Hey everyone, welcome to the Peter Attia Drive. I'm your host, Peter Attia. The drive is a result of my hunger for optimizing performance, health, longevity, critical thinking, along with a few other obsessions I've gathered along the way. I've spent the last several years working with some of those successful top-performing individuals in the world, and this podcast is my attempt to synthesize what I've learned along the way to help you with a higher quality, more fulfilling life.
If you enjoyed this podcast, you can find more information on today's episode and other topics at peterattiamd.com. Welcome to the Peter Attia Drive. In this episode, which I know is long-anticipated, I spoke with Dr. Ronda Patrick from Found My Fitness.
I suspect many of you listening to this know everything about Ronda and have been fans of her for a really long period of time on the off chance of anybody listening who doesn't know who Ronda is. I suspect by the end of this discussion, you will also become a huge fan of hers and her podcast, which is exceptional. So I've known Ronda for quite a while, and despite the fact that we both consider San Diego home, we've just been busy enough that we just haven't had a chance to sit down together in quite a while. So this discussion was kind of long overdue, and it was sort of funny because as soon as Ronda walked in, we just jump right into a really interesting discussion, and then 10 minutes in, I thought, you know, we should probably start recording because this is interesting stuff.
And so we did. And so, I think that's really when the discussion finally ended, we sat around for another 20 minutes talking about a bunch of stuff that I found myself thinking, God, I wish we were still recording this because it's super interesting. So that's just basically to say, I suspect Ronda and I will speak again at some point soon. So don't worry if all of your questions weren't answered here.
The other thing about this podcast, it was a ton of fun, was that in the days leading up to it, she and I had emailed each other a few times back and forth some ideas of things we would talk about. And in the end, neither of us really had any notes sitting in front of us. We just sort of sat there and shot from the hip and didn't follow a script or anything like that and didn't even get to half the things that in our emails we had suggested we would talk about. And all the stuff that we talked about is stuff that I think Ronda brings a great deal of expertise to.
So I don't recall the order, but I know that we certainly touched on IGF and the growth hormone, what I consider a little bit of a paradox, which is on the one hand, we have some evidence to suggest that elevated levels of IGF are bad and that fasting may act in part by reducing those levels. But at the other end of the discussion, you have some confounding and conflicting data around that. We also got into a great discussion about the P-par enzymes, so P-par, alpha, P-par, gamma. One of the things that Ronda does incredibly well on her podcast, and I would encourage those of you who find this episode interesting, who aren't familiar with her work to go back and actually watch some of her stuff.
She doesn't put out a lot of podcasts, but the reason for that is the amount of work she puts into them is enormous. So when she puts out a podcast on video, there's explanations, definitions, and stuff scrolling across the screen. So it's unlike me who's incredibly lazy and can't even stand to listen to a podcast after I record it. Ronda is methodical in her ability to make that easier for the viewer.
So you'll learn a lot about this stuff. You think we're going too quickly over it by probably going back to Ronda's site. We talk a lot about the possible genetic explanations for why some people do and don't respond particularly well to ketogenic diets. And of course, you can think about in two ways.
There's respond as far as the ability to make ketones, but then there's also sort of these patients that I described seeing where you put them on a ketogenic diet and everything seems to go wrong. So at least biochemically wrong. So that's a very interesting discussion. In many ways, I think my favorite part of this discussion was the way it started, which was the first question I asked Ronda, which was kind of a random question.
I think led to some interesting back and forth between us, which was effectively what do you believe today that you didn't believe before and vice versa? And I always find that to be one of the most interesting ways to dive into a discussion with someone who's buried knee deep into science. Because if you're really thinking about science, you have to understand, of course, that virtually all facts have a half life. And our knowledge is constantly evolving.
In many ways, that's what makes the field so difficult to stay on top of, but at the same time so interesting. And so to me, one of the marks of a very thoughtful person is someone whose beliefs are flexible and who's willing to acknowledge that something that they believed was once true or not true can be flipped. And so I think, you know, Ronda and I share that and I think it was actually really fun to see where her beliefs have changed over time. So with that said, I think the show notes for this particular episode are going to be very helpful.
And you can find those at teeteratiamd.com forward slash podcast. And I hope you enjoyed this discussion at least half as much as I did. I suspect it won't be the last. So without further delay, here's my conversation with Dr.
Ronda Patrick. Ronda, so great to have you here. Happy to be here. It's great to see you again.
I can't believe we live in the same city and only see each other once a year. If you win. Well, thank you for taking the trip up here today to my office. My pleasure.
And I'll join the long list of people congratulating you on your 10 month old son. Thank you. Thank you. I almost don't know where to begin because there are so many things that we share in common as far as interests.
But I want to start with a really broad question, which is you spend so much time thinking about many of the same problems I spend time thinking about. What do you believe today that you did not believe four or five years ago? Probably the biggest thing that has changed in what I now believe and I didn't four or five years ago even more is that one of the major modalities where increasing health span, which is the healthy part of your life, delaying the onset of age-related diseases, the major modality for doing that, that would be the best way to do it would be Calwork restriction or dietary restriction. So eating 30% less food than you normally would eat.
I used to really think that was the way to go for doing that. And I think that my beliefs have changed for that. And that being the major modality for a few reasons. One reason is because I think that actually, so one of the things that occurs during Calwork restriction is a major drop in the growth hormone IGF-1.
And that's thought to regulate a lot of the improved health span effects, at least in some organisms like mice and in recess monkeys. But I do believe now, based off of a variety of research from people like Valtter Longo, that periods of growth, actually, specifically periods of IGF-1 are really important. So if you're constantly doing this Calwork restriction, then you're not really going to have that period of growth because you're quantically doing that. And really interesting, I don't know if you saw the recent nature study that came out, I think it was in April of this year on lemurs.
So the study essentially showed, and these are, I guess they're nonhuman primate animal model, but their life span is around six years or something like that. I think their maximum is 11 or 12 years, I don't remember. But the Calwork restriction did increase the median lifespan. It also increased maximum, so they lived a year longer than typically.
And there's a lot of delayed onset of various degenerative diseases. There was a mass of atrophy in gray brain matter in regions of the brain that didn't occur in control animals, which is just another sort of example of how, you know, sometimes some of these what alleys that we think are really good for increasing health span sometimes have other effects. And I think that getting into the IGF-1, I think we'll probably, you and I will talk about that because we both have a shared interest in that. But the periods of growth being necessary for health, I think that's kind of turning point in my mind.
And so now I actually think that perhaps even doing periodic prolonged fasts or a better way of doing that because you can get that IGF-1 boost and you can get the lower IGF-1 among other things that occur. But we can dive into that if you want. But I think that's kind of... We'll be diving.
