Cholesterol, from the Greek chole- (bile) and stereos (solid) followed by the chemical suffix -ol for an alcohol, is an organic chemical substance classified as a waxy steroid of fat. It is an essential structural component of mammalian cell membranes and is required to establish proper membrane permeability and fluidity.
In addition to its importance within cells, cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acids, and vitamin D.<ref name="pmid22217824">Template:Cite journal</ref> Cholesterol is the principal sterol synthesized by animals; in vertebrates it is formed predominantly in the liver. Small quantities are synthesized in other cellular organisms (eukaryotes) such as plants and fungi. It is almost completely absent among prokaryotes (i.e., bacteria).
Although cholesterol is important and necessary for human health, high levels of cholesterol in the blood have been linked to damage to arteries and cardiovascular disease.<ref name="NHS: High cholesterol levels"/>
François Poulletier de la Salle first identified cholesterol in solid form in gallstones, in 1769. However, it was only in 1815 that chemist Eugène Chevreul named the compound "cholesterine".<ref name="pmid9478044">Template:Cite journal</ref>
Since cholesterol is essential for all animal life, each cell synthesizes it from simpler molecules, a complex 37-step process which starts with the intracellular protein enzyme HMG-CoA reductase. However, normal and especially high levels of fats (including cholesterol) within the blood circulation, depending on how it is transported within lipoproteins, are strongly associated with progression of atherosclerosis.
For a man of about 68 kg (150 pounds), typical total body-cholesterol synthesis is about 1 g (1,000 mg) per day, and total body content is about 35 g, primarily located within all the membranes of all the cells of the body. Typical daily dietary intake of additional cholesterol, in the United States, is 200–300 mg.<ref name="cdc-calories">Template:Cite web </ref>
However, most ingested cholesterol is esterified and esterified cholesterol is poorly absorbed. The body also compensates for any absorption of additional cholesterol by reducing cholesterol synthesis.<ref> Template:Cite journal</ref> For these reasons, cholesterol intake in food has little, if any, effect on total body cholesterol content or concentrations of cholesterol in the blood.
Cholesterol is recycled. The liver excretes it in a non-esterified form (via bile) into the digestive tract. Typically about 50% of the excreted cholesterol is reabsorbed by the small bowel back into the bloodstream.
Some plants make cholesterol in very small amounts.<ref name="Plant cholesterol">, http://chemistry.osu.edu/~gopalan.5/file/7B.PDF.</ref> Plants manufacture phytosterols (substances chemically similar to cholesterol produced within plants), which can compete with cholesterol for reabsorption in the intestinal tract, thus potentially reducing cholesterol reabsorption.<ref name="pmid17218830">Template:Cite journal</ref> However, phytosterols are foreign to animal cells and, if absorbed, accelerate the progression of atherosclerosis.Template:Citation needed When intestinal lining cells absorb phytosterols, in place of cholesterol, they usually excrete the phytosterol molecules back into the GI tract, an important protective mechanism.
Cholesterol is required to build and maintain membranes; it modulates membrane fluidity over the range of physiological temperatures. The hydroxyl group on cholesterol interacts with the polar head groups of the membrane phospholipids and sphingolipids, while the bulky steroid and the hydrocarbon chain are embedded in the membrane, alongside the nonpolar fatty-acid chain of the other lipids. Through the interaction with the phospholipid fatty-acid chains, cholesterol increases membrane packing, which reduces membrane fluidity.<ref name="isbn1-4292-4646-4">Template:Cite book</ref> The structure of the tetracyclic ring of cholesterol contributes to the decreased fluidity of the cell membrane as the molecule is in a trans conformation making all but the side chain of cholesterol rigid and planar.<ref name="pmid11694269">Template:Cite journal</ref> In this structural role, cholesterol reduces the permeability of the plasma membrane to neutral solutes,<ref name="pmid1664240">Template:Cite journal</ref> protons, (positive hydrogen ions) and sodium ions.<ref name="Haines_2001">Template:Cite journal</ref>
Within the cell membrane, cholesterol also functions in intracellular transport, cell signaling and nerve conduction. Cholesterol is essential for the structure and function of invaginated caveolae and clathrin-coated pits, including caveola-dependent and clathrin-dependent endocytosis. The role of cholesterol in such endocytosis can be investigated by using methyl beta cyclodextrin (MβCD) to remove cholesterol from the plasma membrane. Recently, cholesterol has also been implicated in cell signaling processes, assisting in the formation of lipid rafts in the plasma membrane. Lipid raft formation brings receptor proteins in close proximity with high concentrations of second messenger molecules.<ref name="pmid10712926">Template:Cite journal </ref> In many neurons, a myelin sheath, rich in cholesterol, since it is derived from compacted layers of Schwann cell membrane, provides insulation for more efficient conduction of impulses.<ref name="isbn0-7817-5056-3">Template:Cite book</ref>
