Plant stanol ester
Encyclopedia
Stanol esters are a heterogeneous group of phytosterol
esters with a saturated sterol ring structure known to reduce the level of low-density lipoprotein (LDL) cholesterol in blood when ingested. The starting material is sterols from plants. These are first hydrogenated to give stanol which is then esterified with a mixture of fatty acids also derived from plants.
Plant stanol ester is a patented ingredient of Raisio Group
for lowering cholesterol
, and the active ingredient of Benecol
products marketed in more than 30 countries.
innovation-based, cholesterol-lowering food ingredient plant stanol ester was recently selected as one of the ten greatest discoveriemepiugru6e7irkvio,
Eur J Clin Nutr 2009; 63: 2-10. The review published in European Journal of Clinical Nutrition in January 2009 presented the greatest discoveries related to nutrition during the past 30 years. The discoveries chosen were based on the views of the world's leading nutrition researchers and solid research data.
-like molecules found in all plant foods, with the highest concentrations occurring in vegetable oils. Plant sterols are plant equivalents of cholesterol
and have a very similar molecular structure. According to their structure, they can be divided into sterols and stanols, stanols being a saturated subgroup of sterols.
Sterols and stanols appear in everyday diets in concentrations too low to change blood cholesterol levels significantly. The use of foods containing plant sterols and stanols provide a novel approach to lowering plasma LDL by dietary means. Known since the early 1950s, they are structurally analogous to cholesterol. Functional foods containing plant stanols have the potential of becoming the basis of cholesterol management for all individuals at risk.
and rye
. The daily intake of stanols in the average western diet is about 60 mg/d, whereas the intake of plant sterols is about 150–300 mg/d and that of cholesterol is 500–800 mg/d. The relatively low natural levels of stanols in the diet are too low to have a significant effect on serum
cholesterol levels.
Plant sterols have traditionally been considered non-absorbable. In humans consuming solid food diets, more than 90% of sitosterol is recovered in the stool. Plant sterol absorption is quite low, particularly for stanols, for which the absorption efficiency is over 10 times lower than for the equivalent sterols. Plasma levels of fat-soluble vitamins and other vegetable-derived compounds have been studied following plant sterol ingestion due to concerns about the possibility of reduced absorption. Alpha
- and beta-carotene
are slightly reduced, although results have been inconsistent. However, no reduction in beta-carotene level was seen when plant sterols or plant stanols were consumed as part of a healthy diet containing fruits and vegetables.
Following evidence from toxicological studies and numerous clinical trials, stanols are characterised as safe by authorities in several EU countries and by the U.S. Food and Drug Administration
(FDA).
, was studying a food ingredient with great promise for heart health. The problem was, the ingredient crystallized when extracted from its natural source, rendering its use in foods technically challenging.
For nearly 6 months, Wester had been looking at a class of molecules called phytosterols. They occur naturally in plants and were known to block absorption of cholesterol in the digestive tract. Wester's 1989 breakthrough gave Raisio a way to produce food-grade, fat-soluble, plant sterols and stanols. Clinical studies showed these products would effectively reduce blood levels of cholesterol
. They could easily be incorporated into foods without compromising taste.
The company patented its process and use of plant stanol ester for reducing elevated blood cholesterol
levels. It engaged with research partners, raised capital and aligned its product testing with an ongoing public-health initiative in Finland
.
Two decades earlier, the North Karelia
region of Finland had begun a major campaign to address chronic health problems. A clinical research study on Benecol
was included in this effort. It was led by the University of Helsinki
's Tatu Miettinen, MD, who early on had suggested looking at phytosterols to help reduce cholesterol.
The double-blind research project showed the ingredient, used in margarine
, reduced harmful LDL cholesterol by 14%. These data were published to great acclaim in the New England Journal of Medicine
in November 1995.
Just as the study was published, Raisio introduced the first ever commercial phytosterol-based food – a margarine product containing Benecol This was a logical route to market. Raisio already held more than half of Finland's margarine market.
. According to their structure, they can be divided into sterols and stanols. Stanols are a saturated subgroup of sterols.
Plant stanol esters in Benecol products are fatty acid
esters of plant stanols. The stanol part of the molecule is sitostanol or campestanol while the fatty acid residue originates from different vegetable oils.
Plant stanol esters have the following physical properties:
These physical properties can be tailored by changing the fatty acid composition. In different technological applications of Benecol products, the fatty acid
part is selected so that the melting properties, texture and other characteristics of the plant stanol ester closely resemble the properties of the fat it replaces.
