TL;DR
A new meta-analysis (Eckert et al., 2025) published in the British Journal of Nutrition shows that creatine supplementation has a small to moderate effect on depressive symptoms – albeit with very low-quality evidence. Creatine is not an antidepressant, but it could be a supporting factor. At the same time, evidence is growing for positive effects on memory, attention, and mental performance in cases of sleep deprivation.
Table of contents at a glance
- Creatine - More than just a muscle supplement
- The 2025 meta-analysis: Creatine and depressive symptoms
- Cognitive effects of creatine: memory, sleep deprivation, and more
- Further creatine benefits at a glance
- Practical advice: Dosage, safety, and for whom it's worthwhile.
- What creatine can do - and what it can't
- Conclusion
- Frequently Asked Questions (FAQ)
- Sources
Written by Ayuba Langer | Founder, Ayuba Nutrition
Last checked: February 2026 | Reading time: approx. 12 minutes
1. Creatine - More than just a muscle supplement
Creatine monohydrate is one of the most intensively researched dietary supplements. For decades, it has been used in competitive sports to increase muscle strength and training performance. What many don't know: Creatine also plays a central role in energy supply in the brain.
The brain consumes around 20 percent of the body's total energy, even though it only makes up about 2 percent of body mass. Creatine and phosphocreatine act as rapid energy buffers for nerve cells, providing adenosine triphosphate (ATP), which is essential for signal transmission between neurons.
In recent years, a new field of research has established itself: nutritional psychiatry. This field investigates whether dietary supplements like creatine can contribute to mental health. A meta-analysis published in November 2025 in the renowned British Journal of Nutrition was the first to systematically address this question. The results are nuanced—and precisely for that reason, worth reading.
definition
Creatine is a naturally occurring organic acid synthesized in the body from the amino acids arginine, glycine, and methionine. It serves as a rapid energy buffer in cells with high energy demands—primarily in skeletal muscle and the brain. There, it regenerates used ATP via the phosphocreatine system, thus supporting both physical and cognitive performance.
2. The 2025 Meta-Analysis: Creatine and Depressive Symptoms
What is a meta-analysis?
Before we delve into the results, a brief explanation of the study type: A meta-analysis mathematically summarizes the data from several independent studies. In evidence-based medicine, it is considered the highest level of evidence because it combines individual results and thus provides a more robust overall picture. However, its quality is only as good as the studies it includes.
The study in detail
The research group led by Igor Eckert from the Federal University of Rio Grande do Sul (Brazil) searched four databases up to February 2025 for randomized controlled trials (RCTs) comparing creatine with placebo. Both individuals with and without diagnosed depression were included.
Study profile: Eckert et al., 2025
| Study type | Systematic review + meta-analysis |
| journal | British Journal of Nutrition (Peer Reviewed) |
| Included studies | 11 RCTs |
| Participant | 1,093 people |
| Effect Size (SMD) | -0.34 (95% CI: -0.68 to -0.00) |
| GRADE rating | Very low quality of evidence |
| Heterogeneity (I 2 ) | 71.3% (substantial) |
The results – honestly assessed
The pooled effect size (SMD) of -0.34 corresponds to a small to moderate effect according to Cohen's convention. Specifically, this would mean an improvement of approximately 2.2 points on the 17-item Hamilton Depression Rating Scale. This sounds promising at first, but it's important to look more closely.
The clinically relevant minimum important difference (MIND) on this scale is 3.0 points. The average effect of 2.2 points is therefore below this threshold. This means that the observed effect might not be noticeable to the individual patient in their daily life.
Furthermore, the heterogeneity between the studies was substantial, with an I² value of 71.3 percent. This means that the individual studies arrived at quite different results. The GRADE assessment rated the overall evidence as "very low," which means that future research could significantly change the findings.
However, a secondary endpoint is of particular interest: the remission rate. Three studies showed a statistically significantly higher chance of remission with creatine (odds ratio: 3.60; 95% CI: 1.76 to 7.56). The effect on treatment response, however, was not significant.
Important classification
Creatine is not an antidepressant and does not replace medical or psychotherapeutic treatment. The authors of the meta-analysis themselves write: The true effect could be "trivial or zero." In cases of clinical depression, professional help is the first and most important step. Creatine could, at best, be a complementary component – more research is urgently needed.
3. Cognitive effects of creatine: memory, sleep deprivation, and more
While data on creatine and depression is still limited, there is now more solid evidence for cognitive effects. Several systematic reviews and meta-analyses have addressed this topic in recent years.
