Cholesterol is a waxy steroid of fat produced in liver or intestine, used for the synthesis of hormones and cell membranes and transported in the blood plasma of all mammals. Cholesterol is a very essential structural component of plasma membrane of mammals required for maintaining proper membrane permeability and fluidity. It is also an important agent required for the manufacture of bile acids, steroid hormones and vitamin D. It is the principal steroid synthesized by animals however, smaller amounts are also produced in plants and fungi.
Cholesterol is entirely absent among prokaryotes. If its concentration increases in blood then the risk of cardiovascular diseases increases so its level must be kept under control. The word cholesterol has originated from a Greek word and was first discovered by Francois Poulletier de la Salle in gallstones in solid form in 1769 but, chemical identification was done by Eugène Chevreul in 1815 who gave the term cholesterine.
Cholesterol participates in the synthesis of male and female steroid hormones especially testosterone and estrogens. About 80% of the body’s cholesterol is synthesized by the liver while rest comes from our diet. The major sources of dietary cholesterol are meat, fish, poultry, and dairy products. Among meat, liver is excessively rich in cholesterol content while foods of plant origin lack cholesterol. After consuming a meal, the dietary cholesterol is absorbed from the intestine and packaged inside a protein coat. This cholesterol-protein coat complex is known as chylomicron which is later stored in the liver. Liver bears the potential of regulating cholesterol levels 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 of atherosclerosis increases. Typically for a person weighing 68 kg the total body cholesterol synthesis is 1 g per day. The daily additional dietary intake of cholesterol in the United States is 200-300 mg. The body maintains equilibrium by minimizing the total amount synthesized in the body 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% of the excreted cholesterol is again reabsorbed in the small intestine and reaches blood stream. Phytosterols can compete with cholesterol reabsorption in the intestine and thus, reduce cholesterol level. Cholesterol is a fat required by the body in small amounts. High blood levels of cholesterol 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 of triglycerides, high density lipoproteins (HDL), low density lipoproteins (LDL) and total cholesterol levels.
Methods for increasing the levels of good cholesterol or lowering blood cholesterol levels include cholesterol reducing drugs like statins, fibrates, niacin and bile acid resins. These drugs are not able 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 the bad cholesterol. We can conclude that the bad cholesterol is responsible for forming plaques in the 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 circulation for excretion via liver.
Three major types of lipoproteins are found in the serum of a fasting individual namely, low density lipoproteins (LDL), high density lipoproteins (HDL) and very low density lipoproteins (VLDL).
1. Low density lipoproteins (LDL) or bad cholesterol and its management
LDL or bad cholesterol comprises 60-70% of the total serum cholesterol. It is the major atherogenic 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 known as cholesterol plaque. This plaque is responsible for the hardening of arterial walls so they become narrow and the process is identified as atherosclerosis.
Liver not only manufactures and secretes LDL cholesterol in the blood stream but also removes it from the blood. A large number of active receptors are present on the surface of liver that actively bind to the LDL cholesterol molecules and remove it from blood. A deficiency of LDL receptors is associated with the higher level of these molecules in the blood.
A number of advantages are known when the levels of bad cholesterol undergo reduction for example, declination in the formation of new plaques on the walls of the arteries, removal of existing plaques from the arterial walls, narrowed arteries attain their normal shape, avoidance of rupturing of plaques which facilitates formation of blood clots and finally the risk of heart attack is reduced.
A number of studies have indicated that the risk of heart attack diminishes by 25% for every 10% drop in the LDL cholesterol level and it is the key factor ensuring that total blood cholesterol level has reached a safer zone. A study carried out with 4,000 individuals has confirmed 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 reduced down to 30% and consumption different kinds of foods rich in carbohydrates, proteins must be increased 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 be classified as saturated and unsaturated fats. Saturated fats are easily available in the meat, dairy products and some vegetable oils especially those derived from coconut, palm and cocoa. Therapeutic lifestyle changes adopted for lowering the levels of bad cholesterol include regular exercise, loss of excess body weight and following a diet with low concentration of saturated fats and cholesterol.
