What Science Says About Your Cholesterol Levels, Dietary Cholesterol, Statins, And Their Role In Cardiovascular Disease, with Dr. Chris Masterjohn, Ph.D.

In this episode, I am speaking with Dr. Chris Masterjohn – who has a Ph.D. in nutritional sciences and who is widely regarded as one of the top nutritional biochemistry experts in the world – about the science on cholesterol levels, dietary cholesterol, statins, and their role in cardiovascular disease.

In this podcast, Dr. Masterjohn will cover:

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What Science Says About Your Cholesterol Levels, Dietary Cholesterol, Statins, And Their Role In Cardiovascular Disease, with Dr. Chris Masterjohn, Ph.D. – Transcript

Ari Whitten:  Hello everyone. Welcome back to the Energy Blueprint Podcast. I’m your host, Ari Whitten. And today I have with me for the second time, my friend Dr. Chris Masterjohn who has a Ph.D. in nutritional sciences and who is widely regarded as one of the top nutritional biochemistry experts in the world. When it comes to the understanding of the biochemistry of nutrition and metabolism of various foods and nutrients, I personally consider him to be really a genius, literally one of the most brilliant people and most knowledgeable people in this field. Especially, when it comes to things like vitamins and minerals and their physiological roles in the body. I literally cannot think of anybody who knows that science better than Chris does.

So, I’m excited to bring him to you guys for the second time. Welcome, Chris.

Dr. Chris Masterjohn:  Thanks, Ari. It’s great to be here. Thank you for that very generous introduction.

Ari Whitten:  Yeah, I mean it. And I want to say that I’ve also been following your work literally for way, way longer than we’ve actually met. We met for the first time, I think a year ago or something like that. But I’ve been following your work, I want to say for at least 10 years maybe. I mean, you were, I think, writing stuff or Weston Price foundation…

Dr. Chris Masterjohn:  Yeah, I started doing this in 2004.

Ari Whitten:  Yeah. So maybe even closer to 15 years ago. Yeah. Now with that in mind, one of the things I want to talk about first is cholesterol. And this is something that I think, if I remember correctly, you actually did your Ph.D. dissertation on a topic related to this, right?

Dr. Chris Masterjohn:  No, I did my dissertation on methylglyoxal and dietary antioxidants and regulating this particular compound that’s a byproduct of diabetes metabolism. But I did make a website about cholesterol in 2005.

Ari Whitten:  Yes.

Dr. Chris Masterjohn:  Way, way, way before I went to Grad school. So that’s been hanging around for longer than my dissertation.

Ari Whitten:  You’ve been studying the science around cholesterol and relevance of that to cardiovascular disease for 15 years?

Dr. Chris Masterjohn:  For the longest. Yeah, yeah, yeah.

 

The connection between cholesterol and heart disease

Ari Whitten:  So, this is a controversial subject. And you know, I know some of the Facebook circles that we run in, sometimes I see debates between you and some other people. And on the one hand, we have people like a lot of the people in the low carb and keto movements who are trying to say, cholesterol doesn’t matter, cholesterol is good. There’s no link with that in cardiovascular disease. And then we have also like the hardcore conventional doctors who are kind of in the standard thinking statins are good, we want to keep LDL as low as possible. And so, there’s this kind of debate out there.

As someone who’s been studying this topic for over 15 years, can you give kind of a big picture overview of what these sort of two schools of thought are and where you lie on the spectrum and what you think the science really tells us about the role of blood lipids and dietary cholesterol in relationship to cardiovascular disease?

Dr. Chris Masterjohn:  Yeah. Well, I’m in the middle. I’ll say that. But less of an in between two extremes and more of a… I guess my basic position is I feel like there are essential components of truth on either side. I don’t think that you would be able to write whatever there are now, six, seven, at least really popular books and probably a lot more than that that are not so popular books on why the whole cholesterol theory is false if there wasn’t something objectionable about some aspects of it. But on the other hand, to say that there was no evidence behind it is really bizarre in the sense that there are few topics that have… There’re a few topics in medicine that have more science behind them than the role of cholesterol and heart disease. The whole theory of cholesterol as the cause of heart disease was a vehicle for major advances in science in a number of ways.

For example, the first Meta-analysis, which is a study about studies, basically. Pulling the results of many studies to have a statistical way to say what does the overall literature say on a subject. The first meta-analysis was done about cholesterol. A lot of the advances that were made in molecular biology, the first example of a receptor that brings something into a cell was the LDL receptor. And now that’s a whole field of molecular biology is those types of receptors. First one was the LDL receptor because everyone was trying to answer the question, how does cholesterol cause heart disease?

So there literally is, there is like nothing in biology that has medical and health relevance that has more science behind it. So, for someone to stand there and say that there was never… and people often do on the cholesterol skeptic side say “there was never any evidence supporting this,” is absurd because if there was nothing as the foundation, how could you have so many advances covering so many areas of science over an entire century of work? You can’t have that if there’s nothing there. So, the basic progress of the theory on cholesterol was as follows. In the turn of the 20th century, there were researchers in several parts of the world, especially in Russia – this was some of the main research – and they were experimenting with rabbits because rabbits are known to develop atherosclerosis pretty easily. And they were trying to answer the question, what is the cause of atherosclerosis? And the dominant viewpoint at that time that the people who thought diet was relevant, that they were arguing against. The dominant viewpoint was atherosclerosis is just an inevitable consequence of aging. And there’s nothing you can do about it. And there’s nothing that causes it except getting old, right? And these researchers were saying, “no, there must be more to it.”

And they had done all kinds of things to the rabbits. Like they would raise their blood pressure by restricting certain blood vessels. They hung them upside down. They injected them with adrenaline and all kinds of toxins. They did this huge laundry list of things to these rabbits and nothing ever caused heart disease until they started feeding the rabbits cholesterol. Or actually, foods that contain cholesterol, meat, brain, eggs, things like that. And now that doesn’t mean that that, so you don’t want to generalize from a rabbit to a human with diet, because rabbits have different ancestral diets than humans do. Our physiology, dietary effects across the animals can vary very widely. But the basic pathological mechanism of atherosclerosis doesn’t vary that much. And the reason that we know that is that first, they showed that cholesterol caused heart disease in rabbits.

