Creatine: The Science Behind It’s Benefits

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Creatine: Benefits, Uses, and Evidence-Based Insights

Creatine is one of the most extensively researched dietary supplements in the fitness and health world, valued for its ability to enhance performance, support muscle growth, and even improve certain aspects of cognitive health. Its safety and efficacy have been validated in hundreds of studies involving athletes, older adults, and clinical populations. Below, we dive deep into the science of creatine, highlighting its mechanisms, benefits, recommended dosages, and the myths surrounding it.

What Is Creatine?

Creatine is a naturally occurring compound found in small amounts in certain foods, such as meat and fish, and synthesised in the body from amino acids (arginine, glycine, and methionine). Most of the body’s creatine—about 95%—is stored in skeletal muscles as phosphocreatine, while the remaining 5% resides in the brain, kidneys, and liver.

Phosphocreatine acts as a rapid energy reserve for cells, particularly during short, high-intensity activities. This role underpins creatine’s effectiveness as a supplement for athletic performance and other physiological benefits.

How Does Creatine Work?

The primary mechanism behind creatine’s effects lies in its contribution to adenosine triphosphate (ATP) production. ATP is the primary energy currency of the body, fuelling cellular activities. During intense, short-duration exercises such as weightlifting or sprinting, phosphocreatine replenishes ATP, allowing muscles to sustain higher performance for longer periods.

Beyond energy production, creatine influences cellular hydration, protein synthesis, and mitochondrial function. These mechanisms contribute not only to athletic performance but also to broader health benefits.

Proven Benefits of Creatine Supplementation

Enhanced Exercise Performance

Creatine supplementation is particularly effective for high-intensity, short-duration exercises. Research shows it improves strength, power, and work capacity by replenishing ATP more efficiently. For example:

• Strength Gains: Studies report up to a 20% increase in strength and performance during resistance training with creatine use​.
• Increased Workload: Athletes can complete more repetitions at higher intensities, supporting hypertrophy and endurance.

Muscle Growth

Creatine promotes muscle hypertrophy both directly and indirectly:

• Direct Effects: Increased water content in muscle cells leads to a temporary volumisation, which may enhance muscle signalling pathways related to growth.
• Long-Term Gains: Over time, creatine supports greater training intensity and volume, leading to increased lean muscle mass.

Cognitive Benefits

Creatine isn’t just for muscles; it also supports brain function. Supplementing creatine has been shown to:

• Improve memory and reasoning in sleep-deprived individuals.
• Enhance cognitive performance in older adults, potentially delaying cognitive decline​.

Another paper stated that creatine supplementation reduces depressive symptoms, particularly when combined with antidepressant medications, and may improve brain energy metabolism and neuroplasticity.” (source)

Finally a study demonstrated that a high single dose (0.35 g/kg) can partially reverse metabolic alterations and fatigue-related cognitive deterioration. (click here)

Improved Recovery

Creatine reduces muscle damage and inflammation following intense exercise, speeding up recovery. It may also decrease markers of oxidative stress and improve cellular repair processes​.

Traumatic Brain Injury

A paper published in 2022 states “creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression.” (source)

Preliminary data suggest that the administration of creatine may be beneficial to patients with traumatic brain injury (click here). A pilot study was conducted to investigate the potential neuro-protective effects of creatine in children and adolescents aged 1 to 18 years who had experienced traumatic brain injury (TBI). The study was designed as a prospective, randomised, open-label comparison. Participants received daily oral doses of creatine, administered as a suspension at 0.4 grams per kilogram of body weight, for a duration of six months.

Creatine supplementation in children with traumatic brain injury (TBI) demonstrated improvements across multiple clinical outcomes. These included a reduction in the duration of post-traumatic amnesia (PTA), intubation time, and intensive care unit (ICU) stays. Positive effects were also observed in measures of disability, recovery quality, self-care abilities, communication, mobility, sociability, and overall neuro-physical and cognitive functioning. Statistically significant enhancements were particularly noted in cognitive abilities, personality and behaviour, self-care skills, and communication, highlighting creatine’s potential role in supporting recovery in paediatric TBI cases.

