Total Cholesterol

Total cholesterol is a vital component of our body's lipid profile and is important in maintaining overall health. However, too much cholesterol is strongly associated with an increased risk for heart disease.  

Total cholesterol refers to the sum of all cholesterol found in the blood, including both high-density lipoprotein (HDL) cholesterol, often termed "good cholesterol," and low-density lipoprotein (LDL) cholesterol, sometimes referred to as "bad cholesterol."

Cholesterol is a waxy, fat-like substance that serves as a structural component of cell membranes and is essential for the production of hormones, vitamin D, and bile acids necessary for digestion. 

While HDL cholesterol aids in the removal of excess cholesterol from the bloodstream, LDL cholesterol can accumulate in the arteries, leading to plaque formation and increasing the risk of cardiovascular diseases such as heart attacks and strokes. 

Understanding the balance between these cholesterol fractions is crucial for maintaining cardiovascular health.

Definition and Function of Total Cholesterol

What is Total Cholesterol?  What Does Total Cholesterol Mean as a Biomarker?

Total cholesterol levels are a fundamental marker for assessing cardiovascular risk.  Some cholesterol is essential for cellular and hormone health, but elevated total cholesterol levels are associated with increased risk of atherosclerosis and coronary artery disease (CAD).  [12.]

Structurally, cholesterol consists of a steroid nucleus composed of four fused hydrocarbon rings, with a hydrocarbon tail extending from one end.  Cholesterol travels in the bloodstream as part of “lipid particles”, which allow cholesterol and other hydrophobic substances to travel through the hydrophilic bloodstream.  

A lipid particle, or lipoprotein, refers to a microscopic structure composed of lipids, which are fats or fat-like substances, and proteins. These particles serve as carriers for lipids throughout the body, transporting them through the bloodstream and facilitating their utilization or storage in various tissues. 

The more hydrophilic components travel closer to the surface, including cholesterol backbones, phospholipids, and others, while more hydrophobic compounds including triglycerides and cholesterol esters travel deeper inside the particles. 

There are five main types of lipoproteins, whose individual cardiac risk, or atherogenicity, depends on their size, the direction in which they’re traveling (to or away from the liver), and the lipoproteins attached to them:  [6.]

• Chylomicrons: chylomicrons contain lipids absorbed from the digestive system and are too large to have a direct effect on cardiovascular health
• High-density lipoprotein (HDL): HDL particles contain the ApoA1 lipoprotein and tends to carry cholesterol back to the liver; therefore, HDl is considered “good” cholesterol.  [13.]
• Non-HDL particles: these include very low-density lipoproteins [VLDL], intermediate-density lipoprotein [IDL], low-density lipoprotein [LDL], and lipoprotein(a), or Lp(a).  These particles all contain Apo-B lipoproteins, are traveling from the liver to peripheral tissues, and are small enough to cause atherosclerosis; for all of these reasons, they are considered to increase cardiovascular risk.  [1.]

In the basic lipid panel, the Total Cholesterol biomarker is used to describe the sum of HDL + Non-HDL particles.  Often, this is similar to HDL + LDL particles (the markers typically present on a standard lipid panel), but not always.  [6.]

Understanding the amounts of each type of lipoprotein present in the bloodstream is essential to understand an individual’s overall cardiovascular risk.  

Total cholesterol is a composite measure that encompasses the sum of HDL, LDL, and other lipid components in the bloodstream. It serves as a key biomarker for assessing overall cholesterol levels and is commonly used to evaluate cardiovascular health. 

Elevated total cholesterol levels, especially when accompanied by high LDL cholesterol and low HDL cholesterol, are indicative of an increased risk of developing atherosclerosis and cardiovascular diseases.  [6.]   Elevated LDL levels are a stronger predictor of risk than total cholesterol.  [2.]

Therefore, monitoring total cholesterol levels, along with individual lipid components, is essential for implementing appropriate preventive measures and managing cardiovascular risk factors.

