00:00
Hey everyone, it's Mikki here. You're listening to Mikkipedia and this week on the podcast I speak to Dr Matt Budoff. Professor Matt is a world renowned cardiologist and researcher who has spent decades at the forefront of cardiovascular imaging and prevention. Known for his pioneering work in coronary artery calcium scoring and computed tomography and geography, CCTA, which we discuss.

00:29
Dr. Bouddhoff has helped transform how do we detect and assess heart disease risk. this conversation, we explore what first sparked his interest in cardiovascular imaging and how his views on lipids, plaque and heart disease risk have evolved over time. We dig into his recent research on lifestyle interventions, particularly low carbohydrate and ketogenic diets and how they affect LDL cholesterol, atherosclerosis and overall coronary health. We also discuss the implications of

00:58
this keto study, which I've linked in the show notes, which found no direct correlation between elevated LDL-C and plaque burden in lean, metabolically healthy individuals following a ketogenic diet. Super interesting, and I'm not sure if you remember, but I believe that Nick Norwitz and I had a conversation about the lean mass hyper responders when Nick was on my podcast maybe about two years ago. So Dr. Matt

01:22
Dr. Burdov is a distinguished cardiologist and professor of medicine at the David Geffen School of Medicine at UCLA. He holds the endowed chair of preventative cardiology at UCLA Medical Center and serves as the program director and director of cardiac CT in the division of cardiology. Dr. Burdov has authored or co-authored over 50 books and book chapters and more than 2,000 articles and abstracts.

01:47
His contributions have been recognised with numerous awards including the gold medal award from the Society of Cardiovascular Computer Tomography and designation as a Master of the Society. So he is well revered in his space. He is just a known expert and I was super appreciative for his time in his very busy schedule. So I have popped links as to how you can connect with Matt.

02:11
Matt's profile and also the study that we chatted about, particularly the Lean Mass Hyper Responders study in the show notes. Before we crack on into the interview though, I would like to remind you that the best way to support this podcast is to hit the subscribe button on your favorite podcast listening platform. That increases the visibility of Micropedia and amongst literally thousands of other podcasts out there. So more people get to hear from the experts that I have on the show like Professor Matt Boodoff. All right team, enjoy this conversation.

02:45
With Dr. Bouddhoff, thank you so much for taking time to speak to me this morning all about a topic which I feel, obviously there is continual, I feel like it's a confusing space for people to negotiate. In fact, even this morning I had a client who told me that she had a high cholesterol level, for example, and then she relayed to me her total cholesterol New Zealand units, 5.5.

03:11
And her ratio was like, I don't know, 3.4 or something. So there is this perception of what a high cholesterol level is, but more importantly, what it means. And this is obviously a space that you must work in every single day. Yes. Yeah. No, I mean, I see a lot of patients now who are very concerned. They feel well, they look well, and they have very, very high

03:40
LDL cholesterol on the ketogenic diet. Yeah. so, of course, I want to talk to you a little bit about cardiovascular imaging. So what people can learn from these more advanced tests and what they tell us about overall risk. that's the thing, right? It's not cholesterol level per se. It's what does it actually mean for their health? No, absolutely. we've gone through such a

04:09
a period of time where everything was just about LDL cholesterol, where if it was high, we'd put them on medications. And if it was normal, we'd say you don't need medications. And clearly that's wrong on many levels. But it's really hard to retrain now society, both the patients who are asking for the meds or not, and the physicians who are reflexly acting on just an LDL level, as if that was the treatment

04:38
That was the reason for treatment by itself. And we just have to continue to re-educate and retool everybody. Yeah. So what sparked your initial interest in cardiovascular imaging, Matt? You know, I started when I was really an intern and resident when I first got to my institution in training. And I went up to the chief of cardiology and I said, I'm interested in cardiology.

05:05
Is there a project I can get involved with? And he says, Oh, you know, we have this new heart scanner. think it's going to be the mammogram of the heart one day where everyone's going to get a heart scan and figure out if they have high risk or not. And he wanted me to work with him. So I started doing research and that was my career. Yeah. And people know about the coronary artery calcium score, the CAC score, but there's also computed tomography

05:35
and geography as well, right? how do they, are they equally available to people? Not that, I mean, I say that, but it's not like you're going to go into your doctor and they're going to be able to easily run it there and then. But what are the differences between the two? Yeah, so coronary artery calcium score or calcium scan, as we call it, is a non-invasive test. There's no dye, there's no catheters.

