#171 - Dr. Nadir Ali: Eat Mostly Fat

[Applause] [Music] [Applause] [Music] [Applause] [Music] hey friends welcome to this week's episode of the health via mr nutrition hvumen podcast this is your host jeffrey wu and i'm a new background new set i'm in montana and like much of us around the world we're doing an international multi-time zone conversation and i'm super excited to be speaking with dr nadir ali dr ali welcome to the program have you been i've been good and i'm honored to be on your podcast and i hope to have a fun fun conversation with you 100 and your name actually came up a number of times in our communities in our comments to speak so we looked into what you're doing and i think it's really cool especially your background in cardiology which is probably one of the more skeptical positions to start as one looks at a low carbohydrate approach it's uh refreshing to see that you came from that background and started using that intervention in your practice so a lot to a lot of ground to cover and i know that as we prepare for the conversation a lot of i think interesting nuances around low carb ketogenic diet as a as it sort of collides or intersects with your specialty area and i really find that surprising about my subspecialty cardiology interventional cardiology because i think that as a group of physicians we have been focusing on cholesterol which is i think the wrong thing i think cholesterol is more or less a surrogate marker for insulin resistance and we should be focusing on quality of cholesterol which is an indirect indication of how good your metabolic health is and i am frankly surprised that my colleagues have not gravitated towards that and then still cling on to this lipid diet lipid heart hypothesis which cannot be more wrong and they seem to be climbing the wrong ladder and not getting the answers that they should get yeah 100 and i think from uh at least from observational interventional perspective i mean statins are some of the most popular drugs which directly target the cholesterol hypothesis yet cardiovascular disease is still one of the biggest killers of americans so definitely at least from uh outside looking in from a very first pass coverage it's like what are we doing wrong if if so many billions of dollars and so much data is being collected on that area and yet the dent in cardiovascular disease is arguably you know not much of a dent so before diving into there and unpacking ldl hdl and you know aoko b some of the more uh specific markers and cholesterol lovely just step back and uh hear your background and story um why cardiology and what got you down that path of looking at uh or at least opening up the conversation around the lipid hypothesis can we give our audience and our listeners the fight you know the quick preview the quick overview of your career trajectory i've described this a few times i'm a very good interventional cardiologist i've spent 25 i mean actually 30 years in the cardiac cath lab the last seven years of those have been a little different because i have modulated to be more of a nutritionist a metabolic health physician but before that i found myself that i could get into the cath lab and if somebody had a blocked blood vessel i could open it very nicely and i could do it better than many of my colleagues could and so i gravitated towards that and i spent like the bulk of my time like 70 of my time just being in the cath lab opening up blood vessels and i used to be very disenchanted seeing patients in the office because i didn't see them improving at all i didn't see their blood pressure is improving i saw them becoming more obese more diabetic and even though their ldl would drop i could never correlate that ldl with any improved outcome in my patients so it was only through like a personal experience that i found a low-carb diet i started looking into metabolic health and what it was is that you see me about 145 pounds in front of you you see my bicycle in the background i have been coming to work on a bike for many many months many years actually but over the last seven months i have not ever come in a car so i belong to a racing team and even though i was never particularly heavy i was up to about 175 pounds despite cycling about a thousand miles a month i mean that's a lot a thousand miles a month yeah 250 miles a week that's a good pace right yeah and i couldn't explain why am i getting heavy and so one day i was listening to this podcast and some information that chris froome who was doing very good in cycling at that time he's a to the front cyclist that he was a low carb athlete that he improved his power to weight ratio which means that the amount of power he can put for his own weight was quite high and it improved with a low carb diet so i said let me try this and within a few months i was down to 160 pounds but since then i've come down to 145 with further fine tuning as i learn more but i said if this is so easy in me why am i not trying it in my patients and that was the most transformative experience for me and since then i have learned so much from my patients that i feel like i am better suited that i have more skills to counsel patients in the office and improve their health and so i've pulled myself away from the cath lab i've hired a couple of colleagues who do my procedures and i spend the bulk of my time counseling patients and it's a learning experience i learn every day and that's what here i am to discuss with you that's a cool trajectory and i think i mean i think i i feel like and maybe this is a larger commentary in the healthcare incentives but it feels like when i speak to a lot of doctors oftentimes they're working towards building codes right because like literally clearly like different incentives or insurance payouts for doing a cat surgery versus a nutritional counseling exercise and it sounds like you've been able to at least work through or overcome some of the institutional hurdles around treating a person as a whole human versus hate like you're uh a sort of a building code that i can do a surgery or procedure on which i think is it you know in itself an interesting conversation so i mean how i mean i mean how have you like managed that because i think a lot of doctors who i think are open to some of the ins the insights that you've uncovered in your practice it's it's hard to even just like fight against a system right because like insurance or the infrastructure you don't get promoted or compensated for nutritional counseling as well as you do by prescribing insulin or doing a heart procedure right i i have a little bit of an advantage out here because i come from inside the system i have a reputation a character out there that many of my referring physicians many of my patients know and more importantly when a patient listens to my advice and he loses weight his blood pressure gets better his sugars get better he comes off diabetic medications he comes off blood pressure medications he feels better that is such a strong validation for him that he goes and tells many of his colleagues saying that hey there is this doctor who's doing something different so being relevant being somebody who can actually improve somebody's health is such an important aspect i'll just give you a small example i think that cardiologists feel very good about themselves when they can alter somebody's cholesterol so you give a statin to somebody and their ldl levels are 150 they come back in two months on a statin and their ldl level is 70 and both the patient is looking at a number and the cardiologist is looking at a number and he says hey this is fantastic look how much we have improved your health except that i think