Health, Aging & Nutrition | The Proof’s 2024 Science-Based Blueprint for Longevity | The Proof EP346

welcome to the best of 2024 on the proof this year we have journeyed through a diverse array of topics with a very impressive lineup of guests delving into science-based strategies for fat loss with Alan Aragon exploring the science of Aging with Nobel Prize winner Dr vinki ramakrishnan and gaining insights into Women's Health with DOs Alysa Olen and Jen Gunter we've tackled protein Omega-3s eggs redefined wealth and even examine the role of relationships in our pursuit of a happier healthier life all of this literally all of this made possible because of you thank you so much

for tuning in engaging with the episodes sharing them with friends and family members supporting our show Partners like 38 teror and momentus and most of all hanging out with me each week or as my mom says putting up with me your curiosity and commitment to Better Health makes this journey incredibly rewarding and meaningful as we embrace the new year I want to leave you with a thought from Robin Sharma all change is hard at first messy in the middle and gorgeous at the end with that keep going enjoy this episode and from my heart to

yours I wish you all the best in 2025 the average person out there right let's let's think about that Avatar so they are overweight or obese so they have excessive osity fat and would you agree they're probably under muscled due to the sedentary lifestyle that they're leaving living and perhaps not completely optimizing protein yeah so where do we where do we start if we're thinking about setting up that person's kind of nutritional framework and and before we get into the actual practicalities of that perhaps emphasize you what what's the problem with a suboptimal body composition

how is that affecting our health or risk of chronic disease why do we actually want to work on this in the first place okay so there's functional um issues and metabolic issues with for example just just looking at the muscle mass side of things being under muscled so the the reason why we would want to focus on increasing and preserving muscle mass and strength especially as as people advance in age is because muscle preserves metabolic function muscle mass a lot of the the the good stuff that happens within the engine of the the body happens

within muscle tissue as far as fuel use fuel partitioning energy use all that um the building of strength would cover the neuromuscular side that makes us functional that prevents Falls prevents uh you know the the complications of of Falls later in life and so you need both of those things so in order to achieve both of those things you need proper nutrition uh holistically not just protein wise but protein and energy and uh essential nutrition good food selection and all of that stuff uh so that's why it is just it's so important and if you

collect body fat in excess then this can actually well it it antagonize antagonizes Health in a number of ways but um when you carry excess body fat this can actually impair the process of increasing and preserving muscle as well and the roots of that are probably as far as we we can hypothesize the roots of that are in a chronic inflammation type of State okay so let's imagine there's someone sitting here with us now and they they want to lose body fat they've listen to everything we've spoken about so far and they they have a

pretty good grip on where they're going to set their protein intake at a high level understanding that resistance training is going to be important we haven't really deep dived that let's just put that to the side that might even be another episode right uh but they want to lose weight so how how important is it for them to think about the energy within their diet and how do they how do they begin that process oh man it's tough it's tough a at at a very simplistic level people have to understand that no matter what your

food selection is I mean you can choose the the most heralded superfoods on the planet you can choose the the the foods with the most accolades and and the most hype behind them as being the healthiest possible foods but people have to understand that unless you are burning more calories than taking it over time you're not going to lose body weight um and so if people understand that from the outset then they have this vague idea that okay I can't eat an unlimited amount of these in quotes healthy foods there has to be some sort

of checks and Balan system on there for me to eat a certain amount now this can be done purposely or it can be done by default but people have to realize when I'm consuming more more protein I'm doing it because I'm trying to increase satiety and control hunger when I'm consuming more let's say unrefined plant foods to get fiber I'm doing that not just for the various health reasons but also that will default me to eating fewer calories because I'll be more satiated that stuff will displace the energy dense type of junk foods that I

would have been eating and at the end of the day at the end of the week it helps me eat less and so there are hyper quantitative and precise ways that you can eat fewer calories per day or per week or there are just a little bit more qualitative ways to do it by eating more of certain foods and less of other foods with the understanding that I'm trying to eat fewer calories by the end of the week it's totally okay to know that this is calorie game and it's totally okay to know for the

more sophisticated folks I'm really trying to lose body fat while hanging onto as much lean mass as possible right so there's a couple different paths you can kind of go down yeah depending on your personality I guess yeah what's going to help you adhere to this best uh is there a rate of weight loss that we're looking for that you would say is safest or the most effective is it possible that if you're losing weight too quickly that that could have a negative effect yeah this has actually been looked at um by G and colleagues

who compared a 1.4% drop per week in body weight with a 7% drop per week in body weight and so you know if you do the math on that with it's going to be like a oh roughly uh 2ish pound two three pound drop with like one to two-ish Pound Drop per week um well more like yeah more more like one pound two two PBS versus one pish so the rapid loss versus a slower loss and the slower loss in this particular population who were athletes were lean athletes they preserved more lean body mass with

the slower rate of weight loss um I did a review paper with with some colleagues like almost N9 years ago now where we issued the recommendation of limiting weight loss to 0.5 to 1.0% of your total body weight per week and this was within the context of preserving a maximum amount of muscle tissue while losing fat in the contest prep context and that actually does apply to the general population as well um I think that getting down to a very simplistic heris with this most people would want to keep their weight loss to 1 to

2 lounds a week and viewing one to two pounds a week as actually fast weight loss is is a healthy thing to do because I mean if you can imagine 50 to 100 pounds lost a a year is is tremendous so um even though in the literature it kind of comes down to this 0.5 to 1.0% of total body weight loss per week I think we can even focus a little bit more on the on the lower end of that half a percent of total body weight per week is perfectly fine and in some of

the literature it shows that quick weight loss at the beginning in the obese population is correlated with greater weight loss and weight loss maintenance in the long term I still think that if we look at it in terms of percentages like that you probably most people probably wouldn't want want to lose more than 1% of their total body weight per week as a goal that's as aggressive as you need to go let me share three important takeaways from this study number one animal protein was associated with increased odds of developing one or more of the

11 chronic diseases you can see that in table three number two animal and plant protein were associated with not having physical limitations but while animal protein increased someone's odds of not being physically limited by 5% Dairy protein did so by 8% and plant protein did so by 41% you can also see that in table three number three and perhaps most important replacing 3% of energy from animal protein with plant protein increased one's odds of healthy aging by 38% you can see that in Figure 1 and supplementary table 4 with all of this in mind I

really do not see how this study is positive for animal protein and if it is it's Dairy protein not animal protein in general later in the video Lane brings up sarcopenia one of the biggest detrimental effects during aging is sarcopenia in fact after age 65 you can tie many many many deaths back to a lack of muscle mass I agree with Lane that sarcopenia is a real problem and that protein is important for avoiding age related muscle and strength loss that we need to keep people physically fit and active and that sceletal muscle and being

strong can help someone avoid chronic disease but I don't think Lane is appreciating the fact that chronic disease itself is a huge risk factor for living a sedentary lifestyle and developing psyopia in the first place when people get cardiometabolic issues or cancer they become less active so this is a bidirectional relationship that's why in my view you need to be optimizing for both chronic disease risk and physical function to truly promote healthy aging remember animal protein in this study was associated with increased odds of having chronic disease and plant protein was associated with the highest

odds of not being physically impaired that's some of the key data points that Lan seem to overlook accordingly based on this study and The Wider body of evidence looking at cardiometabolic disease the best way to optimize for chronic disease and physical function is to ensure that number one you get a good amount of protein in your diet each day in the vicinity of 1.2 to 1.6 G per kilogram number two have a bias towards plant proteins sources and number three do resistance training two to three times per week now how is the average person doing

when it comes to these three things that is a great question let's go back through those three points so for number one the average adult gets about 1 to 1.2 g of protein per kilogram so there's moderate room for improvement or optimization especially for elderly or vegetarians or vegans who tend to fall at the low end of that range number two 70 to 85% of the average protein comes from animal protein so lots of improvement here number three about 70% of adults in the USA fail to meet resistance training guidelines again lots of room for

improvement here so most Focus really needs to be on doing resistance training and replacing calories from animal protein with plant protein then we'll be moving towards a society that has lower cardio metabolic disease risk and lower risk of psyopia and physical impairment does everyone need to stop eating all animal protein and become vegan no of course not and that is not what this study shows or my position but dialing back animal protein for plant protein is a favorable move not just because of this study but plenty of other studies like this metaanalysis of 31 cohort

studies I'm showing on screen with a combined total of over 700,000 people whose conclusion was intake of plant protein can be increased relatively easily by replacing animal protein and could have a large effect on longevity for those of you who are eating some animal protein and I'm drawing from this recent Harvard study that we've discussed today and the broader literature fatty fish eggs and fermented cheese yogurt would be the best animal proteins to include from a cardi metabolic Health point of view a pretty sensible set of guidelines to refer to that summarize this and more

the Danish dietary guidelines 30 303 I've mentioned it a few times people are probably thinking what the hell are they talking about by this point so what is the 30 303 study that you're planning and and then perhaps we can you know jump in and talk to the specific elements of this framework that as we just mentioned are kind of aimed at reducing that hunger Gap and I guess essentially making it easier for people to lose weight and keep and kind of going back back to the implementation part of it so as we've mentioned several

times now um lifestyle change is difficult and some people do really well for a little bit but then Wayne at their motivation or life happens or whatever so trying to come up with something that is simple for them to follow um definitely based on evidence that we have from studies that show we can help people with satiety um through what they're choosing to eat obious vious L lots of evidence about the benefits of exercise some of what we've talked about already today so it's really looking at a program that was Kevin's idea and he can

share his other acronym that he shares but uh I can never remember but 30 30 30 is way easier so 30 uh grams of protein per meale 30 grams of fiber per day and 30 minutes of exercise per day is our 30330 I love that you chose three things that I think are the least controversial I mean there's still controversy probably in certain extreme ends of the nutrition World maybe in the fiber fiber element there's Carnival saying you don't need any fiber and there's probably some people that are staunchly opposed to protein but generally most

people would agree getting enough protein in the diet enough fiber and exercise are three three kind of good first steps yes and and the idea is to deal with both sides of the energy balance equation and so we've got pretty good evidence that higher protein in a meal will produce satiation and then satiety lasts a longer period of time so you you feel full longer can we just quickly Define satiety satiation and hunger because I know we're throwing those around right and and these are slightly they're related but different concepts so satiety is sort of

a feeling of fullness you you've eaten enough so satiation is the process of moving from you know wanting to eat to feeling full satiety is sort of how long that lasts hunger is that you have a physiological drive to eat I you know want food now so when we do studies to look at appetite we ask four questions we ask how full do you feel how hungry do you feel what is your desire to eat and then if you were to eat now how much do you think you would eat prospective consumption and these are

related Concepts but uh you know people who really specialize in this area will tell you that they're they're not identical and you can have situations where you have desire to eat but you're not really hungry um you can have other situations where you have a feeling of fullness um and it's not connected exactly to hunger or uh desire to eat so you know they are related but most people understand you know kind of the physiological sensation of hunger and most people also understand that desire to eat is not always connected to hunger so the old

you know uh example of that is you know there's always room for pie you know yeah it happens to me every night yeah I'm I'm on the couch watching Netflix I've eaten enough food I'm not hungry but for whatever reason I'll go to the kitchen and grab something else to eat exactly and uh you know after 400 p.m. average American consumes more than 50% of their calories after 4 p.m. so they tend to graze through the evening so it's not because they're ravenously hungry after 4 p.m. it's because they're lonely bored they watching TV you're

watching TV and do with your hands exactly so and it becomes a habit a routine routine um so with protein there's an interesting uh relationship of protein to hunger and fullness and what we've found and not everybody agrees with this so I have to say that you know very well-known people in the field you know say no you're full of it I just wrote down Bob rolls y so we come back so actually uh this is going to be very much related to the fiber component especially but with protein um what we found is that

if you add protein in exchange for carbohydrate in a meal you will get more satiation and greater satiety less hunger is that any type of carbohydrate or refin it it seems to be any kind of carbohydrate but um it's tied into the fiber component so it's a little bit complicated but for the most part the studies are gener generally replacing uh refined carbohydrate starches and sugars with protein and what we found is that under 20 grams in a meal doesn't move the needle at all when you get Beyond 20 grams you start to see this

