The TRUTH Behind Statins: Helpful or Harmful? | Mark Hyman & Aseem Malhotra

About 1 billion people around the world are prescribed statins. Total revenues from sales of statins have reached a trillion US dollars. And actually, heart disease, most of heart.

Disease is rooted, the biggest risk factor, if you like, is. The most important thing people need to realize is that heart disease is not a statin deficiency. Number two, that it's primarily driven by lifestyle and primarily by the amounts of carbohydrates that we're eating, sugar and starch, flour and sugar. and three, that the over focus on LDL is misguided. And then in fact, it may be other biomarkers such as triglycerides and HDL or the total cholesterol to HDL ratio, or the inflammation biomarkers or oxidative markers around cholesterol, or the particle number, particle size, things that we're not typically looking at insulin. I mean, if I had one test to look at heart disease actually risk, I would do a glucose tolerance test measuring insulin fasting and one and two hours later. because that, that's gonna tell me almost more than any of the other tests. And it's something that most people don't do. Sure. And then the, the other thing we kind of covered was that we need to do the right cholesterol profile, which is the NMR or Cardio IQ test from LabCorp Quest, which you can get from your doctor. It's a much better way of looking at the total picture along with the other biomarkers of blood sugar, insulin, A1C, inflammation markers, and so forth. And that, and that the good news is that according to the EPIC trial and many other studies, 90% of heart disease could be prevented by simple lifestyle changes, eating a whole foods, real food diet, exercising a little bit, not smoking, keeping to your ideal body weight. I mean, that's pretty simple. And yet on meditation, it might even get a better benefit. That's a 90% reduction, right? Absolutely. It's actually really relevant. And yet statins, although they are good for certain patients with high risk conditions or with lots of plaque or who've had heart attacks, they do form part of the toolkit. But I would just sort of emphasize that I saw this one sort of medical journal that said lifestyle doubles the benefits of statins. And I'm like, oh God, that is such a poor framing, you know? In fact, lifestyle may be all you need if you are aggressive enough. And I, and I have patient after patient, I'm sure you do, who are on all the medications. They're on high blood pressure medication, they're on statins, they're on aspirin, they're on all kinds of cardiology medications, and they've had a heart attack and their numbers are better off the statin once we fix the underlying lifestyle issues. Actually, their whole profile looks better. So that's to say that you need to have a more nuanced view around statins, a nuanced view on heart disease to deal with the root causes of it. 90% of people with prediabetes are completely undiagnosed. And one study I read from, I think it was from the UK, about, if I get the numbers right, I think two-thirds of everybody coming into the hospital with a heart attack had either diabetes or undiagnosed pre-diabetes. That was the biggest driver.

Yeah. So two-thirds of people admitted to a large US study several years ago that showed that two-thirds of people admitted to hospital with heart attacks had metabolic syndrome. So that's the worst type of poor metabolic health, you've got five markers which we'll go through. And if you have three of those abnormal, which basically is linked to high blood pressure, pre-diabetes or type 2 diabetes, increased waist circumference, high blood triglycerides and low HDL, those are the five. If three of those are abnormal, you have metabolic syndrome. 66% of people admitted with heart attacks in the US have metabolic syndrome, so.

Three of those abnormal. But 75% of them had normal LDL and normal cholesterol.

So clearly, what did you just say?

Wait, wait, wait, wait, wait, wait, wait, wait, wait. Slow down. You're talking fast. Slow down. You just said that 75% of people admitted to the hospital with a heart attack have normal LDL cholesterol.

This is from 2009.

Yes, but only 10% had optimal HDL.

Yeah, probably. Yeah, that's true.

I think about 70% had abnormal triglycerides.

Yeah. Right. yeah. So, so the question is at that time, so why have we not changed things? I think one of the things you say you hit on the nail on the head there about lack of awareness of nutrition and that kind of stuff, one of the things that's also, there's a huge lack of awareness is about how rapid lifestyle changes with diet at the forefront, but the other things of course are crucial, can improve those risk markers of metabolic syndrome. So one study showed that in 50% of people with obesity that had a dietary change, which in this particular trial was low carb, okay, reverse their metabolic syndrome within 21 to 28 days, Mark, right? That's massive, right? So those risk markers are triglycerides coming down, HDL coming up, even blood pressure coming down to some degree, getting out of pre-diabetes, getting out of type two diabetes, they start to have an effect. And that's why I wrote this. It wasn't gimmicky. I mean, 21 day immunity plan was also based upon those principles. And the same thing I talk about in this book as well, is that people will see the improvements in those markers very, very quickly if they adhere to the prescription, the lifestyle prescription that we, you know, doctors prescribe for them that really focus on insulin resistance. That's it. If you focus on insulin resistance as your end goal to improve fat through various lifestyle mechanisms, but dietary change alone is the only intervention Mark from any.

Study that lifestyle study that can rapidly improve those markers. What's really striking to me is even at major, major heart hospitals around the world, the heart disease prevention diet, the Cardiology diet again, when they go in the hospital, is a low-fat high carb diet.

I know.

