Dr. Paul Mason - 'The truth about high cholesterol'

[Music] thank you g'day I'm Dr Paul Mason this lecture is about the science which contradicts not only everything I learned about LDL in medical school you may have seen this anti-smoking ad before this is part of an aort the main artery from the heart smoking makes artery walls sticky and collect dangerous fatty deposits this much was found stuck to the aorta wall of a smoker age 32 until recently we tended to blame this disease on the fat and cholesterol within our diet this is known as the lipid hypothesis simplistically eating fat causes our LDL level to rise which then blocks Our arteries and unfortunately when President Eisenhower had his heart attack in 1955 this was the reasoning wheeled out by the most vocal and influential scientists of the time this put the lipid hypothesis on track to haunt us for generations to come the question is what is the evidence that high LDL will kill you this systematic review answered that question 19 prospective cohort studies with over 68 000 participants were reviewed and the overwhelming finding was that individuals with the highest LDL levels lived the longest in fact 16 of the 19 studies found this relationship the higher the LDL level the lower the chance of death and it didn't matter how you sliced it or diced it comparing the very highest LDL group with the lowest or just the second lowest high LDL levels came out on top even when study subjects with terminal diseases heart disease diabetes were excluded the results stayed the same this study found about a 50 reduction in the chance of death in the highest LDL group compared to the lowest in a nutshell the findings of this systematic review are robust and dismissing or ignoring them is scientific fraud let's take a look at exactly what LDL is you may be surprised to see that it doesn't have horns it might also surprise you to see how complex it is in fact the body devotes a lot of resources to producing it it's a complex structure called A lipoprotein it's made of fat cholesterol and protein and remember the term lipoprotein you've probably come to associate LDL with cholesterol though maybe even mistake one for the other in fact many doctors do they often talk about LDL and cholesterol like they're the same thing the thing is LDL is so much more than just cholesterol here you can see that LDL carries cholesterol bound to fatty acids as cargo while also containing cholesterol penetrating its surrounding membrane clearly LDL is more than just cholesterol so both cholesterol and LDL particles can be found in atherosclerotic plaques so does it have a causative role scientifically speaking this is what guilt by association looks like nonsense it's confusing correlation with causation just because two things exist together at the same time doesn't mean one caused the other so let's now take a closer look at all the lipoproteins the first thing to understand is that LDL is only one of five major classes of lipoprotein the most obvious difference between them being by size the Lipo protein on the bottom left is called a kylo micron and it's formed after we eat by the time we do a fasting blood test though mostly this has disappeared so we don't need to worry about that anymore up in the top right you can see HDL which is colloquially known as good HDL for the moment though I just want to focus on the three lipoproteins in the middle the LDL IDL and LDL this stands for very low density intermediate density and low density lipoprotein the smaller the lipoprotein the denser it is and you'll observe that rather than show them separately I've linked them all with arrows and that's because in essence they are all the same particle think of the LDL as a balloon with a slow leak given these lipoproteins are defined by size as it shrinks it arbitrarily becomes another type of lipoprotein eventually becoming LDL so in essence LDL is just a shrunken form of vldl and vld shrinks as it delivers its lipid cargo to various tissues around the body because well that's its job so where does vldl come from in the first place it's made by the liver it then circulates around the blood delivering its lipid cargo first becoming an intermediate density lipoprotein and finally a low density lipoprotein LDL is then taken back up by the liver for recycling I'd like to take a detour for a moment and address the long-standing myth that dietary cholesterol and dietary saturated fat increase LDL levels examine this diagram and ask yourself what factors could increase ldr levels increase production of the LDL precursor of the LDL could be one another is by reducing the reuptake back into the liver here's the thing though cholesterol and saturated fat do neither if dietary cholesterol increased LDL then one would presume that by consuming seven thousand milligrams daily of cholesterol would lead to high ldlers LDL levels and in this quite fabulous study they fed patients 35 Eggs Daily for a month their cholesterol levels remained normal nor does saturated fat increase LDL consider this randomized control trial which gave subjects 50 grams of either coconut oil olive oil or butter for four weeks compare what happened in these subjects who consume the coconut oil which contained 94 saturated fat to those consuming butter containing 66 saturated fat this is what happened in the coconut oil group their LDL level dropped this saturated fat causes LDL to rise Theory isn't looking so good anymore and despite