Function of Total Cholesterol: What Does Cholesterol Do in the Body?  [10.]

Cholesterol is an essential component of cell membranes, and it has other important functions in the body.  

• Cholesterol is a vital component of cell membranes, providing structural integrity and fluidity.

• It serves as a precursor for the synthesis of steroid hormones including cortisol, aldosterone, progesterone, estrogen, and testosterone.

• Cholesterol is necessary for the production of bile acids, which aid in the digestion and absorption of dietary fats as well as fat-soluble vitamins A, D, E and K.

• It is the essential precursor for vitamin D synthesis when the skin is exposed to sunlight.

• Cholesterol is essential for the formation of myelin, a fatty substance that insulates nerve fibers and facilitates rapid nerve impulse transmission.

• It contributes to the maintenance of cell membrane permeability and stability, ensuring proper cellular function.

• The synthesis of cholesterol and coenzyme Q10 share the same initial pathway; this relationship has implications for medication management of high cholesterol.  CoQ10 is crucial for energy production in cells.

• It plays a role in the formation of lipid rafts, specialized regions of the cell membrane involved in signal transduction and cell communication.

Dietary Sources of Cholesterol

Cholesterol is made in the human body, and it is available from the diet.  Dietary sources of cholesterol only come from animal products.

Dietary sources of cholesterol include:

Eggs: Egg yolks are one of the richest dietary sources of cholesterol.

‍Organ meats: Liver, kidney, and other organ meats are high in cholesterol.

Shellfish: Shrimp, crab, lobster, and other shellfish contain varying amounts of cholesterol.

Fatty meats: Beef, pork, lamb, and other fatty cuts of meat contain cholesterol.

Full-fat dairy: Whole milk, cheese, butter, and other full-fat dairy products contain cholesterol.

Poultry: Chicken and turkey also contain cholesterol, primarily in the skin and dark meat.

Processed foods: Some processed foods, such as certain baked goods and fried foods, may contain added cholesterol.

Certain fats: Animal-based fats like lard and tallow contain cholesterol.

Recommended Intake of Cholesterol

Recommended Dietary Intake: How Much Cholesterol Should I Eat?  [2.]

High cholesterol levels have been shown to increase the risk of cardiovascular disease.  Some people have high cholesterol due to excessive dietary intake of cholesterol-rich foods, while others have high cholesterol for genetic reasons including overproduction or over-absorption.  [23.]

The question of how much cholesterol is safe to eat is highly nuanced and very personal.  Observational studies on dietary cholesterol and cardiovascular disease (CVD) risk present inconsistent results, likely due to residual confounding from dietary patterns high in cholesterol or saturated fat.

Meta-regression analyses indicate a dose-response relationship between dietary cholesterol and LDL cholesterol concentrations, even after adjustment for dietary fat type.  Further analyses reveal a significant positive relationship between dietary cholesterol and total cholesterol concentrations, meaning that increased dietary cholesterol seems to increase total and LDL cholesterol concentrations.  [2.]

However, it may not be quite that simple.

Historically, dietary cholesterol limitation was recommended for reducing cardiovascular disease (CVD) risk and optimizing plasma lipoprotein profiles.  However, contemporary guidelines from the American Heart Association (AHA), American College of Cardiology (ACC), and the "2015–2020 Dietary Guidelines for Americans" do not explicitly recommend limiting dietary cholesterol due to inconsistencies in evidence.  [2.] 

Observational studies have generally not supported a significant association between dietary cholesterol and CVD risk, including coronary heart disease (CHD) and stroke.  [2.]

Historically, the dietary cholesterol guidelines were set at 300 mg a day.  Current guidelines provide nuanced statements regarding dietary cholesterol, with a focus on dietary patterns rather than specific numerical limitations.  [26.]

People with high cholesterol or a personal or family history of increased risk of hyperlipidemia and/or cardiovascular disease should consult a medical professional for individualized guidance.  

