Creatine supplementation and respiratory muscle function in health and disease: translational insights from human to mouse

Price, Oliver J. ORCID: https://orcid.org/0000-0001-8596-4949, Brown, James, Storey, Emily ORCID: https://orcid.org/0000-0002-2607-3959, Turner, Louise A ORCID: https://orcid.org/0000-0002-0153-7075, Johnson, Michael, Sharpe, Graham, Wheatcroft, Stephen, Yuldasheva, Nadira, Hendrickse, Paul, Pereira, Marcelo ORCID: https://orcid.org/0000-0002-6670-8031 and Bowen, T. Scott ORCID: https://orcid.org/0000-0002-1740-2474 (2026) Creatine supplementation and respiratory muscle function in health and disease: translational insights from human to mouse. ERJ Open Research. 00305-2026. doi:10.1183/23120541.00305-2026 (In Press)

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Abstract

Background Respiratory muscle weakness contributes to exercise intolerance in both ageing and disease; however current treatment options remain limited. In this study, we investigated the potential for creatine (Cr) supplementation to increase inspiratory muscle strength (PImax) in health and mitigate diaphragm dysfunction in disease. Methods Using a translational approach, we combined a human inspiratory muscle training (IMT) intervention with a mechanistic preclinical heart failure (HF) model. Twenty-nine healthy males (FEV 1 >80% pred) completed 4 weeks of IMT (30-breaths, twice daily, at 50% PImax), either alone (IMT: n=15) or with Cr (IMT+Cr: n=14). PImax and expiratory muscle strength (PEmax) were assessed pre- and post-IMT. Subsequently, isolated diaphragm fibre bundles from healthy and post-myocardial infarction HF mice underwent in vitro analysis following 3 weeks of Cr supplementation or placebo. Results In humans, baseline PImax was similar between groups (p=0.554). The 33% increase in PImax after IMT+Cr was greater than the 18% increase after IMT (condition×time interaction: p=0.031). In mice, Cr had no effect in health but increased diaphragm function in HF with improvements in specific force, twitch relaxation, and fatigue resistance (all p<0.05). Conclusion Cr supplementation was associated with a greater increase in PImax following IMT in healthy adults and improved diaphragm contractile performance in a preclinical model of HF. These findings provide biological plausibility for a potential effect of Cr on intrinsic diaphragm function and warrant confirmation in adequately powered, randomised controlled trials.

Item Type:	Article
Article Type:	Article
Additional Information:	This manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online.
Subjects:	Q Science > QP Physiology R Medicine > R Medicine (General)
Divisions:	Schools and Research Institutes > School of Education, Health and Sciences
Depositing User:	Charlotte Crutchlow
Date Deposited:	07 Jul 2026 09:18
Last Modified:	07 Jul 2026 09:30
URI:	https://eprints.glos.ac.uk/id/eprint/16415

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