Within cells, cholesterol is the precursor molecule in several biochemical pathways. In the liver, cholesterol is converted to bile, which is then stored in the gallbladder. Bile contains bile salts, which solubilize fats in the digestive tract and aid in the intestinal absorption of fat molecules as well as the fat-soluble vitamins, A, D, E, and K. Cholesterol is an important precursor molecule for the synthesis of vitamin D and the steroid hormones, including the adrenal gland hormones cortisol and aldosterone, as well as the sex hormones progesterone, estrogens, and testosterone, and their derivatives.<ref name="pmid22217824" />
Animal fats are complex mixtures of triglycerides, with lesser amounts of phospholipids and cholesterol. As a consequence, all foods containing animal fat contain cholesterol to varying extents.<ref name="isbn0-9531949-5-7">Template:Cite book</ref> Major dietary sources of cholesterol include cheese, egg yolks, beef, pork, poultry, fish, and shrimp.<ref name=USDA/> Human breast milk also contains significant quantities of cholesterol.<ref name=ajcn-breastmilk>Template:Cite journal</ref>
From a dietary perspective, cholesterol is not found in significant amounts in plant sources.<ref name=USDA>Template:Cite web</ref><ref name="Behrman_2005">Template:Cite journal</ref> In addition, plant products such as flax seeds and peanuts contain cholesterol-like compounds called phytosterols, which are believed to compete with cholesterol for absorption in the intestines.<ref name=ostlund2003>Template:Cite journal</ref> Phytosterols can be supplemented through the use of phytosterol-containing functional foods or nutraceuticals that are widely recognized as having a proven LDL cholesterol-lowering efficacy.<ref>Template:Cite web</ref> Current supplemental guidelines recommend doses of phytosterols in the 1.6-3.0 grams per day range (Health Canada, EFSA, ATP III,FDA) with a recent meta-analysis demonstrating an 8.8% reduction in LDL-cholesterol at a mean dose of 2.15 gram per day.<ref> Template:Cite journal </ref> However, the benefits of a diet supplemented with phytosterol has been questioned.<ref name="pmid21257611">Template:Cite journal</ref><ref name="pmid19158117">Template:Cite journal</ref>
Fat-intake also plays a role in blood-cholesterol levels. This effect is thoughtTemplate:By whom to come about by changes in the quantity of cholesterol and lipoproteins that are synthesized by the body. Isocalorically replacing dietary carbohydrates with monounsaturated and polyunsaturated fats has been shown to lower serum LDL and total cholesterol levels and increase serum HDL levels, while replacing carbohydrates with saturated fat was shown to increase total, HDL, and LDL cholesterol levels.<ref name="pmid1386252">Template:Cite journal</ref> Trans fats have been shown to reduce levels of HDL whilst increasing levels of LDL.<ref name="pmid9322581">Template:Cite journal</ref> Based on such evidence and evidence implicating low HDL and high LDL levels in cardiovascular disease (see Hypercholesterolemia), many health authorities advocate reducing LDL cholesterol through changes in diet in addition to other lifestyle modifications.<ref name="NHS: High cholesterol levels">Template:Cite web</ref> The USDA for example recommends that those wishing to reduce their cholesterol through a change in diet should aim to consume less than 7% of their daily energy needs from saturated fat and fewer than 200 mg of cholesterol per day.<ref name="USDA-DGA-2005">Template:Cite web</ref> An alternative view is that any reduction to dietary cholesterol intake could be counteracted by the organs compensating to try to keep blood cholesterol levels constant.<ref name="isbn0-7867-0732-1">Template:Cite book</ref>
However, the The China Study uses epidemiological evidence to claim that casein raises blood cholesterol even more than the ingested saturated fat or cholesterol.<ref name="isbn1-932100-38-5">Template:Cite book</ref>
All animal cells manufacture cholesterol with relative production rates varying by cell type and organ function. About 20–25% of total daily cholesterol production occurs in the liver; other sites of higher synthesis rates include the intestines, adrenal glands, and reproductive organs. Synthesis within the body starts with one molecule of acetyl CoA and one molecule of acetoacetyl-CoA, which are hydrated to form 3-hydroxy-3-methylglutaryl CoA (HMG-CoA). This molecule is then reduced to mevalonate by the enzyme HMG-CoA reductase. This step is the regulated, rate-limiting and irreversible step in cholesterol synthesis and is the site of action for the statin drugs (HMG-CoA reductase competitive inhibitors).
