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 density ...

(LDL)

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

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 is com ...

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

statin Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...

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 stanol ester, stanols. More than 250 sterols and related compounds have been identified ...

s from plants. These are first hydrogenated to give a plant stanol (phytostanol) which is then

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

ified with a mixture of

fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...

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 and oilseed rape and canola, is a bright-yellow flowering member of the family Brassicaceae (mustard or cabbage family), cultivated mainly for its oil-rich seed, which naturall ...

oil-based

margarine Margarine (, also , ) is a Spread (food), spread used for flavoring, baking, and cooking. It is most often used as a substitute for butter. Although originally made from animal fats, most margarine consumed today is made from vegetable oil. The ...

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 () 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 to be recirculated. At the ori ...

. 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 Bile (from Latin ''bilis''), also known as gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is pro ...

. Despite a well documented cholesterol lowering effect, there are no data available indicating that functional foods supplemented with plant sterol esters reduce cardiovascular events. They are used in food products such as Benecol. Sterol esters 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 edible plants. Like animal fats, vegetable fats are ''mixtures'' of triglycerides. Soybean oil, grape seed oil, and cocoa butter are examples of seed ...

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, 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 associated wit ...

foods, mostly

wheat Wheat is a group of wild and crop domestication, domesticated Poaceae, grasses of the genus ''Triticum'' (). They are Agriculture, cultivated for their cereal grains, which are staple foods around the world. Well-known Taxonomy of wheat, whe ...

and

rye Rye (''Secale cereale'') is a grass grown extensively as a grain, a cover crop and a forage crop. It is grown principally in an area from Eastern and Northern Europe into Russia. It is much more tolerant of cold weather and poor soil than o ...

. 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. Following evidence from toxicological studies and numerous

clinical trials Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

, 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 respo ...

(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 (from '' tri-'' and '' glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and other vertebrates ...

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

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 Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. 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

in a number of randomised, placebo-controlled double-blind

. However absolutely no effect on clinical endpoints such as CVD or mortality was demonstrated.

Dual effect of plant stanols

Plant stanols 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 use ...

for

coronary heart disease Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...

(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 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 i ...

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 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, and application of this knowledge to prevent diseases. It is a cornerstone ...

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

and can be divided into two steps: * Step 1:

Cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

absorption occurs via the formation of micelles 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 in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...

. 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

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

metabolism Metabolism (, from ''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 cellular processes; the co ...

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

vitamin Vitamins are Organic compound, organic molecules (or a set of closely related molecules called vitamer, vitamers) that are essential to an organism in small quantities for proper metabolism, metabolic function. Nutrient#Essential nutrients, ...

s and

antioxidant Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...

s, may also be reduced. Like cholesterol,

carotenoid Carotenoids () are yellow, orange, and red organic pigments that are produced by plants and algae, as well as several bacteria, archaea, and fungi. Carotenoids give the characteristic color to pumpkins, carrots, parsnips, corn, tomatoes, cana ...

s and

tocopherol Tocopherols (; TCP) are a class of organic compounds comprising 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 rats, it was named ''t ...

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, sur ...

s. 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 A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

-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

s. 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, also called vitamin A1, is a fat-soluble vitamin in the vitamin A family that is found in food and used as a dietary supplement. Retinol or other forms of vitamin A are needed for vision, cellular development, maintenance of skin and ...

(vitamin A), 25-hydroxyvitamin D and

vitamin K Vitamin K is a family of structurally similar, fat-soluble vitamers found in foods and marketed as dietary supplements. The human body requires vitamin K for post-translational modification, post-synthesis modification of certain proteins ...

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