that they are looking at the wrong marker i think for me the transformative experience is not looking at a number but looking at seeing hey are this is this guy feeling better because his blood sugar is lower are his joints hurting less because he has lower weight is his blood pressure better is he having to spend less money buying medications so i think those are better surrogate markers than a blood marker and it takes time for physicians to do that critical thinking as far as compensation is concerned i think doctors are well compensated and i don't think i i would rather feel more relevant than earning a little less money a typical cardiology concert is that mr so-and-so your stress test is good your ultrasound is good let's go up a little bit on your cholesterol medicine let's increase your blood pressure medicines and by the way eat a low fat low carb diet and exercise and i'll see you in six months 30 seconds and uh so that's about it i mean i think our conversations are a lot more relevant it it would shock a cardiologist who would come to my patient visit because he would not have any idea as to what we are discussing in terms of insulin resistance insulin glucagon ratios inflammation markers the craft insulin response he would if i if i told a cardiology colleague that this patient of mine is a craft five he would have no idea what i'm talking about whereas my patients will so this is the kind of change we are seeing in the consumers because people like you many podcasts that come out many youtube videos that come out the gap between a consumer who knows details about science and about his own condition and what the physician knows is narrowing not completely i think that as healthcare providers we still have a breadth of knowledge that comes in from different standpoints and we can still help people but thank god that this gap is reducing and and that's what's going to improve people's health and i frankly think that as far as chronic diseases is concerned chronic diseases meaning management of high blood pressure diabetes lipids the doctors the mainstream medical profession is really going to get buggy whipped if they don't listen to the consumer yeah if they don't market it i think that's a super refreshing perspective and i think it is the direction the world is moving and the way i think about it is that the internet is democratizing access to knowledge right that's already happened for a lot of aspects of knowledge where the lay consumer can't access the same research papers that that cat the academy used to only have access to right now you have more and more consumer devices that used to only be biosensors that only doctors or hospitals could have but now you have heart rate variability cgm's becoming more and more consumer devices and i think you see cryptocurrencies democratizing access to financial technologies and i think the human performance community biohacking community this increased interest in health and wellness is doing the same thing for health knowledge but i don't think that means that doctors are not useful i think they're even more useful as guides shepherds coaches i think that relationship is going to change where i think it used to be very much like i think from a religious context you would have a pastor or a priest that would interpret the bible and like literally speak out the word of god to their uh congruent or their congregation and i think medicine used to be a little bit like that and now i think it's becoming hey you know more and more people have access to the raw basic text and obviously the people that are more experienced in interpreting and how to actually reconcile the very confusing large data sets i.e folks with medical degrees or phds i think that's kind of like the evolution of how i see the the social cultural relationship between uh the different participants in this healthcare system i couldn't agree more i i well articulated yeah well i i one thing that i think would be helpful as as people are entering and might not have a deep of a background in lipidology or uh cardiology i think people generally have a sense that the traditional academic approaches ldl is the bad cholesterol hdl is a good cholesterol as we mentioned a number of times you kind of want to drop ldl because that's the kind of stuff that clogs arteries atherosclerosis and then you have kind of high blood pressure and it's like you get constricted blood vessels that's generally the story and then the story is okay reduce consumption of cholesterol so you have lower ldl and you have low less of these blockages in in your blood vessels that's like probably like the lay expectation what would you say are like the biggest flaws in that line of reasoning or what are the most compelling data points or observations or studies that led you to reconsider what are the right circuits or biomarkers here i know that some folks who have been studying or following libidology a little bit more explicitly there's i would say a little bit more nuance with like the the particle size of ldl oxidized ldl i think there's starting to be more sophistication in like the particle density particle size can you help kind of break down some of the existing understanding of cardiology and how you're interpreting it in the most modern lens in terms of your clinical experience sure let's break down each and every one of those parts that you mentioned so ldl is considered to be the bad cholesterol and total cholesterol and ldl track each other very well like in other words if you have a high ldl you will have a high total cholesterol and if you have a high total cholesterol you will have a higher deal so they they go together so the first basic thing we want to give people is that there is a lot of discrepancy between what mainstream medicine believes and what demographic data tells us so let's take a population of 50 000 patients studied in netherlands this is the hunt trial 50 000 people over 50 years of age and they were looking at their cholesterol their total cholesterol you could call it the ldl cholesterol higher the ldl cholesterol lower the mortality higher the ldl cholesterol lower the cardiovascular mortality so when you look at large populations of patients who are older and older people are more at risk of heart disease this does not jive well with the mainstream medical concept if you look at works done by ravniskoff and malcolm kendrick they took 60 000 patients from different trials looked at ldl and turned them into turtiles the bottom 20 percent the second 20 the third 20 percent and then the top twenty percent and if i tell you that the top twenty percent had the lowest cardiovascular risk and the lowest mortality then it would make you doubt your hypothesis is ldl really the bad cholesterol why are these people doing so well if you take a look at the monika project now this is information from world health organization 2008 you look at countries like sweden like france like italy they have a higher fat intake they have a higher total cholesterol you take a look at russian republic countries the eastern european countries they have a lower fat intake and lower cholesterol so you should expect that people with low cholesterol and lower fat intake should have lower total mortality lower stroke rate lower cardiovascular mortality but it was the exact opposite people with the highest cholesterol in sweden in france and italy had lower mortality and lower stroke rate made absolutely no sense let's go further let's go to world war ii japan world war ii japan had cholesterol levels that were very low yet the incidence of stroke was tenfold higher compared to that of the united states as japan became