Hypertrophy Evidence Notes
All topics

Supplements

Only creatine has strong evidence. Use caffeine as a tool to improve training quality.

312Last reviewed Verdicts

Bottom line

  • Take 3–5 g/day of creatine monohydrate every day. Timing doesn’t matter
  • Take 210–420mg of caffeine (3–6 mg/kg) 60 minutes before training. For evening sessions, use a dose that doesn’t cut into your sleep
  • If your protein intake is adequate, you don’t need BCAAs or EAAs

Creatine

Adding creatine to resistance training adds about 1.1–1.5kg of lean mass. It works as well in trained lifters as in beginners.

  • In a meta-analysis of 61 trials, lean mass increased by +1.39kg (95% confidence interval 1.07–1.70), with no difference between trained lifters and beginners (Ashtary-Larky 2025)
  • Other meta-analyses agree: +1.14kg (Desai 2024) and +1.46kg in men (Delpino 2022)
  • A 2026 meta-analysis of 63 studies also found a positive effect on lean mass (Wang 2026)

When muscle thickness is measured directly, though, the effect is small. Part of the lean mass gain is water inside the muscle.

A meta-analysis of regional hypertrophy found a small effect size of 0.11 (95% credible interval −0.02 to 0.25) (Burke 2023). It is still cheap and has extensive safety data, so it is well worth taking.

Long-term intake of 3–5g a day is considered safe.

The ISSN position stand considers long-term intake safe for healthy people (Kreider 2017). Loading (about 20g/day for the first 5–7 days) only makes the effect show up sooner. You can skip it.

Caffeine

3–6 mg/kg of caffeine gives a small but reliable boost to strength and power.

  • In a meta-analysis, the effect size was 0.20 for strength and 0.17 for power (Grgic 2018)
  • An umbrella review of 21 meta-analyses also found a consistent effect (Grgic 2020)
  • The ISSN recommends 3–6 mg/kg about 60 minutes before training. The minimum effective dose is about 2 mg/kg (Guest 2021)

There is no evidence that it directly increases hypertrophy. At most, it may help indirectly by improving session quality.

Weak evidence or unnecessary

If protein intake is adequate, adding BCAAs or EAAs does nothing. HMB has mixed results in trained lifters. Herbal testosterone boosters have no good evidence.

References

  1. Ashtary-Larky D et al. 2025. Creatine supplementation and resistance training: a comparison between novice and experienced lifters. JISSN. PMID 41433021
  2. Desai I et al. 2024. The Effect of Creatine Supplementation on Resistance Training-Based Changes to Body Composition. J Strength Cond Res. PMID 39074168
  3. Delpino FM et al. 2022. Influence of age, sex, and type of exercise on the efficacy of creatine supplementation on lean body mass. Nutrition. PMID 35986981
  4. Wang H et al. 2026. Resistance training combined with creatine supplementation: a three-level meta-analysis. JISSN. PMID 42765482
  5. Burke R et al. 2023. The Effects of Creatine Supplementation Combined with Resistance Training on Regional Measures of Muscle Hypertrophy. Nutrients. PMID 37432300
  6. Kreider RB et al. 2017. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. JISSN. PMID 28615996
  7. Grgic J et al. 2018. Effects of caffeine intake on muscle strength and power: a systematic review and meta-analysis. JISSN. PMID 29527137
  8. Grgic J et al. 2020. Wake up and smell the coffee: caffeine supplementation and exercise performance—an umbrella review of 21 published meta-analyses. Br J Sports Med. PMID 30926628
  9. Guest NS et al. 2021. International society of sports nutrition position stand: caffeine and exercise performance. JISSN. PMID 33388079