Yeah. But I think that's probably one of the major things. Yeah, there would be actually another interest that we share. I think it was a lot more skeptical of ketogenic diets about four years ago in terms of being great for long-term health and health span.
And I think that some of my thoughts on that have changed a bit based off of more recent long-term studies in animals, specifically in mice, from work from Dr. Eric Vurdin and also from out of UC Davis showing that ketogenic diets in rodents can increase health span, increase median life span, certainly improve content function. Now, the caveat there is that typically with a ketogenic diet in rodents, it's actually can be most of the time ESO-B-Cgenic and the way that these guys worked around that was they found that they had to limit the calorie. And what was interesting was that...
Or cycle them, right? Well, so Dr. Eric Vurdin, the way they did that was by cycling it. But UC Davis, what they did was actually put a calorie cap and it turns out after talking with Dr.
Sachin Panda that they ended up being on a time restricted feeding schedule. And so the ketogenic diet was, they were basically eating all their food within a certain eight or eight or so or nine-hour window and then they were fasting for... So it's kind of one of those things where in humans, we don't really know. I don't know exactly how people...
I've never actually done a ketogenic diet myself. So I don't know exactly what people are doing if they're eating all the time or what. So I'm also intrigued by that. And in many ways, almost have the mirror of your experience, which was four, five, six years ago, seven years ago, I guess, is when I really, really got into ketogenic diets was on a ketogenic diet for three years, save one day.
And I wouldn't say I have any less faith in them today. I just am personally less interested and find it much harder to do. So just as far as compliance with a ketogenic diet, I think my life is just more complicated today in terms of travel and things like that and kids and stuff. But the thing that surprised me with the recent...
Because those two publications came out in sell, right? The ones... Sell-coballosnoid. Yeah.
I was actually kind of surprised by a couple of things. So one was what you said, which was Eric noting that, hey, when we constitutively gave these guys this food, they just... They got obese. That's really counterintuitive when you think about how ketogenic diets...
You know, they're not going to increase circulating metabolic fuels. And that should down regulate appetite. And I think in humans, there's a huge debate about why do people lose weight on ketogenic diets? Are they losing weight because they're eating less?
Or are they losing weight because they're ramping up fat oxidation, disproportionate to where they were before, which drives up energy expenditure? Of course, I suspect the answer is both. In other words, if you do the latter, the former should happen. So when people say why do you eat less on a ketogenic diet, the question is really...
The thinking would be, are you eating less because you are basically eating yourself more because you're obviously oxidizing all those fatty acids to make a BHB? Or is it some other reason that has to do with the neurochemistry of these things that go beyond sort of the metabolic central... Oh, pardon me, peripheral effects of it. So that's the first thing surprising with that study, which was why were those mice overeating?
Was there something else in them because they couldn't have had that much sucrose? They usually put sucrose in a mouse chow, but there couldn't have been that much sucrose so they wouldn't have been able to get into ketosis. And I think even previous studies, like earlier in the literature showed something similar where it was obese, genetic, now there was certain genetic backgrounds that also seemed to kind of little, you know, regulate that to some degree. But what I was actually thinking, so you brought up some really interesting points, is that thinking of it in the context of like, let's say they're eating, they're constantly eating the fat, whether they're not having the period of rest.
I know that, for example, when you're making malanyl-CoA, which is something that you do when you're oxidizing fat, malanyl-CoA inhibits the conidine-pominsyltransferase, basically the transporter to transport fatty acids into mitochondria. So if you constantly are making malanyl-CoA because you're constantly eating the fat, then you're going to start to have this inhibition and you're going to start to then store the fatty acids in anaphyl-CoA rather than catalyzing them. Right? So it seems to me that...
We don't see that, by the way, with the exogenous ketones, do we? This is something I'm still trying to get a handle on. I agree. I'm extremely interested in exogenous ketones, particularly because I'm...
Okay, you've tried this. I was going to bring you something. I really enjoy the effects they have on my brain. So I use them for endurance, exercise, and I also like it for that as well.
I do notice that I have a little bit of a simple run longer than I usually stop at this point on the beach and I can keep going another. But I really like his... For me, it really helps with focus and lower anxiety levels. So I seem to be able to...
I'm always on to the next. And so this kind of helps me say in the now. At least, and that could be completely people's sleep, but I don't know. But anyway, that's one thing that I like about that.
But to get back to your point, I had one of the same thing because what's the effect of exogenous ketones on normal fatty acid metabolism. And the reason I'd wondered that is because there was a paper that recently came out where I think it was the one that was done in humans where humans, they were given the adiroxide rate ester for endurance and enhanced endurance performance. But they found inhibited... Yes, and also inhibited fatty acid, something to do with lipidotamilizum, which suggested possibly there could be an inhibition.
Now, it's funny. I'm going to see... I'm in New York next week and Dom is going to be in New York. Dom Degas, who obviously know well.
We're grabbing dinner one night and we're going to talk about this paper because I remember when it came out Dom sent me an email with... Pull it up. Then I'll know for sure if you want. I'll send it to you.
Yeah, send it to me for sure. Because there was something about that study that was a little bit off. I need to kind of go back and look at it. But it does beg another question.
So I want to go back because I know there's going to be a theme today, which is multiple threads that are easy for us to go off on. And you and I are right at going on to it. Yeah, yeah, yeah. Let's go back to the mice.
Let's go back to the two studies. Do you recall if in the verdant study, before they started cycling the ketogenic diet, when they were just giving it to them all the time, did they have a window in which they could eat ad libitum that they over ate in or were they given 24-hour access to food? 24-hour. Is that limited?
So what they never tried then was, let's give you food for 10 hours and let you eat ad libitum. Because that would be interesting if they would overeat in that setting. Maybe not that interesting. The other experiment that I don't think has been done is, remember when they took a variant which was high fat but high-ish carb?
And so it wasn't... There was enough carb in the diet that it wasn't producing ketosis but it was still a high fat diet. I'd like to see that experiment repeated with an exogenous ketone because then you could start to identify the effect of the carbohydrate specifically and tease out the effect of the fat and the BHB. Right.
I think I remember one of the big differences between the high-fat low-carb and the actual ketogenic diet was the induction of PPR alpha which makes sense because that's involved in ketogenesis itself. But to what degree that regulates any of the other important properties that were found, including the really profound effects on the brain. So I like to personally get my ketogenesis from my periods of fasting. More so than carbohydrate restriction?
Well, I do refine carbohydrate restriction but I also think there's a lot of benefits and this is part of the reason why for so long I was skeptical of a ketogenic diet is because I think there's a lot of benefits in eating a variety of plants. I think that there's a lot of various micronutrients that are much higher density in plants, folate, magnesium, vitamin K1. But also there's a lot of fermentable fibers and things that are really good for the gut microbiome which I also think is very important for regulating immune function. So that's kind of been my hang up but I think people like Dom seem to be doing a modified ketogenic diet where they're definitely getting the greens, trying to get the leafy greens.
