What are the documented side effects of creatine? Creatine is one of the safest sports supplements. Most common side effects: GI upset (rare; usually loading-related), 1–2 kg intracellular water gain (desirable, not a side effect).

This guide covers the underlying biology, the available evidence, and a practical protocol so you can use creatine safely.

Creatine is a naturally occurring compound synthesized in the liver, kidneys, and pancreas from arginine, glycine, and methionine. About 95% of body creatine resides in skeletal muscle, with the remainder in brain, heart, and other high-energy tissues. Dietary creatine comes primarily from red meat and fish (~1 g/day in omnivores; near-zero in vegans).

Inside cells, creatine is phosphorylated to phosphocreatine (PCr), which serves as a rapid ATP-regeneration system. During short, high-intensity efforts (1–10 seconds), the ATP–PCr system is the dominant energy supplier. Creatine supplementation increases muscle PCr stores by 10–40%, improving repeat-effort performance, strength, and lean mass gains over weeks of consistent training.

Beyond muscle, creatine has well-documented brain effects. The brain uses creatine for cognitive demands and during stress (sleep deprivation, hypoxia, mental fatigue). Vegetarians, vegans, women, and older adults have consistently shown the largest cognitive benefits — likely because their baseline brain creatine is lower. Therapeutic uses are emerging in depression, ADHD, traumatic brain injury, and Parkinson's disease as adjunctive support.