Eric Ravussin, Ph.D.
Appearances
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We don't need many because we need to homogenize the air in the room. I see, so that's the bigger effect. The room is the same as the other corners. That's why, but we have to measure humidity. You have to measure temperature because you have to do this correction, what we call STPD, which is standard pressure, et cetera, to calculate the energy generated by this oxygen.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
But yeah, I mean, it's quite phenomenal, the accuracy of those. And to go back to your question, the accuracy or the precision is about two and a half percent. Now, if you repeat yourself five times and myself, there's a little bit more variability because we vary from one day to another one. And so on.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
But I mean, this is quite amazing that we can calculate so precisely your energy expenditure during a day or two days and so on. I wish we had the same system to calculate the energy that we put in.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
When it's in free living, it's worse. When you do that under supervision and you provide all the meals like Kevin Hall is doing, like we're doing, then you have a good estimate and you subtract what is returned on the plate or this kind of things. But it's not normal life. As soon as you go to normal life and free living conditions, things are falling apart.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yes, but on the other hand, if you take your lifetime history, maybe you're an exception, but I have gained some weight. When I got married in 1975, I weighed 69 kilos. Now I weigh close to 77. Now it's 50 years later, of course, but you have this change. You have also a change in your body composition. And it's very rare that people are staying the same constantly.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I mean, you may be an exception.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I think I had an answer. I hope that I had an answer, but I don't. You know, when leptin was discovered, it was a ha-ha moment. We have a signal which comes from the energy storage, and therefore, you know, it seems to regulate food intake, also energy expenditure and all that. I was fortunate to have access to
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
The three Turkish leptin deficient people that we measured in these chambers in Baton Rouge, we thought that we would have a clue, and it was not the case. We know that leptin is very good to defend against the loss of weight when it becomes extreme, but it doesn't work on the other side of the equation when you creep up.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
with your weight because you become leptin resistant and your leptin is not telling you stop to eat. I think that we learn a lot about the biology of energy balance thanks to leptin. But then we need to think that we have also signals coming from the fat-free mass. Now, what is the fat-free mass?
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We measure it as everything but the fat, and we call that fat-free mass, but it's liver, it's skeletal muscle, it's everything but the fat. And I think that there are signals that we are still chasing. John Blundell showed that we eat according to our fat-free mass.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
which is basically we eat according to our resting metabolic rate, because fat-free mass is the major determinant of your resting metabolic rate. But what are the signals? I don't know. I still don't know. We have to be modest here and say there are still things that we don't understand when it comes to this energy balance.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Now I can understand that why you don't gain five kilograms over this coming year. Because in response to creeping up your weight, you burn more energy. If you do the same physical activity, this extra 5 kilos or 10 pounds is going to cost you more energy. Your resting metabolic rate is creeping up and basically you offset that. But why are we so good at maintaining, like you said,
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
within a couple of pounds over a year or two years or three years or five years. And I think that we are still missing some signals, but I think that there are signals coming from when FGF21, which is a signal coming from the liver, was discovered. I said, oh, maybe that is. Or when you have some of the myokines coming from the skeletal muscle, I said, maybe this is it. And it's not been it.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And I think that we have to be modest and say, hey, we still have things to discover when it comes to this regulation of energy balance. But as a population, we have not been very good. I mean, from the 1980s to 2010, the American population has gained 10 kilograms. It's 22 pounds in 30 years. It means that there is still the major driver is this environment.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And the change in the environment has been the trigger of this weight gain. But of course, some people are successful, some are less, and this is a problem. And of course, now we have an epidemic of obesity. It has replaced the contagious disease of the past, and now we have all these constellations of conditions which are associated with obesity.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah. Peter, when I first joined the NIH, I did a study in Pima Indians, who are very prone to weight gain, as you know. And we measure in 150 people the 24-hour energy expenditure, as well as the resting metabolic rate. And we found that there was large variability in between people after adjusting for their body size, fat free mass and fat mass.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Now we do better because we have organ size and we do MRI and all these kind of things. But there is variability and this variability is associated with family membership. In other words, we can say that there is a genetic background to that. But what we found was that those people in the lower tertile of this metabolic rate adjusted for body size were at much higher risk of gaining weight.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
But when we tried to attribute the weight gain either to energy expenditure being low or the other side of the equation, intake was 80%. It reminds me, there are so many systems which are basically regulating energy expenditure and food intake. Take nicotine. Nicotine is a stimulant of energy expenditure. Smokers have higher metabolic rate. but they have less appetite.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Take the activity of your sympathetic nervous system. It is also thermogenic, but it cut appetite. And I think that we have to understand better these two systems. But to answer your question, I would say 80% is on the side of the energy intake.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And, you know, for example, sorry to interrupt, but we know that exercise is pretty bad for weight loss. If you just tell people, okay, go to the gym three times, or you even do under supervision, people don't lose weight. And Donnelly at University of Kansas has done a ton of study like that. And the physical activity for weight loss is a B minus at best in terms of evidence that it plays a role.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I think, first of all, if you try to put calories on your exercise, it's easy on a bicycle. You know the efficiency, 25%. You know the workload and so on. And you can calculate, or you can use your mask and measure oxygen consumption. It's very easy like that. And I think that there is a compensation. Now, exercise, very vigorous exercise is anorexic.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
You don't want to eat after you finish a marathon, or at least I don't.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
But light exercise has the opposite effect. I think it drives a little bit appetite. And I think Tim Church, who was at Pennington, did a study called E-Mechanic. And basically, they measured every calorie spent. on exercise, on a treadmill, on a bicycle, an ergometer, and all that, and look at the weight of the people with these different doses of exercise, and there was a compensation.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Now, what it didn't measure was to use doubly-labeled water. Did they compensate by being less active out of their periods of exercise? You have 90 minutes of exercise, but then, you know, you relax a little bit more rather than fidgeting or moving and so on, or you sleep a little bit longer. This he didn't measure, but there was this compensation with food intake.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And I think, first of all, I didn't say that exercise is not good for health.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