And I'm like, what's going on here? I know. It's like we're living in the dark ages and the data that's now here is not getting incorporated into the practice of medicine, which is really unfortunate. So I love your work because what you're doing is you're not just taking things at face value. You're looking under the hood. You're looking at the data and you're creating nuanced conversations that aren't black and white. It's like statin's bad, you know, absolutely. It's really about looking at the honest, accounting of what we know and we don't know. And actually, where should we be looking? So as a cardiologist, what really is the best predictor of heart disease if it's not LDL? And what can we do lifestyle-wise to both prevent, treat, and reverse the risk and even the status of actually having heart disease?

Yeah, so Mark, so I think again, I would come back to keeping the basics, stuff that relatively simple to measure. inexpensive. Okay, so what, you know, the things I always go through with my patients, like, so let's go through these, these five markers. What's your blood pressure? You want your blood pressure ideally to be less than 120 over 80. Now the diagnosis is if it's more than one, between 120 and 140 systolic or between, you know, 80 and 90 diastolic, then you have pre-hypertension and that, that doubles your risk of stroke and also contributes to heart disease. So you want to look at the blood pressure. HbA1c should be less than 5.7% between five and different I know different countries have different ranges but essentially between 5.7% and 6.4 is pre-diabetic and 6.5 and above is type 2 diabetic so you want your HbA1c to be less than 5.7% ideally you want your waist circumference for a Caucasian man to be less than 102 centimeters measured around the belly button and less than 90 centimeters if you're female. And then your triglycerides should be ideally less than one millimole per liter, which the equivalent, I think, in the US is, I think, 150 milligrams per deciliter, Mark, you would probably correct me on that if I'm wrong. I think that's the range. It should be less than 150. And the HDL to be similar, so when you're above 150, right? So greater than one millimole per liter. And if you have those all in range, which, as you said earlier on, actually having all those markers in normal range for the average American adult is only about 12% of adults. So 88% of adults in the US don't have those in the normal range, which is very troubling, right? And this isn't just older people, only one in four adults aged between 20 and 40 mark in the US have those in the normal range. And this is what we're dealing with. But the good news is, again, those are really indirect markers of insulin resistance. If you wanna do more, slightly more expensive tests, and people get this in the US more easily than the UK is you do a fasting insulin level and there's a different units. I won't give you, I won't get it wrong with, but there'll be a normal range. I think it's less than, should be less than six international units, I think, if I'm not wrong, in terms of insulin, fasting insulin, right? So that's another marker that you can use. So once any of those are out of, out of, out of the normal range, then you've got some degree of insulin resistance. So the question is, what can you do about it? And then it's, well, let's just go back to very basic principles. I, I keep it simple. So Avoid ultra-processed foods. What are ultra-processed foods? Well, the data now, and I know you've been a big advocate for this, Mark, in recent years as well, and writing about this, is that, you know, more than 50% of the UK diet, more than 60% of the US diet, is now coming in terms of calories from ultra-processed foods. I think kids need 67%.

67%?

Right. It's unbelievable. This is food that comes out of a packet that usually has five or more ingredients. a combination of sugar, starch, unhealthy oils, usually with additives and preservatives. And that's a very simple rule of thumb. So I tell my patients, if it comes out of a packet and has five or more ingredients, it's the ultra process avoided. And that includes even packaged bread, right? So these are things to cut out. And then low quality carbohydrates. So minimize sugar and low quality carbs. So these are refined carbohydrates, like fiber, your white breads, your pastas, your rice, your potatoes. Now, It doesn't mean you have to completely eliminate it. It depends where you're starting from. So a lot of people have awesome metabolic health already who are generally doing this stuff right 80% of the time probably don't need to be as strict. But if you're starting from a position where you're type two diabetic and all your markers are off, then you have to be more extreme to see the bigger benefits, right?

So, what, you know, I mean, listen, I might, I'm like, I have my insulin levels are like less than five, pretty much about two. I have a 6% body fat. Yes, I'm bragging. But I'm pretty metabolic healthy. I exercise a lot. I eat really healthy. And I went to Sardinia last summer and I'm like, you know, here I am for a week. I'm just gonna like eat whatever. And I'm gonna eat the pasta, the bread, I'm gonna drink the wine. And I went, you know, I was treated well and had a very, you know, abundant diet. And I gained like five pounds and I got the belly fat. And, you know, it was so even if you are extremely healthy, if you start to eat more of that stuff, you're going to start accumulating that. And it's really, you know, unless you're just like doing a marathon every day, it's really tough to keep up with that carbohydrate load that we have.

So that's really important point. Yeah, I think we have to be aware of that. Again, we become and different people are more sensitive to these carbohydrates as well. Right. So I think, you know, one of the, there's a quote in the book from Dean Ornish, I quoted him. just to give people a concept to understand a bit of nuance with this management Mark is that it takes more to reverse disease than it does to prevent it.

Well, I think he was borrowing from Benjamin Franklin, which says an ounce of prevention is worth a pound of cure.

