Speaker 1 00:12

Can you just say your name real quick? Sure.

Kevin Maki 00:14

Kevin Mackey,

Speaker 2 00:15

okay. G, say your name.

Dr. Gabrielle Lyon 00:18

G, Lion,

Speaker 3 00:20

okay, we’re recording all cameras. Audio is good.

Dr. Gabrielle Lyon 00:22

Okay, okay, ready. Dr, Kevin Mackey, welcome back to the show.

Kevin Maki 00:38

Thank you. So glad to be back.

Dr. Gabrielle Lyon 00:40

Former President of the National lipid Association, and really an expert on fats, saturated fat, polyunsaturated fat, you name it. But you were president of the National lipid Association. I just want to lay the foundation

Kevin Maki 00:57

I was, and I’m actually currently, the CO editor in chief of the National lipid Association’s journal, Journal of Clinical lipidology,

Dr. Gabrielle Lyon 01:05

tier one journal. That’s actually a big deal for those of you guys listening when we talk about getting high quality evidence, tier one evidence, out into the world. So I don’t know how you do it, and you also run a company and do all these other things, but you know what they say, give the mission or the task to the busiest person, and those are the people that are going to get it done. And today why I really wanted you to come back on. Well, number one, you also have an open invitation to come back on whenever you want.

Kevin Maki 01:35

Thank you

Dr. Gabrielle Lyon 01:36

today, especially in light of the new dietary guidelines where 10% saturated fat still exists and has been in place for quite some time, continues, and also, the American Heart Association just came out with their new guidelines. And all of that is very exciting. With that, there’s a ton of confusion around LDL cholesterol and its role in heart disease, LDL cholesterol and its relationship to saturated fat.

Kevin Maki 02:04

Okay, well, first of all, an elevated level of LDL cholesterol is one of the major risk factors for heart disease and cardiovascular disease in general, which includes strokes as well. And so we know that things that raise LDL cholesterol tend to raise risk for cardiovascular disease, and things that lower LDL cholesterol tend to lower risk for cardiovascular disease. Saturated fat is one thing in the diet that influences LDL cholesterol. Higher saturated fat intake is associated with an increase in LDL cholesterol, but there are other things in the diet that influence the LDL cholesterol level as well. And so you also have dietary cholesterol that has a modest effect. And saturated fat and dietary cholesterol tend to travel as a team, not always, but in many cases, they do. But then there are things in the diet that lower LDL cholesterol. So unsaturated fats, both mono and polyunsaturated fats, as well as viscous dietary fibers, lower LDL cholesterol. And here’s something that is under appreciated, protein compared to carbohydrate, will lower LDL cholesterol. That’s true for animal proteins and plant proteins, but plant proteins do so to a larger degree, and then weight loss will also influence LDL cholesterol. And there’s some other things, like plant sterols, but the key is to maintain as low a level of LDL cholesterol as one can and that’s going to be influenced by genetics and lifestyle, and lower for longer is better when it comes to reducing risk for cardiovascular disease and LDL cholesterol.

Dr. Gabrielle Lyon 03:52

Can I stop you? I have a question. The LDL cholesterol lower is better. And I’ve actually looked at the literature when I think pre teen kids typically have a is it 70 milligrams per deciliter LDL cholesterol?

Kevin Maki 04:05

Yeah. So in when we’re born, our LDL cholesterol level tends to be between about 30 and 60 milligrams per deciliter. And then in kids, it’s quite a bit lower. So it tends to be roughly 20 to 30 milligrams per deciliter, lower than in adults. And so the median 50% above 50% below LDL. Cholesterol level in the US right now is about 100 milligrams per deciliter, and in kids, it’s often 7080, milligrams per deciliter.

Dr. Gabrielle Lyon 04:39

Does that transition happened during puberty?

Kevin Maki 04:42

Puberty is one of the factors that influences LDL, cholesterol, and so one of the things that is recommended for all kids is they have a lipid panel drawn at least once before the age of 11, because then you’re getting it before puberty. And part of the reason for that is to identify the roughly one in 300 people that has a genetic lipid disorder that’s going to put them at increased risk throughout their lives.

Dr. Gabrielle Lyon 05:10

The lipid panel. This is also the first time I’m actually hearing this. You know, I have two little kids. I don’t I cannot imagine them getting their blood drawn. They’re just a little bit bananas. But I think that we’ll probably get more advanced as to how we draw blood included in that lipid panel, is it the following, LP little APO, B cholesterol, the same way that we would think about an adult

Kevin Maki 05:37

when we talk about kids, typically you want non HDL cholesterol because that doesn’t have to be done fasting. And so you get a standard lipid panel, which includes triglycerides, total cholesterol and HDL cholesterol. It doesn’t need to be fasting. So non HDL cholesterol is just the total minus the HDL cholesterol. But if the level is elevated for non HDL cholesterol, or if the triglycerides are high, then that warrants coming back to get an additional panel. Now with regard to LP little a so that’s mostly genetically determined, and so the recommendation is everyone should have it done at least once in their life. And if it’s low, then for the most part, you don’t need to worry about it. There are a few nuances to that. So for instance, women, as they go through the menopause, the LP, little a value, rises roughly 30% and so again, if somebody has a low level, then they mostly don’t.

Dr. Gabrielle Lyon 06:42

How do you would you define 10 or under, 15 or under?

Kevin Maki 06:45

So there are two units that are used. So I’m going to so

Dr. Gabrielle Lyon 06:50

complicated all in all of this stuff.

Kevin Maki 06:52

Tell you both of the units. So the 80th percentile in the population, in milligrams per deciliter is about 50, and then in animals per liter, it’s about 125, and you see different numbers because not everybody agrees. Not all of the assays are exactly the same, and not everybody agrees on what the conversion should be, but let’s say 50 and 125 and so if you’re in that top 20% of the population, one in five people, there is increased risk. And we have drugs in development to treat people with very high levels. And we also have some drugs in development that mainly lower LDL, cholesterol, but they also lower LP, little, a and so I think that right now the main thing is do a screening at least once, and usually that’s in adults, but I hope that eventually that’ll extend to children. But honestly, I don’t know what the distribution looks like in children. And so the current recommendations mostly focus on adults for LP little a, and right now, only about 2% of people are getting it measured. It should be measured in every one, at least once,

Dr. Gabrielle Lyon 08:14

2%

Speaker 1 08:14

of

Kevin Maki 08:15

people, about 2%

Dr. Gabrielle Lyon 08:16

2% of people are getting an LP little a measure.

Kevin Maki 08:18

Yes.

Dr. Gabrielle Lyon 08:20

What about APO B?

Kevin Maki 08:22

And so APO B is a very useful indicator of risk. So let’s talk about the particles circulating in the blood that increase cardiovascular risk. So there are three kinds of particles associated with increased risk. So there are LDL particles, and then there are remnant particles of triglyceride rich lipoproteins, and then LP Little a. Well, here’s the interesting thing, each one of those has a single molecule of APO B. So APO B is a better marker of risk than either LDL cholesterol or non HDL cholesterol, and having said that, it adds an expense, it adds a bit more complexity. So for the most part, what the guidelines are recommending, and there’s some controversy about this

Dr. Gabrielle Lyon 09:15

dietary guidelines,

Speaker 4 09:16

or

Kevin Maki 09:16

this is American College of Cardiology, American Heart Association, multi society guideline that was just released recently,

Dr. Gabrielle Lyon 09:25

two days ago.

