In this episode, I discuss dietary management of familial hypercholesterolemia (HeFH).
This question was asked on the Facebook Live episode from 06/16/2016, “Ask Chris Masterjohn, PhD Anything About Heart Disease,” but I was unable to get to the question within Facebook’s time limit.
Please note that HeFH is a medical issue and the purpose of this episode is not to diagnose or treat anyone with HeFH. This is educational in nature and the information should only be used to manage HeFH under supervision of a qualified health professional.
Herein, I discuss why I believe the Kitavan diet should serve as an ancestral diet on which to model dietary management of HeFH. It is a low-fat, low-cholesterol, high-carbohydrate diet where most of the fat is highly saturated because it comes from coconut, some of it is is from fish, and where the carbohydrate mostly comes from starchy tubers but some comes from fruit.
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Show Notes for Episode 16
The best way to get to the root of the problem in heterozygous FH is to take the one working gene for the LDL receptor and try to bring it up to the expression level that would be found in someone without FH. This can be done by maximizing the biological activity of thyroid hormone (within the range considered euthyroid) and by maximally suppressing PCSK9 activity with the help of strong insulin signaling. These come down to managing good body composition and eating a low-fat, protein-adequate, micronutrient-adequate, high-carbohydrate diet.
Restricting cholesterol may be helpful, but it also comes at the cost of cutting nutrient density, since some of the most nutrient-dense foods — liver and egg yolks — are also rich in cholesterol. Therefore, it should be #2 in the line of defense rather than #1.
Replacing saturated fat with polyunsaturated fat and using statins should both be tools in the kit, but they should be tools much further down the line of resort because they are less related to the root of the problem and they may come at costs that compromise health and longevity.
You can use this to navigate through the episode if you want to find specific parts:
- 0:28 Introducing ChrisMasterjohnPhd.com and the cool trick you can use to find show notes easily: thedailylipid.com/n where “n” is the episode number. So, for example, thedailylipid.com/16 redirects to the show notes you are reading right now (If you link to the show notes, however, please use the actual URL rather than the short cut.)Update: this has been changed to chrismasterjohnphd.com/n
- 4:36 Cliff notes for this episode.
- 6:02 Introduction to heterozygous familial hypercholesterolemia (heterozygous FH or HeFH)
- 11:06 Thyroid hormone and PCSK9 as the two critical regulators of LDL receptor activity
- 11:43 Specific importance of thyroid hormone
- 15:53 Specific importance of PCSK9
- 16:48 PSCK9 responds to the fasting-feeding cycle
- 18:32 PCSK9 responds to inflammation
- 20:14 PCSK9 responds to blood cholesterol levels
- 23:16 Maximizing insulin signaling is the best way to maximally suppress PCSK9 activity
- 24:06 The Kitavan diet can be used as an ancestral diet on which we could model dietary management as the first line of defense against poor LDL receptor activity in HeFH
- 27:53 Potential costs and benefits of restricting dietary cholesterol
- 33:55 Statins and PUFA should be tools in the kit, but shouldn’t be the first or second line of defense.
- 40:19 Catch my upcoming Facebook Live episodes: the next one is this Saturday, June 25 at 2:00 PM eastern time and the theme is “Ask Chris Masterjohn Anything About Methylation!”
- 41:41 Follow me on Snapchat for 23andMe tutorials and other stuff (chrismasterjohn is my username)
Links Related to Episode 16
What Can Familial Hypercholesterolemia Mortality in the 19th Century Teach Us About Genetics? (this covers the potential benefit of high LDL-cholesterol during conditions where early and prevalent mortality is due to infectious disease)
Episode 2 of my 3-part series with Chris Kresser, where we discussed blood cholesterol levels in ancestral populations free of heart disease
Transcript of Episode 16
This transcript was generously provided by Cassandra Barns.
This is Chris Masterjohn and you’re listening to episode 16 of Mastering Nutrition.
