预防心脏病学家马修·布多夫（Matthew Budoff）博士，讨论了一项关于生酮饮食对心脏健康影响的研究。
马修·布多夫博士是加州大学洛杉矶分校（UCLA）医学院医学教授，也是加州托兰斯港口UCLA心脏病学项目主任。他是一位预防心脏病学家，专注于心脏健康研究。
讨论背景：胆固醇与心脏健康
在进入布多夫博士的研究之前先介绍与心脏健康相关的基本概念，特别是胆固醇：
LDL、VLDL和HDL的定义：
Apo B：
Apo B是测量所有“坏颗粒”（包括LDL、VLDL等）的更精确指标，比单独测量LDL更全面。尽管Apo B和LDL与心血管疾病风险相关，但这种关联较弱，不是主要风险标志物。
甘油三酯与HDL比率：
甘油三酯是炎症性脂肪颗粒，高水平不利于健康。HDL高表示代谢健康，通常见于经常锻炼的人。甘油三酯/HDL比率是代谢健康的重要指标：比率低（甘油三酯低、HDL高）表示健康；比率高（甘油三酯高、HDL低）表示代谢不健康。
心脏病风险与斑块：
动脉粥样硬化（斑块堆积）由多种因素引发，包括遗传、糖尿病、高血压等。胆固醇是斑块的主要成分，但高LDL不一定导致斑块，低LDL也不保证无斑块。布多夫强调，需通过CT钙化扫描直接检查动脉斑块，而非仅依赖LDL等生物标志物。
他汀类药物：
他汀类药物通过抑制肝脏胆固醇合成降低LDL，效率约为30-50%。还能减少炎症，逆转动脉斑块（经多项试验证实）。但布多夫指出，如果钙化扫描显示无斑块，即使LDL高，也不需立即使用他汀类药物，因为这是在“治疗数值”而非身体。
饮食与胆固醇：
饮食对血胆固醇的影响有限，仅占约15%。膳食胆固醇（如蛋黄）对血清胆固醇的提升作用微弱。碳水化合物和脂肪可能转化为甘油三酯和LDL，因此饮食质量（如减少加工食品、增加水果蔬菜）比单一营养素更重要。
生酮饮食简介
生酮饮食是一种极低碳水化合物、高脂肪饮食，迫使身体进入酮症状态，依靠酮体而非葡萄糖提供能量。主要用途包括：
瘦体超敏者（Lean Mass Hyperresponder，LMHR）
布多夫的研究聚焦于“瘦体超敏者”，这是一类特殊人群：
研究设计与方法
布多夫的研究旨在验证高LDL是否会导致瘦体超敏者动脉斑块增加。研究设计如下：
研究结果
讨论与批评
对普通人群的建议
布多夫为不同人群提供了心脏健康建议：
典型中年美国人（代谢不健康，如超重、糖尿病前期、高甘油三酯，可能有斑块但无心脏病史）：
健康个体（如精瘦且代谢健康）：
他汀类药物的使用：
布多夫的总体观点
结语
布多夫认为改研究为生酮饮食与心脏健康的关系提供了初步答案，但仍有许多问题待解。他鼓励40岁以上人群进行钙化扫描，以明确是否需要治疗，期待未来研究揭示更多关于饮食、药物和生活方式对心脏健康的影响。
Edit:2025.04.28
采访嘉宾：Matthew Budoff 博士
核心概念背景知识（为后续研究铺垫）
生酮饮食（Ketogenic Diet）与研究
总结与建议
Edit:2025.04.28
[Music]
[Music]
[Music]
Whether food, drugs or ideas, What you
consume influences who you become. On
the Mind and Matter podcast, we learn
together from the best scientists and
thinkers alive today about how your mind
body reacts to what you feed it. Before
starting Mind and Matter, I spent 10
years in academia doing scientific
research. I got a PhD in neuroscience
where I focused on neuroendocrinology
and the neurobiology of behavior. And
before that, I specialized in molecular,
developmental, and evolutionary
genetics. I use my scientific background
to help parse and translate the
information that guests share on the
podcast. In addition to the podcast, I
write long- form written content
inspired by the show where I integrate
what I've learned across episodes. I
also have a free weekly newsletter where
I provide you with upcoming guests,
share links, and provide commentary on
scientific studies and research that I'm
reading and more. Visit mind and
matter.substack.com to find all of my
content.
[Music]
All right, Dr. Matthew Budok, thank you
very much for joining me. Oh, it's a
pleasure. Thank you for having me on the
show. Do you want to just start off by
briefly telling everyone a little bit
about who you are and what your
background is? Yeah, I'm a preventive
cardiologist. I'm a professor of
medicine at the UCLA School of Medicine
here in Los Angeles, California. I'm the
program director for cardiology in
Harbor UCLA in Torrance, California.
Okay. So, you are a heart doctor. You
you know something about the heart. I
that's my been what I've been doing for
a while now. So, before we get to the
study that you just did, you're you're
part of this uh study looking at the
ketogenic diet, following people for a
year and looking at things related to
heart health. We're going to get to
that, but I want to give some people
some background and some basic concepts
to set up this study. Starting with
cholesterol. When people talk about
their cholesterol levels and getting
blood work done and thinking about heart
health, they're typically going to talk
about LDL, VLDL, and HDL. What are these
different things and and what is
cardiology
typically? What is the orthodox view in
cardiology for how we think about these
things in relation to heart health?
Yeah. I mean, so you know, typically,
uh, LDL cholesterol is our most
modifiable risk factor. So once it once
you have established heart disease or
plaque in the arteries, that's our
target for treatment. Not everybody with
high cholesterol gets heart disease and
some people with low cholesterol get
heart disease, but once we know you have
heart disease, we want to lower that
value because it's too high for you.
