Chris Masterjohn on Cholesterol & Heart Disease (Part 2) | Chris Kresser
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Chris Masterjohn on Cholesterol & Heart Disease (Part 2)

by Chris Kresser

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This week we’re glad to welcome Chris Masterjohn back to the show. Chris joined us on Episode 11 to discuss the role of cholesterol in heart disease, and to dispel the many myths associated with those subjects. There was so much to cover, we had to have Chris back for part 2 (and in fact, we still didn’t cover all of the material so he’s going to come back for part 3 in the future!)

In this episode, we discuss (among other things):

  • what is a “normal” cholesterol? what can anthropological studies tell us about this?
  • are lipoprotein particle size tests accurate? what’s the best way of determining particle size?
  • why do some people have high cholesterol (TC & LDL) after adopting a Paleo/WAPF diet? is this something to be concerned about?

Enjoy the show!

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Full Text Transcript

Danny: Hello everyone and welcome to the Healthy Skeptic podcast. My name is Danny Roddy of DannyRoddy.com and with me is Chris Kresser, health detective and owner of ChrisKresser.com, a blog challenging mainstream myths about nutrition and health. Chris, how are you doin’ buddy?

Chris Kresser: I’m great Danny, how about you, how’s Hawaii?

Danny: It’s amazing I can’t ask to spend any more time sitting in the sand looking at the water, it’s amazing.

Chris Kresser: Yeah I admit to some mild jealousy at the moment. I feel like I’ve been a hermit for the past 6 weeks, it’s been amazing spending that time with my daughter but my typical routine at this time of the year is to be out in the sun a lot and surfing and things like that. It’s been more along the changing diapers line lately.

Danny: To be honest I’ve been looking forward the whole trip to interviewing our special guest.

Chris Kresser: We’ve got Chris Masterjohn here back for part 2 of the cholesterol special we’re really happy to have him back. The first show that we did with him was one of our most popular shows ever, and people have been really excited to hear the second part. So Chris, why don’t we do like a 2 minute synopsis of the last show, just for people who might have missed it so they’re not completely lost, and then we’re gonna talk a little bit about some more basics about cholesterol that we didn’t get to during the last show, and then we’re gonna answer a few questions. So why don’t you take it from here Chris.

Chris Masterjohn: Alright, sounds great. Thank you so much it’s great to be here again Chris and Danny, thanks for having me on a second time. So last time we talked about whether cholesterol plays any role in heart disease and of course the roles of cholesterol in the body. Cholesterol does a lot of important things it’s the precursor to sex hormones, highly related molecules the precursor to vitamin D, it’s the precursor to bile acids which help our digestion and so on. But our big concern is does cholesterol cause heart disease and when we go to the doctor and get our blood lipids measured does that have any significance for us. There seemed to be two different camps, where we have the mainstream that says cholesterol is one of the most important causes of heart disease, when its level in the blood rises that cholesterol just kind of bursts into the arterial wall and causes an atherosclerotic plaque. Some of these people, even the nobel prize winning scientists like Michael Brown and Joseph Goldstein call themselves cholesterol warriors cause they’re making a war on cholesterol. Then we have the opposite side of spectrum which are the cholesterol skeptics and they say no, these blood lipids don’t really have anything to do with heart disease. And so they say this idea that they do, the lipid hypothesis, is just totally false. And so what I presented in the last show was basically an attempt to reconcile the evidence that’s used on both sides of this argument. And what I like to say is that the infiltrative lipid hypothesis is false, but the degenerative lipid hypothesis would be a good term for what the science is leading us towards. The reason I use those is words is because when the role of blood lipids in heart disease was first discovered in the cholesterol-fed rabbit model, Nicolai Anitschkov who basically brought that model to the fore said it’s not about degeneration of the arterial wall, it’s about this high concentration of lipids in the blood that’s infiltrating the blood vessel wall. And last time we talked about all the evidence that suggests that it is lipid related so we should have some type of lipid hypothesis, but it’s not about the high concentration, it’s not about the high amount. It’s about the degeneration of those lipoproteins in the blood that are carrying those lipids. So what we wanna do is not seek how to lower the concentration of lipids necessarily but we wanna seek how to prevent the degeneration of those lipids, and we briefly talked about the need to maintain robust thyroid hormone status and good metabolism. The need to get sufficient nutrients to minimize the degeneration of these lipids, and the need to minimize inflammation, infection, and other toxic factors that contribute to their degeneration. So that’s the basic rundown of the last show.

Chris Kresser: Right, he got a lot of things right but he got that one key point wrong. And that seems to have set us on a path that has really distorted what we know now to be true.

