The Paradox of IGF-1: Rethinking Diets for Longevity and Healthspan - Full Transcript

00:00[Music] [Music] hey everyone welcome to the Peter Atia hey everyone welcome to the Peter Atia hey everyone welcome to the Peter Atia drive I'm your host Peter Atia the drive drive I'm your host Peter Atia the drive drive I'm your host Peter Atia the drive is a result of my hunger for optimizing is a result of my hunger for optimizing is a result of my hunger for optimizing performance health longevity critical performance health longevity critical performance health longevity critical thinking along with a few other thinking along with a few other thinking along with a few other obsessions I've gathered along the way obsessions I've gathered along the way obsessions I've gathered along the way I've spent the last several years I've spent the last several years I've spent the last several years working with some of those successful working with some of those successful working with some of those successful top performing individuals in the world top performing individuals in the world top performing individuals in the world and this podcast is my attempt to and this podcast is my attempt to and this podcast is my attempt to synthesize what I've learned along the synthesize what I've learned along the synthesize what I've learned along the way to help you with a higher quality way to help you with a higher quality way to help you with a higher quality more fulfilling life if you enjoy this more fulfilling life if you enjoy this more fulfilling life if you enjoy this podcast you can find more information on podcast you can find more information on podcast you can find more information on today's episode and other topics at today's episode and other topics at today's episode and other topics at Peter Dia MD com welcome to the Peter Peter Dia MD com welcome to the Peter Peter Dia MD com welcome to the Peter attea drive in this episode which I know attea drive in this episode which I know attea drive in this episode which I know is long anticipated I spoke with dr. is long anticipated I spoke with dr. is long anticipated I spoke with dr. Rhonda Patrick from found my fitness I Rhonda Patrick from found my fitness I Rhonda Patrick from found my fitness I suspect many of you listening to this suspect many of you listening to this suspect many of you listening to this know everything about Rhonda and have know everything about Rhonda and have know everything about Rhonda and have been fans of her for a really long been fans of her for a really long been fans of her for a really long period of time on the off chance there's period of time on the off chance there's period of time on the off chance there's anybody listening who doesn't know who anybody listening who doesn't know who anybody listening who doesn't know who Rhonda is I suspect by the end of this

01:00Rhonda is I suspect by the end of this Rhonda is I suspect by the end of this discussion you will also become a huge discussion you will also become a huge discussion you will also become a huge fan of hers and her podcast which is fan of hers and her podcast which is fan of hers and her podcast which is exceptional so I've known Rhonda for exceptional so I've known Rhonda for exceptional so I've known Rhonda for quite a while and just by the fact that quite a while and just by the fact that quite a while and just by the fact that we both consider San Diego home then we both consider San Diego home then we both consider San Diego home then we've just been busy enough that we just we've just been busy enough that we just we've just been busy enough that we just haven't had a chance to sit down haven't had a chance to sit down haven't had a chance to sit down together in quite a while so this together in quite a while so this together in quite a while so this discussion was kind of long overdue and discussion was kind of long overdue and discussion was kind of long overdue and it was sort of funny because as soon as it was sort of funny because as soon as it was sort of funny because as soon as Rhonda walked in we just jumped right Rhonda walked in we just jumped right Rhonda walked in we just jumped right into a really interesting discussion and into a really interesting discussion and into a really interesting discussion and then 10 minutes in I thought you know we then 10 minutes in I thought you know we then 10 minutes in I thought you know we should probably start recording because should probably start recording because should probably start recording because this is interesting stuff and so we did this is interesting stuff and so we did this is interesting stuff and so we did and similarly when the discussion and similarly when the discussion and similarly when the discussion finally ended we sat around from other finally ended we sat around from other finally ended we sat around from other 20 minutes talking about a bunch of 20 minutes talking about a bunch of 20 minutes talking about a bunch of stuff that I found myself thinking god I stuff that I found myself thinking god I stuff that I found myself thinking god I wish we were still recording this cuz wish we were still recording this cuz wish we were still recording this cuz it's super interesting so that's just it's super interesting so that's just it's super interesting so that's just basically to say I suspect Rhonda and I basically to say I suspect Rhonda and I basically to say I suspect Rhonda and I will speak again it at some point soon will speak again it at some point soon will speak again it at some point soon so don't worry if all of your questions so don't worry if all of your questions so don't worry if all of your questions weren't answered here the other thing weren't answered here the other thing weren't answered here the other thing about this podcast that was a ton of fun about this podcast that was a ton of fun about this podcast that was a ton of fun was that was that was that in the days leading up to it she and I in the days leading up to it she and I in the days leading up to it she and I had emailed each other a few times back had emailed each other a few times back had emailed each other a few times back and forth some ideas of things we would and forth some ideas of things we would and forth some ideas of things we would talk about and in the end neither of us talk about and in the end neither of us talk about and in the end neither of us really had any note sitting in front of really had any note sitting in front of really had any note sitting in front of us we just sort of sat there and shot

02:00us we just sort of sat there and shot us we just sort of sat there and shot from the hip and didn't follow a script from the hip and didn't follow a script from the hip and didn't follow a script or anything like that and didn't even or anything like that and didn't even or anything like that and didn't even get to half the things that in our get to half the things that in our get to half the things that in our emails we had suggested we would talk emails we had suggested we would talk emails we had suggested we would talk about that said all the stuff that we about that said all the stuff that we about that said all the stuff that we talked about is talked about is talked about is that I think Rhonda brings a great deal that I think Rhonda brings a great deal that I think Rhonda brings a great deal of expertise to so I don't recall the of expertise to so I don't recall the of expertise to so I don't recall the order but I know that we certainly order but I know that we certainly order but I know that we certainly touched on IGF and the growth hormone touched on IGF and the growth hormone touched on IGF and the growth hormone what I consider a little bit of a what I consider a little bit of a what I consider a little bit of a paradox which is on the one hand we have paradox which is on the one hand we have paradox which is on the one hand we have some evidence to suggest that elevated some evidence to suggest that elevated some evidence to suggest that elevated levels of IGF levels of IGF levels of IGF and that fasting may act in part by and that fasting may act in part by and that fasting may act in part by reducing those levels but at the other reducing those levels but at the other reducing those levels but at the other end of the discussion you you have some end of the discussion you you have some end of the discussion you you have some confounding and conflicting data around confounding and conflicting data around confounding and conflicting data around that we also got into a great discussion that we also got into a great discussion that we also got into a great discussion about the p par enzyme so P power alpha about the p par enzyme so P power alpha about the p par enzyme so P power alpha P power gamma one of the things that P power gamma one of the things that P power gamma one of the things that Rana does incredibly well on her podcast Rana does incredibly well on her podcast Rana does incredibly well on her podcast and I would encourage those of you who and I would encourage those of you who and I would encourage those of you who find this episode interesting who aren't find this episode interesting who aren't find this episode interesting who aren't familiar with her work to go back and familiar with her work to go back and familiar with her work to go back and actually watch some of her stuff Rhonda actually watch some of her stuff Rhonda actually watch some of her stuff Rhonda doesn't put out a lot of podcasts but doesn't put out a lot of podcasts but doesn't put out a lot of podcasts but the reason for that is the amount of

03:00the reason for that is the amount of the reason for that is the amount of work she puts into them is enormous so work she puts into them is enormous so work she puts into them is enormous so when she puts up a podcast on video when she puts up a podcast on video when she puts up a podcast on video there's explanations definitions and there's explanations definitions and there's explanations definitions and stuff scrolling across the screen so stuff scrolling across the screen so stuff scrolling across the screen so it's it's a unlike me who's incredibly it's it's a unlike me who's incredibly it's it's a unlike me who's incredibly lazy and can't even stand to listen to a lazy and can't even stand to listen to a lazy and can't even stand to listen to a podcast after I record it Rhonda is podcast after I record it Rhonda is podcast after I record it Rhonda is methodical in her ability to make that methodical in her ability to make that methodical in her ability to make that easier for the viewer so you'll learn a easier for the viewer so you'll learn a easier for the viewer so you'll learn a lot about this stuff you think we're lot about this stuff you think we're lot about this stuff you think we're going to quickly over it by probably going to quickly over it by probably going to quickly over it by probably going back to Rhonda's site we talked a going back to Rhonda's site we talked a going back to Rhonda's site we talked a lot about the possible genetic lot about the possible genetic lot about the possible genetic explanations for why some people do and explanations for why some people do and explanations for why some people do and don't respond particularly well to don't respond particularly well to don't respond particularly well to ketogenic diets and of course you can ketogenic diets and of course you can ketogenic diets and of course you can think of that in two ways there's think of that in two ways there's think of that in two ways there's respond as far as the ability to make respond as far as the ability to make respond as far as the ability to make ketones but then there's also sort of ketones but then there's also sort of ketones but then there's also sort of these patients that I described seeing these patients that I described seeing these patients that I described seeing where you put them on a ketogenic diet where you put them on a ketogenic diet where you put them on a ketogenic diet and everything seems to go wrong so at and everything seems to go wrong so at and everything seems to go wrong so at least biochemically wrong so now that's least biochemically wrong so now that's least biochemically wrong so now that's a very interesting discussion in many a very interesting discussion in many a very interesting discussion in many ways I think my favorite part of this ways I think my favorite part of this ways I think my favorite part of this discussion was the way it started which discussion was the way it started which discussion was the way it started which was the first question I asked Rhonda was the first question I asked Rhonda was the first question I asked Rhonda which was kind of a random question I

04:00which was kind of a random question I which was kind of a random question I think led to some interesting think led to some interesting think led to some interesting back-and-forth between us which was back-and-forth between us which was back-and-forth between us which was effectively what do you believe today effectively what do you believe today effectively what do you believe today that you didn't believe before and vice that you didn't believe before and vice that you didn't believe before and vice versa and I always find that to be one versa and I always find that to be one versa and I always find that to be one of the most interesting ways to dive of the most interesting ways to dive of the most interesting ways to dive into a discussion with someone who's into a discussion with someone who's into a discussion with someone who's buried buried buried knee-deep into science because if you're knee-deep into science because if you're knee-deep into science because if you're really thinking about science you have really thinking about science you have really thinking about science you have to understand of course that virtually to understand of course that virtually to understand of course that virtually all facts have a half-life and our all facts have a half-life and our all facts have a half-life and our knowledge is constantly evolving in many knowledge is constantly evolving in many knowledge is constantly evolving in many ways that's what makes the field so ways that's what makes the field so ways that's what makes the field so difficult to stay on top of but at the difficult to stay on top of but at the difficult to stay on top of but at the same time so interesting and so to me same time so interesting and so to me same time so interesting and so to me one of the marks of a very thoughtful one of the marks of a very thoughtful one of the marks of a very thoughtful person is someone whose beliefs are person is someone whose beliefs are person is someone whose beliefs are flexible and who's willing to flexible and who's willing to flexible and who's willing to acknowledge that something that they acknowledge that something that they acknowledge that something that they believed was once true or not true can believed was once true or not true can believed was once true or not true can be flipped and so I think you know be flipped and so I think you know be flipped and so I think you know Rhonda and I share that and I think it Rhonda and I share that and I think it Rhonda and I share that and I think it was actually really fun to see where her was actually really fun to see where her was actually really fun to see where her beliefs have changed over time so with beliefs have changed over time so with beliefs have changed over time so with that said I think the show notes for that said I think the show notes for that said I think the show notes for this particular episode are going to be this particular episode are going to be this particular episode are going to be very helpful and you can find those at very helpful and you can find those at very helpful and you can find those at Peter attea MD com forward slash podcast

05:00Peter attea MD com forward slash podcast Peter attea MD com forward slash podcast and I hope you enjoy this discussion at and I hope you enjoy this discussion at and I hope you enjoy this discussion at least half as much as I did I suspect it least half as much as I did I suspect it least half as much as I did I suspect it won't be the last so without further won't be the last so without further won't be the last so without further delay here's my conversation with dr. delay here's my conversation with dr. delay here's my conversation with dr. Rhonda Patrick Rhonda so great to have Rhonda Patrick Rhonda so great to have Rhonda Patrick Rhonda so great to have you here happy to be here it's great to you here happy to be here it's great to you here happy to be here it's great to see you again I can't believe we live in see you again I can't believe we live in see you again I can't believe we live in the same city and only see each other the same city and only see each other the same city and only see each other once a year if you're in well thank you once a year if you're in well thank you once a year if you're in well thank you for taking the trip up here today to my for taking the trip up here today to my for taking the trip up here today to my office my pleasure and I'll join the office my pleasure and I'll join the office my pleasure and I'll join the long list of people congratulating you long list of people congratulating you long list of people congratulating you on your 10 month old son thank you thank on your 10 month old son thank you thank on your 10 month old son thank you thank you I almost don't know where to begin you I almost don't know where to begin you I almost don't know where to begin because there are so many things that because there are so many things that because there are so many things that you know we share in common as far as you know we share in common as far as you know we share in common as far as interests but I want to start with a interests but I want to start with a interests but I want to start with a really broad question which is you spend really broad question which is you spend really broad question which is you spend so much time thinking about many of the so much time thinking about many of the so much time thinking about many of the same problems I spend time thinking same problems I spend time thinking same problems I spend time thinking about what do you believe today that you about what do you believe today that you about what do you believe today that you did not believe four or five years ago did not believe four or five years ago did not believe four or five years ago probably the biggest thing that has probably the biggest thing that has probably the biggest thing that has changed and what I now believe but I

06:00changed and what I now believe but I changed and what I now believe but I didn't four or five years ago even more didn't four or five years ago even more didn't four or five years ago even more is that one of the major modalities were is that one of the major modalities were is that one of the major modalities were you know how increasing healthspan which you know how increasing healthspan which you know how increasing healthspan which is you know the healthy part of of your is you know the healthy part of of your is you know the healthy part of of your life delaying the onset of age-related life delaying the onset of age-related life delaying the onset of age-related diseases the major modality for doing diseases the major modality for doing diseases the major modality for doing that that would be the best way to do it that that would be the best way to do it that that would be the best way to do it would be calorie restriction or dietary would be calorie restriction or dietary would be calorie restriction or dietary restriction so eating you know thirty restriction so eating you know thirty restriction so eating you know thirty percent less food than you normally percent less food than you normally percent less food than you normally would eat I used to really think that would eat I used to really think that would eat I used to really think that was the way to go for for doing that and was the way to go for for doing that and was the way to go for for doing that and I think that my beliefs have changed for I think that my beliefs have changed for I think that my beliefs have changed for that in that being the major modality that in that being the major modality that in that being the major modality for a few reasons for a few reasons for a few reasons one reason is because I think that one reason is because I think that one reason is because I think that actually so one of the things that that actually so one of the things that that actually so one of the things that that occurs during caloric restriction is a occurs during caloric restriction is a occurs during caloric restriction is a major drop in major drop in major drop in the growth hormone igf-1 and that's you the growth hormone igf-1 and that's you the growth hormone igf-1 and that's you know that's thought to regulate a lot of know that's thought to regulate a lot of know that's thought to regulate a lot of the you know improved healthspan effects the you know improved healthspan effects the you know improved healthspan effects at least in in some organisms like mice at least in in some organisms like mice at least in in some organisms like mice and and rhesus monkeys but I do I do and and rhesus monkeys but I do I do and and rhesus monkeys but I do I do believe now based off a variety of believe now based off a variety of believe now based off a variety of research from people like Valter Longo

07:00research from people like Valter Longo research from people like Valter Longo that periods of growth actually that periods of growth actually that periods of growth actually specifically periods of igf-1 are really specifically periods of igf-1 are really specifically periods of igf-1 are really important so you're not you know if important so you're not you know if important so you're not you know if you're constantly doing this calorie you're constantly doing this calorie you're constantly doing this calorie restriction then then you're you're not restriction then then you're you're not restriction then then you're you're not really gonna have that period of growth really gonna have that period of growth really gonna have that period of growth because you're chronically doing that because you're chronically doing that because you're chronically doing that and really interesting I don't know if and really interesting I don't know if and really interesting I don't know if you saw the recent nature study that you saw the recent nature study that you saw the recent nature study that came out it was in April this year on came out it was in April this year on came out it was in April this year on lemurs the so the the study essentially lemurs the so the the study essentially lemurs the so the the study essentially showed and these are you know I guess showed and these are you know I guess showed and these are you know I guess they're not human primate mole animal they're not human primate mole animal they're not human primate mole animal model but their lifespan is in a median model but their lifespan is in a median model but their lifespan is in a median lifespan is around my six years or lifespan is around my six years or lifespan is around my six years or something like that and I think their something like that and I think their something like that and I think their maximum is 11 or 12 years I don't maximum is 11 or 12 years I don't maximum is 11 or 12 years I don't remember but the caloric restriction did remember but the caloric restriction did remember but the caloric restriction did increase the median lifespan it also increase the median lifespan it also increase the median lifespan it also increased maximum so they like lived a increased maximum so they like lived a increased maximum so they like lived a year longer than typically and there's year longer than typically and there's year longer than typically and there's you know a lot of delayed onset of you know a lot of delayed onset of you know a lot of delayed onset of various degenerative diseases but there various degenerative diseases but there various degenerative diseases but there was a massive atrophy and gray brain was a massive atrophy and gray brain was a massive atrophy and gray brain matter in in regions of the brain that

08:00matter in in regions of the brain that matter in in regions of the brain that didn't occur in control animals which is didn't occur in control animals which is didn't occur in control animals which is just another sort of example of how you just another sort of example of how you just another sort of example of how you know sometimes some of these modalities know sometimes some of these modalities know sometimes some of these modalities that we we think are really good for that we we think are really good for that we we think are really good for increasing health span sometimes have increasing health span sometimes have increasing health span sometimes have other effects and I think that getting other effects and I think that getting other effects and I think that getting into the igf-1 I think will probably you into the igf-1 I think will probably you into the igf-1 I think will probably you and I will talk about that because we and I will talk about that because we and I will talk about that because we both have a shared interest in that but both have a shared interest in that but both have a shared interest in that but but the periods of growth and being but the periods of growth and being but the periods of growth and being necessary for health I think I think necessary for health I think I think necessary for health I think I think that's kind of kind of turning point in that's kind of kind of turning point in that's kind of kind of turning point in my mind and so now I actually think that my mind and so now I actually think that my mind and so now I actually think that perhaps even doing periodic you know perhaps even doing periodic you know perhaps even doing periodic you know prolonged fasts or a better way of doing prolonged fasts or a better way of doing prolonged fasts or a better way of doing that because you can you can get that that because you can you can get that that because you can you can get that igf-1 boost and you can get the the igf-1 boost and you can get the the igf-1 boost and you can get the the lower igf-1 among other things that lower igf-1 among other things that lower igf-1 among other things that occur but um I think we can dive into occur but um I think we can dive into occur but um I think we can dive into that if you want but I think that one that if you want but I think that one that if you want but I think that one could be done yeah I think that's could be done yeah I think that's could be done yeah I think that's probably one of the major things the probably one of the major things the probably one of the major things the other would be actually another other would be actually another other would be actually another interests that we share would be I think interests that we share would be I think interests that we share would be I think it was a lot more skeptical of of

09:00it was a lot more skeptical of of it was a lot more skeptical of of ketogenic diets about four years ago in ketogenic diets about four years ago in ketogenic diets about four years ago in terms of being great for long-term terms of being great for long-term terms of being great for long-term health and health span and I think that health and health span and I think that health and health span and I think that some of my my thoughts on that have some of my my thoughts on that have some of my my thoughts on that have changed a bit based off of more recent changed a bit based off of more recent changed a bit based off of more recent long-term studies in animals long-term studies in animals long-term studies in animals specifically in mice from work from dr. specifically in mice from work from dr. specifically in mice from work from dr. Eric Verdun and also from out of UC Eric Verdun and also from out of UC Eric Verdun and also from out of UC Davis showing that ketogenic diets in in Davis showing that ketogenic diets in in Davis showing that ketogenic diets in in rodents can inhale span increase meeting rodents can inhale span increase meeting rodents can inhale span increase meeting life span certainly improve cognitive life span certainly improve cognitive life span certainly improve cognitive function now the caveat there is that function now the caveat there is that function now the caveat there is that typically with a ketogenic diet in in typically with a ketogenic diet in in typically with a ketogenic diet in in rodents it's actually can be most the rodents it's actually can be most the rodents it's actually can be most the time is obesogenic and the way that time is obesogenic and the way that time is obesogenic and the way that these guys worked around that was they these guys worked around that was they these guys worked around that was they found that had they had to limit the found that had they had to limit the found that had they had to limit the calorie and what was interesting was calorie and what was interesting was calorie and what was interesting was that or or cycle them right well so dr. that or or cycle them right well so dr. that or or cycle them right well so dr. Eric Verdun the way they did that was by Eric Verdun the way they did that was by Eric Verdun the way they did that was by cycling it but UC Davis what they did cycling it but UC Davis what they did cycling it but UC Davis what they did was actually put a calorie cap and turns was actually put a calorie cap and turns was actually put a calorie cap and turns out after talking with dr. Sachin panda out after talking with dr. Sachin panda out after talking with dr. Sachin panda that they ended up being on a time

10:00that they ended up being on a time that they ended up being on a time restricted feeding schedule and so the restricted feeding schedule and so the restricted feeding schedule and so the ketogenic diet was you know they were ketogenic diet was you know they were ketogenic diet was you know they were basically eating all their food within a basically eating all their food within a basically eating all their food within a certain like you know eight or eight or certain like you know eight or eight or certain like you know eight or eight or so or nine hour window and then they so or nine hour window and then they so or nine hour window and then they were fasting for so you know it's kind were fasting for so you know it's kind were fasting for so you know it's kind of one of those things where you know in of one of those things where you know in of one of those things where you know in humans we don't we don't really know you humans we don't we don't really know you humans we don't we don't really know you know I don't know exactly know how know I don't know exactly know how know I don't know exactly know how people I've never actually done a people I've never actually done a people I've never actually done a ketogenic diet myself so I don't know ketogenic diet myself so I don't know ketogenic diet myself so I don't know exactly what people are doing if they're exactly what people are doing if they're exactly what people are doing if they're eating you know all the time or what so eating you know all the time or what so eating you know all the time or what so so I'm also intrigued by that and and in so I'm also intrigued by that and and in so I'm also intrigued by that and and in many ways almost have the mirror of your many ways almost have the mirror of your many ways almost have the mirror of your experience which was you know four or experience which was you know four or experience which was you know four or five six years ago seven years ago I five six years ago seven years ago I five six years ago seven years ago I guess is when I really really got into guess is when I really really got into guess is when I really really got into ketogenic diets was on a ketogenic diet ketogenic diets was on a ketogenic diet ketogenic diets was on a ketogenic diet for three years for three years for three years save one day and I wouldn't say I have save one day and I wouldn't say I have save one day and I wouldn't say I have any less faith in them today I just any less faith in them today I just any less faith in them today I just impersonally less interested and find it impersonally less interested and find it impersonally less interested and find it much harder to do so just as far as much harder to do so just as far as much harder to do so just as far as compliance with the ketogenic diet you compliance with the ketogenic diet you compliance with the ketogenic diet you know I think my life is just more know I think my life is just more know I think my life is just more complicated today in terms of travel and complicated today in terms of travel and complicated today in terms of travel and things like that and kids and stuff but

11:00things like that and kids and stuff but things like that and kids and stuff but the thing that surprised me with the the thing that surprised me with the the thing that surprised me with the recent because those two publications recent because those two publications recent because those two publications came out and sell right the ones came out and sell right the ones came out and sell right the ones yeah I was actually kind of surprised by yeah I was actually kind of surprised by yeah I was actually kind of surprised by a couple of things so one was what you a couple of things so one was what you a couple of things so one was what you said which was Eric noting that hey when said which was Eric noting that hey when said which was Eric noting that hey when we constitutively gave these guys this we constitutively gave these guys this we constitutively gave these guys this food they just they got obese that's food they just they got obese that's food they just they got obese that's really counterintuitive when you think really counterintuitive when you think really counterintuitive when you think about how ketogenic diets increase about how ketogenic diets increase about how ketogenic diets increase circulating metabolic fuels and that circulating metabolic fuels and that circulating metabolic fuels and that should down regulate appetite and I should down regulate appetite and I should down regulate appetite and I think in humans you know there's a huge think in humans you know there's a huge think in humans you know there's a huge debate about why do people lose weight debate about why do people lose weight debate about why do people lose weight on ketogenic diets are they losing on ketogenic diets are they losing on ketogenic diets are they losing weight because they're eating less were weight because they're eating less were weight because they're eating less were they losing weight because they're they losing weight because they're they losing weight because they're ramping up fat oxidation ramping up fat oxidation ramping up fat oxidation disproportionate to where they were disproportionate to where they were disproportionate to where they were before which drives up energy before which drives up energy before which drives up energy expenditure of course I suspect the expenditure of course I suspect the expenditure of course I suspect the answer is both in other words if you do answer is both in other words if you do answer is both in other words if you do the latter the latter the latter the former should happen so when people the former should happen so when people the former should happen so when people say why do you eat less on a ketogenic say why do you eat less on a ketogenic say why do you eat less on a ketogenic diet the question is really or the diet the question is really or the diet the question is really or the thinking would be are you eating less thinking would be are you eating less thinking would be are you eating less because you are basically eating

12:00because you are basically eating because you are basically eating yourself more because you're obviously yourself more because you're obviously yourself more because you're obviously oxidizing all of those fatty acids to oxidizing all of those fatty acids to oxidizing all of those fatty acids to make BHB or is it some other reason that make BHB or is it some other reason that make BHB or is it some other reason that you know has to do with the neuro you know has to do with the neuro you know has to do with the neuro chemistry of these things that go beyond chemistry of these things that go beyond chemistry of these things that go beyond sort of the metabolic central pardon me sort of the metabolic central pardon me sort of the metabolic central pardon me peripheral effects of it so that's the peripheral effects of it so that's the peripheral effects of it so that's the first thing that surprised me of that first thing that surprised me of that first thing that surprised me of that study which was why were those mice study which was why were those mice study which was why were those mice overeating was there something else in overeating was there something else in overeating was there something else in them because they couldn't have had that them because they couldn't have had that them because they couldn't have had that much secret they usually put sucrose in much secret they usually put sucrose in much secret they usually put sucrose in Mouse chow but there couldn't have been Mouse chow but there couldn't have been Mouse chow but there couldn't have been that much sucrose or they wouldn't have that much sucrose or they wouldn't have that much sucrose or they wouldn't have been able to get into ketosis and I been able to get into ketosis and I been able to get into ketosis and I think even previous studies like earlier think even previous studies like earlier think even previous studies like earlier in the literature showed something in the literature showed something in the literature showed something similar worried it was obesogenic now similar worried it was obesogenic now similar worried it was obesogenic now there was certain genetic backgrounds it there was certain genetic backgrounds it there was certain genetic backgrounds it also seemed to kind of little you know also seemed to kind of little you know also seemed to kind of little you know regulate that to some degree but what I regulate that to some degree but what I regulate that to some degree but what I was actually thinking so you brought up was actually thinking so you brought up was actually thinking so you brought up some really interesting points is that some really interesting points is that some really interesting points is that thinking of it in the context of like thinking of it in the context of like thinking of it in the context of like let's say they're they're eating they're let's say they're they're eating they're let's say they're they're eating they're constantly eating the fat or they're not constantly eating the fat or they're not constantly eating the fat or they're not they're not having a period of rest I they're not having a period of rest I they're not having a period of rest I know that for example when you're making know that for example when you're making know that for example when you're making malonyl-coa which is something that you malonyl-coa which is something that you malonyl-coa which is something that you do when you're oxidizing fat malonyl-coa do when you're oxidizing fat malonyl-coa do when you're oxidizing fat malonyl-coa inhibits the connoting pontil transfer inhibits the connoting pontil transfer inhibits the connoting pontil transfer is the basically the transporter to

13:00is the basically the transporter to is the basically the transporter to transport fatty acids in the transport fatty acids in the transport fatty acids in the mitochondria so if you constantly are mitochondria so if you constantly are mitochondria so if you constantly are making methanol koay because you're making methanol koay because you're making methanol koay because you're constantly eating the fat then you're constantly eating the fat then you're constantly eating the fat then you're going to start to have this inhibition going to start to have this inhibition going to start to have this inhibition you're going to start to then store that you're going to start to then store that you're going to start to then store that other the fatty acids in adipose tissue other the fatty acids in adipose tissue other the fatty acids in adipose tissue rather than caramelizing them right so rather than caramelizing them right so rather than caramelizing them right so it seems to me that we don't see that by it seems to me that we don't see that by it seems to me that we don't see that by the way with the exogenous ketones do we the way with the exogenous ketones do we the way with the exogenous ketones do we this is something I'm still trying to this is something I'm still trying to this is something I'm still trying to get get get and alone I I agree I'm certain I am I and alone I I agree I'm certain I am I and alone I I agree I'm certain I am I am extremely interested in exhaustion as am extremely interested in exhaustion as am extremely interested in exhaustion as Ketones approach like them okay you yeah Ketones approach like them okay you yeah Ketones approach like them okay you yeah yeah it's gonna bring you someone so I I yeah it's gonna bring you someone so I I yeah it's gonna bring you someone so I I really enjoy effects they have on on my really enjoy effects they have on on my really enjoy effects they have on on my brain so I've used them for like brain so I've used them for like brain so I've used them for like endurance exercise and I also like it endurance exercise and I also like it endurance exercise and I also like it for that as well I do notice that I have for that as well I do notice that I have for that as well I do notice that I have a little bit of a run longer than I a little bit of a run longer than I a little bit of a run longer than I usually stop at this point on the beach usually stop at this point on the beach usually stop at this point on the beach and like I can keep going another you and like I can keep going another you and like I can keep going another you know but what I really like is is for me know but what I really like is is for me know but what I really like is is for me it really helps with focus and lower it really helps with focus and lower it really helps with focus and lower anxiety levels so like I seem to be able anxiety levels so like I seem to be able anxiety levels so like I seem to be able to I'm always on to the next you know to I'm always on to the next you know to I'm always on to the next you know what's and and so this kind of helps me what's and and so this kind of helps me what's and and so this kind of helps me like stay in the now at least I and that