It's too high for that person if the if
they're if they have plaque in the
artery and their LDL is not ideal. I
see. So having high LDL does not
necessarily mean you're going to get
heart disease. But if you already have
plaque buildup or you're prone to heart
disease, then you your LDL can be too
high basically. Exactly. So it's more of
a treatment target than it is a risk
factor. And so when we talk about the
things that really cause heart disease,
when we talk about atherosclerosis and
plaques in our blood vessels, what where
are those plaques coming from? Do we
have a good sense of that? the, you
know, the view that you hear most often
is, oh, that's that's cholesterol. The
cholesterol builds up and and gums up
your gums up your arteries. Is that
what's actually happening? Well, there's
a lot of factors, though, because you
can have a genetic predisposition,
right? If your mom or dad have heart
disease, you're much more likely to be
um to be uh uh affected by heart
disease. Um uh diabetes can can cause
plaque to build up, high blood pressure.
So, so cholesterol is just one factor of
many, but it is the primary component of
the plaque itself. That's why we try to
treat if you have heart disease, we want
to get rid of that plaque, and that's
why we treat the LDL. So, but is is the
LDL is it forming the plaque? Is it
what's causing that or is it getting
there to help clean it up or something
like that? Because I've heard people say
both things.
Um
the so the plaque is
um uh made up of of cholesterol part of
it. Yeah, there's definitely a component
that's that's cholesterol. Um that that
but but again it people have very high
cholesterol. Some of them never develop
plaque in their arteries at all. So it's
not it's not always a onetoone
relationship. Okay. And so what would be
the difference between LDL and VLDLDL?
Um, so VLDLDL is is more fats. That's
the triglycerides. So that's a different
component. The first thing the body
makes is VLDL or very low density
lipoprotein that gets converted to LDL.
LDL is more of the cholesterol particle.
VLDL is more of the fat particle. And
then we've got HDL. How's that
different? HDL is um uh the good
cholesterol. So that's the highdensity
lipoprotein that takes the the
cholesterol from the periphery and
brings it back to the liver for
disposal. So it's kind of the reverse
cholesterol transport we call it. That's
the good stuff. Okay. Okay. And then the
other thing I want to uh cover off on is
apo B. So what is Apo B and how does
that tie into this? Um so APOB is uh a
more accurate measure of all of the bad
particles. So that's includes LDL,
VLDLDL and other particles that are
missed in that in that measurement. So
APOB is another AC more accurate way of
measuring all of the bad particles in
the bloodstream beyond just LDL. Yeah.
And so I would imagine LDL and APOB
correlate with cardiovascular disease
risk. People who get cardiovascular
disease tend to have higher levels of
both of these things. Is that that's
generally true? Yes. But the
relationship is very weak and uh we
don't usually again think very strongly
that that that's our primary risk
factor. So it's it's not a good marker
of risk. It's it's just not it's not a
strong marker. It's a very big
misconception among a lot of people. I
see. I see. Okay. And then I want to
talk about triglycerides a little bit.
So for example, your liver can make
triglycerides and we can talk about what
that is. A common marker that I hear
people refer to in terms of being uh one
way to gauge metabolic health is the
triglyceride to HDL ratio. So what is
that and what does it actually tell us
about overall metabolic health? So yeah,
triglycerides are are bad particles. Uh
they're they're inflammatory. They're
they're the fats. So it's kind of like
the the the bad particles, the fat
particles divided by the good particles,
the the HDL. So if your HDL, your good
cholesterol is high, that's good for
metabolic health. People who exercise a
lot, have good met good health overall
have good HDL. And triglycerides are the
fats and the inflammatory markers. And
if those are high and your HDL is low,
your ratio is very high. So that's kind
of a a bad over relationship. And the
more the bad is or the lower the good
is, the worse those numbers become. I
see. So, so if your triglycerides are if
you're relatively healthy, you're
metabolically healthy and fit, your
triglycerides will tend to be low. Your
HDL will tend to be higher. The
triglyceride HDL ratio will be low. And
we tend to think of that as a good
thing. And then if you're unhealthy, we
see the opposite relationship. That
number goes up. Now, traditionally, I
would assume, you know, based on sort of
the the traditional cardiology uh
beliefs that are out there that are
around how cardiovascular dise disease
starts. If someone is healthy, then you
would expect their triglyceride HDL to
be low and you would also expect their
LDL to be low. But I think what you're
going to tell us is there's actually
cases where people are metabolically
healthy even though their LDL is quite
high.
Yes.
And so when when so sort of in the
classic cardiology literature looking at
atherosclerosis the relationship between
these cholesterol and triglyceride
markers and heart
disease do when when people study these
associations and they find that there's
a statistically significant but you said
weak link say between or weak
association between LDL apop and
cardiovascular disease are is that
literature mostly looking at people in
general. Is it mostly looking at people
that already have issues like high blood
pressure and and plaque buildup or is it
looking at healthy people and sorting,
you know, sorting these different groups
out from each other?
So, yeah, I mean, whenever you look at a
population of people, it's not not
everybody conforms to that. So, we talk
about population-based medicine where we
kind of look at risk factors in general
or we look at individuals and and it
doesn't always correlate. For example,
some people with diabetes don't get
heart disease, but a lot do. So, we
think diabetes is a risk factor, but in
a given individual, they can have raging
diabetes and their coronaries are
completely clear. So, we always have to
look beyond the risk factors to the
individual. And that's why we do the CT
scans and the plaque assessment to see
what's going on in the arteries, not
just what should be going on in the
arteries. Mhm. So based on what you've
told me so far, it sounds like, you
know, as a cardiologist, if someone was
old enough, whatever that means, in
their middle age, and they want to get
an assessment of their heart and
cardiovascular health, it sounds like
you can't solely rely on biomarkers like
LDL and APO B. What would be like the
number one or top couple things you
would do to assess someone, say, who's
middle-aged in terms of what their
plaque buildup looks like or what their
overall cardiovascular disease risk
actually is? Yeah. So, I I recommend and
so does the American Heart Association
and the American College of Cardiology
to do what's called a calcium scan to do
a a simple scan of the heart. It's done
with a CT scanner. It's very, very easy
to do. It just takes a couple minutes
and it looks for plaque buildup in the
arteries. And if you're one of those
people that have a lot of plaque,
regardless of your LDL, we've got to get
on top of that. And if you're somebody
who has a high LDL and a lot of bad
cholesterol and your coronaries are
completely clear, we say don't you don't
need to treat it for the next 5 years.
