Study Overview
Volek et al. (1999) published a study in Medicine and Science in Sports and Exercise examining the performance and muscle fibre adaptations to creatine supplementation during 12 weeks of heavy resistance training in 19 resistance-trained men.
Subjects were randomised to receive either creatine (25g/day for 1 week loading, then 5g/day maintenance) or placebo while following a periodised resistance training program (Volek et al., 1999) .
This was not a hormone study — it did not measure testosterone. Its value is in showing how creatine amplifies muscle growth and strength alongside heavy training.
Key Findings
- Greater fat-free mass: the creatine group increased fat-free mass by 6.3% versus 3.1% for placebo
- Greater strength: bench press rose 24% (vs 16% placebo) and squat 32% (vs 24% placebo)
- Muscle fibre hypertrophy: larger increases in Type I (35% vs 11%), IIA (36% vs 15%), and IIAB (35% vs 6%) fibre cross-sectional area
- Higher muscle creatine: muscle total creatine rose about 22% after the first week and stayed elevated
- No supraphysiological effects: gains were driven by higher training quality, not hormonal manipulation
Creatine and Testosterone — Setting the Record Straight
A common gym myth is that creatine raises testosterone. The evidence does not support this:
- Volek et al. (1999) did not measure testosterone at all — its benefits came from the phosphocreatine energy system, not hormones.
- Op ‘t Eijnde and Hespel (2001) directly tested it and found creatine did not alter testosterone, growth hormone, or cortisol responses to resistance training.
- The only hormonal signal in the literature is a single study (van der Merwe et al., 2009) reporting increased DHT — not testosterone — which has not been reliably replicated (Kreider et al., 2017) .
The practical takeaway: creatine builds muscle through improved training capacity and recovery, not by acting as a hormone or steroid.
Study Limitations
- Relatively small sample size (19 subjects)
- Only resistance-trained men were studied — results may differ in untrained individuals, women, or older adults
- Dietary intake was monitored but not strictly controlled
Mechanism of Action
Understanding the biochemistry behind creatine's effects provides context for the practical recommendations in this guide. Creatine functions primarily through the ATP-phosphocreatine (ATP-PCr) system:
- Storage: Approximately 95% of the body's creatine is stored in skeletal muscle, with the remaining 5% in the brain, kidneys, and liver
- Conversion: The enzyme creatine kinase attaches a high-energy phosphate group to free creatine, creating phosphocreatine (PCr)
- Energy release: During high-intensity activity, PCr rapidly donates its phosphate group to ADP, regenerating ATP within milliseconds
- Resynthesis: During rest periods, the process reverses — ATP donates a phosphate back to creatine, replenishing PCr stores
This cycle operates continuously in all metabolically active tissues. Supplementation increases the total creatine pool by 20-40%, expanding the energy buffer available for intense physical and cognitive work.
Where This Fits in the Evidence
Volek et al. (1999) is one of the cleaner demonstrations that creatine’s muscle benefits are mechanical, not hormonal. Over twelve weeks of heavy resistance training the creatine group out-gained placebo on fat-free mass, strength and muscle fibre cross-sectional area — driven by higher training quality as muscle creatine rose, with no hormonal manipulation involved. That distinction is the page’s whole point: this trial never measured testosterone, and when others tested it directly creatine did not move it. It sits among the solid muscle-and-training RCTs underpinning the ISSN position stand; the wider evidence is in our research library.
Sources & References
This page summarizes Volek JS, Duncan ND, Mazzetti SA, et al. Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Medicine and Science in Sports and Exercise. 1999;31(8):1147-1156. doi:10.1097/00005768-199908000-00011
Hormone evidence: Op ‘t Eijnde B, Hespel P. Short-term creatine supplementation does not alter the hormonal response to resistance training. Med Sci Sports Exerc. 2001;33(3):449-453.