affluent and they started eating animal products the cholesterol went up what happened what happened to the stroke rate did it go up no it came down so you should say why are there so many black swans why do they not agree with the hypothesis that high cholesterol would cause high strokes and high heart disease and high mortality then you look at the ldl data from the but from a biochemical standpoint why do we make ldl what is the purpose of making ldl and i would say ldl is a very important host defense mechanism because there's a lot of biochemical data that shows that ldl participates in neutralizing bacterial and viral toxins and so it's a molecule that is providing host defense what does ldl carry ldl carries inside it antioxidants antioxidants are there to prevent you from getting burn injury from oxidative injury it carries coq10 in it is cocutan important it's vitally important for our muscle function for our brain function for our heart function because without coq10 you cannot really burn fuel you cannot get energy from fuel right it's an important coenzyme in the krebs cycle that's a very important enzyme in the electron transport chain just like you point out to convert glucose and fat into usable energy currency cholesterol is vitally important for brain function in fact cholesterol is so important for the brain that it doesn't delegate the liver to make cholesterol it makes its own cholesterol so all these things and i have pointed out in a number of youtube videos and for somebody who wants to take a deep dive they can go into some of my youtube videos that talk about the functions of ldl cholesterol so from a biochemical standpoint i could never understand people saying zero ldl is good when you could see that it is performing so many biochemical functions now you mentioned oxidized ldl and that's very important i think that the reason the ldl gets oxidized is to protect us from oxidative or burn injury so in other words ldl carries vitamin e it carries many antioxidants like vitamin e it carries coq10 and the function of the ldl is to protect the rest of the body from oxidative injury and when it gets oxidized it's called oxidized ldl and the body behaves very differently when it comes to an oxidized ldl compared to a regular ldl now i have put that out again in another youtube video and if somebody wants to take a deep dive they can go into that but just for the purposes of somebody on this podcast the liver is picking up the regular ldl the reason it's picking up the regular ldl is because cholesterol is a very expensive thing for the liver to make and it takes the ldl so that it can recycle it it can make bile acids so that we can absorb fat that we eat so that we can absorb fat soluble vitamins that we eat that we need whereas the liver will not take up oxidized ldl the reason it will not take up oxidized ldl is because oxidized ldl is like an injured firefighter if you go to the scene of a fire and you see firemen there you're not going to say firemen caused the fire the oxidized ldl was there at the side of the injury to dampen the injury and the body has mechanisms to differentiate between regular ldl and oxidized ldl and oxidized ldl gets picked up by macrophages these are mechanisms through which our body removes damaged and dead material just like the us army would not want to leave an injured soldier behind the body is picking up an ldl and oxidized ldl that has done its function that has protected us and it's going to deal with in in such a way so that it minimizes the amount of injury to our body so we have looked at it from that standpoint now let's look at it from the standpoint of therapeutics there is a very strong incentive to treat people to reduce their ldl levels and we should try to find out what is the degree of benefit so i'll give you i'll start out with the most ridiculous example and then we can come to examples in which ldl may have had reduction of ldl may have had a small degree of benefit but let me take the most ridiculous example you take 28 000 patients 14 000 of them you give them a new drug a pcsk9 inhibitor that drops their ldl to 30 milligrams per deciliter 30 milligrams per deciliter is very low yeah because you and i if you're following a ketogenic diet and we are exercising we are fasting our ldl levels will be 200. yep so 30 is very low and if you treat 14 000 patients who have high blood pressure who've either had previous heart disease or stents who've had previous strokes who have had blockages in their legs this is a high risk population and you say higher the risk greater the benefit in terms of reducing ldl and if you treat 14 000 patients and reduce their ldl to 30 milligrams per deciliter and there is no impact on mortality in other words you don't reduce death rate at all in fact in the group that got given the medicines the death rate is little higher than the control group you would say there is something wrong with this hypothesis yeah so i want to break here and i think we have beaten ldl so much and so wrongly and i think we have lost focus on how to improve somebody's health because everything you do to reduce ldl is going to harm your body in terms of insulin resistance when you remove ldl your insulin receptor doesn't function well your insulin doesn't function well your muscles don't function well your brain does not function well although you have reduced the ldl you have made insulin resistance and everything else worse so why is it that we are clinging on to a hypothesis that has produced ill health in so many different ways rather than focus on root causes which is what you are doing and i hope that was not too long an explanation to unpack that no i think that's very helpful except because again i think i would say that there's definitely a segment of our audience here that's super nerds but i think most people are just starting to unpack this i think it's helpful to start from some basics there i think it's very well explained so if one were to just step in this conversation now they would be saying hey what is going on with the american heart association like like it literally sounds like the standard of care is literally the opposite of what you want to do right because all the things you describe like all these uh international associational observational data negative indication or correlation between ldl status and mortality negative correlation between ldl and stroke rate and all these all these markers so why are cardiologists still prescribing statins why is that still a multi-billion dollar industry is i mean not to go conspiracy theory is this because there's big business to be done or is there some data from the you know i think the big framingham study i think is where in boston and collecting observational data on that population seem to drive a lot of these hypotheses what is the best argument from classical cardiology that would say hey like dr ali like i hear you on all these data points but you forgot or you didn't emphasize these data points that i'm putting my hat on uh what are those arguments there you frame the question very well and i think that should be answered and i want to offer a couple of different perspectives number one is that it is very gratifying to a physician treating somebody to actually look at a blood test and say hey i was able to drop your ldl by 50 to 70 that's gratifying both to the patient as well as to the physician because it is so intuitive to think that hey the blood vessels are clogged with fat and this man has reduced my fat by 70 percent and that's a dramatic you know improvement and so you gravitate towards that the second is the way in which clinical trials have evolved clinical