Cholesterol – Causes, Symptoms, Treatments

What is Cholesterol?

Cholesterol is a waxy, fat-like substance found in all the cells in your body. It’s an essential part of healthy cells, but high levels of cholesterol can increase your risk of heart disease and stroke.

Your body needs cholesterol to make hormones such as estrogen and testosterone, produce vitamin D and to digest foods. 

There are two main types of cholesterol, LDL (low-density lipoprotein), often called “bad” cholesterol. LDL cholesterol can build up in your arteries and form plaque. Plaque narrows your arteries, making it harder for blood to flow through. The other is HDL (high-density lipoprotein), often called “good” cholesterol. HDL cholesterol helps remove LDL cholesterol from your arteries and take it back to your liver, where it can be broken down and removed from your body.

The primary source of cholesterol in the human body is actually internal production by your liver. It synthesizes around 80% of your body’s total cholesterol needs.

Dietary cholesterol, found in animal products like meat, poultry, and eggs, only accounts for the remaining 20%.

Even though dietary cholesterol seems like a smaller factor, it can still influence your overall cholesterol levels, especially when combined with saturated and trans fats from those same food sources. These fats can increase your liver’s cholesterol production.

The Role of Cholesterol in the Body

Cholesterol plays a crucial role within the cells of the body, acting as a key component for both structural integrity and fluidity of cell membranes. Cholesterol molecules integrate within the phospholipid bilayer, the two-layered structure forming the cell membrane. These cholesterol molecules act like sturdy rods dispersed throughout the phospholipids, providing stability and strength. This strong, yet flexible, framework allows the cell membrane to maintain its shape and function properly.

Cholesterol helps regulate the fluidity of the cell membrane. Unlike rigid fats, cholesterol has a specific structure with a more rigid ring system and a flexible hydrocarbon tail. This unique structure allows cholesterol to stop the phospholipids from packing too tightly together, which would make the membrane stiff and hinder essential cellular processes like communication and transport of molecules.

In contrast, at lower temperatures, cholesterol helps prevent the membrane from becoming too fluid, which could lead to leakage of cellular contents.

By providing structural support and regulating fluidity, cholesterol ensures the cell membrane functions optimally. This allows for several important functions such as:

• Selective permeability: The controlled passage of specific molecules into and out of the cell.
• Cell signaling: Communication between cells through interactions with molecules on the cell surface.
• Cellular processes: Efficient functioning of various cellular activities requiring molecules to move across the membrane.

Types of Lipoproteins

Cholesterol travels through your bloodstream packaged within special protein-and-fat carriers called lipoproteins. There are several main types, each playing a distinct role in cholesterol transport.

As previously stated LDL (Low-Density Lipoprotein) is often referred to as “bad” cholesterol. This lipoprotein carries cholesterol from the liver to your tissues throughout the body. When LDL levels are high, excess cholesterol can deposit on the artery walls, forming plaque. This buildup of plaque hardens over time and narrows the arteries (atherosclerosis), restricting blood flow and increasing the risk of cardiovascular events such as heart attack and stroke. 

On the other hand, HDL (High-Density Lipoprotein) is often regarded as the “good” cholesterol, and performs the opposite function of LDL. It picks up excess cholesterol from your tissues and transports it back to your liver for breakdown and removal from the body. Higher HDL levels are beneficial as they help remove LDL cholesterol from the arteries, reducing plaque buildup.

VLDL (Very-Low-Density Lipoprotein) is primarily responsible for transporting triglycerides, another type of fat, from your liver to your cells for energy. When you eat and your body takes in more calories than it needs right away, it converts those extra calories into triglycerides and stores them in fat cells. However, VLDL also carries some cholesterol. As VLDL delivers triglycerides to tissues, it transforms into IDL (Intermediate-Density Lipoprotein).

IDL (Intermediate-Density Lipoprotein) is a leftover particle after VLDL releases triglycerides. It still carries some cholesterol and can either be further broken down by the liver or converted into LDL.

