Whether marine omega-3 fatty acid (n-3 FA) or vitamin D supplementation can prevent cardiovascular disease (CVD) in general populations at usual risk for this outcome is unknown. A major goal of VITAL (Vitamin D and Omega-3 Trial) was to fill this knowledge gap. In this article, we review the results of VITAL, discuss relevant mechanistic studies regarding n-3 FAs, vitamin D, and vascular disease, and summarize recent meta-analyses of the randomized trial evidence on these agents. VITAL was a nationwide, randomized, placebo-controlled, 2×2 factorial trial of marine n-3 FAs (1 g/d) and vitamin D3 (2000 IU/d) in the primary prevention of CVD and cancer among 25 871 US men aged ≥50 and women aged ≥55 years, including 5106 blacks. Median treatment duration was 5.3 years. Supplemental n-3 FAs did not significantly reduce the primary cardiovascular end point of major CVD events (composite of myocardial infarction, stroke, and CVD mortality; hazard ratio [HR], 0.92 [95% CI, 0.80-1.06]) but were associated with significant reductions in total myocardial infarction (HR, 0.72 [95% CI, 0.59-0.90]), percutaneous coronary intervention (HR, 0.78 [95% CI, 0.63-0.95]), and fatal myocardial infarction (HR, 0.50 [95% CI, 0.26-0.97]) but not stroke or other cardiovascular end points. For major CVD events, a treatment benefit was seen in those with dietary fish intake below the cohort median of 1.5 servings/wk (HR, 0.81 [95% CI, 0.67-0.98]) but not in those above (P interaction=0.045). For myocardial infarction, the greatest risk reductions were in blacks (HR, 0.23 [95% CI, 0.11-0.47]; P interaction by race, 0.001). Vitamin D supplementation did not reduce major CVD events (HR, 0.97 [95% CI, 0.85-1.12]) or other cardiovascular end points. Updated meta-analyses that include VITAL and other recent trials document coronary risk reduction from supplemental marine n-3 FAs but no clear CVD risk reduction from supplemental vitamin D. Additional research is needed to determine which individuals may be most likely to derive net benefit from supplementation. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01169259.

中文翻译：

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维生素 D、海洋 n-3 脂肪酸和心血管疾病一级预防的最新证据。


海洋 omega-3 脂肪酸 (n-3 FA) 或维生素 D 补充剂是否可以预防一般人群中常见的心血管疾病 (CVD)，目前尚不清楚。 VITAL（维生素 D 和 Omega-3 试验）的主要目标是填补这一知识空白。在本文中，我们回顾了 VITAL 的结果，讨论了有关 n-3 FA、维生素 D 和血管疾病的相关机制研究，并总结了最近对这些药物的随机试验证据的荟萃分析。 VITAL 是一项全国性、随机、安慰剂对照、2×2 析因试验，研究海洋 n-3 FA（1 克/天）和维生素 D3（2000 IU/天）对 25 871 名美国男性进行心血管疾病和癌症的一级预防年龄≥50岁和年龄≥55岁的女性，其中包括5106名黑人。中位治疗时间为 5.3 年。补充 n-3 FA 并未显着降低主要 CVD 事件的主要心血管终点（心肌梗塞、卒中和 CVD 死亡率的复合终点；风险比 [HR]，0.92 [95% CI，0.80-1.06]），但相关总心肌梗塞（HR，0.72 [95% CI，0.59-0.90]）、经皮冠状动脉介入治疗（HR，0.78 [95% CI，0.63-0.95]）和致命性心肌梗塞（HR，0.50 [95]）显着降低% CI，0.26-0.97]），但不是中风或其他心血管终点。对于主要 CVD 事件，饮食中鱼类摄入量低于队列中位数 1.5 份/周的患者有治疗获益（HR，0.81 [95% CI，0.67-0.98]），但高于摄入量的患者则没有治疗获益（P 相互作用 = 0.045） 。对于心肌梗塞，黑人的风险降低幅度最大（HR，0.23 [95% CI，0.11-0.47]；种族 P 相互作用，0.001）。补充维生素 D 并不能减少主要 CVD 事件（HR，0.97 [95% CI，0.85-1.12]）或其他心血管终点。 更新的荟萃分析（包括 VITAL 和其他最近的试验）记录了补充海洋 n-3 FA 可以降低冠状动脉风险，但补充维生素 D 没有明显降低 CVD 风险。需要进行更多研究来确定哪些个体最有可能从中获得净收益补充。临床试验注册： URL：http://www.clinicaltrials.gov。唯一标识符：NCT01169259。