Because previous cross-sectional studies suggest an association between metabolic disorders and Restless Legs Syndrome (RLS), we prospectively evaluated whether obesity, hypercholesterolemia, and hypertension were associated with increased risk of RLS.

Our study consisted of 42728 female participants from the Nurses’ Health Study II and 12812 male participants from the Health Professionals Follow-up Study, free of RLS at baseline (2002 for men and 2005 for women), and free of diabetes and arthritis through follow-up (2002–2008 for men and 2005–2009 for women). RLS symptoms were assessed using the International RLS Study Group’s standardized questionnaire. We considered RLS symptoms a “case” if the symptoms occurred ≥5 times/month and met International RLS Study Group criteria.

We found that obesity was associated with an increased risk RLS among both men and women (P-difference for sex >0.5). The pooled multivariate-adjusted odds ratio (OR) for RLS was 1.57 (95% confidence interval (CI): 1.33–1.85; P-trend <0.0001) for body mass index >30kg/m² vs ≤23kg/m², and 1.56 (95%CI: 1.29–1.89; P-trend=0.0001) comparing two extreme waist circumference quintiles, adjusting for age, ethnicity, smoking, physical activity, use of antidepressant, and other covariates. A similar significant association was found for high cholesterol; the pooled adjusted OR for total serum cholesterol >240mg/dL vs. <159mg/dL was 1.33 (95%CI: 1.11–1.60; P-trend=0.002). There was no significant association between hypertension and RLS risk (Adjusted OR=0.90, 95% CI: 0.79–1.02).

In this large prospective study we found that obesity and high cholesterol, but not high blood pressure, were significantly associated with an increased risk of developing RLS.