Is High Protein During Weight Loss Bad? Podcast with Stephan Guyenet

Eating lots of protein during weight loss is important, right? Anyone who is interested in the science of dieting knows this, but recent research from Bettina Mittendorfer and her colleagues published in Cell Reports has raised doubts that high protein during weight loss is a panacea. To begin, what did the researchers do?

In the study, the researchers randomized 34 postmenopausal women into 3 groups:

After the participants lost the weight and stabilized at a new, lower weight, the scientists took several measures including body composition, insulin sensitivity, and biochemical assessments of muscle tissue.

First, while both weight loss groups lost the same amount of weight, the group following the high protein diet lost 45% less lean mass! In other words, they preserved more muscle while losing weight. This finding is consistent with many previous studies looking at what happens when people consume different amounts of protein during weight loss.

It’s the other finding, however, that’s received so much attention. While fasting insulin declined by about 30% in both weight loss groups, suggesting insulin sensitivity improved, the high-protein diet appeared to prevent the improvement in insulin signaling at muscles, which is expected to occur with weight loss. One of the major health benefits of weight loss is believed to be the increase in insulin sensitivity that accompanies it. So, if there isn’t an improvement in muscle tissue sensitivity to insulin, should we be reducing protein during weight loss diets?

To shed light on this study and its findings, I invited Dr. Stephan Guyenet to join me on humanOS Radio for a conversation. Perhaps no other person has done more in the last few years to help the general public, and even health professionals, understand new research dealing with energy regulation and weight control. That’s why I chose to work with him on the Ideal Weight Program (available to Pro users).

Stephan has a PhD in neurobiology from the University of Washington, where he also did his post-doctoral work with Professor Michael Schwartz. I’m excited for his new book to be released early next year, which will be entitled The Hungry Brain. I’ve had the pleasure of reading it and it’s an absolute masterpiece on the subject of eating, hunger, energy regulation, and obesity.

Recently, Stephan Hawkins, the famous astrophysicist and public intellectual, stated that obesity is one of the biggest public health issues of our day. Because of the massive importance of this problem, it timely that the best book on the subject – in my informed opinion – is about to be published. I will bring Stephan back onto the show to discuss his book in the future, but for now, I invite you to listen to our conversation on Professor Mittendorfer’s interesting study and its implications for weight loss.

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Stephan Guyenet - 00:06: Protein targets multiple aspects of that starvation response that your brain kicks in when you’re trying to lose fat or when you’re trying to maintain that loss, and so that’s why I view it as a really valuable tool in the fat-loss arsenal.

Kendall Kendrick - 00:24: HumanOS, learn, master, achieve.

Dan Pardi - 00:31: The subject of today’s show is dietary protein. Now, it’s believed by many that a high dietary protein intake can assist with weight loss and weight maintenance, and there’s a good reason for that, which we’ll discuss later. Recently, Bettina Mittendorfer, who’s an associate professor in the Diabetes Research Center at Washington University in St. Louis, published an article in the journal, Cell Reports. This paper is entitled High Protein Intake during Weight Loss Therapy Eliminates the Weight-Loss-Induced Improvements in Insulin Action in Obese Postmenopausal Women.

01:03: This begs the question, if a high-protein intake during weigh loss doesn’t allow for insulin sensitivity to improve, should we aim to have weight-loss diets be comprised of a lower protein intake? To shed light on this subject, I invited obesity researcher and writer and friend, Dr. Stephan Guyenet to join me today. Stephan, welcome to your first visit at HumanOS Radio.

Stephan Guyenet - 01:23: Thanks, Dan. It’s good to be here.

Dan Pardi - 01:24: Yeah. Surely good to have you. To begin, can you first explain what insulin sensitivity even means?

Stephan Guyenet - 01:30: Yeah. Sure. Insulin itself is an ancient hormone that regulates a large number of physiological processes. You see, insulin exists all the way down to insects and maybe even further back than that as a basic regulator of physiological processes. Most of the processes that it regulates revolve around coordinating the metabolism of the body’s primary fuels, which are carbohydrate and fat, and to a lesser extent, protein.