05:59
Very simple test, you can go in dressed as you are, get a scan and leave within about five minutes. So we think of that more as a screening test. Can we see calcified plaque in the arteries, hardening of the arteries? And if we do, we can act on that as a surrogate for heart disease. The CT angiography is a little more complicated. Same machine, same type of scan, but now we're injecting dye contrast into the artery.

06:27
to light up the arteries to look for the non-calcified plaque and the persenstenosis. So we see a lot more, but it is more involved and it is more expensive. They're both fairly well available these days. I would say if we were having this conversation five or 10 years ago, I would have to say you'd have to search out a hospital or an imaging center that can do this. But I think most hospitals and imaging centers now have this capability. Yeah.

06:55
And so Matt, with the CCTA, it measures both non soft plaque and hard plaque and the hardening plaque? Yeah, so the CCTA or the noninvasive angiogram, coronary angiogram, can measure the all types of plaque. So the non calcified or the soft plaque and the calcified plaque. It can also measure

07:21
the percent blockage in the artery. So we can tell you not only do you have a lot of plaque, but it's causing a 30 to 40 % blockage in your left anterior descending. So it's much more informative. Is there a difference in terms of risk when it comes to the non calcified plaque and the calcified plaque? Yes, we think of the calcified plaque as the tip of the iceberg. We think of this as the

07:51
very top of the plaque burden and it's proportional. if you're having, if the Titanic saw a big ship, a big iceberg off its bow, it wouldn't send divers down below to say, I wonder if there's something that can rip the hull, it knew it was in trouble. And calcified plaque is like that. If you have a lot of calcified plaque that we can easily see, we know there must be a lot of other plaque below the surface. So I always advocate for

08:18
for asymptomatic people, for people who don't have known heart disease, to start with the calcium score. And if it's markedly abnormal, we can go to the CT angiogram, but you don't have to start with the more involved test. I think you can start with a simpler test. Yeah. Did your work in the sort of imaging, did that change how you felt about cholesterol and cardiovascular disease risk? Absolutely. I mean, when I first started, when we saw high cholesterol, we were like, wow, you need to be on medicine.

08:48
Now we recognize that about half the people who have really high cholesterols have no plaque at all in their arteries. Their arteries are fine and cholesterol is not going to affect them. They're in that group that doesn't have that need for treatment. And if we see people even with more modest cholesterol abnormalities who have plaque, we say, you know what, you need to be treated for that. Yeah. With the treatment, like obviously there's statin, which everyone is

09:18
sort of familiar with. Does that reverse plaque? Does it get rid of soft plaque? Like what does, how does it work? Yeah, so it converts the soft plaque actually somewhat to the calcified plaque. Calcified plaque is more like a scar tissue in the arteries and it's kind of a wall that we build up to protect the arteries. If you have a lot of it, it's bad because that means you have a lot of plaque in general. But what a statin does is it gets rid of the soft plaque, the lipid component, the fats.

09:47
And it replaces it to some extent with calcified plaque. So we can see regression or less plaque over time if we do the CT angiogram and see the soft plaque going away under the influence of a statin. Can you change the calcified plaque? Not much. We can slow it and stop it from going up, but we can't reverse it. So generally once it's there, we're stuck with it. And a lot of your recent work looks at sort of

10:17
lifestyle factors, particularly diet, and how these affect coronary health. And obviously, we're going to get to the lean mass hyper responders in a minute, which may be the group that you're talking about with the metabolic health outcomes are different from what you'd expect. What led you to study the effects of

10:38
the restriction and the ketogenic diet actually on LDL and atherosclerosis? You know, I was actually approached by a foundation, a research foundation, and they posed this question of could we use CT to look at the effects of a ketogenic diet on the plaque in the arteries. So my interest was actually born out of a research question.

