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权健火疗后,深海鱼油和维生素D的保健品神话也要破灭?3篇NEJM论文质疑其疗效

偶数 偶数 来源:医药魔方Pro
2019-01-08
NEJM
原文

深海鱼油和维生素D是很多人都在吃的一种保健品,近些年关于深海鱼油的宣传也一直很火爆,从美白亮肤改善记忆力到预防癌症、心血管疾病等疾病,可谓是“万能神油”。

 

但是这类保健品真的有如此神奇的功效吗?

 

近日,顶级医学期刊《新英格兰医学杂志》上发表了两篇研究和一篇社论,充分证明饮食中补充鱼油和维生素D并不会降低癌症和心血管疾病的发病率和死亡率。


1、风靡已久的“保健品神话”

 

使用膳食补充剂产品在美国很常见。1999年至2012年进行的全国健康与营养调查显示,超过一半的美国成年人食用膳食补充剂。在过去的十年中,补充鱼油和维生素D的人数分别增加了10倍和4.1倍,但是这些产品对健康的长期益处仍然值得怀疑。

 

20世纪90年代末,一项开放标签的意大利心肌梗死生存研究小组-预防性试验数据证明,深海鱼油中的n-3脂肪酸(俗称ω-3脂肪酸)可以预防冠心病。基于这次的试验结果,美国心脏协会在指南中推荐ω-3脂肪酸用于冠心病的二级预防。此后,相当长的一段时间内,ω-3脂肪酸一直作为冠心病发生后,防止复发的预防手段。但是随着越来越多的大型随机试验证明,补充ω-3脂肪酸对于降低冠心病高危人群心血管事件发生率并没有一致效果。在一项大型的荟萃分析后,美国心脏协会对之前的指南进行了更新。新指南声明,ω-3脂肪酸的使用是合理的,但是并不作推荐。

 

虽然如此,深海鱼油的“神奇功效”还是相当的深入人心。另外,虽然ω-3脂肪酸不能在心血管疾病发生后,防止复发,但是如果是在疾病发生前,用于疾病预防呢?关于这方面的试验数据还是空白。

与ω-3脂肪酸的研究结果相似,大量的观察数据表明,维生素D含量越低,患癌症的风险就越高。这些研究反过来又强调了实施随机对照试验的必要性。


2、一项试验,两个重磅结果

 

为了解决这些疑惑,研究人员进行了一项名为“VITAL”的全国性的随机安慰剂对照试验,采用2×2因子设计,让50岁及以上的男性和55岁及以上的女性每日服用2000 IU维生素D3(胆钙化醇)和1g海洋ω-3脂肪酸,以评估预防癌症和心血管疾病的效果,中位随访5.3年,共25871志愿者参与了此次研究(包括5106名黑人)。

 

该研究的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、卒中或心血管原因死亡的复合事件)。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。研究结果显示:


 


在ω-3脂肪酸试验中,386名参与者和安慰剂组419名患者发生重大心血管事件(风险比,0.92);820名参与者和安慰剂组797名患者中诊断为侵袭性癌症(风险比,1.03)。在关键次要终点的分析中,风险比如下:对于心血管事件的扩展复合终点,风险比为0.93; 总心肌梗死,风险比0.72; 总卒中,风险比为1.04; 因心血管原因死亡,风险比为0.96; 并且因癌症死亡(341人死于癌症),风险比0.97。任何原因导致的死亡(总共978例死亡),风险比为1.02。没有观察到出血或其他严重不良事件的风险。

 

这些数据与最近的ASCEND(一项关于糖尿病心血管事件的研究)的数据基本一致。该研究表明,使用ω-3脂肪酸对糖尿病患者心血管疾病的一级预防没有任何效果。




在维生素D试验中,共有1617名参与者诊断出癌症(维生素D组793例,安慰剂组824例;风险比为0.96)。 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;风险比为0.97)。

 

