Statins and Muscle Weakness

First, a weather report. July, which averages about 3.5 to 4.0 inches of rain per month, saw 2021 as a near-record for Boston, at 10.07 inches, and a record for Worcester, at 13.85 inches. Figure Maynard for in between. It rained on 19 out of 31 days. The official numbers are not yet in to August, but rainfall was at least double the average of 4.0 inches. September started very wet, with the remnants of Hurricane Ida depositing 4.0 inches on Maynard. We may not set a record for precipitation for the year, but it could be close.

And now for something completely different (borrowing a segue from Monty Python's Flying Circus), let’s consider the effects of the cholesterol lowering drugs referred to as ‘statins’ on muscle strength. Statins lower total and low-density lipoprotein cholesterol by blocking cholesterol synthesis. The has been proven to reduce risk of heart attack and stroke. Worldwide, hundreds of millions of people are prescribed one of the six currently approved statin drugs. (For a while there was a seventh – cerivastatin - but it killed too many people.) Among the adverse side effects, the best known is “myopathy,” an umbrella term that includes fatigue, muscle weakness, muscle pain, muscle tenderness or cramps, and tendon pain. Some researchers use the terms “myalgia” or “statin-associated muscle symptoms.” A rare, very severe adverse muscle effect is rhabdomyolysis, characterized by severe muscle pain, liver damage and kidney damage.

   Generic names and brand names

•    Atorvastatin (Lipitor)
•    Lovastatin (Altoprev)
•    Pitavastatin (Livalo, Zypitamag)
•    Pravastatin (Pravachol)
•    Rosuvastatin (Crestor, Ezallor)
•    Simvastatin (Zocor)

Much more common, perhaps on the order of 10 to 20 percent, is a self-diagnosed sense of muscle weakness and ache. The former can be as subtle as needing to do a hand-assist when standing up from a chair. From one study, onset of perceptible muscle symptoms took on average six months. Resolution after the statin was terminated was two to three months. A subset took longer, or felt that they never fully recovered. Myopathy is a reason why people decide to stop taking their prescribed statin, often without consulting with their doctor.

Women are more likely to develop statin-associated myopathy than men, ditto older people than younger, and people with a low body mass index, i.e., slender versus heavier. Having untreated hypothyroidism, high blood pressure, liver disease or kidney disease increase risk, as does heavy alcohol consumption. Interestingly, intense exercise or physical labor increases risk for statin myopathy, because that in-and-of-itself causes muscle damage.

The actual statistics on statins and myopathy get murky. First, there is a proven ‘nocebo’ effect. This term refers to the opposite of a placebo effect. If people have a negative expectation about a medication, they are likely to report the known adverse effects. For example, many people, given an inert pill but told it might cause nausea, experience nausea.  Even in the context of a placebo-controlled trial, the people getting the placebo are likely to report adverse effects, because they understand there is a 50:50 chance they are in the treatment group. In an entirely unethical test for side effects, people would need to be enrolled into a study under false pretenses, perhaps being told they were getting a drug to reduce the risk of the common cold, while really getting a statin or placebo.  

Statins are known to elevate creatine phosphokinase (CPK or CK) in the blood, because that is an indicator of muscle damage. However, some people can have elevated CK with no muscle symptoms, and other people symptoms, but normal range CK. A muscle biopsy (ouch!) can be used to identify muscle damage at the cellular level. For a patient presenting with muscle complaints and elevated CK, a physician may ask them to stop the statin for a month or more, to see if the muscle problems and/or CK resolve. If yes, it may still be possible to reintroduce statin therapy. Within the six available choices, some are known to have a lower risk of adverse effects and/or are still functional at a low dose taken every other day. This is a topic for discussion between a person and their physician.

Lastly, statins are known to suppress synthesis of coenzyme Q10 (CoQ10), which is necessary for generation of cellular energy. CoQ10 is sold in the U.S. as a dietary supplement. Consuming CoQ10 raises blood and organ concentrations of CoQ10. People report feeling that their muscle problems were diminished. However, reviews of multiple human trials of CoQ10 in people who are on statin drugs demonstrated no reduction in incidence or severity of myopathy. There were improvements in the treated group, but similar changes in the control groups, i.e., a placebo effect.

Mark says he is on a doctor-approved "statin holiday" because of modestly elevated CPK and muscle weakness. At one month he is seeing lower CPK and improvements in muscle strength and stamina.