Chris Masterjohn: Absolutely, because of the simple reason that there are some things that relative to other things might raise the concentration of cholesterol in the blood, but those things are sometimes things that are actually really good for us when we look at the bottom line.

Chris Kresser: Yeah, and I think that’s what’s been confusing about this for some people is that neither of the extremes are right there’s a little bit of truth on both sides and so it’s been really difficult to tease out exactly what we can determine from the scientific literature, at least the current scientific literature. So let’s talk a little bit about what a “normal” cholesterol would be, and what do anthropological studies from various traditional cultures around the world tell us about this Chris?

Chris Masterjohn: That’s a great question, I think to even ask it goes back to the idea that Weston Price put forward when he traveled around the world looking at traditional healthy peoples. He was looking at tooth decay and he was saying everyone in this society basically has degenerating teeth, I need to find people who are healthy, people who don’t have tooth decay. And he also took the idea that if we can find people who have superior development compared to what we have in our own society, then this can offer us standards of excellence. So I think we can apply the same thing to heart disease. One, we wanna find are there populations out there that don’t have heart disease and if so, what do they look like. We wanna know what they’re eating, we wanna know what they’re doing, how they’re living and we wanna know what their cholesterol levels are because maybe that can tell us something about what a normal cholesterol level is. And we wanna establish them as standards of evidence because people may say, look at people in our society and say well, anyone who lives as long as we do is gonna die of heart disease eventually cause they’re gonna die of something. If we can establish that there are people out there who are living reasonable long lives and are still free of heart disease, then we’ve established a new standard of excellence and that just provides us with the basic fact that it is possible to live a long, healthy life and be free of heart disease. And if we look around the world we see quite often researchers have documented that with the nutritional transition to modern diets rich in refined foods, we clearly see this increase in degenerative diseases including heart disease and in many cases there’s been at least some investigation showing that traditional peoples before this transition to refined foods seem to have either a low rate of heart disease or freedom from heart disease.

Now I think among the groups that I’ve seen studied so far, it seems that two really stand out in terms of the extent to which they were investigated and those are the Masai and the Kitavans. I think each of these groups of people was studied quite intensively and what’s particularly amazing about them is that they have very different cholesterol levels when you look at them. The Masai for example, are a pastoralist, or cattle herding tribe who occupy a piece of land that crosses the border of Tanzania and Kenya in east Africa. They traditionally raise cattle for subsistence, to eat the meat, drink the milk and the other products that come from them, and also to trade for other products. So they have a diverse diet that varies through the seasons of the year and that also varies year to year according to economic times, because they’ll trade with other groups when their own supply of food is low or other groups are particularly wealthy. At other times they might have just tons and tons of milk and they might focus mostly on consuming the milk. In any case, the Masai have very low cholesterol levels, some of the lowest in the world and a number of groups had studied them in the 1960s and showed that the men tended to have cholesterol levels between 130-135 mg/dl, which is by our standards we would say that’s quite low. The women had somewhat higher cholesterol levels of about 145, and these would tend to rise with age maybe to 170 mg/dl in their 40s and then drop off a little bit as they grew older. It also seemed to rise quite a bit in the 3rd trimester of pregnancy, at least according to one study. Women who were in their 3rd trimester of pregnancy had their cholesterol levels go up to 205 mg/dl. But on the whole they had very low levels of cholesterol with a population mean of around 130-140, and their LDL:HDL cholesterol ratio was about 2. So that’s considered quite good, even by American standards. The medical establishment in our society would love the Masai because they seem to support the lipid hypothesis. They have very low or no rate of heart disease and they have very low cholesterol levels.

But if we look at the Kitavans who live in the Pacific islands and are horticulturalists, we see something very different. This group is living off of a little bit of fish, a little bit of coconut, a lot of tubers, a little bit of fruit. They have a very low fat intake, very intake of saturated fat from coconut, and their cholesterol levels are not through the roof by our standards, but they’re much higher than the Masai. The males, for example, tend to have cholesterol levels around 180 mg/dl, the females again are a bit higher 200-210 mg/dl. Here we’re pushing over the limit of what’s considered healthy in our society, and during their 40s or 50s women might see cholesterol levels rise to about 250 mg/dl and then settle off a little bit. A lot of the Kitavans smoke, and their LDL:HDL cholesterol ratio is 3.3 among the smokers and 2.5 among the non-smokers. And we also have triglyceride information from them, tends to be around 100-110 mg/dl. Now the Kitavans have been investigated very extensively, there are some other people in the Pacific islands who we’ve had smaller investigations that seem to indicate that they’re free of heart disease but they’re really too small to say definitively.

