An analysis of data from nearly 300,000 UK citizens followed for 20 years showed up to a 25% reduction in grip strength and a 73% reduction in appendicular lean mass (ALM) among regular statin users compared to non-statin users.
Grip strength among statin users decreased by an average of 0.315 kg per year, and ALM showed a similar decrease of 0.057 kg per year. Notably, these changes were independent of genetic predisposition to response to statins, as well as of demographic variables including age, sex, BMI, and comorbidities.
“Continuous statin use is associated with declines in muscle function and mass over time, independent of genetic susceptibility to statin response,” wrote the lead investigator. Melissa GentreauPhD, functional pharmacologist at the Department of Surgical Sciences, Uppsala University, Sweden.
Physicians prescribing statins should be careful in monitoring muscle function and pay close attention to nutritional and lifestyle factors that may help maintain or possibly restore muscle mass and function.
“This study highlights the importance of monitoring muscle health in statin users and supports further research into the potential role of a healthy diet and regular physical activity in maintaining muscle function, which may also enhance the cardiovascular benefits of statin therapy.”
Gentreau sheet was published Journal of cachexia, sarcopenia and muscleNovember 2025.
Independent risk
Since the beginning of the statin era, researchers and doctors have known that statins carry a risk of myopathy. But studies looking at the effects of these drugs on muscle function have produced highly variable and inconsistent findings.
This inconsistency has led some researchers to suggest that the muscle effects of statins reflect individual characteristics such as age, comorbidities, and interactions with other medications that patients are taking at the same time. Gentreau’s research challenges this notion by showing an association between long-term statin use and declines in muscle mass and strength, independent of personal variables.
“Overall, this study shows that statin use is associated with a rapid decline in muscle function and mass over time, independent of statin harmocomenomic scores.”
The Uppsala team based their conclusions on a comprehensive analysis of data from 297,977 participants. UK Biobank The project, a prospective cohort study involving around 500,000 middle-aged and older people in the UK. It is almost the same as the Americans NHANES database.
Baseline data were collected between 2006 and 2010 and included information on sociodemographic and lifestyle factors, medical history and medication use, as well as a range of physical measurements and biomarkers. Follow-up visits, which are still ongoing, began in 2014. The dataset used by Gentreau and colleagues was published by Biobank UK in January 2024.
Standard biometrics in UK Biobank studies include grip strength, as measured using a Jamar J00105 manual hydraulic dynamometer and ALM, which was calculated using it bioelectrical impedance analysis.
For their analysis, the Uppsala University researchers excluded patients whose records did not contain information on baseline medication use; those taking other lipid-lowering drugs in combination with statins; those with mental or neuromuscular diseases; those whose records lacked genomic data; and the European race. They also excluded participants who stopped or restarted statins at any point between baseline and follow-up or between the first and second follow-up assessments.
A very clear signal
On the question of whether statin use affects muscles, the signal is very clear: Among 35,557 participants for whom follow-up data were available (mean 10 ± 5 years), continuous statin use was associated with an accelerated decline in grip strength of -0.32 kg/year compared to non-use; ALM in statin users was reduced by -0.06 kg per year compared to never users.
Gentreau and colleagues note that compared to never users of statins, statin users were older (61 versus 56 years) and more likely to be male (63% versus 43%). They also had a higher baseline BMI (29 vs. 27) and were more likely to have diabetes or hypertension.
But in their linear regression analyses, they adjusted for these and other variables that likely influence both statin response and muscle function. The correlation between the use of statins and loss of grip strength and ALM is still maintained.
The Uppsala researchers emphasize that their work should not be misread as a blanket rejection of statins and their potential cardiovascular benefits. Doctors should certainly not take the new findings as advice to stop prescribing them.
Muscle mass and muscle strength also decreased among subjects not taking statins—not surprising, since most people lose some muscle mass as they age. But the decline was much faster among regular statin users.
Influence of genetic factors
The Uppsala team is particularly interested in the influence of genetic factors on both response to statins and susceptibility to muscle-related side effects. To assess this, they developed a pharmacogenomic score (PGS) that combined multiple gene variants associated with statin response. “This polygenic approach includes SNPs strongly associated with statin metabolism, LDL-lowering efficacy, myopathy risk, and liver enzyme elevations identified in genome-wide association studies (GWAS).”