Those are the guidelines. H So that's
that's interesting. So someone in my
family uh who's you know approaching 60
um recently came back and and they were
talking to me and and their doctor said,
“Your LDL's too high. We need to get you
on a statin right now.” And I asked her,
“What does your what does your calcium
scan look like? what do your arteries
look like? And she said, I've never
gotten one. And I said, never, not since
you were 40. Does that surprise you? And
would you, as a cardiologist, would you
put someone on a statin not having
looked at that type of scan? I I mean,
unfortunately, uh there's still a lot of
doctors who just go with the val numbers
and say, “Oh, your LDL is high. Let's
put you on a cholesterol medicine.” And
that's never been the guidelines,
actually. But but that's just a not
natural reflex is that your cholesterol
is high. Let's let's just lower it. But
again, if you have no plaque, you're
you're not treating you're treating a
number. You're not treating your body,
and you're taking a drug that you don't
need. So, I'm not surprised, but it's
unfortunate that we haven't moved beyond
that. And so, give us a very quick
rundown how how statins actually work.
They're used to lower LDL, but what are
they what are they actually doing, and
how how effective are they really? Yeah.
So statins lower LDL by by blocking
production of cholesterol in your in
your in your liver. So that's where we
make all of our cholesterol is in our
liver. We we absorb about
15% of our cholesterol in our diet and
about 85% is made in the liver. So the
vast vast majority um uh would be in the
liver. Um and statins block that uh
absorption. So that's really how they
work and and it's very they're very
effective. They lower cholesterol by
about 30 to 50%. So they cut that LDL
cholesterol in half in many patients. Um
and that that's a we think that's a good
thing if they have plaque and we're
trying to treat the plaque because the
minute the cholesterol drops by
50%. The liver is like saying, “Hey, I
want more cholesterol.” And it starts to
look for for cholesterol from the
bloodstream and it pulls it out of the
bloodstream. So that's where the reverse
cholesterol transport comes in. So so
the response to a statin is to lower LDL
cholesterol by about half. Um if you use
a high high intensity statin, they also
lower inflammation and they also reverse
plaque in the arteries. We know that
we've seen that happen in multiple
trials now where the arteries look
better after one to two years of being
on a statin. They have less plaque in
them. Mhm. So it it sounds like your
basic approach as a cardiologist is if
someone has plaque buildup as shown by
one of these calcium scans and their LDL
is high, then you will likely put them
on a statin to lower those LDL numbers
and hopefully reverse some of that
plaque buildup. But if their SC if their
calcium scan comes back clear and
there's no plaque buildup, even though
their LDL is quote unquote high, you
probably would not put them on a statin
in that case.
Yes, that's correct.
and and so how else can we um change LDL
levels in the body from a dietary
perspective? Um my understanding is that
for example polyunsaturated fatty acids
will tend to uh be associated if you
boost the intake of those that will tend
to lower LDL. Is that true? And and is
that the or or are there other dietary
ways to to change LDL levels?
There are dietary ways, but um the
problem with diet is that it only
controls about 15% of the cholesterol on
average. So,
um even if you went from a relatively
poor diet to an exceptional diet, your
LDL is only going down by about 15%.
Mhm. And so, related to that, what about
dietary cholesterol? a very very
widespread belief out there is that if
you start eating more cholesterol or
foods with high cholesterol levels that
will significantly boost your blood
cholesterol levels. What's the
relationship between dietary cholesterol
intake and the actual serum cholesterol
that would be measured inside of a
person's blood? Yeah, it's a it's a weak
relationship. There is definitely some
some increase, but it's pretty very
modest since cholesterol dietary
cholesterol only only accounts for 15%
of your total cholesterol. dietary
cholesterol accounts for a very small
percentage and triglycerides, fats,
carbohydrates that you eat can convert
into fats and and LDL cholesterol
ultimately. So, it's it's the
carbohydrates are are bad and bad
players and cholesterol itself may not
be the primary problem uh when we talk
about dietary intake of of of nutrients
and what that converts to. Mhm. And so,
you know, starting to think ahead to
this study here. So, when we think about
the carbohydrate and the fat content of
diet, obviously both can be high or low.
You could have a high carb diet that's
low fat or vice versa or it could be
high in both. What are when we when you
think about the the fat and the
carbohydrate content of diet, how does
that start to play into things like
cholesterol levels and how does
something like the ketogenic diet look
different from a cholesterol perspective
from a standard American diet?
So, uh, so, so, so your German, so
ketogenic versus standard.
I'm sorry. Is that the Yeah. Yeah. just
how how does how does the macron let's
just start here. How does the
macronutrient composition with respect
to fat and carbohydrates tend to relate
to things like LDL and blood cholesterol
levels? Yeah. So I mean in general um
your cholesterol intake, your uh fat
intake, um carbohydrate intake can all
slightly affect your blood cholesterol
levels. There's not a very strong
relationship in most people. Um, so if
you eat a lot of lean meats, you might
not have any increase in your
cholesterol. If you eat a lot of
carbohydrates, uh, if you go if you're a
vegan and you eat a lot of French fries,
your cholesterol is going to go up
significantly. So, there's no one diet
that's protective um, uh, towards
cholesterol. Um, there it's just a
different response in different people.
It's based on volume and and your
underlying metabolic health. So, there's
a lot of factors that go into a response
from any given diet. Generally, we think
of a lean, healthy diet being something
that's higher in in uh fruits and
vegetables and and lower in in processed
foods. Um, but but really a lot of it
has to do with the volume of food and
the carbohydrate content of food. And
so, what is a ketogenic diet and what
does that look like? Yeah. Yeah. So
ketogenic diet is one in which um the
body is uh basically starved of
carbohydrates. So it becomes ketoic. It
become goes into a a process of of uh
developing energy through what's called
ketone bodies um um to deliver energy to
the cells because there's not a lot of
carbohydrates floating around.
Carbohydrates are usually our primary
fuel. And when you when you have a keto
diet and you have no no carbs um or very
low carbs, you have to find an
alternative energy source for the body.
I see. So in essence, when someone's in
ketosis from a ketogenic diet or from
fasting, they are using fats as opposed
to carbohydrates for energy. So instead
of using glucose to generate the energy
currents of the cells, they're using
these things called ketone bodies. Yes.