02:03: If we think like an engineer, we can start to think about why insulin might exist and why it works like it does. If you’re trying to design an organism or a machine that can run any mix of fuel that might be available, so like let’s say, a car that could run on ethanol or diesel or regular gasoline, or an animal that can eat almost anything in its environment, whether it’s primarily fat, primarily carbohydrate, primarily protein, then you start to get a picture of what evolution has built into the human body. From an energy perspective, the human body can run itself on any proportion of carbohydrate to fat as long as there’s some certain minimum level of protein.

02:51: Having this flexibility requires sophisticated regulation, because you’re basically having two very different chemicals plugging into the same energy pathways in different proportions, and insulin is a key part of the regulation that allows that to happen. Insulin’s best-known role is in regulating blood glucose levels and keeping them stable, but it also regulates a wide variety of other physiological processes relating to the absorption and assimilation and use of fuels like carbohydrate and fat. For insulin to do its job properly, two criteria have to be met. First of all, there has to be enough insulin around. Second of all, your cells have to be able to hear that insulin properly.

Dan Pardi - 03:38: Okay.

Stephan Guyenet - 03:39: That second factor is called insulin sensitivity, and it appears to be a key determinant of metabolic and cardiovascular disease risk. Basically, how well your cells are able to hear that insulin signal when it’s around, that is insulin sensitivity.

Dan Pardi - 03:57: Okay. That’s good. We want our cells to be sensitive to whatever signal is present and there are certain factors that will make cells less sensitive to that signal, so that’s what we’re talking about here?

Stephan Guyenet - 04:09: Yeah. Exactly. To reap the metabolic and cardiovascular benefits of well-functioning insulin regulation, you want to have a high level of insulin sensitivity.

Dan Pardi - 04:21: Okay, so it’s a marker of metabolic health, if you will?

Stephan Guyenet - 04:23: Yeah. It’s a marker and a driver of metabolic health.

Dan Pardi - 04:26: Great. Okay. Let’s get into the study. What did they do in this study where they were looking at protein in weight loss? Tell us more about that.

Stephan Guyenet - 04:33: Sure. I want to take a little step back, though, before we get into the study. I just want to say that insulin sensitivity, because of its role in physiology and metabolism and because of the fact that it’s typically diminished in context of excess body fatness, so in the context of obesity and overweight, you have reduced insulin sensitivity. When you go on a weight-loss diet or fat-loss diet, I should say, one of your goals is to improve your insulin sensitivity.

05:02: That’s something that you typically see. When you lose excess body fat, you improve your insulin sensitivity, and that’s a really good thing. That’s what we think delivers a lot of the benefits of weight loss, a lot of the metabolic benefits of weight loss. Getting back to the study, like you said, it’s from Bettina Mittendorfer’s group at Washington University, St. Louis. This is a person whose work I've followed in the past, and my impression is that she’s a careful scientist and I’ve been impressed by her previous publications.

05:38: What they did is they took 34 subjects and they randomized them into three groups. The first is a weight maintenance control group, so these people did not lose weight. The second is a 10% weight loss with normal protein group. These people lost 10% of their body weight and ate a normal protein diet, by which I mean 0.8 grams of dietary protein per kilogram of body weight per day.

Dan Pardi - 06:04: Okay.

Stephan Guyenet - 06:05: Then there’s a 10% weight loss with high-protein group that also lost 10% of their body weight, but they were eating 50% more protein, which is 1.2 grams of protein per kilogram of body weight.

Dan Pardi - 06:18: Okay.

Stephan Guyenet - 06:18: This is consistent with the previous high-protein diet studies such as the ones conducted by Margaret [Inaudible 00:06:27] and Claus [Inaudible 00:06:29]. Their studies have shown that that amount of protein aids with weight loss and helps prevent the so called starvation response that fights to regain body fatness after you’ve lost weight. This is really consistent with a lot of previous studies on the benefits of high-protein diets.

Dan Pardi - 06:47: Okay. That’s good. We can compare them slightly.