14:00like stay in the now at least I and that like stay in the now at least I and that could be completely Percy but I don't could be completely Percy but I don't could be completely Percy but I don't know but anyway so that's one thing that know but anyway so that's one thing that know but anyway so that's one thing that I like about that but to get back to I like about that but to get back to I like about that but to get back to your point I had wondered the same thing your point I had wondered the same thing your point I had wondered the same thing because what's the effect of exogenous because what's the effect of exogenous because what's the effect of exogenous ketones on normal fatty acid metabolism ketones on normal fatty acid metabolism ketones on normal fatty acid metabolism and the reason I'd wonder that is and the reason I'd wonder that is and the reason I'd wonder that is because there was a paper that recently because there was a paper that recently because there was a paper that recently came out where I think it was the one came out where I think it was the one came out where I think it was the one that was done in humans where humans that was done in humans where humans that was done in humans where humans they were given the beta hydroxy they were given the beta hydroxy they were given the beta hydroxy butyrate ester for endurance and it butyrate ester for endurance and it butyrate ester for endurance and it enhanced endurance performance but they enhanced endurance performance but they enhanced endurance performance but they found inhibited yes and also it found inhibited yes and also it found inhibited yes and also it inhibited fatty acid something to do inhibited fatty acid something to do inhibited fatty acid something to do with the flip fatty acid transport out with the flip fatty acid transport out with the flip fatty acid transport out of the adipose something to do with of the adipose something to do with of the adipose something to do with where I was like going with some what where I was like going with some what where I was like going with some what some of that had to do with lipid some of that had to do with lipid some of that had to do with lipid metabolism which suggested possibly metabolism which suggested possibly metabolism which suggested possibly there could be in innovation now you there could be in innovation now you there could be in innovation now you know it's funny I'm gonna see I'm in New know it's funny I'm gonna see I'm in New know it's funny I'm gonna see I'm in New York next week and Dom is gonna be in York next week and Dom is gonna be in York next week and Dom is gonna be in New York Dom D'Agostino who obviously New York Dom D'Agostino who obviously New York Dom D'Agostino who obviously you know well and we're grabbing dinner you know well and we're grabbing dinner you know well and we're grabbing dinner one night and I we're gonna talk about one night and I we're gonna talk about one night and I we're gonna talk about this paper because I remember when it

15:00this paper because I remember when it this paper because I remember when it came out Dom sent me an email we'll know came out Dom sent me an email we'll know came out Dom sent me an email we'll know for sure if you want or ever you said it for sure if you want or ever you said it for sure if you want or ever you said it yes and that's for sure yes and that's for sure yes and that's for sure because there was something about that because there was something about that because there was something about that study that was a little bit off I need study that was a little bit off I need study that was a little bit off I need to kind of go back and and and look at to kind of go back and and and look at to kind of go back and and and look at it but it does beg another question so I it but it does beg another question so I it but it does beg another question so I want to go back because we're there's want to go back because we're there's want to go back because we're there's gonna be this I know there's gonna be a gonna be this I know there's gonna be a gonna be this I know there's gonna be a theme today which is multiple threads theme today which is multiple threads theme today which is multiple threads that are easy for us to go off and I are that are easy for us to go off and I are that are easy for us to go off and I are great at going on - yeah yeah let's go great at going on - yeah yeah let's go great at going on - yeah yeah let's go back to the mice let's go back to the back to the mice let's go back to the back to the mice let's go back to the two studies do you recall if in the two studies do you recall if in the two studies do you recall if in the Verdun study when they before they Verdun study when they before they Verdun study when they before they started cycling the ketogenic diet started cycling the ketogenic diet started cycling the ketogenic diet when they were just giving it to them when they were just giving it to them when they were just giving it to them all the time did they have a window in all the time did they have a window in all the time did they have a window in which they could eat ad libitum that which they could eat ad libitum that which they could eat ad libitum that they over a tin or were they given they over a tin or were they given they over a tin or were they given 24-hour access to food 24-hour so what 24-hour access to food 24-hour so what 24-hour access to food 24-hour so what they never tried then was let's give you they never tried then was let's give you they never tried then was let's give you food for 10 hours and let you eat ad food for 10 hours and let you eat ad food for 10 hours and let you eat ad libitum because that would be libitum because that would be libitum because that would be interesting if they would overeat in interesting if they would overeat in interesting if they would overeat in that setting maybe not that interesting that setting maybe not that interesting that setting maybe not that interesting the other experiment that I don't think the other experiment that I don't think the other experiment that I don't think has been done is remember when they did has been done is remember when they did has been done is remember when they did the they took a variant which was high

16:00the they took a variant which was high the they took a variant which was high fat but high ish carb and so it wasn't fat but high ish carb and so it wasn't fat but high ish carb and so it wasn't there was enough carbon the diet that it there was enough carbon the diet that it there was enough carbon the diet that it wasn't producing ketosis but it was wasn't producing ketosis but it was wasn't producing ketosis but it was still a high fat diet I'd like to see still a high fat diet I'd like to see still a high fat diet I'd like to see that experiment repeated but with an X that experiment repeated but with an X that experiment repeated but with an X on Janice ketone because then you could on Janice ketone because then you could on Janice ketone because then you could start to identify the effect of the start to identify the effect of the start to identify the effect of the carbohydrate specifically and tease out carbohydrate specifically and tease out carbohydrate specifically and tease out the effect of the fat and the BHB the effect of the fat and the BHB the effect of the fat and the BHB right I think I remember one of the big right I think I remember one of the big right I think I remember one of the big differences between the the high fat low differences between the the high fat low differences between the the high fat low carb and the actual ketogenic diet was carb and the actual ketogenic diet was carb and the actual ketogenic diet was the the induction of PBR alpha yes which the the induction of PBR alpha yes which the the induction of PBR alpha yes which makes sense because that's involved in makes sense because that's involved in makes sense because that's involved in you know ketogenesis itself but to what you know ketogenesis itself but to what you know ketogenesis itself but to what degree that regulates you know any of degree that regulates you know any of degree that regulates you know any of the other important properties that were the other important properties that were the other important properties that were found including the the really the found including the the really the found including the the really the profound effects on the brain and you profound effects on the brain and you profound effects on the brain and you know so I I like to personally get my know so I I like to personally get my know so I I like to personally get my ketogenesis from from my periods of ketogenesis from from my periods of ketogenesis from from my periods of fasting more so than carbohydrate fasting more so than carbohydrate fasting more so than carbohydrate restriction well i do i do refined restriction well i do i do refined restriction well i do i do refined carbohydrate restriction but i also I

17:00carbohydrate restriction but i also I carbohydrate restriction but i also I think there's a lot of benefits and this think there's a lot of benefits and this think there's a lot of benefits and this is part of the reason why for so long I is part of the reason why for so long I is part of the reason why for so long I was skeptical of the ketogenic diet is was skeptical of the ketogenic diet is was skeptical of the ketogenic diet is because I think there's a lot of because I think there's a lot of because I think there's a lot of benefits in eating a variety of plants I benefits in eating a variety of plants I benefits in eating a variety of plants I think that there's a lot of various think that there's a lot of various think that there's a lot of various micronutrients that are much higher micronutrients that are much higher micronutrients that are much higher density in plants fully magnesium density in plants fully magnesium density in plants fully magnesium vitamin k1 but also there's a lot of vitamin k1 but also there's a lot of vitamin k1 but also there's a lot of fermentable fibers and and things that fermentable fibers and and things that fermentable fibers and and things that are really also really good for the gut are really also really good for the gut are really also really good for the gut microbiome which i think is very microbiome which i think is very microbiome which i think is very important for regulating immune function important for regulating immune function important for regulating immune function so that's kind of been my my hang-up but so that's kind of been my my hang-up but so that's kind of been my my hang-up but I think you know like people like Dom I think you know like people like Dom I think you know like people like Dom seem to be doing a modified ketogenic seem to be doing a modified ketogenic seem to be doing a modified ketogenic diet where they're you know definitely diet where they're you know definitely diet where they're you know definitely getting the greens trying to get the getting the greens trying to get the getting the greens trying to get the leafy greens so I mean I think that you leafy greens so I mean I think that you leafy greens so I mean I think that you know one way to kind of get around that know one way to kind of get around that know one way to kind of get around that plus I think there's also a way to do a plus I think there's also a way to do a plus I think there's also a way to do a ketogenic diet where you're eating a lot ketogenic diet where you're eating a lot ketogenic diet where you're eating a lot of of of salmon avocado nuts you know olive oil salmon avocado nuts you know olive oil salmon avocado nuts you know olive oil and it's not just like butter and keto and it's not just like butter and keto and it's not just like butter and keto bombs and all this like pork rinds and bombs and all this like pork rinds and bombs and all this like pork rinds and stuff where I'm just like where's the stuff where I'm just like where's the stuff where I'm just like where's the nutrient density and some of that you nutrient density and some of that you nutrient density and some of that you know so yeah it's funny I mean I guess

18:00know so yeah it's funny I mean I guess know so yeah it's funny I mean I guess it depends on how many calories you need it depends on how many calories you need it depends on how many calories you need but at the time that during that window but at the time that during that window but at the time that during that window when I was on a ketogenic diet I was when I was on a ketogenic diet I was when I was on a ketogenic diet I was also still very active certainly much also still very active certainly much also still very active certainly much more so than now and I really required a more so than now and I really required a more so than now and I really required a lot of calories I mean I couldn't lot of calories I mean I couldn't lot of calories I mean I couldn't maintain my weight below 4,500 calories maintain my weight below 4,500 calories maintain my weight below 4,500 calories a day and I still stucked a pretty a day and I still stucked a pretty a day and I still stucked a pretty strict absolutes on the protein and strict absolutes on the protein and strict absolutes on the protein and carbohydrates I really kept my carbs and carbohydrates I really kept my carbs and carbohydrates I really kept my carbs and I didn't look at net carbs I hope by the I didn't look at net carbs I hope by the I didn't look at net carbs I hope by the way for those listening and wondering way for those listening and wondering way for those listening and wondering what that noise is this is something what that noise is this is something what that noise is this is something Rhonda and I are very used to those are Rhonda and I are very used to those are Rhonda and I are very used to those are f-18s which how many overhead drive-bys f-18s which how many overhead drive-bys f-18s which how many overhead drive-bys are we gonna get today you've had to are we gonna get today you've had to are we gonna get today you've had to predict anymore yeah I would say predict anymore yeah I would say predict anymore yeah I would say probably between three or four okay probably between three or four okay probably between three or four okay yeah that's the sound of freedom people yeah that's the sound of freedom people yeah that's the sound of freedom people so just get used to me so I was getting so just get used to me so I was getting so just get used to me so I was getting probably 50 grams of carbohydrates total probably 50 grams of carbohydrates total probably 50 grams of carbohydrates total carb everything I should say probably carb everything I should say probably carb everything I should say probably about 80 grams of total carb but you'll about 80 grams of total carb but you'll about 80 grams of total carb but you'll see that what type of carbs it was see that what type of carbs it was see that what type of carbs it was really had to limit protein to about a really had to limit protein to about a really had to limit protein to about a hundred to 110 grams if I went over that hundred to 110 grams if I went over that hundred to 110 grams if I went over that I would get kicked out and so fat made

19:00I would get kicked out and so fat made I would get kicked out and so fat made up about 90% of my total calories and so up about 90% of my total calories and so up about 90% of my total calories and so there's only so many ways you can get there's only so many ways you can get there's only so many ways you can get that much fat and the most efficient way that much fat and the most efficient way that much fat and the most efficient way is actually salad with olive oil I mean is actually salad with olive oil I mean is actually salad with olive oil I mean I couldn't believe the amount of I couldn't believe the amount of I couldn't believe the amount of vegetables I had to consume to stay in vegetables I had to consume to stay in vegetables I had to consume to stay in ketosis you know obviously had to have ketosis you know obviously had to have ketosis you know obviously had to have two huge salads a day where I would make two huge salads a day where I would make two huge salads a day where I would make my own dressing which was a heavy olive my own dressing which was a heavy olive my own dressing which was a heavy olive oil-based dressing and I could probably oil-based dressing and I could probably oil-based dressing and I could probably only have one avocado a day which I only have one avocado a day which I only have one avocado a day which I would always have because I than would always have because I than would always have because I than anything overnight I was getting too anything overnight I was getting too anything overnight I was getting too much carbohydrate so it's like a lot of much carbohydrate so it's like a lot of much carbohydrate so it's like a lot of macadamia nuts a lot of olive oil olive macadamia nuts a lot of olive oil olive macadamia nuts a lot of olive oil olive oil-based everything and then the oil-based everything and then the oil-based everything and then the hardest part for me was clearly being hardest part for me was clearly being hardest part for me was clearly being stingy with the protein what was in stingy with the protein what was in stingy with the protein what was in there what was in the salads like okay there what was in the salads like okay there what was in the salads like okay so I go you know I'm a pretty boring guy so I go you know I'm a pretty boring guy so I go you know I'm a pretty boring guy so it's romaine tomatoes cucumbers so it's romaine tomatoes cucumbers so it's romaine tomatoes cucumbers celery had to kind of like limit the celery had to kind of like limit the celery had to kind of like limit the carrots a little bit I normally love carrots a little bit I normally love carrots a little bit I normally love carrots great tomatoes and everything on carrots great tomatoes and everything on carrots great tomatoes and everything on the kitchen yeah yeah again part of it the kitchen yeah yeah again part of it the kitchen yeah yeah again part of it is I can get away with more cuz I is I can get away with more cuz I is I can get away with more cuz I probably exercise more and I was doing

20:00probably exercise more and I was doing probably exercise more and I was doing this this this four people were sort of putting butter four people were sort of putting butter four people were sort of putting butter in their coffee and stuff like that so in their coffee and stuff like that so in their coffee and stuff like that so that was not I can send a lot of dairy that was not I can send a lot of dairy that was not I can send a lot of dairy though so it's the other thing tons of though so it's the other thing tons of though so it's the other thing tons of cheese tons of sour cream because he cheese tons of sour cream because he cheese tons of sour cream because he just needed those calories and I just needed those calories and I just needed those calories and I actually developed like a spreadsheet actually developed like a spreadsheet actually developed like a spreadsheet that was customized for my caloric needs that was customized for my caloric needs that was customized for my caloric needs but I had this formula of looking at but I had this formula of looking at but I had this formula of looking at every ingredient like could you find the every ingredient like could you find the every ingredient like could you find the food that you could eat without food that you could eat without food that you could eat without restriction that wouldn't destroy your restriction that wouldn't destroy your restriction that wouldn't destroy your ratios and so for me at my caloric ratios and so for me at my caloric ratios and so for me at my caloric levels like cream cheese and sour cream levels like cream cheese and sour cream levels like cream cheese and sour cream were sort of the perfect thing whereas were sort of the perfect thing whereas were sort of the perfect thing whereas even high-fat Greek yogurt had too much even high-fat Greek yogurt had too much even high-fat Greek yogurt had too much protein so I had to consume that in protein so I had to consume that in protein so I had to consume that in moderation that's the other interesting moderation that's the other interesting moderation that's the other interesting thing and I think I talked to Eric about thing and I think I talked to Eric about thing and I think I talked to Eric about this was you know how much of the this was you know how much of the this was you know how much of the effects you know on on health span or effects you know on on health span or effects you know on on health span or due to low protein intake and how much due to low protein intake and how much due to low protein intake and how much were due to you know the actual being in were due to you know the actual being in were due to you know the actual being in ketosis ketosis ketosis yeah I've talked about this with vaulter yeah I've talked about this with vaulter yeah I've talked about this with vaulter a few times we don't see eye to eye on a few times we don't see eye to eye on a few times we don't see eye to eye on this because for several reasons one I'm this because for several reasons one I'm this because for several reasons one I'm not entirely convinced of the igf

21:00not entirely convinced of the igf not entirely convinced of the igf paradigm anymore so that's one thing paradigm anymore so that's one thing paradigm anymore so that's one thing where you know the question I asked you where you know the question I asked you where you know the question I asked you that would be my answer so five years that would be my answer so five years that would be my answer so five years ago I would have said IGF is the devil ago I would have said IGF is the devil ago I would have said IGF is the devil growth hormone is the devil you want growth hormone is the devil you want growth hormone is the devil you want them to be as low as possible I'm not them to be as low as possible I'm not them to be as low as possible I'm not convinced of that today and I can't wait convinced of that today and I can't wait convinced of that today and I can't wait to explore that with you but the other to explore that with you but the other to explore that with you but the other thing is if you really want to produce thing is if you really want to produce thing is if you really want to produce the lowest level of insulin and igf-1 a the lowest level of insulin and igf-1 a the lowest level of insulin and igf-1 a ketogenic diet that is incredibly low in ketogenic diet that is incredibly low in ketogenic diet that is incredibly low in protein incredibly low in carbohydrate protein incredibly low in carbohydrate protein incredibly low in carbohydrate when I go back and look at my blood when I go back and look at my blood when I go back and look at my blood levels because I I check my blood about levels because I I check my blood about levels because I I check my blood about every six to eight weeks and I've been every six to eight weeks and I've been every six to eight weeks and I've been doing this for you know 10 years I mean doing this for you know 10 years I mean doing this for you know 10 years I mean my lowest IGF levels were during the my lowest IGF levels were during the my lowest IGF levels were during the three years I was in ketosis I mean they three years I was in ketosis I mean they three years I was in ketosis I mean they were very low they were I mean not were very low they were I mean not were very low they were I mean not ridiculously low but 25th percentile for ridiculously low but 25th percentile for ridiculously low but 25th percentile for age verses say 75th percentile today so age verses say 75th percentile today so age verses say 75th percentile today so that makes sense to me because if you that makes sense to me because if you that makes sense to me because if you think about you know some of the major think about you know some of the major think about you know some of the major dietary regulators of the igf-1 pathway dietary regulators of the igf-1 pathway dietary regulators of the igf-1 pathway are protein essential amino amino acids are protein essential amino amino acids are protein essential amino amino acids specifically and also insulin insulin specifically and also insulin insulin specifically and also insulin insulin through IGF bp3 through IGF bp3 through IGF bp3 or IP b12 so I mean I think that so for

22:00or IP b12 so I mean I think that so for or IP b12 so I mean I think that so for example you know if if someone's eating example you know if if someone's eating example you know if if someone's eating a low protein and low you're getting you a low protein and low you're getting you a low protein and low you're getting you may not be a vegan but even if you had may not be a vegan but even if you had may not be a vegan but even if you had you're limiting your protein you know you're limiting your protein you know you're limiting your protein you know even to some degree or you're certainly even to some degree or you're certainly even to some degree or you're certainly getting more than someone may be me getting more than someone may be me getting more than someone may be me that's that's that's not doing that really although I do kind not doing that really although I do kind not doing that really although I do kind of limit my protein but it's a of limit my protein but it's a of limit my protein but it's a misconception you see I think a lot of misconception you see I think a lot of misconception you see I think a lot of people assume ketogenic diets or people assume ketogenic diets or people assume ketogenic diets or high-protein diets I think some people high-protein diets I think some people high-protein diets I think some people do consider that yeah but if you're do consider that yeah but if you're do consider that yeah but if you're there may be certain people out there there may be certain people out there there may be certain people out there who can produce ketones with high who can produce ketones with high who can produce ketones with high protein but in my experience personally protein but in my experience personally protein but in my experience personally and more important clinically meaning I and more important clinically meaning I and more important clinically meaning I don't know over the course of my don't know over the course of my don't know over the course of my practice and my career in medicine I practice and my career in medicine I practice and my career in medicine I mean I've probably at least encountered mean I've probably at least encountered mean I've probably at least encountered 50 or 60 patients at a very detailed 50 or 60 patients at a very detailed 50 or 60 patients at a very detailed level on ketogenic diets almost without level on ketogenic diets almost without level on ketogenic diets almost without exception protein is the bigger thing exception protein is the bigger thing exception protein is the bigger thing that fouls people up and and so that's that fouls people up and and so that's that fouls people up and and so that's the thing I've always found a bit the thing I've always found a bit the thing I've always found a bit confusing in some of those discussions confusing in some of those discussions confusing in some of those discussions is and even Eric mentioned this on your is and even Eric mentioned this on your is and even Eric mentioned this on your podcast which is well you got to be podcast which is well you got to be podcast which is well you got to be careful if you're on a ketogenic I you careful if you're on a ketogenic I you careful if you're on a ketogenic I you don't have too much protein and I was don't have too much protein and I was don't have too much protein and I was like those don't go hand-in-hand like those don't go hand-in-hand like those don't go hand-in-hand you're not on a ketogenic diet if you're you're not on a ketogenic diet if you're you're not on a ketogenic diet if you're eating a lot of protein because you

23:00eating a lot of protein because you eating a lot of protein because you won't make the ketones won't make the ketones won't make the ketones that said I wouldn't be surprised if that said I wouldn't be surprised if that said I wouldn't be surprised if there are polymorphisms that allow there are polymorphisms that allow there are polymorphisms that allow people more or less and you've obviously people more or less and you've obviously people more or less and you've obviously talked a lot about the P part or alpha talked a lot about the P part or alpha talked a lot about the P part or alpha is it people are alpha our people are is it people are alpha our people are is it people are alpha our people are gamma where you see the differences in a gamma where you see the differences in a gamma where you see the differences in a person's ability to generate ketones the person's ability to generate ketones the person's ability to generate ketones the people are alpha is is predominantly people are alpha is is predominantly people are alpha is is predominantly found in the liver and it's involved in found in the liver and it's involved in found in the liver and it's involved in in fatty acid catabolism the production in fatty acid catabolism the production in fatty acid catabolism the production of ketone bodies so so that would be the of ketone bodies so so that would be the of ketone bodies so so that would be the major one now there's nothing major one now there's nothing major one now there's nothing empirically I've seen in literature that empirically I've seen in literature that empirically I've seen in literature that to look specifically at P P R alpha to look specifically at P P R alpha to look specifically at P P R alpha and a ketogenic diet or fasting but you and a ketogenic diet or fasting but you and a ketogenic diet or fasting but you know there's most of the literature out know there's most of the literature out know there's most of the literature out there looking at the effects of P P R there looking at the effects of P P R there looking at the effects of P P R alpha with people that are either head alpha with people that are either head alpha with people that are either head or homozygous are or have to do with the or homozygous are or have to do with the or homozygous are or have to do with the context of like high saturated fat low context of like high saturated fat low context of like high saturated fat low polyunsaturated fat guy because polyunsaturated fat guy because polyunsaturated fat guy because polyunsaturated fat activates the PPR polyunsaturated fat activates the PPR polyunsaturated fat activates the PPR you know family of transcription factors you know family of transcription factors you know family of transcription factors which are nuclear hormone receptor which are nuclear hormone receptor which are nuclear hormone receptor transcription factors but the PP r gamma transcription factors but the PP r gamma transcription factors but the PP r gamma is predominately found in like adipose is predominately found in like adipose is predominately found in like adipose tissue I mean they're found in other tissue I mean they're found in other tissue I mean they're found in other tissues but I see predominantly that's tissues but I see predominantly that's tissues but I see predominantly that's like the most they're highly expressed like the most they're highly expressed like the most they're highly expressed in that adipose tissue and it plays a

24:00in that adipose tissue and it plays a in that adipose tissue and it plays a role in basically taking up fatty acids role in basically taking up fatty acids role in basically taking up fatty acids into adipose tissue where is the alpha into adipose tissue where is the alpha into adipose tissue where is the alpha which is liver take plays a role in the which is liver take plays a role in the which is liver take plays a role in the transport catabolism so one would just transport catabolism so one would just transport catabolism so one would just sort of imagine I mean it would be nice sort of imagine I mean it would be nice sort of imagine I mean it would be nice to see that you know someone look at to see that you know someone look at to see that you know someone look at that you know people with these specific that you know people with these specific that you know people with these specific snips and how this Prometheus identify snips and how this Prometheus identify snips and how this Prometheus identify various snips of P power alpha various snips of P power alpha various snips of P power alpha yes but they don't really tell you yes but they don't really tell you yes but they don't really tell you anything they sort of pull abstracts anything they sort of pull abstracts anything they sort of pull abstracts from PubMed and just kind of like dump from PubMed and just kind of like dump from PubMed and just kind of like dump it there so you kind of can start with it there so you kind of can start with it there so you kind of can start with the research there I've been developing the research there I've been developing the research there I've been developing a genetic tool and I just were actually a genetic tool and I just were actually a genetic tool and I just were actually developing it a lot more of a former NIH developing it a lot more of a former NIH developing it a lot more of a former NIH geneticist who's a really phenomenal geneticist who's a really phenomenal geneticist who's a really phenomenal who's been working with me on to help me who's been working with me on to help me who's been working with me on to help me sort of develop those basically look at sort of develop those basically look at sort of develop those basically look at look at you know the literature and see look at you know the literature and see look at you know the literature and see what some of these snips are are doing what some of these snips are are doing what some of these snips are are doing and then in canino in conjunction with and then in canino in conjunction with and then in canino in conjunction with looking at biomarkers various blood looking at biomarkers various blood looking at biomarkers various blood biomarkers to kind of help people guide biomarkers to kind of help people guide biomarkers to kind of help people guide you know what sort of they should do you know what sort of they should do you know what sort of they should do what's a bypass around at a potential what's a bypass around at a potential what's a bypass around at a potential bypass for example so with the PPR alpha

25:00bypass for example so with the PPR alpha bypass for example so with the PPR alpha or gamma I think that the take home at or gamma I think that the take home at or gamma I think that the take home at least from the literature is essentially least from the literature is essentially least from the literature is essentially you want to have a higher ratio of poly you want to have a higher ratio of poly you want to have a higher ratio of poly and monounsaturated effective to and monounsaturated effective to and monounsaturated effective to saturated fat ratio in order to lower saturated fat ratio in order to lower saturated fat ratio in order to lower your type-2 diabetes risk you're saying your type-2 diabetes risk you're saying your type-2 diabetes risk you're saying for any for people with the wild-type or for any for people with the wild-type or for any for people with the wild-type or with people with certain snips with in with people with certain snips with in with people with certain snips with in PBR alpha yeah because and gamma as well PBR alpha yeah because and gamma as well PBR alpha yeah because and gamma as well because to some degree some some of the because to some degree some some of the because to some degree some some of the ones in people are gamma affect the ones in people are gamma affect the ones in people are gamma affect the uptake of fatty acids and adipose tissue uptake of fatty acids and adipose tissue uptake of fatty acids and adipose tissue and so in also muscle and so it kind of and so in also muscle and so it kind of and so in also muscle and so it kind of can affect you know you have a lot more can affect you know you have a lot more can affect you know you have a lot more free fatty acids around and that can you free fatty acids around and that can you free fatty acids around and that can you know have have an effect on insulin know have have an effect on insulin know have have an effect on insulin sensitivity and other things as well so sensitivity and other things as well so sensitivity and other things as well so we should talk about this offline we should talk about this offline we should talk about this offline because I have a subset of patients for because I have a subset of patients for because I have a subset of patients for which we have such rich data and if I'm which we have such rich data and if I'm which we have such rich data and if I'm positive all of them would be interested positive all of them would be interested positive all of them would be interested in knowing this and you know we've in knowing this and you know we've in knowing this and you know we've certainly get their permission but it certainly get their permission but it certainly get their permission but it would be interesting and taking their would be interesting and taking their would be interesting and taking their you know just their straight-up 23andme you know just their straight-up 23andme you know just their straight-up 23andme data okay so here's the pattern I've data okay so here's the pattern I've data okay so here's the pattern I've seen and I'm very curious as to what the seen and I'm very curious as to what the seen and I'm very curious as to what the overlap is so there's a clearly a subset

26:00overlap is so there's a clearly a subset overlap is so there's a clearly a subset of people I think my n is too small to of people I think my n is too small to of people I think my n is too small to quantify it but directionally it seems quantify it but directionally it seems quantify it but directionally it seems like I don't know ten or twenty percent like I don't know ten or twenty percent like I don't know ten or twenty percent of people when you put them on ketogenic of people when you put them on ketogenic of people when you put them on ketogenic diets in the standard way which usually diets in the standard way which usually diets in the standard way which usually ends up meaning you're getting at least ends up meaning you're getting at least ends up meaning you're getting at least forty percent of your calories from forty percent of your calories from forty percent of your calories from saturated fat typically 40 to 45 percent saturated fat typically 40 to 45 percent saturated fat typically 40 to 45 percent from mono and the remainder from Holley from mono and the remainder from Holley from mono and the remainder from Holley everything goes to hell in a handbasket everything goes to hell in a handbasket everything goes to hell in a handbasket and the obvious things that go to hell and the obvious things that go to hell and the obvious things that go to hell in a handbasket have been certainly in a handbasket have been certainly in a handbasket have been certainly written about on the blogosphere and written about on the blogosphere and written about on the blogosphere and Twittersphere which is usually their LDL Twittersphere which is usually their LDL Twittersphere which is usually their LDL particle numbers skyrockets despite the particle numbers skyrockets despite the particle numbers skyrockets despite the fact that their triglycerides go down so fact that their triglycerides go down so fact that their triglycerides go down so they seem to be getting more insulin they seem to be getting more insulin they seem to be getting more insulin sensitive sensitive sensitive but yet inflammation is going up and you but yet inflammation is going up and you but yet inflammation is going up and you see that both specifically cardiac see that both specifically cardiac see that both specifically cardiac specifically so things like oxidized LDL specifically so things like oxidized LDL specifically so things like oxidized LDL and LP PLA - but even non specifically C and LP PLA - but even non specifically C and LP PLA - but even non specifically C reactive protein fiber engine but the reactive protein fiber engine but the reactive protein fiber engine but the deeper level is the Y and what you see deeper level is the Y and what you see deeper level is the Y and what you see is they're making much more cholesterol is they're making much more cholesterol is they're making much more cholesterol markers of cholesterol biosynthesis like

27:00markers of cholesterol biosynthesis like markers of cholesterol biosynthesis like des Marshall all go way up and some of des Marshall all go way up and some of des Marshall all go way up and some of their phytosterols go up which is very their phytosterols go up which is very their phytosterols go up which is very counterintuitive phytosterols would counterintuitive phytosterols would counterintuitive phytosterols would generally go down on a ketogenic diet generally go down on a ketogenic diet generally go down on a ketogenic diet but they're going way up suggesting that but they're going way up suggesting that but they're going way up suggesting that they're absorbing much more cholesterol they're absorbing much more cholesterol they're absorbing much more cholesterol like biliary cholesterol so the first like biliary cholesterol so the first like biliary cholesterol so the first time I noticed this was 2012 and I think time I noticed this was 2012 and I think time I noticed this was 2012 and I think they wrote about this once on a blog but they wrote about this once on a blog but they wrote about this once on a blog but I don't remember maybe I'm thinking of I don't remember maybe I'm thinking of I don't remember maybe I'm thinking of another example and it was this another example and it was this another example and it was this relatively young patient who really relatively young patient who really relatively young patient who really loved being on a ketogenic diet but when loved being on a ketogenic diet but when loved being on a ketogenic diet but when we get his blood tests back I mean his we get his blood tests back I mean his we get his blood tests back I mean his LDL particle number was above 3500 LDL particle number was above 3500 LDL particle number was above 3500 animal per liter and I know there are a animal per liter and I know there are a animal per liter and I know there are a lot of guys out there who seemed to lot of guys out there who seemed to lot of guys out there who seemed to think that as long as you're on a think that as long as you're on a think that as long as you're on a ketogenic diet it doesn't men of this ketogenic diet it doesn't men of this ketogenic diet it doesn't men of this stuff matters I completely don't stuff matters I completely don't stuff matters I completely don't subscribe to that and my view is that's subscribe to that and my view is that's subscribe to that and my view is that's irresponsible so I said to them I said irresponsible so I said to them I said irresponsible so I said to them I said look I don't think the ketogenic diet is look I don't think the ketogenic diet is look I don't think the ketogenic diet is right for you and he said no no it's the right for you and he said no no it's the right for you and he said no no it's the best thing I've ever done like I feel best thing I've ever done like I feel best thing I've ever done like I feel better I look better I'm performing better I look better I'm performing better I look better I'm performing better we got to figure out a way to do better we got to figure out a way to do better we got to figure out a way to do this and I the only thing I could think this and I the only thing I could think this and I the only thing I could think of when I talked with Tom Dayspring

