Dr Sten Ekberg gets fact-checked by MD PhD Doctor

a lot of viewers asked me to take a look at  this video, it's called "your doctor is wrong  

about cholesterol" and it's by Dr Stan Ekberg, I  think that's how you pronounce it so let's take a  

look. if you're a regular viewer you're probably  already familiar with the rules of the house:  

we don't do ad hominems, we don't go after  personality or physical appearance or motive.  

nothing like that. we only care about one thing:  do the claims match the science. that's it. all  

right? let's get into it. when people are changing  their lifestyle and they're getting healthier,  

they're losing weight, they're feeling better,  all their health markers are improving except one.  

yeah I hear this question a lot, people find  a diet, usually in a popular book or on social  

media and they lose some weight, they feel  better but they have some lingering concerns.  

it's different for different diets, with low  fat it's sometimes that triglycerides go up,  

with low carb it might be that the cholesterol  went up, but of course it doesn't have to,  

it's possible to eat low carb diets without  raising your cholesterol, you can even lower your  

cholesterol on a low carb diet, it just depends  how you design it, how you put it together, right?  

so hopefully he's going to cover all that, I don't  want to steal his thunder so let's keep rolling.  

we have bought into the idea, without any good  evidence, that LDL cholesterol is bad cholesterol.  

yeah I'm not a huge fan of these nicknames either,  the good cholesterol and the bad cholesterol,  

I get how this started, I get why people started  calling them that but it can be a little confusing  

and there are better ways to explain this topic  to the public so hopefully he's going to get into  

all that. what I want to help you with today is  to make an informed decision by understanding  

the true factors and what's really going on. yep  that's what it's all about, giving people the best  

scientific information so they can make educated  choices, couldn't agree more, love it. what we  

really want to get away from is the idea that if  cholesterol is over 200, if your total is over  

200, then you get this automatic prescription  for a Statin drug. or if your LDL is over 100,  

that that should be some magical number that now  you get a Statin drug. yeah absolutely, you don't  

prescribe a Statin just because cholesterol  crosses that threshold. lots of examples,  

if you have a 30 year old patient without other  health issues, without a history of heart disease,  

and their LDL cholesterol just crossed that  threshold of 100 milligrams per deciliter,  

just went up to 105, do you automatically  slap that person with a Statin? no,  

there's lots of other things you talk about  first, you advise lifestyle Etc. and by the way,  

the guidelines are explicit on this, a Statin  is not indicated just because someone's LDL  

cholesterol is over 100 milligrams per deciliter,  there's all kinds of other considerations and  

other things you might try, it's only at 190  milligrams per deciliter of LDL cholesterol,  

so almost twice that threshold, that a Statin  is always indicated, and that's because at that  

very high level you start to suspect a genetic  condition. also, if someone has diabetes or if  

calcium score is elevated or if they've already  had a heart attack or something like that,  

these are people at higher risk so a Statin is  always indicated. otherwise you don't dish it out  

automatically just because someone crosses that  100 threshold. so yeah, if a clinician is giving  

out statins automatically for everyone who's LDL  cholesterol happens to be over 100 milligrams per  

deciliter without looking at anything else, yeah  that's not what medical organizations recommend,  

I don't know anybody who does that but if there  is someone doing that reflexively, yeah, that's  

not how it's supposed to be done, I agree. so far  this has been pretty reasonable. oh, real quick,  

since it seems like he's going to go into statins  and people always ask about conflicts of interest,  

mine are real simple, I've never made a dime  from statins or any other drug in my entire life,  

don't have any affiliation with big Pharma or  any industry, we don't even accept sponsorships  

on the channel, we just share the best  science, I don't really care who makes  

money off of it or not. do statin drugs  lower cholesterol? yes absolutely they do,  

but we're going to talk about whether that  is actually a good thing. yeah absolutely,  

statins lower serum cholesterol levels, that's not  controversial, and it sounds like he´s going to go  

beyond just whether they lower cholesterol, which  is excellent. we're going to answer what kind of  

cholesterol do they lower, is that something  we actually want to lower. yeah, what kind of  

cholesterol and also the effect on lipoproteins  is really essential for this topic, so  

sounds like it's going to go into all that,  great. we're going to ask about heart disease,  

does it actually help lower heart disease? and  the answer is, there is no good evidence of that.  

um well that's just unfamiliarity with the  evidence, we have dozens and dozens and dozens  

of placebo-controlled double-blind randomized  clinical trials, so gold standard evidence,  

with thousands and thousands and thousands of  participants, showing that statins lower risk  

of heart disease. not just lowering cholesterol  levels but lowering actual cardiovascular events,  

and duration of treatment, the longer we keep a  risk factor under control the larger the benefit.  

so we could talk about specific numbers,  we can talk about potential side effects,  

those are very frequent questions and  they're important discussions to have  

and we have videos going over all that in  detail but the fact that statins lower risk  

of heart disease is unequivocal, just overwhelming  amount of data at the highest level of scientific  

evidence. and again, risk actually means lower  number of heart attacks for people on the Statin  

versus placebo, it's not some theoretical thing  and it doesn't just mean lower cholesterol level.  

so we're going to keep moving, I think this is  just an introduction for now, he's basically  

going through some bullet points so we'll let him  get to the part where he actually explains where  

he's getting these ideas from, the actual evidence  that he's seen. recent studies actually show the  

opposite, that higher cholesterol actually is  associated with lower all-cause mortality. yeah  

epidemiologically there is that Association, so  this is possibly the number one most frequently  

Asked question around cholesterol and we  actually have a video covering this in detail,  

going over all the evidence and explaining it  step by step, but the quick version is that  

there are several chronic diseases like cancer,  different types of infections, liver disease,  

Frailty, all of those diseases often lower  cholesterol levels. so cancer cells for example,  

they take up a lot of cholesterol from the  blood to support their rapid multiplication,  

and as a result, in people with cancer you often  see cholesterol levels go down. so people with  

these serious diseases, often frail in general,  malnourished, often an older population, they  

go on to die more and they have lower cholesterol  levels so you see that epidemiological Association  

in observational studies. but that has nothing to  do with low cholesterol causing death, right? this  

is a very common confusion between Association and  causation. when you actively lower cholesterol,  

not by people getting cancer but by taking a  Statin for example if they have indication,  

or people who have it genetically lower,  you don't see this association with higher  

mortality and lower cholesterol, in  fact you tend to see the opposite,  

lower risk of death when cholesterol is lowered.  so this is a super understandable confusion and  

not a day goes by that I don't get this question  on social media because it is a little puzzling  

at first glance if you just hear about those  epidemiological findings, it's like, why is it  

going in the opposite direction? right? but if  we step back and look at totality of evidence,  

and when we look at the strongest experimental  designs, the most compelling and the most robust,  

it all makes sense, and it's pretty clear, if you  have lower cholesterol because you have cancer  

or a chronic disease like that that lowers  your cholesterol, then yeah that's bad news,  

but if you have it lower because you made some  lifestyle changes or because you took a Statin  

because you had it higher and you had indication  for a Statin, then the outcomes are good and your  

risk of death, if anything, is reduced. all right,  we're going to move on with this introduction,  

