Why You Can Do Everything ‘Right’ and Still Have High Cholesterol

• Lifestyle habits can help manage cholesterol, but sometimes levels remain high despite best efforts.
• Genetic variants, like familial hypercholesterolemia and ApoE, make some people more susceptible to high cholesterol. 
• Medications, other health conditions, stress and smoking may also play a role.

Over 20 million adults over the age of 20 in the United States have high cholesterol. High cholesterol is often viewed as something you can fix by eating healthier, exercising regularly, choosing lean proteins and limiting saturated fat. And while nutrition and lifestyle habits can make a significant difference, there are other factors that may also affect cholesterol levels. Many people are surprised to learn that they can follow every heart-healthy guideline, eat their vegetables and work out regularly, yet still end up with cholesterol levels higher than expected.

Cholesterol is influenced not only by what you eat but also by how your body processes and produces cholesterol internally. Genetics can affect cholesterol levels, causing levels for some people to stay elevated despite healthy lifestyle habits.

Incorporating heart-healthy habits into your daily regimen is great, but also understanding when genetics may be at play can help reduce frustration and guide you toward the most appropriate strategies, which may include conversations with your health care provider about medication if needed. Let’s take a closer look at how genetics can influence cholesterol levels and what that means for your overall heart health.

How Genetics Can Cause High Cholesterol

Familial Hypercholesterolemia

According to Heather Shasa, M.S., RDN, CLS, genetics can influence high cholesterol in a variety of ways. One specific example is familial hypercholesterolemia, which causes high cholesterol. FH impairs the body’s ability to remove LDL (“bad”) cholesterol from the blood due to a mutation in one of several genes responsible for LDL receptors. Research shows that this inherited disorder affects roughly 1 in 250 people, yet it often goes undiagnosed. “As a result, cholesterol can build up in the bloodstream and the walls of the arteries. Over time, this can lead to plaque and hardening of the artery walls known as atherosclerosis,” adds Shasa.

For someone with FH, lifestyle changes alone are usually not enough. Medications, such as statins or PCSK9 inhibitors, are typically needed to lower cholesterol to safer levels.

ApoE Gene Variants

The apolipoprotein E gene plays a key role in how the body transports and processes fats. There are three common ApoE variants: E2, E3 and E4. According to Sherri Gaw, RDN, CDCES, individuals who are born with the ApoE4 genotype are at higher risk for elevated cholesterol levels, heart disease and even Alzheimer’s disease. Gaw adds that people with ApoE4 may need a more personalized approach to cholesterol management and may be able to manage cholesterol levels best with a low-fat and higher-carb diet, ideally from mostly high-fiber foods like whole grains, beans, fruits and starchy vegetables.

Genetic Variants That Affect Cholesterol Metabolism

There are several genetic variants that can affect how cholesterol is produced and broken down. Some people naturally produce more cholesterol in the liver, while others may reabsorb more cholesterol from the digestive tract. These genetic differences don’t automatically cause dangerously high cholesterol levels on their own, but they can create a situation where cholesterol levels rise more easily, despite a diet low in saturated fat and high in fiber. In other words, your body may simply be programmed to maintain a higher baseline. Understanding how genetics may be playing a role can help you approach cholesterol management with more clarity, and if lifestyle changes aren’t enough, your health care provider can recommend additional cholesterol-lowering strategies.

Genetic Influence on Body Weight and Insulin Sensitivity

Genetics also play a significant role in how the body stores fat, how easily someone gains weight and how efficiently the body manages blood sugar. Most people don’t know this, but insulin resistance can increase triglycerides and lower HDL (“good”) cholesterol.

Even with regular exercise and a healthy diet, someone who is genetically predisposed to insulin resistance may still experience shifts in their cholesterol levels that are hard to manage through lifestyle alone. This doesn’t mean that healthy habits don’t matter, because they absolutely do, but it highlights why some individuals need a broader care plan. Shasa notes that she likes to remind her clients that it’s not a personal failure—it’s information. “I work with them to build a step-by-step game plan, starting with uncovering why diet and exercise may not be enough. We look deeper into possible root causes, including genetics, thyroid function, liver health, medications or other underlying conditions to help them feel empowered, informed and confident in the next steps toward improving their heart health,” adds Shasa.

Other Reasons Your Cholesterol Can Be High

Even if your diet and lifestyle look “perfect,” there are several other factors that can influence cholesterol levels. Here are some contributors that are often overlooked:

• Medications: According to Vahista Ussery, M.S., M.B.A., RDN, certain medications can also increase cholesterol. “If you have high cholesterol, it’s important to ask your doctor about the possibility of adverse side effects influencing cholesterol levels when put on new medications.”
• Thyroid Disorders: Hypothyroidism, which is low thyroid function, can lead to higher LDL levels because the thyroid helps to regulate cholesterol metabolism. Even mild hypothyroidism can have a noticeable impact.
• Chronic Stress: Gaw mentions, “A person who is highly stressed has a higher production of the hormone cortisol, which can impact cholesterol levels.” Stress can also affect sleep, eating habits and inflammation, all of which can contribute to elevated cholesterol levels.
• Smoking or Exposure to Secondhand Smoke: Smoking can impact blood vessels and lower HDL cholesterol, making LDL more harmful. Even exposure to secondhand smoke can have a significant effect on cholesterol levels.

Meal Plan to Try

You Just Found Out You Have High Cholesterol—Try This 30-Day Meal Plan, Created by a Dietitian

Our Expert Take

High cholesterol is a complex health issue that can’t always be solely determined by what’s on your plate. Genetics, hormones, metabolic tendencies, medications and other health conditions all play a role in shaping your cholesterol profile. While lifestyle changes, such as increasing fiber, staying active and reducing your intake of saturated fats, can make a meaningful impact, they may not be enough for everyone.

Understanding the genetic and biological factors at play can help to reduce frustration and shift the focus toward a more compassionate, personalized approach to managing cholesterol. If you’re doing everything “right” and still seeing high numbers, it may be time to talk to your health care provider for a personalized plan.