0:28 Introducing ChrisMasterjohnPhd.com and the cool trick you can use to find show notes easily: thedailylipid.com/n where “n” is the episode number. So, for example, thedailylipid.com/16 redirects to the show notes you are reading right now (If you link to the show notes, however, please use the actual URL rather than the short cut.) (update: this has now been changed to chrismasterjohnphd.com/n)
Today’s episode is about dietary management of heterozygous familial hypercholesterolemia. But before we get into it, I have a really exciting announcement to make. I have a new website: chrismasterjohnphd.com. The entirety of my blog Mastering Nutrition is now being housed there. The entirety of this podcast and all its show notes is now being housed there. So if you want to access either, you go to chrismasterjohnphd.com and in the menu you click on Blog if you want to see blog posts, you click on Podcast if you want to see podcast show notes. But guess what, I also have a new toy for you to find the show notes really easily. Thedailylipid.com/whatever number episode you’re looking for will redirect to the show notes on chrismasterjohnphd.com. Thedailylipid.com is not a website; it is my 301 redirect playground, and you are in on the fun. What this means is that instead of me giving you this big long URL to try to find – which of course is, you know, impossible on audio for you to remember a URL – if it’s simple, like, this is episode 1 ofMastering Nutrition, so go to thedailylipid.com/1, that will redirect you right to where you want to go for the show notes. Remember in the show notes you get not only links to relevant stuff in the episode and eventually you will be seeing transcripts accessible from there, but you also will get a time-based map. So say you don’t want to listen to the whole episode, you just find the key topics and skip ahead to where you want to see. So for example, this is episode 16. So the show notes are at thedailyLipid.com/16. I think this is really valuable now, but it’s gonna be especially valuable going down the road. Imagine when we’re at episode 100 and during episode 100 I say, yeah, remember when I was talking about blah blah blah in episode 7, and you’re like, that sounds really cool, I should listen to episode 7, well you’ll be able to do that whenever you want just by going to thedailylipid.com/7 and it’ll be really really really easy to get there instead of going through and browsing through – you know, scrolling through 100 episodes until you get to the right one. Alright, that’s it for now, so please – everything will be redirecting from blog.cholesterol-and-health.com soon, that will no longer exist except to keep the links unbroken so everything redirects to the current place. But you know, it’s a good idea that if you’re linking to something there, update your links to where it is on chrismasterjohnphd.com; if you’re following the RSS feed I will try to redirect that, but you might want to re-follow fresh on chrismasterjohnphd.com.
Update: This has now been changed to chrismasterjohnphd.com/n
Alright, that’s exciting, but let’s move on to another exciting topic, which is today’s episode about dietary management of heterozygous familial hypercholesterolemia. Without further ado, here it is.
In this episode I want to answer a question from Michael Hicks that was left on the Facebook live episode on heart disease, that I did not get to because of Facebook’s 90 minute limit to the videos. And obviously I cannot turn every unanswered question to a podcast, but in this particular case the question is how do you manage heterozygous familial hypercholesterolemia – and throughout this episode I will be using the abbreviation FH for familial hypercholesterolemia – how do you manage heterozygous FH in a natural way, and when do you decide whether to use statins? And this is really important to get to in part because many people have asked me this over the years, and it is something that I do have a lot of thoughts on, and I think it’s important to share those thoughts.
4:36 Cliff notes for this episode.
So for those of you who are on the go, I’ll give you the cliff notes. And the cliff notes are that heterozygous FH is a particular case that is outside the norm of what I would usually recommend, but here I would say that the number one front-line strategy should be, within the context of maintaining healthy weight and body composition, to eat a diet that contains a minimum adequacy of protein, about 20% of calories from fat – so a low-fat diet – and the remainder from carbohydrates, so a very high carbohydrate diet. I would say the number two strategy would be to limit dietary cholesterol, but to not do so in a way that compromises nutrition and since certain foods are very rich in cholesterol and are also very nutritious, I would say that this strategy should be implemented carefully and it should also be number two rather than number one. And statins and other approaches should be relegated to end-of-the-line strategies rather than front-line strategies. Alright, if that’s – if you’re on the go, then those are the primary conclusions; if you want the nuance and sophistication and the rationale and explanation, then keep listening.
