Unlocking the Brain-Boosting Potential of Creatine: Benefits for Cognitive Function and Its Role in Alzheimer’s Disease

Creatine is widely known as a go-to supplement for athletes looking to enhance muscle performance, but its benefits extend far beyond the gym. Emerging research highlights creatine’s potential to support cognitive function and possibly play a therapeutic role in neurodegenerative diseases like Alzheimer’s. In this blog, we’ll explore how creatine supports brain health, its mechanisms of action, and the latest studies investigating its impact on Alzheimer’s disease, including the most recent clinical trials.

What Is Creatine and How Does It Work in the Brain?

Creatine is a naturally occurring compound synthesized in the body from the amino acids glycine, arginine, and methionine. It’s primarily stored in muscles but also plays a critical role in the brain, where it supports energy metabolism. In the brain, creatine is converted into phosphocreatine, which acts as a rapid reserve for adenosine triphosphate (ATP), the energy currency of cells. This is particularly important for neurons, which have high energy demands during complex cognitive tasks.

By maintaining ATP levels, creatine supports processes like memory, attention, and problem-solving. It may also reduce oxidative stress, protect neurons from damage, and support synaptic plasticity, which is essential for learning and memory. These properties make creatine a promising candidate for enhancing cognitive function and addressing neurodegenerative conditions like Alzheimer’s disease.

Creatine and Cognitive Function: What the Research Says

Numerous studies have explored creatine’s effects on cognitive performance, particularly in healthy individuals and those under stress. Here’s a look at the key findings:

Improved Memory and Processing Speed

A 2024 systematic review and meta-analysis of 16 randomized controlled trials (RCTs) involving 492 participants found that creatine monohydrate supplementation significantly improved memory (standardized mean difference [SMD] = 0.31), attention time (SMD = -0.31), and information processing speed (SMD = -0.51). These effects were more pronounced in individuals with diseases, those aged 18–60, and females. However, no significant improvements were observed in overall cognitive function or executive function, suggesting creatine’s benefits may be domain-specific.

Cognitive Benefits Under Stress

Creatine appears particularly effective in conditions of metabolic stress, such as sleep deprivation. A 2024 study published in Scientific Reports showed that a single high dose of creatine (0.35 g/kg) improved cognitive performance and altered brain energy metabolism in sleep-deprived participants. The study noted enhanced processing capacity and short-term memory, with effects peaking 4 hours after administration and lasting up to 9 hours.

Benefits for Vegetarians

Vegetarians, who may have lower baseline creatine levels due to limited dietary intake from meat, seem to benefit more from supplementation. A 2010 study found that creatine supplementation (20 g/day for 5 days) improved memory performance in vegetarians compared to omnivores, likely due to increased brain creatine stores.

Mixed Results in Healthy Young Adults

While some studies show benefits, others suggest limited effects in healthy, non-stressed young adults. A 2023 RCT, the largest to date, found that 5 g/day of creatine for 6 weeks had a borderline significant effect on working memory (p = 0.064) but no impact on abstract reasoning. The authors concluded that creatine might have a small cognitive benefit, warranting larger studies.

These findings suggest that creatine’s cognitive benefits are most pronounced in specific populations (e.g., those with low baseline creatine, under stress, or with cognitive impairments) and for tasks requiring high energy demands, such as memory and rapid processing.

Creatine’s Role in Alzheimer’s Disease: A Promising Therapeutic Target

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, affecting over 6.5 million older adults in the United States alone. It’s characterized by amyloid-beta (Aβ) plaques, tau tangles, and impaired brain energy metabolism, which precedes cognitive decline. The brain’s creatine system, crucial for maintaining bioenergetic flux, is disrupted in AD, making creatine supplementation a compelling therapeutic target.

Mechanisms in Alzheimer’s Disease

Creatine may benefit AD through several mechanisms:

• Enhanced Brain Bioenergetics: By increasing phosphocreatine stores, creatine supports ATP production, which is critical for neuronal function in AD, where mitochondrial dysfunction is a hallmark.
• Neuroprotection: Creatine has antioxidant properties and may protect neurons from Aβ toxicity and oxidative stress, potentially slowing disease progression.
• Synaptic Plasticity: Studies in AD mouse models suggest creatine upregulates proteins involved in synaptic plasticity, improving memory and learning.
• Reduction of Neuronal Damage: Creatine may reduce neuronal apoptosis and necrosis by increasing ATP availability and down-regulating inflammatory pathways like NF-κB.

Preclinical Evidence

Rodent studies have provided promising insights:

A 2020 study in female 3xTg AD mice found that 8–9 weeks of creatine supplementation improved spatial memory, increased hippocampal synaptic plasticity proteins, and enhanced mitochondrial function. These effects were more pronounced in females, possibly due to greater baseline cognitive impairment. The study suggested that creatine’s benefits stem from improved energy availability rather than reduced Aβ plaque accumulation.