11:05
And that's where I really got my start in this arena. Yeah. Which research foundation? So it's called the Citizen Science Foundation. It's a small research foundation. mostly do crowdfunding. they really wanted to see if this... And they had two people on both sides of the aisle who approached me. One was a believer that this high LDL induced from the ketogenic diet could be very harmful.

11:33
and another person who thought it was not going to be harmful and that it was going to be more of a neutral finding, just changing how we metabolize our fats and lipids. And when you were approached by, I guess, both sides of the aisle, did you have a particular leaning any way of the other? Like, what was your sort of knowledge on it prior to being approached? I mean, I have to say, I thought, you know, people come in with LDL cholesterols of

12:03
you know, 300, which is, you know, around six or higher millimoles per liter. I thought that that would be harmful. I thought that that would cause progression of atherosclerosis and be something that would need to be treated. If you wanted to maintain the ketogenic diet, you'd have to go on a statin or maybe even more to offset that increase in LDL cholesterol. Yeah, because the people in the particular study that you're talking about, like

12:32
What are the characteristics of those individuals outside of just, I guess, their high cholesterol and ketogenic diet? Like anything else? So the people who we were studying were actually called lean mass hyper responders. So they were very healthy people in general. They were thin. They had normal cholesterols before they started this ketogenic diet. And in response to the...

13:00
the begin being in ketosis, their LDLs and HDL cholesterol both went quite high and their triglycerides went quite low. So it wasn't a typical pattern of concern because low triglycerides means there's not a lot of metabolic dysfunction or or you know, pre diabetes type of problems and a high HDL generally is considered protective. So it was a very mixed picture from a normal

13:30
person who walks in with high cholesterol, where their LDL is high, their HDL or good cholesterol is low, and their triglycerides are very high. So they had a different pattern. Yeah. And with regards to the type of ketogenic diet, it like, these people, do these people sort of follow a classical ketogenic diet where it's super high fat, quite low protein, low carb, or are they on more of sort of

13:59
above 70 % fat, more of that modified ketogenic approach that we're seeing more sort of out in the wild. You know, I think there was a mix in the study we did. We didn't pre-specify the exact diet that they were on. They had to be in ketosis. They had to check for ketosis regularly. I would expect most of them were in the latter diet you described, the one that doesn't sound quite so harmful, you know, a very high fat diet.

14:27
But they definitely were, you know, basically zero carbs or as low as they could get to induce that ketosis. Yeah. And what kind of elevations would you like, were you seeing Matt? Like what was the average sort of cholesterol level of these people? Yeah. So they got up to on average about 280 milligrams per deciliter, which again, if my math is correct, is roughly in the sixth range for millimoles per liter.

14:56
For LDL? For LDL. Oh, wow. Yeah, because I think here it's sort three or below is considered sort of normal. So that's sort of double that sort of normal range. So their total would have been up eight or nine, I guess, maybe. Yeah, yeah. Their total would have been even higher, maybe even 10 on average. Literally, were way up, because their HDL cholesterol was elevated as well. So

15:24
Their totals were probably over 10 on average. Yeah. Were they particularly worried? Of the people that you worked with? I mean, so we are recruited from a pretty wide base of people who were in ketosis, who had this hyper response. I think they were a little, some of them were concerned. Some of them believed that the ketogenic diet benefits outweighed any of this LDL changes and that the LDL wasn't pathological or harmful.

15:54
Um, so I think we had a mix also there. Yeah. So, um, what did you find? What did you do? What did you measure the CCTA? Was that the only thing you sort of looked at? Yeah, we did a CCTA at baseline. We, we kept them on the diet for a year. We did a bunch of genetic tests and other values. Uh, and then we followed them over the course of, of a year and then did another CCTA in follow up to see what was their change.

16:24
in plaque over the course of 12 months. with the baseline levels, did you find anything alarming in this particular group or was it very similar to what you might find in any group that just had a normal cholesterol level? Yeah, you know, was actually fairly surprised. There was a fair number of people, about half, who had completely normal CCTAs. They had no plaque at all that I could see. So

16:52
So it was lower, was actually less than what I expected, especially given these market elevations in total cholesterol and LDL cholesterol that they came in with. And what was the average age-ish? I think it was probably in the 50 range. I'd have to look back to be honest, but I think it was around 50. Yeah. And what would you normally expect for someone like, I'm 47, like would I have, if I'm generally healthy endurance athlete?