I don't want to bog this down too much but when he  gets to the part where he actually explains what  

he's basing this on, what evidence he's actually  seen, it's going to get clearer with the actual  

studies. does it improve longevity? does it  help people live longer? and there is no good  

evidence to that either. yeah we just covered  this, when you look at large enough datasets  

that have the statistical power to pick up  differences in total mortality, statins lower risk  

of death and the genetics confirms that, people  who carry mutations that raise cholesterol die  

more and live shorter lives. so again, we'll see  what exactly what he's basing this on when he gets  

to it. what you do get for sure are side effects  and we're going to talk about that as well. you  

don't get them for sure, some people get them  and some people don't, like with any medication  

or any medical intervention, what we have to  explain is the likelihood of a side effect,  

what they mean, how to get around them and what  the potential benefits of the intervention are  

so that people can make an informed decision.  risk:benefit, right? what you stand to gain  

and what the potential risks are. that's what  people need. so hopefully he's going to go over  

all that information. so why then is there a  standard prescription for a Statin? the only  

evidence they're looking for is does it lower  cholesterol? yes absolutely, and there's the  

assumption that cholesterol causes heart disease  and therefore it must be a good thing to lower it,  

and that's a false assumption. yeah this is  the same misunderstanding as before, statins  

are prescribed because they lower events, heart  attacks, Strokes, coronary heart disease death,  

the need for revascularization procedures, what  we call MACE, major adverse cardiovascular events.  

not just because they lower cholesterol. in  fact, there are drugs that lower cholesterol  

and were never approved, never made it to Market  and are not prescribed, because they don't lower  

actual events. for example, some drugs called CETP  Inhibitors, some of those drugs seem to have other  

effects elsewhere and so their net effect, their  overall effect, is not beneficial in these trials  

so they're not used, even though they can lower  cholesterol. that's exactly why it's important to  

run these massive clinical trials with thousands  of volunteers, it's to look at the actual events,  

the actual cardiovascular events. we have these  trials for many different types of statins,  

for many drugs that are not statins, and some  lower events and some don't. this is a massive  

amount of evidence going back 30 plus years.  here's a quick visual, these little symbols,  

these little squares, are different randomized  trials giving people a Statin, and so we see  

that the lower the LDL cholesterol is pushed by  the statin the lower the number of coronary heart  

disease events like heart attacks. so all these  trials done by different teams of researchers  

in different countries using different classes of  statins, all carried out separately, at different  

times over the span of two or three decades,  line up surprisingly well. so in order to make  

an informed decision we have to be familiar with  the existing science otherwise we're just confused

people often ask about funding because a lot of  the Statin trials are funded by pharmaceutical  

Industries, so viewers ask all the time, can we  trust big Pharma? trust is for friends and family,  

it's not for corporations and it's not for  strangers on the internet either. in science we  

look for confirmation. reproducibility. there are  trials in different continents, run by different  

scientists from different institutions, different  universities, looking at different populations,  

consistently showing that statins lower risk of  heart disease. so that raises our confidence.  

there exists trials not funded by Pharma showing  that statins lower heart disease risk. so our  

confidence goes up some more. you can also  look at people with genetic mutations in the  

same enzyme targeted by statins, it's an enzyme in  the cholesterol synthesis pathway called HMG-coa  

reductase. statins inhibit that enzyme and some  people just carry genetic variants of that enzyme  

that are defective, that are less efficient, so  they have lower cholesterol and you can study  

those people and they have less heart disease.  so that has nothing to do with big Pharma,  

right? that's independent confirmation. so  our confidence goes up some more. actually,  

a fascinating realization to emerge from those  genetic studies is that the size of the benefit,  

of the reduction of heart disease risk from  carrying one of those genetic variants is  

much larger than the benefit of taking  a Statin shown in the Statin trials,  

by like two or three-fold, and that makes total  sense because in the case of the genetic variant  

you're protected from birth, for your entire  lifetime, whereas in a Statin trial you're  

lowering someone's cholesterol at middle age after  potentially a history of Decades of exposure to  

the risk factor. so when we familiarize ourselves  with the evidence that exists, the realization is  

that the Statin trials, if anything, underestimate  the benefit of having these risk factors under  

control. a Statin trial lasts for four or five  years, it's a pilot, it's a proof of principle,  

it's not the ceiling of what's possible in terms  of risk factor control and risk minimization. now,  

does that mean we should be passing out  statins like candy or adding them to the  

drinking water? of course not. most people  can control their risk factors with lifestyle.  

but some people have very high cholesterol  genetically, and some people have established  

heart disease later in life. so that's where  the drugs can be life-saving. so lifestyle is  

fantastic but it's not a one size fits-all.  okay, last thing before we move on, there's  

another Super common question about relative risk  and absolute risk and we have a whole video on  

that in detail, but basically let's say I have  a hundred people and I followed them for five  

years and four of them have a heart attack, and  I have another group that's identical and I give  

them a Statin and two people have a heart attack.  so the number of heart attacks was cut in half,  

that's relative risk reduction, but I only avoided  heart attacks in two people, so two percent,  

that's absolute risk reduction. so why does  absolute risk reduction seem small, only two  

percent? well, because there were only four heart  attacks to begin with, so that was our ceiling,  

that was the maximum absolute risk reduction  we could get. why? because it was only four,  

five years. if you follow them for life,  for 30 or 40 years, then you're going  

to get a lot more heart attacks in a western  population, and if you cut that number in half,  

then that's a lot more heart attacks you  avoid, and if instead of 100 people it's  

the entire population of a country, then it's  millions and millions and millions of heart  

attacks that you potentially avoid. and of course  people with higher risk benefit the most from an  

intervention. so this is a really simple concept  to explain but you'll hear this on social media,  

people will look at a five-year trial and say "oh  absolute risk reduction was only three percent,  

three is a small number so this is all a scam".  right? it's just a simple misunderstanding of  

trial design and temporality, most clinical trials  are short compared to human lifetimes but if you  

extrapolate those benefits to a population at  large over the lifespan, I mean, you revolutionize  

Public Health. all right, we're going to move  on, I think the point is clear, we want to allow  

people to make informed decisions but in order  to make informed decisions we need information,  

right? if we're unfamiliar with the last 35 years  of science we can't make an informed decision,  

it's literally an uninformed decision. 190 could  be unhealthy and 350 could be healthy, now this is  

not to say that you should ignore your cholesterol  numbers, they still give you good feedback,  

higher isn't necessarily better but higher isn't  necessarily bad either, we have to understand when  

to pay some attention. yeah this is true and  it's a good point, so he's talking about total  

cholesterol here so these numbers would be in  milligrams per deciliter, and 350 is not a good  

example because it's too high but the general idea  is correct, total cholesterol could be a little  

over 200 milligrams per deciliter which is the  medical cut off for normal and yet not necessarily  

be a problem for some people, and vice versa,  you could be under 200 milligrams per deciliter,  

so in the normal range for total cholesterol,  and yet there could be plaque building,  

so total cholesterol is a pretty rough metric.  anyway, we have a whole video on this question of  

why do some people have heart attacks with normal  cholesterol, it goes over all the physiology, it  

explains why this happens and what it means. kind  of sounds like we have a video on everything but  

yeah, because these are some of the most common  questions in this area, we get them all the time,  

and so over the years we made videos specifically  addressing them. all right, let's keep moving,  

I think this is still introduction, I think  he's still going through kind of bullet points,  

still hasn't gone into any evidence so let's  keep rolling. we want to start fighting,  

we want to start addressing the true cause instead  of the rescue attempt. right, you want to get to  

the cause, you want to focus on things that have  been shown to lower risk, that are causal, right?  

