Dr. Paul Mason - 'High cholesterol on a ketogenic diet (plus do statins work?) - 2019 update'

so good afternoon my name is dr. Paul Mason and I'm a doctor from Sydney in Australia and today I want to take you all on a journey looking at exactly what it is about cholesterol that might be a problem with respect to our health and I'll tell you straight up LDL cholesterol is not one of them not high LDL anyway we're going to look at everything from the idea of small dense particles oxidation rates and we might even have a look at particle count and lipoprotein little a and then we're going to finish by touching on statins and I'm going to include some hopefully quite revelatory data regarding the true side effect rate of statins so by way of disclosures I have a website so I know that's a pretty disappointing disclosure that I run a metabolic clinic with another fellow Australian doctor an orthopedic surgeon by the name of Ron sure and aspirationally at least one day we're going to populate this website with some useful information so let's begin with the biggy LDL LDL is almost uniformly known as bad cholesterol or at least 20 buddy with a medical education and this pejorative nature of the term says it all people are afraid of LDL worried they're just gonna drop off the perch because it's high now because of this there's now more cholesterol-lowering drugs out there than you can poke a stick at and it seems that every second patient he comes into my door is on a statin drug because they're trying to lower their LDL which is funny really because LDL doesn't really appear to be that bad at all this systematic review from 2016 looked at 19 cohort studies with over 68,000 participants and of these 19 studies 16 of them found an inverse relationship between LDL cholesterol and all cause mortality that is the higher your LDL cholesterol the lower your all cause mortality so last year a new patient came into my room and when I saw him I thought to myself this guy's an athlete but this wasn't my Sports Medicine Clinic this was my metabolic clinics I thought ah somebody at the front desk has made a mistake that booked him into their own clinic so anyway he gave me this letter you see he had recently applied for income protection insurance that required medical testing and he had failed so this is him this photo was taken a few days after he received the letter he's 48 years old a regular exerciser and he also happened to be on a high fat killer genic diet this is what's called a DEXA scan this is his DEXA scan showing his body composition the blue areas represent lean tissue and the red areas represent fat so I wasn't getting it why was this guy considered too much of a medical risk to insure well feels his cholesterol levels these are his actual test results the ones the insurer used to make their decision and here are the u.s. values there and on the right hand side you can see the standard reference ranges which his values were meant to reflect and based on these reference ranges his LDL of 6.7 or 259 in US units is where he came unstuck the insurance company was worried that this high LDL level would cause him to have a heart attack after all athos quadric plaques are filled with LDL and cholesterol so high circulating levels must cause it right know this myopic perspective ignores the fact that both LDL and cholesterol are essential for good health indeed they're essential for life full stop and LDL itself can also be good and it can also be bad and the process of turning good LDL into bad LDL isn't driven by fat in the diet is driven by carbohydrate this is because carbohydrates even the so called healthy complex carbohydrates they're literally made of sugar glucose molecules sequence to and when you eat carbohydrates that same glucose enters your circulation and there it can damage the LDL particles so let's take a look at exactly what LDL is let's first clarify some terminology the term cholesterol is often used loosely to refer to these lipoproteins here you see up here on screen on the sole basis that these lipoproteins carry some cholesterol inside them but that's ridiculous that's like mistaking a bus for one of the passengers and it's absolutely ludicrous as it sounds crest roll itself is a small molecule absolutely essential for life and it's very very different to the much larger and much more complex lipoproteins that you see here so there's five major classes of these lipoproteins and we can differentiate them out based on their size and their density so on the bottom left here you can see something called a collar micron now collar microns are formed after we eat and that's how we digest fat but by the time we do a fasting blood test these are disappeared from the circulation so we don't need to worry about them anymore and if you cast your eyes up to the top right of screen to the hydrogel this is smallest and densest lipoprotein and it's colloquially known as good cholesterol higher levels are generally favorable but we're not going to really focus on that much today instead I really want to focus on the three particles in the middle the LDL IDL and LDL these stands for low down very low density intermediate density and low-density lipoprotein and I've linked these three lipoproteins by arrows to demonstrate that they're actually the same particle they start out as vldls which get released from the liver and then they circulate around the body and as they go they release some of their lipid cargo and they donate it to tissues for energy supplies and things like that and as they do they shrink a little bit it's like a deflating balloon and we can identify these particles they've got a unique protein that's embedded in their outer coat and that's called an app Hobie 100 and every one of these particles has exactly one app OB 100 protein contained within the coat and this is a representation of the app OB 100 here and you can see it winding