在次要终点的分析中,风险比如下:癌症死亡(341例死亡)为0.83; 对于乳腺癌为1.02; 对于前列腺癌为0.88; 结直肠癌为1.09; 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; 对于心肌梗死为0.96; 卒中为0.95; 对于心血管原因引起的死亡为1.11。在分析任何原因导致的死亡(978例死亡)时,风险比为0.99。没有发现高钙血症或其他不良事件的风险。

 

这项试验是测试补充维生素D是否能预防心血管疾病或癌症的随机试验中规模最大、时间最长的一项。另外一项在新西兰进行的为期3年的随机安慰剂对照试验——维生素D评估研究(VIDA),5110名患者每月补充高剂量(100,000 IU)的维生素D,也证明补充维生素D对主要心血管事件以及癌症的发生率没有影响。

 

总体而言,与安慰剂相比,补充ω-3脂肪酸和维生素D并不会使侵袭性癌症或心血管事件的发生率降低。


3、试验结果直接适用于大多数患者

 

对于此次试验,John F. Keaney博士在社论中写道,“这次试验有几个地方值得注意。首先,参与者的数量较大,并且参与者中包含了相当大比例的黑人,这使使得此次队列研究更具代表性。在这种情况下,这项试验的结果应该直接适用于大多数患者。其次,虽然基线时血清25-羟维生素D水平中值为每毫升30.8 ng,但大约每13名参与者中有1人的血清25-羟维生素D水平低于每毫升20 ng。即使在这一亚组中,补充维生素D对任何类型的侵袭性癌症的病例数都没有影响。因此,在大范围的血清维生素D水平上,补充维生素D对健康没有好处。

 


Keaney认为,在缺乏其他令人信服的数据的情况下,谨慎的结论是:膳食中补充ω-3脂肪酸或维生素D预防心血管事件或癌症的策略并不理想。


原文:

1. n−3 Fatty Acids and Cardiovascular Disease and Cancer

2. Vitamin D and Cancer and Cardiovascular Disease

3. VITAL Signs for Dietary Supplementation to Prevent Cancer and Heart Disease


机器翻译

Deep-sea fish oil and vitamin D are a kind of health products that many people are eating. In recent years, the publicity of deep-sea fish oil has also been very popular. From whitening skin to improving memory to preventing diseases such as cancer and cardiovascular diseases, it can be described as "universal oil".

But do these health products really have such a magical effect?

Recently, two studies and an editorial published in the top medical journal New England Journal of Medicine have fully demonstrated that dietary fish oil and vitamin D supplementation does not reduce cancer and cardiovascular disease morbidity and mortality.

1, the long-popular "myth of health products"

The use of dietary supplement products is common in the United States.The National Health and Nutrition Examination Survey conducted from 1999 to 2012 showed that more than half of American adults consumed dietary supplements.Over the last decade, the number of people supplemented with fish oil and vitamin D has increased 10-fold and 4.1 times, but the long-term health benefits of these products remain questionable.

In the late 1990s, an open-label Italian Study Group on Survival in Myocardial Infarction – Preventive Trial data demonstrated that n-3 fatty acids (commonly known as omega-3 fatty acids) in deep-sea fish oil can protect against coronary heart disease.Based on the results of this trial, the American Heart Association recommends omega-3 fatty acids for secondary prevention of coronary heart disease.Since then, for quite some time, omega-3 fatty acids have been used as a preventive measure against recurrence after coronary heart disease.However, as more and more large randomized trials have demonstrated, supplementation with omega-3 fatty acids has no consistent effect on reducing the incidence of cardiovascular events in people at high risk of coronary heart disease.After a large meta-analysis, the American Heart Association updated the previous guidelines.The new guidelines state that the use of omega-3 fatty acids is reasonable but not recommended.

Despite this, the "magical effect" of deep-sea fish oil is quite deeply rooted.In addition, although omega-3 fatty acids do not prevent relapse after cardiovascular disease occurs, what if they are used for disease prevention before the disease occurs?The test data on this is still blank.

Similar to findings with omega-3 fatty acids, a large body of observational data suggests that the lower the vitamin D content, the higher the risk of cancer.These studies, in turn, highlight the need to implement RCTs.