Nevertheless, on some of these islands we see even higher cholesterol levels traditionally. If we compare Puka-Puka and Tokelau, Polynesians who also occupy Pacific islands, the Puka-Pukans have a high intake of starches and other carbohydrates, and a fairly meaningful intake of coconut. On Tokelau they have a much higher intake of coconut. And we see on Puka-Puka we have men going from cholesterol levels of around 150-180 with age, but the women going from about 170-190 with age. But if we compare similar people eating more coconut, who also seem to be free of heart disease we see men with cholesterol levels going 180-220 over their lifespans and women going from 200-245 over their lifespans. So if we look at these populations I would say we have a range. I’m not satisfied with the idea that low cholesterol is intrinsically unhealthy, I’m willing to consider it, but I would say that the Masai should constitute the low range of what we might say is possibly healthy, and the Kitavans should probably serve as our high range. I think we could probably say that anything between maybe 140-220 maybe going a little bit higher to 250, might constitute what seems to be normal. And I would caution that the Masai, we don’t know exactly why their cholesterol levels are so low but Paul Jaminet’s been doing a series on the role of infectious diseases and we should note that infectious diseases are quite common in Africa so that might play a role. So it might give us more comfort to say maybe a little bit higher than that 160 or 180, but still we don’t really see healthy populations going through the roof in the high 200s or over 300. That seems to constitute what we can say is normal.

Chris Kresser: And it does depend, as we’ve been discussing I think somewhat on the context right Chris? I mean someone could have a cholesterol of 200 but could relatively unhealthy and at risk for heart disease whereas someone else perhaps has a cholesterol of 220-230 and they may be at still relatively low risk of heart disease depending on their lifestyle and diet and several other factors so it’s not so cut and dry that if you’re in that range you get a hall pass from heart disease.

Chris Masterjohn: Absolutely, if you really want a good example, there’s this myth floating around that because the Framingham study didn’t find anyone with cholesterol levels under 150 that that’s the freedom from heart disease range. And that’s just not true. If you look at these people with the PCSK9 gene mutations who have really high LDL receptor activity there’s been one of them who’s been found who did develop heart disease and his cholesterol was somewhere around 50-60 mg/dl. But he also smoked, he had high blood pressure, he had high LPa through the roof and so on. That’s absolutely true, and we have to realize that when we look at these cholesterol levels, they’re not diagnostics.  It’s heart disease we wanna avoid, any of the mental problems, the tendency towards suicide and the anxiety that comes with low cholesterol. These are things that we wanna avoid. But we always have to remember that there can be many things that lower cholesterol and many things that raise cholesterol and some of those things can be good and some of them bad. If we’re lowering cholesterol because we’re clearing it in to an atherosclerotic plaque, that’s clearly bad. If we’re lowering cholesterol because we’re converting it into sex hormones and bile acids and things that increase our fertility, virility, strength, and digestion and all these positive things then it’s clearly good to lower cholesterol. But if it’s low because we’re not making it, then we don’t have those substances that we need to make all those good things so that’s clearly bad. So we can never judge by the amount of cholesterol in the blood alone, but we have to use it perhaps as a clue to try to understand, with further investigation what’s happening in the body.

Chris Kresser: So Chris, we talked a little bit on the last show about the difference in particle size, small dense LDL particles vs large buoyant LDL particles and what the relevance of that is  to cardiovascular disease risk. As you know there’s these tests out there like the VAP test or the NMR test to measure particle size and early on in my practice I was using these tests to try to get an idea of particle size but then I read several papers which suggested that these tests might not be as accurate as they’re made out to be and I think I sent you some of those papers, so what have we learned in the last few years about the accuracy of these particle size tests?

Chris Masterjohn: Well what I learned Chris, from the papers that you sent me is that if I wanna have pattern A large, fluffy LDL particles, then the best thing that I can do is not change my diet but it would simply be to measure my LDL particle size by tube gel electrophoresis, because 80% of people who measure their particle size by tube gel electrophoresis are classified as pattern A, whereas only 8% of people who use the VAP test are classified as pattern A. So the best thing that you can do to give yourself pattern A is to avoid using the VAP test number one, number two if you can really avoid NMR or gradient gel electrophoresis and go for tube gel electrophoresis that’s really your best bet.