So I think that one way to get around that plus I think there's also a way to do a ketogenic diet where you're eating a lot of salmon, avocado, nuts, olive oil, butter and keto bombs and all this pork rinds and stuff where there's nutrient density and some of that. Yeah, it's funny. I guess it depends on how many calories you need but during that window when I was on a ketogenic diet I was also still very active, certainly much more so than now and I really required a lot of calories. I couldn't maintain my weight below 4,500 calories a day and I still stuck the pretty strict absolutes on the protein and carbohydrates.
I really kept my carbs and I didn't look at net carbs. Oh, by the way for those listening and wondering what that noise is, this is something wrong and I are very used to. Those are FA18s which how many overhead drive-bys we're going to get today if you had to predict? I would say.
Yeah, I would say probably between 4. Okay, yeah, it's the sound of free on people so just get used to it. So I was getting probably 50 grams of carbohydrates total carb. I should say probably about 80 grams of total carb but you'll see what type of carbs it was.
Really had to limit protein to about 100 to 110 grams if I went over that I would get kicked out. So fat made up about 90% of my total calories and so there's only so many ways you can get that much fat and the most efficient way is actually salad with olive oil. I mean I couldn't believe the amount of vegetables I had to consume to stay in ketosis. I basically had to have two huge salads a day where I would make my own dressing which was a heavy olive oil based dressing and I could probably only have one avocado a day which I would always have because I didn't think of it.
I was getting too much carbohydrate so it's like a lot of macadamia nuts, a lot of olive oil, olive oil based everything and then the hardest part for me was clearly being stingy with the protein. What was in salads? Okay, so I'm a pretty boring guy. So it's romaine tomatoes, cucumbers, celery had to kind of like limit the carrots a little bit.
I normally love carrots but... So you eat tomatoes and everything on the kitchen? Yeah, yeah. I can get away with more because I probably exercise more.
And I was doing this before people were sort of putting butter in their coffee and stuff like that. So that was not... I consumed a lot of dairy though so it's the other thing. Tons of cheese, tons of sour cream because you just needed those calories and I actually developed like a spreadsheet that was customized for my caloric needs but I had this formula of looking at every ingredient.
Like could you find the food that you could eat without restriction that wouldn't destroy your ratios? And so for me at my caloric level, like cream cheese and sour cream were sort of the perfect thing whereas even high fat Greek yogurt had too much protein so I had to consume that in moderation. That's the other interesting thing and I think I talked to Eric about this was how much of the effects on health span or due to low protein intake and how much were due to the actual bean and ketosis. Yeah, I've talked about this with Walter a few times.
We don't see eye to eye on this because for several reasons. One, I'm not entirely convinced of the IGF paradigm anymore. So that's one thing where the question I asked you, that would be my answer. So five years ago, I would have said IGF is the devil, growth hormone is the devil.
You want them to be as low as possible. I'm not convinced of that today. I can't wait to explore that with you. But the other thing is if you really want to produce the lowest level of insulin and IGF, I am not aware of a way to do that beyond a ketogenic diet that is incredibly low in protein and incredibly low in carbohydrate.
When I go back and look at my blood levels, because I check my blood about every six to eight weeks and I've been doing this for 10 years, I mean my lowest IGF levels were during the three years I was in ketosis. I mean, they were very low. They were, I mean, not ridiculously low but 25th percentile for age versus say 75th percentile today. So that makes sense to me because if you think about, you know, some of the major dietary regulators of the IGF one pathway are protein, essentially amino acid specifically and also insulin.
And through IGF VP three or IPv one. So I mean, I think that, so for example, you know, if someone's eating a low protein and low, you're getting, you may not be a vegan, but even if you had a limiting your protein, you know, even to some degree, you're certainly getting more than someone, maybe me, that's not doing that really. Although I do kind of what I'm approaching. But it's a misconception.
You see, I think a lot of people assume ketogenic diets are high protein diets. I think some people do consider that. Yeah. But if you're, there may be certain people out there who can produce ketones with high protein, but in my experience personally and more importantly clinically, meaning I don't know over the course of my practice and my career in medicine, I mean, I've probably at least encountered 50 or 60 patients at a very detailed level on ketogenic diets.
Almost without exception, protein is the bigger thing that fouls people up. And so that's the thing I've always found a bit confusing in some of those discussions is any of Eric mentioned this on your podcast, which is well, you got to be careful if you're not a ketogenic diet, you don't have too much protein. And I was like, those don't go hand in hand. You're not on a ketogenic diet.
You're eating a lot of protein because you won't make the ketones. That said, I wouldn't be surprised if there were polymorphisms that allow people more or less. And you've obviously talked a lot about the people are alpha. Is it people are alpha or people are gamma where you see the differences in a person's ability to generate ketones?
The people are alpha is predominantly found in the liver and it's involved in fatty acid catalism So that would be the major one. Now, there's nothing empirically. I've seen a literature that's looked specifically at PPR alpha and a ketogenic diet or fasting. But, you know, there's most of the literature out there looking at the effects of PPR alpha with people that are at their home zygos or have to do with the context of like high saturated fat, low polyunsaturated fat because polyunsaturated fat activates the PPR family of transcription factors, which are in a nuclear hormone receptor transcription factors.
But the PPR gamma is predominantly found in like adipose tissue. I mean, they're found in other tissues, but I see predominantly, that's like the most they're highly expressed in that adipose tissue. And it plays a role in basically taking up fatty acids and adipose tissue, whereas the alpha, which is in the liver, plays a role in the transport, catabolism. So one which I sort of imagine, I mean, it'd be nice to see that, you know, someone look at that, you know, people with these specific SNPs and how to...
Does Prometheus identify various SNPs of PPR alpha? Yes, but they don't really tell you anything. They sort of pull abstracts from PubMed and just kind of like, you know, but there. So you kind of can start with research there.
I've been developing a genetic tool and I just were actually developing a lot more. I have a former NIH geneticist who's really phenomenal, who's been working with me to tell me sort of develop those... Basically, look at, you know, the literature and see what some of these SNPs are doing and then in conjunction with looking at biomarkers, various blood biomarkers to kind of help people guide, you know, what sort of they should do, what's a bypass around it, potential bypass, for example. So with a PPR alpha or gamma, I think that the take home, at least from the literature, is essentially you want to have a higher ratio of poly and mono and saturated fat ratio in order to lower your type diabetes risk.
You're saying for any... For people with a wild type or with certain SNPs? With the SNPs. With the PPR alpha, yeah.