6:02 Introduction to heterozygous familial hypercholesterolemia (heterozygous FH or HeFH)
So here’s the deal. Familial hypercholesterolemia or FH is a condition where either one or both of your genes for the LDL receptor are defective. And in homozygous FH, you have a defective gene from each parent. And in that case – this is the extremely rare case – and in that extremely rare case I think you need to just take everything that medicine can throw at it. We are reaching the point now where someone with homozygous familial hypercholesterolemia, instead of dying as an infant, may make it to childbearing age and in fact, just in the last few years was the first woman with homozygous FH actually pregnant and carried a baby to term. So that’s really serious. With heterozygous FH, that means that you have one defective gene for the LDL receptor from one parent and a good gene for the same receptor from the opposite parent. The LDL receptor of course is the principal means by which we bring LDL particles and thereby bring their cholesterol and their other substances and nutrients into cells. And it is expression of the LDL receptor by the liver – or hepatic LDL receptor expression – that is the primary determinant of cholesterol levels in the blood. It is also – I would say not just in health and nutrition, I would say across biology, there are few specific principles – you know beyond, like, general very broad theories, but there are a few specific biological principles that have any practical relevance for humans that have greater scientific support than the principle that we can protect ourselves from heart disease by having very robust expression of the LDL receptor. I’m not going to justify that statement in this episode, but I will link in the show notes to some of what I’ve written about that where I have justified that statement. If you have heterozygous FH, that doesn’t necessarily mean there’s one single genetic change that causes that, there’s actually a collection of different types of defect in the LDL receptor gene. Some of them are more severe than others. Some of them, for example, make you totally unable to produce an LDL receptor from that gene, and some of them make you produce an LDL receptor that just doesn’t function very well. And that will correlate with your cholesterol levels, and it will correlate with your heart disease risk. But in general we can broadly group all of those into one condition that we can call heterozygous FH. Now, the downside to having this condition is that most people have two copies of the LDL receptor gene, and you only have one. The upside is that you have one good LDL receptor gene, and that means that you can potentially compensate for only having one of those genes by making twice as many LDL receptors with the information in that particular gene. So in theory you could 100 percent compensate. And I’m not saying this will necessarily be the outcome of a good strategy, but in theory we should be able to develop a strategy that, if we know enough about how we regulate the expression of that one gene, we should be able to develop a strategy that brings – that doubles the expression of that one good gene of the LDL receptor and thereby fully compensates for the genetic defect. And so what I want to do here is primarily focus on how to do that. And I want to emphasize that this is a medical condition, I am not a medical doctor so any of these strategies that I talk about should be something that you bring to the doctor that you’re working with on this, that you can solve this together under the proper supervision. And of course that disclaimer should always be made, but this is a serious – this is a serious medical condition that – heterozygous FH is not a ticket to early death necessarily, but you have a much higher risk of heart disease in the earlier decades of your life like 40s, 50s and 60s than you would without heterozygous FH.
11:06 Thyroid hormone and PCSK9 as the two critical regulators of LDL receptor activity
Alright, so here the strategies. LDL receptor expression is partly – half the equation is how do you increase the number of LDL receptors that you make from that one good gene? The other half of the equation is, how do you preserve them? The first half of the equation is primarily influenced by thyroid hormone; the second half of the equation is primarily influenced by PCSK9, which is a molecule that we use in a regulated fashion to degrade LDL receptors according to stimuli from our – primarily from our internal environment.