when you run a K or a mile and so on, versus how quickly you can ingest the calories, the same amount or much more. And I think that there is a difference here that people understand. But exercise and physical activity is the key for weight loss maintenance. And you know the weight registry from Rena Wing and Jim Hill,
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
they showed that those who were successful at maintaining the weight loss at five years after the intervention were those who engaged in more physical activity. And I still believe that a nutritional approach to weight loss without physical activity or exercise prescribed is not a good strategy. We should implement both and try to have people enjoying the exercise.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I think so. I think so. But I have found memories of our interactions.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Most people, I remember one of my colleagues, Richard Bergman, said, I would never exercise. I'd rather be sitting in a cold bathtub to generate some heat rather than exercise. And there are some people who cannot exercise. But I think, again, this is from childhood, that you take the taste of exercise, that you become more physically active in the rest of your life.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
It's not at the age of 40 because you have too much weight that they're going to tell you, oh, you have to do your 150 minutes per week of moderate to vigorous activity and all that. It doesn't work in general, but I think physical activity is a key point in metabolic health in general.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Above your resting?
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I don't have an answer to that because it's not my field, energy intake. But on the other hand, you just mentioned the GLP-1. I think these gut hormones, I mean, you take GLP-1, GIP, CCK, PYY. Glucagon. If you put glucagon in insulin, I was talking about the gut, the GI hormones.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Anyway, I think that there is no question now we start to know more because they are such good targets for weight management. We start to know more about the physiology of these hormones. And I think that there is no question in my mind that the speed at which you deliver this food
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
in the stomach and it leaves the stomach is very important for the kinetic of these gut hormones, which are important for the regulation of your food intake in general. I think this is one of the things that these GLP-1 and combination of peptides now has shed light on is that they are potent modulators of your intake.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Now, the interaction between the exercise that you do before and the meal that you have 20 minutes after and the speed of the meal and all that, I don't know this triangle how it works, but I think it would be a very good topic of research to know the interaction between your physical activity or the bout of exercise, the speed at which you ingest the calories, and the delivery of these gut hormones.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yes, it was the question. Isocaloric is the important word.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Because now, can you do that in the everyday life under not isocaloric condition, but what you want to eat?
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
No, I think it was a question, and we were a little bit skeptical. It was the start of the carbohydrate-insulin model. We're used to the energy balance model, but I think it was a good question, and I like the way we debated that with the red team, the blue team, if I recall correctly, and we were arguing about the best design.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And at the end, now if I had to redesign this study, I would do it differently.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
The experiment was done to do a isocaloric intake over four weeks, I think. We had the baseline diet, which was the SAD diet, the standard American diet, and we had after a low-carbohydrate diet or ketogenic diet for four weeks.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And the hypothesis was that, and this was led by the people who have been bringing up the carbohydrate-insulin model, saying that you create a basically uptake of these substrate from the blood into the storage, mostly the adipose tissue and maybe some in the liver.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
and you deplete from substrate or energy substrate your circulation and it puts you in a state of semi-starvation, what is happening when it goes to the brain when you have semi-starvation, you shut down your energy expenditure and you increase your appetite. And this was playing with that, saying that now if we switch to a diet which is going to be less conducive to storage, i.e.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
less insulin secretion, because he was less than 10% carbohydrate, between 5% and 10%, if I recall correctly, we would cause this, basically, this semi-starvation condition in the systemic circulation. And this would basically increase your energy expenditure. And I think that David Ludwig at the time had some data already showing by doubly labeled water that there was an increase.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
But we are arguing that doubly labeled water is not precise enough. It goes back to our discussion about indirect calorimetry. And we said, why don't we do it in the confinement of a metabolic chamber? And this is what we did.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And to my surprise, there was an increase at least early because we had couples of, I didn't go back to the papers, but we had measurements every week for two days, if I recall correctly, for the four weeks. And the first week and maybe the second week, there was an increase which was significantly higher. in sleeping metabolic rate as well as 24-hour energy expenditure under the ketogenic diet.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And boom, yes, there is an increase. Now, was it a significant physiological increase? I mean, we can argue about that. When we talk about metabolic adaptation, because people are talking about that now, we always say we need at least 150 calories. In the study, we achieved statistical significance, but it was just above 100 calories per day. And I was surprised myself of that.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Now, we didn't measure the appetite of the people. I mean, were they less hungry under the ketogenic diet? Now, it brings us to all the weight loss studies which have been done either with a low-fat diet or low-carbohydrate diet. If you do a meta-analysis, it seems that there is a slight advantage to the ketogenic diet for the weight loss period.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Basically, I was surprised and I was, as a Swiss, I was kind of a little bit more neutral sometime rather than the two camps, the red and the blue. I was surprised that there was this effect, but it disappeared at the fourth week or the third and the fourth week.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We had sleeping metabolic rate of 24 hours.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I have been for 24 years at Pennington. I was associate executive director for clinical science. I'm not the head of the Pennington. I joined after spending two and a half years at Eli Lilly. And before I was 15 years intramural NIH. And the reason I came to this country was to build the first
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I wish I had an answer. I mean, I'm tortured between very well-controlled studies we do, like Kevin Hall does, where you basically domicile the people, you feed them whatever you want, you know exactly what you feed them, and you look at outcomes. I mean, I like that, but then how do you transpose that in real life?