17:22
type person? Is there a number that you would expect someone like me to have? I think you would probably be on average you'd probably have no plaque. Especially females tend to start having plaque a little bit later. But definitely with these LDL cholesterol, I would have expected a whole lot higher. I looked up the mean age, it was 55.

17:51
So it was quite high, quite moderate age group that should have had plaque and the mean plaque was the mean plaque or the median calcium score was zero. So more than half the patients had a score of zero in this baseline cohort. Is this male and female or just male? No, this is male and female. We had a mix of men and women, both of them, you know, obviously

18:20
Many people are interested in this keto diet and we had a pretty good mix of different ages and different sex in the population. 59 % were male, 41 % were female. So it wasn't too bad a distribution. Yeah. And then after a year, Matt, what was the result after a year? Yeah. So

18:47
After the first year, we saw some increases in plaque across the board, but when we looked carefully what was driving the plaque, it was just the patients who had plaque at baseline were progressing. It wasn't related to their LDL or total cholesterol. So the LDL, the high LDL was not driving the atherosclerosis. So we basically concluded that plaque begets plaque.

19:16
Yes, that's the most important thing. If you've got plaque, you're more likely to get plaque. Exactly. So, you know, so it's changed my approach to these patients because now I say, well, that's fine. If your LDL is very high and you have no plaque in your arteries, then carry on. And I'm not going to worry about that, that LDL cholesterol or that total cholesterol because you have no plaque and it's not going to build up. But if you have plaque,

19:41
we need to do something about this if you're going to maintain this keto diet and have a very high LDL cholesterol. Yeah. And at what point would someone consider going on a statin if they have like a CCTA score that was what, like what does constitute like necessary for, for medication? So yeah, normally, so we, if they have plaque in their arteries and they have a

20:10
you as you mentioned earlier, if they have a, above three millimoles of LDL cholesterol, we would generally say, you know, your LDL cholesterol is elevated, you have plaque in your arteries, and you should institute some form of treatment, usually a statin. yeah, okay. So, oh, it's super interesting. And is it hard for you to wrap your head around the idea that this isn't harmful? mean, I mean, how many years have you been

20:39
doing what you've been doing. Well, you know, I've been one of the observations that I made some time ago was that some patients with very high LDL cholesterol just have no plaque in their arteries. So I've kind of already was a little bit conditioned to the concept that maybe there's some decoupling of this LDL and atherosclerosis in everybody that that LDL by itself is not enough to cause

21:09
atherosclerosis. But if you have atherosclerosis, then LDL can be a feeder of that process. And that's why we treat people. Yeah. So Matt, what is it that drives up LDL in lean mass hyper responders? Because as I understand it, and what I've seen is that for some, when they go on a ketogenic diet, they're, you know, when it's all sort of, their health, the metabolic markers improve, so their cholesterol

21:39
improve. So what's driving this change in this group? Yeah, so there's some theories. I don't know if we have all the right answers. But somebody named Nick Norwitz, who's over at Harvard, has written some really interesting papers on this called the Lipid Energy Model. And I've co authored a couple of these with him. But the thought is, at least the leading hypothesis is, is that it's, it's the body is

22:09
is working so hard to change its metabolism from carbohydrates to fats that it just absorbs all of the fats and it causes the body to create more lipoprotein lipase which would then elevate your LDL and HDL and result in a lower triglyceride. the body

22:34
changes its metabolism in response to this absence of carbohydrates, because remember this only happens mostly in lean people. People who are very heavy, who go on the ketogenic diet lose weight, but their LDL doesn't tend to go up much because their body can keep feeding on carbohydrates, that you know, fats that are already existing in the body, but when the body's depleted of fat, and these are lean patients now,

23:03
the body needs to change its metabolism. So the theory is that it changes the metabolism of cholesterol so that triglycerides are available for the muscles and for everything else, and you end up with high LDL and HDL, good cholesterol, both go up, but the triglycerides get used up and end up low. So it looks like a healthier picture, even though that LDL cholesterol is high.

