The effects of high VLDL cholesterol, how to best measure it and maintain healthy levels is still a hot topic of research. It is clear, though, that high VLDL is a major risk factor for heart disease and may contribute to chronic inflammation. Read on to learn more and find out how to lower VLDL with lifestyle and diet changes.
What Is VLDL Cholesterol?
Heart disease is an increasing concern, killing at least 4.5 million people every year. Only a couple of decades ago, it was thought that high cholesterol in the blood was the main cause of heart disease. Now it is obvious that this picture is incomplete and that the levels of different particles that carry cholesterol in the body are more important than total cholesterol levels [1, 2].
There are several types of particles that carry cholesterol through the blood, such as VLDL, HDL, and LDL, each with different effects on the body and functions. The levels of each of these cholesterol-carrying particles and their ratios are more important in terms of health risk .
These particles all lipoproteins – made up of both fats (lipids) and proteins. Since fats do not easily dissolve in the blood, lipoproteins help to transport them .
They are named according to their density and size. HDL stands for high-density lipoprotein and is the densest and smallest of the three. LDL and VLDL stand for low-density lipoprotein and very-low-density lipoprotein, respectively, and they are more likely to cause heart disease than HDL .
Some lipoproteins, like HDL (high-density lipoprotein) and LDL (low-density lipoprotein), mostly transport a type of fat called cholesterol, which is used in cell membranes or as a building block for hormones. These molecules are sometimes grouped together and called “cholesterol” because of this what they mainly transport .
VLDL and Triglycerides
VLDL mainly transports the type of fat known as triglycerides from the liver to various tissues, and only a small amount of cholesterol. Triglycerides are needed to line the organs and muscles and are also stored under the skin as body fat. So while HDL and LDL make up most of the cholesterol in the blood, VLDL makes up most of the triglycerides in the blood .
Though VLDL is required by the body, high levels of VLDL may cause serious health problems .
- Some VLDL particles are larger than others because they contain more fat.
- The protein portion of VLDL may also become oxidized, which can cause oxidative damage to the inner lining of blood vessels, contributing to the formation of plaques in blood vessels.
VLDL vs LDL
LDL stands for low-density lipoprotein and VLDL stands for very-low-density lipoprotein. These names can be somewhat deceptive because VLDL, being denser, is actually the larger particle.
VLDL is made in the liver after the body absorbs fat from dietary sources. The triglycerides (with fatty acids) that make up the VLDL molecule are transported to the muscles and fat tissues, where they are deposited. In return, VLDL takes up cholesterol from the tissues. At the end of this process, VLDL becomes LDL — particles rich in cholesterol and low in triglycerides [3, 3].
It is important to note that the level of VLDL alone is not the only factor that determines the health risks. Many other factors, such as the size and chemical makeup of VLDL, also play a role. Currently, there are no simple tests for these factors, though [5, 7].
- Clogged arteries (atherosclerosis)
- Non-alcoholic fatty liver disease
- Type-2 diabetes
- More severe symptoms of hepatitis C and dengue viruses
Men vs Women
VLDL levels tend to rise in women following menopause. It is not clear if this increase in VLDL levels is due to the drop in hormones, increased body fat after menopause, or other factors .
African American women may produce smaller VLDL particles than Caucasian women according to an observational study of women with type-2 diabetes. Studies on a wider population would need to confirm if this finding also applies to men .
VLDL Blood Test
There is no simple test for directly measuring VLDL levels. Due to the complicated nature of the laboratory techniques needed to measure VLDL, its levels are estimated based on triglyceride levels found in the blood [20, 21].
The most widely used method for estimating VLDL is to divide the level of blood triglycerides by 5. This equation assumes that there is a fixed 5:1 ratio of triglycerides to VLDL particles. This assumption is not always true because the actual ratio varies due to ethnicity, gender, and diet [21, 22, 23].
Requesting the VLDL Test
You can request that your doctor test your VLDL levels. Conventional doctors will look at high or low VLDL levels and not mention anything. Sometimes, a lab result may be in the reference range, but not actually be in the optimal range. Reference ranges are not the same as optimal ranges. This is why even VLDL in the ‘normal’ range can be unhealthy and indicate that certain processes in the body aren’t optimal.
Causes of High VLDL
1) Obesity is Associated with High Levels of VLDL
In a study that compared 12 obese men and 12 lean men, the obese men had increased liver production of VLDL .
2) Insulin Resistance Increases VLDL
A study of 1,850 patients showed that people with greater insulin resistance had not only higher levels of VLDL but also produced larger, fattier VLDL particles. Studies on mice have also confirmed this [28, 29].
Type-1 diabetes was not associated with changes in VLDL levels in response to sugar. This suggests that only insulin resistance, characteristic of type-2 diabetes, adds to the risk of increased VLDL (a study of 8 men with type-1 diabetes) .
3) Metabolic Syndrome Increases VLDL Size
Metabolic syndrome may cause the liver to produce larger VLDL molecules, which hold and transport more fat at one time .
Metabolic syndrome is also marked by insulin resistance, which also increases VLDL levels .
