Coffee intake reduced gout risk by decreasing urate and urea while increasing SHBG levels in plasma: a mediation Mendelian randomization study.

OBJECTIVE

This study aims to investigate the causal relationships between specific dietary habits and the risk of gout, while identifying the mediators involved in these associations.

METHODS

We initially assessed the causal effects of five dietary habits on gout by two-sample Mendelian randomization (MR). Subsequently, we identified mediators from five plasma metabolites by two-step MR, including urate, urea, sex hormone-binding globulin (SHBG), interleukin-18 (IL-18), and C-reactive protein (CRP). Next, we quantified the proportion of mediation effects by multivariable Mendelian randomization (MVMR). Last, we performed reverse MR analyses. Sensitivity analyses were conducted to enhance the robustness of our findings.

RESULTS

Only coffee intake demonstrated a significant negative casual effect on gout (inverse variance weighted: OR = 0.444, p = 0.049). In two-step MR, coffee intake decreased urate and urea while increased SHBG levels, but did not affect IL-18 and CRP levels. Besides, urate and urea showed positive causal effects while SHBG exhibited a negative impact on gout. In mediation analysis, urate, urea, and SHBG respectively mediated 53.60%, 16.43%, and 4.81% of the total causal effect of coffee intake on gout. The three mediators collectively mediated 27.45% of the total effect. Reverse MR analyses suggested no significant reverse causal effects. Sensitivity analyses supported the reliability of our causal inferences.

CONCLUSION

Coffee intake reduced gout risk by decreasing urate and urea while increasing SHBG levels in plasma. These findings accentuate the benefits of coffee intake for gout management. The mediators may provide a novel insight into potential therapeutic targets for gout prevention. Key Points • This study determines the causally protective effect of coffee intake on gout. • We reveal that coffee intake reduced the risk of gout by decreasing urate and urea while increasing SHBG levels in plasma. • Identifying specific mediators in the causal pathway from coffee intake to gout provides valuable information for clinical interventions of gout.