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Peer-reviewedCC BY 4.0Nutrients

A Scoping Review of Creatine Supplementation in Alzheimer’s Disease: Evidence from Preclinical and Clinical Studies

  • Javier Choquet de Isla1,2
  • Javier Riscart-López2,3
  • Ismael Sánchez-Gomar2,4
  • Manuel Bández-Ruiz2,5
  • Ignacio Rosety-Rodríguez2,6
  • Francisco Brenes-Martín2
  • Nicolas G. Bazán7
  • Elkin Navarro Quiroz8
  • Miguel Ángel Rosety-Rodríguez1,2
  • Noelia Geribaldi-Doldán2,6
8 affiliations
  1. 1Department of Didactics of Physical Education, Art and Music, Area of Physical and Sports Education, Faculty of Education, University of Cadiz, 11519 Puerto Real, Spain
  2. 2Biomedical Research and Innovation Institute of Cádiz (INIBICA), 11002 Cádiz, Spain
  3. 3Department of Medicine, Faculty of Medicine, University of Cadiz, 11002 Cádiz, Spain
  4. 4Department of Biomedicine, Biotechnology and Public Health, Area of Physiology, Faculty of Medicine, University of Cadiz, 11002 Cádiz, Spain
  5. 5Department of Biomedicine, Biotechnology and Public Health, Area of Biochemistry, Faculty of Medicine, University of Cadiz, 11002 Cádiz, Spain
  6. 6Department of Basic Medical Science, Area of Human Anatomy and Embryology, Faculty of Medicine, University of Cadiz, 11002 Cádiz, Spain
  7. 7Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health New Orleans, New Orleans, LA 70112, USA
  8. 8Faculty of Basic and Biomedical Sciences, Center for Research in Life Sciences, Universidad Simón Bolívar, Barranquilla 080002, Colombia
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Abstract

Background/Objectives: Although creatine supplementation has a theoretical rationale for neuroprotection, public interest has outpaced available scientific evidence. Alzheimer’s disease (AD), a major and growing global health concern, is among the neurodegenerative diseases proposed to benefit from creatine supplementation. This scoping review systematically maps the existing literature on creatine supplementation for AD to identify gaps that limit translational progress. Methods: Following JBI methodology and PRISMA-ScR guidelines, a search in five electronic databases was conducted for preclinical and clinical studies evaluating creatine interventions in AD. The methodological quality of the studies was appraised using the SYRCLE and NIH tools, respectively. Results: Nine unique studies were included. The preclinical models investigated neuron apoptosis, oxidative stress, neuroinflammation, mitochondrial function, cognitive outcomes, and pathophysiological clearance. Conversely, clinical studies were limited to a pilot trial that suggested preliminary tolerability but could not establish causality. This review identifies six limitations within the current evidence: (1) a reliance on acute or non-transgenic animal models that lack construct validity; (2) a need to address sexual dimorphism; (3) a lack of studies exploring administration routes to bypass the blood–brain barrier; (4) a complete lack of independent randomized controlled trials (RCTs), with all clinical evidence originating from a single research group; (5) an absence of research assessing creatine as a preventive strategy; and (6) a shortage of assessment regarding physical syndromes, such as frailty. Conclusions: The scientific evidence for creatine in AD remains preliminary. Future research should prioritize progressive transgenic models, evaluate noninvasive administration routes, investigate effects on frailty, assess long-term preventive efficacy, account for sex as a variable, and transition to rigorous RCTs.

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Cite

BibTeXRIS
BibTeX
@article{isla2026scoping,
  title = {{A Scoping Review of Creatine Supplementation in Alzheimer’s Disease: Evidence from Preclinical and Clinical Studies}},
  author = {Javier Choquet de Isla and Javier Riscart-López and Ismael Sánchez-Gomar and Manuel Bández-Ruiz and Ignacio Rosety-Rodríguez and Francisco Brenes-Martín and Nicolas G. Bazán and Elkin Navarro Quiroz and Miguel Ángel Rosety-Rodríguez and Noelia Geribaldi-Doldán},
  journal = {Nutrients},
  year = {2026},
  month = oct,
  doi = {10.3390/nu18213477},
  url = {https://www.mdpi.com/2072-6643/18/21/3477},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A Scoping Review of Creatine Supplementation in Alzheimer’s Disease: Evidence from Preclinical and Clinical Studies
AU  - Javier Choquet de Isla
AU  - Javier Riscart-López
AU  - Ismael Sánchez-Gomar
AU  - Manuel Bández-Ruiz
AU  - Ignacio Rosety-Rodríguez
AU  - Francisco Brenes-Martín
AU  - Nicolas G. Bazán
AU  - Elkin Navarro Quiroz
AU  - Miguel Ángel Rosety-Rodríguez
AU  - Noelia Geribaldi-Doldán
PY  - 2026
DA  - 2026/10/23
JO  - Nutrients
DO  - 10.3390/nu18213477
UR  - https://www.mdpi.com/2072-6643/18/21/3477
AB  - Background/Objectives: Although creatine supplementation has a theoretical rationale for neuroprotection, public interest has outpaced available scientific evidence. Alzheimer’s disease (AD), a major and growing global health concern, is among the neurodegenerative diseases proposed to benefit from creatine supplementation. This scoping review systematically maps the existing literature on creatine supplementation for AD to identify gaps that limit translational progress. Methods: Following JBI methodology and PRISMA-ScR guidelines, a search in five electronic databases was conducted for preclinical and clinical studies evaluating creatine interventions in AD. The methodological quality of the studies was appraised using the SYRCLE and NIH tools, respectively. Results: Nine unique studies were included. The preclinical models investigated neuron apoptosis, oxidative stress, neuroinflammation, mitochondrial function, cognitive outcomes, and pathophysiological clearance. Conversely, clinical studies were limited to a pilot trial that suggested preliminary tolerability but could not establish causality. This review identifies six limitations within the current evidence: (1) a reliance on acute or non-transgenic animal models that lack construct validity; (2) a need to address sexual dimorphism; (3) a lack of studies exploring administration routes to bypass the blood–brain barrier; (4) a complete lack of independent randomized controlled trials (RCTs), with all clinical evidence originating from a single research group; (5) an absence of research assessing creatine as a preventive strategy; and (6) a shortage of assessment regarding physical syndromes, such as frailty. Conclusions: The scientific evidence for creatine in AD remains preliminary. Future research should prioritize progressive transgenic models, evaluate noninvasive administration routes, investigate effects on frailty, assess long-term preventive efficacy, account for sex as a variable, and transition to rigorous RCTs.
SN  - 2072-6643
ER  -