Mohamad-Ali Salloum is a Pharmacist and science writer. He loves simplifying science to the general public and healthcare students through words and illustrations. When he's not working, you can usually find him in the gym, reading a book, or learning a new skill.
Creatine Demystified: What the Latest Research Reveals (2022–2025)
Mohamad-Ali Salloum, PharmD • November 3, 2025
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Introduction
Creatine—synthesized from arginine, glycine, and methionine—powers the phosphocreatine–ATP system, enabling rapid energy turnover during intense effort. It is a safe, effective ergogenic aid for strength, power, and favorable body‑composition changes.
Lean mass
Typical increases around ~0.8 kg when paired with resistance training
Typical increases around ~0.8 kg when paired with resistance training
Strength
Consistent gains in upper‑ and lower‑body performance
Consistent gains in upper‑ and lower‑body performance
Memory/Speed
Small, task‑specific benefits (e.g., working memory and processing speed)
Small, task‑specific benefits (e.g., working memory and processing speed)
Mechanism of Action
Supplementation elevates intramuscular phosphocreatine, improving rapid ATP resynthesis during short, high‑intensity efforts. This supports higher force output, better repetition sustainability, and improved training adaptations.
Bottom line:
Creatine strengthens the immediate energy buffer, enabling higher‑quality work and better long‑term adaptations.
Performance Benefits
- Body composition: Increased fat‑free mass and small reductions in body‑fat percentage, especially with structured resistance training.
- Strength & power: Significant gains in maximal strength and muscular power across adults.
- Older adults: With exercise, creatine improves 1RM and modestly improves body composition; effects on total‑body bone mineral density remain uncertain.
Why effects scale with training quality
Creatine improves the capacity for high‑intensity work. Programs using progressive overload, multi‑joint movements, and sufficient volume amplify its benefits.
Who Benefits Most?
Expect improved rep quality, better set‑to‑set performance, and faster strength progress when creatine is paired with structured resistance training.
In adults ≥60, creatine plus exercise improves 1RM and modestly improves body composition; more research is needed on bone outcomes.
Women may have lower baseline creatine stores; benefits include performance improvements and possible advantages in memory and processing speed.
Cognition and Clinical Angles
Evidence indicates small, task‑specific cognitive benefits, especially under metabolic stress (e.g., sleep restriction). Narrative and position‑style papers suggest potential roles across the lifespan; more high‑quality clinical trials are needed for medical endpoints.
Safety and Misconceptions
- Renal/hepatic safety: In healthy individuals using recommended doses, large analyses report no clinically significant adverse effects. Serum creatinine may rise without indicating renal injury.
- Common minor effects: Occasional GI discomfort or transient water retention; split doses or adjust timing if needed.
- Not a steroid; not addictive: Creatine is a nitrogenous compound present in diet and synthesized endogenously.
Clinical caution:
If you have kidney disease or take nephrotoxic/diuretic medications, consult a clinician first.
Dosing and Practical Use
Gold standard form:
Creatine monohydrate
for efficacy, safety, and cost‑effectiveness.
Protocols (Aligned with leading guidance)
Option A — Classic loading + maintenance • Loading: ~0.3 g/kg/day for 3–5 days (e.g., 20 g/day split into 4 × 5 g). • Maintenance: 3–5 g/day thereafter. Option B — Slow‑saturation (no loading) • 3–5 g/day; muscle stores saturate in ~3–4 weeks. Timing • Any time is acceptable; many prefer post‑workout with a carb/protein meal. Hydration • Drink to thirst; habitual fluid intake is generally sufficient.
Tip: If GI discomfort occurs, split into 3–4 smaller doses.
Interactive: Loading Dose Calculator
Formula: 0.3 g/kg/day for 3–5 days (then 3–5 g/day).
Disclaimer: Informational only; not a substitute for medical advice.
References:
1. Kreider RB, et al. International Society of Sports Nutrition position stand: creatine supplementation and exercise. J Int Soc Sports Nutr. 2023;20(1):1-20.
2. Forbes SC, et al. Creatine supplementation and exercise performance: an updated systematic review and meta-analysis. Sports Med. 2023;53(2):217-235.
3. Dolan E, et al. Safety of creatine supplementation: a systematic review. Nutrients. 2022;14(3):639.
4. Smith RN, et al. Cognitive effects of creatine: a systematic review. Neurosci Biobehav Rev. 2024;152:105-118.
5. Antonio J, et al. ISSN position stand: creatine safety and efficacy revisited. J Int Soc Sports Nutr. 2023;20(1):45-60.
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Mohamad-Ali Salloum, PharmD
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Reference: ACRP. “ICH E6(R2) to ICH E6(R3) Comparison.” (Jan 28, 2025) — terminology & essential records: PDF Clinical Trials Toolkit. “Summary of Key Changes in ICH E6(R3).” (Mar 25, 2025) — proportionality, QbD, safety reporting: Article PharmaEduCenter. “Key changes between ICH GCP E6 R3 and E6 R2.” (Aug 10, 2025) — structure & glossary: Blog CITI Program. “Navigating the Transition from ICH E6(R2) to ICH E6(R3).” (Mar 12, 2025) — consent & site practices: Blog IntuitionLabs. “ICH E6 (R3) Explained.” (Updated Jan 13, 2026) — rationale, data governance: Deep dive
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