By Susan J Hewlings PhD, RD, Radicle Science and Substantiation Sciences09.16.24
Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality globally, accounting for roughly one-third of all deaths worldwide, according to the World Health Organization. Elevated blood cholesterol levels, primarily low-density lipoprotein cholesterol (LDL-C), are well-recognized risk factors for CVD. Consequently, lowering cholesterol, particularly LDL-C has been a longstanding public health recommendation to reduce the risk of cardiovascular disease.
The recommendations by most major health organizations mention lifestyle and dietary modifications as an essential part of a treatment protocol to lower CVD risk and LDL-C. Yet, most CVD treatment and prevention protocols in the U.S. focus on drugs. These prevention protocols fail to mention the heavily clinically testeddietary solution that plant sterols and stanols, collectively known as phytosterols (PS), represent that can also be used in association with pharmaceutical regimens. Plant sterol and stanols are part of most European protocols in a healthy cholesterol reduction diet effort.
Notably, plant sterols and stanols have been shown to reduce LDL-C by 10-14%. More than200 randomized control trials (RCTs) and numerous meta-analyses support a similar efficacy of PS for lowering LDL-C cholesterol levels. Due to their effectiveness, the U.S. Food and Drug Administration (FDA) has approved a health claim for sterols and stanols and CVD risk reduction.
Phytosterols offer an effective, yet underutilized plant-based way to lower LDL-C cholesterol levels. Yet, products containing plant sterols or stanols are not readily sought after in many markets worldwide for their benefits.
The various forms of plant sterols and stanols are found primarily in the roots, stems, leaves, fruits, and seeds of plants. As ingredients in food and supplements, the most common sources of plant sterols include pine, soybean, rapeseed, and sunflower. These products are made from the wood and vegetable oil production process.
Globally, the average daily intake of plant sterols ranges from approximately 100 mg per day to 400 mg per day, and as high as 600 mg per day among vegetarians. Plant stanols are less commonly found in foods with an estimateddaily intake of 17–24 mg per day. Globally, the primary dietary sources of plant stanols are cereals and vegetable oils.
Several factors may influence the cholesterol-lowering efficacy of plant sterols. These include the form of a supplement (capsule or tablet), the type of food and its macronutrient composition, whether the PS is free or esterified, and the type of fatty acid used for esterification. Other factors include the frequency of plant sterol consumption and whether or not it is consumed with food.
While the above factors may impact the efficacy of sterols, there does not appear to be a difference in cholesterol-lowering efficacy between non-fat or low-fat foods, in the type of fat used as a carrier, or in free and esterified plant sterols. However, solid foods like margarine or spreads may offer greater benefits compared to liquid foods such as juices or milk.
The frequency of consumption does seem to matter, once a day is the most effective. Additionally, consuming the plant sterols and stanols with a meal may provide additional benefits compared to consuming them on their own. However, it is clear that plant sterols can be added to the diet via a variety of foods and formats to achieve a beneficial effect.
One of the main challenges of adding plant sterols and stanols to foods and beverages is their poor solubility in water, which causes them to crystallize or remain insoluble in gastrointestinal fluids, thereby decreasing their bioavailability. To address this, plant sterol esters were developed, where unsaturated vegetable oil fatty acids are attached to free sterols, making it easier to incorporate them into a wider range of foods.
Numerous studies support the efficacy of plant sterol-fortified dairy products and other foods. For instance, one RCT found that consuming yogurt containing 1-2 g/day of plant sterols significantly lowered cholesterol in individuals with moderate hypercholesterolemia.
Another study found that low-fat yogurt enriched with plant stanol esters (1 g/d) reduced LDL concentrations within just 1 week. Another study utilized plant-sterol-fortified margarine and found that it helped lower LDL-C cholesterol by 8-13% when compared to controls.
In summary, plant sterols and stanols effectively lower LDL cholesterol levels when consumed in the appropriate doses, and various food formats can offer health benefits. While factors such as the type of food and frequency of consumption may influence their effectiveness, research supports including plant sterols in a wide range of food products.
The launch of a plant sterol-fortified spread called Benecol in 1995 was a significant milestone, leading to increased interest in the use of plant sterols and stanols on a population level. Over the last three decades, extensive research evaluated the health benefits of plant sterols, ways to improve their bioavailability, and how to best mix them into foods and beverages.
In 2000, the FDA authorized a CVD risk reduction claim for specific foods and dietary supplements containing plant sterol and esters. Claim language and other requirements can be found in 21 CFR 101.83. Expansion of the claim eligibility was provided in Letters of Enforcement Discretion in 2003, and a revised claim based on higher recommended intake levels (2 g per day) was further published in the Federal Register 2010-2011. As of today, the FDA is permitting the original claim from 2000 as well as the updated versions.