trials have been driven by the pharmaceutical industry the chronic clinical trials give a very misleading magnitude of benefit like for example i will take you back to 1994 when the scandinavian simvastatin trial was done simvastatin is a cholesterol-reducing drug 1994 it was published hundred and forty 4444 patients half on simvastatin half not on simvastatin so if you look at mortality data in that now by the way before i go into mortality data this trial was completely done by merck merck had the biostatisticians they funded the trial they collected all the data they presented all the data even though the physicians presented the paper the data was all gathered by merck so in other words the degree of conflict of interest was very high if i were a pharmaceutical company trying to put out that my drug is beneficial i would want to portray my drug in the best light and in 1994 merck could have done 10 clinical trials with simvastatin and if the 4s trial was the most positive they could have not published the other 9 and published only the 4s trial there was no restriction to publishing all 10 as it is there now there was a significant reduction in cholesterol i think 25 in ldl cholesterol and these numbers may be a little bit off because i'm going off my memory but the most important endpoint was that if you treated 100 patients for one year you would reduce half a death 0.6 deaths half a death so the magnitude of benefit and these were all people who were very sick they had either a previous heart attack they had bypass surgery so this was secondary prevention so if your magnitude of benefit by treating 100 patients for one year in terms of mortality reduction is 0.6 you should say it like that you should not say that there was a 42 reduction in the risk of death and myocardial infarction because that's a relative risk reduction and relative risk reduction is very misleading and i like to use dr kendrick's example in which if the chances of winning the texas lottery and i'm in texas are you in montana i'm currently in montana yes yeah so let's save the texas lotto to win it the jackpot is one in 10 million and you come and you tell me that hey i'm i'm going to double your chances you i'll make improve your chances by a hundred percent that hundred percent really is from one in 10 million to two in 10 million but if you say it as hundred percent it will sound a lot more impressive than if you say i'm going to improve it from 0.601 to 0.602 you see what i mean yeah so the way in which this data is being presented to physicians is wrong because we focus so much on relative risk reduction and we are very happy looking at surrogate endpoints of a reduction in ldl cholesterol and the way healthcare has evolved is that physicians don't want to hear their patient's complaints when the patient comes in and says hey i'm aching all over they're not going to think that it is the statin that made them ache all over saying you're just getting old you're not active you should go active you should eat better if he says hey i am i'm forgetting things and they would never attribute that to a stat they would say hey everybody forgets things so i think these are some of the reasons why the medical community is not doing critical thinking i think we as a group have to move patients in and out and it is much easier to counsel them on saying take this pill rather than to say hey look let's have a real meaningful conversation about the degree of benefit of reducing your cholesterol and the degree of risk you can face because looking at you jeff you look like you are in your late 20s or early 30s early 30s and yes okay so if i take somebody like you i may put you on a cholesterol medicine for 50 years or more is that really fair for a physician to do without really getting into the real conversation what is your degree of benefit what is your degree of risk and over what period of time do you face this risk and by the way jeff you should monitor these symptoms how many times is a cholesterol prescription given and a person is informed it may cause muscle aches and pains your diabetes may get worse you may lose your memory your memory may go bad maybe your infection risk would be a little higher because we are reducing a very important host defense mechanism and i think this is the real conversation that a physician should have but they're simply not trained or equipped to do that or have an incentive to do it yeah i think that's the real failure of medical profession i think you hit it dot on the head and i think because there's so many people within the standard american diet there's so much chronic there's almost an overload on this system and then you're saying hey every doctor needs to have a 30-45 minute long-form discussion around nutrition physiology their their whole life and it's like i i have like five minutes to like go write a prescription and i think it's hopefully these conversations and doctors like yourself leading the way to hopefully change the health care system because if already a sixth you know of our gdp is going to health care our country's not going to be in a good shape if all our conditions are getting worse and worse and worse i mean i'm just kind of from the engineering perspective i just see cardiovascular disease metabolic syndrome obesity diabetes all up into the right our costs are up and to the right and it's like we're spending more money getting worse outcomes something is wrong here right i i couldn't agree with you more why why are we spending so much money and we are not improving health yeah why do we have such better health care and we have rising obesity and diabetes why is uh longevity i mean it is so saddening to see that for the first time in the history of united states in the history of such a great country that our children are going to live a shorter life span than us yeah that's a sobering thought it never happened before every generation lived longer than their previous generation we are obviously doing something wrong yeah and we need to have critical thinking and evaluate what we are doing wrong yeah i can agree much more so what led you to focus on insulin and insulin resistance and that cluster of data points to pivot your attention towards curious to hear you're in and and what does your practice look like today in a little bit more detail absolutely i'd love to talk about that in you can get a little surrogate markers of insulin resistance by just looking at a cholesterol profile like let's say you have one of your listeners listening in and they pull up your cholesterol profile and they're looking at their triglycerides and their hdl if the triglycerides are low which is fat in blood and if their hdl is high that means that they are insulin sensitive if the triglycerides are high and their hdl is low that means that they are potentially insulin resistant what many people don't realize is that insulin is a key factor not only in controlling your blood sugar but in also controlling the lipid metabolism so the health of your fat cells how much fat you can pack into your fat cells how much fat is released from the fat cells is also an important aspect of insulin so it is important for a physician to recognize how insulin resistant that person is so in simple terms let's say you have a normal sugar of about 90 to 100 and if you are needing about four or five of insulin that means that you need a low amount of insulin to hold your sugar there on the other hand to hold a normal sugar of 90 if you need 10 15 20 or higher insulin that means you are insulin resistant because it's taking a lot higher insulin to keep your sugar levels in control which is what most americans are so in