I think the point that this is raising is there’s a lot of disagreement between these different tests. And until we get the science to the point where we can actually agree on the particle size, on what test we use, on what standards we use to classify someone as having this or that particle size or this or that size distribution, I really don’t think we’re at the point yet where we should be ordering these tests for everyone and telling them to change their diet or to do this or that thing in order to alter their particle size. But I think this goes back to a more fundamental question which is, why do we even care about the particle size in the first place. And I think we need to look at the foundation for that hypothesis. So the main reason that this came to the fore was because there were some early studies, first there were retrospective studies meaning looking at people who already had heart disease and just seeing what their particle sizes were, and we saw that people who had the larger particle sizes seemed to have a much lower prevalence of heart disease. Now this is a good observation for generating hypotheses about what the role of these different particle sizes of LDL might play in cardiovascular disease risk. But to simply have a hypothesis doesn’t really cut it, we wanna really understand whether we’re actually diagnosing something, or if we’re not diagnosing something are we getting a metabolic clue, are we helping ourselves to understand what’s going on in this person’s body or are we not. Now if we wanna argue that the small dense LDL is associated with cardiovascular disease, the first thing we would wanna do is verify that it’s a predictor in prospective studies. In other words if we measure people’s particle size now, can we predict whether they develop heart disease in the future. And even these studies have led to some very, at best ambiguous results. So we had a number of these studies and most of them did show that particle size, whether measured by gradient gel electrophoresis, NMR, or in one case it was estimated by the apo B to LDL cholesterol ratio, and the logic of that test is you have one apo B protein per particle, so if you have a higher ratio of particles to cholesterol than presumably you have more small dense particles rather than fewer large buoyant particles. Now all of these different methods did have some success in predicting cardiovascular disease, but in most of these studies when they were adjusted for traditional risk factors, the predictive power was mostly lost.

Perhaps the most successful study I’ve seen was the Quebec Cardiovascular Study where they used gradient gel electrophoresis. And they found that if they looked at the distribution of particle size, it was an independent predictor of heart disease risk. But a number of other studies that came after that failed to bear this out. So the Stanford Five City Project, for example, showed that particle size was useful but once they adjusted for the total:HDL cholesterol ratio, it wasn’t useful anymore. The Physicians Health Study showed that particle size was useful but once they adjusted for triglycerides and total cholesterol it wasn’t useful anymore. The epic Norfolk study measured by NMR, they found that particle size was useful but they found that particle number was much more useful. But when they adjusted particle number for HDL cholesterol and triglycerides once again its usefulness was very questionable. And there was another study, the AMORIS study, the apolipoprotein related mortality risk study, and that looked at particle size estimated by the apo B to LDL cholesterol ratio and once again it seemed useful at first but once they adjusted it to triglycerides or to apo B it lost its usefulness and then finally in the womens health study they also looked at particle size with NMR and once again it lost its usefulness after adjusting for the total:HDL cholesterol ratio.

Chris Kresser: Chris, at the risk of stating something obvious here, how much can we rely on these studies since they’re all using methodologies that we’ve just established are totally in disagreement with one another and not reliable?

Chris Masterjohn: Well, right this is the thing. If we can’t agree on how to quantify the particle size, then we can’t necessarily agree that these studies are showing that particle size isn’t useful. But at the same time, what meaningfulness does that question have to the average person that’s walking to the office and wants a test. Are you gonna get into some really esoteric academic argument about, this test isn’t going to do anything for you but theoretically it could be an imperfect measurement of something out there that does have meaning for you. I mean where are you getting with that? Nowhere.

Chris Kresser: We can neither prove that particle size is not an issue nor prove that it is an issue with the current test because all of that rests on methodology that hasn’t been standardized or agreed upon.

Chris Masterjohn: Exactly, so this is where particle size is useful. The studies that have somewhat ambivalently but nevertheless shown some relationship between particle size and cardiovascular disease risk have left us with several hypotheses that are worthy of investigation. One is that small dense LDL is more likely to oxidize and thereby contribute to plaque development. Another is that it’s more likely to pass through the endothelium and thereby oxidize because it’s behind the blood vessel wall and contribute to plaque development. Another is that it’s more likely to get stuck behind the blood vessel wall and thus contribute to plaque development. And my perspective is, I’ve pointed this out in several places, and I believe I mentioned it in our previous interview, it could also be seen as a marker for poor LDL receptor activity and LDL oxidation because what happens when LDL hangs out in the blood. Well it becomes small and dense because it’s metabolized by a number of different enzymes that make it small and dense and because when it oxidizes, it becomes even more small and dense. So here we have about four different hypotheses that are worthy of investigation, none of which have been confirmed. So it’s highly questionable that we should be going around batting people over the head and say  make sure you do this, this, this, and this, to modify your particle size.