Absolutely, right? So I think with the pay, I think, yeah. But the bigger picture for most adult, you know, in Europe, Americans around the world, the big issue is ultra processed food, low quality carbs, as you said. And I think if you get that, out of the diet, that it's about patient preference and the values. I'm an advocate for the traditional Mediterranean diet, but minus in the way we're living now, you know, the ultra, obviously the starchy stuff, because there is, as you know, we've talked about gut microbiome as well. The positive side comes from with the best available evidence we have and things evolve seem to be that there is antioxidants, anti-inflammatory components with whole fruit and vegetables, you know, extra virgin olive oil, nuts and seeds, you want to be getting obviously enough protein, you want to get all your nutritional requirements as well. So you think about, okay, how am I going to get all my nutritional requirements? So I minimize the need for supplements. I mean, I know supplements have a role, but minimize the need for supplements, right? And also reduce the chances of me developing insulin resistance from the diet. And if you focus on that, that's what I do with my patients, then as long as you get the base of the diet right, other things here or there doesn't matter so much. So get the base right, cut out the crappy stuff, pardon my language, right? And then it's about the practice of values, different cultures, right? different types of foods, Indian food, Chinese food, whatever, there's going to be obviously some big differences in a lot of the food that people eat.

Yeah, I think that's right. And I think the lifestyle stuff is so huge. And you talked about the Pioppi diet, I talked about the Pegan diet. It's essentially focusing on quality. So whatever you're eating, the key concept is it should be high quality, meaning nutrient dense, unprocessed, whole real food. and you can kind of go up the chain, you know, eating a feedlot steak is better than eating, for example, you know, a bunch of bread, right? But it's not as good as eating wild elk or eating a grass-fed steak. So you can keep going deeper in the quality chain. The second is to really understand that food is medicine and that everything you're eating is regulating your biology in real time. And three, it's personal. Everybody's biologically different and some people may be more carbohydrate to tolerate than others. Some people may be more fat intolerant than others. And there are ways to figure that.

Out, which is really important. Absolutely. Absolutely. So that, that really covers a lot of the diet side of stuff. And then obviously, the heart, you know, from a heart disease perspective, exercise, I think we've somehow overedit. The most important message is keep moving, do what you enjoy. Be careful of overdoing it. A lot of people get injuries, they overdo it. There's a, you know, especially if you're stressed out and you're doing more than, say, 60 minutes of moderate to vigorous exercise a day, more vigorous side that can actually worsen your stress. So the data really says that, you know, 30 minutes of moderate activity a day. And you can do different things. You do Pilates, you do yoga, you can do cycling. You know, I'm not a particular big. I used to be a runner. I've kind of shifted more to cycling now because, you know, running on the road generally is not particularly good for your knees. I mean, I do Sprints once a week. I do hits. Right. So all these things are there, but do enough, but don't overdo it. Right. With the exercise. And then the big thing, Mark, something I've discovered, in the last few years, which certainly has a big impact on my patients, is stress, psychological stress, chronic psychological stress, which in its own right, and I read about in this book, is the equivalent of another risk factor, like high blood pressure or type 2 diabetes in terms of this cardiovascular risk. But a lot of people aren't managing that, not realizing how important it is. And of course, it links to inflammation. There's a lot of emerging data. There's stuff related to clotting problems, increase in fibrin in the blood, which is involved as a clotting factor. And what I do with all my heart patients is I ask them, I do a very simple questionnaire kind of on them and I ask them in, you know, 0 to 10 in the last few years, you know, these are people who've already got diagnosed heart disease, some people who've had scans done, they've got some furring of the arteries. And I say to them, you know, where is your stress levels in the last two or three years? I know it's obviously been pandemic time, so it's a bit skewed, but in general, most of them say, you know, that they are stress levels are kind of eight, nine out of 10, right? For the last few years and they've not done anything about it. And then I write about in the book, you know, we need better quality data, more data. But what's fascinating, the largest study on heart disease reversal, which was done in India by an interventional cardiology specialist, Dr. Amitabh Chauhan, called the Mount Abu Healthy Hearts Trial. Basically, it took patients with significant coronary disease, so well over 100 patients, moderate to severe, so at least 50% to 70% blockage in their arteries. These are people that didn't want to have a bypass operation, they didn't want to have stents. And he put them through his healthy lifestyle plan. Now in India, there's a lot of vegetarians. So it was a very high fiber vegetarian diet. There was some starch in there, but it was very high fiber vegetarian diet. It was moderate exercise. So two 30 minute brisk walks a day. Okay. And then it was something called Raja Yoga meditation, which also wasn't just about meditating. It was like, There was a bit of counseling. It was about reconnecting with your family and your friends and the social aspect, trying to reduce stress levels. Long story short, the end of the, you know, after two years of the trial, then followed for five years, they found that in the people that adhered to the lifestyle program, there was a 20% reduction on average in the stenosis of the arteries, which is unheard of, right?

You mean that the clogged arteries got better?

Yes. Yeah. They got better. They reduced from, say, 70%, 50%, 5%, 30%.

I mean, extraordinary, right?