Then they showed that in almost every other species the dozens of species were used to show this. And there were a couple of exceptions, dogs and rats and mice and those exceptions where because those animals happen to clear cholesterol from their blood really fast. And what they did was show that as long as they could raise their blood cholesterol, which they couldn’t do by feeding dietary cholesterol, but they could do by other means, then boom, all of a sudden, they behave just like the rabbit.

And so, at that point, it became clear that it’s not about dietary cholesterol because you can’t generalize from a rabbit to a mouse. On that point, it is about blood cholesterol because you can generalize from the rabbit to the mouse, to the dog, to the chimpanzee. And then there were questions about like how does that happen?

And when researchers started looking at how does that happen, the major advances were done, were made in the late 1970s, early 1980s, where they showed that lipoproteins which carry cholesterol in the blood have to get damaged. And they can get damaged in a number of ways. Some of the ways that they get damages just through things that happen in normal metabolism. But things that are accelerated by inflammatory processes, by exposure to toxins, by metabolic problems. And so, if you’re unhealthy in any of those ways, you will get more damage to the lipoproteins that carry your cholesterol and you’ll be at greater risk for atherosclerosis. But also, if you just don’t clear those lipoproteins from your bloodstream and they hang out there for longer than whatever amount of damaging stuff you have going on there, simply being exposed to those, to that risk for longer causes you to develop atherosclerosis.

And if you look at what they did with this theory in humans is they said, okay, let’s develop drugs to reduce people’s cholesterol levels. Those that… you can argue about some things like is there enough data in women on this. you can argue about are the rates of side effects for statins as low as they say they are? Or are they cooking the books by narrowly restricting the types of people use in these studies to people who are less vulnerable to the side effects compared to what happens in the doctor’s office?

And there are those questions, but the evidence is overwhelming that cholesterol-lowering statin drugs do reduce the risk of heart disease in people who are at high risk of heart disease. And the mainstream conventional viewpoint interprets that as saying, it’s all about the amount of cholesterol in the blood.

Cholesterol skeptics will look at this stuff and they will dismiss most of this evidence when they’re looking at statin… The results of statin trials, they’re usually, in my opinion being too rigorous with the data.

So, for example, they… and people do this all the time with ideas they question. You can find little limitations to any particular set of data. And when people want to dismiss an idea, they will narrow in and hyper-focus on those limitations to say that that data has no value so that they can ignore it. And I think that’s what cholesterol skeptics are mainly doing with that human evidence. But I think that where I come down on this is… I look at this and say, “look, it’s the mechanistic evidence.” So it’s not about the amount of cholesterol in the blood.

When you use these cholesterol-lowering drugs, what you’re doing is you’re clearing lipoproteins in the blood at a faster rate. You’re preventing damage to them through that. And by protecting them from damage, your protecting the arteries. And I think the cholesterol skeptics have a point in the sense that if your cholesterol is out of the range, especially if it’s a mildly out of the range, like for a man, if your total cholesterol is 2.20, it’s out of the range.

And there are probably plenty of men who have cholesterol like that and are perfectly fine, especially if they don’t have chronic inflammation going on. They don’t have diabetes or other metabolic risk factors. They don’t have an underlying disease state. All of those things that predispose you to get more damaged to those lipoproteins.

Also, cholesterol in the blood is an in-out equation. So, if you are making more cholesterol that gets sent out into the blood, but you’re also clearing it at a very fast rate, you’re not going to be at the same risk as making a smaller amount that just stays there, right?

Because it’s that stagnancy that’s staying in the blood that’s actually generating that risk. And you can’t tell if someone has cholesterol of 2.20, whether the extra 30 milligrams per deciliter, that that put them from the Green Zone to the yellow or red zone on that lab results. You can’t tell whether that’s a result of making a little bit more or clearing it a little bit less effectively. And that might make the difference between whether they truly are or are not at greater risk of heart disease.

But I think when you’re dealing with people in the general population who aren’t eating that well, probably most of the time when the cholesterol is high, it does reflect the negative process of not clearing it very effectively.

But then you can have someone who’s super health conscious has chronic inflammation down to a minimum and their cholesterol is a little higher because they’re eating coconut oil. And in that person, it’s probably a little bit higher because they’re making more, they probably are clearing and effectively and it probably isn’t oxidizing.

But on the other hand, if you have someone who’s got a total cholesterol 3.50 and whether they’re in one camp or the other, they probably have a problem there. Because even if you look at the ancestral populations who are not a subject to modern society, they are not eating industrial foods. The highest cholesterol levels in the world are found in on the island of Tokelau where they have the highest saturated fat intake on the planet because they have coconut as a major staple in their diet. And their cholesterol levels will get around 2.20 for men. And for post-menopausal aged women, they’ll get up to like 2.50 to 2.60 and they have zero risk of heart disease there. And so, they kind of, they illustrate that camp, right? Just because of the coconut. Their cholesterol levels are boosted up, but it’s not actually a problem for them. But they also illustrate the point that you don’t see cholesterol levels of 3.50 there, right?

So, no one has a cholesterol level of 3.50 just cause they’re eating coconut.

 

The science on statins

Ari Whitten:  Gotcha. So, a couple of specific questions here. One is on statins specifically. I know you said the data is clear that they do reduce risk of heart disease, of Atherosclerosis, in people who are at risk. Now, I’ve heard a lot of sort of nuanced arguments around this. For example, looking at who are not necessarily at high risk, what is the effect of statin drugs there and that was not particularly effective. And then I’ve also heard some statistics or arguments around how statistics kind of get manipulated in certain ways to… specifically around this idea of the number needed to treat. Like if you look at the statistics one way that they seem very impressive. And then if you look at it another way, it’s like, well, you had to treat a hundred people in order to prevent, to reduce the incidents of heart attacks in two people.

