AccScience Publishing / JBM / Online First / DOI: 10.14440/jbm.0268
BRIEF REPORT

Pre-clinical evaluation of the impact of a natural mixture on cellular energy metabolism for mild cognitive impairment

Marco Trabucchi1 Frati Francesco2 Marta Scquizzato3* Marianna Colasante4 Giulio Torello4
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1 Geriatric Research Group, Faculty of Medicine, University of Rome Tor Vergata, Rome 00133, Italy
2 Department of Medicine and Surgery, Clinic of Otolaryngology, University of Perugia 06123, Italy
3 Department of Science, Global Pharmacies Partner, Milano 20123, Italy
4 Department of Research, TL Pharma Consulting, Pescara 65129, Italy
Submitted: 20 August 2025 | Revised: 14 October 2025 | Accepted: 17 October 2025 | Published: 29 December 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Background: Neurological diseases are pathologies that affect the central nervous system, such as Alzheimer’s disease and other forms of dementia. A correlation between cognitive decline and energy metabolism has been identified, and the potential to treat mental deterioration through the integration of natural mixtures into therapeutic strategies has gained increasing interest. Objective: Given the close relationship between hypometabolism and cognitive impairment, this study investigated the metabolic effects of a mixture containing medium-chain triglycerides, omega-3 fatty acids, and choline bitartrate in a human neuronal cell model, with relevance to cognitive decline. This was achieved by comparing the synergistic effects of the combined ingredients with the effects of the individual ingredients on energy metabolism (ATP) in a human neuronal model. Methods: Starting from the maximum non-toxic concentration common to both the mixture and individual components (1.563 mg/mL), the selected cell model (SH-SY5Y) was incubated for 24 h with decreasing concentrations of the mixture to evaluate ATP levels and to identify the optimal concentration (0.391 mg/mL). The cell viability results of the mixture were compared with the dose–response curves generated from cells treated with the individual components at equivalent concentrations to those present in the mixture. Results: A statistically significant increase (p<0.05) was observed in ATP content following treatment with the mixture compared to the individual active ingredients. Conclusion: The pre-clinical results demonstrate that a mixture containing medium-chain triglycerides, omega-3 fatty acids, and choline bitartrate exerts a synergistic effect on cellular energy metabolism, enhancing ATP production in a neuronal model. This formulation supports energy metabolism and may be beneficial for patients suffering from neurodegenerative diseases.

Keywords
Adenosine triphosphate
Mitochondria
SH-SY5Y cells
Mild cognitive impairment
Medium-chain triglyceride
Omega-3
Choline
Funding
None.
Conflict of interest
Marta Scquizzato is affiliated with Global Pharmacies Partner, whereas Marianna Colasante and Giulio Torello are affiliated with TL Pharma Consulting; however, these entities had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Other authors declare they have no competing interests.
References
[1]
  1. Trushina E, Trushin S, Hasan MF. Mitochondrial complex I as a therapeutic target for Alzheimer’s disease. Acta Pharm Sin B. 2022;12(2):483-495. doi: 10.1016/j.apsb.2021.11.003

 

  1. Maciejczyk M, Żebrowska E, Chabowski A. Insulin resistance and oxidative stress in the brain: What’s new? Int J Mol Sci. 2019;20(4):874. doi: 10.3390/ijms20040874

 

  1. Misrani A, Tabassum S, Yang L. Mitochondrial dysfunction and oxidative stress in Alzheimer’s disease. Front Aging Neurosci. 2021;13:617588. doi: 10.3389/fnagi.2021.617588

 

  1. Rettberg JR, Yao J, Brinton RD. Estrogen: A master regulator of bioenergetic systems in the brain and body. Front Neuroendocrinol. 2014;35(1):8-30. doi: 10.1016/j.yfrne.2013.08.001

 

  1. Rosenberg PB, Mielke MM, Appleby BS, Oh ES, Geda YE, Lyketsos CG. The association of neuropsychiatric symptoms in MCI with incident dementia and Alzheimer disease. Am J Geriatr Psychiatry. 2013;21(7):685-695. doi: 10.1016/j.jagp.2013.01.006

 

  1. Tangalos EG, Petersen RC. Mild cognitive impairment in geriatrics. Clin Geriatr Med. 2018;34(4):563-589. doi: 10.1016/j.cger.2018.06.005