And this is no statin. No statin. This is pre-statin, no statin. And then, when they tried to look into what was the most important factor by far of all the lifestyle factors that contributed to the reversal, it was 40 minutes of meditation a day. Wow. Right, so this is a big missing area, I think. And I think the other thing about the stress reduction, which links to chronic inflammation, that's the mechanism is that we think now Heart disease, these plaques that develop these blockages, they're dynamic processes. So you get some inflammation, you get a plaque formation, it then progresses. You can potentially, it seems that you can potentially reverse those blockages or reduce them. But the biggest factor so far, I think, that's been ignored is stress reduction through meditation. And as you know as well, if people incorporate that, then they're also more likely to sustain the lifestyle the other lifestyle factors in terms of adhering to the diet. But their mental health is better, Mark. So it's quality of life. It's not just about something potentially being helped with in the long term. Within a few weeks when people do this and some people need more help, you know, I find it difficult to meditate just from using an app. I have a Pilates teacher that I started seeing a few months ago that comes to see me once a week. I need to probably do more. It was fascinating within an hour, even that session of Pilates one hour, which is also, you know, it's a great exercise, but it's meditative. Wow, you feed your stress levels, you just feel like a different person.

Yeah, yeah. It's true. I mean, I think that, you know, the mechanisms are interesting. When you look at stress, what it does is a number of things. One, as you mentioned, increases inflammation. Two, it increases cortisol, which is a hormone that your body makes that actually causes your blood sugar to go up, your blood pressure to go up, causes your lipids to get worse. If you look at race car drivers before and after a race, their cholesterol goes up a hundred points. just from the stress. And not only that, but it actually, it actually causes your fat cells to store more fat. So if you eat under stress, there's nerve endings that innervate your fat cells, and the stress response communicates through your nerves and your autonomic nervous system to your fat cells and tells them to store the fat. So it's kind of a big deal. And I, I agree with you. I think, you know, we are under such a barrage of stressors in our lives, whether it's work, family stress is financial stresses, COVID stresses, climate change. I mean, the new, I mean, just, I don't watch the news anymore. It's just too stressful for me. And, and yet it's, it's so simple. It's free, it's accessible. And I, I've, I've been practicing meditation for years, and it's such a key thing to help regulate your life and your biology in so many ways. It improves the stem cell production, it reduces inflammation, improves neuroplasticity, brain connectivity. The data is just so powerful on this. And if anybody's really interested, you can listen to the podcast I did with Daniel Golman about his book Altered Traits, which studied advanced meditators using very advanced imaging technology, looking at their brain function and their brain waves and see what happens when you have somebody who's been meditating for a long time. But it really doesn't, you don't have to be a professional meditator or you're living in a cave for nine years. Just 20 minutes a day or 20 minutes twice a day is very powerful. And I personally use a technique, it's called Ziva Meditation, Z-I-V-A meditation. you can look it up online, you can take an online course, learn how to do it, it's super easy, and you don't need any special equipment except, you know, sit on the floor or a chair. And through that technique, you're gonna have all kinds of benefits, not just heart disease, but all kinds of benefits. So I encourage people to take heart to what you're saying, 'cause I think it is one of those neglected factors. So diet, exercise, stress reduction, sleep. I think the data you presented on the reversal is quite interesting because most of us don't think we can unless we take aggressive high-dose statin, And Dean Ornish's work showed that there may be possibility through lifestyle interventions to change the course and actually reverse the trial.

And Mark, anecdotally, I'm getting patients and I will be writing about this soon and hopefully I'll be able to even fund a trial to try and get a bit more definitive in terms of the answers. But I'm seeing patients, many of my patients coming back who have either halted the progression of heart disease, so from imaging, and some have even had some reversal. One patient recently contacted me and I'd forgotten, you know, I was and they said, you know, Dr. Marta, I saw you in 2019. She'd suffered a TIA, a mini stroke. She'd had a blockage in one of her blood vessels of 75%. And she emailed back saying, I've followed your lifestyle protocol. And I was shocked to receive this. I had to read it again. And she said, I've repeated the imaging and now the reduction is gone to less than 50% within two years. I mean, and I'm just doing what the data, you know, I'm saying the very least that's reduced your risk. I don't give people false hope. Promise it and say, you know, there is some potential here, but your quality of life is going to be improved. We're going to improve your risk factors. And you, and hopefully, you know, there may be some reversal, but at least we can help stop progression at the very least, you know, according to what would happen normally. And, and, and the feedback is extraordinary once people, once people, once people follow it. So we need to try and get this more data, of course, but we.

Need to get this more inculcated into medical practice as well across the board. I mean, the behavior change factor is a huge thing. That's a separate topic, which we could spend hours on. I've had, yeah, had, BJ Fogg talking about behavior change and I talked about the Daniel Plan and behavior change. So the power of community and the power of group support or medically, you know, group appoint medical group appointments or shared medical appointments can be very, very effective. And we've seen this that even getting people to change their lifestyle is and the outcomes are almost three times better using groups than actually one-on-one doctor visits. We've done that at Cleveland Clinic. It's really quite interesting data to see. I have always had a love-hate relationship with stats. because they are a drug which has some benefits. But what seemed to have happened is that there's been a wholesale embracing of this class of medication as the panacea for preventing and treating heart disease. And your book challenges that thesis. One, that LDL cholesterol is the problem, which is primarily what the statins do is lower LDL. And two, that statins are not a free ride, that they come with a lot of inherent risks and side effects. And three, they're actually not that effective and that the data we have has been highly manipulated. And it reminds me of a quote from, I think, Mark Twain or maybe Roger Williams, who said, there's liars, there's damn liars, and there's statisticians. And I think the way that the the data get squeezed and manipulated often give the impression of a profound benefit. But you challenge that whole hypothesis and you challenge us to think differently about statins.

