Taken from JRE #1979 w/Dr. Aseem Malhotra:
https://open.spotify.com/episode/43D9PMFx0j9BdbpcS9meBY?si=90b2b85b819c4f7f

Can you please tell us, like, what is the mechanism?

How do statins work and what does it do to lower cholesterol?

So, for many years, there's been this misconception that high cholesterol is 1 of the most single, well, 1 of the most important risk factors for development of heart disease.

So I broke down the data, and I've published a lot on this stuff, to look at it properly.

And Joe, the association of cholesterol and heart disease came from something called the Framingham study, which was in Massachusetts, started in 1948, carried on for several decades where they followed up 5,000 people, and many risk factors for heart disease came from that correlations, which were then validated, like things like type 2 diabetes and high blood pressure, even smoking, and high cholesterol.

Now what's interesting about Framingham is, when you look at the associations of total cholesterol and heart disease, it was only there when your total cholesterol, the significant association was only there if it was over 300 milligrams per deciliter.

Very few people have total cholesterol that high.

And we have to also understand that most of your cholesterol is genetic.

Since I, because cholesterol's a really important molecule in the body.

It's not just it's you know important for maintaining cell Cell membranes, it's important role in the immune system

hormones vitamin D synthesis all of that stuff, right?

So it's genetic You can alter it with your diet, the components of it, something called triglycerides and HDL, so-called good cholesterol, right?

But so the total cholesterol was not a very good indicator.

So if it was very, very high, there was association.

But that's what's interesting about that is though almost all of those people had a genetic condition which gave them very, very high levels of cholesterol.

And then at the very other end from Framingham, the very low levels of cholesterol, less than 150 milligrams per deciliter or 4 millimoles in European terminology, there was almost no heart disease.

And so basically, people with genetically low cholesterol tend to not develop premature heart disease.

Another interesting caveat, most of that data on the development of heart disease was only up to people who were 50 or 60.

And what wasn't publicized is that once you hit 50, as your cholesterol dropped in Framingham, your mortality rate increased.

thing that really sort of was a nail in the coffin for me in understanding the association of cholesterol and heart disease was very weak, was William Castelli, who's 1 of the co-directors of Framingham, cardiologist, in 1996 did a full summary of Framingham, and he said this, he said, unless you're, because you're gonna talk about, you may be thinking, okay, hold on, there's good cholesterol and bad cholesterol, so he specifically focused on what we call LDL, bad cholesterol, and he said, unless your LDL cholesterol is above 7.8 millimoles per liter, which is something like, Joe, it's probably, yeah, at least 300, pretty much around 300 milligrams per deciliter.

It has no value in isolation of predicting heart disease.

So what they determined from framing them was your risk of heart disease as 1 of the risk factors was something was your total cholesterol Divided by your HDL the good cholesterol the ratio So that's the first thing so the association of cholesterol and heart disease is quite weak, first and foremost.

The second question is, when you try and prove that there is a biomarker that is causal in heart disease, you want to show that if you lower it, then there is a difference in heart attacks and strokes, for example.

And only in 2019, more recently, I co-authored a paper in BMJ Evidence-Based Medicine with 2 other cardiologists.

And what we did was we looked at all the drug trials at lowering cholesterol to find out is this true when you look at it in totality, not cherry-picked evidence, is there a correlation with lowering LDL cholesterol and total cholesterol and preventing heart attacks and strokes?

And this is based upon randomized control trial data.

So this is the most robust evidence you can get.

So that means, so then the next question is, well, hold on, how do statins work?

And that's the question you asked me earlier.

Statins do have a small benefit, but 1 of the properties of statins, which isn't talked about, is they have anti-inflammatory and anti-clotting benefits.

So even though they lower LDL cholesterol, the real benefit in preventing heart attacks and strokes is through that mechanism.

when you break it down, as I said before, your risk is, you know, the benefits are about 1% if you're low risk of heart disease.

a heart attack, and many patients I see have

had heart attacks and they get automatically put on statins, and the cardiologists rarely even check their cholesterol, because in the cardiology community, we kind of knew that.