11:43 Specific importance of thyroid hormone
So the first one – managing thyroid status – I’m gonna say less about that today because I’ve said so much about it elsewhere. So I will link to things in the show notes. But even as recently as episode 11 of this podcast, I’ve talked about why it’s so important to have adequate body fat but not be overweight, and to have adequate carbohydrate and therefore adequate insulin signaling in order to maximize thyroid hormone production and activation. So I would refer you to episode 11 for more details and I’ll just summarize them here. But everything that I said with respect to fertility in that episode could be said with respect to LDL receptor expression here. Because in fact thyroid hormone’s primary influence on fertility is to help increase the expression of the LDL receptor, thereby get cholesterol into sex hormone-producing cells and allow you to make sex hormones from the cholesterol. That exact principle applies to the liver. Everything that thyroid hormone does to sex hormone-producing cells with respect to LDL receptor expression, it also does to the liver. And thyroid hormone doing that at the level of the liver is going to be the primary thing that controls the uptake of most LDL particles from your blood, and the utilization of that cholesterol. To very briefly summarize, you need to have adequate body fat but not be overweight, and you need to have adequate carbohydrate in order to stimulate insulin to produce thyroid hormone and to activate thyroid hormone. In addition, you need to manage your stress response because in both the cases of carbohydrate restriction, but also any type of stress that activates the fight or flight system, you not only get hormones that can counteract the production and activation of thyroid hormone, but you also have elevation of free fatty acids, and free fatty acids can inhibit the binding of thyroid hormone to its nuclear receptor and inhibit its function. So I do think that it’s important to get a full panel of thyroid hormones and thyroid-related markers, but it’s also important to generally look at clinical signs and symptoms related to either thyroid hormone or the stress response, and to assess the diet, the lifestyle, the clinical signs and symptoms and the biomarkers in the blood together. And for that reason I think that it’s important if at all possible to find a high-quality functional medicine practitioner who is accustomed to working with thyroid hormone patients and is accustomed to interpreting these results, but also who understands these principles of why would we be trying to manipulate thyroid hormone status in order to influence heart disease risk, when virtually any other doctor would be using a statin as the first line of defense. So what you want to try to do with thyroid hormone is increase it within the range of what’s healthy – I mean, clearly you have to correct any thyroid disorders if they’re present – but within what’s healthy, there is a range where your thyroid activity could be a little bit lower or could be a little bit higher, and you want to push it towards the upper end of that range, because that’s what’s going to be the primary signal that increases the uptake of LDL – excuse me, the production of LDL receptors from the one good gene that you have.
15:53 Specific importance of PCSK9
Here I want to talk more about PCSK9 because I’ve written and talked about this much less. So PCSK9 I first – I have mentioned it before when discussing the genes related the LDL receptor, but it’s been years since I’ve done that, and most recently I brought it up in the Facebook live episode on heart disease. I’m gonna briefly review what I said about it there so all this is in one place, and I’m gonna expand it slightly because I didn’t talk about its relation to – its regulation of blood cholesterol itself.
Alright, so PCSK9 is basically controlling the degradation of the LDL receptor in response to three things. One is the fasting-feeding cycle. The second is inflammation. And the third is cholesterol levels themselves.
16:48 PSCK9 responds to the fasting-feeding cycle
And so if you look at this from an ancestral perspective or an evolutionary perspective, how would we expect the function of this protein to be shaped by the experience that predominated over the course of our ancestry, over the course of our evolution? Then everything about its regulation makes sense. So if humans were periodically exposed to feasting and famine, or to fasting and refeeding, then we would want LDL receptor to decline in the fasting state, because here you have a limited supply of nutrients, including a limited supply of fats, a limited supply of cholesterol, and a limited supply of the fat-soluble vitamins that are transported in the blood in lipoproteins. And in those cases you want to make sure all the extrahepatic tissues have access to all of those nutrients. And the way that they get that access in that case is, decrease expression of the LDL receptor so that more of that nutrient is circulating in the blood. Because the liver is the main expressor of the LDL receptor, expressing more LDL receptor biases the nutrient flow toward the liver and away from the other tissues. Less LDL receptor expression biases the nutrient flow toward the other tissues. If you have an abundance of nutrients, that part of it doesn’t really matter, but if you have scarcity of nutrients, it’s really important to make sure that tissues besides the liver get their fair share.
