Making Sense with Sam Harris - #328 — Health & Longevity

Episode Date: August 2, 2023

Sam Harris speaks with Peter Attia about his book, “Outlive: The Science and Art of Longevity.” They discuss "healthspan," centenarians, diet and nutrition, sugar, macronutrients, alcohol, fasting and time-restricted eating, exercise, Zone 2 training, heart disease, blood pressure, cholesterol, cancer, brain health, metabolic disorders, proactive medical testing, medication side effects, Rapamycin, emotional health, and other topics. If the Making Sense podcast logo in your player is BLACK, you can SUBSCRIBE to gain access to all full-length episodes at samharris.org/subscribe.   Learning how to train your mind is the single greatest investment you can make in life. That’s why Sam Harris created the Waking Up app. From rational mindfulness practice to lessons on some of life’s most important topics, join Sam as he demystifies the practice of meditation and explores the theory behind it.  

Thank you. of the Making Sense Podcast, you'll need to subscribe at SamHarris.org. There you'll find our private RSS feed to add to your favorite podcatcher, along with other subscriber-only content. We don't run ads on the podcast, and therefore it's made possible entirely through the support of our subscribers. So if you enjoy what we're doing here, please consider becoming one. Welcome to the Making Sense Podcast. This is Sam Harris. Today I'm speaking to my friend Peter Attia. Peter is a doctor and the founder of Early Medical. He received his medical degree from Stanford University,

and then he trained at Johns Hopkins in general surgery. He also trained at the NIH as a surgical oncology fellow and at the National Cancer Institute. And he's also the host of his own podcast, The Drive. But today we focus on his new best-selling book. The title is Outlive, the Science and Art of Longevity. And that really is our focus. We talk about health span, as opposed to mere lifespan, the lessons that can be learned from centenarians and supercentenarians, diet and nutrition, including topics like sugar and macronutrients, alcohol, fasting and time restricted eating, exercise, heart disease, blood pressure, cholesterol, cancer, brain health, metabolic disorders, proactive medical testing, medication side

effects, esoteric drugs like rapamycin, emotional health, and other topics. The full conversation runs three hours, so it is a fairly comprehensive look at most of the variables we might control to maximize the chances of living a long and healthy life. And now I bring you Peter Attia. I am here with Peter Attia. Peter, thanks for joining me. Yeah, Sam, thank you so much for having me. So you have written this amazing book, which we're going to talk about. The title is Outlive, the Science and Art of Longevity. And first of all, congratulations on the book. It really

appears to have been trumpeted from the ramparts everywhere from Oprah on down, and it's really getting out there. So it's got to be gratifying because when you publish any book, to say nothing of a first book, you really have no idea what's on the other side of that printing press. And this is really about as good of an outcome as I can imagine. So it's got to feel good. It does, yeah. And I think I i was this time a year ago i get effective at least when we're recording this was when i really had the thing ripped out of my hands by the publisher and i remember sort of thinking to myself like i'm not happy about this it's not

perfect blah blah i'm sure the same thing that you've thought of many times as you've obviously written a number of successful books. But then I had this thought that sort of calmed me, which was, look, is it at the point now where I will be proud if my kids read this in 20 years? And if I can answer yes to that question, then the rest is sort of out of my hands. And maybe people will hate it, and maybe people will find a bunch of mistakes in it, and all of this sort of insecurities that I'm sure every author goes through. But I know that once I kind of got to that point of saying, as long as my kids will one day be proud of it, which I know it sounds a bit corny, it'll be okay. And then I think the rest sort of took care of itself. Yeah. Well, it's quite a useful book,

and it's a very candid book too, which you really go into your story in considerable depth. book, too, which you really go into your story in considerable depth. Before we jump into the topics at hand, we're going to sort of track through your book. Obviously, there's much more detail in the book, and I recommend people read it if they want more detail on any of the topics we touch. I should also say that you have a podcast, The Drive, which really goes into extraordinary detail on all of the topics we'll touch and many others. So, you know, if we're going to talk for 10 minutes about lipids for cardiovascular health, your podcast probably has 10 hours on that topic. I'm not, I don't think I'm exaggerating. So I recommend that. I think you're underdoing it. I think, I think I have 10,

rating. So I recommend that. I think you're underdoing it. I think I have more than 10 podcasts on it. 30 hours, yeah. So there's quite a wilderness of detail awaiting anyone who wants to follow you into it. But before we jump into the topics, perhaps you can summarize your background and career in medicine because you've had a kind of an interesting story of how you have come to emphasize the kinds of topics you have focused on. Yeah. I didn't want to go to medical school at any point during my life. I was not a pre-med or anything like that. In fact, I'd already finished engineering when I had a change of heart, decided to go back and do medicine. In medical school, like many others, I'm sure I was a little undecided about what to do. Always had an interest in oncology. When I showed up in med school, kind of thought I

might do pediatric oncology. By the end of medical school, realized I had more of a surgical personality and so decided to do surgery with the plan to then go on and specialize in surgical oncology. And after five years of my residency, for a number of reasons, some of which I write about in the book, I just became quite frustrated with what I've later come to call medicine 2.0, although at the time, of course, I had no idea that that's what was really frustrating me. Then I just decided to kind of leave. I sort of felt like the last 10 years had sort of been not a good use of my time, frankly, and I wanted to go back and get another degree, probably an MBA, felt I already had enough debt. So instead I joined a company called McKinsey & Company, which is a consulting firm, called McKinsey & Company, which is a consulting firm. I went down the path of corporate finance and risk there, which was very appealing to me and to my sensibilities around quantitative things. I

