Is High Cholesterol Genetic?

Mark Volmer
Jul 17 · 11 min read

With all the talk about the benefits of the ketogenic diet, you may be wondering where cholesterol fits into the equation.

High cholesterol is still a major concern as it not only contributes to heart problems but also cognitive decline. However, the answer to whether or not cholesterol is a concern for you is hidden in your genes.

I know, the keto diet is all the rage right now. And yes, it will help increase your energy levels. But just like everything else in the world of nutrition, you need to interpret this for yourself. Meaning that eating all the milk and cheese your body can handle may not be the best way to keto for everyone.

There are certain genes that you possess that will influence the way your body handles its fat intake. These genes may require you to make some alterations to your ketogenic diet.

It’s not always as simple as all the fat all the time!

A quick primer on your genome

A genotype is the set of genes in your body. Everyone has a unique genotype (albeit very slight). A phenotype is how those genes are expressed — in other words — what makes you, you.

The other two factors influencing the characteristics expressed by your genes — or your phenotype — are:

  1. Epigenetic factors you inherited from your parents, which determined how your cells express their DNA before you were born;
  2. Environmental factors (like the food you eat or the toxins you’re exposed to).

This means that two people with the exact same genotype could end up looking completely different due to the way their environment affected the expression of their genes.

Of particular interest to ketogenic dieters are the apolipoprotein A (APoA) and apolipoprotein E (APoE) genotypes. These genotypes influence the way your body processes fats and cholesterol. Some of you will have the perfect genes for a keto diet: if this is you, you will be able to eat all the fat you want and it won’t affect your cholesterol.

However others may be negatively affected by high levels of saturated fat intake.

The key takeaway here is that a keto diet consisting primarily of saturated fat is not for everyone! Let’s dive into the keto genes and how they affect your cholesterol levels!

The keto genes

If you’re following the keto diet the genotype you need to worry about is the ApoE (apolipoprotein E) gene. This is the gene strongly correlated to Alzheimer’s disease. (1)

The ApoE gene gives instructions to your body to make a specific protein. As the name suggests, that protein is called apolipoprotein. Apolipoproteins combine with fat (lipid) molecules in your body to form something called lipoproteins (fat-proteins).

Lipoproteins are responsible for packaging cholesterol and other fats and carrying them through your bloodstream. This becomes especially important on a ketogenic diet where you’re taking in high levels of fat on a daily basis. APoE dictates howyour body stores and uses cholesterol.

To get even more specific, the APoE gene comes in three different forms, or alleles. Different alleles on the same gene produce dramatically different effects. On the ApoE gene, the following alleles can occur:

  1. Epsilon 2 (e2)
    Less than 10% of the population carries this form of the gene — and if you have it worry not, you can keto to your heart’s delight. There is no conclusive research linking heart disease, high cholesterol levels, or even cognitive impairment with this gene.
  2. Epsilon 3 (e3)
    Considered the “neutral” genotype of the APOE gene, approximately 79% of the population has this allele. (4) If you have the e3 variant, you too have the green light to keto. Much like the e2 variant, there is no data connecting e3 variants to negative health outcomes as a result of consuming high levels of dietary fat. Bring on the cheese!
  3. Epsilon 4 (e4)
    Approximately 14% of the population carries the ApoE4 gene — and it’s this gene that has the negative health conditions strongly associated with it. The ApoE4 gene has been associated with:
  • Atherosclerosis (the build-up of plaque within your arteries) (8)
  • Alzheimer’s disease (9, 10)
  • Impaired cognitive function (11)
  • Reduced hippocampal volume (12)
  • The hippocampus is the area of your brain that is responsible for short, long, and medium-term memory storage.
  • In Alzheimer’s this area of the brain is the first to be affected.
  • Faster progression of multiple sclerosis (13, 14)
  • Sleep apnea (15, 16)

It’s the ApoE4 gene that poses some problems to keto dieters. If you have one ApoE4 gene (from mom or dad) or, if you have two ApoE4 genes (from mom and dad) you’re at a significantly higher risk for developing increased fat deposits or scarring on the inside of your arteries (atherosclerosis). This can lead to an increased risk of heart attack and/or stroke.

If you have this gene, you’re going to have to revamp your keto diet!

Why did nature select you for such a crappy gene?!

If you learn that you have an ApoE4 gene, it can feel like a pretty bum deal. I know I felt disheartened after learning I had inherited the gene from my dad.

Why would nature select for a gene that’s associated with all these negative health outcomes?

Today, the ApoE4 gene is associated with a number of negative health outcomes, but it wasn’t always that way. In fact, the ApoE4 gene helped your ancestors survive — thrive even — in a very different world than what we see today.

