O uso da creatina como neuroprotetor da doença de Alzheimer

Autores

DOI:

https://doi.org/10.33448/rsd-v14i12.50322

Palavras-chave:

Creatina, Neuroproteção, Doença de Alzheimer, Bioenergética cerebral, Suplementação nutricional.

Resumo

A Doença de Alzheimer é uma condição neurodegenerativa progressiva caracterizada por declínio cognitivo, perda sináptica e alterações bioquímicas associadas ao acúmulo de beta-amiloide, emaranhados de tau e disfunção mitocondrial. O objetivo deste trabalho foi analisar, por meio de uma revisão narrativa da literatura, os mecanismos bioquímicos relacionados ao uso da creatina como intervenção adjuvante no manejo da Doença de Alzheimer, bem como avaliar as evidências clínicas disponíveis, suas limitações metodológicas e perspectivas futuras. A metodologia consistiu em busca estruturada nas bases PubMed, SciELO e ScienceDirect, incluindo artigos publicados entre 2008 e 2025 e selecionados com base na presença de evidências experimentais em modelos animais e ensaios clínicos em humanos que investigaram os efeitos da suplementação de creatina em Alzheimer ou em condições de risco, como o comprometimento cognitivo leve. Os resultados mostram que estudos pré-clínicos apontam melhora da função mitocondrial, aumento das reservas energéticas, redução da excitotoxicidade e modulação de fatores neurotróficos após suplementação. Esses ensaios clínicos piloto também indicam viabilidade, segurança e potenciais benefícios cognitivos em estágios iniciais da doença, embora ainda existam limitações quanto à padronização das doses, duração das intervenções e tamanho das amostras. Conclui-se que a creatina configura-se como uma intervenção nutricional promissora, com potencial para atuar como adjuvante no suporte bioenergético cerebral; contudo, sua eficácia clínica permanece inconclusiva, sendo necessários estudos controlados, robustos e de longo prazo para confirmação de seus efeitos terapêuticos.

Referências

Adhihetty, P. J., & Beal, M. F. (2008). Creatine and its potential therapeutic value for targeting cellular energy impairment in neurodegenerative diseases. NeuroMolecular Medicine, 10(4), 275–290. https://doi.org/10.1007/s12017-008-8034-x

Alzheimer’s Association. (2024). Alzheimer’s disease facts and figures 2024. Alzheimer’s & Dementia. https://www.alz.org

Alzheimer’s Drug Discovery Foundation. (2024). Creatine for Alzheimer’s disease: Clinical evidence update. ADDF.

Bender, A., et al. (2007). Creatine supplementation in Parkinson disease: A randomized controlled trial. Neurology, 67(7), 1262–1264. https://doi.org/10.1212/01.wnl.0000238508.52739.b0

Braak, H., & Braak, E. (1991). Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica, 82, 239–259. https://doi.org/10.1007/BF00308809

Brasil. Agência Nacional de Vigilância Sanitária. (2018). Resolução RDC nº 243, de 26 de julho de 2018: Requisitos sanitários dos suplementos alimentares. Diário Oficial da União.

Cipriani, G., Dichiarlantonio, L., & Borio, E. (2011). Alzheimer’s disease and neurodegenerative disorders: Historical aspects and new perspectives. Journal of Alzheimer’s Disease, 26(1), 3–12.

Consensus Group on Nutrition and Dementia. (2023). Dietary interventions for cognitive decline: Expert consensus recommendations. Journal of Nutrition and Aging, 27(4), 345–358.

Cummings, J., et al. (2023). Advances in therapeutic development for neurodegenerative diseases. Nature Reviews Drug Discovery, 22, 41–58. https://doi.org/10.1038/s41573-022-00643-0

De Wilde, M. C., et al. (2017). The role and bioavailability of nutrients in the prevention and treatment of Alzheimer’s disease: A systematic review. Journal of Alzheimer’s Disease, 55(4), 1493–1508. https://doi.org/10.3233/JAD-160766

DeTure, M. A., & Dickson, D. W. (2019). The neuropathological diagnosis of Alzheimer’s disease. Molecular Neurodegeneration, 14, 32. https://doi.org/10.1186/s13024-019-0333-5

El Gaamouch, F., et al. (2022). Polyphenols in neurodegenerative diseases: Molecular targets and clinical evidence. Antioxidants, 11(6), 1150. https://doi.org/10.3390/antiox11061150

Ellouze, M., Hamden, K., & Ben Amor, H. (2023). Effects of dietary antioxidants on neurodegenerative diseases: Molecular mechanisms and therapeutic perspectives. Journal of Functional Foods, 99, 105–113.

Gadhave, K., Patil, P., & Bhosale, S. (2024). Possible etiological factors of Alzheimer’s disease: An updated review. Neuroscience Letters, 818, 137–145. https://doi.org/10.1016/j.neulet.2023.137145

Gordji-Nejad, A., et al. (2024). Creatine as a therapeutic target for neurodegenerative diseases: Evidence and challenges. Brain Sciences, 14(1), 91–103.

Insausti, R., & Amaral, D. G. (2004). Hippocampal formation. In G. Paxinos (Ed.), The human nervous system (2nd ed., pp. 871–914). Elsevier Academic Press.

Jack, C. R., Jr., et al. (2018). NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia, 14(4), 535–562. https://doi.org/10.1016/j.jalz.2018.02.018

Kovacs, G. G. (2016). Molecular pathological classification of neurodegenerative diseases: Turning towards precision medicine. Acta Neuropathologica, 129(3), 389–408. https://doi.org/10.1007/s00401-016-1605-7

Kreider, R. B., et al. (2017). International Society of Sports Nutrition position stand: Safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition, 14, 18.

