Chris Masterjohn PhD., talks about Dietary Management of Heterozygous Familial Hypercholesterolemia (HeFH)

Mastering Nutrition Episode 16: Dietary Management of Heterozygous Familial Hypercholesterolemia (HeFH)

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Chris Masterjohn, PhD talks about Dietary Management of Heterozygous Familial Hypercholesterolemia (HeFH)

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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Read on for the show notes.

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 and the cool trick you can use to find show notes easily: where “n” is the episode number. So, for example, 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
  • 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

The Facebook Live episode on heart disease.

Genes, LDL-Cholesterol Levels, and the Central Role of  LDL Receptor Activity in Heart Disease

The Central Role of Thyroid Hormone in Governing LDL Receptor Activity and the Risk of Heart Disease

Mastering Nutrition Episode 11: Paleof(x) Grab Bag: Carbs, Sex Hormones, Type 1 Diabetes, and More

PCSK9 and LDL Receptor Degradation: Regulatory Mechanisms in Cicrculation and in Cells

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)

The Kitava Study

Episode 2 of my 3-part series with Chris Kresser, where we discussed blood cholesterol levels in ancestral populations free of heart disease

My writings on fatty liver disease and choline

Coenzyme Q10 protects against PUFA-mediated longevity reduction in rats

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  1. Hi Chris-

    I just now stumbled across this and, unfortunately, I’m already on statins. I’ve never been overweight and am content with my body comp. I could transition to the Kitavan diet quite easily, but I assume that this change would be meaningless since I’m currently taking Lipitor…?

    1. No, you can work with your doctor to see if it can help reduce your need for the Lipitor, or eliminate it.

  2. Hi Chris,

    I really enjoyed this podcast, thank you. Would love to know your thoughts on this article by Zoe Harcombe in the UK. She does a lot of research on cholesterol:

    If you don’t have time to read the whole article I will post the interesting bit here:

    “The classic view of FH is framed by the widespread assumption that blood cholesterol levels are a marker of heart disease. As this post shows, there is a relationship between blood cholesterol levels and all-cause mortality and cardiovascular disease (CVD) mortality – in men and women – but it is inverse i.e. the higher the cholesterol level, the lower the death rate and the lower the cholesterol level, the higher the death rate. That’s for 192 countries for which the World Health Organisation (WHO) has data. That’s a slightly inconvenient truth.

    The classic view of FH argues that people with FH have higher heart disease and high cholesterol and therefore high cholesterol causes heart disease. Does the evidence support this view?

    Because of the rarity of FH, data are not abundant. Most data emanate from the Simon Broome Register Group, which started to study patients with Heterozygous FH (the 1 in 500 form) in 1980. (The Simon Broome Register Group has been funded by Astra Zeneca, Pfizer and Merck Sharpe and Dohme, by the way).

    One of the first publications from the Simon Broome Register Group dates back to 1991. This review analysed standardised mortality ratios (SMR) for 282 men and 244 women aged 20-74 with Heterozygous FH. The participants were followed up for 2,234 person years. The results were that the highest SMRs, relative to the non-FH population, were for the age group 20-39 and the higher death rates for FH sufferers decreased significantly with age, such that mortality was no higher for people aged 60-74 with FH than for people of the same age without FH.

    This widely referenced study also derived from the Simon Broome Register Group. It followed 2,871 patients with Heterozygous FH who were recruited from 21 outpatient lipid clinics in the UK from 1980 to 1998. The patients were followed for 22,992 person years. The standardised mortality ratio (SMR) was calculated for these patients and compared with death rates in the non-FH population in England and Wales. There were 169 deaths recorded, including 102 from coronary heart disease (CHD) and 32 from cancer. The SMR for CHD was 2.5 times higher for the FH sufferers than the general population, but the all-cause death rate was no higher. Non-CHD mortality was significantly lower in men and women. The study found that patients with Heterozygous FH were dying more of CHD, but less from cancer and thus the death rate was no higher overall.

    The combined findings from these two Simon Broome Register Group papers show that, if you genuinely have FH and you are aged 60 or over you should be pleased to know that you have a lower risk of cancer and no greater risk of heart disease. If you have FH and are aged 39 or higher, you are already past the highest risk period of your life for heart disease. Even in the 20-39 age group, there were 6 deaths in 774 person years studied – less than a 1 in 100 incident rate and that’s in 1 in 500 people.

