Can You do Paleo with an ApoE Gene Mutation?

DNA illustration with gene mutation and words ApoE4 and Paleo

Questions about following the Paleo diet when the individual has an ApoE gene mutation have begun to rise in my consultations with clients and creating a lot of confusion. Here’s what you need to know to alleviate your concerns if this is an issue for you.

For those of you who may be unfamiliar with this particular gene mutation, here’s a basic explanation.

The ApoE gene codes for apolipoprotein E, a key player in lipid metabolism. Mark Sisson explains it is, “the string of amino acids that attaches to lipoproteins and allows them to cross the blood-brain barrier and get into the brain to deliver nutrients and cholesterol and remove toxins. If a lipoprotein has the ApoE marker, it will be allowed into the brain to do its work.”

It exists as three different variants: ApoE2, ApoE3, and ApoE4. Considering that we each have two copies of each gene, there are six different ways we may carry this mutation: ApoE 2/2, 2/3, 2/4, 3/3, 3/4 & 4/4. As with any mutation, the risk is usually higher if one carries both copies.

However, ApoE4 (present in 13 to 15 percent of the population) is the only variant that is believed to be associated with negative health risks, mainly Alzheimer’s and other dementias, high cholesterol, and an impaired ability to eliminate heavy metals (particularly lead, copper, and mercury). ApoE2 is correlated with a decreased risk for Alzheimer’s and ApoE3 is neutral.

In regard to ApoE4 and cholesterol, it is believed by many practitioners that consumption of saturated fat when carrying this gene may increase c-reactive protein, as well as LDL particle count and size, all risk factors for cardiovascular disease. People carrying both copies of this allele have up to a twenty-fold increased risk of developing Alzheimer’s disease.

People with this mutation may not see the improvement in numbers on their markers for (c-reactive protein, LDL size and quantity, triglycerides, total cholesterol, etc.) typically seen in people who eat a low-carb, high-fat diet that people without this mutation experience.

Other Confounding Variables

However, there are other confounding variables that can affect whether the ApoE4 mutation will lead to cardiovascular disease or Alzheimer’s. Some studies suggest it only contributes to these problems when the individual smokes, or is under high stress, or is sedentary. It’s possible the negative effects may not happen at all unless these other variables come into play.

For example, some studies show that if the individual with the ApoE4 gene mutation does not smoke, the risk for cardiovascular disease disappears. Another study found that only the ApoE4 people who smoked had higher levels of oxidized LDL.

Additionally, the higher level of cholesterol associated with this mutation may not be the cause of Alzheimer’s. One hypothesis is that the elevation in cholesterol is a protective mechanism, because of the impairment in lipid metabolism, more is needed so that it can cross the blood brain barrier. The elevation helps offset the impairment. Thus, it would be serving you in a positive way.

It’s vital to be aware that low cholesterol is also associated with Alzheimer’s. So, that puts you at risk as well. A high-fat, low-carb (ketogenic) diet helps people with Alzheimer’s to improve significantly. Only five percent of people with Alzheimer’s have the ApoE4 gene mutation.

So one should not automatically assume that their risk is higher for these conditions if they are carrying this mutation.

Also, be sure to note that the ApoE2 affords some protection against Alzheimer’s. Therefore, if it occurs in conjunction with an ApoE4, perhaps the risk is lower or canceled out.

Animal Protein and Fat

If a practitioner is saying that you shouldn’t eat a lot of animal protein or avoid fat altogether and eat more carbs because you have the ApoE4 gene mutation, this is a broad generalization and irresponsible advice.

The brain needs lots of animal protein and fat. It cannot make nor transmit neurotransmitters properly without them. You will be putting yourself at much greater risk for other conditions by eating too many carbs. Additionally, cholesterol is essential for proper brain function, needed for synapse formation, neurotransmission, and the myelin sheath. Human brains contain nearly 25 percent of all the cholesterol in the body.

Even if the gene mutation truly increases the risk for these conditions, it doesn’t mean that you have to cut out animal protein and fat altogether. You can still eat plenty of animal protein but eat leaner cuts.

It’s not animal protein that is the problem. It is the fat. So eat lower fat. Eat lean cuts of meat and fish, but no bacon or ribs.

Stay away from concentrated sources of saturated fat like coconut oil, butter, ghee, and fish oil.

Eat monounsaturated fats.

Avoid PUFAS in nuts and oils.

No dark chocolate.

Eat low-carb vegetables.

It is still important to avoid high carb foods like grains, legumes, potatoes, etc., because ApoE gene or not, it is well established that carbohydrate consumption also increases the risk for Alzheimer’s and cardiovascular disease and causes an elevation in cholesterol, triglycerides, etc. Dr. William Davis points out, that it is not just the fat that needs to be moderated in the ApoE4 gene mutation, but carb as well to avoid the elevations in LDL.

With these simple modifications, the diet will still be in line with the basic Paleo principles. Having the ApoE4 mutation does not negate what we know to be true.

Look at the Whole Picture

Additionally, you must take into account the other health conditions you may be dealing with or other needs you may have in addition to the ApoE4 gene mutation. Don’t throw all other aspects of health out the window because of an ApoE mutation. You must take everything into consideration when designing your diet plan.

For example, if you have SIBO or candida, or sugar and carb addiction, adrenal fatigue, depression or anxiety, and you cut out the animal protein and fat and eat a bunch of carbs, your health is going to suffer worse. The needs for these health conditions must be taken into account.

You must weigh the benefits against the risk of reducing consumption of animal protein and fat.

It’s not going to do you much good if you eliminate animal protein and fat to prevent potential complications by the ApoeE4 mutation, if you’re too depressed to get out of bed or in a constant state of panic because the lack of animal protein inhibits your ability to make vital neurotransmitters that modulate mood; or you end up hospitalized for the removal of your appendix or gallbladder because you are overfeeding your microbes with carbs; or your adrenal glands crash because your cholesterol is too low.

You can’t disregard your needs for other conditions and only accommodate the ApoE marker.

You must look at the whole picture and compromise to meet all of your needs the best that you can.

What Should You Do?

If you have the ApoE4 gene mutation, then keep an eye on your numbers (c-reactive protein, LDL size and quantity, triglycerides, total cholesterol, etc.), but don’t just assume you are doomed and remove animal protein and fat from your diet.

Play around with the macronutrient ratio. Find the ratio of protein, fat, and carb that works best for you and the all conditions you face.

Do not smoke.

Manage your stress.

Don’t be sedentary.

Avoid heavy metals.

Be aware that it is questionable about whether this mutation is truly a risk or not, especially if you are not engaging in the other high-risk behaviors. Individualize your Paleo diet for your needs, but don’t abandon it all together and eat a bunch of carbs.


David Perlmutter, Grain Brain: The Surprising Truth About Wheat, Carbs, and Sugar -Your Brain’s Silent Killers. New York, NY. Little, Brown and Company (2013)

Forever Healthy. APOE4

Mark Sisson. Apoe4 Allele

Stephanie Seneff. APOE-4: The Clue to Why Low Fat Diet and Statins may cause Alzheimer’s.

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