Phytosterol

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b-sitosterol, a prototypical phytosterol Sitosterol structure.svg
β-sitosterol, a prototypical phytosterol

Phytosterols are phytosteroids, similar to cholesterol, that serve as structural components of biological membranes of plants. [1] They encompass plant sterols and stanols. [1] More than 250 sterols and related compounds have been identified. [2] Free phytosterols extracted from oils are insoluble in water, relatively insoluble in oil, and soluble in alcohols.

Contents

Phytosterol-enriched foods and dietary supplements have been marketed for decades. [3] Despite well-documented LDL cholesterol-lowering effects from long-term consumption of phytosterols, there is insufficient evidence for an effect on cardiovascular diseases, fasting blood sugar, glycated hemoglobin, or overall mortality rate. [4] [5]

Structure

Nomenclature of the structure of a tetracyclic damarane triterpene Steroid numbering.svg
Nomenclature of the structure of a tetracyclic damarane triterpene

They have a fused polycyclic structure and vary in carbon side chains and / or presence or absence of a double bond (saturation). [3] They[ clarification needed ] are divided into 4,4-dimethyl phytosterols, 4-monomethyl phytosterols, and 4-desmethyl phytosterols based on the location of methyl groups at the carbon-4 position. [6] Stanols are saturated sterols, having no double bonds in the sterol ring structure.

The molecule in the article lead is β-sitosterol. The nomenclature is shown on the right.

In addition:

Dietary phytosterols

The richest naturally occurring sources of phytosterols are vegetable oils and products made from them. Sterols can be present in the free form and as fatty acid esters and glycolipids. The bound form is usually hydrolyzed in the small intestines by pancreatic enzymes. [7] Some of the sterols are removed during the deodorization step of refining oils and fats, without, however, changing their relative composition. Sterols are therefore a useful tool in checking authenticity.

As common sources of phytosterols, vegetable oils have been developed as margarine products highlighting phytosterol content. [3] Cereal products, vegetables, fruit and berries, which are not as rich in phytosterols, may also be significant sources of phytosterols due to their higher intakes. [8]

The intake of naturally occurring phytosterols ranges between ~200–300 mg/day depending on eating habits. [9] Specially designed vegetarian experimental diets have been produced yielding upwards of 700 mg/day. [10] The most commonly occurring phytosterols in the human diet are β-sitosterol, campesterol and stigmasterol, [3] which account for about 65%, 30% and 3% of diet contents, respectively. [11] The most common plant stanols in the human diet are sitostanol and campestanol, which combined make up about 5% of dietary phytosterol. [12]

Sterol composition in crude oils (as percentage of total sterol fraction) [13]
Cholesterol Brassicasterol Campesterol Stigmasterol β-Sitosterol ∆5-Avenasterol ∆7-Avenasterol ∆7-Stigmasterol
Coconut oil 0.6 – 20 – 0.97 – 1012 – 1850 – 705 – 160.6 – 22 – 8
Corn oil 0.2 – 0.60 – 0.218 – 244 – 855 – 674 – 81 – 31 – 4
Cottonseed oil 0.7 – 2.30.1 – 0.97.2 – 8.41.2 – 1.880 – 901.9 – 3.81.4 – 3.30.7 – 1.4
Olive oil 0 – 0.52.3 – 3.60.6 – 275.6 – 903.1 – 140 – 4
Palm oil 2.2 – 6.718.7 – 29.18.9 – 13.950.2 – 62.10 – 2.80 – 5.10.2 – 2.4
Palm kernel oil 1 – 3.70 – 0.38.4 – 12.712.3 – 16.162.6 – 70.44 – 90 – 1.40 – 2.1
Peanut oil 0.6 – 3.80 – 0.212 – 205 – 1348 – 657 – 90 – 50 – 5
Rapeseed oil 0.4 – 25 – 1318 – 390 – 0.745 – 580 – 6.60 – 0.80 – 5
Soybean oil 0.6 – 1.40 – 0.316 – 2416 – 1952 – 582 – 41 – 4.51.5 – 5
Sunflower oil 0.2 – 1.30 – 0.27 – 138 – 1156 – 632 – 77 – 133 – 6