Before we continue down this track and more detailed discussion, I think what people need to realize is that we are, I am, we are coming from a position about ethical evidence-based medical practice and about giving the right patient the right treatment at the right time with informed consent. And at the same time, Mark, also give people an alternative plan, whether or not they choose to take statin. And again, I would always argue that's the patient's choice ultimately. But also to not be ignoring something that you've pioneered magnificently over many, many years, the impact of lifestyle, which as you know, is more impactful in many ways than medications and come without side effects.

Mostly lifestyle. Lifestyle has a lot of side effects. Well-being, happiness, joy. Good health.

Sorry, yeah, you're right.

All the side effects are good ones. Better sleep, better sex. Weight loss.

100%. That's what it's about, right? Because we were all going to die eventually, but we want to have the best chance of having authentic happiness for as long as possible. And of course, our happiness is very much linked to our physical health as well. So this is really the heart of the book. And, you know, I've researched this as, you know, in detail, probably over a decade, looking at cholesterol, trying to understand the root cause of heart disease and trying to shift the conversation and shift the balance towards, you know, overall improving individual patients' health, but also population health as well. And I think where we've gone wrong is we've grossly, first and foremost, grossly exaggerated the fear of cholesterol in its role of heart disease. We've then now because of that fear, the focus has been that the primary way of preventing heart disease is to reduce cholesterol. And the most effective drugs at doing that have been statins, so widely prescribed, markets estimated potentially about 1 billion people around the world are prescribed statins. It's also one of the most lucrative drugs in the history of medicine. It's estimated I think last year total revenues from sales of statins have reached a trillion US dollars. so there's a lot of money involved as well. And I think that is important for people to be aware because that, I think, introduces a huge bias into the conversation. A lot of vested interests depend on fear of cholesterol lowering and, and statins, you know, and other cholesterol lowering drugs. So it's like, well, actually, let's just break it down so that people are better informed. And then, you know, one of the things I've also advocated for is something called shared decision making, which is an approach where you have a more equal partnership. And when it comes to conversations with patients about any kind of treatment, or investigation that they're going to go through, but except that it's really important that we take into consideration patients' individual preferences and values. So if you look at the evidence-based medicine triad, which is geared towards improving patient outcomes, there are three big components. So you'll use your best available evidence, your individual clinical expertise, and last but not least, patient preferences and values. And if you, if, and what I teach my medical students is if you are adhering to those principles, then you are going to increase your chances of improving your patient's health and well-being. And that's really what it's about. So that's really the background to the book.

That's great. I think that's a very important framework. And what I would like to do is zoom out for a minute and have you answer a couple of key questions. Because I hear conflicting versions of the data from cardiologists. And it seems, yes, number one killer in the world is still heart disease. However, I've heard cardiologists say we're winning the war because death rates are going down. We're better at actually treating the disease or better at preventing the disease. Statins have played a big role in that and we shouldn't ignore that fact. But you suggest that maybe that's not true. And in fact, maybe that the death rates aren't going down, maybe heart attack rates aren't going down. So can you kind of unpack the data for us? And what is the truth about One, this massive drive to put everybody on a statin if your cholesterol is a little high.

Yeah, absolutely.

And the fact that maybe it isn't doing all that it's cracked up to do. So talk about that.

So, yeah, that's a very good point. So let's try and break all of that down. So death rates from heart disease started to increase in the 1920s. Look at data in the US. Let's just look at US data, which pretty much parallels most of Western Europe as well. And it peaked around 1970. And then since 1970, the death rates have started to drop. But, you know, something I've published on the BMJ before is to, if you break that down to try and see what are the different factors that reduced heart disease, the biggest impact actually was reduction in smoking prevalence, probably responsible about 50% reduction in death rates. Other factors, emergency care, emergency treatment of heart attacks. So we have thrombolytics, these drugs called thrombolytics that help people. We had emergency stenting, which in the acute phase in a heart heart attack certainly is life saving, not in the stable phase. That's a different discussion, but certainly in the acute phase, the development of coronary care units. So what a lot of people used to die from heart disease, Mark, because they would suffer even once they were in hospital, they would have a cardiac arrest, which is more likely to happen within 24, 48 hours of having a heart attack. And we then developed coronary care units where we could monitor patients and then defibrillate them.

So it's better rescuing them from what.

