What In The Heck Is “ApoE” And Why Does It Reveal Your Perfect Diet?

Confused by the debate about vegetarianism, coffee, cholesterol and fat? How bout the research that says that the perfect diet for you is genetically determined? Well, read on… this email exchange with a medical student might help.


Note: This is article 2, part 3 to my FREE four-part series about how to build a strong and youthful body.

THERE’S LOTSA confusion in matters of health. These days, coffee is good for you, fat’s OK, and even cholesterol is losing its tarnished image.


Well, like much in life, details matter.  Before we get into the meaty part of this post…

As concerns coffee, cholesterol and fat, my take is:

Coffee is fine if limited to one or two cups, is not drunk in the afternoon, is made from high altitude, organic beans that were air dried in the shade, processed with minimal exposure to myotoxins, is fresh, and not consumed with sugar or lots of cream. (More on coffee here.)

Cholesterol is fine, particularly since you’d be dead without it. So, it’s a question of how much, and more importantly, the composition. You want the so-called “bad” cholesterol – LDL – to be low, and representative of “Pattern A” particle size and density, and the “good” cholesterol – HDL – to be high. (More on cholesterol here and below, particularly regarding LDL Pattern A and B, and what your ApoE genes say about it.)

Fat is fine if its derived from grass fed butter, organic; cold pressed coconut butter; organic, cold pressed, extra virgin olive oil that’s not over-heated; and fish oil that is purified (no heavy metals, PCBs, dioxins, etc.), fresh (not oxidized or rancid), and from sustainably caught fish. (More on fats here and fish oil here.)

And now let’s turn to Alex.


Yes, Alex, second child of Bill and Malin, my college buds. She’s attending medical school in Zurich, and we recently had an email exchange about some health matters that are being debated, even in med school.

The topics we cover include:

  • Vegetarianism
  • Low carb diet
  • Fish oil
  • And the overlooked, mostly unknown elephant in the room — ApoE.

We get deep into the weeds on some of this stuff, so hopefully you’ll uncover something interesting.  And, note, to break up my long emails to Alex, I’ve put in some subject headers that were not in the original email.

With that, let’s begin with how it began — Alex writes me an email…


AlexHi Joe.

Hey so this weekend I discovered the hype about this “raw food vegan diet” / “raw veganism” as Wikipedia calls it.

There are so many different dietary concepts out there, it’s ridiculously easy to get confused about what it is your body needs (even if you’re supposed to be sure of it, like say a medical student).

Alright so my study-based intuition tells me vegan can’t be good – no extremes are, and this is one. Right? I feel you’d almost need medical support to hold a diet like that — B12 shots, iron, good fatty acids (if u exclude nuts) etc. ETC.

Although I do find it a good idea to eat whole foods (as they appear in nature), and have loads of veggies and fruit – just not these only. (Again, right?)

Also another thing. I felt like the high fat low carb diet made more sense to me (oil heating) versus high carb (firewood heating). But in this raw food vegan diet some talk about being “fruitarian”, basically living off of fruit thus fructose and fiber and loads of water, also insuring their followers that you can’t gain weight from fruit.

Counting the calories I’d beg to differ. This one girl eats 15 bananas for breakfast.. In the end it’s input versus output that counts.

What’s your opinion on this vegan craze? I’ve got garmaonhealth open so I’ll go snoop around there as well 🙂




Joe GarmaYou’re digging into a big, complicated topic, Alex, one w/ no absolute answer as far as I can discern.

It seems that they’re are two basic reasons for the complexity:

1. A boat full of experts with diametrically opposed viewpoints on diet (say, vegetarianism vs paleo), both using science to back up their respcective positions; and

2. Individuals are different enough so that there can different responses to the same dietary input.

Your litany of stuff (B12, iron, omega 3 fatty acids) that is either absent or sparse in a veg/vegan diet is one of the major points made by one of the standard bearers of the Paleo movement, Chris Kresser.

Chris Kresser, “Meat is Good”

Chris is a very bright and learned guy and is prone to pouring over research and underscoring why certain conclusions may be wrong. For instance, he often says that studies reporting the meat eaters don’t live as long as non-meat eaters are flawed.

The reason, he says, is that, on average, more of the meat eaters evaluated in the studies are naturally less healthy than their veggie counterparts (more of them smoke, exercise less, etc.), so that the studies are measuring greater mortality in an overall less healthy group — meat not being the causal agent.

For instance, Chris continues, if you study meat eaters who go to health food stores, they are more likely to possess the relatively healthy lifestyle traits of the vegetarians, and they therefore do not have shorter life spans.

For more from Chris Kresser, check out his blog post, Why You Should Think Twice About Vegetarians and Vegan Diets. Note the comments from readers… some are quite vitriolic, underscoring how emotional this subject is for some people.


Dr. Michael Greger, “Meat is Bad”

As a counterpoint to Chris, also familiarize yourself with Dr. Michael Greger at Nutrition Facts. What he does is comb through the research and then presents it via video.

Nearly everything he presents underscores that it’s far better to eat vegetables and fruits and minimize (or eliminate) meat and dairy.

