“When your liver and muscles become filled with glycogen, any glucose remaining in the bloodstream that isn't used in "real time" by your brain or muscles (such as during an intense workout) gets converted into triglycerides in the liver and sent to fat cells for storage." ― Mark Sisson
Introduction | Triglycerides | LDL Cholesterol | Lipoproteins | Metabolism | sdLDL Formation | Hypertriglyceridemia | Cardiovascular Risk | Laboratory Tests |Final Thoughts | Takeaway Points | References | Disclaimer
Introduction
Cholesterol is a well-known cofactor and predictor of cardiovascular health. The terms good and bad cholesterol, which describe the HDL and LDL molecules, respectively, represent a widely held belief among patients and some doctors regarding how we view cholesterol in our blood. However, cholesterol serves a variety of functions in our bodies, and despite the negative implications, not all LDL cholesterol contributes to the development of atherosclerosis. Furthermore, other fats [lipids] in our bloodstream, specifically triglycerides, can influence the metabolism of LDL cholesterol, ultimately leading to its detrimental effects on our health.
What are triglycerides?
Triglycerides [TGs] are fat [lipid] molecules that exist in our bloodstream and are made up of fatty acids. The liver and our adipose tissue can both produce triglycerides on their own, but TGs are also obtained from the food we eat. The main function of triglycerides is to deliver energy to the body. The hormone glucagon stimulates the release of TG molecules during the fasting period between meals[1]. Then the liver secretes them in the form of very low-density lipoprotein [VLDL][2]. VLDLs contain not only triglycerides but also cholesterol and apolipoproteins [Apos], which are distributed to the body's tissues via the bloodstream.
Our diet also has a significant impact on the amounts of triglycerides in our blood. High-carbohydrate meals provide a lot of glucose, which is then converted into triglycerides and stored in fat cells if the body does not require them.
What is LDL cholesterol?
Another type of particle found in our bloodstream is LDL cholesterol, also known as LDL-C, or low-density lipoprotein cholesterol. LDL cholesterol is considered a "bad type" of cholesterol, which means that high levels can indicate health issues. However, the primary function of the LDL particle is to transport cholesterol to various tissues throughout the body. Cholesterol is a lipid [fat] with wax-like properties. It performs a variety of important functions, including [3]:
cell membrane formation and repair,
bile production,
the production of steroid hormones such as estrogen, progesterone, and testosterone,
generation of vitamin D,
nerve conduction,
and cell signaling.
Lipoproteins and their types
Triglycerides and cholesterol are both lipids that are insoluble in water. However, because they cannot travel freely through our bloodstream on their own, they require the presence of water-soluble proteins to be transported and distributed into the tissues. As a result, TGs and cholesterol are combined with apolipoproteins to form a molecule known as a lipoprotein. There are several types of lipoprotein present in the human blood[4]:
VLDL is a very low-density lipoprotein secreted by the liver. It is rich in triglycerides.
IDL is an intermediate-density lipoprotein found in the blood. It contains a reduced number of triglycerides.
LDL is a low-density lipoprotein. It is rich in cholesterol.
LDL fractions, known as sdLDL, are small-dense LDL particles. They carry high levels of cholesterol, leaving fatty deposits in the blood that promote atherosclerosis.
HDL is a high-density lipoprotein. It carries lipids it has extracted from the body's cells. It is therefore considered "good cholesterol" and one that has protective qualities for the cardiovascular system.
Lipoprotein metabolism: from VLDL to LDL
Once the VLDL molecule is secreted into the bloodstream, it then goes through a process of gradual delipidation[5]. It implies that it releases or loses its triglycerides, which the body's various tissues take up. Such a reduced VLDL particle is known as an IDL [intermediate-density lipoprotein] molecule[4]. The next stage of metabolism includes a further release of remaining triglycerides, which results in the formation of LDL molecules, which contain larger amounts of cholesterol than triglycerides[6].
The remaining LDL cholesterol in the blood is either used by various tissues throughout the body that need it to maintain their integrity and function, or it returns to the liver as part of its metabolic pathway.
Abnormal lipoprotein metabolism: sdLDL formation
Hypertriglyceridemia, or high levels of triglycerides in the blood, is linked to problems with VLDL metabolism. The abnormally high levels of TGs do not allow the LDL particle to rid itself of the triglycerides it carries. In response, LDL particles linger longer in the bloodstream and become smaller and denser[5],[7]. They are then called sdLDL [small dense LDL] molecules. Due to their high clearance time [metabolism time], sdLDLs have a tendency to oxidize[5], glycate [8] [when a lipid molecule bonds with sugar], build up in the vascular system, and lead to inflammation. This process results in atherosclerosis and cardiovascular health problems. It then becomes clear that the more triglycerides there are in the circulating blood, the higher the number of sdLDL particles[9].