containing far less saturated fat the butter led to a significant increase in LDL so let's now get back to our lipoproteins vldl IDL and LDL now each of these particles being essentially the same they carry the same unique identifying protein in their membrane is called APO B100 APO B100 serves the essential function of acting like a swipe card that allows these particles to be recognized by receptors on the liver and souls around the body if they can't be identified because the APO B100 is damaged they can't deliver their essential cholesterol cargo here you can see for example LDL is unable to enter the liver these EPO B100 damaged lipoproteins can still reach the receptors they just aren't Less in and this leads to their accumulation in the circulation this leads to what is known as an increased LDL particle count now because they're small the absolute volume of these accumulated particles is actually not that much when it's compared relative to their number count so in essence you end up with lots of particles but not much volume not much what we call LDL cholesterol level which is what's normally measured and this explains why particle number is actually a much better predictor of vascular disease than total LDL volume this 2018 study based on 15 years of follow-up of nearly 28 000 females supports this it found that while the volume of LDL cholesterol didn't predict heart disease at all the particle count did those with a high particle count had an only two and a half times increased risk of heart disease so then the question is if damage to LDL lipoproteins increases the risk of cardiovascular disease can we tell if we have normal or damaged LDL and the answer is yes you see when an LDL lipoprotein gets damaged it functionally shrinks the more damage the greater the shrinkage and the Damage tends to happen in stages which means that damaged LDL tends to have distinct populations evidence of the importance of this in considering risk of heart disease comes from this study more than 11 000 subjects and you can see four different lines each representing varying levels of undamaged LDL and this is often called large buoyant LDL and this is graphed against cardiovascular risk and you can see that increasing levels of undamaged LDL represented by the different colored lines does not increase cardiac risk essentially the four lines are on top of each other compare this then to an analysis of small densed LDL the damaged version of LDL you can clearly see that the elevated levels of small dense LDL are associated with a much greater risk of heart disease even when total LDL levels are low the presence of small dense LDL predicts cardiac risk and this is far from an isolated finding take this eight-year study from Japan which found those with the highest small dense LDL levels were five times more likely to suffer from heart disease and we can test for the presence of small dense LDL using a centrifuge to separate LDL particles based on size and density this is an example of a healthy LDL sample first of all it gets placed in a gel and then spun down so that the different lipoproteins move through the gel based on their size and density the dark lines at the top represent different lipoprotein populations which have moved different distances and the results are presented like this you can see the Peaks matching the dark lines in the gel the height of the Peaks represents the overall volume of each lipoprotein you'll note in the LDL section in the middle that there is only one clear Peak evidence of a single healthy LDL population let's see what an unhealthy LDL sample looks like Focus here on the LDL section within the gel within the yellow box now you can see that there's two distinct populations which on a graph would look like this you can now see two distinct peaks of LDL and further damage to LDL could lead to a third or even a fourth peak in this example you can see that the damaged LDL population is significant much more than the healthy one and you can also see a large amount of lipoprotein in the fourth and fifth bands those vertical columns and the fourth band is where things really start to head up this 2021 study found predictably there was no difference in LDL levels between those with and without coronary artery disease that was just total LDL when they looked at LDL sub-fractions though they found the presence of LDL in band 4 or above was almost always associated with coronary heart disease that means this Twin Peak LDL pattern with LDL extending out to Band 3 might well be okay while this three peaker where you can see LDL going out to band 4 almost certainly indicates a problem and while informative this testing is expensive fortunately we can get some assessment of the likelihood of a pattern B LDL subtraction that is one without damaged LDL based on measures from a standard blood lipid panel the most important marker is triglycerides an analysis of more than 5 000 patients with heart disease found a clear correlation between triglyceride levels and the presence of small dense LDL particles the grouping on the left that represents those patients with small dense LDL and the cluster on the right that sort of L-shaped cluster that represents patients with the large buoyant LDL and the y-axis is the level of triglycerides and you can see that the cluster on the left representing the small dense LDL the damaged LDL they had on average much higher triglyceride levels furthermore you can see as you