An Overview of Creatine: Its Uses, Benefits And Side Effects

Creatine is a naturally occurring nitrogenous organic acid that plays a vital role in cellular energy supply, particularly within muscle cells [1]. The body converts it to phosphocreatine, which aids in the rapid formation of adenosine triphosphate (ATP), the primary energy currency required for muscle contraction and high-intensity, short-duration activities [2].

It is naturally found in red meat and fish, and the human body also synthesises it in the liver, kidneys, and pancreas from the amino acids L-arginine, L-glycine, and L-methionine [3]. Approximately 95% of the body’s creatine stores are located in skeletal muscle [2]. Creatine monohydrate is the most common, extensively studied, and effective form used in supplements [3].

Need for Creatine Supplementation

The body typically needs approximately 1–3 grams of creatine per day to maintain normal reserves [4].

• Approximately half is produced internally (endogenously) in the liver, kidneys, and pancreas.
• The remainder must come from dietary sources, primarily red meat and fish (e.g., 1 pound of raw beef or salmon provides about 1–2 grams) [4].

Athletes and fitness enthusiasts often use creatine supplements to increase muscle stores beyond levels attainable through diet alone, aiming to enhance physical performance, support muscle recovery, and increase muscle mass [1]. Individuals with lower baseline creatine levels (such as vegetarians or vegans) often experience a more significant benefit from supplementation [5].

Uses and Potential Benefits

Creatine is one of the most thoroughly researched supplements and is primarily known for its role in enhancing exercise capacity.

Strength, Muscle Size, and Performance

Creatine supplementation is shown to significantly improve high-intensity exercise performance, such as weight lifting and sprinting, by increasing the availability of ATP [1], [6].

• Muscle Growth: Creatine can promote an increase in lean body mass and muscle size when combined with resistance training [6]. Initial gains are often due to increased water content within muscle cells; over time, it supports muscle fiber growth through cellular signaling pathways [7].
• Intensity: It supports performance in explosive, short-duration activities like Olympic lifting, sprinting, and high-intensity interval training (HIIT) [1].

Injury Prevention and Recovery

There is evidence to suggest that oral creatine may help reduce the incidence of dehydration, muscle cramping, and muscle damage in athletes during intense training periods, potentially aiding in quicker recovery [3].

Cognition and Brain Health

The brain is an ATP-dependent organ, and supplementing with creatine may enhance its function, particularly under stress [8].

In older adults, supplementation may enhance performance in short-term memory tasks and reasoning skills, especially under conditions of mental fatigue or sleep deprivation [8].

Support for Clinical Populations

• Rare Creatine-Metabolising Syndromes: Oral creatine powder may help manage some symptoms in children with specific, rare genetic creatine deficiency syndromes [3].
• Bone Health and Sarcopenia (Age-Related Muscle Loss): Preliminary research suggests that creatine, when combined with resistance training, may help maintain bone mineral density and mitigate age-related muscle loss [5].

Other Uses with Limited Evidence

• Heart Failure: There is insufficient, limited, and conflicting evidence to recommend oral creatine as a routine treatment for heart failure [3].
• Ageing of the Skin: Early research suggests that topical formulations of creatine combined with other compounds (e.g., folic acid) may show cosmetic benefits in improving skin firmness and reducing wrinkles; however, scientific evidence remains limited [3].

Potential Side Effects

Creatine is generally considered a safe and well-tolerated supplement for healthy individuals when taken at recommended dosages [3], [4]. However, users should be aware of potential side effects, which are usually mild.

1. Weight Gain

Initial weight gain is common due to creatine causing muscles to retain water, increasing lean body mass [7]. This is generally considered a desired effect for those seeking muscle bulk but should be noted.

2. Digestive Issues

Taking very large doses at one time may occasionally cause mild stomach problems such as bloating, nausea, or diarrhea [3]. Some research suggests that splitting the daily dose into smaller portions or consuming it with food can help mitigate these issues [3].

