维生素D补充和预防癌症和心血管疾病

StephenW

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In summary, daily supplementation with high-dose vitamin D for 5 years among initially healthy adults in the United States did not reduce the incidence of cancer or major cardiovascular events. BUT there is a signal that after 2 years Cancer Mortality Improved. Jules
Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease
Abstract
Background

It is unclear whether supplementation with vitamin D reduces the risk of cancer or cardiovascular disease, and data from randomized trials are limited.
Methods

We conducted a nationwide, randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D3 (cholecalciferol) at a dose of 2000 IU per day and marine n−3 (also called omega-3) fatty acids at a dose of 1 g per day for the prevention of cancer and cardiovascular disease among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were invasive cancer of any type and major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes). Secondary end points included site-specific cancers, death from cancer, and additional cardiovascular events. This article reports the results of the comparison of vitamin D with placebo.
Results

A total of 25,871 participants, including 5106 black participants, underwent randomization. Supplementation with vitamin D was not associated with a lower risk of either of the primary end points. During a median follow-up of 5.3 years, cancer was diagnosed in 1617 participants (793 in the vitamin D group and 824 in the placebo group; hazard ratio, 0.96; 95% confidence interval [CI], 0.88 to 1.06; P=0.47). A major cardiovascular event occurred in 805 participants (396 in the vitamin D group and 409 in the placebo group; hazard ratio, 0.97; 95% CI, 0.85 to 1.12; P=0.69). In the analyses of secondary end points, the hazard ratios were as follows: for death from cancer (341 deaths), 0.83 (95% CI, 0.67 to 1.02); for breast cancer, 1.02 (95% CI, 0.79 to 1.31); for prostate cancer, 0.88 (95% CI, 0.72 to 1.07); for colorectal cancer, 1.09 (95% CI, 0.73 to 1.62); for the expanded composite end point of major cardiovascular events plus coronary revascularization, 0.96 (95% CI, 0.86 to 1.08); for myocardial infarction, 0.96 (95% CI, 0.78 to 1.19); for stroke, 0.95 (95% CI, 0.76 to 1.20); and for death from cardiovascular causes, 1.11 (95% CI, 0.88 to 1.40). In the analysis of death from any cause (978 deaths), the hazard ratio was 0.99 (95% CI, 0.87 to 1.12). No excess risks of hypercalcemia or other adverse events were identified.
Conclusions

Supplementation with vitamin D did not result in a lower incidence of invasive cancer or cardiovascular events than placebo. (Funded by the National Institutes of Health and others; VITAL ClinicalTrials.gov number, NCT01169259.)
Discussion

In this large primary-prevention trial, supplementation with vitamin D3 (at a dose of 2000 IU per day) did not lead to a significantly lower incidence of invasive cancer of any type or a composite of major cardiovascular events (myocardial infarction, stroke, and death from cardiovascular causes) than placebo. The intervention also did not lead to a lower incidence of total deaths from cancer or a lower incidence of breast, prostate, or colorectal cancer than placebo.

Effects did not vary according to baseline serum 25-hydroxyvitamin D levels. The use of vitamin D did not lead to a significant difference in any of the secondary cardiovascular end points or in the rate of death from any cause in the overall cohort or in subgroups.

In analyses excluding early follow-up data, there was also no significant between-group difference in the incidence of invasive cancer of any type or major cardiovascular events. A post hoc analysis of the rate of death from cancer suggested a possible benefit with respect to the rate of total deaths from cancer after exclusion of early follow-up data, based on an unadjusted 95% confidence interval that does not include 1.
Cancer

The primary end point of invasive cancer of any type developed in 1617 participants, with similar event rates in the vitamin D group and the placebo group (793 and 824 participants with cancer, respectively; hazard ratio, 0.96; 95% confidence interval [CI], 0.88 to 1.06; P=0.47) (Table 2). No significant differences between the two groups were observed with regard to the incidence of breast, prostate, or colorectal cancer. During follow-up, 341 participants died from cancer, with 154 such deaths in the vitamin D group and 187 in the placebo group (hazard ratio, 0.83; 95% CI, 0.67 to 1.02).

The cumulative incidence of invasive cancer of any type (Figure 2A and Table 2) and death from cancer (Table 2, and Figure S2D in the Supplementary Appendix) did not differ significantly between the two groups. No significant differences between the two groups were observed with regard to preplanned analyses of the primary end point of cancer, excluding the first 1 and 2 years of follow-up. However, the test for proportionality over time was significant for the rate of death from cancer. In both an analysis that excluded 1 year of follow-up and an analysis that excluded 2 years of follow-up, neither of which was specified in the protocol, the rate of death from cancer was significantly lower with vitamin D than with placebo (hazard ratio, 0.79 [95% CI, 0.63 to 0.99], and hazard ratio, 0.75 [95% CI, 0.59 to 0.96], respectively). In analyses restricted to 153 deaths from cancer in patients with medical records or other adjudication of the cause of death beyond the NDI coding, the hazard ratios were 0.72 (95% CI, 0.52 to 1.00) over the total follow-up period and 0.63 (95% CI, 0.43 to 0.92) after the first 2 years were excluded. Preliminary analyses of cancer stage at diagnosis showed slightly fewer advanced cancers, metastatic cancers, or both among patients assigned to vitamin D than among those assigned to placebo, but differences were not significant (data not shown). The cumulative incidence rates of site-specific cancers and of death from cancer (prespecified secondary end points) are shown in Figure S2 in the Supplementary Appendix.