And if you get too many of them, you get
ketosis. you get you get measurable
ketone bodies in the urine and in the
blood. And so what are you know the
ketogenic diet has become more common um
in recent history. People are talking
about it more. What are some of the
things that the ketogenic ketogenic diet
is being used for or studied for in
terms of therapeutic and the health side
of this? You know, what types of people
are are looking at the ketogenic diet?
Well, I mean, so yeah, it's it's it's
definitely associated with weight loss.
It's actually a fairly significant way
to lose weight because the low carb uh
low carbs means low calories and and if
you're taking in less calories, you're
going to lose weight. Your body also
shifts to this burning of fats, which is
also good for weight loss. So, so it's a
very dramatic way for some people to
lose weight in the short run. Um um but
but we've seen it for patients with
diabetes um to help uh their blood sugar
control because carbohydrate
carbohydrates become sugar in the
bloodstream. So that that's good for
patients with diabetes both type 1 and
type two diabetes. And it's also been uh
used for things like seizures. Um uh
there's the epilepsy society and
epilepsy foundation have advocated um uh
as an effective way to manage epilepsy.
Um and there's a host of other purported
benefits um in different people have
used it for for gastrointestinal
disorders for for you know problems of
their gut um and and a host of other
other uses that have been purported. I'm
I'm not a I'm not a an expert on the
keto diet to be honest. I I did a
research study on it, but but I know
it's it's used for a fair number of
different people across different uh
aspects of of healthcare. Yeah. Yeah.
So, this ketogenic diet, it's it's being
looked at and used in a variety for a
variety of purposes now, ranging from
something like something very, let's
just call it physical like weight loss,
shedding body fat, but also things like
like mental health and and even things
like epilepsy. That's the sort of
classic first thing I think it was known
for. So before we get to your study, the
one that you just published, um I want
to cover off on a couple more things.
What So there's something called the
lean mass hyperresponder phenotype, and
this is going to tie into how being in
ketosis relates to things like LDL
levels. What is this phenotype, and what
do we actually know about it to set up
the study?
Um, so, um, the so the the the lean mass
hyperresponders is a a group of people
who start out without a lot of body fat.
So, they're they're healthy, they're
lean, um, and for some of them, when you
go on the keto diet, for whatever
reasons that they might choose to do
that, their body um, makes more LDL
cholesterol. So they're called hyper
respponders where their LDL cholesterol
goes up dramatically. It could go up
from from normal values 70 80 milligrams
per deciliter up into the high hundreds.
I've I've heard of people going up to a
thousand LDL cholesterol in response to
this diet. So they're their metabolism
shifts. They're they're probably using
LDL to try to deliver energy because
they don't have a lot of fats. they
don't have a lot of triglycerides and
their LDL particles go up dramatically
and they have a this this hyper
respponse to cholesterol.
Okay. So, so these are lean
metabolically healthy people. So, if you
were to do look at their blood work,
they would have say a low triglyceride
HDL ratio. So, they're they've got
enough HDL. Their triglycerides are low.
That's good. Um but they have very high
LDL numbers even though uh they have
very high LDL numbers on this highfat
low carb diet. even though they are
lean, metabolically healthy and don't
appear to be predisposed to say heart
issues or something like that.
Right. Correct. Okay. So now the
question I guess the question here
naturally is if they look otherwise
healthy but they've got very high LDL
levels which are classically known as
your bad cholesterol. The question is
are they actually at risk? Is this LDL
is this high LDL level actually bad? Um,
so what's been the thinking there going
into your study? And and what are the
sort of different ways that that
cardiologists and people in these fields
would would think about this in terms of
whether or not it's actually going to
turn out to be good or bad for these
lean people. Yeah. You know, and I think
just out of the box people reflex says,
“Oh, if your LDL goes that high, that's
terrible. We have to do something about
it. You're you're at high risk because
your LDL cholesterol is so high.” Um um
and people have said you have to stop
the diet. you have to change your
lifestyle, you have to get on a statin.
Um, there are other people who believe
that because it's just a physiological
response to energy transfer um and these
people are otherwise metabolically very
healthy that it would not be a
significant problem um um and therefore
um would be okay, if you will, to um to
to go through the to to have that high
in LDL cholesterol as long as you're
otherwise healthy. Mhm. So, so what I'm
hearing is, so if the first viewpoint is
correct and having those high LDL levels
is bad, even though these people are
lean and metabolically healthy and
otherwise look good, the prediction
would be that having those sky-high LDL
levels for an extended period of time is
going to cause more plaque buildup. So,
we should see these people build up more
and more arterial plaque given that
their LDL is that high. The alternative
viewpoint or and a different way of
looking at this is that these people are
lean and metabolically healthy. their
body is using more fat for energy as
opposed to carbohydrate. And so the high
LDL is not a reflection of something bad
happening and plaque's going to build
up. It's a reflection of their body
moving around fat to use for energy
basically. Correct. Okay. And so um set
up this study for us a little bit. Um I
think we've we've essentially covered
off on some of the motivation here. What
what what did you do in terms of the
basic setup and methods of this study?
Yes. So we were very careful in our
patient selection. Uh we actually
screened a lot of people to find these
people who were one in ketosis from the
ketogenic diet. So we had to prove that
they were effectively in the keto
ketosis state where ketone bodies
measurable in
their in their blood. Two, they had to
have an LDL well above normal. Um and
three, they had to have a normal LDL
prior to starting the keto diet. So we
excluded patients genetically as well
who could have had um um what we call
hetererozygous FH or or high cholesterol
from a genetic predisposition. So these
were patients who had normal
cholesterol. They had no issues with LDL
cholesterol. It was very normal and then
they went on this diet and it went up
dramatically and those are the people
who we enrolled in the trial. I see. So
you specifically wanted to look at
people that did not have some genetic
predisposition to very high LDL
cholesterol. wanted this to you wanted
their LDL to be high because it was
induced by being in a ketogenic diet
state by being in ketosis. They were
lean and metabolically healthy. So these
are not obese people. They've got good
meaning lower triglyceride numbers.