Chris Kresser: Right, I’ve seen some people, some patients who’ve come to me and also chatter on the internet on my blog and other blogs going to extreme lengths  to try to adjust there ratio as measured by a VAP test or NMR test.

Chris Masterjohn: Yeah absolutely, I will say this. I mentioned as I ran down this list of studies, that the traditional risk factors like triglycerides and total:HDL cholesterol ratio, were the factors that seemed to mitigate the usefulness of these tests, which brings us back to the question, are these tests any useful. Should you measure your total cholesterol or your HDL cholesterol. And I will say that we have many more studies addressing this topic so we’re able to amass a much larger data set and better answer the question. And we also have some, not that it’s without questions, but we have some better agreement on what tests to use to measure these things. And there is good data suggesting that there is, at a population level in the general population, there is predictive value to some of these blood lipid markers and that the best of them is the total:HDL cholesterol ratio. So if we look for example at two meta analyses that were published in the last few years, one was the emerging risk factors collaboration, and that was published in the Journal of the American Medical Association in 2009. And they showed that fasting triglycerides, HDL cholesterol, and non-HDL cholesterol were all useful predictors, but if they adjusted triglycerides for the other predictors triglycerides lost their significance. But if they adjusted HDL and non-HDL cholesterol for triglycerides, non-HDL and HDL cholesterol persisted in their predictive power. And there was another study, the perspective studies collaboration which pooled together results form 61 studies with 900,000 participants that was published in the Lancet in 2007 and they found that if you looked at total cholesterol, HDL cholesterol, or LDL cholesterol or any of the ratios, it was the total:HDL cholesterol ratio that really stood out as the best predictor. Now what can we learn from that. Well, can we use the total: HDL cholesterol ratio as a diagnosis? No, a high ratio is not a disease, a low ratio is not a disease. Can we use it to predict risk? Yes we can at a population level, not at an individual level. I think it’s a logical fallacy to say a population with this mean has such and such a risk therefore if you have that same value, you have such and such a risk. I think that’s bogus reasoning.

Chris Kresser: And it comes up a lot in a lot of different markers. The hemoglobin A1c is another example of that it’s really useful on a population level but it’s not so useful individually because there’s so many different markers that can effect red blood cell turnover which is part of that formula and so it’s really not that useful for individuals.

Chris Masterjohn: Absolutely, there are many things that can effect the total:HDL cholesterol ratio. But does that mean it has no usefulness. Can we use it in some way as a metabolic clue. And I think that we can. But I don’t think that it should ever be used without further investigation to see if that ratio goes out of whack, why is it going out of whack. And the reason that I think it’s valuable is especially because, you recently commented for example, I think this was on twitter, you were talking about people, you see so many people with low thyroid levels and Emily Deans was saying she doesn’t see that many people with low thyroid levels. So why is this, well you say you’re getting a lot of these people who go all these different places and finally come to you because no one else is helping them. So we have to keep in mind that if we’re trying to reach out to people who are seeing mainstream doctors for a lot of those people these are the only things that they’re testing. So when they go to the doctor, the doctor’s not measuring their hepatic triglycerides, the doctor’s not measuring their free T3. I’ve gone to a doctor and said can you give me a full thyroid panel with TSH, free T3, free T4 he says sure. And then the test comes back and it has TSH on it. So your average person going to the doctor, this is what they’re getting. So when they go onto some internet forum and their total cholesterol has gone up to 350 and their HDL cholesterol is really low and they get a bunch of people saying oh these things don’t have anything to do with anything they’re not causal factors just ignore it, that might be fine advice if their doctor had also measured this battery of things that you measure when patients walk into your office, but they’re not. So for those people I think we need to say this needs some follow up. Let’s see if this is going out of whack because of your thyroid, let’s see if this is going out of whack because you have insulin resistance, you have fatty liver, let’s try to look at these further issues, that’s where I think the blood lipids come into usefulness.

Chris Kresser: Yeah. I agree completely and my standard answer and I imagine it’s similar to yours, when someone says is my cholesterol a problem I say I don’t know. Or maybe or it depends. And it definitely requires a lot more investigation and as you pointed out unfortunately that’s rarely done in the conventional model. It’s high cholesterol you get a statin, just like when it’s high TSH or low T3 you get thyroid hormone without looking into the mechanism.

Chris Masterjohn: Exactly so I think those of us who are in the know, who understand that there’s a lot more to the picture, our response has to be exactly what you said, I don’t know let’s look at the big picture.

