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Cholesterol

CHOLESTEROL

CHOLESTEROL. Cholesterol is one of the most widely disseminated organic compounds in the animal kingdom. Almost three hundred years ago, Antonio Vallisnieri observed that gallstones were soluble in turpentine or alcohol. Poulletier de la Salle, some thirty years later, demonstrated that the main constituent of gallstones could be crystallized from alcohol. This substance was thought to be a wax until 1815, when Michel Eugène Chevreul showed that it was not saponifiable and gave it the name "cholesterine" derived from the Greek chole, bile, and steros, solid. Soon thereafter, it was isolated from blood, brain, tumors, and egg yolk. The isolated compounds were shown to be identical. In 1843 Vogel found it in atherosclerotic arteries.

The chemical structure of cholesterol was elucidated over the years beginning in 1859. The compound was shown to contain a secondary hydroxyl group and a double bond. The exact empirical formula (C27H46O) was established in 1888 by Friedrich Reinitzer. Proof of structure was obtained chiefly through the brilliant work of Adolf Windaus and Heinrich Wieland. The structure of cholesterol suggested by Windaus and Wieland in the 1920s was incorrect, but that does not detract in any way from their contribution. The true structure was established in the 1930s based on X-ray diffraction data.

There were many suggestions regarding the biological synthesis of cholesterol. The biosynthetic pathway became accessible with the introduction of radioactive carbon in the 1940s. The biosynthetic scheme was generally elucidated by the work of Konrad Bloch, George Popjak, and John Cornforth. It was first shown that cholesterol could be synthesized in mammals and ergosterol in yeast from small organic molecules. Eventually it was shown that all twenty-seven carbon atoms of cholesterol were derived from the two carbon atoms of acetate. The methyl group of acetate contributed fifteen of the twenty-seven carbons of cholesterol and the carboxyl group contributed twelve. The pathway began with the condensation of two acetate residues to give acetoacetate and addition of one more two-carbon moiety to yield hydroxymethylglutaric acid (HMG). HMG lost a carbon atom and the resulting compound rearranged to provide an isoprene unit. Two five-carbon units combined to give a geranyl derivative that added another isoprene to give a farnesyl unit. Two farnesyl units united to provide squalene (C30H50), a hydrocarbon found in the livers of some species of shark that cyclyzed to yield lanosterol, a thirty-carbon atom sterol also found in sheep wool. In a series of rearrangements and demethylations, lanosterol yielded cholesterol. The key step in this complex synthetic pathway involves the reduction of HMG-CoA. Inhibition of HMG-CoA reductase is the basis of a number of potent new serum cholesterol-lowering drugs.

Cholesterol represents about 0.2 percent of the weight of the human body. As Table 1 shows, the bulk of the body's cholesterol is present in two tissues; one is the brain and nerve tissue, the other is muscle. In the brain, cholesterol is thought to act as an insulator, but there have been relatively few studies of the metabolism of brain cholesterol. The next large reservoir of cholesterol is muscle. Between them, nervous tissue and muscle carry 44 percent of the body's cholesterol. The cholesterol in these reservoirs turns over slowly.

Cholesterol is ubiquitous in the human body, where it plays structural and metabolic roles. Together with phospholipid, cholesterol is present in every cell membrane. In the adrenals, cholesterol is converted to adrenocortical hormones such as cortisone. In the gonads,

Distribution of cholesterol in a 70-kg man
Tissue Cholesterol content (g) % of Total
Brain, nervous system 32.0 23
Connective tissue, body fluids 31.3 22
Muscle 30.0 21
Skin 12.6 9
Blood 10.8 8
Bone marrow 7.5 5
Liver 5.1 4
Heart, lungs, kidneys, spleen 5.0 4
Alimentary tract 3.8 3
Adrenals 1.2 1
Skeleton 0.7
Other glands 0.2

cholesterol is converted to the appropriate sex hormoneestradiol in women, testosterone in men. The cholesterol in skin is the precursor of 7-dehydrocholesterol, which is ultimately converted to vitamin D. The major catabolic products of cholesterol are the bile acidscholic and chenodeoxycholic. These are designated as the primary bile acids; they are metabolized in the liver to deoxycholic and lithocholic acids. It has been estimated that over 90 percent of biologically synthesized cholesterol is metabolized to bile acids. In general, the body synthesizes more cholesterol than it ingests.

In 1912 Nicolai Anitschkow showed that cholesterolfed rabbits developed aortic deposits similar to early human atherosclerosis. His experiments presented a possible explanation of human atherosclerosis and that particular debate has not yet abated. Simultaneously with Anitschkow's studies, A. I. Ignatowski demonstrated the atherogenic potential of animal protein, but compared to work on cholesterol and fat there has only been a desultory interest in protein effects.

Since Anitschkow's results were obtained by dietary manipulation, the view that dietary cholesterol was implicated in atherogenesis was accepted generally. With development of simple, rapid methods of cholesterol analysis, it became possible to screen populations for blood cholesterol content. Large epidemiological studies were launched and their results helped to develop the concept of risk factors for heart disease. Currently, the major risk factors are hypercholesterolemia, hypertension, smoking, obesity, and maleness. However, emerging data suggest that homocysteinemia and inflammation (due to infection with cytomegalovirus or chlamydia pneumoniae ) are also important factors.

When cholesterol is ingested, it is emulsified with phospholipid and absorbed. The absorbed lipid circulates in the blood as a water soluble lipid-protein complex called lipoprotein. Initially, absorbed cholesterol is part of a large, triglyceride-rich particle called the chylomicron. In the course of circulation, the triglyceride is removed by activity of cellular lipases and the particles become smaller and their cholesterol content increases. The cholesterol-containing, lipid-protein complex consists of several fractions that are separable by virtue of their hydrated densities. In general terms, the four major fractions are the triglyceride-rich chylomicrons and very low density (VLDL), the cholesterol-rich low density (LDL), and the protein-rich high density (HDL).

Due to development by John Gofman of methods for ultracentrifugal separation of lipoproteins, researchers have been able to isolate and study lipoproteins. The cholesterol-rich low density lipoproteins (LDL) are thought to be major risk factors for coronary disease. It was demonstrated that oxidized LDL is the real villain in coronary disease. It also was shown that LDL can be subfractionated into small, dense and large "fluffy" particles. The small particles appear to infiltrate the artery preferentially. Researchers also know that the process of atherogenesis is not simple and is mediated by an array of small proteins. The high-density lipoproteins are about 50 percent protein. In the simplest terms, LDL facilitates entry of cholesterol into cells and HDL facilitates its removal. LDL receptors on the cell surface facilitate LDL uptake. The proteins of lipoproteins are very important because they provide recognition by cells, and it is now becoming evident that genetic differences in apolipoproteins may dictate susceptibility to disease as well as chances for the efficacy of medication.

The effects of dietary cholesterol became a concern shortly after Anitschkow's observation and warnings regarding excess levels of cholesterol intake, which constitute one of the foundations of dietary therapy. Since cholesterol occurs only in food of animal origin, it was a simple extension to seek an explanation of the role of cholesterol by examining the lipids of food from animal sources. Although no dietary fat is totally saturated or unsaturated, attention also turned to effects of fat saturation.