28:00of when I talked with Tom Dayspring of when I talked with Tom Dayspring about this and he said let's try an about this and he said let's try an about this and he said let's try an experiment and rip all the saturated fat experiment and rip all the saturated fat experiment and rip all the saturated fat out of his diet he was sort of like me out of his diet he was sort of like me out of his diet he was sort of like me he was eating a lot he meaning his a he was eating a lot he meaning his a he was eating a lot he meaning his a high caloric consumer so that gets high caloric consumer so that gets high caloric consumer so that gets really hard so we created a diet form really hard so we created a diet form really hard so we created a diet form that was only about 20 to 25 grams a day that was only about 20 to 25 grams a day that was only about 20 to 25 grams a day of saturated fat and he ended up getting of saturated fat and he ended up getting of saturated fat and he ended up getting about 65% of his fat calories from mono about 65% of his fat calories from mono about 65% of his fat calories from mono and saturated fat which was pretty gross and saturated fat which was pretty gross and saturated fat which was pretty gross I mean you're drinking olive oil at that I mean you're drinking olive oil at that I mean you're drinking olive oil at that point but he was interested in doing the point but he was interested in doing the point but he was interested in doing the experiment and sure enough after I don't experiment and sure enough after I don't experiment and sure enough after I don't know maybe 8 to 12 weeks same know maybe 8 to 12 weeks same know maybe 8 to 12 weeks same macronutrient distribution in terms of macronutrient distribution in terms of macronutrient distribution in terms of fat protein carbohydrate the only shift fat protein carbohydrate the only shift fat protein carbohydrate the only shift was the type of fat so we just was the type of fat so we just was the type of fat so we just substituted mono for saturated his LDL P substituted mono for saturated his LDL P substituted mono for saturated his LDL P was thirteen hundred animal per liter was thirteen hundred animal per liter was thirteen hundred animal per liter all of the inflammation was gone and all all of the inflammation was gone and all all of the inflammation was gone and all of the sterile biomarkers went back to of the sterile biomarkers went back to of the sterile biomarkers went back to normal normal normal I've since seen I've since seen I've since seen about six times and now I'm wondering if about six times and now I'm wondering if about six times and now I'm wondering if we took those patients and ran them we took those patients and ran them we took those patients and ran them through what you're doing yeah yeah the

29:00through what you're doing yeah yeah the through what you're doing yeah yeah the ones that have those snip and there's a ones that have those snip and there's a ones that have those snip and there's a variety of them that do that so there's variety of them that do that so there's variety of them that do that so there's the P P R alpha P by gamma there's a the P P R alpha P by gamma there's a the P P R alpha P by gamma there's a couple of FTO related snips also that couple of FTO related snips also that couple of FTO related snips also that the road should have saturated and the road should have saturated and the road should have saturated and basically in the literature these basically in the literature these basically in the literature these studies have all looked at the ratio of studies have all looked at the ratio of studies have all looked at the ratio of saturated to mono and polyunsaturated saturated to mono and polyunsaturated saturated to mono and polyunsaturated fat and for whatever reason people with fat and for whatever reason people with fat and for whatever reason people with those snips when they have a higher those snips when they have a higher those snips when they have a higher saturated fat poly your mono and or mono saturated fat poly your mono and or mono saturated fat poly your mono and or mono they have higher inflammation higher they have higher inflammation higher they have higher inflammation higher oxidized LDL higher a small dense LDL oxidized LDL higher a small dense LDL oxidized LDL higher a small dense LDL higher you just you know all these just higher you just you know all these just higher you just you know all these just tell you have a sense of the frequency tell you have a sense of the frequency tell you have a sense of the frequency based on the research you've done on based on the research you've done on based on the research you've done on this how prevalent that is kind of I this how prevalent that is kind of I this how prevalent that is kind of I would say you know I'd have to look back would say you know I'd have to look back would say you know I'd have to look back at the data probably less than 20% so it at the data probably less than 20% so it at the data probably less than 20% so it might be in the ballpark of what I'm might be in the ballpark of what I'm might be in the ballpark of what I'm seeing for this different phenotype seeing for this different phenotype seeing for this different phenotype might be yeah it might be so that would might be yeah it might be so that would might be yeah it might be so that would be really interesting to run him through be really interesting to run him through be really interesting to run him through through my tool and and like I said through my tool and and like I said through my tool and and like I said we're even expanding that a little bit I we're even expanding that a little bit I we're even expanding that a little bit I found I found a few more our patients found I found a few more our patients found I found a few more our patients sending you any of their data or are sending you any of their data or are sending you any of their data or are they doing it on their own and just they doing it on their own and just they doing it on their own and just they're doing it on their own they're doing it on their own they're doing it on their own some people have shared their data with some people have shared their data with some people have shared their data with me because they've emailed me and

30:00me because they've emailed me and me because they've emailed me and something interesting and I'm like oh something interesting and I'm like oh something interesting and I'm like oh wow that's super interesting do you mind wow that's super interesting do you mind wow that's super interesting do you mind sharing that with me and they have so if sharing that with me and they have so if sharing that with me and they have so if anybody is listening to this and they're anybody is listening to this and they're anybody is listening to this and they're saying hey you know I had an advanced saying hey you know I had an advanced saying hey you know I had an advanced lipid test before and after I went on a lipid test before and after I went on a lipid test before and after I went on a ketogenic diet and I looked like this ketogenic diet and I looked like this ketogenic diet and I looked like this situation you described can they reach situation you described can they reach situation you described can they reach out to you through your blog and send out to you through your blog and send out to you through your blog and send this data to you if they can actually this data to you if they can actually this data to you if they can actually just use the genetic tool and then sort just use the genetic tool and then sort just use the genetic tool and then sort of you know share with the other day of you know share with the other day of you know share with the other day they want to share with me the data you they want to share with me the data you they want to share with me the data you know I can't promise anything but but know I can't promise anything but but know I can't promise anything but but they can certainly get the Y themselves they can certainly get the Y themselves they can certainly get the Y themselves by just using genetic tool right now by just using genetic tool right now by just using genetic tool right now which which I have I have free reports which which I have I have free reports which which I have I have free reports for for for example the PPR genes but for for for example the PPR genes but for for for example the PPR genes but then I have a whole comprehensive report then I have a whole comprehensive report then I have a whole comprehensive report that's a $10 recommended so if someone that's a $10 recommended so if someone that's a $10 recommended so if someone doesn't want to pay $10 to do doesn't want to pay $10 to do doesn't want to pay $10 to do comprehensive they can just get the free comprehensive they can just get the free comprehensive they can just get the free report and get the Y potential Y them report and get the Y potential Y them report and get the Y potential Y them alright so I hope that anyone listening alright so I hope that anyone listening alright so I hope that anyone listening to this because I again if I'm seeing to this because I again if I'm seeing to this because I again if I'm seeing this at 10 to 20 percent of the time and this at 10 to 20 percent of the time and this at 10 to 20 percent of the time and you're seeing it and it'd be great to you're seeing it and it'd be great to you're seeing it and it'd be great to get a few hundred people who are that get a few hundred people who are that get a few hundred people who are that phenotype and find out if the phenotype phenotype and find out if the phenotype phenotype and find out if the phenotype match is the genotype right yeah it match is the genotype right yeah it match is the genotype right yeah it would absolutely be and like I said I

31:00would absolutely be and like I said I would absolutely be and like I said I have I have had people have that problem have I have had people have that problem have I have had people have that problem where they've tried occasion a guy and where they've tried occasion a guy and where they've tried occasion a guy and couldn't figure out and they did couldn't figure out and they did couldn't figure out and they did of one or even more than than one of the of one or even more than than one of the of one or even more than than one of the snips that regulate fatty acid snips that regulate fatty acid snips that regulate fatty acid metabolism so and then there's another metabolism so and then there's another metabolism so and then there's another phenotype that fortunately is more rare phenotype that fortunately is more rare phenotype that fortunately is more rare and I also wonder what's going on with P and I also wonder what's going on with P and I also wonder what's going on with P power alpha specifically which is people power alpha specifically which is people power alpha specifically which is people who do everything by the book who do everything by the book who do everything by the book and maybe I'm a sucker and maybe I'm and maybe I'm a sucker and maybe I'm and maybe I'm a sucker and maybe I'm gullible and maybe I believe patients gullible and maybe I believe patients gullible and maybe I believe patients too much but I don't think I've ever had too much but I don't think I've ever had too much but I don't think I've ever had a patient lie to me I really think like a patient lie to me I really think like a patient lie to me I really think like when they're not doing what they're when they're not doing what they're when they're not doing what they're supposed to be doing they tell you I'm supposed to be doing they tell you I'm supposed to be doing they tell you I'm not doing what I'm supposed to be doing not doing what I'm supposed to be doing not doing what I'm supposed to be doing so it's not uncommon in this rare subset so it's not uncommon in this rare subset so it's not uncommon in this rare subset of patients that is where they're doing of patients that is where they're doing of patients that is where they're doing everything by the book I mean they're everything by the book I mean they're everything by the book I mean they're working their tail off to keep their working their tail off to keep their working their tail off to keep their carbs here to keep their protein here to carbs here to keep their protein here to carbs here to keep their protein here to keep their fat here to keep it within keep their fat here to keep it within keep their fat here to keep it within this distribution and they cannot get this distribution and they cannot get this distribution and they cannot get even close to half a mil Imola of bhp in even close to half a mil Imola of bhp in even close to half a mil Imola of bhp in their blood and to me that's a really their blood and to me that's a really their blood and to me that's a really frustrating situation if it's

32:00frustrating situation if it's frustrating situation if it's frustrating for the patient because frustrating for the patient because frustrating for the patient because they're sort of like what the hell I'm they're sort of like what the hell I'm they're sort of like what the hell I'm doing everything right like I'm not doing everything right like I'm not doing everything right like I'm not making ketones and you know I think making ketones and you know I think making ketones and you know I think Steve Finney sort of put out this notion Steve Finney sort of put out this notion Steve Finney sort of put out this notion that the threshold was about 0.5 that the threshold was about 0.5 that the threshold was about 0.5 millimolar I don't have anything to millimolar I don't have anything to millimolar I don't have anything to argue that one way or the other so I argue that one way or the other so I argue that one way or the other so I generally can you know based on my own generally can you know based on my own generally can you know based on my own empirical experience personally I sort empirical experience personally I sort empirical experience personally I sort of felt like 1 millimolar was about the of felt like 1 millimolar was about the of felt like 1 millimolar was about the threshold but but again I think that's threshold but but again I think that's threshold but but again I think that's neither here nor there but when these neither here nor there but when these neither here nor there but when these people are doing what I'm describing and people are doing what I'm describing and people are doing what I'm describing and they're at best point to maybe 0.3 they're at best point to maybe 0.3 they're at best point to maybe 0.3 millimolar it just made me wonder millimolar it just made me wonder millimolar it just made me wonder there's something in their machinery there's something in their machinery there's something in their machinery that's not doing this now the question that's not doing this now the question that's not doing this now the question is is it a lipolysis problem is it an is is it a lipolysis problem is it an is is it a lipolysis problem is it an oxidation problem is it a conversion oxidation problem is it a conversion oxidation problem is it a conversion problem I mean that I don't know but it problem I mean that I don't know but it problem I mean that I don't know but it would also be interesting to understand would also be interesting to understand would also be interesting to understand where could the weak links be in their where could the weak links be in their where could the weak links be in their ketosis machinery right and there's ketosis machinery right and there's ketosis machinery right and there's probably you know there's a variety of probably you know there's a variety of probably you know there's a variety of snips and the in these genes and you snips and the in these genes and you snips and the in these genes and you know there there may be certain snips know there there may be certain snips know there there may be certain snips that haven't even really been tested or that haven't even really been tested or that haven't even really been tested or who knows it sounds it sounds like you who knows it sounds it sounds like you who knows it sounds it sounds like you know to me that there there's there's know to me that there there's there's know to me that there there's there's certainly something going on with with certainly something going on with with certainly something going on with with the process of ketogenesis ins and some

33:00the process of ketogenesis ins and some the process of ketogenesis ins and some of the patients and they're active of the patients and they're active of the patients and they're active they're activity levels or they're they're activity levels or they're they're activity levels or they're active yeah we're pretty I mean we've active yeah we're pretty I mean we've active yeah we're pretty I mean we've evolved a lot in our thinking on how evolved a lot in our thinking on how evolved a lot in our thinking on how those patients can be helped but it those patients can be helped but it those patients can be helped but it seems that the best way to get them over seems that the best way to get them over seems that the best way to get them over that hump is fasting coupled with that hump is fasting coupled with that hump is fasting coupled with exercise if they're capable but it's got exercise if they're capable but it's got exercise if they're capable but it's got to be relatively to be relatively to be relatively it has to be it's not gardening like it has to be it's not gardening like it has to be it's not gardening like it's got to be exercise exercise you it's got to be exercise exercise you it's got to be exercise exercise you know it's they they have to really know it's they they have to really know it's they they have to really deplete glycogen so that's the other deplete glycogen so that's the other deplete glycogen so that's the other thing I sort of wonder and some of these thing I sort of wonder and some of these thing I sort of wonder and some of these folks is what's happening with with folks is what's happening with with folks is what's happening with with gluconeogenesis because I I think until gluconeogenesis because I I think until gluconeogenesis because I I think until you start to dip down and glycogen a you start to dip down and glycogen a you start to dip down and glycogen a little bit it's really hard to do this little bit it's really hard to do this little bit it's really hard to do this and of course we can't do liver biopsies and of course we can't do liver biopsies and of course we can't do liver biopsies wait so fasting does get them into wait so fasting does get them into wait so fasting does get them into ketosis so again we're dealing with such ketosis so again we're dealing with such ketosis so again we're dealing with such a small end that I don't I want to be a small end that I don't I want to be a small end that I don't I want to be thoughtful about not generalizing too thoughtful about not generalizing too thoughtful about not generalizing too much so there's one patient in much so there's one patient in much so there's one patient in particular who is the poster child for particular who is the poster child for particular who is the poster child for couldn't do the ketosis thing couldn't do the ketosis thing couldn't do the ketosis thing straightaway but when we put him on straightaway but when we put him on straightaway but when we put him on every month a five-day FMD so he would

34:00every month a five-day FMD so he would every month a five-day FMD so he would do the five-day FMD but ketogenic not do the five-day FMD but ketogenic not do the five-day FMD but ketogenic not long goes FMD and then the 25 days of long goes FMD and then the 25 days of long goes FMD and then the 25 days of adlib was time restricted eating adlib was time restricted eating adlib was time restricted eating ketogenic then we've seen great results ketogenic then we've seen great results ketogenic then we've seen great results doing that in two people so that would doing that in two people so that would doing that in two people so that would suggest that something again it's not suggest that something again it's not suggest that something again it's not we're not doing this as an experiment at we're not doing this as an experiment at we're not doing this as an experiment at this point it's like clinical it's like this point it's like clinical it's like this point it's like clinical it's like just try to get the job done sort of just try to get the job done sort of just try to get the job done sort of thing but that would suggest it's thing but that would suggest it's thing but that would suggest it's something about the fasting end or the something about the fasting end or the something about the fasting end or the exercise end or the time restriction exercise end or the time restriction exercise end or the time restriction could get them over the hump but it's could get them over the hump but it's could get them over the hump but it's interesting because from an evolutionary interesting because from an evolutionary interesting because from an evolutionary perspective you should have been perspective you should have been perspective you should have been selected out really quickly if you selected out really quickly if you selected out really quickly if you couldn't make ketones efficiently well couldn't make ketones efficiently well couldn't make ketones efficiently well it sounds to me that maybe maybe there's it sounds to me that maybe maybe there's it sounds to me that maybe maybe there's a glycation you know you're not you're a glycation you know you're not you're a glycation you know you're not you're not getting depleting the glycogen - if not getting depleting the glycogen - if not getting depleting the glycogen - if that's you know so maybe it's not to do that's you know so maybe it's not to do that's you know so maybe it's not to do with the production of ketone bodies but with the production of ketone bodies but with the production of ketone bodies but it's actually just takes a long time to it's actually just takes a long time to it's actually just takes a long time to deplete that glycogen I do think there's deplete that glycogen I do think there's deplete that glycogen I do think there's a huge variation obviously physical a huge variation obviously physical a huge variation obviously physical activity plays a role in that as well I activity plays a role in that as well I activity plays a role in that as well I can fast I can do you know like when I can fast I can do you know like when I can fast I can do you know like when I do my time restricted eating ideally I do my time restricted eating ideally I do my time restricted eating ideally I like to do it within you know nine or like to do it within you know nine or like to do it within you know nine or ten hours eat all my food within nine or

35:00ten hours eat all my food within nine or ten hours eat all my food within nine or ten hours and then I you know I like to ten hours and then I you know I like to ten hours and then I you know I like to fast for like 15 hours I can do that and fast for like 15 hours I can do that and fast for like 15 hours I can do that and with my physical activity levels you with my physical activity levels you with my physical activity levels you know I will be closer to 1 millimolar it know I will be closer to 1 millimolar it know I will be closer to 1 millimolar it fast like we will get to 1 millimolar fast like we will get to 1 millimolar fast like we will get to 1 millimolar after 15 hours of fasting I will be after 15 hours of fasting I will be after 15 hours of fasting I will be closer to that when I'm really closer to that when I'm really closer to that when I'm really physically active like during the physically active like during the physically active like during the periods a couple of years ago and I was periods a couple of years ago and I was periods a couple of years ago and I was doing lots of like long like doing lots of like long like doing lots of like long like long-distance running and stuff I can long-distance running and stuff I can long-distance running and stuff I can get closer I mean I mean I'm going off get closer I mean I mean I'm going off get closer I mean I mean I'm going off of like a precision extra which probably of like a precision extra which probably of like a precision extra which probably no no precision extras it's I mean no no precision extras it's I mean no no precision extras it's I mean that's really good that's really good that's really good so I can get between like 0.7 millimolar so I can get between like 0.7 millimolar so I can get between like 0.7 millimolar to like 0.9 but are you consuming a to like 0.9 but are you consuming a to like 0.9 but are you consuming a ketogenic diet during your feeding with ketogenic diet during your feeding with ketogenic diet during your feeding with my diet typically I like I said I've my diet typically I like I said I've my diet typically I like I said I've never really intentionally tried to do a never really intentionally tried to do a never really intentionally tried to do a ketogenic diet but my diet is I pretty ketogenic diet but my diet is I pretty ketogenic diet but my diet is I pretty much eat a lot of the same things and much eat a lot of the same things and much eat a lot of the same things and typically it's salmon a salad or a typically it's salmon a salad or a typically it's salmon a salad or a sauteed vegetables with olive oil some sauteed vegetables with olive oil some sauteed vegetables with olive oil some pasture-raised butter from pasture pasture-raised butter from pasture pasture-raised butter from pasture raised animals and my fruits will be raised animals and my fruits will be raised animals and my fruits will be like blueberries I'll have avocado so

36:00like blueberries I'll have avocado so like blueberries I'll have avocado so I'll have it sometimes obvious movie I'll have it sometimes obvious movie I'll have it sometimes obvious movie with some blueberries avocado and kale with some blueberries avocado and kale with some blueberries avocado and kale and will you have two meals in that and will you have two meals in that and will you have two meals in that window or it depends if I have the or window or it depends if I have the or window or it depends if I have the or not typically I'll have breakfast and not typically I'll have breakfast and not typically I'll have breakfast and then an early dinner and then I'll have then an early dinner and then I'll have then an early dinner and then I'll have like a snack either nuts or the smoothie like a snack either nuts or the smoothie like a snack either nuts or the smoothie the kale with some blueberries and the kale with some blueberries and the kale with some blueberries and avocado so I think it you know I need a avocado so I think it you know I need a avocado so I think it you know I need a lot of nuts too lot of nuts too lot of nuts too you know I probably do what kind of nuts you know I probably do what kind of nuts you know I probably do what kind of nuts walnuts macadamia nuts pistachios walnuts macadamia nuts pistachios walnuts macadamia nuts pistachios cashews almonds I think probably I put cashews almonds I think probably I put cashews almonds I think probably I put cashews in the candy category oh really cashews in the candy category oh really cashews in the candy category oh really no no I just mean like can't stop eating no no I just mean like can't stop eating no no I just mean like can't stop eating this thing so yeah when I when I talk this thing so yeah when I when I talk this thing so yeah when I when I talk about nuts I'm like I eat nuts and about nuts I'm like I eat nuts and about nuts I'm like I eat nuts and sometimes cashews just might as well be sometimes cashews just might as well be sometimes cashews just might as well be eating M&Ms eating M&Ms eating M&Ms well yeah no look all kidding aside when well yeah no look all kidding aside when well yeah no look all kidding aside when I was on the ketogenic diet and I had to I was on the ketogenic diet and I had to I was on the ketogenic diet and I had to be very mindful of this stuff basically be very mindful of this stuff basically be very mindful of this stuff basically I could only consume almonds in I could only consume almonds in I could only consume almonds in macadamia everything else was just a macadamia everything else was just a macadamia everything else was just a little too high in carbohydrate the little too high in carbohydrate the little too high in carbohydrate the cashews just like my own personal demons cashews just like my own personal demons cashews just like my own personal demons okay I don't know what it is about okay I don't know what it is about okay I don't know what it is about cashews like I love watermelon like the

37:00cashews like I love watermelon like the cashews like I love watermelon like the summer like right now oh like my son summer like right now oh like my son summer like right now oh like my son loves we could eat a whole one oh yeah loves we could eat a whole one oh yeah loves we could eat a whole one oh yeah put a little salt on it like my put a little salt on it like my put a little salt on it like my father-in-law's from the south and father-in-law's from the south and father-in-law's from the south and taught me that so in the summer time I taught me that so in the summer time I taught me that so in the summer time I like to I like to eat some watermelon I like to I like to eat some watermelon I like to I like to eat some watermelon I like to eat peaches you know so well like to eat peaches you know so well like to eat peaches you know so well I'll definitely indulge in in more I'll definitely indulge in in more I'll definitely indulge in in more fruits because that's when they're fruits because that's when they're fruits because that's when they're around but you know so I do I think my around but you know so I do I think my around but you know so I do I think my diet tends to be I wouldn't be surprised diet tends to be I wouldn't be surprised diet tends to be I wouldn't be surprised if before you entered you're like so if before you entered you're like so if before you entered you're like so let's say you finish your feeding window let's say you finish your feeding window let's say you finish your feeding window just before you went to bed it wouldn't just before you went to bed it wouldn't just before you went to bed it wouldn't surprise me if you're already at 0.2 or surprise me if you're already at 0.2 or surprise me if you're already at 0.2 or 0.3 millimolar right probably yeah I 0.3 millimolar right probably yeah I 0.3 millimolar right probably yeah I never actually didn't measure there so never actually didn't measure there so never actually didn't measure there so check that yeah and that'll give me a check that yeah and that'll give me a check that yeah and that'll give me a sense because if you are believing is sense because if you are believing is sense because if you are believing is strict because I'm still nursing so I'm strict because I'm still nursing so I'm strict because I'm still nursing so I'm because it's just so hard to like because it's just so hard to like because it's just so hard to like timewise get everything I'm eating timewise get everything I'm eating timewise get everything I'm eating probably more like with probably more like with probably more like with the 11 or 12 hours okay okay well when the 11 or 12 hours okay okay well when the 11 or 12 hours okay okay well when you get back to the 15 I'd be curious you get back to the 15 I'd be curious you get back to the 15 I'd be curious because if you're actually able to go because if you're actually able to go because if you're actually able to go from zero or point 1 millimolar to 0.72 from zero or point 1 millimolar to 0.72 from zero or point 1 millimolar to 0.72 1 millimolar in a 15 hour fast that's 1 millimolar in a 15 hour fast that's 1 millimolar in a 15 hour fast that's impressed so so when I took the impressed so so when I took the impressed so so when I took the exogenous ketones and I've done this did

38:00exogenous ketones and I've done this did exogenous ketones and I've done this did you do the ester I did yesterday mmm I you do the ester I did yesterday mmm I you do the ester I did yesterday mmm I did their instructions which was heated did their instructions which was heated did their instructions which was heated with a heart high carbohydrate diet so I with a heart high carbohydrate diet so I with a heart high carbohydrate diet so I had a below bowl of some whole oats with had a below bowl of some whole oats with had a below bowl of some whole oats with some blueberries in it and then I took some blueberries in it and then I took some blueberries in it and then I took the VHB ester I literally went from like the VHB ester I literally went from like the VHB ester I literally went from like 0.1 millimolar ketone in one hour to 6 0.1 millimolar ketone in one hour to 6 0.1 millimolar ketone in one hour to 6 millimolar Wow 6 1 hour that's really millimolar Wow 6 1 hour that's really millimolar Wow 6 1 hour that's really high high high so that's impressive okay I'm trying to so that's impressive okay I'm trying to so that's impressive okay I'm trying to think I definitely don't get that high think I definitely don't get that high think I definitely don't get that high and that's just with one bottle with one and that's just with one bottle with one and that's just with one bottle with one bottle and then how long did it last do bottle and then how long did it last do bottle and then how long did it last do you recall let's it depends on whether you recall let's it depends on whether you recall let's it depends on whether or not I did exercise like intense or not I did exercise like intense or not I did exercise like intense exercise and so if I did the intense exercise and so if I did the intense exercise and so if I did the intense exercise like an hour later I was down exercise like an hour later I was down exercise like an hour later I was down to like 2 or 3 or something and have you to like 2 or 3 or something and have you to like 2 or 3 or something and have you ever taken it and just done work for ever taken it and just done work for ever taken it and just done work for example where basically the brain is example where basically the brain is example where basically the brain is doing more of the exercise than yeah doing more of the exercise than yeah doing more of the exercise than yeah that's what most way I do it now but I that's what most way I do it now but I that's what most way I do it now but I don't I'm not measuring because I'm don't I'm not measuring because I'm don't I'm not measuring because I'm usually like doing a podcast or going usually like doing a podcast or going usually like doing a podcast or going traveling and doing you know something

39:00traveling and doing you know something traveling and doing you know something but that's that's typical what I use it but that's that's typical what I use it but that's that's typical what I use it for is that so I'm not really doing that for is that so I'm not really doing that for is that so I'm not really doing that using it for exercise yeah they've using it for exercise yeah they've using it for exercise yeah they've really come a long way and taste really really come a long way and taste really really come a long way and taste really they still taste awful yeah you know they still taste awful yeah you know they still taste awful yeah you know it's funny I remember Kevin Rose who's a it's funny I remember Kevin Rose who's a it's funny I remember Kevin Rose who's a good mutual friend of ours when he tried good mutual friend of ours when he tried good mutual friend of ours when he tried them first he texted me and he's like them first he texted me and he's like them first he texted me and he's like dude these things aren't that bad like dude these things aren't that bad like dude these things aren't that bad like you made it sound like these things were you made it sound like these things were you made it sound like these things were horrible and I was like when I had it it horrible and I was like when I had it it horrible and I was like when I had it it I thought I was drinking kerosene or jet I thought I was drinking kerosene or jet I thought I was drinking kerosene or jet fuel I thought I was gonna die go blind fuel I thought I was gonna die go blind fuel I thought I was gonna die go blind first then die he goes not another first then die he goes not another first then die he goes not another stuffs good he goes actually I wouldn't stuffs good he goes actually I wouldn't stuffs good he goes actually I wouldn't call it a sippin ketone but it's call it a sippin ketone but it's call it a sippin ketone but it's actually pretty I was thought the guys actually pretty I was thought the guys actually pretty I was thought the guys at human and the T Delta s folks I think at human and the T Delta s folks I think at human and the T Delta s folks I think they've done a good job kind of making they've done a good job kind of making they've done a good job kind of making them less ridiculous they must really them less ridiculous they must really them less ridiculous they must really have tasted bad when you tried it cuz I have tasted bad when you tried it cuz I have tasted bad when you tried it cuz I personally think it's closer to the personally think it's closer to the personally think it's closer to the kerosene side than though it was so bad kerosene side than though it was so bad kerosene side than though it was so bad rather than there was like a good three rather than there was like a good three rather than there was like a good three month period where my favorite thing to month period where my favorite thing to month period where my favorite thing to do like more than anything in the world do like more than anything in the world do like more than anything in the world was if anyone came over to my house for was if anyone came over to my house for was if anyone came over to my house for dinner they had to try one dinner they had to try one dinner they had to try one finger dip worth Wow of stuff and of

40:00finger dip worth Wow of stuff and of finger dip worth Wow of stuff and of course the first time I drank it I just course the first time I drank it I just course the first time I drank it I just took 50 ml and chugged it neat without took 50 ml and chugged it neat without took 50 ml and chugged it neat without mixing it or anything like that and yeah mixing it or anything like that and yeah mixing it or anything like that and yeah I feel day just getting people to try I feel day just getting people to try I feel day just getting people to try this stuff this stuff this stuff the salts are obviously much more the salts are obviously much more the salts are obviously much more palatable yeah I've studied but I didn't palatable yeah I've studied but I didn't palatable yeah I've studied but I didn't really I wasn't I certainly didn't feel really I wasn't I certainly didn't feel really I wasn't I certainly didn't feel like I had the same effects as the the like I had the same effects as the the like I had the same effects as the the ester and also if I took a really high ester and also if I took a really high ester and also if I took a really high dose of it I felt like I had some GI dose of it I felt like I had some GI dose of it I felt like I had some GI distress absolutely I and I have also distress absolutely I and I have also distress absolutely I and I have also noticed that for some people that is for noticed that for some people that is for noticed that for some people that is for me that's the case so I cannot take the me that's the case so I cannot take the me that's the case so I cannot take the BHB ester on an empty stomach the only BHB ester on an empty stomach the only BHB ester on an empty stomach the only way I can tolerate that at high doses is way I can tolerate that at high doses is way I can tolerate that at high doses is either to put it with powdered MCT or either to put it with powdered MCT or either to put it with powdered MCT or actually just take it with a meal which actually just take it with a meal which actually just take it with a meal which in many ways defeats the purpose because in many ways defeats the purpose because in many ways defeats the purpose because I kind of like it as a way to avoid I kind of like it as a way to avoid I kind of like it as a way to avoid meals did it lower your blood glucose meals did it lower your blood glucose meals did it lower your blood glucose because yes like it like so because yes like it like so because yes like it like so significantly it was like like significantly it was like like significantly it was like like astounding yeah yeah no it's pretty astounding yeah yeah no it's pretty astounding yeah yeah no it's pretty impressive yeah yeah well and I and I impressive yeah yeah well and I and I impressive yeah yeah well and I and I know that Jeff woo the CEO at human is

