==== ====To learn more about Cholesterol and how to reduce it click below:http://www.rmmarketing.biz/cholesterol==== ====Cholesterol is a waxy steroid of fat produced in liver or intestine, used for the synthesis ofhormones and cell membranes and transported in the blood plasma of all mammals. Cholesterol isa very essential structural component of plasma membrane of mammals required for maintainingproper membrane permeability and fluidity. It is also an important agent required for themanufacture of bile acids, steroid hormones and vitamin D. It is the principal steroid synthesizedby animals however, smaller amounts are also produced in plants and fungi. Cholesterol is entirelyabsent among prokaryotes. If its concentration increases in blood then the risk of cardiovasculardiseases increases so its level must be kept under control. The word cholesterol has originatedfrom a Greek word and was first discovered by Francois Poulletier de la Salle in gallstones in solidform in 1769 but, chemical identification was done by EugÃ¨ne Chevreul in 1815 who gave theterm cholesterine.PhysiologyCholesterol participates in the synthesis of male and female steroid hormones especiallytestosterone and estrogens. About 80% of the bodys cholesterol is synthesized by the liver whilerest comes from our diet. The major sources of dietary cholesterol are meat, fish, poultry, anddairy products. Among meat, liver is excessively rich in cholesterol content while foods of plantorigin lack cholesterol. After consuming a meal, the dietary cholesterol is absorbed from theintestine and packaged inside a protein coat. This cholesterol-protein coat complex is known aschylomicron which is later stored in the liver. Liver bears the potential of regulating cholesterollevels in the blood stream. Cholesterol synthesis starts from simpler elements present in the body.In blood circulation it is transported within lipoproteins and if its level increases then the risk ofatherosclerosis increases. Typically for a person weighing 68 kg the total body cholesterolsynthesis is 1 g per day. The daily additional dietary intake of cholesterol in the United States is200-300 mg. The body maintains equilibrium by minimizing the total amount synthesized in thebody if the dietary intake of cholesterol increases.Cholesterol is also recycled, it is excreted by the liver via bile into the digestive tract. About 50% ofthe excreted cholesterol is again reabsorbed in the small intestine and reaches blood stream.Phytosterols can compete with cholesterol reabsorption in the intestine and thus, reducecholesterol level. Cholesterol is a fat required by the body in small amounts. High blood levels ofcholesterol can lead to coronary artery disease and angina. Nitrates are used to relieve angina.Most people require regular tests for knowing blood cholesterol levels that comprise checking oftriglycerides, high density lipoproteins (HDL), low density lipoproteins (LDL) and total cholesterollevels.Methods for increasing the levels of good cholesterol or lowering blood cholesterol levels includecholesterol reducing drugs like statins, fibrates, niacin and bile acid resins. These drugs are notable to reverse calcification and if coronary arteries are blocked then heart attack may occur. The
two chief types of cholesterols are high density lipoproteins (HDL) and low density lipoproteins(LDL). For the sake of simplicity HDL is considered as good cholesterol while LDL is known as thebad cholesterol. We can conclude that the bad cholesterol is responsible for forming plaques inthe arteries and thus, increases the risk of heart attack. The good cholesterol on the other hand,reverses cholesterol transport by taking it out of the plaque and sending it back to blood circulationfor excretion via liver.TypesThree major types of lipoproteins are found in the serum of a fasting individual namely, low densitylipoproteins (LDL), high density lipoproteins (HDL) and very low density lipoproteins (VLDL).1. Low density lipoproteins (LDL) or bad cholesterol and its managementLDL or bad cholesterol comprises 60-70% of the total serum cholesterol. It is the majoratherogenic lipoprotein used in the cholesterol lowering therapy as its higher levels are dangerous.It deposits cholesterol on the walls of arteries resulting in the formation of a hard substance knownas cholesterol plaque. This plaque is responsible for the hardening of arterial walls so theybecome narrow and the process is identified as atherosclerosis. Liver not only manufactures andsecretes LDL cholesterol in the blood stream but also removes it from the blood. A large numberof active receptors are present on the surface of liver that actively bind to the LDL cholesterolmolecules and remove it from blood. A deficiency of LDL receptors is associated with the higherlevel of these molecules in the blood.A number of advantages are known when the levels of bad cholesterol undergo reduction forexample, declination in the formation of new plaques on the walls of the arteries, removal ofexisting plaques from the arterial walls, narrowed arteries attain their normal shape, avoidance ofrupturing of plaques which facilitates formation of blood clots and finally the risk of heart attack isreduced. A number of studies have indicated that the risk of heart attack diminishes by 25% forevery 10% drop in the LDL cholesterol level and it is the key factor ensuring that total bloodcholesterol level has reached a safer zone. A study carried out with 4,000 individuals hasconfirmed that the levels of bad cholesterol and risk of heart attack were reduced to about 25%and 42%by using the drug statin. It is profitable that the daily calorie intake of fat must be reduceddown to 30% and consumption different kinds of foods rich in carbohydrates, proteins must beincreased as the body will convert them into triglycerides which are later stored as fat.Foods rich in saturated fats increase levels of LDL cholesterol in blood stream. Fats may beclassified as saturated and unsaturated fats. Saturated fats are easily available in the meat, dairyproducts and some vegetable oils especially those derived from coconut, palm and cocoa.Therapeutic lifestyle changes adopted for lowering the levels of bad cholesterol include regularexercise, loss of excess body weight and following a diet with low concentration of saturated fatsand cholesterol. When lifestyle changes fail to give desired results then medications are taken intoconsideration. Statins are the most effective drugs giving best results for lowering the levels of badcholesterol and also reducing the risk of heart diseases. Other drugs that can be used includefibrates like gemfibrozin, resins such as cholestyramine, ezetimibe and Zetia. The NationalInstitute of Health, the American Heart Association and the American College of Cardiology havepublished some guidelines that can help the medical experts while dealing with cases of highcholesterol.