18:32 PCSK9 responds to inflammation
The other thing is inflammation. In the case of inflammation, you want more blood lipids, because lipoproteins in the blood help mop up infectious organisms and some of their derivatives like lipopolysaccharide or LPS. And it is desirable in acute infection to have higher blood lipids. And one of the things that stimulates PCSK9 is inflammation – that lowers LDL receptor activity and increases blood lipids. You also in that case want less reverse cholesterol transport. Reverse cholesterol transport is taking cholesterol out of the extrahepatic tissues, meaning the tissues that are not the liver, and carrying them to the liver. And the LDL receptor, since it’s the main way that the liver takes up cholesterol, is a key player in reverse cholesterol transport. The reason you want less reverse cholesterol transport in infection is because greater amount of cholesterol in the cell membrane increases the effectiveness of toll-like receptors or TLRs, which play an important role in the initiation of inflammation. And in an infection, inflammation is your defense against infection. So you want in that case a very robust initiation of the immune system to take care of that infection.
20:14 PCSK9 responds to blood cholesterol levels
And then the third thing that PCSK9 does is it helps the body arrive at a cholesterol level in the blood that is compatible with good health. And the way it does this is that PCSK9 actually binds to LDL particles. So in the blood, if you have more LDL particles circulating, they will bind to PCSK9 and make that PCSK9 unable to bind to hepatic LDL receptors and unable to stimulate the degradation of those receptors. So when you have higher LDL cholesterol, you inhibit PCSK9 activity, which raises LDL receptor activity and helps bring LDL cholesterol levels back to normal. When you have lower LDL cholesterol levels, there’s less LDL particles to bind PCSK9; more of the PCSK9 that circulates in the blood is free, and because it’s free it is able to bind to the LDL receptor, inhibit it, and stimulate its degradation. So PCSK9 is part of a homeostatic feedback mechanism that allows us to equilibrate the amount of LDL cholesterol and the amount of free PCSK9 at just the right amount to produce natural cholesterol levels compatible with good health. And so what we have is, if insulin signaling is normal and inflammation is normal, then PCSK9 is primarily functioning to allow us to reach that equilibrium. But as we move in and out of the feasting-fasting state, and in and out of the acute inflammatory response and the resolution of the inflammatory response, then that cholesterol level in the blood will deviate in order to give priority to those specific other functions that we were just talking about. So that means that one of the things that you have to do is control chronic inflammation. And that’s something that’s beyond this episode – I have written a little bit about it, there’s much written about it out on the Internet. I intend to produce more, so one of the things that I will be promoting when I’m ready to, is a report that is a very practical guide to resolving chronic inflammation. That’ll be very relevant there. But inflammation is something that is broadly applicable to heart disease; everyone who cares about heart disease should care about regulating inflammation, and so I’m gonna consider that beyond the scope of this episode.
23:16 Maximizing insulin signaling is the best way to maximally suppress PCSK9 activity
Assuming that chronic inflammation is not present and that the inflammatory response is isolated to the proper context in your body, then the primary thing that’s regulating PCSK9 is insulin. And you certainly don’t want to be insulin resistant; if you are, that could compromise your LDL receptor activity both because of too much PCSK9 and also because of not enough thyroid hormone production and activation. But you also don’t want to be low in insulin. Just like you want to push thyroid hormone towards the maximum of the healthy range, you also want to push carbohydrate intake towards the maximum of the healthy range, so that you get – assuming good sensitivity and good body composition – so that you get maximal insulin suppression of PCSK9.
24:06 The Kitavan diet can be used as an ancestral diet on which we could model dietary management as the first line of defense against poor LDL receptor activity in HeFH
And I think when you do that, what you want to model the diet after is the Kitavan diet. Because there is certainly a range of carbohydrate and fat throughout ancestral diets, but the Kitavan diet is one of the traditional diets that we know was associated with a zero percent – as far as we can tell – risk of heart disease – and good health, right? There are traditional diets like in the Tukisenta, that are much higher in carbohydrate – I think, you know, 96% carbohydrate was one estimate for the Tukisenta, I think it’s questionable whether that was overestimated by not looking at what they were eating when they were out foraging, and I think Stefan Guyenet gave a presentation on this at Wise Traditions a few years ago, it looked like they were not eating enough protein to have a normal rate of growth. They seemed to have – well, I mean, they eventually attained normal growth, but it seemed like they had a little trouble during the ages when they – when they should’ve been growing the most. So I’m comfortable saying that the Kitavan diet, which is about 20% fat and about 70% of calories is carbohydrate, I’m comfortable saying that that diet is associated with good health. And I think that modeling – including cardiovascular health but just good body composition and length of life in general – and I think that that is the model that you want to follow for heterozygous FH, because that’s the type of diet that would be most effective at maximizing insulin suppression of PCSK9.