other words if you looked at insulin resistant in american population the prevalence of resistance is perhaps three in four 75 percent of americans need more insulin to keep their sugars in control that's crazy yeah so like would you what threshold would you say would be a faster insulin level that you would be that you would say would be indicative of insulin resistance i would say that if your homo score is above one and consistently above one now insulin is a cyclical agent in other words the body releases insulin at baseline let's say you're fasting yeah and the body doesn't release insulin constantly it releases every 10 minutes so 10 minutes it goes up and then it comes down so it's a cyclical release of insulin and the cyclical release of a hormone or a pulsatile release of a hormone is very important to prevent resistance of that hormone our biology is designed like that so within a degree of variability in other words like let's say if i take you and i check you at the peak of your pulse you may be 10 and if i check you at the nader of your pulse that's the lowest of your pulse you might be two or three yeah so when you look at one number you know i don't want people to criticize me saying that i'm giving absolutes and sometimes when you simplify things too much it seems like you could say something wrong but i would say as a rule for health you should aim for a homa score a hundred of insulin and i mean a hundred of sugar and about four or five of insulin that's a homo score of one so you take insulin multiply that by so it's a relationship between facet blood glucose and facet insulin correct and that's a homoscope more or less of one is probably a person who is insulin sensitive now that's only one marker of insulin sensitivity another marker would be the health of your fat cells because eating food is a stressful event for the body you know i didn't recognize that but when you eat food it's very pleasurable but it's a stressful event and the reason it's a stressful event is because our body needs to keep a level of sugar within a certain narrow physiologic range it needs to keep the levels of fat in a narrow physiologic range it needs to take the protein that you have eaten and dispose of the amino acids into new protein new muscle or use it for fuel so the body cannot vary the levels of sugar too much whereas we eat a huge amount of meal a standard american may eat about 400 grams of carbs in one setting so the body needs to pack the carbs it needs to pack the fat so the fat that you have eaten the body takes that fat it puts it into these fat globules called chylomicrons they circulate in the bloodstream and they are cleared and packed into the fat cells in less than five minutes by insulin insulin has to activate an enzyme in your fat cells to do that now if your fat cells are unhealthy if they are over stuffed then the fat remains in the circulation for too long because the fat cells say hey we are already too full we can't take any more fat and we want to become insulin resistant to protect ourselves so the body starts over making insulin to pack more fat into the fat cells and that is an important aspect for any physician who is treating chronic diseases to recognize that hey i want to check this person not just from a cholesterol standpoint but i want to check them and see if they have too high in insulin are there fat cells healthy because high insulin will increase your blood pressure will cause a gout will cause many other chronic ailments and that's where our role is that's where our role is in terms of educating the public to improve their health not through medicines but through a combination of diet intermittent fasting and exercise i think the magnitude of benefit from these three aspects is very underestimated by the medical community because we've gone on this low-fat dogma when you go on a low-fat dogma you can throw all the three things that i'm telling you out of the window because you will not be able to fast you will not be able to eat less and you will not be able to exercise effectively because you have gained too much weight let's definitely talk more about the specific interventions and protocols one thing that you mentioned i think is under discussed is the dynamicism of the human physiology of human system where i think a lot of medical practitioners will diagnose or prescribe towards a snapshot data point but i think what is i think a lot of physicists or chemistry chemists talk about is like the flux the flow the the integral derivative of how these biomarkers or these hormones actually flow through the system i think when you describe insulin yes it's a pulsatile dynamic number and if you take a snapshot when you're at the peak versus the nadir it's a very very different conversation where obviously to do like a blood tap to continuously measure insulin that would be a very cool metric to actually understand right but it's just not that is not able to be done in a commercial lab you could probably do it in a in a research bench lab setting where you're just tapping someone's blood directly and i think a lot of the substrate utilization is again focused on a snapshot rather than actual flux of turning things through right when people talk about ldl as it's just a static number it's not just that there's a lot of fat just sitting in your blood for a lot of people on a low carbohydrate or a fat adapted metabolism that ldl is turning through constantly right there's a super high flux of this cholesterol and i think that you're just i think talking about that i'd love for you to expand on that a little bit more because it's a topic that i think most people just overlook or is just too nuanced in terms of what exists in terms of medical sensors to actually measure snapshots but the human system is cons it is dynamic it's constantly have high flux high high derivatives i could not agree more and i think you have to be an engineer to recognize flux flux is something that very few people recognize the body is in a dynamic flux so let's take insulin release and insulin receptor and let's see how they modulate each other so insulin to be released in a pulsatile manner is important for our biology because insulin is made in the pancreas in the beta cells it's packed into these small granules that mature and they come towards the periphery to be released into the circulation so the insulin producing cell has to take time to make those granules if it's releasing continuously it will get exhausted so it needs a period of rest and the maturation of the granules is time that is cycle to in in the resting state when you're not eating to about once every 10 to 12 minutes let's go to the insulin receptor the receptor at which insulin comes and sits and when the insulin sits on the insulin receptor it activates a series of signals inside the cell one of the signal is that it activates a channel through which the cell takes in sugar it activates certain chemicals inside the cell now let's take a brain cell hemp or hippocampus hippocampus is the area in the brain that facilitates memory memory is vitally important for our human function the hippocampus is very rich in insulin receptors so insulin sits on the hippocampus and it activates a series of chemical reactions through which it makes new protein in the neurons and these new protein increases synaptic plasticity which means that it improves the connection between brain cells so insulin is important for that now once insulin sits on the insulin receptor the receptor gets inactivated for a period of time it gets internalized it's doing its action it takes time for the insulin receptor to come back up to the surface of that cell in an