Plasma and Salivary C-Reactive Protein Responses to Marathon Running: A Systematic Review and Meta-Analysis of Moderating Factors

Document Type : Review Article

Authors

Department of Physical Education and Sport Sciences, Faculty of Education Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran

Abstract
Purpose: Running exercise induces a robust acute‑phase inflammatory response, yet the magnitude and moderators of C‑reactive protein (CRP) elevation remain unclear, with no prior quantitative synthesis distinguishing plasma from salivary measurements.
Method: A systematic search of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar was performed from inception to February 2026. Eligible studies reported CRP levels before and after running exercise of any distance in runners. Random-effects meta-analyses pooled standardized mean differences (SMDs), with subgroup analyses and meta-regression examining age, BMI, and race distance.
Results: Thirty studies (1,247 runners; 72% male) were included. Endurance running significantly increased plasma CRP (SMD=1.207, 95%CI:0.688–1.726; p=0.001) and in the single study with salivary CRP data (three distance subgroups), salivary CRP increased (SMD=1.230, 95%CI:0.136–2.324; p=0.028). Age significantly moderated the response: older runners (>48 years) showed a four‑fold greater effect (SMD=1.642) than younger runners (SMD=0.402; Q=22.873, p<0.001). Race distance was a dominant moderator: ultra‑marathons (>100 km) elicited a nine‑fold larger surge (SMD=3.577) versus standard marathons (SMD=0.404; Q=18.695, p<0.001). BMI did not significantly moderate CRP elevation (Q=1.076, p=0.584). Substantial heterogeneity (plasma: I²=91.99%; salivary: I²=73.36%) and publication bias (plasma: Egger's p=0.003) were observed.
Conclusion: Running exercise significantly elevates plasma and salivary CRP, with age and race distance as potent moderators. BMI does not influence the acute CRP response. Clinicians should avoid general population cutoffs (>3 mg/L) during acute recovery. Salivary CRP requires further validation before clinical adoption. Standardized sampling at 24‑48 hours post‑race is essential for peak detection.

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