Creatine is one of the most extensively researched and effective supplements for enhancing athletic performance. It primarily works by increasing energy availability during high-intensity activities.
What is Creatine?
Creatine was first isolated from skeletal muscle by the French chemist Michel Eugène Chevreul in 1832. It is primarily produced in the liver, with some production also occurring in the kidneys and pancreas.
Creatine stores high-energy phosphate groups in the form of phosphocreatine. These phosphate groups are donated to ADP, regenerating it into ATP, the primary energy currency in the body. Creatine’s role in energy production is particularly crucial for activities with high energy demands, such as intense exercise.
Creatine is found in some animal-based foods, most abundantly in meat and fish. As a sports nutrition supplement, the most common form is creatine monohydrate, which is also one of the most well-researched and evidence-supported supplements. Athletes typically supplement using creatine in powder or capsule form.
Creatine: Longevity Evidence Level B – Why?
In March 2025, a team led by Xiong Wei from the University of Science and Technology of China discovered that 0.25 mM of phosphocreatine could extend the lifespan of nematodes by approximately 40%.
Furthermore, a 2011 study investigated the effects of creatine supplementation on aging in 162 aged wild-type C57BL/6J mice. The results showed that mice fed creatine had a median healthspan that was 9% higher than that of control littermates, and they performed significantly better in neurobehavioral tests.
According to the Longevity Ingredient Rating Standard (2025 Version) established by Changshou.com, creatine has a Level B evidence grade for longevity.
What are the Benefits of Creatine Supplementation?
- Enhanced Exercise Performance / Increased Lean Body Mass (Muscle Gain): A meta-analysis of 23 randomized controlled trials (RCTs), involving 240 subjects with an average age of around 24, found that post-exercise creatine monohydrate supplementation minimized exercise-induced muscle damage.
Three other meta-analyses, with a total sample size exceeding 3000, concluded that creatine supplementation is particularly effective for improving upper body strength, with effects being more pronounced in men compared to women and older adults.
A meta-analysis of 10 RCTs, with a total sample size of 211, showed that creatine combined with resistance training significantly increased muscle strength in older women.
One RCT recruited 63 volunteers, randomly assigned to receive either a placebo or 5 grams/day of creatine monohydrate for 13 weeks. It found that creatine monohydrate increased lean body mass, especially in female subjects; and this effect was largely independent of whether resistance training was performed during supplementation.
However, it should be noted that creatine has little effect on maximal oxygen consumption (VO2max). A meta-analysis of 19 RCTs, involving 424 individuals, suggested that creatine supplementation might negatively affect VO2max, indicating a potential negative effect on aerobic exercise. - Improved Memory: A meta-analysis including 225 subjects showed that creatine supplementation enhanced memory in healthy elderly individuals (aged 66-76).
- Improved Cognition: A randomized, cross-over, double-blind, controlled trial assessed cognitive ability in 123 subjects (including both vegetarians and omnivores) following creatine supplementation. The researchers found that daily supplementation with 5 grams of creatine for 6 weeks led to minimal improvements in cognitive levels, and the supplementation group reported noticeably more side effects.
- Adjunctive Treatment for Depression: An 8-week pilot, double-blind, randomized, placebo-controlled trial enrolled 100 subjects with depression. They were given either creatine (5 g/day) plus cognitive behavioral therapy (CBT) or placebo plus CBT. The study found that the creatine + CBT group led to a significant reduction in depression-related scores compared to the placebo + CBT group.
Safety and Side Effects of Creatine
How Does Creatine Work?
Creatine works primarily through its effects on energy metabolism. Adenosine triphosphate (ATP) is a molecule that carries energy within cells and is the primary fuel source for high-intensity exercise. When cells use ATP for energy, the molecule is converted into adenosine diphosphate (ADP) and adenosine monophosphate (AMP).
Creatine, stored as phosphocreatine, donates a phosphate group to ADP, rapidly regenerating it back to ATP. This process provides a rapid source of energy for short-duration, high-intensity activities, such as sprinting or heavy lifting.
Who Should Use Creatine with Caution?
- Individuals with Kidney Dysfunction: Those with a history of kidney dysfunction or who are taking medications that affect kidney function should avoid creatine supplementation.
- Pregnant and Breastfeeding Women: Due to a lack of sufficient research involving these groups, pregnant and breastfeeding women should avoid using creatine.
- Adolescents: Adolescent athletes are advised to use creatine after the age of 18, at doses not exceeding 3 grams per day.
- Individuals with Digestive System Disorders: Creatine may cause mild digestive discomfort; individuals with gastrointestinal diseases should carefully consider its use.