satiating effect and when you get Beyond 30 grams it's always there and it doesn't really seem to be related to the person's body weight I would have expected that maybe a person who's 240 lbs would require 40 gam of protein whereas somebody who's 120 lb maybe requires only 15 g of protein but that's not what we've seen we've seen that we always see the effect when we get to 30 grams of protein or more so there some type of nutrient sensing that's independent of your body weight yes so that that seems to be the case

at least based on the studies that that we've done so when you replace carbohydrate with protein you get more satiety and uh so that's part of the story and the question is why well arni ASP um and colleagues uh in Scandinavia they have uh done studies on this and they show this dose response effect when you increase protein as an exchange for carbohydrate you get a higher glp1 response and then there's an interesting thing which is that the L cells in the small intestine are not evenly distributed and so you have more of them later

on in the small intestine and so if you can delay protein digestion until later in the small intestine that seems to help increase that glp1 response now glp1 is complicated because we know with glp1 receptor Agonist you're talking about super physiologic levels but then there's a class of drugs called the dpp4 Inhibitors and they basically just slow down the breakdown of glp is that a Cabos or is that no AC carbos is an alpha glucosidase inhibitor yeah um we can talk about that in a minute yeah let's come back to that because now that you're

talking about protein getting to the end of this the small intestine thinking about ways to slow down digestion yeah exactly so glp1 is released um these L cells are releasing glp1 but glp1 has like a two-minute halflife and it's mostly having effects locally but there's a lot of connection between the gut and the brain so you release glp1 that stimulates the vag nerve sends signals up to the brain and then you actually release glp1 in the brain but of course that's hard to study in humans hard to get people to volunteer for you know brain

biopsies and such so which presumably then dampens the drive to eat right dampens the drive to eat and and that's what arnost and others have shown um that you get this larger glp1 response you also have Gip glucose dependent inhib uh insulinotropic polypeptide also known as gastric inhibitory peptide and uh so I won't ask you to spell that one yeah gp1 Gip response go up with more protein so I think we have you know reasonable evidence to support that view even though not everyone agrees with it and so with more protein in a meal you

get more Sati but you have to get to 30 g of protein to consistently see that effect so you got to get to 30 G and then it's improved if you are able to slow down gastric emptying yes so well slow down digestion of the protein and so that's where some of the fiber comes in so as an example viscous fibers like what you get in you know viscous fibers that you might take as a laxative um like a psyllium husk or something cium husk um I try not to use you know brand names but

I'll say the brand name Metamucil that most people are familiar with and so that creates a gel in the intestine and so it slows down digestion because it protects the food from digestive enzymes it just creates a barrier and they uh don't digest as quickly and so it slows down digestion of carbohydrates Ates and proteins and so then you digest the proteins more slowly you get more protein reaching those um L cells and a higher glp1 response that's a hypothesis and then there's another element to it which is for fat which stimulates cck release cck

is a protein that slows gastric emptying um there's also hypothesis that when you have viscous fiber in combination with fat that that is causing the fat to be in contact with the intestinal wall longer and gives you a higher cck response which slows gastric emptying so protein and fiber may be synergistic in terms of helping to control appetite and then there are other things as well that we can talk about separately which is they also affect the other side of the energy balance equation energy expenditure yeah let's make sure we get to that I think

it was on our Zoom call that we did that was the first time I'd heard anyone talk about this interaction between protein and fiber in the same meal with regards to how it affects appetite right and and I will say that we need a lot more studies so these are hypotheses they're somewhat supported by the studies that we've done but we need a lot more to be more confident that this is really happening what does that look like from a a food point of view perspective if if someone's listening and thinking okay I've got a

good idea what 30 grams of protein looks like um and then the 30 G of fiber I'm presuming is not peral that's cross a day that's cross a day let's make that clear I like I thought I said day but def there's there's uh you mentioned there you know there's viscous fiber fiber is an umbrella term although sometimes it could be confused for a single thing there's lots of different types of fiber viscous nonviscous fermentable non pable um is is the simple guide of just getting 30 G from a variety of plants is that enough

to sort of satisfy the body's requirement for viscous fiber and these different types or does the individual need to be a little more specific and perhaps including certain foods that would take the Simplicity away Simon it would so it would be the next step underneath the the 333 framework and and honestly you know like 30 42 30 that's just you know people going have our time with that so 30 30 30 is a simplification we like to make it as simple as is practical right and I should also say for each of these it's at

least at least 30 grams of protein per meal at least 30 grams of fiber per day at least 30 minutes of exercise per day but you're right the the protein part I think people it will be fairly simple although I think some people would struggle as well so giving them options in terms of a protein supplement or something like that but I think with fiber you know just getting people to consume higher fiber foods is going to be important and we're considering maybe we do consider a fiber supplement to get them to the 30 gram

minimum um and and in particular I mean there are you know several foods like oats and barley for instance that have viscous fiber but you know to get the amounts of fiber that we're talking about is a bit of a challenge it can certainly be done with food alone but uh I think uh supplementation with something like Metamucil as an example might be helpful as well um just to make it more practical to do so what is the difference there between maximal and optimal how how do you define maximal versus optimal sure I mean you

could obviously go to Google and Define it but when I think about it from uh a protein metabolic standpoint um so a maximal intake is your only goal is trying to now again I study I do a lot of acute protein synthesis studies so I should make sure we're clear on what I'm talking about um and so what we do is we acutely will manipulate exercise nutrition then see how our muscles remodeling right and normally we are viewing remodeling through the lens of protein synthesis as opposed to breakdown and that's a could be a detailed

conversation in itself but what we see in healthy individuals protein synthesis is the major variable dictating net protein balance okay and if you want to build a bigger muscle or have even a higher metabolic quality of that muscle we need routine periods of a positive net protein balance okay so when I'm studying nutrition or exercise I'm studying to see how protein synthesis is changing and in healthy individuals that's generally given us a good compass for whether or not we're in a positive net protein balance the more more we can manipulate protein synthesis the better net

protein balances all right so protein synthesis another important thing to note is it's not a hypertrophic marker protein synthesis can be non-hypertrophic or hypertrophic in nature so I don't know what it's going to translate into obviously you'd have to run a training study to determine whether that stimulus that you're doing that this induced a large increase in protein synthesis is going to in fact build a bigger muscle but what we can tell you is that you're either expanding that protein pool or you're making renewing it making it higher quality right so protein synthesis comes in

various shapes and sizes and protein synthesis is not a hypertrophic marker I see that confused all the time people always like to say protein synthesis equals growth it never has and it never will it's a it's a remodeling ER and that comes in different forms okay so that's sort of setting the backdrop of defining this maximal question so if I'm trying to get a maximal output my only objective is trying to increase protein synthesis as large as possible and not worrying about any other consequence or any other metabolic fate right so you can eat food

protein in excess or maximally get a large rise in protein synthesis but it's going to be always coupled to a large rise in amino acid oxidation okay and generally you're going to see that oxidative output go up when you're using isolated food protein such as whe any isolated food protein because they're just too fast to get into circulation right so whenever you're using isolated protein powders you're trying to choose or pursue a maximal response okay I'm always more interested in an optimal response and so what an optimal response does it's thoughtful about what is the

other metabolic fate of the amino acids we just ingested the goal with an optimal response is get a large rise in protein synthesis with a little rise in oxidation so we're optimizing the food source right so it's easy to eat food protein in excess and get a large and protein synthesis but you're also wasting a lot is there any problem to that no friends if you're looking to sell products online Shopify is where you need to be sure you can list your product on various marketplaces today but there's a big advantage to having your own

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think we're getting a much better understanding so these these kinds of advice have been around for a long time you know everybody you can you can read uh the anatomist Galen uh from you know ancient uh from The Classical period and and you'll see in in Greek in ancient Greek uh the guy has written about benefits of exercise is so but I think what we're understanding now is what does exercise do and what exercise does is it uh helps with all of these factors involved in regeneration it can regenerate muscle muscle loss is a big

problem as we age and leading to Frailty and it can uh even be involved in regeneration of mitochondria uh so there are number of Pathways that are affected sleep sleep is when many of our repair and maintenance mechanisms operate there's a weird thing about sleep which I didn't realize until I read a very interesting book called why we sleep by Matthew Walker and that and of course once he mentioned it it was obvious that sleep is not just because we have a brain or eyes and we can close our eyes and go to sleep very

primitive animals even unicellular animals have the equivalent of sleep they circadian rhythm which is the the program of gene expression changes uh through the day and so it's a highly conserved process you would think sleep shouldn't evolutionarily exist because we're vulnerable to Predators right extremely in spite of that the fact that we need sleep and it's preserved means it's doing something really really important and some of it is is you know proper development and some of it is is this maintenance of repair during aging and diet of course we've talked about all these Pathways involved

in caloric restriction and and how an important diet is is is is beneficial and more than that a bad diet is also detrimental in many ways for example obesity turns on uh various Pathways which are in know which are harmful and I wouldn't have thought obesity would cause cancer but the link between obesity and cancer is very well established now uh and of course obesity and heart disease and diabetes is is very well known so so I think this Trio uh one thing that we we've learned in the last few decades is how this Trio

actually works in various ways we still don't understand all of the details and there's a lot of work going on but we understand some of the ways in which they affect our metabolis ISM to keep us healthier as we age and that you can think of them as a three-legged stool for example if you exercise you're more likely to sleep better you know if you sleep better you're also going to be less stressed and you're going to uh not overeat and you you maybe more feel more like exercising so they they tend to act in

a synergistic way a bit like a three-legged stool all supporting each other and beyond that they help you with things like stress uh which also uh is delerious for aging and these things I mean they do come with some cost but they're accessible to most to most of us particularly people that are listening to this show right now and have two hours to to spare to to listen to us yeah talk uh versus you know some of the things like Brian Johnson's doing that are extremely expensive yeah although I should say he probably does exercise

and watches diet these are the foundations and I think to his credit one of the thing that things that he uh really under lines and emphasizes to his community is that the majority of the things that we know will influence aging and improve your health span are either free or not that expensive relative to all of the speculative very expensive things that he's doing and that's a good it's a good reminder for people because you could kind of land in this place where you think gosh I just don't have the mains you know even in

the UK which has a National Health Service the life expectance the lifespan difference between the the top 10% and the bottom 10% in terms of wealth is over 10 years and in the US it's over 15 years and even even worse than that if you look at the health span the the difference in health span is almost double the difference in lifespan that means the poor are not only living shorter lives but they're living a bigger fraction of their lives unhealthy okay you know at the end of life and so we talked about these three

measures and how they come at no cost but you know a poor person who's holding down two jobs doesn't have the time time to prepare good food and as to eat on the run you know typically some fast food and as a result is also stressed and doesn't sleep well all these factors act against you if you're poor so it's it's okay to say they're free but they're only free to people who do have the time right that's still a privileged State still a privil I I I can acknowledge that we need to raise the

bars of society and improve quality of life across the board so they become more accessible yeah absolutely earlier you you mentioned that there are some species that live extraordinary extraordinarily long lives major Mitchell's cocko I think you wrote about yes that's in Australian yes I was I was pleasantly surprised to see that in there and and we spoke about the shark the the Greenland shark if we think about the biology of Aging some of these things we've gone through when you when you look at their cells and how they're behaving are they doing a better

job at repairing DNA and and so if you look at these animals many of the animals that are long lived have very slow metabolism for example the Greenland shark has a very slow metabolism uh another darling of Aging researchers with something called the naked mole rat also has a very slow metabolism and that then slows down a lot of the progression of Aging however uh well major Mell cocko doesn't have I mean it's a bird and flies around doesn't have a as slow metabolism one thing they' found with uh some of the whales that are

very long lived and recently the Greenland shark as well is they tend to have uh very extensive uh DNA repair mechanisms in fact where we may have one copy of a DNA repair Gene uh they might have multiple copies and so that's definitely a possibility that their uh ability to repair the fundamental damage you know at the very beginning DNA damage which then may lead to other kinds of uh problems uh are better dealt with and and and we don't know whether their ability to clear Dam AG you know these things called autophagy where we

