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Analysis of data from nearly 300,000 British citizens tracked over 20 years shows up to a 25% reduction in grip strength, and a 73% reduction in lean mass (ALM), among continuous statin users compared with people who never took statins.
Grip strength diminished by 0.315 kg per year from baseline among statin users, and ALM showed a parallel decrease of 0.057 kg per year. Notably, these changes were independent of genetic predisposition to statin response, as well as demographic variables including age, sex, body mass index, and comorbidities.
“Continued statin use is associated with decreased muscle function and mass over time, independent of genetic susceptibility to statin response,” the lead researcher wrote. Melissa GentroPhD in Functional Pharmacology at the Department of Surgical Sciences, Uppsala University, Sweden.
Doctors who prescribe statins need to be more diligent in monitoring muscle function, and pay close attention to nutritional and lifestyle factors that can help maintain or restore muscle mass and function.
“This study underscores 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 maintaining muscle function, which may also enhance the cardiovascular benefits of statin therapy.”
Gentreux paper It was published in Journal of cachexia, muscular dystrophy, and musclein November 2025.
Independent risk
Since the dawn of the statin era, researchers and doctors have also recognized that statins carry some risk of myopathy. But studies examining the effect of these drugs on muscle function have shown highly variable and inconsistent results.
These inconsistencies have led some researchers to suggest that the musculoskeletal effect of statins reflects individual characteristics such as age, comorbidities, and interactions with other drugs that patients may be taking concomitantly. Gentreaux’s study challenges this idea by showing a link between long-term statin use and decline in 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, independent of the adverse statin outcome.”
The Uppsala team bases its conclusions on a comprehensive analysis of data from 297,977 study participants. UK Biobank The project is an ongoing prospective cohort study including approximately 500,000 middle-aged and older individuals in the UK. It is approximately equivalent to being based in the United States Nahanis 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 vital signs. Follow-up visits, which are still ongoing, began in 2014. The dataset used by Gentreau and colleagues was released by UK Biobank in January 2024.
Standard biometrics in the UK Biobank study included grip strength, as measured using… Jamar J00105 Hydraulic hand dynamometer, the ALM, which was estimated using Bioelectrical impedance analysis.
For their analysis, researchers at Uppsala University excluded patients whose records did not contain data on primary medication use; Those taking other lipid-lowering medications with statins; those with pre-existing mental or neuromuscular diseases; those whose records lack genomic data; And those of non-European origins. They also excluded participants who stopped or restarted statins at any time between baseline and follow-up, or between the first and second follow-up assessments.
Very clear signal
Regarding the question of whether statin use affects muscle, the signal is very clear: among 35,557 participants for whom there was follow-up data (on average 10±5 years), continuous statin use was associated with an accelerated decrease in grip strength of -0.32 kg/year compared to no use; ALM decreased by -0.06 kg/year in statin users versus never.
Gentreau and colleagues noted that compared with never users, statin users were older (61 vs. 56 years) and more likely to be male (63% vs. 43%). They also had a higher baseline body mass index (29 versus 27) and were more likely to have diabetes or high blood pressure.
But in their linear regression analyses, they adjusted for these and other variables that could affect statin response and muscle function. Associations between statin use and loss of grip strength and ALM persist.
The Uppsala researchers stress that their work should not be misread as a blanket rejection of statins and their potential cardiovascular benefits. Doctors certainly shouldn’t take the new findings as a warning to stop prescribing them.
Muscle mass and strength also decreased among people who did not take statins, which is not surprising, since most people lose muscle to some extent as they age. But the decline was steeper among persistent statin users.
The influence of genetic factors
The Uppsala team is particularly interested in the influence of genetic factors on both statin response and susceptibility to muscle-related side effects. To evaluate this, they developed a pharmacogenetic score (PGS) that combined multiple genetic variants associated with statin response. “This polygenic approach includes SNPs strongly associated with statin metabolism, LDL-lowering efficacy, myopathy risk and hepatic enzyme elevations that have been identified in genome-wide association studies (GWAS).”
