Effects of six‐month creatine supplementation on patient‐ and clinician‐reported outcomes, and tissue creatine levels in patients with post‐COVID‐19 fatigue syndrome

Dietary creatine has been recently put forward as a possible intervention strategy to reduce post‐COVID‐19 fatigue syndrome yet no clinical study so far evaluated its efficacy and safety for this perplexing condition. In this parallel‐group, randomized placebo‐controlled double‐blind trial, we analyzed the effects of 6‐month creatine supplementation (4 g of creatine monohydrate per day) on various patient‐ and clinician‐reported outcomes, and tissue creatine levels in 12 patients with post‐COVID‐19 fatigue syndrome. Creatine intake induced a significant increase in tissue creatine levels in vastus medialis muscle and right parietal white matter compared to the baseline values at both 3‐month and 6‐month follow‐ups (p < .05). Two‐way analysis of variance with repeated measures revealed a significant difference (treatment vs. time interaction) between interventions in tissue creatine levels (p < .05), with the creatine group was superior to placebo to augment creatine levels at vastus medialis muscle, left frontal white matter, and right parietal white matter. Creatine supplementation induced a significant reduction in general fatigue after 3 months of intake compared to baseline values (p = .04), and significantly improved scores for several post‐COVID‐19 fatigue syndrome‐related symptoms (e.g., ageusia, breathing difficulties, body aches, headache, and difficulties concentrating) at 6‐month follow‐up (p < .05). Taking creatine for 6 months appears to improve tissue bioenergetics and attenuate clinical features of post‐COVID‐19 fatigue syndrome; additional studies are warranted to confirm our findings in various post‐COVID‐19 cohorts.