Effects of high-load, velocity-intentional variable resistance training combined with creatine supplementation on neuroplasticity, oxidative stress, inflammation, physical function, cognitive performance and quality of life in older adults: A randomized, double-blind, placebo-controlled trial

Julio Fernandez-Garrido; Ezequiel G Martin; Angel Saez-Berlanga; Pedro Gargallo-Bayo; Javier Gene-Morales; Carlos Alix-Fages; Pablo Jiménez-Martínez; Oscar Caballero; Rosario Salvador-Palmer; Juan C Colado

doi:10.1016/j.exger.2026.113122

Effects of high-load, velocity-intentional variable resistance training combined with creatine supplementation on neuroplasticity, oxidative stress, inflammation, physical function, cognitive performance and quality of life in older adults: A randomized, double-blind, placebo-controlled trial

Exp Gerontol. 2026 Apr 4:218:113122. doi: 10.1016/j.exger.2026.113122. Online ahead of print.

Affiliations

¹ Nursing Department, Faculty of Nursing and Podiatry, University of Valencia, Valencia, Spain. Electronic address: julio.fernandez@uv.es.
² Research Group in Prevention and Health in Exercise and Sport (PHES), Universitat de València, 46010, Valencia, Spain. Electronic address: ezequielgmnutricion@gmail.com.
³ Research Group in Prevention and Health in Exercise and Sport (PHES), Universitat de València, 46010, Valencia, Spain; Department of Physical Education and Sports, Universitat de València, 46010, Valencia, Spain. Electronic address: angel.saez@uv.es.
⁴ Research Group in Prevention and Health in Exercise and Sport (PHES), Universitat de València, 46010, Valencia, Spain. Electronic address: pedro.gargallo@uv.es.
⁵ Research Group in Prevention and Health in Exercise and Sport (PHES), Universitat de València, 46010, Valencia, Spain; Department of Physical Education and Sports, Universitat de València, 46010, Valencia, Spain. Electronic address: javier.gene@uv.es.
⁶ Research Group in Prevention and Health in Exercise and Sport (PHES), Universitat de València, 46010, Valencia, Spain; Department of Health Research, ICEN Research Center, Santa Cruz de Tenerife, Spain. Electronic address: c.alix@icen.es.
⁷ Research Group in Prevention and Health in Exercise and Sport (PHES), Universitat de València, 46010, Valencia, Spain; Department of Health Research, ICEN Research Center, Santa Cruz de Tenerife, Spain. Electronic address: p.jimenez@icen.es.
⁸ Nursing Department, Faculty of Nursing and Podiatry, University of Valencia, Valencia, Spain. Electronic address: oscar.caballero@uv.es.
⁹ Department of Physiology, Universitat de València, 46010, Valencia, Spain. Electronic address: rosario.salvador@uv.es.
¹⁰ Research Group in Prevention and Health in Exercise and Sport (PHES), Universitat de València, 46010, Valencia, Spain; Department of Physical Education and Sports, Universitat de València, 46010, Valencia, Spain. Electronic address: juan.colado@uv.es.

PMID: 41941966
DOI: 10.1016/j.exger.2026.113122

Abstract

Purpose: To compare two 16-week high-load, velocity-intentional resistance training programs-elastic bands (HL-VIRT-EB) vs. water-based (HL-VIRT-AQ)-combined with creatine or placebo supplementation on neuroplasticity, oxidative stress, inflammation, strength, physical function, cognition, and quality of life in older adults.

Methods: In a randomized controlled trial, 103 community-dwelling older adults (57 women, 46 men; 68.2 ± 4.6 y) were assigned to HL-VIRT-EB + Creatine, HL-VIRT-EB + Placebo, HL-VIRT-AQ + Creatine, HL-VIRT-AQ + Placebo, Control+Creatine, or Control+Placebo. Training was performed 3×/week (60 min). Creatine was consumed daily (3 g). Outcomes included brain-derived neurotrophic factor, F2-isoprostanes (F2-iso), glutathione peroxidase (GPx), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), isokinetic strength (knee/elbow, 60°·s^-1), handgrip, timed up-and-go, 30-s chair-stand, 6-min walk, trail-making test, and SF-36. ANCOVAs and correlations were conducted.

Results: Both training modalities produced significant improvements in neurocognitive biomarkers, oxidative/inflammatory profiles, strength, functional performance and quality of life (p < 0.05). HL-VIRT-AQ yielded greater reductions in F2-iso and TNF-α and larger gains in functional tests compared to HL-VIRT-EB (d = 0.12-1.18), which elicited superior upper-limb strength gains. Creatine provided additional benefits, increasing GPx, reducing IL-6/TNF-α and improving strength and function when combined with exercise modalities. Creatine alone reduced F2-iso and TNF-α and improved perceived health versus placebo.

Conclusions: High-load, velocity-intentional resistance training-on land or in water-effectively improves neurocognition, oxidative balance, inflammation, strength, function, and quality of life in older adults. Aquatic training is particularly effective for attenuating oxidative stress and inflammation. Creatine supplementation confers complementary, modality-specific benefits and supports their use in combination to high-speed resistance exercise to promote healthy aging.

Clinical trial registration id: NCT06620666 (ClinicalTrials.gov).

Keywords: Aging; Aquatic and elastic band training; High-velocity resistance training; Power training; Rating of perceived exertion (RPE); Variable resistance training.

Associated data

ClinicalTrials.gov/NCT06620666