Creatine and Alzheimer’s: What a New Pilot Study Reveals

Alzheimer’s disease (AD) affects millions and currently has limited treatments. In recent years, scientists have begun exploring the brain’s energy system as a novel therapeutic target. The brain is an energy-hungry organ, using about 20% of the body’s energy (Dolan et al., 2019), and Alzheimer’s brains show early defects in energy metabolism. For example, neurons have lower levels of ATP (the cell’s “battery”) and impaired glucose use even before memory problems arise (Swerdlow et al., 2010). Research has also shown that reduced ATP in neurons is linked to amyloid plaque buildup (Flannery & Trushina, 2019). This suggests that boosting brain energy may be important for slowing AD progression. One molecule under investigation for this purpose is creatine.

What Is Creatine and Creatine Monohydrate?

Creatine is a naturally occurring compound found in muscle and brain cells that helps shuttle energy. Inside cells, creatine picks up a high-energy phosphate (becoming phosphocreatine) and later donates it to regenerate ATP (Wyss & Kaddurah-Daouk, 2000). This energy transfer system is especially important in energy-demanding tissues like the brain (Bessman & Carpenter, 1985).

Creatine monohydrate (CrM) is a dietary supplement that safely boosts creatine levels in the body. While commonly used in sports to enhance muscle strength, CrM also increases creatine levels in the brain (Dolan et al., 2019). Preliminary studies suggest CrM may enhance cognitive function in healthy young and older adults (Roschel et al., 2021), and its role in supporting mitochondrial energy production makes it an appealing candidate for Alzheimer's research.

The Creatine Monohydrate Pilot Trial

In 2025, researchers at the University of Kansas Medical Center published the first human trial of CrM in Alzheimer’s patients (Smith et al., 2025). This pilot study, known as the CABA (Creatine to Augment Bioenergetics in Alzheimer’s) trial, tested whether 8 weeks of CrM supplementation was feasible and whether it affected brain creatine levels and cognition.

Twenty participants with clinically diagnosed Alzheimer’s dementia were enrolled and took 20 grams of CrM per day for 8 weeks. Participants underwent cognitive assessments and magnetic resonance spectroscopy (MRS) to measure brain creatine levels before and after the intervention. Blood tests were used to assess compliance and monitor safety.

Compliance was remarkably high—nineteen out of twenty participants took at least 80% of the prescribed doses. No participants dropped out, and only minor side effects (e.g., muscle cramps) were reported, which resolved quickly (Smith et al., 2025). Serum creatine levels increased significantly at 4 and 8 weeks, confirming compliance with the supplementation regimen.

What Did the Study Find?

The study observed the following key outcomes:

• Increased brain creatine: Brain total creatine (tCr) levels rose by approximately 11% over 8 weeks, indicating that CrM successfully reached the brain (Smith et al., 2025).

• Cognitive improvements: Participants showed modest but statistically significant improvements on several cognitive tests, particularly in memory and executive function domains. For example, fluid cognition scores improved significantly (p = .004), along with working memory and oral reading recognition (Smith et al., 2025).

• Feasibility and safety: The CrM regimen was well tolerated and feasible for older adults with AD, with no serious adverse events (Smith et al., 2025).

Limitations and Considerations

As a single-arm, open-label pilot study, the CABA trial did not include a control or placebo group. Therefore, the cognitive gains, while encouraging, must be interpreted cautiously. It’s possible that observed improvements were due to practice effects or other confounding factors (Smith et al., 2025).

Moreover, the study lasted only eight weeks, and the long-term effects of CrM in Alzheimer’s remain unknown. Researchers also noted variability in how much brain creatine increased, potentially due to individual differences in transport across the blood-brain barrier.

Why This Study Matters

This trial is the first to show that creatine monohydrate supplementation is feasible and well-tolerated in people with Alzheimer’s—and that it successfully increases brain creatine. The positive trends in cognitive scores offer preliminary support for the idea that targeting brain energy metabolism may help combat cognitive decline in AD.

Previous research in animal models supports this idea. In mice, CrM has been shown to reduce amyloid and tau pathologies, enhance mitochondrial function, and improve memory (Snow et al., 2018; Mao et al., 2021). Human trials like the CABA study build the foundation for larger, placebo-controlled trials to test CrM’s efficacy more rigorously.

If future research confirms these benefits, creatine could become a low-cost, safe, and accessible adjunct therapy in Alzheimer’s care. For now, the CABA study highlights the promise of targeting bioenergetic pathways in AD—and opens new directions for research.

References

Bessman, S. P., & Carpenter, C. L. (1985). The creatine-creatine phosphate energy shuttle. Annual Review of Biochemistry, 54, 831–862. https://doi.org/10.1146/annurev.bi.54.070185.004151

Dolan, E., Gualano, B., & Rawson, E. S. (2019). Beyond muscle: The effects of creatine supplementation on brain creatine, cognitive processing, and traumatic brain injury. European Journal of Sport Science, 19(1), 1–14. https://doi.org/10.1080/17461391.2018.1500644

Flannery, P. J., & Trushina, E. (2019). Mitochondrial dynamics and transport in Alzheimer’s disease. Molecular and Cellular Neuroscience, 98, 109–120. https://doi.org/10.1016/j.mcn.2019.06.009

Mao, X., Kelty, T. J., Kerr, N. R., Childs, T. E., Roberts, M. D., & Booth, F. W. (2021). Creatine supplementation upregulates mTORC1 signaling and markers of synaptic plasticity in the dentate gyrus while ameliorating LPS-induced cognitive impairment in female rats. Nutrients, 13(8), 2758. https://doi.org/10.3390/nu13082758

Roschel, H., Gualano, B., Ostojic, S. M., & Rawson, E. S. (2021). Creatine supplementation and brain health. Nutrients, 13(2), 586. https://doi.org/10.3390/nu13020586

Smith, A. N., Choi, I.-Y., Lee, P., Sullivan, D. K., Burns, J. M., Swerdlow, R. H., Kelly, E., & Taylor, M. K. (2025). Creatine monohydrate pilot in Alzheimer’s: Feasibility, brain creatine, and cognition. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 11, e70101. https://doi.org/10.1002/trc2.70101

Snow, W. M., Cadonic, C., & Cortes-Perez, C. (2018). Chronic dietary creatine enhances hippocampal-dependent spatial memory, bioenergetics, and levels of plasticity-related proteins associated with NF-κB. Learning & Memory, 25(2), 54–66. https://doi.org/10.1101/lm.046284.117

Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2010). The Alzheimer’s disease mitochondrial cascade hypothesis. Journal of Alzheimer’s Disease, 20(Suppl 2), S265–S279. https://doi.org/10.3233/JAD-2010-100339

Wyss, M., & Kaddurah-Daouk, R. (2000). Creatine and creatinine metabolism. Physiological Reviews, 80(3), 1107–1213. https://doi.org/10.1152/physrev.2000.80.3.1107