Role of Cholesterol

Cholesterol isn’t just a waxy substance in your blood. It’s actually a precursor molecule for a surprising number of important hormones. These hormones play a vital role in several physiological processes that keep us healthy and functioning properly.

One key area cholesterol-derived hormones influence is reproduction. They are essential for the development and function of reproductive organs. In females, estrogen regulates the menstrual cycle, while both sexes rely on progesterone for functions like preparing the uterus for pregnancy. Testosterone, in males, is crucial for sperm production and development of secondary sexual characteristics.

Another important category of cholesterol-based hormones is corticosteroids. The most prominent example is cortisol, a hormone with wide-ranging effects. Cortisol helps regulate metabolism by controlling blood sugar levels and converting food into energy. It also plays a role in the body’s stress response, increasing alertness and energy during challenging situations. Additionally, cortisol suppresses the immune system’s inflammatory response.

Beyond sex hormones and corticosteroids, cholesterol is also a precursor for vitamin D (activated by sunlight) and bile acids. Vitamin D promotes calcium absorption, which is essential for bone health. Bile acids, on the other hand, aid in digestion and absorption of fats from the small intestine.

Cholesterol’s Role in Vitamin D Synthesis and the Benefits of Vitamin D

Cholesterol plays a surprisingly direct role in vitamin D synthesis. Here’s a breakdown:

• Precursor Molecule:  A specific cholesterol derivative called 7-dehydrocholesterol resides in the outer layer of your skin. When exposed to sunlight, particularly ultraviolet B (UVB) rays, this molecule undergoes a chemical reaction.
• Sunlight Triggered Conversion:  The UVB radiation triggers a rearrangement of the molecule’s structure, converting 7-dehydrocholesterol in to pre-vitamin D3. This pre-vitamin D3 is then further converted into the usable form, vitamin D3 (cholecalciferol), through a natural heat or light-dependent process within the skin.

Vitamin D’s Vital Roles:

Once produced or obtained through diet, vitamin D plays a crucial role in several bodily functions, particularly:

• Bone Health: Vitamin D promotes calcium absorption from the intestines. Calcium is essential for building and maintaining strong bones. Without sufficient vitamin D, your body can’t absorb enough calcium, leading to conditions like rickets in children and osteomalacia in adults, both characterized by weakened bones.
• Calcium Regulation: Vitamin D works in conjunction with parathyroid hormone (PTH) to regulate calcium levels in the blood. PTH instructs the bones to release calcium into the bloodstream if levels drop too low. Vitamin D, however, enhances intestinal absorption of calcium, helping to maintain proper blood calcium levels and reducing the need to pull calcium from bones.
• Immune Function:  Vitamin D plays a role in supporting a healthy immune system. It helps regulate immune cell function and may contribute to the body’s defense against infections.

Cholesterol’s Conversion to Bile Acids and Their Role in Fat Digestion

Cholesterol plays a key role in the digestive process by acting as a precursor molecule for bile acids. Here’s a breakdown of the process and the function of bile acids:

Cholesterol as Precursor:

• The liver is the major site for cholesterol breakdown and bile acid production.
• In healthy individuals, the liver continuously removes excess cholesterol from the bloodstream and converts it into bile acids.
• This conversion process involves multiple enzymatic steps.

Bile Acids and Fat Digestion:

• Bile acids are amphipathic molecules, meaning they have a polar (water-loving) and a non-polar (fat-loving) end. This unique structure allows them to perform several essential functions in fat digestion and absorption:
  • Fat Emulsification: Dietary fats are naturally large globules that are insoluble in water. Bile acids act like detergents when released into the small intestine. Their polar ends interact with water, while their non-polar ends can attach to fat molecules. This disrupts the large fat globules and breaks them down into much smaller droplets called micelles.
  • Micelle Formation: By forming micelles, bile acids vastly increase the surface area of the fat particles. This increased surface area makes the fat more accessible to digestive enzymes like lipase, which can then efficiently break down the fats into smaller components like fatty acids and glycerol.
  • Fat Absorption: Once broken down by lipase, the smaller fatty acids and glycerol can be absorbed more easily by the intestinal lining into the bloodstream for transport throughout the body.