Using plant stanol esters in food applications instead of conventional fats does not decrease the shelf life of the end product. As is the case for all fats and oils, stanol esters should be protected from heat, air and light to prevent oxidation. If long-term storage is required, plant stanol esters are typically refrigerated in solid form. Furthermore, the usual antioxidants can be added to plant stanol ester products as they are to other oils or fats to minimise oxidation.
in a number of randomised, placebo-controlled double-blind clinical trials. Cholesterol-lowering effects have been noted:
The first major study about plant stanol ester was published in the New England Journal of Medicine
in 1995. Since then, nearly 60 clinical trials published in peer-reviewed journals show that plant stanol ester is safe and effective. It is apparent from these studies that plant sterols and stanols lower total and LDL cholesterol, but beneficially do not lower good HDL
cholesterol or have any adverse effects on triglyceride
levels.
Furthermore, as plant stanols are absorbed minimally, the lack of bioavailability
after ingestion of plant stanol ester make adverse systemic effects of plant stanols highly unlikely. Plant stanol ester have been generally recognized as safe
(GRAS) in the USA.
They were also evaluated by food authorities in several EU member states before entering the individual markets. Furthermore, Europe
an food authorities evaluated the use of stanols and sterols in foods and recommend a daily intake of 1-3 g phytosterols and stanols.
It has been shown that dietary plant sterols safely reduce serum cholesterol in a broad range of patients, including children.
Daily consumption of 2 g of plant stanols (as 3,4 g of plant stanol ester) is proven to reduce total cholesterol by up to 10 % and reduce LDL (harmful) cholesterol by up to 15 %. Effective results can occur in as little as two weeks.
(CHD). Two ABC transporters (ABCG5 and ABCG8) play an important role in the regulating the intestinal absorption of plant sterols by resecreting previously absorbed plant sterols from the enterocytes back into the intestinal lumen.
Mutations in these transporter proteins lead to a rare congenital disease called sitosterolaemia, which is characterised by:
It was recently shown that polymorphisms in the ABCG5 and ABCG8 genes contribute to modifying serum plant sterol levels in healthy, non-sitosterolaemic individuals. Furthermore, several epidemiological studies have shown that the risk of developing heart disease seems to be increased even at more "normal" plant sterol levels. Since statins were shown to increase serum plant sterol concentrations, patients should probably not be treated with statins alone but with a combination therapy focusing simultaneously on improving the serum lipoprotein profile and lowering serum plant sterol concentrations.
As a consequence of the reduced absorption of cholesterol, the absorption of fat-soluble components other than cholesterol, such as vitamins and antioxidants, may also be reduced. Like cholesterol, carotenoids and tocopherols are transported by lipoproteins. Since the number of LDL particles in circulation decreases after consumption of plant sterols or stanols, plasma concentrations of carotenoids and tocopherols also decrease. This is why these antioxidants are often standardized to plasma lipid concentrations.
The results of randomised, placebo
-controlled trials on the effects of plant sterols or stanols on fat-soluble vitamins and antioxidants were summarised in 2003. Significant reductions were only seen in clinical trials for hydrocarbon carotenoids. These reductions are probably caused by reduced absorption and lower plasma concentrations of the carrier, LDL.
After correcting for cholesterol levels, only the reduction in the β-carotene level remained. It is important, however, that carotenoid and tocopherol levels remained within the normal ranges. Clinical trials also showed that when following the recommended diet, including consumption of vegetables and fruit, carotenoid levels did not decrease. Plasma concentrations of retinol
(vitamin A), 25-hydroxyvitamin D and vitamin K
are unaffected by dietary plant sterols and stanols.
Reducing serum cholesterol through dietary changes often only provides short-term benefits due to the difficulty of making the changes permanent. Benecol products maintain its effectiveness in long-term use, when the product is consumed on a daily basis. In a 12-month trial, serum cholesterol was reduced by 10% and LDL by 14%.
With esterified stanols, combining the data from the clinical studies shows that optimum LDL lowering is attained with an intake of about 2 g/d, and increasing the dose does not further reduce serum LDL levels. The minimum amount of stanols required to significantly lower cholesterol
is about 0.8-1.0 g/d. However, most of the studies focused on higher intake levels, about 2-3 g/d of plant stanols in their esterified, fat-soluble forms.
The plant stanol ester specific cholesterol-lowering effect is of a similar magnitude irrespective of the fat content or quality of the background diet or if the dietary cholesterol intake is high or low. Importantly, plant stanol ester adds to the effect of other dietary changes.
therapy, and is well tolerated and safe. Statins lower cholesterol levels by inhibiting cholesterol synthesis, which leads to an increase in the number of LDL receptors on liver
cells and to higher uptake of LDL-cholesterol. By comparison, plant stanols reduce intestinal absorption of cholesterol. Combining dietary plant stanols with statin therapy will deliver both these effects. The cholesterol-lowering effect is maintained even in combination with a diet low in saturated fat and cholesterol.
Statins are the most widely used cholesterol-lowering drugs currently available. They reduce serum cholesterol concentrations by inhibiting the synthesis of cholesterol. Since statins and stanols have different cholesterol-lowering mechanisms, they act additively in a clinical treatment. For example, the addition of plant stanol margarine to the diets of heart transplant patients reduced cholesterol levels 22% more than statin did on its own. Subsequently, 70% of the patients were able to reduce their statin intake by adding stanol ester margarine to their diets.
