High cholesterol is a significant risk factor for cardiovascular disease. What is the role of cholesterol and how can levels be attenuated with herbal solutions?
What is cholesterol?
Cholesterol is a type of lipid that is present in every cell of the body, and production is highest in the liver (1). As a molecule it is essential for a variety of important body functions:
Cell walls
Cholesterol makes up a high proportion of all animal cell walls. In red blood cells it can make up as much as 40% of their plasma lipid membrane. Structurally, cholesterol in lipid membranes impacts their elasticity, density and strength. Functionally, cholesterol in the membrane is involved in the formation of signalling complexes, such as cell membrane receptors and trafficking of proteins across the membrane (2). Through influencing the structure of the membrane, cholesterol directly impacts molecular transport of sodium and other cations (positively charged ions) across the membrane, an important factor for the production of ATP, the ‘energy currency’ of cells (3). Particularly in skeletal muscle cells, in particular, cholesterol plays a vital role in the normal contractility-excitation function as well as for insulin sensitivity (4).
Nerve cells
Some of the neurons in the body are myelinated, meaning they have a special sheath around their axon, functioning as a kind of insulator. This increases the speed at which impulses can be sent through the axon. Myelination is essential for the proper function of the nervous system and cholesterol is an essential constituent of these sheaths, and makes up 40% of their lipid composition (as compared to normal cells, where it makes up 25%) (5). In experiments on mice it has been shown that cholesterol availability “is a rate-limiting factor for brain maturation” (6).
Cholesterol as a precursor
Cholesterol is a precursor of steroid hormones such as the sex hormones: oestrogen, progesterone and testosterone, as well as the adrenal gland hormones, cortisol and aldosterone. It is also a precursor of 7-dehydrocholesterol, which is needed to synthesise vitamin D3. This synthesis happens in the skin and requires the ultraviolet rays of direct sunlight.
Bile acids
Bile acids are produced in the liver, turned into bile salts, stored in the gallbladder and then excreted into the small intestine. Here they act as a kind of detergent, to emulsify dietary fats and oils so that they can be further digested. They make up most of the bile excreted by the liver and are synthesised by liver cells via an enzyme mediated oxidation of cholesterol in a multi-step process. Approximately 200 to 600 mg of bile salts are synthesised daily to replace bile acids lost in the faeces. Enzymes are down-regulated by high concentration of bile acids and up-regulated by cholesterol.
While 95% of bile acids present in the small intestine are reabsorbed into circulation, 5% travel on into the colon (7). The bile acids that return to the liver, inhibit further production of bile acids and increase their excretion, forming a negative feedback loop. Bile acids additionally play various roles as signalling molecules within the intestine and liver, impacting the glucose, triglyceride and cholesterol homeostasis within the body(8).
Despite how essential cholesterol is in the above processes, too much cholesterol in the blood can lead to severe health problems, including heart disease, stroke, and other cardiovascular issues. High cholesterol, also known as hypercholesterolemia, is a condition that is often referred to as a “silent” health problem because it typically doesn’t present obvious symptoms until significant damage has been done to the arteries and cardiovascular system.
Understanding high cholesterol
High cholesterol simply refers to a high concentration of cholesterol within the blood. This is determined with blood samples, and the measurement of
- Total cholesterol: The overall amount of cholesterol in your blood
- High density lipoproteins (HDLs): Often referred to as “good cholesterol”
- Non-HDLs: The difference between total cholesterol and HDL. Non-HDLs includes low density lipoprotein (LDL), which is often referred to as “bad cholesterol”; however, non-HDL also includes other sources of cholesterol in the blood. Non-HDL cholesterol has been found to be a good marker for the likelihood of future cardiovascular disease development, in particular damage to arteries, buildup of plaques within the arterial walls, which eventually lead to further complications.
- Triglycerides are often measured alongside cholesterol. Elevated triglyceride levels are also associated with an increased risk of heart disease.
Cholesterol transport
Lipids such as fatty acids, triglycerides, phospholipids and cholesterol are all hydrophobic (repel water molecules), which means they cannot just flow in the bloodstream, but instead are transported in transport molecules — lipoproteins. HDLs and LDLs are not cholesterol per se, but transport molecules that are essential for the passage of cholesterol in the blood and therefore its detection via blood tests; hence blood measure associations with either LDL or HDL. Lipoproteins are synthesised by the liver and by enterocytes and have a variety of different functions.
HDL is most well known for its function of returning cholesterol from circulation to the liver, from which it can be either excreted, or transformed into other molecules. This is why HDL is considered “good cholesterol”, it aids in the removal of cholesterol from the body, maintaining homeostasis. LDLs are the primary plasma carriers of cholesterol for delivery to all tissues, and usually carry a far greater amount of lipids.
If a cell requires additional cholesterol, it synthesises the necessary LDL receptors and if it has enough the cell produces a protein that takes the receptors down so that no more LDL is taken up by the cell. While HDL is seen as the main way to transport cholesterol back to the liver, the liver also carries LDL receptors and is able to absorb the cholesterol from LDL molecules.