When lifestyle changes fail to give desired results then medications are taken into consideration. Statins are the most effective drugs giving best results for lowering the levels of bad cholesterol and also reducing the risk of heart diseases. Other drugs that can be used include fibrates like gemfibrozin, resins such as cholestyramine, ezetimibe and Zetia. The National Institute of Health, the American Heart Association and the American College of Cardiology have published some guidelines that can help the medical experts while dealing with cases of high cholesterol.
2. High density lipoproteins (LDL) or good cholesterol and its advantages
HDL cholesterol or the good cholesterol as it prevents atherosclerosis by extracting cholesterol from the arterial walls and disposing them through liver. High levels of LDL cholesterol and low levels of HDL cholesterol are associated with the risk of heart diseases. So the levels must be maintained in order to enjoy a happy and healthy life. HDL cholesterol accounts for 20-30% of the total serum cholesterol. Since it reduces the risk of atherosclerosis its level must be checked from time to time.
Both heredity and diet have a significant effect on a person’s HDL, LDL and total cholesterol levels. Families with low HDL levels are at an elevated risk of heart attack and vice versa. Lifestyle and other factors also influence HDL levels. HDL levels are low in individuals who smoke, are overweight, inactive and suffer from Type II diabetes mellitus. HDL levels are higher in individuals who are lean, exercise regularly and do not smoke. Estrogens also increase HDL levels 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 HDL cholesterol. Reducing LDL and raising HDL levels have a beneficial effect on an individual’s health. Earlier the researchers were much focused on the ways of reducing the levels of bad cholesterol but with advancement in research it became clear that it is better to raise the levels of good cholesterol as it will automatically reduce bad cholesterol levels. The levels may be raised by weight loss, regular exercise and intake of niacin.
Some studies have suggested that drugs like statin when coupled with niacin give better results and women with high levels of HDL have reduced risk of heart attack. The average HDL level for women must be in between 50-55 mg/dL and for men 40-50 mg/dL. The total cholesterol to HDL cholesterol ratio can be of help in estimating 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 the risk of heart attack. For every 1 mg/dL rise in the HDL cholesterol level the risk of coronary heart disease reduces by 2-4%. However, therapeutic lifestyle changes can help in increasing the HDL levels. 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 in raising HDL levels. Regular alcohol consumption for example, taking one drink per day can also help in this regard but as alcohol consumption is coupled with many adverse health effects this criterion is not taken into consideration. Effective drugs include gemfibrozil, estrogen and lower doses of statin. A newer medicine, fenofibrate has also given better results and is used in reducing serum triglycerides.
3. Triglycerides or very low density lipoproteins (VLDL) or ugly cholesterol and its effects
The ugly cholesterol is a triglyceride rich lipoprotein that accounts for 10-15% of the total serum cholesterol. This cholesterol is produced by liver and some remnants of VLDL seem to promote atherosclerosis similar to that of LDL. Triglyceride is a form of fat transported to the tissue through blood. Body’s majority of fatty tissue is composed of triglycerides. Serum triglycerides can be derived from two sources.
The first source is the food that we consume for example, if we consume 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 acids released by the fat cells and ties them in triglyceride bundles that are later utilized as fuel. There is a controversy about the fact that whether high levels of triglycerides alone are responsible for coronary 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 some individuals elevated triglyceride levels are inherited and this condition is identified as hypertriglyceridemia. The common examples of hypertriglyceridemia include mixed hypertriglyceridemia, familial hypertriglyceridemia and familial dysbetalipoproteinemia.
Hypertriglyceridemia can also occur due to some non-genetic factors like obesity, excessive alcohol, diabetes mellitus, kidney disease and use of estrogen containing medicines like birth control pills. The levels can be returned back to normal without medication by taking the help of a physician. The first step involved in the treatment of hypertriglyceridemia includes intake of a diet low in fats with limited consumption of sweets, regular aerobic exercise, loss of excess body weight, reduction of alcohol consumption and quitting smoking. In patients with diabetes mellitus effective control of glucose level is needed.
When medications become necessary statins, fibrates and niacin can be used. Fibrates not only reduce 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 other hand, reduce both triglyceride and LDL levels but are ineffective in raising HDL levels. A newly launched medicine, fenofibrate has shown promising results in lowering triglyceride and LDL levels as well as raising HDL levels especially in those individuals who show sub-optimal responses with fibrates. In some individuals a mixed dose of fibrate or fenofibrate along with statin is prescribed for better results.