in and out of the LDL particle now that's a look at the normal life cycle of one of these up OB 100 carrying lipoproteins so it starts with secretion from the liver and it's worth noting that the LDL secretion is actually significantly increased in states of insulin resistance so the VLDL particle delivers some of its triglycerides to cells around the body and reduces in size first of all that becomes an intermediate density and then a low density of lipoprotein and these LDL particles can then be recognized by these special receptors on the liver using the appo b100 protein and the livers can then recycle the LDL protein back out of the circulation this is normal human physiology now this year is a bit of a close-up of the FO b100 protein and I've just identified a region here which we call the LDL receptor binding site so this is the part of the FO b100 that the liver can recognize without that the liver can't recognize this particle person Oh in a non grata you know you're not coming in here and sugar can damage org like eight this region sugar from carbohydrates and this effectively will stop the LDL receptor on the liver from being able to recognize it and another point this process of glycation also fractionally shrinks the LDL particle just enough for it to be known as a small dense particle ever heard of the small dense LDLs well this is where it starts but then we can further modify LDL the process of glycation generates a lot of what we call oxidant stress and this can also lead to oxidation of the LDL particle and we now call this one a glyco oxidized LDL and this process of oxidation can also lead to shrinkage the LDL particle now it doesn't have to be glycated to be oxidized oxidation can occur for a number of reasons interestingly if you've still got an intact up over 100 receptor site the liver can actually take this oxidized LDL out of circulation and there it can actually create oxygen stress to the liver and there's now an increasing body of literature that demonstrates it's the oxidative stress to the liver in part contributed to by this mechanism that actually leads to alcohol fatty liver disease and furthermore if we put in a potent antioxidant like something like melatonin there's very good evidence that we can ameliorate some of the effects on fatty liver disease but with enough oxidant stress we can actually damage the FOP 100 proteins so it can't be taken up by the liver and that's irrespective of whether it's glycated or not and that little bit of extra oxidation also just makes it that little bit smaller so putting all of this together you can see we've got these different populations of LDL which vary in terms of their size and density based on degree of oxidation and glycation and the key point here is that some of these states are associated with damage to the appo b100 protein which will prevent the liver from recognizing it and being able to take it out of circulation so we end up in a situation here where the modified LDL particles are unable to be taken up by the LDL receptors as normal and over time they begin to accumulate and this leads to what we know as an increased LDL particle count now because they're small the volume of these LDL particles isn't that great but their number certainly is and that's why the particle count is actually a much better predictor of cardiovascular risk than the total LDL volume now this study was published just last year and it was based on a 15-year follow up of nearly 28 failures and females and it was looking at the development of peripheral vascular disease and you can see that while the volume of LDL cholesterol didn't seem to matter too much the particle sound certainly did in actual fact is quite significant so let's look at why these particles are so bad and how exactly do they end up in the blood vessel wall so for oxidized LDL to enter into an atherosclerosis it has to pass through the lining of the artery and first of all it helps to breach this brush-like layer which is called the glycocalyx and you can see a cross-sectional view of a blood vessel here and you can see the Faerie lining which is actually the glycocalyx now the glycocalyx serves several important functions it regulates the tone of the blood vessel the degree of muscular contraction how much Bloods going through it also helps protect the underlying layer that layer of endothelial cells you can see underneath that are joined together on the sides and high levels of blood sugar damage the glycocalyx in this graph here shows the volume of glycocalyx before and after only six hours of elevated blood glucose levels one point to note here is that oscillating blood sugar levels are even more deleterious in actual fact and every if you have a look at these charts here they're from a continuous glucose monitor from some of my patients you can see that the average blood sugar on the top tracing is 4.7 compared to 5 point 6 on the bottom tracing but i'm far happier with the bottom tracing because it lacks these oscillations which are associated with extra oxidative stress we also have these special proteins we can ingest in our diet that are called lectins and they can also damage the glycocalyx so after we ingest them the leptons can actually cross over the intestinal barrier and subsequently they can enter into the circulation after which they can bind to and damage the glycocalyx and what you can see here is that fluorescent labeled wheat germ agglutinin which is a lectin is actually binding to the interior of this blood vessel binding to the glycocalyx the presence of oxidized LDL in the circulation I was probably even more significant in the other factors and the graph here demonstrates how the presence of oxidized LDL precedes the development of atherosclerosis you can see the volume of circulating oxidized LDL decreases shown in yellow at the same time that the size of the astros glory Clark increases