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And one of my mentor was JP Flat, and JP Flat says, obesity scientists, they have a tendency to either look at the expenditure side of the equation or the energy intake, but they never put the two together. And he was right, because a lot of studies, you have an outcome which is on this side or on this side, and you maintain the other one.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And I think that, to me, designing a study would be, first of all, in free living condition, but it would need a lot of people. because you know you can prescribe all what you want to people. They're going to do whatever they want at the end of the day. Some of them, if you screen them very carefully, are going to be much more compliant and adherent to the instruction.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
But this is what needs to be done. And by changing here, we change not the calories, just the composition of the two diet, 10% carbohydrate versus 45% or 50% carbohydrate in the other diet. And that's all what we did. And I think we concentrated only on the energy expenditure, but we even didn't ask very much. They had visual analog scale if they were more hungry or all these kind of things.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
But we kind of ignored the food intake that we were clamping. And this is not real life. If you do something and you talk about engaging on physical activity regimen or exercise and all that, I mean, you have to look at the impact on the other side. And this is the same question that I have. Now, I'm not helping you in designing the perfect study by saying that.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
But on the other hand, again, we have good tools to measure energy expenditure. We have reasonably good tools to measure where do the calories come from. But we have no tools to measure energy intake. But it's going to come.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I bet you that within, I may not be here, but within a couple of decades, we'll have a caller here which is going to measure your calories coming from fat, carbohydrate, or protein.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
metabolic chamber or indirect calorimetry chamber to measure energy expenditure in people over periods of hours and days.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I think you put your finger on the exact point. And now I'm the PI of one of the six clinical sites for nutrition for precision health. This is basically an ancillary study of all of us. All of us is a million Americans who are basically providing biosamples access to the health electronic records and all that.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And then this sub-study is really to look at the intersection between their health and their nutrition. And there is three modules. One is on 10,000 people. And one of the way to measure is exactly this little camera sitting on your glasses and also a system which is measuring if you are chewing or not. It's not enough to see the food and going, but is it chewed? And I agree with you.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I mean, I was not thinking about that. I was thinking about something much more like a CGM. Who was dreaming of CGM 30 years ago? When I was working with the Pima Indians, we were not thinking about that. Now you have CGM, and you can measure probably your insulin from contact lenses and things like that. And I think this progress is going to help us
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Now, are we going to be smarter at designing the study? I'm not so sure, but we'll have the tools to be a little bit more real life rather than incarceration in a metabolic ward.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah, the NIH budget is about $33 to $35 billion, but there is a group which is intramural, but most of the money, 80 to 85%, goes to all the academic institutions doing biomedical research in the country. I like to be intramural.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Also, one thing that I still have in my mind, all the studies which came from Europe about modulating the composition of the diet and look at the impact on the matching of oxidation to the intake. Even Steve Smith, that we're working with, did this study called ADAPT. It was isocaloric all across, but all of a sudden you continue with more fat. The FQ of the diet, the food quotient, goes down.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And then it takes days to basically have a matching of your RQ to the FQ, which means you oxidize what you eat. Whereas if you do the contrary, you increase carbohydrate, it takes one day. And that's why I still believe, and back in Switzerland, we did this study where we were giving extra fat to as LCT, long-chain triglyceride, or MCT, because the MCTs are oxidized quicker.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And we found that, again, the culprit is always the fat. And we are very good at matching carbohydrate oxidation to carbohydrate intake. Very good, it's very difficult. First of all, you have what? 500 grams of glycogen stores. 100 in the liver, 300 to 500 in the muscle. That's all. It means if you have a lot of carbohydrate, that's a huge signal. And protein, the same thing.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
You know how difficult it is to build up your muscle mass or your protein mass in the body by just eating more protein. You have to exercise or you have to take anabolic steroids or whatever. But the fat is the one which is not regulated. That's why I still have this problem with the carbohydrate insulin model. It works. Let's say there was a slight increase in energy expenditure.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
It seems to work for weight loss. It's better with a ketogenic diet than with a low-fat diet. But in your entire life, I don't think it works. And piling the fat, I mean, you have done some of that.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And I was intramural, but based in Phoenix, Arizona, because I worked a lot with the Pima Indians. We have, as you know, the highest prevalence of type 2 diabetes and the second highest prevalence of obesity in the world. But intramural, what I like, you are judged after the facts. You have a budget and you can do whatever you want, but every three years you are judged.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I'm with you, and I think that we are now in the era of precision medicine or personalized medicine, and I think that this is what the NIH is embarking on when they do this Nutrition for Precision Health program.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
When they do this study that I'm also a PI of a clinical site, which is molecular transducers of physical activity, to look at, in lieu of your genetic background, your environment, your socio-economical status, one size does not fit all. We have the dietary guidelines. They are applied for the entire nation.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And they tell you, you know, every time it's the Mediterranean diet or the DASH diet, which are the best and all these kind of things, but not for all. And I think that this is where we are going to have a huge development. It's to go
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I don't think it's going to be individualized, but at least for groups of people having the same, you know, different strategies and restriction has to be one of that. But now how do you restrict? Do you restrict by public policies, by taxing things?
