Stanol esters is a heterogeneous group of

chemical compound A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...

s known to reduce the level of

low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall dens ...

(LDL)

cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...

when ingested, though to a much lesser degree than prescription drugs such as

statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low ...

s. The starting material is

phytosterol Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. They encompass plant sterols and stanols. More than 250 sterols and related compounds have been identified. Free phy ...

s from plants. These are first

hydrogenated Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic ...

to give a plant stanol which is then

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...

ified with a mixture of

fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...

s also derived from plants. Plant stanol esters are found naturally occurring in small quantities in fruits, vegetables, nuts, seeds, cereals, legumes, and vegetable oils. Stanol ester is often added to

rapeseed Rapeseed (''Brassica napus ''subsp.'' napus''), also known as rape, or oilseed rape, is a bright-yellow flowering member of the family Brassicaceae (mustard or cabbage family), cultivated mainly for its oil-rich seed, which naturally contains a ...

oil based margarine or other foods for its health benefits. Studies have indicated that consumption of about 2-3 grams per day provides a reduction in LDL cholesterol of about 10-15%. The compound itself passes through the gut, with very little entering the

stream or

lymph Lymph (from Latin, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues ...

. Its presence in the gut, however, reduces both the amount of

the body absorbs from food and the reabsorption of the cholesterol component of bile. Despite a well documented cholesterol lowering effect, there are no data available indicating that

functional food A functional food is a food claimed to have an additional (often one related to health promotion or disease prevention) by adding new ingredients or more of existing ingredients. The term may also apply to traits purposely bred into existing edib ...

s supplemented with plant sterol esters reduce cardiovascular events. They are used in food products such as

Benecol Benecol is a brand of cholesterol-lowering food products owned by the Finnish company Raisio Group, which owns the trademark. Raisio Group licenses the Benecol brand and sells the ingredient stanol ester to food companies around the world. The ...

Sterol ester Sterol esters are a heterogeneous group of chemical compounds. They are created when the hydroxyl group of a sterol and a fatty acid undergo an esterification reaction. They can be found in trace amounts in every cell type but are highly enriched i ...

s can also be used for the same purpose. These compounds have the same effect to LDL, but they are partially absorbed by the body. The effects of higher serum plant sterol levels are so far not completely understood.

Plant stanols in nature

Plant sterols are

-like molecules found in all plant foods, with the highest concentrations occurring in

vegetable oil Vegetable oils, or vegetable fats, are oils extracted from seeds or from other parts of fruits. Like animal fats, vegetable fats are ''mixtures'' of triglycerides. Soybean oil, grape seed oil, and cocoa butter are examples of seed oils, or f ...

s. Plant sterols are plant equivalents of

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.

Plant stanols in human nutrition

Plant stanols are present in small amounts in human diet. Their main sources are

whole-grain A whole grain is a grain of any cereal and pseudocereal that contains the endosperm, cereal germ, germ, and bran, in contrast to refined grains, which retain only the endosperm. As part of a general healthy diet, consumption of whole grains is a ...

foods, mostly

wheat Wheat is a grass widely cultivated for its seed, a cereal grain that is a worldwide staple food. The many species of wheat together make up the genus ''Triticum'' ; the most widely grown is common wheat (''T. aestivum''). The archaeologi ...

and rye. The daily intake of stanols in the average

western diet The Western pattern diet is a modern dietary pattern that is generally characterized by high intakes of pre-packaged foods, refined grains, red meat, processed meat, high-sugar drinks, candy and sweets, fried foods, conventionally-raised anim ...

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. Following evidence from toxicological studies and numerous clinical trials, stanols are characterised as safe by authorities in several European Union countries and by the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA).

Structure and properties

Stanol esters are a saturated subgroup of sterol esters. Plant stanol esters in Benecol products are

esters of plant sterols. The sterol 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 colour 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

triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''wikt:tri-#Prefix, tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other ...

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

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 Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...

than the commonest

s. 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 Antioxidants are compounds that inhibit oxidation, a chemical reaction that can produce free radicals. This can lead to polymerization and other chain reactions. They are frequently added to industrial products, such as fuels and lubricants, ...

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

in a number of randomised, placebo-controlled double-blind clinical trials. However absolutely no effect on clinical endpoints such as CVD or mortality was demonstrated.

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 In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often ...

for

coronary heart disease Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pl ...

(CHD). Two

ABC transporters The ATP-binding cassette transporters (ABC transporters) are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. It is represented in all extant phyla, from prokaryotes to humans. ABC tran ...

(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 Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase it ...

back into the

intestinal lumen The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...

. 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 Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants of health and disease conditions in a defined population. It is a cornerstone of public health, and shapes policy decisions and evid ...

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:

Cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

absorption occurs via the formation of

micelles A micelle () or micella () (plural micelles or micellae, respectively) is an aggregate (or supramolecular assembly) of surfactant amphipathic lipid molecules dispersed in a liquid, forming a colloidal suspension (also known as associated coll ...

with

bile acids Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts. Prima ...

. 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 protein A transport protein (variously referred to as a transmembrane pump, transporter, escort protein, acid transport protein, cation transport protein, or anion transport protein) is a protein that serves the function of moving other materials within ...

s. It is thus hypothesised that stanols work in

by activating the excretion of cholesterol back into the

. 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 acid

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...

. As a consequence of the reduced absorption of cholesterol, the absorption of fat-soluble components other than cholesterol, such as

vitamin A vitamin is an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Essential nutrie ...

s and antioxidants, may also be reduced. Like cholesterol, carotenoids and

tocopherol Tocopherols (; TCP) are a class of organic chemical compounds (more precisely, various methylated phenols), many of which have vitamin E activity. Because the vitamin activity was first identified in 1936 from a dietary fertility factor in rat ...

s are transported by

lipoprotein A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, su ...

s. Since the number of

LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

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 A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

-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 β-Carotene is an organic, strongly coloured red-orange pigment abundant in fungi, plants, and fruits. It is a member of the carotenes, which are terpenoids (isoprenoids), synthesized biochemically from eight isoprene units and thus having 40 ...

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, also called vitamin A1, is a fat-soluble vitamin in the vitamin A family found in food and used as a dietary supplement. As a supplement it is used to treat and prevent vitamin A deficiency, especially that which results in xeroph ...

(vitamin A), 25-hydroxyvitamin D and

vitamin K Vitamin K refers to structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-synthesis modification of certain proteins that are required for blood coagulation ...

are unaffected by dietary plant sterols and stanols.

References

External links

American Heart Association

American Dietetic Association

Benecol products and research data

Key Clinical Trials

The Official International Site of Benecol
* {{cite journal , doi = 10.1161/01.CIR.103.8.1177 , title = Stanol/Sterol Ester-Containing Foods and Blood Cholesterol Levels : A Statement for Healthcare Professionals from the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association , year = 2001 , last1 = Lichtenstein , first1 = A. H. , last2 = Deckelbaum , first2 = R. J. , journal = Circulation , volume = 103 , issue = 8 , pages = 1177–9 , pmid = 11222485, doi-access = free Steroid esters