Kevin Maki 09:26

No, this one was released in February, okay, so not what we were looking at previously, right? And so there were recommendations from the American Heart Association, a scientific statement that came out about diet. But there were also, there was a guideline that was put out for management of dyslipidemia. So just to recap, we’ve got these three types of particles that increase risk, and we use LDL cholesterol as a proxy for APO B. Apo B is a better. Later than LDL cholesterol, but it’s not really commonly measured in the US, and so LDL cholesterol is the main target and the main goal. And then we also have goals for non HDL cholesterol. Okay, so you’ve got these three particles in the circulation. Each one of them has one molecule of APO B, and so because of that, apo B is a better indicator of risk than LDL cholesterol. But clinically, LDL cholesterol is what’s typically the focus. And there are three goals for LDL cholesterol for primary prevention, and I’ll define that term in just a minute. The goal is less than 100 milligrams per deciliter for secondary prevention. That is, people who have known atherosclerosis for secondary prevention, it’s either less than 70 or less than 55 and there are some nuances, but those three numbers, less than 100 for primary prevention, less than 70 or less than 55 for people who have known atherosclerosis. And so the objective is, number one, maintain as low a level of LDL cholesterol through lifestyle as is reasonable for the lifespan, you know, as early as possible, because lower for longer is better when it comes to cardiovascular risk and LDL cholesterol.

Dr. Gabrielle Lyon 11:34

And you do, you obviously believe that. But do you feel like we have really good evidence? For example, if someone has an LDL cholesterol of 100 and we say, okay, the lower, the better for longer, and the primary outcome we’re looking at is cardiovascular disease. That if we’re looking at cardiovascular disease, we have to recognize that that maybe not, that’s not how we would think about optimal number. Or we don’t really have a number for optimal health, and that’s kind of doesn’t really have a great definition, but we don’t have, okay, so this is the number you want for good performance, versus this is the number you want to prevent heart disease,

Kevin Maki 12:16

and I think it relates to a person’s risk. So the focus is on preventing heart attacks and strokes and revascularization procedures like bypass surgery. So we look at a person and we say, what’s your risk? And LDL, cholesterol is just one factor that we need to take into consideration, and we have to take into consideration all of the other risk factors as well. And so if somebody has an LDL cholesterol of 110 milligrams per deciliter, has no other risk factors, is relatively young, then you would say, we want to focus on your lifestyle and getting that number below 100 if we can. But another person may have genetics that mean that even with the best lifestyle, their LDL cholesterol level is going to be 150 or 160 and so in those people, then you want to assess the risk. And if the risk is high enough, then consideration might be given to drug therapy. But for you know, most of the population, what we’re talking about is maintaining a healthy lifestyle and keeping the LDL cholesterol level as low as possible with lifestyle and then if risk is high enough, considering drug therapy.

Dr. Gabrielle Lyon 13:35

And for the viewer the listener, the definition of normal LDL cholesterol would again, depend on the way in which you’re measuring it. But let’s say half of the US population has an LDL cholesterol of less than 100

Kevin Maki 13:49

Yep, half below, half above,

Dr. Gabrielle Lyon 13:51

half above, yes, and 25% if we’re thinking about and I’m going to bring this back to diet, because we have to touch on diet, 25% of adults have an LDL cholesterol above 130 which means we are thinking about medical intervention,

Kevin Maki 14:08

right? So for those people still, the first step is lifestyle, and if lifestyle isn’t enough, then drug therapy might be considered. But again, LDL cholesterol is just one feature, and so you have to be concerned about the other risk factors. And I’m going to tell you my acronym for all of the risk factors that clinicians have to think about in terms of assessing risk, and that’s flash Glick. So what does flash stand for? F is family history, L is low, HDL cholesterol. A is h, S is smoking, H is hypertension. And then the second half Glick. G is for glucose metabolism. So that’s not just the level of glucose or a 1c It’s also, does the person have insulin resistance? Then l is for lip. Kids, and that’s mainly the things I talked about a moment ago. I is for inflammation, and there are various biomarkers of inflammation, because we know that chronic inflammation increases cardiovascular risk. C is for coagulation, and then K is for kidney health, or kidney function. And so all of these things have to be taken into consideration when assessing someone’s risk. And so in the guideline, there’s formula that can be used. It’s called the prevent equation. And so you estimate risk, but then you also look at other factors that you might have knowledge about. So LP, little a and whether the person’s had a coronary calcium done, if they have evidence of coronary calcium, that means there’s some atherosclerosis there, you look at kidney function. So those are called Risk modifiers. So you say, Well, you know, here’s the level of risk at which we might consider drug therapy, and then for someone who’s kind of at the lower end of that, then do they have risk enhancers, where you say, well, your risk might be a little higher than the equation would predict.

Dr. Gabrielle Lyon 16:11

That makes sense. And what I’m hearing you say, in a very elegant way, is that, and I’m saying this not you, is that we’re really kind of over indexing on LDL cholesterol. Don’t cringe, as the national liver association president or former president cringe when I say that, but that is what I’m hearing you say,

Kevin Maki 16:31

yeah, exactly right. So LDL cholesterol is incredibly important, but it’s only one of several factors that we have to take into account. And for somebody who doesn’t have any other risk factors, their risk still may be low, even with an elevated LDL cholesterol. In contrast, someone who has many risk factors and has evidence of atherosclerosis, then their risk may be high, even if their LDL cholesterol is same, you know, 80 or 90 milligrams per deciliter below the average, but there still may be room to lower future risk by lowering LDL cholesterol.

Dr. Gabrielle Lyon 17:10

And how does this relate to the dietary guidelines and this 10% saturated fat conversation?

Kevin Maki 17:18

Yes, so the 10% saturated fat that’s been in both the dietary guidelines and then also in the American Heart Association scientific statement is basically a cut point that we use. The average American diet right now has about 11% of energy from saturated fat, so we’re not way above that 10% number, but a healthy dietary pattern will be relatively low in saturated fat, and so I have a description that I use, and I say this over and over, and my joke is that I’ve got it tattooed on my forearm. I said that in a talk once, and then people were wanting to see my tattoo. And I don’t have this on my forearm, but

Dr. Gabrielle Lyon 18:01

he just wants to be clear he does any tattoos.

Kevin Maki 18:03

I have no tattoos. Okay, so

Dr. Gabrielle Lyon 18:06

he’s no tattoos, and definitely not the

Kevin Maki 18:07

one in the form, as far as anyone knows, other than my wife, I have no tattoos, but a healthy dietary pattern generally emphasizes whole grains, fruits and vegetables, nuts, seeds, legumes, non tropical oils and seafood, and it’s not excessive. Now, when I say not excessive, I don’t mean that these things have to be eliminated from the diet, but it’s not excessive in saturated fat, salt, added sugars and refined starches. So these are the things that the American diet tends to be higher than might be optimal in tongue in cheek. We call them the four white poisons. We want to emphasize that that’s just a joke. It’s a way to help people remember them. But the American diet tends to be higher in those things than is probably optimal. And so if a person follows a healthy dietary pattern, there is room for animal sources of protein, in my opinion, for sure, and that’s things like red meat and poultry and dairy and eggs. There is room for those things. And having said that, I think the 10% saturated fat is not unreasonable, and a healthy dietary pattern will tend to be below that. But I also think that what is more important than saturated fat is the balance of cholesterol raising and cholesterol lowering factors in the diet. I

Dr. Gabrielle Lyon 19:36

definitely want to come back to that we are going to talk about the ratio before we move on from the diet conversation. If we, from my perspective, we could say that there is various ways to or there are various ways to get a healthy diet, because we’ve got also the Keto people that have higher saturated fat, and some of those have great. Biomarkers. And then, of course, you know, you’ve got vegan and vegetarians, and then you’ve got omnivores. There’s probably multiple there’s probably a multitude of ways, depending on where you are and how your genetics are, to have a healthy dietary pattern for that individual. Is that fair to say?

