Cholesterol is a fatty substance that occurs naturally in the body. It is essential for the creation of every cell in the body, as cholesterol is an essential component of cell membranes, where it provides fluidity to allow transporters, such as those for glucose and hormones, to transverse cell membranes.
Cholesterol is a precursor for the making of the most important steroid hormones in the body, such as cortisol, oestrogen, testosterone, and many others. Cholesterol is also essential for making bile acids, which help with the digestion of food.
Where does cholesterol come from?
The cholesterol in our bodies comes from two different sources, it is either made “afresh” in the cells, a process referred to in biological terms as being synthesised de novo, or we get it as dietary cholesterol from different food sources.
Cholesterol levels in cells are balanced by de novo biosynthesis within the cells, as well as uptake from circulating cholesterol, in the form of lipoproteins, in the bloodstream. Most cells are unable to make enough cholesterol and need top-up cholesterol from the liver, which produces about 75% of all the cholesterol in the body, sending the surplus in the bloodstream to be taken up by cells as needed.
Cells in the liver and intestines synthesize about 80% of the total cholesterol in the body, with the rest taking place in all cells but with higher levels in the brain, adrenal glands, and reproductive organs.
The brain has the highest cholesterol content of any organ in the body, in fact about 20% of all the cholesterol in the body is situated in the brain. As the brain is protected from most substances carried in the bloodstream, including cholesterol, by an intricate filtering system called the blood-brain barrier, the brain must be self-sufficient in terms of cholesterol synthesis. The blood-brain barrier is highly selective, as it only allows the passage of certain small molecules by means of passive diffusion, such as nutrients, ions, and macromolecules, for example glucose and amino acids, from the blood to the brain. Cholesterol carrying lipoproteins are unable to cross the blood-brain barrier.
The cholesterol content in the brain is strictly regulated at a relatively constant level. When this balance is interrupted, it may contribute to neurodegenerative diseases, such as Alzheimer’s disease or Parkinson’s disease.
Role of cholesterol in the body:
Cholesterol forms an integral part of all cell membranes, including that of the skin, where its fatty substance contributes to the “waterproofing” that covers the whole body. Cholesterol is used to make all the steroid hormones, which includes oestrogen, progesterone, testosterone, cortisol and aldosterone. Vitamin D is formed in human skin from cholesterol in the presence of sunlight (UVB rays).
Not only is the liver responsible for making new cholesterol daily, but it is also responsible for breaking down and ridding the body of excess cholesterol, which it releases in bile, as bile salts. Bile salts are vital for your body, as it emulsifies the fats in our food in the intestine, which aids digestion. The body needs about 2 grams of cholesterol per day, with most of this being synthesized in the liver, while the diet supplies the balance.
Cholesterol’s relationship with its transporter, lipoprotein:
The main transport channel in the body is the blood circulatory system and many different molecules, such as glucose (sugar) and electrolytes, are transported without any difficulty, as they are water soluble.
Cholesterol is a fatty substance and not water soluble, which makes this essential component of cells unable to be transported on its own in the watery bloodstream. This vehicle is called a lipoprotein and as the name suggests, it is part lipid (fat) and part protein. This transporter type of vehicle is engineered in such a way that the water-soluble protein is on the outside and the lipid is on the inside, which enable it to move effortlessly though water, the bloodstream in this case. In this way cholesterol gets transported in the body.
The interior structure of lipoproteins consists of a lipid core, which contains waxy fats in the form of triglycerides and cholesterol that circulate in the blood. Both lipids are crucial to our survival. Triglycerides are the most common form of fat in the bloodstream and high levels of triglycerides have been linked to a heightened risk of heart disease.
Lipoproteins have a specific single apolipoprotein, either ApoA or ApoB, embedded in the wall of the lipoprotein, with different lipoproteins containing different apolipoproteins.
The type of apolipoprotein present in the lipoprotein determines its structure and function:
- ApoA is the major apolipoprotein component of HDL (high-density lipoprotein particle) and high levels in the bloodstream usually indicate protective levels and lower risk in terms of atherosclerotic vascular disease. HDL is deemed to transport excess cholesterol back to the liver.
- ApoB is the major apolipoprotein component of low-density lipoproteins. ApoB containing lipoproteins can easily become trapped in arterial walls to form arterial plaque over time and are associated with a high risk for atherosclerotic vascular disease.
Apolipoprotein B is a structural protein, constituting a major component of the various types of low-density lipoproteins, namely very-low-density lipoprotein (VLDL, intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and Lp(a). As each of these lipoproteins carries one ApoB molecule, testing the ApoB level in the bloodstream is excellent marker for the risk associated with cardiovascular disease, as the total ApoB level corresponds with the total number of VLDL, IDL, and LDL particles.
