June 2003

Statins:Cholesterol‑lowering drugs

by Dr. Howard Loomis

This month, I am going to revisit a column I wrote in October of 2001 on statins. At that time a consumer advocacy group requested that the Food and Drug Administration require the makers of cholesterol‑lowering (statin) drugs to warn patients of the associated risk of muscle deterioration. It seems the side effects of statin use are unexplained muscle pain, muscle tenderness, muscle weakness, or general tiredness. These symptoms can indicate drug‑induced muscle deterioration.

Such action was never taken, of course. Instead, the use of drugs such as Lipitor, Pravachol, Zocor, Altace, and Lescol has increased dramatically. In fact, researchers now theorize that the anti‑inflammatory effect of these drugs may be useful in the treatment of multiple sclerosis and perhaps even in all so‑called autoimmune diseases.

Other recent studies of the use of statins include the following:

*** An 18‑to‑25% reduction in heart attacks and strokes in patients who are considered to be at high risk. Only patients with three heart disease risk factors were studied.

*** The use of statins for patients with normal or low cholesterol levels to reduce the risk of ever having a heart attack.

*** A British study calling for much wider guidelines for the use of statins. They found the drugs to be safe and effective for all ages.

*** The use of statins to lower the risk of osteoporosis. Since older women are at risk for both osteoporosis and heart attacks one drug could prevent both conditions.

*** Statins have an anti‑inflammatory effect in blocking a vasoconstrictive substance found to be at high levels in Alzheimer's patients.

*** The drugs are now being suggested for use in children who have a genetic disorder predisposing them to heart disease. In fact, some researchers suggest their use in any child with high cholesterol levels. However, that has caused other scientists to warn of the birth defects caused by statins. They say it is one thing to use statins in adults who have been warned of the problem and still another to use them for patients not mature enough to understand the consequences.

Cholesterol is the precursor of the bile acids and the sex hormones. This connection will be discussed next month when I begin describing the role of protein and fat digestion in each of the five stages of pregnancy. Cholesterol is used in seminal fluid and vaginal lubrication and is an essential part of nerve‑fiber structure. Manufactured primarily in the liver, cholesterol is present in almost all cells and is also high in the brain, nervous tissue, and the blood.

Cholesterol in the blood must be transported by lipoproteins. These proteins must be used to transport cholesterol because fats are not soluble in water (the basic makeup of blood and lymph). The fatty acids in these large lipoprotein molecules are positioned at the inside, as far away from the water as possible. "Density" refers to the ratio of protein to fat within the molecule. There are several important lipoproteins:

‑‑ VLDLs (very‑low‑density lipoproteins) are made in the intestines and the liver to carry fats to the body. They carry mostly triglycerides but can also carry a small amount of cholesterol to the tissues.

‑‑ LDLs (low‑density lipoproteins) originate when fat is lost from the VLDLs, changing the density from "very low" to "low". LDL is the primary carrier of cholesterol in the blood to the organs and cells.

‑‑ HDLs (high‑density lipoproteins) are large and have a much higher amount of protein compared to fat. They can pick up used or unused cholesterol and cholesterol esters and take them back to the liver as part of a recycling process. The liver then converts the cholesterol into bile acids which are then eliminated. Therefore, it is obvious the role that diet as well as good protein and fat digestion can play in preventing buildup of cholesterol and lowering the risk of cardiovascular disease.

An interesting aspect of cholesterol metabolism is how it is taken into the cells. Almost all cells have, on the outer surface of their membranes, receptors that specifically bind LDL. When a cell is short of cholesterol, it synthesizes more LDL receptors and deposits them on its plasma membrane. This allows the cell to bind more LDL, imbibe it, and liberate its cholesterol, which is preferentially used over the cholesterol synthesized by the cell itself.

When examining all of the conditions that statins are useful in preventing, it is worth remembering that statin drugs inhibit the production of the enzyme that is responsible for the formation of the precursor of all sterols, including cholesterol. But, the acquisition of cholesterol from plasma LDL also inhibits this enzyme in the cell's own cholesterol‑synthesizing mechanism.

(Dr. Loomis welcomes input on the subjects covered in this column. To make a comment or ask a question, or to receive a free copy of his video titled, "Using Enzymes in Clinical Practice: The Loomis System," call 800‑662‑2630 or write to him at 6421 Enterprise Lane, Madison, WI 53719. Visit www.loomisenzymes.com online for information on upcoming Loomis Institute seminars.)