    Another widely referenced, long, Dutch, study set out to estimate all-cause mortality from untreated FH. The study was described as a “Family Tree Mortality Study”. It traced back numerous descendents from a single pair of ancestors in the 19th century. Those with a probability of carrying the FH mutation were followed. This involved 250 people analysed for 6,950 person years during which time 70 deaths occurred. The study found that mortality was no higher in carriers of the FH mutation during the 19th and early 20th century. Mortality rose after 1915, peaked between 1935 and 1964 and fell thereafter. Mortality also differed significantly between the branches of the descendents studied. The conclusion was that the risk of death differed too much over time, and too much between different descendents, to support the view that high cholesterol was the factor. The study concluded that environmental factors must play a part and must be researched more thoroughly. Sadly this has not happened, because the cholesterol hypothesis has become the only factor considered important with FH.

    An alternative view of FH

    If you are not limited by the assumption that high cholesterol is bad, you can view FH quite differently.

    My logical consideration of FH suggests to me that the problem is that the LDL receptors don’t work properly and therefore LDLs cannot get into the body’s cells in the way that they are supposed to. This means that cells don’t get the vital LDL, carrying the vital protein, lipids and cholesterol needed for the cell’s health. LDL in the blood stream is high because the LDL has stayed in the blood stream and has not been able to get into the cells – where it is supposed to go. Hence high LDL blood levels are the sign that someone has FH. The high LDL levels are, however, a symptom and not a cause, or a problem per se. The problem is that the health of every cell is compromised by LDL not getting into those cells. This includes heart, brain and muscle cells – all cells. Someone with FH can therefore have heart problems – because of too little LDL reaching the heart cells – not because of too much LDL in the blood stream. How differently things can be seen when one is not blinded by thinking that cholesterol or lipoproteins are bad.

    The heart disease/cancer evidence supports this hypothesis. If the vital substances in LDL cannot get to heart cells, heart disease would be more likely. If the vital substances in LDL cannot get into a cell that has become cancerous, that cell can’t be fed and the cancer is less likely to spread.

    A genetic view of FH

    There are also alternative hypotheses for FH involving genetics more broadly. These make complete sense. This article, cited almost 50 times, studied 1,940 FH patients for 65 polymorphisms (different forms) in 36 different genes and found a significant association between “Prothrombin G20210A” and CVD risk. Don’t worry about the unfamiliar words – all we need to know is that Prothrombin G20210A is a human gene mutation that increases the risk of blood clots. The study found, therefore, that people with FH who had an accompanying genetic mutation that increased blood clots were more likely to suffer CVD. That makes sense, of course. It also makes sense that a genetic defect, which is what FH is, has more than one consequence. Another genetic consequence of FH (completely unrelated to cholesterol) can be increasing the risk of heart disease (and the same genetic consequence or a different one may be reducing the risk of cancer). The raised LDL would, again, be a symptom and not a cause of heart disease in any way.”

    I’d love to know your thoughts on this. Your strategy of trying to increase the expression of the LDL receptor from the normal gene would still be valid, it’s just that maybe we don’t need to view the LDL in the bloodstream as the problem?

    Also this (from the Nourish Balance Thrive podcast – this is from the transcript: )

    “The interesting thing about it is this is what got me kind of worked up about this is if you’re looking at the epidemiological data the people who are at risk of cardiovascular disease or all-cause mortality associated with high levels of cholesterol are people who are young. So like I said, we have a lower optimal reference range for people who are below 60 versus above 60 and the older you get the less cholesterol correlates with all-cause mortality and actually it seems end up becoming protective, so the higher cholesterol the longer you live. There’s a really nice story which goes along with this which mirrors what happens in familial hypercholesterolemia which is something that people I’m very worried about in terms of cardiovascular disease risk. In those people they have a mutation or one of many potential mutations of the LDL receptor, so they clear less LDL out of the blood and they have high levels of LDL.

    In those people, again, they’ve shown this very nicely, that in the young people with familial hypercholesterolemia, and this is usually just one mutation because people who are homozygous for these LDL receptor mutations is very rare. So you have one mutation on your LDL receptor, you have high levels of LDL, and those people with familial hypercholesterolemia are only at increased risk of cardiovascular disease when they’re in their 20s and 40s. When they then get above 60, regardless of what their LDL is, they have normal risk of cardiovascular disease. So it’s very similar to what we see in terms of just the general population that high cholesterol only seems to be associated with something bad when you’re younger. And when they’ve looked at the familial hypercholesterolemia literature they’ve seen something very similar which is if you go back to the 19th century, people in families which have these mutations they seem to be protected, they actually live longer, probably because LDL is really important as part of the immune system and maybe they were protected against certain infections and then they became at increased risk when we started to smoke and we have picked up the Western diet in the 20th century, it’s very much dependent on the environment.

