Creatine supplementation (CS) offers numerous health benefits, with no proven side effects reported to date. CS positively impacts all organs and systems of the body. However, there is an ongoing effort among several creatine-producing companies to develop increasingly pure creatine formulations that generate fewer renal metabolites. Therefore, this study aims to evaluate the effects of a new creatine formulation, CreaSafe®, synthesized by the Chinese company Wenda®, on kidney function in athletes and patients with chronic obstructive pulmonary disease (COPD), as well as its effects on skeletal muscles and cardiopulmonary function. Regarding the athletes (Study 1), the sample will consist of 80 healthy athletes (40 strength-training athletes and 40 middle- and long-distance runners). Among each group of 40 athletes, 20 will receive CreaSafe® creatine (0.03 g/kg/day), while the other 20 will receive a placebo (microcrystalline cellulose; 0.03 g/kg/day), for 90 days, orally administered in water in the morning (between 7:00 a.m. and 9:00 a.m.). For the COPD patients (Study 2), 60 patients with severe and/or very severe COPD will be recruited. Of these, 30 will receive CreaSafe® creatine (0.03 g/kg/day), while the other 30 will receive placebo (microcrystalline cellulose; 0.03 g/kg/day), also administered orally in water for 90 days in the morning (between 7:00 a.m. and 9:00 a.m.). The supplementation period for both studies will last 90 days, with assessments performed at baseline and after 90 days. Kidney function will be evaluated through urinalysis (Urine Type I), the balance of pro- vs. anti-inflammatory cytokines, and levels of urea, creatine kinase (CK), and creatinine. Body composition will be assessed using octopolar and multifrequency bioimpedance, along with circumference measurements of body segments. Muscle strength of different muscle groups will be assessed using the E-lastic dynamometer. Biomarkers of skeletal muscle degradation and recovery will also be measured in plasma, including CK, lactate dehydrogenase (LDH), urea, myoglobin, and the levels of IL-1beta, IL-4, IL-6, IL-10, TNF-alpha, Atrogin-1, MuRF-1, and GDF-8 (myostatin). Whole blood analysis (erythrocytes, leukocytes, and platelets) will be performed using a fully automated blood analyzer (Sysmex XS 800i). Pulmonary function will be assessed through pre- and post-bronchodilator spirometry, as well as maximal inspiratory (PIMax) and expiratory (PEMax) pressures using a manovacuometer. Cardiovascular function will be evaluated using electrocardiography (ECG) and cardiovascular hemodynamics assessed by impedance cardiography (PhysioFlow). GraphPad Prism 5.0 software will be used for statistical analyses and graph generation. Paired Student's t-tests will be used to compare pre- and post-intervention values within each group, and unpaired Student's t-tests will be used to compare deltas between the CreaSafe® and placebo groups. Statistical significance will be considered at p ≤ 0.05.

Inclusion Criteria:

• resistance-trained athletes middle- and long-distance runners severe and/or very severe COPD

Exclusion Criteria:

• Non-athletes and individuals without a diagnosis of COPD