Dr. Chris Masterjohn:  Those are valid arguments about the relative probability that an individual will benefit and their arguments that are relevant to the magnitude of the effect, but they’re not arguments that are relevant to the cause and effect relationship. So, one of the things that come up is absolute versus relative risk. If you say statins reduce the risk of heart disease in this population by 30%, then that sounds really big. But if you say that they’ve reduced the risk from 1% to 0.7% and they reduced it by an absolute factor of 0.3%, then it sounds really unimpressive. But the latter, the absolute risk that’s telling you more about quantitative factors like how many people will use save for heart disease. If you take action x, that’s not what you want to look at. If you want to answer the question, do statins reduce the risk of heart disease?

The relative risk is much more relevant when you’re just asking that question. Do they have the effect? Right? Because if you cut the risk of something in half, you cut the risk of that thing in half. That’s an effect. The question that the other… so they’re both useful. They’re not… It isn’t one is useful and one’s not. Relative risk is a better way of visualizing what the cause and effect relationship between one thing and another thing is. Absolute risk is a much better way to visualize what will be the net total effect on the number of people who have heart attacks if we carry this out on a population-wide policy.

Ari Whitten:  Gotcha.

Dr. Chris Masterjohn:  What none of those things tell you, is anything about what it will do in an individual. Right? So, the number needed to treat is saying “you have to treat a hundred individuals to save three from heart disease”, for example.

But that’s in an individual, you’re either going to save them from heart disease or you’re not. And you don’t know the answer to that question. So, it’s a probability because it’s a fact that you don’t know, and you generalize from these studies to guess your probability and your confidence about that person. But those studies aren’t actually telling you about that person. Those studies are just telling you about the “what happens in a population.” And so, it’s really like nothing tells you what will happen in that individual. Those studies are all just telling you at a population level is if you implement a policy, what’s the net effect of it.

Ari Whitten:  Right. Now, those numbers that you threw out as far as, let’s say, I think you’re just throwing these out as an example, but you’re talking about like, let’s say if it cuts your risk in half, it cuts your risk and half. Are these numbers just an example? Or are you specifically talking about the actual…?

Dr. Chris Masterjohn:  I was just, I was just throwing that out as an example to make the math easy.

Ari Whitten:  Okay. So, can you speak to what you think, like kind of speak to something to estimate the magnitude of the effect size that you’re talking about with regard to statins preventing cardiovascular risks and what specific populations you think?

Dr. Chris Masterjohn:  Yeah. I can’t right now because I don’t have the data in front of me, but I can speak to a couple of principals and I do want to address a couple of things that you brought up. So, one of the problems with the numbers needed to treat data, and this is part of why I don’t bother memorizing any of these numbers, is that they’re all based on the amount of time that the people have been treated with.

And so, if you bring those arguments to cholesterol skeptics make about the high numbers needed to treat to a conventional lipid person. They’re gonna, they’re gonna point out. Yeah. But that trial was done over five years. If you start treating someone’s high cholesterol at 40 until they’re 80 than you have 40 years, the number needed to treat is going to drop down to like zero. They can’t drop down to zero, to one or something like that. Like that would be their argument. But there are no studies carrying these out over 30 or 40 years, which is the length of time that they’re being given. And I think that’s a completely legitimate argument.

And so, it is definitely true. And off the top of my head, I don’t remember the specific numbers, but it’s definitely true that the number needed to treat is very high.

I think something like 300 or 600 a to one when you’re dealing with populations who do not have existing heart disease, right? So, if someone has heart disease, you know they’re at high risk of heart disease because they already have it. And those are the populations where over a five-year study you can show a very big effect.

Ari Whitten:  And just to be clear, when you say they already have it, that’s as verified by what diagnostic tests by a scan where they actually visualize the plaques?

Dr. Chris Masterjohn:  It might. It probably varies from study to study. But generally, like this is someone who’s had a heart attack already.

Ari Whitten:  Okay.

Dr. Chris Masterjohn:  Yeah. So, these are people who have the existing condition where you see the high efficacy. When you look at primary prevention, which means just take a sample of people from the sample of the population that you’d expect to be given these things as in a preventative way in the doctor’s office. And then you follow them over five years. You’re not going to see many people have heart disease or having a cardiovascular event. Therefore, because the number of people who have cardiovascular events is so low, you are not going to see many people saved from heart disease.

And so, the number you need to treat in that population has to be really high. Because if you follow the people for, if you take a hundred people and you follow them for five years and three of them had heart attacks, well, how can you ever get a low number needed to treat when 3% of the people in that five year period even had the problem that you’re trying to treat. You couldn’t have a number needed to treat of one because nowhere near 100% of the people had the problem. And so, if you take those people and you follow them over 50 years, you’re going to get a very different picture. And the number needed to treat is probably gonna be a lot lower. The perceived efficacy is probably going to be a lot higher. I think it’s kind of neither here nor there, in my point of view, because I don’t actually… I think statins are over-prescribed, and I think they’re largely overprescribed because they’re so profitable.

And also, because there’s a bias in medicine of believing that people are not going to comply with lifestyle modifications. And so, they just say, “screw it, we’ll give them a go.” And I think for those two reasons are massively over-prescribed. But like I rarely find myself suggesting anyone go on statins. I think they have a place. But I think their proper place is for people with familial hypercholesterolemia or other problems that, you know, they went the full mile and diet and lifestyle, and they just didn’t get somewhere. I’m not that concerned with the number needed to treat because to me it’s a backup on the backburner anyway, I just raised the point because it’s a key piece of evidence of on the question you posed initially, which is what’s the truth about whether cholesterol causes heart disease?

Ari Whitten:  With that in mind, there’s almost, I know we’re missing some pieces here as far as, there are a lot more nuances we could talk about, but there’s something interesting that standing out here like me, which is, on the one hand, you’re saying there is this very clear mechanistic link between elevated cholesterol levels and elevated risk of cardiovascular disease. On the other hand, you also just said you think statins are over-prescribed. So, let ask you, just to kind of play devil’s advocate. If there is this causal link and statins are effective in lowering cholesterol levels, why wouldn’t you just say let’s put everybody on statin drugs?

Dr. Chris Masterjohn:  Well you could say that. And you can just add them to the water supply…

Ari Whitten:  I know that has already been discussed.

