Apolipoprotein E and the Impact on Your Cholesterol

Lisa Nelson, RD, LN Health Pro
  • Are you someone that has followed a heart healthy diet "to the letter" and still struggled to lower blood pressure or cholesterol levels? If so, it's possible the diet didn't work for you due to your specific genetic makeup.


    Mapping of the human genome (13 year project that identified all genes in human DNA) was completed by scientists in 2003.


    For the most part, genes are the same between individuals, with just a 1% variation. This small difference is what accounts for our unique physical attributes, biological processes, and metabolism. It's also this slight difference that makes one individual more susceptible to heart disease than another.

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    This has opened the door for nutrigenomics and the role it can play disease prevention. You see, dietary recommendations, such as Dietary Reference Intakes and Recommended Dietary Allowances, are established to meet the needs of 99% of the population from a statistical perspective. However, a "one size fits all approach" doesn't necessarily work. Now, don't get me wrong, it's a great foundation to base your diet around, but if you have a specific disease or increased risk for disease, this is where nutrigenomics can step in.


    Nutrigenomics looks at the interaction between nutrients and genes, because how we respond and metabolize nutrients is influenced by our genes.


    Apolipoprotein E


    The Apolipoprotein E (APOE) genotype influences coronary heart disease risk. APOE was discovered back in 1970 and can bind to triglyceride rich lipoproteins and acts as a binding mechanism for receptors.


    There are three APOE variations. To truly understand the three different variations you need to understand alleles and isoforms. I'm not going to get into an explanation of this because it'd just be too confusing. Let's call the three different variations E2, E3, and E4. Those with E2 produce the highest levels of APOE, E3 produces the next highest levels of APOE, followed by E4.


    Apolipoprotein E3 is the most common form across racial groups, followed by E4. Apolipoprotein E2 is the least common form, found to be highest in African Americans. All three forms of apolipoprotein E are connected to coronary heart disease, with E4 having the greatest risk, followed by E3, and then E2 with the lowest risk. As an FYI, African Americans' also tend to be higher in E4.


    What this means in regards to your cholesterol levels


    Apolipoprotein E2 tends to interact with receptors and enzymes at a slower rate, resulting in delayed breakdown of chylomicrons and VLDL cholesterol. Those with E2 tend to have a greater risk for elevated triglycerides while LDL cholesterol remains low.


    Those with apolipoprotein E4 appears to increase VLDL conversion to LDL cholesterol, eventually leading to increased levels of LDL cholesterol in circulation. The apolipoprotein E4 is known as a highly atherogenic and inflammatory lipid profile.


    Dietary fat and apolipoprotein E

    The fat in your diet impacts cholesterol levels. However, how much of an impact dietary fat has is determined by your genes, specifically apolipoprotein E.


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    When comparing the three variations of apolipoprotein E, those with apolipoprotein E4 were shown to have the greatest changes in LDL cholesterol levels by altering dietary fat, but the dietary fat changes had the lowest impact HDL cholesterol levels.


    Research supports a diet composed of 20-25% total fat, mainly from mono- and polyunsaturated fat sources. Dietary fat plays a vital role in health and metabolism, which is why extremely low-fat diets (10-15% calories from fat) should be used with caution.


    Alcohol and apolipoprotein E


    Alcohol consumption was compared between individuals with apolipoprotein E genotypes. Significant LDL cholesterol differences were found between those who consumed alcohol and those who did not. Men and women with apolipoprotein E2 who consumed moderate levels of alcohol had lower levels of LDL cholesterol. However, men and women with apolipoprotein E4 who consumed moderate levels of alcohol had the highest levels of LDL cholesterol. Research does not show alcohol to cause an increase in HDL cholesterol for those with apolipoprotein E genotypes. Guess what? If you have apolipoprotein E4, you should not consume alcohol. The potential benefits of a glass of red wine daily, do not apply to you.


    Dietary fiber and apolipoprotein E


    Canadian researchers evaluated dietary fiber intake (oat bran or wheat bran) on LDL cholesterol levels. LDL cholesterol was reduced in all participants after two weeks, with those carrying apolipoprotein E2 having the greatest response, followed by E3, and then E4.


    Those with apolipoprotein E2 need to be careful because interactions with refined carbohydrates and dietary fiber tend to elevate triglyceride levels. If you have apolipoprotein E2, you may need to limit sugar and total carbohydrates in your diet more.


    Carbohydrates have not been found to have the same effect in individuals with apolipoprotein E3 or E4.


    How to know your genotype


    Laboratories do offer commercial testing for apolipoprotein E. DNA is obtained from either a blood draw or cheek swab. Insurance may or may not cover the test, depending on if it is deemed medically necessary or not.


    Apolipoprotein E testing is most commonly completed for patients with abnormal cholesterol profiles who are not responding to typical diet and lifestyle changes.


    I wouldn't recommend you be tested without working with your physician. The results can be confusing and you'll want a physician to interpret for you. If your physician does work with you to order the test and evaluate the results, a dietitian can assist you in determining which behavior or diet changes would be most effective based on your genotype.


    If you have elevated cholesterol levels, you still need to take the standard steps necessary to lower your levels. You can access the free e-course How to Lower Cholesterol in 8 Simple Steps at http://lowercholesterolwithlisa.com.

Published On: November 12, 2011