The European Commission has also approved the use of sterols in a variety of foods and beverages and has authorized health claims to be used for labeling. Similar approvals for the use of sterols in foods have also been granted in non-EU countries such as Switzerland, Norway, and Iceland. Additionally, multiple global health organizations recommend plant sterols as part of a cholesterol-lowering strategy. The recommendations vary in the dose and detail, however, this is reflective of the strong evidence supporting plant sterols' use for cholesterol management.
Further supporting this opportunity is the consumer demand for plant-based yogurts, cheeses, and creamers, foods that have traditionally incorporated plant sterols. This demand has increased by 55%, 43%, and 131%, respectively, in the U.S.
The effectiveness and safety of plant sterols, combined with the consumer trend of seeking more plant-based, environmentally friendly products, is an untapped opportunity for the functional food market.
Numerous human randomized controlled trials and meta-analyses have shown that plant sterol intake can lower LDL-C and support overall cardiovascular health, even in healthy individuals. The scientific evidence is so robust that several government agencies around the world have approved health claims for food and supplements with added plant sterols and stanols.
Yet, products containing plant sterols and stanols are limited in many worldwide markets. This is an untapped ingredient for functional food brands, as plant sterols contribute to the growing consumer interest in natural ways to lower cholesterol with plant-based and sustainable products.
About the Author: Susan Hewlings, RD, PhD, is Vice President of Research Affairs at Radicle Science, a health-tech B Corp pioneering Proof-as-a-Service through virtual, turnkey clinical trials. She is also the Co-Founder of Substantiation Sciences, a consultancy that offers a range of nutrition science services. She has 10 years of experience in the dietary supplement industry as a consultant and with a CRO, and over 20 years of experience in academia and nutrition research. She received her BS in nutrition, MS in exercise physiology, PhD in nutrition all from Florida State University.
The recommendations by most major health organizations mention lifestyle and dietary modifications as an essential part of a treatment protocol to lower CVD risk and LDL-C. Yet, most CVD treatment and prevention protocols in the U.S. focus on drugs. These prevention protocols fail to mention the heavily clinically testeddietary solution that plant sterols and stanols, collectively known as phytosterols (PS), represent that can also be used in association with pharmaceutical regimens. Plant sterol and stanols are part of most European protocols in a healthy cholesterol reduction diet effort.
Notably, plant sterols and stanols have been shown to reduce LDL-C by 10-14%. More than200 randomized control trials (RCTs) and numerous meta-analyses support a similar efficacy of PS for lowering LDL-C cholesterol levels. Due to their effectiveness, the U.S. Food and Drug Administration (FDA) has approved a health claim for sterols and stanols and CVD risk reduction.
Phytosterols offer an effective, yet underutilized plant-based way to lower LDL-C cholesterol levels. Yet, products containing plant sterols or stanols are not readily sought after in many markets worldwide for their benefits.
Plant Sterol and Stanol Intake
Plant sterols and stanols are bioactive compounds that function similarly to cholesterol but have slight differences in their chemical structure, which explains their health effects in humans. Over 40 different types of phytosterols have been identified within cell membranes and tissues.The various forms of plant sterols and stanols are found primarily in the roots, stems, leaves, fruits, and seeds of plants. As ingredients in food and supplements, the most common sources of plant sterols include pine, soybean, rapeseed, and sunflower. These products are made from the wood and vegetable oil production process.
Globally, the average daily intake of plant sterols ranges from approximately 100 mg per day to 400 mg per day, and as high as 600 mg per day among vegetarians. Plant stanols are less commonly found in foods with an estimateddaily intake of 17–24 mg per day. Globally, the primary dietary sources of plant stanols are cereals and vegetable oils.
Optimal Dose and Delivery Systems
The effectiveness of plant sterols and stanols in promoting cardiovascular health is dose-dependent. To achieve significant benefits, the recommended intake typically ranges from 2 to 3 grams per day. One randomized controlled trial demonstrated an average 9.5% reduction in LDL-C levels after participants consumed 20 g/day of a low-fat spread with 3 g/day of added plant sterols for 12 weeks. While many foods can be fortified with plant sterols, the most common forms are vegetable fat spreads and dairy products.Several factors may influence the cholesterol-lowering efficacy of plant sterols. These include the form of a supplement (capsule or tablet), the type of food and its macronutrient composition, whether the PS is free or esterified, and the type of fatty acid used for esterification. Other factors include the frequency of plant sterol consumption and whether or not it is consumed with food.
While the above factors may impact the efficacy of sterols, there does not appear to be a difference in cholesterol-lowering efficacy between non-fat or low-fat foods, in the type of fat used as a carrier, or in free and esterified plant sterols. However, solid foods like margarine or spreads may offer greater benefits compared to liquid foods such as juices or milk.