Mechanism of Fat Breakdown:

The emulsification process by bile acids can be imagined like this:

1. A large fat globule is like a big oil droplet in water.
2. Bile acids with their polar and nonpolar ends surround the fat globule.
3. The polar ends of bile acids face outwards interacting with the water, while the non-polar ends burrow into the fat droplet.
4. This disrupts the fat globule, breaking it down into numerous tiny micelles.
5. Each micelle is a microscopic sphere with a fatty core surrounded by bile acids on the outside, allowing the fat to be suspended in the watery environment of the intestine.

How does Atherosclerosis Develop?

Elevated LDL cholesterol, particularly when oxidized, plays a role in the development of atherosclerosis, a progressive disease characterized by plaque buildup in the arteries. Here’s a breakdown of the process:

LDL’s Downward Spiral:

1. High LDL Levels: When LDL cholesterol levels become excessively high in the bloodstream, the LDL particles begin to infiltrate the inner lining (endothelium) of your arteries.
2. Oxidation: These LDL particles in the artery wall are susceptible to modification by free radicals, becoming oxidized LDL (oxLDL). OxLDL is even more harmful than regular LDL.
3. Inflammatory Response: The presence of oxLDL triggers an inflammatory response in the artery wall. White blood cells called monocytes are attracted to the inflamed area and migrate through the endothelium, becoming macrophages.
4. Macrophage Overload: Macrophages engulf the oxLDL, transforming into cholesterol-laden foam cells. When too many LDL particles accumulate, the macrophages become overloaded and dysfunctional.
5. Plaque Formation: Over time, dead foam cells, cholesterol crystals, cellular debris, and smooth muscle cells from the artery wall all clump together, forming fatty deposits called atheroma or plaque.

Atherosclerosis and its Consequences:

• Artery Narrowing: Plaque buildup progressively narrows the inner diameter of the artery, a condition known as atherosclerosis. This restricts blood flow to vital organs like the heart and brain.
• Reduced Oxygen Supply: When blood flow is restricted, less oxygen reaches the tissues. In the case of the heart (coronary artery disease), this can lead to chest pain (angina) and potentially a heart attack if a blood clot completely blocks a narrowed artery.
• Stroke Risk: In the brain, narrowed arteries due to atherosclerosis increase the risk of a stroke. If a blood clot forms in a narrowed artery supplying the brain, it can cut off blood flow and cause brain cell death, leading to stroke symptoms like paralysis or weakness.

The Link Between Diet and Cholesterol Levels

Diet plays a crucial role in influencing your cholesterol levels. Different dietary components can impact your cholesterol profile.

Dietary Cholesterol vs. Saturated and Trans Fats:

• Dietary Cholesterol: While dietary cholesterol from animal products like meat, poultry, and eggs can contribute somewhat to your overall cholesterol levels, it’s not the sole culprit. Saturated and trans fats tend to have a more significant impact.
• Saturated and Trans Fats: These types of fats found in red meat, processed meats, full-fat dairy products, fried foods, and baked goods can:
  • Increase LDL (“bad”) cholesterol: Saturated fats promote the production and absorption of LDL cholesterol.
  • Decrease HDL (“good”) cholesterol: Saturated and trans fats can lower the levels of beneficial HDL cholesterol, which helps remove LDL cholesterol from the arteries.