23:30
Yeah, because they're elevated in the bloodstream because it's a constant flux of the fatty acids being delivered to use for energy. Exactly. So it's just providing, I think, the body with the triglycerides and the other energy sources that it can use by metabolizing differently in the liver. It activates the liver to change its metabolism. Yeah.

23:59
Yeah. So you also looked at another paper, Matt, that I was like super interested in looking at younger individuals and so young adults that even if they had like a calcium artery score, I suppose at this time of zero, they had increased non calcified plaque. So you've got

24:27
young adults, and these are individuals that had other metabolic issues, and they had a progression, I suppose, of cardiovascular disease that didn't really, I don't know, like it's, it's, it is a different metabolic picture, isn't it? So young adults, yeah, body size, yeah. Absolutely. So the paper you were referring to is actually patients with, with early type two diabetes. So we're in type one and type two diabetes. These patients had diabetes, but because they were young,

24:57
they didn't develop any calcified plaque yet. And we know that that's a limitation of the coronary artery calcium score is that it tends to happen more in our middle ages, men in their 40s, women in their 50s, where we start to see significant increases in the calcification. So we looked at these people in their 30s and said, well, they don't have much calcium, there's hardly any, even though they have diabetes, but some of them, about a third,

25:25
had non-calcified or soft plaque that we can identify with the CT angio. So a caveat to what I said before, that asymptomatic or patients who are healthy should just get a calcium score. That's only true if you're looking at an older population and a young population, you have to do a CT angiogram if you wanna see the plaque. And is this then therefore standard of care for people who have diabetes to...

25:54
sort of get this level of risk assessment done? No, it's really not yet. It's something that I've been working for for a long time. It's starting to show up in some of the guidelines. But I think one of the things that we've seen routinely is that the patients do not, I mean, the guidelines just say, you know what, if you have diabetes, just go on all these treatments and don't worry about risk.

26:23
but I don't think that's correct. I think not all patients with diabetes have the same risk of heart disease. And some of them have clean coronaries and some of them have very diseased coronaries. And I think we need to take a look. Essentially more, I guess, understanding of, I guess, looking at overall risk picture for anyone. I mean, I guess this is a problem with testing, right? It's not cheap. Oh, absolutely. And I think, you know, as we learn more,

26:52
in patients with diabetes, we're going to be able to better target which one of them deserve more treatment overall. Matt, if someone is following a ketogenic diet, but they're not lean mass hyper responders, they actually do carry a of excess body fat, but their LDLs go up. Do we ever see that pattern? Do you know? I think there's definitely some people with some modest weight

27:21
issues that can have this hyper response to LDL, but most of the time it's largely seen in patients who are fairly lean, who don't have that obesity problem that would be treated differently by the metabolic processes in the body. okay. So in fact, if someone chooses to go on a ketogenic diet, they may have dyslipidemia to begin with, in addition to carrying excess body fat. That's where

27:51
metabolism can switch over and actually likely improve, it increases insulin and all that? Yeah, no, absolutely. We think that, you know, obviously it can induce a lot of, you know, nice findings overall, but I think one of the things you have to remember and what we found is some of the patients who came into our study at baseline had a huge plaque burden. So maybe the reason they went on the ketogenic diet was

28:21
because they had heart disease or they had a lot of risk factors for heart disease and they already had some underlying heart problems. So when I see a new patient who's one of these lean mass hyper responders, one of these thinner patients that have really high LDL cholesterol in response to the ketogenic diet, I get a CT angiogram to say, let's see what your underlying risk is to know

28:51
you know, is this something that we need to be more aggressive with? Or can we, can we just keep an eye on your, on your, on your profile and, let you enjoy the benefits, the health benefits of a ketogenic diet? Yeah, obvious. So the main time I think on the ketogenic diet in your study was just less than five years, like 4.7 years or something. Do you think that that's a long enough time period to understand overall risk or

29:18
Are these people likely, is it in their best interests to continue to get a test every couple of years or whatever just to assess? Yeah, no, it's a great question. And we had some people as long as about 12 years, but your point is a good one. Maybe it takes longer to develop this advanced atherosclerosis than 4.7 years. At follow-up, obviously, they were at 5.7 years when we did our second CT angiogram.