They've got higher HDL numbers. Um and
you know they've got various other
markers indicating that they are not in
chronic inflammation that they're
metabolically healthy. So these are your
the your lean mass metabolically healthy
people and they've got very high LDL
because they're on a ketogenic diet
specifically. Exactly. Exactly. Okay.
And how many how many people did you
look at and what was how did they
reflect the general population in terms
of say their demographic features or
anything else that one might care about
when we start to think about whether
these results will generalize.
Yes. So we enrolled a hundred of these
participants uh scanned them at baseline
using the CT angagram. So that's an
advanced metric of plaque assessment. We
looked at um quantitative plaque in the
coronary arteries. Uh how much plaque is
present, soft plaque, hard plaque, all
the different plaque components. We
followed them for a year. They had to
stay in ketosis. We had we monitored
them. They had to be remaining on the
keto diet. And at the end of one year,
we scan them again to look at the change
in plaque over the course of a one-year
time point. Mhm. And um so did you
remind me, how did you guys confirm that
they were in ketosis the entire time?
And what kind of tracking did you do for
their diet in terms of knowing exactly
what they were eating and what the fat
content was? Yes. So they had to do uh
um regular finger sticks to prove that
they were in ketosis. Um we uh also
measured their LDL and advanced lipids
at baseline and at followup. Um so we
had a a monitoring home monitoring uh
during the year and then we had formal
testing of both ketones and LDL at
baseline and followup um uh in the
trial. So these people are they're
bonafide ketosis. You're you're checking
that you're checking ketone body levels
um and you're measuring uh these lipids
and other things. Before we get into the
results, one more question I have um is
there's not just one way to be in
ketosis, right? Anyone so so all of
these people could be having very very
little to no carbohydrate intake, but
their fat intake could still while it's
high across all of them, it could still
differ a lot from person to person. Some
might be having more saturated fats,
some a lot of polyunsaturated fats and
everything in between. Did you look at
the fatty acid composition of their diet
and how that varied at all?
We we have not we have not we we have
the blood work. We haven't delved a lot
into how they got to ketosis and there
are a variety of ways in a variety of
diets. So, and because it's only 100
people, we're a little bit nervous about
trying to subset it too many times
because it's not a huge cohort. So, you
know, you don't want to do too many what
we call subgroup analyses when you have
a smaller cohort to that you're playing
with. Okay. So maybe maybe a question
for another day or something to keep in
mind for people interested in this stuff
is you know something something I'm very
interested in is you know what happens
if you have a high saturated fat
ketogenic diet versus a high mono or
poly and or polyunsaturated fat
ketogenic diet. We don't know the answer
to that yet and you guys weren't really
in a good position to look at that
specifically here, but you know that
these people are in ketosis because
you're confirming that you're following
them for a year and you've got a hundred
of them and as we said they've got high
LDL because they're on this diet, but
everything else pretty much looks good.
They're lean, they're metabolically
healthy, they're not inflamed. What were
the key things that you measured in
terms of outcomes here and and what were
some of the basic results you found?
Yeah, so the the primary measurement was
change in plaque volume over time. So we
looked at did they build up a lot of
atherosclerosis over the course of a
year. Um and uh we first compared them
to a control group which was a
population-based group of patients uh
from what's called the Miami heart study
who also had quantitative plaque
assessment uh at baseline and they had
very similar plaque components at
baseline. So at least going into the
trial they didn't have a lot of plaque.
They they um even though they were on
keto for on average about four years,
some of them for as long as eight years,
they didn't have a lot of plaque in
their arteries when we first did the
intake. And over the course of a year,
there was some plaque progression. Now,
um we saw um an average plaque
progression that was probably in range
with other studies. So, it didn't look
like they were fueled to go to have very
rapid plaque progression. uh we saw kind
of a more of a modest plaque
progression. And when we looked at the
relationship of what caused the plaque
to to go up, it was not the LDL or the
apo. It was the um it was the um
underlying plaque. So if they had a lot
of plaque at baseline, they got more
plaque over time, which might be
somewhat of an obvious finding, but it
really I think the interesting finding
here was that there was no relationship
between the height or the peak of the
LDL cholesterol that they achieved and
their rates of plaque progression. So
some people with crazy high LDLs had no
plaque progression and other people with
more moderate LDL elevations did have
plaque progression. And and so that is
surprise that would be surprising to a
lot of people, right? So we we sort of
said before that one school of thought
was basically that okay if you raise
your LDL and your Apo B goes up, these
things will be part of the causal chain
that leads to plaque buildup that leads
to heart disease. So the expectation
from that viewpoint would have been if
your LDL is high, your AP is high, those
people specifically should see the most
plaque buildup. But you're saying you
did not see that relationship. Exactly.
Exactly. Yeah. and and therefore, you
know, we we had we always had this at
least uh hypothesis that it wouldn't
just be purely driven by LDL cholesterol
in a metabolically healthy person. So,
in a person whose underlying health is
good, LDL by itself may not be the only
thing that that were the the primary
driver of whether or not they get more
atherosclerosis.
Talk a little bit more about the patient
population, how you recruited them. So
obviously they're lean and metabolically
healthy because you specifically
selected for that. They're also on a
ketogenic diet. Obviously I'm I'm
imagining that, you know, is there any
sense here that these people are a
they're very health-minded people, b
they're interested in sort of trying new
things and new diets, that's why they're
on the ketogenic diet. Are they, you
know, what are all the ways that they
they're deviating from say the the
average American? And is are there any
potential confounds here with respect to
who is actually in the study?
Yeah, I mean, you know, so we we had a
pretty good variety of people from
across the United States. They actually
the the study paid for them to fly in to
get their scans. Uh uh um you know, so I
think that that it was a fairly diverse
population um uh both for age and uh
pretty good uniform across, you know,
sex and and age distributions that we
saw pretty wide variety of patients.
Again, it was only 100 people, so we can
only subgroup it so much. But I do think
that that it was a fairly good
representation of these so-called lean
mass hyperresponders that we did enroll.
And and talk a little bit about the age
distribution. Are these mostly
middle-aged people? What What did the
age dist distribution look like? Yeah.
