Statin Use Is Associated With a Decline in Muscle Function and Mass Over Time

This new study has finally pushed me over the line to stop taking statins:

From the conclusion:
" Conclusions: Continuous statin use is associated with a decline in muscle function and mass over time (25% decline in grip strength and 73% decline in ALM compared to never-users), irrespective of genetic susceptibility to statin response. 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."

The most unexpected result was that physical activity was linked to faster muscle decline in statin users.

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I really wouldn’t expect it to be an issue if one uses a low dose statin and regularly lifts weights.

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You were looking for any excuse to stop your statin (if you were even taking it to begin with), weren’t you?

Wow! And to think that I have been taking atorvastatin for over 30 years.

If I hadn’t taken the statin, would I be much stronger, or would I be dead?

I’m with you, and I am stopping my statin use. I tried bempedoic acid plus ezetimibe alone for a while and it keeps me in the “healthy range”, but not as low as when combined with atorvastatin.

ChatGPT 5;

“So while bempedoic acid may be “gentler” on muscle for many, it is not automatically “safer” overall in older adults.” " Add ezetimibe if LDL is above goal or you want more lowering; ezetimibe is generally well tolerated."

Executive Summary (Bottom Line)

  • The paper is methodologically strong for an observational study and convincingly shows a small but cumulative association between long-term statin use and accelerated loss of muscle strength and mass.

  • The effect is real but modest, clinically meaningful mainly over long time horizons (≈10+ years), and easily missed in short trials.

  • Causality is not proven, and residual confounding and selection bias remain possible.

  • This was not discovered earlier because clinical trials were not designed to detect slow, subclinical sarcopenia, lacked follow-up duration, and focused on catastrophic muscle injury rather than functional decline.

Final Verdict

Credible, well-executed, and overdue.
The effect is real, subtle, cumulative, and biologically plausible.
It was missed not because it was wrong — but because no one was looking the right way for long enough.

“https://tinyurl.com/mvrcyds7”
“https://tinyurl.com/yuee3yjc”
“https://tinyurl.com/4rrfedbv”"

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Yeah except… they also found that physical activity was linked to faster muscle decline in statin users

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LOL

I was reluctantly convinced to start stains about 10 years ago (low dose), but I’ve kept a close watch on the literature ever since.

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That’s a troubling result if it holds up to further scrutiny. It strikes me that very few interventions yield benefit with no cost. Sensible evaluation of tradeoffs is always necessary.

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But what is the mechanism? I am wondering because I do not take a statin but I do take Repatha. My understanding is that statins reduce cholesterol by reducing the amount produced by the liver. Repatha (PCSK9 inhibitor) reduces cholesterol by preventing the destruction of LDL receptors in the liver,

Assuming that this finding about statins were to stand up to scrutiny, what could be construed about whether a PCSK9 inhibitor would have a similar effect? What exactly is it about the statin that causes the muscle function decline?

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In this study 60% of statin users had hypertension, while 20% of non-users had it. Diabetes 16% vs. 1%, CHD 20% vs. 1%.

It could be the statin prescription, but the more likely explanation is an unaccounted factor with such different groups, the researchers attempt to control for them, but they can’t for every one, that requires a different study design. Most likely if you are unhealthy or have heart disease, you should be concerned about that, for muscle function or strength.

Statins have an expected risk reduction for stroke, CVD, and dementia, that cause sarcopenia from immobility, with a larger reduction when taken earlier rather than later.

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When you actually research this question without a relative comparison with residual factors like unhealthiness, statins reduce frailty. That’s what gene studies do.

You’re never going to hear about this on social media though.

We found that individuals predicted to have life-long lowering LDL-C concentrations had substantially lower frailty scores, consistent with, and perhaps exceeding, the degree of cardioprotection expected from lipid lowering. We also profiled gene-specific effects from loci that index the modulation of existing and emerging lipid-lowering drug targets (e.g., HMGCR, APOC3, and LDLR), and found evidence that the on-target effects of classes used to lower LDL-C may contribute notable differences to the overall health of users.

https://www.thelancet.com/article/S2352-3964(19)30442-6/fulltext

I could care less by the way if someone takes or doesn’t take them. It’s not my business.