Mevalonate is then converted to 3-isopentenyl pyrophosphate in three reactions that require ATP. Mevalonate is decarboxylated to isopentenyl pyrophosphate, which is a key metabolite for various biological reactions. Three molecules of isopentenyl pyrophosphate condense to form farnesyl pyrophosphate through the action of geranyl transferase. Two molecules of farnesyl pyrophosphate then condense to form squalene by the action of squalene synthase in the endoplasmic reticulum. Oxidosqualene cyclase then cyclizes squalene to form lanosterol. Finally, lanosterol is then converted to cholesterol through a 19 step complex process.<ref>Template:Cite book</ref><ref name="isbn0-7167-2009-4">Template:Cite book</ref>
Regulation of cholesterol synthesis
Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though the homeostatic mechanisms involved are only partly understood. A higher intake from food leads to a net decrease in endogenous production, whereas lower intake from food has the opposite effect. The main regulatory mechanism is the sensing of intracellular cholesterol in the endoplasmic reticulum by the protein SREBP (sterol regulatory element-binding protein 1 and 2).<ref name="pmid17666007">Template:Cite journal</ref> In the presence of cholesterol, SREBP is bound to two other proteins: SCAP (SREBP-cleavage-activating protein) and Insig1. When cholesterol levels fall, Insig-1 dissociates from the SREBP-SCAP complex, allowing the complex to migrate to the Golgi apparatus, where SREBP is cleaved by S1P and S2P (site-1 and -2 protease), two enzymes that are activated by SCAP when cholesterol levels are low. The cleaved SREBP then migrates to the nucleus and acts as a transcription factor to bind to the sterol regulatory element (SRE), which stimulates the transcription of many genes. Among these are the low-density lipoprotein (LDL) receptor and HMG-CoA reductase. The former scavenges circulating LDL from the bloodstream, whereas HMG-CoA reductase leads to an increase of endogenous production of cholesterol.<ref>Template:Cite journal</ref> A large part of this signaling pathway was clarified by Dr. Michael S. Brown and Dr. Joseph L. Goldstein in the 1970s. In 1985, they received the Nobel Prize in Physiology or Medicine for their work. Their subsequent work shows how the SREBP pathway regulates expression of many genes that control lipid formation and metabolism and body fuel allocation.
Cholesterol synthesis can be turned off when cholesterol levels are high, as well. HMG CoA reductase contains both a cytosolic domain (responsible for its catalytic function) and a membrane domain. The membrane domain functions to sense signals for its degradation. Increasing concentrations of cholesterol (and other sterols) cause a change in this domain's oligomerization state, which makes it more susceptible to destruction by the proteosome. This enzyme's activity can also be reduced by phosphorylation by an AMP-activated protein kinase. Because this kinase is activated by AMP, which is produced when ATP is hydrolyzed, it follows that cholesterol synthesis is halted when ATP levels are low.<ref name="isbn0-7167-4955-6">Template:Cite book</ref>
Plasma transport and regulation of absorption
Cholesterol is only slightly soluble in water; it can dissolve and travel in the water-based bloodstream at exceedingly small concentrations. Since cholesterol is insoluble in blood, it is transported in the circulatory system within lipoproteins, complex discoidal particles that have an exterior composed of amphiphilic proteins and lipids whose outward-facing surfaces are water-soluble and inward-facing surfaces are lipid-soluble; triglycerides and cholesterol esters are carried internally. Phospholipids and cholesterol, being amphipathic, are transported in the surface monolayer of the lipoprotein particle.