Dr. Chris Masterjohn:  Yeah, it has. So first of all, as I said before, I am very sympathetic to the idea that the risk of side effects are underappreciated. And I do think it’s true that the po… I mean, when they do the studies, they basically screen out anyone that they think is at risk of side effects. And in the doctor’s office, they don’t screen people out that rigorously. And so, I think that you have a very “clean population” being used to assess quantitatively the risk of side effects.

And then you have a very messy population in whom the side effects are actually occurring. And so, I think some people claim based on clinical experience which is anecdotal, but some people claim that as many as 10 or 15% of people are getting side effects from statins. And we can’t verify those numbers, but I think they probably have some merit. And you look at like [Duane Graveline’s] story, who was a NASA astronaut, he went on Lipitor twice and he got transient global amnesia both times where he basically forgot who he was or he reverted back to his high school memory and his wife had to lure him into the house with cookies and milk when he was wandering around in the yard and stuff like that. And he made a syndicated column about his experience and you started getting hundreds of letters from people who are saying “the same exact thing happened to me.”

So, I think the side effects are probably a lot more common than what they say for the numbers in the literature. And then the other thing is I’m looking at it biochemically like, so everything that I do is, is all about looking at the mechanisms of stuff and trying to understand like how the body should work. And I base my ideas on what’s a good bad thing. Largely, especially when there are gray areas where we don’t have studies answering clear questions. Which is most of the time. I base my ideas on how things work and how I think the system should not be operating and how it shouldn’t be. And statins are a very blunt tool to lower cholesterol because they don’t actually lower the way that they have their clinical effect is they increase the amount of LDL receptors in the liver, which increases the rate at which lipoproteins are taken out of the blood.

And from my perspective, that’s making them less likely to be damaged, less likely to make it into the artery and that’s why they prevent heart disease. The conventional lipid person is going to say, almost the same thing I just said, that they’re going to say more LDL receptors lowers the cholesterol level in the blood. And because there’s less cholesterol in the blood, they get less heart disease. But statins aren’t a drug that increases LDL receptors. What they do is they decrease the synthesis of cholesterol in the liver. So, the liver wants more cholesterol because it doesn’t have enough, and it starts taking in from the blood. But they don’t directly do that either. They inhibit the synthesis of a compound that is way, way upstream in this pathway of cholesterol synthesis that requires dozens of steps and there are many other things that you make from that thing. Right?

So, statins decrease the synthesis of coenzyme Q10 just as well as they decreased the synthesis of cholesterol and you’re a mitochondria guy. Right. So that you think that’s a good thing or a bad thing?

Ari Whitten:  Yeah. So, I was just going to say to point out specifically some of the side effects of the statins in this… you said 10 to 15%, let’s say it’s 10% of people, roughly. Some of the common side effects, I believe are CoQ10 depletion and potentially mitochondrial damage, muscle weakness, I believe also neuropathy if I remember correctly or nerve weakness or nerve damage. Excuse me. But I know muscle weakness and certainly the CoQ10 depletion. But are there any others…?

Dr. Chris Masterjohn:  The most severe one is Rhabdomyolysis. Which is a condition where muscle sort of gets…. you also see Rhabdo in like really, really over intense exertion and its sort of like a failure of energy metabolism in the muscle that makes it wind up spilling out all its contents into the blood. And then your urine starts turning like dark brown or red because the Myoglobin, which is the key red protein in the muscle… The muscle cells are just falling apart. That’s considered pretty rare at that point. But you know, if rarely people get that, you can imagine that muscle weakness is maybe 10% of that. Right. If a tiny handful of people get that, then a lot of people must get whatever the five to 10% pathway towards that is. And muscle weaknesses is probably a major one.

And the neurological issues probably. Rhabdo is definitely the one that is the paid the most attention to in the literature. If you look anecdotally, then yeah, muscle weakness. I mean certainly, that transient Global Amnesia is an example of pretty significant neurological problems. So, Coenzyme Q 10, I mean, I don’t know if you consider that a… It’s not a clinical side effect and indeed some people would say there was no clinical significance to it. And I think it was Merck patented a combination of CoQ10 with their statin and they never put it on the market. And someone favorable of statins is going to say to them and put it on the market because no one could ever show that there was a clinical effect of the CoQ10 depletion. But the cynic is going to say they never put it on the market because they didn’t want to draw attention to the fact that statins deplete CoQ10. There’s probably some truth to both of that in the sense that no one has gone out and shown; “Oh, and everyone who gets CoQ10 depleted, this clinical thing happens.”

Ari Whitten:  At the same time, it’s not like we know the importance of CoQ10 from a lot of research. It doesn’t take a huge leap of logic to speculate if something depletes CoQ10 that it’s gonna cause some problems and the thing, the roles, the CoQ10 plays in the body.

Dr. Chris Masterjohn:  Absolutely. And part of the problem though is that the… what you would expect to be the symptoms of that are so vague and difficult to identify. Right. So, I think one of the big reasons that fatigue is such a big problem is that you can be fatigued because you didn’t sleep that well last night. You can be fatigued because your motivation is low. You can be fatigued because your mitochondria are screwed up. You can be fatigued because you’ve got a genetic problem and energy metabolism. You can be fatigued because you’re missing one of any, you know, dozen and a half nutrients.

And so, someone goes to the doctor and they’re like, I’m tired all the time. What’s the doctor going to do with that information is if there’s no really good blood tests or something to say…. Like, if you could go into the doctor and saying, “I’m tired all the time” and they’d stick a little, prick in your finger and say, “oh, it’s because your CoQ10 is low.”

That would, you would go somewhere. But with statins and memory loss too. Like, well I’m forgetting my keys where I left my keys more often…The doc… So, when I first got glasses, I asked the doctor I was 17. I asked the doctor,  “why do I need glasses now, and I didn’t need them when I was 15?” He said, “you’re getting older.” And if that’s what he says to me, that I’m 17, then surely someone who’s 47 or 57 who goes in and says, “yeah, I’m forgetting where my keys are more often.” They’re going to say, “hey, you’re getting older. What do you expect?”