The amount of cholesterol in the average American diet is in the range of 300350 mg/day. It used to be much higher. The levels of cholesterol in a number of common animal foods are given in Table 2. It is evident that most muscle contains about the same amount of cholesterol, 81 ± 7 mg/100g. Cholesterol content of butter (per 100 g) is high, but we rarely eat more than 510 g of butter per meal. Shrimp is high in cholesterol but very low in fat. Eggs are also high in cholesterol. Continuing research nevertheless indicates that the cholesterol level of a food per se has little effect on serum cholesterol levels. The cholesterolemic effect is a function of dietary fat saturation. It has been shown that the absorption of cholesterol is more a function of the accompanying dietary fat than of cholesterol itself. Saturated dietary fat leads to higher cholesterol levels than does unsaturated fat. This observation is true for most people who are called "non-responders" (to dietary cholesterol). A small number of people are "responders," meaning they absorb more cholesterol, regardless of accompanying fat. In the late 1960s, Keys and Hegsted developed formulas for estimating changes in serum cholesterol based upon changes in dietary fat. There have been a number of more complex formulas developed, but the originals are referred to most often today. Essentially, they found saturated fatty acids to be hypercholesterolemic and unsaturated fatty acids to lower cholesterol. Stearic acid was considered neutral. The polyunsaturated fats lower cholesterol across the board so that HDL cholesterol (the "good" cholesterol) falls as does LDL cholesterol. Oleic acid seems to affect only LDL cholesterol. The reduction in total cholesterol may not be as profound, but the LDL/HDL cholesterol ratio is improved. Recent findings show that the structure of individual triglycerides may also influence their atherogenicity.

In summary, cholesterol is a substance that appears in all cells and also has a number of metabolic functions.

Cholesterol content (mg/100g) of selected foods
Food source Cholesterol (mg/100g)
Egg 504
Butter 250
Shrimp 150
Mackerel 95
Herring 85
Chicken 81
Turkey 74
Lamb 71
Veal 71
Beef 68
Pork 62
Flounder 50
Milk 15

It is synthesized in the body and is part of every cell membrane. Cholesterol is metabolized to adrenocortical or sex hormones, bile acids, and vitamin D. Levels of serum cholesterol are related to risk of coronary disease, but it should be borne in mind that cardiovascular disease is a metabolic disease, not one of cholesterol deposition. Dietary cholesterol is absorbed, but its effects on serum cholesterol are slight. Generally, there is an increase of about 2 mg of serum cholesterol for every 100 mg ingested. Cholesterol should be viewed as a chemical necessary for life and not as a toxic substance. As with so many other aspects of life, moderation is the key.

See also Fats ; Health and Disease.

BIBLIOGRAPHY

Gibbons, G. F., K. A. Mitropoulos, and Nick B. Myant. Biochemistry of Cholesterol. Amsterdam: Elsevier Biomedical Press, 1982.

Howell, Wanda H., et al. "Plasma Lipid and Lipoprotein Responses to Dietary Fat and Cholesterol: A Meta Analysis." American Journal of Clinical Nutrition 65 (1997): 17471764.

Keys, Ancel, Joseph T. Anderson, and Francisco Grande. "Serum Cholesterol Response to Changes in Diet, IV: Particular Fatty Acids in the Diet." Metabolism 14 (1965): 776787.

Kritchevsky, David. Cholesterol. New York: Wiley, 1958.

Kritchevsky, David. "Food Lipids and Atherosclerosis." In Food Lipids and Health, edited by Richard E. McDonald and David B. Min. New York: M. Dekker, 1996.

Leinoneu, M. "Chlamydia pneumoniae and Other Risk Factors for Atherosclerosis." Journal of Infectious Diseases 181, Suppl. 3 (2000): S414S416.

Myant, Nick B. The Biology of Cholesterol and Related Steroids. London: Heinemann Medical Books, 1981.

Myant, Nick B. Cholesterol Metabolism, LDL, and the LDL Receptor. San Diego, Calif.: Academic Press, Inc., 1990.

David Kritchevsky

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Cholesterol

Cholesterol

Definition

Cholesterol is a fatty substance found in animal tissue and is an important component to the human body. It is manufactured in the liver and carried throughout the body in the bloodstream. Problems can occur when too much cholesterol forms an accumulation of plaque on blood vessel walls, which impedes blood flow to the heart and other organs. The highest cholesterol content is found in meat, poultry, shellfish, and dairy products.

Description

Cholesterol is the Dr. Jekyll and Mr. Hyde of medicine, since it has both a good side and bad side. It is necessary to digest fats from food, make hormones, build cell walls, and participate in other processes for maintaining a healthy body. When people talk about cholesterol as a medical problem, they are usually referring to high cholesterol. This can be somewhat misleading, since there are four components to cholesterol. These are:

  • LDL, the so-called bad cholesterol
  • HDL, the so-called good cholesterol
  • triglycerides, a blood fat lipid that increases the risk for heart disease
  • total cholesterol

The U.S. Food and Drug Administration (FDA) estimates that 90 million American adults, roughly one-half of the adult population, have elevated cholesterol levels. High LDL (low-density lipoprotein) is a major contributing factor of heart disease. The cholesterol forms plaque in the heart's blood vessels, which restricts or blocks the supply of blood to the heart, and causes a condition called atherosclerosis. This can lead to a heart attack , resulting in damage to the heart and possibly death.

In 2001, chemical researchers found a link between cholesterol and Alzheimer's disease . Reducing the amount of cholesterol in the cells appears to block attachment of senile plaques to the brain's neurons. (The plaques begin the process that eventually kills brain neurons.) More study remains to test the effects of cholesterol on Alzheimer's.

The population as a whole is at some risk of developing high LDL cholesterol in their lifetimes. Specific risk factors include a family history of high cholesterol, obesity , heart attack or stroke, alcoholism , and lack of regular exercise . The chances of developing high cholesterol increase after the age of 45. One of the primary causes of high LDL cholesterol is too much fat or sugar in the diet, a problem especially true in the United States. Cholesterol also is produced naturally in the liver and overproduction may occur even in people who limit their intake of high cholesterol food. Low HDL and high triglyceride levels also are risk factors for atherosclerosis.

Causes & symptoms

There are no readily apparent symptoms that indicate high LDL or triglycerides, or low HDL. The only way to diagnose a problem is through a simple blood test. However, one general indication of high cholesterol is obesity. Another is a high-fat diet. In 2001, new research involving twins demonstrated that both genetic factors and diet contribute to cholesterol levels.

Diagnosis

High cholesterol often is diagnosed and treated by general practitioners or family practice physicians. In some cases, the condition is treated by an endocrinologist or cardiologist. Total cholesterol, LDL, HDL, and triglyceride levels as well as the cholesterol to HDL ratio are measured by a blood test called a lipid panel. The cost of a lipid panel is generally $40-100 and is covered by most health insurance and HMO plans, including Medicare, providing there is an appropriate reason for the test. Home cholesterol testing kits are available over the counter but test only for total cholesterol. The results should only be used as a guide and if the total cholesterol level is high or low, a lipid panel should be performed by a physician. In most adults the recommended levels, measured by milligrams per deciliter (mg/dL) of blood, are: total cholesterol, less than 200; LDL, less than 130; HDL, more than 35; triglycerides, 30-200; and cholesterol to HDL ratio, four to one. However, the recommended cholesterol levels may vary, depending on other risk factors such as hypertension , a family history of heart disease, diabetes, age, alcoholism, and smoking .

Doctors have always been puzzled by why some people develop heart disease while others with identical HDL and LDL levels do not. New studies indicate it may be due to the size of the cholesterol particles in the

TYPES OF CHOLESTEROL
Types Levels
Total cholesterol:
Desirable <200
Borderline 200 to 240
Undesirable >240
HDL cholesterol:
Desirable >45
Borderline 35 to 45
Undesirable <35
LDL cholesterol:
Desirable <130
Borderline 130 to 160
Undesirable >160
Ratio of total cholesterol to HDL cholesterol:
Desirable <3
Borderline 3 to 4
Undesirable >4

bloodstream. A test called a nuclear magnetic resonance (NMR) LipoProfile exposes a blood sample to a magnetic field to determine the size of the cholesterol particles. Particle size also can be determined by a centrifugation test, where blood samples are spun very quickly to allow particles to separate and move at different distances. The smaller the particles, the greater the chance of developing heart disease. It allows physicians to treat patients who have normal or close to normal results from a lipid panel but abnormal particle size.