missed my background in mathematics and was happily marching along doing that and sort of spent six years completely away from medicine until my own health became of a high enough priority to me and a high enough interest that the endless pursuit of trying to understand that better kind of gradually led me back into the notion of practicing medicine again, but obviously doing it in a very different way, which is through this lens of prevention as opposed to last-minute treatment. Right. And you've gone very deep into topics like diet and nutrition and exercise, more than the average physician, I would say. And we will cover that. So let's start with what would be our first chapter here on the topic of longevity and really

healthspan, I think is your preferred word, because it's more than a matter of just not dying. How do you think about the main causes of mortality and the main causes of reduced healthspan? And maybe we should define healthspan at the outset here. Yeah. So I think longevity is best explained, at least for me conceptually, I think of longevity as a function of these two things, lifespan and healthspan. Lifespan being the easier to understand because it's the binary one. It's the, you know, you're alive or you're dead, you're respiring or you're not. And the current medical system is really focused mostly on lifespan. It's the metric that gets measured and it's the metric, obviously, that therefore gets managed. Healthspan, which is obviously not binary, is somewhat subjective as well, really speaks to quality of life. And while I think that everybody intuitively gets that, certainly I'm

sure if you ask a person, would you want to live to 100 if the last 20 years of your life you were cognitively or physically debilitated, I think most people would immediately say, no, not really. So very long lifespan in the absence of healthspan is not desirable. But similarly, wonderful healthspan with insufficient lifespan is also undesirable. Sam, if I said, you're going to die at 60, but from now until 60, you're going to be as strong and cognitively sharp as you were in your 20s, I still think we would view that as tragic as well. Your lifespan was cut short. So what we're really trying to do is optimize both.

But I think the biggest insight I've had in the past five years is that if you focus relentlessly on healthspan, you get the lifespan benefits typically along the way. If you do the reverse, that's not necessarily true. If you do the reverse, that's not necessarily true. So what can we learn from centenarians and I guess you call them super centenarians, people who live to be 100 and beyond and in many cases really thrive? I mean, it's almost like their health span is extended by two decades or more with respect to the average population. What have we learned from them, and to what degree do you think they're the correct lens through which to look at the

goal here and the strategy and tactics we might use to extend longevity and healthspan? Well, this is a question I've been interested in for about a decade. And there are two people who have really done a lot of work on the centenarians, the offspring of centenarians, and even the supra centenarians, those who live to be 110 and beyond. And these two folks are both here in the US. So one is a guy named Thomas Pearls at Boston University, and the other is near Barzillai at Albert Einstein College in New York. Now, understandably, most of the work that Pearls and Barzillai have put into this have been focused on the more high-tech side of the question, which is, you know, what are the genes that are associated with this exceptional longevity because it's pretty clear that it's a genetic benefit that's been bestowed on these very infrequent individuals. In fact, from a behavioral standpoint, it's kind of amusing to look at the typical lifestyle of the average centenarian. On average, they're more likely to smoke, more likely to drink to excess, less likely to exercise, and more likely to have poor eating habits. So it didn't take long for people to figure out that

these guys were winning the genetic lottery and not living like monks. And understandably, I think most of the effort has been on what are those genes. I touch on that in the book. what are those genes? I touch on that in the book. But for me, the big aha moment came roughly 2014 when I was kind of reading a paper about centenarian mortality. And I realized that if you look at the mortality tables of centenarians, it looks very similar to the mortality of the rest of us. It just has a 20-year phase shift. And that might sound really obvious, but it's actually not, right? Because what it says is centenarians are just as likely to die from heart disease eventually. They're just as likely to die from cancer eventually. And by the way, they're just as likely to die from cancer once they get a cancer diagnosis as the rest of us. What this tells us is that their superpower, which again is brought on

genetically, is a delay in the onset of disease, not in a resilience to a disease once they have it. I want to have a separate chapter here on specific medications and supplements that might be derived from any insights we've had into the genomes of centenarians and through other means, so things like rapamycin and metformin. But how do you use what we've learned about centenarians so far in your thinking through the strategy and tactics you employ in your medical practice and just personally? and perhaps you want to differentiate between strategy and tactics and how you think about longevity. Yeah. So I think that's a great way to lead into this, which is that insight, which as I say it

sounds relatively so what-ish, I think for me was a real wake-up call, and it made me realize that the only way one is going to somehow improve their longevity is to think about prevention through a much longer lens. So we have to pretend that our coronary arteries at the age of 80, we need to position them to look like they would otherwise look at 60. And the only way to do that is to think about primordial prevention as opposed to just quote unquote primary prevention. So let's use coronary artery disease as an example of that because it is the most ubiquitous cause of death in the United States globally for men and for women. It really is the great equalizer.

for men and for women. It really is the great equalizer. We know this from as early as the early 1970s, late 1960s when they were doing autopsy studies on young men who were dying in Vietnam, that even 18-year-old men have, while not gross evidence of atherosclerosis, i.e. you wouldn't open up their coronary arteries and see clots. Histologically, they already have the process embedded. So in other words, if you look under a microscope at their coronary arteries, you'll see the foam cells, the macrophages that have ingested cholesterol that's been oxidized in the arterial wall, and you realize that that process is actually beginning as we're children. And the slow burn of that process is such that for most people, it doesn't become clinically relevant until you hit about 65. So about 50% of men who are going to have a coronary event in their life will have it before

the age of 65. And about a third of women who will have a coronary event in their life will have it before the age of 65. So that gives you a sense of the timescale. Well, if we want to prevent that, we can't really wait until you're 50. That's effectively the point here. We have to take prevention much more seriously, and we have to significantly bend the arc of the disease curve basically as soon as possible. And we do have examples of this working already, right? So if you take children who are born with something called familial hypercholesterolemia, which is a not terribly uncommon genetic disorder that results in unusually high levels of cholesterol, these are indeed people who can have, you know, MIs, myocardial infarction, heart attack,

