Creatine: Is the Supplement Ready for Clinical Use?
Like endogenous creatine, supplemental creatine is converted into phosphocreatine and stored in skeletal muscle, where it plays a critical role in rapid adenosine triphosphate (ATP) replenishment. 'Supplementation helps accelerate muscle recovery by providing an available energy reserve,' explained Beatriz Leite, clinical nutritionist with a PhD in health sciences from the Federal University of São Paulo and a member of the Multiprofessional Committee of the Brazilian Society of Rheumatology, São Paulo, Brazil.
The body naturally synthesizes around 1-2 g of creatine daily, and the compound is also present in animal-derived foods. About 1 kg of red meat contains roughly 5 g of creatine — so a 200-g serving provides about 1 g. The typical supplementation dose, ranging from 3 to 5 g/d, is designed to complement both endogenous production and dietary intake to support intramuscular creatine accumulation.
Safety Profile
A recent meta-analysis of 685 clinical trials concluded that creatine supplementation is not linked to clinically significant adverse effects and is generally well tolerated — particularly at recommended doses of 3-5 g/d or 0.1 g/kg/d. 'Creatine monohydrate is essentially identical to what the body produces. It's metabolized the same way, and I see no meaningful risk of side effects. It's a very safe supplement,' said Andréa Fioretti, head of the Department of Sports and Exercise Endocrinology at the Brazilian Society of Endocrinology and Metabolism.
Concerns have lingered about creatine's potential to elevate serum creatinine levels and place strain on liver or kidney function. However, a meta-analysis indicates that creatine does not significantly alter serum creatinine. 'Creatine is excreted by the kidneys as creatinine. So when a patient supplements with creatine, the apparent rise in serum creatinine is usually a false signal — not an indicator of renal damage,' Fioretti explained.
Supporting this, a study from the University of São Paulo found that creatine supplementation actually reduced levels of cystatin C, further reinforcing the absence of renal harm.
Nonetheless, Leite advised individualized assessment. 'In patients with renal or hepatic conditions, more careful evaluation is essential. Supplementation should only be considered if there's a clear therapeutic benefit,' she noted.
Gustavo Starling Torres, MD, sports medicine physician and director at the Brazilian Society of Exercise and Sports Medicine, agreed: 'The supplementation protocol should always be individualized, taking into account therapeutic goals, patient tolerance, and overall clinical condition.'
In such cases, renal function testing may be advisable. 'If there's concern about kidney function, a creatinine test can help guide decisions,' said Fioretti. 'This ensures the supplement is used in patients who genuinely need it — those with muscle mass deficiencies.'
Michele Trindade, PhD, adjunct professor in the Department of Physical Education at the State University of Maringá in Maringá, Brazil, and vice president of the Brazilian Association of Sports Nutrition, also advised caution when considering creatine supplementation in pregnant or breastfeeding women and in children. 'They're not currently included in official recommendations because there's insufficient safety and efficacy data for pregnant individuals and fetuses. We also don't yet know how much transfers into breast milk,' she explained.
Regarding children, Trindade added that creatine is not recommended — even in cases of malnutrition. 'When treating a malnourished child, the priority is nutritional rehabilitation. Malnutrition involves more than loss of muscle mass; it includes deficiencies in total caloric intake and essential micronutrients like vitamins and minerals that regulate metabolic function.'
Uncertain Benefits in Neurologic and Muscle Disorders
Like skeletal muscle, the brain depends on the rapid ATP regeneration provided by the creatine-phosphocreatine system, raising interest in its possible neurologic benefits. A systematic review in healthy older adults suggested that 'oral creatine administration may improve short-term memory and intelligence/reasoning of healthy individuals, but its effect on other cognitive domains remains unclear, leaving questions around ideal dosing and the mechanisms underlying potential cognitive enhancement.'
Another review exploring creatine's potential in neurologic conditions noted that while early human studies — particularly in neurodegenerative diseases — are promising, more robust evidence is needed. Well-designed, long-term randomized controlled trials are essential to establish efficacy, cost-effectiveness, and safety in these populations.
Creatine has also been studied as an adjunctive therapy for conditions such as Duchenne muscular dystrophy, amyotrophic lateral sclerosis (ALS), and certain metabolic myopathies. However, the available data remain inconclusive. In the context of muscle disorders, a systematic review observed that creatine monohydrate may help reduce intracellular calcium accumulation and provide energy for muscle contraction, though the optimal dosing and magnitude of effect are still unclear.