The frequency of consumption does seem to matter, once a day is the most effective. Additionally, consuming the plant sterols and stanols with a meal may provide additional benefits compared to consuming them on their own. However, it is clear that plant sterols can be added to the diet via a variety of foods and formats to achieve a beneficial effect.
One of the main challenges of adding plant sterols and stanols to foods and beverages is their poor solubility in water, which causes them to crystallize or remain insoluble in gastrointestinal fluids, thereby decreasing their bioavailability. To address this, plant sterol esters were developed, where unsaturated vegetable oil fatty acids are attached to free sterols, making it easier to incorporate them into a wider range of foods.
Numerous studies support the efficacy of plant sterol-fortified dairy products and other foods. For instance, one RCT found that consuming yogurt containing 1-2 g/day of plant sterols significantly lowered cholesterol in individuals with moderate hypercholesterolemia.
Another study found that low-fat yogurt enriched with plant stanol esters (1 g/d) reduced LDL concentrations within just 1 week. Another study utilized plant-sterol-fortified margarine and found that it helped lower LDL-C cholesterol by 8-13% when compared to controls.
In summary, plant sterols and stanols effectively lower LDL cholesterol levels when consumed in the appropriate doses, and various food formats can offer health benefits. While factors such as the type of food and frequency of consumption may influence their effectiveness, research supports including plant sterols in a wide range of food products.
Plant Sterols and Stanols: An Untapped Market
Before statins were introduced in the U.S. market in the 1980s, sitosterol, marketed as Cytellin, was commonly used to lower cholesterol with an excellent safety profile. However, with the introduction of statins, plant sterols assumed a more secondary role in cholesterol management despite numerous clinical studies confirming their effectiveness as an adjunct therapy with statinsThe launch of a plant sterol-fortified spread called Benecol in 1995 was a significant milestone, leading to increased interest in the use of plant sterols and stanols on a population level. Over the last three decades, extensive research evaluated the health benefits of plant sterols, ways to improve their bioavailability, and how to best mix them into foods and beverages.
In 2000, the FDA authorized a CVD risk reduction claim for specific foods and dietary supplements containing plant sterol and esters. Claim language and other requirements can be found in 21 CFR 101.83. Expansion of the claim eligibility was provided in Letters of Enforcement Discretion in 2003, and a revised claim based on higher recommended intake levels (2 g per day) was further published in the Federal Register 2010-2011. As of today, the FDA is permitting the original claim from 2000 as well as the updated versions.
The European Commission has also approved the use of sterols in a variety of foods and beverages and has authorized health claims to be used for labeling. Similar approvals for the use of sterols in foods have also been granted in non-EU countries such as Switzerland, Norway, and Iceland. Additionally, multiple global health organizations recommend plant sterols as part of a cholesterol-lowering strategy. The recommendations vary in the dose and detail, however, this is reflective of the strong evidence supporting plant sterols' use for cholesterol management.
Further supporting this opportunity is the consumer demand for plant-based yogurts, cheeses, and creamers, foods that have traditionally incorporated plant sterols. This demand has increased by 55%, 43%, and 131%, respectively, in the U.S.
The effectiveness and safety of plant sterols, combined with the consumer trend of seeking more plant-based, environmentally friendly products, is an untapped opportunity for the functional food market.
Conclusion
CVD remains a leading cause of death globally, with elevated LDL-C recognized as a major risk factor. As a result, lowering LDL-C levels is a key focus in public health messaging worldwide. Several bioactive components of a healthy plant-based diet have been identified as effective in reducing LDL-C levels, with plant sterols being among the most significant.Numerous human randomized controlled trials and meta-analyses have shown that plant sterol intake can lower LDL-C and support overall cardiovascular health, even in healthy individuals. The scientific evidence is so robust that several government agencies around the world have approved health claims for food and supplements with added plant sterols and stanols.
Yet, products containing plant sterols and stanols are limited in many worldwide markets. This is an untapped ingredient for functional food brands, as plant sterols contribute to the growing consumer interest in natural ways to lower cholesterol with plant-based and sustainable products.
About the Author: Susan Hewlings, RD, PhD, is Vice President of Research Affairs at Radicle Science, a health-tech B Corp pioneering Proof-as-a-Service through virtual, turnkey clinical trials. She is also the Co-Founder of Substantiation Sciences, a consultancy that offers a range of nutrition science services. She has 10 years of experience in the dietary supplement industry as a consultant and with a CRO, and over 20 years of experience in academia and nutrition research. She received her BS in nutrition, MS in exercise physiology, PhD in nutrition all from Florida State University.
