Beta Sitosterol — Structure, Food Sources, Benefits, and Supplements

Classification & Structure

Sitosterol (β-sitosterol or beta-sitosterol) is a type of plant sterol with a structure similar to cholesterol, like campesterol, stigmasterol, and other sterols. Sitosterol is the most abundant dietary sterol, but unlike cholesterol, it is not synthesized in the human body. It doesn’t dissolve in water and converts to oxidized products when heated (1, 2).

The molecular formula of sitosterol is C29H50O. Sitosterol is a stigmast-5-ene with a β-hydroxy group at 3rd position (3). 

The structural difference between cholesterol and sitosterol is in the presence of an ethyl group at position 24 of the steroid skeleton (4).

Absorption & Interactions With Cholesterol Metabolism

Animal studies suggest the absorption of beta-sitosterol is higher in females than males. Beta-sitosterol is metabolized into different compounds in the liver and other organs and can be stored in the adrenal glands, brain, skin, ovaries, and testicles.

Beta-sitosterol absorption is 5 times lower than cholesterol absorption. The physicochemical competition between cholesterol and beta-sitosterol leads to the interrupted recirculation of bile acids and reduced intestinal absorption of cholesterol.

 About 80% of absorbed beta-sitosterol is excreted via feces and 20% - via skin.

Gut bacteria convert the unabsorbed beta-sitosterol into 24-ethyl-coprostanol, coprostanol, and 24-ethyl-coprostanone (2).

Side Effects & Contraindications

Beta-sitosterol supplements are generally well-tolerated but may cause mild gastrointestinal adverse effects, such as abdominal pain, indigestion, bloating, nausea, and constipation (11, 14).

Beta-sitosterol-containing supplements are contraindicated for people with previous allergic reactions to beta-sitosterol and those with sitosterolemia.

Drug Interactions

Ezetimibe (Zetia) is a medication used to treat elevated cholesterol and sitosterolemia. Ezetimibe inhibits sterol absorption, decreasing sterol levels in the blood (15).

No major pharmacokinetic interactions have been reported between statins and phytosterols.

Cholestyramine intake from phytosterols should be taken at 2-4 hours intervals to avoid binding in the gut (16).

Reduced Cholesterol & Cardiovascular Health

Sterols help alleviate high-fat diet-induced blood lipid abnormalities (decrease triglyceride, total, and LDL cholesterol levels in the blood) and fat accumulation in the liver (fatty liver or MASLD) and decrease the risk of heart disease. Beta-sitosterol’s mentioned effects are due to decreased fat absorption and increased fecal excretion of bile acids, as well as its antioxidant and anti-inflammatory properties (18).

The European ESC/EAS guidelines propose using plant sterols, such as beta-sitosterol, to lower blood cholesterol concentrations. Nevertheless, recently published genetic research suggests that they may increase the risk of atherosclerosis and contribute to the severity of atherosclerotic lesions. Accordingly, the German Society of Cardiology (DGK) states the need for randomized controlled trials before recommending the use of plant sterols for their hypolipidemic effects (19, 20).

An early 2000s study on rats found that vegetable oils rich in plant sterols make red blood cells more rigid and reduce their flexibility, shortening their lifespan (20).

Benign Prostatic Hyperplasia

Benign prostatic hyperplasia (BPH) is a non-cancerous enlargement of the prostate gland, which may cause frequent urination, weak stream, and inability or trouble emptying the bladder.

Beta-sitosterol may be effectively used to treat benign prostatic hyperplasia, improving lower urinary tract symptoms (LUTS) and urinary flow rates and scores in men with mild to moderate BPH (21, 22, 23).

Other Health Effects

Beta-sitosterol is commonly used to lower blood cholesterol levels and improve the symptoms of benign prostatic hyperplasia. Research has demonstrated other effects of beta-sitosterol (2, 7, 8, 17, 24, 25):

• Antioxidant, anti-inflammatory, and immune-modulating properties.
• Anti-microbial effects.
• Anti-cancer properties: Beta-sitosterol is considered to have anticancer properties against prostate, breast, colon, stomach, lung, cervix, and larynx cancers, fibrosarcoma, and leukemia. 
• Anti-diabetic effects: Beta-sitosterol intake may increase fasting plasma insulin, decrease fasting blood glucose levels, and improve oral glucose tolerance test results.
• Diabetic ulcer wound healing (animal studies)
• Angiogenic effects: Beta-sitosterol promotes blood vessel formation and may play a role in wound healing.
• Anti-arthritic activity: Beta-sitosterol may decrease the activation of inflammatory pathways included in arthritis and inhibit synovial angiogenesis in rheumatoid arthritis, alleviating joint swelling and bone destruction in animal models.
• Neuroprotective properties: Beta-sitosterol may enhance spatial learning in Alzheimer’s patients.
• Reduced anxiety and antidepressant-like effects (animal studies).

Sitosterolemia

Sitosterolemia or phytosterolemia is a rare autosomal recessive disorder of plant sterol, especially sitosterol metabolism. This genetic disorder is characterized by excess accumulation of plant sterols in the blood and tissues due to their hyperabsorption and decreased excretion from the GI tract. Sitosterolemia leads to premature cardiovascular disease, atherosclerosis, and xanthomas and may cause enlargement of the liver and spleen, abdominal pain, and arthralgia.

Sitosterolemia is treated with medications and dietary modifications. A major reduction in sterol intake may significantly reduce serum sterol and cholesterol levels in patients with sitosterolemia (15, 26, 27).