Causal relationship between strenuous exercise and muscle injury: a Mendelian randomization study with dual samples

Abstract

Background: Muscle injuries, particularly those resulting from irregular bouts of strenuous exercise, have become a significant public health issue, especially among the athletic population. The physiological mechanisms linking intense physical exertion to muscle damage remain incompletely understood, necessitating further investigation to elucidate the causal pathways involved.

Purpose: The objective of this systematic review is to explore the physiological mechanisms that may underlie the causal relationship between strenuous exercise and the incidence of muscle injury.

Study design: A systematic review was conducted to synthesize available evidence on the topic.

Methods: We utilized advanced Mendelian randomization techniques with dual cohorts to analyze single-nucleotide polymorphisms (SNPs) significantly associated with strenuous exercise (P < 5 × 10^-8). Data on muscle injuries in the wrist and hand muscle, hips, and thighs were sourced from genome-wide association studies (GWAS) databases. A comprehensive sensitivity analysis was performed, incorporating inverse variance weighting, weighted median, MR-Egger regression, multicollinearity assessment, heterogeneity evaluation, and leave-one-out analyses.

Results: Our findings reveal a significant positive correlation between strenuous exercise and the risk of muscle injury in the hips and thighs (OR = 1.0046062, 95% CI [0.0004911795, 0.008700143], p = 0.028195794). In contrast, no causal link was identified between strenuous exercise and muscle injury in the wrist and hand muscle (OR = 0.9989059, 95% CI [-0.01131070, 0.009121317], p = 0.8336501).

Conclusion: The present systematic review suggests that strenuous exercise is positively associated with an increased risk of muscle injury in the lower limbs. This association appears to be mediated through physiological mechanisms that are more pronounced in the lower extremities compared to the wrist and hand muscle. Further research is warranted to dissect the intricate physiological processes that contribute to this differential susceptibility to injury.

Keywords: Lower limb; Mendelian randomization; Muscle injury; Physiological mechanisms; Strenuous exercise; Systematic review; Wrist and hand muscle.