Creatine and the Brain: Meta-Analysis of 16 RCTs on Memory, Attention and Information Processing Speed

Why the Brain Needs Energy and Where Creatine Comes In

The brain accounts for about 2% of body weight but consumes roughly 20% of the body's total glucose. Under cognitive load — concentration, rapid decision-making, memory retrieval — neuronal ATP demand rises sharply. The phosphocreatine/creatine kinase system enables ATP resynthesis from ADP within milliseconds: phosphocreatine donates its phosphate group, "recharging" the ATP molecule without involving the mitochondrial cycle.

The brain expresses a specific isoform of the enzyme — CK-BB (brain creatine kinase). This means the phosphocreatine/CK system is not confined to muscle tissue: it operates in neurons and astrocytes as an energy buffer during peak demand. The hypothesis underlying the cognitive benefit of supplementation rests on this physiological foundation: if the brain is running at high energy demand, additional phosphocreatine theoretically sustains ATP stability and the speed of neuronal processes.

What the 2024 Meta-Analysis of 16 RCTs Found

Xu et al. (Frontiers in Nutrition, 2024, DOI: 10.3389/fnut.2024.1424972) conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. Sixteen RCTs were included (publication period 1993–2024, databases PubMed, Scopus, Web of Science), with a total of 492 participants aged 20.8–76.4 years.

Key effect sizes (standardised mean differences, SMD):

• Memory: SMD = 0.31 (95% CI 0.18–0.44), p < 0.00001. A moderate and reproducible effect — the most robust finding of the review.
• Reaction time (attention): SMD = −0.31 (95% CI −0.58 to −0.03), p = 0.03. A negative sign indicates reduced reaction time, i.e. improvement.
• Information processing speed: SMD = −0.51 (95% CI −1.01 to −0.01), p = 0.04. Significant, but with a wide confidence interval reflecting study heterogeneity.
• Overall cognition: SMD = 0.34 (95% CI −0.20 to 0.88) — not significant.
• Executive functions: SMD = 0.32 (95% CI −0.08 to 0.71) — not significant.

Doses in the included studies ranged from 3–20 g/day. The standard protocol consisted of a loading phase of 20 g/day for 5–7 days followed by a maintenance dose of 5 g/day. Intervention duration ranged from 7 days to 24 weeks. The authors found no difference in cognitive effect between short and longer protocols.

For Whom Is the Effect More Pronounced?

The authors found that the effect is heterogeneous and depends on participant characteristics. More pronounced improvements were observed:

• In women aged 18–60 compared with men of the same age group.
• In people with health conditions (fibromyalgia, Parkinson's disease with mild cognitive impairment, chronic schizophrenia) — in 3 of the 16 included RCTs.

Data on healthy older adults (over 60) are limited. The systematic review by Marshall et al. (Nutrition Reviews, 2025, DOI: 10.1093/nutrit/nuaf135, n=1542, age 55+, 6 studies) showed positive associations in 5 of 6 studies for memory and attention, but most of these were observational studies of low methodological quality. The only included RCT (Alves et al., 2013) found no cognitive effect in healthy older adults.

How Reliable Are the Data?

The authors rated evidence quality using the GRADE system:

• Memory: moderate certainty — the best-supported conclusion of the review.
• Reaction time, information processing speed: low certainty due to protocol heterogeneity and small sample sizes.
• Overall cognition, executive functions: very low certainty.

Limitations: small individual study samples, high methodological heterogeneity (different tests, doses, populations), insufficient representation of older and clinical groups. No publication bias was detected by Egger's test.

Is Creatine Safe?

The International Society of Sports Nutrition (ISSN) has classified creatine monohydrate as one of the best-supported dietary supplements in terms of safety and efficacy (Kreider et al., Journal of the International Society of Sports Nutrition, 2017). Long-term research has found no pathological effect on kidney function in healthy individuals at standard doses (3–5 g/day). People with kidney disease should consult a physician before use.