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Whereas extramural, as you know, we chase these grants and you have to basically provide preliminary data, hypotheses, and you are judged before doing the study. And I think you can be much more creative being intramural than extramural. I'm sure that my colleagues intramural are going to hate me that I say that, but it's true. They should enjoy to be judged after the facts rather than before.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah, you're correct. And I see that with this new study that we are doing. People, when you say the word diet, they think weight loss. They think something miracle is going to happen. And we tell them, no, no, we want to know what you eat in relationship with your health and your genetic makeup and your environment and all these kind of things. I'm with you on that.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Now, I'm a little bit more pessimistic that I always say education is a major cornerstone of that, but we also are going to need to have public health policies. I mean, it's been done with trans fat. It's being done now in South America with black label on dangerous thing in ultra-processed food and all this kind of thing.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I think that the government should work very closely with the nutrition companies. And the nutrition companies have been masters at doing two things, to produce very palatable and very cheap food. I remember John Blundell saying, those are the two things that people don't compromise on. It has to be tasty. They need to enjoy it. And it needs to be cheap. And this is what we have now.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I mean, a lot of added sugar, a lot of fat, and it's very delicious and all these kind of things. But we have to reverse some of that. And I think that now we know enough about that. And I was at a conference a month ago in Sao Paulo, the International Congress of Obesity, and they have been very, very active in South America when it comes to ultra-processed food.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And I was impressed to see even, you know, the protein content of all the ultra-processed food is on the side of 12% to 13%. Whereas, you know, we need something between 15 and 18%. And if you believe in the protein leverage theory, this is an important factor.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I mean, in simple words, is that we eat for a given amount of protein, which is proportional to our body size and all that. And by the way, I remember when I was studying, we were saying during a low calorie diet, you need 1.2 gram of protein per kilogram of body weight or these kinds of things.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
But the experiment started with insects and then they went in rodents and they manipulated the content of protein of the diet. And they found out that basically the intake was all to gravitate around a protein content which was sufficient for the weight of the animal and so on. And this is called the protein leverage theory.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And now I'm a little bit more skeptical when Simpson and the two guys in Australia are saying, the pandemic of obesity has been paralleled by a decrease in the protein content of the diet. And this is what has triggered the increased caloric intake to get the same amount of protein.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
It's becoming, I think, the largest institution for research in nutrition and obesity. We concentrate mostly on nutrition and obesity. We have about 500 people working at Pennington, and everybody is doing research. We have no teaching. I mean, yes, I have postdocs and things like that, but no formal teaching. And we do research, and we chase.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
No, once again, with rodents, you can feed them whatever you want. With people, you don't. I remember Dr. George Bray saying, you know, these dietary recall are not worth the paper on which you write the data.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
This is where we lack tools to know exactly your glasses with the camera or whatever is going to be useful. But I think we need better ways of measuring what people eat and what is the content of their meal and all these kind of things. That's why it's so easy to do that in rodents because you feed them with this or these three diets or five diets and you look at how much they eat.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
You weigh the food and the calories. A little bit more pessimistic.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I think the problem is really jumping from basically nutritional epidemiology to policies or labeling or dietary guidelines. And I think to me, now we are at a point that the epidemiology should basically provide us with hypothesis to be tested in better control situation. and maybe in domiciled with full feeding of people. These studies are expensive, but we're missing a step.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And I think, once again, these new studies from NIH, this Consortium of Nutrition for Precision Health, are going towards this direction of basically, you are right, the food frequency questionnaire is here every day for 10 days in this Module 1 of the study. But then there are these other ways. There is the remote photography system that you take a picture with your phone of the plates.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
You have these cameras and all that. And I think that now I hope that we're not going to make policy only or policy or guidelines only based on the nutritional epidemiology, but also on studies basically testing some hypothesis related to what the nutrition epidemiology has shown.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We have maybe a functional budget of $80 million per year. 50% or 45% of that is NIH, extramural money coming to Pennington. We do some sponsored projects for pharma or biotech. We have grants from associations like the American Diabetes Association or American Heart Association and so on.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah, I was one of the four PIs, but I was the one who drove the write-up and the design of the study and all that. Calorie was an important study. It was funded by the National Institute on Aging, and it was really the first attempt to look at the impact of caloric restriction on biomarkers of aging.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Now, don't ask me what are the biomarkers of aging because there's still a lot of discussion around that. If I tell you it's your fasting insulin going up with life, it's your VO2 max going down, it's not your gray hair or your lack of air or these kind of things. But anyway, you have some more sophisticated protein glycation and production of isoprostane and all that.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
It's great that you asked the question because now there is a calorie legacy study, which is to follow up these people, but also there is a biorepository of all the plasma samples, muscle biopsies, fat biopsies at Duke, which was the coordinating center. And these samples are available, of course, with a request And the PI of that is Bill Kraus. You may know the name.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
He's a cardiologist, but he's at Duke. And it's interesting that you ask that because one of my colleagues just published a paper in Science on a postdoc analysis of adipose tissue in these people before and after caloric restriction. He found a gene of interest. He's an immunologist.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Deep Dixit is at Yale, and he really mined these transcriptomes from adipose tissue and found a gene which is related to the immune function and found that if you knock out this gene in mice, they are resistant to weight gain. This is like a calorie restriction mimetic, and they improve the immune function and all that. Yeah, your question is very appropriate. There are still samples available.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Of course, they become less and less available or more and more difficult. I'm just digging in some of the samples that we had to send to somebody at UT Southwestern because he has a new molecule that he would like to test before and after weight loss in non-obese people. But the goldmine of these studies is really to be able to bank biosamples.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And we do basic science, clinical science, and population science, basically, which is to reach the community and implement some of the discovery into the community.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We all bank the data and the results, but the biosamples, it's very, very important.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