41:00know that Jeff woo the CEO at human is know that Jeff woo the CEO at human is very interested in that and I republish very interested in that and I republish very interested in that and I republish to post I wrote five years ago in to post I wrote five years ago in to post I wrote five years ago in exhaustion his ketones like a couple exhaustion his ketones like a couple exhaustion his ketones like a couple weeks ago and a lot of scientists have weeks ago and a lot of scientists have weeks ago and a lot of scientists have reached out and said hey we're really reached out and said hey we're really reached out and said hey we're really interested in studying this like what interested in studying this like what interested in studying this like what can you tell us about this in anything can you tell us about this in anything can you tell us about this in anything so I think people are starting to so I think people are starting to so I think people are starting to realize that's an interesting way to realize that's an interesting way to realize that's an interesting way to lower glucose really significantly i lower glucose really significantly i lower glucose really significantly i person i dropped 30 points hydrate after person i dropped 30 points hydrate after person i dropped 30 points hydrate after a high carbohydrate like I said I had a high carbohydrate like I said I had a high carbohydrate like I said I had oatmeal with some blueberries there's oatmeal with some blueberries there's oatmeal with some blueberries there's nuts nuts nuts of course my my blood sugar because at of course my my blood sugar because at of course my my blood sugar because at the time too I mean I've just been the time too I mean I've just been the time too I mean I've just been nursing at night and so I'm waking up nursing at night and so I'm waking up nursing at night and so I'm waking up multiple times it has tear is terrible multiple times it has tear is terrible multiple times it has tear is terrible in your for your blood glucose levels in your for your blood glucose levels in your for your blood glucose levels and such but so they were a little and such but so they were a little and such but so they were a little higher than usual but yeah I drop me 30 higher than usual but yeah I drop me 30 higher than usual but yeah I drop me 30 points well yeah that's more than we points well yeah that's more than we points well yeah that's more than we typically see is it yeah on the topic of typically see is it yeah on the topic of typically see is it yeah on the topic of blood glucose have you ever experimented blood glucose have you ever experimented blood glucose have you ever experimented with akribos no I've experimented with with akribos no I've experimented with with akribos no I've experimented with it in with cells and culture but not it in with cells and culture but not it in with cells and culture but not like personally the stuffs pretty like personally the stuffs pretty like personally the stuffs pretty interesting it works quite well yeah interesting it works quite well yeah interesting it works quite well yeah I'll certainly if I'm going to indulge

42:00I'll certainly if I'm going to indulge I'll certainly if I'm going to indulge in some high carb action I'm gonna take in some high carb action I'm gonna take in some high carb action I'm gonna take a hundred milligrams of akribos a hundred milligrams of akribos a hundred milligrams of akribos beforehand and just flatline my glucose beforehand and just flatline my glucose beforehand and just flatline my glucose you know in many ways I find it actually you know in many ways I find it actually you know in many ways I find it actually more potent than metformin at glueck more potent than metformin at glueck more potent than metformin at glueck reduction I mean I think metformin has reduction I mean I think metformin has reduction I mean I think metformin has many other effects that we'll probably many other effects that we'll probably many other effects that we'll probably get into as well so let's go back to the get into as well so let's go back to the get into as well so let's go back to the IGF thing because this is sort of the IGF thing because this is sort of the IGF thing because this is sort of the thing that here's the thing I'll just thing that here's the thing I'll just thing that here's the thing I'll just jump right to my punchline in my jump right to my punchline in my jump right to my punchline in my question with this there are two issues question with this there are two issues question with this there are two issues I now have with things I used to take to I now have with things I used to take to I now have with things I used to take to be the God's honest truth actually three be the God's honest truth actually three be the God's honest truth actually three things the first is I found Cynthia things the first is I found Cynthia things the first is I found Cynthia Kenyans work on the daf-16 mutants in C Kenyans work on the daf-16 mutants in C Kenyans work on the daf-16 mutants in C elegans to be the most convincing elegans to be the most convincing elegans to be the most convincing evidence of the role of IGF or evidence of the role of IGF or evidence of the role of IGF or attenuating IGF in longevity and I now attenuating IGF in longevity and I now attenuating IGF in longevity and I now question that not question the work but question that not question the work but question that not question the work but question the inference that that can be question the inference that that can be question the inference that that can be applied to humans given the fact that applied to humans given the fact that applied to humans given the fact that only their germ cells divide and only their germ cells divide and only their germ cells divide and therefore cancer in that organism looks

43:00therefore cancer in that organism looks therefore cancer in that organism looks nothing like cancer in us cancer in that nothing like cancer in us cancer in that nothing like cancer in us cancer in that organism is only a cell getting larger organism is only a cell getting larger organism is only a cell getting larger there is no proliferation we have to there is no proliferation we have to there is no proliferation we have to sort of I mean it's obvious it's the sort of I mean it's obvious it's the sort of I mean it's obvious it's the risk of stating the obvious which is risk of stating the obvious which is risk of stating the obvious which is we're not worms but that's a huge we're not worms but that's a huge we're not worms but that's a huge difference in biology so that's that's difference in biology so that's that's difference in biology so that's that's the first thing let me let me let you the first thing let me let me let you the first thing let me let me let you comment on that yes because I've done comment on that yes because I've done comment on that yes because I've done those experiments so that probably what those experiments so that probably what those experiments so that probably what straight out of college and I went to straight out of college and I went to straight out of college and I went to work at the Salk Institute with Andrew work at the Salk Institute with Andrew work at the Salk Institute with Andrew Dylan who trained with Cynthia Cynthia Dylan who trained with Cynthia Cynthia Dylan who trained with Cynthia Cynthia Kenyon I was a chemistry major in Kenyon I was a chemistry major in Kenyon I was a chemistry major in college and I decided I kind of wanted college and I decided I kind of wanted college and I decided I kind of wanted to try some real biology because I only to try some real biology because I only to try some real biology because I only had a little bit of biology in college had a little bit of biology in college had a little bit of biology in college and so I went to work at the Salkin and and so I went to work at the Salkin and and so I went to work at the Salkin and really was like those first experiments really was like those first experiments really was like those first experiments I did with worms where you know we would I did with worms where you know we would I did with worms where you know we would knock down the the insulin igf-1 knock down the the insulin igf-1 knock down the the insulin igf-1 signaling pathway also known as the signaling pathway also known as the signaling pathway also known as the daf-2 and their worms would live like daf-2 and their worms would live like daf-2 and their worms would live like literally a hundred percent longer or literally a hundred percent longer or literally a hundred percent longer or like they don't go from two weeks to like they don't go from two weeks to like they don't go from two weeks to four weeks right yeah I mean it was like four weeks right yeah I mean it was like four weeks right yeah I mean it was like and not only that like the worms were so and not only that like the worms were so and not only that like the worms were so youthful like you would look at these youthful like you would look at these youthful like you would look at these worms you know cuz it's all I would do worms you know cuz it's all I would do worms you know cuz it's all I would do day after day under the microscope is

44:00day after day under the microscope is day after day under the microscope is just picking and poking and looking at just picking and poking and looking at just picking and poking and looking at the worms and how they move and you know the worms and how they move and you know the worms and how they move and you know as they get older they start to become as they get older they start to become as they get older they start to become less mobile and I mean it's just fair less mobile and I mean it's just fair less mobile and I mean it's just fair it's the most convincing day it is very it's the most convincing day it is very it's the most convincing day it is very convincing and now it's me in my mind convincing and now it's me in my mind convincing and now it's me in my mind was kind of like when I was like oh like was kind of like when I was like oh like was kind of like when I was like oh like we have a gene that sort of homologous we have a gene that sort of homologous we have a gene that sort of homologous to this and this is happening in those to this and this is happening in those to this and this is happening in those worms like I want to understand that worms like I want to understand that worms like I want to understand that like and here's the thing about that like and here's the thing about that like and here's the thing about that data and this is what I think if you get data and this is what I think if you get data and this is what I think if you get rid of another gene that's homologous to rid of another gene that's homologous to rid of another gene that's homologous to fall fall fall so - Oh deaf sixteen is right that's too so - Oh deaf sixteen is right that's too so - Oh deaf sixteen is right that's too far completely obliterates the lifespan far completely obliterates the lifespan far completely obliterates the lifespan extension meaning it's the Fox o3 that extension meaning it's the Fox o3 that extension meaning it's the Fox o3 that seems to be really important for we have seems to be really important for we have seems to be really important for we have how many we have for foxes yeah you mean how many we have for foxes yeah you mean how many we have for foxes yeah you mean different fox genes okay yeah I don't different fox genes okay yeah I don't different fox genes okay yeah I don't know exactly how many but the Fox oh we know exactly how many but the Fox oh we know exactly how many but the Fox oh we have three we have one two and four was have three we have one two and four was have three we have one two and four was it one two and there was our one two it one two and there was our one two it one two and there was our one two four or five but but their analog is four or five but but their analog is four or five but but their analog is sixteen I remember that right there sixteen I remember that right there sixteen I remember that right there daf-16 is basically our Fox Oh Fox oh daf-16 is basically our Fox Oh Fox oh daf-16 is basically our Fox Oh Fox oh yeah so okay well anyways yeah I'm not yeah so okay well anyways yeah I'm not yeah so okay well anyways yeah I'm not sure I'm getting confused with you know

45:00sure I'm getting confused with you know sure I'm getting confused with you know this but what is interesting is that the this but what is interesting is that the this but what is interesting is that the lifespan extension was completely like lifespan extension was completely like lifespan extension was completely like ameliorated did their health spend curbs ameliorated did their health spend curbs ameliorated did their health spend curbs cuz the experiment you're describing and cuz the experiment you're describing and cuz the experiment you're describing and no one can see what I'm doing but you no one can see what I'm doing but you no one can see what I'm doing but you know what I'm talking about like the the know what I'm talking about like the the know what I'm talking about like the the natural was a two-week lifespan where natural was a two-week lifespan where natural was a two-week lifespan where for the first week their youthful and for the first week their youthful and for the first week their youthful and then they have a declining health span then they have a declining health span then they have a declining health span curve so at the time of their death curve so at the time of their death curve so at the time of their death they're totally decrepit in the they're totally decrepit in the they're totally decrepit in the experiment you were describing if I'm experiment you were describing if I'm experiment you were describing if I'm thinking of the same one you doubled the thinking of the same one you doubled the thinking of the same one you doubled the lifespan and their longevity curve lifespan and their longevity curve lifespan and their longevity curve became a square function it just went became a square function it just went became a square function it just went out kind of yeah exactly out kind of yeah exactly out kind of yeah exactly yeah that's exactly what happened but yeah that's exactly what happened but yeah that's exactly what happened but you get rid of the daf-16 and they're you get rid of the daf-16 and they're you get rid of the daf-16 and they're like wild type oh they're like wild type like wild type oh they're like wild type like wild type oh they're like wild type yes I think so but and that largely has yes I think so but and that largely has yes I think so but and that largely has to do with you know so that the igf-1 to do with you know so that the igf-1 to do with you know so that the igf-1 insulin-like linked pathway both inhibit insulin-like linked pathway both inhibit insulin-like linked pathway both inhibit Fox o3 so if you get rid of that Fox o3 so if you get rid of that Fox o3 so if you get rid of that inhibition constitutively if Fox or 3 is inhibition constitutively if Fox or 3 is inhibition constitutively if Fox or 3 is constantly active in those worms I mean constantly active in those worms I mean constantly active in those worms I mean it's just like super in there making it's just like super in there making it's just like super in there making superoxide dismutase they're making more superoxide dismutase they're making more superoxide dismutase they're making more stem cells they're making just stem cells they're making just stem cells they're making just everything's active you know more etaf everything's active you know more etaf everything's active you know more etaf EG more stret like all these stress EG more stret like all these stress EG more stret like all these stress resistance pathways I mean Fox o3 is a

46:00resistance pathways I mean Fox o3 is a resistance pathways I mean Fox o3 is a transcription factor it regulates whole transcription factor it regulates whole transcription factor it regulates whole host of genes many of which have to do host of genes many of which have to do host of genes many of which have to do with DNA repair at ah Fuji stem cell with DNA repair at ah Fuji stem cell with DNA repair at ah Fuji stem cell function production of antioxidants and function production of antioxidants and function production of antioxidants and anti-inflammatory pathway so it's a lot anti-inflammatory pathway so it's a lot anti-inflammatory pathway so it's a lot of really good stuff you want active all of really good stuff you want active all of really good stuff you want active all the time so there's that component to the time so there's that component to the time so there's that component to the longevity pathway and actually if the longevity pathway and actually if the longevity pathway and actually if you look at the animal data from rodents you look at the animal data from rodents you look at the animal data from rodents where they're calorie restricted if you where they're calorie restricted if you where they're calorie restricted if you get rid of the Fox o3 the median get rid of the Fox o3 the median get rid of the Fox o3 the median lifespan extension is gone so the lifespan extension is gone so the lifespan extension is gone so the lifespan extension depends on Fox or 3d lifespan extension depends on Fox or 3d lifespan extension depends on Fox or 3d the cancer stuff was still like it the cancer stuff was still like it the cancer stuff was still like it didn't matter so the cancer didn't matter so the cancer didn't matter so the cancer reduction didn't depend on Fox or 3 only reduction didn't depend on Fox or 3 only reduction didn't depend on Fox or 3 only the lifespan extension so I think there the lifespan extension so I think there the lifespan extension so I think there may be a nun coupling between may be a nun coupling between may be a nun coupling between humans in igf-1 one of the major humans in igf-1 one of the major humans in igf-1 one of the major problems with igf-1 is actually cancer problems with igf-1 is actually cancer problems with igf-1 is actually cancer and if you if you look at you know and if you if you look at you know and if you if you look at you know animal studies if you look at humans to animal studies if you look at humans to animal studies if you look at humans to human studies like humans that have human studies like humans that have human studies like humans that have polymorphisms that make them have more polymorphisms that make them have more polymorphisms that make them have more igf-1 they have much higher cancer igf-1 they have much higher cancer igf-1 they have much higher cancer incidence vice versa so if you look at incidence vice versa so if you look at incidence vice versa so if you look at people that have polymorphisms is that people that have polymorphisms is that people that have polymorphisms is that is that the case I mean we look at the is that the case I mean we look at the is that the case I mean we look at the opposites right we look at the ones that

47:00opposites right we look at the ones that opposites right we look at the ones that have low GH and by proxy low IGF and have low GH and by proxy low IGF and have low GH and by proxy low IGF and have less cancer so you're talking about have less cancer so you're talking about have less cancer so you're talking about learn syndrome yes oléron syndrome yes learn syndrome yes oléron syndrome yes learn syndrome yes oléron syndrome yes yes they do but I think there's also yes they do but I think there's also yes they do but I think there's also another one in IGF there's Hetson igf-1 another one in IGF there's Hetson igf-1 another one in IGF there's Hetson igf-1 receptor so this is you're not talking receptor so this is you're not talking receptor so this is you're not talking about acromegaly or people that are about acromegaly or people that are about acromegaly or people that are making too much th they also are more making too much th they also are more making too much th they also are more susceptible to to cancel cancer as well susceptible to to cancel cancer as well susceptible to to cancel cancer as well yes I am talking about them as well yes I am talking about them as well yes I am talking about them as well actually the people with acromegaly are actually the people with acromegaly are actually the people with acromegaly are more susceptible to cancer maybe I am more susceptible to cancer maybe I am more susceptible to cancer maybe I am that's what I was referring to with they that's what I was referring to with they that's what I was referring to with they have higher circulating levels of igf-1 have higher circulating levels of igf-1 have higher circulating levels of igf-1 so you're saying you can't uncouple the so you're saying you can't uncouple the so you're saying you can't uncouple the growth hormone from yeah that's that's growth hormone from yeah that's that's growth hormone from yeah that's that's been one of the things I've struggled been one of the things I've struggled been one of the things I've struggled with is it's hard to uncouple the gh the with is it's hard to uncouple the gh the with is it's hard to uncouple the gh the effect of GH on the liver yes exactly effect of GH on the liver yes exactly effect of GH on the liver yes exactly that has been uncouple like if you if that has been uncouple like if you if that has been uncouple like if you if you do any sort of tumor transplant you do any sort of tumor transplant you do any sort of tumor transplant animals and then make them have high gf1 animals and then make them have high gf1 animals and then make them have high gf1 through a variety of modalities the through a variety of modalities the through a variety of modalities the cancer will grow rapidly so how do we cancer will grow rapidly so how do we cancer will grow rapidly so how do we explain the human epidemiology which and explain the human epidemiology which and explain the human epidemiology which and I'm like there are a few people that are I'm like there are a few people that are I'm like there are a few people that are more critical of Epidemiology than me

48:00more critical of Epidemiology than me more critical of Epidemiology than me I'm not a particular fan of it but I I'm not a particular fan of it but I I'm not a particular fan of it but I find it to be quite interesting in the find it to be quite interesting in the find it to be quite interesting in the negative meaning the contrapositive x' negative meaning the contrapositive x' negative meaning the contrapositive x' with an epidemiology can be quite with an epidemiology can be quite with an epidemiology can be quite interesting so this is the next thing interesting so this is the next thing interesting so this is the next thing that kept me going wait a minute and that kept me going wait a minute and that kept me going wait a minute and that was there's a u-shaped mortality that was there's a u-shaped mortality that was there's a u-shaped mortality curve that is skewed to the right for curve that is skewed to the right for curve that is skewed to the right for IGF and all cause mortality cancer IGF and all cause mortality cancer IGF and all cause mortality cancer mortality cardiovascular mortality and mortality cardiovascular mortality and mortality cardiovascular mortality and neurodegenerative mortality but when you neurodegenerative mortality but when you neurodegenerative mortality but when you uncouple them by disease you see a very uncouple them by disease you see a very uncouple them by disease you see a very interesting pattern so all cause interesting pattern so all cause interesting pattern so all cause mortality as IGF goes up it actually mortality as IGF goes up it actually mortality as IGF goes up it actually starts to go down it Nader's at the 70th starts to go down it Nader's at the 70th starts to go down it Nader's at the 70th percentile and then it starts to rise percentile and then it starts to rise percentile and then it starts to rise but it doesn't get as high as it started but it doesn't get as high as it started but it doesn't get as high as it started I know for people listening this is I know for people listening this is I know for people listening this is confusing so we'll include the figures confusing so we'll include the figures confusing so we'll include the figures of all these from the papers but the of all these from the papers but the of all these from the papers but the point is it's not that as IGF goes up point is it's not that as IGF goes up point is it's not that as IGF goes up eyetality goes up it's the opposite for eyetality goes up it's the opposite for eyetality goes up it's the opposite for 70% of the ledger only at the very end 70% of the ledger only at the very end 70% of the ledger only at the very end in other words only high levels of IGF

49:00in other words only high levels of IGF in other words only high levels of IGF if' seem problematic and as I know if' seem problematic and as I know if' seem problematic and as I know you've talked about I've heard you talk you've talked about I've heard you talk you've talked about I've heard you talk about this on your podcast you have to about this on your podcast you have to about this on your podcast you have to then disaggregate that by age the older then disaggregate that by age the older then disaggregate that by age the older you get the better IGF seems to be you get the better IGF seems to be you get the better IGF seems to be presumably because of the preservation presumably because of the preservation presumably because of the preservation of lean tissue it turns out that most of of lean tissue it turns out that most of of lean tissue it turns out that most of the uptick in the mortality above the the uptick in the mortality above the the uptick in the mortality above the 70th percentile is driven by cancer but 70th percentile is driven by cancer but 70th percentile is driven by cancer but actually cardiovascular disease and actually cardiovascular disease and actually cardiovascular disease and neurodegenerative disease seem to get neurodegenerative disease seem to get neurodegenerative disease seem to get they flatlined by the end so meaning they flatlined by the end so meaning they flatlined by the end so meaning there was no benefit to being at the there was no benefit to being at the there was no benefit to being at the hundredth percentile or the 99th hundredth percentile or the 99th hundredth percentile or the 99th percentile versus the 80th versus the percentile versus the 80th versus the percentile versus the 80th versus the 70th but you weren't getting penalized 70th but you weren't getting penalized 70th but you weren't getting penalized for it which suggested to me that low for it which suggested to me that low for it which suggested to me that low IGF might not be the ticket maybe it's IGF might not be the ticket maybe it's IGF might not be the ticket maybe it's some combination of cycling high and low some combination of cycling high and low some combination of cycling high and low IGF but living at around the median to IGF but living at around the median to IGF but living at around the median to slightly above that the 60th 70th slightly above that the 60th 70th slightly above that the 60th 70th percentile and again that's probably percentile and again that's probably percentile and again that's probably more a function of my misunderstanding more a function of my misunderstanding more a function of my misunderstanding of the literature five years ago but I of the literature five years ago but I of the literature five years ago but I really came away thinking IGF we've got really came away thinking IGF we've got really came away thinking IGF we've got to keep that as low as possible it's

50:00to keep that as low as possible it's to keep that as low as possible it's funny you and I kind of have had we've funny you and I kind of have had we've funny you and I kind of have had we've evolved in the very similar because I evolved in the very similar because I evolved in the very similar because I now also think that you know so igf-1 now also think that you know so igf-1 now also think that you know so igf-1 does play a very important role does play a very important role does play a very important role obviously in development but also in the obviously in development but also in the obviously in development but also in the repair of muscle in the growth of muscle repair of muscle in the growth of muscle repair of muscle in the growth of muscle preserving muscle mass also it gets preserving muscle mass also it gets preserving muscle mass also it gets transport across the blood-brain barrier transport across the blood-brain barrier transport across the blood-brain barrier plays an important role in neurogenesis plays an important role in neurogenesis plays an important role in neurogenesis and allowing existing neurons to survive and allowing existing neurons to survive and allowing existing neurons to survive which kind of brings me back to that which kind of brings me back to that which kind of brings me back to that gray matter thing with the lemurs but gray matter thing with the lemurs but gray matter thing with the lemurs but you know so and the thing that was you know so and the thing that was you know so and the thing that was interesting to me was the effect of interesting to me was the effect of interesting to me was the effect of exercise on igf-1 and the fact that for exercise on igf-1 and the fact that for exercise on igf-1 and the fact that for one it's been shown that the the boost one it's been shown that the the boost one it's been shown that the the boost in neurogenesis after exercise in the in neurogenesis after exercise in the in neurogenesis after exercise in the brain via brain revenue is requires brain via brain revenue is requires brain via brain revenue is requires igf-1 animal studies have shown that igf-1 animal studies have shown that igf-1 animal studies have shown that mostly in rodents have shown that that mostly in rodents have shown that that mostly in rodents have shown that that exercise causes igf-1 across the exercise causes igf-1 across the exercise causes igf-1 across the blood-brain barrier getting to the brain blood-brain barrier getting to the brain blood-brain barrier getting to the brain but in human studies I've also seen some but in human studies I've also seen some but in human studies I've also seen some showing that it does lower serum levels showing that it does lower serum levels showing that it does lower serum levels I think presumably it's also going into I think presumably it's also going into I think presumably it's also going into the muscle and the brain so I think that the muscle and the brain so I think that the muscle and the brain so I think that you know people that are exercising you know people that are exercising you know people that are exercising they're putting that igf-1 to the places

51:00they're putting that igf-1 to the places they're putting that igf-1 to the places where it's supposed to go where it's supposed to go where it's supposed to go muscle tissue brain tissue as well but muscle tissue brain tissue as well but muscle tissue brain tissue as well but in addition to that and this is kind of in addition to that and this is kind of in addition to that and this is kind of what's what's what's recent work from dr. falter Longo is recent work from dr. falter Longo is recent work from dr. falter Longo is that we know that this he does he's that we know that this he does he's that we know that this he does he's prolonged fast and I think the prolonged prolonged fast and I think the prolonged prolonged fast and I think the prolonged fasting is extremely interesting for a fasting is extremely interesting for a fasting is extremely interesting for a couple of main reasons and one is I couple of main reasons and one is I couple of main reasons and one is I think that it has tremendous potential think that it has tremendous potential think that it has tremendous potential for the treatment of autoimmune disease for the treatment of autoimmune disease for the treatment of autoimmune disease and also cancer based on on you know his and also cancer based on on you know his and also cancer based on on you know his work and what he has shown now in animal work and what he has shown now in animal work and what he has shown now in animal studies and some pilot clinical studies studies and some pilot clinical studies studies and some pilot clinical studies is that doing a prolonged fast and or in is that doing a prolonged fast and or in is that doing a prolonged fast and or in some cases the fasting mimicking diet some cases the fasting mimicking diet some cases the fasting mimicking diet causes this massive shrinking of organs causes this massive shrinking of organs causes this massive shrinking of organs where now he doesn't know how much of where now he doesn't know how much of where now he doesn't know how much of it's due to cell size decreasing versus it's due to cell size decreasing versus it's due to cell size decreasing versus apoptosis he does know a puppet apoptosis he does know a puppet apoptosis he does know a puppet apoptosis is occurring and he has showed apoptosis is occurring and he has showed apoptosis is occurring and he has showed that in multiple publications like that in multiple publications like that in multiple publications like there's a massive induction of apoptosis there's a massive induction of apoptosis there's a massive induction of apoptosis after a prolonged fest and you know after a prolonged fest and you know after a prolonged fest and you know which makes sense because it's a very which makes sense because it's a very which makes sense because it's a very strong stress and then after during the

52:00strong stress and then after during the strong stress and then after during the refeeding phase their organs basically refeeding phase their organs basically refeeding phase their organs basically come back they come back they grow come back they come back they grow come back they come back they grow regrow and presumably selectively regrow and presumably selectively regrow and presumably selectively repopulate yes so he's shown that these repopulate yes so he's shown that these repopulate yes so he's shown that these stem cells get activated so that the stem cells get activated so that the stem cells get activated so that the basically they have to be activated by basically they have to be activated by basically they have to be activated by the low igf-1 but then to proliferate the low igf-1 but then to proliferate the low igf-1 but then to proliferate and differentiate into whatever tissue and differentiate into whatever tissue and differentiate into whatever tissue type we're talking about let's say we're type we're talking about let's say we're type we're talking about let's say we're talking about the immune system then talking about the immune system then talking about the immune system then igf-1 is required for that proliferation igf-1 is required for that proliferation igf-1 is required for that proliferation and differentiation and repopulation of and differentiation and repopulation of and differentiation and repopulation of the tissue which means you can't just the tissue which means you can't just the tissue which means you can't just keep the igf-1 keep the igf-1 keep the igf-1 Wow the refeeding is just as important Wow the refeeding is just as important Wow the refeeding is just as important as the deprivation and the igf-1 is key as the deprivation and the igf-1 is key as the deprivation and the igf-1 is key in that and so you know what he's shown in that and so you know what he's shown in that and so you know what he's shown now is that you can take for example in now is that you can take for example in now is that you can take for example in the multiple sclerosis animal model you the multiple sclerosis animal model you the multiple sclerosis animal model you can actually cause stem cells to be can actually cause stem cells to be can actually cause stem cells to be activated through the prolonged fast and activated through the prolonged fast and activated through the prolonged fast and then during the refeeding phase the stem then during the refeeding phase the stem then during the refeeding phase the stem cells make non dysfunctional so they're cells make non dysfunctional so they're cells make non dysfunctional so they're making normal non auto immune cells he's making normal non auto immune cells he's making normal non auto immune cells he's done like a pilot clinical study with done like a pilot clinical study with done like a pilot clinical study with multiple sclerosis people with multiple multiple sclerosis people with multiple multiple sclerosis people with multiple sclerosis and it's helped with symptoms sclerosis and it's helped with symptoms sclerosis and it's helped with symptoms but he's also done these cancer studies but he's also done these cancer studies but he's also done these cancer studies and this is kind of where there's been

53:00and this is kind of where there's been and this is kind of where there's been some some clinical studies that he's some some clinical studies that he's some some clinical studies that he's been involved with like a 48-hour water been involved with like a 48-hour water been involved with like a 48-hour water fast that that's been done in patients fast that that's been done in patients fast that that's been done in patients undergoing standard of care treatment undergoing standard of care treatment undergoing standard of care treatment and he's shown that it was tolerable not and he's shown that it was tolerable not and he's shown that it was tolerable not only that there seemed to be less my low only that there seemed to be less my low only that there seemed to be less my low toxicity less neutropenia so basically toxicity less neutropenia so basically toxicity less neutropenia so basically there and it sensitized cancer cells to there and it sensitized cancer cells to there and it sensitized cancer cells to death death death so not only where the cancer cells so not only where the cancer cells so not only where the cancer cells more but less of the normal cells were more but less of the normal cells were more but less of the normal cells were dying and then he's gone ahead and shown dying and then he's gone ahead and shown dying and then he's gone ahead and shown this in animal models also with the this in animal models also with the this in animal models also with the fasting mimicking diet and it's like if fasting mimicking diet and it's like if fasting mimicking diet and it's like if you look at the data particularly in the you look at the data particularly in the you look at the data particularly in the animal model because they can you know animal model because they can you know animal model because they can you know do all the tissue harvesting and stuff I do all the tissue harvesting and stuff I do all the tissue harvesting and stuff I mean it's like it's so phenomenal that I mean it's like it's so phenomenal that I mean it's like it's so phenomenal that I would not be surprised that in the next would not be surprised that in the next would not be surprised that in the next ten years it will be required part of ten years it will be required part of ten years it will be required part of standard of care because it seems to be standard of care because it seems to be standard of care because it seems to be so incredibly robust at selectively so incredibly robust at selectively so incredibly robust at selectively killing cancer cells which you know killing cancer cells which you know killing cancer cells which you know makes sense I mean oncogenes they screw makes sense I mean oncogenes they screw makes sense I mean oncogenes they screw up all sorts of things one of them is up all sorts of things one of them is up all sorts of things one of them is the the stress response and you know the the stress response and you know the the stress response and you know cancer cells can't respond just read cancer cells can't respond just read cancer cells can't respond just read their prime to die I mean it's I spent a their prime to die I mean it's I spent a their prime to die I mean it's I spent a long time meena studying cancer cell long time meena studying cancer cell long time meena studying cancer cell metabolism apoptosis with Doug green and

54:00metabolism apoptosis with Doug green and metabolism apoptosis with Doug green and Joseph opperman at st. Jude Children's Joseph opperman at st. Jude Children's Joseph opperman at st. Jude Children's Research Hospital and and that's kind of Research Hospital and and that's kind of Research Hospital and and that's kind of one of the primary ways that a lot of one of the primary ways that a lot of one of the primary ways that a lot of these chemo therapeutic drugs if they these chemo therapeutic drugs if they these chemo therapeutic drugs if they can get to the tumor site work is that can get to the tumor site work is that can get to the tumor site work is that because it's a stress cancer cells can't because it's a stress cancer cells can't because it's a stress cancer cells can't handle it you know they die so I kind of handle it you know they die so I kind of handle it you know they die so I kind of went off on a tangent here so to get went off on a tangent here so to get went off on a tangent here so to get back to the igf-1 let me say one thing back to the igf-1 let me say one thing back to the igf-1 let me say one thing going back to what you just said that is going back to what you just said that is going back to what you just said that is also interesting but in the same thing also interesting but in the same thing also interesting but in the same thing so I agree that I think that it would so I agree that I think that it would so I agree that I think that it would really be great if patients had a better really be great if patients had a better really be great if patients had a better insight into nutrition going into insight into nutrition going into insight into nutrition going into chemotherapy and the few times I go and chemotherapy and the few times I go and chemotherapy and the few times I go and give talks at hospitals or go and talk give talks at hospitals or go and talk give talks at hospitals or go and talk it like a cancer meeting I'm amazed at it like a cancer meeting I'm amazed at it like a cancer meeting I'm amazed at how resistant the oncologists are on how resistant the oncologists are on how resistant the oncologists are on average obviously there were exceptions average obviously there were exceptions average obviously there were exceptions but on average to interfering with but on average to interfering with but on average to interfering with nutrition because in many ways their nutrition because in many ways their nutrition because in many ways their primary concern tragically is preserving primary concern tragically is preserving primary concern tragically is preserving weight and so I always get a little weight and so I always get a little weight and so I always get a little verklempt when I walk through an verklempt when I walk through an verklempt when I walk through an oncology ward and I see patients oncology ward and I see patients oncology ward and I see patients drinking in Shore I couldn't think of a drinking in Shore I couldn't think of a drinking in Shore I couldn't think of a worse thing you'd want to consume when worse thing you'd want to consume when worse thing you'd want to consume when you have cancer and yet the goal is hey you have cancer and yet the goal is hey you have cancer and yet the goal is hey we got to fatten these people up so I