Beneficial Dietary Components:

• Unsaturated Fats: Monounsaturated and polyunsaturated fats, found in sources like olive oil, avocados, nuts, and fatty fish, can help:
  • Lower LDL cholesterol: Replacing saturated fats with unsaturated fats can contribute to a decrease in LDL levels.
  • Raise HDL cholesterol: Unsaturated fats, particularly monounsaturated fats, can help elevate HDL cholesterol levels.
• Soluble Fiber: Foods rich in soluble fiber, such as oats, beans, lentils, and some fruits, can help reduce LDL cholesterol by:
  • Binding cholesterol: Soluble fiber forms a gel-like substance in your digestive system that traps cholesterol, preventing its absorption into the bloodstream.

Dietary Cholesterol and Overall Impact:

While dietary cholesterol can have some influence, it’s generally considered less impactful than saturated and trans fats. However, for individuals with a genetic predisposition for high cholesterol, even moderate dietary cholesterol intake might be more significant.

Dietary Strategies for Healthy Cholesterol:

Here are some dietary strategies to promote healthy cholesterol levels:

• Limit saturated and trans fats: Choose lean protein sources, low-fat dairy products, and limit processed foods.
• Include unsaturated fats: Opt for olive oil, avocado, nuts, and fatty fish like salmon in your diet.
• Incorporate soluble fiber: Increase your intake of whole grains, beans, lentils, and fruits like apples and berries.
• Moderate dietary cholesterol intake: If you have high cholesterol, especially with a genetic risk, consider limiting your intake of egg yolks, red meat, and processed meats.

The Link Between Genetics and High Cholesterol

Genetics play a significant role in cholesterol levels, alongside diet and lifestyle factors. Here’s a breakdown of how genes can influence cholesterol and some specific conditions that arise from genetic variations:

Genetic Influence:

• Inherited Blueprint: Our genes act as an instruction manual for the body, including how efficiently it produces, transports, and removes cholesterol. Variations in certain genes can affect these processes, leading to naturally higher or lower cholesterol levels.
• Examples of Genetic Variations: Several genes can influence cholesterol metabolism, and mutations in these genes can have a significant impact:
  • LDL Receptor Gene (LDLR): Mutations in this gene can hinder the liver’s ability to remove LDL cholesterol from the bloodstream, leading to a buildup of LDL (“bad”) cholesterol.
  • APOB Gene: Variations in this gene can affect the structure or function of apolipoprotein B, a protein involved in transporting cholesterol. This can lead to higher LDL levels or abnormal lipoprotein particles.
  • PCSK9 Gene: Mutations in this gene can increase the levels of circulating LDL cholesterol by affecting how the liver removes it.

Genetic Cholesterol Disorders:

Several specific conditions can arise due to genetic variations affecting cholesterol metabolism:

• Familial Hypercholesterolemia (FH):  This is a group of inherited disorders characterized by very high LDL cholesterol levels from birth. It’s often caused by mutations in the LDLR gene or other genes involved in LDL metabolism. FH significantly increases the risk of early-onset heart disease.
• Familial Combined Hyperlipidemia (FCHL):  This is a common inherited condition causing elevated LDL cholesterol, high triglycerides (another type of fat), and potentially low HDL cholesterol. Multiple genes are likely involved, and the severity can vary.
• Other Lipid Disorders: Several other genetic conditions can affect cholesterol levels and triglyceride levels, some with additional symptoms. These require specific diagnosis and management.

Importance of Genetic Testing:

In some cases, genetic testing can identify individuals at higher risk for cholesterol problems due to their genes. This allows for early intervention and more aggressive cholesterol management strategies, potentially including medications, to reduce the risk of cardiovascular complications.

How do Lifestyle Choices Affect Cholesterol Levels?

Engaging in regular physical activity, like brisk walking, swimming, or cycling for at least 30 minutes most days of the week, offers several benefits for cholesterol:

• Increases HDL (“good”) cholesterol: Exercise promotes the production of HDL cholesterol, which helps remove LDL cholesterol from the arteries.
• May slightly decrease LDL (“bad”) cholesterol: Regular physical activity can contribute to a modest reduction in LDL levels.
• Improves overall cardiovascular health: Exercise strengthens the heart, improves blood flow, and aids in weight management, all of which are important for reducing the risk of heart disease.