In addition to providing a soluble means for transporting cholesterol through the blood, lipoproteins have cell-targeting signals that direct the lipids they carry to certain tissues. For this reason, there are several types of lipoproteins within blood called, in order of increasing density, chylomicrons, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). The more lipid and less protein a lipoprotein has the less dense it is. The cholesterol within all the various lipoproteins is identical, although some cholesterol is carried as the "free" alcohol and some is carried as fatty acyl esters referred to as cholesterol esters. However, the different lipoproteins contain apolipoproteins, which serve as ligands for specific receptors on cell membranes. In this way, the lipoprotein particles are molecular addresses that determine the start- and endpoints for cholesterol transport.
Chylomicrons, the least dense type of cholesterol transport molecules, contain apolipoprotein B-48, apolipoprotein C, and apolipoprotein E in their shells. Chylomicrons are the transporters that carry fats from the intestine to muscle and other tissues that need fatty acids for energy or fat production. Cholesterol that is not used by muscles remains in more cholesterol-rich chylomicron remnants, which are taken up from here to the bloodstream by the liver.
VLDL molecules are produced by the liver and contain excess triacylglycerol and cholesterol that is not required by the liver for synthesis of bile acids. These molecules contain apolipoprotein B100 and apolipoprotein E in their shells. During transport in the bloodstream, the blood vessels cleave and absorb more triacylglycerol from IDL molecules, which contain an even higher percentage of cholesterol. The IDL molecules have two possible fates: Half are into metabolism by HTGL, taken up by the LDL receptor on the liver cell surfaces, and the other half continue to lose triacylglycerols in the bloodstream until they form LDL molecules, which have the highest percentage of cholesterol within them.
LDL molecules, therefore, are the major carriers of cholesterol in the blood, and each one contains approximately 1,500 molecules of cholesterol ester. The shell of the LDL molecule contains just one molecule of apolipoprotein B100, which is recognized by the LDL receptor in peripheral tissues. Upon binding of apolipoprotein B100, many LDL receptors become localized in clathrin-coated pits. Both the LDL and its receptor are internalized by endocytosis to form a vesicle within the cell. The vesicle then fuses with a lysosome, which has an enzyme called lysosomal acid lipase that hydrolyzes the cholesterol esters. Now within the cell, the cholesterol can be used for membrane biosynthesis or esterified and stored within the cell, so as to not interfere with cell membranes.
Synthesis of the LDL receptor is regulated by SREBP, the same regulatory protein as was used to control synthesis of cholesterol de novo in response to cholesterol presence in the cell. When the cell has abundant cholesterol, LDL receptor synthesis is blocked so new cholesterol in the form of LDL molecules cannot be taken up. On the converse, more LDL receptors are made when the cell is deficient in cholesterol. When this system is deregulated, many LDL molecules appear in the blood without receptors on the peripheral tissues. These LDL molecules are oxidized and taken up by macrophages, which become engorged and form foam cells. These cells often become trapped in the walls of blood vessels and contribute to atherosclerotic plaque formation. Differences in cholesterol homeostasis affect the development of early atherosclerosis (carotid intima-media thickness).<ref name="pmid20976107">Template:Cite journal</ref> These plaques are the main causes of heart attacks, strokes, and other serious medical problems, leading to the association of so-called LDL cholesterol (actually a lipoprotein) with "bad" cholesterol.<ref name="isbn0-7167-4955-6"/>
Also, HDL particles are thought to transport cholesterol back to the liver for excretion or to other tissues that use cholesterol to synthesize hormones in a process known as reverse cholesterol transport (RCT).<ref name="pmid15976321">Template:Cite journal</ref> Having large numbers of large HDL particles correlates with better health outcomes.<ref name="pmid2642759">Template:Cite journal</ref> In contrast, having small numbers of large HDL particles is independently associated with atheromatous disease progression within the arteries.