Because... and gamma as well, because to some degree, some of the ones in PPR gamma affect the uptake of fatty acids and adipose tissue and also in muscle. And so it kind of, you know, you have a lot more fatty acids around and that can, you know, have an effect on insulin sensitivity and other things as well. So...
We should talk about this offline because I have a subset of patients for which we have such rich data and if I'm positive, all of them would be interested in knowing this and, you know, we'd certainly get their permission, but it would be interesting in taking their, you know, just their straight up 23andMe data. So here's the pattern I've seen and I'm very curious as to what the overlap is. So there's a clearly a subset of people. I think my N is too small to quantify it, but directionally it seems like, I don't know, 10 or 20% of people.
And you put them on ketogenic diets in the standard way, which usually ends up meaning you're getting at least 40% of your calories from saturated fat, typically 40 to 45% from mono and the remainder from poly. Everything goes to hell in a hand basket. And the obvious things that go to hell in a hand basket have been certainly written about in the blogosphere and Twittersphere, which is usually their LDL particle numbers skyrocket despite the fact that their triglycerides go down. So they seem to be getting more insulin sensitive, but yet inflammation is going up and you see that both specifically, cardiac specifically, so things like oxide LDL and LPPLA2, but even non-specifically, C-rected protein fiber engine.
But the deeper level is the why. And what you see is they're making much more cholesterol. Markers of cholesterol biosynthesis like Desmacherolol go way up. And some of their phyto-sterols go up, which is very counterintuitive.
Phyto-sterols would generally go down on a ketogenic diet, but they're going way up, suggesting that they're absorbing much more cholesterol, like billy or cholesterol. So first time I noticed this was 2012, and I think I wrote about this one son of a log, but I don't remember, maybe I'm thinking of another example. And it was this relatively young patient who really loved being on a ketogenic diet. But when we get his blood test back, and his LDL particle number was about 3,500 per liter.
And I know there are a lot of guys out there who seem to think that as long as you're on a ketogenic diet, it doesn't. None of this matters. I completely don't subscribe to that. And my view is that's irresponsible.
So I said to him, I said, look, I don't think a ketogenic diet is right for you. And he said, no, no, no, it's the best thing I've ever done. Look, I feel better. I look better.
I'm performing better. We got to figure out a way to do this. And the only thing I could think of, and I talked with Tom Dase Brink about this, and he said, let's try and experiment and rip all the saturated fat out of his diet. He was sort of like me.
He was eating a lot. He was a high caloric consumer. That gets really hard. So we created a diet form that was only about 20 to 25 grams a day of saturated fat.
And he ended up getting about 65% of his fat calories from mono and saturated fat, which was pretty gross. I mean, you're drinking olive oil at that point, but he was interested in doing the experiment. And sure enough, after, I don't know, maybe eight to 12 weeks, same macronutrient distribution in terms of fat protein carbohydrate, the only shift was the type of fat. So we just substituted mono for saturated.
His LDLP was 1300 animal per liter. All of the inflammation was gone. And all of the sterile biomarkers went back to normal. I've since seen that about six times.
And now I'm wondering if we took those patients and ran them through what you're doing, maybe the ones that have those SNPs. And there's a variety of them that do that. So there's the PPR alpha, PPR gamma. There's a couple of FTO related SNPs also that the ratio of saturated.
And basically in the literature, these studies have all looked at the ratio of saturated to mono and polyunsaturated fat. And for whatever reason, people with those SNPs, when they have a higher saturated fat, polyurmono and romano, they have higher inflammation, higher oxidized LDL, higher LDL, and just, you know, all these just terrible. Do you have a sense of the frequency based on the research you've done on this? How prevalent that is?
Kind of. I mean, I'd have to look back at the data probably less than 20%. So it might be in the ballpark of what I'm seeing for this different phenotype. It might be.
Yeah, it might be. So that would be really interesting to run them through my tool. And like I said, we're even expanding that a little bit. I found a few more.
Are patients sending you any of their data? Or are they doing it on their own and just? They're doing it on their own. Some people have shared their data with me because they've emailed me and something interesting.
And I'm like, oh, wow, that's super interesting to you mind sharing that with me. And they have. So if anybody's listening to this and they're saying, hey, you know, I had an advanced lipid test before an Afro-NQ-JNic diet. And I looked like this situation you described.
And they want to share with me the data. I can't promise anything, but they can certainly get the why themselves by just using genetic tool right now, which I have free reports for, for example, the PPR genes, but then I have a whole comprehensive report that's $10 recommended. So someone doesn't want to pay $10 to do the comprehensive. They can just get the free report and get the potential why themselves.
So I hope that anyone listening to this, because again, if I'm seeing this at 10% to 20% of the time and you're seeing it, then it'd be great to get a few hundred people who are that phenotype and find out if the phenotype matches the genotype. Right, yeah, it would absolutely be. And I have had people have that problem where they've tried to get a guy and couldn't figure out and they did have one or even more than one of the SNPs that really fat, asymptalism. And then there's another phenotype that fortunately is more rare.
And I also wonder what's going on with PPR alpha specifically, which is people who do everything by the book. And maybe I'm a sucker and maybe I'm gullible and maybe I believe patients too much, but I don't think I've ever had a patient lie to me. I really think like when they're not doing what they're supposed to be doing, they tell you, I'm not doing what I'm supposed to be doing. So it's not uncommon in this rare sub-subatic patient set is where they're doing everything by the book.
I mean, they're working their tail off to keep their carbs here, to keep their protein here, to keep their fat here, to keep it within this distribution. And they cannot get even close to half a millimolar of VHB in their blood. And to me, that's a really frustrating situation, frustrating for the patient because they're sort of like, what the hell I'm doing? Everything right.
Like I'm not making ketones. And I think Steve Finney sort of put out this notion that the threshold was about 0.5 millimolar. I don't have anything to argue that one way or the other. So I generally can, based on my own empirical experience personally, I sort of felt like one millimolar was about the threshold.
But again, I think that's another here and we're there. But when these people are doing what I'm describing and they're at best 0.2, maybe 0.3 millimolar, it just made me wonder, there's something in their machinery that's not doing this. And the question is, is it a like, policies problem? Is it an oxidation problem?
Is it a conversion problem? I mean, that I don't know. But it would also be interesting to understand where could the weak links be in their ketosis machinery? Right.
And there's probably, you know, there's a variety of snips in these genes and, you know, there may be certain snips that haven't even really been tested or who knows. But it sounds like, you know, to me that there's certainly something going on with the process of ketogenesis and some of the patients and their activity levels, are there active? Yeah, we're pretty. I mean, we've evolved a lot in our thinking on how those patients can be helped.
But it seems that the best way to get them over that hump is fasting, coupled with exercise if they're capable, but it's got to be relatively, it has to be, it's not gardening. Like it's got to be exercise exercise, you know, they have to really deplete glycogen. So that's the other thing I sort of wonder in some of these folks is what's happening with gluconeogenesis because I think until you start to dip down in glycogen a little bit, it's really hard to do this. And of course, we can't do liver biopsies.