Now, for the general population I don’t think that you necessarily need to go to that level of carbohydrate intake. There are clearly other traditional diets are higher in fat and lower in carbohydrate that were also associated with freedom from cardiovascular disease. It’s just that in this particular case, getting maximum benefit of that insulin is going to help conserve the LDL receptors, and getting maximal thyroid biological activity is going to help make the LDL receptors. And you cannot change your genetic information, so you cannot correct the exact root of the problem, but if you can take the one good gene and make more LDL receptors from them, and conserve those LDL receptors so that your cumulative LDL receptor expression is the same as or similar to someone who has normal genetics and has two good LDL receptor genes, then that is as close as possible that you could ever come to actually fixing the root of that problem. And so that should be the first strategy, because the strategy that takes a diet from within the range of healthy traditional diets that has a good track record in human history and applies that diet to normalizing the expression of the one thing that’s wrong, I think that would have the least possibility of negative side effects out of any approach, and it would have the most likelihood of causing – of providing benefit because it’s so close to the root of the problem.
27:53 Potential costs and benefits of restricting dietary cholesterol
Now I think a number two strategy should be, with moderation and care in the implementation, I think you want to limit cholesterol intake. And I say this because when you consume cholesterol, part of the response to that is to lower cholesterol production in the liver to compensate for that, but part of the response that the liver has is also to lower LDL receptor expression. And so probably there are a range of balances between those two mechanisms of compensating for dietary cholesterol. It’s probably the case that some people have a greater response in lowering LDL receptor expression, other people have a greater response in lowering cholesterol synthesis, so I don’t think that it’s gonna have the exact same effect in everyone. But it’s probably the case that incrementally less cholesterol will provide incremental improvements to LDL receptor expression. So I would say implement the first strategy and see what you can accomplish, and then whatever the residual problem is as measured by – principally by your blood lipids, implement the number two strategy to try to get rid of that residual problem. In other words, say we look at the Pacific island diets, Kitava for example, and even if you take islands where they’re consuming a lot of saturated fat like on Tokelau, if you look at these ancestral diets – and if you really want quantitative data, I will link in the show notes to the second part of my three-part podcast series with Chris Kresser on this topic where I talked about this in detail – but in general I think you want to see, for a man or a pre-menopausal woman, cholesterol dropping down at least to around 220 or so, and for a peri-menopausal or menopausal women you may allow an additional window up to 250 or so. I think you want to get those – and those ranges are less severe than what the current guidelines are, but they’re not that far off from them. So I would be a little bit more liberal with them, but not much more than 220/250, and I would say that you want to see your total to cholesterol – the total-to-HDL cholesterol ratio dropping down as close as possible to three, right, so 3.5 is not panic zone, but definitely don’t want it up at 5, 6, 7. So if the number one strategy gets you pretty close to there, then I would say tweak your cholesterol intake to try to match the rest of that. But if the first strategy only gets you 70%, then maybe be a little bit more aggressive with tweaking the cholesterol intake and see what that can do.
