things that are always going to be true for everyone or virtually everyone? And, you know, one of the tippy top things on that list, in my view is, is basically what you just said, it's processed versus Whole Foods and Whole Foods is basically always going to be better. Totally. So the other thing here is, so if we think about, Well, excellent, let's actually go to the question I wanted to get to before, which is alright, let's now imagine we are a obese person. And we're in middle age. So this is a very large and growing sector of the world that we live in, middle aged person obese, they want to lose weight and get down to a good healthy weight. What does that macronutrient composition look like for their diet?

Stephen Simpson 1:32:24

So what what we're asking them? And this is a really, it's a really important distinction, where we're asking what is how can we use diet therapeutically, to support weight loss and to inhibit rate at weight regain, both of which are hard? And the answer there is that there's various tricks that come to do with the timing of feeding, not eating at night, some degree of restriction during the day when when you do eat, but a higher percent protein diet coupled with healthy carbohydrates and fats and lots of fiber, low energy dense, in other words, is going to be the combination that will most likely satiate and restrict energy intake and hence support weight loss. Now, that particular diet combination will come with some side effects, which may be to speed up longevity or speed speed up the biology of aging marginally. But in those circumstances, it's worth paying because the benefits for a person with obesity far outweigh the costs,

Nick Jikomes 1:33:46

basically. So yeah, because you know that the higher protein content might speed up aging a little bit, but probably not as much as metabolic syndrome and maintaining that obesity. So it sounds like basically, the takeaway there is if you're obese, and you want to lose weight, one thing you should definitely do is have fewer processed foods and more whole foods. And one thing you should probably also want to do is index a bit lower on carbs and a bit higher on protein.

Stephen Simpson 1:34:12

Yep. Well, it could be that.

Nick Jikomes 1:34:15

Okay, carbs and fat. Yeah,

David Raubenheimer 1:34:17

really important to emphasize that we're not obesity clinicians. So we're not providing specifically dietary advice, but we are doing is we're communicating what our research with our observations of the literature and our own research are telling us. Yes, somebody who's chronically obese needs to seek professional medical typesetting. Absolutely.

Nick Jikomes 1:34:41

Yes. And as I like to put on all my content, absolutely nothing on this podcast is medical advice. We're just we're just talking about what, what, what we've observed out there and experiments and stuff. So, okay, so we've got this trade off between longevity and reproduction. We've talked about carbs versus proteins. And we just talked about, you know, what the diet could look like if you want to lose weight if you are obese and what some of the trade offs are there. How do you guys think about your I mean, after everything that you've learned across your whole career, and knowing where you're at, and you know your life history, and knowing everything that you guys know, how do you guys think about your personal diet today? Is it basically what we've been talking about where you're trying to get as many whole foods as possible, and getting enough protein, but not more than that? But how do you guys think about that?

Stephen Simpson 1:35:39

Yes, absolutely. So avoiding avoiding sugar sweetened beverages, and ultra processed foods, tote that except as special treats. I think that's, that's number one. Number two is have a love for cooking, the sharing and enjoyment of food and different food cultures, very easy to do here in Australia, where we have such wonderful ingredients. And in both our cases, we were hunter gatherers, to some degree, fishing. Collecting and growing our own food is something we both get a lot of pleasure out of, and our families do, too. So it's immersing yourself in the pleasure of food, and letting our appetites do the rest and not putting ourselves in temptation, when it comes to the siren call of the ultra processed food world because they're designed to be eaten. And whereas susceptible is anybody? Well, I certainly Yeah.

David Raubenheimer 1:36:55

I totally agree. Very similar to what Steve was saying, I would add one thing, in my case that I really emphasize strongly the food environment, I can't change the Australian or even the Sydney food environment. But what I can change is the food environment that matters most to me. And that's my domestic food environment. So my rule is to shop with your brain and eat with your appetites, what I'd limit is the amount of highly processed foods that I bring into the house. Because I know if I'm hungry, I'm going to reach for those if they are there, in the way that I do it. When I'm hungry, I reach for something that is not a processed food. And ultimately, it's a much more enjoyable experience in any case, and it gives my biology the opportunity to do for me to watch it evolved to do for me, and as is true of all the species that we've studied and discussed today.

