Table of Contents
Introduction
Plant sterols are one of the commonest supplements used to lower LDL cholesterol (LDL-C). You will commonly find them added to margarines, yoghurts and spread, being sold under brand names like “Benecol”. They are marketed as an easy way to lower cholesterol through diet.
They are big business and promoted by large food companies in a market estimated to be around 300million per year.1 In this article we will explore how effective phytosterols are at lowering cholesterol, and more importantly, if they are safe to take.
What Are Plant Sterols (Phytosterols)?
Phytosterols are plant molecules that have a similar structure to cholesterol. They are poorly absorbed by humans, and they are thought to lower LDL-C by blocking absorption of cholesterol in the intestines.
There are 2 types of phytosterols – Stanols and sterols, each has a slightly different molecular structure.
- Stanols – Sitostanol and campestanol
- Sterols – Campesterol, stigmasterol, B-sitosterol
How Are Plant Sterols Taken?
Plant sterols are in everyone’s diet. The standard western diet is typically low in plant sterols. It is estimated that the western diet contains around 400mg on average.2 They have no biological function in the human body, so we do not make them ourselves.
The only way we can get them into our body is by eating them. There are now a large number of products on the market enriched with plant sterols; margarines, yoghurt, milk, cereal. Many people buy these as a simple and natural way to lower their cholesterol.
Cholesterol Absorption
Cholesterol is an essential substance in the body. It is an essential component of cell membranes and it is a precursor for certain hormones. Most cholesterol used by the body, is made by the body. However, a small amount of cholesterol is absorbed from the diet.
In the gut, cholesterol is transported through the gut cells and is incorporated into chylomicrons to transport around the body. In the intestine, phytosterols interfere with the absorption of cholesterol.3 A decrease in cholesterol absorption leads to an increase in the LDL-receptors in the liver that pull LDL-particles out of circulation. This results in a fall in LDL – C.
Do all people respond to phytosterols equally?
People’s ability to absorb cholesterol from their diet is variable. Some people are poor cholesterol absorbers, and they are unlikely to respond to phytosterol supplementation.
Do plant sterols really lower cholesterol?
High intake of phytosterols lowers LDL – C. There is a dose dependent relationship between phytosterol intake and LDL-cholesterol reduction. One meta-analysis of 124 human studies showed that around 1g per day led to an LDL-C reduction of 5% whereas 3.3g/day resulted in 12.4% reduction.4
But, just because something lowers LDL-C doesn’t mean it lowers the risk of heart disease and stroke. What if that substance had other untoward effects on the body?
What do the guidelines say?
The international heart disease guidelines are split on their recommendations. The ESC guidelines recommend 2g per day in patients with high cholesterol at low to intermediate risk, and also that they can be used in patients not reaching targets on statins.4 However, this is the opposite of both the UK and German guidelines who do not recommend phytosterol use. 2 But why is there such dichotomy in the recommendations?
Are plant sterols safe?
If you eat high doses of plant sterols in your diet, then some of them will be absorbed into the body. Now remember, plant sterols have no biological purpose in the body and they are not supposed to enter it. Besides from reducing cholesterol absorption, do phytosterols have any other effects in the body when they are absorbed?
Potential adverse effects
• Alterations in cell membranes – Cholesterol makes up an important part of cell membranes in every human cell. Phytosterols have been shown to be incorporated into these membranes and alter the structure of the cell. In animals this has been shown to make red blood cells more fragile.5 This has not yet been shown in humans.
• Testosterone metabolism – Animal studies have suggested that phytosterols can inhibit 5 alpha reductase, reducing the conversion of testosterone to dihydrotestosterone.6 Side note – this is how drugs like finasteride stop hair loss in men. A study in humans over 1 year showed no change in serum total testosterone concentrations.
• Sitosterolemia – is a rare genetic disease where individuals have dramatically higher rates of absorption of phytosterols in the intestine. These individuals have very high plasma levels of phytosterols. They often develop early atherosclerosis and lipid deposit on their tendons.
• Vitamin absorption – Consumption phytosterols can possibly affect the absorption of fat soluble vitamins like vitamin E and A.
Do phytosterols increase the risk of CVD?
When people take phytosterols they are not just looking for a lower LDL-C they are actually trying to reduce their risk of heart disease and stroke. We know phytosterols lower LDL, but does that translate into less heart disease?
There have been no large trials examining their effect on rates of heart attacks and strokes in humans. A number of other experiments have been done2:
• Cells – In cell experiments (in vitro studies) they were shown to be toxic to endothelial cells and macrophages. Both cell types are involved in atherosclerotic plaque formation.
• Animals – They have been shown to lower LDL-C in animals. However, in a direct comparison of phytosterols with ezetimibe (a LDL lowering drug) phytosterols were seen to have twice the rate of atherosclerosis than ezetimibe.
• Humans – It is concerning that patients with sitosterolemia often get severe coronary artery disease. This suggests that the presence of phytosterols in the body can potentially promote coronary artery disease.
A recent genome wide association study potentially confirms this.7 Concentrations of phytosterols in the blood are under tight genetic control. Certain mutations In a gene called ABCG5/G8 can result in a condition with very high phytosterols – mainly sitosterolemia.
This GWAS study looked at common variations in the genes that control phytosterol levels in the body. They looked at data from 9758 people, and found that higher levels of sitosterol in the blood increased the risk of coronary artery disease, independent of its effects on plasma cholesterol.
Should we take phytosterols to prevent heart disease?
They do lower LDL-C however, there is mounting evidence that they have the potential to actually increase atherosclerosis. Until definitive trials are done to look at how they impact the rate of heart attack and stroke, I think they should be avoided.
Conclusion
Phytosterols come from plants and are molecules with a similar structure to cholesterol. They lower LDL-C by around 10-15% by inhibiting cholesterol absorption in the diet. They can also be absorbed by the body and potentially affect important processes.
There is no evidence that the reduce the risk of heart disease or stroke. There are potential reasons that they could increase the risk of heart attack and stroke. Given their potential adverse effects I think we should not utilise them to lower cholesterol until we have clinical trials proving their safety.
References:
1 – https://www.grandviewresearch.com/industry-analysis/phytosterols-market
2 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410723/
3 – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317074/
4 – https://doi.org/10.1093/eurheartj/ehz455
5 – https://pubmed.ncbi.nlm.nih.gov/10801914/
6 – https://pubmed.ncbi.nlm.nih.gov/14699915/
7- https://www.nature.com/articles/s41467-021-27706-6D