Stephan Guyenet - 06:49: Yeah. To a degree.

Dan Pardi - 06:50: Yeah. To a degree.

Stephan Guyenet - 06:51: Yeah. They provided all food to increase the control over the diets, which is good. They achieved the high-protein diet intake with whey protein bars. The high-protein group was eating these whey protein bars to supplement their protein intake.

Dan Pardi -07:08: Okay.

Stephan Guyenet - 07:08: Then after they lost weight and stabilized for a few weeks, they took body composition measurements by DEXA, which is a gold standard measure that tells you fat mass and lean mass. Importantly, they did something called a euglycemic hyperinsulinemic clamp. I’m just going to call it the clamp for short. This is a gold standard measure of insulin sensitivity.

Dan Pardi - 07:33: Okay.

Stephan Guyenet - 07:34: Most studies that measure insulin sensitivity use indirect methods such as HOMA that are not gold standard. This is important that they use a gold standard method for determining insulin sensitivity.

Dan Pardi - 07:47: Okay.

Stephan Guyenet - 07:47: Then they took muscle biopsies and did a bunch of biochemical and genetic measurements on them. I want to make an additional point and that is that the change in insulin sensitivity by clamp was the primary outcome. For listeners, this is a really important point, because what that means is that they declared in advance before having any data in their hands that this was going to be the most important outcome of the study.

08:16: What that does is it protects us against researcher bias. This means, they can’t take 20 different measurements, figure out which one supports what they want it to support and focus on that one in the paper. When you declare a primary outcome in advance, you have no choice but to focus on that predefined primary outcome once you publish the paper. Everything about this study is very robust.

Dan Pardi - 08:42: Got it. How did they collect that data?

Stephan Guyenet - 08:44: Yeah. Essentially, the way it works is you put an IV in a person and you put insulin into their blood stream, so that’s the hyperinsulinemic part of the name. You increase their insulin level. What that does normally is it would suppress your blood glucose level by causing that glucose to be taken up by tissues and by reducing the amount of glucose produced by your liver and pumped into the blood stream. That’s one of the main roles that insulin has is constraining blood sugar. Normally, when insulin goes up, your blood glucose goes down. What you do in a clamp is you infuse glucose into that IV such that your blood glucose level does not go down.

Dan Pardi - 09:35: Right.

Stephan Guyenet - 09:35: That’s the euglycemic part. Euglycemic means maintenance of blood glucose level. Essentially, what you’re measuring, the main outcome is how much glucose do you have to infuse into a person’s blood stream to prevent glucose from dropping with a given amount of insulin. What that tells you is how much that insulin would have affected your blood glucose if you hadn’t been infusing that extra glucose. Basically, it’s the direct measure of the ability of insulin to suppress blood glucose in your body.

Dan Pardi - 10:14: Great. Therefore, a measurement of insulin sensitivity?

Stephan Guyenet - 10:18: Exactly. You’re measuring how much insulin it takes to have one of the primary physiological effects of insulin, so yeah, it’s a direct measure of insulin sensitivity.

Dan Pardi - 10:28: Okay. Great. I’ll do a quick summary in this research protocol. They took 34 subjects, divided them into three groups. One was a control group, protein intake which was facilitated with whey protein bars. After the weight loss, then they did this gold standard euglycemic hyperinsulinemic clamp and they were able to measure insulin sensitivity that way. Good summary so far?

Stephan Guyenet - 10:50: Yes. Absolutely.

Dan Pardi - 10:52: Okay. Great. The design of the study was also excellent as well. They a priori determine before the study began that this is going to be their primary endpoint, which makes the study more robust. Great. What did they find?

Stephan Guyenet - 11:04: By design, both weight-loss groups lost the same amount of weight, so this is something that was pre-specified. It wasn’t really a study trying to figure out which one causes more weight loss. What they found was that, for that given amount of weight loss, for that 10% weight loss, the high protein group lost 45% less lean mass. Basically, it cut the loss of lean mass in half.

Dan Pardi - 11:27: Wow.