completely agree with that. if you come to a fire,  then there is probably some people from the fire  

department. cholesterol always shows up at the  accident site just like the First Responders show  

up at the accident site. that does not imply  causation. right, it doesn't prove causation,  

just because two things co-occur doesn't mean one  causes the other, just like we saw with mortality  

a minute ago, right? low cholesterol co-occurs  with higher mortality epidemiologically but that  

doesn't mean one causes the other. so cholesterol  is always present in plaque but that fact alone  

doesn't tell me if it's the cause of plaque,  that's true and it's good, clear thinking. so  

this is why scientists do interventions, actually  going in and lowering cholesterol and seeing if  

things get better or worse. so that's the clinical  trials and the genetics, we touched on all that,  

you lower cholesterol, you get less heart  attacks, we went over that. actually,  

they've directly measured plaque size and its  progression over time and when you go in and lower  

cholesterol with a Statin or other drugs that  do similar things, you slow down plaque growth,  

and you lower cholesterol enough you stop plaque  growth altogether, so that's been shown in about  

a dozen randomized trials or so, so the  causality there has been directly tested,  

far beyond just "oh there's cholesterol present  in plaque", far beyond just the correlation. quick  

visual just to show you that: again, the little  symbols on there are different randomized trials,  

this line down here is the cholesterol level  after they were put on cholesterol lowering  

meds like statins for example, and on the left you  have the change in plaque size over time, so this  

is looking at the plaque in the artery wall with  imaging techniques and measuring how fast plaque  

grows over time. now, the line in the middle is  zero, so above that line is plaque growth and  

below that line is plaque reduction, what we call  plaque regression, the plaque actually getting  

smaller with time. so you see that in Trials where  cholesterol was highest, plaque was still growing,  

as cholesterol level is pushed lower, plaque  grows slower, and at one point it stops growing,  

it hits zero, and eventually you go low enough,  you start having plaque reduction over time,  

plaque is slowly regressing a bit. and the  values here, just for you to have an idea,  

around that point where it crosses zero it's  about two millimole per liter LDL cholesterol,  

which is roughly 80 milligrams per deciliter,  a little below 80. what then is the real cause  

of heart disease and plaques? and the real causes  are inflammation, a low-grade chronic inflammation  

which is associated often with insulin resistance  and/or oxidative stress. based on what?  

what evidence has he seen that has convinced  him that these are the real causes? there is a  

strong correlation between cardiovascular  disease and these three things. that´s  

it? strong correlation? didn't he just give  a big speech about fire and firefighters and  

Association and causation and don't be confused  by that? now he's making this whole argument based  

on "they correlate with cardiovascular disease".  he went directly from explaining the mistake to  

making the mistake. I don't know if maybe they  shot this separately and then somebody edited  

this for him and it ended up back to back, because  it's weird that he would make this whole argument  

based on a logic he just told us to be wary of.  six minutes in, he's made like a dozen bold bold  

claims so far, still hasn't shown a shred  of evidence. still plenty of time to do it,  

it's still another 20 minutes of video to go. are  there any links to studies in the description box?  

let me just check real quick. subscribe to the  channel, join this channel. isn't that the same as  

subscribing? other videos of his to watch, share  this video with a friend, contact, disclaimer.  

yeah there's no scientific references here. so I  don't know when he's gonna start getting into the  

substance. let's just cover the basic concepts of  cardiovascular disease real quick because that'll  

make it easier going forward. so basically  cholesterol is a lipid, kind of a type of fat,  

and it travels in our bloodstream in  little carriers called lipoproteins.  

you've heard of LDL, you've heard of HDL, and  those are both lipoproteins. so lipoproteins  

are tiny clumps of fat and protein, as the name  indicates, that travel around the blood, they're  

Transporters of fats in the blood. okay, why does  any of this matter? because most of the evidence  

in cardiovascular research points to the number  of lipoproteins in our blood being the problem,  

the main reason that the risk of plaque and heart  disease goes up. one way to remember this is  

that it's the number of vehicles on the road that  causes a traffic jam. whether those vehicles have  

more or less passengers inside doesn't matter that  much. now, not all lipoproteins are a problem,  

there's basically two families, the HDL family  doesn't cause heart disease, the other family  

includes LDLs, VLDLs and a few others, and  is problematic if there are too many of them,  

they're called the APO B lipoproteins because  they carry this little protein called ApoB,  

kind of like a tag, and you can actually measure  them, you can measure ApoB and that tells you the  

number of those lipoproteins. these authors stated  it very clearly; it's the number of ApoB particles  

(particles is just another name for lipoproteins),  so it's the number of ApoB lipoproteins, rather  

than the mass of cholesterol (rather than the  amount of cholesterol) within them, inside them,  

that determines risk. okay so if it's about the  carriers and the lipoproteins and this ApoB thing,  

how come we always hear about cholesterol,  which is the passenger traveling inside the  

lipoproteins? in fact, all the values in our  blood work, LDL cholesterol, HDL cholesterol,  

triglycerides etc those are all lipids carried  inside lipoproteins. for example LDL cholesterol  

is the cholesterol carried inside the  LDL lipoproteins. HDL cholesterol is  

the cholesterol carried inside the, you guessed  it, HDL lipoproteins. in general, the more fats  

I have being carried inside these lipoproteins,  the more lipoproteins I have. in general. so if  

my LDL cholesterol goes up, the cholesterol  being carried inside the LDL lipoproteins,  

chances are the number of LDL lipoproteins also  goes up. so historically a lot of these clinical  

trials used LDL cholesterol as an indicator,  but it's basically a marker of the number  

of these apob lipoproteins, it's a proxy, and  it's not a perfect marker, and you can see why.  

maybe I have higher cholesterol but  the number of carriers hasn't changed,  

they're just fuller. right? that happens. it's  not the most common case but it does happen. and  

if you're thinking "this is a nightmare and we  should just measure ApoB and be done with it",  

there's a lot of leading experts that agree with  you, and that is the direction this is all moving  

in but as usual with these institutional  things, it's slow. so that right there,  

the carriers and the passengers, is the basic  concept behind all this mess of lipids and  

cardiovascular disease. now, there are more risk  factors, we all know this, high blood pressure,  

diabetes, tobacco, they all raise risk. so we say  heart disease is multi-factorial. it's not all  

just one thing. incidentally, these factors are  not essential, you can have normal blood pressure,  

no diabetes and not smoke and still have heart  disease. of course those things make it worse  

but they're not absolutely necessary. okay, what  about the ideas he has on there? inflammation.  

well, inflammation is also a cardiovascular risk  factor, there are clinical trials where they took  

people with generalized inflammation,  with elevated inflammatory markers,  

and gave them an anti-inflammatory and  it lowered their heart disease risk,  

just like we saw with statins in the Statin  trials, so generalized inflammation makes  

things worse, but just like tobacco or high  blood pressure, it's not necessary, people  

who have high cholesterol have higher risk even if  their inflammatory markers are completely normal.  

and if you lower their cholesterol and their  lipoproteins, that ApoB that we talked about,  

without significantly affecting their inflammatory  markers, their risk of heart disease comes down.  

so generalized inflammation is a factor, it's not  a good thing, but it's not necessary for heart  

disease. what about insulin resistance? people  with markers of insulin resistance like low HDL  

cholesterol and high triglycerides, that combo  often indicates insulin resistance and people  

with that combo have higher risk of heart disease,  but again, it's not necessary, people with good  

HDL cholesterol and triglycerides can still have  plaque growing, and the higher the cholesterol  

the more plaque. in fact, you can sometimes  worsen insulin resistance while lowering risk  

of heart disease. so different classes of statins  have different effects on insulin resistance,  

some lower, it some make it better, some have  no significant effect and some worsen it, raise  

insulin resistance. but they all help prevent  heart disease events like myocardial infarctions,  

like heart attacks, in clinical trials. so with  some statins you have insulin resistance getting  

worse while at the same time risk of heart  disease is getting better, is getting lower.  

now, that doesn't rule out that insulin  resistance may play a role in heart disease,  

and nobody recommends ignoring insulin resistance,  you should address it, but this idea that it's the  

real cause of heart disease, I don't see how we  can justify that based on the existing evidence. I  

look forward to seeing what else he's basing this  on other than just it correlates better. and then  

oxidative stress. it's a broad concept, it's not  one reaction or one metric. so for example smoking  

is oxidative and it's bad for heart disease,  but exercise can cause oxidative stress and  

it's good for the heart. so it's not this simple.  oxidative stress in what context? measured how?  

