About Cholesterol
Cholesterol is a lipid (one of the major classifications of biological substances). Lipids are also called fats. Olive oil, lard, and most of the stuff in butter are lipids, and lipids are present in pretty much all foods.
In addition to lipids consumed in the diet, the body manufactures
lipids. An adult produces about 1 gram of cholesterol 
every day, and
a typical diet includes 0.3 grams of cholesterol per day. Your body
uses lipids in many ways, including the very membranes around cells,
and cholesterol is a normal part of your body. We need cholesterol. It is when the cholesterol level in your bloodstream
gets too high that you can be at risk
for long-term chronic diseases of the cardiovascular system.
Cholesterol is a specific form of lipid called a steroid. Other steroids include the major sex hormones testosterone and estrogen as well as the common medication cortisone and other prescription drugs used for allergies and anti-inflammation and birth control. The steroids you hear about that some bodybuilders and athletes use to build muscle are also in the same chemical class.
Cholesterol in the bloodstream ("serum cholesterol") can be divided into high-density lipids (HDL) and low-density lipids (LDL). There are several subforms of HDL, one of which is called alpha HDL and within alpha HDL there are different types.
A more precise division breaks down blood (plasma) lipoproteins into five major families:
-
chylomicrons
-
very low-density lipoproteins (VLDL)
-
intermediate-density lipoproteins (IDL)
-
low-density lipoproteins (LDL)
-
high-density lipoproteins (HDL)
Scientists think that alpha-1 is the type of cholesterol that should be increased to help, while other types (alpha-2 and alpha-3) should be low. The ideal cholesterol medication would raise alpha-1, lower alpha-2, alpha-3, and LDL. The ideal drug would also have a high affinity for the enzyme active site and hence a selective inhibition of HMGR in the liver.
\Does high LDL "cause" cardiovascular disease? Or is it more appropriately called a "risk factor"? While decades ago the more amorphous "risk factor" may have been an appropriate description, science has found such strong connections that the word "cause" is probably appropriate.
Patient cholesterol is measured in a routing blood test. The "lipid panel" done at many clinics gives total cholesterol, high-density lipid cholesterol, and low-density lipid cholesterol levels. Some doctors do not prescribe statins after the first problemetic lipid report. They feel readings at more than one office visit are more reliable.
Cholesterol levels are reported in milligrams per decliter - mg/dl. If someone says their total cholsterol is 200, that means the concentration is 200 mg/dl. Academic papers report cholesterol concentrations in mmol/liter. You can convert mg/dl to mmol/liter by dividing by 38.7.
| mg/dl | mmol/liter |
| 70 | 1.81 |
| 100 | 2.59 |
| 130 | 3.36 |
| 150 | 3.87 |
| 170 | 4.40 |
| 200 | 5.17 |
Synthesis and absorption of cholesterol are interrelated and the body's processes for regulating cholesterol levels in the bloodstream are complex. This is why any external intervention (such as drug therapy) can be fraught with risks.
Diessenters
A minority of scientists and doctors think there is no connection between cholesterol and heart disease, although even these people concede statins are effective. They just think the mechanism by which statins work is different from the official story. However, studies show that people with a mutation in the PCSK9 gene, who have low cholestrol levels their whole lives, have lower incidence of cardiovascular problems. Drug companies were trying to find PCSK9 inhibitors that could be developed into clinical drugs. These companies saw how much money statins made when they were under patent and were looking for something new they could patent. The corporations Amgen and Sanofi developed antibodies to interfere with PCSK9 ( Repatha and Praluent), but they never saw much commercial success as the medical establishment They are priced at over $10,000 per year per patient. In 2017, the results of a large study were released and showed some efficacy of Repatha in reducing cardiovascular risk. However, the risk was only 15 percent lower than when people took statins, so industry commenters thought it was a failure, given the high cost of the drug.
Origin
The liver releases a liquid called bile. It was known in ancient times; today we know bile helps the body absorb fats in the diet. Cholesterol was first identified as a constituent of bile. "Chole" means "from bile" and "sterol" is a suffix on many biochemicals, referring to steroid alcohols. Steroids are a class of chemicals found in the body. By one account, scientists first identified cholesterol in 1888 from gallstones and named it cholesterine which is Greek for "solid bile".
The bile also contains "bile salts" and "bile acids". These are chemically similar to cholesterol - indeed cholesterol is a starting point in the body’s synthesis of bile acids. In the intestines, bile acts to emulsify the fats in the diet, permitting easier absorption of the fats into the bloodstream.
Cholesterol is also a starting point for the body’s manufacture of the sex hormones testosterone, estrogen, and progesterone. Cholesterol in the skin is converted to Vitamin D. This conversion is triggered by exposure to sunlight.
Gallstones sometimes form. They are mineralized particles that get stuck in digestive tissue and can cause medical problems The gallstones are composites of several constituents, and cholesterol is one of those constituents. Gallstones with a large portion of cholesterol are called "cholesterol stones".
Some people go through life with high cholesterol and never have any adverse cardiovascular events. Others have low levels of LDL and get a heart attack nevertheless. You can’t definitively say the person with high cholesterol will suffer a stroke or angina.
Over time cholesterol can deposit in plaques on the arteries, which increases the risk of heart attack and stroke. Plaque is a hard composite material composed of cholesterol, other lipids, calcium, and collagen as well as embedded white blood cells. It takes high cholesterol levels (specifically LDL-C) and time (years) to build up a restriction in the arteries.
The cholesterol in your body comes from the stuff you make yourself (most of it) and what came through your diet. Over the years the medical community has come to the conclusion that cholesterol in the diet has little effect on serum cholesterol levels. The Canadian Guidelines have dropped the admonition against eating a high-cholsterol diet.
Can cholesterol levels get too low? As a practical matter, there is no evidence of overly low low-density cholesterol levels (LDL) causing health problems. Clinical trial measurements have not found negative effects when drugs are used to lower LDL.