55:00we got to fatten these people up so I we got to fatten these people up so I agree with you and I really hope that agree with you and I really hope that agree with you and I really hope that this research is accelerated because I this research is accelerated because I this research is accelerated because I do think patients would benefit greatly do think patients would benefit greatly do think patients would benefit greatly from this and the other application that from this and the other application that from this and the other application that I saw this several years ago this is I saw this several years ago this is I saw this several years ago this is quite old now but it blew my mind I'm quite old now but it blew my mind I'm quite old now but it blew my mind I'm not sure familiar with Jay Mitchell's not sure familiar with Jay Mitchell's not sure familiar with Jay Mitchell's work up at Harvard he did an experiment work up at Harvard he did an experiment work up at Harvard he did an experiment where he took three yeah three groups of where he took three yeah three groups of where he took three yeah three groups of mice so the first group were mice so the first group were mice so the first group were constitutively calorically restricted constitutively calorically restricted constitutively calorically restricted for their entire life these were for their entire life these were for their entire life these were probably like one and a half year old probably like one and a half year old probably like one and a half year old mice so they're about halfway through mice so they're about halfway through mice so they're about halfway through their life starting starting yeah so their life starting starting yeah so their life starting starting yeah so these these animals were these these animals were these these animals were constantly at 70% caloric intake the constantly at 70% caloric intake the constantly at 70% caloric intake the next group was your control group and next group was your control group and next group was your control group and then your third group was ad libitum then your third group was ad libitum then your third group was ad libitum diet until two days before an operation diet until two days before an operation diet until two days before an operation and at which point they were calorie and at which point they were calorie and at which point they were calorie restricted to a near fast and I'd have restricted to a near fast and I'd have restricted to a near fast and I'd have to go back and look I can't member if it to go back and look I can't member if it to go back and look I can't member if it was 24 or 48 hours of fasting it was 24 or 48 hours of fasting it was 24 or 48 hours of fasting it might've been a 24-hour fast 48 would be might've been a 24-hour fast 48 would be might've been a 24-hour fast 48 would be pretty extreme for mice pretty extreme for mice pretty extreme for mice so in summary you've got control there's so in summary you've got control there's so in summary you've got control there's straight-up eating you've got 70% or 30%

56:00straight-up eating you've got 70% or 30% straight-up eating you've got 70% or 30% CR forever and then you've got control CR forever and then you've got control CR forever and then you've got control and then fasted for a day all the mice and then fasted for a day all the mice and then fasted for a day all the mice were then operated on where their were then operated on where their were then operated on where their femoral arteries were like ated held for femoral arteries were like ated held for femoral arteries were like ated held for a period of time and then they were a period of time and then they were a period of time and then they were Reaper fused for people not familiar Reaper fused for people not familiar Reaper fused for people not familiar with what that means so that means you with what that means so that means you with what that means so that means you you open the animal up you put clamps on you open the animal up you put clamps on you open the animal up you put clamps on the femoral arteries which would the femoral arteries which would the femoral arteries which would basically stop all perfusion of blood to basically stop all perfusion of blood to basically stop all perfusion of blood to the lower part of the body and then the lower part of the body and then the lower part of the body and then after some period of time just before after some period of time just before after some period of time just before you kill the animal you release that and you kill the animal you release that and you kill the animal you release that and then you Reaper use the blood basically then you Reaper use the blood basically then you Reaper use the blood basically the oxygen Reaper fuses the organism the oxygen Reaper fuses the organism the oxygen Reaper fuses the organism that's considered a reperfusion injury that's considered a reperfusion injury that's considered a reperfusion injury which is about one of the most stressful which is about one of the most stressful which is about one of the most stressful things you can do to an organism so that things you can do to an organism so that things you can do to an organism so that you can really rapidly kill someone by you can really rapidly kill someone by you can really rapidly kill someone by doing that and that's something that in doing that and that's something that in doing that and that's something that in surgery happens quite a bit for example surgery happens quite a bit for example surgery happens quite a bit for example you end up having to clamp something off you end up having to clamp something off you end up having to clamp something off to repair something downstream of that to repair something downstream of that to repair something downstream of that okay so what happened was all of the okay so what happened was all of the okay so what happened was all of the control animals died without exception control animals died without exception control animals died without exception of the other two groups the groups that of the other two groups the groups that of the other two groups the groups that were either calorie-restricted for life

57:00were either calorie-restricted for life were either calorie-restricted for life or transiently starved before the or transiently starved before the or transiently starved before the surgery a significant subset did not die surgery a significant subset did not die surgery a significant subset did not die and I can't remember the number and and I can't remember the number and and I can't remember the number and again I know we're gonna probably link again I know we're gonna probably link again I know we're gonna probably link to this study so people are gonna listen to this study so people are gonna listen to this study so people are gonna listen to this and go that idiot got all those to this and go that idiot got all those to this and go that idiot got all those details wrong but this is the gist of it details wrong but this is the gist of it details wrong but this is the gist of it a non-trivial subset of them lived and a non-trivial subset of them lived and a non-trivial subset of them lived and what's interesting is you could get the what's interesting is you could get the what's interesting is you could get the same benefit by an acute period of same benefit by an acute period of same benefit by an acute period of caloric restriction in proximity to an caloric restriction in proximity to an caloric restriction in proximity to an insult that you could get by a lifelong insult that you could get by a lifelong insult that you could get by a lifelong of caloric restriction and the third of caloric restriction and the third of caloric restriction and the third piece would that was interesting was the piece would that was interesting was the piece would that was interesting was the group that were just starved transiently group that were just starved transiently group that were just starved transiently actually had a faster recovery which actually had a faster recovery which actually had a faster recovery which again they were fitter organisms I again they were fitter organisms I again they were fitter organisms I remember the first time I came across remember the first time I came across remember the first time I came across that thinking there's got to be that thinking there's got to be that thinking there's got to be something to cycling and people used to something to cycling and people used to something to cycling and people used to always ask me like why are you on a always ask me like why are you on a always ask me like why are you on a ketogenic diet every minute of every day ketogenic diet every minute of every day ketogenic diet every minute of every day would there be any benefit in cycling would there be any benefit in cycling would there be any benefit in cycling now I still don't know the answer to now I still don't know the answer to now I still don't know the answer to that question that question that question but I'm more curious about it now based but I'm more curious about it now based but I'm more curious about it now based on what you just described from vaulters on what you just described from vaulters on what you just described from vaulters work plus this type of stuff plus just work plus this type of stuff plus just work plus this type of stuff plus just the general ethos of the way we evolved the general ethos of the way we evolved the general ethos of the way we evolved we've fasted we fed we fasted we fed we

58:00we've fasted we fed we fasted we fed we we've fasted we fed we fasted we fed we fasted a long time we gorged like it fasted a long time we gorged like it fasted a long time we gorged like it just seems we've evolved for cycling just seems we've evolved for cycling just seems we've evolved for cycling right yeah I agree it's really that with right yeah I agree it's really that with right yeah I agree it's really that with falters work I just I'm so excited about falters work I just I'm so excited about falters work I just I'm so excited about about the prolonged fasting and the the about the prolonged fasting and the the about the prolonged fasting and the the potential benefits of it I think that potential benefits of it I think that potential benefits of it I think that actually something that you and I actually something that you and I actually something that you and I discuss several years ago and I had you discuss several years ago and I had you discuss several years ago and I had you I interviewed you on my podcast that you I interviewed you on my podcast that you I interviewed you on my podcast that you brought up that I thought was really brought up that I thought was really brought up that I thought was really interesting had to do with like the interesting had to do with like the interesting had to do with like the failed clinical trials with binding failed clinical trials with binding failed clinical trials with binding igf-1 and cancer and vulture brought up igf-1 and cancer and vulture brought up igf-1 and cancer and vulture brought up something interesting in a conversation something interesting in a conversation something interesting in a conversation I had with him and that is possibly that I had with him and that is possibly that I had with him and that is possibly that we now know IG f1 having low and high G we now know IG f1 having low and high G we now know IG f1 having low and high G f1 is important so if you're constantly f1 is important so if you're constantly f1 is important so if you're constantly having low igf-1 and the igf-1 is having low igf-1 and the igf-1 is having low igf-1 and the igf-1 is important for the immune system or important for the immune system or important for the immune system or population you can imagine in the population you can imagine in the population you can imagine in the context of cancer when you're giving context of cancer when you're giving context of cancer when you're giving other treatments along with it that other treatments along with it that other treatments along with it that would be important because your immune would be important because your immune would be important because your immune system is key in in warding off cancer system is key in in warding off cancer system is key in in warding off cancer and I thought that was a really and I thought that was a really and I thought that was a really interesting point of course we don't interesting point of course we don't interesting point of course we don't have evidence of that but I think you have evidence of that but I think you have evidence of that but I think you know it's something that would be

59:00know it's something that would be know it's something that would be interesting to investigate and it makes interesting to investigate and it makes interesting to investigate and it makes sense yeah I definitely am on the same sense yeah I definitely am on the same sense yeah I definitely am on the same page with you if I don't I'm not and page with you if I don't I'm not and page with you if I don't I'm not and like I started out with saying I don't like I started out with saying I don't like I started out with saying I don't think that chronic caloric restriction think that chronic caloric restriction think that chronic caloric restriction and low igf-1 is the essential like way and low igf-1 is the essential like way and low igf-1 is the essential like way for improving health span I do think for improving health span I do think for improving health span I do think that igf-1 you want it to go to your that igf-1 you want it to go to your that igf-1 you want it to go to your muscle you want to go to your brain so I muscle you want to go to your brain so I muscle you want to go to your brain so I think people should definitely be active think people should definitely be active think people should definitely be active especially if they're eating a especially if they're eating a especially if they're eating a high-protein and or even high high-protein and or even high high-protein and or even high carbohydrate or something that's gonna carbohydrate or something that's gonna carbohydrate or something that's gonna produce a lot of insulin you know they produce a lot of insulin you know they produce a lot of insulin you know they shouldn't be eating refined carbs but shouldn't be eating refined carbs but shouldn't be eating refined carbs but people do they're eating them they people do they're eating them they people do they're eating them they should definitely be exercising that's should definitely be exercising that's should definitely be exercising that's another change in my belief system I another change in my belief system I another change in my belief system I think today versus I don't know five or think today versus I don't know five or think today versus I don't know five or six years ago I think five or six years six years ago I think five or six years six years ago I think five or six years ago I didn't think exercise was that ago I didn't think exercise was that ago I didn't think exercise was that important to longevity which actually important to longevity which actually important to longevity which actually sounds ridiculous for anyone who knows sounds ridiculous for anyone who knows sounds ridiculous for anyone who knows me because I was probably exercising me because I was probably exercising me because I was probably exercising four hours a day but not because I four hours a day but not because I four hours a day but not because I believed it would make me live longer it believed it would make me live longer it believed it would make me live longer it was just sort of soothing my addictions was just sort of soothing my addictions was just sort of soothing my addictions but I think today I feel I am much more but I think today I feel I am much more but I think today I feel I am much more convinced by a lot of the data you've convinced by a lot of the data you've convinced by a lot of the data you've described certainly the central stuff described certainly the central stuff described certainly the central stuff when we published this paper earlier

1:00when we published this paper earlier when we published this paper earlier this year with Richard Isaac's and that this year with Richard Isaac's and that this year with Richard Isaac's and that you and I were talking about it before you and I were talking about it before you and I were talking about it before we started recording we wanted to get a we started recording we wanted to get a we started recording we wanted to get a sense of like if you took a completely sense of like if you took a completely sense of like if you took a completely unbiased approached and look at the unbiased approached and look at the unbiased approached and look at the literature what was the single most literature what was the single most literature what was the single most compelling thing you could do to compelling thing you could do to compelling thing you could do to generate or preserve brain health and we generate or preserve brain health and we generate or preserve brain health and we came away thinking that it was actually came away thinking that it was actually came away thinking that it was actually exercise and I remember when the exercise and I remember when the exercise and I remember when the analysts were kind of going through this analysts were kind of going through this analysts were kind of going through this and showing me all the data I was like and showing me all the data I was like and showing me all the data I was like come on guys there's no way exercise come on guys there's no way exercise come on guys there's no way exercise could be the most important thing for could be the most important thing for could be the most important thing for brain health and again I'm saying this brain health and again I'm saying this brain health and again I'm saying this is a guy who loves exercise more than is a guy who loves exercise more than is a guy who loves exercise more than anybody but it just struck me as there's anybody but it just struck me as there's anybody but it just struck me as there's no way and again I think part of it was no way and again I think part of it was no way and again I think part of it was I was just thinking about it through the I was just thinking about it through the I was just thinking about it through the vascular lens and obviously you know I vascular lens and obviously you know I vascular lens and obviously you know I think better than I do that when you think better than I do that when you think better than I do that when you start to think about brain health you start to think about brain health you start to think about brain health you have to think about it through a have to think about it through a have to think about it through a vascular lens and metabolic lens growth vascular lens and metabolic lens growth vascular lens and metabolic lens growth factor lens I mean there were factor lens I mean there were factor lens I mean there were overlapping but distinct pathways that overlapping but distinct pathways that overlapping but distinct pathways that are going to influence brain health and are going to influence brain health and are going to influence brain health and so I was kind of humbled by that and now so I was kind of humbled by that and now so I was kind of humbled by that and now I guess in many ways I'm a little more

1:01I guess in many ways I'm a little more I guess in many ways I'm a little more adamant about it with my patients not adamant about it with my patients not adamant about it with my patients not that I wasn't you know adamant before that I wasn't you know adamant before that I wasn't you know adamant before but this is like boy if you're if you're but this is like boy if you're if you're but this is like boy if you're if you're not active every day like we got to not active every day like we got to not active every day like we got to change that I actually the the main change that I actually the the main change that I actually the the main reason I exercise is from my brain it's reason I exercise is from my brain it's reason I exercise is from my brain it's certainly just not only for you know certainly just not only for you know certainly just not only for you know preventing neurogenic disease and preventing neurogenic disease and preventing neurogenic disease and atrophy and all that but just because it atrophy and all that but just because it atrophy and all that but just because it affects my executive function it affects affects my executive function it affects affects my executive function it affects my anxiety levels it affects my ability my anxiety levels it affects my ability my anxiety levels it affects my ability to make decisions I absolutely if I have to make decisions I absolutely if I have to make decisions I absolutely if I have something that's bothering me you're something that's bothering me you're something that's bothering me you're giving me anxiety or have to make a giving me anxiety or have to make a giving me anxiety or have to make a really important decision going for a really important decision going for a really important decision going for a long run really helps me and there's long run really helps me and there's long run really helps me and there's been studies showing that it helps with been studies showing that it helps with been studies showing that it helps with executive function how long-term executive function how long-term executive function how long-term planning like aerobic exercise planning like aerobic exercise planning like aerobic exercise specifically you know and then high specifically you know and then high specifically you know and then high intensity interval training all that intensity interval training all that intensity interval training all that stuff they all they all do different stuff they all they all do different stuff they all they all do different things that's the thing we couldn't we things that's the thing we couldn't we things that's the thing we couldn't we couldn't tease this out of the couldn't tease this out of the couldn't tease this out of the literature which again probably is just literature which again probably is just literature which again probably is just a limitation of shitty human clinical a limitation of shitty human clinical a limitation of shitty human clinical trials but that's the second order trials but that's the second order trials but that's the second order question right which is if you're gonna question right which is if you're gonna question right which is if you're gonna take the Tim Ferriss approach which is take the Tim Ferriss approach which is take the Tim Ferriss approach which is what's the minimum effective dose what's the minimum effective dose what's the minimum effective dose because there are some people like maybe

1:02because there are some people like maybe because there are some people like maybe URI who I think just generally like URI who I think just generally like URI who I think just generally like exercise and also get these other exercise and also get these other exercise and also get these other benefits these endorphin benefits but benefits these endorphin benefits but benefits these endorphin benefits but there are some people who are like look there are some people who are like look there are some people who are like look what do I need to do like I'm gonna what do I need to do like I'm gonna what do I need to do like I'm gonna treat exercise like medicine treat exercise like medicine treat exercise like medicine and I think in that setting I'm still and I think in that setting I'm still and I think in that setting I'm still not clear so if you were that person not clear so if you were that person not clear so if you were that person would I say Rhonda as long as you are would I say Rhonda as long as you are would I say Rhonda as long as you are lifting weights one hour three times a lifting weights one hour three times a lifting weights one hour three times a week like if you can only give me three week like if you can only give me three week like if you can only give me three hours would that be how I'd want you to hours would that be how I'd want you to hours would that be how I'd want you to spend it or would I rather you be doing spend it or would I rather you be doing spend it or would I rather you be doing anaerobic aerobic type thing like I mean anaerobic aerobic type thing like I mean anaerobic aerobic type thing like I mean that's to me those are where these that's to me those are where these that's to me those are where these biomarkers start to become very biomarkers start to become very biomarkers start to become very important because we're not going to important because we're not going to important because we're not going to generate hard outcome studies with that generate hard outcome studies with that generate hard outcome studies with that level of control once you you know try level of control once you you know try level of control once you you know try to control that many variables and be to control that many variables and be to control that many variables and be that strict about it you're gonna very that strict about it you're gonna very that strict about it you're gonna very much lose a heart outcome prospectively much lose a heart outcome prospectively much lose a heart outcome prospectively but if we knew what to measure right and but if we knew what to measure right and but if we knew what to measure right and that's you know would we be measuring an that's you know would we be measuring an that's you know would we be measuring an integral of IGF for example so how much integral of IGF for example so how much integral of IGF for example so how much it rises how much it falls and then what it rises how much it falls and then what it rises how much it falls and then what that looks like over time but I guess that looks like over time but I guess that looks like over time but I guess that's the funny thing right like the that's the funny thing right like the that's the funny thing right like the more we learn the less we know yeah more we learn the less we know yeah more we learn the less we know yeah absolutely I think that we definitely

1:03absolutely I think that we definitely absolutely I think that we definitely don't know the answer to that question don't know the answer to that question don't know the answer to that question but I think there's a lot of data out but I think there's a lot of data out but I think there's a lot of data out there showing for example strength there showing for example strength there showing for example strength training you know there's benefits on training you know there's benefits on training you know there's benefits on the brain that's been shown published the brain that's been shown published the brain that's been shown published this benefits on preventing muscle this benefits on preventing muscle this benefits on preventing muscle atrophy there's benefits on preventing atrophy there's benefits on preventing atrophy there's benefits on preventing cancer incident like that's all been cancer incident like that's all been cancer incident like that's all been shown for strength training for aerobic shown for strength training for aerobic shown for strength training for aerobic and you know this high-intensity and you know this high-intensity and you know this high-intensity interval training is also also seems to interval training is also also seems to interval training is also also seems to be making its way as well like like be making its way as well like like be making its way as well like like there was a study that I that I found there was a study that I that I found there was a study that I that I found vo2 max this is you know the ability of vo2 max this is you know the ability of vo2 max this is you know the ability of your body to transport oxygen during your body to transport oxygen during your body to transport oxygen during exercise which also is an indicator of exercise which also is an indicator of exercise which also is an indicator of when you're not exercising and obviously when you're not exercising and obviously when you're not exercising and obviously transporting oxygen brain for example is transporting oxygen brain for example is transporting oxygen brain for example is extremely important vo2 max declines extremely important vo2 max declines extremely important vo2 max declines with age like 1 percent per year with age like 1 percent per year with age like 1 percent per year I forgot starting at what age but you I forgot starting at what age but you I forgot starting at what age but you know so 10 percent per decade so that's know so 10 percent per decade so that's know so 10 percent per decade so that's almost parallels the muscle master almost parallels the muscle master almost parallels the muscle master column does it does parallel exactly and column does it does parallel exactly and column does it does parallel exactly and there was a study showing that 24 there was a study showing that 24 there was a study showing that 24 sessions of high-intensity interval sessions of high-intensity interval sessions of high-intensity interval training where it was like a 45-minute training where it was like a 45-minute training where it was like a 45-minute sessions five minute warm-up 5-minute sessions five minute warm-up 5-minute sessions five minute warm-up 5-minute cooldown and then you know in between cooldown and then you know in between cooldown and then you know in between the max intervals which were like pretty

1:04the max intervals which were like pretty the max intervals which were like pretty long like a minute there was you know long like a minute there was you know long like a minute there was you know the 70% of max water anyway so 24 of the 70% of max water anyway so 24 of the 70% of max water anyway so 24 of those increased vo2 max by 12% so you're those increased vo2 max by 12% so you're those increased vo2 max by 12% so you're literally taking an entire decade of literally taking an entire decade of literally taking an entire decade of decline and like reversing it with the decline and like reversing it with the decline and like reversing it with the 24 yeah that's that's actually a good 24 yeah that's that's actually a good 24 yeah that's that's actually a good point when I was more active as it sort point when I was more active as it sort point when I was more active as it sort of competitive you know in cycling you of competitive you know in cycling you of competitive you know in cycling you we would get our vo2 max tested about we would get our vo2 max tested about we would get our vo2 max tested about twice a year Ryan Flaherty who we were twice a year Ryan Flaherty who we were twice a year Ryan Flaherty who we were talking about before the talking about before the talking about before the she's one of my close friends and you've she's one of my close friends and you've she's one of my close friends and you've got to know him as well I learned from got to know him as well I learned from got to know him as well I learned from Ryan that actually vo2 max is not the Ryan that actually vo2 max is not the Ryan that actually vo2 max is not the most important indicator as a runner or most important indicator as a runner or most important indicator as a runner or cyclist it's V vo2 Max or P vo2 max that cyclist it's V vo2 Max or P vo2 max that cyclist it's V vo2 Max or P vo2 max that matters in other words for a runner V matters in other words for a runner V matters in other words for a runner V vo2 Max is much more predictive of vo2 Max is much more predictive of vo2 Max is much more predictive of performance which is the velocity you performance which is the velocity you performance which is the velocity you carry at vo2 Max and for a cyclist it's carry at vo2 Max and for a cyclist it's carry at vo2 Max and for a cyclist it's P vo2 max which is the power output at P vo2 max which is the power output at P vo2 max which is the power output at vo2 max that said every time you go to vo2 max that said every time you go to vo2 max that said every time you go to test you wanted to test well so you know test you wanted to test well so you know test you wanted to test well so you know over time I learned how to game the over time I learned how to game the over time I learned how to game the system you know I want to make sure my system you know I want to make sure my system you know I want to make sure my vo2 max is in the 70s which again to put vo2 max is in the 70s which again to put vo2 max is in the 70s which again to put that in perspective like that's not at

1:05that in perspective like that's not at that in perspective like that's not at the level of a professional athlete or the level of a professional athlete or the level of a professional athlete or something like the guys that are winning something like the guys that are winning something like the guys that are winning the Tour de France are in the high 80s the Tour de France are in the high 80s the Tour de France are in the high 80s or low 90s in terms of milligrams per ml or low 90s in terms of milligrams per ml or low 90s in terms of milligrams per ml per kilogram but nevertheless just per kilogram but nevertheless just per kilogram but nevertheless just altering my training for three weeks altering my training for three weeks altering my training for three weeks before a vo2 max test and dropping my before a vo2 max test and dropping my before a vo2 max test and dropping my weight so if I shed two kilograms and weight so if I shed two kilograms and weight so if I shed two kilograms and did those types of intervals I actually did those types of intervals I actually did those types of intervals I actually had it down to a science where there was had it down to a science where there was had it down to a science where there was a workout I would do you know in Carmel a workout I would do you know in Carmel a workout I would do you know in Carmel Valley you've got the 56 that goes out Valley you've got the 56 that goes out Valley you've got the 56 that goes out and it's got a bike path next to it and it's got a bike path next to it and it's got a bike path next to it there's a section of that bike path that there's a section of that bike path that there's a section of that bike path that is 1.6 miles long and it goes up at is 1.6 miles long and it goes up at is 1.6 miles long and it goes up at about 4% and just doing repeat intervals about 4% and just doing repeat intervals about 4% and just doing repeat intervals of that which takes about four minutes of that which takes about four minutes of that which takes about four minutes all out to go one direction and then all out to go one direction and then all out to go one direction and then about six minutes to cruise back four of about six minutes to cruise back four of about six minutes to cruise back four of those that was it twice a week for like those that was it twice a week for like those that was it twice a week for like three weeks and your vo2 max exploded three weeks and your vo2 max exploded three weeks and your vo2 max exploded now of course the question is is that now of course the question is is that now of course the question is is that like you know cramming for the test like you know cramming for the test like you know cramming for the test getting the result but not necessarily getting the result but not necessarily getting the result but not necessarily like you have to keep doing that to get like you have to keep doing that to get like you have to keep doing that to get the decade-long benefit I don't know the

1:06the decade-long benefit I don't know the the decade-long benefit I don't know the answer but I agree that like if you can answer but I agree that like if you can answer but I agree that like if you can maintain muscle mass and you can maintain muscle mass and you can maintain muscle mass and you can maintain peak aerobic performance it's maintain peak aerobic performance it's maintain peak aerobic performance it's not it doesn't even matter at that point not it doesn't even matter at that point not it doesn't even matter at that point if you're living longer if you're living longer if you're living longer you're clearly living better right like you're clearly living better right like you're clearly living better right like if you if you don't budge anything on if you if you don't budge anything on if you if you don't budge anything on maximum lifespan maximum lifespan maximum lifespan you've dramatically improved median you've dramatically improved median you've dramatically improved median lifespan right and that's a you know I lifespan right and that's a you know I lifespan right and that's a you know I think for most people that's what think for most people that's what think for most people that's what matters it is yeah I'm for me it is I matters it is yeah I'm for me it is I matters it is yeah I'm for me it is I mean I what's the what's the maximum mean I what's the what's the maximum mean I what's the what's the maximum lifespan that like a humans live 120 124 lifespan that like a humans live 120 124 lifespan that like a humans live 120 124 or something 124 1.10 124 something like or something 124 1.10 124 something like or something 124 1.10 124 something like that yeah living beyond that I mean that yeah living beyond that I mean that yeah living beyond that I mean that's I think the goal is really to that's I think the goal is really to that's I think the goal is really to for me I think that's a lot more for me I think that's a lot more for me I think that's a lot more achievable is increasing my my median achievable is increasing my my median achievable is increasing my my median health span of my my health span you health span of my my health span you health span of my my health span you know so so basically preventing staving know so so basically preventing staving know so so basically preventing staving off cardiovascular disease cancer also off cardiovascular disease cancer also off cardiovascular disease cancer also much disease those sorts of things so much disease those sorts of things so much disease those sorts of things so that I'm so that I'm living healthier that I'm so that I'm living healthier that I'm so that I'm living healthier and also you know a little bit longer and also you know a little bit longer and also you know a little bit longer but obviously not one hundred and twenty but obviously not one hundred and twenty but obviously not one hundred and twenty five or six yeah I don't really

1:07five or six yeah I don't really five or six yeah I don't really subscribe to the theory that we're gonna subscribe to the theory that we're gonna subscribe to the theory that we're gonna meet some take off point where you know meet some take off point where you know meet some take off point where you know there's immortality I'm really not there's immortality I'm really not there's immortality I'm really not convinced that that's that that's sort convinced that that's that that's sort convinced that that's that that's sort of biologically possible and I don't of biologically possible and I don't of biologically possible and I don't suspect they'll be alive at a time when suspect they'll be alive at a time when suspect they'll be alive at a time when it would ever come to fruition I don't it would ever come to fruition I don't it would ever come to fruition I don't remember the journal it was a paper that remember the journal it was a paper that remember the journal it was a paper that came out of Japan and the study looked came out of Japan and the study looked came out of Japan and the study looked at a variety of people of different ages at a variety of people of different ages at a variety of people of different ages so elderly population centenarians which so elderly population centenarians which so elderly population centenarians which are 100 semi super centenarians richer are 100 semi super centenarians richer are 100 semi super centenarians richer between a hundred and hundred and five between a hundred and hundred and five between a hundred and hundred and five and then super centenarians which are and then super centenarians which are and then super centenarians which are 105 plus and looked at a variety of 105 plus and looked at a variety of 105 plus and looked at a variety of biomarkers for health and aging so biomarkers for health and aging so biomarkers for health and aging so telomere senescence kidney function telomere senescence kidney function telomere senescence kidney function glycated hemoglobin lipid the whole glycated hemoglobin lipid the whole glycated hemoglobin lipid the whole lipid panel triglycerides kidney lipid panel triglycerides kidney lipid panel triglycerides kidney function him out of Isis like all that function him out of Isis like all that function him out of Isis like all that stuff was looked at inflammatory stuff was looked at inflammatory stuff was looked at inflammatory biomarkers and what was found is that biomarkers and what was found is that biomarkers and what was found is that aside from age what was predictive of aside from age what was predictive of aside from age what was predictive of being able to basically stay alive was being able to basically stay alive was being able to basically stay alive was low inflammation like more than

1:08low inflammation like more than low inflammation like more than hematopoiesis more than glycated hematopoiesis more than glycated hematopoiesis more than glycated hemoglobin blood glucose levels lipid hemoglobin blood glucose levels lipid hemoglobin blood glucose levels lipid all that stuff it was basically the all that stuff it was basically the all that stuff it was basically the ability suppress inflammation like that ability suppress inflammation like that ability suppress inflammation like that was predictive of cognitive function and was predictive of cognitive function and was predictive of cognitive function and also basically staying alive do you also basically staying alive do you also basically staying alive do you remember what they looked at were they remember what they looked at were they remember what they looked at were they looking at c-reactive protein and things looking at c-reactive protein and things looking at c-reactive protein and things like that like that like that general markers no look at her Lukens general markers no look at her Lukens general markers no look at her Lukens and stuff TNF they looked at a whole and stuff TNF they looked at a whole and stuff TNF they looked at a whole panel of and also some immune cells that panel of and also some immune cells that panel of and also some immune cells that are indicative of inflammation so there are indicative of inflammation so there are indicative of inflammation so there was a whole panel of biomarkers that was a whole panel of biomarkers that was a whole panel of biomarkers that were looked at for inflammation HPV were looked at for inflammation HPV were looked at for inflammation HPV tighter or something was also looked at tighter or something was also looked at tighter or something was also looked at so the the interesting thing about that so the the interesting thing about that so the the interesting thing about that study was that the inflammation was so study was that the inflammation was so study was that the inflammation was so key for each age group right like even key for each age group right like even key for each age group right like even more than all this other stuff like that more than all this other stuff like that more than all this other stuff like that I've thought about like senescence and I've thought about like senescence and I've thought about like senescence and telomeres and low blood glucose levels telomeres and low blood glucose levels telomeres and low blood glucose levels and all that stuff and so I really and and all that stuff and so I really and and all that stuff and so I really and and if you look at some of the rodent and if you look at some of the rodent and if you look at some of the rodent literature literature literature for example I remember the study where for example I remember the study where for example I remember the study where NF kappa-b which is classically thought NF kappa-b which is classically thought NF kappa-b which is classically thought about as an inflammatory mediators which about as an inflammatory mediators which about as an inflammatory mediators which it is it also has an anti inflammatory

