Muscles and Statins
The effect of statins on muscles and muscle fibers is not understood completely, but docotrs know that muscle pain and weakness is a side effect of statin medication. It is one of the most common complaints of patients.
Muscle pain – formally called myopathy - can be divided into:
Myalgia - soreness, tenderness or weakness of muscles. This is a symptom, not a sign. In other words, patients report feeling this weakness but scientists have not discovered a biomarker or physiological changes that correspond to the myalgia. (A diagnostic biomarker is one with high specificity and sensitivity, one that can show the severity of disease and which allows for the monitoring of therapeutic effects.) Pain in the tendons or joints are also considered myalgia.
Myositis is inflammation of muscle tissue; it causes soreness and pain. Myositis is caused by many diseases and conditions, even heavy exercise. The difference between myosiss and myalgia is in the blood tests. Myosistis results in measurable levels of creatine kinase (CK) greater than ten-times the upper limit of normal. Unusual levels of antibodies may show up in the muscle if there is an autoimmune disease. Creatine kinase levels are usually the first step in the diagnosis because they are easy to do. Complex cases of mycositis are sometime diagnosed with muscle biopsy.
Myoglobin is the muscle equivalent to the blood’s hemoglobin. It contains iron and moves oxygen to the muscle cells. It also is associated with the pigment heme, which largely gives red meat its color. Myoglobin the blood or urine is a sign of muscle breakdown.
Rhabdomyolysis is the clinical name for severe myopathy caused by damaged muscles and the release of myoglobin into the circulation. The kidneys can be damaged as they try to remove things from the blood that aren’t normally there. To officially be rhabdomyolysis, muscle breakdown must result blood analysis showing creatine kinase levels >10,000 IU/l (international units per liter) as well as worsening renal function.
Rhabdomyolysis is very bad and can damage the body. It can be caused when parts of the body are crushed under large weight (and the muscle tissue is physically broken.) Insect bites can also cause it. Large-scale studies show less than 10 cases of rhabdomyolysis per 100,000 years of statin use, and only 10% of those cases result in death.
One hypothesis points to statin disruption of muscle cell functioning.
The myocyte, a type of cell found in muscles, relies on regulatory proteins that may be inhibited by the statins. That’s one idea, but there is no definitive explanation. Creatine is a major factor in energy expression and the enzyme creatine kinase breaks down creatine. When elevated levels of creatine and/or creatine kinase are found in the blood, it is a sign of muscle damage.
How many statin patients get muscle-related injuries as a side effect? This is not clear. In the clinical studies and trials employed during the development of statins, a small percentage got them. One criticism of clinical trials is that they accept only a select type of patient – otherwise healthy, within a particular age range, not taking other medications – and this skews the results to suggest lower rates of side effects.
Many doctors and observers claim that the “in the field” – that is, among real-life patients - side effects are more prevalent than clinical trial results predict. A study of US patients who were prescribed statins, called the Understanding Statin Use in America and Gaps in Education (USAGE) found that muscle-related side effects were reported by 60% of former and 25% of current users. Self-reporting by patients is notoriously unreliable though, and people who quit statins may be using side effects as a reason when the actual cause was more complex.
Inflammation and Painful Muscles
Most cases of myalgia are due to sprains and strains, but there can be any of a number of causes. Myalgia is considered a known and usually not significant side effect of statin use. Much bodily pain is due to inflammation and that’s why anti-inflammatory drugs are useful for alleviating pain. Aspirin, ibuprofen, etc. reduce inflammation and are called anti-inflammatories. Statins also have anti-inflammatory properties, so whatever the causes of this muscle pain are, they are probably not due to inflammation.
Why do some people experience muscle problems and some don't? Scientists found that a gene involved in the encoding for glycine aminotransferase (GATM) – part of the energy generation system in cellular mitochondria – affects whether a person is susceptible to statin-induced myopathy. GATM is involved with synthesis of creatine, a key factor in providing skeletal muscles with energy. One mechanism that has been suggested for how myopathy arises from statin use involves the biochemical class isoprenoids. There are lipids produced by HMG-CoA reductase pathway in the body’s normal metabolism. Statins interfere in this pathway and consequently lower the concentration of isoprenoids in muscle tissue, which may signal cells to die.
Does this help anyone or is it purely interesting science? Well, it shows a biological underpinning for the myopathy and that people who have it are not just hypochondriacs. A company called Sage Bionetworks may be working on an assay to quickly determine whether someone has this gene variant, although there is no guarantee an inexpensive and fast marker test will be found.
Response to Myopathy
Simple weakness is usually brushed off by doctors and the patients are told they should live with it. Weakness may be a reason people stop using their statins. In a recent study scientists gave people who had never taken a statin high dosages of atorvastatin for six months. No reduction in strength was found. The people in the study who took the statins could exercise at the same intensity as those who took placebos. However, scientists did detect higher rates of myalgia in the statin patients. And the statin patients had higher levels of the muscle breakdown product creatine.
Nevertheless many doctors take their patients complaints seriously and also take the risk of cardiovascular disease seriously enough that they want to keep the patients in some sort of control therapy. Rather than simply stopping statins, maybe a better strategy is to switch to a therapy that does not cause muscle problems. Duke University doctors report niacin and bile acid sequestrants are not associated with myopathy. Whether they are as effective as statins in controlling cholesterol levels is another question. Fibrates are used to treat cholesterol problems but they people who have myopathy from statins often get it from fibrates, too. There has been some testing on the use of the dietary supplements Coenzyme Q and Vitamin D as a means to mitigate myopathy. While some efficacy was found, the trials were too small for doctors to base a credible routine prescription of these supplements for this purpose.