Wait, so fasting does get them into ketosis? And so again, we're dealing with such a small end that I don't, I want to be thoughtful about not generalizing too much. So there's one patient in particular who's the poster child for couldn't do the ketosis thing straight away. But when we put him on every month, a five day FMD, so he would do the five day FMD, but ketogenic, not long as FMD.
And then the 25 days of ad lib was time restricted eating ketogenic. Then we've seen great results doing that in two people. So that would suggest that something again, we're not doing this as an experiment at this point. It's like clinical, it's like just try to get the job done sort of thing.
But that would suggest that something about the fasting and or the exercise and or the time restriction could get them over the hump. But it's interesting because from an evolutionary perspective, you should have been selected out really quickly if you couldn't make ketones efficiently. Well, it sounds to me that maybe there's a glycogen, you're not getting the glycogen too. If that's, you know, so maybe it's not to do with the production of ketone, but it's actually just takes a long time to complete that glycogen.
I do think there's a huge variation. Obviously physical activity plays a role in that as well. I can fast. I can do, you know, like when I do my time restricted eating, ideally I like to do it within nine or ten hours, eat all my food within nine or ten hours and then I like to fast for like 15 hours.
I can do that. And with my physical activity levels, you know, I will be closer to one millimolar. Fasten like a new. You will get to one millimolar after 15 hours of fasting.
I will be closer to that when I'm really physically active. Like during the period, a couple of years ago, and I was doing lots of like long, long seasons running and stuff, I can get closer. I mean, I'm going off of like a precision extra, which probably is not very. No, no, no precision extra is, it's, I mean, that's really good.
Yeah. So I can get between like 0.7 millimolar to like 0.9. But are you consuming a ketogenic diet during your feeding? So my diet typically, like I said, I've never really intentionally tried to do a ketogenic diet, but my diet is, I'm pretty much eat a lot of the same things.
And typically it's salmon, a salad or a sauteed vegetable with olive oil, some pasteurized, butter from pasteurized animals. And my fruits will be like blueberries, avocado. And I'll have it sometimes obviously with blueberries, avocado and kale. And will you have two meals in that window?
Or three? It depends. If I have this, you're not typically, I'll have breakfast and early dinner. And then I'll have like a snack, either nuts or this, maybe the kale with some blueberries and avocado.
So I think it, you know, any lot of nuts too. You know, I probably do. What kind of nuts? Walnuts, macadamia nuts, pistachios, cashews, almonds, I think probably.
I put cashews in the candy category. Oh really? No, no, I just mean like I can't stop eating those things. Oh yeah.
When I talk about nuts, I'm like, I eat nuts and sometimes cashews because like I just, I'm just eating M&Ms. Is that for me? Well, yeah, well, yeah, I'll get inside. When I was on the ketogenic diet and I had to be very mindful of this stuff, basically I could only consume almonds and macadamia.
Everything else was just a little too high in carbohydrate. The cashews just like personal demons. I don't know what it is about cashews. I love watermelon like the summer.
Like right now, oh, like my son loves watermelon. You get the whole one? Oh yeah. Like put a little salt on it.
Like my father-in-law's from the south and taught me that. And the summertime, I like to eat some watermelon. I like to eat peaches. You know, so I'll definitely indulge in more fruits because that's when they're around.
But you know, so I do, I think my diet tends to be. So I wouldn't be surprised if before you entered your, like, so let's say you finish your feeding window just before you went to bed. It wouldn't surprise me if you're already at 0.2 or 0.3 millimolar, right? Probably, yeah.
I never actually did measure the right thing. So check that. And that'll give me a sense because if you're going- Well, I'm not doing as strict because I'm still nursing. So I'm because it's just so hard to like, time-wise everything I'm eating probably more like within the 11 to 12 hour.
Okay. Well, when you get back to the 15, I'd be curious because if you're actually able to go from zero or 0.1 millimolar to 0.7 to 1 millimolar in a 15 hour fast, that's impressive. So when I took the exogenous ketones and I've done this one. Did you do the ester?
I did the ester by HBMN. I did their instructions, which is eat it with a high carb hydrate diet. So I had a bowl of some whole loads with some blueberries in it. And then I took the BHB ester.
I literally went from like 0.1 millimolar ketone in one hour to six millimolar. Wow. Six. One hour.
That's really high. So that's impressive. Okay. I'm trying to think.
I definitely don't get that high. And that's just with one bottle? With one bottle. And then how long did it last?
Do you recall? It depends on whether or not I did exercise like intense exercise. And so if I did the intense exercise like an hour later, I was down to like two or three or something. And have you ever taken it and just done work, for example, where basically the brain is doing more of the exercise than...
Yeah. That's what most of what I do it now, but I'm not measuring because I'm usually like doing the podcast or going traveling and doing something. But that's to go what I use for. Is that?
So I'm not really doing the using for exercise. Yeah. They've really come a long way in taste. Really?
They still taste awful. Yeah. You know, it's funny. I remember Kevin Rose who's a good mutual friend of ours, when he tried them first, he texted me and he's like, dude, these things aren't that bad.
Like you made it sound like these things were horrible. And I was like, when I had it, I thought I was drinking kerosene or jet fuel. I thought I was going to die. Go blind first, then die.
He goes, no, no, no, this stuff's good. He goes, actually, I wouldn't call it a sipping ketone, but it's actually... I was something I was a human in the T-doll, so I think they've done a good job kind of making them less ridiculous. They must really have tasted bad when you tried it because I personally think it's closer to the kerosene side than that.
It was so bad, Ron. There was like a good three month period where my favorite thing to do. Like more than anything in the world was if anyone came over to my house for dinner, they had to try one finger dip worth of stuff. And of course, the first time I drank it, I just took 50 ml and chugged it neat without mixing it or anything like that.
And yeah, I feel day just getting people to try this stuff. The salts are obviously much more palatable. Yeah, I just love it. Less studied, but more...
I wasn't... I certainly didn't feel like I had the same effects as the ester. And also, if I took a really high dose of it, I felt like I had some GI distress. Absolutely.
And I have also noticed that for some people, that is... For me, that's the case. So I cannot take the BHB ester on an empty stomach. The only way I can tolerate that at high dose is either to put it with powdered MCT or actually just take it with a meal, which in many ways defeats the purpose because I kind of like it as a way to avoid meals.
Does it lower your blood glucose? Because so significantly it was like a sounding. Yeah, no, it's pretty impressive. That's pretty impressive.