 

  1. Small GW, Kepe V, Ercoli LM, et al. PET of brain amyloidand tau in mild cognitive impairment. N Engl J Med. 2006;355(25):2652-2663. doi: 10.1056/NEJMoa054625

 

  1. Chen GF, Xu TH, Yan Y, et al. Amyloid beta: Structure, biology and structure-based therapeutic development. Acta Pharmacol Sin. 2017;38(9):1205-1235. doi: 10.1038/aps.2017.28

 

  1. Guo RW, Xie WJ, Yu B, et al. Rotating magnetic field inhibits Aβ protein aggregation and alleviates cognitive impairment in Alzheimer’s disease mice. Zool Res. 2024;45(4):924-936. doi: 10.24272/j.issn.2095-8137.2024.034

 

  1. Sarkar S, Gupta S, Mahato C, Das D, Mondal J. Elucidating ATP’s role as solubilizer of biomolecular aggregate. Elife. 2024;13:RP99150. doi: 10.7554/eLife.99150

 

  1. Coskuner O, Murray IV. Adenosine triphosphate (ATP) reduces amyloid-β protein misfolding in vitro. J Alzheimers Dis. 2014;41(2):561-574. doi: 10.3233/JAD-132300

 

  1. Barón-Mendoza I, González-Arenas A. Relationship between the effect of polyunsaturated fatty acids (PUFAs) on brain plasticity and the improvement on cognition and behavior in individuals with autism spectrum disorder. Nutr Neurosci. 2022;25(2):387-410. doi: 10.1080/1028415X.2020.1755793

 

  1. Yang L, Zhao F, Sun Y, et al. N-3 polyunsaturated fatty acids in elderly with mild cognitive impairment: A systemic review and meta-analysis. J Alzheimers Dis. 2024;99(s1):S81-S95. doi: 10.3233/JAD-220863

 

  1. Welty FK. Omega-3 fatty acids and cognitive function. Curr Opin Lipidol. 2023;34(1):12-21. doi: 10.1097/MOL.0000000000000862

 

  1. Yuan J, Liu X, Liu C, et al. Is dietary choline intake related to dementia and Alzheimer’s disease risks? Results from the framingham heart study. Am J Clin Nutr. 2022;116(5):1201-1207. doi: 10.1093/ajcn/nqac193

 

  1. Liu L, Qiao S, Zhuang L, et al. Choline intake correlates with cognitive performance among elder adults in the United States. Behav Neurol. 2021;2021:2962245. doi: 10.1155/2021/2962245

 

  1. Judd JM, Jasbi P, Winslow W, et al. Inflammation and the pathological progression of Alzheimer’s disease are associated with low circulating choline levels. Acta Neuropathol. 2023;146:565-583. doi: 10.1007/s00401-023-02616-7

 

  1. Xu Q, Zhang Y, Zhang X, et al. Medium-chain triglycerides improved cognition and lipid metabolomics in mild to moderate Alzheimer’s disease patients with APOE4-/-: A double-blind, randomized, placebo-controlled crossover trial. Clin Nutr. 2020;39(7):2092-2105. doi: 10.1016/j.clnu.2019.10.017

 

  1. Avgerinos KI, Egan JM, Mattson MP, Kapogiannis D. Medium chain triglycerides induce mild ketosis and may improve cognition in Alzheimer’s disease. A systematic review and meta-analysis of human studies. Ageing Res Rev. 2020;58:101001. doi: 10.1016/j.arr.2019.101001

 

  1. Goodwin CJ, Holt SJ, Downes S, Marshall NJ. Microculture tetrazolium assays: A comparison between two new tetrazolium salts, XTT and MTS. J Immunol Methods. 1995;179(1):95-103. doi: 10.1016/0022-1759(94)00277-4

 

  1. Owen L, Sunram-Lea SI. Metabolic agents that enhance ATP can improve cognitive functioning: A review of the evidence for glucose, oxygen, pyruvate, creatine, and L-carnitine. Nutrients. 2011;3(8):735-755. doi: 10.3390/nu3080735
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Journal of Biological Methods, Electronic ISSN: 2326-9901 Print ISSN: TBA, Published by POL Scientific