based on what evidence? is it human data, is  it Mouse data, is it cells in a petri dish?  

he doesn't show any evidence, he doesn't link to  anything so I can't tell exactly what he means,  

I'm not sure where he heard this idea. one  specific metric that people often ask about  

is oxidized LDL or oxLDL for short. we've  covered this before, blood levels of oxLDL  

is a metric that correlates with heart disease  risk, like a million things do, but it doesn't  

seem to actually cause it, several clinical  trials have looked at this specific question  

and in general it was a flop, trying to modulate  blood levels of oxLDL directly doesn't seem to  

modulate risk of heart disease, unlike what we  saw with cholesterol and ApoB and inflammation  

Etc so now oxLDL is thought to be a  bystander in the cardiovascular field,  

basically a reflection of other factors but not  a cause itself. now there is another way that  

inflammation and oxidation are related to heart  disease. there is a localized inflammatory process  

with oxidation in the plaque, so maybe that's what  he's talking about? not generalized inflammation,  

not generalized oxidative stress in the plasma  or all over the body but this localized process  

in the plaque. so what happens is, those little  carriers, those little lipoproteins can get stuck  

inside the artery wall, and when that happens  that then triggers this localized process with  

inflammation and oxidation. so if that's what he's  talking about, okay, it's part of the process,  

I don't know why you'd call those steps the real  cause and not the steps right before or the steps  

right after, because those are consequences of  the lipoproteins getting stuck, they don't need  

to be there previously for the process to begin,  but sure, they're part of the causal chain. but  

more important than any of this mechanistic  story is that once the lipoproteins get stuck  

inside the artery wall there's no known way to  stop that localized inflammation and oxidation,  

the way to avoid the whole thing is to avoid the  lipoproteins from getting stuck inside the artery  

wall in the first place, which is done by keeping  ApoB in the healthy range, with LDL cholesterol  

being this indicator of apob levels if there is  no apob reading. what's an apoB in the healthy  

range? depends a little bit who you ask but under  80 milligrams per deciliter is a pretty good rule  

of thumb for people who are not at very high risk,  who haven't had a heart attack or something like  

that. and also to keep blood pressure and glucose  and body weight in the healthy range, not smoking  

Etc. controlling generalized inflammation,  for people who have an inflammatory condition,  

those are the factors we can control and that have  been convincingly shown to lower risk. most people  

can control these risk factors with lifestyle.  exercise, healthy diet, not smoking Etc. some  

people need the extra boost of medication and it's  there for them. so we can talk about molecules and  

biochemical Pathways for hours, I love it, but  at the end of the day what really matters is what  

has been demonstrated as causal, what actions have  been shown to lower risk, that's what people want  

to know and that's what will deliver the goods. so  again, really important to learn what's been done  

scientifically before we form these strong views  about what is causal and what isn't causal and  

the real cause, otherwise we're just forming  beliefs in a vacuum and it's just confusion.  

okay last thing before we move on, can something  correlate and not be the real cause? sure, people  

with gray hair die more and it's not the real  cause. what about something that is a real cause  

but I don't see a correlation, is that possible?  if we have two populations, both diabetic but one  

also smokes and has high blood pressure,  these guys are going to have higher risk,  

and diabetes is not going to explain the risk  difference, diabetes is not going to associate  

well with risk because they both have it, it  doesn't mean diabetes is not a real cause, so  

we have to go beyond just "does this correlate",  "does this correlate better than that". it's  

not quite that simple. like he said, fire and  firefighters. so how do we test if an association  

is the real deal, like smoking and lung cancer  for example? several ways, we can use statistical  

adjustment models, we can run genetic studies, we  can run a randomized clinical trial. so you change  

one factor, like you give Statins only to half of  them and you try to keep everything else constant,  

right? you can't always do an RCT, you can't  do a randomized trial with Tobacco For example,  

so there you have to rely on the statistical  adjustment models and more recently, genetics,  

but with cardiovascular disease and cholesterol  and statins we can do randomized clinical trials  

and it's been done dozens of times. all right,  moving on. all right looks like we're past that  

introduction, the bullet points, and he's going  over somebody's blood work. so this person has a  

total cholesterol of 286 and it's supposed to be  a hundred to 199. so that is obviously very high  

so it's marked with a flag, and I would be a  lot more concerned if your cholesterol total  

was a hundred than if it was 286. it depends why  it's a hundred, if it's the person's normal levels  

from a young age that's great news, maybe they're  some of those people that won the genetic Lottery.  

now, 286 is very high so this person probably  does have increased number of carriers,  

of lipoproteins, of ApoB lipoproteins, so you  definitely want to look into it and to investigate  

so hopefully he will. then we look at his HDL  cholesterol and this person has 46. but is that  

high enough? it's above that threshold but is it  enough to kind of offset the total cholesterol?  

right so this is one of the most common  misunderstandings in cardiovascular disease,  

that HDL cholesterol offsets risk. this comes from  epidemiological studies where people with higher  

HDL cholesterol tend to have lower risk. again,  Association and causation, fire and firefighters,  

it's always the same story. raising HDL  cholesterol directly provides no benefit,  

this has now been tested in dozens of randomized  controlled trials with Placebo, genetic studies,  

it's well accepted. HDL can correlate  populationally because it can mirror some  

risk factors like obesity or diabetes but  a patient having high HDL cholesterol does  

not mean no risk, that's a common mistake.  if the carriers are high, if ApoB is high,  

high HDL cholesterol does not offset that. so now  we look at the total cholesterol to HDL ratio,  

I'd like to see this ratio in the three to  three and a half range. right, the ratios,  

super common question, dividing total cholesterol  by HDL cholesterol and all this different math.  

yeah these ratios correlate populationally with  heart disease but do they cause anything? it's  

always the same story. given what we just saw with  HDL cholesterol, it should be obvious why ratios  

that include HDL cholesterol aren't reliable.  HDL cholesterol does not affect risk itself  

so I can double my HDL cholesterol,  which makes the ratios look a lot better,  

but it doesn't necessarily do anything to my risk.  so these ratios can mirror things like insulin  

resistance for example but you don't want to lean  on them too hard when it comes to cardiovascular  

risk because they're unreliable. the ratio can  change dramatically while the risk doesn't budge.  

you can even go in the opposite direction of  risk. so we want to focus on the causal factors,  

just like he said in the beginning, real  causes, right? apoB, blood pressure, smoking  

Etc. so you can see that the whole video  so far is a string of arguments all hinging  

essentially on the same misunderstanding, this  conflation between Association and causation,  

which he explained himself early in the  video, the fire and the firefighter, right?  

I don't even think this video requires fact  checking per se, I think any viewer that's paying  

attention to what he himself explained in the  beginning can then see through it at every step.  