clear out debris and un you know Mis dysfunctional uh components from the cell uh we don't know if that's better in these uh species or not so it's going to be interesting to study them but I'm not sure how much relevance that has for humans okay it's interesting as to study to see what's happening uh but then to how how would you implement that in in humans are we going to do gene therapy and clone in multiple copies of these DNA repair genes we don't know and we don't know uh whether that's safe and what

that what consequence that'll have uh so I I think uh right now it's in the realm of academic research while we're on cholesterol here kellyanne which was one of two new risk factors added to this latest report along with I think it was a vision loss or hearing lost one of those two um so I think people listening that are kind of following along and I appreciate this is quite detailed it's been covered in some previous episodes um but hopefully we're we're covering enough detail to help people kind of grab a hold of it they

might be thinking okay I understand that the lipoproteins in the periphery are distinct and separate from lipoproteins in the brain but then your saying high LDL cholesterol is a risk factor for dementia if if low density lipoproteins or APO containing lipoproteins like Tom and I have discussed previously which is probably a little more specific are not crossing the blood brain barrier and depositing cholesterol in brain circuitry within neurons uh how what's the proposed mechanism by which elevated ldo cholesterol in the periphery is having an effect on dementia yeah so just because it's not crossing the

blood brain barrier doesn't mean it's not accumulating in the blood vessels that feed the brain the small blood vessels the large inoc cranial vessels The KDs of course the brain needs two primary things to be healthy we're going to talk about the activation component but it also needs fuel fuel comes in the form of blood flow oxygen vitamins nutrition if you're cutting off glucose all those things if you're cutting off blood flow delivery to the brain because there's atherosclerotic disease that's obviously a problem in itself but also think about the downstream inflammatory inflammation that happens

with aoso disease in the periphery that inflammation while LDL isn't crossing the bloodb brain barrier we do know that that inflam can cross the bloodb brain barrier we do know that there's this relationship between High sensitivity CRP AOS orotic disease but also brain atrophy and dementia Tom do you have any other mechanisms there no I think you're exactly right high LDL cholesterol is usually associated with a bunch of other metabolic abnormalities and the most common cause of lipid apob disturbances nowadays is insulin resist resistance so uh is that part of the explanation why hey high

ldlc is associated with it town get real ugly Kelly and an and I discovered within the last year uh apob B you know we don't all produce the exact same type of apob there are variants of apob and some researchers have identified a couple of apob variants produced in the liver that if that's the type of apob you out in wrapping your particles that seems to be a compared to regular apob that is not of these variants is significantly associated with Alzheimer's disease again I don't think we know why what does is that a type

of apob that just is formed frust for atherosclerosis in the cranial arteries but there's always more to any study so there are different variants of apob they're rare so this is not the run-of- the-mill apob that most people have but there's more to the story as always okay folks just us again for another quick breakout there are a few points here that I really want to stick number one cholesterol levels in the brain are separate to the periphery although LDL cholesterol is a risk factor for dementia it's not that cholesterol in your blood that you

test on a blood test in these lowdensity lipoproteins crosses into the brain that does not happen number two high LDL cholesterol is thought to primarily increase risk of Dementia by causing atherosclerosis in arteries that Supply the brain with blood and therefore key nutrients this atherosclerosis in arteries supplying the brain with blood is also thought to increase inflammatory proteins that can cross the bloodb brain barrier and damage cells in the brain number three getting your LDL cholesterol or more specifically APO B to goal as early in life as possible is one of the most important things

that you can do do to prevent dementia the 2024 Lancet report suggests that one can reduce their risk of Dementia by 7% by addressing this single risk factor this can be achieved with lifestyle which I outlined in my recent video on dietary fats and or using lipid lowering medications depending on the person okay back to the episode to clarify a statement made in the 2024 Lancer report on preventing dementia that contradicts this idea that lowdensity lipoproteins or LDL do not cross the blood brain barrier there's a paragraph in this report that confuses me and I

suspect it will confuse others given what we've spoken about here about the blood brain barrier and cholesterol not Crossing it and it says excess brain cholesterol is associated with increased stroke risk and deposition of brain amalo beta and Tow suggesting a potential mechanism for the link between LDL cholesterol and dementia is that confusing to you too yeah and there's no peer review on that article because if I'm doing peer review how the hell would you measure brain cholesterol would be my first question and if they can't report that then how do you know there's too

much cholesterol in the brain you know so I think they confuse brain cholesterol with LDL cholesterol has to be my guess yeah I this is the same school of thought I came from before I met Tom thinking that you know LDL cholesterol goes into the brain but it it clearly doesn't so I think it's a a poorly worded sentence the kind of take-home Point here when we're considering LDL cholesterol is that even though it's in the periphery and lowdensity lipoproteins are not crossing the bloodb brain barrier it is advantageous from a dementia prevention point of

view to get ldo cholesterol down to a certain goal and maybe we can discuss what that looks like uh to prevent certain pathology in the periphery that can affect brain function brain health yeah and I this was one of the most modifiable risk factors in their report they attributed 7% of dementia cases to elevated ldlc cholesterol and I I think that that could be variable dependent on the person so maybe in an apoe4 carrier we're having high ldlc having high apob is a primary driver for their disease process that could be a huge huge portion

of their dementia prevention risk uh strategy and my two favorite preventive neurologists are very aggressive in making sure apob is controlled in their patients because it's one part of this uh scenario there what are your kind of just general views on dietary patents and and dementia prevention and if someone was you know wanting to look something up online is there like a resource that you would recommend so I also was very surprised and disappointed that diet didn't make it into one of their modifiable risk factors um especially because of the overwhelming evidence I think what's

really tricky and this is with a lot of these risk factors it's hard to study dietary interventions but there is a plethora of evidence that things like Ultra processed foods are bad for brain health and there's ample studies that support the Mediterranean and mind diet in terms of being associated with the lowest risk for cognitive decline and honestly Parkinson's too dementia Parkinson's all of them so I think that there is a brain healthy diet and I think if someone really wants to learn more about what foods May benefit the brain most they should read more

about the Mind diet right okay cool I think that was Professor Martha Morris I think she was the the main kind of uh creator of the Mind diet and and researched various studies um looking at how adherence to a mind diet affected risk of dementia so that's a good resource look up the Mind diet um and Martha mors I think even has a book on that what about supplements is there we've kind of spoken about DHA are there are there any like known supplements or isolated nutrients that you would be like yep people should definitely

be supplementing these to reduce their risk of dementia so there's no one supplement that I would recommend for everybody and the lanc commission also does not recommend any supplements that's not to say that I don't think that certain supplements can help somebody the right person at the right time at the right dose um so I'll just do a double click on since we talked about Omega-3s I'll do a double click on B vitamins I don't think that everyone needs to be supplementing B vitamins but we do understand that B vitamins are so important for various

neuronal processes and that people with B12 deficiency which may not even show up as deficiency um based on some labs have cognitive impairment and it's a reversible cause of dementia so B vitamin should really be optimized in everybody and if you aren't for various dietary reasons if you're vegan or vegetarian you may be low on B vitamin so it might be something that's worth considering um depending on your individual case but at minimum checking levels of B12 folate I know people are like no one's folate deficient yes they are are I've seen it and homosysteine

can be really helpful okay so you just touched on homosysteine that was my next question so you're you're looking like at blood work you're looking at homine and maybe some of these other markets like MMA which I know a lot of people order that to get a a deeper look at at B12 than just kind of standard serum B12 yeah and of course there are limitations with using homocystine and various reasons for why someone might have elevated homosysteine that have nothing to do with B vitamins but for a lot of people elevated homosysteine is related

to B vitamin deficiencies and elevated homocysteine is that is is that associated with increased risk of dementia is that something that if you say on a blood test you're like right we're going to try and find out what the root cause of that is yeah there have been lots of ss looking at this and um homoy High elevated levels of homosysteine are associated with brain atrophy on brain MRI specifically and the temporal lobe so another thing that we really think about um and whether that's the homosysteine itself or the homosysteine just a marker for other

Badness that's happening we don't know the answer to that but if it's something that we could correct with very lowrisk intervention I think it's worth exploring okay so nutrition to summarize check out the Mind diet uh look at look at that as just a kind of high level framework and then individualize it to to suit you um optimize omega-3 index could we say that yeah something talked about with Tom right so that could be and this so we you could go back to our last episode with Dr dpring and I've had other episodes on that

that could be achieved through your diet or some combination of of fatty fish and supplement um so there's different strategies depending on uh the individual there and then specific supplementation after that uh really just to be guided based on blood work and presentation there's no magic uh supplement out there at the moment unfortunately we do not have a magic pill to prevent Alzheimer's disease it sounds like it's not really an even playing field like some people are dealing with heightened relative to the next person is it is it that you you put on weight and

then as a result of that you become leap intolerant or is it that be it genetics or other reasons certain people are just more leap intolerant or have less jp1 sensitivity um from birth yes well this is a very good question um and we tend to uh to believe these days that and this is the our culture out there right that there should be no differences everybody's equal and we are equal and right but in terms of our genetics we are so similar but also so different right some of us have a predisposition right to

be more obese or to be less obese right or predisposition to develop diabetes even if you have obesity I mean let's let's go deeper if I may right um not each and every and we have realized that not each and every obesity is also the same so some of us have more or less storage space in their adpost tissue all of us have the subcutaneous adpost tissue I've heard people describe that as a personal fat threshold there is a threshold right so some of us have a small storage space like think about your apartment your

house right and you have your storage room right some people have little storage space others have plenty of it right so for those of of us who are fortunate to have a lot of storage space potentially in our subcutaneous [ __ ] tissue you can store their fat your body weight can increase and to the extent that fat remains where it is supposed to be in the subcutaneous OST tisue you have no medical problems so if it stays in the storage room not a problem not a problem but if it's overflowing into the living room

in the kitchen that's when you start creating problems right so about 20 22% of um people especially women maybe slightly more obese if fat is not uh spilling over in other organs we call them metabolically healthy obese could be chubby or obese there is no problem no need to treat them right but if the fat goes where it should not be liver can cause fatty liver disease can cause curosis and liver failure death over a period of decades right not over a period of months if it goes to muscle it causes insulin resistance for people

who are predisposed to to develop insulin resistance and the longer and the higher the degree of insulin resistance the higher the risk to develop diabetes if it goes to our vasculature it's the same process atherosclerosis atherosclerosis it goes to our brain right and cause inflammation uh neurocognitive decline Alzheimer's so you got to keep fat out of the muscle fat out of the arteries fat out of the liver fat out of the brain and the right and the the the the very first right and um most indicative marker is the belly fat intraabdominal fat right so

if you see intraabdominal fat you know that most probably you have fat in muscle you have fat in the liver you have ectopic fat once you understand where this liver fat comes from you can take actionable steps to reverse your metabolic Health to restore optimal metabolic Health depending on how long the fat has been accumulating there's a strong chance that you can turn things around before we get to what we can do about it now that you understand the physiology that underpins increasing liver and pancreatic fat and the onset of type 2 diabetes I want

to quickly answer two questions that may be on your mind number one why is it that two overweight people with the same body fatness can have different metabolic Health one with type 2 diabetes and one without and number two two how is it that one out of six people who develop type 2 diabetes have a normal BMI they aren't overweight this first scenario is explained by the personal fat threshold concept that we went through earlier two people that are overweight both of the same body fatness can have very different levels of fat inside their organs

person a may have a much greater capacity to store fat subcutaneously than person B so for a given amount of total body fat less fat enters person A's liver and pancreas and thus they're less like to develop type 2 diabetes of course if they gain more weight and exceed their personal fat threshold they too can develop type 2 diabetes but for that to happen it will take more body fat compared to person B it's also worth noting that just because person a does not have type 2 diabetes someone who may be described as having metabolically

