APOE: Your Genes, Your Health, Your Choices

We often think of our genes as a fixed script. Something that determines our future with no say in the matter. I’ve heard people say there’s no reason to test them, because “what’s the point, you can’t change your DNA.”

But that’s not how it works. Genes like APOE are more like spotlights. They illuminate areas where we may need to pay closer attention. And when we know where to look, we can act early, and powerfully, to change the story.

What Is APOE?

APOE (apolipoprotein E) is a gene that helps move fats (cholesterol and triglycerides) through your bloodstream and into your cells. Everyone inherits two copies of APOE (one from each parent), and there are three main versions (alleles):

• E2 – Less common, may be protective for brain health, but can be linked to higher

  triglycerides.

• E3 – The most common, considered “neutral.”

• E4 – Associated with higher risk of Alzheimer’s disease, cardiovascular disease, insulin

  resistance, and lipid challenges. Roughly 1 in 4 people carry at least one APOE4 allele.

Your combination (E2/E3, E3/E3, E2/E4, E3/E4, E4/E4, etc.) gives valuable insight into how your body handles lipids, blood sugar, inflammation, and brain health.

I often suspect an APOE4 genotype in a person whose lipids and blood sugar remain elevated despite a healthy diet and active lifestyle (though many genes contribute to this picture).

Why It Matters

APOE4 carriers often:

• Have higher LDL cholesterol and are more prone to insulin resistance.

• Struggle with transporting omega-3 fatty acids (especially DHA) into the brain — a

  challenge more pronounced in women.

• Show increased vulnerability to inflammation and oxidative stress.

Here’s the good news: APOE is not destiny. It’s information, and information gives you power. When we know your genetic profile, we can create a targeted nutrition and lifestyle plan to tip the odds in your favor.

Personalized Diet by Genotype

Not everyone needs the same approach. Your APOE status can guide dietary strategies to optimize insulin sensitivity, lipid profiles, and long-term brain and heart health:

• E2 Carriers – Tend to have lower LDL but may develop higher triglycerides. Reducing

  refined carbs and emphasizing healthy fats and fiber helps balance blood sugar and lipids.

• E3/E3 (Neutral) – Usually thrive on a general whole-food, plant-forward diet while

  minimizing processed foods, added sugars, and inflammatory oils.

• E4 Carriers – More sensitive to saturated fats and prone to insulin resistance. They do

  best with a low-saturated-fat, plant-rich diet emphasizing polyphenols, fiber, and omega-

  3s. Limiting red and processed meats, fried foods, and ultra-processed foods is especially

  helpful.

A Real-Life Example

One of my patients, a 54-year-old man with type 2 diabetes and elevated lipids, came to me eating a very low-fat, whole-food, plant-based diet. He was doing everything he could, yet his LDL cholesterol, triglycerides, and insulin resistance worsened. He felt frustrated and said, “It can’t possibly be stricter with my diet.”

We ran an APOE test and found he was E2/E3. This suggested his body might not respond well to a very low-fat, high-carbohydrate plan. We shifted his approach — adding healthy fats (nuts, seeds, avocado) while slightly reducing starches.

Within months, his blood sugar, HbA1c, cholesterol, LDL, and triglycerides all improved. His energy stabilized, and he felt empowered instead of defeated.

This is why personalization matters. The “perfect diet” is not one-size-fits-all. Tracking your

numbers with your healthcare provider is key to finding what works best for you.

Protecting Your Brain and Heart (Especially with APOE4)

1. Optimize Omega-3s (Focus on DHA): Essential for brain health. Those with APOE4

   may need extra support to get DHA into the brain, women even more so than men. Check

   your levels and supplement with omega-3 fatty acids as needed.

2. Choose the Right Fats: A low-saturated-fat, plant-predominant diet is beneficial. In

   addition to omega 3s, monounsaturated fats can be beneficial. Studies show that just ½

   tablespoon of olive oil daily may support brain health.

3. Focus on Polyphenols & Fiber: Colorful fruits, vegetables, legumes, and whole grains

   provide antioxidants and feed your gut microbiome — reducing inflammation.

4. Avoid Pro-Inflammatory Foods: Limit fried foods, refined sugar, inflammatory oils,

   red/processed meats, and ultra-processed foods.

5. Exercise Daily: Improves insulin sensitivity, strengthens blood vessels, boosts brain

   blood flow, and stimulates growth factors that help new brain cells connect. Include both

   resistance and cardio type exercises.

6. Prioritize Sleep: Deep sleep clears amyloid proteins from the brain, balances hormones,

   and repairs cellular damage; crucial for APOE4 carriers.

7. Manage Stress: Chronic stress and high cortisol shrink the hippocampus (your memory

   hub). Mind-body practices, breathwork, time in nature, journaling, and meaningful

   connection help restore balance.