Raisio Group
, Ingredients Division for lowering cholesterol, and the active ingredient of Benecol products.
The first Benecol product was a stanol ester-enriched margarine and was launched in Finland
in November 1995. Today, Raisio Group
markets plant stanol ester ingredient internationally to food companies all over the world.
products are targeted to individuals who want to lower their serum cholesterol levels through diet. Every Benecol -labelled product contains enough plant stanol esters to lower cholesterol. This effect is demonstrated when the product is consumed daily at normal dietary levels.
Benecol products are also tailored to have a profile that is healthy for the heart, such as low fat content and a nutritionally desirable fatty acid
profile. At their best, Benecol products give consumers dietary choices for a healthy heart.
The best-known Benecol products are yogurt drink and margarine.
Although chemically stanol ester is a fat, it can also be added to many low-fat foods. Benecol food applications vary from high-fat margarines to dairy and cereal foods where the stanol ester is the product's only fat source.
Clinical tests were conducted for each new type of Benecol products to ensure that the cholesterol-lowering effect of stanol ester is not lost when the product platform is changed.
Stanol esters should be added to the end product formulation in the same way as the fat which they replace. Basically, the same processing equipment can be used for manufacturing a stanol ester-enriched product which is used for the basic product. The higher viscosity of stanol esters (compared with normally used oils and fats) must be taken into account when adding stanol esters into a food matrix. Effective mixing may be required to achieve a homogeneous mixture or emulsion
.
Stanol esters with different fatty acid profiles can be selected for different food types. The type of stanol ester is chosen according to its texturising properties to provide properties which correspond to those of the saturated fat which is being replaced.
and trans-unsaturated hard fat with stanol esters results in a 45% reduction in the saturated fatty acid content of the spread, but only a 5% resp. 10% reduction in monounsaturated and polyunsaturated fatty acids. The structurising effect of stanol esters can be used particularly for low-fat spreads to even fully replace hard fat containing nutritionally undesirable saturated and trans-saturated fatty acids, as in the fat blends of spreads.
The energy content of stanol ester-enriched spreads is typically lower than that of the corresponding conventional spreads. This is because the stanol part, which represents 60% of the stanol ester molecule, cannot be absorbed and hence not a source of energy in the product.
One of the nutritional benefits of Benecol spreads is that the content of unsaturated fatty acids can be increased in significant amounts in the product. The cholesterol-lowering effect of Benecol spreads is an additional effect of the stanol esters and unsaturated fatty acids in the product.
-lowering foods, dairy foods are gaining in popularity. Although yoghurt
remains a common product, yoghurt drinks have been the most popular version of new dairy Benecol products in recent years.
Plant stanol esters give dairy products a creamy texture with a very low fat content. Furthermore, because the fatty acids of stanol esters are derived from vegetable oils, the product's fatty acid profile is high in unsaturated and very low in saturated fatty acids.
Different soy- and cereal
-based non-dairy alternatives are also potential platforms for Benecol products. Especially in the USA, Asia
and Central Europe
, soy- and cereal-based non-dairy
foods are gaining in popularity as dietary choices for good heart health. Plant stanol esters can be added to these foods using a technology similar to that used in the dairy industry. Stanol esters have an additional benefit in soy and cereal food applications because they can mask some of the off flavour these foods may have.
Furthermore, stanol esters can also mask bitterness. When added to soy products, less sugar or other sweetener is required to obtain a more pleasant taste and feeling to the mouth.
. As in spreads and margarines, stanol esters replace part or all of the hard fat in granulated muesli products, thus lowering the saturated fatty acids content.
Phytosterol
Phytosterols, which encompass plant sterols and stanols, are steroid compounds similar to cholesterol which occur in plants and vary only in carbon side chains and/or presence or absence of a double bond. Stanols are saturated sterols, having no double bonds in the sterol ring structure. More than...
esters with a saturated sterol ring structure known to reduce the level of low-density lipoprotein (LDL) cholesterol in blood when ingested. The starting material is sterols from plants. These are first hydrogenated to give stanol which is then esterified with a mixture of fatty acids also derived from plants.
Plant stanol ester is a patented ingredient of Raisio Group
Raisio Group
Raisio Oyj, known internationally as Raisio Group , is a Finnish company that makes cereal products, animal feeds and engage in life-sciences. Raisio produces Benecol, a ingredient used in a range of Cholesterol-reducing spreads, dairy products and condiments marketed under its Benecol brand name...
for lowering cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
, and the active ingredient of Benecol
Benecol
is a brand of cholesterol lowering food products owned by and is a trademark of Finnish company Raisio Group.Raisio Group licenses the Benecol brand and sells the effective and safe cholesterol lowering ingredient, Plant stanol ester, to food companies around the world...
products marketed in more than 30 countries.