0 or 1 is not a good number because then  you would have virtually no cholesterol in  

your body and that is an essential nutrient.  uh cholesterol is a non-essential nutrient,  

right? the definition of an essential nutrient is  something your body does not produce and needs to  

get from the outside. cholesterol is produced all  over the body, all tissues produce cholesterol so  

it's a stereotypical example of a non-essential  nutrient. he probably meant essential molecule  

which just means something your body needs to  have, which is why our body produces so much  

cholesterol. and I'm sure he knows the difference  between the two, he probably just misspoke in the  

moment and it ended up in the video. it happens.  leaving aside the terminology, what he said there  

was that if your cholesterol level in the blood  is low, then you have virtually no cholesterol in  

your body. that's a very common misunderstanding,  the cholesterol in our blood is a small part of  

all the cholesterol in our body, most of the  cholesterol we have is tucked away inside cells,  

where it's produced and where it's utilized, so  the fraction floating around in the blood, in the  

lipoproteins, in the carriers, is a minority. the  reason this matters and the reason it's important  

to explain this is that you often hear this  idea that cholesterol plays all these important  

physiological roles so why would I want to lower  my blood level? that's just a misconception,  

most tissues make their own cholesterol, the  brain for example makes its own cholesterol,  

so keeping blood cholesterol levels in the  physiological range doesn't mean lowering  

it in the tissues where it's needed. also, the  little receptors on the surface of cells that  

bind to the lipoproteins and can suck up some of  these lipids, they saturate at very low levels,  

much lower than our regular cholesterol levels,  so this idea you often see on social media that  

cholesterol plays important physiological  roles so let's keep it high in the blood,  

is confusion. imagine applying this logic to  any other physiological metric. glucose plays  

important roles throughout the body so let's keep  it high in the blood. that's called diabetes.  

potassium and sodium play key physiological roles  throughout your body, if you don't have potassium  

and sodium you're not alive, so let's keep them  high in the blood. well, high potassium level in  

the blood is called hyperkalemia, it's potentially  lethal, it can cause cardiac arrest. so we want to  

base these decisions on scientific evidence and  be careful with knee-jerk logic: this molecule  

is important for some things so let's just crank  it up. it doesn't work that way. your liver wants  

to recycle this LDL, it wants to keep it going,  so it has receptors and if this LDL is normal  

then this system works like a revolving door,  this healthy LDL fits into the revolving door,  

but this oxidized LDL does not, the liver  cannot reabsorb this LDL. Okay so there´s  

the oxidized LDL, the oxLDL we talked about  earlier. now, this idea that it can't be  

recognized by the liver, can't be removed from  circulation. again, I can't tell where he got this  

because he doesn't show any evidence, he doesn't  explain, but this is called clearance, the rate  

of removal of lipoproteins from circulation, and  the evidence I've seen on this rate of clearance  

of oxidized LDL is usually done in lab models,  so things like mice or cells in a Petri dish,  

things like that, which doesn't mean it's bad  evidence, it's just good to bear that in mind,  

and all of that evidence that I've seen  points to the opposite of what he's saying,  

oxidized lipoproteins being removed faster from  circulation, not slower. so here for example:  

any oxidized lipoproteins that might appear  in plasma (plasma is basically blood) would  

be rapidly removed by the liver. in this study,  clearance of oxLDL (so, oxidized LDL) was very  

rapid. and you can see that OxLDL was almost  entirely removed from circulation in minutes  

whereas the non-oxidized LDL, the native LDL,  stayed stable. this one explains it even better:  

mildly oxidized LDL is removed from circulation  faster than LDL (so, than non-oxidized LDL),  

but much slower than heavily oxidized LDL. so  the more oxidized, the faster it's removed,  

the exact opposite of the idea he's voicing.  so I'm not sure where he's getting this,  

this is why it's so important that we show  sources when we make claims in science,  

otherwise I don't know if it's a personal  opinion, if he read about this in a blog, if  

he misunderstood it, there's no way to know. the  good news is we're now talking about lipoproteins,  

which are the pillar of cardiovascular  disease, so that's good. so let's keep  

moving. here is the real cause of atherosclerotic  plaques: this oxidized LDL can do some damage,  

so what this oxidized LDL does, it damages the  inside layer and makes the gaps grow bigger.  

okay so we touched on this already, this idea that  oxidized lipoproteins in circulation, in plasma,  

are the real cause of heart disease, like he  said, this is a specific hypothesis proposed  

decades ago, it was directly tested over and  over in trials and the strongest tests failed,  

so it's generally accepted that OxLDL, oxidized  LDL, lipoproteins in circulation, in plasma,  

is most likely not causal, most likely does not  play a causal role. in fact, most lipidologists  

I talk to don't even look at oxLDL, they don't  request it, they just don't use it, if you look at  

the video we have with the low carb cardiologist  Dr Ethan Weiss, we go into this specifically. so  

as we said earlier, the bulk of the oxidation  takes place inside the artery wall after the  

lipoprotein crosses into the artery wall and gets  stuck, that's when it gets extensively oxidized,  

not in circulation, not in the plasma, because  number one, oxidation is inhibited by plasma,  

and number two, like we saw, the few lipoproteins  that get minimally oxidized seem to get quickly  

removed from circulation anyway, that clearance  process we looked at. what this oxidized LDL does,  

it damages the inside layer and makes the gaps  grow bigger and now this oxidized LDL which is  

Tiny can slip through the crack and start getting  into the wrong place. right, this is a super  

common question, this idea that there's damage to  the wall that allows the lipoproteins to get in,  

the crack in the wall like he said. this was an  idea proposed in the late 70s called the response  

to injury hypothesis, that something would cause  damage to the wall which would then allow the  

lipoproteins to slip in through that damage, kind  of like a passive leakage. this idea has largely  

fallen out of favor for a couple reasons: first,  when you examine arterial plaque microscopically,  

especially early plaque, it's usually found under  an intact arterial lining, What's called the  

endothelium, so there's no overt damage there  most of the time, and second, scientists have  

actually figured out how lipoproteins get  carried across the artery wall, there's a  

process of active transport called transcytosis.  trans just means through and cyto means cell,  

so it's just a process of carrying the lipoprotein  across a cell, so there are specific receptors and  

an internalization process and vesicles that  transport the lipoproteins, so it's an active  

transport mechanism, you don't need damage,  you don't need cracks. it's spelled out here:  

as transcytosis across the intact  endothelial barrier occurs in Vivo (so,  

in a living organism), endothelial injury is  not required for lipid accumulation in the  

sub endothelium (sub-endothelium just means under  the endothelium, so inside the artery wall). now,  

if you have extensive damage and your artery  wall is all torn up, might you get even more  

lipoproteins rushing in? yeah that probably does  make it worse, but it's not needed for plaque to  

grow and most plaque is seen starting and growing  without overt damage. all right, we're going to  

move on but just another little tidbit, I told  you that the response to injury hypothesis has  

largely been abandoned. so what's the reigning  view now? it's called the response to retention.  

lipoproteins cross into the artery wall, many of  them leave the wall again but some can get stuck,  

retained, and that triggers the plaque process.  oxidation, aggregation, inflammation, engulfment  

Etc. so retention is seen as the initiating step.  so what determines if a lipoprotein gets retained  

or not? there are some genetic differences  person to person like with everything else  

and then the modulating factors that have been  identified are the ones we already talked about,  

keeping ApoB low, the lower the apob  the fewer lipoproteins get retained,  

also good blood pressure, not smoking etc etc.  all of those factors can slow down that process.  

there's something called a macrophage that starts  following this bad guy in through that crack,  

its job is to go after and Gobble up this LDL, now  it encloses this and it becomes a foam cell. yeah  

that's all true, once the lipoprotein is stuck  inside the artery wall, then it gets oxidized,  

there's aggregation, there's inflammation, there's  phagocytosis by the macrophage and it becomes a  

foam cell, that's all true. alright he's back to  some blood work, not sure if it's the same person  

as before or not. we did one test on January  25th and we did another one on April 5th, we  

started off with a total cholesterol of 297 which  was flagged as high and 70 days later it is still  

high but it's a couple of points higher at 299.  right so very high total cholesterol, not sure  

that those values are significantly different,  it's within the error margin of the assay  

but yeah, both very high, this is someone you'd  want to investigate because they probably do have  

high ApoB and are at higher risk. we look  at LDL cholesterol which is traditionally  

considered bad, and that was 225, and  the later test was still 225. right,  

so at this level, this High, depending on the  person's history you start suspecting a genetic  

disease like FH, familial hypercholesterolemia.  this guy was a patient who had been doing some  

changes in his lifestyle, doing low carb high fat  diet and let me tell you, his medical doctor was  

not impressed, he was asked very sternly or told  to get on a Statin drug. okay, so low carb high  

fat doesn't necessarily raise your cholesterol,  you can even lower your cholesterol depending how  

you do it, so it hinges on the type of fat that  you eat, not how much fat but the type of fat,  

as well as some other things like how much  fiber is in your diet and type of fiber,  

so it's totally doable to eat low carb for people  who prefer that without jacking your cholesterol,  

in fact that video with the cardiologist who  likes to eat a low carb diet, he explains exactly  

what he does to keep his ApoB low, so it's not  either/or. he says the doctor prescribed a Statin.  

