Transcription
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?
Yeah, so for many years, there's been this misconception that high cholesterol is one of the most important risk factors for the development of heart disease. I broke down the data and I've published a lot on this stuff to look at it properly.
Joe, the association of cholesterol and heart disease came from something called the Framingham study, which was in Massachusetts. It started in 1948 and carried on for several decades, where they followed up 5,000 people. Many risk factors for heart disease came from that, including correlations that were then validated, like type 2 diabetes, high blood pressure, smoking, and high cholesterol.
Now, what's interesting about Framingham is that when you look at the associations of total cholesterol and heart disease, the significant association was only there if your total cholesterol was over 300 milligrams per deciliter. Very few people have total cholesterol that high.
We also have to understand that most of your cholesterol is genetic—80 percent of the cholesterol is genetic. Since cholesterol is a really important molecule in the body, it's not just a simple fat; it's important for maintaining cell membranes, playing a role in the immune system, hormones, and vitamin D synthesis, all of that stuff.
So, total cholesterol was not a very good indicator. If it was very high, there was an association, but almost all of those people had a genetic condition that gave them very high levels of cholesterol. It's called familial hyperlipidemia, which affects one in 250 people.
At the very other end, from Framingham, those with very low levels of cholesterol—less than 150 milligrams per deciliter, or four millimoles in European terminology—had almost no heart disease. So again, there are genetic factors at play. People with genetically low cholesterol tend to not develop premature heart disease.
Another interesting caveat is that most of the data on the development of heart disease was only up to people who were 50 or 60. What wasn't publicized is that once you hit 50, as your cholesterol dropped in Framingham, your mortality rate increased. This was never really discussed.
So, I looked at all of this. That's interesting, but I think the thing that really was a nail in the coffin for me in understanding the association of cholesterol and heart disease was very weak. William Castelli, who was one of the co-directors of Framingham, a cardiologist, in 1996 did a full summary of Framingham. He said this: unless your LDL cholesterol is above 7.8 millimoles per liter—which is something like, Joe, probably around 300 milligrams per deciliter—it has no value in isolation in predicting heart disease.
What they determined from Framingham was that your risk of heart disease, as one of the risk factors, was your total cholesterol divided by your HDL, the good cholesterol, or the ratio. So that's the first thing: the association of cholesterol and heart disease is quite weak, first and foremost.
The second question is, when you try to 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. Only in 2019, more recently, I co-authored a paper in BMJ Evidence-Based Medicine with two other cardiologists.
What we did was look at all the drug trials on lowering cholesterol to find out if this is 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? 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. It's a very weak association, if anything. So then the next question is, well, hold on, how do statins work? And that's the question you asked me earlier, and it's a great question—it's a really important one.
Statins do have a small benefit, but one of the properties of statins that isn't talked about is that 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.
But when you break it down, as I said before, your risk is... the benefits are about 1 percent if you're at low risk of heart disease. But if you've had a heart attack—and many patients I see have had heart attacks—they automatically get put on statins, and that cardiologists read even checked their cholesterol.
In the cardiology community, we kind of knew that 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 really crucial and important.
This isn't cherry-picked stuff; this is what all the evidence shows, and it's been peer-reviewed, etc. If you've had a heart attack, a patient comes to me and says, "Doc, shall I carry on the statin?" or "I've been put on the statin," or "I'm getting side effects," I say to them, "Listen, let me just explain to you the benefits first so that you don't have an exaggerated fear of stopping a 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 five-year period, if you take your statin religiously and don't get side effects—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, and 1 in 39 for preventing a further heart attack.
Now, a lot of people find that quite underwhelming. Another way of looking at the statistics, Joe, and this is important for populations, is looking at those trials. When I talk at conferences to doctors and general practitioners, there's often a gasp from the audience when I tell them this.
This is published in the BMJ. In the randomized trials, if I ask you this question: you've had a heart attack, and statins are one of the most prescribed drugs, the miracle cure, whatever—the most potent beneficial drugs in the history of medicine. If you take a statin for five years after having had a heart attack, how much do you think or hope it would add to your life expectancy?