healthy obesity it does not mean that they are at less risk of chronic disease than a normal weight person it's pretty well established in the literature and this is often a point of confusion that even someone who's classified as having metabolically healthy obesity is still at significantly higher risk of a number of chronic diseases compared to someone of normal BMI this second scenario also comes back to the personal fat threshold a minority of people have a very small subcutaneous fat storage compartment which means even at a normal BMI excess energy is stored within their organs

this is the person who develops pre-diabetes or type 2 diabetes who doesn't really look overweight from the outside side the good thing is in both context be it overweight or not people can put their type 2 diabetes into remission if they take action soon enough this brings us to the next crucial topic how to reduce ectopic and visceral fat stores to restore metabolic Health thanks to Professor Roy Taylor's research We Now understand that in many cases people can restore their metabolic Health even those with type 2 diabetes who are on the far right end of

the metabolic Health Spectrum the goal as you might now expect is getting fat out of your liver and pancreas and Roy Taylor's work has identified how much weight people need to lose on average to achieve this if someone is overweight or obese they need to lose approximately 15% of their body weight so if someone weighs 250 lb they would need to lose about 372b in order to get below their personal fat threshold and see these important biomarkers that we've discussed move into a more favorable Direction This of course needs to be done under medical supervision

because as the weight comes out of these organs and blood glucose control gets better you are going to very likely need a lower dose of blood glucose lowering medications the risk here is that if you lose this weight and don't titrate your dose down with your doctor you may end up with low blood glucose which can be very dangerous what I think is really interesting is that in Roy Taylor's trials it became clear that if people lost 15% of their body weight and kept the weight off they were able to stay free of diabetes even

if they were still overweight or obese What mattered was getting under their personal fat threshold to get enough fat out of the pancreas and liver of course if they were to regain that weight the diabetes would come back now you might be thinking you mentioned that one in six people with type 2 diabetes are not overweight is it really safe for them to lose 15% of their body weight great question actually until very recently it wasn't even understood if liver and pancreatic fat was to blame for type 2 diabetes in people with a normal BMI

just last year Roy Taylor and his team published a study called the Rune study that confirmed the twin cycle model applies to all people with type 2 diabetes even those who are a normal BMI the only difference is that these people do not need to lose 15% of their body weight to put type 2 diabetes into remission 70% of subjects in this study entered remission with an initial weight loss of 62% of their total body weight so for a 170 lb individual that's about 11 lb of weight loss and while we don't have this data

these weight loss targets would presumably be even less if someone had pre-diabetes the same principle applies weight loss is required to get below your personal fat threshold how much weight will depend on your starting point but really one should work with their doctor and be guided by biomarkers hba1c fasting blood glucose apob waste a height ratio HDL cholesterol and blood pressure when we're trying to optimize metabolic Health we're looking to normalize these markers as blood glucose lowering medications are titrated down while one could do a myriad of scans to quantify fat in their liver and

pancreas it's really the normalization of these markers that matters most they tell you that there is less fat in the liver and pancreas and their function is normal or improving and moving towards normal before we discuss how to lose weight it's really important to note the importance of timing here the earlier you get below your personal fat threshold the better in these studies people who have had type 2 diabetes for a few years are much much more likely to reverse the condition than those who have had type 2 diabetes for 10 or more years much

of this comes down to the health of the pancreas if the beta cells are still functional which is often the case when someone has had type 2 diabetes for only a few years with weight loss they can come off all blood glucose lowering medications however it is common for people who have had diabetes for over 10 years that those beta cells are completely dysfunctional and they won't regain function with weight loss this doesn't mean that weight loss for this person isn't helpful it still is but they may still require insulin and other blood glucose lowering

drugs to make up for that loss of pancreatic function this episode is proudly brought to you by Nord V VPN my go-to VPN for secure internet browsing at home or on the go a VPN or virtual private Network creates a private secure Connection by routing your internet traffic through a middleman server protecting your data from hackers this is especially important on public Wi-Fi places like airports or hotels cafes places that I tend to be quite regularly where our information is most most vulnerable Beyond protecting you from risks like identity and credit card fraud nordvpn is

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nordvpn.com slthe prooof our link will also give you four extra months on the 2-year plan there's no risk with nord's 30-day money back guarantee you can find this link in the Epis so description when you say uh high risk CU I I realize we haven't really defined this yet but let's say someone goes out and they do measure nanomoles per liter so they get a a kind of particle count and I've looked at risk thresholds from different consensus guidelines it seems to be a little different across the the world with you know some guidelines suggesting

anything over 100 nanom per liter is kind of you're in high-risk territory some saying over 125 nanomoles per liter so I'll get you to comment on what you think is high risk but then also Tom what how is that affecting because here we're talking about atherosclerosis I want to come back to aortic valve complications which because you kind of said at the beginning we need to treat these two separately but if we think about what we would say is an elevated LP little a whatever that figure is how much is that increasing someone's risk of

atherosclerosis well you're going to be speaking in generalities just like with high aob B there are some people who got scary levels and they don't seem to manifest AOS scris they're a minority but as scary as LP little a is which I started off the first statement it's the most inheritable uh cause of atherosclerosis is there are people with high LP little a who do not get Arcos or aortic stenosis if you're a clinician and you measure and it's very high you should assume that person is going to be a very high risk but one

day perhaps and I think it will come with accessory tests that we can evaluate my God you're the one person with very high LP little a we don't have to worry about but for now let's use what is considered you're in the danger zone or you're not with LP little a and there would be two sets of matric metrics depending whether you're looking at milligrams per decil LP a mass or molar concentrations LP a particle number so uh with the mass normal is considered under 30 milligrams per deciliter but the guidelines will tell you ah

you're not going to be in big trouble until it starts hitting 50 milligrams per deciliter and maybe even when it gets to 70 that's the really high risk would help and but you know the 30th 30 milligrams per deciliter is the 70th percentile of the human race so that's a pretty high thresold and you know when you're starting to talk 50 and 70 you're you're into the 90th percentiles of what they should they they should be scary levels uh with respect to particle counts normal would be an LP little a particle number under 15 animals

per liter and the guidelines will and they differ a little bit as you said you might see 100 nanal per liter 125 nanal per liter as oh my God you're now in the high risk territory cuz you're starting to approach the 80th and 90th percentiles of LP little a in the population now there are some people who go up to 200 300 I I mean there are some oddballs out there with 500 or 600 nanal per liter but I I don't know are they at that much more risk than the people who have 250 15

animals per liter before I said well maybe the super extreme ones would have a little worry for Venus thrombosis too but I think they're AOS scerotic risk is very high like everything else it's B there have been Suggestions by some of the experts no guideline says it per se but if we had two people with the exact same uh high it's in the highrisk territory is there way of saying who would even be higher risk you basically start looking at other risk factors so if you also have an extremely high LDL cholesterol non-hl cholesterol apob

beyond your LP little a if you have hypertension if you're a smoker if if you have coagulation disorders diabetes they would make whatever a given LP little a number is worse but that's almost true with apob too so if you had an isolated apob and I subsequently found out oh my God you're hypertensive diabetic you know strong family history you'd worry about that apob b a little bit more so it can be influenced by what else you might be dealing with with a person but those are the numbers that at least would scale you into

the lower intermediate or higher risk Zone with LP little a Tomas if someone's listening and thinking okay I I haven't measured LP little a and I've heard Tom say that LP little a is one of the these apob containing lipoproteins it falls into that family and they have measured apob and it is optimal so let's say it's physiologic it's I don't know 30 to 50 milligram per deciliter or even lower and let's just presume in this um example that we're talking about someone with amazing genes or someone that's taking lipid lowering drugs to get down

to that level and they're thinking well I've kind of measured a b and LP little a Falls underneath that umbrella is there a need for me to even go out and measure LP little a uh the answer would be yes twofold one you can do Cascade testing in your first-degree relatives your children your brothers and sisters aunts and uncles say Hey you go get LP little a check so it is a an abnormal genetic uh Disorder so you can advise relatives to get it checked if you have discovered it uh but if you have an

apob B of 30 or or less here's where I think you still could be at risk and this comes out of the the two recent pcsk9 trials Fier and odyssey pcsk9 Inhibitors are basically the only drugs that are on the market that in addition to lowering APO lipoprotein B dramatically do lower APO lipoprotein little a concentrations in the 20 to 30% range and they looked at the fer area in the Odyssey trial when they gave those people obviously one got aload and the other trial ocad the two pcsk9 monoclonal antibodies that we use here and

they did notice that even once their ldlc and they was corrected if you also lowered LP little a there was additional lessening of residual risk additional event reduction and it seemed to optimize when you got the LDL cholesterol down to around 30 so for some reason maybe you have a genetic LDL cholesterol of 10 would High LP little a not matter I mean that would be a guess at this time and but uh and I I don't know that anybody has done a a genetic study to look at that but using what the pcsk9 inhibitor

is reducing it you got to really reduce it a lot and you know most people have elevated LDL cholesterol apob who are taking the standard lipid modulating drugs statins or aetam never reduce their LDL cholesterol below 50 some of them do their apob below 60 or 50 so LP little and those drugs would not be doing anything to LP little a even though you would say hey you've reached the ldlc goal under 70 of the guidelines LP little a is still causing residual risk we actually have data from the Staten trials that show that and

so that residual risk just to make sure I'm hearing that correctly so you can you can enroll subjects in a study who have pre-existing cardiovascular disease you can put them on lipid lowering drugs get them to goal so get their APO B down to 30 Mig per deciliter so LDL is right right down but there's still going to be some people that have cardiovascular events so are we saying here that it might be that those events that are occurring despite very low APO B could be driven by elevations in LP little a and the effect

that that is having on preexisting plaque yeah or it's LP little a is part of initiating plaque also not making existing plaque worse which it does but it's part of the initial atherogenesis Cascade also because of of what it's bringing into the artery wall basically starts the inflammatory process a lot sooner but uh there is another little part of the story that shows you how much perhaps you have to reduce uh lipoprotein little a it's from the mandelian studies where they certainly have shown its causal High LP little a is causal of both aortic disease

and the other aside the a calcific Aortic Stenosis but we're talking about AOS scerotic disease and you from the mandelian data you can deduce well how much do you really have to lower LP little a before all of a sudden the AOS scerotic signal disappears in the mandelian and the first one that was published was a big uh evaluation shows you probably have to reduce LP ltil a concentrations by 100 nanomoles per liter so that's excuse me 100 milligrams per deciliter so that's a big drop and even C sk9 Inhibitors which I just told you

do seem to reduce risk a bit not totally they're only reducing it by 20 30% you're never going to drop an LP little a by that magnitude with a pcsk9 inhibitor that will be the realm of the new drugs that are coming that we alluded to that interfere with the construction of LP littlea either genetically or with the marriage of apol little a to uh APO B within the liver so it would you you're pretty much always going to have to worry about LPA most doctors who are even treating lipid disorders are not lowering Lal

cholesteral to 30 or apob B to 30 some in the know are on the avanguard are but most are not they're saying hey if I can get your LDL cholesterol below 70 uh I'm doing a good job and one reason they say that is because to drive it any further you start have to adding a third and a fourth drug to to drop it so much with the current state and that gets to be problematic for a lot of reasons so there is residual risk the biggest trial that sort of showed that was first was

the Jupiter I think the heart protection also showed it is in the Jupiter trial which is a lot of people and they were tested with rzua Statin uh which is very good drug at lowering LDL cholesterol but they had a number of uh participants who had high LP little a uh most people know statins do not decrease LP little a so if you're going to give rosuvastatin to somebody with high LP little a you will reduce their Lal cholesterol their APO B of the non apol little a LDL particles but you won't reduce LP little

a mass or particle number but in the people with high LP little a ruas satin did lessen the occurrence of Mace now they didn't lessen it as much as they did as resua Statin to the people who didn't have high LP little a which just goes to show you lowering apob by itself for LDL cholesterol helps a lot but there will be residual risk if LP little a remains high and so you can't lower it with a Statin so statins are a key part of getting LDL cholesterol and apob of the regular ldls to go

but you're not going to solve any LP little a mediated pathology with a Statin aomi likewise has no effect on LP little a has a nice effect on apob and LDL cholesterol but you're going to have residual risk with that so uh that's why ultimately we're going to need apol litta lowering therapies and we will talk more about the pcsk9 whenever as to how that lowers hey little a lot of people including my friend Dr Paul saladino believe that apob is overhyped and suggest that instead we should be focusing on the triglyceride to HDL ratio