8. Sauna Therapy: Finnish studies show regular sauna use (4–7x/week) lowers

   cardiovascular and dementia risk, improves circulation, and supports brain perfusion.

9. Stay Social & Curious: Lifelong learning, creativity, and meaningful relationships build

   cognitive reserve and protect against decline.

Emerging Therapies

10. Consider Hormone Therapy: Emerging research suggests estrogen therapy may interact

with APOE4 status and offer neuroprotection for women — decisions should always be

individualized.

11. Creatine for Brain Energy: Although better known for supporting muscle strength,

creatine also fuels brain cells by recycling ATP (your cells’ energy currency). APOE4

carriers may have lower baseline brain creatine levels, which are linked to cognitive

decline. Early studies suggest creatine supplementation can raise brain creatine stores and

improve memory, attention, and working memory — particularly in older adults or those

under metabolic stress. If considering creatine, work with your healthcare provider to

ensure kidney health and choose a clean, third-party-tested creatine monohydrate

supplement.

The Big Picture

Knowing your APOE status allows you to create a plan tailored to you — whether your goal is

protecting arteries, balancing blood sugar, or keeping your brain sharp for decades.

Your genes are not your destiny. They’re a guide — a nudge toward better self-care. When you

act on that knowledge, you can lower risk, protect your brain, and age with vitality.

4 Things You Can Do Today

Even if you don’t know your APOE status, you can start now:

1. Optimize Omega-3s: Eat two servings of omega-3-rich foods (chia, flax, walnuts, or

   SMASH fish if you eat fish) this week, or take a high-quality DHA/EPA supplement.

2. Move Your Body: Aim for 30 minutes of daily movement — walking, resistance

   training, biking — to improve blood sugar and brain blood flow.

3. Prioritize Sleep: Set a regular bedtime, dim lights an hour before, and aim for 7–8 hours

   of restorative sleep.

4. Load Up on Plants: Fill your plate with colorful produce, beans, and whole grains to

   fight inflammation and feed your microbiome.

These four steps protect your heart, brain, and metabolism — no matter what your genes say.

Resources

• FINGER Trial – Multidomain Lifestyle Intervention Ngandu T, et al. Lancet. 2015.

  Landmark trial showing that diet, exercise, cognitive training, and vascular risk management slowed cognitive decline — even in APOE4 carriers.

• PREDIMED Trial – Olive Oil & Cognitive Health Martínez-Lapiscina EH, et al. J Neurol Neurosurg Psychiatry. 2013. Mediterranean diet + olive oil improved cognition compared to a low-fat diet, supporting the brain-protective power of healthy fats.

• Olive Oil & Dementia Mortality Study Tessier A-J, Cortese M, Yuan C, et al. JAMA Netw Open. 2024. Large U.S. cohort (92,383 adults, 28 years follow-up) found that consuming >7g/day of olive oil (about ½ tablespoon) was associated with a 28% lower risk of dementia-related death, even after adjusting for APOE4 status and diet quality.

• Kuopio Ischaemic Heart Disease Study – Sauna Therapy Laukkanen T, et al. JAMA Intern Med. 2015. Frequent sauna bathing (4–7x/week) was linked to lower cardiovascular and dementia risk — a simple, enjoyable prevention tool.

• APOE4 & Omega-3 Transport Yassine et al. – Front Aging Neurosci. 2020. Review article showing APOE4 carriers may have impaired DHA transport to the brain — making omega-3 optimization especially important.

• Exercise & Brain Health Sofi F, et al. J Intern Med. 2011; Erickson KI, et al. PNAS. 2011. Meta-analysis showing moderate-to-high physical activity lowers dementia risk by ~35%. Aerobic exercise trial demonstrating increased hippocampal volume and memory improvements — key for APOE4 carriers.

• Sleep & Brain Clearance Xie L, et al. Science. 2013; Sabia S, et al. Nat Commun. 2021. Mechanistic study showing deep sleep clears beta-amyloid from the brain.

  Longitudinal study linking <6 hours sleep/night in midlife to 30% higher dementia risk.

Emerging Strategies

• Hormone Therapy & Brain Metabolism Kantarci K, et al. Neurology. 2016; Whitmer RA, et al. Neurology. 2011. Transdermal estradiol preserved brain glucose metabolism in APOE4 carriers. Early initiation of hormone therapy near menopause was linked to reduced dementia risk, whereas late initiation may increase risk.

• Creatine & Brain Bioenergetics O’Gorman Tuura RL, et al. Neurobiol Aging. 2003; Benton D, et al. Nutr Rev. 2023. MRS study showing lower brain creatine levels in APOE4 carriers, linked to worse cognitive performance. Review summarizing that creatine supplementation raises brain creatine stores and improves memory and executive function, particularly in older adults or those under metabolic stress.

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