Avgerinos et al. 2018: Systematic Review of Creatine's Effects on Cognitive Function

TL;DR — Avgerinos et al. 2018

In 2018, Avgerinos and colleagues published a rigorous systematic review of randomized controlled trials examining creatine’s effects on cognitive function in healthy individuals. Published in Experimental Gerontology, the review found that creatine supplementation significantly improved short-term memory and reasoning/intelligence (KI et al., 2018) . The most notable finding was that cognitive benefits were greatest in individuals under physiological stress — such as sleep deprivation or aging — and in vegetarians who have naturally lower creatine stores.

Study Background and Rationale

While creatine’s muscle-building benefits had been firmly established for decades, its role in brain function was a newer area of investigation. The brain is a metabolically demanding organ, consuming approximately 20% of the body’s total energy despite representing only about 2% of body weight. Like muscle, the brain relies on the phosphocreatine-creatine kinase system to buffer ATP and maintain energy homeostasis.

Earlier individual studies had shown promising cognitive effects. Rae et al. (2003) demonstrated improvements in working memory and intelligence with creatine supplementation (C et al., 2003) , while McMorris et al. (2006) showed creatine could mitigate cognitive decline from sleep deprivation (T et al., 2006) . However, no systematic review had synthesized all the available RCT evidence on creatine and cognition in healthy people.

Avgerinos et al. set out to fill this gap with a methodologically rigorous systematic review, applying strict inclusion criteria to ensure only high-quality evidence was considered.

Study Design and Methodology

The review followed the PRISMA guidelines for systematic reviews:

Search strategy:

• Comprehensive searches across PubMed, Scopus, and the Cochrane Library
• Search terms related to creatine supplementation AND cognitive function
• No language restrictions applied

Inclusion criteria:

• Randomized controlled trials only (the gold standard of clinical evidence)
• Healthy individuals (no clinical populations)
• Cognitive outcomes measured using validated tests
• Creatine monohydrate as the intervention

Quality assessment:

• Risk of bias assessment for each included study
• Evaluation of blinding, randomization, and outcome reporting

Studies included: Six RCTs met all inclusion criteria, encompassing 281 total participants with supplementation periods ranging from 5 days to 6 weeks and doses from 5 to 20 g/day.

Key Findings

The systematic review yielded several important conclusions:

1. Creatine improved short-term memory

Across the included studies, creatine supplementation produced statistically significant improvements in short-term memory tasks. This included tests of working memory, digit span, and recall — the kinds of cognitive abilities that are essential for daily functioning, academic performance, and professional productivity.

2. Reasoning and intelligence scores improved

Beyond memory, the review found evidence that creatine supplementation enhanced performance on reasoning and intelligence tests. This suggests that creatine’s cognitive effects extend beyond simple recall to higher-order cognitive processing.

3. Stressed and depleted individuals benefited most

The most striking finding was the moderating effect of physiological stress. Individuals who were sleep-deprived, mentally fatigued, or aging showed the most pronounced cognitive benefits from creatine supplementation. This makes biological sense: when the brain is under energetic stress, additional creatine may help maintain ATP levels and support cognitive function.

4. Vegetarians showed enhanced responses

Consistent with earlier findings by Rae et al. (2003), vegetarians and vegans appeared to derive greater cognitive benefits from creatine supplementation. Since dietary creatine comes almost exclusively from animal products, vegetarians typically have lower brain creatine levels and therefore more room for improvement through supplementation.

5. Doses of 5-20 g/day for 5 days to 6 weeks were effective

The review found cognitive benefits across a range of dosing protocols, from high-dose short-term loading (20 g/day for 5 days) to moderate chronic supplementation (5 g/day for 6 weeks). This suggests that the standard supplementation protocols used for muscle benefits are also sufficient for cognitive effects.

Why This Review Matters

The Avgerinos 2018 systematic review was a watershed moment for creatine research for several reasons:

It legitimized creatine as a cognitive supplement. Before this review, creatine was primarily associated with gym culture and muscle building. By demonstrating cognitive benefits through rigorous systematic review methodology, Avgerinos et al. opened the door to viewing creatine as a brain health supplement as well.

It identified who benefits most. The finding that stressed, sleep-deprived, and vegetarian individuals benefit most has enormous practical implications — particularly for students during exam periods, shift workers, frequent travelers, and anyone following a plant-based diet.

It informed subsequent research. The Avgerinos review has been widely cited in later publications, including Roschel et al. (2021), which built upon these findings to advocate for creatine’s broader role in brain health (H et al., 2021) .

Malaysian Context

The findings of Avgerinos 2018 are particularly relevant for several Malaysian populations:

Students: Malaysia’s competitive academic environment means many students experience sleep deprivation during exam periods. The evidence suggests creatine could help maintain cognitive function during these demanding times. University students in UM, UTM, UKM, and other institutions may benefit from creatine supplementation during study-intensive periods.

Shift workers: Malaysia’s manufacturing and service sectors employ many shift workers who regularly experience sleep disruption. Creatine may offer some cognitive protection during overnight shifts.

Vegetarians and vegans: While Malaysia is not predominantly vegetarian, the Indian-Malaysian community includes many vegetarians, and plant-based diets are growing in popularity across all demographics. These individuals stand to gain the most cognitive benefit from creatine supplementation.

Limitations

The review had several important limitations:

• Small number of included studies: Only six RCTs met the strict inclusion criteria, limiting the statistical power of the analysis
• Modest sample sizes: With only 281 total participants, the findings need replication in larger trials
• Heterogeneous cognitive tests: Different studies used different cognitive assessments, making direct comparisons challenging
• Short supplementation durations: The longest study was only 6 weeks — long-term cognitive effects remain unknown
• Healthy participants only: The review excluded clinical populations, so findings may not generalize to those with cognitive impairments or neurological conditions

Practical Implications

1. Consider creatine for brain health, not just muscles: The evidence supports cognitive benefits, especially for memory and reasoning
2. Prioritize creatine if you are sleep-deprived: Students, shift workers, and new parents may benefit the most
3. Vegetarians should seriously consider creatine: Lower baseline creatine levels mean greater potential for improvement
4. Standard dosing works for the brain too: 3-5 g/day of creatine monohydrate appears sufficient for cognitive effects
5. Combine with good sleep habits: Creatine may buffer cognitive decline from sleep loss, but it is not a replacement for adequate sleep

Full Citation

Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D. Effects of creatine supplementation on cognitive function of healthy individuals: a systematic review of randomized controlled trials. Experimental Gerontology. 2018;108:166-173. doi:10.1016/j.exger.2018.01.013

Sources & References

This article is based on the systematic review published in Experimental Gerontology (2018) and contextualized with findings from Rae et al. (2003), McMorris et al. (2006), Roschel et al. (2021), and Kreider et al. (2017). All citations link to PubMed-indexed publications.

Further Reading

• creatine dosage guide
• creatine safety profile
• creatine monohydrate
• creatine for muscle building
• creatine for brain health
• how creatine works