in their 20s. And these are kids that actually have to be medicated as youngsters. And if you do that, and if you do it aggressively, these kids can go on to live normal lives. Well, we'll have a separate chapter on heart health and cardiovascular disease here, but let's talk about diet and nutrition. This is really the first stop in most people's thinking with respect to how to prevent really all of the diseases of aging and to live a healthy life. I consider it one of the great scandals of medicine and science generally that there's still any uncertainty about what constitutes a healthy human diet. I mean, it's just amazing to me that there's such a diversity of opinion on this topic. I mean, there are people who will tell you that whole grains and legumes

are among the healthiest things you can eat. And there are people who will tell you with equal confidence that they're just pure poison and there are whole diets marketed around these antithetical views. And so I had thought prior to this conversation that the one totally uncontroversial point in nutrition now is that refined sugar is generally bad for us, and maybe that's still the case. I mean, I think it's generally described as the dietary equivalent of smoking. But right before getting on the mic with you, I think it was yesterday, I stumbled upon this YouTuber who apparently spent 100 days on a diet consisting of nothing but 2,000 calories of ice cream and 500 calories of protein powder plus booze, and he lost 32

pounds and totally revamped his lipid profile. Obviously, that's just an N of 1, and who knows if it's true, but what do we absolutely know is true about diet and nutrition at this point? So let's go through gradations of certainty here. What are you sure of with respect to diet and nutrition that is generically applicable to more or less everyone who would listen to this? And what do you think is just very likely to be true? And let's just track through with those two flags with respect to our epistemic certainty as we touch the various topics.

How should people think about diet and nutrition here? And is there anything on this landscape that is the equivalent of a generic certainty, like it's not a good idea to smoke cigarettes, which I think is a piece of health wisdom we have truly conquered at this point. Yeah. I like the way you framed the question, Sam. And it's sort of funny because, you know, as you know, you've read the book, there's like 17 chapters, two of them are on nutrition, three of them are on exercise, everything else gets one chapter, right? So clearly exercise and nutrition get a little extra attention in part due, I suppose, to their complexity in the case of nutrition and the

impact in the case of exercise. However, during the first writing of the book, I was so annoyed by the problem you describe that I very sort of cheekily sent my editor a one-page version of the nutrition chapter. And I said, this is the chapter. And it was what you just said. It's like, here's what we know. And it was like, I don't know, six bullet points. And I said, how about I just do this and spare myself and the readers all of the crap that follows where I have to start getting into some uncertainty. Needless to say, that didn't go over very well. But what I basically said is, here's what we know. We know that when it comes to nutrition, too much and too little are problematic, though generally on different timescales. Let's expand on that for a second. We've been around for, depending on where you want to draw the line in the sand of where we

began as homo sapiens versus previous forms. Let's just make it easy and say a couple hundred thousand years. For most of that period of time, food has been relatively scarce. So that's fact one. Fact two is, I would argue this, I think you would probably agree, Sam, what separates us as humans from every other species on this planet is our brain. That's our superpower, right? It's certainly not how strong we are or how fast we are or any other sort of physical power. It's really our brains that differentiate us. That brain is an insanely energetic organ. So roughly 25% of our caloric need goes to servicing that organ that constitutes 2% of our mass. Therefore, the trick that allowed us and only us to leapfrog out of the swamp ahead of every other species was the capacity to store energy. And it's important to understand

just how profound that is, right? If we couldn't store weeks and weeks of energy, we wouldn't be here. Now, we store most of that as fat. So obviously excess fat gets stored as fat. Excess carbohydrate gets stored as fat beyond the paltry amount we can store as glycogen, which is just a fancy word for the storage form of glucose. And in times of relatively short fasts, we just break that fat down and use it as energy. And in relatively long periods of fasts, we turn that fat into something called ketones and we use those as energies. But regardless, we can go a relatively long time without food. By comparison, of course, a mouse can go like two days without food before it dies. Even a lean person could go 20 or 30 days without eating. So what's the price we pay for that superpower? Well, up until relatively recently, we've paid no price for that superpower.

It's only in the last hundred or so years where we have shifted from hundreds of thousands of years of food scarcity to tragic food abundance, are we starting to show that actually the drawback of this remarkable capacity to store excess energy is X, Y, and Z, and there are these metabolic consequences of doing so. Now again, those are chronic problems, not acute problems, and therefore on a relatively long time scale, food scarcity or food shortage is still a much greater evolutionary concern. In fact, you would argue the natural selection has really no interest in the problem of overnutrition. But to go back to your question, what can I say definitively? I can say that too much nutrition

is going to be bad chronically. We'll go into more can say that too much nutrition is going to be bad chronically, we'll go into more detail, and too little nutrition is going to be bad acutely. That's fact one. Fact two is there are certain amino acids and fatty acids that are absolutely essential for life, meaning there are certain types of foods primarily in the form of fats and proteins that we must consume in some quantity from the outside world, and failure to do so will result in horrific consequences. So, you know, not just general caloric malnourishment, but, you know, deficiencies in cartilage, bone, muscle, things of that nature. There are also certain nutrients, essential vitamins and minerals that are absolutely essential for life. Everybody of course knows the story of the sailors who were