Happens once you get a heart attack. Absolutely, and in fact they are lifesaving. If you have a cardiac arrest and it's witnessed then you have, oh you're in hospital and it's because of a heart attack, nine times out of ten you'll be saved from a defibrillator and then you're fine and your prognosis is the same as somebody that didn't have a cardiac arrest. So all these things are there, maybe to some degree the reduction of trans fats in the food supply as well, that also had a role. But when you look at statins, and this is something that's actually recently being analyzed, they looked at Western European countries over 12 years since 2000-2012, right? To see had an increase in statin prescription for different risk groups, low risk and high risk, did that correlate with any reduction in cardiovascular death, death rates from heart disease? And the answer was no. The question is, well, how can that be explained? So again, let's break the data down. If you look at the average increase in life expectancy from taking statins from industry sponsored data. So we take that with a pinch of salt because industry sponsored studies, which are most of the statin studies in general, are designed and the results are geared to kind of exaggerate the benefits and minimize the harms. But if we take that at face value, okay, even though- I want you.

To stop there for a minute because it's such an important point.

Yeah.

Most of the data we have on statins is from drug company funded studies. Yeah. In which they actually often are contracting with research organizations to do the research. They're hiring essentially Hitman names to put their name on the study. They design the study, they write up the study, and then they get a bunch of cardiologists to sign off on it. Is that fair to say?

Yeah, Mark, absolutely. You're spot on. In fact, just to take a step back for a second, if you look at the issues around health misinformation, you know, we have something called the Health Misinformation Mess, a quote I take from John Ioannidis, Professor of Medicine at Stanford. Yes. And there's something called the Seven Sins that contribute to misinformed doctors and misinformed, unwittingly harmed patients. They're rooted in biased funding of research, right? So research that's funded because it's likely to be profitable, not beneficial for patients, biased reporting in medical journals, bias reporting in the media, bias patient pamphlets, commercial conflicts of interest, defensive medicine, and an inability of doctors to correctly communicate health statistics to patients and also doctors to not understand health statistics properly. That's something that isn't taught very well at medical school and it's certainly not something we're encouraged to do. So I've been involved with the BMJ and the medical colleges in the UK in 2015 to try and help revolutionize medical practice through medical education and postgraduate teaching. But it takes time. I mean, I was reading somewhere that when you try and revolutionize or change an approach to something that's been embedded for a very long time within medical practice, apparently it takes 17 years, Mark, before that change happens. So we've got to keep fighting and campaigning for it. But you're right. This is the issue with statins is not dissimilar to many other drugs. And given that information, given those biases, even if you take all those biases consideration. Best case scenario, there was an analysis done to look at randomized control trials of statins in people with heart disease. Forget about prevention for a second. Statins benefits seem to be there much stronger in people who've already had a heart attack or people who've been diagnosed with severe blockages in their arteries. Okay, if you look at the, if the, from those people from the trials who took statins religiously every day for about five years, because the trials only tend to last about five years. before they're approved and before it changes practice. The average or median increase in life expectancy is over a five-year period, 4.2 days. So if we accept that slight increase in life expectancy over a five-year period, and then you add in the real world mark, within a few years of statin prescription, even people at high risk of heart disease, at least 50% of those patients stop taking statins within two to three years. you can understand from a scientific perspective, from a data perspective, forget about any fraud or any conspiracy theories, just from the data that's already there, you can explain why statins may have not had any impact on reducing death rates from heart disease in the population. Now, when you look at individuals, and this is what doesn't often take place in the conversation between doctors and cardiologists and patients, and you know, to be fair and honest on this, I mean, I think most doctors actually don't even know this information. That's another reason I wrote the book is to educate doctors so they can have better discussions with their patients. If you've had a heart attack, and this is by the way what I do all the time in my practice, so all my patient letters that go back to general practitioners, all the patients I see, I always put this in there, you know, in the discussion. If you've had a heart attack over a five-year period from an individual, the benefit of a statin taken religiously over five years is it prevents one in 39 of those patients from having a further heart attack, and one in 83 in terms of delaying their death or saving their life. Right?

Now, these are the people who already have had a heart attack or are at very high risk.

Absolutely.

We're not talking, and by the way, for everybody listening, 75% of the prescriptions for statins are not for people who have had heart disease or very high risk. It's for primary prevention.

Absolutely.

And the data on that is even worse. And I want you to explain that after you kind of unpack the fact that, gee, only 1 in 83 people have a death prevented. It means 83 people have to take this drug for five years with all the risks and side effects for one death to be prevented.