Metabolism, recycling and excretion
Cholesterol is susceptible to oxidation and easily forms oxygenated derivatives known as oxysterols. Three different mechanisms can form these; autoxidation, secondary oxidation to lipid peroxidation, and cholesterol-metabolizing enzyme oxidation. A great interest in oxysterols arose when they were shown to exert inhibitory actions on cholesterol biosynthesis.<ref name="pmid663671">Template:Cite journal</ref> This finding became known as the “oxysterol hypothesis”. Additional roles for oxysterols in human physiology include their: participation in bile acid biosynthesis, function as transport forms of cholesterol, and regulation of gene transcription.<ref name="pmid11111082">Template:Cite journal</ref>
In biochemical experiments radiolabelled forms of cholesterol, such as tritiated-cholesterol are used. These derivatives undergo degradation upon storage and it is essential to purify cholesterol prior to use. Cholesterol can be purified using small Sephadex LH-20 columns.<ref name="HanukogluJefcoate1980">Template:Cite journal</ref>
Cholesterol is oxidized by the liver into a variety of bile acids.<ref name="pmid8001744">Template:Cite journal</ref> These, in turn, are conjugated with glycine, taurine, glucuronic acid, or sulfate. A mixture of conjugated and nonconjugated bile acids, along with cholesterol itself, is excreted from the liver into the bile. Approximately 95% of the bile acids are reabsorbed from the intestines, and the remainder are lost in the feces.<ref name="pmid12529265">Template:Cite journal</ref> The excretion and reabsorption of bile acids forms the basis of the enterohepatic circulation, which is essential for the digestion and absorption of dietary fats. Under certain circumstances, when more concentrated, as in the gallbladder, cholesterol crystallises and is the major constituent of most gallstones. Although, lecithin and bilirubin gallstones also occur, but less frequently.<ref name="pmid17547709">Template:Cite journal</ref> Every day, up to 1 g of cholesterol enters the colon. This cholesterol originates from the diet, bile, and desquamated intestinal cells, and can be metabolized by the colonic bacteria. Cholesterol is converted mainly into coprostanol, a nonabsorbable sterol that is excreted in the feces. A cholesterol-reducing bacterium origin has been isolated from human feces.<ref name="pmid17616613">Template:Cite journal</ref>Template:Primary source-inline
Template:Main According to the lipid hypothesis, abnormal cholesterol levels (hypercholesterolemia) — that is, higher concentrations of LDL and lower concentrations of functional HDL — are strongly associated with cardiovascular disease because these promote atheroma development in arteries (atherosclerosis). This disease process leads to myocardial infarction (heart attack), stroke, and peripheral vascular disease. Since higher blood LDL, especially higher LDL particle concentrations and smaller LDL particle size, contribute to this process more than the cholesterol content of the HDL particles,<ref name="pmid18375431">Template:Cite journal</ref> LDL particles are often termed "bad cholesterol" because they have been linked to atheroma formation. On the other hand, high concentrations of functional HDL, which can remove cholesterol from cells and atheroma, offer protection and are sometimes referred to as "good cholesterol". These balances are mostly genetically determined, but can be changed by body build, medications, food choices, and other factors.<ref name="pmid12957096">Template:Cite journal</ref> Resistin, a protein secreted by fat tissue, has been shown to increase the production of LDL in human liver cells and also degrades LDL receptors in the liver. As a result, the liver is less able to clear cholesterol from the bloodstream. Resistin accelerates the accumulation of LDL in arteries, increasing the risk of heart disease. Resistin also adversely impacts the effects of statins, the main cholesterol-reducing drug used in the treatment and prevention of cardiovascular disease.<ref name=Canadian scientists discover cause of high cholesterol>Template:Cite web </ref>
Conditions with elevated concentrations of oxidized LDL particles, especially "small dense LDL" (sdLDL) particles, are associated with atheroma formation in the walls of arteries, a condition known as atherosclerosis, which is the principal cause of coronary heart disease and other forms of cardiovascular disease. In contrast, HDL particles (especially large HDL) have been identified as a mechanism by which cholesterol and inflammatory mediators can be removed from atheroma. Increased concentrations of HDL correlate with lower rates of atheroma progressions and even regression. A 2007 study pooling data on almost 900,000 subjects in 61 cohorts demonstrated that blood total cholesterol levels have an exponential effect on cardiovascular and total mortality, with the association more pronounced in younger subjects. Still, because cardiovascular disease is relatively rare in the younger population, the impact of high cholesterol on health is still larger in older people.<ref name="pmid18061058">Template:Cite journal</ref>