4) Low Thyroid Function is Linked to Increased VLDL
In a study of 45 women, women with slightly lower thyroid function had higher levels of VLDL than women with normal thyroid function. Women with slightly higher thyroid function had lower levels of VLDL .
Another study of 113 patients, both male and female, confirmed that patients with slightly less active thyroid were more likely to have higher levels of VLDL and larger-sized VLDL .
5) Chronic Kidney Disease Can Cause High VLDL
In a study of 12 patients with chronic kidney disease, patients produced VLDL at a normal rate but were less able to remove the VLDL from the blood once it had been released by the liver. As a result, they had higher VLDL levels than the control group .
6) Liver Nerve Damage May Increase VLDL
Liver nerves play a large role in maintaining healthy levels of VLDL and other fats. Damage to the nerves in the liver caused mice to release more VLDL into the bloodstream .
In humans, damage to the liver nerves is most often caused by liver surgery, such as liver transplants. Though not yet confirmed in humans, it is possible that liver surgery and other causes of liver nerve damage may contribute to high VLDL .
7) Excess Calories Cause Inflammation that Increases VLDL
Metabolic inflammation is a general term used to describe the recurring, low-level inflammation that is caused by excess calories .
In mice, metabolic inflammation resulted in increased production of the inflammatory TNF-alpha, which in turn increased VLDL. TNF-alpha stimulated the production of an essential building block of VLDL (apoB protein) .
8) Food Preservative Sodium Sulfite May Increase VLDL
Sodium sulfite, a chemical commonly used as a food preservative for meats, increased the production of VLDL in a study done on human liver cells .
How to Reduce High VLDL
- Lowering body fat or increasing lean muscle mass – especially if obese
- Both aerobic and resistance exercise lower VLDL by increasing the rate it is removed from the blood
- Controlling diabetes and insulin levels
- Reducing insulin resistance
- Increasing adiponectin levels, which can be done by losing weight or increasing dietary intake of fiber and fish oil
- Increasing Growth Hormone levels, which can be done through fasting or by taking glycine supplements
- HDL (high-density lipoprotein) protects against some of the harmful effects of excessive VLDL, so factors that increase HDL are beneficial though they may not directly lower VLDL levels
- Following a Mediterranean-style diet, rich in extra virgin olive oil, for 3 months lowered VLDL size in 50 patients. A Mediterranean-style diet rich in nuts, however, did not decrease VLDL size or levels but did increase HDL levels, which may counteract negative effects of VLDL.
- Limiting the number of calories from sugar or fat consumed in a single meal, as well as avoiding high-calorie meals
- While low-fat diets do not lower the total amount of VLDL, they may prevent VLDL from damaging the lining of blood vessels, which contributes to the build-up of plaques in the blood vessels.
- Fasting/calorie deficit diets reduce VLDL levels for short periods, up to 24 hours.
- Eating plant proteins from chickpeas and lentils resulted in lower VLDL levels in mice compared to mice fed protein from dairy, suggesting that replacing dairy with legumes may lower VLDL.
- The effect of dietary carbohydrates on VLDL levels is not well understood, with some studies showing that high carbohydrate diets (50% of total calories coming from carbohydrates) raise VLDL and other studies showing the opposite – that low carbohydrate diets (20% or less) raise VDLD.
- Eating Atlantic salmon twice a week
- Fenugreek seeds (in mice)
- Fish oil (n-3 fatty acid) reduces the size of VLDL particles
- Plant sterols and stanols can bind to fats
- Grape seed proanthocyanidin extract lowers VLDL spikes after meals (in mice)
- SAMe (S-Adenosyl-L-methionine), reduced VLDL in mice
- Glycine (in mice)
- Complex sugars from kombu (Laminaria japonica), a type of seaweed (in mice)
- Cold-pressed minke whale oil (in mice)
Estradiol, a form of estrogen sometimes used in hormone replacement therapy for menopausal women, reduced VLDL levels by 30% in a study of 27 postmenopausal women treated with 0.1 mg/day of estradiol for about 3 months .
- Diabetes medications, such as Exenatide and Metformin (in rats)
- Statins, such as Atorvastatin and Rosuvastatin, reduce VLDL by lowering adiponectin and VLDL activity (via receptors)
- Fenofibrate, which is used to treat high cholesterol levels
- Orlistat, used to treat obesity, reduces the rise in VLDL that typically follows meals
Health Dangers of High VLDL
1) High VLDL Can Cause Fatty Liver Disease
High VLDL levels can cause non-alcoholic fatty liver disease. Fat may build up in the liver when it is unable to move all the VLDL cholesterol to the blood. Reducing VLDL levels may reduce fat build-up fat in the liver, which may improve symptoms of the non-alcoholic fatty liver syndrome and diabetes [77, 78].
A study of 128 patients with non-alcoholic fatty liver disease showed that the larger the VLDL particles a patient had, the more severe the disease was. Larger VLDL molecules can carry more fat than smaller ones. Another study of 25 obese people also showed that those with fat in their liver had increased production of VLDL [12, 13].
