Q&A: Is creatine only for athletes?​ ​​ ​

​​Take-Home Messages 🔑 

Introduction

Creatine (from the Greek word “kreas” meaning meat) is a naturally occurring nitrogen-containing compound that serves as a reservoir of energy. Creatine has well studied for exercise performance but lately it is being studied for cognitive and mental health benefits among others.

In this review, I explore creatine synthesis and function, natural dietary sources of creatine, supplementation practices and diverse health effects. The latter includes its role in exercise, cognition, hypoxic conditions, cancer treatment and prevention, heart failure, cardiovascular disease risk factors, type 2 diabetes, depression, Parkinson’s disease, Alzheimer, sleep deprivation, mild traumatic brain injuries and osteoarthritis while also addressing safety concerns.

Creatine metabolism and the ATP-PCr energy system

Creatine is synthesised in the body from the amino acids arginine, glycine and methionine. Its production occurs through a two-step enzymatic process. First, arginine:glycine amidinotransferase (AGAT) catalyses the transfer of an amidino group from arginine to glycine, forming guanidinoacetic acid (GAA) and ornithine. Next, in the liver, guanidinoacetate N-methyltransferase (GAMT) methylates GAA using S-adenosylmethionine (SAM), producing creatine and S-adenosylhomocysteine (1). The latter is subsequently converted to homocysteine, linking creatine biosynthesis to amino acid metabolism and methylation balance (2).

Creatine is primarily synthesised in the kidneys and liver, with some contribution from the pancreas, at a rate of approximately 1–2 g per day. About 95% of the body’s creatine is stored in skeletal muscle, while the remainder is distributed to the brain and other tissues. The brain also produces creatine locally. This endogenous synthesis is essential for meeting the brain’s high energy demands.

Creatine functions as a storage form of high-energy phosphate in muscle by forming phosphocreatine. The creatine phosphate energy system, also known as the adenosine triphosphate–phosphocreatine (ATP-PCr) or phosphagen system, is the body’s fastest mechanism for regenerating adenosine triphosphate (ATP) to fuel muscle contraction. ATP and adenosine diphosphate (ADP) serve as the body’s energy currency. ATP, containing three phosphate groups, is analogous to a fully charged battery; when one phosphate group is cleaved, energy is released to power muscular, neural and cellular processes. The resulting ADP, with two phosphate groups, represents a partially discharged battery. The ATP-PCr system rapidly restores ATP by transferring a phosphate group from phosphocreatine to ADP, a reaction catalysed by the enzyme creatine kinase. Because this process involves a single, direct reaction, it provides immediate energy but only for approximately 10–15 seconds, making it particularly effective for short-duration, high-intensity activities such as sprinting or heavy lifting. Its limitation lies in the finite phosphocreatine stores within muscle, after which slower metabolic pathways such as glycolysis and oxidative phosphorylation must sustain energy production. In the brain, creatine serves a comparable role by buffering energy supply, ensuring neurons have rapid access to ATP during periods of high demand, thereby supporting cognitive function, memory and resilience under stress.

Creatinine is formed when creatine phosphate, the quick-release energy reserve in muscle, breaks down during normal activity. Because this breakdown happens at a steady rate, creatinine enters the bloodstream consistently and is then filtered out by the kidneys. Clinicians use blood creatinine levels as a convenient marker of kidney function, because impaired kidneys struggle to clear it, leading to elevated levels. However, when someone supplements with creatine, more creatine is available in the body, which can slightly increase creatinine levels without necessarily indicating kidney damage. For this reason, doctors often look at additional markers—such as estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN) or cystatin C—to get a more accurate picture of kidney health in people using creatine.

Natural dietary sources 🥩

Creatine has no established Recommended Dietary Allowance (RDA) because it is synthesised naturally in the body, with about 1–2 g/day sufficient to replace daily losses and maintain stores in healthy adults. It is found in animal-based foods such as red meat, poultry, and fish, where it comes alongside other nutrients and compounds—including saturated fat and, depending on cooking methods such as grilling or smoking, potentially harmful heterocyclic amines and polycyclic aromatic hydrocarbons(3-5). By contrast, supplementation provides creatine in isolation, making it a practical option since achieving 5 g from food alone would require roughly 1 kg of beef or 700–800 g of herring. While dietary creatine intake from meat has been linked to lower cancer risk in large cohorts (6), the broader evidence indicates that any cancer concerns stem from the meat matrix and preparation methods, not creatine itself.

