Creatine is one of the most widely used and extensively studied supplements on the market. While it’s most often associated with sports performance and strength training, clinicians are increasingly being asked about its safety—both in the general population and among those with kidney disease.
This post is the first in a four-part series exploring the safety and clinical implications of creatine supplements.
Subsequent posts will cover:
- Part 2: Creatine Supplements in Special Populations
- Part 3: Creatine Supplements and Kidney Health
- Part 4: Creatine Supplements in End-Stage Kidney Disease
The following systematic reviews, published in 2025, provide the foundation for this series:
- Gutiérrez-Hellín J, et al. Creatine Supplementation Beyond Athletics: Benefits of Different Types of Creatine for Women, Vegans, and Clinical Populations. Nutrients 2025;17(1):95.
- Matczak M, et al. The Impact of Creatine Supplementation on the Development of Kidney Disease – Literature Review. Quality in Sport 2025;38:57864.
- Villa A, Trotta L, Faraci G. The Impact of Creatine Supplementation on Renal Function: A Case Report and Literature Review. 2025.
What Is Creatine?
Creatine is a compound synthesized primarily in the liver, kidneys, and pancreas from the amino acids glycine and arginine. Its main role is to help recycle adenosine triphosphate (ATP)—the body’s key energy currency.
Not surprisingly, creatine is concentrated in tissues with high energy demands, particularly skeletal muscle and the brain. When phosphorylated (bound to a phosphorus molecule), creatine forms phosphocreatine, an important energy reserve in these tissues.
Creatine vs. Creatinine
Clinicians are likely already familiar with creatinine, a key laboratory marker used to estimate glomerular filtration rate (eGFR). Creatinine is the end product of creatine metabolism.
Because most of the body’s creatine is stored in muscle, creatinine excretion correlates with muscle mass—higher muscle mass results in greater creatinine production and excretion.
Sources of Creatine
There are three main sources of creatine:
| Source | Description |
|---|---|
| Endogenous production | Synthesized from glycine and arginine in the liver, kidneys, and pancreas |
| Dietary sources | Found naturally in meat and fish (typical intake: 1–2 g/day) |
| Supplements | Commercial creatine products available in various forms |
Types of Creatine Supplements
The most common types of creatine supplements are summarized below.
| Type | Description | Safety Comments |
|---|---|---|
| Creatine Monohydrate | Most common and extensively studied form | Generally safe at recommended doses; high doses or combination with other supplements have been linked to rare liver and kidney complications |
| Creatine Ethyl Ester | Creatine bound to esterified ethanol for enhanced bioavailability | Not recommended for pregnant/lactating women, children, or individuals with liver or kidney dysfunction due to ethanol content |
| Creatine Gluconate | Bound to glucose molecules to facilitate uptake into muscle cells | Effectiveness and safety require further study |
| Creatine Citrate | Bound with citric acid for improved solubility and reduced GI discomfort | More long-term data needed on efficacy and safety |
| Creatine Magnesium Chelate | Bound to magnesium to enhance absorption | Limited long-term safety data |
| Creatine “Cocktails” | Combined with other ergogenic agents (protein, caffeine, vitamins, herbal extracts) | Limited evidence on health and safety |
Commonly Studied Doses
Creatine supplementation protocols typically include two phases:
| Stage | Dose | Duration |
|---|---|---|
| Loading | 0.3 g/kg/day | 5–7 days |
| Maintenance | 0.03 g/kg/day | 4–6 weeks |
Studies have also shown that muscle phosphocreatine levels can increase without a loading phase, though changes occur more gradually.
How Does Creatine Work?
Approximately 95% of creatine is stored in skeletal muscle, where about 60% exists as phosphocreatine and 40% as free creatine.
During transitions from rest to exercise, phosphocreatine donates a phosphate group to adenosine diphosphate (ADP) to rapidly regenerate ATP—providing an immediate energy source for the first 6–8 seconds of high-intensity activity, before glycolysis becomes the primary energy pathway.
Reported Benefits
When combined with resistance or sprint training, creatine supplementation has been shown to:
- Increase muscle strength and power
- Enhance recovery following intense exercise
- Support gains in fat-free mass
Emerging research also suggests possible benefits in cognitive function, sarcopenia, and cachexia, though evidence remains preliminary. I will review the literature on these potential benefits in parts 2 and 3 of this series.
Limitations of Current Literature
Interpretation of creatine’s reported benefits should consider the following:
- Most studies have been conducted in young, healthy male athletes, limiting generalizability to women, older adults, or sedentary individuals.
- Data on non-athletic populations are limited, and extrapolation should be done cautiously.
Exercise Types Most Likely to Benefit
Creatine appears most beneficial for intermittent, high-intensity activities that require short bursts of energy followed by recovery (e.g., sprinting, weightlifting).
In contrast, endurance performance (e.g., distance running or cycling) does not consistently improve with creatine supplementation.
Potential Adverse Effects
As with any intervention, “there’s no free lunch in medicine.” The following adverse effects have been reported:
| Adverse Effect | Comments |
|---|---|
| Reduced endogenous creatine production | During supplementation, the body’s natural production decreases temporarily but typically returns to baseline within 4–6 weeks. |
| Gastrointestinal side effects and cramps | Usually mild; creatine citrate may help reduce GI discomfort. |
| Fluid retention | Body mass may increase by 1–3 kg after 5–7 days due to osmotic shifts; this typically resolves within 4–6 weeks. |
| Renal function | Creatine supplementation raises serum creatinine, lowering eGFR readings without necessarily indicating reduced kidney function—this will be discussed further in Part 3: Creatine Supplements and Kidney Health. |
Key Takeaways
- Creatine supplements are popular, well-researched, and generally safe for healthy adults.
- Creatine monohydrate remains the gold-standard form.
- Greatest benefit is seen in high-intensity, short-duration activities.
- While creatine supplementation can transiently raise serum creatinine, current evidence does not indicate kidney injury in healthy individuals.
If you enjoyed this post, continue the series:
? Part 2: Creatine Supplements in Special Populations
? Part 3: Creatine Supplements and Kidney Health
? Part 4: Creatine Supplements in End-Stage Kidney Disease
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