And I know that Jeff Wu, the CEO at human, is very interested in that. And I republished a post I wrote five years ago on Exogenous Ketones a couple of weeks ago. And a lot of scientists have reached out and said, hey, we're really interested in studying this. What can you tell us about this?
And so I think people are starting to realize that's an interesting way to lower glucose. Really significantly. More than 20%. I dropped 30 points.
Wow. Yeah, that's perfect. After high carbohydrate, like I said, I had oatmeal with some blueberries. It was nuts.
My blood sugar, because at the time too, I've just been nursing at night and so waking up multiple times, it's terrible for your blood glucose levels and such. But so they were a little higher than usual. Yeah, I draw me 30 points. Yeah, that's more than we typically see.
Is it? Yeah. On the topic of blood glucose, have you ever experimented with acrobose? No, I've experimented with it with cells in culture, but not personally.
This stuff's pretty interesting. It works quite well. Yeah, I'll certainly, if I'm going to indulge in some high carb action, I'm going to take 100 milligrams of acrobose beforehand and just flatline my glucose. Wow.
In many ways, I find it actually more potent than metformin at glucose reduction. I think metformin has many other effects that we'll probably get into as well. So let's go back to the IGF thing. Because this is sort of the thing that here's the thing, I'll just jump right to my punchline in my question with this.
There are two issues I now have with things I used to take to be the gods on a street. Actually three things. The first is I found Cynthia Kenyon's work on the DAF16 mutants in C. elegans to be the most convincing evidence of the role of IGF or attenuating IGF in longevity.
And I now question that, not question the work, but question the inference that can be applied to humans, given the fact that only their germ cells divide. And therefore, cancer in that organism looks nothing like cancer in us. Cancer in that organism is only a cell getting larger. There is no proliferation.
We have to sort of, I mean, it's obvious, the risk of stating the obvious, which is we're not worms, but that's a huge difference in biology. So that's the first thing. Let me let you comment on that. Yes, because I've done those experiments actually, that's probably what straight out of college, I went to work at the Salk Institute with Andrew Dillon who trained with Cynthia Kenyon.
I was a chemistry major in college and I decided I wanted to try some real biology because I only had a little bit of biology in college. And so I went to work at the Salk and really it was like those first experiments I did with worms where we would knock down the insulin, IGF-1, insulin pathway, also known as the DEF2, and the worms would live literally 100% longer. You'd go from two weeks to four weeks, right? Yeah.
And not only that, the worms were so youthful. You would look at these worms because all I would do day after day after a microscope was just picking and poking and looking at the worms and how they move. And as they get older, they start to become less mobile. It's the most convincing thing.
It's very convincing. And that was to me, in my mind, when I was like, we have a gene that's sort of homologous to this and this is happening in those worms, I want to understand that. And here's the thing about that data. And this is what I think.
If you get rid of another gene that's homologous to Foxxo, Daphxo. Daphxo. Oh, Daphxine is right. That's homologous.
It completely obliterates the lifespan extension, meaning it's the Foxxo 3 that seems to be really important for... We have how many? We have four Foxxos? You mean different Foxx genes?
Yeah. I don't know exactly how many, but the Foxxo, we have three. We have one, two, and four. Was it one, two, and three?
It was like one, two, four, five. But their analog is 16. I remember that, right? Their Daphx 16 is basically our Foxxo.
Yes, Foxxo. Yeah. And then they're health span curves, because the experiment you're describing, and no one can see what I'm doing, but you know what I'm talking about. The natural was a two week lifespan where for the first week, they're youthful, and then they have a declining health span curve.
So at the time of their death, they're totally decrepit in the experiment. You were describing if I'm thinking of the same one, you doubled the lifespan and their longevity curve became a square function. It just went out kind of. Yeah, exactly what happened.
But you get rid of the Daphx 16 and they're like, well, type. Oh, they're like, well, type. Yes. I think so.
And that largely has to do with, you know, so the IGF-1 insulin signaling pathway both inhibit Foxxo 3. So you get rid of that inhibition considerably. Foxo 3 is constantly active on those ones. It's just like super, you know, making super-oxide dysmutas and making more stem cells and making just everything's active, you know, more autophagy, more stress, like all these stress resistance pathways.
I mean, Foxo 3 is a transcription factor. It regulates whole host of genes, many of which have to do with DNA repair, autophagy, stem cell function, production of antioxidants and anti-inflammatory. So it's a lot of really good stuff. You want to act up all the time.
So there's that component to the longevity pathway. And actually, if you look at the animal data from rodents, whether you color-restricted, if you get rid of the Foxo 3, the median lifespan extension is gone. So the life function depends on Foxo 3. The cancer stuff was still, it didn't matter.
So the cancer reduction didn't depend on Foxo 3, only the lifespan extension. So I think there may be an uncoupling between humans and IGF-1. One of the major problems with IGF-1 is actually cancer. And if you look at animal studies, if you look at human studies like humans that have polymorphisms that make them have more IGF-1, they have much higher cancer incidence versus if you look at people that have polymorphisms.
I mean, is that the case? I mean, we look at the opposites, right? We look at the ones that have low GH and by proxy-low IGF and have less cancer. So you're talking about larynz syndrome?
Yeah. So larynz syndrome, yes, yes, they do. But I think there's also another one in IGF. There's HETs and IGF-1 receptor.
So you're not talking about acromegaly or people that are making too much GH. They also are more susceptible to cancer as well. Yes, I am talking about them as well, actually. The people with acromegaly are more susceptible to cancer.
Maybe that's what I was referring to with that have higher circling levels of IGF-1. So you're saying you can't uncouple the growth hormone from IGF-1? Yeah, that's been one of the things I've struggled with. It's hard to uncouple the GH, the effect of GH on the liver.
The humans. Yes, exactly. But animal studies that has been uncoupled. Like if you do any sort of tumor transplant animals and then make them have IGF-1 through a variety of modalities, the cancer will grow rapidly.
So how do we explain the human epidemiology, which, and I'm like, there are a few people that are more critical of epidemiology than me. I'm not a particular fan of it. But I find it to be quite interesting in the negative, meaning the contra-positives within epidemiology can be quite interesting. So this is the next thing that got me going, wait a minute.
And that was, there's a U-shaped mortality curve that is skewed to the right for IGF. And all cosmortality, cancer mortality, cardiovascular mortality, and neurodegenerative mortality. But when you uncouple them by disease, you see a very interesting pattern. So all cosmortality, as IGF goes up, it actually starts to go down.
It naders at the 70th percentile, and then it starts to rise. But it doesn't get as high as it started. I know for people listening, this is confusing, so we'll include the figures of all these from the papers. But the point is, it's not that as IGF goes up, mortality goes up.
It's the opposite for 70% of the ledger, only at the very end. In other words, only high levels of IGF, very high levels of IGF seem problematic. And as I know you've talked about it, I've heard you talked about this in your podcast, you have to then desegregate that by age. The older you get, the better IGF seems to be, presumably because of the preservation of lean tissue.