    So again, in that literature, they say that environment is much more important than cholesterol and again, if you look at people with familial hypercholesterolemia, and it’s very similar in general population, too, people who have heart attacks, their LDL cholesterol is pretty much exactly the same as people who don’t have heart attacks. So other stuff is important like insulin resistance and any kind of other associated problems with that. If you’re looking at these people who are at high risk, they both in familial hypercholesterolemia literature and in the general population, they’re at high risk of cardiovascular disease, so particularly we’re going back to that because that’s what people are worried about in young people with high cholesterol, they appear to have some kind of insulin resistance and that could be high levels of insulin, elevated HbA1c, they could be smokers. So anything in that kind of arena, that seems to be what’s causing the risk, and then the cholesterol maybe makes that worse but it’s sort of along for the ride, that’s not what’s causing the problem.

    So the more I looked at this the more I realized that we have it flipped around. We should be maybe focusing on people who are young who have high cholesterol and then figuring out why that cholesterol is high. Again, if we’re talking about LDL, you might have a thyroid problem or you might be insulin-resistant and that is where you need to focus because insulin resistance changes how you produce and clear the LDL receptor, the thyroid is also really important for that thyroid hormone function. So if that’s what you’re worried about we should be looking at this in young people and figuring out what the problem is, is it insulin resistance, is it problems with thyroid, I think those are going to be the two most common, we should be focusing on that. Then when you get older, when you get into your 60s or 70s, actually cholesterol doesn’t really matter that much.”

    Thanks for reading!

  3. Hi, I have something of what might be considered odd evidence. My mothers side of the family has a history of FH, but no history of CVD. My fathers side of the family has what most would consider ideal cholesterol lvls with perhaps slightly lower HDL sometimes, they however do have a history of CVD.
    Considering these facts and my lack of other risk factors, I currently just try to eat a healthy diet (doing IF, eating whole foods), I do however feel best on a higher fat diet and from experience egg and fat consumption doesn’t seem to affect my cholesterol lvls at all aside from lowering my hdl very slightly.

    I’m mostly curious what your take on this is.

  4. Hi Chris, I’m reporting back on my results after following the advice in this podcast for the last couple of months. In August of 2016 my numbers were:
    Cholesterol – 340
    Trig – 42.5
    HDL – 63.4
    LDL – 268.4

    Over the last couple of months, I increased my dietary carbs from fruits veggies and tubers, and decreased my added fats and cooking fats, like butter and lard. Although I ate more carbs and less fat, I’m pretty sure I’m still not as high carb as you recommend! Also, I’m still eating about 12 eggs per week, and using some coconut oil in cooking, as well as coconut milk in thai curries now and then, and as a topping for berries. I just got the following results:

    Cholesterol – 308.6
    Trig – 52.2
    HDL – 62.6
    LDL – 235.5

    As you can see, the numbers are down, so I’m happy, but my doctor is still unhappy. I,m not sure at this point if I want to get more aggressive with my diet, but I wanted to let you know that there’s been some improvement! Maybe I need to cut back on the eggs etc?

    Thanks Chris!

  5. Hello Chris,

    I found your website and podcast while searching for dietary advice for kids with familial hypertriglyceridemia. I have a cousin who has three girls (3 months, 4 & 6 years old) with this condition and recently one of them got acute pancreatitis due to an increase in her triglycerides. Would the Kitavan diet help in such case as well? She is also concerned since they are at the growth stage and she wants to know if it’s ok to give them milk and eggs. She is also concerned for the 3 months old, what type of milk she can give her and what she should feed her when she starts eating?

  6. Thanks Chris. I aprreciate the replies, and all the info. I’m going to research insulin, and hopefully increase my understanding! I have been influenced by Gary Taubes etc. To believe that insulin=bad. Apparently I have a lot to learn.