Elevated levels of the lipoprotein fractions, LDL, IDL and VLDL are regarded as atherogenic (prone to cause atherosclerosis).<ref name=NCEPIII>Template:Cite web</ref> Levels of these fractions, rather than the total cholesterol level, correlate with the extent and progress of atherosclerosis. Conversely, the total cholesterol can be within normal limits, yet be made up primarily of small LDL and small HDL particles, under which conditions atheroma growth rates would still be high. In contrast, however, if LDL particle number is low (mostly large particles) and a large percentage of the HDL particles are large, then atheroma growth rates are usually low, even negative, for any given total cholesterol concentration.Template:Citation needed Recently, a post hoc analysis of the IDEAL and the EPIC prospective studies found an association between high levels of HDL cholesterol (adjusted for apolipoprotein A-I and apolipoprotein B) and increased risk of cardiovascular disease, casting doubt on the cardioprotective role of "good cholesterol".<ref name="pmid18261682">Template:Cite journal</ref>
Elevated cholesterol levels are treated with a strict diet consisting of low saturated fat, trans fat-free, low cholesterol foods,<ref name="urlHow Can I Lower High Cholesterol?">Template:Cite web</ref><ref name="urlGood Cholesterol Foods">Template:Cite web</ref> often followed by one of various hypolipidemic agents, such as statins, fibrates, cholesterol absorption inhibitors, nicotinic acid derivatives or bile acid sequestrants.<ref name=NICE67>Template:NICE</ref> Extreme cases have previously been treated with partial ileal bypass surgery, which has now been superseded by medication. Apheresis-based treatments are still used for very severe hyperlipidemias that are either unresponsive to treatment or require rapid lowering of blood lipids.Template:Citation needed
Multiple human trials using HMG-CoA reductase inhibitors, known as statins, have repeatedly confirmed that changing lipoprotein transport patterns from unhealthy to healthier patterns significantly lowers cardiovascular disease event rates, even for people with cholesterol values currently considered low for adults.Template:Citation needed Studies have also found that statins reduce atheroma progression.<ref name="pmid18666843">Template:Cite journal</ref> As a result, people with a history of cardiovascular disease may derive benefit from statins irrespective of their cholesterol levels,<ref name="pmid12114036">Template:Cite journal</ref> and in men without cardiovascular disease, there is benefit from lowering abnormally high cholesterol levels ("primary prevention").<ref name="pmid7566020">Template:Cite journal</ref> Primary prevention in women is practiced only by extension of the findings in studies on men,<ref name="pmid17494017">Template:Cite journal</ref> since in women, none of the large statin trials has shown a reduction in overall mortality or in cardiovascular endpoints.<ref name="pmid17494018">Template:Cite journal</ref>
|Level mg/dL||Level mmol/L||Interpretation|
|< 200||< 5.2||Desirable level corresponding to lower risk for heart disease|
|200–240||5.2–6.2||Borderline high risk|
|> 240||> 6.2||High risk|
The 1987 report of National Cholesterol Education Program, Adult Treatment Panels suggests the total blood cholesterol level should be: < 200 mg/dL normal blood cholesterol, 200–239 mg/dL borderline-high, > 240 mg/dL high cholesterol.<ref name="pmid3422148">Template:Cite journal</ref> The American Heart Association provides a similar set of guidelines for total (fasting) blood cholesterol levels and risk for heart disease:<ref name="urlCholesterol">Template:Cite web</ref>
However, as today's testing methods determine LDL ("bad") and HDL ("good") cholesterol separately, this simplistic view has become somewhat outdated. The desirable LDL level is considered to be less than 100 mg/dL (2.6 mmol/L),<ref name=AHA>"About cholesterol" – American Heart Association</ref> although a newer upper limit of 70 mg/dL (1.8 mmol/L) can be considered in higher-risk individuals based on some of the above-mentioned trials. A ratio of total cholesterol to HDL—another useful measure—of far less than 5:1 is thought to be healthier. Of note, typical LDL values for children before fatty streaks begin to develop is 35 mg/dL.Template:Citation needed
