Analysis of data from nearly 300,000 UK citizens tracked over a 20-year period shows a decline of up to 25% in grip strength, and a 73% drop in appendicular lean mass (ALM), among continuous statin users compared with people who’d never taken statins.
Grip strength diminished by a mean of 0.315 kg per year from baseline among the statin users, and ALM showed a parallel reduction of 0.057 kg per year. Notably, these changes were independent of genetic predisposition to statin responsiveness, as well as demographic variables including age, gender, BMI, and co-morbidities.
“Continuous statin use is associated with a decline in muscle function and mass over time, irrespective of genetic susceptibility to statin response,” writes lead investigator Mélissa Gentreau, PhD, a Functional Pharmacologist at the Department of Surgical Sciences, Uppsala University, Sweden.
Physicians who prescribe statins do need to be more diligent in their monitoring of muscle function, and pay close attention to nutritional and lifestyle factors that can help preserve or potentially restore muscle mass and function.
“This study emphasizes the importance of monitoring musculoskeletal health in statin users and supports further research into the potential role of a healthy diet and regular physical activity in preserving muscle function, which may also reinforce the cardiovascular benefits of statin therapy.”
Gentreau’s paper was published in the Journal of Cachexia, Sarcopenia, and Muscle, in November 2025.
An Independent Risk
Since the dawn of the statin era, researchers as well as clinicians have been aware that statins carry some risk of myopathy. But studies looking at the impact of these drugs on muscle function have turned up highly variable and inconsistent findings.
These inconsistencies have led some researchers to suggest that the musculoskeletal impact of statins reflects individual characteristics such as age, co‐morbidities and interactions with other drugs the patients may be taking concurrently. The Gentreau study challenges that notion by showing a link between long-term statin use and degradation of muscle mass and strength, independent of personal variables.
“Overall, this study shows that statin use is associated with an accelerated decline in muscle function and mass over time, irrespective of statin harmacogenomic Score.”
The Uppsala team bases its conclusions on a comprehensive analysis of data from 297,977 participants in the UK Biobank project, an ongoing a prospective cohort study involving roughly 500 000 middle‐aged and elderly individuals in the United Kingdom. It is roughly equivalent to the US-based NHANES database.
The baseline data were collected between 2006 and 2010, and included information on sociodemographic and lifestyle factors, medical history, and pharmaceutical use, as well as a host of physical measurements and biomarkers. Follow-up visits, which are still ongoing, began in 2014. The dataset used by Gentreau and colleagues was released in by UK Biobank in January 2024.
The standard biometrics in the UK Biobank study included grip strength, as measured using a Jamar J00105 hydraulic hand dynamometer, and ALM, which was estimated using bioelectrical impedance analysis.
For their analysis, the Uppsala University researchers excluded patients whose records did not have data on baseline medication use; those taking other lipid-lowering drugs along with statins; those with pre-existing mental or neuromuscular diseases; those whose records lacked genomic data; and those of non-European ancestry. They also excluded participants who stopped or re-started statins at any point between the baseline and follow-up, or between the first and second follow-up assessments.
A Very Clear Signal
On the question of whether statin use impacts muscle, the signal is very clear: Among 35,557 participants for whom there was follow‐up data (average of 10 ± 5 years), continuous statin use was associated with an accelerated decline in grip strength of −0.32 kg/year compared with non-use; ALM diminished by -0.06 kg/year in statin users versus never users.
Gentreau and colleagues note that compared to never-users, the statin users were older (61 vs. 56 years), and more likely to be male (63% vs. 43%). They also had higher baseline BMI (29 vs. 27), and were more likely to be diabetic or hypertensive.
But in their linear regression analyses, they adjusted for these and other variables that could potentially impact both statin responsiveness and muscle function. The correlations between statin use and loss of grip strength and ALM still held.
The Uppsala researchers stress that their work should not be mis-read as a categorical dismissal of statins and their potential cardiovascular benefits. Doctors should definitely not take the new findings as an admonition to stop prescribing them.
Muscle mass and strength also declined among the subjects not taking statins—which is not surprising, given that most people lose muscle to some degree as they age. But the decline was much sharper among continuous statin users.
Impact of Genetic Factors
The Uppsala team is particularly interested in the impact of genetic factors on both statin responsiveness and susceptibility to muscle-related side-effects. To asess this, they developed a pharmacogenomic score (PGS) that aggregated multiple gene variants associated with statin response. “This polygenic approach incorporates SNPs strongly associated with statin metabolism, LDL‐lowering efficacy, myopathy risk and hepatic enzyme elevations identified in genome‐wide association studies (GWAS).”
