BackgroundThe correlation between altitude and metabolic syndrome has not been extensively studied, and the mediation effects of diet and physical activity remain unclear. We evaluated the cross-sectional correlations between altitude and metabolic syndrome and the possible mediation effects of diet and physical activity in China.MethodsWe included 89 485 participants from the China Multi-Ethnic Cohort. We extracted their altitude information from their residential addresses and determined if they had metabolic syndrome by the presence of three or more of the following components: abdominal obesity, reduced high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, elevated glucose, and high blood pressure at recruitment. We conducted multivariable logistic regression and mediation analyses for all and separately for Han ethnic participants.ResultsThe participants had a mean age of 51.67 years and 60.56% were female. The risk difference of metabolic syndrome was -3.54% (95% confidence interval (CI) = -4.24, -2.86) between middle and low altitudes, -1.53% (95%CI = -2.53, -0.46) between high and low altitudes, and 2.01% (95% CI = 0.92, 3.09) between high and middle altitudes. Of the total estimated effect between middle and low altitude, the effect mediated by increased physical activity was -0.94% (95% CI = -1.04, -0.86). Compared to low altitude, the effects mediated by a healthier diet were -0.40% (95% CI = -0.47, -0.32) for middle altitude and -0.72% (95% CI = -0.87, -0.58) for high altitude. Estimates were similar in the Han ethnic group.ConclusionsLiving at middle and high altitudes was significantly associated with lower risk of metabolic syndrome compared to low altitude, with middle altitude having the lowest risk. We found mediation effects of diet and physical activity.