activated form what are we doing as humans to mess up with our biology is that we eat several times a day we eat a large amount of carbs we have a refrigerator at our home we have a supermarket right around the corner none of these things are good for our human biology if we don't recognize how the human body works because if you're eating frequently you're pouring a large amount of insulin into the circulation insulin was designed to be released infrequently because when you have high insulin there at the level of the brain all the time you're going to down regulate the insulin receptor the insulin receptor is going to go inside the cell and hide and this high insulin is not going to be there to do its action you're not going to improve memory in fact one of the reasons why there is such a high incidence of age-related dementia in this country is because of brain insulin resistance you have down regulated insulin receptors in the brain at which time you are no longer capable of forming the kind of connections between brain cells that you lose your memory yeah and if you actually do energy uptake scans you actually see less glucose uptake in an alzheimer's brain than a healthy normal brain so it's i mean this is not just theory this is actually showing up in brain energy scans jeff we were having such an amazing and wonderful conversation and i was just a little disappointed that there's a tropical storm in houston area for the last five days and we've really not seen any sunlight and it knocked our internet connection off and now we're going to stitch back this and the previous verse previous part together so now we're back for the last few minutes we actually had the realities of weather patterns coming in so as we lost connection there but as dr ellie was just saying there's been a tropical storm out there and i i'm normally based in san francisco california we had our own troubles with weather and fires and smoke ourselves so uh realities of of being physical creatures right but we were on a roll uh jeff i think we were having such a good conversation about flux and about how the body handles the entry of fat and how insulin plays a role on in packing fat into the fat cells and how nutrient homeostasis is so well orchestrated in the body like for example as soon as you eat food even before the glucose gets into the circulation the gut is already sending hormones to the pancreas the gip that makes the pancreas know how much food is coming in so that it can prepare the amount of insulin it's going to release it knows how much protein is coming in because the gut is signaling to the pancreas hey i'm going to dump so much protein into the circulation it's also signaling how much fat you're going to send into this circulation and we were talking about fat and at one point we were thinking that we wanted to touch on lipo toxicity and this might be a very good segue into that and the reason i say that is that when we eat in a lot of fat fat is pretty toxic if it is left in the circulation in other words if you were to give me a marker of health and say take somebody with high ldl i'd say yeah this guy's going to live long but if you give me somebody with high triglycerides which is high amount of fat and blood i would say something is seriously wrong with this person's metabolic health and that they can get into trouble so what one may ask is lipotoxicity and lipotoxicity is that in reality whether you are a low carb individual or whether you are a pure vegan or whether you are eating a standard american diet you're by design going to eat fat and that fat is absorbed by the body in fat globules and it needs to be packed into the fat cells you cannot leave it in the circulation you cannot burn all that fat right after you have eaten you have to store it and if your fat cells are full if they are inflamed if they are insulin resistant what insulin resistance simply means is that the insulin receptor at the level of the fat cells is not working because it's down regulated because you've had too much insulin in your circulation for too long and so the fat cell cannot take in the fat that you have eaten and it remains in the circulation and that's bad for us to just clarify and interject here so i think when people are skeptical about the ketogenic diet or a high fat approach it is typically around lipotoxicity and i think and and to clarify if if you have a similar point of view or not is that when one takes a lot of exogenous fat in there will be a spike in chylomicrons as you your body needs to you know somehow transport the consumed fat into our adipose tissue so you might see an acute spike in chylomicrons and fat but if someone is metabolically healthy and insulin sensitive that fat is packed away very very quickly now the problem is if there is insulin resistance that fat does not get shuttled away and stored in quickly it just hangs around and that's where lipotoxicity and the inflammation is really problematic is that another way to rephrase uh what you're saying there that's a very good way to rephrase it and it's a it's a nice synopsis of what lipo toxicity potentially can mean but many people who are obese who are metabolically unhealthy by the way there can be several several obese people who are insulin sensitive whose fat cells are healthy and then when they take in the fat they pack it in quickly so you can have a metabolically healthy obese person also but if somebody is insulin resistant and obese i would perhaps not advise them to eat a large amount of fat these people may first need to improve their health through a regimen of fasting through a regimen of protein sparing modified fast through a regimen of exercise because you don't get lipotoxicity lipo toxicity necessarily by eating too much fat you can get lipotoxicity by not being able to burn the fat fat oxidation is an important aspect of health so where the low carb community needs to individualize health care is if a person comes in who is heavy and obese who's gone on a low carb diet who is not eating any carbs yet you're not seeing a weight loss yet you're not seeing an improvement in their cholesterol quality which is low triglycerides high hdl and in this individual you may say hey listen we are not going to be like every traditional mainstream healthcare provider we are not going to tell you that it is your fault we think that people have don't have the moral courage to go away from food to step away from food that obesity is their fault that's not true most americans try to follow an advice given by a professional and so we need to take a step back and say hey maybe our advice is wrong in this individual maybe there is such a thing as eating too much fat that night that might not be good for you so what does happen in these people is that when they have eaten the fat just like you mentioned you're not able to pack it it remains in circulation now this fat that remains in circulation is going to try to find a place for it to go so it's going to end up as visceral fat it's going to end up in your pancreas when your pancreas gets fatty it becomes insulin resistant and we can talk about what pancreatic that means pancreas itself is insulin resistant it can get into the liver and it can cause non-alcoholic fatty liver disease when the fat cells are insulin resistant they are not only not able to keep the fat inside them but they are spewing fat into the circulation they're spewing fat as fatty acids now that fatty acid one of the most common one is called palmitic acid that combines with a breakdown product of protein metabolism called serine and when you join the palmitic acid and the protein byproduct you make a compound called ceramide