Yeah, and Matt, to add a caveat in that, what's interesting is these are also most likely the patients that tolerated the statin and didn't get side effects. Because those people are somehow weeded out of the trials. Often we have something called the pre-randomization running period before a randomized controlled trial starts, where patients who don't tolerate the drug or non-compliant, they use this word non-compliant, okay? Which doesn't make sense to me because if you're enrolling in a trial and you volunteered, you're likely to be somebody who's enthusiastic about taking a drug, right? So that doesn't make sense to me. But very likely that people with side effects are weeded out within the first few weeks of a trial. and then you then report on the results on the people who tolerated the drug. Okay, so this is still a bias. So I talk to my patients, say, well, it's more likely those 1 in 83, 1 in 39 figures are people that tolerated the drug and were able to take it for five years. If you add in people who get genuine side effects, and sometimes we don't know whether the side effects they experience are statin or not, and I'll explain why I do with my patients to kind of weed that out, it's highly likely that that benefit is much smaller, if not even potentially non-existent. You know, we don't really know, but there's a chance that it's non-existent and that's uncertainties. And we have to have those discussions with patients. I think doctors aren't necessarily very good at saying, listen, there's a lot of things we don't know. But let's just tell you what we do know. And of course, the potential biases and uncertainties. And Mark, in my experience with all the patients I've had these discussions with, even about talking about industry bias and all that kind of stuff, patients appreciate that. they want honesty from their doctors. Anyway, so that's on the secondary prevention, the high risk. If you look at primary prevention, and you're absolutely right, Mark, most of the people prescribed statins around the world are not high risk, okay? These are people who have got maybe a slightly high cholesterol or even have a risk profile, more importantly, that suggests they may have, say, a 10 to 20% risk of having a heart attack or stroke in the next 10 years. And there are risk calculators people can go online and look at those risk calculators. If you have a less than 20% risk, if you're lower risk of having, you're not high risk from having heart attack or stroke in the next 10 years, then the statin data suggests approximately convicting data, a 1% benefit. So, 1 in 100 in preventing a non-fatal heart attack or stroke over five years. But this is crucial. No mortality benefit. You're not going to live one day longer.

That's right.

And when you look at data, and studies looking at when we presented this sort of information to patients in this way, and this is without talking about potential side effects, not even gone there yet, most of those patients, Mark, would choose not to take the pill. Can you think, is this extraordinary? So if we are actually adhering to the principles of ethical, evidence-based medical practice and informed consent, in my view, most people who are prescribed statins around the world would choose probably not to take the pill.

Now, that's not to say that cholesterol isn't a problem. The question is, how is it a problem and why is it a problem? And it's quite different than what we think. And the overarching narrative has been that LDL cholesterol is the cause of heart disease. And it's convenient because that is what statins do. But it reminds me of that joke of this guy who lost his keys on the street and he's looking under this lamppost and his friend comes by and he says, Hey, what are you doing? He says, I'm just looking for my keys. He says, Where did you drop them? Well, I dropped them down the street. He says, why are you looking over here? He says, well, the light's better here. So, we have a drug that can treat LDL, but it actually doesn't deal with the real root causes. And I just want to take a second for people to unpack why we're looking at the wrong thing when we measure cholesterol today for the most part. Most people get a total cholesterol, HDL, LDL triglycerides. But it turns out that LDL isn't even that good of a predictor of heart disease.

Absolutely. Yeah. Really good point, Mark.

So, yeah, absolutely. Let me just finish this thought. And the Jupiter trial, which is one of the largest trials looking at statins and heart disease, found that if the statin lowered the LDL cholesterol, but not the CRP. In other words, if the C-reactive protein or the inflammation marker was high and you lowered LDL, it didn't really have an impact only if the inflammation was lowered. And so we now know that the underlying risks for heart disease are inflammation and insulin resistance, which drives something that we call atherogenic dyslipidemia or a kind of cholesterol profile that makes you prone to heart disease. So tell us about a new way we need to be thinking about cholesterol rather than just a simplified, oversimplified dogma of LDL statin, LDL statin, LDL statin, which you hear all day long. What is the things we should be looking at and what are those things and what are the causes of abnormalities in the real biomarkers of cardiovascular disease?

Sure. Great points you make, Marc. So taking a step back for a second just so people kind of understand where we've gone wrong with the science on cholesterol or why certainly it's outdated. And it's important for people to realize, I think a lot of people have this misconception that medicine is an exact science. And if something is truthful at one time, it must be absolute truth and it can't be challenged.

But the reality is 50.

Well, yeah, exactly. But you and I know, I mean, the, the founder, if you like, one of the founding fathers of the evidence-based medicine movement, David Sackett said 50 of what you learn in medical school will turn out to be either outdated or dead wrong within five years of your graduation. The trouble is nobody can tell you which half, so you have to learn to learn on your own. So I bring that concept into also how I started questioning that dogma. And I don't think this was a conspiracy theory or malicious. I think vested interests have taken advantage of what is now outdated science, but traditionally, when people are trying to investigate the cause of heart disease up until the, you know, the 50s, 60s, 70s, we knew that we found, and this is still true, is that people with genetically very high levels of LDL cholesterol, okay? So this would be people who, not everybody, but usually at least have an LDL of more than 4.9 millimoles, which I think in US units is translated to 139 milligrams per deciliter mark, right? So those people with, who had at least an LDL of that level, most of those people had the genetic condition which affects one in 250 people. They had a very strong association with the development of heart disease. At the same time, people who had genetically low cholesterol and total cholesterol, certainly, we're talking about less than 3.8 millimoles per liter, which I think would be, I can't remember the cut off, but I think it's probably less than 150, if I'm not wrong, total cholesterol. Those people, one milligrams per deciliter, would have less heart disease, although they won't live any longer. But most of the people in the middle, when you looked at that data from Framingham, which is one of the original big studies that followed up 5,000 people in Framingham, Massachusetts, starting in the late 40s over several decades to try and find links and associations with various markers or risk factors in heart disease, in that they found that there wasn't really a strong association if you didn't have cholesterol at the extreme ends. So the next question then is, does lowering cholesterol, if we move fast forward, does lowering LDL cholesterol mark make any significant impact on reducing heart disease? Is there a correlation? And I published a systematic review in 2020 in BMJ evidence-based medicine. We investigated this two other, I was co-author with two other cardiologists, and we found there's this mantra which comes out from cardiology societies that There's something with every one, you know, millimole lowering of LDL, you have a 20% risk reduction in heart attack, stroke, whatever cardiovascular events. It was simply not true. It was not true. We falsified it. We said there was no correlation. So there is no consistent, if I'm being, you know, skeptical of my own research, I can say there is no consistent evidence to show reducing LDL reduces your risk of heart attack or stroke or cause mortality. Then you add in the other issue is something other research helps involved in. is if you're over 60, we did a systematic review published in BMJ Open several years ago as a co-author. If you're over 60, there is no association at all between LDL cholesterol development.

