The Study
The degree of p70S6k and S6 phosphorylation in human skeletal muscle in response to resistance exercise depends on the training volume
This study found that doing more sets of weightlifting made certain tiny signals in your muscles get stronger right after you finish. But it didn’t measure if your muscles actually got bigger or stronger over time — so we can’t say more sets definitely make you bigger, just that the signals changed.
Analysis score
Maximum 90 for a randomized controlled trial.
Where the score came from
When guys who don't lift weights do leg presses, doing more sets turns on a muscle-building switch called S6 — but only if they do enough sets.
Where does this study sit?
Reviews of RCTs (Meta-analyses)
Max 100Randomized Trials
Max 90Reviews of Cohort Studies
Max 85Cohort Studies
Max 72Reviews of Case-Control Studies
Max 63Case-Control Studies
Max 58Cross-Sectional & Case Series
Max 50Expert Opinion
Max 553 / 100
Quality score
Participants are randomly assigned to treatment or control groups, minimizing bias. The gold standard for testing whether an intervention causes an effect.
Key takeaways
Summary
Based on the study abstract and findings.
- 1Yes — 5 sets triggered the strongest signal for muscle building, but even 3 sets did almost as well, suggesting you don't need tons of sets to activate growth pathways.
- 21 set: no change.
- 33 sets: S6 up 30x.
- 45 sets: S6 up 55x.
- 5Akt and mTOR stayed the same no matter how many sets.
Score breakdown, methodology, conflicts of interest, evidence analysis & raw study data
Publication
Journal
European Journal of Applied Physiology
Year
2010
Authors
G. Terzis, K. Spengos, H. Mascher, G. Georgiadis, P. Manta, E. Blomstrand
Related Content
Claims (6)
Doing more workout volume doesn’t necessarily make your muscles grow more—your body’s internal muscle-building signals stay about the same no matter how much you train.
When guys who don’t normally lift weights do a tough leg workout on an empty stomach, their muscles show a big spike in two specific signals that tell the body to build more muscle, and this might mean doing more sets makes those signals even stronger.
If untrained guys lift weights on an empty stomach, doing 5 sets of exercise really ramps up a key muscle-building signal in their cells—but just 1 set doesn’t do much, suggesting you need more than a little effort to kickstart muscle growth.
When guys who don’t work out lift weights, their muscles turn on a specific stress signal—no matter if they do 1 set or 5 sets. It’s like the signal just needs the weight to be lifted, not how many times they do it.
For guys who don’t lift regularly, doing weight exercises doesn’t change a specific body signal (ERK1/2) 30 minutes after working out, no matter how hard or long they train — so this signal probably isn’t what tells their muscles to grow right after a fasted workout.
When guys who don’t lift regularly do weight training, even doing more sets doesn’t change certain key muscle signals called Akt and mTOR—so those signals must already be maxed out at low workout levels, and something else is driving the bigger changes seen in other muscle signals.
Not medical advice. For informational purposes only. Always consult a qualified healthcare professional before making health decisions.