In a study involving 107 patients with probable or confirmed ALS, daily creatine monohydrate was well tolerated and associated with a trend toward increased survival — mirroring findings from an earlier trial. However, the authors concluded that supplementation at 5 g/d did not significantly improve markers of disease progression or reduce fatigue during isometric contraction, despite anecdotal reports from participants.
Geriatric Use
Findings on creatine supplementation in older adults remain mixed. 'Evidence is very limited in this population. Few studies have demonstrated improvements in physical performance or muscle strength,' said Ivan Aprahamian, MD, PhD, internal medicine and geriatrics specialist and a member of the Brazilian Society of Geriatrics and Gerontology.
Aprahamian noted that creatine may serve as a helpful adjunct in managing sarcopenia. 'In older adults with reduced muscle mass or strength who are engaged in resistance training, creatine may support improvements in muscle health,' he explained. The recommended dosage remains 3-5 g/d, taken consistently.
In such cases, Fioretti recommended first screening for sarcopenia using the SARC-F questionnaire — which assesses autonomy and independence — alongside grip strength testing. 'If reduced strength is confirmed, further evaluation of muscle mass using bioimpedance or DEXA, followed by a physical performance assessment, is warranted,' she said.
On the basis of results, a resistance training program can be initiated in combination with creatine supplementation and appropriate carbohydrate and protein intake. 'Older adults often consume excessive carbohydrates and insufficient protein. After approximately 6 months, it's advisable to repeat assessments to monitor improvements in muscle mass and physical function,' Fioretti added.
Leite agreed: 'Creatine is not a miracle solution. It must be combined with a well-structured dietary plan.' Even in sedentary seniors, she noted, supplementation may still offer benefits. 'While it may not significantly increase muscle mass, it can help reduce the rate of muscle loss,' she explained.
For physically inactive older adults, the standard dose of 3-5 g/d is still recommended. 'This may support musculoskeletal health, though the effect on strength is modest,' said Trindade, who also cautioned that responses may vary by sex. Limited data suggest that women — who typically have higher baseline intramuscular creatine levels — may be less responsive to supplementation. 'We don't fully understand why, but it's likely related to hormonal differences.'
Established Benefits
Despite a growing number of hypotheses, robust evidence currently supports creatine supplementation primarily in the context of sports medicine. Misconceptions persist — particularly the belief that creatine directly causes muscle hypertrophy. 'In high-intensity, short-duration resistance training, where energy reserves are quickly depleted, creatine helps by rapidly replenishing ATP. This indirectly supports muscle hypertrophy,' explained Leite.
In athletic settings, creatine can be taken either before or after exercise, with comparable benefits. 'Scientific literature shows that timing matters less than consistency. Regular use is key to saturating muscle creatine stores,' said Torres.
Creatine's effect is cumulative. 'What matters is the total amount stored in muscle,' noted Trindade. 'After ingesting monohydrate, blood levels peak at around an hour, and the creatine is distributed to muscles that haven't yet reached storage capacity. Once saturated, muscles rely on these reserves.'
For fitness professionals, the benefits are often seen in practice. 'Among clients who take creatine after workouts, I've observed better lean mass gains — which is often their primary goal,' said Celina Moreno, a trainer since the 1970s who witnessed the early rise of powdered supplements in gyms.
Alexandre Pereira da Costa Filho, who works at a chain of fitness centers, takes 9 g of creatine before bed — about 0.1 g/kg/d for his 86 kg body weight. He cautioned that loading protocols involving high initial doses followed by lower maintenance levels should be guided by a professional. 'Only do this under the supervision of a nutritionist. Always consult a qualified professional before making decisions,' he advised.
For those seeking faster performance gains, Trindade recommended a loading phase: 20 g/d, divided into four doses, for 5 days, followed by a maintenance dose of 3-5 g/d.
However, this protocol may cause fluid retention and modest weight gain. 'Most people don't notice it, but it depends on whether they're exercising enough to compensate,' added Fioretti.
Quality Control
In April, Brazil's national health regulatory agency, Anvisa, published an analysis of 41 creatine supplements from 29 manufacturers. Only one product had an incorrect concentration, but 40 showed labeling discrepancies. 'Some products may contain less creatine than declared — or even contaminants, especially when unregulated,' warned Torres. He advised choosing certified products to minimize risk.
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