Treatment

The primary goal of cholesterol treatment is to lower LDL to under 160 mg/dL in people without heart disease and who are at lower risk of developing it. The goal in people with higher risk factors for heart disease is less than 130 mg/dL. In patients who already have heart disease, the goal is under 100 mg/dL, according to FDA guidelines. Also, since low HDL levels increase the risks

of heart disease, the goal of all patients is more than 35 mg/dL.

In both alternative and conventional treatment of high cholesterol, the first-line treatment options are exercise, diet, weight loss, and stopping smoking. Other alternative treatments include high doses of niacin, soy protein, garlic , algae, and the Chinese medicine supplement Cholestin (a red yeast fermented with rice).

Diet and exercise

Since a large number of people with high cholesterol are overweight, a healthy diet and regular exercise are probably the most beneficial natural ways to control cholesterol levels. In general, the goal is to substantially reduce or eliminate foods high in animal fat. These include meat, shellfish, eggs, and dairy products. Several specific diet options are beneficial. One is the vegetarian diet. Vegetarians typically get up to 100% more fiber and up to 50% less cholesterol from food than non-vegetarians. The vegetarian low-cholesterol diet consists of at least six servings of whole grain foods, three or more servings of green leafy vegetables, two to four servings of fruit, two to four servings of legumes, and one or two servings of non-fat dairy products daily.

A second diet is the Asian diet, with brown rice being the staple. Other allowable foods include fish, vegetables such as bok choy, bean sprouts, and black beans. It allows for one weekly serving of meat and very few dairy products. The food is flavored with traditional Asian spices and condiments, such as ginger , chilies, turmeric , and soy sauce.

Another regimen is the low glycemic or diabetic diet, which can raise the HDL (good cholesterol) level by as much as 20% in three weeks. Low glycemic foods promote a slow but steady rise in blood sugar levels following a meal, which increases the level of HDL. They also lower total cholesterol and triglycerides. Low glycemic foods include certain fruits, vegetables, beans, and whole grains. Processed and refined foods and sugars should be avoided.

Exercise is an extremely important part of lowering bad cholesterol and raising good cholesterol. It should consist of 20-30 minutes of vigorous aerobic exercise at least three times a week. Exercises that cause the heart to beat faster include fast walking, bicycling, jogging, roller skating, swimming, and walking up stairs. There also are a wide selection of aerobic programs available at gyms or on videocassette.

Garlic

A number of clinical studies have indicated that garlic can offer modest reductions in cholesterol. A 1997 study by nutrition researchers at Pennsylvania State University found men who took garlic capsules for five months reduced their total cholesterol by 7% and LDL by 12%. Another study showed that seven cloves of fresh garlic a day significantly reduced LDL, as did a daily dose of four garlic extract pills. Other studies in 1997 and 1998 back up these results. However, two more recent studies have questioned the effectiveness of garlic in lowering "bad cholesterol."

Cholestin

Cholestin hit the over-the-counter market in 1997 as a cholesterol-lowering dietary supplement. It is a processed form of red yeast fermented with rice, a traditional herbal remedy used for centuries by the Chinese. Two studies released in 1998 showed Cholestin lowered LDL cholesterol by 20-30%%. It also appeared to raise HDL and lower triglyceride levels. Although the supplement contains hundreds of compounds, the major active LDL-lowering ingredient is lovastatin, a chemical also found in the prescription drug Mevacor. The FDA banned Cholestin in early 1998 but a federal district court judge lifted the ban a year later, ruling the product was a dietary supplement, not a drug. It is not fully understood how the substance works and patients may want to consult with their physician before taking Cholestin. No serious side effects have been reported, but minor side effects, including bloating and heartburn , have been reported.

Other treatments

A study released in 1999 indicated that blue-green algae contains polyunsaturated fatty acids that lower cholesterol. The algae, known as alga Aphanizomenon flosaquae (AFA) is available as an over-the-counter dietary supplement. Niacin, also known as nicotinic acid or vitamin B3, has been shown to reduce LDL levels by 10-20%, and raise HDL levels by 15-35%. It also can reduce triglycerides. But because an extremely high dose of niacin (2-3 grams) is needed to treat cholesterol problems, it should only be taken under a doctor's supervision to monitor possible toxic side effects. Niacin also can cause flushing when taken in high doses. Soy protein with high levels of isoflavones also have been shown to reduce bad cholesterol by up to 10%. A daily diet that contains 62 mg of isoflavones in soy protein is recommended, and can be incorporated into other diet regimens, including vegetarian, Asian, and low glycemic. In 2003, research revealed that policosanol, a substance made from sugar cane wax or beeswax, lowered LDL cholesterol nearly 27% in study subjects in a Cuban study.

Allopathic treatment

A wide variety of prescription medicines are available to treat cholesterol problems. These include statins such as Mevacor (lovastatin), Lescol (fluvastatin), Pravachol (pravastatin), Zocor (simvastatin), Baycol (cervastatin), and Lipitor (atorvastatin) to lower LDL. A group of drugs called fibric acid derivatives are used to lower triglycerides and raise HDL. These include Lopid (gemfibrozil), Atromid-S (clofibrate), and Tricor (fenofibrate).

A new class of drugs was identified late in 2001 that work differently from the statin drugs. These drugs rely on compounds that bind to a sterol that regulates protein (called SCAP) and speds up removal of cholesterol from the plasma (the fluid part of the blood.) Doctors decide which drug to use based on the severity of the cholesterol problem, side effects, and cost.

Expected results

High cholesterol is one of the key risk factors for heart disease. Left untreated, too much bad cholesterol can clog the blood vessels, leading to chest pain (angina ), blood clots , and heart attacks. Heart disease is the number one killer of men and women in the United States. By reducing LDL, people with heart disease may prevent further heart attacks and strokes, prolong and improve the quality of their lives, and slow or reverse cholesterol buildup in the arteries. In people without heart disease, lowering LDL can decrease the risk of a first heart attack or stroke.

KEY TERMS

Polyunsaturated fats
A non-animal oil or fatty acid rich in unsaturated chemical bonds not associated with the formation of cholesterol in the blood.

Prevention

The best way to prevent cholesterol problems is through a combination of healthy lifestyle activities, a primarily low-fat and high-fiber diet , regular aerobic exercise, not smoking, and maintaining an optimal weight. In a small 2003 Canadian study, people who ate a low-fat vegetarian diet consisting of foods that are found to help lower cholesterol dropped their levels of LDL cholesterol as much as results from some statin drugs. But for people with high risk factors for heart disease, such as a family history of heart disease, diabetes, and being over the age of 45, these measures may not be enough to prevent the onset of high cholesterol. There are studies being done on the effectiveness of some existing anti-cholesterol drugs for controlling cholesterol levels in patients who do not meet the criteria for high cholesterol but no definitive results are available.

Resources

BOOKS

Bratman, Steven and David Kroll. Natural Pharmacist: Natural Treatments for High Cholesterol. Roseville, CA: Prima Publishing, 2000.

Ingels, Darin. The Natural Pharmacist: Your Complete Guide to Garlic and Cholesterol. Roseville, CA: Prima Publishing, 1999.

Murray, Michael T. Natural Alternatives to Over-the-Counter and Prescription Drugs New York: William Morrow & Co., 1999.

Trubo, Richard. Cholesterol Cures: From Almonds and Antioxidants to Garlic, Golf, Wine and Yogurt. Emmaus, PA: Rodale Press, 1996.

PERIODICALS

"Both Genetics and Diet Influence Cholesterol Levels." Heart Disease Weekly (October 14, 2001).

Carter, Ann. "Cholesterol in Your Diet." Clinical Reference Systems (July 1, 1999): 282.