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It’s likely not the lipid lowering per se. It’s more likely connected with the mechanism behind myalgia symptoms in some users, which has been put down to statins affecting calcium channels (essentially they keep them open in muscles constantly which has deleterious effects). All statins do that, but some individuals are more susceptible to perceptible side effects. As other LLT agents don’t have this effect, it’s likely not an issue, i.e. just lowering ApoB/LDL by itself is not the problem.

The decision as to whether taking statins makes sense must be individualized. You have to look carefully at your specific situation. You may reach the conclusion that even with muscle deterioration or some other side effects, it’s still worth taking statins, not just because on balance they allow you better healthspan and prevent CVD related problems. That’s the “easy” part. The more difficult problem complicating the decision is the larger context. For example, what if you have drug X, which makes your muscles somewhat weaker, but adds 10 years to your lifespan? As long as the muscle weakening is not debilitating, and as long as big muscles are not your life goal in and of itself, then I’d take the extra 10 years. We often keep failing to tackle antagonistic pleiotropy in our decision making.

What if - as happens not infrequently - you are trading some fitness for a longer lifespan. What if great fitness is incompatible with a long lifespan? You may still opt for a shorter lifespan because as I mentioned, the cost is unacceptable. Example: there’s a whole thread here positing how castration can be lifespan prolonging at the cost of loss of strength and all the other things that go with castration. Many of us (myself included) would not trade an extra 3-5 years for lifelong castration. Of course, give me a 200 year advantage and I’d likely ask for some dull scissors. Now, trading off procreation for longevity is as old as the hills - CR is a prime example (for both males and females, amenorrhea for the latter). But this extends to tons of other tradeoffs. Going in the other direction - GIGANTIC muscles a la bodybuilders may result in a shortened lifespan. Then what if at the other end is “mediocre” muscles, but 10 extra years? A bodybuilder would not agree. I would, as I don’t care if my muscles are not tip top - as long as it doesn’t impact my ADL, I don’t care if the day before I die I can lift 150lbs vs 200lbs. For muscles, I say, I’m OK with “good enough”. Btw. even here it might not be so clear cut. For example, with CR you definitely have lower muscle mass and bone density and fertility. BUT. It transpires that the muscle tissue is preserved for longer than the “burn bright but burn short” big muscles (as well as things like hormones - testosterone is lowered on CR, but then ends up at a higher level than the sharp drop with age experienced by ad-lib folks), and the bone has superior architecture and fertility can be restored much later in life compared to the faster burning non-CR candle. Again, trade offs.

Bottom line, to me, it’s not so simple as to say “statins are bad for muscles” I quit. Way, way too simplistic. It’s actually very complicated. Statins do much more for the health than lower lipids and ameliorate CVD. There are pleiotropic benefits which might be enough to push me to take them even if I do not need them to lower my lipids or affect my CVD. I’m playing a much longer game. And in that game, it might make sense to sacrifice a degree of muscle fitness for those benefits, exactly as in CR. To me, as long as my ADL is not affected, I don’t care. But if you have different goals and values, that might be a bridge too far. In essence, what I am saying is: this is complicated. How much worse do the muscles get - wheelchair level? What are the compensating benefits, if any? Do I have CVD and atherosclerosis already? And so on. Some of this data we don’t actually have at present, which makes all this even more fraught. But that’s true of almost all the pharmaceuticals we take - we trade off risks vs benefits and operate in an environment of incomplete information (so brush up on mathematical game theory!).

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I have taken a low dose statin (10mg Crestor) for 15 years. I continue to take it even though I have been on Repatha for two years and my cholesterol is well within range. I continue to take it because statins have been shown to help stabilize plaque (of which I have plenty). FWIW, N=1, I probably have more muscle mass and as much strength now, at 69, that I have ever had. Granted, I’m on TRT and work out very hard.