shown in red so why is oxidized LDL so bad how can it increase the rate of transfer of LDL across the wall of the blood vessel by 20 times well it's particularly damaging to the glycocalyx and this disruption of the glycocalyx results in a loosening of the tight Junction proteins which actually holding the epithelial cells together and this allows these oxidized LDL particles and cells called circulating monocytes to actually migrate into what we call the sub endothelial space and once there these monocytes turn into another type of cell called a macrophage and these macrophages Express something called a scavenger receptor and this scavenger receptor can actually recognize and bind to the damaged LDL particles that the liver receptors could not and this results in these damaged LDL particles being ingested by the macrophages leading to the formation of something called a foam cell which is basically a macro fire just packed with lipid and this is what it looks like under a microscope and these foam salts are contained within our throes caloric plaques and this is the end result this is a left anterior descending artery of the heart and this is more commonly in medicine known as a Widowmaker it's kind of useful and you can see how the internal lumen of this artery is so narrow that there's only a trickle of blood that's getting through now it's not a good state to be in so that's the process that causes blockage of arteries you have oxidized LDL and now they have blood sugar levels and their significant contributors so eating saturated fat might increase your LDL level but it doesn't make it go bad it's eating carbohydrates that makes the LDL go bad and then we come to the question that's relevant to my patient how do I know if he's got oxidized LDL any circulation well we can actually analyze LDL using centrifugation so this is an example here of the healthy LDL sample so first of all we place it into the gel and then we spin it down so that the different lipoprotein populations move through the gel to different distances based on their size and their density and the dark lines in the gel represent different populations which have traveled different distances and the results are presented like this and you can see that dark lines within the gel actually match the peaks in the graph and the height of the peaks actually represents the overall volume of volume of each LDL or lipoprotein sub fraction and if we put it back into the nomenclature that we saw before you can see you've got the LDL IDL and HDL are also demonstrated there so let's see how an unhealthy LDL population would look on this so I want you to just focus on this yellow box and then we'll put in the unhealthy sample here and what you can see is that once this has been spun down you can actually now see two distinct populations and if we had a look at them on a graph under the LDL section we would actually see two distinct Peaks or two distinct populations this is now starting to look not so good but we saw before that we've got more than two potential populations of LDL well these are some of my other patients this is a triple burner or perhaps you know getting this person should start on their wine cellar pretty soon or they should change their lifestyle so we can actually test for oxidized LDL in another way and we can use something called anti-bot so the surface particles of molecules on the surface of oxidized LDL are changed from normal and we can use something called antibodies which have very specific affinity for some of these changed particles and basically these antibodies will only attached to oxidized LDL and not to native or healthy LDL and this is the results from one of my patients using this test and she was shown to have an elevated oxidized LDL level now if you understand how this antibody test works then you can understand something called lipoprotein little a now this lipoprotein little a has been strongly shown by the evidence to be associated with adverse cardiovascular outcomes but there's a lot of confusion about why that is it seems that a lot of people don't really understand what's going on with it so what is it well it's basically we take an LDL particle like this with an a Popey 100 protein winding around it and then we get something called in a little a Poe a protein and attach it that's that's what lipoprotein little a is is just this little extra protein just being attached to the side now it's often been said that lipoprotein little a levels are genetically determined but this doesn't stack up with the science for instance in babies the average lipoprotein little a level is about five times lower than in adults and when we look at the levels in babies there's absolutely no differences based on gender or racial differences so pretty strongly suggesting that genetics aren't really playing a big role rather lipoprotein little a levels reflect changes in metabolic health now there's a little bit of information that I haven't given you yet and that's because the lipoprotein little a will only have an attraction for an LDL particle that's been oxidized so this ditch is not correct because that's a non oxidized LDL so in reality lipoprotein little a is not going to attach to that and that means if the particle is not oxidized it will not form a protein little a so the presence of this whole molecule the lipoprotein little a is nothing more than a marker of oxidation so it's absolutely analogous to the antibody based blood test that we can do for LDL cholesterol for oxidized LDL and this is why the predictive value of oxidized LDL and lipoprotein little a is so similar they're effectively measuring the same thing and when we do look at the intervention Studies on reducing oxidized LDL we also see we get reductions in lipoprotein little life they're just travelling along together now I'd just like to briefly talk about statins and their influence on LDL so