Université Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Villejuif, 94805, France.
Inserm U1018, CESP, Hôpital Paul-Brousse, bâtiment 15/16, 16, avenue Paul-Vaillant-Couturier, Villejuif cedex, 94807, France.
Eur J Epidemiol. 2024 Sep;39(9):1023-1036. doi: 10.1007/s10654-024-01152-2. Epub 2024 Sep 18.
Previous studies showed positive associations between milk intake and Parkinson's disease (PD) in men but not in women, but few studies were available in women. Due to the long prodromal PD phase, reverse causation represents a major threat to investigations of diet in PD; cohort studies with a long follow-up are needed. We investigated associations between intake of milk and other dairy products with PD incidence in women from the E3N cohort study (1993-2018). PD diagnoses were validated using medical records and drug claim databases. Diet was assessed via a dietary questionnaire. Hazard ratios (HR) were estimated using multivariable Cox regression models. Exposures were lagged by 5y in main analyses and longer lags in sensitivity analyses. We examined the impact of adjustment for premotor symptoms (constipation/depression). During a mean follow-up of 18.8y, 845 of 71,542 women developed PD. Main analyses showed a J-shaped association between total milk intake and PD (P-non linearity = 0.045), with a significant linear positive association among drinkers (HR/1-SD = 1.09, 95% CI = 1.01-1.18, P = 0.024), that was explained in secondary analyses by a different pattern of association for plain milk (alone or with cereals) and milk added to drinks (tea/coffee/chicory). PD incidence increased significantly with plain milk consumption (HR/1-SD = 1.08 [1.02-1.14], P = 0.014). A U-shaped relation was observed for milk added to drinks (P-non linearity = 0.038), with lower PD incidence in women with moderate consumption (HR = 0.77 [0.61-0.97], P = 0.030) and no difference between non-drinkers and those with the highest consumption (HR = 0.98 [0.79-1.21], P = 0.848). Findings were similar in analyses using longer lags and adjusted for constipation/depression. Consumption of other dairy products was not associated with PD. A J-shaped association between total milk intake and PD was explained by a different pattern of association for plain milk intake and milk added to drinks. Reverse causation is unlikely to explain a positive association of plain milk with PD incidence in women. The U-shaped relation for milk added to drinks could be explained by an interaction between milk and coffee/tea/chicory. Further studies are warranted to elucidate the underlying mechanisms.
先前的研究表明，男性摄入牛奶与帕金森病（PD）之间存在正相关关系，但女性则不然，但女性的相关研究较少。由于 PD 的前驱期较长，反向因果关系对 PD 饮食的研究构成了重大威胁；需要进行随访时间较长的队列研究。我们调查了 E3N 队列研究（1993-2018 年）中女性摄入牛奶和其他乳制品与 PD 发病率之间的关系。使用病历和药物索赔数据库验证 PD 诊断。通过饮食问卷评估饮食。使用多变量 Cox 回归模型估计风险比（HR）。在主要分析中，暴露滞后 5 年，在敏感性分析中滞后时间更长。我们检查了调整前驱症状（便秘/抑郁）的影响。在平均 18.8 年的随访期间，71542 名女性中有 845 人患上 PD。主要分析显示，总牛奶摄入量与 PD 之间呈 J 形关联（P-非线性=0.045），在饮酒者中存在显著的线性正相关关系（每 1-SD 的 HR=1.09，95%CI=1.01-1.18，P=0.024），在二次分析中，这归因于普通牛奶（单独或与谷物一起）和添加到饮料中的牛奶（茶/咖啡/菊苣）的关联模式不同。PD 发病率随着普通牛奶的消耗而显著增加（每 1-SD 的 HR=1.08[1.02-1.14]，P=0.014）。添加到饮料中的牛奶呈 U 形关系（P-非线性=0.038），中等摄入量的女性 PD 发病率较低（HR=0.77[0.61-0.97]，P=0.030），非饮酒者与最高摄入量者之间无差异（HR=0.98[0.79-1.21]，P=0.848）。使用更长的滞后时间和调整便秘/抑郁的分析得出了类似的结果。其他乳制品的消耗与 PD 无关。总牛奶摄入量与 PD 之间的 J 形关联可以通过普通牛奶摄入量和添加到饮料中的牛奶的不同关联模式来解释。反向因果关系不太可能解释普通牛奶与女性 PD 发病率之间的正相关关系。添加到饮料中的牛奶的 U 形关系可以通过牛奶和咖啡/茶/菊苣之间的相互作用来解释。需要进一步的研究来阐明潜在的机制。