When they studied testing PGS against observed changes in grip strength and ALM, they found that while statin users with high PGS scores tended to have the lowest levels of grip strength and ALM measurements, genetic factors did not account for the rate of decline in muscle mass or observed strength over time.
“Overall, this study shows that statin use is associated with an accelerated decline in muscle function and mass over time, independent of statin PGS,” the authors say.
One interesting observation from this new study is that persistent statin users tend to have higher core muscle strength and mass compared with non-users. This is partly due to the fact that a higher proportion of those prescribed statins were men (70%), and men generally have higher grip strength and muscle mass than women. In the United Kingdom, as in the United States, doctors tend to underestimate the risk of cardiovascular disease in women, and are more likely to prescribe statins to men versus women.
Still, higher baseline muscle health did not prevent the drug-related muscle decline observed over time.
Multiple biological mechanisms
The associations reported by Gentreau and colleagues are strong. But as with all epidemiological studies, they do not and cannot prove a definitive causal relationship.
However, there are multiple biological mechanisms through which statins can alter muscle structure and function. Its myotoxicity is reflected by the elevated creatine kinase levels that can be observed in long-term users.
These drugs not only inhibit HMG-CoA reductase (the rate-limiting enzyme in hepatic cholesterol synthesis) but also inhibit it. A major intermediate block in the mevalonate pathway, such as isoprenoids and coenzyme Q10. “Depletion of these intermediates has been linked to impaired protein synthesis, mitochondrial dysfunction and inhibition of protein synthesis, all of which may contribute to muscle atrophy,” the researchers note.
Statins also promote apoptosis and disrupt calcium homeostasis. Type II fast-twitch muscle fibers, which contribute primarily to muscle mass, appear to be particularly vulnerable to the harmful effects of statins. This may be a major contributor to the apparent decrease in ALM revealed by this study.
Beyond direct muscle toxicity, statins can also do this Promote insulin resistance and may increase the risk of diabetes. and Statin-associated rhabdomyolysis It can lead to systemic phosphate toxicity, which accelerates aging and reduces overall health status. “These pathways suggest that statin-associated muscle decline is not an isolated effect on muscle fibers, but rather part of a broader spectrum of metabolic disorders,” says Dr. Gentreau.
Watch carefully
A 2020 position paper by the International Lipid Expert Committee Regarding the issue of statin use in athletes, it states that very active people are particularly sensitive to the myotoxic effects of these drugs. “This sensitivity may help explain why decreased muscle mass is observed among physically active statin users,” Gentreau notes.
However, the Uppsala researchers stress that their work should not be misread as a blanket rejection of statins and their potential cardiovascular benefits. Doctors definitely should no Take the new findings as a warning to stop prescribing them.
“Besides cholesterol-lowering properties, statins exert pleiotropic effects, including anti-inflammatory, antioxidant, and endothelial-stabilizing benefits, which contribute to plaque stabilization and reduced cardiovascular events,” they wrote.
But doctors who prescribe statins need to be more diligent in monitoring muscle function, and pay close attention to nutritional and lifestyle factors that can help maintain or restore muscle mass and function in patients taking these drugs.
“Current evidence suggests that moderate exercise is generally safe under statin treatment, with no worsening of exercise-induced muscle injury, and that the benefits of physical activity outweigh the potential harms.”
Because statins are among the most widely prescribed drugs worldwide, especially for people over 50 years of age, and the risk of developing muscle atrophy and weakness naturally increases with age, regardless of pharmaceutical use, these are important considerations.
Gentreau’s study has several key strengths compared to previous studies of statins and muscle. First, the study population is large, with a long follow-up period (median 10 years), giving it great 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 has some limitations, the biggest of which is that statin use was self-reported, based on verbal interviews. The UK Biobank does not include confirmed prescription data, nor does it include information on statin doses, or use of these medications prior to registration. The fact that the Uppsala team excluded people of non-European ancestry means that the results may not be generalizable to people of African, Asian, Oriental or Native American ancestry.
However, this is the largest and most comprehensive study to date looking at the effect of statins on muscle. Its main message — that long-term statin use depletes muscle mass and strength — must be taken seriously.
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