"Chemical Engineers Suggest Alzheimer Onset Tied to Cholesterol." Pain and Central Nervous System Week (December 24, 2001):3.

"Eating a Vegetarian Diet that Includes Cholesterol-lowering Foods may Lower Lipid Levels as Much as Some Medications." Environmental Nutrition (March 2003):8.

"Researchers Identify New Class of Cholesterol-Lowering Drugs." Heart Disease Weekly (December 23, 2001):14.

Sage, Katie. "Cut Cholesterol with Policosanol: This Supplement Worked Better than a Low-fat Diet in One Study." Natural Health (March 2003):32.

Marandino, Cristin. "The Case for Cholesterol." Vegetarian Times (August 1999): 10.

Schmitt, B.D. "Treating High Cholesterol Levels." Clinical Reference Systems (July 1, 1999): 1551.

VanTyne, Julia, and Davis, Lori. "Drop Your Cholesterol 25 to 100 Points." Prevention (November 1999): 110.

ORGANIZATIONS

National Cholesterol Education Program. NHLBI Information Center, P.O. Box 30105, Bethesda, MD 20824-0105. http://www.nhlbi.nih.gov.

Ken R. Wells

Teresa G. Odle

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Cholesterol-Reducing Drugs

Cholesterol-Reducing Drugs

Definition

Cholesterol-reducing drugs are medicines that lower the amount of cholesterol (a fat-like substance) in the blood.

Purpose

Cholesterol is a chemical that can both benefit and harm the body. On the good side, cholesterol plays important roles in the structure of cells and in the production of hormones. But too much cholesterol in the blood can lead to heart and blood vessel disease. To complicate matters, not all cholesterol contributes to heart and blood vessel problems. One type, called high-density lipoprotein (HDL) cholesterol, or "good cholesterol," actually lowers the risk of these problems. The other type, low-density lipoprotein (LDL) cholesterol, or "bad cholesterol," is the type that threatens people's health. The names reflect the way cholesterol moves through the body. To travel through the bloodstream, cholesterol must attach itself to a protein. The combination of a protein and a fatty substance like cholesterol is called a lipoprotein.

Many factors may contribute to the fact that some people have higher cholesterol levels than others. A diet high in certain types of fats is one factor. Medical problems such as poorly controlled diabetes, an underactive thyroid gland, an overactive pituitary gland, liver disease or kidney failure also may cause high cholesterol levels. And some people have inherited disorders that prevent their bodies from properly using and eliminating fats. This allows cholesterol to build up in the blood.

Treatment for high cholesterol levels usually begins with changes in daily habits. By losing weight, stopping smoking, exercising more and reducing the amount of fat and cholesterol in the diet, many people can bring their cholesterol levels down to acceptable levels. However, some may need to use cholesterol-reducing drugs to reduce their risk of health problems.

Description

There are four different classes of cholesterol lowering drugs:

Bile acid sequesterants are drugs that act by binding with the bile produced by the liver. Bile helps the digestion and absorption of fats in the intestine. By blocking the digestion of fats, bile acid sequesterants prevent the formation of cholesterol. Drugs in this class include: cholestyramine (Questran); colestipol (Colestid); and colesevalam (Welchol).

HMG-CoA inhibitors, often called "statins," are drugs that block an enzyme called "3-hydroxy-3-methyl-glutaryl-coenzyme A reductase." This blocks one of the steps in converting fat to cholesterol. These are the most effective cholesterol lowering agents available and in recent years have received increased attention for their benefits beyond helping patients with high cholesterol. In 2003, researchers reported that people with heart failure but no coronary artery disease received benefits after only 14 weeks of statin therapy. In addition, some research has connected the drugs to reduced risk for depression and dementia. Drugs in this group include: atorvastatin (Lipitor); cerivastatin (Baycol); fluvastatin (Lescol); lovastatin (Mevacor); pravastatin (Pravachol); simvastatin (Zocor); and the newest approved drug rosuvastatin (Crestor).

Fibric acid derivatives include clofibrate (Atromid-S); gemfibrozil (Lopid); and fenofibrate (Tricor). Although these drugs are less effective than the statins at lowering total cholesterol, they may be able to lower the low-density lipoprotein (LDL) cholesterol while raising the high-density lipoprotein (HDL) cholesterol. They probably act by inhibiting lipoprotein lipase activity.

Niacin, or vitamin B-3, also is effective in lowering cholesterol levels. Although the normal vitamin dose of niacin is only 20 mg, the dose required to reduce cholesterol levels is at least 500 mg each day. Niacin probably helps reduce cholesterol by inhibiting very low density lipoprotein (VLDL) secretion in the bloodstream.

Recommended dosage

The recommended dosage depends on the type of cholesterol-reducing drug used. The prescribing physician or the pharmacist who filled the prescription can advise about the correct dosage.

Cholesterol-reducing drugs should be taken exactly as directed and doses should not be missed. Double doses should not be taken to make up for a missed dose.

Physicians may prescribe a combination of cholesterol-reducing drugs, such as pravastatin and colestipol. Following the directions for how and when to take the drugs is very important. The medicine may not work properly if both drugs are taken at the same time of day.

Niacin should not be taken at the same time as an HMG-CoA inhibitor, as this combination may cause severe muscle problems. If niacin is taken in an over-the-counter form, both the prescribing physician and pharmacist should be informed. There are no problems when the niacin is taken in normal doses as a vitamin.

The prescription should not be stopped without first checking with the physician who prescribed it. Cholesterol levels may increase when the medicine is stopped, and the physician may prescribe a special diet to make this less likely.

Precautions

Seeing a physician regularly while taking cholesterol-reducing drugs is important. The physician will check to make sure the medicine is working as it should and will decide whether it is still needed. Blood tests and other medical tests may be ordered to help the physician monitor the drug's effectiveness and check for side effects.

For most people, cholesterol-reducing drugs are just one part of a whole program for lowering cholesterol levels. Other important elements of the program may include weight loss, exercise, special diets, and changes in other habits. The medication should never be viewed as a substitute for other measures ordered by the physician. Cholesterol-reducing drugs will not cure problems that cause high cholesterol; they will only help control cholesterol levels.

People over 60 years of age may be unusually sensitive to the effects of some cholesterol-reducing drugs. This may increase the chance of side effects.

Anyone who is taking an HMG-CoA reductase inhibitor should notify the health care professional in charge before having any surgical or dental procedures or receiving emergency treatment.

Special conditions

People who have certain medical conditions or who are taking certain other medications may have problems if they take cholesterol-reducing drugs. Before taking these drugs, the prescribing physician should be informed of any of the following conditions:

ALLERGIES. Anyone who has had unusual reactions to cholesterol-reducing drugs in the past should inform the prescribing physician before taking the drugs again. The physician also should be told about any allergies to foods, dyes, preservatives, or other substances.

PREGNANCY. Studies of laboratory animals have shown that giving high doses of gemfibrozil during pregnancy increases the risk of birth defects and other problems, including death of the unborn baby. The effects of this drug have not been studied in pregnant women. Women who are pregnant or who may become pregnant should check with their physicians before using gemfibrozil.

Cholesterol-reducing drugs in the group known as HMG-CoA reductase inhibitors (such as lovastatin, fluvastatin, pravastatin and simvastatin) should not be taken by women who are pregnant or who plan to become pregnant soon. By blocking the production of cholesterol, these drugs prevent a fetus from developing properly. Women who are able to bear children should use an effective birth control method while taking these drugs. Any woman who becomes pregnant while taking these drugs should check with her physician immediately.

Cholestyramine and colestipol will not directly harm an unborn baby, because these drugs are not taken into the body. However, the drugs may keep the mother's body from absorbing vitamins that she and the baby need. Pregnant women who take these drugs should ask their physicians whether they need to take extra vitamins.