Plant stanol ester
The FinnishFinland
Finland , officially the Republic of Finland, is a Nordic country situated in the Fennoscandian region of Northern Europe. It is bordered by Sweden in the west, Norway in the north and Russia in the east, while Estonia lies to its south across the Gulf of Finland.Around 5.4 million people reside...
innovation-based, cholesterol-lowering food ingredient plant stanol ester was recently selected as one of the ten greatest discoveriemepiugru6e7irkvio,
Eur J Clin Nutr 2009; 63: 2-10. The review published in European Journal of Clinical Nutrition in January 2009 presented the greatest discoveries related to nutrition during the past 30 years. The discoveries chosen were based on the views of the world's leading nutrition researchers and solid research data.
Plant stanols in nature
Plant sterols are cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
-like molecules found in all plant foods, with the highest concentrations occurring in vegetable oils. Plant sterols are plant equivalents of cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
and have a very similar molecular structure. According to their structure, they can be divided into sterols and stanols, stanols being a saturated subgroup of sterols.
Sterols and stanols appear in everyday diets in concentrations too low to change blood cholesterol levels significantly. The use of foods containing plant sterols and stanols provide a novel approach to lowering plasma LDL by dietary means. Known since the early 1950s, they are structurally analogous to cholesterol. Functional foods containing plant stanols have the potential of becoming the basis of cholesterol management for all individuals at risk.
Plant stanols in human nutrition
Plant stanols are present in small amounts in our daily diet. Their main sources are whole-grain foods, mostly wheatWheat
Wheat is a cereal grain, originally from the Levant region of the Near East, but now cultivated worldwide. In 2007 world production of wheat was 607 million tons, making it the third most-produced cereal after maize and rice...
and rye
Rye
Rye is a grass grown extensively as a grain and as a forage crop. It is a member of the wheat tribe and is closely related to barley and wheat. Rye grain is used for flour, rye bread, rye beer, some whiskeys, some vodkas, and animal fodder...
. The daily intake of stanols in the average western diet is about 60 mg/d, whereas the intake of plant sterols is about 150–300 mg/d and that of cholesterol is 500–800 mg/d. The relatively low natural levels of stanols in the diet are too low to have a significant effect on serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
cholesterol levels.
Plant sterols have traditionally been considered non-absorbable. In humans consuming solid food diets, more than 90% of sitosterol is recovered in the stool. Plant sterol absorption is quite low, particularly for stanols, for which the absorption efficiency is over 10 times lower than for the equivalent sterols. Plasma levels of fat-soluble vitamins and other vegetable-derived compounds have been studied following plant sterol ingestion due to concerns about the possibility of reduced absorption. Alpha
Alpha-carotene
α-Carotene is a form of carotene with a β-ring at one end and an ε-ring at the other. It is the second most common form of carotene.-Human physiology:...
- and beta-carotene
Beta-carotene
β-Carotene is a strongly-coloured red-orange pigment abundant in plants and fruits. It is an organic compound and chemically is classified as a hydrocarbon and specifically as a terpenoid , reflecting its derivation from isoprene units...
are slightly reduced, although results have been inconsistent. However, no reduction in beta-carotene level was seen when plant sterols or plant stanols were consumed as part of a healthy diet containing fruits and vegetables.
Following evidence from toxicological studies and numerous clinical trials, stanols are characterised as safe by authorities in several EU countries and by the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA).
Discovery
Plant Stanol was discovered by a Finnish chemist Ingmar Wester. in 1989 His firm, Raisio MargariiniRaisio Group
Raisio Oyj, known internationally as Raisio Group , is a Finnish company that makes cereal products, animal feeds and engage in life-sciences. Raisio produces Benecol, a ingredient used in a range of Cholesterol-reducing spreads, dairy products and condiments marketed under its Benecol brand name...
, was studying a food ingredient with great promise for heart health. The problem was, the ingredient crystallized when extracted from its natural source, rendering its use in foods technically challenging.
For nearly 6 months, Wester had been looking at a class of molecules called phytosterols. They occur naturally in plants and were known to block absorption of cholesterol in the digestive tract. Wester's 1989 breakthrough gave Raisio a way to produce food-grade, fat-soluble, plant sterols and stanols. Clinical studies showed these products would effectively reduce blood levels of cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
. They could easily be incorporated into foods without compromising taste.
The company patented its process and use of plant stanol ester for reducing elevated blood cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
levels. It engaged with research partners, raised capital and aligned its product testing with an ongoing public-health initiative in Finland
Finland
Finland , officially the Republic of Finland, is a Nordic country situated in the Fennoscandian region of Northern Europe. It is bordered by Sweden in the west, Norway in the north and Russia in the east, while Estonia lies to its south across the Gulf of Finland.Around 5.4 million people reside...
.