in Mill per decil as a proxy for insulin resistance Paul claims that you want your triglyceride to HDL ratio to be under two as an indication that you have good metabolic Health you're not suffering from insulin resistance and therefore you don't have to worry about your high apop or high LDL cholesterol his point being that whether or not apob or LDL cholesterol is atherogenic depends on context if you're metabolically healthy his position as far as I can tell is that you need not worry about about your APO or LDL cholesterol level he thinks we're blaming

the wrong thing for what it's worth let's entertain this notion that triglyceride to htl ratio is a marker of metabolic health for just a moment after converting my results to milligrams per deciliter my triglyceride to HL ratio is 1.1 well below Po's less than two recommendation back to Po's claim that its metabolic Health as indicated by triglyceride to HDL ratio or even HDL itself that matters not APO B I think we need to put this under the microscope now so you know that I'm not misrepresenting Paul trying to represent his position as best as possible

here he is discussing this very claim on the minimalist podcast if you look at the framing ham data overall as you go up it's a it's a straight line that kind of goes up to the right meaning the more cholesterol the more heart disease but if you break the cohort down by a third variable and that variable gives you some indication of your metabolic health or your insulin sensitivity a very different patter emerges and you get four lines based on the metric that I've seen used is HDL cholesterol so HDL is canonically thought of as

good cholesterol but it's much more complicated than that but in this case HDL is a good proxy for insulin sensitivity because generally people who are more insulin resistant which is synonymous with pre-diabetes and diabetes have lower HDL diabetics tend to waste HDL it's just human physiology that a pre-diabetic or diabetic State results in higher triglycerides and lower HDL so if you if you subfractionate the total toal cohort of the Framingham study by HDL you get four lines right HDL less than 25 or 25 or less HDL 25 to 50 HDL 50 to 75 or HDL

above 75 you can choose whatever cut offs you want and the people with the highest HDL there's essentially these are people who are going to have generally insulin sensitivity they're going to be metabolically healthy right people with the lowest HDL most likely to be diabetic pre-diabetic insulin resistant okay follow me so far y the people with highest HDL in the Framingham cohort have basically a straight line that's flat they don't have any connection between the amount of LDL in their body and the incidents of coronary heart disease oh wow the people with or like a

very very small UPS slope very small now please note before I get to my main point here something I want to make very clear is that Paul is referring in this clip to the Framingham study which is an observational population or epidemiology study the type of science that he usually says is highly unreliable the fact that he's decided decided here to support his argument well that's a story for another day let's keep going while there is definitely some truth to what Paul is saying that people with poor metabolic Health have a higher risk of coronary

artery disease he claimed that risk does not increase or only slightly increases as cholesterol goes up in metabolically healthy individuals is something I would disagree with Paul's own graph which he refers to in this clip and also in his episode on The Joe Rogan podcast shows this and I believe that graph comes from a 1977 paper published on the Framingham study as far as I can tell anyway for those watching on YouTube I've put the graph that Paul is referring to on screen and for those listening Along on audio I'll do my best to explain

it it's clear that the group with the highest HDL which Paul says suggests that they are most metabolically healthy still have an almost doubling in risk of coronary artery disease as their cholesterol goes up when you plot that group of subjects those with the highest HDL on a graph by themselves that doubling in Risk becomes more obvious which I'm showing on screen now sure granted that their risk isn't the same as someone who has poor metabolic health and high LDL cholesterol but that's kind of expected in one scenario you are stacking multiple risk factors and

the other you just have one to say that there's no increased risk in coronary artery disease or little increased risk with high cholesterol as long as you're insulin sensitive is just inaccurate furthermore and maybe Paul just missed this but there's a specific paper on the Framingham Offspring cohort published in 2016 so much more recent than the 1977 P by Hees sites which again shows that low LDL cholesterol results in a lower risk of coronary artery disease than high LDL cholesterol even in the context of high HDL cholesterol and low triglycerides I.E even when people are

metabolically healthy per pulse definition it's better to have lower LDL cholesterol one of the main reasons that high LDL cholesterol or apob still increases risk of atherosclerosis in metabolically healthy people is because the cells that line artery walls endothelial cells they can be compromised at specific locations in the arterial system simply due to the high press local environment that they're in unlike endothelial cells in veins which are in a much lower pressure environment this local environment is enough for APO containing lipoproteins like low density lipoproteins to cross into the artery wall become retained and Kickstart

an inflammatory process that leads to atherosclerosis cholesterol being deposited in the artery wall and this happens when apob or LDL cholesterol rises above those physiologic levels here's a quote from a recent review on this atherosclerotic lesions in the arterial tree often occur especially at bations I.E at sites exposed to turbulent blood flow leading to Mechanical sheer stress on the vessel wall that affects the endothelial cell homeostasis by for example pro-inflammatory activation interestingly lesions do not develop in veins under normal environment of low pressure and high flow but when veins are used as arterial bypass for

example A Auto coronary Venus bypass they may develop atherosclerotic lesions probably because they are subjected to high pressure end quote the take-home point being that at a certain concentration cholesterol on its own is enough to cause our throat sclerosis in arteries even with good metabolic health because arteries are prone to damage simply because they're arteries and blood is being pumped through them under high amounts of pressure keep ldo cholesterol down on to physiologic levels 20 to 40 mg per decil and there's not enough of these lipoproteins to pose a threat here's another quote from Peter

Libby preventative cardiologist and professor at Harvard Medical School that speaks to this and a quote if the entire population maintained LDL concentrations akin to those of a neonate or to those of adults of most other animal species atherosclerosis might well be an orphan disease meaning that AOS osis the number one cause of death globally would be incredibly rare with this in mind my view is to optimize both get aoba goal depending on your risk profile and be insulin sensitive I.E have good metabolic Health which per the results that I've just shared with you is what

my lifestyle has helped me achieve Paul's way of eating optimizes his insulin sensitivity but because of the large amounts of saturated fats that he's consuming it comes at the expense of his apob my way of eating optimizes insulin sensitivity and apob how do you feel about the whole cholesterol years concept have you seen that where it's it's kind of uh akin to pack years with cigarettes so kind of Lifetime exposure to cholesterol and I can kind of in I can remember a chart that I've seen in the paper and it's when you go over a

certain sort of thousand milligrams of per diler of uh cholesterol then you're at uh a stage where you I believe you may start to see symptomatic atherosclerotic cardiovascular disease have you seen that graph that I'm talking about I have it um I think conceptually it it makes a lot of sense um I actually have a have a Graphic that I use in my teaching that sort of uses the same concept um but I think in the clinic um it it it doesn't really resonate for me partly because you know I don't know what their levels

have been that whole time I would have to extrapolate based upon where they are now people you know LDL cholesterol levels don't change that much over time but they do change they change with puberty they change uh throughout adulthood there's a gradual increase and menopause big changes and uh and by the way when I say LDL cholesterol I'm also including APO we're going to come back to a which is meant to be what the I know that's okay uh yeah we we kind of digress a little bit there but um when in clinic would you

not order apob is there ever a scenario where LDL cholesterol non-hdl cholesterol HDL cholesterol and triglycerides tells you everything you need to know and there wouldn't be any kind of extra information that you would get from apob that would change your kind clinical management of that patient yes I think there are scaras where I don't need to know somebody's apob I I have to think about when that is um mostly my first thought about that is that it's after I've already established that their apob matches their LDL cholesterol so when it's so-called concordant with their

LDL cholesterol so if I if I can learn that from the LDL cholesterol uh the current standard now is that if I want to know somebody's apob I have to order that as a separate test and every time I order a separate test for an individual I generate a bill right the the lab is going to charge that person and their proxy money to to me do that measurement so someone has to pay for that and what percentage of the population would you say a correlates really well to LDL cholesterol I think the number is

around 75 to 80% okay that the discordance rate is somewhere in the and maybe I overstated that I think it's somewhere in the oneir kind of range I think I maybe overstated that so maybe 60 to 70% is concordant and so discordance in that say 25% or or whatever it is is when you measure their LDL cholesterol it's a certain number you then measure apob and that apob is dramatically lower or higher than you would have predicted discordance is not well defined in the medical literature I think I know it when I see it but

there's a lot of different ways that you can you can describe it when there's a major discordance it's it's obvious but there's also minor discordance so the the the concept of concordance or versus discordance is based upon populationbased tables so in our paper we described uh we looked at tables from three different dat sets the first one is the national health and nutrition survey the enhan and using data in untreated adults over the age of 18 between the years of 2005 to 2016 because that was the database that we had and in untreated individuals you

can form a data table of what the range of LDL cholesterol is in that population and it's a survey and I if I remember the number correctly it was something over 12,000 individuals in that in that data set so the you know the range of LDL cholesterol it may not you know you may not capture anybody with like rare diseases or anything but it's meant to be representative of the society at large and then you get a similar range of apob so that data set we had apob levels on all those all those individuals as

well and you can see whose level is in the fifth percentile for apob and the fifth percentile for LD cholesterol you can see who's in the 50th percentile for both you can see you know what the numbers are for the 75th percentile and so they you can create a table and put them next to each other and see if they line up so we made a table using uh desiles and um if somebody's in a different desile you could I suppose refer to them as being discordant so if you're in the 20th percentile for LDL

cholesterol the 30th percentile for APO B you're discordant mildly yeah but it probably doesn't matter biologically but if you're in the 20th percentile for LDL cholesterol and the 80th percentile for APO B it probably does matter so so the issue is if you I mean I'll get you to elaborate on this there's probably a couple different issues that could arise in clinic but I come in to see you uh I show you my LDL cholesterol it's let's say it's 80 milligrams per decer and you're thinking and let's say I'm untreated you're thinking well that's not

too high um could be lower but it's not it's not crazy high by any means you don't measure my apob you just assume that it's correlated Meanwhile my AP apob could be 120 130 so they're discordant and because apob is what really is determining risk not LDL cholesterol I'm now someone who's untreated with higher risk than you thought exactly that that's our that's one of my greatest fears is that we have untreated patients who we're undertreating because we think they look fine and you know that discordance if you don't measure apob you don't even know

that that's the case you can also do this with NMR and ion mobility and look at LDL particle number but in the you know I I don't want to get too much into that because I know less about uh measuring particle number than I do about apob B but APO B is a well validated reproducible inexpensive way to estimate the number of atherogenic lipoproteins and so we have these now now we have these populationbased tables that we can really look at that and we can do what are known as discordance analyses definitely not my expertise

in how those are done but there's a lot of different ways that discordance analyses have been done you you can look at above the mean versus below the mean and call that discordant but that also means that if you're in the 49th percentile for one in the 501 percentile for another you're discordant and that doesn't distinguish between 20th versus 80th unless you you know I'm sure there's some parameters to how that's done too but that's one way is just above versus below the mean for for n for numbers does it really matter if you're discordant

or not the kind of the label or is it just about getting LD and APO to some desirable level based on who you are oh yeah thank you for cutting right to that cuz because I to that that's actually where I was going which is I none of that really matters what I will tell you is that all the different discordance analyses that have been done have confirmed that if you're trying to predict who's has more residual risk on treatment apob is a much better tool for doing that whether you're using the older freeden wal

formula for calculating LDL cholesterol or the newer Martin Hopkins or Samson NIH formula it doesn't matter what LDL cholesterol formula you use apob B is still going to outperform LDL cholesterol this episode is proudly brought to you by 38 Tera try 38 tera's dmn Prebiotic the science-based daily multivitamin for your gut microbes a simple and delicious way to take your gut health to the next level now back in stock in new and improved packaging for customers living in the United States Australia and New Zealand get 10% off your dmn at 38 tera.com using the code

the proof that's 38t r.com and use the coupon code the proof for 10% off at a very high level when you say micro vessels what we're talking about here are you you said arterials so arterials which is uh kind of the end part of the system that's bringing blood towards some type of tissue capillaries and then uh venal venal yeah right so the capillaries are connecting the arterials and the venal yes okay and that's that's where the uh nutrient exchange kind of takes place M so the blood's flowing through the arterials into the capillaries it's