1:09it is it also has an anti inflammatory it is it also has an anti inflammatory component to it and if you get rid of component to it and if you get rid of component to it and if you get rid of the anti inflammatory component rodents the anti inflammatory component rodents the anti inflammatory component rodents will have this sort of low level of will have this sort of low level of will have this sort of low level of chronic inflammation because every time chronic inflammation because every time chronic inflammation because every time it's activated there's not that it's activated there's not that it's activated there's not that infantile inflammatory part that's kind infantile inflammatory part that's kind infantile inflammatory part that's kind of keep it in a check and so there's of keep it in a check and so there's of keep it in a check and so there's kind of like this like lower chronic kind of like this like lower chronic kind of like this like lower chronic inflammation that's happening and those inflammation that's happening and those inflammation that's happening and those animals live like 30 percent less so animals live like 30 percent less so animals live like 30 percent less so that so their lifespan is cut short by that so their lifespan is cut short by that so their lifespan is cut short by about 30 percent so that's kind of about 30 percent so that's kind of about 30 percent so that's kind of interesting right that just just getting interesting right that just just getting interesting right that just just getting rid of that little anti inflammatory rid of that little anti inflammatory rid of that little anti inflammatory component of this one major regulator of component of this one major regulator of component of this one major regulator of immune system hasn't a profound effect immune system hasn't a profound effect immune system hasn't a profound effect on lifespan and then of course if you on lifespan and then of course if you on lifespan and then of course if you look at snips and stuff of course so you look at snips and stuff of course so you look at snips and stuff of course so you can always find you know well scenarios can always find you know well scenarios can always find you know well scenarios have a higher percentage of 10 and have a higher percentage of 10 and have a higher percentage of 10 and anti-inflammatory anyways you know so anti-inflammatory anyways you know so anti-inflammatory anyways you know so the inflammation it's an interesting the inflammation it's an interesting the inflammation it's an interesting finding that keep suppressing finding that keep suppressing finding that keep suppressing inflammation seems to be important for inflammation seems to be important for inflammation seems to be important for at least you know according to that at least you know according to that at least you know according to that study for making it to every part of you study for making it to every part of you study for making it to every part of you know I don't know what you would call it know I don't know what you would call it know I don't know what you would call it every basically progressing to the every basically progressing to the every basically progressing to the maximum level that maximum lifespan maximum level that maximum lifespan maximum level that maximum lifespan level that humans can possibly live well

1:10level that humans can possibly live well level that humans can possibly live well there was a clinical trial published there was a clinical trial published there was a clinical trial published either earlier this year or last year either earlier this year or last year either earlier this year or last year that looked at an il-1 antagonist and so that looked at an il-1 antagonist and so that looked at an il-1 antagonist and so this was a study that took people and this was a study that took people and this was a study that took people and made no change in their lipid metabolism made no change in their lipid metabolism made no change in their lipid metabolism lipid biomarker you know this was they lipid biomarker you know this was they lipid biomarker you know this was they they didn't do anything to the patients they didn't do anything to the patients they didn't do anything to the patients as far as differentiating the groups by as far as differentiating the groups by as far as differentiating the groups by traditional biomarkers of cardiovascular traditional biomarkers of cardiovascular traditional biomarkers of cardiovascular disease but one group was given a disease but one group was given a disease but one group was given a placebo one group was given an il-1 placebo one group was given an il-1 placebo one group was given an il-1 antagonist and the question was could antagonist and the question was could antagonist and the question was could that impact cardiovascular mortality and that impact cardiovascular mortality and that impact cardiovascular mortality and we've long talked about how we've long talked about how we've long talked about how cardiovascular disease is sort of this cardiovascular disease is sort of this cardiovascular disease is sort of this trifecta of lipoproteins inflammation trifecta of lipoproteins inflammation trifecta of lipoproteins inflammation and endothelial dysfunction but this was and endothelial dysfunction but this was and endothelial dysfunction but this was in many ways the most elegant first test in many ways the most elegant first test in many ways the most elegant first test of that in humans using heart outcome so of that in humans using heart outcome so of that in humans using heart outcome so major adverse cardiac event stroke MI major adverse cardiac event stroke MI major adverse cardiac event stroke MI death the hypothesis was found to be death the hypothesis was found to be death the hypothesis was found to be correct so the patients getting the il-1 correct so the patients getting the il-1 correct so the patients getting the il-1 antagonist despite having no difference antagonist despite having no difference antagonist despite having no difference in lipids or any other biomarker had an in lipids or any other biomarker had an in lipids or any other biomarker had an improved outcome with respect to improved outcome with respect to improved outcome with respect to cardiovascular health about a month ago

1:11cardiovascular health about a month ago cardiovascular health about a month ago another trial that another trial that another trial that using low dose of methotrexate which is using low dose of methotrexate which is using low dose of methotrexate which is an immune suppressant was halted early an immune suppressant was halted early an immune suppressant was halted early and the results will not be announced and the results will not be announced and the results will not be announced until this fall but if you read kind of until this fall but if you read kind of until this fall but if you read kind of the fine print it does not appear it was the fine print it does not appear it was the fine print it does not appear it was halted for a bad reason meaning it might halted for a bad reason meaning it might halted for a bad reason meaning it might have been halted actually for basically have been halted actually for basically have been halted actually for basically early efficacy which presumably would early efficacy which presumably would early efficacy which presumably would have been in the group getting the have been in the group getting the have been in the group getting the methotrexate so again we won't know that methotrexate so again we won't know that methotrexate so again we won't know that until the meeting in October I think until the meeting in October I think until the meeting in October I think when this will be presented but if that when this will be presented but if that when this will be presented but if that turns out to be the case that's pretty turns out to be the case that's pretty turns out to be the case that's pretty interesting because now you've taken interesting because now you've taken interesting because now you've taken something that we practically have great something that we practically have great something that we practically have great examples of like the one you've given examples of like the one you've given examples of like the one you've given and now potentially there's ways to and now potentially there's ways to and now potentially there's ways to think about using it so taking a step think about using it so taking a step think about using it so taking a step back from all of this stuff like you back from all of this stuff like you back from all of this stuff like you know of course I think about it at the know of course I think about it at the know of course I think about it at the level of like I'm just a mechanic right level of like I'm just a mechanic right level of like I'm just a mechanic right it's like how can you manipulate these it's like how can you manipulate these it's like how can you manipulate these things in people like cycling you know things in people like cycling you know things in people like cycling you know using nutrition and fasting to cycle IGF using nutrition and fasting to cycle IGF using nutrition and fasting to cycle IGF maybe even using an exaggerated growth maybe even using an exaggerated growth maybe even using an exaggerated growth hormone for all we know maybe you know hormone for all we know maybe you know hormone for all we know maybe you know I've always been quite skeptical of

1:12I've always been quite skeptical of I've always been quite skeptical of growth hormones use in in the field of growth hormones use in in the field of growth hormones use in in the field of longevity but maybe periods of longevity but maybe periods of longevity but maybe periods of oscillating rapamycin and growth hormone oscillating rapamycin and growth hormone oscillating rapamycin and growth hormone and fasting where you're cycling high and fasting where you're cycling high and fasting where you're cycling high periods of anabolic high periods of periods of anabolic high periods of periods of anabolic high periods of catabolic phase maybe there's something catabolic phase maybe there's something catabolic phase maybe there's something to it and then cycling agents like to it and then cycling agents like to it and then cycling agents like methotrexate and all these things so I methotrexate and all these things so I methotrexate and all these things so I don't know that's my hope is like in ten don't know that's my hope is like in ten don't know that's my hope is like in ten years we've got a complete personalised years we've got a complete personalised years we've got a complete personalised toolkit for how everybody could you know toolkit for how everybody could you know toolkit for how everybody could you know figure out exactly what drugs or figure out exactly what drugs or figure out exactly what drugs or hormones or nutrients to take and cycle hormones or nutrients to take and cycle hormones or nutrients to take and cycle and how to do it and then of course the and how to do it and then of course the and how to do it and then of course the key is you have to be able to measure key is you have to be able to measure key is you have to be able to measure stuff you know the the with the stuff you know the the with the stuff you know the the with the cardiovascular rated mortality the cardiovascular rated mortality the cardiovascular rated mortality the desana is something that is interesting desana is something that is interesting desana is something that is interesting to me for that for that reason because to me for that for that reason because to me for that for that reason because of the profound effects that it has of the profound effects that it has of the profound effects that it has specifically on lowering cardiovascular specifically on lowering cardiovascular specifically on lowering cardiovascular related mortality and of course just related mortality and of course just related mortality and of course just some clinical trials showing that you some clinical trials showing that you some clinical trials showing that you know there's a variety of other know there's a variety of other know there's a variety of other biomarkers and magnet potential biomarkers and magnet potential biomarkers and magnet potential mechanisms by that which that's mechanisms by that which that's mechanisms by that which that's happening but if you look at some of the happening but if you look at some of the happening but if you look at some of the data and by dr. yar allow cannon out of data and by dr. yar allow cannon out of data and by dr. yar allow cannon out of Finland if you look at some of the the

1:13Finland if you look at some of the the Finland if you look at some of the the observational studies you know where observational studies you know where observational studies you know where there's like a couple thousand men that there's like a couple thousand men that there's like a couple thousand men that we're doing it saunas so ubiquitous in we're doing it saunas so ubiquitous in we're doing it saunas so ubiquitous in Finland but if you look at for example Finland but if you look at for example Finland but if you look at for example men that are using it two to three times men that are using it two to three times men that are using it two to three times a week versus four to seven times a week a week versus four to seven times a week a week versus four to seven times a week versus once a week and you look at for versus once a week and you look at for versus once a week and you look at for example cardiovascular mortality two to example cardiovascular mortality two to example cardiovascular mortality two to three times a week it's lowered by like three times a week it's lowered by like three times a week it's lowered by like 20 20 20 % but when you jump to 47 times a week % but when you jump to 47 times a week % but when you jump to 47 times a week it all cause mortality goes to 40 all it all cause mortality goes to 40 all it all cause mortality goes to 40 all clothes mentality is also lowered clothes mentality is also lowered clothes mentality is also lowered dementia and Alzheimer's disease again dementia and Alzheimer's disease again dementia and Alzheimer's disease again like like 20% lowered if you're doing 2 like like 20% lowered if you're doing 2 like like 20% lowered if you're doing 2 to 3 I'm so glad you brought this up to 3 I'm so glad you brought this up to 3 I'm so glad you brought this up because I almost forgot and I wanted to because I almost forgot and I wanted to because I almost forgot and I wanted to talk about this this is one of those talk about this this is one of those talk about this this is one of those things where I think three years ago I things where I think three years ago I things where I think three years ago I was completely dismissive of this stuff was completely dismissive of this stuff was completely dismissive of this stuff which is to say I still love going into which is to say I still love going into which is to say I still love going into asana because the one thing that I felt asana because the one thing that I felt asana because the one thing that I felt sana really mattered for was sleep and sana really mattered for was sleep and sana really mattered for was sleep and not for the growth hormone level but not for the growth hormone level but not for the growth hormone level but because I think there's pretty good data because I think there's pretty good data because I think there's pretty good data that a great way to sleep is to create a that a great way to sleep is to create a that a great way to sleep is to create a high gradient of temperature so the high gradient of temperature so the high gradient of temperature so the faster the more negative the derivative faster the more negative the derivative faster the more negative the derivative of temperature DT by DT when you sleep

1:14of temperature DT by DT when you sleep of temperature DT by DT when you sleep the faster you'll go to sleep in the the faster you'll go to sleep in the the faster you'll go to sleep in the longer you'll stay asleep so a sauna longer you'll stay asleep so a sauna longer you'll stay asleep so a sauna before bed if you could jump in the before bed if you could jump in the before bed if you could jump in the sauna then take a cold shower then jump sauna then take a cold shower then jump sauna then take a cold shower then jump into a cold bed you're gonna sleep like into a cold bed you're gonna sleep like into a cold bed you're gonna sleep like a baby I've done it it's absolutely just a baby I've done it it's absolutely just a baby I've done it it's absolutely just remarkable yeah so I always accepted remarkable yeah so I always accepted remarkable yeah so I always accepted that but I looked at all of that that but I looked at all of that that but I looked at all of that epidemiologic stuff and I was like the epidemiologic stuff and I was like the epidemiologic stuff and I was like the healthy user bias here is through the healthy user bias here is through the healthy user bias here is through the roof like I came up with a hundred roof like I came up with a hundred roof like I came up with a hundred reasons why I just couldn't believe it reasons why I just couldn't believe it reasons why I just couldn't believe it including saunas are painful so if you including saunas are painful so if you including saunas are painful so if you are fit enough to sit in a sauna seven are fit enough to sit in a sauna seven are fit enough to sit in a sauna seven days a week versus the guy who could days a week versus the guy who could days a week versus the guy who could only sit in it one day a week like how only sit in it one day a week like how only sit in it one day a week like how do I know that that's not driving it now do I know that that's not driving it now do I know that that's not driving it now since that time I've become a lot more since that time I've become a lot more since that time I've become a lot more interested because now the mechanisms interested because now the mechanisms interested because now the mechanisms are starting to become more well are starting to become more well are starting to become more well understood and so I'd love to have you understood and so I'd love to have you understood and so I'd love to have you talk a little bit more about this talk a little bit more about this talk a little bit more about this because I know you've talked about this because I know you've talked about this because I know you've talked about this a lot on you on your podcast but in many a lot on you on your podcast but in many a lot on you on your podcast but in many ways your pursuit of this has become one ways your pursuit of this has become one ways your pursuit of this has become one of the more convincing arguments in in of the more convincing arguments in in of the more convincing arguments in in my thinking on the actual health

1:15my thinking on the actual health my thinking on the actual health benefits of this independent of the benefits of this independent of the benefits of this independent of the healthy healthy user benefits of this healthy healthy user benefits of this healthy healthy user benefits of this you know the healthy user benefits it's you know the healthy user benefits it's you know the healthy user benefits it's of course and with with the uri's work of course and with with the uri's work of course and with with the uri's work he's tried to correct for all that he's tried to correct for all that he's tried to correct for all that physical activity then he's done physical activity then he's done physical activity then he's done everything like looking at lipid blood everything like looking at lipid blood everything like looking at lipid blood cholesterol numbers LDL number like just cholesterol numbers LDL number like just cholesterol numbers LDL number like just like really you know try to try his best like really you know try to try his best like really you know try to try his best to kind of correct for that healthy user to kind of correct for that healthy user to kind of correct for that healthy user bias and of course there's a dose bias and of course there's a dose bias and of course there's a dose dependence which always makes it more dependence which always makes it more dependence which always makes it more convincing but he's then since published convincing but he's then since published convincing but he's then since published some some clinical trials where he's some some clinical trials where he's some some clinical trials where he's looked at for example the arterial looked at for example the arterial looked at for example the arterial comply comply comply and of course blood pressures that's one and of course blood pressures that's one and of course blood pressures that's one of the main things that's effective is of the main things that's effective is of the main things that's effective is blood pressure but also just like the blood pressure but also just like the blood pressure but also just like the ability of the arteries to like expand ability of the arteries to like expand ability of the arteries to like expand and contract in response to pressure and contract in response to pressure and contract in response to pressure like that's improved which is really like that's improved which is really like that's improved which is really important so I think that you know important so I think that you know important so I think that you know obviously the sauna the heat itself does obviously the sauna the heat itself does obviously the sauna the heat itself does does affect you know blood flow plasma does affect you know blood flow plasma does affect you know blood flow plasma volume all that stuff is changed so so I volume all that stuff is changed so so I volume all that stuff is changed so so I think that the cardiovascular aspects think that the cardiovascular aspects think that the cardiovascular aspects and Yardies trying to really kind of and Yardies trying to really kind of and Yardies trying to really kind of tease apart more mechanisms because he's tease apart more mechanisms because he's tease apart more mechanisms because he's a he's an MD ph.d he's a cardiologist by

1:16a he's an MD ph.d he's a cardiologist by a he's an MD ph.d he's a cardiologist by training but he's also got a PhD so he's training but he's also got a PhD so he's training but he's also got a PhD so he's he's trying you know really hard to kind he's trying you know really hard to kind he's trying you know really hard to kind of understand exactly what's going on of understand exactly what's going on of understand exactly what's going on but I do think that it really seems but I do think that it really seems but I do think that it really seems convincing it's really convincing convincing it's really convincing convincing it's really convincing with the cardiovascular related with the cardiovascular related with the cardiovascular related mortality specifically it's very robust mortality specifically it's very robust mortality specifically it's very robust personally it's kind of interesting to personally it's kind of interesting to personally it's kind of interesting to think about how much of you know think about how much of you know think about how much of you know exercise also elevates your core body exercise also elevates your core body exercise also elevates your core body temperature I mean there's this overlap temperature I mean there's this overlap temperature I mean there's this overlap there you know and when I sit in a sauna there you know and when I sit in a sauna there you know and when I sit in a sauna my heart rate starts to elevate like I'm my heart rate starts to elevate like I'm my heart rate starts to elevate like I'm doing cardiovascular and that's that's doing cardiovascular and that's that's doing cardiovascular and that's that's what happens like I'm doing what happens like I'm doing what happens like I'm doing cardiovascular exercises start to sweat cardiovascular exercises start to sweat cardiovascular exercises start to sweat I mean a lot of the same adaptations I mean a lot of the same adaptations I mean a lot of the same adaptations that happen with exercise are happening that happen with exercise are happening that happen with exercise are happening when you're you're sitting in a hot when you're you're sitting in a hot when you're you're sitting in a hot sauna and in even a hot bath like more sauna and in even a hot bath like more sauna and in even a hot bath like more recently another study came out trying recently another study came out trying recently another study came out trying hot bath effect it had a positive effect hot bath effect it had a positive effect hot bath effect it had a positive effect on a variety of cardiovascular related on a variety of cardiovascular related on a variety of cardiovascular related markers as well which again if but you markers as well which again if but you markers as well which again if but you have to sit in it long enough you know have to sit in it long enough you know have to sit in it long enough you know to experience some of those effects or to experience some of those effects or to experience some of those effects or the elevation of the heart rate and all the elevation of the heart rate and all the elevation of the heart rate and all that stuff but there's also really that stuff but there's also really that stuff but there's also really profound effect on the immune system profound effect on the immune system profound effect on the immune system like part of the benefit of exercise is like part of the benefit of exercise is

1:17like part of the benefit of exercise is that it is an acute oxidative stress that it is an acute oxidative stress that it is an acute oxidative stress burst an acute inflammatory burst burst an acute inflammatory burst burst an acute inflammatory burst you know there's then a response to that you know there's then a response to that you know there's then a response to that and the net response is a positive and the net response is a positive and the net response is a positive anti-inflammatory and antioxidant anti-inflammatory and antioxidant anti-inflammatory and antioxidant response but the inflammatory and response but the inflammatory and response but the inflammatory and oxidant response is required to get that oxidant response is required to get that oxidant response is required to get that and something similar is happening with and something similar is happening with and something similar is happening with with the sauna as well recently there with the sauna as well recently there with the sauna as well recently there was a study looking by dr. Charles Rosen was a study looking by dr. Charles Rosen was a study looking by dr. Charles Rosen he had made this like fancy contraption he had made this like fancy contraption he had made this like fancy contraption where he elevated core body temperature where he elevated core body temperature where he elevated core body temperature and he had a sham control so actually and he had a sham control so actually and he had a sham control so actually people the Sham control also made people people the Sham control also made people people the Sham control also made people a little bit hot and they thought they a little bit hot and they thought they a little bit hot and they thought they were actually getting the treatment but were actually getting the treatment but were actually getting the treatment but it had a very strong antidepressant how it had a very strong antidepressant how it had a very strong antidepressant how do they do that he explains it on my do they do that he explains it on my do they do that he explains it on my podcast so you can go to the transcript podcast so you can go to the transcript podcast so you can go to the transcript you can just that strikes me as one of you can just that strikes me as one of you can just that strikes me as one of the the the few things you can't placebo he they did few things you can't placebo he they did few things you can't placebo he they did some crafty thing which I not going to some crafty thing which I not going to some crafty thing which I not going to try to explain but I will absolutely try to explain but I will absolutely try to explain but I will absolutely botch it they did it and and they had a botch it they did it and and they had a botch it they did it and and they had a sham control and in fact about he said sham control and in fact about he said sham control and in fact about he said about seventy percent of the people that about seventy percent of the people that about seventy percent of the people that had the sham control thought they had had the sham control thought they had had the sham control thought they had the actual treatment so it were like

1:18the actual treatment so it were like the actual treatment so it were like there was definitely a they were trying there was definitely a they were trying there was definitely a they were trying to control for the placebo effect what's to control for the placebo effect what's to control for the placebo effect what's interesting is I even the reason I got interesting is I even the reason I got interesting is I even the reason I got into the sauna was the effects that I into the sauna was the effects that I into the sauna was the effects that I felt on my mood when I was in graduate felt on my mood when I was in graduate felt on my mood when I was in graduate school like I lived across the street school like I lived across the street school like I lived across the street from YMCA and so I started using this on from YMCA and so I started using this on from YMCA and so I started using this on and it was like very black-and-white and it was like very black-and-white and it was like very black-and-white like I was like wow this is amazing like like I was like wow this is amazing like like I was like wow this is amazing like I can handle all this was a wet sauna I can handle all this was a wet sauna I can handle all this was a wet sauna dry sauce this was this is a dry sauna dry sauce this was this is a dry sauna dry sauce this was this is a dry sauna do we have a sense of dry sauna versus do we have a sense of dry sauna versus do we have a sense of dry sauna versus IR versus all the different yeah so I IR versus all the different yeah so I IR versus all the different yeah so I mean the infrared saunas are like they mean the infrared saunas are like they mean the infrared saunas are like they only get to like about 140 degrees only get to like about 140 degrees only get to like about 140 degrees Fahrenheit I mean it's not very hot if Fahrenheit I mean it's not very hot if Fahrenheit I mean it's not very hot if you look at Yowies work like their you look at Yowies work like their you look at Yowies work like their saunas that they're using in Finland saunas that they're using in Finland saunas that they're using in Finland they do they have a lot of what they they do they have a lot of what they they do they have a lot of what they call low Lu or something which is like call low Lu or something which is like call low Lu or something which is like they throw the water on makes the humid they throw the water on makes the humid they throw the water on makes the humid which makes it really hot I've been to which makes it really hot I've been to which makes it really hot I've been to Finland and try them try the their Finland and try them try the their Finland and try them try the their saunas before but basically the saunas before but basically the saunas before but basically the temperature gets to around 170 between temperature gets to around 170 between temperature gets to around 170 between 175 and 79 degrees Fahrenheit and most 175 and 79 degrees Fahrenheit and most 175 and 79 degrees Fahrenheit and most of the men in these studies are doing of the men in these studies are doing of the men in these studies are doing about 20 minutes to get the maximum about 20 minutes to get the maximum about 20 minutes to get the maximum benefits eleven minutes had some

1:19benefits eleven minutes had some benefits eleven minutes had some benefits sitting in 11 minutes but there benefits sitting in 11 minutes but there benefits sitting in 11 minutes but there was a stronger effect they say it took was a stronger effect they say it took was a stronger effect they say it took 20 minutes so if you're in a infrared 20 minutes so if you're in a infrared 20 minutes so if you're in a infrared sauna that only gets to 140 degrees sauna that only gets to 140 degrees sauna that only gets to 140 degrees Fahrenheit you probably would have to Fahrenheit you probably would have to Fahrenheit you probably would have to stay on a much longer to get the same stay on a much longer to get the same stay on a much longer to get the same benefit I see so the IR doesn't doesn't benefit I see so the IR doesn't doesn't benefit I see so the IR doesn't doesn't get deeper penetration thereby get deeper penetration thereby get deeper penetration thereby alleviating the need to stay in at a alleviating the need to stay in at a alleviating the need to stay in at a higher temperature it doesn't I mean higher temperature it doesn't I mean higher temperature it doesn't I mean sometimes people talk about there's a sometimes people talk about there's a sometimes people talk about there's a lot of marketing involved strip that out lot of marketing involved strip that out lot of marketing involved strip that out though if you strip that out the the though if you strip that out the the though if you strip that out the the infrared saunas do affect the sweating infrared saunas do affect the sweating infrared saunas do affect the sweating mechanisms like something to do with the mechanisms like something to do with the mechanisms like something to do with the penetration there you do sweat which is penetration there you do sweat which is penetration there you do sweat which is great because you actually do excrete great because you actually do excrete great because you actually do excrete things like BPA and phthalates and things like BPA and phthalates and things like BPA and phthalates and mercury and heavy metals and things like mercury and heavy metals and things like mercury and heavy metals and things like that from sweat so that is that's what a that from sweat so that is that's what a that from sweat so that is that's what a lot of those mark the straight-up dry lot of those mark the straight-up dry lot of those mark the straight-up dry sauna to 170 degrees spend three or four sauna to 170 degrees spend three or four sauna to 170 degrees spend three or four nights a week in that my favorite yeah nights a week in that my favorite yeah nights a week in that my favorite yeah that's personally I I would much prefer that's personally I I would much prefer that's personally I I would much prefer sitting in a regular dry sauna or even a sitting in a regular dry sauna or even a sitting in a regular dry sauna or even a sauna that you can throw one control sauna that you can throw one control sauna that you can throw one control just not infrared sauna yeah so that so just not infrared sauna yeah so that so just not infrared sauna yeah so that so that would be you know the obviously

1:20that would be you know the obviously that would be you know the obviously they're the the fire hazard risk is more they're the the fire hazard risk is more they're the the fire hazard risk is more when you're having a sauna like that when you're having a sauna like that when you're having a sauna like that versus just an infrared and the infra versus just an infrared and the infra versus just an infrared and the infra red ones are I think cheaper as well so red ones are I think cheaper as well so red ones are I think cheaper as well so it's certainly more convenient to have it's certainly more convenient to have it's certainly more convenient to have an infrared sauna but personally I an infrared sauna but personally I an infrared sauna but personally I prefer for the other like the barrel prefer for the other like the barrel prefer for the other like the barrel saunas are really nice there's a also an saunas are really nice there's a also an saunas are really nice there's a also an effect on the immune system I was effect on the immune system I was effect on the immune system I was mentioning Charles race on he met he mentioning Charles race on he met he mentioning Charles race on he met he measured il-6 which is also it's part of measured il-6 which is also it's part of measured il-6 which is also it's part of the Janus cytokine because it does like the Janus cytokine because it does like the Janus cytokine because it does like it's it's got like multiple pleiotropic it's it's got like multiple pleiotropic it's it's got like multiple pleiotropic effects and it's it's acutely released effects and it's it's acutely released effects and it's it's acutely released upon exercise as well and it has it's upon exercise as well and it has it's upon exercise as well and it has it's very important for a you know an anti very important for a you know an anti very important for a you know an anti inflammatory response releasing Myo inflammatory response releasing Myo inflammatory response releasing Myo kinds and all these things and muscles kinds and all these things and muscles kinds and all these things and muscles so it has it's important for insulin so it has it's important for insulin so it has it's important for insulin sensitivity a lot of the insulin sensitivity a lot of the insulin sensitivity a lot of the insulin sensitivity effects exercise has so so sensitivity effects exercise has so so sensitivity effects exercise has so so the sauna does the same thing that the the sauna does the same thing that the the sauna does the same thing that the exercise does where there's just a rapid exercise does where there's just a rapid exercise does where there's just a rapid io6 io6 io6 release at least according to Charles release at least according to Charles release at least according to Charles Mason's data and he said that actually Mason's data and he said that actually Mason's data and he said that actually correlates with things you know I've correlates with things you know I've correlates with things you know I've never looked at I wear a continuous never looked at I wear a continuous never looked at I wear a continuous glucose monitor a lot but I've never glucose monitor a lot but I've never glucose monitor a lot but I've never really paid much attention to it in the really paid much attention to it in the really paid much attention to it in the sauna and I don't have a sauna but I'm

1:21sauna and I don't have a sauna but I'm sauna and I don't have a sauna but I'm gonna be this weekend at a friend's gonna be this weekend at a friend's gonna be this weekend at a friend's place who has a barrel sauna and so I'll place who has a barrel sauna and so I'll place who has a barrel sauna and so I'll make sure that I document what my make sure that I document what my make sure that I document what my glucose levels doing because you would glucose levels doing because you would glucose levels doing because you would think transiently would go up right think transiently would go up right think transiently would go up right right but I know that at least there right but I know that at least there right but I know that at least there isn't one animal study where the heat isn't one animal study where the heat isn't one animal study where the heat stress quote-unquote animal sauna it stress quote-unquote animal sauna it stress quote-unquote animal sauna it actually increases glucose transporters actually increases glucose transporters actually increases glucose transporters and a type-2 diabetic model that and a type-2 diabetic model that and a type-2 diabetic model that actually improved insulin sensitivity actually improved insulin sensitivity actually improved insulin sensitivity and lowered blood glucose because the and lowered blood glucose because the and lowered blood glucose because the glucose was now being taken up into glucose was now being taken up into glucose was now being taken up into muscle butter so I wonder you know how muscle butter so I wonder you know how muscle butter so I wonder you know how much of the again it's like you're much of the again it's like you're much of the again it's like you're you're affecting the aisle six is really you're affecting the aisle six is really you're affecting the aisle six is really important for that and I all six is important for that and I all six is important for that and I all six is released upon heat stress without released upon heat stress without released upon heat stress without without the exercise so uncoupling you without the exercise so uncoupling you without the exercise so uncoupling you know how much of the benefits from know how much of the benefits from know how much of the benefits from exercise there's certainly some overlap exercise there's certainly some overlap exercise there's certainly some overlap and I think that there's also there are and I think that there's also there are and I think that there's also there are separate benefits that exercise has as separate benefits that exercise has as separate benefits that exercise has as well independent of the heat stress well independent of the heat stress well independent of the heat stress component of it but I certainly think component of it but I certainly think component of it but I certainly think there is a lot of overlap between those there is a lot of overlap between those there is a lot of overlap between those two things and so the sauna becomes very two things and so the sauna becomes very two things and so the sauna becomes very interesting and there's the whole heat interesting and there's the whole heat interesting and there's the whole heat shock protein part where you know the shock protein part where you know the shock protein part where you know the heat stress is one of the major ways to