now ceramide is a toxic fat when it gets into the pancreas it destroys the insulin-making machinery when it gets into the skeletal muscle it causes insulin resistance when it gets into the brain it causes insulin resistance so there are many places where ceramide makes insulin resistance worse or destroys the insulin-making machinery and ceramide is a way in which we get lipotoxicity by having too many fatty acids now people will say hey when you're fasting your fatty acids are high so isn't that a lipotoxic situation and that is incorrect that is not correct because these fatty acids are now being taken over by the muscles to be burned for fuel a liver that is insulin sensitive will take the fatty acids and convert 80 of those fatty acids in a fasted state to ketones whereas a liver that is insulin resistant will take those fatty acids and recycle them back as triglycerides and that's bad for you because you are not breaking the fatty acids into usable fuel for the brain you are sending it back out as triglycerides the fat cells don't want it because they are already stuffed and over full where is this fat extra that the liver is spewing out is going to end up it's going to end up in the pancreas it's going to end up in the liver it's going to end up in the heart and cause disease so it is important for somebody who's already struggling with insulin resistance who is obese who's not losing weight for them to recognize that modifying their lifestyle with fasting under supervision with increasing their exercise to improve fat oxidation by reducing their fat intake by focusing on a protein sparing modified fast may be the right answer and that is where the low carb community can differentiate itself and say hey we are going to a different bar we are not just telling you low carb low carb we are actually getting into the science we are actually getting into individualized medical care and conversations like this and the community getting together in conferences and us investigating patients on a daily basis as our clinical experience increases as we get venture capitalist involved in funding studies into this is how we are going to improve our health care we should not just rest on our laurels and say we've done great work and we are finished by no means our knowledge and the method in which we are treating patients is constantly evolving i hope i was not too philosophical on that no i i want to unpack it a little bit more and but before talking about i think the future i think it is interesting i think worth ex in hammering home the difference between i think like the typical nutrition or diet dogma which is like one size fits all in terms of we think ketogenic diets great so even if you're obese and potentially have insulin resistance problems still consume 80 90 fat calories and i think the subtlety in the way i think about it is that fasting or protein sparing fast is simply instead of eating exogenous fat you are essentially that calorie that color of deficit in terms of that fat is really just eating your own fat so it ends up being the same macro nutrient ratio of a quote-unquote ketogenic diet you're not just dumping extra fat because it's unnecessary as a system with a lot of adipose or visceral fat tissue you have plenty of fat for your body to metabolize so allow yourself to actually metabolize that stored fat i couldn't have said it better essentially right and i think that's where i think this makes so much sense from a systems perspective because if you under actually understand the mechanisms then you can reason about the expected outcomes right like if we think of ketogenic we're depleting glycogen having a little bit of energy deficit so it forces conversion of fat stores in the ketones well you can do that through exogenous fat consumption uh if one is more on the lean side or one has more athletic demand in terms of more exercise but if one is a different context right if someone's already obese has too much energy already yeah just shift where you're taking that fat from don't eat it just use your own fat slips very elegantly said i could not have said it better i think it's important to recognize that marker of health is how willing your fat cells are to receive and pack the fat that you have eaten and another important marker of health is to see how well suited your body is at fat oxidation in other words when you burn fat you get this rq ratio this is called respiratory quotient and an rq ratio in this in that is that you for every 100 molecules of oxygen that you consume you have to only eliminate 70 molecules of carbon dioxide when you're burning pure fat so your rq ratio is 0.7 so co2 over oxygen consumed whereas if you're burning pure carbohydrates it's a one-on-one ratio hundred to hundred so if you can measure somebody's rq and it's a little complicated method of measuring it a healthier person is burning more fat their rq ratio is lower a healthier person once they eat fat very soon if you measure the fat in their bloodstream it would have disappeared so and the reason that is the case is just what you said this person has given himself the opportunity to consume the fat that he has stored so that he emptied the fat cells reduced the inflammation in the fat cells so now the fat cells are ready and willing to pack in the fat that you have eaten so excellent i think uh you clarified that quite i mean it's just a beautiful system i think i mean from my perspective like you're just trying to understand why our machinery has evolved in such a way and it's like wow the more you understand it's like is this arbitrary or is this an elegant way that this very complicated sophisticated machinery is maintaining homeostasis and trying to resolve its own problems it's like wow it's cool even how insulin resistance even functions right like just too much of this insulin signaling we need to like basically down regulate our response and it just makes sense right so it's like our body's trying to save ourselves but in doing so now you're creating new problems and i think now once you understand that you can start the reasoning about an intervention to help resolve that and i think that's interesting from rq ratio maybe to pivot it towards future and for performance perspectives i know that you're an avid cyclist we work with a lot of professional cyclists one of an interesting conversation was actually talking to lance armstrong around uh some of his experimentation and it was kind of fun to chat about when he was obviously hopped up in terms of all the extracurricular activities kind of what performance he was driving one of the interesting metrics is that rq ratio and some of the most highly highly adapted athletes burns athletes like you hit vo2 max and never fully crossover to be lactic burning i mean they basically can maintain predominant fat burning up until vo2 max which is fascinating right because like most athletes or most just casual people just turn over to lactate pretty quickly on that vo2 max threshold so i'm curious in terms of your own personal performance i mean i have a road bike i've done a few loops around moraine golden gate great biking area so if you're ever in the bay area we've got to do some uh some some road biking but uh 250 miles a week is no joke i mean you know i'm curious in terms of some of the metrics uh you know what kind of uh have you done rt testing on yourself uh in terms of athletic performance kind of how are you kind of optimizing on that front if that's something of interest to you i have not done rq testing one myself but i can tell you that i'm a much better cyclist now than i used to be before and i can routinely do three hour rides on a fasted state