Abstract
Objective：To examine whether high milk consumption is associated with mortality and fractures in women and men.
Design：Cohort studies.
Setting：Three counties in central Sweden.
Participants：Two large Swedish cohorts, one with 61 433 women (39-74 years at baseline 1987-90) and one with 45 339 men (45-79 years at baseline 1997), were administered food frequency questionnaires. The women responded to a second food frequency questionnaire in 1997.
Main outcome measure：Multivariable survival models were applied to determine the association between milk consumption and time to mortality or fracture.
Results：During a mean follow-up of 20.1 years, 15 541 women died and 17 252 had a fracture, of whom 4259 had a hip fracture. In the male cohort with a mean follow-up of 11.2 years, 10 112 men died and 5066 had a fracture, with 1166 hip fracture cases. In women the adjusted mortality hazard ratio for three or more glasses of milk a day compared with less than one glass a day was 1.93 (95% confidence interval 1.80 to 2.06). For every glass of milk, the adjusted hazard ratio of all cause mortality was 1.15 (1.13 to 1.17) in women and 1.03 (1.01 to 1.04) in men. For every glass of milk in women no reduction was observed in fracture risk with higher milk consumption for any fracture (1.02, 1.00 to 1.04) or for hip fracture (1.09, 1.05 to 1.13). The corresponding adjusted hazard ratios in men were 1.01 (0.99 to 1.03) and 1.03 (0.99 to 1.07). In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF2α (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker).
Conclusions：High milk intake was associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. Given the observational study designs with the inherent possibility of residual confounding and reverse causation phenomena, a cautious interpretation of the results is recommended.
《英国医学杂志》2014;349:g6015doi:10.1136/bmj.g6015（2014年10月27日发表）
【标题】女性和男性的牛奶摄入量和死亡率及骨折风险：队列研究
【作者】Karl Michaëlsson professor【1】，Alicja Wolk professor【2】，Sophie Langenskiöld senior lecturer【3】，Samar Basu professor【3】，Eva Warensjö Lemming researcher【1，4】，Håkan Melhus professor【5】，Liisa Byberg associate professor【1】
1. 瑞典乌普萨拉大学外科学系
2. 瑞典卡罗林斯卡学院环境医学研究所
3. 瑞典乌普萨拉大学公共卫生及护理科学系
4. 瑞典国家食品局
5. 瑞典乌普萨拉大学医学系
【摘要】
1. 目的：探讨牛奶高摄入量是否与女性和男性的死亡率及骨折有关联。
2. 实验设计：队列研究。
3. 实验地点：选取瑞典中部三个县。
4. 参与者：在瑞典的两个大队列，一个有61433名女性（在1987-1990年期间参与到研究中，年龄在39-74岁之间），一个有45339名男性（在1997年参与到研究中，年龄在45-79岁之间），两个队列同时接受食物频率问卷调查。这些妇女在1997年完成了第二份食物频率问卷。
5. 主要测定项目：应用多变量生存模型来确定牛奶摄入量与死亡或骨折时间之间的关系。
6. 结果：在随访的平均20.1年期间，有15541名女性死亡，有17252人骨折过，其中4259例是髋部骨折。在随访的平均11.2年的男性队列中，有10112名男性死亡，5066人骨折，其中1166例为髋部骨折。在妇女队列中，每天喝三杯或三杯以上牛奶与每天喝少于一杯牛奶的校正死亡率危险比为1.93（95%置信区间为1.80至2.06）。对于每喝一杯牛奶，校正后的全因死亡率危险比分别为女性1.15（1.13至1.17）和男性1.03（1.01至1.04）。对女性来说，每一杯牛奶的摄入，并没有降低骨折的风险，同样，当摄入更多的牛奶时，也没有降低任何部位骨折（1.02，1.00至1.04）或髋部骨折（1.09，1.05至1.13）的风险。对于男性，这个相应的校正危险比为1.01（0.99至1.03，身体其它部位骨折）和1.03（0.99至1.07，髋部骨折）。在另外两个队列的亚样本中，一个样本都是男性，另一个样本都是女性，牛奶摄入量与尿8-iso-PGF2α（氧化应激的生物标志物）和血清白细胞介素6（一种主要的炎症生物标志物）呈正相关。
7. 结论：高牛奶摄入量与一组队列女性和另一组队列男性较高的死亡率相关，与女性较高的骨折发生率相关。鉴于观察研究设计存在固有的残余混杂因素和反向因果现象的可能性，建议对结果进行谨慎解释。