yeah because these are extreme levels. I'm not  sure if the doctor went over dietary habits or  

not, if this is a recent rise, depending how  this diet is being done it could be potentially  

a result of the diet. we ordered an NMR profile,  we had this on both occasions, which is where  

you measure the particle count. okay, LDL-P,  that's another metric, the P stands for particle  

which is the same as lipoprotein, and so don't  confuse LDL-P with LDL-C. LDL-P is the number of  

LDL lipoproteins and LDL-C is the cholesterol  being carried inside the LDL lipoproteins.  

I know scientists suck when it comes to coming  up with these names and these acronyms. so  

LDL-P measures the number of lipoproteins,  it's essentially the same as the ApoB test,  

very little difference between the two.  now, with someone who has cholesterol levels  

this extreme you pretty much know their ApoB,  their number of carriers, is going to be high.  

sometimes with more borderline values there's  mismatch but here it's not going to happen. we  

want this number to be under a thousand  and it is 3448. yeah it's astronomic,  

his LDL-P, his number of LDL lipoproteins, is  over three times the ceiling of the recommended  

range. his LDL particle count went down from  3400 to 2900, we had a change, a reduction in  

455. yeah he went in the right direction, he's  not explaining what changed between the two  

values and it's still astronomical, it's  still, it went from 3.5 Times Higher  

than the maximum to three times higher than  the maximum but yeah the nudge was in the  

right direction. a 15% reduction in the number of  cells. number of cells? number of lipoproteins.  

he misspoke there again. I'm sure he knows the  difference. the number of LDL lipoproteins came  

down 15%. nothing to do with cells. but more  importantly, what kind of cells? which cells  

were reduced? he just keeps saying cells. so maybe  it wasn't a mistake, maybe he doesn't understand  

the difference between a cell and A lipoprotein. A  lipoprotein is a tiny ball of lipids and proteins,  

there are no organelles, it doesn't have the  structure of a cell and it's about two to three  

hundred times smaller than a Red blood cell for  example. in fact, lipoproteins can go inside  

cells, so it's a completely different biological  entity, right? and the test he's talking about,  

LDL-P measures lipoproteins, not cells. so now  we look at the small LDL count and that went  

from 1653 to 1227. so what we see here is crucial,  almost all of the reduction was the small damaging  

oxidized LDL particles, the ones that cause the  plaquing and the Damage. right so this is the very  

common question about lipoprotein size: is it  true that only the small ldls are atherogenic,  

are potentially harmful, and the large ldls are  harmless? so we have a whole video published a  

couple months ago, like a 40 minute video  going over the evidence on this in detail,  

I'm not going to go over all of that again  but the bottom line is that particle size  

correlates with risk but in all likelihood,  judging by the strongest evidence available,  

is not causal for risk. does that sound  familiar? we should start a drinking game,  

every time I say fire and firefighters we take  a shot. so it's the exact same thing here,  

small ldls associate with risk better than large  fluffy ldls but when we dig deeper, is it just  

Association or is it causation, right? whether  we adjust for particle size or whether we look  

at genetic studies, all LDL sizes, small and large  ldls and even particles that are much larger than  

even the largest ldls, like idls and even some  vldls, much larger particles than any LDL size,  

all are potentially atherogenic. I'll just show  you a couple passages from the medical literature:  

the association of LDL size with cardiovascular  risk typically loses statistical significance  

when adjusted for ApoB. so the size of  the LDL lipoproteins Associates with risk,  

correlates with risk, but this Association is  gone when we account for apob, for the number  

of these lipoproteins, which is the key metric.  so remember, fire and firefighters, some things  

associate but don't actually pan out when we dig  deeper. another line of evidence: patients with  

familial hypercholesterolemia, which is a genetic  disease where you have very high cholesterol,  

very high ApoB and very high risk of heart  attacks at a very young age, even in children,  

so patients with this disease have primarily  large ldls and they are at high risk for ascvd,  

atherosclerotic cardiovascular disease, indicating  that large, buoyant (that's another name for  

large ldls) are not benign. and this summarizes  the current understanding: all ApoB lipoproteins  

less than 70 nanometer in diameter freely flux  across the endothelium (That's The Superficial  

layer of the artery wall), where they can become  retained in the artery wall. okay what on Earth  

is 70 nanometer? a nanometer is a measure of size,  it's a fraction of a meter, there are one million  

nanometers in a millimeter, so LDL lipoproteins  start at about 18 nanometer of diameter and go up  

to 25 nanometer, so the smallest ldls are around  18, the largest around 25, then they're idls which  

are other lipoproteins in the same family and  then there are vldls which go from around 30  

to 80 and higher. so the cutoff is 70 nanometer,  which means that all ldls, all sizes can get into  

the artery wall and be part of atherosclerotic  plaque and contribute to heart disease, all idls  

can do it and many vldls even can do it except for  the very largest. not only that, but all of these  

varieties seem to be about equally atherogenic  particle for particle regardless of their massive  

difference in size. we have two videos going over  all of the studies on that so check those out for  

details. so in this patient it looks like most  of the reduction was in the small LDL particles.  

that's fine, it's a step in the right direction,  if it was in the large ldls it would also be good,  

if it was in the vldls that were reduced it would  probably also be good, but yeah even his small  

ldls where you saw the reduction, they're still  through the roof, more than twice the recommended  

range, so yeah this patient needs a lot of  attention, a genetic condition needs to be  

investigated, I sincerely hope they're seeing a  good cardiologist or a clinical lipidologist or  

somebody with deep understanding of this field.  so what does a Statin drug do? it increases the  

number of receptors to reabsorb LDL particles.  absolutely, yeah it's called the LDL receptor,  

pretty self-explanatory, and it increases on  the surface of the hepatocytes, the liver cells.  

absolutely right. if we take a Statin, then we  will see these numbers of LDL particles go down,  

we're going to see a dramatic decrease of  these fluffy LDL particles. but we also said  

if you remember, that these small ones, they  are not recognized by these receptors so the  

statin drug will decrease total cholesterol but  it will only reduce the cholesterol that we want,  

it will not reduce the cholesterol that we're  trying to get rid of, the damaging cholesterol,  

there is no change. okay there's a little bit  of confusion here, it is true that statins  

preferentially reduce larger ldls but that is also  beneficial as we just saw, because those particles  

are also atherogenic. in fact, if you think about  it, statins are one line of evidence that large  

ldls are not harmless because we already know  they lower risk of heart disease events like heart  

attacks from dozens of outcome trials, and because  they mainly lower the larger ldls, like he said,  

correctly, that suggests those lipoproteins are  not harmless, and in fact that's exactly what we  

see from the other lines of evidence, whether it's  adjustment models or genetics Etc, that all of  

these lipoproteins are atherogenic, the small and  the large ldls and even members of the same ApoB  

family that are much larger than any LDL size. so  this is a really interesting point here because  

you can see exactly where he got confused and you  can see kind of the anatomy of the process. his  

thinking process there is, statins mainly lower  the larger ldls so that's not useful because it's  

the smaller ldls we want to lower, and that makes  sense, it's not an unreasonable thought process  

if we're missing all those Decades of Trials  and genetics and we're not quite sure what  

effect statins have in the first place. if you  remember from the very beginning of the video, his  

introduction, he seems to be under the impression  that all we know about statins is that they lower  

serum cholesterol levels, and everything else, any  effect on cardiovascular disease and any outcomes  

is all a guess. in reality we already know they  lower risk, and actually all of the evidence  

on particle size perfectly matches that, those  trials, because it indicates that all of these LDL  

sizes are atherogenic. so we're going to move on,  I just thought this was important to emphasize,  

this realization that it's not about who's  smarter or who presents things better,  

it's about a general familiarity with the existing  evidence so that we can make informed decisions.  