BREASTFEEDING. Because cholestyramine and colestipol interfere with the absorption of vitamins, women who use these drugs while breastfeeding should ask their physicians if they need to take extra vitamins.

Women who are breastfeeding should talk to their physicians before using gemfibrozil. Whether this drug passes into breast milk is not known. But because animal studies suggest that it may increase the risk of some types of cancer, women should carefully consider the safety of using it while breastfeeding.

HMG-CoA reductase inhibitors (such as lovastatin, pravastatin, fluvastatin and simvastatin) should not be used by women who are breastfeeding their babies.

OTHER MEDICAL CONDITIONS. Cholesterol-reducing drugs may make some medical problems worse. Before using these drugs, people with any of these medical conditions should make sure their physicians are aware of their conditions:

  • stomach problems, including stomach ulcer
  • constipation
  • hemorrhoids
  • gallstones or gallbladder disease
  • bleeding problems
  • underactive thyroid
  • heart or blood vessel disease

In addition, people with kidney or liver disease may be more likely to have blood problems or other side effects when they take certain cholesterol-reducing drugs. And some drugs of this type may actually raise cholesterol levels in people with liver disease.

Patients with any of the following medical conditions may develop problems that could lead to kidney failure if they take HMG-CoA reductase inhibitors:

  • treatments to prevent rejection after an organ transplant
  • recent major surgery
  • seizures (convulsions) that are not well controlled

People with phenylketonuria (PKU) should be aware that sugar-free formulations of some cholesterol-reducing drugs contain phenylalanine in aspartame. This ingredient can cause problems in people who have phenylketonuria.

USE OF CERTAIN MEDICINES. Cholesterol-reducing drugs may change the effects of other medicines. Patients should not take any other medicine that has not been prescribed or approved by a physician who knows they are taking cholesterol-reducing drugs.

Side effects

Gemfibrozil

Studies in animals and humans suggest that gemfibrozil increases the risk of some types of cancer. The drug may also cause gallstones or muscle problems. Patients who need to take this medicine should ask their physicians for the latest information on its benefits and risks.

Patients taking gemfibrozil should check with a physician immediately if any of these side effects occur:

  • fever or chills
  • severe stomach pain with nausea and vomiting
  • pain in the lower back or side
  • pain or difficulty when urinating
  • cough or hoarseness

HMG-CoA reductase inhibitors

These drugs may damage the liver or muscles. Patients who take the drugs should have blood tests to check for liver damage as often as their physician recommends. Any unexplained pain, tenderness or weakness in the muscles should be reported to the physician at once.

All cholesterol-reducing drugs

Minor side effects such as heartburn, indigestion, belching, bloating, gas, nausea or vomiting, stomach pain, dizziness and headache usually go away as the body adjusts to the drug and do not require medical treatment unless they continue or they interfere with normal activities.

Patients who have constipation while taking cholesterol-reducing drugs should bring the problem to a physician's attention as soon as possible.

Additional side effects are possible. Anyone who has unusual symptoms while taking cholesterol-reducing drugs should get in touch with his or her physician.

Interactions

Cholesterol-reducing drugs may interact with other medicines. When this happens, the effects of one or both of the drugs may change or the risk of side effects may be greater. Anyone who takes cholesterol-reducing drugs should let the physician know all other medicines he or she is taking and should ask whether the possible interactions can interfere with drug therapy. Examples of possible interactions are listed below.

Some cholesterol-reducing drugs may prevent the following medicines from working properly:

  • thyroid hormones
  • water pills (diuretics)
  • certain antibiotics taken by mouth, such as tetracyclines, penicillin G and vancomycin
  • the beta-blocker Inderal, used to treat high blood pressure
  • digitalis heart medicines
  • phenylbutazone, a nonsteroidal anti-inflammatory drug

Taking some cholesterol-reducing drugs with blood thinners (anticoagulants) may increase the chance of bleeding.

KEY TERMS

Cell The basic unit that makes up all living tissue.

Cholesterol Fatty substance found in tissue. Necessary to maintain a healthy body.

Enzyme A type of protein, produced in the body, that brings about or speeds up chemical reactions.

Hormone A substance that is produced in one part of the body, then travels through the bloodstream to another part of the body where it has its effect.

Phenylketonuria (PKU) A genetic disorder in which the body lacks an important enzyme. If untreated, the disorder can lead to brain damage and mental retardation.

Pituitary gland A pea-sized gland at the base of the brain that produces many hormones that affect growth and body functions.

Combining HMG-CoA reductase inhibitors with gemfibrozil, cyclosporine (Sandimmune) or niacin may cause or worsen problems with the kidneys or muscles.

Resources

BOOKS

Nesto, R. W., and L. Christensen. Cholesterol-Lowering Drugs: Everything You and Your Family Need to Know. New York: Morrow, William & Co, 2000.

PERIODICALS

"Cholesterol Drug Helps Heart Failure Patients Without High Cholesterol." Heart Disease Weekly August 24, 2003: 33.

"Link to Cholesterol Drugs Disputed." Cardiovascular Week September 29, 2003: 73.

Mechcatie, Elizabeth. "FDA Okays Rosuvastatin for Hypercholeterolemia: Most Potent Statin to Date." Internal Medicine News September 1, 2003: 30-31.

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Cholesterol Test

Cholesterol Test

Definition

The cholesterol test is a quantitative analysis of the cholesterol levels in a sample of the patient's blood. Total serum cholesterol (TC) is the measurement routinely taken. Doctors sometimes order a complete lipoprotein profile to better evaluate the risk for atherosclerosis (coronary artery disease, or CAD). The full lipoprotein profile also includes measurements of triglyceride levels (a chemical compound that forms 95% of the fats and oils stored in animal or vegetable cells) and lipoproteins (high density and low density). Blood fats also are called "lipids." It is estimated that more than 200 million cholesterol tests are performed each year in the United States.

The type of cholesterol in the blood is as important as the total quantity. Cholesterol is a fatty substance and cannot be dissolved in water. It must combine with a protein molecule called a lipoprotein in order to be transported in the blood. There are five major types of lipoproteins in the human body; they differ in the amount of cholesterol that they carry in comparison to other fats and fatty acids, and in their functions in the body. Lipoproteins are classified, as follows, according to their density:

  • Chylomicrons. These are normally found in the blood only after a person has eaten foods containing fats. They contain about 7% cholesterol. Chylomicrons transport fats and cholesterol from the intestine into the liver, then into the bloodstream. They are metabolized in the process of carrying food energy to muscle and fat cells.
  • Very low-density lipoproteins (VLDL). These lipoproteins carry mostly triglycerides, but they also contain 16-22% cholesterol. VLDLs are made in the liver and eventually become IDL particles after they have lost their triglyceride content.
  • Intermediate-density lipoproteins (IDL). IDLs are short-lived lipoproteins containing about 30% cholesterol that are converted in the liver to low-density lipoproteins (LDLs).
  • Low-density lipoproteins (LDL). LDL molecules carry cholesterol from the liver to other body tissues. They contain about 50% cholesterol. Extra LDLs are absorbed by the liver and their cholesterol is excreted into the bile. LDL particles are involved in the formation of plaques (abnormal deposits of cholesterol) in the walls of the coronary arteries. LDL is known as "bad cholesterol."
  • High-density lipoproteins (HDL). HDL molecules are made in the intestines and the liver. HDLs are about 50% protein and 19% cholesterol. They help to remove cholesterol from artery walls. Lifestyle changes, including exercising, keeping weight within recommended limits, and giving up smoking can increase the body's levels of HDL cholesterol. HDL is known as "good cholesterol."
  • Lipoprotein subclasses. By identifying levels of multiple subclasses of lipid abnormalities, physicians can do a better job of prescribing lipid-lowering therapies, particularly in high-risk patients such as those with type 2 diabetes.

