How can sterols be used to treat high cholesterol?

Using Plant Sterols to Treat High Cholesterol

Plant sterols can reduce LDL cholesterol by 9-20% at doses of 2-3g per day and should be considered as an adjunctive therapy when LDL-cholesterol goals are not achieved with primary lipid-lowering medications. 1

Mechanism of Action

• Plant sterols and stanols work by inhibiting cholesterol absorption from the intestine, leading to reduced circulating levels of cholesterol 2
• Both sterol esters and stanol esters have comparable efficacy in lowering cholesterol, with stanols being virtually unabsorbable making them potentially more ideal hypocholesterolemic agents 2
• For commercial use, plant sterols are often esterified to increase solubility and sometimes saturated to form stanol esters, which can be incorporated into various food products 1

Recommended Dosage and Efficacy

• The optimal dose of plant sterols/stanols is 2-3g per day, which can reduce LDL cholesterol by 9-20% 1
• Intakes exceeding 3g/day do not provide additional cholesterol-lowering benefits 1, 3
• A meta-analysis of 124 studies confirmed that plant sterols and stanols at doses of 0.6-3.3 g/d gradually reduce LDL-cholesterol concentrations by 6-12% 3
• Both plant sterols and stanols show clear and comparable dose-response relationships up to approximately 3 g/d, with an average maximum effect of 12% 3

Clinical Applications and Guidelines

• According to the International Atherosclerosis Society, plant sterols (stanols) should be considered as adjunctive therapies if LDL-cholesterol goals are not achieved with diet, maximally tolerated statins, and ezetimibe 4
• The American Heart Association recommends the addition of plant stanol/sterols (2 g per day) as a reasonable approach to further lower LDL-C 4
• Plant sterols are particularly useful as part of a comprehensive approach to managing hypercholesterolemia, especially in patients with familial hypercholesterolemia 4
• The Academy of Nutrition and Dietetics recommends that individuals with dyslipidemia incorporate 2-3g of plant sterol and stanol esters per day as part of a cardioprotective diet 1

Treatment Algorithm for Using Plant Sterols

1. First-line therapy: Maximally tolerated high-potency statins with or without ezetimibe and/or bempedoic acid, combined with a fat-modified, heart-healthy diet 4
2. Second-line adjunctive therapy: If LDL-cholesterol goals are not achieved, add plant sterols (stanols) at 2-3g per day 4
3. Third-line therapy: PCSK9-targeted therapy should be added if LDL-cholesterol goals are still not achieved with diet, maximally tolerated statins, ezetimibe, bempedoic acid, and other adjunctive therapies including plant sterols 4

Forms and Administration

• Plant sterols can be incorporated into various food products such as margarine, yogurt, milk, and other foods 5
• Fatty acid esters of stanols are particularly helpful because they readily mix with dietary fats and their hypocholesterolemic efficacy is greater than in the free form 6
• Plant sterols should be taken with meals to maximize their cholesterol-lowering effect 1

Special Populations

• Studies in people with diabetes have shown similar efficacy of plant sterols in lowering cholesterol compared to people without diabetes 1
• Plant sterols have been studied in children with familial hypercholesterolemia, showing reductions in LDL cholesterol levels, though without demonstrated improvement in endothelial function 4

Safety Considerations

• Some concerns exist regarding plant sterols potentially decreasing plasma levels of fat-soluble vitamins and antioxidants 1
• A meta-analysis of 10-15 trials showed that plasma levels of vitamins A and D are not affected by stanols or sterols, while alpha carotene, lycopene, and vitamin E levels remained stable 7
• Beta carotene levels may decline with plant sterol use, but adverse health outcomes are not expected 7
• Plant sterols are generally considered safe, with no evidence of increased risk for common diseases 7

Limitations

• While plant sterols effectively lower cholesterol, there is currently no direct evidence that they reduce the risk of coronary heart disease mortality, despite their cholesterol-lowering effects 1
• The effect of plant sterols is additive with diet or drug interventions: eating foods low in saturated fat and cholesterol and high in stanols or sterols can reduce LDL by 20% 7
• Adding sterols or stanols to statin medication is more effective than doubling the statin dose 7