2. High density lipoproteins (LDL) or good cholesterol and its advantagesHDL cholesterol or the good cholesterol as it prevents atherosclerosis by extracting cholesterolfrom the arterial walls and disposing them through liver. High levels of LDL cholesterol and lowlevels of HDL cholesterol are associated with the risk of heart diseases. So the levels must bemaintained in order to enjoy a happy and healthy life. HDL cholesterol accounts for 20-30% of thetotal serum cholesterol. Since it reduces the risk of atherosclerosis its level must be checked fromtime to time. Both heredity and diet have a significant effect on a persons HDL, LDL and totalcholesterol levels. Families with low HDL levels are at an elevated risk of heart attack and viceversa. Lifestyle and other factors also influence HDL levels. HDL levels are low in individuals whosmoke, are overweight, inactive and suffer from Type II diabetes mellitus. HDL levels are higher inindividuals who are lean, exercise regularly and do not smoke. Estrogens also increase HDLlevels so women have high HDL cholesterol levels as compared to men.Lowering of the LDL cholesterol level is however easier than elevating the levels of HDLcholesterol. Reducing LDL and raising HDL levels have a beneficial effect on an individualshealth. Earlier the researchers were much focused on the ways of reducing the levels of badcholesterol but with advancement in research it became clear that it is better to raise the levels ofgood cholesterol as it will automatically reduce bad cholesterol levels. The levels may be raised byweight loss, regular exercise and intake of niacin. Some studies have suggested that drugs likestatin when coupled with niacin give better results and women with high levels of HDL havereduced risk of heart attack. The average HDL level for women must be in between 50-55 mg/dLand for men 40-50 mg/dL. The total cholesterol to HDL cholesterol ratio can be of help inestimating the risk of atherosclerosis. An average ratio must be in between 4-5.Studies have indicated that even a small increase in the level of HDL cholesterol can reduce therisk of heart attack. For every 1 mg/dL rise in the HDL cholesterol level the risk of coronary heartdisease reduces by 2-4%. However, therapeutic lifestyle changes can help in increasing the HDLlevels. When these changes fail to give positive results then medication is taken into account.Regular aerobic exercise, loss of excessive body weight and cessation of smoking are helpful inraising HDL levels. Regular alcohol consumption for example, taking one drink per day can alsohelp in this regard but as alcohol consumption is coupled with many adverse health effects thiscriterion is not taken into consideration. Effective drugs include gemfibrozil, estrogen and lowerdoses of statin. A newer medicine, fenofibrate has also given better results and is used in reducingserum triglycerides.3. Triglycerides or very low density lipoproteins (VLDL) or ugly cholesterol and its effectsThe ugly cholesterol is a triglyceride rich lipoprotein that accounts for 10-15% of the total serumcholesterol. This cholesterol is produced by liver and some remnants of VLDL seem to promoteatherosclerosis similar to that of LDL. Triglyceride is a form of fat transported to the tissue throughblood. Bodys majority of fatty tissue is composed of triglycerides. Serum triglycerides can bederived from two sources. The first source is the food that we consume for example, if weconsume a diet rich in fats then intestine packs some of them while rest is transported to the liver.The second source is the liver itself. When fats are received by the liver, it takes fatty acidsreleased by the fat cells and ties them in triglyceride bundles that are later utilized as fuel. There isa controversy about the fact that whether high levels of triglycerides alone are responsible forcoronary heart disease or not.
