Causal Relationship Between 38 Dietary Factors, Including Sugar and Alcohol Intakes, and Polycystic Ovary Syndrome: A...

Emerging evidence suggests that diets high in sugar consumption may be implicated in the development of polycystic ovary syndrome (PCOS), but the causal nature of these associations remains unclear. This study aimed to explore the potential causal links between 38 specific dietary factors (including alcohol and added sugar), particularly sugar-sweetened beverage intake, and the risk of PCOS.

A two-sample Mendelian randomization (MR) approach was employed using genome-wide association study summary statistics. The inverse-variance weighted (IVW) method served as the primary analytical tool, with supplementary assessments conducted using the weighted median, weighted mode, and MR-Egger regression methods. Cochran's Q test evaluated heterogeneity, while MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) analysis were applied to detect horizontal pleiotropy. Robustness of findings was further assessed through leave-one-out analysis, along with visualization via forest and funnel plots.

The IVW analysis indicated potential causal associations between PCOS and alcohol intake frequency (OR = 1.39, 95% CI: 1.03-1.88, P = 0.03) and sugar added to tea (OR = 0.43, 95% CI: 0.21-0.89, P = 0.022); these associations were only supported by the IVW method and not by the other MR methods. No significant associations were observed for the 36 other dietary factors. For all 38 dietary factors, the sensitivity analyses confirmed that the results were not driven by individual instrumental variables, no significant heterogeneity was observed using Cochran's Q test, and MR-Egger regression and MR-PRESSO detected no evidence of horizontal pleiotropy or outliers.

Genetically predicted alcohol intake frequency was causally associated with PCOS. Although the initial hypothesis considered added sugar as a potential risk factor, the observed protective association of "sugar in tea" could reflect a proxy effect of tea consumption itself rather than a direct benefit of sugar. Further population-based studies are warranted for validation.