Stephan Guyenet - 11:28: Yeah. They kind of downplayed it in the study, but I think that’s a pretty amazing result. It cut the loss of lean mass in half.

Dan Pardi - 11:36: Wow.

Stephan Guyenet - 11:37: This is something that body builders have known for a long time. They go through bulking and cutting phases where they eat lots of calories, they try to put on as much muscle as possible, and then they cut their calories back right before competition to try to lose that excess fat. At the same time they try to eat as much protein as possible, so that that weight loss does not take muscle along with it, which it normally would, or at least to minimize the degree to which that weight loss takes their muscles. I see that as a very good thing and the effect was quite large there.

Dan Pardi - 12:12: Yeah.

Stephan Guyenet - 12:13: Fasting insulin decline by about 30% in both weight-loss groups. Normally, this would suggest an increase in insulin sensitivity. If your insulin levels go down without any change in your blood glucose, that’s suggesting that less insulin is doing more. Sometimes fasting insulin can be misleading and now we come to the key result, which is that using this gold standard clamp technique, they found that insulin sensitivity improved in a normal protein group but not in a high protein group despite equivalent weight loss.

Dan Pardi - 12:47: Yeah. That was surprising.

Stephan Guyenet - 12:48: Yeah. It was surprising for me, too. Definitely. When they look at the biopsies, they did some biochemical measures in those muscle biopsies, they found that this was associated with less of an increase in phosphorylated Akt.

Dan Pardi - 13:02: Okay.

Stephan Guyenet - 13:03: This is the protein that’s involved in the insulin signaling cascade inside the cell. Basically, what this result does is it corroborates the clamp measurements and it says, in muscle, the high protein group did not see the expected increase in insulin signaling inside the cell that the normal protein group saw. We can say pretty confidently that, at least in muscles tissue, that expected increase in insulin sensitivity did not occur. Muscle tissue is an important tissue in terms of whole body metabolism. It’s one of the primary consumers of glucose, so its ability to remain sensitive to insulin is important.

Dan Pardi - 13:45: Okay. Just a little summary here, a 50% increase in protein intake led to a 58% almost improvement in the amount of muscle that was retained. The people that were on a higher protein intake had less of a improvement in the sensitivity of their insulin in their muscle, and that was corroborated with biopsies where they could actually see these important proteins that are involved in the insulin cascade. They were actually not adjusting as much as they were in the group that had the lower protein intake with the same amount of weight loss.

Stephan Guyenet - 14:18: Yeah. Absolutely. If you look at the numbers, it’s very clear. I mean, you see about a 25% increase in insulin sensitivity in a normal protein group and that’s essentially completely prevented in the high-protein group. It’s a very clear difference. There is a little asterisk here and the authors bring it up in their discussion, because there’s still this interesting decline in fasting insulin to contend with, which is surprisingly incongruent with the clamp measurement.

14:51: They speculate that there may actually have been an increase in insulin sensitivity in certain tissues such as the liver, but that the clamp technique just may not have been sensitive enough to detect that. What we can be really confident about is that there was not an increase in muscle insulin sensitivity in the high-protein group, and they really kind of hammered that in the paper. It seems as if there may actually still have been an improvement in insulin sensitivity in other tissues including the liver, and there were a couple of different suggestions of that in the paper. It’s not quite as clear-cut as it might seem initially.

Dan Pardi - 15:31: Yeah. That’s interesting. Due to the limitations of the way that they were measuring insulin sensitivity, again, there is this asterisk we might see that there is an improvement in insulin sensitivity in some tissues. We know that there wasn’t in muscle, so maybe we could talk about protein’s influence. Why would we want to have a higher protein intake in general when we’re trying to help people lose weight? Then what does this finding mean to that interpretation, should the guidance of having a high-protein intake for weight loss change in response to what we see here?

Stephan Guyenet - 15:58: Yeah. That’s a really important point. I mean, why would we want to have a high-protein diet to begin with? There are actually a lot of really compelling reasons to have a high protein diet and these are the reasons why the Ideal Weight program that you and I co-designed, one of the primary elements of guidance is that people should eat high protein. Basically, protein helps with appetite control, that’s one of the most important things that it does. If you eat a higher protein diet, typically, it helps spontaneously reduce your calorie intake without you having to actively restrict calories. That’s really, really important because appetite is really a major roadblock to fat loss and maintenance.