Other clinical conditions frequently coupled with high triglyceride levels are high blood pressure,obesity, diabetes, chronic kidney, liver and circulatory disease and hypothyroidism. In someindividuals elevated triglyceride levels are inherited and this condition is identified ashypertriglyceridemia. The common examples of hypertriglyceridemia include mixedhypertriglyceridemia, familial hypertriglyceridemia and familial dysbetalipoproteinemia.Hypertriglyceridemia can also occur due to some non-genetic factors like obesity, excessivealcohol, diabetes mellitus, kidney disease and use of estrogen containing medicines like birthcontrol pills. The levels can be returned back to normal without medication by taking the help of aphysician. The first step involved in the treatment of hypertriglyceridemia includes intake of a dietlow in fats with limited consumption of sweets, regular aerobic exercise, loss of excess bodyweight, reduction of alcohol consumption and quitting smoking. In patients with diabetes mellituseffective control of glucose level is needed.When medications become necessary statins, fibrates and niacin can be used. Fibrates not onlyreduce the triglyceride levels but also raise the HDL levels and particle size of LDL molecules.Same task is done by niacin but it lowers the levels of Lp (a) cholesterol. Statins on the otherhand, reduce both triglyceride and LDL levels but are ineffective in raising HDL levels. A newlylaunched medicine, fenofibrate has shown promising results in lowering triglyceride and LDL levelsas well as raising HDL levels especially in those individuals who show sub-optimal responses withfibrates. In some individuals a mixed dose of fibrate or fenofibrate along with statin is prescribedfor better results.FunctionCholesterol is needed for building and maintenance of membranes as it modulates membranefluidity over a wide range of physiological temperatures. The hydroxyl group located on thecholesterol molecule interacts with the polar head groups of membrane phospholipids andsphingolipids and thus, reduces permeability of membrane to protons. Within the cell membrane italso functions in intracellular transport, nerve conduction and cell signaling. Cholesterol is alsovery essential for the structure and function of invaginated caveolae and clathrin coated pits inendocytosis. Recently, it has been suggested that cholesterol also plays some role in cell signalingprocess by assisting in formation of lipid rafts in plasma membrane. In many neurons a cholesterolrich myelin sheath is present which is derived from the compact layers of Schwann cell membranehelping in efficient nerve conduction. This layer also provides insulation. Within cells cholesterolalso acts as a precursor molecule for several biochemical processes. In liver, cholesterol isconverted into bile which is then stored in gallbladder. Bile is rich in bile salts which activelysolubilize fat molecules in the digestive tract and thus, aid in intestinal absorption of fat moleculesand fat soluble vitamins like A,D,E and K. It is also an essential precursor molecule for thesynthesis of vitamin D and steroid hormones.Biosynthesis and RegulationAll animal cells manufacture cholesterol but the rate of production varies depending upon the celltype and the organ involved. About 20-25% daily production of cholesterol occurs in the liver andrest in intestines, adrenal glands and reproductive organs. Synthesis of cholesterol within the bodystarts with one molecule of acetyl- CoA and one molecule of acetoacetyl-CoA that are hydrated toform 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). The HMG-CoA so formed is reduced to form
mevalonate by the enzyme HMG-CoA reductase. This step is the rate limiting and irreversible stepin the cholesterol synthesis. The mevalonate so formed is converted into 3-isopentenylpyrophosphate in three reactions that need ATP. Mevalonate is then decarboxylated to formisopentenyl pyrophosphate. Then three molecules of isopentenyl pyrophosphate collaboratetogether to form farnesyl pyrophosphate in the presence of geranyl transferase. Two molecules offarnesyl pyrophosphate join to form squalene in the endoplasmic reticulum and the reaction iscatalyzed by squalene synthase. Oxidosqualene cyclase then converts squalene to lanosterol thatfinally forms cholesterol. The mechanism and regulation of cholesterol was worked out by KonardBloch and Feodor Lynen for which they received Noble Prize in Physiology or Medicine in 1964.The biosynthesis of cholesterol is under the strict control of the cholesterol levels but homeostaticmechanisms involved in its regulation are partly understood. A higher intake of cholesterol fromfood results in a net decrease in endogenous production and vice versa. The main mechanisminvolved comprises sensing of intracellular cholesterol by the protein SREBP (sterol regulatoryelement-binding protein 1 and 2) located on the endoplasmic reticulum. In the presence ofcholesterol this protein binds with two other proteins namely, SCAP (SREBP-cleavage-activatingprotein) and Insig 1. When the cholesterol level declines Insig 1 dissociates from the SREBP-SCAP complex, allowing entry of this complex into the Golgi apparatus, where SREBP