Hotzies and an inverse association with LDL cholesterol. It means that when you're older, if.

Your cholesterol is higher, you live longer. Absolutely.

Statistically live longer.

But then that may be confounded by other factors. So go ahead. Of course. But one of the explanations is cholesterol has a crucial role in the immune system. and there's a very interesting, so that may be why they're protected, okay? People are older with higher cholesterol. And actually, if you go look at the 19th century, you go back when our average life expectancy, for example, is about 40 or 50 years, people with FH, genetically high cholesterol, Mark, live longer than average. And the reason for that is likely because, well, infectious diseases was the biggest cause of death there. So it wasn't, you know, so this is really interesting. It's just something to think about. on the other side of it, the most recent data published in BMJ, and this was last year, a Danish study looking at 100,000 people following them up over 10 years, different age groups, they found when you look at all causes of death, the optimal LDL cholesterol was 3.6 millimoles, right? Which is way higher.

How would you translate that to American units? Because that's- I think that would be-.

Yeah, it would probably be if we say that It would probably be in between 200-250, something like that. It was much higher than what people are recommended to lower LDL. Sorry, no, LDL, it was something like, I think, 100-120, something like that.

Okay.

Okay. Well, people should clarify that. I can't remember the conversion at the moment, but that paper's there and it's translated. So Danish study, maybe we can pull it up later. And it looked at the optimal for all-cause mortality. What they found is if your LDL was very low, okay, then there was an increased risk of death from cancer. So there is this association with very low levels of cholesterol and cancer, and it could be again an immune system mechanism. So it just encourages us to think a little bit differently. We shouldn't be obsessing as our primary focus in managing heart disease at the very least about lowering cholesterol, the better now. How do you reconcile this information, Mark, with statins benefits? And you've alluded to this already, is statins. Most people are not aware of this. Statins have an independent effect. So they may lower LDL, but they also have a slight anti-inflammatory and anti-clotting mechanism.

Yeah.

And heart disease is a chronic inflammatory disease exacerbated by something called insulin resistance, which we'll talk about, but also linked to abnormal clotting. And the reason I bring up the clotting issue is when you look, and we published on this as well, and it's in the book, if you look at FH patients, So, about 70% of.

FH patients who are female- Familial hyperlipidemia. Familial hyperlipidemia, genetic condition where your cholesterol is like 300-400. It's really high.

They will not, 70% of those will not develop premature heart disease without treatment. About 50% of men, right? Well, not. So, the question is, are we able to differentiate in the FH patients, the ones that will develop heart disease and the ones that don't? Now, the first thing that's really interesting is we found there's no difference in their LDL between the ones that develop heart disease and the ones that don't, which makes you think, well, hold on, then LDL probably isn't even the issue with them. What is an issue, and there is some research on this, is that they tend, the people that tend to develop heart disease have some abnormal clotting factors, not your routinely measured ones, there's all sorts of different things that people can check. But that seems to be from lab studies and from other studies that suggest that FH people with heart disease have clotting abnormalities. this is the good news. When you look at the risk, what do I do with my FH patients? Well, of course, statins may have a role from anti-inflammatory processes, so you could still prescribe it from them. But we don't have this data about 1 in 39, 1 in 83. There's never been a randomized controlled trial to break down the absolute benefits and those. So we're presuming there's some benefit. But the people who had low insulin levels and low waist circumference had the lowest risk of developing heart disease, almost only slightly higher than the average person. which is really interesting. So the focus on FH patients should be lifestyle that targets insulin resistance, okay? Which is basically, you know, your body's getting resistant to the hormone insulin. You've spoken about this, Marco, but, you know, because of lifestyle factors, high glycemic index carbohydrates, ultra-processed foods, not getting enough sleep, being overstressed, being inactive, all these things contribute to insulin resistance. So that should be the lifestyle approach. And actually, heart disease, most of heart disease is rooted the biggest risk factor, if you like, is insulin resistance. and you asked me the question about what you look in the cholesterol profile, which is a marker of its resistance. Yeah. And that's having high.