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  1. 1. Cholesterol Fact vs. Fiction For many of us the word cholesterol brings both a sense of fear, and a degree of uncertainty. Most of us have heard the word, yet what exactly is it about cholesterol that has gotten it such an infamous name?
  2. 2. What is cholesterol? <ul><li>Cholesterol is a lipidic, waxy alcohol found in the cell membranes and transported in the blood plasma of all animals. </li></ul><ul><li>It is an essential component of mammalian cell membranes where it is required to establish proper membrane permeability and fluidity. </li></ul><ul><li>Cholesterol is the principal sterol synthesized by animals, but small quantities are synthesized in other eukaryotes, such as plants and fungi. It is almost completely absent among prokaryotes. </li></ul><ul><li>Cholesterol is classified as a sterol (a contraction of steroid and alcohol). </li></ul>
  3. 3. Where does it come from? <ul><li>Cholesterol is synthesized in virtually all cells, and significant amounts of it can be absorbed from the diet. </li></ul><ul><li>Most of the cholesterol in the body is synthesized therein; some is absorbed in the diet </li></ul><ul><li>Cholesterol is primarily synthesized from acetyl CoA through the HMG-CoA reductase pathway in many cells and tissues. About 20–25% of total daily production (~1 g/day) occurs in the liver; other sites of high synthesis rates include the intestines, adrenal glands, and reproductive organs. </li></ul><ul><li>Major dietary sources of cholesterol include cheese, egg yolks, beef, pork, poultry, and shrimp. [13] </li></ul>
  4. 4. Why does it have a bad rap? <ul><li>Although cholesterol is essential for life, high levels in circulation are associated with atherosclerosis. </li></ul><ul><li>Trans and saturated fats are significant contributors to elevated cholesterol levels in the blood stream. </li></ul><ul><li>“ Bad cholesterol” or the cholesterol carried by LDL is also a common phrase in the discussion of health and nutrition. </li></ul>
  5. 5. HDL vs. LDL <ul><li>For those that have heard of cholesterol, usually HDL and LDL are the most familiar terms associated with it. </li></ul><ul><li>Both are lipoproteins that transport cholesterol. </li></ul><ul><li>HDL is considered the ‘good cholesterol.’ </li></ul><ul><ul><li>It is hypothesized that HDL can help remove cholesterol from atheroma accumulations within arteries and transport it back to the liver for excretion or re-utilization </li></ul></ul><ul><ul><li>HDL are the smallest of the lipoprotein particles. </li></ul></ul><ul><ul><li>They are the densest because they contain the highest proportion of protein. </li></ul></ul><ul><li>LDL is considered the ‘bad cholesterol.’ </li></ul><ul><ul><li>Too much LDL circulating in the blood can slowly build up in the inner walls of the arteries forming atheromas. </li></ul></ul><ul><ul><li>LDL also regulates cholesterol synthesis. </li></ul></ul>
  6. 6. An Incomplete Investigation <ul><li>Given the well-recognized role of cholesterol in cardiovascular disease, it is surprising that some studies have shown an inverse correlation between cholesterol levels and mortality in subjects over 50 years of age—an 11% increase overall and 14% increase in CVD mortality per 1 mg/dL per year drop in cholesterol levels. </li></ul><ul><li>In the Framingham Heart Study, the researchers attributed this phenomenon to the fact that people with severe chronic diseases or cancer tend to have below-normal cholesterol levels. [28] </li></ul><ul><li>This explanation is not supported by the Vorarlberg Health Monitoring and Promotion Programme, in which men of all ages and women over 50 with very low cholesterol were increasingly likely to die of cancer, liver diseases, and mental diseases. </li></ul><ul><li>Framingham studies and others have shown that the average LDL cholesterol of those that suffer from heart-disease is not much higher than the healthy. </li></ul>
  7. 7. A closer look <ul><li>LDL is only one of five major groups of lipoproteins. </li></ul><ul><li>These five groups include: </li></ul><ul><ul><li>1) Chylomicrons * </li></ul></ul><ul><ul><li>2) Very low-density lipoprotein (VLDL) </li></ul></ul><ul><ul><li>3) Intermediate-density lipoprotein (IDL) </li></ul></ul><ul><ul><li>4) Low-density lipoprotein (LDL) </li></ul></ul><ul><ul><li>5) High-density lipoprotein (HDL) </li></ul></ul>* Chylomicrons (density < 0.95) are not shown because of their enormous size (about 100 x the size of VLDL).