It was like it doesn't matter what your cholesterol is, let's put them on

a statin because the trials show there are benefits.

But what are those benefits when you break them down in absolute terms?

This is what all the evidence shows and it's been peer reviewed, et cetera.

If you've had a heart attack, patient comes to me, doc, shall I carry on the statin, or I've been put on the statin, or I'm getting side effects, I say to him, listen, let me just explain to you the benefits first, so that you don't have an exaggerated fear of stopping your statin, And you also don't go around with the illusion of protection thinking, that's the only thing I need to do now.

Over a 5 year period, if you take your statin religiously and don't get side effects, right?

Because remember the trials took out people with side effects.

So best case scenario, your benefit of a statin is 1 in 83 for saving your life, right, and 1 in 39 in preventing a further heart attack.

A lot of people find that quite underwhelming.

Another way of looking at the statistics, Joe, and this is important for populations, looking at those trials.

And what I'm about to tell you, when I talk at conferences to doctors and general practitioners, and there's like a gasp from the audience, right, when I tell them this, And this is published in the BMJ.

So in the randomized trials, you look at an average,

you that question, right, you've had a heart attack, let's say for example, and statins are 1 of the most prescribed drugs that are, you know, miracle cure, whatever, 1 of the most potent beneficial drugs in the history of medicine.

If you take those, if you take a statin for 5 years, having had a heart attack, in that 5 year period, how much would you think or hope it would add to your life expectancy?

You've literally survived a heart attack, right?

And now you've been given this pill, which your doctor's telling you, this is, you must never stop.

How much would you hope it would add to your life expectancy over a 5 year period, over that period?

And you know, but this is, so and the reason I'm mentioning that is when you look back over the last few decades and People talk about what has driven down death rates from heart disease.

There's this assumption It's been the mass prescription of stands millions of people think stands But the evidence suggests to the separate analysis done They looked in European countries high risk and low risk people of heart disease over 12 years.

Was there a difference in, was there a reduction in heart disease death rates because of statins?

And that doesn't mean that the data is fraudulent, it's been misrepresented.

But if you accept, say it's a 4 day increase, right?

But these are in people who didn't get side effects who were adherent to statins.

And real world data tells us, Joe, even people who've had heart attacks, maybe 50% of them will stop taking it just within a few years, mainly because of side effects, you can understand why that hasn't had an impact on the population.

This is 1 of the most powerful, lucrative drugs in the history of medicine, And this is how marginal, let's be polite here, how marginal the benefits are.

Now, once this information has been out there and it's been published

and you've had these talks and people are aware of this, what has

And has there been any change in how it's prescribed?

So I then, so after this publication the BMJ initially and then I you know I had to get another job right so I lost that job in that hospital.

I then ended up working for free briefly in another NHS hospital, cardiology department, that I worked for free, doing 1 day a week, because I had another role with health policy, which I'll come on to, you know, that they were paying me some money and I didn't wanna stop seeing patients.

So I was working for free in 1 hospital for a year in a cardiology department.

In sort of March 2014, I got a phone call, in fact an email initially, from the editor of the British Medical Journal.

And she said, Asim, let's have a meeting.

I think I went to meet her, and she said, there is a man called Professor Sir Rory Collins.

Professor Rory Collins is probably considered in the world the lead statin researcher.

his work on statins He has said that you need to retract Abramson and Malhotra's papers because there is a significant error on the side effect issue and this is going to cause harm, people are going to stop their statins.

And she said straight away, no I'm not going to retract it, but we're very happy if you would like to publish it, you know, send a critique and then we'll publish it.

But for some reason he decided he didn't want to do that.

So this back and forth was going on, And then out of the blue, he decides, whether it was him or somebody else, to go to the Guardian newspaper.

from the Guardian and the BBC, which again was headline news, that what Abramson and Malhotra had done, which became a news story, front page of the Guardian, was so damaging in terms of their error on the statin side effects issue that people will die, essentially.

This is almost as bad as they were trying to make parallels with Andrew Wakefield and the whole Meals on Mumps Rubella issue that happened many, many years ago.

