Can High Cholesterol Cause Fatigue?

In this article, we will take a close look at the complex relationship between high cholesterol and fatigue. We will explore the role of cholesterol in the body, the health risks associated with high cholesterol, and how it can indirectly lead to fatigue. Additionally, we will look at the the effects of low cholesterol and its potential health implications.
Jakub Gwiazdecki

Jakub Gwiazdecki

Fifth year medical student at the Medical Faculty of Comenius University in Bratislava.

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Can high cholesterol cause fatigue?

No, cholesterol itself does not directly cause fatigue. However, it's important to note that high cholesterol can lead to conditions such as heart disease, which can cause fatigue. For instance, fatigue is a common symptom in patients with chronic heart failure. This is a condition that can be influenced by high cholesterol levels [1].

Moreover, medications used to treat high cholesterol can have certain not wanted effects. One of these drugs are statins, which have been associated with fatigue as a side effect [2]. It's also worth noting that some studies have found a correlation between fatigue and altered lipid metabolism [3].

The relationship between high cholesterol and fatigue is complex. It can be influenced by various factors, including lifestyle changes, like regular exercise. But it is impacted also by other health conditions, and individual responses to medication.

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What is fatigue?

Fatigue describes an overall feeling of tiredness and lack of energy. It is not the same as simply feeling drowsy or sleepy. When fatigued, one has no motivation and no energy. However, even when not being the same being sleepy may be a symptom of fatigue [4].

Fatigue mirrors the exhaustion of the physiological reserves of an individual. One of the underlying mechanism of fatigue is inadequate nutrition. Modifications in food intake and body composition changes seem to influence the perception of fatigue. It does so probably through the mechanisms of inflammation and/or mitochondrial dysfunction [5].

Chronic fatigue is a typical symptom of neurological diseases. It occurs in multiple sclerosis, postpoliomyelitis, poststroke, and in chronic fatigue syndrome [6].

Also, fatigue is a significant problem for patients with primary biliary cirrhosis. Although it is experienced less by patients with primary sclerosing cholangitis, a minority still report significant fatigue. Fatigue is the symptom with the greatest impact on quality of life [7].

In relation to cholesterol, fatigue is a frequent symptom in multiple sclerosis (MS). The role of cholesterol and lipids in MS fatigue has been investigated. The results were that lower fatigue is associated with greater high-density lipoprotein cholesterol (HDL-C) and lower total cholesterol to HDL-C ratio [8]. It means that in MS patients the lower general cholesterol levels (total cholesterol) can exhibit less fatigue.

What is cholesterol?

Cholesterol is a waxy, fat-like substance that is found in all the cells in your body. It is a vital component of life. Cholesterol is needed to make hormones, vitamin D, and substances that aid in digestion, like the bile [9]. It is also a structural component of cell membranes, helping to maintain their fluidity and permeability [10, 11].

Normally, the body produces all the cholesterol it needs, primarily in the liver. However, cholesterol is also found in foods from animal sources, such as egg yolks, meat, and cheese [9, 12].

Cholesterol, after absorption or production, travels in the blood in the form of lipoproteins. Those are tiny molecules of fat wrapped in protein. There are two major types of cholesterol: low density lipoproteins (LDL) and high density lipoproteins (HDL) [12, 13]. LDL is often referred to as bad cholesterol. The reason for it is that when an excess LDL is found in blood, it can contribute to the buildup of plaque in the arteries. With time this buildup leads to atherosclerosis. HDL, on the other hand, is known as good cholesterol. It is responsible for transport of cholesterol from the tissues to the liver, where it is removed from the body in bile [12, 13].

What does high cholesterol cause?

High cholesterol, particularly when it's chronic, can lead to a range of health issues.

One of the most significant health risks associated with high cholesterol is the development of atherosclerosis. This condition is characterized by the buildup of plaques in the blood vessels. Those plaques are made of cholesterol, fats, and other substances, like calcium and inflammatory cells. With time they can form a significant obstruction in the lumen of the artery, which can restrict blood flow [14, 15, 16].

An additional problem is that these fatty deposits can sometimes burst, causing a blood clot to form. If a clot completely blocks an artery leading to the heart, it can cause a heart attack. Similarly, if it blocks an artery leading to the brain, it can result in a stroke [17].

High cholesterol levels can also lead to coronary artery disease. When the coronary arteries are affected by atherosclerosis, the heart may not receive the amount of oxygen-rich blood it needs to function properly, leading to symptoms like chest pain, called angina, and heart arrhythmias [16]. Eventually, it also leads to a heart attack.

In case of diseases linked to the heart, cholesterol causes indirectly the symptom of fatigue by contributing to the diseases as an aetiology and risk factor

In addition to these cardiovascular disease, high cholesterol has been linked to skeletal and muscular problems. High levels of this fat in the blood flow increase the risk of tendon injuries and impaired healing. This is due to the release of pro-inflammatory cytokines and the upregulation of matrix-degrading proteins in hypercholesterolemic conditions. Thus high cholesterol levels lead to an increase in tendon stiffness and elastic modulus [18].

What happens when cholesterol is low?

When cholesterol levels are too low, a condition known as hypocholesterolaemia, can lead to several health issues.

One of the primary concerns is the influence of the thyroid gland. The thyroid produces hormones that help the body use energy and break down lipids, including cholesterol. There are two of these hormones: thyroxine (T4) and triiodothyronine (T3). When a disease occurs where there are more of the hormones produced (hyperthyroidism), the cholesterol breakdown can exceed its creation. This leads to cholesterol levels dropping very low, sometimes low enough to be classified as hypocholesterolaemia [19]. Low cholesterol levels can be linked to anaemia, specifically pernicious anaemia. One of the symptoms of anaemia is fatigue. However, some research also suggests anaemia can lead to lower concentrations of cholesterol in your blood [19].

Another condition associated with low cholesterol is sepsis, a severe response to an infection. It occurs when bacteria or immunologically active parts of them reach the blood. This can happen in severe pneumonia. Because of the overreaction of the organism, the metabolism and production of cholesterol are compromised leading to hypocholesterolaemia [19].

The liver is the centre of cholesterol metabolism, due to this fact all chronic liver diseases, like hepatitis, can often result in low blood cholesterol levels. Normally, the lower cholesterol levels are the more severe the liver disease is [19].

Malabsorption, a condition where the small intestine cannot absorb nutrients at all or absorbs them only partially, can also lead to hypocholesterolaemia. Conditions that can cause malabsorption include celiac disease, Crohn’s disease, ulcerative colitis, chronic pancreatitis, and cystic fibrosis [19].

However, hypocholesterolaemia can be inherited from the family. The inherited low cholesterol disorders come from the impairment of biosynthesis of this fat. Characteristics for them are multiple morphogenic and congenital anomalies including internal organ, skeletal, and/or skin abnormalities [20].

Low cholesterol levels can also affect the brain. Cholesterol is essential for neuronal physiology, and disturbances in cholesterol metabolism may contribute to neurological syndromes, such as Alzheimer's disease, Huntington's disease or Parkinson's disease [21].

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Jakub Gwiazdecki

Jakub Gwiazdecki

Jakub is in his fifth year as a medical student at Comenius University in Bratislava, Slovakia. He has special interested in cardiology and in patient-centered medicine. His love for heart health isn't just book-smarts; he wants to know how it works, what it means for our feelings, and how key it is for health and happiness. Jakub thinks real good health care comes from always putting the patient at the centre, treating each person as a whole.