bringing um nutrients and and other important compounds and then the metabolic kind of byproducts waste products are carried away from the tissue from venal yeah in in venal which then coales into larger veins okay and then carry it back to Central circulation so you've said a few times these are really really really small so how how do you study those I know you said you canul them what does that mean how do we actually look inside some type of blood vessel that's thinner than a strand of human hair well if we're looking at the blood

vessel itself we we can dissect it out so with practice working under a dissection microscope with very fine um dissection instruments you can dissected away from tissue it's these another way of thinking of these small microcircuit blood vessels uh they're the ones that are inside the tissue um so you've got to get it away from the tissue to be able to to be able to look at it and we simply dissect it out and when I say cannulate we're taking small glass tubes and we're putting those glass tubes into the inside of the blood vessel

or the Lumen and then we take very fine suture and TI the wood vessel down onto that tube and we do that at both ends um so you've got this canulated vessel connected to two bits of glass which are then connected to pressure reservoirs to um keep a static pressure within the within the blood vessel and we can change that blood that pressure and we've spoken about some of the downstream I guess complications from microvascular dysfunction in people with diabetes so we spoke about neuropathy retinopathy what about outside of the setting of diabetes um if

you have dysfunction of of these small vessels supplying the heart tissue or sceletal muscle presumably we're seeing other complications in that setting yes we're we're learning more more and more about that um you uh cardiac events you think of obstruction of blood vessels um in the coronary circulation is is leading to some plar being disrupted and then going down and um blocking the small vessels but it's it's now realize that in a lot of cases when people come in with chest pain and they have to go to the catheterization laboratory to to be studied to

to look to see whether they should have a stent or something to unblock the arteries that a lot of people don't have any evidence of a blockage or a significant blockage and it's thought what H is happening is that there's dysfunction of the downstream microvessels and they're becoming over contractile and um which means they're constricting constrict more than they would in a physiologic set yes so in a pathophysiologic setting they tightening yeah so that you end up with um angina or ES schic pain within within the heart because you're not delivering the tissue which is

active enough uh enough nutrients so what's the what's the working hypothesis that would would explain why these small vessels that are kind of infiltrating heart tissue would constrict ases I come back to the function and health of the larger blood vessels I know you've spoken to me previously about like the stiffness of the big arteries affecting the small blood vessels this is probably a more functional um constriction within the blood vessels so that's going to occur in small arteries or arterials just above the capillaries and it's probably occurring because there's some sort of uh dysfunction

of the endothelium either it's inability to make a dilator like nitric oxide or that it's making an excessive amount of aaso constrictor which constricts the blood vessels as opposed to dilates them what would potentially explain why that's happening is that is that age related it changes is it genetics is there some type of modifiable risk factor like inflammation or insulin resistance you know what why would that be happening well it's probably a mixture of many many things but there um is certainly likely to be a uh inflammatory um um reactive oxygen species sort of uh

uh environment that's that's in CA causing it so some of those uh are potentially modified through modifiable through lifestyle can you get blockages in these small vessels so we often hear pretty much always he that atherosclerosis you know it's occurring in cred or coronary artery and they're much bigger in terms terms of diameter now presumably this whole system all the way from the big arteries down to the arterials are exposed to the same kind of APO containing lipoproteins or LDL cholesterol the same inflammatory proteins and I think if you were to kind of hypothesize without

knowing everything about the system you would think block blockages would probably first occur in the tiny tiny vessels that have a much smaller diameter um but then there's different environments in terms of pressure so like what what what explains why we see Aros sclerosis in bigger arteries not in arterials well there can be a number of uh different reasons but the physical forces and the flow patterns are different in those larger blood vessels so there are areas of the circulation that are more susceptible to the development of aristic plock um I think in reality that

you probably going to be seeing a mix of these two things that there is Aros orotic development it's just not at a point of um yeah critical blockage it's not explaining the angina what you're saying is in some cases the enginer yes is explained by the kind of collapse can is that is that an appropriate term no it's not collapse it's an active constriction active constriction yeah but subconscious yes you've got no control over it unfortunately um but you you you likely see interactions that occurring too between the the small vessels of the heart and

the larger vessels so that if you get this enhanced constriction of the uh um microcirculation it it wouldn't be surprising if that changes the pressure and flow patterns up Upstream um which could uh make vulnerable plaque or plaque that's more likely to come off so are there drugs that people are testing or have been clinically studied that could modulate that or uh attenuate some of that constriction um yeah people can take f phaso dilators um but in terms of um more specifically doing it I mean there are trials that are going on that are looking

at blocking anti-inflammatory events for example this probably also gets to the question that I often see from people that I think take the position that LDL cholesterol or apob containing proteins aren't really a problem um which is certainly a kind of anti-c consensus position I would say uh they they often say well why why don't we see blockages occurring in the Venus system why don't veins get artherosclerosis and I'm sure given your research into the pressure differences in in in vessels that's something that you've come across well the pressures and the the hemodynamic profiles are

very different but the cells are also very different if you um if if you if you do a uh um some some sort of screening profile where you look at the the makeup of the endothelial cells and the endothelium on a um a vein is is different from the endothelium on an artery so to assume that something because it happens in one part of the circulation and should happen in all parts of the circulation is it's it's doubtful when you say welfair or adequately fed we've kind of we've spoken a bit about carbohydrates but you

mentioned protein earlier I mean what are the foundations look like for you is it that you're do you like many people are here in this space kind of say set your protein get enough carves and then fill the rest with fat how do you approach this so I think yes I'm I'm very Pro moderate to high protein intake for women across the entire lifespan I think that that is something that many people neglect or struggle with I think a lot of women struggle to get enough protein intake in either because one your caloric needs are

lower so it's harder to have like almost a higher relative percent it feels like to you to get that in or that appetite might not be there or just not something that you historically have done um so I do think that having that like and I think there is some data that suggests that like you know females don't necessarily need all the way up to that 1 to 1.2 that sometimes is recommended so I'm okay with like that 08 to 0.9 up to 1.0 grams per pound of body weight you guys can do the kilo

Mass on my head yeah per pound you'll have to divide that by 2.2 so to speak or one gram per pound of lean body mass or about two grams per pound of kilo of lean body mass I think is also a helpful tool for people if you have body composition data and you know that as like a minimum like let's eat to at least support our lean mass I think that's more helpful with people who have a good bit of lean mass two grams per kilogram of lean body mass yeah give or take yeah which

is probably around 1.6 or a little bit higher grams per kilogram of total body yeah I would say that 1.6 to 1.8 is probably grams per kilo now that I like I'm like seeing a slide from my back in my head that I made Once on This for kilo is probably about that range I don't think that we have to go to that perfect one .0 or I think it's like or two grams per kilo of body weight for that I think that you know I've seen some data where it kind of flattens out on

the curve after that like 8ish for for women but it I think there's benefits across the entire lifespan for that but especially if you are struggling with your your hunger and satiety and you feel like you can't lose fat and you feel like you're not making progress in the gym and you're not recovering like that's usually a sign that hey maybe increasing my protein might help that CU it increases satiation um if you are someone who struggles with that hunger and satiety it's going to improve your exercise recovery you're going to be giving the amino

acids that your body needs um and then especially like when we think about you know the ludal phase or menopause like those are time periods where that's probably even more important to be more dialed in with that I'm of the stance that like you don't need to periodize your protein to your period because you just should eat enough all of the time um but you might need those higher demands but I think that that's that you know I have these Keith these like three key things that I think are the most important for for for

women and females and it's enough protein enough carbs and enough calories that doesn't mean to say fat isn't important um so to go back to your industry of like standard of like set the protein and let your carbs and fats kind of fall where they are I'm I think that's great for regular everyday people but if you're shifting that volume or intensity up on your training you're probably going to have to shift that carb preference little bi to to Cobbs which means dialing the fat down a little and dialing fat down a little bit and

so that's something I see a lot too especially like when I people struggle also too because they're like I gained weight when I train for a race or gain weight when I trained for a marathon or whatever that looks like and I'm like because you're hungry and you're not eating enough carbs and so your body's increasing that hunger because it it's wanting to recover and replenish and restore those but everything around us is hyper palatable and everything around us is high fat and I struggle with this right like I'm aware of this and I have

a really high carbohydrate demand and I joke I say fats fine me like no matter like I have to be super and I'm not restricting fats by any means but I still have to be super diligent that I'm not like blowing up my calories with fats when I know my body needs the carbs to support and recover me and so that's where I'm like okay as you start to shift past maybe those exercise guidelines if you're like two and a half hours a week in the exercise guidelines and you're regular person doing stuff just like

eat enough carbs to support yourself um but once you start getting into that okay I'm exercising three four five or if you're doing even more than that like you're training for that first marathon and you've never trained for a marathon before like you're going to have to shift that preference of that intake and it will make you feel Fuller you'll recover better you'll perform better you're going to feel better like it's really scary for people because the narrative around cards but I think it's really important for me to really reiterate that your body isn't just

storing these and causing these massive insulin spikes it's using them for to replenish your glycogen storage they're going into storage they're not even necessarily like I mean your body goes in and out of fat storage and burning throughout the day but they're you're you're refilling your glycogen stores or your body is using it for energy for recovery and repair it's not like I think that's a hard thing for people because they only think of food going in to be stored and turned to Fat rather than well your body is using that to to sustain and

fuel the recovery or performance or training that you are doing and again not everyone has those high performance goals but I see all the time I see my Jung pop clients to start training for the first half marathon or their marathon and that's the first really big spike in cardiovascular activity they've do done or they've always ran and they decide they're like hey I need to add in strength training and they're like why am I always under recovered or this is really hard or I'm not adapting and it's because they didn't adjust their food intake

to that increased demands on their body and that's where I kind of have that view of like don't bring a diet view to your training always make sure that you're feeding and feeling yourself for the activity that you're doing and that's not to say you can have fat loss goals but you probably shouldn't be training for a marathon and having a fat loss goal at the same time like that might be something that you need to separate so that you can focus on the thing that you need to be doing at the same time someone

listening yeah and she's like I just want to grow my booty yeah right so let's focus on one body part here one body part all right okay what principles does she need to be thinking about what does she need to adhere to follow in order to get that muscle group to respond yeah one I won't rant on this but I will say well because we just talked about this if you want to grow your butt you're gonna have to eat that's the first mistake that people make when they're trying to grow their butt it takes

a lot of calories to grow a butt so I'm just going to put that out there two you want to think about mechanical tension so mechanical tension is going to be the biggest driver of muscle growth and hypertrophy and that is putting tension on the muscle so it's it's it's essentially stretching to that load and then you want to think about really going through the full range of motion and getting the the most out of that tension when you're when you're doing strength training programs so you don't want to be doing like so for example

like the hip thrust is really popular for females and I I'm I'm transparently a little bit of a hip thrust hater I just don't really like it as much but I think that they they miss out on the fact that like that's a complement to things like that but you want to still be doing these training moves that are doing full range of motion that you can load heavy and put tension on the muscle that you're trying to go where that's like a that's a good example of like a partial range of motion or a

top range of motion focused exercise I don't think that what's the benefit or advantage of going like all the way to the end closer to the end of the yeah you're getting that full stretch of that muscle and a lot of the I'm and I'm not like the hypertrophy expert from what I know from this field though as though like that full range of motion is where you're getting the most benefit and most hypertrophy potential or the greatest results there's some stuff coming out now about like partials and if you should do short range or

long range but for 99% of individuals who aren't in that bodybuilding sphere doesn't matter like like for Mo especially the people that are probably listening to this and consuming this you don't need to get into the weeds of that because what we know makes you grow is going to be going through the full range em motion so we're talking like full range em motion squat patterns and it doesn't have to be just barbell squats it can be like your split squat or your lunges those are great for like glute development or lower body development which

