Selenium levels as a sex-specific predictor of migraine in the ELSA-Brasil study

BackgroundEmerging evidence suggests a link between migraine and selenium (Se). Se is related to systemic low-grade inflammation and thyroid function, which in their turn are also linked to migraine. Thus, we aimed to explore these relationships and hypothesized that higher Se levels would be related to decreased risk of migraine with an influence of systemic low-grade inflammation and thyroid function.MethodsIn a prospective analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), measurements of serum Se levels, dietary Se intake, high-sensitivity C-reactive protein (hs-CRP) and thyroid function hormones at baseline (2008-2010) and migraine incidence (2013-2014) were assessed. Serum Se was quantified by inductively coupled plasma mass spectrometry, a validated Food Frequency Questionnaire estimated dietary Se intake and hs-CRP was measured by the quantitative nephelometry method. Diagnosis of migraine without aura (MWO) and migraine with aura (MWA) followed International Classification of Headache Disorders, 3rd edition, criteria, while chronic migraine (CM) was defined according to headache attack frequency. Modified Poisson regression models estimated risk ratios (RR) for migraine subtypes, along with 95% confidence intervals, according to serum Se levels (continuous or quartiles).ResultsAmong 2355 adults (mean age: 52.4 ± 9.1 years, 48.8% female), 20.0% were diagnosed with overall migraine between 2013-14. The mean ± SD follow-up time was 4.1 ± 0.37 years. Compared to no migraine, the overall migraine group had significantly lower median (interquartile range) serum Se levels (70.8 μg/l (60.4-82.8) vs. 177.0 μg/l (149.0-220.7), p = 0.017) and dietary Se intake (170.9 μg/l (147.4-200.3) vs. 177.0 μg/l (149.0-220.7), p = 0.018), while no between-group differences for hs-CRP and thyroid function hormones was found. There was a significant positive association between Se levels and dietary Se intake, while both were negatively associated with hs-CRP levels. Compared to the lowest quartile of serum Se levels, the highest quartile was associated with a lower risk of overall migraine (RR = 0.56 (0.31-0.99), p = 0.046) in the models adjusted for sex, age, body mass index, race, household income, schooling, marital status, smoking status, alcohol consumption, and use of migraine prophylactic medication, thyroid function hormones and hs-CRP. In the sex-stratified analysis considering the same confounders, a decreased risk of MWO was observed among males (RR =0.53 (0.29-0.94), p = 0.026) and CM among females (RR = 0.71 (0.51-0.98), p = 0.038) within the highest quartile of serum Se.ConclusionsIn the ELSA-Brasil Study, diet-related higher Se levels were associated with a lower risk of migraine regardless of systemic low-grade inflammation and thyroid hormones, with migraine type- and sex-specific associations. Further studies are warranted to confirm the involvement of Se in the risk of migraine and migraine progression.