Kevin Maki 20:18

I think that’s absolutely true. Now I tend to try to stay away from the extremes, you know, like a keto diet for some specific purposes, I think may have a role, but I think healthy dietary patterns have a balance of foods that ensures enough intake of fiber, enough intake of various minerals, for instance, that tend to be lower than is optimal. So potassium and magnesium as examples of things that often people don’t get enough of, and also polyphenols that are found in various plant foods that are not found in animal foods. And so what I say is that I think there’s a wide range of intakes that can be healthy, and it isn’t a one size fits all. The dietary pattern for which we have the best evidence from randomized, controlled trials is the Mediterranean dietary pattern. And of course, you hear lots of people saying, well, you know, how do you define it? Well, I define it the way they defined it in the trials and the recommendations they gave to the participants and in two trials, PREDIMED and cordial prev the Mediterranean diet group that was randomly assigned to that as compared to what they called a low fat dietary pattern, but it wasn’t really terribly low in fat, but it was lower in saturated fat, and so the Mediterranean dietary pattern was associated with a 25 to 30% lower incidence of major adverse cardiovascular events. So that’s where we have the best evidence, and then we have evidence that’s a little less strong, I would say, for other dietary patterns like the DASH diet and healthy us dietary pattern, I think you can be healthy on a vegan or vegetarian pattern. Having said that, I think there are more risks that those people will have insufficiencies, and so my tendency is to be somewhere in the middle. So you know, the extremes people who want to recommend a very low fat vegan diet, for instance, like the Dean Ornish approach, I think that’s kind of extreme, and I think that has some challenges. And then a ketogenic diet may have specific applications where it’s useful, but I also think that for most people, that’s not going to be an optimal diet

Dr. Gabrielle Lyon 22:55

there. There seems to be a wide range. And if we can base some of our and, you know, I also think that we should touch on, we create these guidelines, or we create these guidelines. These guidelines then inform schools, military, again, nursing homes, anyone that receives federal funding. And that’s why these are created. It’s, it’s, there’s a range for everything. The challenge becomes, if we over, and, you know, I, as I’m saying this, I still think protein is finally having its moment. It’s really important for aging, for sarcopenia, and then, on the same hand, I think that the 10% saturated fat, which, why are we? You know, again, you probably, you’re probably so sick of hearing about this, but becomes a challenge, because if we look at how we are framing the conversation, 10% saturated fat, the reason, typically, people are saying to reduce that is because of its impact on cholesterol, LDL cholesterol, and if 50% of the population has an LDL cholesterol and are low risk of 100 milligrams per deciliter. And 25% of the population has higher LDL cholesterol above 130 then as we restrict saturated fat, we’re no longer talking about dietary recommendations if we are doing it to target that LDL of 130 just go with me. Here. We are now talking about medical intervention. And so when we say we should reduce to 10% saturated fat, and we have healthy foods, like an egg that might have higher, you know, even though it has a total of what, one gram, six grams of fat, and a portion of that is saturated fat, then by definition, that that egg is not going to be considered healthy.

Kevin Maki 24:50

Yeah, I think you know, eggs actually aren’t super high in saturated fat. I would also say that red. Meat in terms of LDL cholesterol, it’s not really the fat in red meat that is raising LDL cholesterol, it’s the cholesterol content. So in a study we did just recently, we had people eat two servings a day of red meat. Which

Dr. Gabrielle Lyon 25:16

study was this? Was this the effects of diets containing beef compared with

Kevin Maki 25:20

beef compared with chicken.

Dr. Gabrielle Lyon 25:21

Yeah, this is this a great study. We’ll link it,

Kevin Maki 25:23

yep. So we had people consume two servings a day, which is more than is recommended. But the objective of this study was to look at cardio metabolic risk factors, especially those for diabetes. And so we took people with pre diabetes for a month, we gave them two servings a day of beef, and it wasn’t especially low fat beef, and we gave them two servings a day of chicken. Now, chicken has less saturated fat than beef, but if you look at the fatty acid profile of beef, roughly half is saturated and half is unsaturated, and of the saturated fat, half of that is stearic acid, and stearic acid is fairly neutral with regard to effects in LDL cholesterol. So at the end of four weeks on the chicken diet, the LDL cholesterol concentration in our sample was 112 milligrams per deciliter. At the end of the four weeks with the beef diet, the LDL cholesterol level was 112 milligrams per decilit was exactly the same.

Dr. Gabrielle Lyon 26:28

Couldn’t plan that. Could you

Kevin Maki 26:29

and we couldn’t plan it. In fact, I, in fact, I double and triple checked the numbers because I thought this can’t be true. This

Dr. Gabrielle Lyon 26:36

is a typo,

Kevin Maki 26:37

but we showed the same thing in a study we published in 1999 when we compared beef and chicken. So again, the question becomes, is it the total amount of saturated fat in the diet, or is it the balance of saturated and unsaturated fats in the diet that is most important for LDL cholesterol? And the answer, I think pretty conclusively is it’s the balance, and not just of saturated and unsaturated fats, but other factors that raise or lower LDL cholesterol.

Dr. Gabrielle Lyon 27:10

Could you rank the importance of the balance? So the balance between tonight, you’re not talking about Omega three and Omega six, because there’s a ratio there that we have spoken about that is probably very important.

Kevin Maki 27:25

Yes,

Dr. Gabrielle Lyon 27:26

there you are now talking about the actual food matrix, composition of the fat within the food, the kind of is it the kind of fats or the kind of saturated fat and the kind of monounsaturated

Kevin Maki 27:40

Yeah, so saturated fats. We talked about saturated fat, but it’s actually a number of different types of fatty Do you

Dr. Gabrielle Lyon 27:48

know Tom Brenna?

Kevin Maki 27:49

I do. Yes. He

Dr. Gabrielle Lyon 27:50

is on. He came on the show. He was hilarious, and his episode comes out on Tuesday.

Kevin Maki 27:55

Oh, looking forward to that. So you know, we’ve got some saturated fatty acids, 12 to 16 carbon saturated fatty acids, neuristic, lauric and palmitic acid that raise LDL cholesterol, and we’ve got stearic acid that is pretty neutral. And then we’ve got monounsaturated fatty acids like you find in avocado oil and olive oil and peanut oil, and those lower LDL cholesterol. And then we’ve got polyunsaturated fatty acids, and they lower LDL cholesterol mostly. But you’ve got two varieties of those. You’ve got omega threes and Omega sixes. So the main Omega six polyunsaturated fatty acid is linoleic acid, and that lowers LDL cholesterol. So

Dr. Gabrielle Lyon 28:54

you can considerably. You know, as I’m hearing you talk, I’m thinking, okay, notably if someone has LDL cholesterol above 130 we have to make the decision, is it genetic? Is it diet? We decide that we are going to really double down on this balance of fatty acid profiles. How do we and we say it’s going to lower it. Is it going to lower it in a clinically significant way from I’ll let you answer that,

Kevin Maki 29:23

yeah. And I think the answer is yes, it can. And so we did a study where we gave people all of the food they consumed, and we gave them 54 grams a day of either extra virgin olive oil or corn oil.

Dr. Gabrielle Lyon 29:40

54 grams meaning table. We’re talking tablespoons

Speaker 1 29:43

or

Kevin Maki 29:43

tablespoons a day. Now, they didn’t go down. Mixed it into philosophy so and both of them lowered LDL cholesterol. So with the corn oil, it was about 11% and with the olive oil it was about three. A half percent, but the olive oil had some additional beneficial effects. It lowered heart rate and it lowered blood pressure, and we think that’s because of the polyphenols that are in the olive oil. And so I think there’s good news for seed oils.

Dr. Gabrielle Lyon 30:20

Stop the press. Yes,

Kevin Maki 30:21

good news for seed oils, and there’s good news for olive oil and avocado oil and so forth. I think they have generally beneficial effects on risk factors for cardio metabolic disease. And there’s a lot of controversy, and we can get into I love controversy about seed oils. Yes.