1:22heat stress is one of the major ways to heat stress is one of the major ways to increase heat shock proteins which do increase heat shock proteins which do increase heat shock proteins which do you play an important role in near you play an important role in near you play an important role in near general preventing neurodegenerative general preventing neurodegenerative general preventing neurodegenerative diseases and I do think it's also really diseases and I do think it's also really diseases and I do think it's also really hard to hard to hard to the effects on the the vascular system the effects on the the vascular system the effects on the the vascular system which is important right as well because which is important right as well because which is important right as well because it's having such a profound effect on it's having such a profound effect on it's having such a profound effect on the back of their system the heat stress the back of their system the heat stress the back of their system the heat stress it's hard to uncouple well how much of it's hard to uncouple well how much of it's hard to uncouple well how much of the staving off of dementia and the staving off of dementia and the staving off of dementia and alzheimerís has to do with that versus alzheimerís has to do with that versus alzheimerís has to do with that versus heat shock proteins you know this is to heat shock proteins you know this is to heat shock proteins you know this is to me the biggest challenge with me the biggest challenge with me the biggest challenge with Alzheimer's disease just is you know Alzheimer's disease just is you know Alzheimer's disease just is you know we're talking about it in a pretty we're talking about it in a pretty we're talking about it in a pretty nuanced way but I think unfortunately nuanced way but I think unfortunately nuanced way but I think unfortunately clinically it's still considered one clinically it's still considered one clinically it's still considered one disease but you know to the best of my disease but you know to the best of my disease but you know to the best of my understanding it's really several understanding it's really several understanding it's really several diseases that all have a very similar diseases that all have a very similar diseases that all have a very similar common final pathway you know for common final pathway you know for common final pathway you know for example like going back some of the example like going back some of the example like going back some of the ketone data you know why why does ketone ketone data you know why why does ketone ketone data you know why why does ketone enhance memory and some in some models enhance memory and some in some models enhance memory and some in some models certainly even going back Oh God ten certainly even going back Oh God ten certainly even going back Oh God ten years you see a lot of anecdote of years you see a lot of anecdote of years you see a lot of anecdote of people in early stage dementia who when people in early stage dementia who when people in early stage dementia who when given even MCT oil would see transient given even MCT oil would see transient given even MCT oil would see transient improvements in cognition now Richard improvements in cognition now Richard improvements in cognition now Richard Veatch did some of the most elegant work

1:23Veatch did some of the most elegant work Veatch did some of the most elegant work on this on this on this Richard Veatch by the way is the guy who Richard Veatch by the way is the guy who Richard Veatch by the way is the guy who along with Kieran Clark created the along with Kieran Clark created the along with Kieran Clark created the ketone ester that T Delta s licenses to ketone ester that T Delta s licenses to ketone ester that T Delta s licenses to human and you know they showed I think human and you know they showed I think human and you know they showed I think quite convincingly in this animal model quite convincingly in this animal model quite convincingly in this animal model that the bhp was basically bypassing that the bhp was basically bypassing that the bhp was basically bypassing pyruvate dehydrogenase and so all of a pyruvate dehydrogenase and so all of a pyruvate dehydrogenase and so all of a sudden you know you think about the sudden you know you think about the sudden you know you think about the energy deficit that a neuron would energy deficit that a neuron would energy deficit that a neuron would experience if you have insulin experience if you have insulin experience if you have insulin resistance at PD H so if you know resistance at PD H so if you know resistance at PD H so if you know glucose is going to pyruvate and glucose is going to pyruvate and glucose is going to pyruvate and pyruvate can't get in because PD H is pyruvate can't get in because PD H is pyruvate can't get in because PD H is resistant giving BHB would just bypass resistant giving BHB would just bypass resistant giving BHB would just bypass it you go straight into the krebs cycle it you go straight into the krebs cycle it you go straight into the krebs cycle you make all the ATP you want but that you make all the ATP you want but that you make all the ATP you want but that might only be a subset of people that might only be a subset of people that might only be a subset of people that are you know suffering right there's are you know suffering right there's are you know suffering right there's also going to be the microvascular also going to be the microvascular also going to be the microvascular variant and then there's going to be the variant and then there's going to be the variant and then there's going to be the sort of more toxin variants so the nice sort of more toxin variants so the nice sort of more toxin variants so the nice thing about sauna - just thinking about thing about sauna - just thinking about thing about sauna - just thinking about it is if I can't becoming more convinced it is if I can't becoming more convinced it is if I can't becoming more convinced of this it's actually like a really of this it's actually like a really of this it's actually like a really pleasant thing that you can do to pleasant thing that you can do to pleasant thing that you can do to potentially live longer and certainly potentially live longer and certainly potentially live longer and certainly live better because many of the things live better because many of the things live better because many of the things we talked about I mean let's call a

1:24we talked about I mean let's call a we talked about I mean let's call a spade a spade fastings not fun I wish I spade a spade fastings not fun I wish I spade a spade fastings not fun I wish I could tell you that you know not eating could tell you that you know not eating could tell you that you know not eating is fun but like I just love eating so is fun but like I just love eating so is fun but like I just love eating so anytime I'm not eating I'm sort of like anytime I'm not eating I'm sort of like anytime I'm not eating I'm sort of like there's a discipline that's required to there's a discipline that's required to there's a discipline that's required to do it but I don't know sitting in the do it but I don't know sitting in the do it but I don't know sitting in the sauna for 20 minutes before you go to sauna for 20 minutes before you go to sauna for 20 minutes before you go to bed is pretty enjoyable of course the bed is pretty enjoyable of course the bed is pretty enjoyable of course the problem is it's not it's nothing it's problem is it's not it's nothing it's problem is it's not it's nothing it's not accessible you don't like not accessible you don't like not accessible you don't like Luzerne point you it's enjoyable until Luzerne point you it's enjoyable until Luzerne point you it's enjoyable until you like holy [ __ ] it's hot I want to you like holy [ __ ] it's hot I want to you like holy [ __ ] it's hot I want to get out it's knowing that like you get get out it's knowing that like you get get out it's knowing that like you get to get out and then that that jump into to get out and then that that jump into to get out and then that that jump into the pool or the whatever it is is yeah the pool or the whatever it is is yeah the pool or the whatever it is is yeah yeah the discomfort you experience from yeah the discomfort you experience from yeah the discomfort you experience from from like the heat stress where you're from like the heat stress where you're from like the heat stress where you're like really hot is actually I think key like really hot is actually I think key like really hot is actually I think key for the positive benefits at least for for the positive benefits at least for for the positive benefits at least for me it was on my mood where I was just me it was on my mood where I was just me it was on my mood where I was just like felt so good so what about the like felt so good so what about the like felt so good so what about the reciprocal of that cold so I used to do reciprocal of that cold so I used to do reciprocal of that cold so I used to do a lot of cold therapy but all for Dom a lot of cold therapy but all for Dom a lot of cold therapy but all for Dom still delayed onset muscle soreness so still delayed onset muscle soreness so still delayed onset muscle soreness so that was my main interest was you know that was my main interest was you know that was my main interest was you know back in the olden days I would go out back in the olden days I would go out back in the olden days I would go out and buy hundred pounds of ice or 50 and buy hundred pounds of ice or 50 and buy hundred pounds of ice or 50 pounds of ice I guess throw it in the pounds of ice I guess throw it in the pounds of ice I guess throw it in the bathtub cold water and I would immerse

1:25bathtub cold water and I would immerse bathtub cold water and I would immerse myself and that was unbearable but that myself and that was unbearable but that myself and that was unbearable but that really sped up my recovery from really sped up my recovery from really sped up my recovery from difficult workouts it's a pain in the difficult workouts it's a pain in the difficult workouts it's a pain in the ass so I started doing cryo and the data ass so I started doing cryo and the data ass so I started doing cryo and the data I was pretty convinced that whole body I was pretty convinced that whole body I was pretty convinced that whole body cryotherapy comparable effect in Dom's cryotherapy comparable effect in Dom's cryotherapy comparable effect in Dom's but a fraction of the time and 10x the but a fraction of the time and 10x the but a fraction of the time and 10x the cost but I've also had people talk to me cost but I've also had people talk to me cost but I've also had people talk to me about and I've never really looked into about and I've never really looked into about and I've never really looked into this but I'm guessing you have ice cold this but I'm guessing you have ice cold this but I'm guessing you have ice cold showers for you know increasing showers for you know increasing showers for you know increasing norepinephrine levels things like that norepinephrine levels things like that norepinephrine levels things like that mood altering have you had you looked mood altering have you had you looked mood altering have you had you looked into this I've looked into the into this I've looked into the into this I've looked into the literature yeah it's something that I literature yeah it's something that I literature yeah it's something that I did that I did notice from from doing did that I did notice from from doing did that I did notice from from doing cold showers and sometimes I'll do one cold showers and sometimes I'll do one cold showers and sometimes I'll do one before like a big talk or something before like a big talk or something before like a big talk or something because it does help me focus and it because it does help me focus and it because it does help me focus and it helps with my anxiety kind of so yeah I helps with my anxiety kind of so yeah I helps with my anxiety kind of so yeah I was gonna say so how did we square the was gonna say so how did we square the was gonna say so how did we square the two completely different things right two completely different things right two completely different things right you would you'd sit in the sauna to help you would you'd sit in the sauna to help you would you'd sit in the sauna to help with anxiety and then you could have the with anxiety and then you could have the with anxiety and then you could have the cold shower well I didn't start getting cold shower well I didn't start getting cold shower well I didn't start getting into the cold shower until probably a

1:26into the cold shower until probably a into the cold shower until probably a couple of years ago the sauna I started couple of years ago the sauna I started couple of years ago the sauna I started doing in grad school yeah long time doing in grad school yeah long time doing in grad school yeah long time probably about 2008 so a long time ago probably about 2008 so a long time ago probably about 2008 so a long time ago so they're they're completely uncoupled so they're they're completely uncoupled so they're they're completely uncoupled in my experience so do you think the in my experience so do you think the in my experience so do you think the sauna is working more through gh and sauna is working more through gh and sauna is working more through gh and others I think this sauna has a very others I think this sauna has a very others I think this sauna has a very profound first it affects the immune profound first it affects the immune profound first it affects the immune system and that inflammation has a major system and that inflammation has a major system and that inflammation has a major effect on brain and I think that that's effect on brain and I think that that's effect on brain and I think that that's work from Charles rays on it's pretty work from Charles rays on it's pretty work from Charles rays on it's pretty clear it's definitely there's definitely clear it's definitely there's definitely clear it's definitely there's definitely an antidepressant effect that seems to an antidepressant effect that seems to an antidepressant effect that seems to correlate with biomarkers of the immune correlate with biomarkers of the immune correlate with biomarkers of the immune system so system so system so so the more potent the il-6 response the so the more potent the il-6 response the so the more potent the il-6 response the more potent the antidepressant response more potent the antidepressant response more potent the antidepressant response in addition to that there's a very in addition to that there's a very in addition to that there's a very strong effect on bated orphans baited strong effect on bated orphans baited strong effect on bated orphans baited orphans are dumped and also this other orphans are dumped and also this other orphans are dumped and also this other system called dine orphan which is you system called dine orphan which is you system called dine orphan which is you know yeah and and what's interesting is know yeah and and what's interesting is know yeah and and what's interesting is that when you activate dine orphan that when you activate dine orphan that when you activate dine orphan through the the cap opioid pathway through the the cap opioid pathway through the the cap opioid pathway instead of MU opioid you feel instead of MU opioid you feel instead of MU opioid you feel uncomfortable and it's the part where I uncomfortable and it's the part where I uncomfortable and it's the part where I was talking about your relation and ha I

1:27was talking about your relation and ha I was talking about your relation and ha I want to get out it's the part when want to get out it's the part when want to get out it's the part when you're exercising where you're like oh you're exercising where you're like oh you're exercising where you're like oh this you know it's that uncomfortable this you know it's that uncomfortable this you know it's that uncomfortable feeling well that's you're making dine feeling well that's you're making dine feeling well that's you're making dine orphan partly because it cools your body orphan partly because it cools your body orphan partly because it cools your body down so it's kind of a response to you down so it's kind of a response to you down so it's kind of a response to you elevate I'm convinced by the way there elevate I'm convinced by the way there elevate I'm convinced by the way there are a subset of athletes that don't are a subset of athletes that don't are a subset of athletes that don't produce that at the same level I mean produce that at the same level I mean produce that at the same level I mean seriously like there are people I think seriously like there are people I think seriously like there are people I think who there are yeah because we talk about who there are yeah because we talk about who there are yeah because we talk about like a why can that guy tolerate so much like a why can that guy tolerate so much like a why can that guy tolerate so much more pain than that guy and at some more pain than that guy and at some more pain than that guy and at some point it's possible that they're point it's possible that they're point it's possible that they're actually experiencing less pain there actually experiencing less pain there actually experiencing less pain there there there definitely are variants in there there definitely are variants in there there definitely are variants in in the capital good receptor your in the capital good receptor your in the capital good receptor your pathway and and all that so I'm pathway and and all that so I'm pathway and and all that so I'm surprised that hasn't become a surprised that hasn't become a surprised that hasn't become a performance-enhancing drug which is you performance-enhancing drug which is you performance-enhancing drug which is you know blocking that receptor the pain know blocking that receptor the pain know blocking that receptor the pain receptor in the brain which is a you receptor in the brain which is a you receptor in the brain which is a you know a very interesting thought but now know a very interesting thought but now know a very interesting thought but now so then on the cold front what do you so then on the cold front what do you so then on the cold front what do you think's mediating that neurotransmitters think's mediating that neurotransmitters think's mediating that neurotransmitters so basically on the cold front the so basically on the cold front the so basically on the cold front the norepinephrine your it's that's been norepinephrine your it's that's been norepinephrine your it's that's been shown so animal studies have shown or shown so animal studies have shown or shown so animal studies have shown or norepinephrine released in the locus norepinephrine released in the locus norepinephrine released in the locus coleus treason or the brain after cold coleus treason or the brain after cold coleus treason or the brain after cold exposure and a variety of cold water

1:28exposure and a variety of cold water exposure and a variety of cold water exposure cryotherapy if you're doing a exposure cryotherapy if you're doing a exposure cryotherapy if you're doing a cold water 50 degree you know if it's cold water 50 degree you know if it's cold water 50 degree you know if it's like 50 degrees Fahrenheit you gotta like 50 degrees Fahrenheit you gotta like 50 degrees Fahrenheit you gotta stay in a little longer than like a stay in a little longer than like a stay in a little longer than like a couple of minutes in a really cold couple of minutes in a really cold couple of minutes in a really cold cryotherapy chamber but in humans plasma cryotherapy chamber but in humans plasma cryotherapy chamber but in humans plasma norepinephrine has been looked at which norepinephrine has been looked at which norepinephrine has been looked at which does seem to sort of correlate with the does seem to sort of correlate with the does seem to sort of correlate with the release and it's so hard though to look release and it's so hard though to look release and it's so hard though to look at the plasma to understand I know I at the plasma to understand I know I at the plasma to understand I know I know it is it is so I do I do think that know it is it is so I do I do think that know it is it is so I do I do think that that some of the mood is affected by the that some of the mood is affected by the that some of the mood is affected by the norepinephrine as well have you norepinephrine as well have you norepinephrine as well have you experimented with the stacking which is experimented with the stacking which is experimented with the stacking which is go do the sauna for 20 minutes then go go do the sauna for 20 minutes then go go do the sauna for 20 minutes then go do the ice shower for whatever 10 do the ice shower for whatever 10 do the ice shower for whatever 10 minutes and you get an additive effect minutes and you get an additive effect minutes and you get an additive effect in time feel really good yeah I feel in time feel really good yeah I feel in time feel really good yeah I feel really good and and that's when I did really good and and that's when I did really good and and that's when I did notice that my sleep was really notice that my sleep was really notice that my sleep was really profoundly affected what's interesting profoundly affected what's interesting profoundly affected what's interesting is there some studies showing that that is there some studies showing that that is there some studies showing that that heat stress at least in piglets does heat stress at least in piglets does heat stress at least in piglets does affect actually it seems to elongate the affect actually it seems to elongate the affect actually it seems to elongate the REM REM REM sleep stage which I don't know how you sleep stage which I don't know how you sleep stage which I don't know how you know what what all that means but so know what what all that means but so know what what all that means but so there's there certainly an effect of there's there certainly an effect of there's there certainly an effect of heat on sleep and then of course cold heat on sleep and then of course cold heat on sleep and then of course cold isn't you know lowering your body body isn't you know lowering your body body isn't you know lowering your body body temperature is important for sleep onset

1:29temperature is important for sleep onset temperature is important for sleep onset but I don't know there's something about but I don't know there's something about but I don't know there's something about the combination of the two absolutely the combination of the two absolutely the combination of the two absolutely like I sleep amazing after doing that like I sleep amazing after doing that like I sleep amazing after doing that the combination of both the combination of both the combination of both I think cold is really interesting for I think cold is really interesting for I think cold is really interesting for the effects on mitochondrial biogenesis the effects on mitochondrial biogenesis the effects on mitochondrial biogenesis I mean exercise is probably one of the I mean exercise is probably one of the I mean exercise is probably one of the best ways to increase mitochondrial best ways to increase mitochondrial best ways to increase mitochondrial biogenesis but cold exposure has been biogenesis but cold exposure has been biogenesis but cold exposure has been shown human studies both an adipose shown human studies both an adipose shown human studies both an adipose tissue and in muscle tissue to to boost tissue and in muscle tissue to to boost tissue and in muscle tissue to to boost biomarkers of mitochondrial biogenesis biomarkers of mitochondrial biogenesis biomarkers of mitochondrial biogenesis well it depends on what tissue we're well it depends on what tissue we're well it depends on what tissue we're looking at still a you know P G c1 alpha looking at still a you know P G c1 alpha looking at still a you know P G c1 alpha would be would probably be one of the would be would probably be one of the would be would probably be one of the best I would say for muscle tissue in in best I would say for muscle tissue in in best I would say for muscle tissue in in adipose tissue perhaps the same I would adipose tissue perhaps the same I would adipose tissue perhaps the same I would say P G c1 alpha is probably one of the say P G c1 alpha is probably one of the say P G c1 alpha is probably one of the best best best it's another downstream one I can't for it's another downstream one I can't for it's another downstream one I can't for some reason I'm drawing a blank yeah so some reason I'm drawing a blank yeah so some reason I'm drawing a blank yeah so that that that's interesting to me that that that that's interesting to me that that that that's interesting to me that the the effect on mitochondrial the the effect on mitochondrial the the effect on mitochondrial biogenesis but personally I like the biogenesis but personally I like the biogenesis but personally I like the exercise you know for my mitochondrial exercise you know for my mitochondrial exercise you know for my mitochondrial biogenesis I'm not like doing cold biogenesis I'm not like doing cold biogenesis I'm not like doing cold exposure all the time it's not like exposure all the time it's not like exposure all the time it's not like something that I do often like I said

1:30something that I do often like I said something that I do often like I said I'll do it once in a while before a big I'll do it once in a while before a big I'll do it once in a while before a big event I have to talk at or something event I have to talk at or something event I have to talk at or something just because it does seem to help me just because it does seem to help me just because it does seem to help me with have you ever swum in water that's with have you ever swum in water that's with have you ever swum in water that's so cold that you actually feel like so cold that you actually feel like so cold that you actually feel like you're on fire yeah I have been yeah you're on fire yeah I have been yeah you're on fire yeah I have been yeah uh-huh that's bad to me as an amazing I uh-huh that's bad to me as an amazing I uh-huh that's bad to me as an amazing I assume it's through to the assume it's through to the assume it's through to the vasoconstriction vasoconstriction vasoconstriction but it's the coldest water I ever swam but it's the coldest water I ever swam but it's the coldest water I ever swam and was in the Colorado River it was 42 and was in the Colorado River it was 42 and was in the Colorado River it was 42 degrees which is I mean that's that's degrees which is I mean that's that's degrees which is I mean that's that's unusually cold and the only reason I unusually cold and the only reason I unusually cold and the only reason I think I was able to swim in it was it think I was able to swim in it was it think I was able to swim in it was it was May and so the Sun was it was about was May and so the Sun was it was about was May and so the Sun was it was about 90 degrees Fahrenheit was the air 90 degrees Fahrenheit was the air 90 degrees Fahrenheit was the air temperature so you could like I wouldn't temperature so you could like I wouldn't temperature so you could like I wouldn't be able to swim in 42 degree water on a be able to swim in 42 degree water on a be able to swim in 42 degree water on a cloudy day for example or a cold day but cloudy day for example or a cold day but cloudy day for example or a cold day but I couldn't believe the sensation of I couldn't believe the sensation of I couldn't believe the sensation of feeling like I had jumped into boiling feeling like I had jumped into boiling feeling like I had jumped into boiling oil it was incredible oil it was incredible oil it was incredible which is very different from my normal which is very different from my normal which is very different from my normal exposure to cold I used to swim a lot in exposure to cold I used to swim a lot in exposure to cold I used to swim a lot in the ocean and you know if you do a the ocean and you know if you do a the ocean and you know if you do a 3-hour swim at 50 degrees Fahrenheit or 3-hour swim at 50 degrees Fahrenheit or 3-hour swim at 50 degrees Fahrenheit or 50 to 53 50 to 53 50 to 53 you get a little bit of that effect but

1:31you get a little bit of that effect but you get a little bit of that effect but you know more you know more you know more you can still you still know you're in you can still you still know you're in you can still you still know you're in Coldwater but this particular time I Coldwater but this particular time I Coldwater but this particular time I remember and I probably spent 15 to 20 remember and I probably spent 15 to 20 remember and I probably spent 15 to 20 minutes in this 42 degree temp the minutes in this 42 degree temp the minutes in this 42 degree temp the entire time I felt like I was burning entire time I felt like I was burning entire time I felt like I was burning Wow and again III know no idea why I Wow and again III know no idea why I Wow and again III know no idea why I guess it's my assumption was that's such guess it's my assumption was that's such guess it's my assumption was that's such profound vasoconstriction in the profound vasoconstriction in the profound vasoconstriction in the periphery that you know the one thing periphery that you know the one thing periphery that you know the one thing that I wanted to mention that when you that I wanted to mention that when you that I wanted to mention that when you brought this up for recovery is because brought this up for recovery is because brought this up for recovery is because um there is some evidence that for um there is some evidence that for um there is some evidence that for whatever reason strength training when whatever reason strength training when whatever reason strength training when you do cold exposure like immediately you do cold exposure like immediately you do cold exposure like immediately after strength training if you do it after strength training if you do it after strength training if you do it within its let's say before like within its let's say before like within its let's say before like sometimes with it sometime within an sometimes with it sometime within an sometimes with it sometime within an hour before or for sorry absolutely hour before or for sorry absolutely hour before or for sorry absolutely after strength training it seems to after strength training it seems to after strength training it seems to blunt some of the hypertrophy effects blunt some of the hypertrophy effects blunt some of the hypertrophy effects yes yes and and and actually it's in you yes yes and and and actually it's in you yes yes and and and actually it's in you say that that's the exact reason I would say that that's the exact reason I would say that that's the exact reason I would never take like ibuprofen or any never take like ibuprofen or any never take like ibuprofen or any anti-inflammatory agent III would limit anti-inflammatory agent III would limit anti-inflammatory agent III would limit it even that day I wouldn't take any of it even that day I wouldn't take any of it even that day I wouldn't take any of those agents because you're impairing those agents because you're impairing those agents because you're impairing that that rebuild yeah yeah so that so

1:32that that rebuild yeah yeah so that so that that rebuild yeah yeah so that so that's also interesting that the timing that's also interesting that the timing that's also interesting that the timing of it seems to be you know again there's of it seems to be you know again there's of it seems to be you know again there's it's been shown that about an hour after it's been shown that about an hour after it's been shown that about an hour after exercise is when the the anti exercise is when the the anti exercise is when the the anti inflammatory response starts to peak and inflammatory response starts to peak and inflammatory response starts to peak and so it's like if you can basically if so it's like if you can basically if so it's like if you can basically if you're within that hour window when the you're within that hour window when the you're within that hour window when the inflammation is happening to create that inflammation is happening to create that inflammation is happening to create that anti inflammatory response you don't anti inflammatory response you don't anti inflammatory response you don't want to dampen that at least that's it want to dampen that at least that's it want to dampen that at least that's it seems to be what I I think and and seems to be what I I think and and seems to be what I I think and and literature seems to suggest and there's literature seems to suggest and there's literature seems to suggest and there's of course mechanisms where it's like of course mechanisms where it's like of course mechanisms where it's like specific macrophages and muscle tissue specific macrophages and muscle tissue specific macrophages and muscle tissue are really important for activating all are really important for activating all are really important for activating all these things that you know eventually these things that you know eventually these things that you know eventually result in satellite cell proliferation result in satellite cell proliferation result in satellite cell proliferation you know and of course igf-1 is in there you know and of course igf-1 is in there you know and of course igf-1 is in there somewhere so again you know the immune somewhere so again you know the immune somewhere so again you know the immune system activation is important for a lot system activation is important for a lot system activation is important for a lot of the benefits of exercise including of the benefits of exercise including of the benefits of exercise including muscle hypertrophy so there's one more muscle hypertrophy so there's one more muscle hypertrophy so there's one more topic I just want to get to if we can topic I just want to get to if we can topic I just want to get to if we can spare a bit more time which is which is spare a bit more time which is which is spare a bit more time which is which is nad the precursor is the whole shtick nad the precursor is the whole shtick nad the precursor is the whole shtick you spend a lot of time thinking about you spend a lot of time thinking about you spend a lot of time thinking about this what is your current thinking on is

1:33this what is your current thinking on is this what is your current thinking on is having more nad to NADH matter the the having more nad to NADH matter the the having more nad to NADH matter the the thing about the nad I guess I should thing about the nad I guess I should thing about the nad I guess I should provide context for people why am I provide context for people why am I provide context for people why am I asking this question right so there's asking this question right so there's asking this question right so there's lots of supplements out there now that lots of supplements out there now that lots of supplements out there now that are you know either giving NR or nad and are you know either giving NR or nad and are you know either giving NR or nad and the claim is that these things can the claim is that these things can the claim is that these things can enhance longevity you could live longer enhance longevity you could live longer enhance longevity you could live longer and that also you live better you have and that also you live better you have and that also you live better you have more energy all of these other things more energy all of these other things more energy all of these other things and so in the mitochondria you have and so in the mitochondria you have and so in the mitochondria you have complex one which converts NADH to nad complex one which converts NADH to nad complex one which converts NADH to nad and the idea is we do know that as you and the idea is we do know that as you and the idea is we do know that as you age that ratio of nad to NADH goes down age that ratio of nad to NADH goes down age that ratio of nad to NADH goes down and so part of the thinking is well and and so part of the thinking is well and and so part of the thinking is well and this is outside of this or too and this is outside of this or too and this is outside of this or too and pathway but this is upstream of that but pathway but this is upstream of that but pathway but this is upstream of that but if that you give more of either the if that you give more of either the if that you give more of either the precursor or nad you're basically fixing precursor or nad you're basically fixing precursor or nad you're basically fixing something that is getting worse as you something that is getting worse as you something that is getting worse as you age yeah so that I mean the question is age yeah so that I mean the question is age yeah so that I mean the question is why does it go down and that's I think why does it go down and that's I think why does it go down and that's I think there's multiple reasons for that at there's multiple reasons for that at there's multiple reasons for that at least that's been shown in literature least that's been shown in literature least that's been shown in literature nad is a very important cofactor for nad is a very important cofactor for nad is a very important cofactor for mitochondria I mean obviously mitochondria I mean obviously mitochondria I mean obviously mitochondria or making NADH and that

1:34mitochondria or making NADH and that mitochondria or making NADH and that hydrogen the proton is used and hydrogen the proton is used and hydrogen the proton is used and electrons are used to basically generate electrons are used to basically generate electrons are used to basically generate energy through the electron transport energy through the electron transport energy through the electron transport chain and it's also generating the chain and it's also generating the chain and it's also generating the mitochondrial membrane potential by mitochondrial membrane potential by mitochondrial membrane potential by kicking out the the proton so that kicking out the the proton so that kicking out the the proton so that that's really important for that's really important for that's really important for mitochondrial function and respiratory mitochondrial function and respiratory mitochondrial function and respiratory function energy production which is like function energy production which is like function energy production which is like the key of everything right but in the key of everything right but in the key of everything right but in addition to that you have as you addition to that you have as you addition to that you have as you mentioned sirtuins which are histone mentioned sirtuins which are histone mentioned sirtuins which are histone deacetylases which have a whole host of deacetylases which have a whole host of deacetylases which have a whole host of functions that they're doing regulating functions that they're doing regulating functions that they're doing regulating tons and tons of different pathways tons and tons of different pathways tons and tons of different pathways there also seem to be very important for there also seem to be very important for there also seem to be very important for healthspan and then in addition to that healthspan and then in addition to that healthspan and then in addition to that there's a very important DNA repair there's a very important DNA repair there's a very important DNA repair enzyme part that literally syncs up nad enzyme part that literally syncs up nad enzyme part that literally syncs up nad I mean it's like an nad sync I mean it I mean it's like an nad sync I mean it I mean it's like an nad sync I mean it you know so you know we're constantly you know so you know we're constantly you know so you know we're constantly having damage where does it reside that having damage where does it reside that having damage where does it reside that enzyme we're in the cell yeah enzyme we're in the cell yeah enzyme we're in the cell yeah is it nuclear it must be right yeah and is it nuclear it must be right yeah and is it nuclear it must be right yeah and the reason I ask is how do we know that the reason I ask is how do we know that the reason I ask is how do we know that these supplements that we take orally these supplements that we take orally these supplements that we take orally are going to actually reach their are going to actually reach their are going to actually reach their bioavailability in the place we want bioavailability in the place we want bioavailability in the place we want them okay but that said we'll come back

1:35them okay but that said we'll come back them okay but that said we'll come back to that after um I think it's in the to that after um I think it's in the to that after um I think it's in the nucleus I mean it would otherwise the nucleus I mean it would otherwise the nucleus I mean it would otherwise the shuttles there but I think it is so it's shuttles there but I think it is so it's shuttles there but I think it is so it's very important for repairing you know very important for repairing you know very important for repairing you know DNA damage and so that's one of the DNA damage and so that's one of the DNA damage and so that's one of the major sinks and actually inflammation major sinks and actually inflammation major sinks and actually inflammation all these things are kind of upstream all these things are kind of upstream all these things are kind of upstream apart activation so the more that's apart activation so the more that's apart activation so the more that's happening the more parts being activated happening the more parts being activated happening the more parts being activated so you kind of have you have nad going so you kind of have you have nad going so you kind of have you have nad going there there there so one argument just to make sure I so one argument just to make sure I so one argument just to make sure I understand what you're saying is look if understand what you're saying is look if understand what you're saying is look if you're getting older you're gonna have you're getting older you're gonna have you're getting older you're gonna have more DNA damage that's just stochastic more DNA damage that's just stochastic more DNA damage that's just stochastic and if your little guy that repairs it and if your little guy that repairs it and if your little guy that repairs it requires nad as fuel requires nad as fuel requires nad as fuel that would explain one reason that would explain one reason that would explain one reason potentially why nad would decline as we potentially why nad would decline as we potentially why nad would decline as we age yeah it's and it's certainly a sink age yeah it's and it's certainly a sink age yeah it's and it's certainly a sink for it yeah and the other so the other for it yeah and the other so the other for it yeah and the other so the other thing is well if your immune systems thing is well if your immune systems thing is well if your immune systems can't constantly you know activate too can't constantly you know activate too can't constantly you know activate too if a more inflammation you have all that if a more inflammation you have all that if a more inflammation you have all that energy is required so nad is being energy is required so nad is being energy is required so nad is being consumed more for that as well so that's consumed more for that as well so that's consumed more for that as well so that's sort of another thing basically nad sort of another thing basically nad sort of another thing basically nad levels decline with age and it's levels decline with age and it's levels decline with age and it's probably because it's just getting used