29:47
But we are trying to raise funds to do a three-year follow-up. So that would give us three more years. So that would give us almost a nine-year average duration. And I think that's a pretty good look at the process. Yeah, absolutely. Matt, I've seen the Lean Mass Hyper Responder cohort being described as athletes. Would you say that these people are athletes? What does that even mean? What is it?

30:16
Like, cause in my head, an essay to someone who, who does, spends a lot of time in physical activity, whereas I haven't actually seen good reports on what these people's physical activity is. Yeah. You know, to be honest, I don't know if we broke down. I'm sure we did collect data on physical activity. I, my, my, you know, from meeting a lot of these patients, they were very physically, you know, generally physically fit. don't know how we would classify them exactly athlete or non, but I think these are patients who came in.

30:47
thin, exercising, healthy looking, and then we would look into their heart and keep an eye on things. definitely, I'm sure their exercise on average was a lot better than our normal population because their body mass index was low and they looked very, very healthy. So I'm sure most of them were pretty good exercisers. Yeah.

31:14
Matt, do we know of any genetic predisposition that puts people that might shift them into the lean mass hyper responder category? What is the information there? Yeah, so we ruled out that they had a genetic predisposition to having high cholesterol or what we call familial hypercholesterolemia. We did genetic testing on everybody before they were allowed to be entered in the trial to make sure that they didn't have.

31:45
familial hypercholesterolemia. So we ruled out those patients where their LDL was high from birth or their LDL was high because of genetics. We haven't done a lot of fancy genetics to see do they have a certain gene that causes them to have this response. And while we were talking, I looked up their total cholesterol, it was around 10.

32:11
millimoles on average. That was their average total cholesterol when they came into the trial on the ketogenic diet. And I guess the thing with genetics is they're like, we know a lot about a lot of genes, but there's lots of people talk about how there's so much we don't know about genetics. Yeah, you know, we've, I'd say as a group failed in identifying the gene or the genes that are specifically responsible for heart disease so far.

32:40
A lot of money was spent, a lot is still being spent to try to investigate, to try to see if we can figure out the genetic profile of a person who develops heart disease. But we still don't have the genes like we do with some cancers where we know what gene it is that's causing them to have a predisposition for breast cancer or colon cancer or other diseases. How have your colleagues responded or

33:07
Have you talked to your colleagues much about the findings of this study and has it, have they come up with some, I don't know, hard questions or concerns or anything, or are they like, hey, who knew? This is good information. Yeah, so, know, when I first presented the baseline data showing that half the people had no plaque, it was actually quite...

33:32
interesting response from people in the audience. I presented it at one of the medical meetings and I got some pushback, I got some accolades. I think it was a little surprising to most, because when you look at these values, some people would describe them as scary, seven millimoles of LDL cholesterol coming out.

33:59
in that form, you know, for these patients. So I think I definitely got a mix where we're about to present the main data and it'll be interesting to see all of the response as we show our follow-up data to the world. Yeah. I mean, what kind of pushback would you get? Like, I mean, the numbers are the numbers.

34:24
Yeah, people thought, they're not on, like, as you raised this question, the duration of ketogenic diet isn't long enough there. You you didn't control them well enough. You know, I mean, there's all kinds of different things of people who are trying to hold on to this concept that every human being whose LDL cholesterol is elevated needs to be on treatment. And, you know, I was pushing back against that a little bit saying,

34:51
You know, the median score was zero. They're okay right now. They're doing okay. You know, we need to keep an eye on them. It's not a forever, but at the moment, more than half the people had no plaque at all. And I wouldn't treat patients with a drug to reduce plaque unless they had plaque. I don't use chemotherapy unless they have cancer. So I don't treat these patients unless I can identify a problem. Okay.

35:19
And then, so if you've got, because as I understand, like 50 % of people who have a heart attack have low LDL cholesterol. So they wouldn't, and that's, I don't know if general knowledge is quite the right term, but that's been well understood for, I think, a few decades. I'm sure I that in my nutrition school, but there are still people that sort of live and die by the idea that LDL is the thing that's driving heart disease.