Humans are living longer than ever before. In the past, your ancestors were lucky if they made it to 40 years old. If you died before the age of 40, it’s unlikely you would have experienced any cognitive decline or Alzheimer’s/dementia-like symptoms. You simply weren’t living long enough to have the illness develop.

For 99% of human existence, humans lived in small hunter-gatherer tribes. In stark contrast to today’s almost sterile municipalities, the environment your ancestors lived in did not cater to sanitation. Infections were common and often fatal. The ApoE4 gene evolved to protect you from the infectious burden of the environment.

If you do not have the ApoE4 gene, over the long term you’ll experience cognitive decline when you have parasites in your body.

Those with the ApoE4 gene have been shown to have improved levels of cognitive function while under high levels of parasitic load. (17) The ApoE4 gene protects you from infectious disease. It has even been shown to convey immunity to childhood infections like giardia and hepatitis. (18)

The trouble with the ApoE4 gene is that it thrives under an infectious load — and omdern society is anything but infectious. It borders on sterile. Unfortunately, this is a complete mismatch for those of you with an ApoE4 gene. And as you’ll soon find out, so too might a keto diet high in saturated fat!

ApoE4 & the keto diet

The ketogenic diet is a high-fat, low-carbohydrate way of eating. It forces your body to use fat (ketones) to create energy instead of carbohydrates (glucose). And while I recommend a keto diet to the majority of my patients, I’ve come to learn that a keto diet needs to be far more nuanced than simply amping up the butter, cheese, and bacon intake. This is especially true for those of us with the ApoE4 gene.

Nigerians have the highest prevalence of ApoE4 genes in the world, yet they have incredibly low levels of Alzheimer’s disease. However, when you compare Nigerians living in Nigeria to Nigerians living in America, the Nigerians living in America have far higher levels of LDL cholesterol (that’s the bad cholesterol) and much higher rates of Alzheimer’s/dementia. (19, 20)

Those with ApoE4 status are experts — and not in a good way — at making LDL cholesterols. (22) Research is suggesting that cholesterol levels, specifically LDL-c particles, are the biggest risk factor for developing cognitive decline and/or Alzheimer’s disease, not the ApoE4 gene. (21) And this is where the ketogenic diet enters the conversation.

If you have the ApoE4 gene and you consume a standard ketogenic diet — a high intake of dairy products, fatty cuts of meat, and oils — your body will likely produce very high levels of LDL cholesterol. (23) And it’s this cholesterol that could be putting you at risk for cognitive decline!

Your healthy ketogenic diet could actually be putting your brain at serious risk!

So, is a diet higher in carbohydrates the answer for ApoE4s?

You’d think that if a high-fat diet raised cholesterol in ApoE4s then a low-fat, high-carb diet should lower cholesterol. But that’s not what happens! Research has shown that a high carbohydrate diet also raised cholesterol levels in ApoE4s (even higher than the high-fat diet!). Both a high-fat low-carb (paleo/keto) diet and a low-fat, high-carb (standard American diet) made things worse for people with ApoE4 status.

What’s an ApoE4 to do?

How an ApoE4 should eat

If you’re an ApoE4, you don’t have many options when it comes to diet. The upside to this is it makes determining your ideal diet quite easy. High-fat diets raise your cholesterol. Low-fat diets raise your cholesterol. But diets high in monounsaturated fatty acids (MUFAs) result in a dramatic drop in cholesterol levels. (24) But here’s the kicker: this way of eating only works for ApoE4s (both homozygous and heterozygous). (25)

What the heck is a MUFA?

There are three basic varieties of fats:

  1. Saturated fatty acids (SFA) — fat found in animal products such as dairy, fatty meats as well as some vegetable products like coconut oil.
  2. Poly-unsaturated fatty acids (PUFA) — fats that are liquid both at room temperature and when chilled. Examples include vegetable oils like cottonseed, walnut, sesame, peanut and flaxseed.
  3. Mono-unsaturated fatty acids (MUFA) — fats that are usually liquid at room temperature, but when you chill them, they turn solid. Think olive oil, peanut butter, avocado and many nuts and seeds.

Dr. Steven Gundry has laid out a stellar set of dietary rules all ApoE4s should follow. These include:

  • Limit fat intake from animals.
  • Avoid dairy fats (especially cheese!)
  • Dairy fats have the strongest correlation to the production of unwanted LDL.
  • Simply removing dairy often dramatically improves the cholesterol levels of ApoE4s.
  • Limit your intake of sugars, fruits, and seeded vegetables.
  • These foods contain the highest levels of fructose. Fructose is changed into triglycerides. High levels of triglycerides result in elevated LDL cholesterol levels.
  • Shellfish should be your animal protein of choice.
  • These have been shown to lower LDL levels.
  • Consume generous amount of olive oil
  • Don’t be shy — I’m talking more than one litre per week!