It turns out that most of the uptick in the mortality above the 70th percentile is driven by cancer. But actually cardiovascular disease and neurodegenerative disease seem to get, they flatline by the end. So meaning there was no benefit to being at the 100th percentile, but 99th percentile versus the 80th versus the 70th, but you weren't getting penalized for it. Which suggested to me that low IGF might not be the ticket.
Maybe it's a combination of cycling high and low IGF, but living around the median, just slightly above that, the 60th, 70th percentile. And again, that's probably more a function of my misunderstanding of the literature five years ago, but I really came away thinking, IGF, we've got to keep that as low as possible. It's funny, you and I kind of have a- We've evolved any- Very similar because I now also think that IGF one does play very important obviously in development, but also in the repair of muscle, in the growth of muscle, preserving muscle mass. Also, it gets transferred across the blood brain barrier, plays important role in neurogenesis, and allowing existing neurons to survive, which kind of brings me back to that gray matter thing with the lures.
But you know, so- And the thing that was interesting to me was the effect of exercise on IGF one. And the fact that for one, it's been shown that the boost in neurogenesis after exercise in the brain via brain drive is- requires IGF one. Animal studies have shown that mostly in rodents have shown that exercise causes IGF one across the blood brain barrier getting to the brain. But in human studies, I've also seen some showing that it does lower serum levels, I think presumably it's also going into the muscle and the brain.
So I think that people that are exercising, they're putting that IGF one to the places where it's supposed to go, muscle tissue, brain tissue as well. But in addition to that, and this is kind of what's more recent work from Dr. Balitolongo, is that we know that he does these prolonged fasts, and I think the prolonged fasting is extremely interesting for a couple of main reasons. And one is, I think that it has tremendous potential for the treatment of autoimmune disease and also cancer based on his work.
And what he has shown now in animal studies and some clinical studies is that doing a prolonged fast and or in some cases, the fasting-making diet causes this massive shrinking of organs, where he doesn't know how much of it's due to cell size decreasing versus apoptosis. He does know apoptosis is occurring and he has showed that in multiple publications. Like there is a massive induction of apoptosis after a prolonged fast, which makes sense because it's a very strong stress. And then after during the refeeding phase, their organs basically come back, they come back, they grow, regrow.
And presumably selectively repopulate. Yeah, so he's shown that these stem cells get activated, so that basically they have to be activated by the low IGF one, but then to proliferate and differentiate into whatever tissue type we're talking about, let's say we're talking about the immune system, then IGF one is required for that proliferation and differentiation and repopulation of this tissue, which means you can't just keep the IGF one low. Right, the refeeding is just as important as a deprivation. And the IGF one is key in that.
And so what he's shown now is that you can take, for example, multiple sclerosis, animal model, you can actually cause stem cells to be activated through the prolonged fast, and then during the refeeding phase, the stem cells make non-disfunctional, so they're making normal non-automium cells. And he's done a pilot clinical study with multiple sclerosis, people with multiple sclerosis, and it's helped with symptoms. But he's also done these cancer studies. And this is kind of where there's been some clinical studies that he's been involved with, like a 48-hour water fast that's been done in patients undergoing standard of care treatment.
And he's shown that it was tolerable. Not only that, there seem to be less, myelotoxicity, less, and neutropenia. So basically there, and it sensitized cancer cells to death. So not only were the cancer cells dying more, but less of the normal cells were dying.
And then he's gone ahead and shown this in animal models, also with a fasting mimicking diet. And it's like, if you look at the data, particularly in animal model, because they can do all the tissue harvesting and stuff, I mean, it's so phenomenal that I would not be surprised that in the next 10 years it will be required part of standard of care, because it seems to be so incredibly robust at selectively killing cancer cells, which makes sense. I mean, oncogenes, they stir up all sorts of things. One of them is the stress response.
And cancer cells can't respond to their prime to die. And I spent a long time studying cancer cell metabolism apoptosis with a dug-green just for upper-minute St. Jude's research hospital. And that's kind of one of the primary ways that a lot of these chemotherapeutic drugs, if they can get to the tumor site work, is that because it's a stress, cancer cells can't handle it.
They die. So I kind of went off on a tangent here. So to get back to the IGF-1. Let me say one thing going back to what you just said that is also interesting, but in the same thing.
So I agree that I think that it would really be great if patients had a better insight into nutrition going into chemotherapy. And the few times I go and give talks at hospitals or go and talk at a cancer meeting, I'm amazed at how resistant the oncologists are on average. Obviously, there are exceptions, but on average to interfering with nutrition, because in many ways their primary concern, tragically, is preserving weight. And so I always get a little verclampt when I walk through an oncology ward and I see patients drinking in shore.
I couldn't think of a worse thing you'd want to consume when you have cancer. And yet the goal is, hey, we've got to fatten these people up. So I agree with you. And I really hope that this research is accelerated, because I do think patients would benefit greatly from this.
And the other application that I saw of this several years ago, this is quite old now, but it blew my mind. I'm not sure if I'm here with Jay Mitchell's work up at Harvard. He did an experiment where he took three groups of mice. So the first group were consistently calorically restricted for their entire life.
These were probably like one and a half year old mice. So they're about halfway through their life. So these animals were constantly at 70% caloric intake. The next group was your control group.
And then your third group was at a little bit of diet until two days before an operation, and at which point they were calorie restricted to a near fast. I have to go back and look. I can't remember if it was 24 or 48 hours of fasting. It might have been a 24 hour fast.
48 would be pretty extreme for mice. So in summary, you've got control, this straight up eating, you've got 70% or 30% CR forever. And then you've got control and then fasted for a day. All the mice were then operated on where their femoral arteries were ligated, held for a period of time, and then they were reprefused for people not familiar with that.
That means that that means you open the animal up, you put clamps on the femoral arteries, which would basically stop all perfusion of blood to the lower part of the body. And then after some period of time, just before you kill the animal, you release that and then you reprophuse the blood, basically the oxygen reprefuses the organism. That's considered a refusion injury, which is about one of the most stressful things you can do in organisms. So that, you can really rapidly kill someone by doing that.
And that's something that in surgery happens quite a bit. For example, you end up having to clamp something off to repair something downstream of that. Okay, so what happened was all of the control animals died without exception. Of the other two groups, the groups that were either calorie restricted for life or transiently starved before the surgery, a significant subset did not die.
And I can't remember the number. And again, I know we're going to probably link to this study. So people are going to listen to this and go, that idiot got all those details wrong. But this is the gist of it.