So, you know, we did have a nice uh uh
spread in age. Um uh I think the uh I'll
have to look back. I think the youngest
person in the trial um was in their 30s.
Um and the uh and the the spread in the
age was actually quite nice. Uh the mean
age was 55, but we did have a pretty
good range of ages in the trial. So um
so it was middle-aged, but there was a
spread of younger and older people also
enrolled in the study. We didn't we
didn't just limit it to people in their
50s, for example. Mhm. And so based on
just your experience as a cardiologist
and what's out there in the literature
and has been out there for a long time,
if you were to just take random people
from the US population, say rand totally
random sample of people and you were to
follow them for one year, regardless of
if they were healthy, unhealthy,
ketogenic diet, any, you know, just
random people, would you tend on average
to see a little bit of plaque buildup
year by year simply as a a matter of
age? For sure. For sure. Yeah. Age is a
major driver because whatever your risk
factors are, they've been affecting your
arteries for yet another year and
another year and another year. So the
older you are, the more plaque people
tend to have. But again, we see 80 year
olds with clean coronaries and I see 30
year olds that look quite ill. So it's
not it's not always a very linear
response. And what are the, you know,
are there clear-cut things that explain
the the two ends of that spectrum there?
When you see someone who's pretty young
and they've got really badl looking
arteries when you do these scans, what
are the things that associate with that?
And then, you know, the opposite, the
some someone who who goes to advanced
age and still has really clear vascule.
Yeah. I mean, I think that's always been
a a very interesting question and and
why some people get spared. And
obviously, there are some things we
still don't understand. For example,
genetics. We don't even know the genes
that drive atherosclerosis yet. We've
been looking for a long time and can't
find like the one seinal gene. It's
probably a host of multiple genes. But
some people just might have better
genetic makeup and be more immune to
atherosclerosis or immune to high LDL
cholesterol whereas other people may be
very susceptible to it. Um uh and that's
why we really have to look into the
arteries and to do those heart scans to
say are you being affected by these
values and if the answer is yes we have
good treatments to to then delve into.
And so what um for you what would you
say sort of the the major takeaway of
the study is? And then you know people
have been talking about the study quite
a bit. It's starting to get a lot of
attention. So, what's the main takeaway
and conclusion for you personally? And
then what are some of the best
fair-minded criticisms or questions that
you've seen come up around how the study
was done?
Yes. So, you know, I mean, uh, as far
as, you know, uh, I mean, obviously, it
would have been nice to have a control
group where we had a group of people who
are matched exactly who underwent the
same two scans, uh, but were not ketoic,
right? who were not in this keto not on
a ketogenic diet but we just this was
funded by a foundation. Um so this was
you know kind of group funding and we
just did not have resources to do a
larger you know scale trial. We are
going longer. We are we are going to
follow these people out further. This
was the first year. Um, and we are going
to uh uh hopefully get uh these patients
back in to get a third scan over some
interim time period so we can see what
the long-term changes are on this on
these plaque results. Uh but but I I do
think it was, you know, an interesting
finding that that that this really high
LDL, this this some people would say
even call it a scary high LDL, um did
not directly impact the the uh coronary
arteries um uh uh directly. It wasn't it
wasn't based on that elevation in LDL
did was the was the reason or the or the
direct relationship with having more
plaque at the end of the trial. Yeah.
And so, so you guys are doing longer
term studies. I would imagine that
there's probably quite a few people out
there of the mindset that okay, you only
that this is great, but you only follow
them for a year. If if you do 5 years,
10 years, and so forth, then their LDL
will become predictive of plaque
buildup. And is that is that what some
people are saying? And is that what you
guys are basically going to look at
eventually? Yeah. Yeah. And our goal was
always to to to try to come up with more
funding and do a further longer term
followup at 5 years to see what the
five-year changes are over time. Um, and
we are um I'm pretty confident bringing
back these patients in the short run um
a shorter run than 5 years to see a
third point in time to see what's been
going on um um as this gets further out.
So um stepping back for a second. So, I
am 37. I'm approaching 38. I've never
had my my arteries looked at. I've never
had a plaque scan or anything like that.
Is that something that you would
generally recommend? So, I'm I'm lean.
I'm metabolically healthy. Um, you know,
and all that stuff. Is that something I
should start thinking about at my age
slash, you know, at what age would you
start recommending people get regular
scans to look at the the potential
plaque buildup in their vessels? Yeah, I
mean, generally we talk about men
roughly age 40 and older. So that's
usually the age of atherosclerosis.
Women 45 to 50, they tend to get heart
disease a little bit later. Uh maybe
around the time of menopause, women
should start thinking more about their
heart and you know obviously focus on
that as their primary cause of of harm
there. Uh you know uh a lot of women
focus on breast cancer. Uh but after
menopause 10 to one they will die of
heart disease and not breast cancer. 10
10 to one. So I think you know at at
menopause I try to convince women to uh
around that time to get their heart
scan. Men in their 40s or early 40s
usually depending on risk factors and
how healthy they are they can wait a
little while they can get it a little
bit earlier but roughly 40 is a good age
for for for men. And you said that's
that's an easy scan to do. Is that
something that people can or should
proactively ask their physicians about?
Yeah. Yeah. uh should be widely
available now in the US and some
insurance just cover it. If not, it's
usually like a $99 or $100 test. It's
usually not an expensive medical test to
get the heart scan done. Okay. So, so
basically after roughly the age 40,
there's there's no reason not to do it.
It's not prohibitive. Your doctor
shouldn't say no. There's no reason not
to do it. And it's it's only about a
hundred bucks. Correct. Okay. Okay.
What? So, so in your how did you sort of
get into uh uh this group to do this
study? What was making you think about
the ketogenic diet? And you know, did
you is this something that that you
started getting interested in recently
or have you had these ideas for a while?
Um you know, like how did you get in as
a cardiologist? How did you move into
the realm of looking at the ketogenic
diet which in some ways it's sort of a
very it's a new and uh um not exactly
mainstream thing to look at within
cardiology.