Dan Pardi - 16:43: Let me ask you a question about that.

Stephan Guyenet - 16:44: Yeah.

Dan Pardi - 16:45: When we talk about reductions in appetite with higher protein intake, is that acute as in it has an immediate effect within a meal? Okay, I want to eat, let’s say, 75% of what I would have, or are we talking about having a high-protein intake has an effect on how much you want to eat possibly the next day or the day after? What do we know about protein and appetite both short and longer term?

Stephan Guyenet - 17:08: Yeah. That’s a great question. It appears to be both. I like to think about appetite in terms of two systems in the brain primarily. We really know quite a bit about how appetite is regulated, and we know that it’s regulated by the brain. Obviously, eating is a behavior. When you’re doing behaviors, that’s something that’s coming from the brain, so your food intake is clearly generated by the brain. What makes the brain make you hungry or not hungry makes you reach for the food or not reach for the food. That’s a complex question, but when it comes down specifically to appetite, you’re kind of like visceral energy drive to eat.

17:48: There are two systems, there’s one in the brain stem that regulates your meal-to-meal satiety. That’s accumulating information about what you ate and basically turning off your desire to continue eating at a meal. Protein is the most satiating macronutrient, so per unit calorie, it creates more of that fullness sensation that terminates a meal than either fat or carbohydrate. It has that powerful acute effect on those brain stem circuits that are regulating your short-term intake, your single meal intake.

18:24: Then in the longer term, you have these systems in the hypothalamus that are accumulating more long-term information from your body fat via leptin, from all these other hormones that are coming up from your gut, from pancreas, other places and integrating that information into your long-term energy status. That information is used to set your longer term appetite among other things. It turns out that protein also acts in those circuits, the higher your protein intake is, the less of a drive your brain has to eat more to curtail calorie expenditure and to gain or regain fat.

19:08: Basically, to summarize that, protein affects the set point. It affects the level of body fatness that your brain is actively trying to defend against changes. When you eat a high-protein diet, that seems to go down. Part of what we see from that is the reduction in appetite, but on the other side of the energy equation, high-protein diets also prevent the disproportionate decrease in calorie expenditure that happens with fat loss.

19:38: When people lose fat, normally, the brain goes into a sort of starvation mode and it starts to both increase appetite and curtail the number of calories that it’s burning, so your metabolism slows, you start to feel sluggish, you start to feel cold. There’s pretty good evidence that protein attenuates that response. Basically, protein targets, multiple aspects of that starvation response that your brain kicks in when you’re trying to lose fat or when you’re trying to maintain that loss. That’s why I view it as a really valuable tool in the fat-loss arsenal.

Dan Pardi - 20:16: I'll add a point here. Thank you for that great summary. There’s a lot of different ways to lose weight, but really, when we’re thinking about what everybody actually wants, whether they articulate it or not, is to lose weight in a manner where you can keep your results. Nobody wants to lose weight only to gain it back right away. The evidence suggests that having a higher protein level in your diet might facilitate greater ability to stay at a reduced weight once you achieve it, and also help you get there. Protein helps you feel full from within a meal.

20:45: That’s going to help prevent you from overeating calories, help you feel more satisfied on fewer calories and it’s going to then, on the longer term, help you possibly drive down the set point to help you lose weight, and then also keep you there. That’s a great summary, Stephan. Makes a lot of sense to say having a high-protein intake in your diet is a very good thing for anybody who’s interested in weight loss and weight-loss maintenance. Then comes this study. I think now, we have this very interesting, somewhat dichotomous argument of protein is really good for you, but also appears here that it doesn’t improve insulin sensitivity even if you lose weight. How do you interpret all this?

Stephan Guyenet - 21:23: Yeah. This new study does not challenge any of what we just said. In fact, it supports aspects of it, particularly the fact that protein can maintain lean mass in the phase of a weight loss. All of these good things that protein does to help with fat loss and maintenance help make it easier and help make it more sustainable. None of those things are challenged by the study.

