Inflammation Factors Mediate Association of Muscle Mass and Migraine: NHANES 1999-2004 and Mendelian Randomization.

PURPOSE: The relationship between adipose-muscle distribution and its effect on migraine remains unclear. This study examines the association between muscle mass and migraine prevalence and evaluates potential mediation by systemic inflammatory biomarkers.

METHODS

Using a cross-sectional design, we analyzed data from 10,400 participants in the National Health and Nutrition Examination Survey (NHANES) (1999-2004). The association between appendicular lean mass normalized to body mass index (ALM/BMI) and migraine prevalence was evaluated through weighted logistic regression and subgroup analyses. Mediation analyses were conducted to examine the potential mediating roles of inflammatory markers, including C-reactive protein (CRP), white blood cell count (WBC), and neutrophils, in the relationship between ALM/BMI and migraine prevalence. Genetic causality was investigated via two-sample Mendelian randomization (MR) using genome-wide association study (GWAS) data.

RESULTS

20% of total participants reported migraines. A higher ALM/BMI ratio was inversely associated with migraine after full adjustment (OR = 0.243; 95% CI: 0.122-0.487, p < 0.001). Vigorous activity reduced migraine susceptibility by 24% (OR = 0.760; 95% CI: 0.663-0.872, p < 0.001). CRP, WBC and neutrophils mediated 2.0% (p = 0.024), 3.1% (p = 0.011), and 2.8% (p = 0.019) of the ALM/BMI-migraine association, respectively. The inverse-variance weighted approach (IVW) in MR analysis indicated that higher basal metabolic rate (BMR) reduced migraine risk (OR = 0.996, 95% CI: 0.992-0.998, p = 0.004) and headache risk (OR = 0.998, 95% CI: 0.997-1.000, p = 0.018). Fat-free mass also exhibited protective effects on migraines (OR = 0.997, 95% CI: 0.994-1.000, p = 0.045).

CONCLUSION

Increased muscle mass is associated with reduced migraine risk, partially mediated by attenuating systemic inflammation. These findings provide us with an approach of health management to prevent migraines.