1:36probably because it's just getting used probably because it's just getting used up more or the other the alternative is up more or the other the alternative is up more or the other the alternative is you know is there something else going you know is there something else going you know is there something else going on in terms of like this whole salvage on in terms of like this whole salvage on in terms of like this whole salvage pathway there's another pathway that you pathway there's another pathway that you pathway there's another pathway that you can do to regenerate aid nad and if can do to regenerate aid nad and if can do to regenerate aid nad and if that's kind of going wrong and I think that's kind of going wrong and I think that's kind of going wrong and I think there's some increasing evidence for there's some increasing evidence for there's some increasing evidence for that as well would that make metformin a that as well would that make metformin a that as well would that make metformin a bad idea from this standpoint because bad idea from this standpoint because bad idea from this standpoint because metformin inhibits complex one so Matt metformin inhibits complex one so Matt metformin inhibits complex one so Matt Forman lowers the ratio of nad to NADH Forman lowers the ratio of nad to NADH Forman lowers the ratio of nad to NADH does it has that been shown so you're does it has that been shown so you're does it has that been shown so you're saying it should lower it it should saying it should lower it it should saying it should lower it it should lower it now of course that's lower it now of course that's lower it now of course that's counterintuitive because we know it counterintuitive because we know it counterintuitive because we know it activates AMPK so I probably have to sit activates AMPK so I probably have to sit activates AMPK so I probably have to sit down and think about this but we do know down and think about this but we do know down and think about this but we do know metformin inhibits complex one and we metformin inhibits complex one and we metformin inhibits complex one and we know that complex one turns NADH to nad know that complex one turns NADH to nad know that complex one turns NADH to nad which makes me wonder does is it which makes me wonder does is it which makes me wonder does is it possible that metformin would impair DNA possible that metformin would impair DNA possible that metformin would impair DNA repair through that mechanism by repair through that mechanism by repair through that mechanism by reducing substrate I have no idea well reducing substrate I have no idea well reducing substrate I have no idea well I'm gonna write that down because I I'm gonna write that down because I I'm gonna write that down because I wasn't aware of the I didn't understand wasn't aware of the I didn't understand wasn't aware of the I didn't understand that at length yeah yeah I think that's

1:37that at length yeah yeah I think that's that at length yeah yeah I think that's a major one I literally think that's a a major one I literally think that's a a major one I literally think that's a major thing for it I think that the PARP major thing for it I think that the PARP major thing for it I think that the PARP is I think it's just like going there is I think it's just like going there is I think it's just like going there yeah so the animal evidence you yeah so the animal evidence you yeah so the animal evidence you mentioned some of the supplements you mentioned some of the supplements you mentioned some of the supplements you know precursors that can form nad I know precursors that can form nad I know precursors that can form nad I think that the animal evidence suggests think that the animal evidence suggests think that the animal evidence suggests that it can at least in rodents improve that it can at least in rodents improve that it can at least in rodents improve health span particularly in models with health span particularly in models with health span particularly in models with light that are heavily dependent on light that are heavily dependent on light that are heavily dependent on mitochondria like muscle myopathy models mitochondria like muscle myopathy models mitochondria like muscle myopathy models or something like that I think I think or something like that I think I think or something like that I think I think that was one and also the brain so I that was one and also the brain so I that was one and also the brain so I think those are the two the two organs think those are the two the two organs think those are the two the two organs I've seen like major positive effects I've seen like major positive effects I've seen like major positive effects with with nad supplementation and then with with nad supplementation and then with with nad supplementation and then there's some of course pilot clinical there's some of course pilot clinical there's some of course pilot clinical studies showing that yes you can take studies showing that yes you can take studies showing that yes you can take for example in the coton for example in the coton for example in the coton right right beside and it does seem to right right beside and it does seem to right right beside and it does seem to increase nad levels in plasma in a increase nad levels in plasma in a increase nad levels in plasma in a dose-dependent manner now again you race dose-dependent manner now again you race dose-dependent manner now again you race no idea if it's getting in the was no idea if it's getting in the was no idea if it's getting in the was getting in the cell is it getting in the getting in the cell is it getting in the getting in the cell is it getting in the way now we do know in animal studies way now we do know in animal studies way now we do know in animal studies that I think that has been shown because that I think that has been shown because that I think that has been shown because it's affecting the might of contacted it's affecting the might of contacted it's affecting the might of contacted those animal models of myopathy and those animal models of myopathy and those animal models of myopathy and stuff and mitochondrial function was stuff and mitochondrial function was stuff and mitochondrial function was improved and all that stuff so so when improved and all that stuff so so when improved and all that stuff so so when animal models it obviously is affecting

1:38animal models it obviously is affecting animal models it obviously is affecting mitochondrial function so it must be mitochondrial function so it must be mitochondrial function so it must be getting to the right place I don't know getting to the right place I don't know getting to the right place I don't know why I have found myself kind of why I have found myself kind of why I have found myself kind of skeptical of this I think it's good to skeptical of this I think it's good to skeptical of this I think it's good to start with skepticism I mean I think start with skepticism I mean I think start with skepticism I mean I think that nad levels or you can you can that nad levels or you can you can that nad levels or you can you can increase them with fasting so when you increase them with fasting so when you increase them with fasting so when you fast you know as you mentioned you fast you know as you mentioned you fast you know as you mentioned you convert nad into NADH in the presence of convert nad into NADH in the presence of convert nad into NADH in the presence of of energy because that's basically when of energy because that's basically when of energy because that's basically when you have a substrate like glucose or a you have a substrate like glucose or a you have a substrate like glucose or a fatty acid that's when you produce nadh fatty acid that's when you produce nadh fatty acid that's when you produce nadh or fadh2 so in the absence of those or fadh2 so in the absence of those or fadh2 so in the absence of those substrates then you start to meet your substrates then you start to meet your substrates then you start to meet your nad starts to build up so back to your nad starts to build up so back to your nad starts to build up so back to your metformin question you said I know who metformin question you said I know who metformin question you said I know who to ask I definitely know I'm gonna ask to ask I definitely know I'm gonna ask to ask I definitely know I'm gonna ask Navin Dell he will know the answer to Navin Dell he will know the answer to Navin Dell he will know the answer to this I follow a lot of his work when I this I follow a lot of his work when I this I follow a lot of his work when I was in grime Ralph Jabbar Dinis I did was in grime Ralph Jabbar Dinis I did was in grime Ralph Jabbar Dinis I did because I was doing a lot of cancer because I was doing a lot of cancer because I was doing a lot of cancer metabolism metabolism mitochondrial metabolism metabolism mitochondrial metabolism metabolism mitochondrial function and stuff so I followed a lot function and stuff so I followed a lot function and stuff so I followed a lot of do you have NAB's book navigating of do you have NAB's book navigating of do you have NAB's book navigating metabolism oh I don't know I just used metabolism oh I don't know I just used metabolism oh I don't know I just used to read his papers back when I was a to read his papers back when I was a to read his papers back when I was a graduate school just yeah so nav and

1:39graduate school just yeah so nav and graduate school just yeah so nav and David Sabatini were in town a couple of David Sabatini were in town a couple of David Sabatini were in town a couple of weeks ago and I was leaving town the day weeks ago and I was leaving town the day weeks ago and I was leaving town the day they were coming into town so we hung they were coming into town so we hung they were coming into town so we hung out for three hours near the airport and out for three hours near the airport and out for three hours near the airport and I was just reminded of how much fun it I was just reminded of how much fun it I was just reminded of how much fun it is to talk about mitochondria yeah for is to talk about mitochondria yeah for is to talk about mitochondria yeah for sure what is the most interesting sure what is the most interesting sure what is the most interesting question you feel you don't yet know the question you feel you don't yet know the question you feel you don't yet know the answer to but you feel is knowable that answer to but you feel is knowable that answer to but you feel is knowable that you're sort of actively putting in lots you're sort of actively putting in lots you're sort of actively putting in lots of your clock cycles on thinking about I of your clock cycles on thinking about I of your clock cycles on thinking about I would really like to know if for example would really like to know if for example would really like to know if for example someone who is like myself who I don't someone who is like myself who I don't someone who is like myself who I don't have a lot of body fat I'm active I eat have a lot of body fat I'm active I eat have a lot of body fat I'm active I eat a pretty healthy diet you know I don't a pretty healthy diet you know I don't a pretty healthy diet you know I don't smoke I don't have any of those bad smoke I don't have any of those bad smoke I don't have any of those bad habits if I were to do a prolonged fast habits if I were to do a prolonged fast habits if I were to do a prolonged fast a couple days a year would that truly a couple days a year would that truly a couple days a year would that truly have an effect on increasing my stem have an effect on increasing my stem have an effect on increasing my stem cell production potentially you know cell production potentially you know cell production potentially you know getting rid of any dysfunctional immune getting rid of any dysfunctional immune getting rid of any dysfunctional immune cells just funk cells just funk cells just funk liver cells dysfunctional whatever you liver cells dysfunctional whatever you liver cells dysfunctional whatever you know muscle cells and repopulating them know muscle cells and repopulating them know muscle cells and repopulating them with like healthy new cells like with like healthy new cells like with like healthy new cells like basically this rejuvenation like could I

1:40basically this rejuvenation like could I basically this rejuvenation like could I get this like bursts of rejuvenation a get this like bursts of rejuvenation a get this like bursts of rejuvenation a couple times a year and would that have couple times a year and would that have couple times a year and would that have in turn have an effect on delaying the in turn have an effect on delaying the in turn have an effect on delaying the onset of age-related diseases improving onset of age-related diseases improving onset of age-related diseases improving my health span you know keeping my stem my health span you know keeping my stem my health span you know keeping my stem cells less damaged that would be very cells less damaged that would be very cells less damaged that would be very interesting to me because to me that's interesting to me because to me that's interesting to me because to me that's something that's very doable for myself something that's very doable for myself something that's very doable for myself I mean the experiment to figure that out I mean the experiment to figure that out I mean the experiment to figure that out was different because it's you know in was different because it's you know in was different because it's you know in humans and so that's gonna be really humans and so that's gonna be really humans and so that's gonna be really hard you have to figure out like if you hard you have to figure out like if you hard you have to figure out like if you can even look at certain biomarkers to can even look at certain biomarkers to can even look at certain biomarkers to know that but I feel like that would be know that but I feel like that would be know that but I feel like that would be something that's so easy for someone to something that's so easy for someone to something that's so easy for someone to do it's interested in in longevity and do it's interested in in longevity and do it's interested in in longevity and you think it would be sort of once or you think it would be sort of once or you think it would be sort of once or twice a year doing like a five-day water twice a year doing like a five-day water twice a year doing like a five-day water only mineral well the question is how only mineral well the question is how only mineral well the question is how often how long like so you know we have often how long like so you know we have often how long like so you know we have a lot of the studies coming out of a lot of the studies coming out of a lot of the studies coming out of animal data which these rodents they animal data which these rodents they animal data which these rodents they lose 20% of their body weight after a 48 lose 20% of their body weight after a 48 lose 20% of their body weight after a 48 hour water fast yeah I find it hard to hour water fast yeah I find it hard to hour water fast yeah I find it hard to infer anything from rodents when it infer anything from rodents when it infer anything from rodents when it comes to fasting because MICEX act comes to fasting because MICEX act comes to fasting because MICEX act reason it's like Ida even the Jay reason it's like Ida even the Jay reason it's like Ida even the Jay Mitchell stuff I talked about earlier I

1:41Mitchell stuff I talked about earlier I Mitchell stuff I talked about earlier I mean I think it's an interesting proof mean I think it's an interesting proof mean I think it's an interesting proof of concept but I don't actually know how of concept but I don't actually know how of concept but I don't actually know how you would apply that to humans right so you would apply that to humans right so you would apply that to humans right so the question is it's like okay so if you the question is it's like okay so if you the question is it's like okay so if you have a 48-hour fasts and in a row yeah have a 48-hour fasts and in a row yeah have a 48-hour fasts and in a row yeah so I guess I'll expand my sort of answer so I guess I'll expand my sort of answer so I guess I'll expand my sort of answer that question like maybe do a prolonged that question like maybe do a prolonged that question like maybe do a prolonged water fasts like time right what's the water fasts like time right what's the water fasts like time right what's the frequency what's the duration to get the frequency what's the duration to get the frequency what's the duration to get the maximum benefit yeah and I am maximum benefit yeah and I am maximum benefit yeah and I am specifically interested in this specifically interested in this specifically interested in this shrinking of the organs and then shrinking of the organs and then shrinking of the organs and then regrowing like this potential robust regrowing like this potential robust regrowing like this potential robust activation of stem cells clearing away activation of stem cells clearing away activation of stem cells clearing away you know we're not just talking about a you know we're not just talking about a you know we're not just talking about a toffee we're not just talking about toffee we're not just talking about toffee we're not just talking about clearing away damaged mitochondria a clearing away damaged mitochondria a clearing away damaged mitochondria a pieces of DNA protein a great you are pieces of DNA protein a great you are pieces of DNA protein a great you are getting that but well in theory in getting that but well in theory in getting that but well in theory in humans in addition to that I mean I'm humans in addition to that I mean I'm humans in addition to that I mean I'm talking about clearing away the damage talking about clearing away the damage talking about clearing away the damage to the whole cell like just getting rid to the whole cell like just getting rid to the whole cell like just getting rid of it and replacing it with a brand-new of it and replacing it with a brand-new of it and replacing it with a brand-new young healthy cell like that's what I'm young healthy cell like that's what I'm young healthy cell like that's what I'm interested in you know I would I would interested in you know I would I would interested in you know I would I would love to you know even just the hope that love to you know even just the hope that love to you know even just the hope that that's possible you know based off of that's possible you know based off of that's possible you know based off of some of the pilot studies that voltar some of the pilot studies that voltar some of the pilot studies that voltar has done in humans and certainly the the

1:42has done in humans and certainly the the has done in humans and certainly the the animal evidence like I'm convinced I'm animal evidence like I'm convinced I'm animal evidence like I'm convinced I'm gonna at least try because it seems gonna at least try because it seems gonna at least try because it seems it seems very possible I know I know it seems very possible I know I know it seems very possible I know I know that he is trying to find the best that he is trying to find the best that he is trying to find the best biomarkers to look at for you know stem biomarkers to look at for you know stem biomarkers to look at for you know stem cell activation it's not quite as cell activation it's not quite as cell activation it's not quite as straightforward can't just you know straightforward can't just you know straightforward can't just you know harvest a bunch of tissues and look at harvest a bunch of tissues and look at harvest a bunch of tissues and look at things but I certainly have gotten some things but I certainly have gotten some things but I certainly have gotten some anecdotes from people that have had anecdotes from people that have had anecdotes from people that have had autoimmune like diseases and things said autoimmune like diseases and things said autoimmune like diseases and things said that fastings like completely reversed that fastings like completely reversed that fastings like completely reversed some of it like eczema or something no some of it like eczema or something no some of it like eczema or something no it's right where it's anecdotal but it's right where it's anecdotal but it's right where it's anecdotal but certainly when you start to have enough certainly when you start to have enough certainly when you start to have enough people saying the same thing it's like people saying the same thing it's like people saying the same thing it's like wow that's interesting that you've heard wow that's interesting that you've heard wow that's interesting that you've heard that five five or six times now yeah I that five five or six times now yeah I that five five or six times now yeah I think that would that's a good one I think that would that's a good one I think that would that's a good one I guess I think of a very similar question guess I think of a very similar question guess I think of a very similar question with rapamycin rapamycin yeah what what with rapamycin rapamycin yeah what what with rapamycin rapamycin yeah what what dose and what frequency to produce the dose and what frequency to produce the dose and what frequency to produce the best longevity phenotype do you know the best longevity phenotype do you know the best longevity phenotype do you know the interesting thing with the rapa myosin interesting thing with the rapa myosin interesting thing with the rapa myosin is the effect on the senescence cells is the effect on the senescence cells is the effect on the senescence cells like that's so interesting to me I like that's so interesting to me I like that's so interesting to me I didn't know really about that until I

1:43didn't know really about that until I didn't know really about that until I listened to your podcast with Judith listened to your podcast with Judith listened to your podcast with Judith yeah she's amazing she's really she's yeah she's amazing she's really she's yeah she's amazing she's really she's really she was really great and very really she was really great and very really she was really great and very knowledgeable in the whole senescent knowledgeable in the whole senescent knowledgeable in the whole senescent field yeah I had no I had no idea either field yeah I had no I had no idea either field yeah I had no I had no idea either the life's expanding effect is is that the life's expanding effect is is that the life's expanding effect is is that males only or was it both male male and males only or was it both male male and males only or was it both male male and female and it's across I mean it's it's female and it's across I mean it's it's female and it's across I mean it's it's everything from yeast to worms to flies everything from yeast to worms to flies everything from yeast to worms to flies to mammals I mean it's the only drug to mammals I mean it's the only drug to mammals I mean it's the only drug that's uniformly extended life across a that's uniformly extended life across a that's uniformly extended life across a billion years of evolution I mean and billion years of evolution I mean and billion years of evolution I mean and there's really interesting work I mean I there's really interesting work I mean I there's really interesting work I mean I think Matt quebra like maximum lifespan think Matt quebra like maximum lifespan think Matt quebra like maximum lifespan or are we talking median actually in the or are we talking median actually in the or are we talking median actually in the mice it was I think I can look it's not mice it was I think I can look it's not mice it was I think I can look it's not the time it's median but yeah yeah and the time it's median but yeah yeah and the time it's median but yeah yeah and what was interesting in the mice as they what was interesting in the mice as they what was interesting in the mice as they started late in life they started at 600 started late in life they started at 600 started late in life they started at 600 days which is that's about 60 years old days which is that's about 60 years old days which is that's about 60 years old yeah that's that's like starting is with yeah that's that's like starting is with yeah that's that's like starting is with this room that was really late in life this room that was really late in life this room that was really late in life for the my yeah yeah I was Wow made it for the my yeah yeah I was Wow made it for the my yeah yeah I was Wow made it that much more impressed that is that is that much more impressed that is that is that much more impressed that is that is very interesting so Kay Berlin's work do very interesting so Kay Berlin's work do very interesting so Kay Berlin's work do you know Matt up at the University of you know Matt up at the University of you know Matt up at the University of Washington he is giving rapamycin to

1:44Washington he is giving rapamycin to Washington he is giving rapamycin to dogs but these are pets right so these dogs but these are pets right so these dogs but these are pets right so these are not laboratory animals which is what are not laboratory animals which is what are not laboratory animals which is what makes it really interesting is you've makes it really interesting is you've makes it really interesting is you've got animals that live in our environment got animals that live in our environment got animals that live in our environment that are and dogs sort of have a very that are and dogs sort of have a very that are and dogs sort of have a very predictable demise right they're either predictable demise right they're either predictable demise right they're either gonna be you know died in an accident be gonna be you know died in an accident be gonna be you know died in an accident be euthanized euthanized euthanized cardiomyopathy or die of cancer that's cardiomyopathy or die of cancer that's cardiomyopathy or die of cancer that's basically how dogs died and the basically how dogs died and the basically how dogs died and the cardiomyopathy that they get is not an cardiomyopathy that they get is not an cardiomyopathy that they get is not an asterisk erotic cardiomyopathy they get asterisk erotic cardiomyopathy they get asterisk erotic cardiomyopathy they get a cardiomyopathy where the muscles are a cardiomyopathy where the muscles are a cardiomyopathy where the muscles are actually just getting weaker and weaker actually just getting weaker and weaker actually just getting weaker and weaker and their ejection fraction is going and their ejection fraction is going and their ejection fraction is going down and in studies as short as 12 weeks down and in studies as short as 12 weeks down and in studies as short as 12 weeks they're seeing a 10% increase in they're seeing a 10% increase in they're seeing a 10% increase in ejection fraction of these dogs and so ejection fraction of these dogs and so ejection fraction of these dogs and so the question is how much of that is the question is how much of that is the question is how much of that is working through senescence just working through senescence just working through senescence just selectively knocking out senescence selectively knocking out senescence selectively knocking out senescence cells and letting myocytes regenerate cells and letting myocytes regenerate cells and letting myocytes regenerate yeah that study out of the Mayo Clinic yeah that study out of the Mayo Clinic yeah that study out of the Mayo Clinic where they did some drugs like where they did some drugs like where they did some drugs like selectively targeted senescence cells selectively targeted senescence cells selectively targeted senescence cells and it it's a 20 percent increase in and it it's a 20 percent increase in and it it's a 20 percent increase in median lifespan sort of an interesting

1:45median lifespan sort of an interesting median lifespan sort of an interesting proof of principle how just well that proof of principle how just well that proof of principle how just well that was an I think an accelerated aging was an I think an accelerated aging was an I think an accelerated aging model so they had accumulated model so they had accumulated model so they had accumulated Marchioness themselves obviously they Marchioness themselves obviously they Marchioness themselves obviously they had to do something like that but but it had to do something like that but but it had to do something like that but but it all comes back to this idea of all comes back to this idea of all comes back to this idea of specificity and selection you know specificity and selection you know specificity and selection you know everything we've talked about if you everything we've talked about if you everything we've talked about if you really stop to think about it comes down really stop to think about it comes down really stop to think about it comes down to how could you target this tissue and to how could you target this tissue and to how could you target this tissue and leave that tissue alone or how could you leave that tissue alone or how could you leave that tissue alone or how could you target this cell and leave that cell target this cell and leave that cell target this cell and leave that cell alone and in many ways I think that's alone and in many ways I think that's alone and in many ways I think that's kind of got to be the next frontier here kind of got to be the next frontier here kind of got to be the next frontier here is you know even if you think about is you know even if you think about is you know even if you think about something as crude as chemotherapy it is something as crude as chemotherapy it is something as crude as chemotherapy it is not hard to kill a cancer cell with a not hard to kill a cancer cell with a not hard to kill a cancer cell with a chemical that's trivial it's hard to chemical that's trivial it's hard to chemical that's trivial it's hard to kill a cancer cell and not a normal cell kill a cancer cell and not a normal cell kill a cancer cell and not a normal cell and that's why chemotherapy obviously and that's why chemotherapy obviously and that's why chemotherapy obviously targets rapidly dividing cells and it's targets rapidly dividing cells and it's targets rapidly dividing cells and it's still very crude but the stuff we're still very crude but the stuff we're still very crude but the stuff we're talking about is like taking that to the talking about is like taking that to the talking about is like taking that to the next level which is how could you get next level which is how could you get next level which is how could you get this enzyme to work more efficiently but this enzyme to work more efficiently but this enzyme to work more efficiently but in this subset of cell you know just in in this subset of cell you know just in in this subset of cell you know just in the muscle but not in the fat or not in the muscle but not in the fat or not in the muscle but not in the fat or not in the liver in there yeah and that's again the liver in there yeah and that's again the liver in there yeah and that's again where the fasting is just so impressive where the fasting is just so impressive where the fasting is just so impressive to me the fact that you know all the

1:46to me the fact that you know all the to me the fact that you know all the normal cells is you're enhancing all normal cells is you're enhancing all normal cells is you're enhancing all these stress response pathways so the these stress response pathways so the these stress response pathways so the chemo drug becomes that much more or chemo drug becomes that much more or chemo drug becomes that much more or less almost less you know efficacious less almost less you know efficacious less almost less you know efficacious like it's like almost like a lower dose like it's like almost like a lower dose like it's like almost like a lower dose because it's like got these robust because it's like got these robust because it's like got these robust anti-apoptotic in anti stress response anti-apoptotic in anti stress response anti-apoptotic in anti stress response genes that are dealing with that sort of genes that are dealing with that sort of genes that are dealing with that sort of stress and so it's like it can take the stress and so it's like it can take the stress and so it's like it can take the toxic and sole because of that toxic and sole because of that toxic and sole because of that upregulation that fasting is doing and upregulation that fasting is doing and upregulation that fasting is doing and the cancer cells just can so I'm I'm so the cancer cells just can so I'm I'm so the cancer cells just can so I'm I'm so glad that that works being done I hope glad that that works being done I hope glad that that works being done I hope that there is more funding that goes in that there is more funding that goes in that there is more funding that goes in that area I think that it is a really that area I think that it is a really that area I think that it is a really important important important area of research again like I said with area of research again like I said with area of research again like I said with it you know this is and this is all from it you know this is and this is all from it you know this is and this is all from from vaulters working some of some of from vaulters working some of some of from vaulters working some of some of his colleagues so I'm just kind of like his colleagues so I'm just kind of like his colleagues so I'm just kind of like the fangirl you know but I'm certainly the fangirl you know but I'm certainly the fangirl you know but I'm certainly I'm happy someone's doing that research I'm happy someone's doing that research I'm happy someone's doing that research and I would love to see that be used as and I would love to see that be used as and I would love to see that be used as a standard of care someday for sure so a standard of care someday for sure so a standard of care someday for sure so Rhonda many of the people listening to Rhonda many of the people listening to Rhonda many of the people listening to this will know everything about where to this will know everything about where to this will know everything about where to find you but for the let's assume find you but for the let's assume find you but for the let's assume there's someone here who this is their there's someone here who this is their there's someone here who this is their first time meeting you where can they first time meeting you where can they first time meeting you where can they learn more about you and how can they learn more about you and how can they learn more about you and how can they interact with you I have a podcast interact with you I have a podcast interact with you I have a podcast it's called found my fitness you can it's called found my fitness you can it's called found my fitness you can find it on iTunes and on my website

1:47find it on iTunes and on my website find it on iTunes and on my website found my fitness comm all the episode found my fitness comm all the episode found my fitness comm all the episode pages there with links to the video pages there with links to the video pages there with links to the video which and your videos are remarkable which and your videos are remarkable which and your videos are remarkable because you put so much work into because you put so much work into because you put so much work into actually like a podcast like this actually like a podcast like this actually like a podcast like this unfortunately we're too lazy like I'm unfortunately we're too lazy like I'm unfortunately we're too lazy like I'm not gonna actually do much except create not gonna actually do much except create not gonna actually do much except create show notes but on yours it's like it's show notes but on yours it's like it's show notes but on yours it's like it's like a Khan Academy right it's like like a Khan Academy right it's like like a Khan Academy right it's like everything is being explained in the everything is being explained in the everything is being explained in the video as well like yeah any text video as well like yeah any text video as well like yeah any text explaining the figures definitions and explaining the figures definitions and explaining the figures definitions and all that are there in the video and also all that are there in the video and also all that are there in the video and also on I think we're having now definitions on I think we're having now definitions on I think we're having now definitions and stuff on the website so people can and stuff on the website so people can and stuff on the website so people can the the goal is to definitely showcase the the goal is to definitely showcase the the goal is to definitely showcase you know a lot of the the researchers you know a lot of the the researchers you know a lot of the the researchers and scientists that I interview and also and scientists that I interview and also and scientists that I interview and also to educate people as well so found my to educate people as well so found my to educate people as well so found my fitness someone iTunes and my website fitness someone iTunes and my website fitness someone iTunes and my website and social media you can find me on and and social media you can find me on and and social media you can find me on and what do you like most is Twitter the what do you like most is Twitter the what do you like most is Twitter the easiest place for people to get better easiest place for people to get better easiest place for people to get better Facebook Instagram I'm all over yeah and Facebook Instagram I'm all over yeah and Facebook Instagram I'm all over yeah and what's your handle found my fitness what's your handle found my fitness what's your handle found my fitness that's all for my fitness that's all for my fitness that's all for my fitness yeah so you were ahead of me on this yeah so you were ahead of me on this yeah so you were ahead of me on this like you you immediately recognized the like you you immediately recognized the like you you immediately recognized the value of exercise I'm a late comer to value of exercise I'm a late comer to value of exercise I'm a late comer to this I mostly from from personal

1:48this I mostly from from personal this I mostly from from personal experience I realized I was like this is experience I realized I was like this is experience I realized I was like this is like this is great for my brain and from like this is great for my brain and from like this is great for my brain and from there I just kind of dove into it it was there I just kind of dove into it it was there I just kind of dove into it it was convinced yeah for sure Rhonda I can't convinced yeah for sure Rhonda I can't convinced yeah for sure Rhonda I can't thank you enough this has been awesome I thank you enough this has been awesome I thank you enough this has been awesome I don't suspect it's the last time we'll don't suspect it's the last time we'll don't suspect it's the last time we'll talk about this stuff so until next time talk about this stuff so until next time talk about this stuff so until next time awesome awesome awesome you can find all of this information and you can find all of this information and you can find all of this information and more at Peter Tiye MD com forward slash more at Peter Tiye MD com forward slash more at Peter Tiye MD com forward slash podcast there you'll find the show notes podcast there you'll find the show notes podcast there you'll find the show notes readings and links related to this readings and links related to this readings and links related to this episode you can also find my blog and episode you can also find my blog and episode you can also find my blog and the nerd Safari at Peter TMD com the nerd Safari at Peter TMD com the nerd Safari at Peter TMD com what's a nerd Safari you ask just click what's a nerd Safari you ask just click what's a nerd Safari you ask just click on the link at the top of the site to on the link at the top of the site to on the link at the top of the site to learn more maybe the simplest thing to learn more maybe the simplest thing to learn more maybe the simplest thing to do is to sign up for my subjective lean do is to sign up for my subjective lean do is to sign up for my subjective lean on lame once a week email where I'll on lame once a week email where I'll on lame once a week email where I'll update you on what I've been up to the update you on what I've been up to the update you on what I've been up to the most interesting papers I've read and most interesting papers I've read and most interesting papers I've read and all things related to longevity all things related to longevity all things related to longevity science performance sleep etc on social science performance sleep etc on social science performance sleep etc on social you can find me on Twitter Instagram and you can find me on Twitter Instagram and you can find me on Twitter Instagram and Facebook all with the ID Peter attea MD Facebook all with the ID Peter attea MD Facebook all with the ID Peter attea MD but usually Twitter is the best way to but usually Twitter is the best way to but usually Twitter is the best way to reach me to share your questions and reach me to share your questions and reach me to share your questions and comments now for the obligatory comments now for the obligatory comments now for the obligatory disclaimer this podcast is for general

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02 Rhonda Patrick Ph D paradox of IGF 1 ketogenic diets and genetics benefits of