Cholesterol is a type of fat (sterol). Cholesterol is used to build cell membranes, hormones, tissue, and vitamin D. Cholesterol is ingested through different foods such as eggs, meat, butter, and whole-milk dairy products [R, R].
Our body depends on cholesterol. Humans have over 100 genes that affect cholesterol production, movement, and breakdown. Cholesterol and its breakdown products are vital for dietary nutrient absorption, reproduction, water regulation, salt regulation, and calcium metabolism [R].
Cholesterol plays a big role in steroid production. It is broken down (by cytochrome P450scc) in the adrenal cortex to create pregnenolone, which is used to make all steroids [R].
The most important function of cholesterol is for cell membranes. Cholesterol controls the movement of molecules through cell membranes, helping cells to communicate [R].
Cholesterol is created in the liver, gut, and other organs. Most of cholesterol is made outside the liver [R].
On average, humans make 10 mg of cholesterol per day per kg of body weight. The production depends on the needs of the person. If you eat foods high in cholesterol, less needs to me made in the body [R].
Total cholesterol is measured using a method called a blood fat profile test. The test measures up to 4 parameters [R]:
Every person over the age of 45 should get a fat profile test. People under the age of 45, but with a family history of heart disease, diabetes, or chronic kidney disease, should be tested earlier [R].
While total cholesterol is the easiest and cheapest parameter to measure, it is advised to measure LDL and HDL as well, as they can be better markers for heart disease [R].
Cholesterol is the precursor to LDL, HDL, and very-low-density lipoprotein (VLDL) cholesterol. VLDL makes LDL, which is clogs the arteries (atherosclerosis), while HDL can help prevent heart diseases [R, R, R, R].
Diet heavily influences the relationship between cholesterol and these fats. With low-cholesterol diets, the liver rapidly clears both LDL and VLDL, so LDL levels in the blood remain very low [R].
With cholesterol-heavy diets, the clearance of VLDL decreases. This increases LDL production, which can be harmful. HDL production also increases with more cholesterol [R].
However, these values are not the only indicators of health. Two people with the same cholesterol levels may differ up to a 4.5 times in their risk of stroke, depending on other factors like genetics, blood pressure, and smoking [R].
Cholesterol levels are very tightly regulated by the body. Therefore, increasing cholesterol slightly and infrequently is usually not a problem. However, when cholesterol levels are increased consistently, it can lead to problems.
The biggest problem with elevated cholesterol is the buildup of LDL, which increases the risk of heart disease. Cholesterol in the arteries can cause atherosclerotic plaques, which are fatty buildups that cause narrowing of the blood vessels and decrease blood flow [R, R, R].
The clogged arteries can eventually close fully, leading to heart attack or stroke. In some cases, plaque can rupture causing the fatty buildups to enter into the bloodstream. This results in blood clotting and decreased blood flow elsewhere in the body [R, R].
Cholesterol is also toxic to certain cells and can cause an immune response leading to destruction of the artery walls. This reduces blood flow to tissues and causes damage [R].
Although an unhealthy lower level of total cholesterol has not been fully validated, it is thought that < 140 mg/dL of cholesterol will produce negative effects [R].
There are links between lowered cholesterol and psychiatric disorders. In a study of 394 patients (observational), depression was 3 times more common in those with lowered cholesterol levels [R].
When comparing medical and criminal records, having lowered cholesterol increased the chances of violent crime. Other studies found links between lowered cholesterol and antisocial personality disorders as well as anxiety [R, R, R].
Studies have also linked low levels of cholesterol to cancer. In a study (RCT) of 12,241 patients, those with reduced cholesterol levels (< 159 mg/dL) had higher chances of developing cancer [R].
Low levels of cholesterol, especially in the developing years, can lead to a wide variety of different syndromes. These syndromes are mainly due togenetic problems in creating cholesterol. Dietary cholesterol supplements may help, but prognosis is poor [R, R].
One’s diet plays an important role in balancing cholesterol. High levels of saturated fat can increase blood cholesterol levels dramatically. This increase is worsened by obesity [R].
The body has many protective mechanisms to stop drastic increases in cholesterol. The health risks due to high cholesterol levels take many years to develop and are a result of eating high fat foods consistently [R].
The main sources of cholesterol come from egg, dairy products, and meat. It is estimated that 24.6% of the total cholesterol intake in the U.S. diet comes from eggs and egg-mixed dishes. Chicken and beef make up 12.5% and 11%, respectively [R].
Whether cholesterol from diet can cause heart disease is still unclear. According to a large meta-analysis (of 40 studies and 362,555 patients), it may not. In the U.S., it’s still not recommended to consume more than 300 mg/day of cholesterol R, R].