Ari Whitten:  There’s something I want to add to your point about going to the doctor when you have this kind of vague symptom like lack of energy, fatigue. There’s actual research on this where they’ve assessed how often is specifically in the context of fatigue. And I’m happy to share this post to link to it. It’s called “Fatigue, an overview” and it was basically a review of the literature and evidence-based practice guidelines published in the American Journal of the Family Physician. Basically, they state very directly that standard blood tests or what’s recommended when you are treating a patient with fatigue. But 95% of the time they will find nothing of value on that test that leads to any practical recommendation. So probably roughly 5% of the time, maybe they find anemia or hypothyroidism or something to that effect that they can see and might be related to the fatigue and they treat it. But 95% of the time they’re not finding anything. So, to your point, yeah, like CoQ10 depletion can absolutely result in a symptom like fatigue. And there are no tests to specifically identify that the CoQ10 depletion cause that symptom.

Dr. Chris Masterjohn:  Yeah. And I think like it’s, it should be really obvious, right? Statins do not deplete cholesterol any more or less than they deplete CoQ10. It’s not a side effect of statins. It is a drug effect of statins. So, statins block you from making this thing that makes cholesterol and makes CoQ10. So that’s not a side effect. That’s an effect of the drug.

Ari Whitten:  Right.

Dr. Chris Masterjohn:  And so, if you are using a dose of the drug that is meant to deplete cholesterol to clinically significant levels, then why would you think that the degree of CoQ10 would not be to a clinically significant level? Yeah. Right. Like you are using the drug in that dose for that reason and it does that thing. Yeah. And it’s not just CoQ10. MK4, which is a specific type of vitamin K2 is also downstream in that pathway. And there’s a bunch of other things, but that’s another nutritionally significant thing there. And MK4 is involved in cancer prevention. It’s involved in regulating your calcium to get into your bones and teeth and not into your blood vessels where it causes heart disease, not into your kidneys where it causes kidney stones.

Ari Whitten:  … It’s factor x, right?

Dr. Chris Masterjohn:  Yeah. But it’s also very important for Myelin synthesis in the brain. And one area where there’s gotta be some really important stuff here. But exactly what it is, no one knows. They’re a huge portion of the vitamin K in a cell is found in the Mitochondria. And it’s possible that it does something very similar or the same as CoQ10 but is not well researched enough to be included in the textbook discussion of the electron transport chain. It’s possible that it should be the little thing there, right next to CoQ10 passing the electrons on.

 

The role of dietary cholesterol and how it relates to cardiovascular risk

Ari Whitten:  Yeah. Now we’re, we’ve spent a lot of time on this subject, but it’s so fascinating and I’m really enjoying this conversation and there’s actually two more sorts of nuances that I want to dig into here.

One specifically the role of dietary cholesterol in relationship to all of this topic. And there’s a lot of controversy there too, right? So, there’s controversy around the whole relationship of blood cholesterol numbers to cardiovascular risk. We covered that. You covered that. I won’t take credit for your work there. And, then there’s this controversy around dietary cholesterol and you know, that keeps reemerging, that reemerged recently with another epidemiological study that was looking at, you know, egg consumption and said eggs. Basically, there were all these headlines in the media yet again saying, hey, we thought dietary cholesterol wasn’t a big deal, but now there’s a new study and it’s a big deal again. Right. So, can you kind of give your quick summary about the role of dietary cholesterol and how that relates to cardiovascular risk?

Dr. Chris Masterjohn:  Yeah. So, in about two-thirds of people, dietary cholesterol has very minimal, if any, effect on blood cholesterol. And that’s because when you have more cholesterol, you make less. And so, if you make less than you take in more, it just all kind of balances itself out. And about a third of people with cholesterol does rise appreciably, but in those people, it tends to increase LDL and HDL cholesterol equivalently. And so, a lot of conventional people would say that that doesn’t change the heart disease risk. Some people who dispute that. It’s really only about 1% of people where their LDL skyrockets and response to consuming three to four eggs worth a day. One of the points that people make who are very, very anti dietary cholesterol is that all those studies are done with people who are consuming usually at least an eggs worth of cholesterol a day.

Even if they’re not consuming an egg a day, they are consuming that amount of cholesterol from other animal products. And, I don’t think this is well studied. But I think it probably is true that if you put someone on a zero-cholesterol diet, you’re probably going to take them out of that range where everything kind of stays the same and you’re going to lower their cholesterol by bringing it down to zero. I know my total cholesterol was 1.06 when I was a vegan, which is very low. For most people who are not zero cholesterol vegans, it’s not a major thing impacting blood cholesterol levels. In a study like that… I’ll be blunt I honestly think it’s a stupid question to ask, “do eggs increase the risk of cholesterol?” because I think by now it’s really clear that nutritional needs and vulnerabilities vary from person to person. And we have a lot of core information, try to determine how to individualize questions like, and I think in 2019 a valid research or a useful research question is not for the 30,000th time do eggs cause heart disease or not.

There’s a bunch of conflicting, massive evidence from the last decades. It’s probably because we didn’t ask good enough questions. How can we make the question better? And one of the ways we could make the question better would be “can we identify a subset of people who shouldn’t eat very much dietary cholesterol?” I know we can. An example of these people would be people with familial hypercholesterolemia. These people cannot eat very much cholesterol without their blood cholesterol skyrocketing because their means of clearing it from the blood is defective. On the other hand, are there are people who should definitely be eating dietary cholesterol? My guess is yes. So, there’s at least one to 3% of the population has a partially defective cholesterol synthesis and those people are … their health is not well studied, but they’re at increased risk for violent suicide. And that generally reflects the fact that low cholesterol levels are associated with poor neurological health and that makes sense because the brain is 2% of the body’s weight and 25% of it’s cholesterol. Cholesterol is the limiting factor for synapse formation. Virtually everything in the brain is signaling that’s happening between proteins that are anchored in cell membranes by cholesterol. So, a better question is how can we identify the large mass of people for whom this question is totally useless and then a small percentage on either end who should or should not be eating three or four eggs a day?

Ari Whitten:  Right. Just one quick point on this, the people with familial hypercholesterolemia, this is what, less than 1% of the population, I’m guessing.