Results of prespecified subgroup analyses are presented in Table 3. The findings suggest that BMI may have modified the effect of vitamin D on cancer.

StephenW

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总之，在美国最初健康的成年人中，每日补充高剂量维生素D 5年并未降低癌症或主要心血管事件的发生率。但是有一个信号表明，2年后癌症死亡率提高了。儒勒
维生素D补充和预防癌症和心血管疾病
抽象
背景

目前尚不清楚补充维生素D是否可降低患癌症或心血管疾病的风险，随机试验的数据有限。
方法

我们进行了一项全国性，随机，安慰剂对照试验，采用2×2因子设计，维生素D3（胆钙化醇），剂量为2000 IU /天，海洋n-3（也称为omega-3）脂肪酸在美国，50岁或以上的男性和55岁或以上的女性，每天1克的剂量用于预防癌症和心血管疾病。主要终点是任何类型的侵袭性癌症和主要心血管事件（心肌梗塞，中风或心血管原因死亡的复合物）。次要终点包括位点特异性癌症，癌症死亡和其他心血管事件。本文报道了维生素D与安慰剂的比较结果。
结果

共有25,871名参与者，包括5106名黑人参与者，接受了随机化。补充维生素D与任何一个主要终点的风险较低无关。在中位随访5。3年期间，1617名参与者诊断出癌症（维生素D组793例，安慰剂组824例;风险比0.96; 95％置信区间[CI]，0.88-1.06; P = 0.47 ）。 805名参与者发生了一次重大心血管事件（维生素D组396人，安慰剂组409人;风险比0.97; 95％CI，0.85-1.12; P = 0.69）。在次要终点的分析中，风险比如下：癌症死亡（341例死亡），0.83（95％CI，0.67至1.02）;对于乳腺癌，1.02（95％CI，0.79至1.31）;对于前列腺癌，0.88（95％CI，0.72至1.07）;结直肠癌，1.09（95％CI，0.73-1.62）;对于主要心血管事件加冠状动脉血运重建的扩展复合终点，为0.96（95％CI，0.86至1.08）;对于心肌梗死，0.96（95％CI，0.78至1.19）;中风，0.95（95％CI，0.76至1.20）;对于心血管原因引起的死亡，1.11（95％CI，0.88-1.40）。在分析任何原因导致的死亡（978例死亡）时，风险比为0.99（95％CI，0.87至1.12）。没有发现高钙血症或其他不良事件的过度风险。
结论

与安慰剂相比，补充维生素D不会导致侵袭性癌症或心血管事件的发生率降低。 （由美国国立卫生研究院和其他机构资助; VITAL ClinicalTrials.gov编号，NCT01169259。）
讨论

在这项大型初级预防试验中，补充维生素D3（每天2000 IU的剂量）不会导致任何类型的侵袭性癌症或主要心血管事件（心肌梗塞，中风和心血管原因死亡）比安慰剂。与安慰剂相比，干预措施也没有导致癌症总死亡率降低或乳腺癌，前列腺癌或结直肠癌发病率降低。

根据基线血清25-羟基维生素D水平，效果没有变化。维生素D的使用并未导致任何次要心血管终点或整个队列或亚组中任何原因的死亡率的显着差异。

在排除早期随访数据的分析中，任何类型或主要心血管事件的侵袭性癌症的发病率之间也没有显着的组间差异。癌症死亡率的事后分析表明，根据未经调整的95％置信区间（不包括1），排除早期随访数据后，癌症总死亡率可能获益。
癌症

在1617名参与者中发展的任何类型的侵袭性癌症的主要终点，在维生素D组和安慰剂组中具有相似的事件发生率（分别为793和824名癌症患者;风险比，0.96; 95％置信区间[CI] ，0.88至1.06; P = 0.47）（表2）。在乳腺癌，前列腺癌或结肠直肠癌的发病率方面，没有观察到两组之间的显着差异。在随访期间，341名参与者死于癌症，维生素D组有154人死亡，安慰剂组有187人死亡（风险比率为0.83; 95％CI，0.67至1.02）。

任何类型的侵袭性癌症（图2A和表2）和癌症死亡（表2和补充附录中的图S2D）的累积发生率在两组之间没有显着差异。对于癌症的主要终点的预先计划分析，除了第1年和第2年的随访之外，两组之间没有观察到显着差异。然而，随着时间的推移对比例性的测试对于癌症的死亡率是显着的。在排除1年随访的分析和排除2年随访的分析中，均未在方案中指明，维生素D导致的癌症死亡率明显低于安慰剂（危害）比率，0.79 [95％CI，0.63至0.99]和风险比，分别为0.75 [95％CI，0.59至0.96]。在NDI编码以外的医疗记录或其他死因判决患者中，仅有153例因癌症死亡的分析，在总的随访期内风险比为0.72（95％CI，0.52至1.00），为0.63（排除前2年后95％CI，0.43至0.92）。诊断时癌症分期的初步分析显示，接受维生素D治疗的患者中晚期癌症，转移性癌症或两者均略低于分配给安慰剂的患者，但差异不显着（数据未显示）。特定癌症和癌症死亡（预先指定的次要终点）的累积发病率显示在补充附录中的图S2中。

预先指定的亚组分析结果列于表3.研究结果表明，BMI可能已经改变了维生素D对癌症的影响。分析结果列于表3.研究结果表明，BMI可能已经改变了维生素D对癌症的影响。