A non trivial subset of them what's interesting is you could get the same benefit by an acute period of caloric restriction in proximity to an insult that you could get by a lifelong of caloric restriction. And the third piece was interesting was the group that were just starved transiently actually had a faster recovery. But again, they were fitter organisms. I remember the first time I came across that thinking there's got to be something to cycling.
And people used to always ask me, like, why are you on a ketogenic diet every minute of every day? Would there be any benefit in cycling? I still don't know the answer to that question, but I'm more curious about it now based on what you just described from Valtors work, plus this type of stuff, plus just the general ethos of the way we evolved. We fasted.
We fed. We fed. We fed. We fasted a long time.
We gorged. Like it just seems we've evolved for cycling. Right. Yeah, I agree.
It's really that with Valtors work, I just I'm so excited about the prolonged fasting and the potential benefits of it. I think that actually something that you and I discussed several years ago and I had you on interview you on my podcast that you brought up that I thought was really interesting how to do with like the failed clinical trials with binding IGF-1 and cancer. And Valtor brought up something interesting in a conversation I had with him. And that is possibly that we now know IGF-1 having low and high IGF-1 is important.
So if you're constantly having low IGF-1 and the IGF-1 is important for the immune system or population, you can imagine the context of cancer when you're giving other treatments along with it, that would be important because your immune system is key in working on cancer. And I thought that was a really interesting point. Of course, we don't have evidence of that, but I think it's something that would be interesting to investigate and it makes sense. Yeah, I definitely am on the same page with you.
I'm not in like I started out with saying I don't think that chronic calor restriction and low IGF-1 is the essential way for improving health span. I do think that IGF-1, you want it to go to your mouse, you want it to go to your brain. I think people should definitely be active, especially if they're eating a high protein and or even high carb hydrate or some that's going to produce a lot of insulin. They shouldn't be eating refined carbs, but people do.
They're eating them. They should definitely be exercising. That's another change in my belief system I think today versus, I don't know, five or six years ago. I didn't think exercise was that important to longevity, which actually sounds ridiculous for anyone who knows me because I was probably exercising four hours a day, but not because I believed it would make me live longer.
It was just sort of soothing my addictions. But I think today I feel I am much more convinced by a lot of the data you've described, certainly the central stuff. When we published this paper earlier this year with Richard Isaacs and you and I were talking about it before we started recording, we wanted to get a sense of like, if you took a completely unbiased approach and looked at the literature, what was the single most compelling thing you could do to generate or preserve brain health? We came away thinking that it was actually exercise.
And I remember when the analysts were kind of going through this and showing me all the data, I was like, come on guys, there's no way exercise could be the most important thing for brain health. And again, I'm saying this is a guy who loves exercise more than anybody, but it just struck me as there's no way. And again, I think part of it was I was just thinking about it through the vascular lens. And obviously, you know, I think better than I do that when you start to think about brain health, you have to think about it through a vascular lens, a metabolic lens, growth factor lens.
I mean, they're overlapping, but distinct pathways that are going to influence brain health. And so, I was kind of humbled by that. And now, I guess in many ways, I'm a little more adamant about it with my patients, not that I wasn't adamant before, but this is like, boy, if you're not active every day, we got to change that. I actually, the main reason I exercise is for my brain is certainly just not only for preventing neurogenesis and atrophy and all that, but just because it affects my executive function, it affects my anxiety levels, it affects my ability to make decisions.
I absolutely, if I have something that's bothering me, you're giving me anxiety or have to make a really important decision, going for a long run really helps me. And there's been studies showing that it helps with executive function, long-term planning, aerobic exercise, specifically, you know, and high-intensity interval training, all that stuff, they all do different things. Well, that's the thing we couldn't tease this out of the literature, which, again, probably is just a limitation of shitty human clinical trials, but that's the second-order question, right? Which is if you're going to take the Tim Ferriss approach, which is what's the minimum effective dose?
Because there's some people like maybe you or I who I think just generally like exercise and also get these other benefits, these endorphin benefits, but there are some people who are like, look, what do I need to do? Like, I'm going to treat exercise like medicine. And I think in that setting, I'm still not clear. So if you were that person, what I say, Rhonda, as long as you are lifting weights one hour, three times a week, like if you can only give me three hours, would that be how I want you to spend it?
Or would I rather you be doing anaerobic aerobic type thing? I mean, that's, to me, those are where these biomarkers start to become very important because we're not going to generate hard-outcome studies with that level of control. Once you, you know, try to control that many variables and be that strict about it, you're going to very much lose a hard outcome, prospectively. But if we knew what to measure, right?
And that's, you know, would we be measuring an integral of IGF, for example? So how much it rises, how much it falls, and then what that looks like over time. But I guess that's the funny thing, right? Like, the more we learn, the less we know.
Yeah, absolutely. I think that we definitely don't know the answer to that question. But I think there's a lot of data out there showing the, for example, strength training, you know, there's benefits on the brain that's been shown published, this benefits on preventing muscle atrophy, there's benefits on preventing cancer, incident, like that's all been shown for strength training for aerobic. And you know, this high intensity interval training also seems to be making its way as well.
Like, like, there was a study that I found the V O2 Maxxis is, you know, the ability of your body to transport oxygen during exercise, which also is an indicator of when you're not exercising. And obviously, transporting oxygen to the brain, for example, is extremely important. V O2 Maxx declines with age, like 1% per year, I forgot starting at what age, but, you know, it's a 10% per decade. So that's almost parallel as the muscle mass to clean up.
Yes, it does parallel exactly. And there was a study showing that 24 sessions of high intensity interval training, where it was like a 45 minute session, five minute warm up, five minute cool down on them, you know, in between the max intervals, which were like pretty long, like a minute, there was, you know, the 70% max work. Anyway, so 24 of those increased V O2 Maxx by 12%. You're literally taking an entire decade of the climb and like reversing it with the 24 sessions.
Yeah, that's actually a point when I was more active as a sort of competitive, you know, in cycling, we would get our V O2 Maxx tested about twice a year. Ryan Flaherty, who we were talking about before that podcast, who's one of my close friends and you've got to know him as well, I learned from Ryan that actually V O2 Maxx is not the most important indicator as a runner or cyclist, it's V V O2 Maxx or P V O2 Maxx. In other words, for a runner V V O2 Maxx is much more predictive of performance, which is the velocity you carry at V O2 Maxx. And for a cyclist, it's P V O2 Maxx, which is the power output at V O2 Maxx.
That said, every time you go to test, you want to test well. So, you know, over time, I learned how to game the system. You know, I want to make sure my V O2 Maxx is in the 70s, which again, to put that in perspective, like that's not at the level of professional athlete or something like the guys that are winning the Tour de France or in the high 80s or low 90s in terms of milligrams per mill per kilogram. But nevertheless, just altering my training for three weeks before a V O2 Maxx test and dropping my weight.