Because of the difference in density and cholesterol content of lipoproteins, two patients with the same total cholesterol level can have very different lipid profiles and different risk for CAD. The critical factor is the level of HDL cholesterol in the blood serum. Some doctors use the ratio of the total cholesterol level to HDL cholesterol when assessing the patient's degree of risk. A low TC/HDL ratio is associated with a lower degree of risk.

Purpose

The purpose of the TC test is to measure the levels of cholesterol in the patient's blood. The patient's cholesterol also can be fractionated (separated into different portions) in order to determine the TC/HDL ratio. The results help the doctor assess the patient's risk for coronary artery disease (CAD). High LDL levels are associated with increased risk of CAD whereas high HDL levels are associated with relatively lower risk.

In addition, the results of the cholesterol test can assist the doctor in evaluating the patient's metabolism of fat, or in diagnosing inflammation of the pancreas, liver disease, or disorders of the thyroid gland.

The frequency of cholesterol testing depends on the patient's degree of risk for CAD. People with low cholesterol levels may need to be tested once every five years. People with high levels of blood cholesterol should be tested more frequently, according to their doctor's advice. The doctor may recommend a detailed evaluation of the different types of lipids in the patient's blood. It is ideal to check the HDL and triglycerides as well as the cholesterol and LDL. In addition, the National Cholesterol Education Program (NCEP) suggests further evaluation if the patient has any of the symptoms of CAD or if she or he has two or more of the following risk factors for CAD:

  • male sex
  • high blood pressure
  • smoking
  • diabetes
  • low HDL levels
  • family history of CAD before age 55

The necessity of widespread cholesterol screening is a topic with varying responses. In 2003, a report demonstrated that measuring the cholesterol of everyone at age 50 years was a simple and efficient way to identify those most at risk for heart disease from among the general population.

Precautions

Patients who are seriously ill or hospitalized for surgery should not be given cholesterol tests because the results will not indicate the patient's normal cholesterol level. Acute illness, high fever, starvation, or recent surgery lowers blood cholesterol levels.

Description

A pharmaceutical corporation announced in the spring of 2004 that it had received an application to patent a device that could use saliva to determine cholesterol levels. If the test becomes available, it could make screening much more convenient and accessible.

The cholesterol test requires a sample of the patient's blood. Fasting before the test is required to get an accurate triglyceride and LDL level. The blood is withdrawn by the usual vacuum tube technique from one of the patient's veins. The blood test takes between three and five minutes.

Preparation

Patients who are scheduled for a lipid profile test should fast (except for water) for 12-14 hours before the blood sample is drawn. If the patient's cholesterol is to be fractionated, he or she also should avoid alcohol for 24 hours before the test.

Patients also should stop taking any medications that may affect the accuracy of the test results. These include corticosteroids, estrogen or androgens, oral contraceptives, some diuretics, haloperidol, some antibiotics, and niacin. Antilipemics are drugs that lower the concentration of fatty substances in the blood. When these are taken by the patient, blood testing may be done frequently to evaluate the liver function as well as lipids. The patient's doctor will give the patient a list of specific medications to be discontinued before the test.

Aftercare

Aftercare includes routine care of the skin around the needle puncture. Most patients have no after-effects, but some may have a small bruise or swelling. A washcloth soaked in warm water usually relieves discomfort. In addition, the patient should resume taking any prescription medications that were discontinued before the test.

Risks

The primary risk to the patient is a mild stinging or burning sensation during the venipuncture, with minor swelling or bruising afterward.

Normal results

The "normal" values for serum lipids depend on the patient's age, sex, and race. Normal values for people in Western countries were once presumed to be 140-220 mg/dL in adults, although as many as 5% of the population has TC higher than 300 mg/dL. Among Asians, the figures are about 20% lower. As a rule, both TC and LDL levels rise as people get older. However, in 2001, the NCEP released stricter guidelines for LDL and total cholesterol.

Some doctors prefer to speak of "desired" rather than "normal" cholesterol values, on the grounds that "normal" refers to statistically average levels that may still be too high for good health. The NCEP has outlined the levels according to desirable and risk:

  • Optimal LDL cholesterol: less than 100 mg/dL and total cholesterol less than 160 mg/dL
  • Desirable LDL cholesterol: 100-129 mg/dL; total cholesterol 160-199 mg/dL
  • Borderline high risk: LDL cholesterol 130-159 mg/dL; total cholesterol 200-239 mg/dL
  • High risk: LDL cholesterol greater than 160 mg/dL; total cholesterol greater than or at 240 mg/dL.

Abnormal results

It is possible for blood cholesterol levels to be too low as well as too high.

Abnormally low levels

TC levels less than 160 mg/dL are associated with higher mortality rates from cancer, liver disease, respiratory disorders, and injuries. The connection between unusually low cholesterol and increased mortality is not clear, although some researchers think that the low level is a secondary sign of the underlying disease and not the cause of disease or death.

Low levels of serum cholesterol are also associated with malnutrition or hyperthyroidism. Further diagnostic testing may be necessary in order to locate the cause.

Abnormally high levels

Prior to 1980, hypercholesterolemia (an abnormally high TC level) was defined as any value above the 95th percentile for the population. These figures ranged from 210 mg/dL in persons younger than 20 to more than 280 mg/dL in persons older than 60. It is now known, however, that TC levels over 200 mg/dL are associated with significantly higher risk of CAD. Levels of 280 mg/dL or more are considered elevated. Treatment with diet and medication has proven to successfully lower risk of heart attack and stroke.

Elevated cholesterol levels also may result from hepatitis, blockage of the bile ducts, disorders of lipid metabolism, nephrotic syndrome, inflammation of the pancreas, or hypothyroidism.

KEY TERMS

Atherosclerosis A disease of the coronary arteries in which cholesterol is deposited in plaques on the arterial walls. The plaque narrows or blocks blood flow to the heart. Atherosclerosis sometimes is called coronary artery disease, or CAD.

Fractionation A laboratory test or process in which blood or another fluid is broken down into its components. Fractionation can be used to assess the proportions of the different types of cholesterol in a blood sample.

High-density lipoprotein (HDL) A type of lipoprotein that protects against coronary artery disease by removing cholesterol deposits from arteries or preventing their formation.

Hypercholesterolemia The presence of excessively high levels of cholesterol in the blood.

Lipid Any organic compound that is greasy, insoluble in water, but soluble in alcohol. Fats, waxes, and oils are examples of lipids.

Lipoprotein A complex molecule that consists of a protein membrane surrounding a core of lipids. Lipoproteins carry cholesterol and other lipids from the digestive tract to the liver and other body tissues. There are five major types of lipoproteins.

Low-density lipoprotein (LDL) A type of lipoprotein that consists of about 50% cholesterol and is associated with an increased risk of coronary artery disease.

Plaque An abnormal deposit of hardened cholesterol on the wall of an artery.

Triglyceride A chemical compound that forms about 95% of the fats and oils stored in animal and vegetable cells. Triglyceride levels sometimes are measured as well as cholesterol when a patient is screened for heart disease.

Resources

PERIODICALS

Capriotti, Teri. "Stricter Cholesterol Guidelines Broaden Implications for the "Statin' Drugs." MedSurg Nursing February 2003: 51-57.

"Cholesterol Test at Age 50 Spots Those in Greatest Danger." Heart Disease Weekly July 27, 2003: 3.

"Company Wins U.S. Patent for Saliva Cholesterol Test." Heart Disease Weekly May 23, 2004: 66.

"Study Shows Expanded Cholesterol Test Sparked Use of Lipid-lowering Therapy." Heart Disease Weekly July 13, 2003: 20.

