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Cholesterol

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  • 1. CHOLESTEROLCholesterol is a lipid (fat) which is produced by the liver. Cholesterol is vital fornormal body function. Every cell in our body has cholesterol in its outer layer.Cholesterol is a waxy steroid and is transported in the blood plasma of all animals. It isthe main sterol synthesized by animals - small amounts are also synthesized in plantsand fungi. A sterol is a steroid sub-group.Cholesterol levels among US adults today are generally higher than in all otherindustrial nations. During the 1990s there was some concern about cholesterol levels inAmerican children. According to the CDC (Centers for Disease Control andPrevention), nearly 1 in every 10 children/adolescents in the USA has elevated totalcholesterol levels; and this was after concentrations had dropped over a 20-year period.The word "cholesterol" comes from the Greek word chole, meaning "bile", and theGreek word stereos, meaning "solid, stiff".The function of cholesterolCholesterol is required to build and maintain membranes; it modulatesmembrane fluidity over the range of physiological temperatures. The hydroxyl group oncholesterol interacts with the polar head groups of the membrane phospholipids andsphingolipids, while the bulky steroid and the hydrocarbon chain are embedded in themembrane, alongside the nonpolar fatty-acid chain of the other lipids. Through theinteraction with the phospholipid fatty-acid chains, cholesterol increases membranepacking, which reduces membrane fluidity.[10]The structure of the tetracyclic ring ofcholesterol contributes to the decreased fluidity of the cell membrane as the molecule isin a trans conformation making all but the side chain of cholesterol rigid and planar. Inthis structural role, cholesterol reduces the permeability of the plasma membrane toneutral solutes, protons, (positive hydrogen ions) and sodium ions.Within the cell membrane, cholesterol also functions in intracellular transport,cell signaling and nerve conduction. Cholesterol is essential for the structure andfunction of invaginated caveolae and clathrin-coated pits, including caveola-dependentand clathrin-dependent endocytosis. The role of cholesterol in such endocytosis can beinvestigated by using methyl beta cyclodextrin (MβCD) to remove cholesterol from theplasma membrane. Recently, cholesterol has also been implicated in cell signalingprocesses, assisting in the formation of lipid rafts in the plasma membrane. Lipid raftformation brings receptor proteins in close proximity with high concentrations ofsecond messenger molecules. In many neurons, a myelin sheath, rich in cholesterol,since it is derived from compacted layers of Schwann cell membrane, providesinsulation for more efficient conduction of impulses.
  • 2. Within cells, cholesterol is the precursor molecule in several biochemicalpathways. In the liver, cholesterol is converted to bile, which is then stored in thegallbladder. Bile contains bile salts, which solubilize fats in the digestive tract and aid inthe intestinal absorption of fat molecules as well as the fat-soluble vitamins, A, D, E,and K. Cholesterol is an important precursor molecule for the synthesis of vitamin Dand the steroid hormones, including the adrenal gland hormones cortisol andaldosterone, as well as the sex hormones progesterone, estrogens, and testosterone, andtheir derivatives. Some research indicates cholesterol may act as an antioxidant.There are three main types of lipoproteinsCholesterol is carried in the blood by molecules called lipoproteins. Alipoprotein is any complex or compound containing both lipid (fat) and protein. Thethree main types are:• LDL (low density lipoprotein) - people often refer to it as bad cholesterol. LDLcarries cholesterol from the liver to cells. If too much is carried, too much for thecells to use, there can be a harmful buildup of LDL. This lipoprotein canincrease the risk of arterial disease if levels rise too high. Most human bloodcontains approximately 70% LDL - this may vary, depending on the person.• HDL (high density lipoprotein) - people often refer to it as good cholesterol.Experts say HDL prevents arterial disease. HDL does the opposite of LDL -HDL takes the cholesterol away from the cells and back to the liver. In the liverit is either broken down or expelled from the body as waste.• Triglycerides - these are the chemical forms in which most fat exists in the body,as well as in food. They are present in blood plasma. Triglycerides, inassociation with cholesterol, form the plasma lipids (blood fat). Triglycerides inplasma originate either from fats in our food, or are made in the body from otherenergy sources, such as carbohydrates. Calories we consume but are not usedimmediately by our tissues are converted into triglycerides and stored in fatcells. When your body needs energy and there is no food as an energy source,triglycerides will be released from fat cells and used as energy - hormonescontrol this process.Increase Our HDL Levels• Aerobic exercise. Many people dont like to hear it, but regular aerobicexercise (any exercise, such as walking, jogging or bike riding, that raisesyour heart rate for 20 to 30 minutes at a time) may be the most effective wayto increase HDL levels. Recent evidence suggests that the duration ofexercise, rather than the intensity, is the more important factor in raisingHDL choleserol. But any aerobic exercise helps.