Memory and attention
A meta-analysis by Xu et al. (2024), published in Frontiers in Nutrition, evaluated 16 RCTs with 492 participants aged 20 to 76 years. The results showed significant positive effects of creatine on memory (SMD = 0.31; 95% CI: 0.18 to 0.44) and attention time (SMD = -0.31; 95% CI: -0.58 to -0.03). Processing speed also improved. However, no significant effect was found for general cognitive function or executive functions.
The GRADE assessment rated the evidence for memory as moderate – a significantly stronger signal than for the depression data. Subgroup analyses showed that women and individuals with certain conditions benefited more.
An earlier meta-analysis by Prokopidis et al. (2023) in Nutrition Reviews also confirmed the positive effects on memory, especially in older adults between 66 and 76 years of age.
Creatine and lack of sleep
The results under stress conditions are particularly interesting. A controlled crossover study by Gordji-Nejad et al. (2024), published in Scientific Reports, investigated the effect of a single high dose of creatine (0.35 g/kg) during sleep deprivation. The researchers at Forschungszentrum Jülich used MR spectroscopy to measure changes in brain chemistry in real time.
The result: Creatine was able to mitigate the changes in phosphocreatine and ATP levels in the brain caused by sleep deprivation. At the same time, working memory and processing speed improved compared to placebo – an effect that was measurable as early as three hours after ingestion and lasted for up to nine hours.
Important: This study used a significantly higher dose than the usual 3 to 5 grams daily. Whether similar effects occur with standard doses still needs to be investigated.
Vegetarians and vegans – a special case?
Since creatine is primarily found in meat and fish, vegetarians and vegans tend to have lower creatine levels in their muscles. It is therefore reasonable to hypothesize that this group in particular could benefit from supplementation.
The pioneering study by Rae et al. (2003) showed significant improvements in working memory and intelligence test scores in 45 young vegetarian subjects after six weeks of creatine supplementation (5 g/day). Benton and Donohoe (2011), in their study with 128 female participants, found that creatine improved memory in vegetarians but not in meat-eaters.
However, not all studies have been able to confirm these results. Solis et al. (2017) showed that a common loading protocol (0.3 g/kg for 7 days) did not increase phosphocreatine levels in the brain in either vegetarians or omnivores – suggesting that higher doses or longer supplementation periods may be necessary to effectively cross the blood-brain barrier.
Creatine and the brain: an overview of the evidence
4. Further benefits of creatine at a glance
While brain research is still evolving, the classic applications of creatine are well documented. Here are the most important ones, supported by numerous meta-analyses and reviews:
The 6 best-documented benefits of creatine monohydrate
- Maximum strength: Increase in strength output during high-intensity, short loads by an average of 5 to 15 percent.
- Muscle mass: Increase in fat-free mass, partly through intracellular water retention, partly through increased protein synthesis.
- Recovery: Faster regeneration of phosphocreatine stores between exercise intervals
- Memory: Significant improvements in short-term and working memory, especially in older adults and those with low baseline levels.
- Mental resilience: Mitigating cognitive decline due to sleep deprivation and mental fatigue
- Safety: Over 500 published studies confirm the safety of long-term use at usual doses (3 to 5 g/day) in healthy adults.
One area currently being intensively researched is the potential neuroprotective effect of creatine. Preclinical data suggest that creatine possesses antioxidant properties and could support mitochondrial function. However, clinical evidence in humans is still very limited, and we at Ayuba Nutrition would consider it irresponsible to derive any health claims from this.
5. Practical application: Dosage, safety, and for whom it is worthwhile.
dosage
The scientific consensus is clear: 3 to 5 grams of creatine monohydrate daily is sufficient to replenish stores in muscles (and probably also in the brain) over a period of 3 to 4 weeks. The timing of intake is secondary – consistency is more important than timing.
A so-called loading phase (20 g/day for 5 to 7 days, divided into 4 individual doses) can replenish stores more quickly, but is not absolutely necessary. For those with sensitive stomachs, the loading phase can lead to gastrointestinal discomfort, which is why most experts now recommend low-dose continuous intake.
Safety and compatibility
According to current research, creatine monohydrate is considered one of the safest supplements available. The International Society of Sports Nutrition (ISSN) confirmed in its 2017 position paper and 2021 update that short- and long-term supplementation (up to 30 g/day for 5 years) does not cause any clinically relevant side effects in healthy individuals.