Two decades earlier, the North Karelia
North Karelia
North Karelia is a region in eastern Finland. It borders to the regions of Kainuu, Northern Savonia, Southern Savonia, South Karelia and to Russia.The city of Joensuu is the centre of the North Karelia region.- Municipalities :...
region of Finland had begun a major campaign to address chronic health problems. A clinical research study on Benecol
Benecol
is a brand of cholesterol lowering food products owned by and is a trademark of Finnish company Raisio Group.Raisio Group licenses the Benecol brand and sells the effective and safe cholesterol lowering ingredient, Plant stanol ester, to food companies around the world...
was included in this effort. It was led by the University of Helsinki
University of Helsinki
The University of Helsinki is a university located in Helsinki, Finland since 1829, but was founded in the city of Turku in 1640 as The Royal Academy of Turku, at that time part of the Swedish Empire. It is the oldest and largest university in Finland with the widest range of disciplines available...
's Tatu Miettinen, MD, who early on had suggested looking at phytosterols to help reduce cholesterol.
The double-blind research project showed the ingredient, used in margarine
Margarine
Margarine , as a generic term, can indicate any of a wide range of butter substitutes, typically composed of vegetable oils. In many parts of the world, the market share of margarine and spreads has overtaken that of butter...
, reduced harmful LDL cholesterol by 14%. These data were published to great acclaim in the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
in November 1995.
Just as the study was published, Raisio introduced the first ever commercial phytosterol-based food – a margarine product containing Benecol This was a logical route to market. Raisio already held more than half of Finland's margarine market.
Structure and properties
Plant sterols are plant equivalents of cholesterol and have a very similar molecular structureMolecular structure
The molecular structure of a substance is described by the combination of nuclei and electrons that comprise its constitute molecules. This includes the molecular geometry , the electronic properties of the...
. According to their structure, they can be divided into sterols and stanols. Stanols are a saturated subgroup of sterols.
Plant stanol esters in Benecol products are fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
esters of plant stanols. The stanol part of the molecule is sitostanol or campestanol while the fatty acid residue originates from different vegetable oils.
Plant stanol esters have the following physical properties:
- Fat-like with a waxy texture
- Creamy white color in the solid form
- Viscous clear liquid with a bright yellow colour, bland odour and taste
- Insoluble in water and soluble in fat (hydrophobic)
- Viscosity higher than that of the triglycerideTriglycerideA triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....
oil with the same fatty acid composition.
These physical properties can be tailored by changing the fatty acid composition. In different technological applications of Benecol products, the fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
part is selected so that the melting properties, texture and other characteristics of the plant stanol ester closely resemble the properties of the fat it replaces.
Oxidative and processing stability
Under normal storage and food preparation conditions, plant stanol esters are very stable because they are more resistant to oxidation than the commonest vegetable oils.Using plant stanol esters in food applications instead of conventional fats does not decrease the shelf life of the end product. As is the case for all fats and oils, stanol esters should be protected from heat, air and light to prevent oxidation. If long-term storage is required, plant stanol esters are typically refrigerated in solid form. Furthermore, the usual antioxidants can be added to plant stanol ester products as they are to other oils or fats to minimise oxidation.
Lowering cholesterol
Esterified plant stanols have been proven to reduce cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
in a number of randomised, placebo-controlled double-blind clinical trials. Cholesterol-lowering effects have been noted:
- in normo- and hypercholesterolaemicHypercholesterolemiaHypercholesterolemia is the presence of high levels of cholesterol in the blood. It is not a disease but a metabolic derangement that can be caused by many diseases, notably cardiovascular disease...
individuals - in women and men, as well as children
- in patients with coronary heart diseaseCoronary heart diseaseCoronary artery disease is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium with oxygen and nutrients. It is sometimes also called coronary heart disease...
- in patients with type 1 diabetes
- in patients with type 2 diabetes
- in conjunction with cholesterol-lowering statinStatinStatins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
therapy
The first major study about plant stanol ester was published in the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
in 1995. Since then, nearly 60 clinical trials published in peer-reviewed journals show that plant stanol ester is safe and effective. It is apparent from these studies that plant sterols and stanols lower total and LDL cholesterol, but beneficially do not lower good HDL
HDL
HDL may refer to one of the following:* Hardware description language* High-density lipoprotein, so-called "good cholesterol".* Hong Kong Disneyland, in China.* Les Hurlements d'Léo, an alternative rock band from France.* GE HDL diesel engine...
cholesterol or have any adverse effects on triglyceride
Triglyceride
A triglyceride is an ester derived from glycerol and three fatty acids. There are many triglycerides, depending on the oil source, some are highly unsaturated, some less so....
levels.
Safety
Extensive safety studies in humans and animals showed that plant stanol ester is:- safe to use,
- well tolerated, and
- have no adverse effects.