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cholesterol

cholesterol Many people are now aware of their own blood cholesterol level, have it measured regularly and eat diets high in polyunsaturates. This is because they know that high cholesterol levels in the blood, and fat-rich diets, are likely to lead to heart attacks and strokes, particularly in later life. Some also know that the narrowing of arteries, particularly the coronary arteries, is due to the deposition of atherosclerotic plaques, made largely of cholesterol, on the walls of the vessels. Narrowing of the arteries reduces the flow rate, especially as flow depends on the fourth power of the radius. Thus, at a given pressure, reducing the radius to one half of normal would reduce the flow rate to one sixteenth of the original value. Adequate flow can then only be maintained by a rise in blood pressure.

The importance of cholesterol in the body can be gauged from the words of Brown and Goldstein in their Nobel Prize Lecture in 1985. They described cholesterol as the ‘most decorated’ molecule in biology, as no less than 13 Nobel awards had been made to those who spent their lives studying the substance, adding that ‘the property that makes it useful in cell membranes, namely its absolute insolubility in water, also makes it lethal’.

Cholesterol was first isolated from gallstones in 1784. It is a neutral lipid, a sterol, and an important constituent of cell membranes. Cholesterol is obtained through the diet and synthesized in the body, in the liver and the intestine. When the intake is high, synthesis is suppressed. The cholesterol molecule has 27 carbon atoms, yet the synthesis of this complex molecule is from 2-carbon fragments (acetyl CoA) in a very complex biosynthetic process. Cholesterol is the necessary precursor of several sterol (steroid) hormones, such as the sex hormones testosterone and oestrogens, and the adrenal steroid hormones, including cortisol. Not surprisingly — remembering that cholesterol was found first in gall stones — cholesterol is used to make bile salts, the constituents of bile which take an essential part in fat absorption from the gut.

To understand how atherosclerotic plaques become deposited in arteries it is necessary to understand how the highly insoluble cholesterol is moved about the body. The agents which transport cholesterol are the lipoproteins — consisting, as their name implies, of a lipid and a protein component. Fats and cholesterol absorbed from the diet are transported as ‘chylomicrons’ from the intestine to the liver, where the fats are rapidly metabolized, and cholesterol is incorporated into low density lipoprotein (LDL) along with phospholipid molecules and one molecule of a huge protein called B-100. LDL is the main cholesterol transporter, transferring it from the liver to all other parts of the body. Since cholesterol is an essential component of all cell membranes it will be needed anywhere new cells are being formed.

The B-100 protein is a key component of LDL, as it is the molecule that is recognized by LDL receptors in the membrane of all cells. After this recognition, the LDL complex is internalized and broken down in the cell, which thus has its vital supply of cholesterol delivered to it. The LDL receptor is recycled back to the membrane to wait for another LDL. When the supply of cholesterol is plentiful the LDL receptors are ‘down regulated’ (their numbers are reduced), leaving low density lipoprotein circulating in the blood with its potentially lethal cargo of cholesterol. Eventually the cholesterol is deposited in a variety of sites, including the skin, but it is the deposition in blood vessels that leads to the start of atherosclerotic disease.

These processes were worked out in the researches of Brown and Goldstein in the 1970s from studies on patients with familial hypercholesterolamia — excessively high blood cholesterol. In this genetic disease, LDL membrane receptors are absent, so the uptake of LDL into cells is prevented. Heterozygotes (who have inherited one normal gene and one gene for this disease from their parents) have only half the normal number of LDL receptors. Normal persons have about 175 mg cholesterol per 100 ml of blood plasma, while those with the disease have over 600 mg/100 ml and heterozygotes about 300 mg/100 ml. Homozygotes with the disease usually die in infancy of coronary artery occlusion.

Alan W. Cuthbert


See also bile; fats; gall bladder.

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Cholesterol

Cholesterol

Cholesterol is a waxy substance found in the blood and body tissues of animals. It is an important structural component of animal cell membranes. Cholesterol is a lipid, a group of fats or fatlike compounds that do not dissolve in water. More specifically, it is a type of lipid known as a steroid. Other steroids include hormones, which are chemical substances produced by the body that regulate certain activities of cells or organs.

Cholesterol in the human body

Cholesterol is a biologically important compound in the human body. It is produced by the liver and used in the manufacture of vitamin D, adrenal gland hormones, and sex hormones. Large concentrations of cholesterol are found in the brain, spinal cord, and liver. Gallstones that occur in the gall bladder are largely made up of cholesterol. It is also found in bile (a fluid secreted by the liver), from which it gets its name: chol (Greek for "bile") plus stereos (Greek for "solid").

Normally, cholesterol produced by the liver circulates in the blood and is taken up by the body's cells for their needs. Cholesterol can also be removed from the blood by the liver and secreted in bile into the small intestine. From the intestine, cholesterol is released back into the bloodstream.

The body does not need cholesterol from dietary sources because the liver makes cholesterol from other nutrients. Eating saturated fats can cause the liver to produce more cholesterol than the body needs. Therefore, a diet high in saturated fats and cholesterol can raise blood cholesterol levels. Excess cholesterol that is not taken up by body cells may be deposited in the walls of arteries.

Cholesterol and heart disease. There has been much debate in the scientific community concerning the relationship between eating foods high in cholesterol and developing atherosclerosis (the blockage of coronary arteries with deposits of fatty material). Atherosclerosis impairs the flow of blood through arteries and leads to heart disease. A high blood cholesterol level is a risk factor for coronary artery disease.

Studies have shown that the major dietary cause of increased blood cholesterol levels is eating foods high in saturated fats (found mostly in animal products)not foods containing cholesterol, as was once believed. Smoking, lack of exercise, obesity, caffeine, and heredity are other factors influencing blood cholesterol levels.

Words to Know

Atherosclerosis: A disease in which plaques composed of cholesterol and fatty material form on the walls of arteries.

Bile: A fluid secreted by the liver that aids in the digestion of fats and oils in the body.

High-density lipoprotein (HDL): A lipoprotein low in cholesterol that is thought to protect against atherosclerosis.

Lipoprotein: A large molecule composed of a lipid (a fat or fatlike compound), such as cholesterol, and a protein.

Low-density lipoprotein (LDL): A lipoprotein high in cholesterol that is associated with increased risk of atherosclerosis.

Proteins: Large molecules that are essential to the structure and functioning of all living cells.

Saturated fat: Fats that are solid at room temperature or that become hard when exposed to cold temperatures.

"Good" cholesterol and "bad" cholesterol

Cholesterol is carried in the blood bound to protein molecules called lipoproteins. Most of the cholesterol is transported on low-density lipoproteins (LDLs). LDL receptors on body cell membranes help regulate the blood cholesterol level by binding with LDLs, which are then taken up by the cells. However, if there are more LDLs than LDL receptors, the excess LDLs, or "bad" cholesterol, can be deposited in the lining of the arteries. High-density lipoproteins (HDLs), or "good" cholesterol, are thought to help protect against damage to the artery walls by carrying excess LDL back to the liver.

[See also Circulatory system; Heart; Lipid; Nervous system ]

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Cholesterol

Cholesterol


Cholesterol is the most abundant sterol in animal tissues, making up as much as 25 percent of cell membranes. Cholesterol may be found free or as part of cholesteryl esters . It is a precursor molecule for many steroid hormones, including glucocorticoids , androgens and estrogen , aldosterone, and mineralocorticoids. A major component of lipoproteins, it is also the precursor for bile salts and bile acids, which are necessary for digestion. Gallstones contain large amounts of cholesterol.

Cholesterol is a seventeen-carbon polycyclic compound made up of three six-membered and one five-membered fused rings. The molecule is relatively nonpolar and hydrophobic , but is slightly polar due to the presence of an alcohol functional group .

Plants contain no cholesterol. In animals cholesterol synthesis occurs in many cells, but most cholesterol synthesis occurs in the liver. Food products from animals contain cholesterol, and the average adult consumes around 450 milligrams (0.016 ounces) per day. Dairy products and egg yolks are particularly rich in cholesterol. Diets low in fat content and high in vegetables, especially those containing polyunsaturated lipids , can help to lower plasma cholesterol levels. Many physicians recommend that their patients try to maintain cholesterol levels below 200 milligrams per deciliter.