      1. Hi Chris, I’ll try to remember to post my numbers when I get tested again this summer. I have been following your dietary suggestions for a week or so now. Also, I have been adding some seaweed/kelp/dulse to my diet every second day or so, and I’m hoping that this will nourish my thyroid. With the increased carbs, I have been feeling more alert and energetic and digestion has really been humming along (maybe from increased fiber?). Strangely, I have been sleeping better too. Also, despite worrying about maybe gaining fat from upping my carbs (I told you I was influenced by Taubes, eades, etc!!) I appear to be leaning out, and find myself a couple of pounds lighter.
        Thanks again for this article. My total-C and LDL numbers are pretty scary, and I’m hoping that finally I may have found something that will work. We’ll see!


        1. Dan, that’s great to hear. Your improved sleep is not even slightly strange. Nor is your leaning out.

          1. Hi Chris,
            I have one more question. What would your dietary approach for FH do to A1C and fasting blood glucose, in the context of an otherwise healthy, insulin-sensitive person? would these be impacted negatively, given increased carbs in the diet?


  7. I have an additional question. Assuming an insulin sensitive individual of good weight and body comp but very high LDL, eating mixed meals tending toward low carb: would switching to a diet similiar to the kitivans erode insulin sensitivity and move this individual back into insulin resistance, or would going to around 70% carb maintain insulin sensitivity?

  8. Hi Chris,
    This is good stuff, and gives me some hope of improving my numbers without statins. One question – I have read widely over the last couple of years and I think i understand the role and function of insulin pretty well, but i have never come across the term “insulin signalling”. Could you briefly explain this term, and say a few words about it in the context of this article?


    1. Hi Dan, if you have never heard that phrase I feel very confident that you do not understand insulin very well at all. I say that not as a criticism, but simply to mean that nothing you’ve read about insulin can possibly have been deep enough to give you even a basic sense of how it works. Insulin is a hormone. A hormone is something that communicates. Signaling is the process of communication. Hope that helps, Chris

  9. Dear Chris,
    Thanks for this great podcast! I am someone with FH and have been exploring strategies outside of statins (I was on them for a while, but found a functional medicine doctor and have been trying other options: mainly diet and vitamins/antioxidants). I would like to implement this diet and see how it helps me, but I’m not sure where to start. Tubers, fruit, fish and coconut is straightforward, but is proving a bit difficult in practice. Is there somewhere I could look for meal ideas based on this diet? Also, would nuts and legumes also be helpful to incorporate? Thanks!

    1. Hi Jonathan,

      I’m not sure where to look for meals and recipes.

      Legumes, yes. Nuts I would keep in moderation.


  10. I appreciate this info. It is hard figuring out what diet might work for HeFH. Starchy tubers are usually high oxalate, which people have to avoid if they have kidney stones. And coconut makes LDL levels go very high for some people. Any thoughts on alternatives for starchy items and fat?

    1. Starchy tubers are not generally high in oxalate, only some are. There are lots of foods rich in starch that are not high in oxalate.


      1. Thanks for your response, Chris. Sorry I misspoke. I didn’t realize when posting, that I was thinking in terms of the items that are currently available to me with additional dietary restrictions, due to autoimmune conditions. For instance, things like certain kinds of rice and potatoes, which can be low oxalate, are currently off the table.

        And I haven’t found a really suitable, consistently available starchy food that meshes with the low levels of oxalate I have to stick to. I had several fairly large calcium oxalate stones and a raised oxalate level.

        The usual oxalate food lists that are available are extremely inaccurate. More precise testing methods have been developed, but many lists haven’t been updated for years. I was able to get access to a very good list from Susan Costen Owens’ group.

        The lower oxalate winter squashes seem like the best starchy foods left in my diet, and they aren’t always available. Things like turnips and rutabagas aren’t particularly filling and I’m never able to find them organic where I live.

        Sorry for the long response. Thanks for all the information that you make available, there are so many interesting things to read at your site.

  11. Chris,

    Over what timeframe would you expect dietary changes to affect total cholesterol or TC/HDL ratio? I’d think within several months or less. What do you think about a couple of weeks?

    Thanks for the episode!

    1. Hi Griffin,

      I think you would probably see changes in a few weeks, but unless there is an emergency I would give it three month. And if the dietary change causes a change in body weight or body composition, I would wait for that to plateau and test the blood lipids three months after reaching steady weight


  12. Thanks so much for this excellent and really timely podcast Chris. We’ve been working with a client who is currently awaiting confirmation of FH and your advice here confirms that we’ve been taking the correct dietary strategy.

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