That was the scientist that lost his license because he linked the MMR vaccine to autism.

So they were trying to create that kind of frenzy.

So I went on BBC and I stood my ground and and and that I think put the BMJ under pressure.

And then the next thing that happens is, I remember I was with my cousin in New York, I'll never forget this, and I get an email, a press release from the BMJ, which I knew was gonna, you know, and this is, to be honest, it's an attack on one's credibility, but the BMJ then decided they were gonna send our articles for an independent review, whether or not they should be retracted.

And Joe, just to put things in context here, that's potentially career destroying in the sense that if my article got retracted, it got so much publicity, and I genuinely believe what I said was correct, but it gets retracted, then your credibility is undermined pretty much forever and your career's, you know, it would be career-destroying for me.

So I was on trial essentially for 2 months, if you like.

There was a panel, they convened, they asked me to, you know, send in responses and then whatever else, I didn't know what was gonna happen.

And then I think it was August 2014, I remember it broke the news and it was, you know, I got an email and basically the panel had come back six-zero, unanimous in our favor.

Because John Abramson went through a lot during that period as well.

When that happened, Joe, there were 2 things I could have done.

I'm just gonna, you know, I'm gonna hide away and just keep a low profile.

This is about ethical evidence-based medical practice.

There were some corrections that needed to be done, some caveats that they added in, into the papers around the side effects issue.

I carried on publishing in other journals, kept talking about transparent communication, ethical evidence-based medicine, statin over prescription.

There are other things we can be doing in terms of lifestyle, right, which are gonna be more powerful, you know, whether it's low-carb Mediterranean diet, exercise, why are we not focusing our attention there rather than just giving people all these pills that they think is gonna protect them from heart attacks, and in most cases it doesn't.

And in that journey, and this went on for a few years, this is where things got really interesting.

So to answer your question, yes, there was a lot of backlash.

But I realized then, as a public health advocate, that you've got to have a thick skin and grow a rhinoceros hide.

And those are the words from a man called Simon Chapman.

Simon Chapman is a professor of psychology in Australia.

He was considered the lead campaigner in making sure there was tobacco control in Australia.

And he wrote a paper talking about his 38-year career in public health advocacy and gave 10 lessons.

As soon as your work threatens an industry or an ideological cabal, you will be attacked, sometimes unrelentingly and viciously.

And I thought, you know what, I'm up for it.

So many more people came out of the woodwork to support me.

And I thought this is about truth and transparency and about ethical medicine and highlighting all the corruption and the conflicts of interest.

1 of the things that Professor Collins hadn't been made apparent is his department had taken over 200 million pounds at Oxford for doing research into statins from the drug industry, and they also kept the data commercially confidential.

So most of the publications and guidelines that were coming on statins were coming from, emanating from that department where no 1 had been able to independently verify the data.

And he is quoted in the Guardian saying, only problematic side effects from statins affect 1 in 10,000 people.

So I thought this is something, this doesn't add up.

I think these are biases, conflicts of interest.

I'm not saying that he was deliberately malicious, but I think there's a huge conflict of interest there that is clouding his judgment.

Plus he's not a clinician, he doesn't see patients.

So there's all of those things that I think limit his ability to really look at the evidence properly.


Speaker 0: The Joe Rogan Experience. Can you please tell us, like, what is the mechanism? How do statins work and what does it do to lower cholesterol?

Speaker 1: Yeah. So, for many years, there's been this misconception that high cholesterol is 1 of the most single, well, 1 of the most important risk factors for development of heart disease. So I broke down the data, and I've published a lot on this stuff, to look at it properly. And Joe, the association of cholesterol and heart disease came from something called the Framingham study, which was in Massachusetts, started in 1948, carried on for several decades where they followed up 5,000 people, and many risk factors for heart disease came from that correlations, which were then validated, like things like type 2 diabetes and high blood pressure, even smoking, and high cholesterol. Now what's interesting about Framingham is, when you look at the associations of total cholesterol and heart disease, it was only there when your total cholesterol, the significant association was only there if it was over 300 milligrams per deciliter.