is cleavedby S1 and S2 proteases. These proteases are activated by SCAP when cholesterol levels decline.The cleaved SREBP then migrates towards the nucleus to act as a transcription factor and here itbinds to the sterol regulatory element (SRE) which stimulates transcription of many genes forexample, scavenging of circulating LDL from the blood stream by low density lipoprotein (LDL)receptor and increase in the endogenous production of cholesterol by HMG-CoA reductase. Alarger part of this signaling pathway was worked out by Dr. Michael S. Brown and Dr. Joseph L.Goldstein in 1970s for which they received Noble Prize in 1985.Cholesterol synthesis can be terminated when cholesterol levels are high. HMG-CoA reductasebears both cytosolic and membrane domains. The membrane domain is sensitive for the signalsresponsible for its degradation. Increased concentration of cholesterol causes a change in theoligomerized state of domain that makes it more susceptible to destruction by proteosome. Theactivity of this enzyme can also be reduced by phosphorylation by an AMP activated proteinkinase. Cholesterol is only slightly soluble in water and can be dissolved in water-based bloodstream but travels at exceedingly small concentrations. As cholesterol is insoluble in blood it istransported in the circulatory system within the lipoprotein complexes whose outer part is made upof amphiphilic proteins and lipids. Triglycerides and cholesterol esters are carried internally.Lipoproteins provide cholesterol a soluble medium to be transported through blood and for thisreason lipoproteins are carried in different forms within blood namely, chylomicrons, very lowdensity lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL)and high density lipoproteins (HDL).Chylomicrons are the least dense type of cholesterol transporting molecules whose shells are richin apolipoprotein B-48, apolipoprotein C and E. They carry fats from intestine to muscles and othertissues that require fatty acids for energy. Cholesterol that is not used by the muscles remains inthe form of chylomicron remnant which is later taken up by the liver through blood stream. VLDLmolecules produced by the liver are loaded with triacylglycerol and cholesterol that are not neededby the liver for the production of bile acids. These molecules contain apolipoprotein B100 andapoplipoprotein E in their shells. During transport the blood vessels cleave and absorbtriacylglycerol from IDL molecules that have high concentration of cholesterol. LDL molecules are
the major carriers of cholesterol in the blood and each molecule contains about 1,500 cholesterolesters. The shell of LDL molecule contains only one molecule of apolipoprotein B100 that isrecognized by the LDL receptors present on the peripheral tissues. During binding ofapolipoprotein B100 many LDL receptors become localized in the clathrin-coated pits. Both LDLand its receptors are internalized by endocytosis to form a vesicle within the cell which then fuseswith the lysosome containing lysosomal acid lipase that hydrolyzes cholesterol esters. At thisstage cholesterol can be used for the biosynthesis of membrane and can be stored within the cell.Synthesis of LDL receptor is regulated by SREBP protein. When the cell has sufficient amount ofcholesterol, LDL receptor synthesis is blocked and no more molecules of cholesterol can enterinside the cell. When the cell is deficient in cholesterol more LDL receptors are formed. When thissystem is deregulated more LDL molecules without LDL receptors appear in the bloodstreamespecially near the peripheral tissues. These molecules are then oxidized and taken up by themacrophages forming foam cells and contributing in the formation of atherosclerotic plaques onthe walls of the arteries causing heart attack. HDL molecules participate in reverse cholesteroltransport as they return cholesterol back to the liver for excretion. Cholesterol is susceptible tooxidation and can easily form oxysterols that are the oxygenated derivatives. Oxysterols can begenerated through three mechanisms especially by autoxidation, secondary oxidation to lipidperoxidation and cholesterol metabolizing enzyme oxidation. Oxysterols also participate in bileacid biosynthesis, transport of different forms of cholesterol and regulation of gene transcription.Cholesterol is oxidized by the liver into a variety of bile acids which are in turn conjugated withglycine, taurine, glucuronic acid. A mixture of both conjugated as well as non-conjugated bile acidsalong with cholesterol is excreted from the liver into bile. About 95% of the bile acids arereabsorbed from the intestines while rest is lost in faeces. The excretion and reabsorption of bileacids form the basis of enterohepatic circulation essential for digestion and absorption of thedietary fats. In certain circumstances, cholesterol crystallizes and forms gallstones especially inthe gallbladder. Lecithin and bilirubin gallstones are also known to occur but their percentage islow. Everyday about 1 g of cholesterol is known to enter the colon which comes from diet, bile,desquamated intestinal cells and can be metabolized by the colonic bacteria. Cholesterol is mainlyconverted into coprostanol which is a