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

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. 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. 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. 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. NCT06620666 ( ClinicalTrials.gov ) • Sixteen weeks of high-load, velocity-intent training improved BDNF, oxidative balance, inflammation, strength, function and QoL in older adults. • Aquatic high-velocity resistance produced greater reductions in F2-isoprostanes and TNF-α and superior functional gains vs elastic band land modality • Creatine supplementation added benefits—higher GPx, lower IL-6/TNF-α—and enhanced strength (land) and TUG performance (water). • Combined exercise+creatine yielded the largest overall effects and creatine alone still reduced oxidative and inflammatory markers in controls. • Findings support accessible high-speed resistance modalities plus creatine as a practical strategy to counteract neurocognitive and physical aging.