Chris Kresser: So Chris, this question that just comes up all the time in the blogosphere, it’s this question of why is my cholesterol so high after adopting a nutrient dense, whether we’re talking about a Paleo or a Weston A Price style diet that’s higher in saturated fat. There’s been a lot written about that Paul Jaminet in fact just wrote an article about this question yesterday and he’s been blogging about it recently. You’ve written about it, can we do a little summary of the possible factors there and as a corollary is it something that people need to be concerned about when their LDL cholesterol goes up on this type of diet.

Chris Masterjohn: Absolutely, but first let’s outline how do we know that it’s actually gone up. Because quite often there are some confounding factors, or people don’t realize how much they can expect these values to fluctuate just on a regular basis. So for example let’s say I went and got my cholesterol tested once while I was on diet A, and it’s 180 mg/dl. And I get it tested once when I’m on diet B and it’s 200 mg/dl. Can I conclude that it’s gone up since I’ve been on diet B. And the answer is an emphatic no, you cannot conclude that it’s gone up. And this is the reason, there is very large fluctuation in total cholesterol, LDL cholesterol, HDL cholesterol, the ratio, and triglyceride levels. Just on a week to week or month to month basis without making any dietary changes. And studies that have been done to try to address the question, if we keep diet and lifestyle constant how much can we expect this to vary if we make these measurements several times over the course of several months. And these are basic answers, we can expect a single person to have a standard deviation in their total cholesterol of about 17 mg/dl. Now what does this mean, well it means that if we haven’t done anything to assess for example, my individual variation over time, we should assume that if you measured my cholesterol 100 times you’d find some true mean, some true average cholesterol level. But we could expect without any changes it to go up about 2 standard deviations so about 35 mg/dl, or down about 35 mg/dl for no reason at all.

Chris Kresser: That is a huge range. That could be the difference between statin or no statin just depending on what day somebody chose to go into the doctor’s office.

Chris Masterjohn: Oh absolutely. Exactly, so when you go into the doctor’s office and your LDL cholesterol has gone up 30 mg/dl and your doctor days oh no your cholesterol’s gone up so much you need Lipitor, the best answer for that is not ‘yeah but what’s my particle size, I bet it’s large and fluffy’, the best answer for that is, did you know that the standard deviation of the intra-individual variation in one person can be 17 mg/dl and that this is within the range and you do not have 95% confidence that my cholesterol level has even increased since the last time I came up here. I think you should go look at this, this, and this study.

So here’s the general rule. If you’ve only measured it two times, you should expect to see an increase or a decrease greater than 35 mg/dl before you can be 95% confident that your cholesterol has increased or decreased. You should expect your HDL cholesterol to go up either 9 or 10 mg/dl or down 9 or 10 mg/dl before you can say with 95% that it’s increased or decreased. You can expect your LDL cholesterol to go up either 30 mg/dl or down 30 mg/dl before you can conclude that it’s different. If you’re looking at the ratio you should expect the ratio of LDL:HDL cholesterol or total:HDL cholesterol to go up by 0.8 or down by 0.8 before you can conclude it’s changed. And you should expect your triglycerides to go up by at least 40 mg/dl or down by at least 40 mg/dl before you can conclude that they’ve changed.

Chris Kresser: Wow, I mean talk about problems with testing. I have a little n=1 story about this cause I recently, being a new dad, decided to get life insurance. I had to take this test of my lipids, I new I wasn’t obviously gonna be able to convince the insurance company, no, no really, if my cholesterol’s a little high it’s not a problem, it’s all about oxidized LDL, that obviously wasn’t gonna happen. And so being a clinician I ordered some tests for myself as the time was approaching to see where I was at, cause the better the numbers are the better the rate, and I was buying a ten year policy. The first time I tested my cholesterol it was 185 I think, my total, which was significantly lower than it was the last time I tested it six months ago. And I thought okay that’s fine and I tested it again a couple of weeks before the test and it was 220, and I thought my rate’s gonna go up. And I didn’t make any changes because I was a aware of this research too. And then I tested it the day before the test and it was 193 and then I took the test the very next day and they just mailed me the results yesterday and it was 205 which incidentally was under their cutoff so I got the good rate but that’s just a single person example and that was over only a four week period.