Dr. Gabrielle Lyon 30:40

I mean, I don’t really, but okay,

Kevin Maki 30:42

but we just finished a study. It’s published currently online. It hasn’t appeared in the journal yet, where we looked at linoleic acid in relationship to biomarkers of inflammation. So hold on to that thought, yes, going back to

Dr. Gabrielle Lyon 31:02

Matt, pause this for the team. We’ll link the study to

Kevin Maki 31:07

So going back to lipids, and you know, well, the question is, well, if somebody starts with LDL, cholesterol level of 130 milligrams per deciliter, and you lower that by 10% Well, you know over a long period of time that can be important. So in general, if you lower LDL cholesterol by one millimole per liter, and one millimole per liter is about 39 milligrams per deciliter. You’re going to reduce risk over five years by 20 to 30% and it depends on the characteristics of the person, but over five years by 20 to 30% but if you lower it and keep it down by one millimole per liter for 40 years, you lower risk by over 50% about 54%

Dr. Gabrielle Lyon 32:09

meaning there’s a 55% less likelihood of Is it a major cardiac event

Dr. Gabrielle Lyon 32:17

or adverse

Kevin Maki 32:18

cardiovascular event, which is basically heart attack, stroke or revascularization procedure,

Dr. Gabrielle Lyon 32:24

okay,

Kevin Maki 32:25

and so that’s why we say lower for longer is better. And so genetic variants that lower LDL cholesterol by just a small amount, but are maintained throughout a person’s life, they really do lower risk, much more than you would expect based on results from clinical trials that are only five years or so in length,

Dr. Gabrielle Lyon 32:48

and that’s in someone who has a higher risk profile. Yeah, is that

Kevin Maki 32:55

that’s in these studies. These are called Mendelian randomization studies. They’re just looking at people who inherit, you know, either a genetic disposition toward higher or lower levels of LDL cholesterol.

Dr. Gabrielle Lyon 33:11

My follow up question to that would be, if someone has or their level is at 100 and we lower it to 70, do we then impact risk?

Kevin Maki 33:21

The answer is yes, and almost certainly we do. Across the risk spectrum, lower always seems to be better. There doesn’t seem to be any threshold below which you know you don’t see additional benefit. But of course, if you’re talking about drug therapies, there’s risk involved in drug therapies. There’s costs involved in drug therapies. Some people have side effects, and so because of that, you have this situation where you don’t want to put everybody on cholesterol lowering medication, but people who have a high enough risk. It is demonstrated in lots of randomized, controlled trials now that if you lower LDL cholesterol, you lower risk. It happens across the risk spectrum. But of course, the greatest absolute benefit is going to be in people who are at the highest risk to start with. Yeah,

Dr. Gabrielle Lyon 34:16

and that’s typically less lifestyle. That’s more, I mean, it’s obviously a combination,

Kevin Maki 34:23

but it’s always a combination. But

Dr. Gabrielle Lyon 34:24

you would say that there is this genetic risk that seems to kind of trump everything potentially.

Kevin Maki 34:31

So at one end of the spectrum, you have people who have familial hypercholesterolemia, and they have high levels of LDL cholesterol throughout their lives, and they have very high risk. And then at the other end of the spectrum, you have things like a beta lipoproteinia, where you have very, very, you know, almost no APO B in circulation, and they have very low risk. And then you’ve got all sorts of genetic variants that put people. Different places on the spectrum, and what we see very consistently is the higher the level of LDL cholesterol, the greater the risk. And we see in clinical trials, if you lower the level of LDL cholesterol with all kinds of interventions. We have many drug therapies. We even have something called, you know, that was done with ileal bypass surgery to lower LDL cholesterol. I know that seems kind of crazy now, but that lowered risk. And so we have all kinds of interventions that have been shown to lower risk. You lower the LDL cholesterol, you lower the risk.

Dr. Gabrielle Lyon 35:32

LDL cholesterol is that clinical biomarker, if you lower do we know the effect of so if you lower APO B, do we know at what because APO B contributes to obviously cardiovascular disease? When you lower LDL cholesterol, what is the relationship between that and lowering APO b? Or is it multi factorial?

Kevin Maki 35:55

Yeah, it’s. It’s pretty closely related. So when you lower LDL cholesterol, you almost always lower APO B. Apo B doesn’t go down quite as much. So if you lower LDL cholesterol by 30% you may lower APO b by 20% and so we use LDL cholesterol as the clinical marker, but what we’re really doing is lowering APO B. I think it all relates to the number of atherogenic particles that you have, even though there may be a little bit of gradient across different types of particles and how bad they are, I think that we shouldn’t worry about that little gradient. We should just worry about keeping the number as low as possible.

Dr. Gabrielle Lyon 36:36

The Do you think they’ll ever switch over? I mean, because you’re kind of in the know that they’ll switch over from getting from thinking about LDL cholesterol to APO B.

Kevin Maki 36:46

I’d love to see that new guideline came out. They acknowledged APO B. They acknowledged that APO B is a better predictor, but they did not give a strong recommendation to measure APO B in everyone. They basically said, people with elevated triglycerides, you should measure APO B, which

Dr. Gabrielle Lyon 37:05

is so weird, because elevated triglycerides, that’s a carbohydrate

Kevin Maki 37:08

problem. It is a carbohydrate problem. So saturated fat raises LDL cholesterol, but carbohydrates raise triglycerides. And so you know, when we talk about what people eat too much of about 50% of the calories in the average American diet come from carbohydrates, and largely those are refined starches and added sugars, and that’s a place where I think we would do very well to substitute Some of the calories from added sugars and refined starches with calories from things like protein and unsaturated fatty acids.

Dr. Gabrielle Lyon 37:48

If you could have reworked the guidelines in the way that perhaps has taught to clinicians and consumed, no pun intended by the public, it would you say that it makes more sense to say, Okay, if you have elevated triglycerides, you are the person that we’re going to focus on, perhaps lowering your carbohydrate ingestion by below 130 let’s just say so if the RDA Recommended Dietary Allowance is 130 I mean, chances are they’re getting double that right, and that you are someone, based On your blood levels, should reduce your carbohydrate intake versus if you are someone who has LDL cholesterol that’s above 130 perhaps you are someone that should focus on your saturated

Speaker 1 38:30

fat.

Kevin Maki 38:30

And I would say that we have to separate the American Heart Association scientific statement, which is a basic statement for the public on maintaining optimal cardiovascular health. And then I would point to a different statement that I was involved in generating, and that’s the NIAID nutrition interventions for adults with dyslipidemia. And in the NIAID document, we do exactly that. We say, Well, if you have elevated triglycerides, here is where the focus should be. If you have elevated LDL cholesterol, here is where the focus should be. If you have both, then you need to think about both of those sets of recommendations. And so I think our recommendations are more specific to people with lipid issues that you’re trying to address with diet

Dr. Gabrielle Lyon 39:22

that is helpful, because ideally, then that’s much more specific and meaningful for the person, versus okay, just reduce your saturated fat, or, you know, eat this number of carbohydrates. If you knew the idea that we shift from macronutrients to the profile of fatty acids, which is really not something that is discussed often. How far along are we? For example, if I you know, I still see patients our medical practice is called strong Mass. Medical. It’s kind of a good name, rather than, you know, weak and decrepit medical, but strong medical, very, you know, we believe in building stronger humans. Early on in my career, we would do fatty acid profiles. And again, I started my career many years ago. We didn’t necessarily know what to do with it. How are we looking and also, because nutrition, the flux is so fast, how can we know, as you’re talking about these profiles and these matrix and these ratios?

Kevin Maki 40:33

So one thing you hear a lot about is the Omega six to Omega three ratio in the diet, but then also in the blood, or in red blood cells, as an example. And people say, well, a high ratio of omega six to Omega three is associated with adverse outcomes. Well, that’s kind of true, but it’s more nuanced than that. Higher Omega six in the blood is associated with better outcomes. Higher Omega three in the blood is also associated with better outcomes. So when they say a higher ratio is problematic, what’s really problematic, in my view, in my interpretation of the available evidence is that most people are not getting enough omega three fatty acids, and so I like the Omega three index, and the Omega three index is a way to assess, are you getting enough omega three fatty acids? I think that a level between eight and 11% and what do I mean by percent? That’s red blood cell membranes have fatty acids. And if eight to 11% of the fatty acids in red blood cell membranes are EPA plus DHA, ikosa, pentanoic acid, docosa hexanoic acid,

Dr. Gabrielle Lyon 41:57

I know you practice those.

