What is LDL-Cholesterol?
Low-density lipoprotein (LDL) is a particle made of fats surrounded by proteins. Since fats do not mix with water, they are packaged inside proteins for delivery to cells. LDL is one of five such packages (lipoproteins) that transport fat throughout the body .
LDL has the highest cholesterol concentration of all lipoproteins. It is the major cholesterol carrier in the body. LDL contains:
Functions of LDL
- Transfers fat and cholesterol around the body for cells to use .
- Binds certain toxins, making them unable to trigger harmful immune responses. LDL binds toxins produced by bacteria (Staphylococcus) and the toxin lipopolysaccharide (LPS) [3, 4].
- Helps repair damaged blood vessels. When arteries become damaged, LDL binds to the artery wall to aid the healing process. This helps the artery in the short-term but can be harmful long-term .
When LDL gets inside the damaged artery wall to help the healing process, it undergoes a change and becomes oxidized. Oxidized LDL is toxic to artery wall cells. To remove oxidized LDL, inflammatory cells migrate to the artery wall .
Cholesterol, other fats, and more inflammatory cells can accumulate to form a fatty plaque in the artery. The plaque may grow large enough to restrict blood flow. For this reason, oxidized LDL contributes to heart disease .
In a meta-analysis (of 12 studies), those with oxidized LDL had a higher risk of heart disease .
LDL particles differ in size and density. Small, dense LDL particles are associated with higher heart disease risk than large, less dense particles. This is because small, dense LDL passes easily into blood vessels and becomes oxidized .
Lowering LDL is the primary goal for people with high cholesterol .
A fasting LDL blood test estimates the amount of cholesterol carried by all LDL particles. The following equation estimates LDL:
LDL-cholesterol = Total cholesterol – HDL-cholesterol – (Triglycerides/5) .
This equation can underestimate LDL if fat (triglycerides) levels are extremely high (> 400 mg/dL) .
LDL particles can also be directly measured in the blood, which is more accurate than the equation. However, this method is expensive and not widely available .
The main factors affecting blood LDL levels are the amount of cholesterol that is :
- Absorbed in the gut from food and bile
- Produced in the liver
- Used by cells
- Removed by the liver and HDL
The first two raise blood LDL, while the second two lower it.
Optimal, Normal, and Elevated LDL Levels
Below are LDL guidelines for people with low risk of heart disease .
- Normal < 100 mg/dL
- Borderline High: 100 – 129 mg/dL (still acceptable in healthy individuals)
- High: 130 – 190 mg/dL
- Very High: > 190 mg/dL
Recommendations encourage LDL levels < 70 mg/dL for individuals with high heart disease risk .
LDL vs. HDL
LDL and HDL work together to maintain cholesterol levels. LDL delivers cholesterol from the liver to organs that use it. HDL gathers unused cholesterol from organs and returns it to the liver for reuse .
High LDL-Cholesterol Levels
Causes of High LDL Cholesterol Levels
In obesity, the number of harmful (small, dense) LDL particles increases. Total LDL levels increase slightly .
Obesity also reduces the number of LDL receptors in the body, which reduces response to LDL and raises its levels in the blood .
2) High Cholesterol Diet
3) High Trans Fat and Saturated Fat Diet
Consuming a high-saturated fat diet for 3 weeks increased LDL and harmful (small, dense) LDL particles in a study of 53 adults .
4) Physical Inactivity
In a study of 1,331 adults, physical inactivity was linked to LDL .
5) Type 2 Diabetes
Patients with type 2 diabetes have elevated small, dense LDL particles and oxidized LDL. Total LDL levels remain normal or increase only slightly .
LDL particles remain in the blood longer for individuals with type 2 diabetes. This increases the likelihood of LDL depositing into blood vessels .
Insulin-resistant individuals, such as those with metabolic syndrome or type 2 diabetes, produce more LDL. These people respond better to cholesterol-lowering drugs (statins), which block cholesterol production .
LDL (including harmful small, dense LDL) is elevated during pregnancy, particularly in the second half of pregnancy. This increase is due to sex hormone (estrogen, progesterone) changes [33, 34, 35, 36, 37].
Animal studies suggest that mothers with high LDL in pregnancy deliver offspring with elevated heart disease risk .
7) Short Sleep
In a small study of 10 healthy older women, LDL increased after 3 consecutive nights of sleeping only 4 hours/night .
8) Kidney Disease
A low-functioning thyroid gland (hypothyroidism) can increase LDL .
In a study of 106 adults, patients with subclinical hypothyroidism had higher LDL than those with a healthy thyroid .
Many drugs raise LDL as a side effect. They include muscle building steroids, retinoids (often used for skin problems), anti-seizure drugs, corticosteroids and drugs that suppress the immune system [46, 47, 48, 49, 50, 51, 52, 49, 53, 54].
11) Alcohol Consumption
Alcohol intake may increase oxidized LDL but is also associated with lower overall LDL levels.
In a study of 587 adults, alcohol consumption was positively associated with oxidized LDL .