nonabsorbable sterol excreted in faeces. A cholesterolreducing bacterium has also been isolated from human faeces. Some cholesterol derivatives areknown to generate liquid crystalline cholesteric phase.Dietary sources of cholesterolAnimal fats are complex mixtures of triglycerides having lower proportions of phospholipids andcholesterol. Major dietary sources of cholesterol include cheese, egg yolks, beef, pork, shrimp andpoultry. Human breast milk also contains sufficient amounts of cholesterol. The amount cholesterolpresent in the plant sources is lesser when compared with the animal sources. Plant products likepeanuts and flax seeds bear phytosterols which are cholesterol like compounds helping to lowerserum cholesterol levels. The total fat intake especially in the form of saturated and trans fats playgreater role in blood cholesterol rather than the intake of cholesterol itself. Saturated fats areabundantly present in the full fat dairy products, animal fats, chocolate and several types of oils.Trans fats are obtained by the partial hydrogenation of unsaturated fats and do not occur insignificant amounts in nature. They are present in good amounts in the margarine, hydrogenatedvegetable fats and in many fast foods like snacks, fried or baked goods. Avoiding consumption of
cholesterol rich animal products not only reduces the amount of cholesterol taken through the dietbut also reduces the synthesis of cholesterol. Individuals interested to reduce their cholesterollevels through diet must consume less than 7% of their daily energy needs from the animal fatsand fewer than 200 mg of cholesterol per day. It is debatable that reduced consumption of dietaryfat and cholesterol can lower blood cholesterol levels because any declination in the dietaryuptake of cholesterol is compensated by the organs involved in its synthesis so that the levels canbe kept constant.Foods that might cholesterolDietary fibers play a major role in maintaining our health as well as also protect us from a numberof diseases like diabetes and heart diseases. Oats, oat bran and oat meal contain a special type ofsoluble fiber known as beta-glucan that helps in reducing the levels of LDL cholesterol. Oat fibersare different from other fibers in the manner that they reduce the levels of bad cholesterol whilethe levels of good cholesterol remain unchanged. So we can say that oat fibers help in reducingthe risk of coronary heart disease. Studies have also indicated that if individuals with high levels ofHDL consume 3 g of soluble oat fiber per day the total cholesterol levels may be declined. Soyprotein also protects against heart diseases and hypercholesterolemia as it reduces the badcholesterol and raises the good cholesterol. It also prevents the oxidation of bad cholesterol sothat it may not coagulate on the arterial walls.Several studies have indicated that drinking of green or black teas also reduce the bloodcholesterol concentration, blood pressure and inhibit blood clotting and also provide someprotection against cardiovascular diseases. Green tea is rich in catechins while black tea containsflavins that inhibit oxidation of bad cholesterol. Tea also contains folic acid that helps in reducingthe risk of heart attack and cancer. A person can get 25% of RDA for folic acid by drinking fivecups of tea in a day. Several studies have indicated that barely has some unique health promotingeffects especially for the heart. The cholesterol fighting efficiency of barley is more pronouncedthan that of oats. Studies have indicated that it can reduce up to 15% of total cholesterol levels inindividuals with elevated cholesterol levels. Barley is also a rich source of beta-glucan whichretards fat and cholesterol absorption by the intestines. The fiber is known to bind bile salts andthus, removes cholesterol from the body. Psyllium husk is also a rich source of soluble andinsoluble fibers known to reduce the risk of cardiovascular diseases, serum cholesterol, LDLlevels, triglycerides and apolipoprotein B. Psyllium husk is rich in a fiber known as beta-sitosterol.Cholesterol testing and reducing high cholesterolThe American Heart Association recommends that the cholesterol levels of individuals above 20years of age must be checked in every five years. A blood sample after 12-hour fasting is taken bythe medical expert for the determination of the lipoprotein profile. This determines LDL, HDL, totalcholesterol and triglyceride levels. Causes of high cholesterol may vary from person to person andare influenced by the lifestyle and gender of an individual. A number of steps can be taken in orderto reduce high cholesterol levels for example loss of excessive body weight. Avoidance ofconsumption of foods derived from animal fats, regular physical activity and exercise can also helpin maintaining low cholesterol levels. Levels of cholesterol in both males and females increaseafter a certain age and the levels in women tend to increase after menopause. Genes also play animportant role in a persons health.
Navodita MauriceArticle Source:http://EzineArticles.com/?expert=Navodita_Maurice==== ====To learn more about Cholesterol and how to reduce it click below:http://www.rmmarketing.biz/cholesterol==== ====