not given enough vitamin C in their rations, developed scurvy, et cetera, things like that. There are certain things that are toxic to us acutely. So, you know, we don't do very well with certain types of bacteria. So, you know, E. coli in our food, relatively problematic. That's about where it ends, Sam. That's, you know, that's about all I can tell you with capital T truth written all over it. Meaning those are the things that are kind of universally true for which there's no ambiguity. If we start to get into how many grams of protein a day do you need? Why is it that someone can eat 7,000 or pardon me, 2,000 calories of sugar per day and still lose weight? I mean, I have lots of thoughts on those things, and I hopefully have more insight on those things than maybe the average person on Twitter, but we are definitely less able to reliably say things. I guess that speaks to another element of the problem, which is the human body has a remarkable

dampening factor quality when it comes to nutrition. right? So if you think of a system, like an engineering system where you put inputs into it and then you get the outputs out, I think of the body as this remarkable dampener where when you put things in, it sort of squashes the output. So it's very difficult to, in the short term, discern how the input affected the output, to, in the short term, discern how the input affected the output. So body weight is an example. What you ate the day before, from a caloric standpoint, believe it or not, doesn't have an enormous impact on your body weight the next day. That's probably more a function of water weight and sodium than the actual weight of the food, because most food comes with so much water in it. So therefore, looking at your body weight five times a day is not really a good way

to determine energy balance. There's so many other movement systems in it. Furthermore, there's so much variability in our system with how we process nutrients with respect to other variables, such as sleep. So we'll maybe talk about sleep, but a poor night of sleep impacts insulin signaling more than most people would appreciate, and certainly several nights of poor sleep would have an even bigger effect. And the impact of that, i.e. insulin sensitivity on fuel partitioning, meaning how you store the nutrients you consume them and then how you go back to the energy well to draw them from storage,

is quite significant actually. So under two nearly identical circumstances, food-wise, two different nights of sleep could also impact things. So all of these things make it very difficult to study the problem. Yeah, yeah. Well, so one point about evolution, and you actually make this in the book, I mean, evolution can't see really anything we care about. And surprisingly to many people, it can't see the variables that would determine our health span and longevity past, certainly past our 50s, right? I mean, we're just, it just simply doesn't care about you living to a ripe old age and being able to swing kettlebells into your 80s. It just cares about you spawning and maybe helping your children

secure their spawning period so that, you know, maybe there's that maybe you can be a young grandparent from the point of view of evolution and still have some genetic utility. But after that, evolution is blind to what we care about. And so I guess I'm always hesitant to, when I hear of a diet that is using our evolved environment as a reference point, like the paleo diet, right, where it seems to put a lot of stock in the 200,000 years that preceded the present moment. about how you view the limitations of the lessons we can draw from that. It just seems to me that we're living in the world of science fiction now. If we care about living to 120 with anything like a modicum of healthspan, we have to figure it out on the basis of principles that evolution has never anticipated. Yeah, that's a very interesting question, and it's one I think a lot about.

And you're absolutely right, by the way. In fact, just taking us back for a second, I could point to a couple of genes that persisted because of evolutionary advantage that are a distinct disadvantage today. So the LP little a phenotype, which comes from the LPA gene and the APOE4 gene. So these are both genes that are highly prevalent today and highly associated with disease, cardiovascular disease and Alzheimer's disease, respectively. It might be tempting to ask the question, why the heck do these genes exist? And we know that the APOE gene, the E4 isoform was the original isoform. Well, I think the easiest answer is one, evolution doesn't care about Alzheimer's disease because nobody's getting it before reproduction.

But even two, it's that the ApoE4 isoform offered protection in a world where infection ran rampant. And the same is probably true of LPA. It certainly increased blood clotting, which would have been a huge advantage if you can think about it, right? Hundreds of thousands of years ago, if not just a few hundred years ago, to have a greater likelihood of clotting in the event of a cut would have been an enormous advantage. Today, it's not so much an advantage and all the negative consequences of LPA work against you. With all that said, lots of examples of those situations. When it comes to nutrition, I find it hard to make the case that any extreme diet is our optimal diet. But I find myself relying on an evolutionary example here, which is we were the most opportunistic omnivores around. So I can certainly make the case for extreme diets to treat disease, meaning if a person has type 2 diabetes, then maybe some extreme diet or some

sort of extreme dietary restriction is the optimal diet. But I would certainly argue that if you don't have, you know, if you're just starting from a place of health, I feel like one shouldn't have to be that restrictive. Though maybe I find myself making this argument based on the fact that we have lots of evidence that at least to certain age, and this of course is based on looking at the few remaining hunter-gatherer societies that do still manage to make it into old age, consuming basically opportunistic omnivore diets. So it's a little bit of evolution, but it's also a little bit of looking at, for example, certain hunter-gatherers that still do exist, for example, in Australia and Africa. Okay, so let's talk about macronutrients, right?

We're talking about fat, protein, and carbs. I guess to come back to the crazy example I started with of the guy who ate nothing but ice cream or 2,000 calories of ice cream plus 500 calories of protein powder and alcohol. So he sounded like he had fun, at least for the first week. The fact that it was ice cream rather than Skittles makes me think that maybe it's not quite as insane a story as it might seem. Because I remember the one time I tracked my blood glucose

for 14 days. I was actually surprised to find that ice cream, I assume because the sugar is being mediated by fat, was not as high a glycemic load as many other things that were ostensibly much healthier that I might eat. I remember a vegetarian burrito just sent my blood sugar off the charts, whereas ice cream was pretty unspectacular. But in any case, how do you think about fat, protein, and carbs in general? What generically can you say about what most human beings most of the time require on that front, and how can you extrapolate from those principles to what we might assume is a, if not the perfect diet, at the very least, a very safe bet for a healthy one. So I think about this in kind of a formulaic way that maybe

takes a little bit of the romance out of eating, which doesn't mean that I necessarily adhere to it with that rigor. If I'm going to think about this as an engineering problem, it's actually, I think, quite simple. Before I do that, I think it's worth addressing perhaps the mystery in the ice cream man. Let's assume that this is correct. I think that's not an assumption one should take lightly, right? So I think the whole, I did this on YouTube, therefore it's true, is one needs to have a healthy degree of skepticism. And it would be more interesting to see that in a clinical trial. But let's just assume there was a clinical trial that said we took 700 overweight people whose average caloric intake in the run-in period was X and we created a 25% caloric deficit that consisted of what you just described. Do you think they're going to lose weight?