First of all, I became interested in caloric restriction because of, I don't know if you remember, Peter, Biosphere 2.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
It was a glass and steel structure southeast of Phoenix, in between Phoenix and Tucson. And eight people went into this biosphere. They had seven different biomes. There was desert, marsh, ocean, agriculture. How big was it? habitat. It was about three acres. And this was a rich Texan donor who wanted to do that basically for the sake of NASA to know how people can live in Otacy. Otacy.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Anyway, eight people entered this Biosphere 2. It's called 2 because Biosphere 1 was the Earth, and they decided to call it 2. Among these eight people, there was a faculty from UCLA, Roy Walford, who wrote the textbook with Rick Weindruck on caloric restriction.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And while they were in the biosphere and I was in Phoenix, Roy called me and said, we would like to do measurements of energy expenditure. Can we sneak in a Delta track or metabolic cart to measure our energy expenditure? And I said, oh, absolutely. And we can also measure your free living energy expenditure using doubly labeled water. And we did that anyway.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
from 1991 to 1993. Roy Warford was a physician of the group, but he was very, very interested in caloric restriction. What he didn't know, things went south. The agriculture, you know, they had pests, they couldn't control some of the insect, they had goats dying, and very quickly they didn't have enough food. And they lost on average 15% of their weight.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
None of them except one was maybe a BMI of 26 or 7. They were all between 20 and 25. And they became calorie restricted. And you had the guy who was writing the textbook on calorie restriction being the physician in the Biosphere 2.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We started to collaborate, and then when this RFA came out in the early 2000, a request for application grant from the NIA, immediately I called Roy and I said, Roy, we have done this study of energy expenditure, and they came and they stayed in the chamber, five of them, for one day, right when they came out of the biosphere.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And we need you as a consultant, and we want to write a grant which is going to be competitive. I'm not known in aging research. He accepted.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
It was low. I mean, very low because of their caloric restriction. We had to compare to a group of 72 people. I mean, it's all published, and I can send you some of the papers. They were about 200 calories below what you would expect for their weight and body composition.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah. Three of them said, hey, we have been stuck for two years now in this biosphere. We don't want to go to a metabolic chamber in Phoenix. But the five who came, they came back six months later, and they regained their weight. They were normal weight, like at the entry, and we published this data.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah, normalized. There's this argument with metabolic adaptation, how long does it last and these kind of things, but it was normal.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah, he blamed it on biosphere a little bit because they were supposed to be totally independent except for light from the rest of the world, but a few times they had to purge CO2 and influx O2, but he said there was probably gases, but it was his story. I don't know how true it was, but he said that he was intoxicated by gas in the biosphere.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah. Now, move almost 10 years later, Roy Walford and I don't remember the name of the investigator in San Antonio came. We brainstormed what should be the hypothesis. I was very serious. I wanted to have this grant. And we said, what are we going to test? Because if you ask Steve Orsted how many theories behind calorie restriction, he's going to tell you more than 50 or 100 and so on.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Myself, I was pretty convinced by two things. The rate of living theory, the higher your metabolism is, the shorter your life. And the elephant has a very low metabolism per unit of tissue compared to a shrew and all these kind of things. And the oxidative stress theories.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
You can look at the Kleiber book. You have the energy metabolism.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
It's probably 7 or 8X. They are all on the same line.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We brainstormed for three or four days. I have beautiful memories of this time. And we said, okay, we're going to write a grant. It was a seven-year grant. The first two years, which was you do a study, show us that you can recruit people and maintain them in calorie restriction, and they have to be not obese. They can be overweight.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And the second is from the three chosen group, we're going to design one study and it's going to be a two-year intervention. And the first study we decided was basically to test if caloric restriction decrease your energy metabolism more than what you would expect on the basis of the body weight. And in other words, do you become more efficient? And the answer is yes.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And we talk about metabolic adaptation. Now, this is in non-obese people here, but they become more efficient.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
You're right. And when I did studies of efficiency of athletes or do they have a higher, a more efficient resting metabolic rate and therefore can have more energy for the exercise or the task that they are doing, you cannot win both sides. Like you said, you are better at controlling your weight when you are a little bit more inefficient, but you are less performant and all these kind of things.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Potentially, energy efficiency can be very good for longevity, and it has been shown in some studies. The Baltimore Longitudinal Study showed that some people with lower metabolic rate were living longer. On the other hand, energy efficiency is a liability for weight gain, for example, because you are more efficient and you are more prone to weight gain.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And I think it's a balance between the two. But anyway, I think there is no right answer. But having a high metabolic rate can be a liability because associated with the generation of ATP, you have some what we call production of reactive oxygen species.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
In other words, the efficiency of the transfer of oxygen into ATP is not perfect, and sometimes you have some reactive oxygen species being generated by the mitochondria, and these reactive oxygen species can damage not only your DNA, but your protein, your lipids, and so on. And this is one of the theory of aging.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
It is too many reactive oxygen species and therefore a higher degree of oxidative stress. And when we designed the first part of our calorie study, it was a six-month intervention. We had four groups, a ad libitum group, 25% caloric restriction, another group being 25% energy deficient, but half by caloric restriction, 12.5%, and half by increasing energy expenditure by exercise.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And the last group was weight loss 10% with very low calorie diet and maintenance of this weight loss. It means you are in calorie restriction compared to that baseline.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah, there's two things, indirect calorimetry and direct calorimetry. You generate your energy metabolism or ATP by oxidative process and you oxidize carbohydrate, fat and a little protein. You don't want to oxidize too many proteins. And this basically build up these ATPs, which are used online for generation or maintenance of the cells or activity and so on.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I think it was a lot of work with our psychology group who said, we have to screen the people. We have to screen them for barriers to the intervention, for adherence and so on. And there was a lot, a lot of screening of our volunteers.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