Now, consider how flummoxed are we wee mortals when we try to determine who is right, Chris Kresser or Michael Greger! Both are very learned and credentialed. And, although they do have some common ground, they’re anti-polar when it comes to the healthiness of meat, among other things.


ApoE: Your Genes Matter

Turning to #2, “differences among individuals”, one thing I’ve recently learned about is Apolipoprotein E (ApoE).

From wikipedia:

“ApoE is a class of apolipoprotein found in the chylomicron and Intermediate-density lipoprotein (IDLs) that is essential for the normal catabolism of triglyceride-rich lipoprotein constituents.”

Explaining the function of ApoE, the U.S. National Institute of Health reports:

“The ApoE gene provides instructions for making a protein called apolipoprotein E. This protein combines with fats (lipids) in the body to form molecules called lipoproteins. Lipoproteins are responsible for packaging cholesterol and other fats and carrying them through the bloodstream. Apolipoprotein E is a major component of a specific type of lipoprotein called very low-density lipoproteins (VLDLs).

“VLDLs remove excess cholesterol from the blood and carry it to the liver for processing. Maintaining normal levels of cholesterol is essential for the prevention of disorders that affect the heart and blood vessels (cardiovascular diseases), including heart attack and stroke.

“There are at least three slightly different versions (alleles) of the ApoE gene. The major alleles are called e2, e3, and e4. The most common allele is e3, which is found in more than half of the general population.”

Now, the reason I’ve gotten deep with this ApoE stuff is that I’m beginning to wonder if this genetic trait is the key to determining how certain combinations of macronutrients (protein, fat, carbs) effect people. Consider this chart:

Apoe dietary effects[Got this chart here from Berkeley HeartLab, but it’s no longer there.]

A few things to note…

  • Fish Oil affects different ApoE genotypes differently. ApoE2 Response people do well on Fish Oil (lowers triglycerides and small particle LDL, raises HDL), but for ApoE4 Response people LDL goes up, even though the particle size diminishes.
  • A Low Fat Diet affects different ApoE genotypes differently. For ApoE2 the overall LDL count declines, but at the expense of increased numbers of small particle, arteriosclerosis-promoting LDL, which make up the so-called undesirable “Pattern B”. For ApoE3 the Low Fat Diet is more beneficial than it is for ApoE2 because the small particle LDL is unaffected. For ApoE4 the results are the best — a dramatic decrease in LDL and a reduction in small particle size.
  • A Moderate Fat Diet affects different ApoE genotypes differently. It has no effect on ApoE2. It works best for ApoE3, reducing both LDL and its particle size.  For ApoE4, a  Moderate Fat Diet is abysmal, decreasing the “good” HDL and increasing the “bad” LDL forms of cholesterol.

Pattern A is preferred, for the LDL particles in Pattern A are large and “fluffy” and therefore do not damage arterial walls.

Pattern B LDL is comprised of small dense particles that can and do rupture arterial walls, thus enabling the formation of cholesterol plague that can lead to blood flow occlusion, and could — depending if the blood vessels lead to the heart or brain — result in either a heart attack or stroke.

For more about ApoE genetic variants and what they suggest for dietary considerations, you can read what Dr. Weil has to say about it here, and watch this video of nutritionist Pam McDonald discussing a diet she developed based on ApoE:


Make Your Diet Insulin-Friendly

The all-fruit diet you mentioned is not a good idea. Some fruit has fiber. None has much protein or fat, unless you include avocado, which technically is a fruit and has lots of high quality fat.

And, you’re right, that the calorie count can get high on all-fruit. Moreover, most fruit has a high glycemic index (and glycemic load), meaning that it’s a simple, sugary carb that spikes blood glucose levels, requiring the pancreas to go into overdrive to create the necessary insulin to shuttle all these carbs into the cells.

Insulin is a key factor to consider when evaluating diets. Biochemically, and hormonally, it’s not as simple as calories in/ calories out. The food source impacts the various hormones, insulin being the most important, as well as gut microbiota (see Can The Right Gut Bacteria Fight Obesity and Slay Metabolic Syndrome?)

When out of balance, hormones and microbiota can alter how well a body metabolism, and other factors that impact calorie expenditure.

OK, that’s enough to chew on for now, Dr. Alexandra!



AlexWow what a great response! Thanks Joe, I feel flattered you’d take the time to reply so extensively!

I spent my entire night yesterday on Nutritionfacts.com — it’s soo cool! Really great! Thank you so much!! Of course I do think it’s important to keep in mind all the confounding factors that Chris Kresser talks about. We’ve learned a bit about interpretation of clinical trials in my program as well 🙂 Lucky me, although Dr Michael Greger makes it very understandable

Okay so I will continue my research and report back!

Concerning ApoE, I’m familiar with the cholesterol pathway and yep, in the end it’s all in our genes which makes everything individual of course. We had a lot of biochemistry and digestion in our second year, so I know how detailed digestion actually is.

Ideally we could all get tested for our metabolism rates and gene activities, but it’s typically far too expensive, especially if it’s for personal interest and not medical necessity.