When they plotted the PGS against the observed changes in grip strength and ALM, they found that while statin users with high PGS scores tended to have the lowest grip strength and ALM measures, the genetic factors did not account for the rate of decline in muscle mass or strength observed over time.
“Overall, this study shows that statin use is associated with an accelerated decline in muscle function and mass over time, irrespective of statin PGS,” the authors state.
One interesting observation from this new study is that that the continuous statin users tended to have higher baseline muscle strength and mass compared with non‐users. That’s due partly to the fact that a higher proportion those prescribed statins were men (70%), and men generally have higher grip strength and more muscle mass than women. In the UK, as in the US, physicians tend to underestimate cardiovascular risk in women, and are more likely to prescribe statins to men versus women.
Still the higher baseline muscle health did not avert the drug-related muscle declines observed over the time.
Multiple Biological Mechanisms
The correlations reported by Gentreau and colleagues are strong. But as the case with all epidemiological studies, they do not—and cannot–prove a definitive causal relationship.
Still, there are multiple biological mechanisms through which statins can alter muscle structure and function. Their myotoxicity is reflected by elevated creatine kinase levels observable in long-term users.
These drugs not only inhibit HMG‐CoA reductase (a rate-limiting enzyme in hepatic cholesterol synthesis) they also block key intermediates in the mevalonate pathway, such as isoprenoids and coenzyme Q10. “Depletion of these intermediates has been linked to impaired protein prenylation, mitochondrial dysfunction and inhibition of protein synthesis, all of which may contribute to muscle atrophy,” the authors note.
Statins also promote apoptosis, and disrupt calcium homeostasis. Type II fast‐twitch glycolytic muscle fibers, which are primary contributors to muscle mass, appear to be especially vulnerable to the detrimental effects of statins. This could be a major contributor to the pronounced ALM decline revealed by this study.
Beyond direct myotoxicity, statins can also promote insulin resistance and may increase diabetes risk. And statin-associated rhabdomyolysis can trigger systemic phosphate toxicity, which accelerates aging and diminishes overall health status. “These pathways suggest that statin‐related muscle decline is not an isolated effect on muscle fibres, but part of a wider spectrum of metabolic disturbances,” says Dr. Gentreau.
Monitor Carefully
A 2020 position paper by the International Lipid Expert Panel on the matter of statin use in athletes, states that highly active people are especially sensitive to the myotoxic effects of these drugs. “This sensitivity may help explain why we observed a decline in muscle mass among physically active statin users,” Gentreau notes.
All that said, the Uppsala researchers stress that their work should not be mis-read as a categorical dismissal of statin drugs and their potential cardiovascular benefits. Doctors should definitely not take the new findings as an admonition to stop prescribing them.
“Beyond their cholesterol‐lowering properties, statins exert pleiotropic effects, including anti‐inflammatory, antioxidant, and endothelial‐stabilizing benefits, contributing to plaque stabilization and reduced cardiovascular events,” they write.
But physicians who prescribe statins do need to be more diligent in their monitoring of muscle function, and pay close attention to nutritional and lifestyle factors that can help preserve or potentially restore muscle mass and function in patients on these drugs.
“Current evidence suggests that moderate exercise is generally safe under statin therapy, with no exacerbation of exercise‐induced muscle injury, and that the benefits of physical activity outweigh potential harms.”
Given that statins are among the most widely prescribed drugs worldwide, especially to people over age 50, and that risk of sarcopenia and frailty naturally increase with age, independent of pharmaceutical use, these are important considerations.
The Gentreau study has several major strengths compared with previous studies of statin and muscle. For one, the study population is massive, and it has a long follow-up period (median 10-years), which gives it considerable statistical power. It also adjusts for a wide range of potentially confounding variables, and includes genetic data and objective measurements of muscle mass and strength.
However, it does have some limitations, the biggest one being that statin use was self-reported, based on verbal interviews. The UK Biobank does not include confirmatory prescription data, nor does it include information on statin dosing, or use of these drugs prior to enrollment. And the fact that the Uppsala team excluded people of non-European ancestry means that the findings may not be generalizable to people of African, Asian, Near Eastern, or indigenous American heritage.
Still, this is the largest and most comprehensive study to date, looking at the impact of statins on muscle. Its main message—that long-term statin use depletes both muscle mass and muscle strength—should be taken seriously.
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