Table: Creatine content of selected foods

Vegetarians and vegans generally have lower baseline creatine levels because plant-based foods contain little to no creatine, leaving them dependent on endogenous synthesis (7). Because creatine production requires the amino acids arginine, glycine and methionine, diets that are limited in these precursors may further restrict synthesis capacity. Consequently, individuals following vegetarian or vegan diets may benefit from creatine supplementation to optimise muscle energy stores and support both physical and cognitive performance (7).

Supplementation

Creatine is supplemented as a powder or in capsules. Creatine monohydrate, is the most researched, effective and affordable form compared to newer alternatives that lack strong evidence (as reviewed by (1, 8)). Versions other than creatine monohydrate mainly aim to improve solubility or comfort but never consistently outperform it (1). Quality and purity are critical, so opt for products with third‑party certification to ensure they are free of contaminants and unnecessary additives. In the table below, I provide an overview of the different forms of creatine supplements.

Table: Main forms of creatine

Creatine degradation depends on a combination of high temperature, low pH and prolonged exposure, but when dissolved in neutral liquids and consumed shortly after mixing, breakdown is negligible. Creatine remains effective when added to warm or hot drinks (e.g. coffee or tea), as the short preparation‑to‑consumption time prevents significant conversion to creatinine.

Health benefits

Strength and power output improvements in exercise🏋️

It is important to note that creatine is not a steroid, this is a common misconception. Creatine enhances high-intensity exercise capacity and reduces fatigue. A systematic review and meta-analysis (42 trials, n = 1,229) found that creatine supplementation enhances muscle strength compared to controls (9). Greater benefits were observed in untrained individuals, at low-to-moderate doses and when combined with high-intensity training, while age-related differences remained inconclusive (9). A systematic review including nine randomised controlled and prospective trials on creatine supplementation in vegetarians reported increased muscle creatine, phosphocreatine, lean mass, strength, type II fiber size and certain cognitive measures, often surpassing levels seen in omnivores (7). Another systematic review and meta-analysis of eight randomised controlled trials (n = 482) examined the effects of creatine supplementation combined with resistance training (2–3 sessions/week for 8–104 weeks) versus placebo plus resistance training in older adults with sarcopenia-related outcomes (10). Sarcopenia is a medical condition characterised by the progressive, age-related loss of skeletal muscle mass, strength and function. Creatine plus resistance training improved lower limb strength and lean tissue mass overall, with greater benefits observed in interventions lasting ≤32 weeks, highlighting a duration-dependent effect (10).

Cognitive function 🧠

The CONCRET-MENOPA randomised, double-blind trial involving 36 perimenopausal and postmenopausal women received low- or medium-dose creatine hydrochloride, creatine hydrochloride plus creatine ethyl ester or placebo for eight weeks to assess cognitive, metabolic and neurochemical outcomes (11). Medium-dose creatine hydrochloride (1,500 mg/day) improved reaction time, increased frontal brain creatine levels with a trend toward reduced mood swings and no serious adverse effects (11). Similarly a systematic review examined six studies on creatine and cognition in older adults and found that five reported positive associations, particularly in memory and attention, though overall methodological quality was mixed (12).

Hypoxic conditions ⛰️

Because of creatine’s role in cellular energy buffering and neuroprotection, creatine supplementation has been investigated under hypoxic conditions. In the brain, creatine can replenish ATP without oxygen and studies show it enhances corticomotor excitability and cognitive performance during oxygen deprivation (13). Hypoxia reduces creatine uptake in cardiomyocytes, but supplementation appears to enhance hypoxia-inducible factor (HIF) activation, which may support adaptive cellular responses (14). However, more clinical trials needed to establish efficacy.

Cancer

A double‑blind, randomised controlled trial enrolled 30 colorectal cancer patients undergoing chemotherapy to receive creatine or placebo for 8 weeks (15). Creatine did not improve muscle function, body cell mass or quality of life overall, but increased phase angle (a marker of cell integrity), with benefits in body cell mass observed only among patients receiving less aggressive chemotherapy, suggesting creatine may help preserve nutritional status in milder treatment settings (15). Using data from NHANES 2007–2018, researchers analysed 25,879 U.S. adults aged ≥20 years and found that each 1‑standard‑deviation increase in dietary creatine intake (≈0.26 g/day) was linked to about a 5% lower prevalence of cancer. Subgroup analyses showed stronger protective associations in men (7%), overweight individuals (8%) and adults over 60 (14%) (6).

Cardiovascular health

A double‑blind, placebo‑controlled crossover trial enrolled 20 patients with congestive heart failure to receive creatine supplementation (4 × 5 g/day) or placebo for 6 weeks each (16). Creatine increased skeletal muscle strength, but had no effect on peak oxygen uptake, walking distance, ejection fraction or quality of life, and the benefits were limited to the supplementation period (16).