Kevin Maki 41:58

I’ve I’ve been immersed in fish oil for many years. So when you have eight to 11% that’s associated in observational studies with the best outcomes. Now I have to acknowledge the evidence that we have is mostly from observational studies. We have some randomized, controlled trials, the results have been kind of mixed, and I have some ideas about why that might be, but basically, what I try to do myself is I try and maintain my omega three index between eight and 11% the average in the US right now, we just looked at a sample of a little over 2000 people, and it was almost identical to the average in the US, around 4.6%

Dr. Gabrielle Lyon 42:47

I would have guessed that.

Kevin Maki 42:48

And so how much EPA plus DHA do you need to get up to eight if you’re at 4.6 and the answer is about a gram and a half to do two grams a day. So most people are not going to eat enough fish to get to that level.

Dr. Gabrielle Lyon 43:02

How much would how much fish would you have to eat?

Kevin Maki 43:04

I think that it would require about if I’m doing the math in my head, which is a dangerous thing, I think it would require about four servings of fatty fish a week, and very few people are consuming that level. And so I take an omega three fatty acid supplement to maintain that. And here’s the interesting thing, I was taking a supplement, and then I was at a meeting with Bill Harris, and Bill Harris founded a laboratory called omega quant, and they measure this omega three index. And so I was at a meeting, and he said, Hey, you want to give me your finger? I’ll stick it and I’ll put the blood on a piece of paper, and I’ll measure your Omega three index. And I was very confident that, because I took a supplement every day, that I’d have a level that was, you know, eight or very close to it, no, 4.7 and so I said, Wow, I would not have expected that. And it turns out there’s a lot of variability. So two people can eat the same amount of omega three fatty acids, but have very different Omega three index values. So I personally, and this is not any organization recommending this. This is just my own opinion. I think that maintaining an Omega three index in that range is very helpful from a health perspective. I think omega threes are very much involved in the balance of inflammation and resolution. So you have inflammation, that’s an active process, and you have resolution, that’s an active process that shuts down the inflammation. And a lot of the benefits, I think, of omega three fatty acids come from influencing resolution and maintaining a proper balance between those two things, and then also they have effects on platelet activation.

Speaker 1 45:00

And which

Kevin Maki 45:00

I think is important, because when a person has a heart attack or a stroke, what’s typically happening is they have a place where they’ve either had a fissure or erosion in a plaque, and then a clot thrombus forms at that location and then stops off the blood flow. And so if you are tending to over clot, it’s going to make you more likely to have an event. So two people at the same level of atherosclerosis, the same level of plaques, one may be at higher risk of an event because of being more apt to form a big clot, and the other person, who’s less apt to form a big clot, may never have an event, even though there’s a lot of atherosclerosis.

Dr. Gabrielle Lyon 45:47

The amount, and you’re saying this omega three index amount in the blood should be from your perspective and from the literature, between eight and 11. I agree. We shoot for around 10 for our patients. As you’re talking I’m thinking there’s some in red blood cells, and then there’s some in the tissue. Obviously, we’re not doing tissue biopsies. Do some people have higher Is there a genetic variation where some people have higher tissue saturation than others, potentially.

Kevin Maki 46:23

Yeah, we have kind of limited evidence. But the evidence we have when you look at different tissues, the level in buccal cells from the cheek, the level in heart tissue and heart transplant patients and some other tissues, the red blood cell membrane level correlates very strongly with the level in other tissues. And so I think it’s the level in the tissues that’s most important for maintaining membrane fluidity and also for having these effects as they relate to inflammation and resolution.

Dr. Gabrielle Lyon 47:01

Is there any utility in measuring things like stearic acid, some of the other fatty acids that you had mentioned, profile wise,

Kevin Maki 47:08

I think clinically right now, probably not, but in terms of what they can tell us, the different fatty acids have different relationships to diet. So when it comes to linoleic acid, which is the main fatty acid in seed oils, linoleic acid is an essential fatty acid, so body doesn’t make it. So if it’s in your bloodstream, it came from your diet, and so linoleic acid correlates very strongly with dietary linoleic acid. So linoleic acid in the blood, very good marker for dietary linoleic acid. Same thing in red blood cells. So red blood cells reflect the diet you’ve eaten over, you know, several weeks, whereas in the blood, it really reflects mainly the diet that you’ve eaten in the last few days. Now, when it comes to other things, saturated fatty acids? Well, then it gets a little more complicated, because some comes from the diet, and some comes from conversion of carbohydrate into mainly palmitic acid, which is a saturated fatty acid. So that’s more complicated. And then with the monounsaturated fatty acids, that doesn’t seem to correlate very well with how much you have in the diet. So with where

Speaker 1 48:23

does

Dr. Gabrielle Lyon 48:23

it come from? Is it just within the tissue?

Kevin Maki 48:26

Yeah, it so you get inter conversion of fatty acids. So as an example, Stearic acid, which is a saturated fatty acid, gets converted to oleic acid. And so that’s one of the reasons that it doesn’t raise cholesterol, because most of it is converted to oleic acid. So it’s a little bit complicated, but the two kinds of fatty acids where what is in the blood gives you a good indication of what is in the diet are the polyunsaturated Omega six and omega threes. And so, you know, it’s not a perfect correlation, but it’s a good biomarker for what people are eating. And I talked about inflammation and seed oils.

Dr. Gabrielle Lyon 49:10

Yeah, I’m looking here we you know, you can’t go anywhere without hearing that seed oils are driving inflammation and chronic disease,

Kevin Maki 49:17

right? And RFK Jr, or HHS Secretary has promoted this idea that seed oils produce inflammation, mitochondrial dysfunction and are basically problematic from a health perspective. And the first thing I have to say is we have a very limited database from randomized, controlled trials where we look at outcomes like heart attacks and strokes and incident diabetes and so forth. So got to acknowledge that uncertainty, but having said that, the data we have would fairly strongly, in my opinion, support the idea that linoleic acid from seed oils is associated with. Health benefits. So I mentioned the study we did that showed linoleic acid lowered LDL cholesterol. Okay, then a lot of the narrative is that linoleic acid can get oxidized, and then that can trigger inflammation. And so if that was clinically important. What you would expect to see is, the higher the linoleic acid level in the blood, the higher the level of inflammation.

Dr. Gabrielle Lyon 50:31

But when we say inflammation, you’re saying oxidized LDL, oxidized LDL particles. How are we we

Kevin Maki 50:38

have biomarkers of inflammation. The most commonly used one is C reactive protein. And so if a higher linoleic acid intake in the diet was driving inflammation, you know these linoleic acid was getting oxidized, and then that was causing an inflammatory response, you would expect higher linoleic acid in the blood would be associated with higher levels of C reactive protein. So I mentioned this study. We had a little over 2000 people. It was the Aegis study. Now one of your recent guests, David Allison. He and I were co principal investigators for the Aegis study, and it was a covid related study, had nothing to do with diet, but we were interested in whether covid infection would change the cardio metabolic risk factor profile. So we measured a lot of things at baseline and then during follow up as well, but we used the baseline data little over 2000 people, and we looked at the fatty acids in blood, and the higher the linoleic acid level in the blood, the lower was the C reactive protein level. We also looked at four other biomarkers of inflammation, so three of the five that we looked at showed this relationship, higher linoleic acid, the lower the level of the biomarker of inflammation. And we created a composite of all five, and it was like a stair step, higher linoleic acid, lower biomarkers of inflammation. And when we look at the limited data set we have from clinical trials that are intervention studies. This was observational, but it does not our results do not support the narrative that linoleic acid is pro inflammatory. When we look at randomized clinical trials, we either see a neutral effect, or we see a slightly favorable by favorable, I mean lower inflammation when more linoleic acid from seed oils is consumed.

Dr. Gabrielle Lyon 52:53

Do you think the confusion, perhaps is maybe seed oils are used, is a term a proxy for processed the fat in processed foods, or is it hydrogenated because there’s probably a ton of different seeds. Yeah.