in his shoes, if nobody had showed me 30 or  40 Years of research on this topic, I have no  

doubt I would probably hold very similar views.  so once again, we can talk about particle sizes  

and oxidation and all these molecular things but  at the end of the day what matters is what actions  

have been demonstrated to lower risk in humans?  apoB in the healthy range, with genetics if you  

have the right parents, if not, with lifestyle, we  have a whole video going over the research on diet  

tips to lower ApoB, and for people who need it,  medications like statins, as well as, of course,  

the other risk factors, healthy body weight, blood  pressure, glucose Etc. that's home base. the rest,  

the fluffy particles, the oxLDL, we can talk  about all that for hours but that's not where  

risk minimization is going to come from and it can  sometimes be a distraction. okay so now he's going  

over statin side effects, very important topic,  very important to give people reliable information  

on this because there's a lot of questions on  this issue. statin drugs cause muscle fatigue,  

muscle pathology and weakness. in people who  report side effects, muscle pain, myalgia is  

the most common by far, so we'll let him explain  the specifics and what this means and how to  

navigate it. so now the heart has to work harder  and we often get heart pathology like cardiomegaly  

and things like that. I mean, where's the  explanation of the muscle pains and the myopathy?  

he just moved on. maybe he'll come back to  it? I don't really understand the structure,  

he seems to do this,, he throws some things  into the air doesn't really go into it, doesn't  

really explain it and just moves on. so now he's  talking about the possibility of cardiomegaly,  

which is an enlarged heart, megaly means big,  so what's the actual evidence on this? I've  

seen a couple studies pertaining to statins and  cardiomegaly. there's a couple non-randomized ones  

finding no significant difference in cardiomegaly  in people on statins versus not on statins, and  

one actually found that Statin-untreated patients  were more likely to have ventricular dysfunction,  

cardiomegaly and symptoms of heart failure, but  the experimental design of those studies isn't  

the best, it's not very compelling. what about  randomized studies? those are more conclusive.  

there's a meta-analysis of randomized Trials where  they looked at people with chronic heart failure,  

which is a condition where we often see a dilation  of the heart chambers and the walls can get  

stretched and thinner and weaker and the heart  function can suffer, and they found that Statin  

treatment actually countered this trend and helped  bring the diameter of the chambers back down,  

which is beneficial in this population, and  in fact there was an overall Improvement not  

only in ventricular remodeling, so the shape got  better, but also cardiac function and symptoms,  

so basically the exact opposite of the question  we heard him raise that statins might cause  

cardiomegaly and enlarge the heart. now, more  important than any of this, whether the heart gets  

a little bigger or smaller, the wall gets a little  thicker or thinner, are the actual outcomes,  

and for people at risk, who have an indication,  statins reduce risk of heart attacks and  

cardiovascular mortality so it's a net benefit  for the heart specifically. we can speculate that  

maybe there's this effect, that other effect,  based on mechanisms, and it's good to ask  

questions, it's good to keep investigating, but  we already know the overall effect is positive,  

less heart attacks, less death. another  very hard-working organ is the liver,  

so first we interfere with the production of  cholesterol so it has to try even harder to  

make and reabsorb cholesterol and then we block  the energy production to that. and then there's  

one more place that uses more energy than any  other and that is your brain. it's two percent  

of your body weight, uses 20% of all the energy in  your body, so let's take some statins so we block  

the energy production to that as well. again,  just some vague comments but it doesn't really  

give people the information they need. do statins  cause brain issues, yes or no? what's the effect  

on the heart? positive or negative? two percent  of body weight, blocks the energy Supply... what's  

the actual effect of the drug on these organs?  that's what people need to know. we have Decades  

of evidence on this specifically, hundreds of  analyses looking at safety data, looking at side  

effects, looking for side effects and tabulating  them. that's what we need to share with people,  

not speculate that there could be a problem and  then move on to another topic. how does that help  

people make an informed decision? so let's go over  these one by one real quick. muscle symptoms. most  

people on a Statin don't report muscle problems  but some definitely do. the exact number depends  

based on whether it's a randomized controlled  trial or observational data, from one percent  

all the way up to 20 something percent of people  prescribed a statin. here's the fascinating part  

about this: if you take people who report symptoms  of Statin intolerance like muscle pain or weakness  

and you split them randomly and half gets a  Statin and the other half gets a placebo pill  

with no Statin in it but they don't know which  is which, in both cases they report symptoms.  

same intensity, no significant difference. so  there's a huge component of expecting a Statin to  

cause muscle pains and sure enough, feeling more  pain, or noticing more pain and attributing to  

statins even though the pill we're taking contains  no Statin. this is called the nocebo effect.  

Placebo is when I think I'm on a drug and I  feel better even though I'm not taking the  

drug. nocebo is when I think I'm on a drug and I  feel worse even though I'm not taking that drug.  

and large analyses indicate that over 90 percent  of reports of muscle symptoms on a Statin are not  

actually due to the Statin itself. I don't rule  out that some people have an actual intolerance  

to the Statin molecule itself, and I suspect  that is the case in a percentage of people,  

but there seems to be a big component  of the bad reputation that statins have,  

on social media and on TV, especially with regards  to muscle pains, and in fact a large percentage of  

people who report Statin intolerances and who stop  taking them are able to go back on a Statin later  

on and tolerate them, between 50 and 90 percent  depending on the analysis. just a quick note  

that the nocebo effect doesn't mean the pain isn't  real, it's very real, and telling people "it's all  

in your head" is not a good approach, but being  aware of the nocebo effect and how common it is  

opens the possibility, at an individual level,  for people who are open to trying a re-challenge.  

so that's one option. another option is trying  a lower dose of Statin, often that gives good  

results. yet another option is trying a different  class of Statin, there are six or seven classes,  

some people might have a legitimate intolerance  to one statin but not another. and yet another  

option is to just give up on the statins. maybe  consider trying something else. statin intolerance  

used to be a big deal 20 years ago when there  was not much else we could offer these patients  

but now there's ezetimibe, there's pcsk9  inhibitors, there's all kinds of meds that have  

been shown to lower cholesterol, lower ApoB, and  importantly, lower actual cardiovascular events  

in randomized trials. most data with those newer  meds is from trials where they were used on top of  

a Statin but there is some data on monotherapy, so  that's something to discuss with your doctors. and  

another one that's brand new is called bempedoic  acid and it's somewhat similar pharmacologically  

to statins but it's more organ selective so it  probably affects the muscles less than statins.  

okay, so we touched on muscle, we touched on  heart, third word he has on there is liver.  

statins can cause a mild elevation of  some liver enzymes called transaminases,  

this happens in about one to two percent  of patients and it's usually not clinically  

relevant and it's transient, it comes back down  again after a while. serious, clinically relevant  

liver problems linked to statins are rare. okay,  last word he has on there is brain. people often  

ask about cognitive function and dementia, and  there are dozens of studies investigating this.  