  8. 8. Chylomicrons <ul><li>Chylomicrons transport exogenous lipids to liver, adipose, cardiac and skeletal muscle tissue where their triglyceride components are unloaded by the activity of lipoprotein lipase. </li></ul><ul><li>Nascent chylomicrons are created by small intestine and enter the blood stream. </li></ul><ul><li>While circulating, high-density lipoproteins (HDL) donate components to chylomicron, forming a mature chylomicron. </li></ul><ul><li>Once triglyceride stores are distributed, Chylomicron remnants are broken down by the liver. </li></ul>
  9. 9. Very low-density lipoprotein (VLDL) <ul><li>Triglycerides in the blood are primarily carried by VLDL, while cholesterol by LDL. </li></ul><ul><li>As triglycerides is removed from the VLDL via the action of the LPL enzyme, the composition of the molecule changes, and it becomes intermediate density lipoprotein (IDL). </li></ul><ul><li>VLDL levels have been correlated with accelerated rates of atherosclerosis, and are elevated in a number of diseases and metabolic states. </li></ul><ul><li>Both VLDL and LDL can be quantified by the number of apo B protein. These appear high in heart-disease patients. </li></ul>
  10. 10. Intermediate-density lipoprotein (IDL) <ul><li>IDLs are a result from the degradation of very low density lipoproteins (VLDLs). </li></ul><ul><li>In the case of carbohydrate abundance: </li></ul><ul><ul><li>The oil droplets are larger and IDL can be further degraded to a smaller and denser LDL particle. </li></ul></ul><ul><li>In the case of carbohydrate scarcity: </li></ul><ul><ul><li>The oil droplets are smaller and IDL can be further degraded to a fluffier, less-dense LDL particle. </li></ul></ul>
  11. 11. Connecting the Dots of Heart Disease <ul><li>Recall that triglycerides in the blood are primarily carried by VLDL, while cholesterol is primarily handled by LDL. </li></ul><ul><li>Thanks to a lipid metabolism specialist Ronald Krauss, we know there are actually seven discrete subclasses of LDL! </li></ul><ul><li>According to Krauss LDL can come in two varieties: </li></ul><ul><ul><li>(Pattern A) A fluffy lipoprotein full of cholesterol. </li></ul></ul><ul><ul><li>(Pattern B) A denser LDL with less cholesterol. </li></ul></ul><ul><li>He noted that only the densest LDL (Pattern B) seemed to be linked to heart disease, and it also was invariably linked to decreased levels of HDL (the ‘good’ cholesterol). </li></ul><ul><li>It seems that if the cholesterol that fills the LDL balloon was not in sufficient quantities, we would be at higher risk of heart diseases (and perhaps explains the inverse relationship seen between cholesterol and mortality in those over 50). </li></ul>
  12. 12. The Problem: Triglycerides & Carbohydrates, not Cholesterol <ul><li>While we have seen that cholesterol is a very important molecule, the real problem lies in the fact that carbohydrate-rich meals result in the liver converting excess glucose into triglycerides. </li></ul><ul><li>Remembering the triglycerides are transported by VLDL, we would see an increase in VLDL by consuming carbohydrates. These particles then deliver the triglycerides throughout the body, and end their life as a smaller and denser LDL. </li></ul><ul><li>The result of seven trials of Krauss demonstrated that diets lower in fat and higher in carbohydrates resulted in smaller and denser LDL particles. </li></ul><ul><li>Some of the work by Professor Stephen Phinney, has also noted a statistically significant decrease in the size of LDL associated with carbohydrate-rich diets. </li></ul><ul><li>This explains how triglycerides, more so than cholesterol, is the determining factor in obesity. </li></ul>