Weight Management:

• Maintaining a healthy weight: Being overweight or obese can significantly increase LDL cholesterol levels and decrease HDL cholesterol. Losing excess weight can improve your overall cholesterol profile.

Smoking:

• Smoking cessation: Smoking is a major risk factor for heart disease and has a detrimental effect on cholesterol. Quitting smoking can significantly improve HDL cholesterol levels and reduce overall cardiovascular risk.

Stress Management:

• Chronic stress: Chronic stress can contribute to unhealthy lifestyle choices and potentially elevate LDL cholesterol levels. Techniques like yoga, meditation, or deep breathing exercises can help manage stress and potentially improve cholesterol health.

Alcohol Consumption:

• Moderate alcohol intake: Moderate consumption of alcohol (one drink per day for women, two drinks per day for men) may modestly raise HDL cholesterol levels. However, excessive alcohol intake can have the opposite effect and increase triglycerides, another type of fat in the blood.

Importance of a Holistic Approach:

By incorporating healthy lifestyle habits, you can significantly improve your cholesterol profile and reduce your risk of heart disease. Remember, a combination of a balanced diet, regular exercise, weight management, stress management, and responsible alcohol consumption can make a big difference.

How is high cholesterol Diagnosed?

There’s no outward sign or symptom that definitively tells you if you have high cholesterol. The only way to know for sure is to get a blood test. Lipid Panels are the most common blood test used to assess cholesterol levels. It measures several key components related to cholesterol:

• Total Cholesterol: This is the sum of all cholesterol in your blood, including LDL (“bad”) cholesterol, HDL (“good”) cholesterol, and other types.
• LDL Cholesterol: This is often referred to as “bad” cholesterol because high levels contribute to plaque buildup in arteries.
• HDL Cholesterol: This is known as “good” cholesterol because it helps remove LDL cholesterol from the bloodstream and transport it back to the liver for processing.
• Triglycerides: This is another type of fat in your blood. While not directly cholesterol, high triglyceride levels can also contribute to heart disease risk.

In most cases, you will need to fast for 9-12 hours before the blood test to ensure accurate results.

Your doctor will review your lipid panel results and compare them to established guidelines, such as those set by the American Heart Association (AHA). If your cholesterol levels fall within the desirable ranges set by the AHA, it suggests a low risk associated with cholesterol.

If some of your cholesterol values fall into borderline ranges, your doctor might recommend lifestyle changes, like dietary modifications or increased physical activity, to keep your cholesterol in check. They may also suggest more frequent monitoring.

If your cholesterol levels, particularly LDL, are significantly elevated, your doctor will likely recommend a more aggressive approach to manage your cholesterol. This could involve lifestyle modifications combined with medication to lower LDL levels and reduce your risk of heart disease.

Additional Considerations:

• Age: AHA cholesterol guidelines consider age when evaluating risk factors. Younger adults might have slightly higher thresholds for desirable levels compared to older adults.
• Risk Factors: Your doctor will consider your overall cardiovascular risk profile when interpreting your cholesterol levels. Factors like family history of heart disease, high blood pressure, diabetes, and smoking can influence treatment decisions.

American Heart Association (AHA) Guidelines for Cholesterol Checkups and Optimal Levels:

The American Heart Association (AHA) recommends the following guidelines for cholesterol level check-ups and optimal levels in adults aged 20 years and older:

Frequency of Checkups:

• Age 20-40:  For adults with no risk factors for heart disease, the AHA recommends checking cholesterol levels at least once every 5 years.
• Age 40+ or with Risk Factors:  For adults with a higher risk of heart disease due to factors like family history, high blood pressure, diabetes, smoking, or obesity, the AHA recommends more frequent cholesterol checks, typically every 1-2 years.