  • 3. • Lose weight. Obesity results not only in increased LDL cholesterol, but alsoin reduced HDL cholesterol. If you are overweight, reducing your weightshould increase your HDL levels. This is especially important if your excessweight is stored in your abdominal area; your waist-to-hip ratio isparticularly important in determining whether you ought to concentrate onweight loss.• Stop smoking. If you smoke, giving up tobacco will result in an increase inHDL levels. (This is the only advantage I can think of that smokers haveover non-smokers -- it gives them something else to do that will raise theirHDL.)• Cut out the trans fatty acids. Trans fatty acids are currently present inmany of your favorite prepared foods -- anything in which the nutrition labelreads "partially hydrogenated vegetable oils" -- so eliminating them from thediet is not a trivial task. But trans fatty acids not only increase LDLcholesterol levels, they also reduce HDL cholesterol levels. Removing themfrom your diet will almost certainly result in a measurable increase in HDLlevels. Click here for a quick and easy review of trans fatty acids and theheart.• Alcohol. With apologies to the American Heart Association, whichdiscourages doctors from telling their patients about the advantages ofalcohol: one or two drinks per day can significantly increase HDL levels.More than one or two drinks per day, one hastens to add, can lead tosubstantial health problems including heart failure -- and there areindividuals who will develop such problems even when limiting theiralcohol intake to one or two drinks per day. Click here for a quick and easyreview of alcohol and the heart.• Increase the monounsaturated fats in your diet. Monounsaturated fatssuch as canola oil, avocado oil, or olive oil and in the fats found in peanutbutter can increase HDL cholesterol levels without increasing the totalcholesterol.• Add soluble fiber to your diet. Soluble fibers are found in oats, fruits,vegetables, and legumes, and result in both a reduction in LDL cholesteroland an increase HDL cholesterol. For best results, at least two servings a dayshould be used.• Other dietary means to increasing HDL. Cranberry juice has been shownto increase HDL levels. Fish and other foods containing omega-3 fatty acidscan also increase HDL levels. In postmenopausal women (but not,apparently, in men or pre-menopausal women) calcium supplementation canincrease HDL levels.
  • 4. Decrease LDL Without DrugsJoseph Keenan, a cardiology researcher and professor emeritus at the Universityof Minnesota, has a love-hate relationship with statins. On the one hand, he prescribesthem to many patients. On the other, he cant use them to control his own dangerouslyhigh cholesterol. Like many of the 25 percent or so of patients prescribed statins whoabandon them within six months, Keenan has had unpleasant side effects, such asmuscle spasms, and blood tests indicate muscle damage. "It came as a shock," he saysof finding out hed have to do without his Lipitor.What recourse do people like Keenan have? Some doctors, such as StevenNissen of the Cleveland Clinic, are so convinced of statins lifesaving power that theyfirst require patients to try all six before considering them intolerant. Next, patientsmight try a nonstatin drug such as Zetia, which lowers cholesterol by inhibiting itsabsorption in the intestine. But there are other weapons besides drugs in the cholesterolwars. For those intolerant of statins—and for people taking them as well—the followingstrategies can help defeat unhealthy cholesterol.