So I’m really just trying to see if there could be some type of diet that will work for most everyone (of course degrees of how well vary).

Not only for myself, but also for my future patients – I want to be able to lead them in the right direction.

I will continue to eat fish and chicken and try to fill min. half my plate with only veggies, preferably dark greens. Also: more whole foods.

I’ve been trying to force myself to eat red meat, since after 7 iron infusions this winter and an all-time low of Hb at 7.6g/dl and my Ferritin at <3mg/L, I’m desperate to keep my treated iron level high now.

An Expository Email Thread Interruption

“Hb” is hemoglobin, which is a protein in red blood cells that carries oxygen to your body’s organs and tissues and transports carbon dioxide from your organs and tissues back to your lungs. For women, a normal range is 12.0 to 15.5 grams per deciliter (120 to 155 grams per liter), and for men, 13.5 to 17.5 grams per deciliter (135 to 175 grams per liter), according to the Mayo Clinic. 7.6g/dl suggests anemia.

Ferritin is a blood cell protein that contains iron, and the test measures the amount of ferritin in your blood. For women, a normal range is 11 to 307 nanograms per milliliter (standard units) or 11 to 307 micrograms per liter (international units), and for men, 24 to 336 nanograms per milliliter (standard units) or 24 to 336 micrograms per liter (international units), says the Mayo Clinic. Less than 3mg/L suggests iron deficiency/anemia.

But yah the red meat things isn’t working out, I just can’t swallow it, I feel like I might as well be eating a human arm or something. So I’ve just been (irregularly) taking iron supplements…hmmm…

Also, I think I’m going to start taking fish oil! to reduce inflammation? Yes please!

Hey Joe, thanks!

[Alex continues in a separate email…]

AlexOkay so remember how I said 15min ago I was going to start taking fish oil?

Right, so according to Greger it’s simply a hype: http://nutritionfacts.org/video/is-fish-oil-just-snake-oil/. And as a Dr you should advise your patients NOT to take it!

But just last night I watched this at Dr. Sears … (then again he’s talking about medical doses):

(Here’s some more from him: http://crossfitimpulse.com/why-fish-oil )

Joe, oh darwin, now what?

Are you satisfied with your diet the way it is? And is fish oil included?


Joe GarmaHey Alex.

Like so much of health information there seems to be conflicts re the benefits of fish oil.

So, yes, Dr. Greger cites studies concluding that there are no benefits to taking fish oil in the video you linked to, but in one about mercury in fish, he cites evidence that the omega-3 fatty acids in the fish oil is beneficial to the brain:

For him, it might come down to the source of omega-3s, fish. Many species of fish are loaded with mercury, a very toxic heavy metal. When I searched for “omega-3” on Dr. Greger’s site, I found a summary that pretty much says that there’s lots of benefits to omega-3s, but beware the fish: http://nutritionfacts.org/topics/omega-3-fatty-acids/

From my reading on the subject, the numerous health benefits of omega-3-fatty acids are widely extolled. Typically, fish oil is considered more beneficial than plant-derived sources such as flax and chia seeds.


The bottom line for me is:

  1. Eat only very low/no mercury fish such as anchovies, sardines, herring, non-farmed salmon, fresh water trout and tilapia: http://americanpregnancy.org/pregnancyhealth/fishmercury.htm.
  2. Supplement with only the very finest quality fish oil to ensure there’s no mercury: http://chriskresser.com/the-definitive-fish-oil-buyers-guide.
  3. Consume plenty of plant sources of omega-3s, favoring chia seeds and avocados to flax seeds, the oil in which gets rancid quickly… am consistently tweaking it. Right now…


Re my diet

  • I’m being very selective with carbs (mostly veggies, lentils, mung beans, a bit of other beans that I repeatedly rinse and then let sprout a bit to help expunge the phytic acid contained therein ).
  • Get much of my protein from powders consisting of hemp, peas, whey and sprouts, along with organic chicken (once week), pasture raised meat (less than once week), eggs (six week).
  • Fats from nuts, seeds, avocados, coconut oil and a bit of extra virgin cold pressed olive oil and grass fed butter.
  • Try to time most of my carbs to post exercise, and often don’t eat my first meal till 1:00, so that I get some of the purported benefits of 15 or so hours of fasting (say from 8:00 PM till 1:00 PM the next day).



 [End of Email Exchange]


And that, dear reader, concludes the email thread between Alex and me.

No doubt it’s given you a sense for how confusing are health matters, even to people who study such things.

In the end, you have to experiment and settle in on what feels right to you. But do try to have some recognized science and experienced practitioners backing what you do.

Ciao for now…

Last Updated on September 29, 2022 by Joe Garma

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Joe Garma

I help people live with more vitality and strength. I'm a big believer in sustainability, and am a bit nutty about optimizing my diet, supplements, hormones and exercise. To get exclusive Updates, tips and be on your way to a stronger, more youthful body, join my weekly Newsletter. You can also find me on LinkedIn, Twitter and Instagram.

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