Effects of Chronic Creatine and Beta-Hydroxy-Beta-Methylbutyrate Supplementation on Oxidative Stress, Inflammation, Muscle Strength, and Body Composition in Individuals With Down Syndrome

This study is an 8-week randomized, placebo-controlled, crossover trial designed to evaluate the effects of daily supplementation with creatine monohydrate (3 g) and beta-hydroxy-beta-methylbutyrate (HMB, 3 g) on body composition, muscle strength, balance, cognitive function, and biomarkers of oxidative stress and inflammation in individuals with Down syndrome. Participants will receive nutritional education throughout the intervention to support a balanced diet. Primary outcomes include lean mass measured by dual-energy X-ray absorptiometry (DXA). Secondary outcomes include fat-free mass (bioimpedance), bone mineral density (DXA), handgrip strength, lower limb strength (Five Times Sit-to-Stand Test), upper and lower body isometric strength (K-Pull test), balance (4-Stage Balance Test), and cognitive function assessed by the Timed Up and Go Dual Task. Blood biomarkers of oxidative stress and inflammation, including reduced glutathione (GSH), superoxide dismutase (SOD), C-reactive protein (CRP), interleukins (IL-1, IL-6, IL-7), and tumor necrosis factor-alpha (TNF-α), will be assessed before and after each supplementation period. All assessments will be performed at baseline and at the end of each 8-week supplementation phase, allowing for evaluation of both physiological and functional responses to creatine and HMB supplementation in this population.