My answer to that question would be yes. I would expect them to lose weight? My answer to that question would be yes, I would expect them to lose weight. In other words, I think that the single greatest determinant of energy balance is indeed, or maybe a better way to say this, the single greatest determinant of weight loss is going to be energy imbalance, would be maybe the most accurate way I could say that. In other words, a caloric deficit, no matter what you're eating. No matter what it's constituted by. That's right. So if we did another thought experiment and we said, look, we're going to take a thousand people who are all ostensibly overweight, and let's just make it really elegant and say that they're all basically genetically equivalent, so it's just like a bunch of mice and they're all

coming in at 3,500 calories per day and their weight stable at 3,500 calories per day. We're going to divide them into two groups. And the first group is going to go on a 2,800 calorie a day diet of junk food. The other group is going to go on a 4,000 calorie a day diet of whole foods, right? The best, you know, whatever, come up with your favorite best diet. There's no doubt in my mind that that group eating 4,000 calories per day is going to be heavier when the trial is done than the other group. And by the way, they might also be less healthy, that big of a gap because of something we should probably talk about, which is why is it that excess energy is harmful? Because it's not the aesthetics. It's not because you lose your six-pack that you're unhealthy. There's something

going on that's much more important to understand. With all of that said, how do I think about the problem? I think about the problem? I think about the problem by saying, and there's really a fourth macronutrient, Sam, that we should at least mention, which is alcohol. And the reason is alcohol is so calorically dense, right? So I think most people know that carbs and proteins are roughly four kilocalories per gram. Fat is nine kilocalories per gram. Well, ethanol is seven. So one has to be mindful if they're in the business of trying to lose weight of just mindlessly consuming alcohol for at least two reasons. The first being the energetic reason. The second being if you're anything like me,

there's no greater way to reduce my inhibition around food than to give me a couple of drinks. So I start with protein because protein is the most important in my view. And there's different ways to think about this, but I would just start by saying that the RDA, the recommended dietary allowance, is clearly incorrect. And I go to great lengths in the book to kind of explain this. I've also written about this elsewhere. I've got multiple podcasts on the topic. The RDA, which offers something to the tune of 0.5 grams of protein per kilogram of body weight, or 0.5 to 0.8, I think is the RDA. That's what it takes to not have malnourishment. But if we want to really talk about thriving, especially in people over 50, it's probably closer to 0.8 to one gram per pound of body weight. So again, that's a huge difference, right? So if you take a person who weighs 175 pounds or 80

kilos, the RDA would say that person can get away with 60 grams of protein. I'm arguing that person should be between about 150 and 180. So it's a huge difference. And I'm certainly not saying this alone. Some people much smarter than me would agree with that. So we start with that. The next thing I'm thinking about in the formula is what is your carbohydrate tolerance? So you mentioned a moment ago that you'd worn a glucose tracking device, I assume a continuous glucose monitor for a couple of weeks. Yeah. So I think those are really helpful tools to give people a sense of what I mean by carbohydrate

tolerance. Carbohydrates are also very important. And I unfortunately bear a tiny bit of responsibility in a previous life for probably demonizing them too much. But the reality of it is, you know, carbohydrates are important. They're our most abundant and quickest source of energy. So there's nothing you can do to turn food source into ATP quicker than glucose. And it is the preferred fuel of our brains. In fact, even in a state of total starvation, 40 days without food, which believe it or not, was actually studied by George Cahill at Harvard back in the 1960s, not a study to be replicated. They had subjects that fasted for 40 days. They were still getting 50% of the energy to their

brain was coming from glucose. The other 50% was coming from ketones. If you ask where does that glucose come from when you're starving, it's because making the ketones and breaking down the fat to do so creates a byproduct that gets recycled into glucose called glycerol. But anyway, glucose is important. The problem with glucose is too much of it chronically is harmful, not acutely. Acutely, we are much more interested in protecting against the downside and not having enough of it. So hypoglycemia is acutely fatal. Hyperglycemia is not outside of very extreme circumstances that can only exist if you have type 1 diabetes. So the body, again, going back to kind of the

evolutionary thing we talked about earlier, isn't really working that hard to protect you from a blood glucose of 150 milligrams per deciliter, which is about 50% higher than normal. It doesn't truly care. However, the effect of that over many years is devastating. It will destroy your kidneys. It will destroy your heart. It will destroy anything in your body, including your brain, that has small blood vessels. And that's why people with type 2 diabetes have twice the risk of most diseases, right? Cancer, heart disease, Alzheimer's disease, etc. But that's not a huge difference, right? So we have to figure out what's our limit. And I think there's sort of two ways to think about this. What's your average blood glucose and how much

variability is there in what you eat? And again, you can figure this out using traditional biomarkers. You can figure this out using a continuous glucose monitor. But basically, once you figure out how much protein you need, the next question is, how much carbohydrate can you tolerate while keeping yourself in those parameters? I offer some suggestions for these, but I think if you're going to be really aggressive and have, if you want sort of an A-plus on your report card here, I would say having an average blood glucose below 100 milligrams per deciliter. That takes into account all the peaks and valleys, would be considered excellent. That would correspond to about a hemoglobin A1c of 5.0. Now, what determines that? Well, your activity level, how much muscle mass you have,