• Diet. The foundation of any cholesterol-lowering regimen is a balanced diet.That doesnt mean you have to buy only products whose labels scream "lowcholesterol." In fact, says Christopher Gardner, a researcher at StanfordUniversity who specializes in nutrition, a varied diet that emphasizes plants,fish, legumes, whole grains, and fruits is significantly better at loweringproblematic cholesterol than a more conventional diet of prepared foods equallylow in saturated fats and cholesterol. Why? Components of plant-based dietsactively interact to improve cholesterol profiles, he suggests. That said, youllstill want to limit your intake of red meat, eggs, and cheese.The so-called Mediterranean diet, the dash (Dietary Approaches to StopHypertension) diet, and the Ornish Diet (which is particularly low in meat anddairy) are variations on this approach. One study found that a balanced diet did justas well as a statin at reducing bad cholesterol. Dean Ornish, the founder of thePreventive Medicine Research Institute in Sausalito, Calif., has shown that hismultipronged approach (diet, exercise, stress reduction, and social support), whilenot easy to maintain, can lower LDL by nearly 40 percent and even cause plaques inarteries to shrink—which not even statins have been proven to do.• Exercise. Regular exercise is also critical. Some studies show that regularaerobic exercise for a period of about 12 weeks can modestly increase beneficialHDL cholesterol—between 5 and 10 percent, and more for some people. Yourtriglyceride level and blood pressure should respond, too. Shoot for at least 30minutes of moderate aerobic exercise five to seven days a week.• Supplements. Natural food stores and the Internet are awash with productsclaiming to improve cholesterol profiles. For most, there is little or no evidenceof an effect on cholesterol levels (though some—Omega-3 fatty acids, for
  • 5. example—have not been studied rigorously enough to say definitely that theydont work).Notable exceptions worth exploring include niacin, plant sterols, and solublefiber supplements. Though niacin can raise blood sugar and cause flushing, a dailydose can raise HDL levels by 15 to 35 percent and lower LDL levels by about 20percent. Niacin has a risk of side effects, however, especially when combined with astatin. A daily serving of plant sterols (about 2 grams), in fortified foods such asmargarine, orange juice, and rice milk, can also lower LDL by about 15 percent.Eating plenty of soluble fiber, which occurs naturally in products such as oats, nuts,flax, and psyllium husk and in dietary supplements such as Metamucil, can alsodrop LDL. Red rice yeast, a popular dietary supplement, also works. But be warnedthat it contains lovastatin, the active ingredient in Mevacor, a prescription statin, andis "essentially an unregulated statin," says Robert Vogel, a cardiologist at theUniversity of Maryland.Lifestyle interventions often dont work nearly as well as a statin can. Exercise, abetter diet, and supplements can generally reduce bad cholesterol by 20 to 40percent, compared with 60 to 70 percent for statins. But Keenan estimates that 70percent of people with problematic cholesterol levels could gain control withlifestyle changes alone. He has. His LDL levels are down by about 60 percentthanks to diet, exercise, niacin and other supplements. Thats as good a job, he says,as Lipitor did.Symptoms of high cholesterol (hypercholesterolaemia)Symptoms of high cholesterol do not exist alone in a way a patient or doctorcan identify by touch or sight. Symptoms of high cholesterol are revealed if youhave the symptoms of atherosclerosis, a common consequence of having highcholesterol levels. These can include:• Narrowed coronary arteries in the heart (angina)• Leg pain when exercising - this is because the arteries that supply the legs havenarrowed.• Blood clots and ruptured blood vessels - these can cause a stroke or TIA (mini-stroke).Ruptured plaques - this can lead to coronary thrombosis (a clot forming in one of thearteries that delivers blood to the heart). If this causes significant damage to heartmuscle it could cause heart failure.Xanthomas - thick yellow patches on the skin, especially around the eyes. They are, infact, deposits of cholesterol. This is commonly seen among people who have inheritedhigh cholesterol susceptibility (familial or inherited hypercholesterolaemia).
