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Ostojic et al., 6-month trial (Food Science & Nutrition): https://pmc.ncbi.nlm.nih.gov/articles/PMC10630839/ creatine helped long covid

Sep 2, 2026 · 16 sources used · OpenNeedle synthesis
The short version: one small trial says creatine helped, but the evidence is too thin to trust.

The Ostojic trial [1] is the only record that directly tests creatine for long COVID. It gave 12 adults with post-viral fatigue syndrome 4 grams of creatine monohydrate daily for six months and reported improvements in fatigue, exercise tolerance, and several symptoms. But the sample is tiny — 12 people — and the trial was published in a journal called Food Science & Nutrition, not a top medical journal. There is no funding disclosure in the evidence record, so we do not know who paid for it. The same research group also published a second study [1] that measured creatine levels in the muscle and brain of 19 long COVID patients and found they were low, which is a plausible mechanism but not a treatment trial.

The rest of the evidence covers creatine in healthy soldiers [3], older adults [6], and athletes [4]. None of it tests long COVID. The 1999 study [4] even found that creatine loading raised muscle creatine levels but did not improve sprint performance — a reminder that a biochemical change (higher tissue creatine) does not automatically translate to a clinical benefit.

StudyNWhat it testedKey finding
Ostojic 2025 [1]12Creatine 4 g/day vs placebo, 6 monthsImproved fatigue, exercise tolerance, symptoms
Ostojic 2025 [1]19Creatine levels measured in muscle/brainLevels low in long COVID, correlated with myalgia
1999 study [4]14Creatine loading, 5 daysMuscle creatine rose, but no performance gain

My call: one small trial with no disclosed funding source is not enough to recommend creatine for long COVID. The mechanism is plausible but unproven. Confidence: low.

Keep digging

Sources used 16

  1. Creatine as a mitochondrial theranostic in predictive, preventive, and personalized medicine EPMA Journal (2025) Thin

    This mini-review advocates creatine as a mitochondria-targeted theranostic within predictive, preventive, and personalized medicine (PPPM), synthesizing mechanistic evidence of mitochondrial support with clinical data showing diagnostic potential and therapeutic benefits in cond…

    DOI: 10.1007/s13167-025-00420-9
  2. The acute effect of beta‐guanidinopropionic acid versus creatine or placebo in healthy men (ABC‐Trial): A randomized controlled first‐in‐human trial British Journal of Clinical Pharmacology (2017) Thin

    This study investigates the tolerability of beta-guanidinopropionic acid (GPA), a creatine analogue and competitive creatine kinase inhibitor, compared to creatine and placebo in a randomized controlled trial involving 24 healthy men, finding that GPA is well tolerated with no s…

    DOI: 10.1111/bcp.13390
  3. Effects of creatine hydrochloride supplementation on physical performance and hormonal changes in soldiers Physical Activity Review (2021) Thin

    A double-blind, randomized controlled trial evaluating whether two weeks of creatine hydrochloride (CrHCl) supplementation improves military soldiers' physical performance (vertical jump, power, and 1RM back squat) and hormonal profile (testosterone and cortisol) versus placebo,…

    DOI: 10.16926/par.2021.09.11
  4. Creatine supplementation increases muscle total creatine but not maximal intermittent exercise performance Journal of Applied Physiology (1999) Thin

    Creatine loading increases muscle total creatine and creatine phosphate but does not enhance maximal intermittent sprint performance, with observed performance gains in both groups likely due to placebo effects rather than the supplementation.

    DOI: 10.1152/jappl.1999.87.6.2244
  5. A whey protein-based multi-ingredient nutritional supplement stimulates gains in lean body mass and strength in healthy older men: A randomized controlled trial PLOS ONE (2017) Thin

    A randomized, double-blind, placebo-controlled trial in 49 healthy older men found that twice-daily intake of a whey protein–based multi-ingredient supplement increases lean body mass and strength, with additional gains in upper-body strength and metabolic health when combined w…

    DOI: 10.1371/journal.pone.0181387
  6. Combined creatine and HMB co-supplementation improves functional strength independent of muscle mass in physically active older adults: a randomized crossover trial GeroScience (2025) Thin

    In physically active older adults, six weeks of combined creatine monohydrate and HMB supplementation with an integrated physical conditioning program improved functional strength and muscular endurance beyond placebo, with gains largely independent of muscle mass, suggesting ne…