As lipoproteins circulate in the bloodstream, triglycerides are rapidly removed from the bloodstream to be used as metabolic fuel in cells or stored in fat tissue in the body, to act as reserves for future energy needs. As triglycerides are progressively removed the lipoproteins become smaller and denser in the form of low-density lipoproteins, which results in lipoproteins very rich in cholesterol and depleted of triglycerides.
Cholesterol levels in the bloodstream are commonly (and mistakenly) referred to as LDL and HDL, while they should be correctly named, and measured in the bloodstream, as LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C).
The generally referred to “good HDL cholesterol”” and “bad LDL cholesterol” are also a misnomer, as after all cholesterol is cholesterol. The cholesterol is the same in both lipoproteins, but the lipoprotein transport vehicles are quite different, being of a high-density or low-density nature.
A buildup of too much low-density LDL-C in the bloodstream can narrow the arteries through plaque buildup and even block them. LDL-C plaque can rupture, resulting in a blood clot forming which can block the artery, resulting in a heart attack or stroke. A buildup of LDL-C can also provoke inflammation in the arteries, contributing to the formation of artery-blocking clots.
HDL-C in the bloodstream is deemed to carry unused or excess cholesterol from the body’s tissues back to the liver, for the cholesterol to be broken down into bile acids and utilized during digestion to break down fats and eventually excreted. Bile salts solubilize fats and aid in intestinal absorption.
For optimum protection against cardiovascular disease, there needs to be healthy levels of LDL-C, HDL-C, and triglycerides. ApoB levels are a very good marker to evaluate the risk for cardiovascular disease. It is advisable to have these important markers for atherosclerotic vascular disease, namely ApoB and ApoA included in your annual blood tests.
High ApoB levels would require dietary changes to reduce this important marker.
- Reducing the intake of carbohydrates would lower triglycerides, resulting in lower ApoB levels. Carbohydrates in the diet should be chosen wisely, cutting back on easily digestible carbohydrates such as white bread and other refined foods, as well as sugar-laden foods and beverages.
- The intake of saturated fats would need to be dramatically reduced, as too much saturated fat in the diet results in the liver downregulating its LDL receptors, as it is getting more than ample cholesterol from the diet, resulting in less LDL being pulled from blood circulation and LDL levels in the bloodstream that skyrocket. Cutting down on saturated fats means the liver will want more cholesterol coming in from the bloodstream and will upregulate LDL receptors to pull more LDL out of circulation.
- A low-carb and low-saturated fat diet will indeed lower ApoB levels, reducing the risk of atherosclerotic vascular disease.
Conclusion:
Cholesterol has a bad reputation as a health villain that’s commonly associated with heart attack, stroke, and other cardiovascular diseases. This bad reputation is truly unwarranted, as the health dangers do not lie with the substance itself, but with the way it is transported in the bloodstream. In fact, our bodies need cholesterol as an essential component in every cell.
References:
How low should LDL cholesterol go? Published 1 June 2024. Harvard Health Publishing. Harvard Medical School. (www.health.harvard.edu)
Taming high triglycerides. Published 1 May 2024. Harvard Health Publishing. Harvard Medical School. (www.health.harvard.edu)
A closer look at high cholesterol. Published 1 March 2023. Harvard Health Publishing. Harvard Medical School. (www.health.harvard.edu)
Apolipoprotein B. Published online and updated 8 July 2021. Medscape. (www.emedicine.medscape.com)
Cholesterol. Published online. Wikipedia. (www.wikipedia.org)
Cholesterol metabolism in the brain and its association with Parkinson’s disease. Published October 2019 in the journal Experimental Neurobiology. National Centre for Biotechnology Information. US National Library for Medicine. National Institutes of Health. USA. (www.ncbi.nlm.nih.gov)
Understanding cholesterol in the brain. Published 22 July 2022. Better Aging. (www.betteraging.com)
Intracellular cholesterol synthesis and transport. Published 21 March 2022 in the journal Frontiers in Cell and Developmental Biology. National Centre for Biotechnology Information. US National Library for Medicine. National Institutes of Health. USA. (www.ncbi.nlm.nih.gov)
Brain cholesterol homeostasis and its association with neurodegenerative diseases. Published December 2023 in Neurochemistry International. Volume 171. Science Direct. (www.sciencedirect.com)
Intro to lipids & lipoprotein: Why there is no “bad” or “good” cholesterol. YouTube video by Dr Peter Attia. Canadian author, physician, and researcher. (www.peterattiamd.com)
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