Health claims

EFSA

The European Foods Safety Authority (EFSA) concluded that blood cholesterol can be reduced on average by 7 to 10.5% if a person consumes 1.5 to 2.4 grams of plant sterols and stanols per day, an effect usually established within 2–3 weeks. Longer-term studies extending up to 85 weeks showed that the cholesterol-lowering effect could be sustained. [14] Based on this and other efficacy data, the EFSA scientific panel provided the following health advisory: "Plant sterols have been shown to lower/reduce blood cholesterol. Blood cholesterol lowering may reduce the risk of coronary heart disease". [15]

FDA

The FDA has approved the following claim for phytosterols: For plant sterol esters : (i) Foods containing at least 0.65 g per serving of plant sterol esters, eaten twice a day with meals for a daily total intake of at least 1.3 g, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease. A serving of [name of the food] supplies ___grams of vegetable oil sterol esters. [16] For plant stanol esters: (i) Foods containing at least 1.7 g per serving of plant stanol esters, eaten twice a day with meals for a total daily intake of at least 3.4 g, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease. A serving of [name of the food] supplies ___grams of plant stanol esters. [17] Reviewing clinical trials involving phytosterol supplementation, the FDA concluded that when consumed in the range of 1 to 3 grams in enriched foods, phytosterols resulted in statistically significant (5-15%) reductions in blood LDL cholesterol levels relative to placebo. The FDA also concluded that a daily dietary intake of 2 grams a day of phytosterols (expressed as non-esterified phytosterols) is required to demonstrate a relationship between phytosterol consumption and cholesterol lowering for reduced CVD risk. [18]

Health Canada

Health Canada reviewed the evidence of 84 randomized controlled trials published between 1994 and 2007 involving phytosterol supplementation. An average 8.8% reduction in LDL-cholesterol was observed at a mean intake of 2 grams per day. [19] Health Canada concluded that sufficient scientific evidence exists to support a relationship between phytosterol consumption and blood cholesterol lowering. Based on this evidence, Health Canada approved the following statements for qualifying foods intended for hypercholesterolemic individuals: Primary statement: "[serving size from Nutrition Facts table in metric and common household measures] of [naming the product] provides X% of the daily amount* of plant sterols shown to help reduce/lower cholesterol in adults." Two additional statements that could be used in combination or alone, adjacent to the primary statement, without any intervening printed, written or graphic material: "Plant sterols help reduce [or help lower] cholesterol." This statement when used, shall be shown in letters up to twice the size and prominence as those of the primary statement. "High cholesterol is a risk factor for heart disease." This statement when used, shall be shown in letters up to the same size and prominence as those of the primary statement.

Cholesterol lowering

The ability of phytosterols to reduce cholesterol levels was first demonstrated in humans in 1953. [20] [21] From 1954 to 1982, phytosterols were subsequently marketed as a pharmaceutical under the name Cytellin as a treatment for elevated cholesterol. [22]

Unlike the statins, where cholesterol lowering has been proven to reduce risk of cardiovascular diseases (CVD) and overall mortality under well-defined circumstances, the evidence has been inconsistent for phytosterol-enriched foods or supplements to lower risk of CVD, with two reviews indicating no or marginal effect, [23] [4] and another review showing evidence for use of dietary phytosterols to attain a cholesterol-lowering effect. [24]

Coadministration of statins with phytosterol-enriched foods increases the cholesterol-lowering effect of phytosterols, again without any proof of clinical benefit and with anecdotal evidence of potential adverse effects. [23] Statins work by reducing cholesterol synthesis via inhibition of the rate-limiting HMG-CoA reductase enzyme. Phytosterols reduce cholesterol levels by competing with cholesterol absorption in the gut via one or several possible mechanisms, [25] [26] [27] an effect that complements statins. Phytosterols further reduce cholesterol levels by about 9% to 17% in statin users. [28] The type or dose of statin does not appear to affect the cholesterol-lowering efficacy of phytosterols. [29]

Because of their cholesterol reducing properties, some manufacturers are using sterols or stanols as a food additive. [3] [30]