Chris Masterjohn: Yeah, absolutely that’s the kind of variation you can expect for biological reasons. I’m citing these values on variation by the way, from studies where they used the same method at the same lab from these people. Where they analyzed the samples in duplicate showing that the actual variation due to the lab assay was very small, like 1-2%, and that most of this variation is biological. In order to conclude that it’s even changed outside of your normal variation when everything’s staying the same, those are the large kind of values that you need. Now the second thing you need, the one exception to this by the way, would be if you had an average while you were on one diet and you had measured it 3 or 4 or 5 or 6 times, and then you do the same on a new diet, then you have a sense of your own variation so you can compare them. But in the absence of that, you just measured a couple times, once on an old diet once on a new diet, you need really large changes to conclude something’s different. Now the second thing is, I often get these questions from people who say I went on this diet and my triglycerides went through the roof, my this or that went through the roof. And I say, one of the first questions I’ll ask these people is, did your weight change. And quite often they say oh yeah that’s true. And here’s the thing, there’s really no good research I’ve seen so far about the effects of weight loss, fasting, and caloric reduction, on blood lipids. There are a lot of fairly poorly designed studies, and I’ve reviewed a lot of them, and they’re at wild conflict with one another. But this is what I’ve basically concluded as tentative working hypothesis, if you are obese or overweight and you normalize your weight and normalize all your metabolic parameters, you should expect in the long term, after your weight has stabilized, your blood lipids to mostly improve according to the conventional paradigm of risk factors.

But in the meantime what happens, triglycerides are especially sensitive to fasting, when you eat a meal your triglycerides are gonna go up, your triglycerides are always going to be lowest when you’ve been fasting in the morning so especially with triglycerides you always wanna measure them the same time of day and always in the same amount of fasting since your last meal so that’s another confounder. But what happens when someone fasts for a long period of time to their triglycerides well the answer is it depends. Usually, because you don’t have food in your system  your triglycerides are gonna get cleared over the course of a day of fasting or so, but what also happens is you need to start burning your own energy stores. So when you start to shift towards burning fat from your adipose stores you start releasing free fatty acids into the blood. Now these free fatty acids basically have three important fates. One is they go to the liver, the liver burns them for energy, the liver makes ketones so the rest of your body can burn them for energy. But two other things happen in the liver, one those free fatty acids can interfere with certain signals for example they interfere with thyroid hormone signaling, and as we know especially in the blogosphere recently and as we talked about last time, interfering with thyroid signaling itself can affect blood lipids. But here’s the other thing, if the liver’s capacity to burn the fatty acids for energy is overwhelmed, the liver makes triglycerides out of them and sends the triglycerides into the blood. So one person who has a very high capacity to burn fatty acids for energy might see their triglycerides go down as they’re losing weight, but another person who’s releasing more triglycerides from their adipose tissue than their liver can handle might see their triglycerides go up as they lose weight.

Danny: What type of fatty acids were those that inhibited thyroid function?

Chris Kresser: Free fatty acids.

Chris Masterjohn: There’s good preliminary evidence that any unsaturated free fatty acids are quite good at inhibiting thyroid function. And it’s not just PUFAs, even oleic acid is pretty good at it, and there’s really nothing you can do to suppress oleic acid in your body cause you can make it yourself. PUFAs also play a role it’s just that you have a lot more oleic acid. So basically any release of free fatty acids is probably going to inhibit thyroid signaling and the best evidence for this is at the level of thyroid binding to the nuclear receptor and then binding to DNA. It seems that the concentrations of free fatty acids do get high enough in the nucleus of the cell to inhibit signaling there and that will not be reflected by free T3 levels in the blood or anything like that. So it would be very difficult to detect it clinically, but it’s probably a fact during weight loss or during any kind of dieting that leads to large increases in free fatty acids.

So here’s the thing, many people when they lose weight will see their triglycerides go up. They may see their cholesterol go up and so on too, but it’s all highly dependent on the person. So someone who has very good micronutrient status, all the micronutrients that they need to burn energy, has good thyroid hormone status, has all the things that we would expect to promote burning energy at the liver, this person might just burn that energy really efficiently and their blood lipids might improve the whole time. Someone else who’s losing adipose mass might see quite different results. They may develop fatty liver if they don’t have enough choline to get rid of the fatty acids that they can’t burn so they get stuck in the liver. But if they have enough choline, for example if they’re on a paleo diet with a lot of liver and egg yolks, so they’re getting lots of choline but they’re not getting enough of some other nutrient or some other factor that’s needed to burn that energy, they’re gonna see their triglycerides go up and they might see their cholesterol and other things go up as well.

So this would be my advice first make sure that the difference is large enough to say it’s actually increased. Second, if you’ve been losing weight don’t even look at your blood lipids until your weight is stable. If you’re obese and overweight, normalize your metabolism, normalize your weight, normalize your body fat, wait til it’s stable for a few months and then test your blood lipids. And if it’s triglycerides make sure it’s fasting, make sure it’s been the same length of time since your last meal and those things. Only then should we even begin to say okay there is an increase or there is a decrease that’s  meaningful.

