The Inverted U-Shaped Association of Caffeine Intake with Serum Uric Acid in U.S. Adults

BACKGROUND AND AIMS: Caffeine is a worldwide popularly consumed constituent in foods that can exert physiological effects. However, previous researches about the relationship between caffeine intake and serum uric acid (SUA) were limited and controversial. Therefore, we sought to investigate that relationship in U.S. adults. METHODS: In this cross-sectional study, the total sample of 7888 selected participants (3838 males and 4050 females) were identified from the National Health and Nutritional Examination Surveys (NHANES) 2015-2018. All subjects were tested for serum uric acid levels (μmmol/L), and their daily caffeine intakes (mg/d) were obtained by an average of two 24-hour dietary recalls. Multivariate linear regression models were used to evaluate the association between two variables in total subjects and subgroup analyses. Generalized additive models with smooth curve fittings were also performed. RESULTS: Multivariate regression analyses showed caffeine intake was negatively correlated with SUA after adjustment of other confounders. The subgroup analyses stratified by gender showed the negative correlation of caffeine intake with SUA was statistically significant in males but not in females. Furthermore, we observed a nonlinear inverse association of caffeine intake with SUA (P nonlinear <0.001) in the generalized additive model, followed by an inverted U-shaped curve (inflection point: 60.5mg/d) for all participants. This inverted U-shaped relationship between them could also be found in both genders, individuals aged below 60 years old, overweight (BMI of 25 to 30), and Non-Hispanic White individuals. CONCLUSIONS: This study indicated that caffeine intake exhibited an inverse correlation with SUA, especially in males. In addition, this inverse relationship was nonlinear, which followed an inverted U-shaped curve.