Furthermore, as plant stanols are absorbed minimally, the lack of bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
after ingestion of plant stanol ester make adverse systemic effects of plant stanols highly unlikely. Plant stanol ester have been generally recognized as safe
Generally recognized as safe
Generally recognized as safe is an American Food and Drug Administration designation that a chemical or substance added to food is considered safe by experts, and so is exempted from the usual Federal Food, Drug, and Cosmetic Act food additive tolerance requirements.-History:On January 1, 1958,...
(GRAS) in the USA.
They were also evaluated by food authorities in several EU member states before entering the individual markets. Furthermore, Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
an food authorities evaluated the use of stanols and sterols in foods and recommend a daily intake of 1-3 g phytosterols and stanols.
It has been shown that dietary plant sterols safely reduce serum cholesterol in a broad range of patients, including children.
Up to 15% cholesterol reduction
Reducing serum cholesterol through dietary changes often only provides short-term benefits due to the difficulty of making the changes permanent. Benecol products maintain its effectiveness in long-term use, when the product is consumed on a daily basis.Daily consumption of 2 g of plant stanols (as 3,4 g of plant stanol ester) is proven to reduce total cholesterol by up to 10 % and reduce LDL (harmful) cholesterol by up to 15 %. Effective results can occur in as little as two weeks.
Dual effect of plant stanol
Plant stanol reduce both cholesterol and plant sterol levels in serum. This may be of importance since elevated plant sterol concentrations have been identified as an independent risk factor for coronary heart diseaseCoronary heart disease
Coronary artery disease is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium with oxygen and nutrients. It is sometimes also called coronary heart disease...
(CHD). Two ABC transporters (ABCG5 and ABCG8) play an important role in the regulating the intestinal absorption of plant sterols by resecreting previously absorbed plant sterols from the enterocytes back into the intestinal lumen.
Mutations in these transporter proteins lead to a rare congenital disease called sitosterolaemia, which is characterised by:
- severely elevated serum plant sterol concentrations,
- normal to moderately increased serum cholesterol concentrations, and
- a high risk of developing CHD at a very early age.
It was recently shown that polymorphisms in the ABCG5 and ABCG8 genes contribute to modifying serum plant sterol levels in healthy, non-sitosterolaemic individuals. Furthermore, several epidemiological studies have shown that the risk of developing heart disease seems to be increased even at more "normal" plant sterol levels. Since statins were shown to increase serum plant sterol concentrations, patients should probably not be treated with statins alone but with a combination therapy focusing simultaneously on improving the serum lipoprotein profile and lowering serum plant sterol concentrations.
Cholesterol absorption
The molecular mode of actions of stanols has been described in several preclinical and clinical trials and can be divided into two steps:- Step 1: CholesterolCholesterolCholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
absorption occurs via the formation of micelles with bile acids. Stanols displace cholesterol from these micelles so that less cholesterol is absorbed. Stanols need to be taken as part of a meal in order to be incorporated in the micelles.
- Step 2: In vitro studies have shown that stanols activate LXR alpha, LXR beta and ABCA1 transporter proteins. It is thus hypothesised that stanols work in enterocytes by activating the excretion of cholesterol back into the intestinal lumen. Only stanols have been proven to retain their efficacy in long-term use, most likely due to the minimal absorption of stanols, and consequently their lack of effect on bile acidBile acidBile acids are steroid acids found predominantly in the bile of mammals. Bile salts are bile acids compounded with a cation, usually sodium. In humans, the salts of taurocholic acid and glycocholic acid represent approximately eighty percent of all bile salts. The two major bile acids are cholic...
metabolismMetabolismMetabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
.
As a consequence of the reduced absorption of cholesterol, the absorption of fat-soluble components other than cholesterol, such as vitamins and antioxidants, may also be reduced. Like cholesterol, carotenoids and tocopherols are transported by lipoproteins. Since the number of LDL particles in circulation decreases after consumption of plant sterols or stanols, plasma concentrations of carotenoids and tocopherols also decrease. This is why these antioxidants are often standardized to plasma lipid concentrations.
The results of randomised, placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
-controlled trials on the effects of plant sterols or stanols on fat-soluble vitamins and antioxidants were summarised in 2003. Significant reductions were only seen in clinical trials for hydrocarbon carotenoids. These reductions are probably caused by reduced absorption and lower plasma concentrations of the carrier, LDL.
After correcting for cholesterol levels, only the reduction in the β-carotene level remained. It is important, however, that carotenoid and tocopherol levels remained within the normal ranges. Clinical trials also showed that when following the recommended diet, including consumption of vegetables and fruit, carotenoid levels did not decrease. Plasma concentrations of retinol
Retinol
Retinol is one of the animal forms of vitamin A. It is a diterpenoid and an alcohol. It is convertible to other forms of vitamin A, and the retinyl ester derivative of the alcohol serves as the storage form of the vitamin in animals....
(vitamin A), 25-hydroxyvitamin D and vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
are unaffected by dietary plant sterols and stanols.