When you do tweak your cholesterol intake, you have to be mindful of the fact that certain foods like liver and egg yolks are really important sources of nutrients. Between liver and egg yolks, liver is more nutrient-dense and has a broader range of nutrients. So I would say prioritize liver over egg yolks, but if you’re comparing this to say, cream and tallow and things like that, I think that you really want to favor egg yolks over those fats. So it really comes down to, try to hold on to the liver once a week, see how many egg yolks per week you can get away with and experiment with them to see what effect that has on your cholesterol levels. Limit the egg yolks before you would limit the liver, from a nutritional perspective. And if you’re looking at the fats in the Kitavan diet, the Kitavan diet is pretty low in cholesterol because the fat – even though the fat is coming from coconut, which is high in saturated fat, it’s not high in cholesterol because it’s a plant food. So in that strategy you also want to be conscious of the fact that limiting egg yolks is going to decrease your choline requirement – excuse me, going to decrease your choline intake. And in the context of healthy body composition and a carbohydrate-dominant diet, I think that, you know, most people could get away with a lower choline intake, but, you know, if you are dealing with heterozygous FH and you’re also dealing with defects in folate metabolism, and so on and so forth, then there are a lot of nutritional considerations that come into play with choline. So I think that one strategy that you could use is to emphasize the plant foods that are richest in choline, because the choline to cholesterol ratio is high in them, even though the total choline is not as much as in egg yolks and liver, and I will link to an article that I wrote on meeting the choline requirement in the show notes to help you do that. And then you can always – you know, if you are concerned about choline status then choline supplements – and I would consider lecithin or phosphatidylcholine the default if you don’t have a specific reason to use another form. Choline supplements could have a place in that, to try to compensate for that.
33:55 Statins and PUFA should be tools in the kit, but shouldn’t be the first or second line of defense.
So then there is the question of, what about other strategies? Well, so the most common strategy to use is statins. And statins work by inhibiting cholesterol synthesis in the liver, thereby decreasing the pool of free cholesterol in the liver, thereby increasing the liver’s sense that it needs more cholesterol, thereby increasing the liver’s expression of the LDL receptor, thereby lowering blood cholesterol. So statins are accomplishing that, it’s just that they’re doing it in a way that is very indirect and very far away from the root cause. Because statins are inhibiting the production of mevalonate, which is a precursor not only to cholesterol but to many other compounds, including coenzyme Q10. Polyunsaturated fatty acids also will increase the LDL receptor, because they are more effectively esterified to cholesterol in the liver than other fats, and so if the cholesterol in the liver becomes esterified, the pool of free cholesterol declines, that increases the liver’s sense that it needs more cholesterol, increases the LDL receptor, decreases blood cholesterol – everything down from esterifying the cholesterol is very similar to what statins are doing. But the overall effect is just to move cholesterol from the blood into other compartments such as the liver, and you don’t promote the utilization of that cholesterol. So it’s not like thyroid hormone, where you’re taking cholesterol in from the blood and then you’re doing something with it because you’re ramping up the metabolic rate; you’re just basically stuffing cholesterol into those tissues, and it’s not clear that that’s ideal. But the main thing I would be concerned about with polyunsaturated fatty acids is that they increase LDL membrane PUFAs, and that makes the LDL particles more vulnerable to oxidation. And it is oxidation and not presence of the LDL particle in the blood that drives atherosclerosis. So it’s not – using statins and PUFAs could be – they should be in the toolkit, but they shouldn’t be the number one or the number two strategy; they should be towards the end of the line. And I would also say that, in rodents at least, you can – by feeding PUFAs, you decrease lifespan and you compensate for that effect by supplementing with coenzyme Q10, which is important for energy metabolism and as an antioxidant. So if you’re using statins and PUFAs as your first line of defense, if we can generalize from those experiments, that might just be an effective disease substitution, where you’re dying earlier from something besides heart disease rather than anything that actually addresses the root cause. So I would say if you do wind up using PUFAs or statins in your toolkit, you also want to dig into coenzyme Q10 to help protect against both of those tools. But, you know, ideally what you want to do is say, how can I replicate an ancestral diet that has a macronutrient ratio consistent with helping me address LDL receptor activity. And so I would say, overall you want – you know, if you look at the RDA for protein it’s 0.8 g per kilogram lean mass; I would say that there’s pretty good evidence that for body composition you want to improve that to 1.2 g per kilogram. There is evidence that more protein could help you maximize muscle mass. But I think that in the case of heterozygous FH, that’s not your priority; your priority is how much carbohydrate can you fit into the diet without causing the diet to be hypercaloric. Right, so you – normalizing body composition has to be very important, and if you are in a weight loss phase to achieve ideal body composition, then that’s where protein intake around 1.2 g per kilogram target lean mass and a resistance-based exercise program to provide an anabolic stimulus is very important for lean body mass preservation during weight loss. When you are at your body composition, then I think the priority becomes, without putting on excess fat, how can you maximize carbohydrate intake and still meet your other nutritional needs. And I would model that after the Kitavan diet. So 1.2 g per kilogram lean mass of protein, about 20% of calories from fat, and the remainder from carbohydrate. And the carbohydrate should be from whole foods with a balanced nutrient profile. So if you look at the Kitavan diet, that carbohydrate is – a small amount is coming from fruit, a large amount is coming from starchy tubers. You want to mix these traditional foods up in a way that gives you a good micronutrient profile; you do not want to be getting your carbs from – primarily from pasta made from refined flour, or from low-fat cheese pizza or something like that.