how insulin sensitive you are, how well you sleep, how much hypercortisolemia is going on, genetic factors certainly play a role in it. All of these things will matter. And even for a given individual, they'll change. So when I was a cyclist, I could consume 800 grams of carbohydrates a day and still be within that band. Today, it's much lower than that. So you sort of have to know what that looks like. And then the final point is that fat makes up the difference. And the total amount of fat that goes in as basically a plug is to determine where you need to be on energy balance. So believe it or not, in a reasonably healthy diet, your appetite can serve

as a reasonable backstop for how much you need to eat. And by the way, going back to the funny example you gave of the guy eating ice cream all day, one thing I'm always interested in, and I don't know if the guy talked about this in his video, is what was his degree of satiation? In other words, when you're eating 2,000 calories of ice cream a day, what kind of cravings was he having for other food? And was he satiated? Did he go to bed at night feeling like I'm full? Or did he kind of go to bed starving because his body was actually demanding more, but he was kind of capping it artificially? Did he comment on that? I don't remember. I remember that the punchline was that he was ultimately quite miserable on this diet. I mean, he was surprised to be as unhappy as he was, despite the improvements

in his weight and lipid profile, but he was not having fun ultimately. But there's another component to that, right? Which I think is, you know, I think you asked earlier, like what, what would, what would we agree on is universally true? Another way to ask that question is if you had all the experts in the room, could they agree on what is the driver of the modern epidemic of obesity? So it's a different question, but they're related, right? Yeah. Well, why have we never had an answer to that? And I think the answer is that the nature of science is that most people study one pathway or one vehicle. And in obesity, I think there are so many that I think there are a dozen plausible explanations. individual who's obese is, their obesity may be driven by two or three of those as the dominant drivers versus others. For example, one theory of obesity is that our food is so much less nutrient dense than it used to be. This is one thing I actually didn't write about in the book that I really wanted to, but there simply wasn't enough room to get into nutrient density and to talk about, for example, soil health and how soil

health impacts plant health and how that impacts animal health, et cetera. But there's very little doubt that food today, whether it be spinach or beef or barley or whatever, has fewer nutrients in it than it did 100 years ago. And the question is, are we intrinsically innately wired to seek a certain volume of nutrient? As the nutrient density of our food goes down, are we simply seeking more calories to meet our nutrient needs? That's an argument. There's another argument that says the same thing. We're hardwired to get a certain amount of protein, but as our sources of protein are getting diluted,

we're seeking out higher and higher caloric volumes of food to meet the same protein requirements. Other theory, of course, is that it's all driven by palatability. The more palatable the food, the more likely we are to seek it out. You get the idea that there's multiple theories. It's also possible they're all kind of partially right. So on this question of protein, I think in your book you emphasize, as you did here, that as you get older, it becomes even more important to focus on how much protein you're getting. What are the prospects of getting sufficient protein, as sufficient as just defined by you, something like a gram per pound of body weight if you're a vegetarian or a vegan. I realize this is dangerous territory with respect

to getting put on the radar of the vegan mafia, but what are your thoughts about cutting meat and even all animal protein out of one's diet and still getting the requisite amount of protein as one gets older? I mean, I think it's still possible. It just gets harder. There's no question. It's a trade-off. What you're referring to is anabolic resistance, and that starts roughly in your 50s, but certainly increases probably non-linearly from there. And that's where you probably have to start getting closer to that one gram per pound of body weight to maintain maximal muscle protein synthesis, the process by which muscle gets broken down and rebuilt. And the reason this is so important is that sarcopenia is an enormous problem of the elderly.

Sarcopenia is the disorder of low muscle mass. And with sarcopenia and frailty comes enormous mortality. I think this is actually kind of the hidden epidemic of aging. You know, I do write about this, but I think I write about it a little bit more in the exercise chapter, which is once a person reaches the age of 65, if they fall and break their hip, and I can't imagine there's a person listening to us speak now, Sam, who doesn't know somebody for whom that's happened, right? It's like, oh, my friend's mother or somebody, right? I've literally talked to two patients in the last week who have had parents go through this. So if you're over the age of 65, you fall and break your femoral neck or your femur,

there's a 15 to 30% chance you will be dead in the next 12 months. And if you don't die in the next 12 months, of those who survive, meaning of the 70 to 85% who survive, there's a 50% chance you will have a full-scale reduction in your mobility for the remainder of your life. Meaning, if before this incident, you walked freely, you will forever be using a cane. If before this incident, you were using a cane, you will be in a walker, et cetera, et cetera, all the way down to a wheelchair. So accidental deaths due to falling is the leading cause of accidental death for people over the age of 75 at a level that exceeds even what we see for accidental overdoses

for people under 65. I think most people are probably now aware that accidental death due to overdose has become the most common cause of accidental death for people under 65, eclipsing even automotive accidents. So with all of that said as the background, frailty and sarcopenia are an enormous problem. And not just because of what they do showing up on death certificates, but because of how much they rob people of healthspan. So even if it doesn't kill you, it can easily ruin the last decade of your life. So with all that said, the antidote to this is to have as much muscle as possible,

to be as strong as possible, to be as fit as possible. I make this joke all the time, but it's true. I mean, how many people have existed, Sam? It's like there's 8 billion now. How many billion were there before us? Isn't it about another? I think it's about 110 billion. Okay. I'm willing to bet, and I don't know how we could ever verify this, but my bet would be in the entire history of that 100 billion people, I would bet that no one in the final days of their life said, I wish I had less muscle. I wish I was less strong. It's simply not possible. So protein intake is an essential component of maintaining muscle mass. And of course,