It is in the console diagram of the publication. I know, if I recall correctly, for the two-year study, we screened more than 5,000 people to enroll 225.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Telephone, web screening, telephone screening, in-person screening visit. And there were five screening visits to make sure that they show up. If they don't show up for the screening visit, forget them. And the first study, we published that in JAMA, and we did find that there was metabolic adaptation or you become more efficient. And we had also some indication of less oxidative stress.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We did what we call a COMET assay. You look at damage of DNA in nucleated blood cells, and we measure isoprostane and all that. After that, the three sites were Washington University with John Hollowsey, was Tufts in Boston with Susan Roberts, and us in Baton Rouge. Our study was six months, our preliminary study. Theirs were one year.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
But after two years, when we analyzed the data and all that, we started to design the study, which was going to be the same for the three sites.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
No, they were all different. We insisted to have these four groups ourselves in the preliminary study. Boston had only two groups, low glycemic index versus higher glycemic index in the diet of the caloric restriction. And Washu, I don't remember the details, but there was a component of physical activity in their study. He was, John Hollis, he was a biochemist of exercise and all that.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
But after that, we compared our endpoints and our basically intervention, and we designed this study. Now, the RFA was specifying that they have to be non-obese. In our preliminary study, we didn't want to go because of this 10% weight loss. If you start with a BMI of 26, you are 70 kilos, and you have to lose 7 kilos, you become thin.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We decided about the range of BMI and we decided for the study to go from 22 to 27.9 of BMI for admission, means normal weight,
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Up to 27.9. We knew that they were going to lose at least 10%. And therefore, you cannot take somebody with a BMI of 20 to start with. You would have problems with bone mineral density. You may have problems with some safety concerns.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Men and women.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We didn't have that in the final protocol, but in our preliminary protocol, it was over three months. It was a low-calorie diet. It was like 800 and some calories per day. It was all liquid diet.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah. But we could do muffins and things like that from these. It's called Health One Diet. And it's still on the market, by the way. The two-year study, then we decided, to my surprise, that they agreed to do the rate of living slash oxidative stress first endpoint. Let's go back to the subject. Age 21 to 47 for women and 55 for men. BMI 22 to 28.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Now, when you have this metabolism, you produce heat. If you have no exercise, no external work, all the energy which is provided in generating this ATP is lost as heat. And this is direct calorimetry. And I was fortunate when I did my PhD back in Lausanne, Switzerland, to have access to both indirect and direct calorimetry. You can really do fantastic studies.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And then going through a lot of screening to make sure that they were going to stick with us. And I can tell you, we randomized two to caloric restriction, 25%, for one to ad libitum. We had 95% completion in the ad libitum group and 85% in the calorie restriction. It's amazing for a two-year study. And the retention was spectacular. They were randomized 2 to 1 to caloric restriction.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Unlike the preliminary study we did in which we fed them entirely, they came to Pennington to basically learn how to cook whatever diet they wanted. It could be a low-fat diet, a low-carbohydrate diet, a med diet.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
It was based on two measurements of doubly labeled water. The average, I just checked that this morning, the average energy requirement was 2,400. It means, on average, they were cut by a little bit more than 500, 600 calories. And for two years. And the first three months, they could come whenever they wanted to learn to cook. And they were also provided some of the meal if they needed to.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I remember one is still our star of the volunteers. His daughter thought he was working at Pennington because he was going every day to Pennington. And his daughter was five when they asked her at the kindergarten, where does your dad work? Oh, he works at Pennington. And he was a volunteer for our study.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
After that, we had a lot of measurements about resting metabolic rate, about oxidative stress. And the endpoints were really the first RMR. the second ROS formation, and after that it was CVD markers, it was insulin sensitivity, immune function, neuroendocrine parameters, quality of life, and cognitive function.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
One year, the average was 12%, and at two years, it was 10.4%. Now, the caloric restriction that we kind of estimated by doubly labeled water, it's called the intake balance method. You measure energy expenditure, you measure change in body composition. We had about almost 20% of caloric restriction for the first six months. And this is where the weight loss.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And after that, it started to decrease to close to 15% at one year. And then at the end of the two years, the overall caloric restriction was 12.5%. Basically, we got half of what we were asking for, which is not bad for, like you said, it's an important cut in your intake, and it was square from day one. It was not a ramping up.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And then we did these measurements at six months, 12 months, 18, and 24 months.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
My original grant was $10.4 million, and it was in 2003. And after that, because we were recruiting so well, they asked us to boost up our recruitment, and they gave us another million and a half. Yeah, close to $13 million.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
No, plus indirect. Total cost.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah, yeah, yeah.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We did a study of measuring in vivo what we call the PO ratio. How many oxygen do you need to generate one ATP and all these kind of things by the combination of these two techniques. Now, going to indirect calorimetry, this is an easier one than direct.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
One amazing was the retention rate. I thought that it was exceptional that between the three sites, and it was much more difficult in Boston, to be honest, than it was in Baton Rouge or even in St. Louis. But anyway, retention was exceptional.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
It's interesting that you are asking because we have been interested in that and we are even now following up these people who were studied from 2005 to 2008. And they are part of this legacy study, Calary legacy study. He was really building a team between the investigators and the study coordinators and study managers and all that and the people.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
He was also providing them with some of the results. And we had to fight for that because normally you don't want to have people having their results. But we said it's not going to change their behavior if we tell them about their total cholesterol. Right.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