Lamptey, R. B., et al. (2022). Neurodegenerative diseases: Risk factors, mechanisms and therapeutic strategies. Biomedicine & Pharmacotherapy, 145, 112–124. https://doi.org/10.1016/j.biopha.2021.112124

Lou, Y., et al. (2023). Nutritional interventions and cognitive decline: An updated systematic review. Nutrients, 15(8), 1856. https://doi.org/10.3390/nu15081856

Malek-Ahmadi, M., et al. (2020). Braak staging and cognitive decline in Alzheimer’s disease. Journal of Alzheimer’s Disease, 78(4), 1487–1495.

McGeer, P. L., & McGeer, E. G. (2011). Neuroinflammation in Alzheimer’s disease and mild cognitive impairment: A field in its infancy. Journal of Alzheimer’s Disease, 19(1), 355–361.

McMorris, T. (2024). Creatine supplementation and cognition: Unresolved questions and research gaps. Nutrients, 16(3), 512–528.

Morris, M. C., et al. (2015). MIND diet slows cognitive decline with aging. Alzheimer’s & Dementia, 11(9), 1015–1022. https://doi.org/10.1016/j.jalz.2015.04.011

Moutinho, S. (2025). Women twice as likely to develop Alzheimer’s disease as men — but scientists do not know why. Nature Medicine, 31, 704–707.

Muddapu, V. R., et al. (2020). Neurodegenerative diseases — A mechanistic overview of common pathways. Frontiers in Neuroscience, 14, 213. https://doi.org/10.3389/fnins.2020.00213

Nucci, A., et al. (2024). Mediterranean diet and neurodegeneration: An updated review. Nutrients, 16(11), 2145.

Ostojic, S. M. (2022). Creatine as a brain energy buffer: Targeting bioenergetic failure in neurodegeneration. Aging and Disease, 13(8), 2036–2048.

Pereira, A. S., et al. (2018). Metodologia da pesquisa científica. [free ebook]. Santa Maria. Editora da UFSM.

Pfrieger, F. W. (2021). Neurodegenerative diseases: Common and divergent pathways toward a shared goal of neuronal dysfunction. Frontiers in Aging Neuroscience, 13, 766587. https://doi.org/10.3389/fnagi.2021.766587

Pless, I., et al. (2023). Progression of Alzheimer pathology: From neuropathological stages to clinical symptoms. Brain Pathology, 33(1), e13067. https://doi.org/10.1111/bpa.13067

Rae, C., et al. (2014). Oral creatine monohydrate supplementation improves brain performance: A double-blind, placebo-controlled, cross-over trial. Proceedings of the Royal Society B: Biological Sciences, 281(1780), 2014–2140. https://doi.org/10.1098/rspb.2014.2140

Ramsay, A., et al. (2024). Creatine to augment bioenergetics in Alzheimer’s (CABA): Protocol for a single-arm pilot trial. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 10(1), e12498. https://doi.org/10.1002/trc2.12498

Rother, E. T. (2007). Revisão sistemática x revisão narrativa. Acta Paulista de Enfermagem, 20(2), 5–6.

Scheltens, P., et al. (2021). Alzheimer’s disease. The Lancet, 397(10284), 1577–1590.

Smith, R. A. (2023). Creatine supplementation and cognitive function: Current evidence and future directions. Journal of Neurochemistry, 166(4), 512–528.

Smith, R. A., et al. (2025). The role of creatine metabolism in neurodegenerative disorders: Translational insights. Nutrients, 17(2), 310–322.

Soininen, H., et al. (2021). Nutritional strategies for Alzheimer’s disease: A comprehensive review. Ageing Research Reviews, 70, 101–124. https://doi.org/10.1016/j.arr.2021.101124

Turner, C. E., Miller, A. L., & Wilson, M. A. (2023). Bioenergetic interventions in Alzheimer’s disease: Evaluating creatine through neuroimaging and metabolic biomarkers. Journal of Neurodegenerative Research, 45(2), 112–128.

Van der Velpen, I., et al. (2018). Systematic review and meta-analysis of circulating inflammatory biomarkers in Alzheimer’s disease. Alzheimer’s & Dementia, 14(8), 993–1011. https://doi.org/10.1016/j.jalz.2018.02.002

Wei, Z., et al. (2023). Dietary patterns and risk of Alzheimer’s disease: A meta-analysis. Nutrition Reviews, 81(6), 701–718.

Wang, X., et al. (2021). Molecular mechanisms underlying Alzheimer’s disease and potential biomarkers. Reviews in the Neurosciences, 32(6), 563–579. https://doi.org/10.1515/revneuro-2021-0030

Xu, Y., et al. (2024). Creatine supplementation as a potential therapeutic strategy in Alzheimer’s disease: Bioenergetic and neuroprotective perspectives. Frontiers in Neuroscience, 18, 145–162.

Yiannopoulou, K. G., & Papageorgiou, S. G. (2023). Current pharmacological treatments for Alzheimer’s disease. Journal of Central Nervous System Disease.

Zhang, C., et al. (2024). New and emerging drug therapies for Alzheimer disease. CNS Drugs, 38, 213–230. https://doi.org/10.1007/s40263-024-01083

Zhang, J., et al. (2024). Recent advances in Alzheimer’s disease: Mechanisms and therapeutic strategies. Signal Transduction and Targeted Therapy.

Downloads

Publicado

2025-12-09

Edição

Seção

Artigos de Revisão

Como Citar

O uso da creatina como neuroprotetor da doença de Alzheimer. Research, Society and Development, [S. l.], v. 14, n. 12, p. e71141250322, 2025. DOI: 10.33448/rsd-v14i12.50322. Disponível em: https://rsdjournal.org/rsd/article/view/50322. Acesso em: 16 dez. 2025.