    DOI: 10.1007/s11357-025-01889-y
  7. Prevalence and risk factors of muscle complications secondary to statins Muscle & Nerve (2011) primary study Strong

    In a prospective comparative study of 345 statin users versus 85 matched controls, muscle symptoms were reported by 21% vs 5.9% (P=0.0013), with objective weakness in 15% of symptomatic patients (3.2% of the total cohort) and not in controls, and older age, longer statin use, di…

    DOI: 10.1002/mus.22205
  8. Age Differences in Becoming COVID Long-Haulers and in Post-Acute Sequelae of SARS-CoV-2 Innovation in Aging (2021) primary study Strong

    In a nationally representative sample of 608 adults with COVID-19, age was not a significant determinant of post-acute sequelae symptom count or becoming a long-hauler, with about half reporting symptoms three months after diagnosis.

    DOI: 10.1093/geroni/igab046.054
  9. Cytokine profiles associated with persisting symptoms of post-acute sequelae of COVID-19 The Korean Journal of Internal Medicine (2025) Thin

    This study investigates the immunological aspects of persistent symptoms associated with post-acute sequelae of COVID-19 (PASC) by analyzing cytokine profiles in patients diagnosed with COVID-19, revealing that certain cytokines may contribute to symptom clusters sharing common …

    DOI: 10.3904/kjim.2024.217
  10. Clinical Practice Guideline Recommendations for Post-Acute Sequelae of COVID-19 Infection & Chemotherapy (2025) Thin

    A Korean Clinical Practice Guideline revision updating evidence-based recommendations for the diagnosis, evaluation, treatment, and prevention of Post-Acute Sequelae of COVID-19 (PASC), emphasizing multidisciplinary care, early antiviral therapy, vaccination to reduce risk, and …

    DOI: 10.3947/ic.2025.0151
  11. A Mouse-adapted SARS-CoV-2 Model for Investigating Post-acute Sequelae of COVID infection Thin

    This study establishes a mouse-adapted SARS-CoV-2 model to investigate the neurological impairments and chronic immune responses associated with post-acute sequelae of COVID-19 (PASC) in C57BL/6J mice following mild infection.

    DOI: 10.1101/2024.11.10.622868
  12. Therapeutic options for the treatment of post-acute sequelae of COVID-19: a scoping review BMC Infectious Diseases (2025) Thin

    A scoping review synthesizing nine potential pharmacologic options for post-acute sequelae of COVID-19 (PASC), summarizing mechanisms, evidence, and gaps, and concluding that heterogeneity of symptoms necessitates standardized, targeted trials.

    DOI: 10.1186/s12879-025-11131-x
  13. Using machine learning involving diagnoses and medications as a risk prediction tool for post-acute sequelae of COVID-19 (PASC) in primary care BMC Medicine (2025) Thin

    This study demonstrates that machine learning, specifically stochastic gradient boosting, can effectively predict post-acute sequelae of COVID-19 (PASC) using prior diagnoses and medications from primary care data.

    DOI: 10.1186/s12916-025-04050-w
  14. Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19 International Journal of Molecular Sciences (2022) Thin

    This article argues that melatonin may regulate SARS-CoV-2 viral phase separation and host epitranscriptomic processes (notably m6A and LINE1) to limit viral replication and mitigate post-acute sequelae, through mechanisms involving N protein LLPS, DDX3X, GSK-3, mitochondria pro…

    DOI: 10.3390/ijms23158122
  15. Leveraging Temporal Learning with Dynamic Range (TLDR) for Enhanced Prediction of Outcomes in Recurrent Exposure and Treatment Settings in Electronic Health Records Thin

    This study introduces the Temporal Learning with Dynamic Range (TLDR) framework, which significantly improves predictive accuracy for post-acute sequelae of SARS-CoV-2 infection (PASC) by effectively utilizing temporal data from electronic health records (EHRs).

    DOI: 10.1101/2025.03.19.25324272
  16. Long COVID: A Comprehensive Overview of the Signs and Symptoms across Multiple Organ Systems Korean Journal of Family Medicine (2024) Thin

    This study provides a comprehensive overview of the signs and symptoms of Long COVID across multiple organ systems, highlighting the complexity and variability of post-acute sequelae of COVID-19.

    DOI: 10.4082/kjfm.24.0085

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