People who abused alcohol had higher oxidized LDL compared to moderate drinkers in a study of 530 Finnish men .
However, alcohol intake was associated with lower LDL in a study of 993 Japanese men .
Additionally, wine intake was linked to reduced oxidized LDL in a study of 551 older Italian adults .
12) Mental Stress
In one of the above studies of 199 middle-aged adults, those with greater LDL increases during the stressful task were more likely to have elevated LDL 3 years later .
In a study of 308 people, current cigarette smoking and tobacco waterpipe smoking were associated with elevated LDL .
Smoking was also associated with increased oxidized LDL in a study of 28 adults .
14) Elevated Ferritin
In studies of over 11,000 people, those with higher blood ferritin levels were more likely to have increased LDL. It is not known whether elevated ferritin is a cause or result of elevated LDL [65, 66].
15) Fish Oil Supplementation
In a meta-analysis, taking DHA increased LDL 7.23 mg/dL on average compared to placebo .
Conditions Associated with High LDL-Cholesterol Levels
1) Heart Disease
By far the biggest problem with elevated LDL is its accumulation in arteries. This can create fatty plaques that restrict blood flow and harden the blood vessels. Clogged arteries can become completely blocked, causing a stroke or heart attack, while hardened arteries lead to high blood pressure [69, 70, 71].
Even at very low levels, LDL was associated with artery hardening in a study of 1,779 adults .
2) Chronic Obstructive Pulmonary Disease (COPD)
In a study of 48 COPD patients and 32 healthy adults, those with COPD had higher oxidized LDL. Oxidized LDL was linked with poor lung function and inflammation .
LDL levels were linked with poor lung function in a study of 82 COPD patients and 43 healthy participants 
In a study of 60 people, LDL was 3 times higher among those with anxiety compared to those without anxiety .
4) Gum Disease
In a meta-analysis (of 19 studies), patients with gum disease had higher LDL than individuals without gum disease .
Low LDL-Cholesterol Levels
Low LDL reduces heart disease risk. In a meta-analysis involving 38,153 adults with high cholesterol, very low LDL (< 50 mg/dL) was associated with lower heart disease risk than LDL 75 – 100 mg/dL .
However low LDL can contribute to health problems because cholesterol plays many roles in the body.
Causes of Low LDL-Cholesterol Levels
Cholesterol-lowering drugs (statins) are prescribed to people with high cholesterol. These drugs lower LDL 25 – 35% on average and can reduce LDL below 30 mg/dL .
Conditions Associated with Low LDL-Cholesterol Levels
In a study of 70,179 adults, LDL levels in the bottom 10% (< 87 mg/dL) were associated with a 43% increased risk of developing cancer .
2) Depression and Suicide
In a study of 60 people, those with depression had lower LDL compared to healthy subjects .
In a meta-analysis (of 65 studies and over 500,000 participants), suicidal patients had lower LDL compared to both non-suicidal patients with a mental disorder and healthy patients .
3) Infectious Disease
Individuals with low LDL (< 70 mg/dL) had increased sepsis, a life-threatening complication of infections, and fever risk compared to those with LDL > 70 mg/dL in a study of 203 people .
In a study of more than 100,000 people, those with low total cholesterol were more likely to be admitted to the hospital for an infectious disease .
4) Type 2 Diabetes
In a study of over 400,000 people, lower LDL was associated with a higher risk of developing type 2 diabetes .
5) Risk of Dying
In studies including over 130,000 people, low LDL was associated with increased risk of death in many different populations. These include Danish adults, elderly adults, and heart attack, pneumonia and sepsis patients [98, 99, 100, 101, 102, 103].
6) Other Conditions
Low LDL due to genetic problems in creating cholesterol can lead to many different disorders. These conditions delay growth, behavior, and mental function in children .
LDL levels are influenced by your genes. If you’ve gotten your genes sequenced, SelfDecode can help you determine if your levels are high or low as a result of your genes, and then pinpoint what you can do about it.
Here’s a breakdown of some genes that can influence LDL levels:
- Abetalipoproteinemia is a rare disease where LDL is almost absent. This is due to a poor ability to absorb fat (caused by a mutation in the microsomal transfer protein (MTP) gene) .
- Familial hypobetalipoproteinemia is another rare condition where LDL levels are below 50 mg/dL. The cause is a mutation of the apoprotein B (APOB) gene .
- Some people have reduced activity of genes that break down cholesterol (ATP-binding cassette (ABC) transporters). This can increase LDL levels and lower response to cholesterol medication .
- In a study of 599 patients with elevated LDL, carrying an apolipoprotein 5 (APOA5) SNP was associated with smaller LDL particle size and higher oxidized LDL levels .
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) breaks down the LDL receptor, resulting in the accumulation of LDL in the blood. Variants of PCSK9 can cause either elevated or low cholesterol .
These mutations cause problems in removing LDL from the blood, resulting in elevated LDL .
Irregular LDL Levels?
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