Kevin Maki 53:12

So when you look at things that are high in fat, so olives and avocados, for instance, how do you get the oil out? Well, you really just squeeze them and the oil comes out because they have enough fat in them that you can do that. So it’s called cold pressed. I

Dr. Gabrielle Lyon 53:25

wonder if I should try that with my avocados.

Kevin Maki 53:27

Yeah, so

Dr. Gabrielle Lyon 53:29

anyway, I’ve never tried it, so I don’t

Speaker 1 53:31

know what

Dr. Gabrielle Lyon 53:32

for the kids to do.

Speaker 1 53:32

I’ve

Kevin Maki 53:33

actually done studies with avocados, and so, you know, avocados are great and they’re high in monounsaturated fatty acids. But avocados, olives, you squeeze them, get the oil out. It’s cold pressed to get the oil out of something like a soybean or corn or canola seeds, also known as rape seeds. It’s obviously a PR disaster, disaster rapeseed, but you have to process them. So what do you do? You use a solvent like hexane, and you heat it, and you extract the oil. And so this is what people say. This is very unnatural. It oxidizes fatty acids. It creates all of these problems. Well, if you analyze what’s sold in the supermarket, you don’t have any hexane in the bottle. I mean, you have undetectable levels of hexane in the finished product. And then one of the things that I’ve heard people say is, well, then it’s you have all of these oxidized fatty acids, and it’s deodorized to cover up the smell from the oxidized fatty acids. Well, that’s really not how it works. The deodorization process is removing the oxidized fatty acids, and that removes any smell from oxidized fatty acids. So. Where does this idea that seed oils are driving? I mean, it exploded, yeah, honestly, there are a few vocal influencers online who have promoted this idea.

Speaker 1 55:15

They

Dr. Gabrielle Lyon 55:15

must have read it somewhere. There must have been some misinterpretation of perhaps foundational science?

Kevin Maki 55:21

Well, I think that it’s based on biochemical pathways. So there are two biochemical pathways that I think are the culprits here, and I’ll also say that there are some animal studies that suggest that these might be important, but they don’t seem to be important in humans. So the first one is that linoleic acid can be converted to arachidonic acid. Now, arachidonic acid competes with omega three fatty acids for enzymes that create things called leukotrienes and prostaglandins. Well, the arachidonic acid when it’s a precursor, it generates versions of these things that are more inflammatory and have more of an effect to promote blood clotting than the ones generated by omega three fatty acids.

Dr. Gabrielle Lyon 56:16

But I mean, are you saying in this is mechanistic or clinical outcome,

Speaker 1 56:22

this is

Kevin Maki 56:23

mechanistic. So that that is true, but here’s the rub. The rub is linoleic acid can be converted to arachidonic acid, but that saturates at a very low intake. So on an average American diet, you’re way above that saturation level. So the higher the linoleic acid intake, you don’t see any increase in arachidonic acid. But here’s how you lower your arachidonic acid level by taking enough EPA and DHA omega threes. When you do that, you see the arachidonic acid level in the blood dropping. So I think part of the benefit of EPA and DHA, which I recognize, is mostly from observational studies, so we’ve got to be a little careful on over interpreting those. But I think some of the benefit, which I think is probably there, relates to higher omega three index being associated with lower circulating levels of arachidonic acid. So that’s one the other is this oxidation question. And I just think the evidence we have does not support an important role for oxidized Omega six fatty acids in human health, at least for the things that we have looked at, I can’t say that I’ve studied everything, but for the things that we’ve looked at, there’s no evidence of an adverse effect.

Dr. Gabrielle Lyon 57:49

The other thing that comes to mind is this idea that there are polyphenols, and there are these other components that we get from olive oil, probably avocado, which may have a inflammation lowering effect, potentially, it seems as if. And I wonder, and this is just speculation, on my part, is if seed oils are or these oils are kind of devoid of it’s kind of like the equivalent of eating boiled chicken. You know, maybe we are not exposing our body to the natural food matrix compounds that would come with these types of oils.

Kevin Maki 58:29

Yeah, and, you know, I think there this is one of the reasons that I talk about a diet that is rich in whole grains, fruits and vegetables, nuts, seeds, legumes, non Trejo and seafood. So I say, Well, you know, let’s have a variety of things. And do I think you should be, you know, having tablespoons of corn oil, for example? No, I think but

Dr. Gabrielle Lyon 59:00

the evidence would suggest just that maybe it would lower. I don’t know it would improve the ratio of

Kevin Maki 59:09

but do I think

Dr. Gabrielle Lyon 59:10

Would it

Speaker 1 59:11

improve?

Kevin Maki 59:11

And

Dr. Gabrielle Lyon 59:12

you guys can take that out the Omega six?

Kevin Maki 59:14

No. So I mean, again, I don’t think the ratio is important. I think having enough omega threes is important. And I think that the higher the Omega six, there’s probably some ceiling on that, but from the observational evidence, the higher the Omega six, the better things look, and the better the outcomes have been in observational studies. So we

Dr. Gabrielle Lyon 59:36

don’t need to be afraid of seed

Kevin Maki 59:37

oils. So I don’t think we need to be afraid of seed oils. But what I would say is, well, don’t eat exclusively seed oils. Eat some seed oils, you know, canola oil, corn oil, but include some olive oil. And if you want to have some avocado oil, that’s fine. Mix it up. And also eat these plant sources where you’re going to be getting the. Compounds that are coming along with those. We don’t necessarily understand all of them. There are 1000s of them. So if you eat, you know, balanced diet that has lots of sources of fatty acids, focusing, you know, on the unsaturated fatty acids and getting enough of those, I think that you’re likely to have a better profile than somebody who focuses on just seed oils, or is on, say, a carnivore diet where there is almost none of those. Now, for certain individuals, you know they may respond well to a carnivore diet. There are lots of anecdotal reports of people with autoimmune conditions responding to that. So I’m not saying that Absolutely. There’s never a case where that might not be worth a try, but I think for most people, a balanced diet is what you’re looking

Dr. Gabrielle Lyon 1:00:58

for. Is there a moment in time where we will get to I really find it fascinating, this idea of, we’re talking about monounsaturated, we’re talking about saturated, but and also, Tom Brenna was mentioning this, that there’s, you know, so many different fatty acids that I just can’t help but think about This idea of personalized nutrition that a fatty acid might be relevant for me, say, at a higher level than might be for you, and if we’re ever going to get there to that, because right now, we get the big markers that we’re looking at, we’re looking at LDL, cholesterol, we’re looking at a bob. But when we think about really doubling down on that food matrix and subsequently the metabolomics of it.

Kevin Maki 1:01:44

I think we have a lot to learn, and I’ll say two things. One is, we’re not doing a great job of just controlling the big risk factors for cardio metabolic diseases. You know, my flash click. So there’s a lot of work to do in just dealing with those risk factors, managing blood pressure, managing lipids, managing carbohydrate metabolism to minimize the risk of developing diabetes for people with pre diabetes, okay, so a lot of work to be done there. Then scientifically, I think that there’s a lot of potential for identifying subgroups of people who are going to respond differently. I’ll give you one example. There are these fatty acid Desaturase enzymes, and there are different subsets. So you can have sort of subset A or subset B, so they’re genetically determined. And it does seem that there is a different inflammatory response depending on the type of fads, enzyme type that you have, and so we have a lot to learn about these things. So I think for the most part, we can study large groups of people and say this is what happens on average. But that doesn’t mean it’s always going to be what happens in an individual case, because both the phenotype and the genotype, phenotyping those characteristics that you can observe and genotyping the genes that the person brings to the party can influence response to dietary and drug interventions.

Dr. Gabrielle Lyon 1:03:19

I hear you say that, but I also have to just highlight you’ve done a really good job. You’re and you guys can Google, you can check out Dr Kevin Mackey’s Google Scholar page, but you have been able to answer certain questions that I think people have been asking for a long time, like red meat versus chicken. What is the effect all things being equal on lipid profiles, it’s it’s the same.