Alright, so again remember that this is – what I’m providing you is information from my academic experience and expertise that is designed to help you work with a healthcare professional to manage this condition, and it is not a substitute for medical advice. Heterozygous FH is a medical condition and I’m not – on this podcast I’m not diagnosing or treating anyone or providing you advice that should detract from the medical advice and medical treatment that you should have with your – with a healthcare professional that you have a good relationship with. And again I want to emphasize that in this case you really have to find a functional medicine practitioner who really understands thyroid hormone and understands the rationale for using thyroid status as part of a strategy to normalize blood lipids.
40:19 Catch my upcoming Facebook Live episodes: the next one is this Saturday, June 25 at 2:00 PM eastern time and the theme is “Ask Chris Masterjohn Anything About Methylation!”
Alright, that’s it for this episode. I want to remind you that if you want to come live on Facebook, these are great opportunities to have a very participatory and interactive discussion, so I would love it if you could show up and provide the questions that become the show. And the schedule of upcoming events is: Saturday, June 25 at 2:00 PM Eastern time, ask me anything about methylation nutrients – that includes B12, folate, choline and many more; Wednesday, June 29 5 PM Eastern time, ask anything about vitamins A, D and K; And Saturday, July 9 2:00 PM Eastern time, ask me anything about anything related to health, fitness and nutrition – that is a free-for-all like the first episode. So I would love to see you at those. Remember that you have to adjust that your time zone if you’re not on Eastern daylight time like I am. And all you have to do is show up to my Facebook page – the public figure page, not my personal page – just show up there at the appropriate time and start watching and start leaving comments as questions that I can see and respond to. And if you show up right at the time and you don’t see the video, just refresh the screen because you will – you’ll have to go either right after I started the video, or you’ll just have to hit refresh so that the video pops up.
41:41 Follow me on Snapchat for 23andMe tutorials and other stuff (chrismasterjohn is my username)
In addition to that, I would like to invite you to follow me on Snapchat, where the latest thing I’ve been doing is posting some video tutorials about using 23andMe. And the first one that I left was, if you got 23andMe after the FDA dispute so that you do not have access to their Alzheimer’s report, how do you determine your ApoE genotype. And so I posted a video tutorial of how you can hack the lack of an Alzheimer’s report to figure out your ApoE genotype. And I’ll be doing things on Snapchat like that in the future. And eventually these things – these types of things will – I will publish YouTube videos about how to do them that are embedded in blog posts about their practical relevance. But, you know, it takes me quite a while to actually put something like that together, and so what you can – if you’re interested in following me on Snapchat, one of the advantages that you get is that, you know, while I’m figuring this stuff out or while I’m thinking about it, you get kind of a – in this case could be a one month in advance sneak preview about this, and you can always save and download those videos to actually use them yourself and figure some things out while you’re waiting three or four weeks for me to figure out how to put together a really good blog post and a permanent video on YouTube about it.
Alright, that is it for today. I hope you enjoyed this and found it useful and I will see you next episode.
Alright, that was the episode. I just want to pop in here at the end to remind you that you can get the show notes by scrolling through the episodes at chrismasterjohnphd.com – click on Podcast. Or get the show notes for this episode with a quick link by going to thedailylipid.com/16.
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