Frequently expressed concerns about kidney damage, hair loss, or dehydration are not supported by current research. However, those with pre-existing kidney disease should consult their doctor before taking this product.
For beginners
Just starting out with supplements? Creatine monohydrate is your best first step. 5g daily, dissolved in water, that's it. No complex stacks, no loading protocols needed.
For advanced users
Do you train regularly and want to optimize strength and cognition? Creatine plus Omega-3 is an evidence-based stack. Both are well-researched and both have synergistic potential for brain and body.
For professionals & biohackers
Are you optimizing at a high level? Combine creatine with L-tryptophan for sleep quality and mood, and omega-3 for long-term cognitive health. All three substances have independent evidence and complement each other logically.
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View Creapure Creatine now6. What creatine can do - and what it can't
Transparency is one of our core values at Ayuba Nutrition. Therefore, here is an honest breakdown – even if it's inconvenient from a marketing perspective:
What creatine can do
- Increase maximum strength and sprint performance
- Supporting muscle mass during strength training
- May improve memory (especially in older people, vegetarians)
- Mitigating cognitive impairment due to sleep deprivation
- It can be taken long-term as a safe, inexpensive supplement.
What creatine cannot do
- Curing depression or replacing therapy
- Preventing neurodegenerative diseases (unproven)
- Significantly improve endurance performance
- Burn fat or speed up your metabolism
- Provide additional benefits for already full storage capacities
At Ayuba, we believe a supplement doesn't need hype when the real evidence is already impressive enough. Creatine is the most researched supplement on the market. The data for muscle strength and training performance is excellent. Evidence for cognitive effects is growing. For mental health, it's too early for definitive statements.
7. Conclusion
Creatine monohydrate remains the supplement with the strongest evidence base for physical performance in 2026. The new meta-analysis by Eckert et al. (2025) shows that the research horizon is expanding: creatine is increasingly being viewed as a substance that supplies not only the muscles but also the brain.
The results regarding mood and depressive symptoms are preliminary and should be interpreted with caution. The average effect is below the clinical relevance threshold, and the quality of evidence is very low. At the same time, the remission data and the growing body of cognitive research are encouraging enough to continue.
In practical terms, this means that those already supplementing with creatine may also experience cognitive benefits – in addition to the well-documented effects on muscles. For those wanting to start with creatine, 3 to 5 grams of creatine monohydrate daily is one of the best-researched and safest supplement options available.
Further research in the form of larger, methodologically sound RCTs will show in the coming years whether creatine truly deserves a place in nutritional psychiatry. We are monitoring developments and will keep you updated.
Medical note
This article is for informational purposes only and does not replace medical advice, diagnosis, or treatment. Dietary supplements are not a substitute for a balanced diet and a healthy lifestyle. If you have a pre-existing medical condition or are taking medication, please consult your doctor before taking creatine or other supplements. If you are experiencing depressive symptoms or mental health issues, consult a medical professional or therapist.
8. Frequently Asked Questions
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9. Sources
- Eckert I, Lima J, Dariva AA. Creatine supplementation for treating symptoms of depression: a systematic review and meta-analysis. Br J Nutr. 2025;134(11):947-959. PubMed
- Xu C, Bi S, Zhang W, Luo L. The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis. Front Nutr. 2024;11:1424972. PubMed
- Prokopidis K, Giannos P, Triantafyllidis KK, et al. Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev 2023;81(4):416-427. PubMed
- Gordji-Nejad A, Matusch A, Kleedörfer S, et al. Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation. Sci Rep 2024;14(1):4937. PubMed
- McMorris T, Harris RC, Swain J, et al. Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. Psychopharmacology. 2006;185(1):93-103. PubMed
- Rae C, Digney AL, McEwan SR, Bates TC. Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial. Proc Biol Sci. 2003;270(1529):2147-2150. PubMed
- Benton D, Donohoe R. The influence of creatine supplementation on the cognitive functioning of vegetarians and omnivores. Br J Nutr. 2011;105(7):1100-1105. PubMed
- Marshall S, Kitzan A, Wright J, et al. Creatine and Cognition in Aging: A Systematic Review of Evidence in Older Adults. Nutr Rev. 2025. PubMed
- EFSA Panel on NDA. Creatine and improvement in cognitive function: Evaluation of a health claim. EFSA Journal. 2024. EFSA
- McMorris T, Hale BJ, Pine BS, Williams TB. Creatine supplementation research fails to support the theoretical basis for an effect on cognition: Evidence from a systematic review. Behav Brain Res. 2024;466:114982. ScienceDirect
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