Mitochondrial Dysfunction

Creatine monohydrate (CrM) supplementation shows promise in enhancing cellular bioenergetics, particularly in conditions associated with mitochondrial dysfunction, ischemia, and injury-related pathologies. This improvement in energy metabolism suggests potential therapeutic benefits for managing these conditions. However, to fully establish its efficacy and safety, larger and more comprehensive clinical trials are essential (click here).

Creatine supplementation has been shown to enhance the availability of high-energy phosphates and exhibit multiple beneficial effects, including anti-oxidative, neuro-protective, anti-lactic acid, and calcium homeostasis properties. These effects are particularly significant for maintaining mitochondrial function and health, especially under stress conditions such as ischemia or injury. By supporting energy metabolism and cellular defence mechanisms, creatine may play a protective role in preserving mitochondrial integrity during such challenges.

Cardiovascular Health

Creatine has demonstrated several non-energy-related functions, including acting as a direct and indirect antioxidant and exerting anti-inflammatory effects. Despite recent advancements highlighting its clinical benefits, limited research exists on creatine’s impact on cardiovascular disease (CVD), which remains the leading cause of death worldwide. Considering these non-energy-related properties, this review (click here) suggests that creatine supplementation could potentially be used as a complementary therapy to improve vascular health and manage CVD risk in vulnerable populations. Further studies are needed to explore these promising possibilities in greater depth.

Benefits for Older Adults

Creatine supplementation helps combat sarcopenia (age-related muscle loss), enabling older adults to maintain strength and functionality. This is particularly important for preserving independence and reducing the risk of falls. In fact sarcopenia is associated with a higher mortality rate than those without the condition. A meta-analysis of 7,367 individuals found that participants with sarcopenia had a significantly higher rate of all-cause mortality than those without. (source)

Methylation

Creatine supplementation can reduce the body’s demand for methylation, which can help with methylation-related health problems. Creatine can reduce methylation demand by up to 50%, freeing up methyls for other biochemical systems.

How Much Creatine Per day?

1. Loading Phase

The traditional dosing protocol involves a loading phase:

• Dosage: 20 grams per day, split into four 5-gram servings, for 5-7 days.
• Purpose: Rapidly saturates muscle stores.

This isn’t always necessary however.

2. Maintenance Phase

After loading, a maintenance dose of 3-5 grams per day is sufficient to maintain elevated muscle creatine levels. For individuals who prefer to skip the loading phase, taking a daily dose of 3-5 grams will achieve saturation within 3-4 weeks.

When To Take Creatine

Creatine can be taken at any time, but many studies suggest post-workout timing may enhance uptake due to improved insulin sensitivity​.

It’s important to note that the optimal dosing to support cognition is currently unknown, however, it appears that creatine is most likely to be beneficial when cognitive processes are stressed, e.g. during sleep deprivation, experimental hypoxia, or during the performance of more complex, and thus more cognitively demanding tasks. (source)

Doses For Brain health

There is evidence that ≥ 20 g/day or 0.3 g/kg/day for ≤ 7 days or ≥ 4 g/day for several months is likely required to increase total brain creatine concentrations. (source)

Confounding variables

There are numerous confounding variables discussed in the above paper however, such as” baseline (pre-supplementation) tissue creatine levels, muscle fiber morphology, bone remodelling/repair processes, brain bioenergetics, habitual dietary intake of creatine, biological sex, age, and physical activity likely dictate the dose of creatine required to produce a meaningful tissue response. (source)

Is Creatine Bad For You?

1. Kidney Health

Decades of research indicate no adverse effects on kidney function in healthy individuals consuming creatine at recommended dosages. Myths about creatine harming kidneys likely stem from misinterpretations of blood creatinine levels, which naturally rise with supplementation​.