21:48: What the study does say is that if you do use this technique to lose fat, you may not be reaping all of the metabolic benefits that you would reap if it were not a high-protein diet. That is kind of concerning. Health is obviously one of the major reasons that people want to lose fat, and that’s something that we care about a lot in our program. That’s something that we really focus on is fat loss as a way to improve health. One key question here is, should we believe this result?

Dan Pardi (22:22): Sure.

Stephan Guyenet - 22:23: Is this something that is robust enough and broadly applicable enough that it should affect our thinking about the world?

Dan Pardi - 22:32: Yeah. It’s a good point. I’ll add, the way that they measured this was very specifically tested under this protocol. Does that mean that every high-protein intake diet is going to have equivalent results, or is the interpretation of this result limited to exactly how the protein was administered, timing of the meals, whey protein bars, etc.?

Stephan Guyenet - 22:51: Yeah. Absolutely, and the specific study population. I think that we really don’t have answers to all those questions. What I can say is that I think the study was well-conducted, I think we can draw conclusions from it, but when we try to apply this to the broader population of people who might be interested in fat loss, it becomes a little bit more murky. First of all, the used a whey protein supplement, we know that different sources of protein have different physiological effects, so it’s not entirely clear that a different source of protein such as meat or soy or dairy … I guess it was a type of dairy, whey protein. It’s not entirely clear that a different source of protein would have had the exact same effect.

23:37: Now, to be clear, I don’t have any specific reason to think that the effect would be different with a different type of protein, but that’s just something that is left unresolved. What else? It was a small study, 34 people, so that leaves 11 or 12 in each group. That’s large enough to come to a statistically valid conclusions, which the study did, but I think that it would have been more compelling if it’d been a larger number of people in each group. As much as I think that this study appears solid to me, I think that replication will make it more solid. The other thing is it’s conducted in obese postmenopausal women.

24:17: This is a very specific group of subjects, and so we can’t be confident that these same results would apply more generally, for example, to young men who are overweight or to people with a different racial or ethnic context than was studied in the study. Again, I want to be clear that I don’t have any specific reasons to believe that you would get a different result by studying different types of people. There’s not any specific metabolic or physiological reason for me to suspect that. However, we don’t really know, that remains an area of uncertainty for us.

Dan Pardi - 24:53: Yeah.

Stephan Guyenet - 24:54: I think that we can believe the result in terms of how it applies to this specific intervention in this specific group of people, but I think it becomes a little bit more murky when we try to extrapolate outside of this specific intervention and outside of this specific group of people.

Dan Pardi - 25:10: Right. They are also sedentary people as well, so they had less than an hour and a half of exercise per week. Of course, we know that exercise has a big impact on insulin sensitivity, too. Would a high-protein diet with the other influence of having more physical activity in their lives would that have an impact as well? Of course, we know that there’s other factors that matter, too.

Stephan Guyenet - 25:32: Yes. That’s a good point.

Dan Pardi - 25:33: Okay. Great. Protein quality matters as population of people is not representative of everybody. We also know that they were sedentary, but it is an interesting finding. Does it change how you would design a weight-loss program or a weight-maintenance program? Of course, that’s an important question because we have designed one. Did you feel that there was a need to modify what we’ve created to help people?

Stephan Guyenet - 25:59: Yeah. I think this study comes in the context of a broader literature. Typically, one study is not going to completely change your view on the world and that is true of this study. As I said, it doesn’t really change all of the benefits of high-protein diets that had been uncovered by previous research. I think a really important point is, that this study does not address, is that protein helps you get the weight loss in the first place. In this study, they stipulated equal weight loss in both groups.

26:32: What you would see in real life is that the high-protein diet group, as long as they were actually eating a high-protein diet, which is challenged in certain studies, they would have reduced their calorie intake and their body fatness to a greater degree, they would see better maintenance, they would see benefits in a lot of different areas. If you think about it that way in terms of the group with a normal protein might not even have lost much weight to begin with, so we probably wouldn’t have seen those metabolic benefits to begin with, at least not to the same degree. I think that in the context of the real life picture, a high-protein diet is still pretty valuable.