Optimal Cholesterol Levels:

Here’s a breakdown of the desirable cholesterol levels according to the AHA guidelines:

• Total Cholesterol: Less than 200 mg/dL
• LDL Cholesterol: Less than 100 mg/dL (< 70 mg/dL for very high-risk individuals)
• HDL Cholesterol: 60 mg/dL or higher
• Non-HDL Cholesterol: This is calculated by subtracting HDL cholesterol from total cholesterol. Ideally, non-HDL cholesterol should be less than 130 mg/dL.

How is High Cholesterol Treated?

High cholesterol requires a two-pronged approach for effective management: lifestyle modifications and, in some cases, medication. Here’s a breakdown of the treatment strategies:

Lifestyle Changes:

A heart-healthy diet is the cornerstone of managing high cholesterol. This involves reducing the amount of saturated and trans fats you consume. These can typically be found in red meat, processed meats, full-fat dairy products, fried foods, and baked goods. Additionally, increasing intake of monounsaturated and polyunsaturated fats from sources like olive oil, avocado, nuts, and fatty fish.

Consuming more soluble fiber found in oats, beans, lentils, and some fruits like apples and berries can help trap cholesterol and reduce absorption. If you have significantly high cholesterol, especially with a genetic predisposition, limiting egg yolks, red meat, and processed meats might be recommended.

Engaging in regular physical activity, like brisk walking, swimming, or cycling for at least 30 minutes most days of the week, offers several benefits:

• Increases HDL (“good”) cholesterol: Exercise promotes the production of HDL cholesterol, which removes LDL cholesterol from the arteries.
• May slightly decrease LDL (“bad”) cholesterol: Regular physical activity can contribute to a modest reduction in LDL levels.
• Improves overall cardiovascular health: Exercise strengthens the heart, improves blood flow, and aids in weight management, all of which are important for reducing the risk of heart disease.

If you’re overweight or obese, losing excess weight can significantly improve your cholesterol profile. Smoking is also a major risk factor for heart disease and has a detrimental effect on cholesterol. Quitting smoking can significantly improve HDL cholesterol levels and reduce overall cardiovascular risk.

Chronic stress can contribute to unhealthy lifestyle choices and potentially elevate LDL cholesterol levels. Techniques like yoga, meditation, or deep breathing exercises can help manage stress and potentially improve cholesterol health.

What Medications are Most Often Prescribed for High Cholesterol?

If lifestyle changes alone aren’t sufficient to lower LDL cholesterol to recommended levels, your doctor might prescribe medications. Statins are the most commonly prescribed medication for high cholesterol.

These medications work by inhibiting an enzyme in the liver called HMG-CoA reductase, which is a key component in cholesterol production. By reducing the liver’s ability to produce cholesterol, statins effectively lower LDL (“bad”) cholesterol levels in the bloodstream. Some commonly prescribed statins include atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor, Altocor), pravastatin (Pravachol), rosuvastatin (Crestor), and simvastatin (Zocor).

While statins are the first-line treatment, other medications can be used alone or in combination with statins depending on individual needs and treatment goals. One of these medications is Ezetimibe (Zetia). This medication works by inhibiting cholesterol absorption in the small intestine. It’s often prescribed in combination with statins for individuals who need a more aggressive approach to lowering LDL cholesterol.

Bile Acid Sequestrants (Colestid, Questran, Welchol) bind to bile acids in the digestive system. Bile acids are derived from cholesterol by the liver, and by binding to them, these medications prevent their reabsorption and promote their excretion through feces. This forces the liver to use more cholesterol to produce new bile acids, ultimately lowering LDL levels in the blood. However, bile acid sequestrants can cause side effects like constipation and bloating.

PCSK9 Inhibitors (Praluent, Repatha) are newer injectable medications that target a protein called PCSK9. PCSK9 helps regulate LDL receptors on liver cells. By inhibiting PCSK9, these medications allow the liver cells to remove more LDL cholesterol from the circulation, offering a powerful option for individuals with severe or familial hypercholesterolemia, or when statins are not tolerated.