move towards the right in the graph where the LDL was larger or more buoyant High triglyceride levels become quite rare in fact a triglyceride level of less than 0.8 millimoles or 70 milligrams a deciliter is predictive of a low risk of having small dense LDL conversely a trigoside level of over 2.8 millimoles a liter or 250 milligrams a deciliter is bad news bare and this data correlates very well with previous research this study was from 1990 and you can see that only about five percent of subjects had small dense LDL when their triglyceride was less than 0.8 millimoles a liter or about 70 milligrams a deciliter and I'd also like to point out that at less than 0.5 millimoles a liter or 40 micrograms a deciliter the incidence of small dense LDL approaches zero and we now come to HDL where a higher level is desirable here it is clear that the rate of small dense LDL is increased substantially with HDR levels below about 1.3 millimoles a liter or 52 micrograms a deciliter even better than triglycerides or HDL in isolation when predicting for small dense LDL is the ratio between the two you can see here that a ratio of over about 0.9 in millimoles or liter units or over 2.0 in milligram of deciliter units is associated with a greater probability a small dense LDL I therefore think that this is a reasonable algorithm to assess the probability that a lipid profile is either atherogenic or non-athrogenic that is artery clogging or not artery Club I'm now going to muddy the waters a little bit I've demonstrated that higher ldr levels are on average associated with longevity that doesn't mean that every case of LDL elevation is a good thing however of LDL versus mortality you can clearly see on the left that that the greatest risk of death is with the lowest level of LDL you can also see that risk increases although less so with the highest levels of LDL and this is not surprising because several factors can increase vldl production ultimately increasing the number of LDL particles the most obvious of these is insulin resistance and something that may surprise you is that insulin resistance can increase on low carbohydrate diets often in association with increased LDL and usually in the context of a high Dairy consumption you see Dairy can contribute to insulin resistance this study found a high Dairy intake predicted insulin resistance in middle age females a finding supported by this experimental study which compared diets rich in Dairy to a diet rich in red meat while maintaining a constant weight over four weeks the subjects consuming the high dairy diet were found to experience an increase in their fasting insulin levels consistent with insulin resistance despite having a normal glucose tolerance at the start of the study and one caveat is that while Dairy can worsen insulin resistance it's still not as bad as most of the foods on a standard Western diet and this is why population studies can indicate that Dairy is associated with improved insulin resistance because Dairy is taking the place of some pretty bad food it's also easy to over consume Dairy and I believe one of the reasons for this is that it naturally contains a version of morphine for many who are struggling to give up the warm hug that you get from sugary Foods provided by that dopamine Rush Dairy can simply become a replacement it becomes a go-to and incidentally this is one of the reasons while Dairy can be constipating the constipating effects of morphine being well known there's also good evidence that B12 deficiency is causally associated with increased LDL here you can see a significant increase in cholesterol synthesis due to low vitamin B12 and don't for a second think that the standard B12 reference interval reliably identifies B12 deficiency it's a reflection of population averages and given that B12 deficiency is increasingly common many cases go missed another potential cause of elevated LDL relates to inflammation in particular a signaling protein that often circulates in the blood in inflammatory States this is called tumor necrosis Factor Alpha this study used Syrian golden hamsters whose lipid system closely resembles that of humans and demonstrated that tumor necrosis Factor Alpha caused overproduction of the LDL the LDL precursor up times normal in fact so when I observe an unexpectedly high LDL level I'm always on the lookout for sources of inflammation and along a similar vein I'd just like to point out that there are numerous potential causes for elevated triglyceride levels besides sugary carbs and alcohol some of the most common ones I come across include an underactive thyroid kidney disease diabetes hemochromatosis and numerous drugs including beta blockers and corticosteroids so as with LDL if you see an unexpectedly elevated triglyceride level be sure to consider more than just diet in closing the story we've been fed about LDL is the major cause of heart disease is clearly nonsense when LDL becomes oxidized however it can become a problem and the triglyceride to HDL ratio is a reliable way of predicting this even if LDL is not oxidized a very elevated ldr level may be symptomatic of another issue that ought not be overlooked thank you [Music]

Channel: Low Carb Down Under

Views: 420,110

Keywords: Low Carb Down Under, LCDU, www.lowcarbdownunder.com.au, Low Carb Gold Coast 2022, Paul Mason, LDL, Cholesterol, Cardiovascular Disease, Lipoprotein

Id: rdgS3PuSuyg

Length: 20min 43sec (1243 seconds)

Published: Sat Nov 19 2022