27:14: On the other hand, although it’s especially valuable during weight loss, I think when you’re talking about weight maintenance when you’re looking at what you’re going to be doing for the rest of your life, then you really start thinking harder about what [inaudible 00:27:28] metabolic consequences of this type of diet. I think this study is part of a broader picture that has changed my thinking a little bit about that longer term maintenance phase. You and I are redesigning the Ideal Weight program right now from the ground up, and I’m really excited about the new program that we’re putting together.

27:49: One of the things that we’ve done is in the Lean Maintenance Diet, which is our weight-loss maintenance diet, we’ve shifted that more toward a Mediterranean-style template. There’s pretty good evidence and growing evidence that a Mediterranean-type diet really helps to facilitate long-term weight maintenance. That’s not really a high-protein diet, but it does a lot of the same things that a high-protein diet does. Our new version of the Ideal Weight program, the Lean Maintenance Diet, I should say, it's a little bit high protein. It’s high protein for breakfast, so that helps give you that appetite control throughout the day, but in terms of your overall protein intake, it’s not really that high.

28:31: The other thing with protein, this is just a broader issue, that concerns me is that in terms of your life-long protein intake, what you’re going to be doing for the long run, the higher your protein intake, the higher your environmental footprint. That’s something that is going to happen particularly if you’re eating animal protein from conventionally raised animals, especially cows. That’s something that makes me feel somewhat uncomfortable. That’s part of the idea in moving away from the very high-protein maintenance diet.

29:04: I think it still makes a lot of sense to leverage that high protein during the fat loss phase, because that’s when you’re really going to need the biggest push. Then for maintenance, I think shifting away from that and more toward a Mediterranean template, there’s really good evidence that that’s going to help you maintain that loss, but also it’s going to give you a really good shot at reaping the maximum cardiovascular and metabolic benefits that you can reap from that fat loss and maintenance.

Dan Pardi - 29:33: As you know, I’ve been writing about aging and fasting, and sometimes how they relate and sometimes separately, but this idea of antagonistic pleiotropy, something that might be good for a body that is still in its reproductive years might actually have not such a good effect when somebody is beyond that window. That’s an interesting kind of an idea here, and a lot of the aging research is looking at a lower protein intake as well, which might make sense after a certain age. I think having a higher protein intake for breakfast, you get the satiety control which helps you with weight maintenance, which is also important for a better aging.

30:07: You’re not necessarily trying to optimize protein intake at every meal, which we are trying to do when somebody’s trying to reduce the amount of fat that they have from their body. Separately, this is speculative, but I’m interested in those who maintain a higher protein diet, can fasting help in off periods where you actually reduce your protein intake substantially for whether 24 hours, 18 hours, sometimes even longer periods of time, can that have an impact on dual benefit of maintaining insulin sensitivity but also getting the benefits of higher protein intake both on satiety and on muscle maintenance for both weight loss and weight maintenance?

30:40: Interesting to then try to conflate these different ideas all coming at. It’s one of the reason why people think, this is really confusing stuff. It kind of depends on the lens you’re looking at the subject through. Overall, I think there’s very few compromises to what we have setup. It’s also really important to note that both you and I are always critical of what we put out there to say the goal is not to defend what we’ve done at all cost, but it’s always to say what is the best way to help people that are looking to us for information about how to achieve certain goals. I’m proud of that approach.

Stephan Guyenet - 31:11: Absolutely. Me, too.

Dan Pardi - 31:12: Stephan, thanks so much for joining. Your wealth and knowledge on the subject is extremely valuable and helpful, and I always learn something every time we speak. Thank you again for joining HumanOS Radio. I can’t wait to have you back on.

Stephan Guyenet - 31:23: Thanks, Dan. It’s been a pleasure.

Kendall Kendrick - 31:27: Thanks for listening, and come visit us soon at HumanOS.me.