Creatine supplementation on fatigue related to post-COVID-19 condition—fatigue study: a randomized controlled trial

Background Post-COVID-19 condition (PCC) is characterized by fatigue, dyspnea, and muscle pain, with treatment including physical exercise and nutritional support. Creatine supplementation under these conditions may increase the total body creatine pool, thereby increasing muscular phosphocreatine availability and improving the energy substrate supply to sustain activity and reduce fatigue. This study investigated the efficacy of creatine supplementation in alleviating fatigue symptoms in patients with PCC, as well as its effects on quality of life, lung function, physical performance, body composition, and muscle strength. Methods This randomized, single-blind, placebo-controlled pilot study assessed supplementation with either 6 g or 18 g of creatine per day or 6 g of maltodextrin (placebo) combined with physical activity three times a week over 4 weeks. Participants with PCC who experienced fatigue [score ≥4 on the revised Piper Fatigue Scale (PFS-R)] underwent physical examination; laboratory evaluation; pulmonary function tests; muscle ultrasound; respiratory and peripheral muscle strength assessments; body composition analysis; physical capacity tests; and questionnaires on quality of life, dyspnea, anxiety, and depression before and after the intervention. Difference-in-differences (DID) between these two time points were compared across the intervention groups and the control arm. Results Sixty-seven individuals were randomized. Participants were predominantly female (76.6%), with a mean age of 52 ± 12 years, body weight of 82.6 (73.1–93.4) kg, and height of 1.63 ± 0.07 m. A total of 58 completed the protocol: 21 in the 6 g/day group, 19 in the 18 g/day group, and 18 in the placebo arm. When the difference-in-differences (DiD) in the PFS-R before and after the intervention was assessed, a score change of −2.05 was observed in the 6 g/day arm [95% confidence interval (CI): −3.47 to −0.63; p = 0.005]. Additionally, this same group showed a significant increase in handgrip strength [mean difference (DiD estimate): 4.40 kgf; 95% CI: 0.27 to 8.52; p = 0.037]. Adverse events were minimal, transient, and did not require medical intervention. Conclusions Creatine supplementation at 6 g/day was associated with improvements in fatigue and peripheral muscle strength in patients with PCC, with a favorable safety profile.