Long term effects
Daily intake of 2.5 g for 4 weeks of esterified plant stanols once at lunch was as effective in lowering serum LDL-cholesterol concentrations as when the dose was divided over three meals. Effective results can occur in as little as two weeks.Reducing serum cholesterol through dietary changes often only provides short-term benefits due to the difficulty of making the changes permanent. Benecol products maintain its effectiveness in long-term use, when the product is consumed on a daily basis. In a 12-month trial, serum cholesterol was reduced by 10% and LDL by 14%.
Dosages
Most of the studies on stanol consumption assessed the effects of using stanol divided over two or more dosages. However, Plat and Mensink showed that daily intake of 2.5 g for 4 weeks of esterified plant stanols once at lunch was as effective in lowering serum LDL-cholesterol concentrations as when the dose was divided over three meals. Effective results can occur in as little as two weeks.With esterified stanols, combining the data from the clinical studies shows that optimum LDL lowering is attained with an intake of about 2 g/d, and increasing the dose does not further reduce serum LDL levels. The minimum amount of stanols required to significantly lower cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
is about 0.8-1.0 g/d. However, most of the studies focused on higher intake levels, about 2-3 g/d of plant stanols in their esterified, fat-soluble forms.
The plant stanol ester specific cholesterol-lowering effect is of a similar magnitude irrespective of the fat content or quality of the background diet or if the dietary cholesterol intake is high or low. Importantly, plant stanol ester adds to the effect of other dietary changes.
Effective in conjunction with statin medication
The cholesterol-lowering effect of plant stanols provides an additional effect in combination with statinStatin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
therapy, and is well tolerated and safe. Statins lower cholesterol levels by inhibiting cholesterol synthesis, which leads to an increase in the number of LDL receptors on liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
cells and to higher uptake of LDL-cholesterol. By comparison, plant stanols reduce intestinal absorption of cholesterol. Combining dietary plant stanols with statin therapy will deliver both these effects. The cholesterol-lowering effect is maintained even in combination with a diet low in saturated fat and cholesterol.
Statins are the most widely used cholesterol-lowering drugs currently available. They reduce serum cholesterol concentrations by inhibiting the synthesis of cholesterol. Since statins and stanols have different cholesterol-lowering mechanisms, they act additively in a clinical treatment. For example, the addition of plant stanol margarine to the diets of heart transplant patients reduced cholesterol levels 22% more than statin did on its own. Subsequently, 70% of the patients were able to reduce their statin intake by adding stanol ester margarine to their diets.
Benecol products
Plant stanol containing Benecol products have been developed for people who wish to reduce their serum cholesterol levels through diet. Plant stanol ester is a patented ingredient of FinnishFinland
Finland , officially the Republic of Finland, is a Nordic country situated in the Fennoscandian region of Northern Europe. It is bordered by Sweden in the west, Norway in the north and Russia in the east, while Estonia lies to its south across the Gulf of Finland.Around 5.4 million people reside...
Raisio Group
Raisio Group
Raisio Oyj, known internationally as Raisio Group , is a Finnish company that makes cereal products, animal feeds and engage in life-sciences. Raisio produces Benecol, a ingredient used in a range of Cholesterol-reducing spreads, dairy products and condiments marketed under its Benecol brand name...
, Ingredients Division for lowering cholesterol, and the active ingredient of Benecol products.
The first Benecol product was a stanol ester-enriched margarine and was launched in Finland
Finland
Finland , officially the Republic of Finland, is a Nordic country situated in the Fennoscandian region of Northern Europe. It is bordered by Sweden in the west, Norway in the north and Russia in the east, while Estonia lies to its south across the Gulf of Finland.Around 5.4 million people reside...
in November 1995. Today, Raisio Group
Raisio Group
Raisio Oyj, known internationally as Raisio Group , is a Finnish company that makes cereal products, animal feeds and engage in life-sciences. Raisio produces Benecol, a ingredient used in a range of Cholesterol-reducing spreads, dairy products and condiments marketed under its Benecol brand name...
markets plant stanol ester ingredient internationally to food companies all over the world.
Food applications
BenecolBenecol
is a brand of cholesterol lowering food products owned by and is a trademark of Finnish company Raisio Group.Raisio Group licenses the Benecol brand and sells the effective and safe cholesterol lowering ingredient, Plant stanol ester, to food companies around the world...
products are targeted to individuals who want to lower their serum cholesterol levels through diet. Every Benecol -labelled product contains enough plant stanol esters to lower cholesterol. This effect is demonstrated when the product is consumed daily at normal dietary levels.
Benecol products are also tailored to have a profile that is healthy for the heart, such as low fat content and a nutritionally desirable fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
profile. At their best, Benecol products give consumers dietary choices for a healthy heart.
The best-known Benecol products are yogurt drink and margarine.