Cholesterol in blood plasma is conjugated with other lipid molecules and with carrier proteins. These lipoprotein complexes may form droplets called chylomicrons, but cholesterol is usually transported as part of a number of larger lipoproteins, including low density lipoprotein (LDL), which carries cholesterol from the liver to muscle and other tissues, and high density lipoprotein (HDL), which carries cholesterol to the liver for conversion to bile acids. Physicians are especially concerned when patients have high levels of LDL (the so-called bad cholesterol) in blood; moderate exercise and low-cholesterol diets help to increase HDL (the so-called good cholesterol). Either high fat intake or problems with the transport of cholesterol to and from cells can lead to atherosclerosis (hardening of the arteries), which in turn can contribute to heart attack (myocardial infarction) or stroke.

Humans do not oxidize cholesterol for energy. Instead, cholesterol is converted to bile acids such as cholic acid and deoxycholic acid in liver tissue. Bile acids and salts are secreted into bile, which passes into the intestine and emulsifies fats for digestion. Although some bile acids may be reabsorbed in the intestine along with lipids, much cholesterol leaves the body in feces in the form of metabolites such as bile acids and salts.

Diets rich in oatmeal or other vegetable products are believed to help to lower plasma cholesterol levels. Soluble fibers from the vegetable materials absorb cholesterol and help to prevent absorption in the intestine.

see also Low Density Lipoprotein; Steroids.

Dan M. Sullivan

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cholesterol

cholesterol (kəlĕs´tərōl´), fatty lipid found in the body tissues and blood plasma of vertebrates; it is only sparingly soluble in water, but much more soluble in some organic solvents. A steroid, cholesterol can be found in large concentrations in the brain, spinal cord, and liver. The liver is the most important site of cholesterol biosynthesis, although other sites include the adrenal glands and reproductive organs. By means of several enzymatic reactions, cholesterol is synthesized from acetic acid; it then serves as the major precursor for the synthesis of vitamin D3, of the various steroid hormones, including cortisol, cortisone, and aldosterone in the adrenal glands, and of the sex hormones progesterone, estrogen, and testosterone. Cholesterol is excreted from the liver in the form of a secretion known as bile; it sometimes crystallizes in the gall bladder to form gallstones. The insolubility of cholesterol in water is also a factor in the development of atherosclerosis (see arteriosclerosis), the pathological deposition of plaques of cholesterol and other lipids on the insides of major blood vessels, a condition associated with coronary artery disease. This buildup of cholesterol in the blood vessels may constrict the passages considerably and inhibit the flow of blood to and from the heart. Recent research has shown that the relative abundance of certain protein complexes, called lipoproteins, to which cholesterol becomes attached may be the real cause of cholesterol buildup in the blood vessels. High-density lipoprotein (HDL) carries cholesterol out of the bloodstream for excretion, while low-density lipoprotein (LDL) carries it back into the system for use by various body cells. Researchers believe that HDL and LDL levels in the bloodstream may be at least as important as cholesterol levels, and now measure both to determine risk for heart disease. Reducing consumption of foods containing cholesterol and saturated fat has been found to lower blood cholesterol levels. Cholesterol levels can also be reduced with drugs, most especially with HMG-CoA reductase inhibitors (commonly called "statins" ), such as lovastatin (Mevacor) and atorvastatin (Lipitor), and by regular exercise.

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cholesterol

cholesterol The principal sterol in animal tissues, an essential component of cell membranes and the precursor for the formation of the steroid hormones. It is transported in the plasma lipoproteins. Not a dietary essential, since it is synthesized in the body. Eggs contain about 450 mg, milk 14 mg, cheese 70–120 mg, brain 2.2 mg, liver and kidney 300–600 mg, poultry 70–100 mg, and fish 50–60  mg/100 g.

An elevated plasma concentration of cholesterol is a risk factor for atherosclerosis. The synthesis of cholesterol in the body is increased by a high intake of saturated fats, but apart from people with a rare genetic defect in the regulation of cholesterol synthesis, dietary intake of cholesterol does not affect the plasma concentration very much, since there is normally strict control over the rate of synthesis. See also hypercholesterolaemia; hyperlipidaemia; HMG CoA reductase inhibitors; lipids, plasma.

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Cholesterol Test

CHOLESTEROL TEST

A lipid profile test measures the lipids in the bloodstream most associated with risk of atherosclerosis. Lipids measured with this test include total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides. Originally, this was done by a lengthy ultracentrifugation of serum or plasma, which created zones of particles with different densities. More recently the process has been automated using rapid enzymatic processes that measure total cholesterol, HDL cholesterol, and triglycerides. In the fasting state, one can then use the Friedwald formula to calculate LDL cholesterol: LDL cholesterol = total cholesterolHDL cholesteroltriglycerides. The ratio of total cholesterol divided by HDL cholesterol is used to predict the risk of coronary heart disease.

Donald A. Smith

(see also: Atherosclerosis; Blood Lipids; Cholesterol Test; HDL Cholesterol; LDL Cholesterol; Triglycerides; VLDL Cholesterol )

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cholesterol

cholesterol A sterol (see also steroid) occurring widely in animal tissues and also in some plants and algae. It can exist as a free sterol or esterified with a long-chain fatty acid. Cholesterol is absorbed through the intestine or manufactured in the liver. It serves principally as a constituent of blood plasma lipoproteins and of the lipid–protein complexes that form plasma membranes. It is also important as a precursor of various steroids, especially the bile acids, sex hormones, and adrenocorticoid hormones. The derivative 7-dehydrocholesterol is converted to vitamin D3 by the action of sunlight on skin. Increased levels of dietary and blood cholesterol have been associated with atherosclerosis. However, it is now thought that damage to blood vessels is caused by high levels of low-density lipoproteins (LDLs) in the blood; LDLs are the principal form in which cholesterol is transported in the bloodstream.

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"cholesterol." A Dictionary of Biology. . Encyclopedia.com. 22 Oct. 2017 <http://www.encyclopedia.com>.

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cholesterol

cholesterol White, fatty steroid, occurring in large concentrations in the brain, spinal cord and liver. It is synthesized in the liver, intestines and skin, and is an intermediate in the synthesis of vitamin D and many hormones. Gallstones are composed mainly of cholesterol. Meat-rich diets may produce Low-density lipoprotein cholesterol (LDL-cholesterol), which can become high cholesterol in blood vessels and lead to atherosclerosis (hardening of the arteries) and arteriosclerosis (degenerative disease of the arteries). High-density lipoprotein cholesterol (HDL-cholesterol) is a beneficial form that reduces LDL-cholesterol and fat by transporting them to the liver which breaks them down. Certain diets, such as those reducing saturated fat, can lower the dangers of cholesterol. Home kits are available to check cholesterol levels.

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cholesterol

cho·les·ter·ol / kəˈlestəˌrôl; -ˌrōl/ • n. a compound of the sterol type, C27H45OH, found in most body tissues, including the blood and the nerves. Cholesterol and its derivatives are constituents of cell membranes and precursors of other steroid compounds, but high concentrations in the blood are thought to promote atherosclerosis.

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cholesterol

cholesterol (kŏl-est-er-ol) n. a fatlike material (a sterol) present in the blood and most tissues, especially nervous tissue. Elevated blood concentration of cholesterol (hypercholesterolaemia) is often associated with atheroma, of which cholesterol is a major component. Cholesterol is also a constituent of gallstones.

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cholesterol

cholesterol The most abundant sterol in animal tissues, which strengthens cell membranes. It is derived endogenously from acetyl coenzyme A, or exogenously from food. It is a precursor of steroid hormones and bile acids.

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cholesterol

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