Chris Kresser: Chris, thank you so much we’re gonna have to have you back for part three it looks like cause we’re out of time for today. But we’re so grateful to have you on the show it’s really exciting to get all of this super current information. I tweeted this out right before we started the show, I honestly believe that if people listen to part 1 and part 2 of this podcast about cholesterol they’re gonna know more about it than probably 99% of doctors at this point.

Chris Masterjohn: Yeah well I think this was a great show and I think this is the testing blood lipids show and if we have a part 3, then part 3 can be if you have all of those factors that convince you your blood lipids are actually changed what do we do about it.

Chris Kresser: That’s the cliffhanger. Sorry to leave you hanging folks but this is obviously as not as simple as it’s made out to be in the conventional paradigm. We’ll definitely have Chris back if he’ll join us again.

Chris Masterjohn: Absolutely thank you so much Chris and thank you so much Danny it was great to be here.

Chris Kresser: You’re welcome, Danny take it away.

Danny: That’s gonna bring us to the end of this week’s episode. Chris Masterjohn where can we find more of your work on the internet this week?

Chris Masterjohn: You can find me at cholesterol-and-health.com and my blog the daily lipid, and there I also post all the links to my mother natured obeyed blog over at WestonAPrice.org and you can also follow my on facebook and twitter.

Danny: Mr. Kresser, same question to you.

Chris Kresser: Same place, we’re at Chriskresser.com now, the Healthy Skeptic is retired, is no longer. It’s all there at ChrisKresser.com and then join me at Facebook, Twitter. I’m writing a series I just published the first article yesterday on low T3 syndrome. Some of this is gonna dovetail what we’re talking about with Chris on the show today about cholesterol. If you’ve got low T3 but your TSH is either normal or even low, which is not the typical hypothyroid presentation, you might wanna check this series out. And then I’m still finishing up the series on natural childbirth. I’ve got one more article to write on the potential side effects and complications of cesarian sections. So look for that in the next week or so, that’ll wrap that series up.

Danny: You can find all of Chris’ work at Chriskresser.com. You can find me at Dannyroddy.com. Keep sending us your questions at thehealthyskeptic.org using the podcast submission link. If you enjoy listening to this podcast head over to iTunes and leave us a review. Thank you for listening and thank you for your support.

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  1. awesome podcast series! Just wondering if you could provide the references for the individual variability in the various cholesterol measurements – mentioned in the last 15min of the podcast? It’s always good to have a copy of the source for the inevitable challenges…

    Thanks!

  2. I found a transcript for part 1 at blog.superbootcamps.co.uk/2012/diet-and-nutrition/the-healthy-skeptic-podcast-transcript-episode-11-chris-masterjohn-on-cholesterol-heart-disease-part-1/. I couldn’t find a transcript for part 2, though.

  3. I was just wondering if you have part 1 and 2 in transcript form like you do for part 3? I too was concerned about my resent lab work since adapting to Paleo about a year ago. TC 234, HDL 84, Triglycerides 61, LDL 138, VLDL 12. Of course the doc said to lower the intake of meats, dairy and eggs to bring it down. Argh! I am a healthy 51 year old. Weight on average, 125. I hope that you are still responding to this topic since it’s a few months old. I read part 3, but sometimes it gets overwhelming as to what to do! Thank you so much for all of your hard work gentlemen!

  4. If I might add:
    How do we know if he has oxidized Ldl? Does the blood work show that?
    My husband is 56 years old – if that is a factor here.

    • There aren’t any commercial tests for ox-LDL right now. If he’s eating a lot of polyunsaturated fats and isn’t eating antioxidant rich foods, he probably ox-LDL.

  5. Hi Chris,
    My husband recently had blood work done which shows his blood cholesterol at 310, triglycerides at 154, Hdl at 40 and Ldl at 239. We are not concerned about the cholesterol number but I gather from some of what you’ve said that some of his ratios could show he’s at risk for heart disease. Would that be accurate?
    Thanks, Anita

  6. I was excited to see that there would be a discussion about raised TC from paleo or HF diets. However, I was quite stunned to hear that a 17mg/dl changed is called “huge”! I have my lipid profiles for six years now, dating from when I ate a conventional diet, through strict paleo, then into high-fat so a good baseline. During that time my trigs fell (300 to 100) while my LDL rose (200 to 300). In spite of trying to keep up with all the latest knowledge on this subject, I’m still at a loss as to whether I should do anything about this. It looks like I have either high TGs or high LDL, depending on what I eat. (HDL has always been good, >70).

    It can be frustrating and scary to think that you’ve changed your nutrition for the better only to have your lab tests put your doctors into freak-out mode…

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