without eating anything it's always so overnight fasted you wake up you just blast out like 50 miles that's correct i have done a 60 mile ride in three hours uh waking up in a fasted state and not have to take any gels never bonking and it has been a great experience now i do put a little salt in my water and perhaps at the end of three hours if i just have a few nuts it would be enough for me and my power to weight ratio has not gone down i can measure my power to weight ratio because i have a power meter on my bike and because i have lost weight i am able to be more competitive since i have not lost my power to weight ratio but you're right i think i should consider doing a vo2 max study as well as an rq ratio yeah that would provide more more data yeah have you i mean how how much watts are you holding when you're sprinting i think the craziest stat that i got from lance was like apparently at his peak he was holding over 500 watts for 30 minutes like at its peak i'm like that is friggin insane for anyone that knows anything about power and wattage i mean like for for casuals like if you're at like a soul cycle or like a peloton thing like i bet it's like very even hard it's like very hard to even like break 200 or 250 for like more than you know 30 seconds right i think uh like for example that just a few days ago the tour de france was won by uh tarjay uh a young slovenian cyclist uh poachkar i'm maybe messing up his name i apologize but 21 years of age and in the last 30 minutes of the time trial that he did to win the tour de france he was putting 7 watts per kilogram which is like totally incredible seven watts per kilogram is totally incredible so like let's say i'm a much older cyclist and i can perhaps maintain about three and a half to maybe four watts per kilogram for maybe 20 minutes so that that in and off itself is a totally incredible feat i'm sure that lance armstrong was right up there at about seven plus watts per kilogram in his peak days and by the way i'm a big fan of la lance armstrong i mean despite uh his takedown with the drugs and all that i think at that time everybody was doing drugs and so i i don't know if i would fault him for the way he behaved but i in my mind he's still a champion yeah i think that and i think ever after getting to know him a little bit having some conversations with them i think it's uh yeah i think the past is a past but like what he did was amazing given the context of the time and like if you look at the facts like everyone was on drugs and like that doesn't excuse anyone for doing or not doing drugs that was just a fact of that era so you know on to just you know happier topics in in terms of not doping and getting busted and getting stripped and everything uh what it what are in the in the books for you for the rest of 2020 sounds like the practice is going well and i think that's really i think the future of medicine i think there will be practitioners doctors like yourself who are i just honestly just like a lot more thoughtful and i think this is not to denigrate like what i've seen for a lot of doctors but it feels like a lot of doctors end up being like like like uh technicians right it's just like algorithm in oh like high blood sugar okay metformin oh insulin right like oh high cholesterol high blood pressure medicine and like maybe that's like the first line of defense so we just need to like kind of get people enough prescription drugs but it has to move more towards the the way that you're practicing medicine which is actually having conversations with the individual actually improving educating about a better lifestyle and not necessarily using the crutch of a pill to then like kind of push down the the like the real the real serious things an extra couple years what can we do to keep fighting that fight i mean well you know you're obviously busy in the practice but you also run i know that you eat mostly fat channel anything else you're doing on that front in terms of helping change the way we do medicine in our country today so i really actually have a request to your listeners and to people who listen to this podcast is that i really want your help because i want to modulate my practice to do more of what i just described in here i want to counsel people i want to measure their insulin and glucagon ratios and i would like you to invite me back on another time so that we can discuss how the insulin producing machinery of the pancreas and how the glucagon producing machinery interacts with each other in a paracrine way which means that these two cells are right next to either each other they are juxtaposed and why is that interaction and relationship important and i think i'm probably one of the only practitioners in the world who's measuring those things and i'm finding some very intriguing and interesting data through which i can help people so my request to people who hear me is that help me do this and the way you can help me do that is changing my practice so i want you to consult me online if it is of benefit to you if it's something that you need so that i can move away from doing regular garden variety cardiology spending having to spend in the cath lab opening up people with stents and do more of this work so that i learn and i feel that this is the service through which i can benefit my patients i'm very interested in putting out this information i put it out in youtube videos either through eat mostly fats channel or through another different channel that you can find easily by googling my name so that is my request my humble request to people is that find me on the internet see if you need to consult me so that i can do more online consulting work and less of the regular cardiology work so that i improve in my knowledge and i can do this better yeah i think that's you know for folks that you know i think that resonate with this conversation absolutely so that email that link is eat mostlyfat.com to go and find you is that correct yes sir that's good yeah and i think that like that's the and i think again we have to i mean vote with their dollars or vote for with our time and attention towards the practices that we think should succeed i think that's kind of also the beauty of the competition of ideas right if we choose to spend our time our energy with with the system that we actually don't fundamentally think is the right way moving forward well your behavior action is is dictating your voice so if we can move our attention our resources towards these more enlightened approaches that in itself will will change the healthcare system around us so absolutely 100 you know happy to help push and and endorse on that front so absolutely i know that we wanted to talk talk insulin and glucagon because we hear insulin all the time but glucagon is essentially the opposite hormone of of insulin is glucagon and it's much less well understood so we'll have to have you back on next time to talk more about that specific topic so thanks so much dr nadir ali on on taking the time here i know it's a little bit of a craziness with hurricane and all of this stuff but glad this worked out glad this that we connected and we'll talk soon i like it jeff and i like it especially that we are ending on a cliffhanger and the cliffhanger is that hey tune back into jeff's podcast again because you need to learn about insulin glucogon all right we'll leave it there thanks so much take care everyone

Channel: Ketone-IQ

Views: 180,044

Keywords: Eat Mostly Fat, HVMN Podcast, Podcast, Dr Nadir Ali, Low Carbohydrate, high fat, LDL, Cholesterol, insulin, medicine, fat, heart disease

Id: zul-maTs--c

Length: 74min 51sec (4491 seconds)

Published: Mon Oct 05 2020