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Very helpful posts, thank you. We need an algorhythm that requires the user to plug in all the information:eg. age, gender, what is your APOB, your Lp(a), BMI, etc – it would be a very long list. Without this algorhythm we are all back-of- the-envelope doing this anyway. I decided to take Repatha and not a statin primarily because my Lp(a) was slightly too high (40 then, now 27). I’m not sure it is really “justifiable.” But for me it seemed the best choice given not only the Lp(a), but everything else I knew (e.g.statins can actually raise Lp(a). But there is so much I don’t know about Repatha, and so many factors to be considered.

Having said this, I would not want this algorhythm to be in the hands of doctors only. Another n=1 experience: There is a fairly simplistic algorythm, developed by Sloan Kettering, intended to guide on whether to take radiation therapy for estrogen driven breast cancer. Five years ago when I had a very indolent, tiny (2mm) ER/PR+ cancer, I played around with it, inputting different variables, and came to the conclusion that I should not take RT. But, fearing I might be missing some information I went for a consultation with a radiation oncologist. Well, she came to the meeting with a sheet of paper – the exact same Sloan Kettering algorhythm I had been using at home – and demonstrated to me that radiation would significantly improve my chances of not having a remission. Thing is, she plugged in numbers that were just wrong, and thankfully, since I had studied my pathology and so many other factors, I was in a position to know this. That meeting reinforced my growing conviction that I should make my own decisions.
So, having started down that path, I am so appreciative of all the information here at Rapamycin News.

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I used Google Gemini Deep Research to evaluate the paper. Here are some possible action plans to consider:

Economic & Therapeutic Strategy Analysis

The ultimate biohack may be to remove the offending agent entirely. We must weigh the cost of “protecting” the muscle on statins versus switching to non-statin alternatives.

6.1 Cost-Benefit Analysis of Protocols

Protocol A: The “Armored Statin” (Generic Statin + Supplements)

  • Generic Atorvastatin/Rosuvastatin: ~$5 - $10 / month (GoodRx).
  • Ubiquinol (200mg): ~$30 / month.
  • Geranylgeraniol (300mg): ~$40 / month.
  • Creatine (5g): ~$5 / month.
  • Total Monthly Cost: ~$80 - $90.
  • Efficacy: High CVD protection. Unknown muscle protection (theoretically sound, but Gentreau suggests decline persists).

Protocol B: The “Statin Bypass” (Non-Statin Therapies)

  • PCSK9 Inhibitors (Repatha/Praluent):
    • Mechanism: Monoclonal antibodies that degrade PCSK9, increasing LDL receptor recycling. Mechanism does NOT inhibit Mevalonate pathway. No CoQ10/GG depletion. Zero muscle risk.
    • Cost: List price ~$500-$600/month. With insurance/copay card: $5 - $50/month.
    • Barrier: Requires “Prior Authorization.” Must document “Statin Intolerance” or failure to reach LDL targets on statins.
  • Bempedoic Acid (Nexletol):
    • Mechanism: ACL inhibitor. Blocks cholesterol synthesis upstream of statins but is a pro-drug activated only in the liver (requires ACSVL1 enzyme). Skeletal muscle lacks this enzyme, so the drug is inactive in muscle.
    • Cost: ~$350 - $420 / month (Cash). Insurance coverage is improving but often requires PA.
      NOTE: India Sources for Bempadoic Acid: 200 tablets of Bemdac EZ by Zydus ~80$ ($0.40 per day, or $12 per month).

The Verdict: For the biohacker with excellent insurance or high disposable income, Protocol B (PCSK9i or Bempedoic Acid) is clinically superior for longevity. It decouples lipid lowering from muscle toxicity entirely. For those restricted to Protocol A, the “Anti-Atrophy Stack” is mandatory, but rigorous functional monitoring is required to ensure it is working.