What causes hypertriglyceridemia?
Hypertriglyceridemia is defined not only by an increase in triglyceride levels but also by high LDL levels and low HDL counts[10]. The metabolic syndrome and a variety of metabolic health conditions are strongly linked to hypertriglyceridemia.
"In daily practice, elevated serum triglycerides are predominantly observed in persons with metabolic syndrome. Many previous studies indicate that hypertriglyceridemia is strongly associated with all components of metabolic syndrome. Patients with metabolic syndrome who have hypertriglyceridemia most often exhibit elevated level of triglyceride-rich lipoproteins which are considered atherogenic." [11]
Abnormally high levels of triglycerides are very common in overweight and obese [especially abdominally obese] individuals. Additionally, a high-carbohydrate diet, a fructose-rich diet, excessive alcohol consumption, and a lack of physical activity can also increase the level of TGs. Furthermore, hypertriglyceridemia is one of the most common lipid metabolism disorders in people with insulin resistance and type 2 diabetes. High blood sugar levels and insulin insufficiency slow down the breakdown of VLDLs and ultimately lead to the glycation of these molecules [12], which are known to cause further damage to the body and contribute to the development of athersclerosis[8], increased CVD risk, and renal failure [chronic kidney disease].
Additionally, the use of some prescription drugs, such as corticosteroids, antipsychotics, beta-blockers, and oral estrogens, can result in hypertriglyceridemia.
Also, some genetic conditions, like familial combined hyperlipidemia, familial hypertriglyceridemia, familial dysbetalipoproteinemia, and familial chylomicronemia syndrome, can change the way lipids are used in the body.
Triglycerides, LDL cholesterol, and cardiovascular risk
Modern laboratory tests can measure both triglyceride and LDL cholesterol levels in the blood. Because we frequently associate LDL particles with the "bad cholesterol" that contributes to our heart issues, their elevated levels immediately raise concern. However, as was previously mentioned, not all LDL cholesterol is associated with heart issues. The LDL family member known as sdLDL, which is not specifically screened for in routine blood tests, is the most problematic. Knowing that sdLDL predominantly appears in the blood when accompanied by an excessive amount of TGs, triglycerides become a better marker for cardiovascular risk. High blood triglyceride levels signify that our body has trouble metabolizing them, which suggests that LDLs will take longer to clear from the circulatory system. The risk of developing sdLDL and vascular plaque [atherosclerosis] rises with their longer clearance times.
Available laboratory tests
The availability of laboratory tests can greatly aid in assessing our cardiovascular health. A full lipid panel can consist of as many as 20 different tests. Most commonly performed blood tests include such parameters as HDL and LDL cholesterol levels, triglyceride [TG] levels, and total cholesterol [TC] levels. However, in light of what has been discussed above, these single numbers can be somewhat misleading in their analysis. It is therefore imperative to look at some of them together and calculate their ratios for a more accurate outcome. The most accurate ratios that can indicate the presence of sdLDL particles in the blood include:
Some doctors also ask to test the Apo-A1 and Apo-B biomarkers, or their ratio[13]. Depending on the underlying cause of your hypertriglyceridemia, different tests might present the best cardiovascular assessment for each individual. The best person to give advice on the recommended lipid panel is a trained medical professional.
Final Thoughts
Assessing cardiovascular risk involves determining the cause of hypertriglyceridemia as well as understanding how to interpret biomarker results obtained through a blood test. The case of LDL cholesterol and its negative impact is not as simple as it once was. The common misconception is that all LDL cholesterol is bad for you and causes disease. The accumulation of sdLDL particles, which only make up a small portion of the LDL family, is what causes atherosclerosis. Because sdLDL cholesterol levels cannot be directly measured, understanding the mechanisms and metabolic pathways that lead to their formation will help you understand why triglycerides can be used as a better indicator of possible sdLDL presence in the bloodstream. The ratio of two lipid biomarkers, such as total cholesterol or triglyceride levels, in correlation to HDL cholesterol can then be used to assess cardiovascular risk.
Takeaway Points
Triglycerides are fat molecules composed of fatty acids.
Cholesterol is a wax-like fat that performs multiple important functions throughout the body.
Lipoproteins are molecules composed of triglycerides, cholesterol, and apolipoproteins.
Hypertriglyceridemia is a condition characterized by elevated triglyceride and LDL levels, as well as a low level of HDL cholesterol.
sdLDL particles are the main cause of atherosclerosis.
There are a wide variety of laboratory tests that measure various lipid biomarkers.
Trglyceride levels can help determine if there are sdLDL molecules present in the bloodstream.
References
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