Although chemically stanol ester is a fat, it can also be added to many low-fat foods. Benecol food applications vary from high-fat margarines to dairy and cereal foods where the stanol ester is the product's only fat source.
Clinical tests were conducted for each new type of Benecol products to ensure that the cholesterol-lowering effect of stanol ester is not lost when the product platform is changed.
Different kinds of food
All foods containing edible oils and fats are potential candidates for stanol ester enrichment, as do products which naturally contain stabilisers or emulsifiers or where these are added to attain specific properties. Stanol esters can also be used in low-fat foods.Stanol esters should be added to the end product formulation in the same way as the fat which they replace. Basically, the same processing equipment can be used for manufacturing a stanol ester-enriched product which is used for the basic product. The higher viscosity of stanol esters (compared with normally used oils and fats) must be taken into account when adding stanol esters into a food matrix. Effective mixing may be required to achieve a homogeneous mixture or emulsion
Emulsion
An emulsion is a mixture of two or more liquids that are normally immiscible . Emulsions are part of a more general class of two-phase systems of matter called colloids. Although the terms colloid and emulsion are sometimes used interchangeably, emulsion is used when both the dispersed and the...
.
Stanol esters with different fatty acid profiles can be selected for different food types. The type of stanol ester is chosen according to its texturising properties to provide properties which correspond to those of the saturated fat which is being replaced.
Stanol esters in spreads
Replacing traditional saturatedSaturated fat
Saturated fat is fat that consists of triglycerides containing only saturated fatty acids. Saturated fatty acids have no double bonds between the individual carbon atoms of the fatty acid chain. That is, the chain of carbon atoms is fully "saturated" with hydrogen atoms...
and trans-unsaturated hard fat with stanol esters results in a 45% reduction in the saturated fatty acid content of the spread, but only a 5% resp. 10% reduction in monounsaturated and polyunsaturated fatty acids. The structurising effect of stanol esters can be used particularly for low-fat spreads to even fully replace hard fat containing nutritionally undesirable saturated and trans-saturated fatty acids, as in the fat blends of spreads.
The energy content of stanol ester-enriched spreads is typically lower than that of the corresponding conventional spreads. This is because the stanol part, which represents 60% of the stanol ester molecule, cannot be absorbed and hence not a source of energy in the product.
One of the nutritional benefits of Benecol spreads is that the content of unsaturated fatty acids can be increased in significant amounts in the product. The cholesterol-lowering effect of Benecol spreads is an additional effect of the stanol esters and unsaturated fatty acids in the product.
Stanol esters in low-fat foods, dairy and non-dairy foods
Of the cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
-lowering foods, dairy foods are gaining in popularity. Although yoghurt
Yoghurt
Yoghurt, yogurt or yogourt is a dairy product produced by bacterial fermentation of milk. The bacteria used to make yoghurt are known as "yoghurt cultures"...
remains a common product, yoghurt drinks have been the most popular version of new dairy Benecol products in recent years.
Plant stanol esters give dairy products a creamy texture with a very low fat content. Furthermore, because the fatty acids of stanol esters are derived from vegetable oils, the product's fatty acid profile is high in unsaturated and very low in saturated fatty acids.
Different soy- and cereal
Cereal
Cereals are grasses cultivated for the edible components of their grain , composed of the endosperm, germ, and bran...
-based non-dairy alternatives are also potential platforms for Benecol products. Especially in the USA, Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
and Central Europe
Central Europe
Central Europe or alternatively Middle Europe is a region of the European continent lying between the variously defined areas of Eastern and Western Europe...
, soy- and cereal-based non-dairy
Dairy
A dairy is a business enterprise established for the harvesting of animal milk—mostly from cows or goats, but also from buffalo, sheep, horses or camels —for human consumption. A dairy is typically located on a dedicated dairy farm or section of a multi-purpose farm that is concerned...
foods are gaining in popularity as dietary choices for good heart health. Plant stanol esters can be added to these foods using a technology similar to that used in the dairy industry. Stanol esters have an additional benefit in soy and cereal food applications because they can mask some of the off flavour these foods may have.
Furthermore, stanol esters can also mask bitterness. When added to soy products, less sugar or other sweetener is required to obtain a more pleasant taste and feeling to the mouth.
Cereal foods and pasta
Cereal foods, especially those rich in soluble fibre, are widely acknowledged as part of a healthy heart diet. Different types of cereal foods are therefore another potential Benecol application. The first cereal-based Benecol product was dry pasta, first marketed in Finland at the beginning of 2003. Stanol ester can also be added to breakfast cereals, such as muesliMuesli
Muesli is a popular breakfast cereal based on uncooked rolled oats, fruit and nuts. It was developed around 1900 by Swiss physician Maximilian Bircher-Benner for patients in his hospital...
. As in spreads and margarines, stanol esters replace part or all of the hard fat in granulated muesli products, thus lowering the saturated fatty acids content.