Yeah. No, I mean I was approached by
this uh foundation and asked if I would
um do a study if uh in this population
and we helped design the study and I'm I
I was you know I I was really agnostic
on what what it would show. I didn't I
I'm not I'm not a keto ketogenic diet
expert, but um I I you know I read the
literature and it seemed like there was
a a fair chance that it it would that
these lean mass hyperresponders because
they're un overwhelmingly so healthy
otherwise that they may not have a lot
of heart disease and conversely you know
this high LDL may be driving cholesterol
into the arteries and causing problems.
So I thought it'd be a good question to
answer. So, I thought it was uh
appropriate to answer it whenever we
have that that uh equivocal, you know,
uh information. It's healthy to do a
research study and try to answer some of
those questions. And I think we answered
at least a little bit of the questions
that are being raised and there's more
there's a lot more to be done.
Okay. So, so you didn't really have
strong expectations as to what the
result would be. Um but you were
surprised uh to some extent by by what
was found. Yeah. Yeah, I mean I have to
say even at the baseline scans when I
was taking these patients with LDLs of
400 and 500 milligrams per deciliter and
doing scans on them and seeing clean
coronaries, I was quite surprised. Uh to
be honest, I thought that they would
have much more advanced heart disease
even over the four to five years that
they've been on the keto diet. Um and
again, these patients were in their 50s,
so it wasn't like they were young kids
that we were studying. We were studying
middle-aged people who should have some
plaque. And then you would think if you
fed that plaque aggressively that they
would have a lot of plaque, but clearly
they did not. Um at least at our
baseline study. Yeah. Okay. So these
were people many of them were
middle-aged as we said. Um many of them
so even though you this is a one-year
study were for what you guys did in this
particular paper most or many of these
people had already been on a ketogenic
diet for several years. Yeah. The
average I think was about four and a
half years coming into the study. Mhm.
And what were some of like do you guys
know like what were some of the reasons
that these people got on a ketogenic
diet ketogenic diet to begin with? Were
many of them overweight and obese and
then became lean or were most of them
already healthy the whole time? I I
think my understanding is and I didn't
interview all of them but a lot of these
people were were healthy people who
turned to the keto diet for maintenance
of their health. Um um there were some
that had other medical problems. Um but
if they had diabetes, if they had other
medical problems, they were not allowed
in the trial. We were looking for lean
healthy people who were having this
hyper response because those other
people typically the LDL actually goes
down. If you read about the ketogenic
diet when you lose weight, your and your
blood sugar gets better, your LDL
cholesterol should come down to some
degree. It's actually a way to control
your cholesterol. So, we're talking
about these outliers that have this
remarkable response uh this almost
paradoxical response to their their diet
where their LDL cholesterol goes up
really high. Yeah. So, so it really is a
lean mass hyperponder phenotype spec
like it it it truly is these lean
metabolically healthy people that see
these high LDL levels on a ketogenic
diet. What you're saying is actually
people who don't fit the mold there,
people who are overweight or otherwise
unhealthy, they will often actually see
the opposite. Their LDLs may actually
come down on a ketogenic diet. In most
people, it comes down. Uh so again,
these are the these are
the the less common uh denominator of of
these lean mass hyper respponders is is
the less common response to this diet.
Mhm. So, so given your background as a
cardiologist and you know a variety of
the things that we've mentioned already,
I want to ask you a little bit more
about statins because this is I believe
statins are the most widely prescribed
drug out there um as a category. How how
exactly how effective are they? Do you
think they're
overprescribed? And and what are your
general thoughts there from a cardiology
perspective?
Well, I mean, if you look at people who
have already had a heart attack, they
all need to be on a statin. And if
they're not on a statin, then it's being
underprescribed. Uh because once you've
had enough plaque in the arteries to
cause a heart attack or a stroke, you
have too much plaque and we need to
reduce it. And statins are the way to do
that. For the vast majority of people
who are being treated just because their
LDL value is high, some of them are
being overtreated and it's not
necessary. But overall, we believe that
statins are still underused based on the
prevalence of heart disease and
high-risisk people in our population.
But it may not be it may just be the
wrong people are being treated. And
that's where I'm hoping the heart scans,
the coronary calcium scans that we
discussed can help direct those people
who need treatment. They have a positive
scan. They have plaque in their
arteries. They need to be treated and
find those patients who have no plaque
scores of zero. they have no detectable
plaque and don't need to be treated and
we can better delineate who needs
therapy. Yeah. And so just to reiterate,
you know, what you've said before, you
need to know what that plaque buildup
looks like and so you need one of those
scans. Just knowing your LDL number and
your cholesterol biomarkers is not
enough because if you have clean
arteries and your LDL is quote unquote
high, it's a very different situation
than if you've already had a heart
attack or you've already got a lot of
plaque buildup. So there's there's no
reason certainly past the age of 40 it
sounds like not to get one of these
scans at least every few years I would
imagine. Right. Yeah. I I think Yeah.
And if it's completely zero we say you
can wait up to 5 years. If it's abnormal
you might want to repeat it a little bit
earlier to see if it's getting worse.
Yeah. Yeah. Yeah. Um okay. So so remind
us again you're you're What are the next
steps with this study and this line of
research? It sounds like are you
following the exact same people for 5
years or are you doing other types of
experiments as well? No, no, same
people. Yeah, we're going to try to
maintain these 100 participants. We've
already been following them. The scan
the first scans were done a few years
ago, so we're already a few years in
from their baseline scan, and we're
going to, I think, bring them back in
shorter order to to address any
questions about um going untreated or
or, you know, uh uh putting anybody uh
at question. Um, so we're going to try
to get them in, I think, sooner, uh,
than five years and then hopefully also
uh again at at a full 5-year followup at
least, um, to have longer term followup
and look at the influence on the
coronaries. So, uh, a couple final
questions here because I know we don't
have much time. Um, let's imagine you're
talking to a couple different types of
people. So, the first type will be what
we might just call like a typical
middle-aged American.
So, let's say that they have never had a
heart attack or anything like that, but
they're not exactly metabolically
healthy. Maybe they're pre-diabetic or
diabetic. Maybe they've got high
triglyceride levels. Maybe they've got
some plaque buildup. They're they're
they're certainly not in the pinnacle of
health, but they haven't had a heart
attack or anything like that either.
