Importance Low levels of 25-hydroxyvitamin D have been associated with higher risk for depression later in life, but there have been few long-term, high-dose large-scale trials. Objective To test the effects of vitamin D3 supplementation on late-life depression risk and mood scores. Design, Setting, and Participants There were 18 353 men and women aged 50 years or older in the VITAL-DEP (Vitamin D and Omega-3 Trial-Depression Endpoint Prevention) ancillary study to VITAL, a randomized clinical trial of cardiovascular disease and cancer prevention among 25 871 adults in the US. There were 16 657 at risk for incident depression (ie, no depression history) and 1696 at risk for recurrent depression (ie, depression history but no treatment for depression within the past 2 years). Randomization occurred from November 2011 through March 2014; randomized treatment ended on December 31, 2017, and this was the final date of follow-up. Intervention Randomized assignment in a 2 × 2 factorial design to vitamin D3 (2000 IU/d of cholecalciferol) and fish oil or placebo; 9181 were randomized to vitamin D3 and 9172 were randomized to matching placebo. Main Outcomes and Measures The primary outcomes were the risk of depression or clinically relevant depressive symptoms (total of incident and recurrent cases) and the mean difference in mood scores (8-item Patient Health Questionnaire depression scale [PHQ-8]; score range, 0 points [least symptoms] to 24 points [most symptoms]; the minimal clinically important difference for change in scores was 0.5 points). Results Among the 18 353 randomized participants (mean age, 67.5 [SD, 7.1] years; 49.2% women), the median treatment duration was 5.3 years and 90.5% completed the trial (93.5% among those alive at the end of the trial). Risk of depression or clinically relevant depressive symptoms was not significantly different between the vitamin D3 group (609 depression or clinically relevant depressive symptom events; 12.9/1000 person-years) and the placebo group (625 depression or clinically relevant depressive symptom events; 13.3/1000 person-years) (hazard ratio, 0.97 [95% CI, 0.87 to 1.09]; P = .62); there were no significant differences between groups in depression incidence or recurrence. No significant differences were observed between treatment groups for change in mood scores over time; mean change in PHQ-8 score was not significantly different from zero (mean difference for change in mood scores, 0.01 points [95% CI, -0.04 to 0.05 points]). Conclusions and Relevance Among adults aged 50 years or older without clinically relevant depressive symptoms at baseline, treatment with vitamin D3 compared with placebo did not result in a statistically significant difference in the incidence and recurrence of depression or clinically relevant depressive symptoms or for change in mood scores over a median follow-up of 5.3 years. These findings do not support the use of vitamin D3 in adults to prevent depression. Trial Registration ClinicalTrials.gov Identifiers: NCT01169259 and NCT01696435.

中文翻译：

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长期补充维生素 D3 与安慰剂对抑郁或临床相关抑郁症状风险以及情绪评分变化的影响

重要性 低水平的 25-羟基维生素 D 与晚年患抑郁症的风险较高有关，但很少有长期、高剂量的大规模试验。目的 测试补充维生素 D3 对晚年抑郁症风险和情绪评分的影响。设计、设置和参与者 VITAL-DEP（维生素 D 和 Omega-3 试验-抑郁症终点预防）的辅助研究 VITAL 是心血管疾病和癌症的随机临床试验，共有 18 353 名年龄在 50 岁或以上的男性和女性美国 25 871 名成年人的预防措施。有 16657 人有抑郁症发作风险（即无抑郁症病史），1696 人有抑郁症复发风险（即有抑郁症病史但在过去 2 年内未接受过抑郁症治疗）。随机化发生在 2011 年 11 月至 2014 年 3 月；随机化治疗于 2017 年 12 月 31 日结束，这是随访的最后日期。干预 在 2 × 2 析因设计中随机分配维生素 D3（2000 IU/d 胆钙化醇）和鱼油或安慰剂；9181 人被随机分配到维生素 D3 组，9172 人被随机分配到匹配的安慰剂组。主要结果和测量 主要结果是抑郁症或临床相关抑郁症状的风险（事件和复发病例总数）和情绪评分的平均差异（8 项患者健康问卷抑郁量表 [PHQ-8]；评分范围， 0 分 [症状最少] 到 24 分 [症状最多]；分数变化的最小临床重要差异为 0.5 分）。结果 在 18353 名随机参与者中（平均年龄 67.5 [SD, 7.1] 岁；49.2% 为女性），中位治疗持续时间为 5。3 年和 90.5% 完成了试验（93.5% 的试验结束时还活着）。抑郁症或临床相关抑郁症状的风险在维生素 D3 组（609 起抑郁症或临床相关抑郁症状事件；12.9/1000 人年）和安慰剂组（625 起抑郁症或临床相关抑郁症状事件；13.3/1000 人年）之间没有显着差异1000 人年）（风险比，0.97 [95% CI，0.87 至 1.09]；P = .62）；抑郁症的发生率或复发率在各组之间没有显着差异。随着时间的推移，情绪评分的变化在治疗组之间没有观察到显着差异；PHQ-8 评分的平均变化与零没有显着差异（情绪评分变化的平均差异为 0.01 分 [95% CI，-0.04 至 0.05 分]）。结论和相关性 在基线时没有临床相关抑郁症状的 50 岁或以上的成年人中，与安慰剂相比，维生素 D3 治疗在抑郁症或临床相关抑郁症状的发生率和复发或情绪变化方面没有产生统计学上的显着差异在 5.3 年的中位随访期间得分。这些发现不支持在成人中使用维生素 D3 来预防抑郁症。试验注册 ClinicalTrials.gov 标识符：NCT01169259 和 NCT01696435。与安慰剂相比，维生素 D3 治疗在抑郁症或临床相关抑郁症状的发生率和复发率或情绪评分变化方面均未产生统计学上的显着差异，中位随访时间为 5.3 年。这些发现不支持在成人中使用维生素 D3 来预防抑郁症。试验注册 ClinicalTrials.gov 标识符：NCT01169259 和 NCT01696435。与安慰剂相比，维生素 D3 治疗在抑郁症或临床相关抑郁症状的发生率和复发率或情绪评分变化方面均未产生统计学上的显着差异，中位随访时间为 5.3 年。这些发现不支持在成人中使用维生素 D3 来预防抑郁症。试验注册 ClinicalTrials.gov 标识符：NCT01169259 和 NCT01696435。