Safety

Phytosterols have a long history of safe use, [3] dating back to Cytellin, the pharmaceutical preparation of phytosterols marketed in the US from 1954 to 1982. [22] Phytosterol esters have generally recognized as safe (GRAS) status in the US. [31] Phytosterol-containing functional foods were subject to postlaunch monitoring after being introduced to the EU market in 2000, and no unpredicted side effects were reported. [32]

A potential safety concern regarding phytosterol consumption is in patients with phytosterolaemia, a rare genetic disorder which results in a 50- to 100-fold increase in blood plant sterol levels and is associated with rapid development of coronary atherosclerosis. Phytosterolaemia has been linked to mutations in the ABCG5/G8 proteins which pump plant sterols out of enterocytes and hepatocytes into the lumen and bile ducts, respectively. Plant sterol levels in the blood have been shown to be positively, negatively or not associated with CVD risk, depending on the study population investigated. [33] [34] [35] [36] [37] [38] [39] [40]

The link between plant sterols and CVD or CHD risk is complicated because phytosterol levels reflect cholesterol absorption. (See Phytosterols as a marker for cholesterol absorption).[ citation needed ]

Sterol vs stanol

The equivalent ability and safety of plant sterols and plant stanols to lower cholesterol continues to be a hotly debated topic. Plant sterols and stanols, when compared head-to-head in clinical trials, have been shown to equally reduce cholesterol levels. [41] [42] [43] A meta-analysis of 14 randomized, controlled trials comparing plant sterols to plant stanols directly at doses of 0.6 to 2.5 g/day showed no difference between the two forms on total cholesterol, LDL cholesterol, HDL cholesterol, or triglyceride levels. [44] Trials looking at high doses (> 4 g/day) of plant sterols or stanols are very limited, and none have yet to be completed comparing the same high dose of plant sterol to plant stanol.

The debate regarding sterol vs. stanol safety is centered on their differing intestinal absorption and resulting plasma concentrations. Phytostanols have a lower estimated intestinal absorption rate (0.02 - 0.3%) than phytosterols (0.4 - 5%) and consequently blood phytostanol concentration is generally lower than phytosterol concentration. [23]

Research

Phytosterols are under preliminary research for their potential to inhibit lung, stomach, ovarian and breast cancers, [45] [46] as well as colon and prostate cancers. [47]

Functions in plants

Sterols are essential for all eukaryotes. In contrast to animal and fungal cells, which contain only one major sterol, plant cells synthesize an array of sterol mixtures in which sitosterol and stigmasterol predominate. [48] Sitosterol regulates membrane fluidity and permeability in a similar manner to cholesterol in mammalian cell membranes. [49] Plant sterols can also modulate the activity of membrane-bound enzymes. [49] Phytosterols are also linked to plant adaptation to temperature and plant immunity against pathogens. [50]

Related Research Articles

<span class="mw-page-title-main">Cholesterol</span> Sterol biosynthesized by all animal cells

Cholesterol is the principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.

High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle. HDL particles enlarge while circulating in the blood, aggregating more fat molecules and transporting up to hundreds of fat molecules per particle.

<span class="mw-page-title-main">Low-density lipoprotein</span> One of the five major groups of 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, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL is involved in atherosclerosis, a process in which it is oxidized within the walls of arteries.

<span class="mw-page-title-main">Atherosclerosis</span> Form of arteriosclerosis

Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. These lesions may lead to narrowing of the arteries' walls due to buildup of atheromatous plaques. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. In severe cases, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney disorders, depending on which body parts(s) the affected arteries are located in the body.

<span class="mw-page-title-main">Statin</span> Class of drugs used to lower cholesterol levels

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 commonly prescribed cholesterol-lowering drugs.

Lipid-lowering agents, also sometimes referred to as hypolipidemic agents, cholesterol-lowering drugs, or antihyperlipidemic agents are a diverse group of pharmaceuticals that are used to lower the level of lipids and lipoproteins such as cholesterol, in the blood (hyperlipidemia). The American Heart Association recommends the descriptor 'lipid lowering agent' be used for this class of drugs rather than the term 'hypolipidemic'.