remember that the healthy native LDL is removed from the circulation by the LDL receptors expressed on the liver well statins they inhibit something called hmg-coa reductase and this actually results in the increased expression of these receptors on the liver and that's how they actually lower LDL more receptors it takes more of the cholesterol out of circulation except we've just learnt that these receptors don't bind to oxidized LDL you know the bad ones so they take the good stuff and they leave the bad stuff behind so by reducing the total volume of LDL particles there's going to be less LDL particles around in the future to be oxidized so in the longer term they might actually be able to reduce oxidized LDL levels but the ratio between the two is going to be much less favorable and this ratio between oxidized LDL and healthy LDL has actually been strongly associated with poorer cardiovascular outcomes and this study actually was based on a statin study of 16 weeks of a very high dose statin and it actually reduced or increased the ratio of the oxidized LDL to the healthy stuff by about 10% so based on this kind of study you'd think that the likely benefit of statins would be pretty minimal and you'd probably be right so most people take statin medications to stop themselves from dying but that's not the way you should think about it because you're gonna die anyway what they might do they might delay you dying so that's a much better question to ask if I take this medication for X number of years on average how much longer will I live so this review was based on data from eleven studies over 90,000 participants and it followed them up for four and a half years so just a quick show of hands here who here would take a statin medication if it would increase your lifespan by one week okay what about one year guys about five years come on yeah I mean five years is good right five years is good so let's have a look at what this study showed so if you had a history of cardiovascular disease and you took a statin as per the protocol here you'd get another five days but what happens if you didn't have heart disease most of you guys haven't had heart attacks before well then you get three days and in experimental studies where LDL levels are reduced they also have similar findings so this was a really neat study so it was performed on a people with a condition called familial hyperlipidemia which is a genetic condition that just puts your LDL levels through the roof and it makes a lot of doctors nervous so when a new drug came out a group called pcsk9 inhibitors a lot of doctors got really excited because for people with both genes affected in this condition it could lower your cholesterol your LDL levels by about 60% absolutely massive reduction so what did this study find the clinical benefit was of this kind of reduction in this population well unfortunately there was no statistically significant findings that's you know the thought was there so then the question is what about side effects that's something you know we always argue about that now we've got the Sir Rory Collins who reassures us that the rate of side effects from statins is less than 1% and I'd really like that to comfort me but it's a bit tough because it's totally false it's actually closer to 25% about one in four and thanks to this paper on pcsk9 inhibitors we have the data to prove it because you see one of the entry criteria of this study was that participants be on statin therapy except when I went to have a look at all the the data the study participant information it seemed that not all of them were and that's because some patients simply can't tolerate the statins so by reviewing the data and crunching a few simple numbers I was actually able to come up with the true side-effect rate of statins and these were big numbers so you can see the numbers that they're based on there so you know thousands of people there so one in ten patients could not tolerate any statin that was tested at the lowest available dose and the criteria were very explicit you had to have medically documented intolerance to at least two different types of stands including at least one of those being used at the lowest possible dose and even in then one in ten people couldn't tolerate it and what about standard dose statin therapy well one in five twenty percent of people couldn't tolerate that because they had a level of side-effects that was too significant for them and the death Nishan of the standard dose certain therapies is 50% of the dose the maximum dose in a single tablet that you can get in the market that's basically the way you can think about it and despite all of these people who had these side-effects being excluded of not taking statins 5% of them still had clinically diagnosed myalgia or muscle pain far in excess of the background rate so that would suggest adding on that extra 5% that at least one in four people are intolerant the standard statin doses and that's where I'll finish so please remember it's a carbohydrates not the saturated fat that damages LDL and the benefits of statins have probably been exaggerated and the harm certainly appears to have been minimized I think everybody should have access to accurate information so they can make their own informed decisions and oh yeah my patient his lipid profile was awesome thank you

Channel: Low Carb Down Under

Views: 232,602

Rating: 4.9123287 out of 5

Keywords: Low Carb Down Under, LCDU, www.lowcarbdownunder.com.au, Low Carb Denver 2019, #LowCarbDenver, LDL cholesterol, ketogenic diet, LCHF, Low Carb High Fat, carbohydrate restriction, athrosclerosis, heart disease, statins, Low Carb Doctors, statin intolerance, bad cholesterol

Id: TRB0jOfymLk

Length: 27min 23sec (1643 seconds)

Published: Sat Jul 20 2019

Reddit Comments

[u/RandomDog61]

Excellent stuff and accessible for the non-scientist.

[u/xsizo]

anyone got a tldr version?