3. Cramps or Dehydration

Some anecdotal reports exist regarding muscle cramps or dehydration. However, well-controlled clinical studies have not confirmed an increased risk of dehydration when supplementing with creatine. Maintaining adequate hydration is always recommended for individuals, especially athletes, using creatine [3].

4. Kidney and Liver Function

Creatine supplementation can elevate serum creatinine levels, which is a normal metabolic breakdown product. This elevation may be misinterpreted as impaired kidney function [3]. For the vast majority of healthy individuals, creatine has not been shown to cause kidney or liver damage [4]. However, individuals with pre-existing kidney or liver disease should consult a doctor before use due to the metabolic load [3].

5. Potential Drug Interactions

Creatine may potentially interact with certain medications.

Nephrotoxic medications (drugs toxic to the kidneys, such as some nonsteroidal anti-inflammatory drugs (NSAIDs like ibuprofen) and aminoglycosides) may increase the risk of kidney strain if combined with high-dose creatine [3].

Diuretics (water pills) or other medications affecting hydration levels may also require careful monitoring [3].

Blood sugar-lowering agents may need adjustment, as creatine could have a mild effect on glucose metabolism [3].

Pregnant or breastfeeding individuals and those with pre-existing heart, kidney, or liver disease should always consult a doctor before initiating creatine use [3].

Key Takeaway

Creatine is a highly effective and well-researched supplement that, when combined with resistance training, can safely support:

• Muscle performance and strength
• Muscle growth and lean body mass
• Cognitive function, especially under stress

Always consult a healthcare provider before starting any supplement regimen to ensure it is appropriate for your individual health status, particularly if you have underlying medical conditions or are taking prescription medications.

References

[1] Hall, M., Manetta, E., & Tupper, K. (2021). Creatine Supplementation: An Update. Current Sports Medicine Reports, 20(7), 338–344. https://doi.org/10.1249/jsr.0000000000000863

[2] Kreider, R. B., & Stout, J. R. (2021). Creatine in health and disease. Nutrients, 13(2), 447. https://doi.org/10.3390/nu13020447

[3] Kreider, R. B., Jagim, A. R., Antonio, J., Kalman, D. S., Kerksick, C. M., Stout, J. R., Wildman, R., Collins, R., & Bonilla, D. A. (2025). Creatine supplementation is safe, beneficial throughout the lifespan, and should not be restricted. Frontiers in Nutrition, 12, 1578564. https://doi.org/10.3389/fnut.2025.1578564

[4] Kreider, R. B., Kalman, D. S., Antonio, J., Ziegenfuss, T. N., Wildman, R., Collins, R., Candow, D. G., Kleiner, S. M., Almada, A. L., & Lopez, H. L. (2017). International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14, 18. https://doi.org/10.1186/s12970-017-0173-z

[5] Gutiérrez-Hellín, J., Del Coso, J., Franco-Andrés, A., Gamonales, J. M., Espada, M. C., González-García, J., López-Moreno, M., & Varillas-Delgado, D. (2024). Creatine Supplementation Beyond Athletics: Benefits of Different types of creatine for women, vegans, and Clinical Populations—A Narrative Review. Nutrients, 17(1), 95. https://doi.org/10.3390/nu17010095

[6] Wu, S.-H., Chen, K.-L., Hsu, C., Chen, H.-C., Tsai, T.-Y., Chang, C.-C., & Huang, K.-C. (2022). Creatine supplementation for muscle growth: A scoping review of randomized clinical trials from 2012 to 2021. Nutrients, 14(6), 1255. https://doi.org/10.3390/nu14061255

[7] Rawson, E. S., Persky, A. M., & Greenhaff, P. L. (2024). Creatine. Advances in Nutrition, 15(1), 100142. https://doi.org/10.1016/j.advnut.2023.10.009

[8] Avgerinos, K. I., Spyrou, N., Bougioukas, K. I., & Kapogiannis, D. (2020). Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Experimental Gerontology, 133, 110834. https://doi.org/10.1016/j.exger.2020.110834