More Sets, More Muscle
Five sets beat three sets for muscle and strength in trained lifters.
Do you need to do three sets or five sets per exercise to really maximise your muscle growth? This randomised controlled trial compared high-volume resistance training (HVRT) at five sets per exercise versus low-volume resistance training (LVRT) at three sets per exercise in 40 trained individuals over eight weeks. They examined not just muscle and strength outcomes, but also the molecular mechanisms driving these adaptations.
Aim
The purpose of this investigation was to compare the effects of HVRT and LVRT on muscle hypertrophy and strength in trained athletes, while examining the underlying molecular mechanisms, specifically mTOR signaling and myostatin levels.
Methods
Forty trained individuals (20 males, 20 females, ages 20-30) with at least one year of consistent resistance training experience participated in this eight-week randomised controlled trial. Participants were randomly assigned to either an HVRT group, which performed five sets per exercise, or an LVRT group, which performed three sets per exercise, with both groups training three times per week. The training protocol included major compound lifts targeting all muscle groups, including squats, bench presses, deadlifts, and lat pulldowns. Muscle hypertrophy was measured using dual-energy X-ray absorptiometry (DXA), strength gains were assessed through one-repetition maximum (1RM) tests, and blood samples were collected to analyse mTOR signalling and myostatin levels.
Results
Muscle Hypertrophy and Strength Gains
Both training approaches produced significant improvements, but HVRT demonstrated superior outcomes across all measurements. The HVRT group achieved a lean mass increase of 4.2 kg compared to 2.8 kg in the LVRT group, representing a statistically significant difference.
Strength improvements in the HVRT group exceeded those in the LVRT group across all major lifts. For the squat, HVRT participants gained 18.5 kg compared to 10.2 kg in the LVRT group. Bench press strength increased by 12.1 kg in HVRT versus 7.8 kg in LVRT, while deadlift strength improved by 14.3 kg in HVRT compared to 8.9 kg in LVRT.
Molecular Mechanisms
The molecular analysis revealed important differences in the pathways driving muscle growth. HVRT produced a 28% increase in mTOR phosphorylation compared to a 16% increase in LVRT, indicating greater activation of this critical muscle protein synthesis pathway. Additionally, myostatin levels, which negatively regulate muscle growth, decreased by 26% in the HVRT group versus only 14% in the LVRT group.
Post-exercise blood lactate concentrations were significantly higher in the HVRT group at 8.2 mmol/L compared to 6.4 mmol/L in the LVRT group, reflecting greater metabolic stress. Hormonal responses also favoured HVRT, with this group experiencing a larger increase in testosterone and lower cortisol levels compared to LVRT, suggesting a more favourable anabolic environment.
Practical Takeaways
For lifters looking to maximise muscle growth and strength, these findings show that higher training volumes provide a clear advantage. Implementing five sets per exercise rather than three sets can produce approximately 50% greater lean mass gains and substantially larger strength improvements across major lifts. The molecular evidence indicates that this advantage stems from enhanced activation of muscle-building pathways and suppression of growth-limiting factors. While higher volume requires more time and recovery capacity, trained individuals with adequate recovery strategies and nutrition appear to benefit significantly from this approach. For those plateauing with lower volume programs, gradually increasing to higher volumes may unlock additional gains by providing the mechanical tension, metabolic stress, and hormonal responses necessary to drive continued adaptations.
Key Takeaways
High-volume resistance training consistently outperforms low-volume training for both muscle hypertrophy and strength development in trained individuals. The superior results are supported not only by physical measurements but also by molecular evidence showing greater mTOR pathway activation, reduced myostatin levels, increased metabolic stress, and a more favourable hormonal environment. These findings indicate that volume remains a critical variable in resistance training programming for those looking to maximise muscular adaptations.
Reference
EFFECTS OF HIGH-VOLUME AND LOW-VOLUME RESISTANCE TRAINING ON MUSCLE HYPERTROPHY AND STRENGTH. (2025). Pakistan Journal of Medical & Cardiological Review, 4(4), 69-78. https://doi.org/10.64105/z6ytfn58
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