Other lifestyle factors such as smoking can also influence cholesterol levels. Quitting smoking can increase HDL levels by 24 times, as seen in a study (DB-RCT) of 1,504 smokers [R].
Exercise has also been shown to increase HDL levels while decreasing LDL levels. Therefore, lack of physical activity can increase bad cholesterol [R].
In a study (RCT) of 26 male volunteers, increased mental stress increased total cholesterol levels [R].
People who are resistant to insulin or can’t break down glucose or fatty acids can also have high cholesterol levels [R].
Some people have reduced activity of genes that break down cholesterol (ATP-binding cassette (ABC) transporters). This can increase cholesterol levels and lower response to cholesterol medication [R].
Familial hypercholesterolemia is a heritable disease that is caused due to mutations in several genes, including those that make [R]:
This causes problems in clearing LDL [R].
Lifestyle modifications can go a long way in helping maintain healthy levels of cholesterol. In one study (DB-RCT) of 923 adult smokers, quitting smoking increased HDL levels by 2.4 mg/dL [R].
A study comparing women smokers and non-smokers also found that smokers had greater total cholesterol levels (197 mg/dL vs. 189.1 mg/dL) and had lower HDL levels (45 mg/dL vs. 52.1 mg/dL) [R].
Increasing exercise can reduce cholesterol levels. In a study of 123 children, increasing exercise helped increase HDL levels, while decreasing LDL and total cholesterol [R].
The same effect is seen in adults. A meta-analysis of 51 studies and 4,700 adults found that aerobic exercises such as jogging, running, and biking increased HDL by 4.6% and decreased LDL by 5%. Another study (RCT) of 235 adults showed that exercise also decreased total cholesterol [R, R, R].
A healthy diet is key to weight loss. The American Heart Association Step 2 diet, which consists of increasing fish, vegetable, fruit, and low-fat dairy products while decreasing salt and alcohol intake, lowers total cholesterol. This diet also reduces LDL by up to 20% [R, R, R].
The right diet can cause significant weight loss. In a study (DB-RCT) of 384 patients, weight loss caused total cholesterol levels to decrease by 25 to 30 mg/dL [R].
Reducing stress can help lower cholesterol levels. In a study of 26 adults, increased mental stress increased total cholesterol levels. The cholesterol remained high even once the stress went away, pointing to long-term consequences [R].
Another study of 40 college teachers and 40 housewives compared the stress levels between the 2 groups. The housewives showed greater environmental, psychological, and physiological stress, which caused higher total cholesterol and LDL levels [R].
Cholesterol can be reduced with drugs such as statins that decrease the amount of cholesterol the liver makes. Statins increase LDL uptake in the liver, while also raising HDL cholesterol. They are viewed as very safe [R, R].
In a large study (RCT of 284 patients with dementia and 1080 healthy), statins reduced the risk of developing dementia in healthy participants. A different study (RCT) of 60,349 patients found that taking statin reduces the chances of acquiring Alzheimer’s by 60 to 73% [R, R].
Another study (RCT) of 4,444 patients with heart disease found that simvastatin decreased total cholesterol by 26%, LDL by 36%, and death by 30%. Lowering LDL always proved beneficial for fighting heart disease [R].
Although the main drugs for lowering cholesterol are statins, other drugs such as bile acid sequestrants are useful. Depending on dose, these drugs reduce LDL by up to 30% and decrease risk of heart disease [R].
Therapies that reduce cholesterol can cause some side effects as well. Statin therapy, which is the first-line treatment to reduce cholesterol, can cause muscle pain (myalgia) or inflammation (myositis) in 8 to 9% of patients [R].
Statin therapy may also increase incidences of type 2 diabetes, as seen in a meta-analysis of 13 trials and 91,140 patients [R].
A procedure called lipoprotein apheresis removes LDL from the blood. It’s an option for people who don’t respond to drugs and have very high cholesterol levels. This method reduces LDL by up to 60% in patients with familial hypercholesterolemia [R].
Another study of 45 patients with high cholesterol resistant to drugs found that lipoprotein apheresis lowered total cholesterol by 57%, LDL by 55.9%, and increased HDL by 14.3%. Improvements in life quality and performance were seen in almost all patients [R].
In another study of 14 hypercholesterolemic patients, lipoprotein apheresis was safe long-term (for over 10 years) and caused an average decrease of LDL by 82% [R].
There are different types of lipoprotein apheresis [R]:
All can decrease total cholesterol and LDL and increase HDL. Immunoadsorption may be the best for reducing another fat called lipoprotein (a) [R].