LDL and it's not going to change anything or their body composition. They love to see this DEXA, my percent body fat went from 15 to 12 in a guy and so on. And he was kind of building a, we had Mardi Gras with the volunteers. We had every two months, we had a reception and all that, sending postcards for birthdays and all these kinds of things.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
are part of the retention and building a team between the investigators and the study volunteers. And I think we succeeded in that. But again, this was the screening, which was essential. Because you are right. I remember the first person that we randomized, she ended up in the AdLib group.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
She came to my office and said, I want to do this study because I have read about what it does to your metabolic health, to your cholesterol, to your body composition, and I'm in the control group. She was crying and said, but we're going to give you data and after we're going to offer you maybe a weight loss or help you for caloric restriction and all these kind of things.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Of course, two years later, we still see them, but not on a regular basis like during the study. It's a lot of investment from the investigative group and also for the study participants because they had so many visits.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I think, first of all, there was quite a lot of press around the study at the time, done at a national level as well as local levels. And they like to know and to know that they are part of an important study. It's like this Nutrition for Precision Health Now or Motorpack are things which get some press and all that. Most of the people like to be part of a key study.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
The second thing was really building this relationship between the investigators and the study volunteers and also the return of results and the sharing of experience with other people. You were asking, you know, how long does it last to have this problem with hunger, suffering and all that? And it seems that for most people, after one month, he was totally manageable.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We taught them also to increase the volume and decrease the fat content to satisfy on a volumetric basis how much food they were eating with less fat and less calorie density in the diet against the ketogenic diet here.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We have published, I don't remember exactly if there was a clear-cut impact of being in the caloric restriction group versus the ad-lib group. This I don't know, but I know that quite a few people wanted to make a difference in their diet, and they wanted to know more about the med diet, the DASH diet, the low-fat diet, and all that.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And surprisingly, there are some people, and like I said in this legacy study, and Dr. Redman is the PI now, people are still, a lot of them did not regain all the weight, and now it's more than 15 years after. And they are still using what they have learned during these two years because there was a lot of learning.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Like I said, this legacy study is targeting all the people. Now, I don't know how many, but I'm pretty sure we're going to get... But we don't have the results yet. No. No, it's ongoing now. But us, we did a six-month follow-up study at Pennington. And here, they were continuing. That's not the thing they said, oh, heck with this study. I go back to my normal life.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Now, we can do that in humans. I was fortunate to be at a place which had one of the two direct calorimeter. At the time, there was one in Bethesda. It doesn't exist anymore. The one in Switzerland doesn't exist anymore. I wish I had a picture to show you, but this is a basically, I would say, 1.2 meters by 1.2. It's a little bit bigger than a cubic meter box.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
He was a game changer for their lifestyle, for these people.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We didn't do clams. Let me tell you, there are two kinds of aging. There's primary aging, which is more like senescence or mitochondrial dysfunction, leaky membrane. And there is secondary aging, which is basically the impact of your environment and your lifestyle. When you ask about insulin sensitivity or cardiovascular factor, it's more secondary aging. And here we did a lot of measures.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Bill Kraus published a quite cited paper five years after the end of the study in JAMA on all the cardiovascular, cardiometabolic risk factors. And everything was tremendously improved despite the fact that these people were healthy to begin with. BMI 22 to 27.9 and so on. And remarkable improvement in all these markers of secondary aging.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Now, when it comes to primary aging, that's a different story because it's much more difficult to measure autophagy, to measure mitochondrial function, to measure leakiness of a cell membrane in these people. And what we ended up to measure was really some of these hallmarks of aging. You have probably seen these papers. There was one in 2012 and one 10 years later.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We don't have as many data that we would like. But for example, we did measure mitochondrial biogenesis by looking at the relationship between nuclear markers and mitochondrial DNA. And we observed in humans that there was an increased mitochondrial biogenesis. Despite the fact that you use less energy, you become more efficient.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
You increase your biogenesis of mitochondria, which is quite spectacular because the ROS production of these reactive oxygen species are produced by older mitochondria. The new mitochondria are much more efficient. They don't produce as many ROSs.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
In the muscle, skeletal muscle, it was.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Absolutely right. I think it's both. When it comes to mitophagy, these old mitochondria, it's been shown in insects, in rodents, that this is improved with caloric restriction. Autophagy, of course, all these organelles in the cells.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
No, no. But we measured mitochondrial turnover by this method, and we found that it was increased with caloric restriction. And I think you are right on the point here. There's both mechanisms, less energy requirement, but also more efficient mitochondria.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And you recover all the heat, and you have dry heat by convection, and you have a layer, a gradient layer, capturing the heat production. You collect the evaporative heat losses from perspiration, expiration, and so on. And you merge all that, and you have a complete heat balance of the person. And we measure these two kinds of heat, and this is basically equal to your metabolic rate.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah, I mean, we did. We did at 6, 12, 24 months. We didn't do 18 months for that. But we had the whole panel of inflammation and high sensitivity CRP and then all the interleukin, TNF alpha and all that.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Now everything improved. One thing which was spectacular when it comes to immune function, we did some imaging of the thymus and there was loss of fat.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
There was a reduction of fat in the thymus, and our friend, Deep Dixit, was all excited by that, and this is why he pursued all the immune responses from transcriptomics in different tissues and all that. But chronic inflammation, first of all, it was not abnormal to begin with, but there was tremendous improvement.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And I think that Bill Kraus, in the discussion of his paper, if I recall, he used the Framingham Index of Cardiometabolic Health, and there was an improvement in the age. I don't know exactly the index.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And it was quite spectacular. It was like they were gaining 10 years in two years.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I would have to go back to the publication exactly. He was less than a quarter.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We didn't restrict physical activity, but to be enrolled, they had to be screened for not being regular exercises, for example. Do you know the cronies, the Calorie Restriction Optimal Nutrition Society?