7. Ten High-Value Questions for the Clinician

Based on this research, a proactive patient should present the following questions to their medical provider:

  1. “In light of the Gentreau 2025 study showing a 73% accelerated loss of lean mass in continuous users, can we establish a baseline grip strength measurement today to track my functional trajectory?”
  2. “Does my insurance plan recognize ‘functional muscle decline’ (documented by dynamometry) as a valid criteria for ‘statin intolerance’ to qualify for PCSK9 inhibitors?”
  3. “Considering that Bempedoic Acid (Nexletol) is not activated in skeletal muscle, would switching to this agent eliminate the risk of the accelerated sarcopenia seen in this study?”
  4. “Can we screen for the specific genetic variants used in the Pharmacogenomic Score, or should we assume I am susceptible given the study found the decline was irrespective of genetic risk?”
  5. “Would a hydrophilic statin like Rosuvastatin be less likely to penetrate my muscle tissue compared to lipophilic Atorvastatin, and does the Gentreau data support this distinction?”
  6. “Should I supplement with Geranylgeraniol to bypass the mevalonate blockade and support protein prenylation, specifically to protect my Type II muscle fibers?”
  7. “Can we add Ezetimibe to my protocol to allow for a lower dose of statin, thereby reducing the degree of HMG-CoA reductase inhibition in my peripheral tissues?”
  8. “Given the link between Vitamin D deficiency and statin myopathy, can we check my 25(OH)D levels and aim for a target of >40 ng/mL?”
  9. “Should I adjust my resistance training to avoid heavy eccentric loading, which might be more damaging to statin-compromised muscle membranes?”
  10. “Are there emerging biomarkers, such as plasma microRNAs (e.g., miR-126), that we can use to detect early sub-clinical muscle stress before functional loss occurs?”

See the full Google Gemini Deep Research analysis: https://gemini.google.com/share/645f425ae08e

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Thank you for this. According to this overview of the three agents, it appears that there are no downsides to the PCSK9 inhibitor (other than high cost). Is that a valid takeaway?

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In the study :

  • statin users were older
  • statin users had higher bmi
  • statin users were more like to have other issues like hypertension, cvd, diabetes.
  • statin users were more likely to be on more medication

Color me completely unsurprised about the conclusion of the study. Demographics is destiny, like someone said

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Association between atorvastatin and sarcopenia: a study based on NHANES and FAERS databases

Hao Zhang et al. Naunyn Schmiedebergs Arch Pharmacol. 2025.

Abstract

Post-marketing surveillance data suggest a potential link between atorvastatin use and sarcopenia. However, further large-scale observational studies are needed to confirm this preliminary finding. This study aims to comprehensively investigate the relationship between atorvastatin exposure and sarcopenia, with the goal of providing more accurate safety and efficacy profiles to guide its clinical use. We utilized two primary datasets: the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 and the Food and Drug Administration Adverse Event Reporting System (FAERS) from 2004 to 2018. Using a multi-step analytical approach that included descriptive statistical analysis, multivariable logistic regression, and receiver operating characteristic (ROC) curve analysis, we systematically assessed the relationship between atorvastatin exposure and the incidence of sarcopenia. In the NHANES cohort analysis, after adjusting for demographic variables, lifestyle factors, and other confounders in the multivariable logistic regression model, atorvastatin use was associated with an increased risk of sarcopenia (OR = 2.21; 95% CI: 1.07-4.55; p = 0.032). An analysis of the FAERS database identified 13,625 adverse event reports related to atorvastatin, of which 5370 specifically documented myasthenia-related events. Independent analyses from both population-based epidemiological surveys and pharmacovigilance systems consistently indicate that atorvastatin use may increase the risk of sarcopenia. Based on these findings, we recommend that healthcare providers implement comprehensive risk communication strategies before prescribing atorvastatin, with particular emphasis on the need for regular musculoskeletal assessments in patients undergoing long-term statin therapy. [PMID: 41060387]

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Are you stopping for aesthetic reasons, or you believe muscle strength is more tied to longevity than low ldl?

I believe the study cited here was an association study, which is lower level evidence than RCT’s for example. I think our best evidence is contrary to this article, and I’d not think it wise to have this concern be a reason not to be on a statin. From my perspective they are great drugs, I take one myself.

Here is a summary … just to annoy everyone posted from Vera-Health.ai
According to the 2018 AHA/ACC Multisociety Cholesterol Guidelines 1 I, long‑term statin therapy is not associated with clinically meaningful loss of muscle mass or function; the principal adverse muscular event is statin‑associated muscle symptoms (SAMS), occurring in 1–5% of participants in randomized trials and up to 10% in observational cohorts.

