Barrero-Osorio · Healthcare (Basel, Switzerland) 2026 · systematic review and meta-analysis of randomized controlled trials · n=5 studies (116 participants)

Effects of Physical Exercise on Circulating Serotonin Levels: A Systematic Review and Meta-Analysis.

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Level 1 - systematic review of randomized trials

Systematic review and meta-analysis of randomized controlled trials

PubMed 41754045 · doi:10.3390/healthcare14040532 · record verified 2026-08-29

What was done

Systematic review and random-effects meta-analysis (PRISMA-guided) searching PubMed, Web of Science, and Scopus. The review included randomized controlled trials comparing physical exercise interventions to non-exercise usual care control groups that measured circulating (serum or plasma) serotonin concentrations. Study quality was evaluated using the PEDro scale, and sensitivity analyses tested pre-post correlation assumptions (r = 0.6 to 0.9).

What was found

Five RCTs with a total of 116 participants (all female) were included. Physical exercise showed a non-significant effect on circulating serotonin levels (SMD 1.48, 95% CI -0.46 to 3.42, p = 0.135) with extreme heterogeneity (I² = 94.63%). Sensitivity analyses across correlation assumptions also remained non-significant with high heterogeneity. Study quality on the PEDro scale ranged from acceptable to good (scores 4 to 7).

Why it matters

Despite common assumptions that physical exercise modulates serotonin, existing trial evidence does not demonstrate a statistically significant change in circulating serotonin levels.

Limits

The total sample size is very small (5 trials, 116 subjects) and includes exclusively female participants, preventing generalization to males. Heterogeneity was extremely high (I² > 94%), methodological quality was moderate, and measurement protocols and exercise modalities were not standardized.

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