Cholesterol-lowering drugs and the effect on muscle repair and regeneration

HILTON HEAD, SC—Statins are powerful drugs that reduce "bad" cholesterol and thus cut the risk of a heart attack. While these medications offer tremendous benefits to millions, they can carry side effects for some. The most frequently reported consequence is fatigue, and about nine percent of patients report statin-related pain. Both can be exacerbated when statin doses are increased, or physical activity is added. The results of a new study may offer another note of caution for high-dose statin patients. Working with primary human satellite cell cultures, researchers have found that statins at higher doses may affect the ability of the skeletal muscles–which allow the body to move–to repair and regenerate themselves.
The study is entitled "Simvastatin Reduces Human Primary Satellite Cell Proliferation in Culture." It was conducted by Anna Thalacker-Mercer, Melissa Baker, Chris Calderon and Marcas Bamman, University of Alabama at Birmingham. They will discuss their findings at the American Physiological Society (APS; www.The-APS.org) conference, The Integrative Biology of Exercise V. The meeting is being held September 24-27, 2008 in Hilton Head, SC.

The Study

Statins have been reported to have adverse effects on skeletal muscle in both human and animal models causing cramping and fatigue and potentially myopathy. Relatively little is known regarding the effect of statins on the muscle progenitor cells (i.e., satellite cells (SC)) which play a key role in skeletal muscle repair and regeneration following exercise or injury. SC remain in a quiescent state until stimulated to proliferate. Statins are known to have antiproliferative effects in other cell types and therefore may inhibit or effect this critical step in muscle repair. Thus it is important to understand the influence of statins on SC function which may further affect the overall health and physiology of human skeletal muscle..

The study examined the proliferative capacity of human satellite cells in culture, which were exposed, to a lipophilic statin: simvastatin. The aim of the study was to determine SC viability during proliferation when treated with statins which may be indicative of the ability of SCs to undergo mitosis (i.e. divide to make new cells).

The research team used primary cell lines isolated from quadriceps muscle biopsies. SC were mixed and grown for 48 hours with several concentrations of statin: 0.0, 0 plus the solvent DMSO (control), 0.05, 0.1, 1.0, 10, or 100µM. The MTS assay was utilized to measure cell viability/reproducibility.

Additionally the investigators determined the effects of varying concentrations of simvastatin on SCs in different states (i.e., undergoing differentiation or differentiated into myotubes).

Key Findings

The researchers found the following:

There was a dose dependent decrease in the viability of the satellite cells at 1.0, 10 and 100µM concentrations of simvastatin. At approximately 5.0 µM concentration the viability of the proliferating cells was reduced by 50% (equivalent to the availability of simvastatin in circulation from a 40 milligram dose per day used in some patients). Specifically, the higher end concentrations led to reduced SC proliferation, which would likely negatively affect the muscle's ability to heal and/or repair itself.
There was no change in the viability of satellite cells at concentrations of 0.05 or 0.1µM.
Cell viability was reduced by approximately half in differentiating cells and myotubes with concentrations of 1.0 and 5.0 µM, respectively.
Next Steps

According to Dr. Thalacker-Mercer, a member of the research team, "While these are preliminary data and more research is necessary, the results indicate serious adverse effects of statins that may alter the ability of skeletal muscle to repair and regenerate due to the anti-proliferative effects of statins."

Looking ahead, she added, "We are very interested in these effects in the older population. It is possible that older adults may not be able to distinguish between muscle pain related to a statin effect or an effect of aging and therefore adverse effects of statins in older adults may be under-reported. Therefore, our next step is to examine statins among older adults."