What is cholesterol?
Cholesterol is not technically a fat; rather, it is classified as a “sterol,” which is a combination of a steroid and alcohol. Cholesterol is essential to all animal life. It plays a crucial structural role in the cell membrane, which controls how a cell moves, interacts with other cells, and what can enter and exit the cell.
Functions of cholesterol
Cholesterol is a sterol molecule synthesised by all animal cells. It is an essential structural component comprising about thirty percent of animal cell membranes, where its function is to maintain membrane structural integrity and fluidity. In addition, cholesterol is a precursor for the synthesis of steroid hormones, bile acids and myelin.
Cell membranes: All animal cells are surrounded by a lipid bi-layer that comprises phospholipids (a phosphate group attached to a saturated or unsaturated fatty acid), membrane proteins and cholesterol. Through its interaction with the phospholipid fatty-acid chains, cholesterol alters membrane fluidity and maintains membrane integrity. Within the cell membrane, cholesterol also functions in intracellular transport and cell signalling.
Steroid hormones: Within cells, cholesterol is a precursor molecule for the
synthesis of vitamin D and all steroid hormones, including the adrenal gland
hormones cortisol and aldosterone, and the sex hormones progesterone,
oestrogen and testosterone.
Bile acids: Bile acids are derivatives of cholesterol synthesised by hepatocytes
Myelin: Babies and children especially need cholesterol to ensure proper growth
and development of their brains. Twenty percent of myelin (the material that
forms a sheath around neurons) is cholesterol, and synapse formation in the brain
is almost entirely dependent upon its availability (neurons communicate with each
other across synapses).
Intestinal permeability: Cholesterol helps maintain the integrity of the intestinal
lining, which keeps foreign substances out of our body and protects against
autoimmunity and allergy.
Antioxidant: HDL cholesterol is an antioxidant that helps prevent oxidative
damage which is associated with everything from heart disease to Alzheimer’s to
ageing. Coenzyme Q10, a critical antioxidant nutrient, is synthesised by the same
pathway as cholesterol.
Sources of cholesterol
Since all animal cells manufacture cholesterol, all animal-based foods contain cholesterol in varying amounts. The body contains between 1,100 and 1,700mg of cholesterol at any one time. Twenty-five percent of that comes from diet and the rest is made in the body, mostly in the liver. The body cannot absorb much of the cholesterol found in food, and most of the cholesterol in the gut is of endogenous origin (i.e. synthesised by the liver). The body tightly regulates the amount of cholesterol in the blood by controlling internal production; when cholesterol intake in the diet goes down, the body makes more. When cholesterol intake in the diet goes up, the body makes less. Therefore, dietary cholesterol intake does not correlate well with blood plasma cholesterol levels. On the other hand, there is a correlation between saturated fat intake and cholesterol levels.
Major dietary sources of cholesterol include cheese, egg yolks, beef, pork, poultry, fish and shrimp. Human breast milk also contains significant quantities of cholesterol.
Synthesis and transport of cholesterol
Synthesis of cholesterol within the body starts with the ‘mevalonate pathway’ where two molecules of acetyl CoA condense to form acetoacetyl-CoA. This is followed by a second condensation reaction that is catalysed by the enzyme HMG CoA reductase – this is the rate-limiting step in the synthesis of cholesterol and the primary mechanism of statins is to inhibit this enzyme and thus reduce cholesterol synthesis (coenzyme Q10 synthesis is also inhibited, an unwanted side effect of statins). The HMG CoA reductase enzyme is not the final step in the pathway; over thirty enzyme steps are involved in the synthesis of cholesterol. A decrease in cholesterol synthesis results in intracellular cholesterol becoming depleted. To compensate for this the number of LDL receptors on the cell surface increases – to allow more cholesterol to enter the cell.
Cholesterol is transported in the plasma within lipoproteins, particles with watersoluble proteins on the outer surface and lipid soluble triglycerides and cholesterol on the inner surface. There are several types of lipoproteins in the blood. In order of increasing density, they are: chylomicrons, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL).
Chylomicrons, which are the least dense cholesterol transport molecules, are
assembled in the intestinal cells and carry fats from the intestine to muscle and
other tissues in need of fatty acids for energy or fat production. The entire process
of chylomicron metabolism is relatively rapid and the presence of chylomicrons in
the serum after an overnight fast is considered an indicator of defective lipoprotein
Very Low Density Lipoproteins (VLDL) are produced by the liver from
triglycerides and cholesterol. VLDL vary in triglyceride content which they exchange
with both LDL and HDL for a cholesterol molecule. Triglyceride enriched LDL
molecules are then processed through another reaction that removes the triglycerides
provided by VLDL. The result is small LDL particles, which contribute the most to
atherosclerotic disease (i.e. LDL particles exist as ‘large’ or ‘small’ LDL particles).