35:49
Right, so LDL is the most treatable risk factor for sure. So once we identify heart disease, LDL cholesterol is a good treatment target, but LDL is not the best predictor of who's going to have heart disease. And my own theory is that you probably need a two-hit or three-hit hypothesis where you need more than one factor to cause heart disease.

36:17
Just cholesterol by itself is not enough. Just like smoking by itself, not everybody who smokes develops lung cancer. But clearly there's a portion of patients who do and it's devastating. So there's probably something else going on in those patients who smoked and developed, ended up developing lung cancer. Maybe they had a genetic predisposition, maybe they had another trigger. I think it's the same idea that you might need more than one trigger.

36:46
to go down that pathway of heart disease and cholesterol by itself may not be enough for most people. Yeah. Do you have an idea of other triggers? Like what is your, what are your thoughts around that? I I think it's largely probably some combination of genetics. I think it's also environment. think there are people who, you know, and other risk factors, right? Smoking, for example, diabetes. You know, there are other people who have

37:13
multiple reasons to get heart disease. It's not just a cholesterol. And I see this every day. When I take care of patients in the intensive care unit who just had a heart attack, they're like, I don't understand it. My cholesterol has always been good. I'm like, well, cholesterol is one risk factor out of many. And your family history and what happened to your dad or your mom, your blood pressure, your...

37:41
your smoking history, your diabetes could all play a role independent of your cholesterol. So it's not all about the cholesterol. But once we know you had a heart attack, we certainly want to get that cholesterol down. Yeah. And is that why cholesterol is pushed as low as possible because of that pre-existing sort of heart disease? Yeah. I I kind of think of it as whatever your cholesterol is when you have your heart attack, it was too high for you.

38:09
Your cholesterol was too high for your individual situation, regardless of all the other risk factors. And even if your cholesterol is low, I'm going to push it lower. Because obviously we don't want that to contribute to the furthering of your heart disease and have another heart attack or a stroke or something terrible. Yeah, no, absolutely. And then Matt, if I go back to the lean mass hyper responders, like I've seen information where just merely by increasing carbohydrate, even by

38:39
to 50 grams a day, think, so not a lot, can actually drop down that LDL. Like, is there a case for that here or actually, it really depends on the plaque burden that that individual has maybe? So I advocate for my patients who have a lot of plaque and are on the ketogenic diet who have this response, this lean mass hyper responder, if they have underlying plaque, I suggest to them that

39:08
they should probably moderate their diet a little bit and add in little bit of carbohydrates. Now some of the ketogenic people will say, that's absolutely terrible, you get out of ketosis and you lose all of the benefits of ketosis. In those cases, I say, okay, then I want you to treat your LDL cholesterol independently of this.

39:32
ketogenic diet because you have high cholesterol and you have heart disease, you have a positive CCT angiogram, and you need to be on something. So either one works. There was an interesting study, Nick Norwitz did a trial where he introduced Oreo cookies into his diet and his LDL cholesterol dropped dramatically. And obviously we're not advocating that Oreo cookies are good.

39:58
for lowering cholesterol in general, but it broke the ketosis and with carbohydrates and therefore his LDL cholesterol went back down to his baseline. yeah, which is, it seems really crazy that something so that it could be that simple. Like, a lot of people don't love statins and would prefer, I talk to a lot of people in there, they're almost scared to go on statins for the

40:27
perceived side effects or that they've heard of side effects. What are the options outside of statins for most people? Was it actually just a different type of statin or? No, so luckily today and a few years ago, I would have said you just have to take your chances and I believe strongly based on 30 years of statin use or 40 years now in the literature,

40:49
that it doesn't cause any long-term consequences that are bad. you can, your blood sugar can go up and you can get borderline diabetes, but we can either treat that or you can stop the statin and it goes away. It can affect your muscle, but if it does and we stop the statin, it goes away. So if you do get the side effect, we can just stop the medicine. There's no long-term harm. But there are people who will refuse to even try it.

41:16
We now have other therapies. We have these injectable therapies called PCSK9 inhibitors. They are very potent, more potent than statins at lowering LDL cholesterol. We have a new drug called Bempadoic Acid. It's only a couple of years old, but it lowers LDL cholesterol completely independent of statins. So we have some alternatives to statins for those people who need treatment.