<span class="mw-page-title-main">Cardiovascular disease</span> Class of diseases that involve the heart or blood vessels

Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, arrhythmia, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis.

<span class="mw-page-title-main">Hypercholesterolemia</span> High levels of cholesterol in the blood

Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia, hyperlipoproteinemia, and dyslipidemia.

Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular diseases (ASCVD), which include coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for ASCVD, abnormal levels don't mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.

<span class="mw-page-title-main">Stanol ester</span> Class of chemical compounds

Stanol esters is a heterogeneous group of chemical compounds known to reduce the level of low-density lipoprotein (LDL) cholesterol in blood when ingested, though to a much lesser degree than prescription drugs such as statins. The starting material is phytosterols from plants. These are first hydrogenated to give a plant stanol which is then esterified with a mixture of fatty acids also derived from plants. Plant stanol esters are found naturally occurring in small quantities in fruits, vegetables, nuts, seeds, cereals, legumes, and vegetable oils.

Hyperlipidemia is abnormally high levels of any or all lipids or lipoproteins in the blood. The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding. Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing medication to control blood lipid levels.

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 in foam cells and are common components of human skin oil.

<span class="mw-page-title-main">Campesterol</span> Chemical compound

Campesterol is a phytosterol whose chemical structure is similar to that of cholesterol, and is one of the ingredients for E number E499.

<span class="mw-page-title-main">Stigmasterol</span> Chemical compound

Stigmasterol – a plant sterol (phytosterol) – is among the most abundant of plant sterols, having a major function to maintain the structure and physiology of cell membranes. In the European Union, it is a food additive listed with E number E499, and may be used in food manufacturing to increase the phytosterol content, potentially lowering the levels of LDL cholesterol.

<i>beta</i>-Sitosterol Chemical compound

β-sitosterol (beta-sitosterol) is one of several phytosterols with chemical structures similar to that of cholesterol. It is a white, waxy powder with a characteristic odor, and is one of the components of the food additive E499. Phytosterols are hydrophobic and soluble in alcohols.

<span class="mw-page-title-main">Benecol</span> Brand of cholesterol-lowering food products

Benecol is a brand of cholesterol-lowering food products owned by the Finnish company Raisio Group, which owns the trademark.

<span class="mw-page-title-main">Sitosterolemia</span> Medical condition

Sitosterolemia is a rare autosomal recessively inherited lipid metabolic disorder. It is characterized by hyperabsorption and decreased biliary excretion of dietary sterols. Healthy persons absorb only about 5% of dietary plant sterols, but sitosterolemia patients absorb 15% to 60% of ingested sitosterol without excreting much into the bile. The phytosterol campesterol is more readily absorbed than sitosterol.

<span class="mw-page-title-main">Familial hypercholesterolemia</span> Genetic disorder characterized by high cholesterol levels

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol, in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly. Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH. Nevertheless, treatment is usually effective.

The chronic endothelial injury hypothesis is one of two major mechanisms postulated to explain the underlying cause of atherosclerosis and coronary heart disease (CHD), the other being the lipid hypothesis. Although an ongoing debate involving connection between dietary lipids and CHD sometimes portrays the two hypotheses as being opposed, they are in no way mutually exclusive. Moreover, since the discovery of the role of LDL cholesterol (LDL-C) in the pathogenesis of atherosclerosis, the two hypotheses have become tightly linked by a number of molecular and cellular processes.

Therapeutic Lifestyle Changes, also known as the TLC Diet, is a dietary pattern recommended by the National Cholesterol Education Program, part of the National Institutes of Health, to control hypercholesterolemia. This pattern focuses on saturated fats and cholesterol, dietary options to enhance LDL cholesterol lowering, weight control, and physical activity.

References

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  2. ↑ Akhisa, T.; Kokke, W. (1991). "Naturally occurring sterols and related compounds from plants". In Patterson, G. W.; Nes, W. D. (eds.). Physiology and Biochemistry of Sterols. Champaign, IL: American Oil Chemists' Society. pp. 172–228.
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