Lab Testing for Cholesterol Levels

General Testing Information and Sample Type

Typically, cholesterol assessment starts with a lipid panel, which includes the following biomarkers: total cholesterol, LDL and HDL cholesterols, and triglycerides.

People are increasingly aware of the benefits of advanced testing for cholesterol levels in order to support wellness, reduce their risk of cardiovascular disease, and inform personalized medical decisions.  To address the desire for more information about cholesterol health, lab companies are increasingly offering more comprehensive assessments.  

A few examples include:

The Cardiometabolic Profile by Doctor’s Data

The CadioPro Advanced Profile by Access Medical Labs

The Cardiometabolic Comprehensive Profile by BostonHeart Diagnostics

The LPP Plus by Spectracell Laboratories

These tests, including the standard lipid profile, are all blood tests that require a venipuncture.  Fasting is typically recommended for these tests.  In some cases, a mobile phlebotomist can come to you to have the blood draw performed from the home or office, and the sample can then be taken to the lab by the phlebotomist. 

Interpreting Test Results

Reference Range for Total Cholesterol

Total cholesterol levels for adults are set at the following:

Adults: <200 mg/dL (<5.17 mmol/L)

Clinical Significance of High Levels of Total Cholesterol

A total cholesterol level of <200 mg/dL is considered optimal.  Total cholesterol is considered borderline high between 200 mg/dL to 239 mg/dL, and a level of 240 mg/dL or more is considered high. 

Cholesterol goals may be lower in patients at high risk for coronary heart disease.  [16.]

High cholesterol is also called hypercholesterolemia, and should be addressed appropriately.  

Research indicates a direct relationship between serum total cholesterol and LDL cholesterol levels and the incidence of coronary heart disease (CHD), with higher cholesterol levels correlating with increased atherosclerosis and CHD risk across populations.  [5.]

Therapies may include diet and lifestyle adjustments, supplementation, and/or medication may be considered to reduce cholesterol levels, and consequently the individual’s risk of heart disease.

Clinical Significance of Low Levels of Cholesterol  [11.]

Clinically, hypolipidemia is considered to be a total cholesterol level below 120 mg/dL, or LDL cholesterol below 50 mg/dL.  [11.]

It can be primary, or caused by genetic factors, or secondary, which is much more common and usually caused by: 

• Some chronic infections
• Hematologic or other cancers
• Hyperthyroidism
• Malabsorption or undernutrition

Cholesterol is essential for various physiological processes, including cell membrane integrity, hormone synthesis, and bile acid production. Extremely low levels of cholesterol may indicate a need for additional fat intake as well as supplementation of fat-soluble vitamins.   

Additionally, low cholesterol levels have been associated with an increased risk of certain health complications, including hemorrhagic stroke, and may be associated with some cancers. [8., 19., 25.] 

Therefore, monitoring and addressing low cholesterol levels are crucial to prevent potential adverse health outcomes and ensure overall well-being.

Related Biomarkers: What Should Be Tested Besides Total Cholesterol?

The standard lipid panel is a good place to begin to evaluate an individual’s risk of developing heart disease.  There are a variety of other biomarkers available that can provide increased information above and beyond a standard lipid panel.  Some of these include: 

VLDL Particles: very-low-density lipoprotein (VLDL) particles are a precursor to LDL particles and play a crucial role in lipid metabolism. Elevated VLDL levels are associated with increased risk of atherosclerosis and cardiovascular disease.  [4.]

Total LDL Particles (LDL-P): measuring the number of LDL particles gives different information than LDL-C, which is the amount of cholesterol that’s carried by LDL particles.  

Knowing the number of LDL particles present in the bloodstream provides a more comprehensive assessment of cardiovascular risk than LDL-C alone because the size of LDL particles also confers cardiovascular risk, with smaller LDL particles being more atherogenic.  