Evidence summary (ranked by strength):

  1. Randomized controlled trials and meta‑analyses
  • The Cholesterol Treatment Trialists’ Collaboration meta‑analysis of 19 RCTs (123,940 participants, median 4.3 years) found only a 7% relative increase in self‑reported muscle pain/weakness in year 1, with no excess thereafter and no increase in objective weakness or CK elevation 2 I.
  • The STOMP RCT (420 healthy adults, 6 months of atorvastatin 80 mg) showed no decline in measured muscle strength or exercise performance despite mild CK elevation and more myalgia reports 3 I.
  • A 2006 Circulation systematic overview of 35 RCTs (74,102 participants) found no significant increase in myalgia, myopathy, or rhabdomyolysis compared with placebo 4 I.
  1. Large observational and population‑based studies
  • A 2025 UK Biobank cohort (n = 297,977; mean follow‑up ≈ 10 years) reported that continuous statin use was associated with accelerated decline in grip strength (−0.32 kg/year) and appendicular lean mass (−0.06 kg/year) versus non‑users; however, absolute changes were small and not linked to clinical sarcopenia 5 II.
  • In contrast, a 2024 Japanese longitudinal cohort (n = 1,636; median 10 years) found no increased risk of incident sarcopenia or muscle mass loss (aHR 1.09 [0.66–1.82]) with long‑term statin use 6 II.
  • CT‑based longitudinal analysis in 756 AAA patients also found no difference in skeletal muscle loss between statin users and non‑users 7 II.
  1. Mechanistic and translational data
  • High‑dose atorvastatin (80 mg × 56 days) in humans reduced skeletal muscle mitochondrial respiratory capacity by > 30%, supporting a potential mechanism for fatigue or mild weakness under prolonged exposure 8 II.
  • Mouse and cell models show geranylgeranyl‑pyrophosphate (GGPP) depletion–mediated myostatin overexpression as a plausible pathway for atrophy in susceptible individuals 9 III.
  1. Genetic and Mendelian randomization evidence
  • Genetic proxies for HMG‑CoA reductase inhibition (the statin target) show no causal reduction in muscle mass, whereas PCSK9 inhibition—not statins—was linked to lower lean mass 10 II.
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Journal & Publication Quality

  • Journal: Journal of Cachexia, Sarcopenia and Muscle (JCSM).
  • Status: High-impact, top-tier specialty journal.
  • Metrics: It consistently holds a high Impact Factor (typically ~9–12 range), ranking Q1 in Geriatrics & Gerontology and Medicine (General & Internal).
  • Reputation: It is arguably the leading journal globally for research specifically focused on muscle wasting, cachexia, and sarcopenia. The peer-review standards are rigorous.

Study Design & Methods

  • Type: Large-scale Observational Cohort Study (Retrospective/Prospective analysis of UK Biobank data).
  • Participants:
    • Cross-sectional: 297,977 participants (mean age ~56).
    • Longitudinal: 35,557 participants with ~10-year follow-up data.
  • Methods: The study used linear regression models adjusted for a wide array of confounders (age, sex, BMI, smoking, chronic diseases, physical activity levels).
  • Validity: The methods are robust for epidemiology. The use of “Appendicular Lean Mass” (ALM) via bioelectrical impedance and grip strength via dynamometer are standard, validated clinical measures for sarcopenia.
  • Limitations: As an observational study, it cannot prove strict causality (reverse causality is possible, though less likely given the longitudinal design). It relies on self-reported medication use and prescription records.

References & Author Credibility

  • Authors: Researchers from Uppsala University (Department of Surgical Sciences, Functional Pharmacology). The team has a strong track record in epidemiology and pharmacogenomics.
  • Bias: No obvious commercial conflicts of interest were flagged in the snippets; the study is academic in nature.
  • References: The paper cites relevant, current literature on statin myopathy, mitochondrial dysfunction, and sarcopenia consensus definitions.