Very few people have total cholesterol that high. And we have to also understand that most of your cholesterol is genetic. 80% of your cholesterol is genetic. 80%? 80%.

Since I, because cholesterol's a really important molecule in the body. It's not just it's you know important for maintaining cell Cell membranes, it's important role in the immune system

Speaker 2: Hormones

Speaker 1: hormones vitamin D synthesis all of that stuff, right? So it's genetic You can alter it with your diet, the components of it, something called triglycerides and HDL, so-called good cholesterol, right? But so the total cholesterol was not a very good indicator. So if it was very, very high, there was association. But that's what's interesting about that is though almost all of those people had a genetic condition which gave them very, very high levels of cholesterol.

It's called familial hyperlipidemia. Affects 1 in 250 people, right? And then at the very other end from Framingham, the very low levels of cholesterol, less than 150 milligrams per deciliter or 4 millimoles in European terminology, there was almost no heart disease. So again, there's genetic factors there. And so basically, people with genetically low cholesterol tend to not develop premature heart disease.

Another interesting caveat, most of that data on the development of heart disease was only up to people who were 50 or 60. And what wasn't publicized is that once you hit 50, as your cholesterol dropped in Framingham, your mortality rate increased. Never really discussed.

Speaker 3: So I looked at all of this. That's interesting. But I think the

Speaker 1: thing that really sort of was a nail in the coffin for me in understanding the association of cholesterol and heart disease was very weak, was William Castelli, who's 1 of the co-directors of Framingham, cardiologist, in 1996 did a full summary of Framingham, and he said this, he said, unless you're, because you're gonna talk about, you may be thinking, okay, hold on, there's good cholesterol and bad cholesterol, so he specifically focused on what we call LDL, bad cholesterol, and he said, unless your LDL cholesterol is above 7.8 millimoles per liter, which is something like, Joe, it's probably, yeah, at least 300, pretty much around 300 milligrams per deciliter. It has no value in isolation of predicting heart disease. So what they determined from framing them was your risk of heart disease as 1 of the risk factors was something was your total cholesterol Divided by your HDL the good cholesterol the ratio So that's the first thing so the association of cholesterol and heart disease is quite weak, first and foremost. The second question is, when you try and prove that there is a biomarker that is causal in heart disease, you want to show that if you lower it, then there is a difference in heart attacks and strokes, for example.

And only in 2019, more recently, I co-authored a paper in BMJ Evidence-Based Medicine with 2 other cardiologists. And what we did was we looked at all the drug trials at lowering cholesterol to find out is this true when you look at it in totality, not cherry-picked evidence, is there a correlation with lowering LDL cholesterol and total cholesterol and preventing heart attacks and strokes? And this is based upon randomized control trial data. So this is the most robust evidence you can get. Joe, No clear correlation.

It was BS. The whole thing was BS in that sense. Like, it's a very weak, if anything. So that means, so then the next question is, well, hold on, how do statins work?

Speaker 3: And that's the question you asked me earlier. And it's

Speaker 1: a great question. It's a really important 1. Statins do have a small benefit, but 1 of the properties of statins, which isn't talked about, is they have anti-inflammatory and anti-clotting benefits. So even though they lower LDL cholesterol, the real benefit in preventing heart attacks and strokes is through that mechanism.

Speaker 0: But

Speaker 1: when you break it down, as I said before, your risk is, you know, the benefits are about 1% if you're low risk of heart disease. But if you've had

Speaker 3: a heart attack, and many patients I see have

Speaker 1: had heart attacks and they get automatically put on statins, and the cardiologists rarely even check their cholesterol, because in the cardiology community, we kind of knew that.

Speaker 3: It was like it doesn't matter what your cholesterol is, let's put them on

Speaker 1: a statin because the trials show there are benefits. But what are those benefits when you break them down in absolute terms? This is really crucial and important. And this isn't cherry pick stuff. This is what all the evidence shows and it's been peer reviewed, et cetera.