2. Water Retention and Bloating

Short-term water retention may occur during the loading phase as muscle cells retain more water. However, this is not harmful and often subsides with continued supplementation.

3. Does Creatine Cause Hair Loss?

Some studies suggest creatine may increase dihydrotestosterone (DHT) levels, which could theoretically contribute to hair loss in individuals predisposed to androgenic alopecia. However, direct evidence linking creatine to hair loss is weak.

Forms of Creatine

• Creatine Monohydrate: The most researched and effective form.
• Buffered Creatine: Claims reduced stomach discomfort, but lacks strong evidence of superiority.
• Micronised Creatine: Smaller particles for better solubility.
• Creatine Ethyl Ester and Hydrochloride: Marketed as advanced forms but generally less effective than monohydrate.

Recommended Product

100% Creatine by Kinetica.

Common Myths About Creatine

1. “Creatine is a steroid.” Creatine is a naturally occurring compound, not a steroid or hormone. It works via energy metabolism rather than hormonal pathways.
2. “Creatine causes dehydration and cramps.” Studies debunk these claims, showing no increased risk of dehydration or cramping during supplementation​
3. “Creatine is only for bodybuilders.” Creatine benefits a broad range of populations, including endurance athletes, older adults, and even individuals with certain diseases.
4. “Other forms of creatine are better than monohydrate.” Creatine monohydrate remains the gold standard due to its extensive evidence base.

Future Directions in Creatine Research

While creatine is well-established for athletic and health benefits, emerging research is exploring its role in:

• Mental health conditions like depression and anxiety.
• Enhancing sleep quality and recovery.
• Application in clinical populations for improving quality of life.

Conclusion

Creatine supplementation is one of the safest and most effective dietary interventions for enhancing physical performance, supporting cognitive health, and improving overall well-being. With decades of research affirming its benefits, creatine remains a staple for athletes and non-athletes alike. Whether you’re looking to increase strength, improve recovery, or support brain health, creatine offers a science-backed solution.

References

1. Antonio J, Candow DG, Forbes SC, et al. Common questions and misconceptions about creatine supplementation: What does the scientific evidence really show? J Int Soc Sports Nutr. 2021;18(1):12.
2. Kreider RB, Kalman DS, Antonio J, et al. International society of sports nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017;14:18. (click here)
3. Gualano B, Rawson ES, Candow DG, et al. Creatine supplementation in the aging population: effects on skeletal muscle, bone, and brain. Nutrients. 2021;13(2):449.
4. Tarnopolsky M, Safdar A. Creatine and its potential therapeutic value in muscle disorders and neuromuscular diseases. Muscle Nerve. 2008;37(6):705-717.
5. Candow et al., (2024) Does one dose of creatine supplementation fit all? Advanced Exercise and Health Science (click here)
6. Sandkühler et al., (2023) The effects of creatine supplementation on cognitive performance-a randomised controlled study, BMC Med,  15;21(1):440 (click here)
7. Jujeja et al., (2024) Creatine Supplementation in Depression: A Review of Mechanisms, Efficacy, Clinical Outcomes, and Future Directions, Cureus. 16;16(10):e71638 (click here)
8. Dolan et al., (2019) Beyond muscle: the effects of creatine supplementation on brain creatine, cognitive processing, and traumatic brain injury, Eur J Sport Sci.;19(1):1-14 (click here)
9. Sakellaris et al., (2006) Prevention of complications related to traumatic brain injury in children and adolescents with creatine administration: an open label randomized pilot study, J Trauma;61(2):322-9 (click here)
10. Marshall et al., (2022) Role of Creatine Supplementation in Conditions Involving Mitochondrial Dysfunction: A Narrative Review, Nutrients, 26;14(3):529 (click here)
11. Gordji-Nejad et al., (2024) Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation, Sci Rep, 28;14(1):4937
12. Johnstone et al., (2021) The Potential Role of Creatine in Vascular Health, Nutrients, 5;13(3):857 (click here)