resistance training is as well. So to your question, can a person who morally or philosophically doesn't want to consume meat or who doesn't want to consume animal protein still avoid sarcopenia? I think the answer is yes, but they have to acknowledge that they're in for a harder ride, meaning they're going to have to work harder at eating than maybe you or I do if we're willing to consume meat and animal products. Yeah. On this issue of sparing muscle mass, I mean, there's this, I guess, two questions. Well, one actually has a potential, poses a potential puzzle with respect to evolution. So when you just stop eating, when you start fasting and even start starving, and you rely on your fat stores, as evolution has permitted, why doesn't that reliance spare muscle systematically until you lose all your fat? Because my understanding is if you start fasting, there is some considerable

risk that you are going to be losing lean muscle mass during that fast. Why is that? It seems like evolution would have recognized that more muscle is generally better for all sorts of things, and the fat store has been put there for a reason to be utilized under just these circumstances. So why doesn't it just spare muscle systematically? Yeah, it's a great question. So below a certain calorie threshold, we will use protein for energy. So for example, if you went on a thousand calorie a day fast, but that thousand calories was 250 grams of protein, right? So 250 grams of protein is about a thousand calories. You'd lose weight, but you'd probably lose muscle as well. So why is that? Well, first of all,

the body does have a pretty remarkable tool to prevent the complete emaciation of muscle, and that is ketosis. So earlier I mentioned glycogen, which is the storage form of glucose. So we can store, I don't know, somebody your size or my size, Sam, we could probably store 400 grams of carbohydrates. So you could probably put 300 grams of glucose into your muscles. So that's about 1200 calories. And you can put another 100 into your liver. And by itself, if you never made any other tweak to the system, that's like a day's worth of energy. Obviously, lots of times when we need to go more than a day without eating, as sort of our ancestors at least did. What you don't want to do at that point is immediately start tapping muscle. Because if you did, you would break down muscle

in a really rapid fashion. In other words, if we broke down muscle for amino acids and sent those amino acids to the liver to undergo a process called gluconeogenesis, we would make glucose out of the muscle. I'd have to do the math on it. I've never done it, but I think it would be just a matter of a week or so until you'd be completely broken down. So while that is happening somewhat, it's more happening because we are not providing new amino acids for the muscle protein synthesis. So we constantly break down muscle and replace it partially with amino acids that we

already have broken off muscle and partially with new amino acids that we're eating. So it's actually a very, the only way you can tease this out, by the way, in research is to do labeled studies. So you give people amino acids that have tracers on them, and then you can distinguish between how much of the muscle protein synthesis is coming from the exogenous amino acids versus the endogenous amino acids, and what you realize is it's actually a pool of both. So I don't know if I'm making sense to the listener. I think you understand what I'm saying. But basically, in a form of starvation, you've taken away half of your amino acid pool,

which is the exogenous pool, and you're only able to then rely on the endogenous pool for muscle protein synthesis. And that's why you will experience muscle wasting. But that's far better because at least you're not using muscle to then make glucose via gluconeogenesis. That would be a catastrophic problem. So I guess what your question is, is why hasn't the body figured out a way to undergo muscle protein synthesis without exogenous amino acids? But honestly, I think that's sort of like asking, why do we need food? So yeah, let's touch this final topic under nutrition of fasting and time-restricted eating, because I know you've experimented a lot with this personally, and many people are interested in this as just a way of reducing caloric intake. I mean,

just shrinking the time window in which you eat as a strategy for not living with a toxic surplus of calories. What are your thoughts on this now? And I guess, obviously, it connects with a certain strand of research on the topic of longevity where caloric restriction has, I think, across every species in which it's been looked at, shown to be correlated with longevity. How do you think about this now? So I guess I would just sort of put this all in the context of the broader problem, right? So if the problem is, what do you do in the case when an individual is overnourished, which I think is just kind of a technical way to say they have too much stored energy and it is exceeding the point of utility. And it's now that energy is spilling over into other areas and causing problems. So that fat is spilling into

the space between their organs. It's getting into their muscles directly. It's getting into their pancreas and it's toxic, right? It's inflammatory, it increases insulin resistance, which exacerbates the problem, all of these things. The solution to that is reduction of energy input, right? So you have to create a caloric deficit in that situation. Broadly speaking, there are three ways to do that. broadly speaking there are three ways to do that the first is to directly day in and day out minute by minute think about reducing intake so that's the example i think of uh you know what what we've just been talking about right it's like okay i've been you know i eat 3 000 calories a day and i i need to i need to lose fat i have to reduce,500. I'm going to track those macros and count up to 2,500

calories a day. The other way to do it is dietary restriction. Come up with a restrictive diet and focus on excluding as many things as possible. The more restrictive that diet, the more likely you are to achieve energy imbalance. If you go on the no lettuce diet, it's not going to be very restrictive. You're not going to lose weight. But if you go on the potato only diet, you almost assuredly will lose weight. Now, the third strategy is what you're talking about, which is time restriction. Just create a narrow enough window in which to eat such that at some point, the window becomes narrow enough that you're going to create an energy deficit. So calorie restriction is the direct way to do it. Dietary and time restriction are the indirect ways to do it. I was sort of, I would say probably six, seven years ago of the view,