If you've had a heart attack, patient comes to me, doc, shall I carry on the statin, or I've been put on the statin, or I'm getting side effects, I say to him, listen, let me just explain to you the benefits first, so that you don't have an exaggerated fear of stopping your statin, And you also don't go around with the illusion of protection thinking, that's the only thing I need to do now. Over a 5 year period, if you take your statin religiously and don't get side effects, right? Because remember the trials took out people with side effects. So best case scenario, your benefit of a statin is 1 in 83 for saving your life, right, and 1 in 39 in preventing a further heart attack. A lot of people find that quite underwhelming.

Another way of looking at the statistics, Joe, and this is important for populations, looking at those trials. And what I'm about to tell you, when I talk at conferences to doctors and general practitioners, and there's like a gasp from the audience, right, when I tell them this, And this is published in the BMJ. So in the randomized trials, you look at an average,

Speaker 3: how much, if I ask

Speaker 1: you that question, right, you've had a heart attack, let's say for example, and statins are 1 of the most prescribed drugs that are, you know, miracle cure, whatever, 1 of the most potent beneficial drugs in the history of medicine. If you take those, if you take a statin for 5 years, having had a heart attack, in that 5 year period, how much would you think or hope it would add to your life expectancy? You've literally survived a heart attack, right? And now you've been given this pill, which your doctor's telling you, this is, you must never stop. This is gonna save your life.

How much would you hope it would add to your life expectancy over a 5 year period, over that period?

Speaker 0: You know, we can incrementally. 25%, 30%.

Speaker 1: Yeah, okay, so a few years,

Speaker 3: about a few years extra, yeah? You want the answer?

Speaker 1: Yes. Just over 4 days.

Speaker 0: 4 days?

Speaker 1: 4 days.

Speaker 0: Maybe those are great days though.

Speaker 3: Well, no,

Speaker 1: fair enough, absolutely. And you know, but this is, so and the reason I'm mentioning that is when you look back over the last few decades and People talk about what has driven down death rates from heart disease. There's this assumption It's been the mass prescription of stands millions of people think stands But the evidence suggests to the separate analysis done They looked in European countries high risk and low risk people of heart disease over 12 years. Was there a difference in, was there a reduction in heart disease death rates because of statins? And the answer was no.

And that doesn't mean that the data is fraudulent, it's been misrepresented. But if you accept, say it's a 4 day increase, right? But these are in people who didn't get side effects who were adherent to statins. And real world data tells us, Joe, even people who've had heart attacks, maybe 50% of them will stop taking it just within a few years, mainly because of side effects, you can understand why that hasn't had an impact on the population. But think about that.

This is 1 of the most powerful, lucrative drugs in the history of medicine, And this is how marginal, let's be polite here, how marginal the benefits are.

Speaker 2: Now, once this information has been out there and it's been published

Speaker 0: and you've had these talks and people are aware of this, what has

Speaker 4: been the reaction? And has there been any change in how it's prescribed?

Speaker 1: So I then, so after this publication the BMJ initially and then I you know I had to get another job right so I lost that job in that hospital. I then ended up working for free briefly in another NHS hospital, cardiology department, that I worked for free, doing 1 day a week, because I had another role with health policy, which I'll come on to, you know, that they were paying me some money and I didn't wanna stop seeing patients. So I was working for free in 1 hospital for a year in a cardiology department. In sort of March 2014, I got a phone call, in fact an email initially, from the editor of the British Medical Journal. And she said, Asim, let's have a meeting.

I think I went to meet her, and she said, there is a man called Professor Sir Rory Collins. Professor Rory Collins is probably considered in the world the lead statin researcher. He's at Oxford University. He got his knighthood

Speaker 3: from the Queen because of

Speaker 1: his work on statins He has said that you need to retract Abramson and Malhotra's papers because there is a significant error on the side effect issue and this is going to cause harm, people are going to stop their statins. And she said straight away, no I'm not going to retract it, but we're very happy if you would like to publish it, you know, send a critique and then we'll publish it. But for some reason he decided he didn't want to do that. So this back and forth was going on, And then out of the blue, he decides, whether it was him or somebody else, to go to the Guardian newspaper.