When they plotted PGS against observed changes in grip strength and ALM, they found that while statin users with higher PGS scores tended to have lower grip strength and ALM measures, genetic factors did not account for the rate of decline in muscle mass or strength over time.
“Overall, this study suggests that statin use is associated with a faster decline in muscle function and mass over time, independent of statin PGS,” the authors say.
An interesting observation from this new study is that regular statin users have greater baseline strength and muscle mass compared to non-users. This is partly due to the fact that the majority of those prescribed statins were men (70%), and men tend to have greater grip strength and muscle mass than women. In the UK, as in the US, doctors underestimate cardiovascular risk in women and are more likely to prescribe statins to men than to women.
However, higher levels of muscle health did not prevent drug-related muscle decline over time.
Multiple biological mechanisms
The correlations reported by Gentreau and colleagues are strong. However, as with all epidemiological studies, they do not and cannot prove a strict causal relationship.
However, there are multiple biological mechanisms by which statins may alter muscle structure and function. Their myotoxicity is reflected by the high levels of creatine kinase observed in long-term users.
These drugs not only inhibit HMG-CoA reductase (the limiting enzyme in the synthesis of cholesterol in the liver) key intermediates in the mevalonate pathway, such as isoprenoids and coenzyme Q10. The authors note that depletion of these mediators is associated with impaired protein prenylation, mitochondrial dysfunction, and inhibition of protein synthesis, all of which may contribute to muscle atrophy.
Statins also promote apoptosis and disrupt calcium homeostasis. Glycolytic type II muscle fibers, which are the major contributors to muscle mass, are particularly vulnerable to the adverse effects of statins. This may be a major contributor to the apparent reduction in ALM that this study revealed.
In addition to direct myotoxicity, statins can also increases insulin resistance and may increase the risk of diabetes. And Statin-associated rhabdomyolysis can cause systemic phosphate toxicity that accelerates aging and reduces overall health. “These pathways suggest that statin-induced muscle wasting is not an isolated effect on muscle fibers, but is part of a broader spectrum of metabolic disorders,” says Dr. Gentreau.
Monitor carefully
A 2020 Position Paper by the International Lipid Expert Group on the issue of statin use in athletes notes that active people are especially sensitive to the myotoxic effects of these drugs. “This sensitivity may explain why we observed a decrease in muscle mass among physically active statin users,” notes Gentreau.
All that said, the Uppsala researchers emphasize that their work should not be misread as a blanket rejection of statin drugs and their potential cardiovascular benefits. Doctors should definitely no take the new findings as advice to stop prescribing them.
“In addition to their cholesterol-lowering properties, statins exert pleiotropic effects, including anti-inflammatory, antioxidant, and endothelium-stabilizing benefits that help stabilize plaques and reduce cardiovascular events,” they write.
But physicians who prescribe statins should be more diligent in monitoring muscle function and pay close attention to nutritional and lifestyle factors that may help maintain or potentially restore muscle mass and function in patients taking these drugs.
“Current evidence suggests that moderate exercise during statin therapy is generally safe, without exacerbating exercise-induced muscle damage, and that the benefits of physical activity outweigh the potential harms.”
Given that statins are among the most commonly prescribed drugs worldwide, especially for people over 50 years of age, and that the risk of sarcopenia and frailty naturally increases with age, regardless of drug use, these are important considerations.
Gentreau’s study has several strengths compared to previous statin and muscle studies. For one, the study population is large and it has a long follow-up period (on average 10 years), which gives it considerable statistical power. It also adjusts for a wide range of potentially confounding variables and includes genetic information and objective measurements of muscle mass and strength.
However, it has some limitations, the biggest being that statin use was self-reported based on oral interviews. The UK Biobank does not include data confirming prescriptions, nor does it include information on statin doses or use of these drugs prior to enrolment. And the fact that the Uppsala team excluded people of non-European ancestry means the findings may not be generalizable to people of African, Asian, Middle Eastern or Native American heritage.
However, this is the largest and most comprehensive study looking at the effects of statins on muscle. Its basic message—that long-term use of statins reduces both muscle mass and muscle strength—should be taken seriously.
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