Approximately 70% of circulating LDL is cleared via hepatocyte LDL receptor mediated endocytosis with the remainder taken up by extrahepatic tissues. Thus expression of LDL receptors by liver cells, represents a key factor in the body’s ability to regulate circulating LDL levels(9). Although there are other forms of lipoprotein carriers involved in the transport of cholesterol, they are usually ignored.
What is the pathophysiology of high cholesterol?
Cholesterol was first thought to be intrinsic to heart disease in 1953, when Ancel Key introduced his lipid–heart hypothesis which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease.
While this hypothesis is still widely embraced by national and international dietary guidelines, and consequently given advice accordingly, numerous observational, epidemiological, interventional, and autopsy studies have failed to solidly validate this hypothesis in the long run (10), it seems that while there is a connection between diet and cholesterol levels, it appears to be not as straightforward as initially thought. However, while there are a variety of reasons that can lead to raised cholesterol, how does high cholesterol itself cause problems in the body?
When there is too much cholesterol in the bloodstream, and in particular when there are too many LDLs present, they can infiltrate the walls of blood vessels, especially the coronary arteries. Over time, this leads to the formation of plaques made up of cholesterol, fat, and other substances. These plaques can build up gradually, leading to the thickening and hardening of the artery walls. As the plaques grow, they narrow the arteries, reducing the flow of oxygen-rich blood to vital organs, including the heart and brain. This can lead to various complications, including coronary artery disease, stroke, or peripheral artery disease.
Understanding the root of high cholesterol
High cholesterol can arise from both genetic and environmental factors. There are various aspects that can raise LDL levels and lower HDL levels, and it is likely that multiple causes will be relevant to an individual with hypercholesterolaemia that is not due to a genetic variability.
- Genetic factors
- Insulin resistance
- Dietary Habits
- Lack of physical activity
- Obesity
- Smoking
- Alcohol consumption
A long standing recommendation, even today, is that one should reduce dietary cholesterol. However, the literature shows conflicting results, in some individuals dietary cholesterol is associated with an increase in LDL and in others it isn’t, pointing to other potential factors, impacting the body’s ability to regulate cholesterol homeostasis, but not cholesterol consumption per se (10).
Increased cholesterol is also associated with certain conditions:
- Non-alcoholic fatty liver disease
- Hypothyroidism
- Kidney disease
Several medications are also known to elevate cholesterol levels:
- Beta blockers
- Corticosteroids
- Diuretics — thiazide and loop diuretics
- Oral contraceptives
- anticonvulsants — carbamazepine and phenytoin
As well as the genetic, dietary, lifestyle, pathological and pharmacological risk factors, with age also comes increased blood lipid levels and incidence of high cholesterol. Whether this age-related increase is associated with cardiovascular disease is yet to be determined.
Signs and symptoms of high cholesterol
One common sign with high cholesterol are xanthomas, yellowish fatty deposits that can appear as bumps on the skin, often around the eyes, elbows, knees, or tendons. These deposits are associated with high cholesterol and are sometimes an early warning sign of lipid imbalance. Otherwise, there are typically no symptoms for high cholesterol, making it difficult to detect without a blood test.
However, if due to endothelial dysfunction, inflammation and oxidation plaques develop, the incidence of cardiovascular conditions, which will bring on their own symptom picture, depending on the area affected, and may be the first indicator of elevated cholesterol.
Herbal solutions
High cholesterol is a complex subject, and we are still lacking the full understanding of its implications. There is a correlation between high levels of cholesterol and a greater incidence of cardiovascular disease, however, this correlation is not always there, which points to the fact that high cholesterol is not always the underlying cause, but sometimes more of a calamity, because of another underlying cause. Unless a genetic condition is the underlying cause, which means the body is not able to self regulate the lipid household. This has to be considered when one wants to find the correct herbal treatment, to treat high cholesterol.
Endothelial health is crucial, as is protection against oxidation and inflammation. Flavonoids, such as rutin, quercetin and kaempferol, and herbs containing such compounds, seem to be of particular value when it comes to improving and protecting endothelial function (11). Flavonoids are well known for their antioxidant properties. Antioxidants are able to neutralise free radicals, without becoming a free radical themselves, thus breaking the oxidative chain. As discussed, oxidation is a major pathway through which damage is caused to LDL molecules, and eventually the endothelium, antioxidant herbal remedies are therefore also indicated.
But a herbal practitioner may also choose to address the liver, which is the major organ for the production of lipoproteins, but also for elimination of cholesterol through the bile. The latter may indicate the use of bitters, which stimulate the flow of bile. And liver health is directly connected to its ability to excrete excess cholesterol, and thus liver trophorestorative herbs may be indicated. Certain herbs have been shown to lower cholesterol levels or triglyceride levels directly, other herbs might primarily be indicated to protect the cardiovascular system from the buildup of plaques. If other issues are implicated, they may have to be addressed separately.
