Why do statins cause so many side effects? To answer this question requires explaining all the crucial roles that cholesterol plays in maintaining the integrity and functioning of the body's cells. However, statins interfere not only with the synthesis of cholesterol, but also with the synthesis of an enzyme, coenzyme Q10, that plays a critical role in energy metabolism in all cells. A deficiency in both cholesterol and coenzyme Q10, over time, leads to a huge list of potential health problems. Exactly how an individual responds depends upon their genetic make-up: faced with a deficiency, the body will decide to sacrifice certain cell types in order to safeguard certain other cell types. So, one person may develop Alzheimer's because the brain's neurons are sacrificed, while another succumbs to heart failure or rhabdomyolysis (skeletal muscle wasting).
Statins suppress a critical early step in the multi-step biological pathway that leads to cholesterol synthesis. This is why statins are able to dramatically reduce the blood serum levels of cholesterol. Specifically, statins interfere with the production of the enzyme, HMG-Coenzyme A Reductase, which catalyzes production of mevalonate from its precursor, HMG-Coenzyme A. Several more steps produce cholesterol from mevalonate. Mevalonate is also the precursor to a large number of other biologically active molecules that are important for proper cell function. These include the antioxidants, coenzyme Q10 and the dolichols, as shown in the figure to the right.
The so-called "bad" cholesterol, LDL, delivers cholesterol, fats, and antioxidants from the liver to all the cells of the body. All cells need both fats and cholesterol to maintain healthy membranes, not only in the outer cell wall, but also in the membranes encasing the nucleus, the mitochondria (energy producing units), and the lysosomes (the cell's digestive system). Antioxidants are critical for neutralizing the damaging effects of oxygen exposure, always an issue whenever energy is generated in the mitochondria through a chemical reaction between food sources and oxygen.
In a double-blind placebo controlled study , it has been shown that statins can reduce serum levels of coenzyme Q10 by as much as 40%. Coenzyme Q10 is not only a powerful antioxidant, but it also plays a crucial role in the process that breaks down glucose in the presence of oxygen to yield carbon dioxide and water. This metabolic pathway, which is essentially the burning of glucose as fuel, takes place in the mitochondria via the well-known citric acid, or Kreb's cycle. The energy that is released through this process is packaged up in the form of ATP (Adenosine Triphosphate), the currency that all cells use to store their energy reserves.
The dolichols play a special role for the lysosomes . The lysosomes are walled off "rooms" that contain digestive enzymes to break down debris from damaged cell parts so that they can be recycled into useful materials. Lysosomes must maintain a highly acidic internal environment in order for the digestive enzymes to work properly. The dolichols are responsible for pumping hydrogen ions into the lysosomes to keep them highly acidic.
A final way that statins can damage cells is through their entry mechanism. Statins belong to a class of drugs called "amphiphilic" drugs  that manage to break through the cell wall in spite of being relatively large. They act like a soap by essentially dissolving a section of the cell membrane. This leaves behind a hole in the wall, which needs to be patched up, as well as debris which must be cleaned up and recycled by the lysosomes. To patch the hole requires new sources of both fats and cholesterol, which come from the LDL particles, whose supply is greatly reduced due to the statin drug. So it becomes increasingly difficult over time for the cell to repair all the holes introduced by the statin drug molecules. As the cell wall becomes more permeable due to previous exposure to an amphiphilic drug, the amount of drug that successfully enters the cell steadily increases over time, leading to ever greater internal concentrations of the drug.