Blood lipids🩸

Supplementation with creatine monohydrate has been associated with reductions in triglycerides, particularly when combined with resistance training (17). In individuals with type 2 diabetes, creatine supplementation alongside exercise improved glycaemic control, with modest but directionally favourable changes in lipid parameters (18). More recently, the CONCRET-MENOPA trial reported improvements in serum lipid profiles following supplementation with creatine hydrochloride (1.5 g/day) compared with placebo; however, interpretation is constrained by the small sample size (n = 36) and short intervention duration (8 weeks) (11).

Homocysteine

A randomised, placebo‑controlled study in healthy adults found that four weeks of oral creatine supplementation lowered plasma homocysteine concentrations compared to controls (19). The results suggest creatine may serve as a useful adjunct to vitamin supplementation for reducing homocysteine levels, which are linked to cardiovascular risk among others (19). Creatine supplementation lowered homocysteine and markers of lipid peroxidation in rats, suggesting a protective role against oxidative damage (20). However, because modulating homocysteine formation may also influence glutathione synthesis, creatine’s impact on the cellular redox state requires careful consideration (20).

Type 2 diabetes

A 12‑week randomised, double‑blind, placebo‑controlled trial investigated creatine supplementation (5 g/day) in 25 type 2 diabetic patients undergoing exercise training. Compared with placebo, the creatine group showed reductions in glycated haemoglobin (HbA1c) and glucose levels during a meal tolerance test, along with increased glucose transporter type 4 (GLUT‑4) translocation in muscle. GLUT‑4 is a protein found mainly in skeletal muscle and adipose (fat) tissue. When insulin is released after eating, GLUT‑4 moves from inside the cell to the cell membrane, allowing glucose to enter the cell for energy or storage. This insulin‑dependent translocation of GLUT‑4 is one of the body’s primary mechanisms for maintaining normal blood glucose levels.

Depression 🌧️

Creatine may improve depressive symptoms, particularly in women and individuals with treatment-resistant depression, by enhancing ATP availability in the brain (21, 22). A recent systematic review and meta-analysis concluded that creatine shows promise in reducing depressive symptoms, but results remain inconsistent and inconclusive, with variability across populations and study design (23).

Parkinson’s disease

A Cochrane review assessed creatine supplementation for Parkinson’s disease by analysing two randomised controlled trials with a total of 194 participants (24). Both trials compared creatine to placebo over one to two years but showed no clear benefits for motor function, daily living or quality of life and reported some gastrointestinal side effects (24). Overall, the evidence was limited by small sample sizes and methodological weaknesses and larger, long-term trials are needed.

Alzheimer’s

Creatine supplementation is being investigated as a potential supportive therapy for Alzheimer’s disease, primarily due to its role in enhancing brain energy metabolism and ATP regeneration (25). Early pilot studies suggest that creatine may improve cognitive functions such as working memory, attention and fluid intelligence in Alzheimer’s patients, while also increasing muscle strength and brain creatine levels (26, 27). Larger, long-term studies are needed to confirm its efficacy for Alzheimer’s disease.

Sleep and sleep deprivation 😴

A small randomised, double‑blind, placebo‑controlled crossover study in fourteen physically active men tested creatine monohydrate supplementation (20 g/day for 7 days) against placebo while keeping exercise routines standardised (28). Creatine improved subjective sleep quality and was linked to earlier bedtimes, though objective sleep measures such as latency, efficiency and total sleep time were unchanged (28).

A double‑blind, placebo‑controlled trial tested creatine supplementation (5 g/day for 7 days) during 24 hours of sleep deprivation with mild exercise and showed that creatine improved mood and performance on tasks heavily reliant on the prefrontal cortex, while catecholamine and cortisol levels were unaffected (29). Similarly, a randomised, double‑blind, placebo‑controlled study examined creatine supplementation (5 g/day for 7 days) during sleep deprivation combined with intermittent moderate exercise (30). Among the measured outcomes, creatine improved performance on complex central executive tasks at 36 hours of sleep loss, while no differences were observed for memory, reaction time, balance, mood or hormonal markers, indicating its effects were specific to higher‑order cognitive functioning under fatigue (30). Another randomised study where participants were deprived of sleep for 21 hours showed that creatine helped mitigate deficits in memory, processing speed and attention and also reduced some of the negative metabolic changes associated with prolonged wakefulness (31). More research is needed to confirm its effectiveness across different populations and dosing strategies.