Nick Jikomes 1:37:51

Yeah, no, I think I think that's really good shop with your brain, eat with your appetite. And I take a similar approach, I just because I just know myself, if I, whatever I buy, I'm going to eat it if it's here. So I spent a lot of time not buying many things and not having them in the home, because that's just what it takes for me. And I think it's what it takes for most people to like, if it's there, most people are going to eat it.

David Raubenheimer 1:38:14

Absolutely. I don't one further sort of sub rule to that which I violated yesterday, never shop when I'm hungry. I went to the gym and had to stop in to buy a few things. And I was a big battle not to fill my basket with a whole lot of processed foods, because my appetites were screaming for them at that point. Really important.

Nick Jikomes 1:38:39

So So we've got this key factor of whole versus processed. And essentially, I think we can say safely, it's always probably better to do whole foods rather than processed foods. And then depending on someone's specific life history and specific current state of metabolic health, that's where you have to do some homework to figure out you know, what is the balance of carbs and protein and other things. The other thing I want to come back to that you mentioned, Stephen is the 10 Poor temporality here how the when you eat, and I know that you guys have looked at this to some extent, and you talked about it in the book, but I think a good question maybe to ask here to get into this is I don't know if you guys have done it, but I'm sure someone's done it like the experiment where you've got two groups of animals, same exact diet, same number of calories, same nutrient profile, but one group gets to eat that whenever they want, and the other one is restricted in time in some way. How does that factor of when you eat start to come into this?

Stephen Simpson 1:39:33

It comes in pretty profoundly and we were starting to understand why and that's there are really fundamental interactions between the circadian clock system which really structures our physiology and our behavior across the 24 hour day and is expressed in every single cell in your body and it's controlled All by a master regulator in the Supra cosmetic nuclei in your brain, that biology intersects profoundly with your metabolism. So insulin receptor, and clock genes, for example, are talking to one another. So, the timing of feeding restriction, throughout the day of periods when you don't eat all of these things, there's good evidence influencing metabolic outcomes. But again, it's probably simpler to think of it in terms of our biology as it evolved, we have as a species, until recently not eaten during the night when we would otherwise be asleep, we've tended to be a diurnal species, and sleep at night. So we know that sleep and eating aren't able to happen. Well, they perhaps and some people do happen simultaneously, but they're normally not supposed to. And simply by not eating at night. And therefore, having a period of overnight fasting when you're asleep, is as simple a way to get 90% towards a healthy outcome, then embarking on five to diets or, you know, 18, six periods of eating and fasting and eating, and so on and so forth. I think it's just simpler than that. Try not to snack throughout the day eating relatively main meals and don't eat at night that that starts to impose a regularity that reflects our circadian biology and hence, our healthy metabolism.

Nick Jikomes 1:41:59

Yeah, I mean, I personally think that I think this is an uncontroversial statement. You know, if you're doing daily intermittent fasting, even if you're just saying, like, what I do in my own life is at least 90% of the time, I'm only eating between the hours of 12 noon and 8pm. And I work fairly hard to don't have to work that hard to do that, that level of intermittent fasting, and sometimes I throw in longer periods, you know, once or twice a month. But I think that is probably good advice for pretty much anyone, right? Don't be eating at all hours.

Stephen Simpson 1:42:33

Exactly, exactly. And it coming back to this interplay between aging and reproduction, or growth and longevity, those, those two things have essentially opposing metabolic substrates. So if you're growing and reproducing, you tend to down regulate the pathways that would otherwise maintain tissues for the long term, and vice versa. And you can, you can actually manage those two processes on a daily basis by the patenting of your feeding. So when you eat, you need to turn on growth and all the pathways that you need to grow and maintain tissues, but you don't want them turned on endlessly. So if you eat and then have a period without eating, you get the opportunity to flip back into the longevity mode from the growth mode. And so you're managing that you're titrating, those two things which account about they countermanding one another when it comes to long, healthy life?