41:46
Yeah, and are they readily available, Matt? Yeah, no, I think they're widely available. I think, you know, these newer ones that I mentioned are not yet generic, so they're probably a little more expensive or you need some type of coverage to get them. But they're definitely, you know, widespreadly available, at least here in the States. I can't speak locally, but I'm sure they're available worldwide. Yeah, nice one. So Matt.

42:14
Finishing up then, you mentioned that you're looking for a grant to do an extended follow-up on the lean mass hyper responders. Any other plans looking at that particular group and assessing other health outcomes or interventional studies or anything? Yeah, so we want to do a couple different studies. One, we want to do the three-year follow-up of these same patients to see what happens over time.

42:42
on the ketogenic diet and maybe some of them left the ketogenic diet and we can compare them to the people who maintain the ketogenic diet. And then we also want to do a matched study where we take half the patients on a ketogenic diet and half the patients on a different diet and compare what happens over time. Yeah, interesting. That's, mean, these are all, it's.

43:07
I think it's super interesting this whole area because it really sort of turns on its head what we think we understand about diet and risk and potential sort of health outcomes. I think it's great that the Citizen Science Research Group has been able to access the likes of you to do these studies to get it out there in a peer-reviewed way at least, because it brings a bit more concrete, I guess, analysis to the area. It's not just anecdotes.

43:37
No, absolutely. And I have to say it's been disappointing in this field that we haven't had a lot of good prospective trials comparing diets. And for whatever reason, and it's not just one group or another, there's just not a lot of studies, good studies on the effects of diet on the heart. And since the number one cause of death for men and women around the world is heart disease, we need to understand these better.

44:06
And I think that's why when I first presented this keto diet and this data, you know, on YouTube, it got over a million views, you know, and, and, you know, because it's just people are hungry for any information on diet and its effects. And we just have, we just don't have enough of that yet in the literature. Yeah, no, I completely appreciate. did working on this study and getting more involved in

44:34
knowing about the ketogenic diet, I'm not sure what your knowledge base was like earlier, but has it changed any of your personal habits? You know, I've definitely cut down on carbs. I find that if I eat too many carbs, I gain weight anyway. So to maintain my weight, I typically do a low carb diet. I have not gone to a ketogenic diet, to be honest. I enjoy meats and other, you know, but I do enjoy carbs to some degree and I'm not a...

45:02
ketogenic person myself. Yeah, yeah. And to be fair, think for the majority of people, the health benefits probably lie in that low carbohydrate sort of space anyway, you get, you know, not a balanced on a balanced diet, but at least you have a bit more balance in all the nutrients you're getting because you're not crowded out with all those carbohydrates. Yeah, I think so. I carbohydrates just kind of turn to fats and sugars and

45:29
They do all the bad things. They taste wonderful though. Yeah, totally. Matt, thank you so much for your time this morning. I really appreciate it because I know you're very busy. I'll pop the link to the YouTube that you're talking about in the show notes along, course, with the paper that you most recently published as well. But I really appreciate you taking the time. No, it's been a pleasure. Thank you so much for having me. Thank you.

46:08
Alrighty, hopefully you enjoyed that chat. And so it is really interesting as the science community continues to gather more information about heart disease risk, about the whole full picture. And it isn't always just about LDL cholesterol. And of course, you know, this is a, there was obviously that follow-up period, but it would be super interesting to know what things are gonna be like in 10 years time. But anyway.

46:35
So far so good and watch this space. Next week on the podcast guys, I speak to Dr. Christine Harton, all about sulforaphane. And this has become somewhat of an interest topic for me as I remind myself about the importance of this superstar of a plant chemical. So we discussed that. Before then though, you can touch base with me. I'm on Instagram, Threads and X @mikkiwilliden, Facebook @mikkiwillidenNutrition.

47:05
head to my website @,mikkiwilliden.com and book a call with me or do whatever you like over there. Join my recipe portal, sign up to one of my fat loss plans. I've got a lot of options. Alright team, you have the best week. See you later.