Kevin Maki 1:03:42

And I’ll also say that we looked at lots of other things. We looked at C reactive protein as a biomarker for inflammation, we looked at responses for the hormones that control glucose metabolism. Absolutely no difference. And it’s a short study. We have to acknowledge the limitations, but the problem that I see with a lot of the observational evidence is that you have all sorts of correlations. So as an example, higher red meat consumption is associated with higher risk of developing diabetes. But

Dr. Gabrielle Lyon 1:04:22

what’s the mechanism of

Dr. Gabrielle Lyon 1:04:23

action there? How

Kevin Maki 1:04:24

is that working? Is my question. There are some plausible mechanisms that that could explain it, but you might expect that if you do feeding studies, then you would see differences, and we haven’t seen that. We need longer studies and so forth. But one of the problems is that higher red meat consumption, as an example, is associated with higher risk of dying in an auto accident

Dr. Gabrielle Lyon 1:04:48

or eating margarine and Maine.

Kevin Maki 1:04:50

So, you know, I think that you have a lot of difficulty because you can’t statistically unravel all. These things, so higher red meat intake is associated with adverse lifestyle habits, and so that’s an issue. And I’ll just give one quick example, and I don’t want to get into the you know, covid vaccination controversies, but I’ll say that there was a huge study in France where they looked at the French population, and the study was in almost 30 million people, and about 22 million people had been vaccinated, and about 6 million people had not been vaccinated against covid. The people who were vaccinated had 25% lower total mortality. And you say, Wow, covid vaccines saving lives left and right, but they also had 25% lower mortality from auto accidents. Do we think that covid vaccination is making people better, a better driver? Well, the answer is no, it’s probably not. It’s probably a healthy user bias. People who got vaccinated on average, were healthier than people who didn’t. The covid vaccination was associated with 80% lower death from covid. And I would suggest that that was probably a combination of healthy user effect plus an actual benefit of the vaccine. And so, you know, that’s an example of how you can have something, an association that is present but is not causal, and it’s really hard to untangle that.

Dr. Gabrielle Lyon 1:06:40

And then on top of that, we have to recognize that we have inherited scientific beliefs.

Kevin Maki 1:06:46

We do

Dr. Gabrielle Lyon 1:06:46

as much as we would hate to admit. I’ll just give you a few of my favorites, the idea, and you’re gonna laugh at me because you are a legitimate scientist. So I’m gonna start with the simple one. You should wait an hour after you eat to then go swimming, right there. You know that there’s absolutely no scientific for example,

Kevin Maki 1:07:08

yeah, no

Dr. Gabrielle Lyon 1:07:08

scientific data. Even potentially the 10,000 steps came from a study in Japan from a pedometer company,

Kevin Maki 1:07:17

yes, for and, and interestingly, subsequently, lots of studies have been done, and they do actually tend to show that you get benefits at less than 10,000 steps, but it really starts to plateau beyond 10,000 steps. So it seems like they got it about right in terms of where you’re going to get most of the benefit. But who knows where they came up with that. What

Dr. Gabrielle Lyon 1:07:42

about the drinking eight glasses of water?

Kevin Maki 1:07:44

Drinking eight glasses of water? Absolutely no scientific support for that.

Speaker 1 1:07:49

And

Dr. Gabrielle Lyon 1:07:50

then I’m going to make a big jump. You’re not going to like this jump.

Kevin Maki 1:07:52

Okay, I’m ready.

Dr. Gabrielle Lyon 1:07:54

But when we think about the idea of a healthy diet, will people say, Oh, well, that’s obvious, fruits and vegetables and grains and proteins. And then in my mind, I’m thinking, Yeah, but is it? Is this, you know, because breakfast was a construct, the idea that we’ll have cereal, you know, all of these things. I mean, I think left to someone’s own devices, or just allowing a human in the wild, which we don’t have. I think, Okay, well, maybe there’s a relationship with a protein leverage hypothesis, but we I

Kevin Maki 1:08:30

just have to

Dr. Gabrielle Lyon 1:08:31

check myself.

Kevin Maki 1:08:32

You know, the trouble is, we have all of these things that we may believe or we may have been taught. And I’ve been around long enough and doing this long enough that some of the things that I was taught in my training turned out to be not only not true, but the opposite turned out to be

Dr. Gabrielle Lyon 1:08:48

true. You had mentioned butter and saturated fat, was that the story there was one thing that there we talked about, I think maybe last year, year and a half ago. Well,

Kevin Maki 1:08:56

butter is interesting because their dairy fat is high in saturated fats, and butter will raise LDL cholesterol

Dr. Gabrielle Lyon 1:09:06

by how much.

Kevin Maki 1:09:08

Well, the The answer depends on how much you eat and you know your responsiveness, and so forth, but butter will raise LDL cholesterol. But the same amount of saturated fat in cheese has a pretty neutral effect, or a very modest effect. So it turns out it’s more than just the saturated fat. And then to add further to it, dairy fats have some specific fatty acids that you don’t find elsewhere in the diet for the most part,

Dr. Gabrielle Lyon 1:09:35

that are protective,

Kevin Maki 1:09:37

that may be protective. So in observational studies, these particular fatty acids. So they’re odd, carbon 15 O, 17 O, saturated fatty acids

Dr. Gabrielle Lyon 1:09:47

I was going to ask you about if I didn’t know if I wanted

Kevin Maki 1:09:49

to bring it up. So, you know, in observational studies, again, we have to be careful, because we don’t have randomized, controlled trials. But in observational studies, higher levels of those are associated with more favorable. Cardiovascular and metabolic outcomes. So

Dr. Gabrielle Lyon 1:10:03

I was going to ask you about that. For example, does that mean that we should supplement with carbon 15 or something like that?

Kevin Maki 1:10:12

So there, I mean, there’s a product, fatty 15. It’s getting a lot of attention, a lot of people promoting it. And what I would say is, I’m waiting for the clinical trials in humans to show me a benefit. Now, is it conceivable there might be a benefit? Absolutely, and

Dr. Gabrielle Lyon 1:10:31

I’ve thought a lot about this, just because that’s what I do. And you know, I’m a very fun Friday night type of gal. It’s let’s talk about fatty acids.

Kevin Maki 1:10:40

Fatty acids, yeah.

Dr. Gabrielle Lyon 1:10:41

But for those that are not eating high fat dairy, then essentially their diet would be devoid of that. And in my mind, what are the, what are the things that we’re missing, potentially fatty 15. And there is data for, you know, animal models, and then in humans, I, you know, I’ve, I’ve tried it.

Kevin Maki 1:10:58

I think the original data came from a veterinarian who was studying dolphins. That’s

Dr. Gabrielle Lyon 1:11:04

right,

Kevin Maki 1:11:04

and so you know, having said that, what I’d like to see is clinical trials in humans that show me that when you take this, it moves the needle. Now, what we found in a study we did comparing full fat to low fat fermented dairy products, we looked at the red blood cell fatty acid profile, and we saw no change. Over 12 weeks, we saw no no difference at all. That’s surprising, and I was surprised. And in conversations with some folks who have data that are not published, I can’t talk about the details, but they’ve said the same thing, we couldn’t find any change in, say, red blood cell membrane levels of fatty acids. Now that doesn’t mean there isn’t a potential benefit. I just think we need to do the studies to find out. I

Dr. Gabrielle Lyon 1:11:55

don’t know how we got lost on that tangent, but I think it was the things that you were surprised by, and it was the high fat dairy potentially.

Kevin Maki 1:12:03

Yeah, high fat dairy did surprise me a few years ago, so we’ve done a more recent study, but a few years ago, we did a study, and we compared dairy foods to foods that are higher in carbohydrate, and the dairy foods had more saturated fat, and they did not raise LDL cholesterol, and I was surprised by that at the time, it was not what I was expecting. And we were focusing in that study on blood pressure, and dairy intake has been associated with lowering of blood pressure, so we saw no effect on LDL cholesterol, which I expected to find. And then we saw no effect on blood pressure, either, but we did see in a subset that had endothelial dysfunction that their endothelial function was improved when they were consuming the dairy. So as often is the case you do a study, you have certain expectations. Sometimes it turns out the way you expect, sometimes it doesn’t, and often you end up with more questions than before you started.