when we look at the largest randomized trials  available, statins don't seem to affect cognitive  

function even when cholesterol is pushed very low.  the non-randomized studies go even further, this  

analysis pooled 46 observational studies and found  that statins are associated with decreased risk of  

dementia and Alzheimer's disease. but of course  we take this association with a grain of salt,  

they're not randomized trials so we don't jump to  a conclusion. so that's the results of the largest  

studies all together. on the other hand there  are many anecdotal reports of people reporting  

forgetfulness and confusion and cognitive  symptoms like that on a Statin and we can  

find smaller studies here and there suggesting  it also, so when we put all of it together,  

the bulk of the evidence indicates that statins  don't significantly affect cognitive function in  

most people but it is possible that in specific  contexts they could have an effect, it's possible  

they lower risk of dementia and Alzheimer's in  people at risk and it's possible they cause these  

episodes of forgetfulness and confusion in people  with susceptibility, there's enough of these case  

reports, and it's not just "oh I felt this",  several cases of people who stop the Statin,  

the symptoms go away, they go back on  the Statin and the symptoms come back,  

this is called a re-challenge, so I think  there could be a real reaction to the Statin  

in some people, it's just not very frequent and  that's possibly why it doesn't show up in those  

large trials. so in people who report these  issues, who don't tolerate the Statin well,  

I think it makes sense to either try a lower dose,  or a different Statin, some studies suggest less  

issues with hydrophilic statins like pravastatin  or rosuvastatin as opposed to lipophilic like  

atorvastatin. or just stopping the Statin  altogether for people who can't tolerate it,  

and again, we now have many Alternatives,  ezetimibe, pcsk9 Inhibitors, beempedoic acid Etc.  

okay another common question pertaining to the  brain is stroke. there are two types of stroke,  

ischemic and hemorrhagic. ischemic strokes happen  when an artery is clogged with plaque or with a  

clot or an embolus and so not enough blood gets  through to the brain area and you have a stroke.  

hemorrhagic stroke, as the name indicates, happens  when the artery bleeds out and so not enough blood  

gets to the brain area that's supposed to be  irrigated. ischemic Strokes are much more common,  

about 90 percent of Strokes are ischemic. so  statins lower total Strokes, they lower ischemic  

strokes and they have no significant effect on  hemorrhagic stroke for the population in general.  

now, for people who have a high risk of  hemorrhagic stroke specifically, like people who  

have a history of hemorrhagic stroke for example,  there is some mixed evidence, it's not entirely  

clear but there's a possibility that statins May  raise risk of hemorrhagic stroke specifically,  

so this is what I would do if it were a family  member, if there's a high risk of hemorrhagic  

stroke, like a history of hemorrhagic stroke or  high risk for some other reason, that's something  

I would weigh the pros and cons carefully and  something to discuss with your doctor. for most  

everybody else, statins lower risk of total  Strokes. so we've covered the words he has on  

there, there is one other side effect I think is  worth touching on and that's type 2 diabetes. in  

people at risk of type 2 diabetes, with obesity  or pre-diabetes or metabolic syndrome, statins  

can speed up the progression to type 2 diabetes by  five to six weeks, whereas in people without those  

risk factors statins don't significantly  affect risk of diabetes. importantly,  

they've found that even in those people at higher  risk of developing type 2 diabetes statins still  

reduce heart attacks and total deaths, which makes  sense because the main cause of death for people  

with type 2 diabetes is cardiovascular disease.  so a large analysis concluded "the cardiovascular  

and mortality benefits of statins exceed the  diabetes Hazard even among people at higher risk  

for developing type 2 diabetes". also, that  progression to type 2 diabetes that is seen  

in people at risk can be prevented with healthy  lifestyle: diet, exercise, maintaining healthy  

body weight Etc. we have a whole video going over  the details of type 2 diabetes and statins and all  

the evidence. so overall, because most of the  potential side effects of statins are uncommon,  

with the possible exception of the muscle aches  which we touched on and in the cases where you  

can't get around them you stop the Statin and  the muscle aches go away, and because statins  

lower risk of heart disease, heart attacks,  total strokes and mortality, the systematic  

overviews of all of the evidence usually conclude  that "in patients with an indication for Statin,  

the benefits greatly outweigh the risks". I know  you've probably heard all kinds of stuff on social  

media, and if you've already decided against  taking any meds, that's entirely your right,  

this is just to explain scientifically why  you'll hear doctors and scientists recommend  

medication in some situations, for people who have  an indication, it doesn't mean "oh so these people  

must be getting kickbacks from Big Pharma" or  "they're indoctrinated by the system" or any of  

these stories you'll hear on social media,  I make zero money from any of this and I'm  

more than happy to advise against any medication  that doesn't have the evidence behind it and more  

than happy to tell you when lifestyle is enough.  for most people, starting early enough, it is.  

sometimes it isn't. okay, moving on. so you could  take a statin drugs and you can interfere with all  

of this or you could just stop eating sugar and  get healthy. yeah that´s just a false dichotomy,  

why would it be one or the other? it's like  saying you can exercise or you can stop smoking.  

how about both? intake of refined carbohydrate, of  white sugar, is a risk factor for cardiovascular  

disease, there's substantial evidence for  that, so recommending moderation of refined  

carbohydrates is a great message for a western  audience especially, but you don't want to do  

that at the expense of other risk factors.  heart disease is multifactorial, as we said,  

I know it was a while ago. diet absolutely  matters, ApoB matters, blood pressure, tobacco  

Etc. it's not all one thing. also, very important  in nutrition, we don't just want to tell people  

to stop eating food X without explaining what  they should replace it with, because we know  

from past research that cutting back on refined  carbohydrates may or may not help depending what  

you eat instead. replace refined grains with  trans fats, you're probably worse off. replace  

with saturated fat, risk is not improved. replaced  with unsaturated fats or whole carbohydrates or  

protein, risk comes down. so that's things like  fatty fish, nuts and seeds, fruits and vegetables,  

maybe some plain yogurt, legumes etc etc. that's  the empowering message, not just "cut sugar,  

forget about everything else", you risk sending  people in the wrong direction. if you enjoyed  

this video you should really take a look at that  one now". yeah so that's the end of the video,  

so that whole introduction in the beginning,  those five or six minutes of bullet points,  

he just never went back to some of those  things, like the all-cause mortality, longevity,  

those points he said "we're going to talk about  this", just never went back. maybe they had some  

pieces of footage lying around and they kind of  put a video together? so overall, nice delivery,  

speaks nice and slow, seems like a really nice  person, a lot of confusion on the science,  

just a general unfamiliarity with the  basic concepts of this field. now,  

the point is not to tear into this one person  or this one channel, there's a million people on  

social media saying random stuff off the cuff, the  point is how do you as a consumer of information  

navigate this confusion on the internet? we  have to scrutinize information, we have to  

demand evidence for claims, we have to fact check  everything nowadays, and that goes for my videos  

too, don't just trust me, go through the sources,  everything is linked Below in the description.  

triangulate with other sources, take your time,  this doesn't happen overnight. be careful forming  

views based on what we would like to be true,  science can be pretty cold, science doesn't  

care what we prefer. a word for viewers who may  follow this channel, who may like this channel,  

maybe he helped you lose weight or feel better  or overcome something. fantastic, nobody's  

taking that away from you, in fact if you consume  this content you should want it scrutinize more,  

not less, because you want to know if it stands  scrutiny. science works by criticizing ideas,  

it's not an attack on the individual. if the idea  matches the evidence, it survives. if it doesn't,  

we toss it. of course, all done professionally,  the minute you start hearing insults and screaming  

matches it's an emotional argument, it's not a  test of an idea. so here's what we're going to do,  

we'll contact him, we'll share all the scientific  sources, we don't want any credit, no promotion,  

nothing like that, happy to talk offline, provide  any resources he wants or needs, maybe he'll take  

the information on board and course correct the  content himself, that would be ideal for everybody