because we really didn't have the data at the time, that thought there was something beneficial to time restriction beyond the caloric deficit. In other words, I believed that the act of not eating for 18 to 20 hours per day, in and of itself, brought a metabolic benefit independent of the caloric deficit. I would say that that view has been refuted by at least two studies in the past three years, two years, that have, when controlling for intake, demonstrated two things. feeding seem to come down to the reduction in calories. But a more important finding has been that there may actually be a downside to time-restricted feeding, which is that many people are incapable of consuming sufficient enough protein in that window. And while they do lose weight, they may disproportionately be losing muscle. Interesting. Just to backtrack for a second,

so the restriction of specific foods, do you think there's any metabolic magic there where you hear someone who's on an all-meat diet, say, and they're losing weight versus any other strategy? If you are emphasizing one macro over another, do you think it isn't, at the end of the day, just a matter of calories in with respect to energy balance? Is there metabolism working above the mere caloric physics that accounts for weight loss on certain restricted diets? I don't think so. And I do think now we're clearly, if we go back to the way you posed the questions at the outside of our discussion vis-a-vis nutrition, I think we are clearly in

the area where we need to have a lot of humility and just acknowledge we're now speaking in the unknowns. But my intuition based on the existing body of literature is that from an energy balance perspective, a calorie is a calorie. So I do not believe that we are... Because the only way that it's not is to say you are impacting energy expenditure. So does the body metabolize these calories different from those calories? And the short answer, I guess, is yes, there's a little bit of that. So there's something called the thermogenic effect of food, where we require more energy to energize, to break down protein than we do carbohydrates and fats. And so there is a slight discount metabolically that comes from that. Do I think that that is why a carnivore diet being basically, I don't know, it depends on what kind

of meat you consume, but a carnivore diet could easily be one-third protein, two-thirds fat from a macro perspective. Do I think that that explains the profound weight loss that people experience when they experience it on a carnivore diet? I don't think so. I think that really comes down to just reduced intake. But this gets to an important point, right, which is the point of satiety. And this is the hardest thing to study because, you know, if you're doing a really well-controlled study, you actually want to feed people prescribed amounts of food, thereby ignoring or negating the benefits or disadvantages of a change in satiety. But in the real world, satiety might be the single most important factor in determining

long-term compliance, right? Right. I don't believe that most people can exist in a state of perpetual hunger, day in and day out. Clearly, some people can, but I don't think that's the norm. in and day out. Clearly some people can, but I don't think that's the norm. And therefore, whatever is at the root of the societal energy imbalance we have must have at its basis something to do with satiety. Unless you believe people are just mindless eating machines, and I'm just not sure I'm ready to fully concede that point yet. Do you happen to know what the experience is of

people who have taken the caloric restriction principles to a proper extreme? I mean, I know there are food scientists and doctors and a few other people who have decided that the data are in. We know what happens to mice. We know what happens to yeast. If you dial down the calories to the absolute minimum maintenance level, you increase lifespan by an enormous amount. And so there are people walking around, you know, I don't know what their caloric ceiling is, maybe something like 1500 calories. They're living on a diet that abstemious for years at a stretch, is their experience one of being perpetually hungry or do they reset and experience kind of a normal level of satiety? I haven't studied them.

I know anecdotally a little bit just from, I have a couple of colleagues who have even gone and spoken at their conferences because there are societies of CR out there. There's caloric restriction societies of people who do exactly what you're describing. I think it's probably closer to 1,800 to 2,000 calories per day. But yes, I think it's an interesting question. I mean, there's two interesting questions there, right? At least two, right? So one is, what is their subjective state of existence? Are they constantly thinking about food? I will say this, I've definitely spoken to a lot of bodybuilders, and that's about the amount of calories they're on during a cutting phase.

Yeah. And Sam, I've never spoken to one of them who hasn't said that they don't want to end their life during that phase. Yeah, yeah. So now again, you could argue, well, they're only doing that for 12 weeks, and maybe that's not long enough to acclimate. And they're also asking a lot of themselves because they have to exercise during that period of time. So that's not an apples to apples comparison, but that's question one. I think the more important question in as much as it's academically interesting is,

does the draconian step that they're taking translate to an improvement in lifespan and healthspan for the species of interest, which is humans. So everything you said is true, right? We know that yeast and worms and fruit flies and rodents, at least in a laboratory environment, will live longer under CR conditions. But we don't know if that's true for humans who live in the real world. And as I devote probably half a chapter to in the book, when I go through the NIH Wisconsin NIA experiment with rhesus monkeys, it turned out to not even be clear that CR was beneficial there. Yeah. You mentioned alcohol as a fourth macro here. I was going to ask you about it under the heading of lifestyle, but maybe we'll just discuss it here.

about it under the heading of lifestyle, but maybe we'll just discuss it here, is maybe it's been 10, 15 years since the emergence of a kind of cottage industry in hopeful articles about the health benefits of alcohol, some of which I think in retrospect were sponsored by the alcohol industry. It's not to say that a conflict of interest always proves that the science is bad, but what do we know about the health impacts of alcohol? And perhaps we can boil it down to kind of a personal punchline. I mean, just how is it that you approach this yourself personally? What have you decided is the risk-reward trade-off that you're comfortable with in your own life? Yeah, I mean, I'll just give you my answer for me, but then I can sort of explain it or defend it or explain why it might be illogical. So my view is I do continue to

consume alcohol, but I think from a risk standpoint... If you'd like to continue listening to this conversation, you'll need to subscribe at SamHarris.org. Once you'd like to continue listening to this conversation, you'll need to subscribe at SamHarris.org. Once you do, you'll get access to all full-length episodes of the Making Sense podcast, along with other subscriber-only content, including bonus episodes, NAMAs, and the conversations I've been having on the Waking Up app. The Making Sense podcast is ad-free

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