Therefore, in two people with the same LDL-C number, the person with a higher LDL-P (and therefore more small LDL particles present in his or her bloodstream) has a higher risk for a cardiovascular event than the person with the lower LDL-P.  [17.]

Remnant Lipoprotein: remnant lipoproteins, remnants of VLDL and chylomicrons after triglyceride hydrolysis, are atherogenic particles associated with increased risk of cardiovascular events, even in individuals with normal LDL cholesterol levels. [18., 27.]

Dense LDL III and Dense LDL IV: small dense LDL (sdLDL) subfractions, particularly LDL III and LDL IV, are more atherogenic than larger, buoyant LDL particles. Measuring these subfractions provides additional information for assessing cardiovascular risk beyond traditional lipid panels.  [20.]

Buoyant HDL 2b: buoyant HDL 2b particles are considered particularly cardioprotective due to their role in reverse cholesterol transport. Higher levels of buoyant HDL 2b are associated with reduced risk of cardiovascular events.  [9.]

Lipoprotein(a): Elevated lipoprotein(a) levels are an independent risk factor for cardiovascular disease, particularly in individuals with a family history of premature heart disease.  It is important to note that Lp(a) levels are genetically determined and change little, if at all, in response to diet and lifestyle.  [22.]

Apolipoprotein B (ApoB): Apolipoprotein B is a structural component of atherogenic cholesterol particles including VLDL, IDL, LDL and Lp(a)  particles and is considered a more accurate predictor of cardiovascular risk compared to LDL cholesterol levels alone, particularly in the setting of insulin resistance and diabetes.  [1.]

Apolipoprotein A1 (apoA1): apoA1 is attached to the surface of HDL particles, and is associated with a cardioprotective effect.  Elevated apoA1 levels are associated with improved HDL functionality and reduced cardiovascular risk, while low levels are independently linked to increased risk of cardiovascular events. 

Monitoring apoA1 levels allows for better risk prediction and assessment of therapeutic efficacy in managing cardiovascular disease risk. [13.]

hs-CRP (High-Sensitivity C-Reactive Protein): elevated hs-CRP levels are indicative of systemic inflammation and are associated with increased risk of cardiovascular events, including myocardial infarction and stroke.  [7.]

Homocysteine: elevated homocysteine levels are associated with increased risk of cardiovascular disease, including atherosclerosis, stroke, and venous thromboembolism.  [21.] 

How to Support Healthy Cholesterol Levels

Lifestyle Modifications

• Maintain a healthy weight through regular physical activity and a balanced diet.  [29.]
• Reduce sedentary behavior and incorporate more movement throughout the day to support a healthy metabolism.
• Manage stress levels through relaxation techniques such as meditation or yoga. High stress has been correlated with metabolic dysfunction.  [28.]
• Ensure adequate sleep duration and quality to support metabolic health.  [24.]

Dietary Changes  [3.]

• Consume a diet rich in whole foods, including fruits, vegetables, whole grains, lean proteins, and healthy fats.  
• Limit intake of highly processed foods, sugary beverages, and foods high in saturated and trans fats.
• Increase fiber intake from sources like legumes, nuts, seeds, and whole grains to promote satiety and regulate blood sugar levels.
• Monitor portion sizes and practice mindful eating to prevent overeating and promote weight management.
• Follow a plant-based diet, and reduce intake of high-fat animal products. 

Exercise Recommendations  [15., 29.]

• Engage in a combination of aerobic exercise, strength training, and flexibility exercises to improve metabolic function.
• Aim for regular physical activity throughout the week, incorporating both cardiovascular exercise and resistance training sessions.
• Gradually increase exercise intensity and duration over time to challenge the body and promote fitness gains.
• Incorporate activities you enjoy to increase adherence to exercise routines and maintain long-term consistency.
• Consult with a healthcare provider or fitness professional to develop a personalized exercise plan based on individual fitness levels and health goals.

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