Another study in rats with lipopolysaccharide-induced mild cognitive impairment (MCI) showed that creatine supplementation (1.542 g/kg/day loading, 0.385 g/kg/day maintenance) improved performance in memory tasks and upregulated mTORC1 and synaptic plasticity proteins.

These preclinical findings highlight creatine’s potential to mitigate cognitive deficits and support brain health in AD models.

Recent Human Trials in Alzheimer’s Disease

Until recently, no human trials had directly investigated creatine supplementation in AD patients. However, the Creatine to Augment Bioenergetics in Alzheimer’s Disease (CABA) study, a single-arm, open-label pilot trial, has provided groundbreaking preliminary data. Published in 2025, this trial is the first to examine creatine’s effects in AD patients. Here are the key details:

Study Design: The CABA study involved 20 patients with cognitive impairment due to AD, who received 20 g/day of creatine monohydrate for 8 weeks. The primary aim was to assess feasibility, with secondary aims to evaluate changes in brain creatine levels, cognition, mitochondrial function, and muscle strength.

Results:

• Brain Creatine Levels: Brain creatine concentrations increased by 11%, confirming that supplementation can elevate neural creatine stores in AD patients.
• Cognitive Improvements: Significant improvements were observed across multiple cognitive domains, including memory, attention, and processing speed. These findings align with preclinical data and suggest creatine’s potential to enhance cognitive function in AD.
• Feasibility: The study demonstrated that 20 g/day of creatine was well-tolerated, with high compliance and no significant adverse effects reported.
• Implications: The CABA study provides the first human evidence that creatine supplementation may be a viable strategy for supporting cognition in AD. However, as a pilot study, it lacks a control group, and larger, randomized controlled trials are needed to confirm efficacy.

Ongoing and Future Research

The CABA study is a critical first step, but several gaps remain:

• Larger Trials: The small sample size and lack of a placebo group in CABA limit generalizability. Future RCTs with larger cohorts are essential.
• Optimal Dosing: The 20 g/day dose used in CABA is higher than typical maintenance doses (3–5 g/day). Research is needed to determine the minimum effective dose for brain health.
• Long-Term Effects: Most studies, including CABA, have short durations (e.g., 8 weeks). Long-term trials are needed to assess sustained benefits and safety in AD.
• Mechanistic Insights: While preclinical studies suggest creatine improves mitochondrial function and synaptic plasticity, human studies must confirm these mechanisms using advanced imaging and biomarkers.

Ongoing trials, such as those at the University of Kansas Medical Center, are using magnetic resonance spectroscopy to further explore creatine’s impact on brain metabolism in AD.

Practical Considerations for Creatine Supplementation

For those considering creatine for cognitive health, here are some key points:

• Form and Dosage: Creatine monohydrate is the most studied and effective form. Typical doses for cognitive benefits range from 5–20 g/day, with higher doses (e.g., 20 g/day) potentially needed to increase brain creatine stores.
• Safety: Creatine is generally safe, with hundreds of studies confirming its tolerability. However, excessive use may reduce endogenous creatine production, and individuals with kidney issues should consult a healthcare provider.
• Dietary Sources: Creatine is found in red meat and fish, but supplementation is often needed to achieve therapeutic levels, especially for vegetarians.

Conclusion: A Promising Frontier for Brain Health

Creatine is emerging as a versatile supplement with potential to enhance cognitive function and support brain health in Alzheimer’s disease. Its ability to boost brain energy metabolism, protect neurons, and improve memory and processing speed makes it a compelling candidate for further research.

The recent CABA study marks a significant milestone, providing the first human evidence of creatine’s cognitive benefits in AD patients. However, while these findings are exciting, they are preliminary, and larger, controlled trials are needed to establish creatine’s efficacy and optimal use.

For now, creatine remains a safe, accessible, and well-studied supplement that may offer cognitive benefits, particularly for those under stress or with low baseline creatine levels. As research progresses, creatine could become a cornerstone in the fight against cognitive decline and neurodegenerative diseases like Alzheimer’s.

References

Avgerinos KI, Spyrou N, Bougioukas KI, et al. (2018). Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials. Experimental Gerontology, 108, 166–173.

Smith AN, Morris JK, Carbuhn AF, et al. (2023). Creatine as a Therapeutic Target in Alzheimer’s Disease. Current Developments in Nutrition, 7, 102011.

Prokopidis K, Giannos P, Triantafyllidis KK, et al. (2024). The effects of creatine supplementation on cognitive function in adults: a systematic review and meta-analysis. Frontiers in Nutrition.

Roschel H, Gualano B, Ostojic SM, et al. (2023). The effects of creatine supplementation on cognitive performance—a randomised controlled study. BMC Medicine.

Forbes SC, Candow DG, Ferreira LHB, et al. (2023). “Heads Up” for Creatine Supplementation and its Potential Applications for Brain Health and Function. Sports Medicine.

Taylor MJ, Smith AN, Carbuhn AF, et al. (2024). Protocol for a single-arm, pilot trial of creatine monohydrate supplementation in patients with Alzheimer’s disease. Pilot and Feasibility Studies.