I know a lot of women want to grow their lower body um or like full range emotion rdls or you know thinking about large muscle group activation getting the most bang for your buck and then yes like with things like the glutes you can refine like maybe you are doing some hip thrust as a complimenting or you're doing maybe some isolation stuff of you know the smaller muscle groups but the things that are going to get you the most bang for the buck are the movements that are going to take you through that full range

of motion and that you can load heavy like a heavy stepup is going to get you probably way more of a stimulus for growth than like your 30 lound banded gluc Ki back so to speak like you want to be able to put load and tension on that muscle and and then of course there's a component of volume that we talked about earlier which the load itself is part of the equation of volume so volume is going to be your reps and sets by load and then it's like essentially total tonnage or Pounds or kilos

that you essentially moved in that training session and you want to progress over time so the way that you do that is either you do more sets or you do more load and you don't want to sacrifice like load for intensity like you don't want to go to like 30% of your one rep max and not do it for enough reps in sets so to speak you still want to make sure it's a high enough for that stimulus um but and you can only really increase sets per week to a certain point where yeah you

know those workouts just become way too long and and I think that's there's a pretty big consensus like yeah you can go up to 20 or 20 plus high volume for Hy hyper sets per week and there's this big conversation around that right now but you don't necessarily need 20 sets per week to make something grow but you need it's more about the quality of the sets that you're doing and I think a lot of women fall into the Trap of doing a lot of quantity but not that quality because they and this isn't just

women like I I think everyone genp underloads their their weight training they don't lift heavy enough or they can do more than what they're doing is it normal for for uh women or people who m that spend time with one another for their Cycles to sink up no it's a myth everybody gets really upset about it seriously I'm like who do you think sponsoring me like big non period syncing um yeah it's a myth so where does that come from and if someone's like well hang on actually you know my girlfriends and I we we

all have our period at the same time like what's happening yeah so there's great explanations for it it says just a really fascinating social or cultural phenomenon so I don't know the history meaning did people believe it in the 1600s or do people believe in the 1800s I I don't really know but you have to also know that they didn't know about hormones and they didn't know about things so they they were just very concerned about making sure people menstruated because they thought it was a built-up of toxins so I don't think they were like

really specifically thinking about that maybe they weren't I don't know but in the early 80s there was a study that suggested that menstrual sinking or menstrual synchronicity that sounds like a like a album doesn't it like what's new album It's menstrual synchronicity it's dropping soon call me Taylor um so so this there was a study that suggested it now if you go back and look at the study that has some flaws with it and isn't you know probably wouldn't have been accepted today the way it was in the early 80s that's also pretty common from

a lot of studies right you know we learn more we you know have different methods we couldn't do hormone tests and things in the early 80s the way we can do them today so there's a lot of things that change it's been looked at by several different researchers since in larger studies with you know better design and hasn't shown and there's no biological reason it could happen so the people who propose it never propose a biologically plausible hypothesis so people what about pheromones well so no one has actually ever proven the existence of human pheromones

yet I know the perfume industry like everybody think otherwise but it's never been proven and Jen Gunter busting my left right and Center I'm so mean this is what people think I'm mean how dare you I know how dare I I and it's because we don't have a functioning vomero nasal organ so and that's what dogs and cats and animals that can detect pheromones have and so ours doesn't work so so what's traveling through the ether from me to somebody else and if you think about it on um on a different level I find it

really distasteful because it kind of makes women sound like they're seasonal breeders right that there's this alpha female that can drag all these other like Lester females into her menstrual orbit I don't know it just it whenever any so when you hear these myths very few people kind of follow them through to their logical conclusion so what does that really like if we keep going on that line of thinking what's that telling me and almost always when you go along that line of thinking it starts to sound like worse and worse and worse for how

you're talking about women sometimes it can sound like a nice story for example like in this example I've heard people say well the the ancestral or evolutionary explanation is that perhaps there was survival benefit if women were going through their pregnancy at the same time and giving birth to babies at the same time well so we would know it though because that wouldn't have been a trait that we would have lost so we would be seeing people coming in all the pregnancies happening at the same time and then for two or three weeks and labor

and Del like we would see that so so that's not something that happens and there's no biological basis for it your own body controls your cycle you have agency I don't mean that you think it to happen but your body is your own agency it's not somebody else isn't controlling you we don't ever say that about men we don't ever say that like wow testosterone is such a powerful hormone it can drag all men into having erections right slightly related yet unrelated uh it gets me thinking about is it is it accurate or is there

any truth to the idea that when a woman is on oral contraception on the pill her taste in men is different than if she was not taking the pill no have you heard that yeah I've heard it the research is not very solid there are other people who have disproven it and you know none of these studies control for reasons that people get divorced right so people might stop the pill because they're not planning on having sex with the guy that they dislike and are wanting to get divorced from right so stomping the pill had

nothing to do with oh wow I'm with the wrong man it was a planned decision because why would I take contraception for someone I'm not having sex with so there isn't any good data to support that and I think that people need to be very very careful making Grand proclamations based on not solid data at all there's no evidence to support it and of course all my friends I have a couple friends who've never taken any hormonal contraception they're like well how do I explain my three divorces you know you know and and and so

also that kind of positions men as not having responsibility in a relationship falling apart right it's all about you and your hormones really really really so yeah um like the grander the claim the more extravagant the claim the grander the evidence needs to be and it doesn't exist it seems to serve a very specific narrative um of uh of you know keeping people away from using medication that can be very useful for them so there's one other thing I'd like people to think about when they think about they believe that they've had menstrual sinking uh

is that think about a time when you've been driving and your windshield wipers are going and it's raining and the car in front of you windshield wipers are going and there's times where your wipers are matching up exactly with them and then there's times where they don't and then they match up again and then they don't and that's what's happening when you notice somebody's cycle being the same as yours you're only remembering the time where they are matching up because of random things this is a random change so if you have two events that are

occurring randomly they will match up at times and then they won't and then they will and then they won't but because of recall bias you just remember the times that they were but Jen I want to believe that when I look at my phone magically it's always 11-11 I know humans you know we're we are weird creatures and and we like to hold on to little beliefs and and again I just think that um it's I just believe it's important to have the facts because while we can say well what's the problem with having a

menstrual sinking myth okay well you know there isn't really a problem except well what if it makes one person feel like they're always submissive to the group what if one person's made to feel like they're always like following do you think that might like maybe affect them a little bit well that's a possibility and these myths and this is also an issue are weaponized by you know the wellness Movement by people trying to tell you that oh well you you shouldn't be on hormonal contraception because you're going to miss all these important rhythms that we

learn because of cycle sinking you know so it becomes part of this narrative that's very easily warped or used in another way so I just think it's that's why it's important to know so if you want to believe something that's not true about your body okay that's totally fine but just remember that these things are often misused by people who have ill intentions and so the chapter you mentioned is recruit a dead board of directors I think that is in the I think that's in the chapter the the fifth form of wealth which is money

and so you I think it's really important to spend your to surround yourself with people whose lives you want to be living and so if one of the forms of wealth is money and there's nothing wrong with it you know what I'm trying to to say in the book is money is only one of the eight forms of wealth but I'm not saying money is not important and it's dirty and there's something wrong with it you can do amazing things with Financial Freedom and the chapter is recruit a dead board of directors which is you

want to learn how to be a financial Tycoon read FR Frank Brady's book on Onasis you want to learn how to be forgiving read about Mother Teresa if you want to read about being an athlete read the books about from the great athletes so we often say well you know how do I do it or I'd love to have a mentor just go buy their books and recruit this dead board of directors to advise you and and read their books be influenced by their approach and their philosophy and their habits and then maybe if you

have a key Choice go into your quiet room close your eyes and ask this silent board of directors what their advice is and imagine what Mandela would say and Mahatma Gandhi and whoever it might be it's clever you mentioned Journal tactics and I if we don't cover that come back and cover it there'll be people saying in the comments section you had Robin charmer on and he mentioned Journal tactics and you didn't dig in what are what are the main Journal tactics that you would want to leave someone with how do you journal in a

way that is going to be most productive most influential on your life well I would say first of all do it every morning what you do daily is so much M more important than the few things you do annually Amen to that and and that's one of the most key things I I would humbly offer all of your viewers from around the world your days are your life in miniature if you want to predict your future look at what you're doing today okay let's bring this home with a summary the five key takeaways number one

eggs while low and saturated fat making up just 2 and a half% of the saturated fat in the average American diet do contain a significant amount of cholesterol about 200 Mig of dietary cholesterol per egg this can affect blood cholesterol levels differently depending depending on the individual about 30% of the population are considered cholesterol hyper absorbers meaning they absorb a larger amount of cholesterol from that diet potentially leading to higher blood cholesterol levels number two to determine if you're a hyper absorber of dietary cholesterol consider testing your phytosterol levels particularly beta cytool and campesterol this

can be done at various Labs worldwide and the results will help you tailor your dietry and health strategies number three if you're identified as a hyper absorber and have high apop lowering cholesterol rich foods in your diet can make a big difference for some especially those at low risk of cardiovascular disease simply reducing animal-based proteins like eggs shellfish meat and organ meats and increasing plant-based foods such as Tempe tofu chickpeas lentils beans Etc will be enough to get you to your target APO B level number four for those at moderate to high risk of cardiovascular

disease dietary changes alone may not be suffice in these cases discussing lipid lowering medications like aetam with your physician is important aetam is particularly effective for hyper absorbers as it blocks cholesterol absorption from both food and bile essentially offsetting the function of those genes that are working against you number five if you are not a hyper absorber so about 70% % of the population that means foods like eggs and shellfish that are rich in cholesterol but relatively low in saturated fat at the same time probably aren't affecting your AO B dramatically they'll still have some

effect but the lever that you're going to want to focus mostly on is lowering saturated fat in your diet in exchange for mono and polyunsaturated fats if your cholesterol levels or more specifically apop is high I would focus here initially and then look at dietary cholesterol and foods like eggs if you can't get to an APO of 80 mg per deciliter or lower I go through how saturated fat affects cholesterol and these dietary swaps in more detail in a recent video I did on dietary fats that you can watch here I'll put the link to

that in the show notes for those listening on audio for people with healthy blood cholesterol levels one to two eggs a day can feature within a healthy high fiber plant predominant dietary pattern Mediterranean diet pescatarian diet vegetarian diet Etc but equally speaking eggs don't have to feature and one of the inevitable questions that comes up here is but what about Coline eggs are rich in Coline and Coline is important for the brain so what happens to your brain health if you remove eggs completely I've added Coline to my list to tackle in an upcoming video

so hit subscribe and follow if you're listening on audio on Spotify or apple and you can tune into that in the not to distant future imagine your body's omega-3 level as a fuel gauge just as you wouldn't try to fill up your car car without checking the fuel level first it's important to understand your current omega-3 status before making changes that's where testing comes in by measuring your omega-3 levels with an omega-3 index test we establish a baseline that allows us to tailor our approach to your specific needs once we know your Baseline omega-3 index

level we can explore the various supplementation options my omega-3 supplement strategy is as follows it seems sensible to supplement with the minimum dosage of DHA and EPA per day to get us to an optimal omega-3 index so we can optimize for long-term health benefits minimize adverse effects like atrial fibrillation and save some pennies along the way for most people that's going to be in the ballpark of 1 to 1.5 G of active DHA and EPA per day I've personally done this supplementing with about 1.5 G of DHA and EPA per day and over around 9

months I saw my IM 3 index go from 5.76% to 99.44% now that I'm above 8% I'm actually going to slightly reduce my dose to approximately 1 gram of DHA and EPA per day and then retest four months after making that change to see if I'm still above 8% with that slightly lower dose why 4 months well the omega-3 index is based on the fatty acid composition of red blood cells and red blood cells take about 4 months to turn over so if you change your diet or supplement protocol wait at least 4 months before

you retest your omega-3 index Omega Quant who I have zero affiliation with but highly recommend for omega-3 index testing actually has a dosing calculator on their website which suggests that someone like me could get to 8% with around 810 milligram of DHA and EPA per day if I could achieve that I'd be very happy you might be thinking why 8% why not 12% this is something that I asked Dr Harris are there continued benefits of the grabs going up above 8% to 12% and Beyond in Practical terms it's far more uh important to just at

least get to 8% so few people are at 8% that to try to worry about being at 12% is almost a Fool's errand um we haven't got very much data on om on large groups of people with omega-3 levels at 10 11 12% there just aren't that many people like that so we really don't know that's kind of why we our limit is say 8 to 12 and above 12 we just don't know um we're not going to make any promises there is some evidence so from Japan uh that people that were at 11% omega-3

index compared to uh those at 8% they had lower risk of I think myocardial infarction so in Japan you can do things like that you can look at those sort of levels um so that was some evidence and there was a paper recently we not recently but a few years ago that pointed that there might be even additional benefits above 8% for cardiovascular um but I think that's still yet to be really studied well when choosing off the shelf supplements I recommend opting for brands that have gone through thirdparty testing for Purity oxidation and contamination

