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Nutrients
Volume 17
Issue 9
10.3390/nu17091431
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Article

Dietary Nucleotides Enhance Neurogenesis, Cognitive Capacity, Muscle Function, and Body Composition in Older Adults: A Randomized, Triple-Blind, Controlled Clinical Trial

by
Javier Gene-Morales
1,2,
Alvaro Juesas
2,3,
Angel Saez-Berlanga
1,2,
Ezequiel G. Martin
2,
Luis Garrigues-Pelufo
2,
Brayan S. Sandoval-Camargo
2,
Fernando Martin-Rivera
1,2,
Iván Chulvi-Medrano
1,2,
Pablo Jiménez-Martínez
2,4,
Carlos Alix-Fages
2,4,
Pedro Gargallo
2,
Julio Fernandez-Garrido
5,
Oscar Caballero
5,
Agustín Jerez-Martínez
4,6,* and
Juan C. Colado
1,2
1
Department of Physical Education and Sports, University of Valencia, 46010 Valencia, Spain
2
Research Group in Prevention and Health in Exercise and Sport (PHES), University of Valencia, 46010 Valencia, Spain
3
Department of Education Sciences, CEU Cardenal Herrera University, 46115 Castellón, Spain
4
ICEN Research Center, Department of Health Research, 38002 Santa Cruz de Tenerife, Spain
5
Nursing Department, Faculty of Nursing and Podiatry, University of Valencia, 46010 Valencia, Spain
6
Faculty of Sports Sciences, Catholic University of Murcia (UCAM), 30107 Murcia, Spain
*
Author to whom correspondence should be addressed.
Nutrients 2025, 17(9), 1431; https://doi.org/10.3390/nu17091431
Submission received: 7 April 2025 / Revised: 20 April 2025 / Accepted: 23 April 2025 / Published: 24 April 2025
(This article belongs to the Section Sports Nutrition)
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Abstract

Background/Objectives: this study evaluated the differential effects of two distinct dietary nucleotide supplements, combined with spontaneous physical activity, on neuromuscular, cognitive, and metabolic adaptations in older adults. Methods: Sixty-nine physically independent older adults (aged 60–75 years) were randomly assigned to three groups: (1) a yeast nucleotides formulation (YN) standardized in a high content of free nucleotides (>40%) rich in all macro and micro nutrients naturally occurring in yeast cell (amino acids, minerals and B-group vitamin); (2) a neuro-based formulation (NF) consisting of a blend of monophosphate nucleotides 5′; or (3) a placebo. Participants maintained their spontaneous physical activities without structured exercise during a 10-week intervention. Assessments included physical function, cognitive performance, body composition, quality of life, and serum biomarkers of oxidative stress, inflammation, and neurogenesis. Results: Both nucleotide-supplemented groups demonstrated significant improvements compared to placebo in physical performance (p ≤ 0.045), cognitive function (Trail Making Test B [TMT-B]: p ≤ 0.012), oxidative stress biomarkers (p ≤ 0.048), inflammatory cytokines (p ≤ 0.023), and quality-of-life parameters (p ≤ 0.047). Body composition remained stable in supplemented groups, whereas placebo increased fat mass (5.04%) and decreased muscle mass (−2.18%). Conclusions: Dietary nucleotide supplementation enhances the benefits of spontaneous physical activity across all measured variables in older adults, highlighting nucleotides as promising nutritional support for healthy aging. YN exhibited a trend toward greater inflammatory modulation, whereas NF showed a tendency toward enhanced neurotrophic effects and functional improvements, with a statistically significant improvement in the Timed Up and Go Test (p = 0.014). These findings underscore the potential for tailored nucleotide-based interventions to optimize distinct physiological domains in aging populations.
Keywords: gerontology; inflammatory modulation; redox balance; physical activity; neuroplasticity gerontology; inflammatory modulation; redox balance; physical activity; neuroplasticity

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MDPI and ACS Style

Gene-Morales, J.; Juesas, A.; Saez-Berlanga, A.; Martin, E.G.; Garrigues-Pelufo, L.; Sandoval-Camargo, B.S.; Martin-Rivera, F.; Chulvi-Medrano, I.; Jiménez-Martínez, P.; Alix-Fages, C.; et al. Dietary Nucleotides Enhance Neurogenesis, Cognitive Capacity, Muscle Function, and Body Composition in Older Adults: A Randomized, Triple-Blind, Controlled Clinical Trial. Nutrients 2025, 17, 1431. https://doi.org/10.3390/nu17091431

AMA Style

Gene-Morales J, Juesas A, Saez-Berlanga A, Martin EG, Garrigues-Pelufo L, Sandoval-Camargo BS, Martin-Rivera F, Chulvi-Medrano I, Jiménez-Martínez P, Alix-Fages C, et al. Dietary Nucleotides Enhance Neurogenesis, Cognitive Capacity, Muscle Function, and Body Composition in Older Adults: A Randomized, Triple-Blind, Controlled Clinical Trial. Nutrients. 2025; 17(9):1431. https://doi.org/10.3390/nu17091431

Chicago/Turabian Style

Gene-Morales, Javier, Alvaro Juesas, Angel Saez-Berlanga, Ezequiel G. Martin, Luis Garrigues-Pelufo, Brayan S. Sandoval-Camargo, Fernando Martin-Rivera, Iván Chulvi-Medrano, Pablo Jiménez-Martínez, Carlos Alix-Fages, and et al. 2025. "Dietary Nucleotides Enhance Neurogenesis, Cognitive Capacity, Muscle Function, and Body Composition in Older Adults: A Randomized, Triple-Blind, Controlled Clinical Trial" Nutrients 17, no. 9: 1431. https://doi.org/10.3390/nu17091431

APA Style

Gene-Morales, J., Juesas, A., Saez-Berlanga, A., Martin, E. G., Garrigues-Pelufo, L., Sandoval-Camargo, B. S., Martin-Rivera, F., Chulvi-Medrano, I., Jiménez-Martínez, P., Alix-Fages, C., Gargallo, P., Fernandez-Garrido, J., Caballero, O., Jerez-Martínez, A., & Colado, J. C. (2025). Dietary Nucleotides Enhance Neurogenesis, Cognitive Capacity, Muscle Function, and Body Composition in Older Adults: A Randomized, Triple-Blind, Controlled Clinical Trial. Nutrients, 17(9), 1431. https://doi.org/10.3390/nu17091431

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