Garlic (Allium sativum)
Garlic has long been used for its cardiovascular benefits, and has been shown to lower cholesterol concentrations.
Hawthorn (Crataegus spp.)
Most commonly known as a tonic for the heart, hawthorn is commonly used to strengthen the heart and improve circulation. Hawthorn is high in flavonoids, which were mentioned earlier, and research also suggests that it might help to enhance endothelial function. Although studies have been done with different species, including C. oxyacantha, and C. anamesa (12).
Turmeric (Curcuma longa)
Turmeric reduces inflammation, aids the excretion of bile and improves lipid profiles (13).
Artichoke (Cynara scolymus)
Perhaps one of the classic bitter herbs, artichoke leaf has a long history of use for liver conditions. A systematic review and meta-analysis concluded that it has lowering effects on total cholesterol, LDL and triglycerides (14). Additionally, it was observed to reduce insulin resistance (15). It is also anti-inflammatory, antioxidant, enhances bile production by increasing biliary acids and cholesterol elimination with bile, all of which are relevant with high cholesterol (16)
Fenugreek (Trigonella foenum-graecum)
Fenugreek has also been reported to ameliorate blood lipid profiles, triglyceride levels as well as glucose levels, and aid with insulin resistance. Therefore, fenugreek may be useful in treating hypercholesterolaemia, particularly if issues with glucose metabolism coexist.
Red rice yeast (Monascus purpureus)
Red rice yeast is a traditional remedy from traditional Chinese medicine. It contains monacolin K, which is chemically identical to lovastatin, a drug that is used to lower LDL cholesterol. A meta-analysis from 2014 concluded that it was effective at lowering LDL levels but had no effect on HDL levels (17).
These are but a few herbs that might be implicated, depending on the underlying causes.
Holistic solutions
Diet
While traditional advice ought to be revised, it seems advisable to reduce the amount of refined carbohydrates consumed (such as many cereals, jams, honey, juices, refined flour products and sweets) and instead the diet should be centred around a whole food diet, including natural sources of protein and fats, as well as whole grain carbohydrates. Processed foods often include trans-fats which are particularly toxic to the cardiovascular system.
Deep fried foods have often been cooked at temperatures that increase the likelihood of free radicals and they also tend to carry large amounts of calories, and increased calorie intake tends to disrupt the lipid balance in the body. Soluble fibre found in oats, linseeds, beans, lentils, and nuts can help reduce LDL cholesterol by binding to it in the digestive tract, as well as slow down the uptake of sugars, so fibre rich foods should be encouraged. Nuts and seeds are a great source of healthy fats, fibre and other valuable nutrients.
When it comes to the questions which types of fats to consume, once again, the more unrefined, the more unprocessed, the better. Olive oil is a healthy option for most occasions. Fish such as salmon, mackerel, or sardines are good sources of omega 3 oils. Almonds, walnuts, hazelnuts are good sources of plant based omega 3 oils. Brazil nuts have been shown to protect LDL from peroxidation, and improve endothelial function, blood pressure, and lipid metabolism(18). Although due to their high selenium content, consumption should be limited to 1 to 2 brazil nuts a day(19).
Current evidence suggests that saturated fatty acid intake should ideally be less than 10% of total daily energy for the general healthy population and further (e.g., to 5–6% of total daily energy) for patients with hypercholesterolemia (20). Dairy products tend to contain saturated fats, but they also contain many essential nutrients which are beneficial for cardiovascular health, which should be taken into consideration as well(20).
It is very easy to get too focused on counting calories, focusing on single macronutrients and extrapolating from that nutrient onto the whole food. Michael Pollan offers a beautifullystraightforward approach, “Eat food*. Not too much. Mostly plants”(21). Perhaps, also, to add diversity and colour to the diet, include an abundance of colourful plant pigments (such as in carrots, beetroots, red onions and many berries), for their rich source of antioxidants.
* by this he means real foods as opposed to processed food.
Regular exercise
Physical activity is vital for maintaining healthy cholesterol levels. Aerobic exercises, such as walking help lower LDL cholesterol and improve the LDL/HDL ratio (22).
Adequate sleep
Getting enough quality sleep is crucial for overall health. Insufficient sleep can contribute towards disruptions in glucose and cholesterol homeostasis and a higher risk of heart disease (23).
Relaxation
Animal models show that chronic stress has atherogenic (plaque developing) effects (24,25). Practicing relaxation techniques such as yoga, meditation, breathing practices, or mindfulness can reduce stress and subsequently may help protect the cardiovascular system.
Other lifestyle factors
Reducing or quitting smoking and alcohol intake is another valuable consideration, to avoid the damaging effects they pose to cardiovascular health and cholesterol homeostasis.
References
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- Pöhnl, M., Trollmann, M.F.W. & Böckmann, R.A. Nonuniversal impact of cholesterol on membranes mobility, curvature sensing and elasticity. Nat Commun 14, 8038 (2023). https://doi.org/10.1038/s41467-023-43892-x
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