Dr. Chris Masterjohn:  Yeah. It is less than 1% of the population. I don’t remember the exact stats and it varies from population to population. It’s fairly uncommon. I mean, there are other familial hyperlipidemia and if you add them all up, you’re probably getting somewhere around half a percent or 1 percent of the population, something like that.

Ari Whitten:  I just like to clarify in case there are people listening.

Dr. Chris Masterjohn:  It’s not like a third…

Ari Whitten:  Like 50% of the people that maybe [crosstalk] have familial hypercholesterolemia.

Dr. Chris Masterjohn:  Yeah. Well, you probably don’t, but if your total cholesterol was over 300, you should get checked.

Ari Whitten:  Okay. So, my last question on this is something that drives me a little bit nuts, to be honest with you. When I see some of these debates back and forth. Like I know you published with Alex Leaf who’s a mutual friend this video recently on niacin and the potential role of niacin in lowering LDL and things like that. And then, other mutual friends of ours, Spencer And Casey Nadolski came in and they’re conventional doctors who are kind of always there to argue in favor of statins and the sort of conventional thinking around that.

I’ll be honest, one of the things that drive me a bit crazy is it seems like everybody’s losing sight of the fact that lifestyle factors and nutrition factors are the main key to cardiovascular disease. And it’s like that whole thing is being ignored in favor of statins. And whether statins are good or bad. And I’m like, “why are we even talking about this?” Like how much, how much of the people, how much of what portion of the population is actually doing nutrition and lifestyle really well and still has some kind of cholesterol problem? In my opinion, it’s less than probably 3% of people. If that. Maybe less than 1%. So, from my perspective, the whole thing, the whole focus should just be shifted to nutrition and lifestyle.

Dr. Chris Masterjohn:  Spencer and Casey got a little riled up on the post that I had about safety precautions to take when using niacin to lower cholesterol. The episode before that directly before that, which was linked to in the description of that, although this debate largely occurred on a Facebook share of the Instagram posts that didn’t have the links to the old episode because you can’t put links in Instagram captions. But anyway. The previous episode was, should you use niacin to lower your cholesterol? And what I said was, look, the data’s controversial number one. Number two, the generous view of the data, like the pro-niacin side says that for, and this goes back to the numbers needed to treat what you brought up at the beginning for every 18 people, that take niacin, one will get saved from heart disease.

What was it? 18 I got to go back and look at those answers. The math works out a look at those numbers, I think I’m messing it up. The math works out that for every, and I know I have this number right. The math works out that for every seven people that you save from heart disease with niacin using the generous view of those numbers, three of them are going to get diabetes. And I think this is where numbers needed to treat are, you know, this is pretty useful because you can kind of use it for cost-benefit analysis. It’s another question to ask does “niacin reduce the risk of heart disease”, right? Like two separate things. But what I said was, well in the next video I’ll give you some tips on how to not get diabetes when you use niacin. But for now, shouldn’t we be trying to do things that the risk of heart disease and the risk of diabetes instead of things that reduce the risk of heart disease by increasing the risk of diabetes?

Ari Whitten:  And could also be true almost for statins, right? Like shouldn’t we be discussing things which reduced the risk of heart disease and also translate into improved energy levels, improved mitochondrial function, and improved muscle strength? And a host of other positive side effects instead of reduced cardiovascular risk and also have a bunch of negative side effects.

Dr. Chris Masterjohn:  Yeah, I agree with that. And niacin reduces heart disease risk. If it does, it does it by lowering free fatty acid levels in the blood. And so, what else lowers free fatty acid levels well optimizing your body composition, exercising, achieving insulin sensitivity, increase including healthy carbs in your diet once you’re insulin sensitive. And like all of these things are anti-diabetes and are going to make you feel better. And they’re also really basic things. Right? Like you were saying like who’s got the basics, right? Not that many people. Right. But also, like who consume health information like this? The highly motivated people that can, that can, right. And so, I think sometimes not just Spencer and Casey, but doctors in general when they’re, the ones who do pay attention to social media are they’re thinking of their patient population and the concerns that they need to… like, they don’t want the Joe Schmo to like go home and sit on the couch eating burgers and fries and taking a high dose niacin while he sits on the couch.

Ari Whitten:  Understandably.

Dr. Chris Masterjohn:  But that’s not whom any of this information is marketed to. Right? Like, if you have a podcast about health and nutrition, by definition, your audience is in the top one or 2% of highly motivated individuals that either want to or have taken control of their health in ways that most people won’t. And that changes everything because those are the people that you can reach with diet and lifestyle messages.

Ari Whitten:  Yeah. I know we’ve spent most of this podcast on cardiovascular disease, which is cool. I’m actually, I love this content and I’m really excited about how this played out and this is going to be a great podcast on this whole topic that I’m excited to share with people.

Because I feel like the, on the podcasts I’ve done thus far, I’ve either had the sort of very conventional thinking around cholesterol sort of. And, and oftentimes that’s associated with like the vegan people who are also infusing sort of animal food avoidance into that message and avoidance of dietary cholesterol and avoidance specifically of animal foods. Or I’ve had the sort of the cholesterol skeptics who want to deny any relationship here at all. So, I think this is really important information and I thank you for it.

 

The importance of niacin

One more topic. We have time for one more topic and I want to do something that’s maybe a little bit connected to what we were just talking about niacin. And specifically, I know you’ve done some videos recently. I’m not just nice and, but also nicotinamide riboside, nicotinamide mononucleotide. And there’s a lot of talk of nicotinamide riboside and NAD+, and that’s becoming quite popular. A lot of people are looking at supplementing with that for increased energy levels, longevity and so on.

So, talk about what the relationship is there. Talk about why these compounds are important, why NAD+ is important and sort of the lowdown on how to increase it with these compounds. And then some of them, I know there’s some potential downsides to using these compounds and how to mitigate that.

