Beyond physical exhaustion: Understanding overtraining syndrome through the lens of molecular mechanisms and clinical manifestation

Ondrej Fiala , Michaela Hanzlova , Lenka Borska , Zdenek Fiala , Drahomira Holmannova

Sports Medicine and Health Science ›› 2025, Vol. 7 ›› Issue (4) : 237 -248.

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Sports Medicine and Health Science ›› 2025, Vol. 7 ›› Issue (4) : 237 -248. DOI: 10.1016/j.smhs.2025.01.006
Review

Beyond physical exhaustion: Understanding overtraining syndrome through the lens of molecular mechanisms and clinical manifestation

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Abstract

Background: Overtraining Syndrome (OTS) is a condition resulting from excessive physical activity without adequate recovery, predominantly affecting elite athletes and military personnel. While overreaching can be a temporary state, non-functional overreaching may progress to chronic OTS. This review explores various hypotheses regarding the pathogenesis of OTS, including glycogen depletion, dysregulated cytokine response, oxidative stress, and alterations in the autonomic nervous system function. It also highlights the systemic impact of OTS on multiple organ systems, immune function, and overall health, linking the condition to chronic inflammation and an increased disease susceptibility. Additionally, it addresses the role of the gut microbiome in health modulation through physical activity.

Methods: This narrative review was conducted through a structured search of peer-reviewed journal articles in databases such as PubMed, Web of Science, and Google Scholar, focusing on studies involving human participants and published in English.

Results: OTS has systemic effects on multiple organ systems, immune function, and overall health, leading to chronic inflammation and increased disease susceptibility. Athletes with OTS exhibit higher morbidity rates, influenced by factors such as sleep deprivation and stress. The review also emphasizes the role of the gut microbiome as a significant modulator of health through physical activity.

Conclusion: Balanced training and recovery are crucial for preventing OTS and maintaining optimal health and quality of life in physically active individuals. Understanding the complex pathophysiology of OTS is essential for developing effective prevention and treatment strategies.

Keywords

Overtraining syndrome / Overreaching / Training / Performance / Exhaustion / Inadequate recovery

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Ondrej Fiala, Michaela Hanzlova, Lenka Borska, Zdenek Fiala, Drahomira Holmannova. Beyond physical exhaustion: Understanding overtraining syndrome through the lens of molecular mechanisms and clinical manifestation. Sports Medicine and Health Science, 2025, 7(4): 237-248 DOI:10.1016/j.smhs.2025.01.006

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CRediT authorship contribution statement

Ondrej Fiala: Writing - review & editing, Writing - original draft, Conceptualization. Michaela Hanzlova: Writing - review & editing, Visualization. Lenka Borska: Supervision, Funding acquisition. Zdenek Fiala: Writing - review & editing. Drahomira Holmannova: Writing - review & editing, Writing - original draft, Data curation, Conceptualization.

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

The work was supported by the project SVV-2023-260656 and the Cooperatio Program, research area HEAS.

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