Nick Jikomes 1:43:53

So can you remind everyone, let's just remind them one more time, what's the name of your book? And is there anything that you feel like we haven't touched on? And in terms of some of the major themes and topics that that you got into in that book?

Stephen Simpson 1:44:11

Well, the books called Eat like the animals. And, Dave, do you think I think we've touched upon much, if not most?

David Raubenheimer 1:44:23

Yeah. I, I think we have as well.

Nick Jikomes 1:44:30

Is there anything? So I don't actually remember when the book was written. I just read it a few months ago. Is there anything since it's come out that's changed that that sort of we've learned because this is a very fast moving area of science, I think and like, is there anything that's, that's changed in terms of your understanding of how a lot of this stuff works? That has come since the book has been out?

Stephen Simpson 1:44:51

That's really interesting. So 2020 It was a COVID. Baby. It came out in March 2020. It's now you in 10 languages, I think, Dave, isn't it where the Chinese edition is coming out soon? We've been asked to write i think i 11. Is it okay, so 11 languages. There is nothing that we say in the book that has turned out not to be supported by all the evidence since rather the opposite. So I think anything that we've said has been reinforced in recent times the evidence base for? Well, protein leverage has has grown substantially. We're currently writing the latest update on the state of evidence in regards to it. The story about protein and longevity is now incredibly well supported by research and labs around the world that that a lower protein higher carbohydrate diet extends lifespan, particularly in midlife. And I think all of the associations around Ultra processed foods and the changing food environment have have also been reinforced. And there's been a growing emphasis on ultra processed foods and their role in the obesity epidemic.

David Raubenheimer 1:46:20

And they've been a really important part of it is there have not been several population studies, observational studies, which totally support protein leverage. I know there's a tendency in the nutrition literature to criticize observational studies in human populations as being uncontrolled, therefore unreliable. Our view is that they're absolutely necessary. They're as necessary as randomized controlled trials, because various randomized control trials can establish causality, you need observations in real food environments to establish the relevance of the causality that you've studied in randomized controlled trials. And they've not been several population studies that completely aligned with the story that we outlined in the in the in the book about protein leverage interacting with protein dilution by processed foods in transitioning food environments to drive an epidemic of obesity and disease.

Nick Jikomes 1:47:22

Yeah, so just to say it one more time there, it sounds like you would agree that there's reasonably good evidence that at least a major driver of the obesity epidemic, is maybe it's I'll say, it's two pronged one, it's eating a lot of processed foods, but sort of deeper than that, it's that because we are a protein leverage species, if you're getting too much carbohydrate, and compared to protein coupled that with not enough fiber, that energy, and fat and fat adding fat, carb, high carb, high fat compared to protein is a recipe for weight gain. Right? Right. Yep. All right. Well, I mean, this was, again, this is one of my favorite books that I read last year. So I think it's really accessible to it's not, it's not super technical, you don't need to be scientific expert to get a lot from this book. I love that you guys take the evolutionary ecological lens so that everything is sort of appropriately contextualized in terms of what our species is supposed to be doing in terms of how it evolved and the type of environments we evolved in. I love all the comparative stuff. I think that's always very instructive thinking about our species compared to other species, what the similarities and differences are. I think there's a lot of key takeaways from this book, many of which that we talked about that are super practical for people. So thank you guys, for taking the time and for tuning in all the way from Australia. I'll give you one more chance if there's anything you want to say or reiterate. Before we head off here.

Stephen Simpson 1:48:54

Nick, just to say thank you for a really fascinating and deeply considered discussion. So thank you for that.

David Raubenheimer 1:49:04

And likewise, thanks.

Nick Jikomes 1:49:06

All right, Stephen Simpson and David Robin Heimer. Thank you guys for your time. And if people are interested in the book, I'll you know, I'll put a link in the episode description. And that's it. Really nice


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