Total cholesterol is defined as the sum of HDL, LDL, and VLDL. Usually, only the total, HDL, and triglycerides are measured. For cost reasons, the VLDL is usually estimated as one-fifth of the triglycerides and the LDL is estimated using the Friedewald formula (or a variant): estimated LDL = [total cholesterol] − [total HDL] − [estimated VLDL]. VLDL can be calculated by dividing total triglycerides by five. Direct LDL measures are used when triglycerides exceed 400 mg/dL. The estimated VLDL and LDL have more error when triglycerides are above 400 mg/dL.<ref name="pmid2297909">Template:Cite journal</ref>
Given the well-recognized role of cholesterol in cardiovascular disease, some studies have shown an inverse correlation between cholesterol levels and mortality. A 2009 study of patients with acute coronary syndromes found an association of hypercholesterolemia with better mortality outcomes.<ref name="pmid19645040">Template:Cite journal</ref> In the Framingham Heart Study, in subjects over 50 years of age, they found an 11% increase overall and 14% increase in cardiovascular disease mortality per 1 mg/dL per year drop in total cholesterol levels. The researchers attributed this phenomenon to the fact that people with severe chronic diseases or cancer tend to have below-normal cholesterol levels.<ref name="pmid3560398">Template:Cite journal</ref> This explanation is not supported by the Vorarlberg Health Monitoring and Promotion Programme, in which men of all ages and women over 50 with very low cholesterol were likely to die of cancer, liver diseases, and mental diseases. This result indicates the low-cholesterol effect occurs even among younger respondents, contradicting the previous assessment among cohorts of older people that this is a proxy or marker for frailty occurring with age.<ref name="pmid15006277">Template:Cite journal</ref>
The vast majority of doctors and medical scientists consider that there is a link between cholesterol and atherosclerosis as discussed above;<ref name="isbn0-12-373979-9">Template:Cite book</ref> a small group of scientists, united in The International Network of Cholesterol Skeptics, questions the link.<ref>Template:Cite book</ref>
Abnormally low levels of cholesterol are termed hypocholesterolemia. Research into the causes of this state is relatively limited, but some studies suggest a link with depression, cancer, and cerebral hemorrhage. In general, the low cholesterol levels seem to be a consequence, rather than a cause, of an underlying illness.<ref name="pmid18061058"/>
Template:Globalize The American Heart Association recommends testing cholesterol every five years for people aged 20 years or older.<ref name="urlHow To Get Your Cholesterol Tested">Template:Cite web</ref>
A blood sample after 12-hour fasting is taken by a doctor, or a home cholesterol-monitoring device is used to determine a lipoprotein profile. This measures total cholesterol, LDL (bad) cholesterol, HDL (good) cholesterol, and triglycerides. It is recommended to test cholesterol at least every five years if a person has total cholesterol of 200 mg/dL or more, or if a man over age 45 or a woman over age 50 has HDL (good) cholesterol less than 40 mg/dL, or there are other risk factors for heart disease and stroke. (In different countries measurements are given in mg/dL or mmol/L; 1 mmol/L is 38.665 mg/dL.)
Interactive pathway map
Cholesteric liquid crystals
Some cholesterol derivatives (among other simple cholesteric lipids) are known to generate the liquid crystalline "cholesteric phase". The cholesteric phase is, in fact, a chiral nematic phase, and it changes colour when its temperature changes. This makes cholesterol derivatives useful for indicating temperature in liquid crystal display thermometers and in temperature-sensitive paints.
- Arcus senilis "Cholesterol ring" in the eyes
- Bile salts
- Cholesterol embolism
- Cholesterol total synthesis
- Diet and heart disease
- Lipid profile
- List of cholesterol in foods
- Niemann–Pick disease Type C
- Vertical Auto Profile
Steroidogenesis, using cholesterol as building material
- Cholesterol Spacefill.jpeg
Space-filling model of the Cholesterol molecule
- Trimethyl steroid-nomenclature.png
Numbering of the steroid nuclei
- Cholesterol bound to proteins in the PDB
- Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults US National Institutes of Health Adult Treatment Panel III
- Aspects of fat digestion and metabolism – UN/WHO Report 1994
- American Heart Association – "About Cholesterol"
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