2026 — Creatine RCT in post-COVID-19 condition fatigue
One-paragraph summary
Randomized, single-blind, placebo-controlled trial of creatine supplementation in patients with post-COVID-19 condition (PCC). Mechanism rationale: creatine supplementation increases total body creatine pool, raising muscle phosphocreatine availability, improving energy-substrate supply, and reducing fatigue. Outcomes included PCC fatigue symptoms, quality of life, lung function, physical performance, body composition, and muscle strength. For the project, this paper directly tests a mitochondrial-protective adjunct (creatine) in the post-COVID-condition population that the v0.3 cube identifies as a candidate fifth dimension. Creatine joins idebenone / MitoQ / elamipretide / metformin in Hypothesis 1's mitochondrial-quality-control intervention class (B19 bridge). Drug-repurposing tier — generic supplement, established safety, no IND.
Claims as triples
creatine — modulates → post_covid_syndrome[evidence: PCC fatigue RCT; confidence: emerging]creatine — modulates → mitochondrial_dysfunction[evidence: phosphocreatine-mediated energy-substrate support, mechanism rationale; confidence: bridging]creatine — bridges → fm_central_only[evidence: extrapolation from PCC to post-COVID-FM cube cell; confidence: bridging]
Triangulation notes
- Adds creatine to the Hypothesis 1 mitochondrial-protective intervention class alongside idebenone, MitoQ, elamipretide, metformin. B19 bridge (mitochondrial-quality-control therapy class) reinforced.
- PCC-specific evidence — directly relevant to v0.3 cube's post-COVID-FM dimension (Giménez-Orenga 2025 differentiation panel; Q36 NfL test).
- Discovered via Probe 3 (muscle mitochondrial function); scored ingestion-worthy in the over-regulation audit; promoted to ingestion in Recommendation 3.
Open questions raised
- Does creatine reduce fatigue preferentially in HERV-W-positive PCC subset?
- Combination with metformin (also AMPK / mitochondrial pathway) — additive or redundant?