Dr. Gabrielle Lyon 1:13:05

You’ve been a career scientist for how long now,

Kevin Maki 1:13:09

35 ish years,

Dr. Gabrielle Lyon 1:13:10

have you found your ability to tolerate not getting the answer that you want has improved over time?

Kevin Maki 1:13:18

You know, honestly, from early in my career, I just wanted to know the answer to the question, and I would go in with expectations. And what I’ve found is my predictions are about like predicting the sex of a baby. I’m right about half the time, and certain things have been very consistent. We see it over and over again, and other things have surprised me, and there’s a great expression, which is the greatest scientific discoveries are rarely heralded with the cry of Eureka. More often, it’s more like, Huh. That’s funny, because it gives you, you know, you expect one thing, that’s not what happens, and then you have more questions, and you can design more studies to address those questions, because lots of things, as I said that I was taught, turned out to be not only untrue, but the opposite turned out to be true. And this is left me realizing that, you know, it’s great to think you know something, but really check the evidence. And then often we have to acknowledge our uncertainty. We have to do the studies to really understand what’s going

Dr. Gabrielle Lyon 1:14:27

on you’ve been working on. I mean, you’ve been very busy. So I think I have, 12345, I don’t know, 10 new papers that from 25 to 2026, quite a few new papers that are out or coming out.

Kevin Maki 1:14:44

We’ve we’ve been busy.

Dr. Gabrielle Lyon 1:14:47

Can I just ask you quickly about exercise in terms of, then again, you guys can cut this if you if you want or not. But do we know the. Fact, both short term and long term on meaningful biomarkers like HDL, I think I told you, Faden magos. Do you know him? He’s on with Atherton, and

Kevin Maki 1:15:13

I know of him. I don’t really know very

Dr. Gabrielle Lyon 1:15:16

dear friend. He’s hilarious. He lives in Greece. Faden can come visit any time, and he’s really began to exercise. And one of the questions I have is that, as we start to recognize muscle as this organ of longevity is truly an endocrine organ, just as important as the heart, what are the changes by utilizing muscle? What are the overall changes that we would see with both short term and long term with HDL and LDL?

Kevin Maki 1:15:47

So exercise has lots of benefits, and so it favorably affects lots of risk markers for cardio metabolic disease, and sometimes it’s underestimated because it has a little bit of an effect here and a little bit of an effect

Dr. Gabrielle Lyon 1:16:04

here, and a little bit I like that

Speaker 1 1:16:05

over

Kevin Maki 1:16:06

here. Also, what I tell people, insulin sensitivity, I think, is a really important factor in both cardiovascular disease and diabetes risk. Well, when you exercise for about 48 hours after you exercise, you have improved insulin sensitivity. And so what I tell people is it’s like a pill that you take. It just takes you 30 minutes to swallow it. And if you stop taking your blood pressure drug, your blood pressure will go up. Well, if you stop exercising, your insulin sensitivity will get worse. And so I think exercise has lots of benefits now, as far as HDL cholesterol, one of the main things exercise does is it increases the clearance of triglycerides. Whenever you lower triglycerides, you tend to raise HDL cholesterol. So I think the most consistent effects of exercise as far as lipids go is to lower triglycerides, raise HDL cholesterol. And then, you know, there are both shorter term immediate effects and then longer term effects. And so exercise is one of those things where the observational evidence, I think, pointed us in exactly the right direction that higher exercises associated with more favorable outcomes for all kinds of

Dr. Gabrielle Lyon 1:17:24

things. And again, whether it’s resistance training or cardiovascular activity, I think that we’ve just

Kevin Maki 1:17:31

and yeah, both, both are really important. And I think resistance training has been the somewhat ignored stepchild in the exercise arena. But that’s changing, that

Dr. Gabrielle Lyon 1:17:44

that is changing. And you know, as I was thinking about today’s episode, we have pre diabetes markers, we have ways in which we can risk stratify mace or cardiovascular disease. And they’re thinking, we don’t really have great pre clinical sarcopenia measures, or, you know, just all of a sudden someone becomes sarcopenia. Well, we know that that didn’t happen.

Kevin Maki 1:18:12

Well, here’s the thing where we talked when we were before we were recording, we talked a bit about AI. There’s something called Jevons paradox, and Jevons paradox says when you make something cheaper, you will increase the demand for it. And so everyone’s worried that all of these jobs are going to be eliminated by AI. And that’s true, there will be some jobs eliminated by AI, but using imaging, medical imaging, as an example, well, what we’re going to have is a situation where you need 1/5 or so of the number of radiologists to read the images that are created. So you can read just as many images, and you need one radiologist instead of five to review the images, but that’s going to bring down the cost of doing the imaging, and so you’re going to have a lot more imaging being done. So eventually you’ll probably need more radiologists. You’re doing 10 times as many scans, and you need 1/5 as many, you know, for a given number of scans, but you’re doing 10 times as many. You need more radiologists, not fewer. Well, I think that imaging is going to really benefit from AI, and I think that we’re going to be able to use imaging much more effectively and precisely to measure things like sarcopenia and to measure things like progression of atherosclerotic disease, so that we can test interventions and we can also stratify risk much better than we can today. So very excited about the potential for imaging to really revolutionize prevent. Active medicine. And what

Dr. Gabrielle Lyon 1:20:03

is that called? What

Kevin Maki 1:20:05

was the Jevons paradox? Jevons,

Dr. Gabrielle Lyon 1:20:07

I’ve never heard that.

Kevin Maki 1:20:08

Yeah, so Jevin was an economist and realized that, you know, every technological revolution, people are afraid that jobs are going to be eliminated. And you know, when Henry Ford created the assembly line to create cars, it did eliminate all the buggy whip manufacturers, but it created other jobs. And so I think that the concern about AI eliminating too many jobs, it’s going to displace people. But I think ultimately will result in more jobs, not less

Dr. Gabrielle Lyon 1:20:45

all. I’m always interested in your perspective, because you have been, I don’t know if the right word is decades ahead, but you’ve been thinking about things. And I think good scientists are thinking about things before they’re happening because they have questions.

Kevin Maki 1:21:02

Yeah, and one thing I’ve learned is, you know, science, in large part, is about understanding how things work so that you can make predictions, but I think we also need to be humble about what we know and what we don’t know, and so we also have to understand that a lot of predictions don’t come to pass,

Dr. Gabrielle Lyon 1:21:20

especially the weather. I have a closing question for you, if someone wants to reduce their long term cardiovascular risks and live a healthy life from an evidence based perspective, what are the few things that they should be doing?

Kevin Maki 1:21:37

Well, the first thing is, know your risk factors. The big numbers are the ABCs, so a 1c which relates to glucose control, b is your blood pressure and C is your cholesterol level, so LDL cholesterol, so know your ABCs and then have a healthy lifestyle. So that is a healthy diet, physical activity, including getting your steps in resistance training, stress management and adequate sleep. I think I was hoping you’re

Dr. Gabrielle Lyon 1:22:06

leaving that out

Kevin Maki 1:22:07

those and avoiding tobacco. So you know, if you do those things, you’re ahead of large percentage of the population. And I think we’ve got good evidence, some things stronger than others, but I think we’ve good evidence that if you do those things, you’re going to really improve your chances.

Dr. Gabrielle Lyon 1:22:25

Dr, Kevin Mackey, it is always such a pleasure to have you on thank you so much for your time.

Kevin Maki 1:22:30

Thank you for the invitation that it’s really been fun.

Dr. Gabrielle Lyon 1:22:34

Okay, some strong, sweet questions.

Speaker 2 1:22:36

Good job.

Dr. Gabrielle Lyon 1:22:38

I have so many questions. I was trying to stay on track, like, for example, I’ve been.