Speaker 3: And I get a phone call

Speaker 1: from the Guardian and the BBC, which again was headline news, that what Abramson and Malhotra had done, which became a news story, front page of the Guardian, was so damaging in terms of their error on the statin side effects issue that people will die, essentially. This is almost as bad as they were trying to make parallels with Andrew Wakefield and the whole Meals on Mumps Rubella issue that happened many, many years ago. That was the scientist that lost his license because he linked the MMR vaccine to autism. Right. So they were trying to create that kind of frenzy.

And I'm like, whoa, this is OK. So I went on BBC and I stood my ground and and and that I think put the BMJ under pressure. And then the next thing that happens is, I remember I was with my cousin in New York, I'll never forget this, and I get an email, a press release from the BMJ, which I knew was gonna, you know, and this is, to be honest, it's an attack on one's credibility, but the BMJ then decided they were gonna send our articles for an independent review, whether or not they should be retracted. And Joe, just to put things in context here, that's potentially career destroying in the sense that if my article got retracted, it got so much publicity, and I genuinely believe what I said was correct, but it gets retracted, then your credibility is undermined pretty much forever and your career's, you know, it would be career-destroying for me. I'm at the beginning of my career.

So I was on trial essentially for 2 months, if you like. And, you know, that was, it was tough. It was very, very tough. There was a panel, they convened, they asked me to, you know, send in responses and then whatever else, I didn't know what was gonna happen. And then I think it was August 2014, I remember it broke the news and it was, you know, I got an email and basically the panel had come back six-zero, unanimous in our favor.

There was no call for retraction. Because John Abramson went through a lot during that period as well. I know you interviewed him. And we talked and whatever else. When that happened, Joe, there were 2 things I could have done.

1 was, wow, this is like too much. I don't think I can handle this. I'm just gonna, you know, I'm gonna hide away and just keep a low profile. But I thought, no, you know what? This is about ethical evidence-based medical practice.

There were some corrections that needed to be done, some caveats that they added in, into the papers around the side effects issue. So I carried on this campaign. I carried on publishing in other journals, kept talking about transparent communication, ethical evidence-based medicine, statin over prescription. There are other things we can be doing in terms of lifestyle, right, which are gonna be more powerful, you know, whether it's low-carb Mediterranean diet, exercise, why are we not focusing our attention there rather than just giving people all these pills that they think is gonna protect them from heart attacks, and in most cases it doesn't. And in that journey, and this went on for a few years, this is where things got really interesting.

So to answer your question, yes, there was a lot of backlash. It was tough. There was a bit smearing going on. But I realized then, as a public health advocate, that you've got to have a thick skin and grow a rhinoceros hide. And those are the words from a man called Simon Chapman.

Simon Chapman is a professor of psychology in Australia. He was considered the lead campaigner in making sure there was tobacco control in Australia. And he wrote a paper talking about his 38-year career in public health advocacy and gave 10 lessons. And 1 of those lessons is this. As soon as your work threatens an industry or an ideological cabal, you will be attacked, sometimes unrelentingly and viciously.

So grow a rhinoceros hide. And I thought, you know what, I'm up for it. I'm up for it. So many more people came out of the woodwork to support me. Other doctors said, you're right.

And I thought this is about truth and transparency and about ethical medicine and highlighting all the corruption and the conflicts of interest. 1 of the things that Professor Collins hadn't been made apparent is his department had taken over 200 million pounds at Oxford for doing research into statins from the drug industry, and they also kept the data commercially confidential. So most of the publications and guidelines that were coming on statins were coming from, emanating from that department where no 1 had been able to independently verify the data. And he is quoted in the Guardian saying, only problematic side effects from statins affect 1 in 10,000 people. So I thought this is something, this doesn't add up.

I think these are biases, conflicts of interest. I'm not saying that he was deliberately malicious, but I think there's a huge conflict of interest there that is clouding his judgment. Plus he's not a clinician, he doesn't see patients. So there's all of those things that I think limit his ability to really look at the evidence properly.

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Cardiologist on the Over-Prescribing of Statins for Heart Disease