Dr. Chris Masterjohn:  Yeah. niacin is vitamin B3 and it is used to make, to primarily make two compounds NAD+ and NADpH. NAD+ is used in oxidative catabolism, which is the breakdown of food for energy. And it is one of the… one of maybe probably niacin and vitamin B5 are the two most universal players in energy metabolism. And you can say certain things like riboflavin is more important for fat burning. Thiamin was important for carb burning. NAD+ is across the board for everything. And then NADpH is primarily used for building things up, anabolic synthesis. So, you use it for nutrient recycling and use it to recycle glutathione, which is an antioxidant and a detoxifier. Use it for detoxification in general,. You use it for making cholesterol and fatty acids. You use it for making neurotransmitters. You use it, in fact, to make everything else that is a player in energy metabolism, like even make NAD+ from niacin for example.

When your niacin status declines, generally you conserve NADpH more than you conserve NAD+ because the antioxidant function is so essential from preventing the whole structure of your cells from falling apart. And so, usually, people are thinking mostly about trying to boost levels of NAD+. And NAD+ is not just used in energy metabolism to make you feel energetic. That’s one of the central things it does. It’s also used to lengthen telomeres, which are the little end caps on your chromosomes. Every time your chromosomes divide, you lose a little bit of the ends and the telomeres, have places where they rebuild them to try to keep them long. And it’s thought that a part of aging is just losing the telomere length. Cause as you just basically, you’ll eventually, you’ll start to lose genes that are functional in those cells if you don’t rebuild that at the end caps. And it’s also used for DNA repair. So, every time you breathe in air, you’ve got oxygen that’s damaging some stuff. You’d go out in the sun, great for your circadian rhythm, great for Vitamin D, but it’s causing DNA damage with every drop of sunlight that you get and you’re constantly repairing it. And in severe niacin deficiency you can’t go out in the sun because of your skin will get wrecked just by normal sunlight exposure. So, people want to use niacin to increase NAD+ levels. And when you eat it, like let’s say supplement with something called niacin or niacinamide, which niacin is another name for nicotinic acid. Niacinamide is another name for nicotinamide. Any of those have to go through a multistep process to be made into NAD+ and nicotine mononucleotide, which is NMN and nicotinamide riboside just NR both kind of higher up, the higher up the ladder in that synthesis and they’re more easily made into it.

So, there’s a system in place that when you consume… Oh, one other thing that you use niacin for that I didn’t mention is to release all your neurotransmitters. You break down NAD+ and that’s completely independent of its role in energy metabolism.

So, in energy metabolism, you use NAD+ basically by cycling electrons from the food you eat. And so, you, you like electrons go on it, they go off it, they go on it, they go off. If they go on it, they go off it. Doing that process you never break down the NAD+ you still have whatever you had. But for telomere lengthening, for DNA repair and for neurotransmitter release, all of those processes break down the NAD+.  they break it down to nicotinamide, which ultimately ideally you would want to recapture salvage and produce NAD+ from it again.

However, as a negative feedback loop, when you make nicotinamide, if it accumulates, it’ll shut down all those enzymes. And that’s basically because if you don’t have anything to do with it, you don’t want to keep making it. And so, your cells are set up to say, “okay, we have Nicotinamide, we’re going to try to make NAD+, but if we can’t, we’re going to get rid of it. How do we get rid of it? We detoxify it with methylation.

So, there are basically two principals here. One is, if you have nicotinamide mononucleotide NMN or nicotinamide riboside NR, you are past nicotinamide. You’re halfway up the ladder to get to NAD+. You’ll make NAD+ before you ever have nicotinamide.

And so, you’re never at risk of peeing it out, methylating it and peeing it out in the urine before you are making NAD+, it’s basically a guarantee that you’re going to get more bang for the buck of NAD+. Another implication of this is that because all niacin, no matter whether it’s niacin, niacinamide, NR, NMN, any of them are ultimately somewhere in that cycle are going to be made into nicotinamide. That’s going to pose an accumulation risk, the body is going to have to get rid of it or risk getting rid of it. And if it does so it will do so by methylating it. And so, all forms of niacin will deplete methyl groups. Right? And that’s a risk because you need methyl groups to synthesize creatine, which is important for muscular performance, for energy, for feeling energetic, for mental health.

You use methyl groups to regulate your dopamine in a way that keeps you motivated in a way that keeps you from getting mentally stuck on things that you don’t want to be thinking about or focusing on. You use methylation for supporting your liver health, not getting fatty liver. So, you don’t want to be losing methyl groups unnecessarily, but you will, if you take way more niacin than you need, no matter what form it is. So, the take-home points are if you want to increase NAD+ levels, use NMN or NR instead of using niacin or niacinamide.

And second take home is don’t take more than you need, right? So, if you get a positive effect from 150 milligrams and you don’t get an increased effect from 300, don’t take 300. Certainly, don’t take two milligrams, I’m sorry, two grams. It’s in milligram.

So yeah, 150 milligrams, you’re getting a positive effect. Don’t take more, but some people might need to take 300 milligrams. But do that if you get a positive effect from it, not just because other people are doing it.

And then my recommendation to… there are no studies of this, but my recommendation is to step in and say, “hey, pair that with some trimethyl glycine which is a [methyl donor] and that gets rid of the risk that you’re gonna lose methyl groups. And so, TMG capsules, usually 500 milligrams, the dosing, sort of like if you’re at if you’re under 500 milligrams of niacin the dosing doesn’t really matter. One capsule will cover the whole thing.

If you’re starting to use high doses, I would use, I would match 500 milligrams of TMG to every 500 milligrams of niacin or niacinamide and to every 1000 milligrams of NR or a nicotinamide mononucleotide. And so, since I just said use NMN and NR instead of the other two, we can just say that for the NAD+ boosting benefits, start with the low dose, maybe work your way up possibly to 2000 milligrams if you need it. But take half the dose, whatever the dose NMN or NR you’re taking. take half the dose of TMG.

Ari Whitten:  Excellent. Last point on this. I know when your video on the subject you mentioned… not going to directly quote you, but it’s something to the effect of, the caveat here as far as the potential for losing methyl groups is a reason why you recommend getting most of your food from whole foods. And I’m just curious, are there any dietary sources of nicotinamide riboside or nicotinamide mononucleotide or can we only get niacin and niacinamide?