The steps I’ve laid out for all ApoE4s to follow closely resemble that of a Mediterranean diet. But I want to be crystal clear that the typical Mediterranean diet is not one that puts you in ketosis. The ideal diet for ApoE4s is a ketogenic Mediterranean diet. This is especially true if you have the ApoE4 gene AND you’re dealing with fatigue.

Why do ApoE4s need to eat this way?

Simply put, ApoE4s need to eat this way to ensure their brains remain healthy. This group of the population needs to ensure that their LDL cholesterol does not get out of control as that seems to be the biggest predictor of cognitive decline.

A 6 year follow-up study showed that following a Mediterranean diet — a diet exceptionally high in olive oil and nut consumption — is strongly correlated with an improvement in cognitive function. (26) This study did not control for ApoE4 status. If they did, I suspect it is a reasonable hypothesis that the cognitive and cholesterol improvements would have been even more dramatic.

To summarize, all you ApoE4s out there need to get as much extra virgin olive oil into your mouth as you can. Do as they do in Crete — each person consumes upwards of two litres of olive oil every single week. The other foods you eat should serve only as olive oil delivery devices.

Can ApoE4s follow a ketogenic diet?

Indeed they can. In fact, I strongly encourage all fatigue patients to follow a ketogenic diet — regardless of your genetic status. But the ApoE4 group needs to be mindful of the type of fat and protein they consume on a day-to-day basis. Below I lay out the dos and don’t for those of you with ApoE4 genes.

ApoE4 do list:

  • Eat as much olive oil as possible
  • Remember, 1 liter per person of extra virgin olive oil every week.
  • Get the majority of your animal protein via shellfish.
  • Shellfish have been shown to lower LDL cholesterol and raise HDL cholesterol. (27)
  • If you’re going to eat fruits, take grapeseed extract with them.
  • Grapeseed extract has been shown to increase your body’s ability to excrete the cholesterol formed from high fructose foods (like fruits!). (28)
  • Check your cholesterol on the regular
  • Make sure you’re keeping your LDL levels within healthy ranges.

ApoE4 don’t list:

  • Avoid traditional paleo or ketogenic diets.
  • Both diets are too high in animal fats and proteins for your genes.
  • Adherence to either will create negative health outcomes.
  • I’m going to say it one more time — if you have the ApoE4 gene, do not follow a paleo or keto diet without making the modifications I mentioned.
  • Eliminate (or severely restrict) your intake of dairy products.
  • Be incredibly mindful of your saturated fat intake.
  • You’re going to want to limit this type of fat as much as possible in your diet.
  • That includes coconut oil!
  • Stick with monounsaturated and polyunsaturated fats instead.
  • Regular, intense physical exercise is not ideal for ApoE4s.
  • Limit this intensity level to 1–2x/week.
  • I’m not saying don’t exercise, weight training is probably one of the healthiest activities you can do. Just be mindful of the intensity level.

How do you know you have the ApoE4 gene?

To find this out, you’re going to have to do genetic testing. If you’re simply curious, and you don’t have a strong family history of Alzheimer’s disease or cognitive decline, 23andme can be an inexpensive way to learn about your genome. Do not use 23andme to make diagnostic decisions. It is not 100% accurate.

If your 23andme results reveal an ApoE4 gene, ask your family doctor to run a genetic test to confirm the results. If the result from your doctor comes back positive for ApoE4, you can confidently use the result to make clinical decisions. The first of which should be to decrease the amount of saturated fat in your life!

Please note that for females running the 23and me genetic test, you will only get half of your genome sequenced. Meaning, you’ll only know your mom’s genetic information. You’ll need to have a first-degree male relative (brother or father) also run 23andme in order to see what genes you’ve inherited from your father.

If you have inherited the Apoe4 gene from mom or dad, you are what is known as heterozygous for ApoE4. If you inherited the ApoE4 gene from mom and dad you’re what’s known as homozygous for ApoE4. If you are homozygous for ApoE4, you need to follow my above recommendations without deviation. It is so important for your health and longevity to limit saturated fat intake.

If you are heterozygous for ApoE4, I recommend you heed all the recommendations I laid out. And check your cholesterol levels regularly. You may not need to be as strict with limiting your animal fat intake — but regularly check your LDL cholesterol levels to confirm. I think that completely avoiding the saturated fat in dairy products is good practice.

Ok, now you know the genetics behind high cholesterol. Now, I want to hear from you!

How do your genes affect your cholesterol level?

What diet have you found to help balance your cholesterol levels?

Leave your answers in the comments section below!

And if you want to know more about how to eat for energy, click here!

Do you need help improving your fatigue?


Originally published at Fatigue to Flourish.

Mark Volmer

Written by

I help those with fatigue naturally reclaim their energy and share their gifts with the world.

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