A non-alcoholic fatty liver disease can eventually cause liver damage that prevents the liver from producing VLDL, so VLDL levels may be lower in people with long-term non-alcoholic fatty liver disease .
2) High VLDL Can Lead to Clogged Arteries or Plaques
A study of 30,378 people of Chinese descent showed that those with high levels of VLDL (30 mg/dL or more) were 2-3 times more likely to develop a buildup of fat in the heart arteries (coronary heart disease) .
When VLDL is broken down by the body, it is turned into byproducts that also contribute directly to the blocking of arteries. In addition, larger molecules of VLDL carry more fat that is then more likely to becomes stuck to the walls of the blood vessels. Lowering the size and levels of VLDL may protect against this effect [79, 51].
3) Increased VLDL May Lead to Type-2 Diabetes
Metabolic syndrome is marked by insulin resistance and often leads to type-2 diabetes. People with large VLDL particles, but small LDL and HDL, had the worst symptoms of metabolic syndrome, and a higher risk of developing type-2 diabetes (study with 1,036 people) .
Increased VLDL levels occurred before the development of type-2 diabetes in patients with metabolic syndrome, suggesting that the high VLDL contributes to this progression .
4) High VLDL Causes Inflammation
Lowering levels of VLDL can prevent damage to the inner lining of the blood vessels. High levels of VLDL led to inflammation in the lining of the arteries. It increased an inflammation-promoting protein (CASPASE-1 protease), which increased other inflammatory compounds (cytokines IL-1beta and IL-18) [81, 82].
VLDL activated another inflammatory pathway (via nuclear factor-kappa B) in the linings of the blood vessels, further promoting inflammation .
5) High VLDL Increases Fats in Blood After Meals
Having excess fats, or triglycerides, in the bloodstream after a meal is a risk factor for heart disease. This increase in triglycerides is mostly due to a simultaneous increase in VLDL, which occurs naturally following meals [84, 85].
People with high VLDL levels had larger spikes in VLDL after eating a high-fat meal than people with normal VLDL levels (a study of 1048 people). Lowering VLDL may then decrease the risk for heart disease by lowering post-meal blood triglyceride levels .
6) VLDL Promotes the Growth of Breast Cancer Cells
VLDL increased the growth and spread of breast cancer cells by increasing their ability to move and divide in a cell study .
7) High VLDL + Alcohol May Damage the Pancreas
When combined with alcohol, high VLDL levels — like those that occur after a high-fat meal — caused damage and killed pancreas cells in mice .
8) High VLDL May Increase Blood Pressure
Obesity often leads to high blood pressure, which may be caused by high levels of VLDL. Lowering VLDL levels may reduce obesity-related high blood pressure .
9) Excess VLDL May Worsen Hepatitis C
The most common cause of liver failure in the United States is the hepatitis C virus, which depends on VLDL molecules to divide in the body. Higher levels of VLDL may increase the symptoms of Hepatitis C [92, 93, 94].
Patients with Hepatitis C had more virus particles bound to VLDL molecules following a meal in a study of 10 people. This indicates that high VLDL may directly contribute to higher virus levels .
10) Excess VLDL May Worsen Dengue Infections
Dengue fever is caused by the dengue virus. This virus binds to VLDL molecules as a critical part of its life cycle, which is why high levels of VLDL could worsen dengue fever .
Patients with severe cases of dengue virus infection had higher levels of VLDL than patients with more mild infections (in a study with 98 people) .
Limitations and Caveats
Of the supplements that may lower VLDL levels, only fish oil, and plant stanols have been tested in placebo-controlled studies in humans. The health effects of other supplements listed have only been confirmed in studies without a control group or in mice [60, 61, 62, 63].
The study that indicated that the hormone estradiol reduced VLDL in menopausal women was small and needs to be confirmed with further studies .
The research showing that high VLDL is associated with breast cancer growth and inflammation of the pancreas (pancreatitis) were done in cells taken from mice and have not yet been confirmed in humans [86, 87].
The study showing that sodium sulfite may increase VLDL levels was only done in liver cells .
The study suggests that only type-2, and not type-1 diabetes, led to an increase in VLDL levels had only 8 subjects and no control group .
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Lipases are a group of enzymes that help to break down VLDL. A mutation in the lipoprotein lipase gene has been associated with larger VLDL particles in people with metabolic syndrome. Other mutations in this gene result in low levels of the lipoprotein lipase protein and higher VLDL [96, 97].
Apolipoprotein E (ApoE)
ApoE is a protein found in VLDL molecules. As a result of mutations in the gene that encodes the protein, different versions of this it exists. A version known as ApoE4 is found to produce more inflammation in the blood vessels after meals than the normal version, ApoE3 [99, 100].
Having a defective copy of ApoE contributes to high VLDL levels, but this factor alone does not enough raise VLDL levels .
Other Relevant Genes
High levels of the gene Trib1 have been shown to result in lower levels of VLDL in mice .
A form of the gene PNPLA3 (patatin-like phospholipase domain-containing protein 3), also known as adiponutrin, decreased the liver’s ability to export VLDL into the blood, contributing to non-alcoholic fatty liver disease .
Irregular VLDL Levels?
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