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
There is about 200 self-imposed calorie-restricted people. They are afraid of exercise. They don't exercise at all because they are afraid that exercise is going to increase their appetite and their food intake. And they are religious with that.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And that's why, I mean, your question about sarcopenia, when you start with people with a BMI of 24 and you lose your 10, 12 percent and you keep this 12 percent off and you go in your 70s and 80s, what is happening to your muscle mass and these kind of things? And I don't think we have an answer.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
You generate energy by oxidation of substrate, and the byproduct is heat. And without exercise or external work, energy in is equal energy out. And this is what we measured, and I did a lot of these studies during my PhD. But then at that time, we decided to build a metabolic chamber, which is like an hotel room in which you can live one day or two days.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
It's been a little bit of a roller coaster, the CR mimetics. You remember all the Sir Twain stories.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah, okay. And you pick metformin, and of course, I'm sure you know neobazali.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I mean, the GLP-1 are so potent when it comes to weight loss, metabolic health, and all that. I mean, there's not a week without a new paper on GLP-1. I know.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Why would that be? Because when you calorie restrict yourself, you eat less, and therefore you stimulate less these GI peptides.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
If you tell me, I mean, are they true caloric restriction mimetics and do they decrease oxidative stress? Do they improve insulin sensitivity and all that? Among the one you cited, there's a lot of those. Now, the question is, how do you go about to test that?
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Of course, there is all these failed drugs and things which have been tested for toxicity and safety and all that, that some people want to recycle in aging, and I'm not sure where it's going to be. To me, the secondary aging, which is the impact of your lifestyle and your environment, is what we should target first.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
The primary aging, I like to hear David Clark talking about autophagy or the people on the East Coast and all that, but what do you do to have more autophagy or more mitophagy and all that? I don't know.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And I think you stayed for two days in one of these rooms at Pennington in Baton Rouge. And here we measure oxygen consumption and CO2 production. Oxygen is used to oxidize a substrate. It produces CO2 and water. And knowing oxygen consumption, CO2 production, you can calculate the energy expenditure or the energy generated by this oxidative process.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
My pleasure. Stay tuned because you mentioned time-restricted eating, and now there is a study which is going to be implemented in a year or two, a five-year intervention, calorie restriction versus time-restricted eating.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I don't know the details. The protocol is not finalized. It's one of these exercises where we were part of one of the studies and now you put all the brain together. But it's going to be probably eight hours a day.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
The first study we did was six hours. Yeah.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yep. Interesting you bring that up. But our study was the first in humans. And this was Courtney Peterson who did that. And we had six hours. And people said it would be easier with eight hours and all that. But after, if I recall correctly, after two weeks anyway, they were perfectly fine with six hours. Even if at the end, the exit interview, they said it would be easier for eight hours.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
But I think it was at the start. And you can maybe ramp it down from eight to six hours.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
All right. Thank you very much, Peter. A pleasure.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
And you can also calculate the substrate that you oxidize. If the ratio between the VCO2, the CO2 production and the oxygen consumption is one, you oxidize carbohydrate. If it's 0.7, you oxidize fat. And protein is something in between, 0.82, depending of the protein.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
Yeah, when I was at NIH, we did a lot of reliability testing in the same person. Or you can calibrate the system. You calibrate the system with standard gas that you know the exact concentration to calibrate the analyzers. But you can also mimic someone by burning alcohol or propane. And you can vary the rate of burning. And this is what we did when we did this study with four different chambers.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
We validated the chambers once against the other one, and we accepted to have 3% deviation for CO2 or oxygen. Based on stoichiometry, you know exactly how much alcohol or propane you burn. You know how much CO2 should be produced and how much oxygen has been consumed. And this is what we did. And you are right. They are very, very precise. And you don't have the inconvenience of the mask.
The Peter Attia Drive
#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.
I mean, you couldn't measure with a mask for 24 hours or two days.