I've managed to get this information from thirdparty testing that I've pay to access from organizations like consumerlab.com or directly from the brands themselves providing they were happy to make their third party testing reports available I've also ensured that the brands that I recommend contain DHA and EPA not just DHA because as I mentioned earlier there is mechanistic evidence that suggests EPA may be more important for stabilizing existing plaque that we have in our arteries shout out to previous guest and friend Dr Alan Flanigan for bringing that to my attention please note I said the target

range for most people should be 1 to 1.5 G of active DHA and EPA per day when you read omega-3 supplement labels be careful not to look at the total oil per serve but rather the total amount of DHA and EPA it's the ladder that should add to 1 to 1.5 G per day there can be other oils in the capsule hence it's important to only pay attention to the DHA and EPA content based on all of this criteria the brands that I recommend to help you optimize your omega-3 index are as follows starting with

algae oil because it's more sustainable than fish oil and quite frankly I'd love it if everyone adopted an algae oil where possible mindset here three capsules per day of either the AA 3 algae oil or A's optimal Omega Plus at the time of this video Costco has a very good deal on the AA 3 algae oil for those based in America $29.99 for a 2mon supply I'm actually shocked by how cheap this is it's cheaper than almost all high quality fish oils that I've been able to find algae is the original source of DHA and

EPA the Omega-3s that eventually make their way up the food chain and are found in fish by going straight to the source we can obtain these vital nutrients without the concerns associated with over fishing or contaminants found in some fish it really is a win-win effective for our health and friendly to our environment and contrary to views that you may encounter on social media algae oil has indeed been shown in clinical studies to reliably raise someone's omega-3 index to an optimal level I asked Dr Harris if there was any difference between the effectiveness of algae

oil and fish oil and here's what he had to say in terms of being absorbed and getting into tissues yeah it's absolutely as as well absorbed and as well distributed in the body if you cannot get a vega3 in your location or aren't a member of Costco and price is an issue or for whatever reason you would prefer fish oil I personally haven't come across any other reasons than price my recommendation would be Carlson's maximum Omega 2000 two capsules per day will give you a little under two gram of combined DHA and EPA so you'll

likely only need to take this four times per week an alternative to this is Garden of life's do formulated Advanced Omega one serving per day provides 1.3 G of combined DHA and DPA Dr Bill Harris recommends a reesterified triglyceride form of fish oil he has his own brand parasol nutrition which provides 1,400 migrs of DHA and DPA in a two capsul dose this is what Bill personally takes each day at $69.95 for a 3mon supply it's more cost effective than Carlson's maximum Omega but surprisingly more expensive than the aega three algae oil at Costco I

say surprisingly because usually algae oil is more expensive than fish oil but that is not the case here for seeing there will be comments if Dr Harris sells Omega-3 supplements he must be biased could be or it could be that he's so convinced by the evidence for supplementing Omega-3s that he wanted to produce a highquality supplement his positions seem logically consistent at least to me anyway so I'm of the belief it's the lad if someone's wondering why measure LDL cholesterol and not LDL particle or APO that some some folks might say they're they're even more

predictive of cardiovascular disease that's a good question yeah if if I had if I could go back I would do that if I had more money I could go back and actually I have stored blood I could look at the apob um you can also look at the triglycerides as a hint uh and here's an an interesting critique of the study also is that people that if you look at the main results the triglycerides um were up a little in the vegans and didn't change so much in the omnivores which a lot of people that

favor that small dense LDL particle size hypothesis say oh my God they totally blew it they didn't look the triglycerides were way higher in the vegans not true if you look at the P value they weren't significantly High P value wasn't even close to significant and really what happens in triglycerides is you have these massive massively wide confidence intervals because human triglyceride levels are much more variable than LDL or HDL sorry to geek out there yeah you mentioned HDL before and the difference in HDL was nonsignificant right but went down a little more in vegans

went down a little more in vegans and that was another criticism that Mark Heyman had he wondered why in the abstract you only spoke about LDL cholesterol and not HDL my take on on that or I'm presuming that's because the LDL cholesterol finding was significant and the HDL was not it was primary and it was significant and usually in the abstract you can't go through all the secondary outcomes that you did there isn't enough room in the abstract I feel like these days HDL isn't as exciting as it used to be a lot of people

are considered it less of a causal factor and we've actually had rcts where they raised HDL and it was not protective it's been some more along the lines of observational that wow it sure looks like people with high HDL have better health outcomes that doesn't necessarily mean raising it will help does that mean lowering it hurts so I don't think anybody's everever tried to lower HDL to see if it would decrease your lifespan but there I've seen much less enthusiasm for HDL these days but when you do this type of study if you didn't list

LDL HDL and triglyceride a reviewer would critique right away and say where are where's the full lipid profile yeah I I know someone like Thomas dpring who's been on this show would say he doesn't trust any ratio with HDL in it anymore yeah as a predictor of risk of cardiovascular disease I just thought then though you don't have apob data uh but I think non HDL very closely approximates apob yeah which could be analyzed without having to run more tests I could definitely go back and look at that we could pay more money in thaw

and blood and look at apob I I'd be happy to do that in the future how are the results analyze because I know this was an open label study in that you can't blind the subject to what diet they're eating you kind of know if you're in the omnivorous or the vegan group but the researchers in your team they were blinded absolutely so not the dietitians who are asking what they're eating not the health Educators who were telling them how to eat the most healthful diet they all knew but anyone analyzing results was blinded we

said orange and purple mhm you know and so nobody knows till the end till we unblind that's why the folks doing the biological clock said God can you please tell us which one this is multiple times Louie the producer came to us and said when when can we unblind because something's different and I I can't wait to see what it is and I'm praying and hoping for the sake of my film that this works but nobody's telling me which direction they're going in we keep it blinded till the end and what what were the main

takeaways or main results for these cardiometabolic markers LDL was lower insulin was low signic lower and body weight was lower which I hadn't expected in that short amount of time LDL one thing that not many people have picked up on which I think is interesting um just because you randomize doesn't mean people will be exactly the same and it's impossible that they're exactly the same on everything given that LDL was the primary outcome the vegans had a lower LDL at Baseline than the ones that SED to omnivore they had less room for improvement they were

you might have the numbers in front of you and I'm not sure I remember but it's something like the vegans were about 100 and the omnivores were about 110 or 114 maybe at Baseline can you at Baseline vegans were 110 and the omnivores were 118 okay so that means there's less room for improvement right and so the vegans so the outcome of of interest is the change so one of the worst things in science is if you have two groups like this and at the end of the day this group lowers it to here I

don't know who's watching and who's listening right now so I can't see what I just did with my hands right so I'll just say if you were let's say you're were 118 sorry what were the vegans again 110 110 yeah so what if one group lowered from 118 to 110 and 110 stayed the same and you get to say fabulous this group lowered their outcome and this group remain the same they win and somebody else looks at it and says they both ended up at 110 how does that mean somebody one maybe 110 is the

basement and you can't go any lower than 110 but it might be easier to F the high you are yeah so that and I've seen a couple studies like that and then you have to trip all over yourself trying to come up with the words to explain why I know they ended up in the same place but I still think it's important in this case the vegans who were already lower lowered their LDL cholesterol by another 14 points or something like that and the omnivores barely moved so not only did they have more than a

10% drop in LDL cholesterol they did it in the face of having an unwanted lower LDL than the omnivores at Baseline maybe too geeky but I actually think that strengthens the point definitely that they did better yeah I was trying to interpret what that means for risk of cardiovascular disease oh and I'll share with you where you know how I kind of tried to calculate that and you can tell me what you think um so I looking at the paper I think the difference was about 14 milligrams per deciliter in terms of the lowering of

LDL cholesterol between the two groups so the vegans had a you know 14 milligrams per decil greater reduction in LDL cholesterol over eight weeks and do you know Kevin Macky have you come across his work sure oh you know him yeah so he wrote this paper I'll put this into the show notes that was trying to determine the reduction in in cardiovascular disease risk that you get when adopting a plant-based dietary pattern uhuh and one of the the kind of neat things that he did was he went and looked at genetic mandelian randomization studies and

looked at okay we we know we have these populations of people that have genetically low LDL cholesterol we can now work out for every 1 milles per liter lowering which is 18 mg per decil I'm going off my head here uh when know that if exposed to that over a lifetime yep because that matters right cholesterol years then these people have about a 50 to 55% reduction in risk of cardiovascular disease so 18 milligrams per deil for every 18 migs per decil lower LDL cholesterol if maintained over the lifetime you get this 50 to 55%

reduction okay so then I was looking at your results it's a 14 mgram per decil difference so not all the way to to this 18 yeah but it's about 40% of it sorry it's about 80% of it yeah which we we could kind of extrapolate and say that if the subjects in this study were able to maintain that diet uhuh over Decades of their life it could be you know around a 40% reduction in risk of cardiovascular disease yeah it's not true it's clinically significant that Dro in my day back 30 years ago uh we

used cut points of 130 160 and 190 and so if you had people I would often recruit people with elevated LDL which was between 130 and 160 and try to get it below 130 today that would be a joke the drugs there are there to put the LDL at 50 or 70 so the goal now is under 100 or to 70 or under 70 or to 50 so diet's not going to do that but that drop you just mentioned is clinically significant could be not being on a drug or could be on a lower dose

of drug if you add a diet to it clinically relevant absolutely how much of that reduction is due to the difference in calorie intake and weight loss A so you could tease that apart if you wanted uh and you could tease apart the amount due to the fiber and the part due to the saturated fat and you could tease it all apart which is why there should be multiple studies is not just one so we only have one we didn't tease it apart if you would guess HTH you could so one of my studies years

ago one of my first big published studies was in the anal anals of internal medicine and we made two lowfat diets and one was very convenience food based and one was very plant food based and so convenience food had chicken without the skin and mashed potatoes with light margarine and um sugar-free cookies and the other one had lentil soup with cheese on it whole grain bread with butter on it and a salad with egg in it and the reason I said lentil with uh cheese and bread with butter and salad with egg is we match

the saturated fat and total fat and cholesterol in the two diets in a feeding study and we forc them to keep the same calories so actually we fed them for a month and done what Pera wanted you to do so every you know so every three days if their weight was up or down in One Direction they got more calories added or calories taken away so this is a 2005 publication and uh I never said it out loud uh but it was a vegetarian versus an omnivore diet so just because those words can be polarizing

I just said this is a plant-based diet and this is uh a t a more typical diet and when we did that we doubled the LDL cholesterol lowering in the group that did plant-based at the same level of total fat and the same level of saturated fat very different fiber very different antioxidants but weight was maintained so the convenience food group lowered their LDL by 7 milligrams per deciliter because it was a lower saturated fat diet than their usual and the plant-based folks lowered it by 14 milligrams per Deiter same number so so essentially what

that tells us is that independent of any weight loss or difference in saturated fat there are other properties of a plant-based diet that can lead to cholesterol lowering and that could be uh it could be fiber uh it could be less dietary cholesterol as well which might have a little bit of an impact little yeah yeah tiny tiny tiny I think there you have it friends I hope you enjoyed this episode if you did and want to stay up to date with future episodes be sure to hit that subscribe button on YouTube and follow on

Apple or Spotify finally thank you for showing up and the effort that you're making to take control of your health I look forward to hanging out with you again in the next episode