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

[Curtis_Hibbs]

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

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

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.

[LukeMV]

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

[Virilius]

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

[desertshores]

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”"

[Curtis_Hibbs]

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

[Curtis_Hibbs]

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.

[Barnabas]

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.

[Deborah_Hall]

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?

[A_User]

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.

[A_User]

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.

[CronosTempi]

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!).

[Pestodude]

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.

[Deborah_Hall]

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.

[RapAdmin]

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