2, a trial with two heavy outcomes

To address these doubts, the investigators conducted a nationwide, randomized, placebo-controlled trial called "VITAL" with a 2 × 2 factorial design in which men aged 50 years and older and women aged 55 years and older were given 2000 IU of vitamin D3 (cholecalciferol) and 1 g of marine omega-3 fatty acids daily to assess the effect of preventing cancer and cardiovascular disease, with a median follow-up.5Three years, a total of 25,871 volunteers participated in the study (including 5,106 blacks).

The primary endpoint of the study was any type of invasive cancer and major cardiovascular events (composite of myocardial infarction, stroke, or death from cardiovascular causes).Secondary endpoints included site-specific cancer, cancer death, and other cardiovascular events.The results of the study showed that:

In the omega-3 fatty acid trial, 386 participants and 419 in the placebo group had major cardiovascular events (hazard ratio, 0.92); 820 participants and 797 in the placebo group with a diagnosis of invasive cancer (hazard ratio, 1.03).In the analysis of the key secondary end points, the risk was described as follows: for the extended composite of cardiovascular events, the hazard ratio was 0. 5.93; total myocardial infarction, hazard ratio 0.72; total stroke, hazard ratio 1.04; death due to cardiovascular causes, hazard ratio 0.96; and death from cancer (341 deaths from cancer), hazard ratio 0.97. Death from any cause (total 978 deaths), hazard ratio 1.02. No risk of bleeding or other serious adverse events was observed.

These data are generally consistent with those of the recent ASCEND, a study of cardiovascular events in diabetes.The study showed that the use of omega-3 fatty acids did not have any effect on the primary prevention of cardiovascular disease in diabetic patients.

In the vitamin D trial, a total of 1,617 participants had a diagnosis of cancer (793 in the vitamin D group and 824 in the placebo group; hazard ratio 0.96).One major cardiovascular event occurred in 805 participants (396 in the vitamin D group and 409 in the placebo group; hazard ratio 0.97).

In the analysis of secondary endpoints, the risk is as follows: cancer death (341 deaths) is 0.83; for breast cancer 1.02; 0 for prostate cancer.88; colorectal cancer as 1.09; extended composite endpoint for major cardiovascular events plus coronary revascularization was 0.96; for myocardial infarction is 0.96; stroke is 0.95; for death from cardiovascular causes 1.11. In the analysis of deaths from any cause (978 deaths), the hazard ratio was 0. 1.99. No risk of hypercalcemia or other adverse events was found.

This trial is one of the largest and longest randomized trials testing whether vitamin D supplementation prevents cardiovascular disease or cancer.A three-year randomized placebo-controlled trial in New Zealand, the Vitamin D Assessment Study (VIDA), in which 5,110 patients received monthly high-dose vitamin D supplementation (100,000 IU), also demonstrated no effect of vitamin D supplementation on major cardiovascular events and the incidence of cancer.

Overall, supplementation with omega-3 fatty acids and vitamin D did not reduce the incidence of invasive cancer or cardiovascular events compared with placebo.

3, and the trial results are directly applicable to most patients

For this trial, John F.Dr Keaney wrote in the editorial, "There are several points worth noting in this trial.First, the large number of participants and the fact that a significant proportion of the participants were black make this cohort study more representative.In this case, the results of this trial should be directly applicable to the majority of patients.Second, although the median serum 25-hydroxyvitamin D level at baseline was 30 per milliliter.8 ng, but approximately 1 in 13 participants had serum 25-hydroxyvitamin D levels below 20 ng per mL.Even in this subgroup, vitamin D supplementation had no effect on the number of cases of any type of invasive cancer.Therefore, vitamin D supplementation is not good for health over a wide range of serum vitamin D levels.

Keaney believes that in the absence of other convincing data, the cautious conclusion is that dietary supplementation with omega-3 fatty acids or vitamin D is not an ideal strategy to prevent cardiovascular events or cancer.

Original:

1.n − 3 Fatty Acids and Cardiovascular Disease and Cancer

2.Vitamin D and Cancer and Cardiovascular Disease

3.VITAL Signs for Dietary Supplementation to Prevent Cancer and Heart Disease

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