Dr. Chris Masterjohn:  There’s a lot of NAD and NADpH there’s a lot of nicotinamide, there’s a lot of nicotinic acid. It varies food by food, but generally, in plant foods, you’re getting more nicotinic acid and animal foods you’re getting more nicotinamide when you eat the food. But answer your question directly, there’s a little bit of NMN in a small selection of foods and I don’t remember what they are off the top of my head, but they’re not significant in terms of like the contribution to total niacin. They’re pretty meaningless. And nicotinamide riboside is only found in trace quantities and milk. So it’s essentially not found in the food supply.

I don’t think getting it from whole foods because of the forms that are found in whole foods is really protecting you from methyl group loss. It’s just that when you’re getting it from whole foods, you’re not going to be taking in 300 milligrams, let alone 2000 milligrams. So, the capacity to meaningfully tax the methyl groups is just not there. And you are getting methyl groups from methyl donors in those foods, right? So, it’s really hard to disturb that balance when you’re getting it from food. And that’s not an argument against using supplements. If you have a condition that’s lowering your NAD+ levels, which could be as simple as you’re getting older, it could be or at least that’s a leading hypothesis, is that NAD+ levels declined to a meaningful extent during aging, and that’s part of the aging process.

You’re never going to get 300 milligrams of any form of niacin from foods. It’s not gonna happen. Right? And so, if you benefit building up your NAD+ levels from 300 milligrams of nicotinamide riboside, the only way to do that is to take nicotinamide riboside. It’s just now you have sort of exited the realm of dosages that you could get from food and you’ve now entered into this place that requires tinkering and micromanaging. So, you shouldn’t be treating that as having equal cost and benefit analysis of eating food that has niacin. You should be thinking about it as, “I’m deliberately tinkering with the system. I should understand the system well enough to know how to do that safely and effectively.”

Ari Whitten:  Yeah. And it seems that even the supplement formulators in many cases don’t because they’re not adding methyl donors to most of these supplements. I mean, most of the supplements on the market that are either NR or NMN are not including methyl donors there. So, it seems a lot of even the people formulating those are not privy to this knowledge. But at least now everybody listening to this podcast is.

Dr. Chris Masterjohn: I had an interesting Twitter exchange with Charles Brenner, who is the head of the company [crumbled x that makes true nitrogen]. And, he basically is arguing that they showed that homocysteine and that’s identity on the finding levels in the blood are not affected by 2000 milligrams of their supplement. They’re going to publish the data later. So, they have proven that my concern, while valid doesn’t play out. And so I responded to him and said that what you would expect, and I could don’t have, we don’t have time to go into why here, but what you would expect is the most sensible thing would be declining a synthesis of creatine, not elevated homocysteine or decreased SAM. And he just sort of ignored all those points. And so, I think it’s simpler for him to just say that they dismissed that thing they don’t need to include, but that’s sorta like statins and CoQ10 right? Like you may know that that like Merck may have patented that thing in case they’re pushed into putting it on the market, but you don’t really want to market it. It’s, it just, it comes out of marketing risk because now you’re sort of admitting that there might be this negative consequence to your supplement and that’s why you’re putting it in there. And it makes for better marketing to just say this is an unambiguously positive effect on your health.

Ari Whitten:  Right. Yeah, absolutely. Well, Chris, let me put it this way. I have like eight topics, nine topics listed out of things to discuss today, and we covered two of them. Okay. So, I’m going to have to have you on for a second and probably a third podcast, which I’m actually excited about. I love having you on the show and you’re a wealth of knowledge. Also, I want to say to everybody listening especially if you didn’t catch the previous episode that we did together where I had Chris on the show. Chris has a new cheat sheet that’s for testing, nutritional status. And basically this is a guide to help you figure out exactly if there are any nutritional deficiencies that are related to your symptoms, to your fatigue struggles and exactly how to figure out based on your symptoms, if those deficiencies might be present and exactly what the specific best tests are to validate if those deficiencies are actually present and how to fix them and what foods are rich in that specific nutrient and so on.

As far as I’m concerned, this is a must-have tool. Also, if I mean it’s, it’s literally like the Bible for understanding nutritional deficiencies. What vitamins and minerals do in the body and how they relate to various symptoms and potentially your energy struggles. As an added bonus, this thing is only $30, which is kind of amazing. It’s in my opinion, easily a $100 or $200 worth of value, uh, and Chris is offering it at a discount, 20% off. You can get it at Chrismasterjohnphd.com/ari. And Chris, do you have any words that you want to say about the cheat sheet in case I maybe left something out?

Dr. Chris Masterjohn:  No, I think you did a great job. It’s called The Testing Nutritional Status The Ultimate Cheat Sheet. It’s called a cheat sheet because it’s designed so that you have to do a minimum amount of work. You can read five of the pages and get your hand held as you walk through, how to decide which data you should be collecting, how you collect the data and how you interpret it. And then there’s, it’s called The Ultimate Cheat Sheet because then there are 78 pages total and the rest of it is stuff where you might be pointed to it on that need to know basis. And look, if you deal with clients, you might want to read the whole thing, but if you don’t, you might only need to read six pages of it to be able to get your start to an action protocol.

Ari Whitten:  For everybody listening, in my opinion, this is an absolute must-have tool. It’s only 30 bucks. It’s actually 24 bucks. So, there’s no reason not to buy it. It’s like as much as a book from Amazon or a couple of books from Amazon and it’s potentially life-changing information.

Chris, thank you so much again for coming on the show and we’ll schedule the podcasts that we’re going to do next week or so.

 

What Science Says About Your Cholesterol Levels, Dietary Cholesterol, Statins, And Their Role In Cardiovascular Disease, with Dr. Chris Masterjohn, Ph.D. – Show Notes

The connection between cholesterol and heart disease (02:22)
The science on statins (14:26)
The role of dietary cholesterol and how it relates to cardiovascular risk (35:32)
The importance of niacin (47:38)

Links

Get your personal The Testing Nutritional Status The Ultimate Cheat Sheet here

You can read the study “Fatigue, an overview” mentioned in the podcast