Mild traumatic brain injury

Creatine supplementation has been proposed as a potential intervention following mild traumatic brain injury because its cellular role overlaps with the neuropathology observed after injury (32). Evidence suggests that creatine can reduce neuronal damage, buffer against energy crises and improve both cognitive and somatic symptoms when administered before or after traumatic brain injury (32). Although research in mild traumatic brain injury populations is limited, the slow uptake of creatine into neural tissue indicates that pre‑emptive supplementation in at‑risk groups may offer greater neuroprotective benefits (32).

Osteoarthritis

A randomised, double‑blind, placebo‑controlled trial tested creatine supplementation alongside resistance training in postmenopausal women with knee osteoarthritis (33). Creatine improved physical function, lower limb lean mass, stiffness and quality of life compared to placebo, while both groups experienced reductions in pain and gains in muscle strength from exercise (33).

Health concerns⚠️

Kidney Health

Evidence shows creatine supplementation is generally safe and does not impair kidney or liver function, even with long-term use(34, 35). A systematic review and meta‑analysis found that creatine supplementation causes a modest, transient rise in serum creatinine (a breakdown product), reflecting increased metabolic turnover rather than kidney damage (36). Importantly, no changes were observed in glomerular filtration rate (GFR), indicating preserved renal function (36). Overall, the evidence suggests creatine is safe for kidney health in healthy individuals, despite small fluctuations in creatinine levels. High doses should be avoided in those with pre-existing renal disease (35).

Water retention and weight gain💧

Creatine supplementation causes water retention because creatine is osmotically active i.e. when it enters muscle cells, it increases intracellular solute concentration, drawing water into the fibres and leading to mild weight gain and bloating. Creatine alters body water distribution by increasing intracellular hydration, which is generally harmless and reflects effective creatine storage in muscle (as reviewed by (8)).

Mild gastrointestinal discomfort

Creatine supplementation may cause mild, dose-dependent gastrointestinal symptoms—most commonly diarrhoea, bloating, cramping and nausea—particularly during high-dose loading phases due to its osmotic effect in the intestine (24, 37). These effects are usually minimised by dividing doses, avoiding large single boluses, taking creatine with meals, and maintaining adequate hydration.

Hair loss

A 12‑week randomised controlled trial in healthy young men found that creatine supplementation did not alter dihydrotestosterone (DHT) levels or negatively affect hair follicle health compared with placebo (38). These results provide evidence against the claim that creatine contributes to hair loss.

Recommendations

In healthy adults, a typical protocol is 3–5 g/day (with or without a loading phase of ~20 g/day for 5–7 days), provided renal function is normal. In sleep-deprived adults, studies investigating cognitive resilience typically use standard creatine monohydrate loading doses of ~20 g/day (≈0.3 g/kg/day) divided into 4 doses for 5–7 days, followed by a maintenance dose of 3–5 g/day. Some acute protocols have used single high doses (15–20 g) prior to total sleep deprivation to attenuate declines in working memory and reaction time, but these are short-term experimental designs rather than routine recommendations. Practically, if the goal is to buffer cognitive decline during anticipated sleep loss (e.g., shift work, prolonged wakefulness, jet lag), a loading phase completed in advance is more physiologically plausible than taking creatine only after sleep deprivation has already occurred.

Creatine supplementation during pregnancy and lactation has not been well established. Also creatine supplementation in children has mainly been studied in clinical contexts such as neuromuscular and metabolic disorders, where it has shown safety and potential therapeutic benefits under medical supervision (as reviewed by (39)). Routine use in healthy children for sports performance is not widely supported and should only be considered with professional guidance (39) but seems to be safe (as reviewed by (8)).

Conclusion

Creatine supplementation offers benefits that extend well beyond bodybuilding, with evidence supporting roles in muscle health, cognition and certain clinical conditions. While generally safe, considerations such as kidney health and water retention highlight the importance of balanced evaluation and individualised use. Overall, creatine represents a versatile nutrient where supplementation may be preferred over dietary sources, especially when aiming to avoid the risks associated with high meat consumption.

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Reflections 🤔

- Do you know someone who has supplemented with creatine or have you tried it yourself? Reflect on whether you noticed benefits such as improved energy, cognition or recovery, or if you experienced side effects like bloating or discomfort.

- If you are vegan or vegetarian and consume little to no animal sources of creatine, would you consider supplementation as a way to support muscle or cognitive health?

- For those who have supplemented in the past, did you recognise any changes in focus, memory, or attention or did you find the effects negligible?

- Think about whether supplementation aligns with your health goals, lifestyle and values, and whether you would prefer creatine from diet or supplements.

References 📚

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In developing this work, the author utilised Copilot to assist with language editing.