What should they be thinking about? So,
let's say they need to lose weight and
get somewhat more metabolically healthy,
but their LDL's higher than average. And
and I'll let you maybe steer us in terms
of the numbers we should be looking at
here. What should they be thinking about
in terms of whether or not to be
thinking about statins, whether or not
to be thinking about changing their
diet, potentially trying something like
the ketogenic diet? How would you start
to to steer someone to think about their
overall health when they look like that
kind of typical middle-aged American?
Yeah. I mean, I So, I I think, you know,
if they want to lose weight, uh
obviously we have some great weight loss
drugs now, but uh if they want to lose
weight through diet, keto is probably
the best diet for weight loss. it's
going to be the most uh uh the quickest
uh and probably the most exped
expeditious
uh way to lose weight uh from a dietary
standpoint. The Mediterranean diet is
great for longevity, but doesn't come
with much weight loss. Uh and a lot of
the other diets have just failed over
time. So, I think I think if they want
to lose weight, I I'm not against the
keto diet. Uh I track their LDL. If they
have that hyper response, they have to
get a scan. they have to get they have
to see if they have coronary artery
disease. And if they have underlying
disease, then then I'm I'm a little bit
more anxious about not treating them
with something, whether that's a statin,
whether that's aspirin, whether that's
other therapies to make sure that we're
treating the underlying risk um that may
or may not be exacerbated by this diet.
Mhm. How do you think about so so on a
patient by patient basis, how do you
personally with your patients think
about how high is too high when it comes
to things like LDL given what that
patient's, you know, sort of specific
characteristics are and then thinking
about like what the guidelines actually
say. So, so to say that another way, you
know, are are there cases where a
patient has an LDL that technically is
is higher than what the guidelines say
it should be, but you don't think it's
inappropriately high?
Yeah. So, I think that the guidelines
talk about LDLs of 190 milligrams per
deciliter as being too high and
warranting therapy. I I think that's
overtly incorrect if they have no plaque
in their coronaries. And we have great
data over lifetimes of patients. I'm not
talking about now a one-year trial with
keto. I'm talking about a lifetime of of
treatment where patients um are treated
with high with uh or have high LDL
cholesterol. They're never treated and
they never develop heart disease or
plaque in their coronary arteries. So I
say if their LDL is elevated or their
cardiovascular risk is elevated from
other factors, age, blood pressure,
diet, I mean um
diabetes, history of smoking, family
history that they undergo a heart scan.
And if the heart scan is zero, they
don't need to be treated for the next 5
years for their cholesterol. It's okay
because it's not causing plaque. If
their if their heart scan is abnormal,
then they need to think about treatment.
And the higher the heart scan, the more
plaque we find, the more aggressive we
get with treatments. Mhm. And so remind
us, you mentioned this briefly towards
the beginning, but is is when you start
to have some plaque buildup, is is this
something you're stuck with forever or
is that at least partially reversible?
So it definitely can be halted and in
some cases can be the the soft plaque
the non-calified plaque can definitely
be reversed for sure. We definitely have
seen regression of plaque. What we
haven't seen is regression of the
calcium the calcified plaque that seems
to be more of a scar tissue or a
permanent finding uh in that in the in
the arteries.
Well uh first of all I want to thank you
for your time uh Dr. Dr. Budov, he's a
busy guy, everyone. Um, and I got him
here for an hour. So, thank you very
much for doing that. Um, this is a
really exciting study. Anything you want
to reiterate about the study or any
final thoughts you want to leave people
with in terms of just heart health and
thinking about how to manage that and
track that over a lifetime. Yeah. You
know, I mean, I just we're we're we're
not good at looking at the outside of a
person and understanding what's going on
inside. And you'd be surprised. I see
these people who they they're excellent
athletes. They're in great shape.
they've eaten well their whole life and
their arteries are clogged up because of
genetics or because of bad luck or
whatever that is. And conversely, I have
people who probably shouldn't be alive.
They they they've done everything wrong.
They they're overweight. They never
exercise and their arteries are
relatively clear. So, I think you know a
simple test to say are you in that group
or not is you like we talk about
mammograms and you know, do you have
breast cancer or not? We can't just look
at you and say, “Oh, you look healthy.
You probably don't have breast cancer or
you look sick. You might have it.” We do
mamography. This is the mamogram of the
heart. We're going to look into the
coronary arteries. We're going to say
you do have disease or you don't have
disease. And if you don't have disease,
you can work work on those risk factors
and be healthier, of course, but there's
nothing urgent to start a statin or
start other treatments. If we find a lot
of plaque, despite your good lifestyle,
it's time to think about treatments. And
there's other treatments beyond statins.
I know not everybody likes to take
statins. They've heard negative things
about them. I think some of those are
over overblown. But if the for my
patients who are reluctant or refuse to
take a statin, we do have a good number
of alternatives now to help manage their
risk and give them a longer lifestyle
lifetime uh by by treating their
underlying risk factors. And we just
need to identify who to treat. And
that's where I think the heart scan
becomes critical. And we're going to
learn more about the keto diet. We're
going to learn more about different
therapies like the injectables, the
people that are using the GLP-1s to
inject themselves to lose weight. Are
those good for the arteries or not? We
don't know yet and we're learning. So,
we're going to get more and more
information about a lot of different
treatments by by watching what happens
to an individual over time under the
influence of drug X or diet Y or
lifestyle Z. Mhm. So, it sounds like one
thing I'm taking away from everything
you've said is despite everything we've
learned, despite, you know, all of the
studies and and all of the years um that
have gone by, there's we should still be
humble because there's a lot of mystery
here. You still get plenty of people
that do everything by the book. They
exercise, they eat right, but their
arteries are clogged. And then you also
get the opposite. People who, you know,
spend a lifetime doing all the unhealthy
stuff and for whatever reason, we can't
explain it, their arteries sometimes
look clean.
That's true. That is absolutely correct.
All right. Well, Dr. Matthew Budof,
thank you very much for your time and I
look forward to uh seeing what the the
next uh five-year result looks like.
It's been a pleasure talking with you
and I hope this was helpful for your
listeners as
[Music]
well. Visit mind and matter.substack.com
substack.com to find all of my content.
Edit:2025.04.28