Low Density Lipoproteins (LDL) are the major blood cholesterol carriers;
they carry cholesterol to cells that need it. Each one contains approximately 1,500
molecules of cholesterol. As explained above, LDL molecules are derived mostly
from VLDL metabolism and can be described as ‘small’ or ‘large’; it is the ‘small’ LDL
that are the most damaging.
High Density Lipoprotein (HDL) particles transport cholesterol back to the
liver, either for excretion or for other tissues that synthesise hormones, in a process
known as ‘reverse cholesterol transport’. Large numbers of HDL particles correlate
with better health outcomes. HDL can remove cholesterol from the macrophages
of the arterial wall through a number of mechanisms including an active transport
mechanism. Therefore increased concentrations of HDL correlate with lower rates of
atheroma progression and thus HDL is sometimes referred to as “good cholesterol”.
Metabolism, recycling and excretion
Cholesterol is oxidised by the liver into a variety of bile acids. These, in turn, are
conjugated with glycine, taurine, glucuronic acid or sulphate. A mixture of conjugated
and non-conjugated bile acids, along with cholesterol itself, is excreted from the
liver into the bile. Every day up to one gram of cholesterol enters the colon.
Whilst approximately ninety-five percent of the bile acids are reabsorbed from
the intestines, between fifteen and seventy-five percent of cholesterol excreted in
the bile is eliminated in the faeces (i.e. predominantly non-conjugated cholesterol).
Cholesterol from diet and shedding of intestinal cells is also eliminated in the faeces.
Causes of high cholesterol
Smoking: A chemical found in cigarettes called acrolein stops HDL transporting cholesterol from fatty deposits to the liver, leading to narrowing of the arteries
(atherosclerosis). Quitting smoking has been shown to rapidly improve HDL levels
Diabetes: High cholesterol (and hypertension) are established comorbidities of diabetes
Chronic infections: Chronic infections such as Helicobacter pylori
Thyroid: Poor thyroid function
Environmental toxins: Environmental toxins, particularly mercury exposure
Genetics: An inherited genetic condition, called familial hypercholesterolaemia, can cause high cholesterol
Contrary to popular belief, a high fat diet may not be the cause of high cholesterol
unless the genetic condition familial hypercholesterolaemia is present. Research has
been put forward that links high carbohydrate intake and high insulin levels with
elevated LDL levels, reduced HDL levels and elevated triglycerides.
Dietary fibre can help maintain healthy cholesterol and triglyceride levels through a number of mechanisms:
- it encourages the growth of friendly gut bacteria that can have beneficial effects on cholesterol levels
- it provides bulk for elimination and so excess cholesterol can be eliminated via the bowel. Constipation will result in lower amounts being excreted and more being reabsorbed into circulation.
- it helps with glycaemic control (i.e. blood sugar regulation) – high blood sugar can increase VLDL/triglyceride production by the liver.
Choose foods such as oats, legumes, apples, carrots and broccoli high in soluble fibre.
Oats contain a soluble fibre called beta-glucan 1,3 1,4 which reduces cholesterol.
Carbohydrates stimulate the production of triglycerides, which are then transported in VLDL particles. So reducing carbohydrate consumption is an important part of cholesterol management. Choose low glycaemic carbohydrates e.g. sweet potatoes and oats and eat small portions only.
Plants do not contain cholesterol, but they contain similar substances called phytosterols, which can interfere with intestinal absorption of cholesterol. Some ‘functional foods’ have been developed containing these substances but they may have other undesirable features, so it is best to obtain plant sterols from natural sources such as vegetables, olive oil, nuts (almonds), seeds and legumes.
Monounsaturated fats (found in nuts, seeds and avocado) and omega-3 fats (found in oily fish) have been shown to reduce levels of LDL cholesterol and increase HDL. In addition, omega-3 fatty acids decrease triglyceride concentration by reducing VLDL production. Avoid foods containing trans fats – these are found particularly in processed foods. Foods high in saturated fatty acids may be eaten in moderation (e.g. red meat, butter).
It is oxidised cholesterol that is the most damaging, so a diet high in plant food antioxidants to protect against oxidative stress and cholesterol becoming oxidised is important.
Garlic has been shown to have cholesterol lowering effects and its antioxidant properties may protect cholesterol from oxidation. One study found this effect was enhanced when garlic was taken in conjunction with fresh lemon juice.
Green tea contains compounds, which have been found to lower cholesterol. It also has antioxidant properties.
Red rice yeast
Red rice yeast (found in supplements) contains naturally occurring statin-like metabolites. Red rice yeast has been used for centuries as a natural food preservative
Fermented foods and/or consider a probiotic supplement - for example, Lactobacillus plantarum has been shown to have beneficial effects on cholesterol levels.
Chronic stress increases demand for steroid hormones and the synthesis of cholesterol by the liver increases to meet demand resulting in raised cholesterol levels in the blood. So it is important to address stress reduction and management as well.