You've literally survived a heart attack, and now you've been given this pill, which your doctor is telling you, "You must never stop; this is going to save your life." How much would you hope it would add to your life expectancy over a five-year period?
You might think, "25, 30?"
Okay, so a few years?
Actually, the answer is just over four days.
Four days?
Four days.
Maybe those are great days, though.
Well, no, fair enough, absolutely. But 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 that it's been the mass prescription of statins—millions of people taking statins.
But the evidence suggests there's a separate analysis done. They looked in European countries, high-risk and low-risk people for heart disease over 12 years. Was there a reduction in heart disease death rates because of statins? The answer was no.
That doesn't mean that the data is fraudulent; it's been misrepresented. But if you accept that four-day increase, these are in people who didn't get side effects and who were adherent to statins. Real-world data tells us, Joe, even people who have had heart attacks—maybe 50 percent 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 one of the most powerful, lucrative drugs in the history of medicine, and this is 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 been the reaction, and has there been any change in how it's prescribed?
So, after this publication in the BMJ, initially, I had to get another job. I lost that job in that hospital. I then ended up working for free briefly in another NHS hospital cardiology department, doing one day a week, because I had another role with health policy, which I'll come on to. They were paying me some money, and I didn't want to stop seeing patients, so I was working for free in one hospital for a year in a cardiology department.
In March 2014, I got a phone call—in fact, an email initially—from the editor of the British Medical Journal. She said, "Aseem, 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 at Oxford University. He got his knighthood from the queen because of 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."
She said straight away, "No, I'm not going to retract it, but we're very happy if you would like to publish a critique, and we'll publish it." 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 decided—whether it was him or somebody else—to go to the Guardian newspaper. I get a phone call from the Guardian and the BBC, which again was headline news. What Abramson had done became a news story. The front page of the Guardian was so damaging in terms of their error on the statin side effects issue that people would die. Essentially, this was almost as bad as they were trying to make parallels with Andrew Wakefield and the whole measles, mumps, rubella issue that happened many years ago.
That was the scientist who lost his license because he linked the MMR vaccine to autism. They were trying to create that kind of frenzy, and I'm like, "Well, this is okay." So I went on the BBC and I stood my ground, and I think that put the BMJ under pressure.
Then the next thing that happens is I remember I was with my cousin in New York. I'll never forget this. I get an email, a press release from the BMJ, which I knew was going to be an attack on one's credibility. The BMJ then decided they were going to send our articles for an independent review of whether or not they should be retracted.
I know, Joe, just to put things in context here, that's potentially career-destroying. If my article got retracted, it got so much publicity, and I genuinely believe what I said was correct. But if it gets retracted, then your credibility is undermined pretty much forever, and it would be career-destroying for me. I'm at the beginning of my career, so I was on trial essentially for two months, if you like.
That was tough; it was very, very tough. There was a panel they convened. They asked me to send in responses and whatever else. I didn't know what was going to happen. Then I think it was August 2014 when I remember it broke the news. I got an email, and basically, the panel had come back 6-0 unanimous in our favor.
Wow.
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 two things I could have done. One was, "Wow, this is too much. I don't think I can handle this. I'm just going to hide away and 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 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 that are going to be more powerful, whether it's a low-carb Mediterranean diet, exercise.
So why are we not focusing our attention there rather than just giving people all these pills that they think are going to protect them from heart attacks when, in most cases, they don't?
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 of 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.
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. He wrote a paper talking about his 38-year career in public health advocacy and gave ten lessons.
One 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. I thought, "You know what? I'm up for it."
So many more people came out of the woodwork to support me. Other doctors said, "You're right." I thought this is about truth and transparency and ethical medicine, highlighting all the corruption and the conflicts of interest.
One of the things that Professor Collins hadn't made apparent is that his department had taken over 200 million pounds at Oxford for doing research into statins from the drug industry. They also kept the data commercially confidential.
So most of the publications and guidelines that are coming on statins were emanating from that department, where no one had been able to independently verify the data. He is quoted in the Guardian saying only problematic side effects of statins affect one in ten thousand people.
So I thought, "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 are all of those things that I think limit his ability to really look at the evidence properly.