Markers of clinical and mitochondrial adaptation in response to moderate intensity continuous training: A systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of prospective exercise intervention studies
PubMed 41481647 · doi:10.1371/journal.pone.0339902
What was done
A systematic review and meta-analysis (PROSPERO CRD42024611640) searched PubMed and CINAHL for studies published since 2010 examining moderate-intensity continuous training (MICT) lasting at least 2 weeks in adults. Eligible studies required pre- and post-training vastus lateralis skeletal muscle biopsies. Inverse-variance random-effects meta-analyses were performed for cardiorespiratory fitness (VO₂max) and molecular markers of mitochondrial adaptation and biogenesis (MitoVD, CS, MFN2, TFAM, DRP1, and PGC-1α) reported in at least three studies.
What was found
Across 14 studies (n = 184), MICT significantly increased mitochondrial volume density (MitoVD, p < 0.00001) and VO₂max (p < 0.0001), with modest increases in citrate synthase activity (CS, p = 0.05) and mitofusin 2 expression (MFN2, p = 0.01). No statistically significant changes were observed for TFAM, DRP1, or PGC-1α. Point estimates, effect sizes, and confidence intervals were not reported in the abstract.
Why it matters
This review synthesizes skeletal muscle biopsy data to show that chronic MICT reliably stimulates mitochondrial structural and functional adaptations alongside cardiorespiratory fitness in adults.
Limits
The total sample size across 14 trials was very small (184 participants, averaging ~13 per study). The abstract does not report numerical effect sizes or confidence intervals. Overall certainty of evidence was rated very low to low, with potential heterogeneity introduced by unmeasured moderators including exercise modality, training duration, and participant sex.
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