  • 6. Causes of high cholesterolLifestyle causes• Nutrition - although some foods contain cholesterol, such as eggs, kidneys, eggsand some seafoods, dietary cholesterol does not have much of an impact inhuman blood cholesterol levels. However, saturated fats do! Foods high insaturated fats include red meat, some pies, sausages, hard cheese, lard, pastry,cakes, most biscuits, and cream (there are many more).• Sedentary lifestyle - people who do not exercise and spend most of their timesitting/lying down have significantly higher levels of LDL (bad cholesterol) andlower levels of HDL (good cholesterol).• Bodyweight - people who are overweight/obese are much more likely to havehigher LDL levels and lower HDL levels, compared to people who are ofnormal weight.• Smoking - this can have quite a considerable effect on LDL levels.• Alcohol - people who consume too much alcohol regularly, generally have muchhigher levels of LDL and much lower levels of HDL, compared to people whoabstain or those who drink in moderation.High cholesterol levels can cause:Atherosclerosis - narrowing of the arteries.• Higher coronary heart disease risk - an abnormality of the arteries that supplyblood and oxygen to the heart.• Heart attack - occurs when the supply of blood and oxygen to an area of heartmuscle is blocked, usually by a clot in a coronary artery. This causes your heartmuscle to die.• Angina - chest pain or discomfort that occurs when your heart muscle does notget enough blood. Other cardiovascular conditions - diseases of the heart andblood vessels.Stroke and mini-stroke - occurs when a blood clot blocks an artery or vein,interrupting the flow to an area of the brain. Can also occur when a blood vesselbreaks. Brain cells begin to die.
  • 7. If both blood cholesterol and triglyceride levels are high, the risk of developingcoronary heart disease rises significantly.The treatments for high cholesterol?LifestyleMost people, especially those whose only risk factor has been lifestyle, cangenerally get their cholesterol and triglyceride levels back to normal by:Doing plenty of exercise (check with your doctor)Eating plenty of fruits, vegetables, whole grains, oats, good quality fatsAvoiding foods with saturated fatsGetting plenty of sleep (8 hours each night)Bringing your bodyweight back to normalAvoiding alcoholStopping smokingMany experts say that people who are at high risk of developing cardiovasculardisease will not lower their risk just by altering their diet. Nevertheless, ahealthy diet will have numerous health benefits.Cholesterol-controlling medicationsIf your cholesterol levels are still high after doing everything mentionedabove, your doctor may prescribe a cholesterol-lowering drug. They may includethe following:• Statins (HMG-CoA reductase inhibitors) - these block an enzyme in your liverthat produces cholesterol. The aim here is to reduce your cholesterol levels tounder 4 mmol/liter and under 2 mmol/liter for your LDL. Statins are useful forthe treatment and prevention of atherosclerosis. Side effects can includeconstipation, headaches, abdominal pain, and diarrhea. Atorvastatin, fluvastatin,lovastatin, pravastatin, rosuvastatin and simvastatin are examples of statins.• Aspirin - this should not be given to patients under 16 years of age.• Drugs to lower triglyceride levels - these are fibric acid derivatives and includegemfibrozil, fenofibrate and clofibrate.• Niacin - this is a B vitamin that exists in various foods. You can only get veryhigh doses with a doctors prescription. Niacin brings down both LDL and HDLlevels. Side effects might include itching, headaches, hot flashes (UK: flushes),and tingling (mostly very mild if they do occur).
  • 8. • Anti hypertensive drugs - if you have high blood pressure your doctor mayprescribe Angiotensin-converting enzyme (ACE) inhibitors, Angiotensin ||receptor blockers (ARBs), Diuretics, Beta-blockers, Calcium channel blockers.In some cases cholesterol absorption inhibitors (ezetimibe) and bile-acidsequestrants may be prescribed. They have more side effects and requireconsiderable patient education to achieve compliance (to make sure drugs aretaken according to instruction).Statins (or HMG-CoA reductase inhibitors) are a class of drugs used to lowercholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a centralrole in the production of cholesterol in the liver. Increased cholesterol levels have beenassociated with cardiovascular diseases,[1]and statins are therefore used in theprevention of these diseases. Research has found that statins are most effective fortreating cardiovascular disease (CVD) (secondary prevention), with questionable benefitin those without previous CVD, but with elevated cholesterol levels.[2][3]Statins haverare but severe adverse effects, particularly muscle damage, and some doctors believethey are overprescribed.