Vitamin E's Lack Of Heart Benefit Linked To Dosage 心脏病患者应用维生素e 与其剂量有关 Science Daily — The reported failure of vitamin E to prevent heart attacks may be due to underdosing, according to a new study by investigators at Medical Center. 据科学日报报道——一项来自Vanderbilt University医学中心的最新研究表明,剂量的不足可能是导致维他命E不能预防心脏病的发作的原因。 The findings, published early online in Free Radical Biology and Medicine, suggest that these earlier studies all had a fundamental flaw -- the doses used weren't high enough to have a significant antioxidant effect. In fact, no studies have ever conclusively demonstrated the dose at which vitamin E can be considered an antioxidant drug, the researchers report. 结果发表在年初公布在网上“自由基生物学和医学”,表明这些早期的研究都有一个根本缺陷-剂量使用不够高,从而未达到明显抗氧化作用。事实上,没有研究证明维生素e可视为一种抗氧化药物,研究者报告。
Oxidant injury, or oxidative stress, occurs when highly reactive molecules called free radicals attack and damage cellular proteins, lipids (fats) and DNA. Free radicals, which are byproducts of normal metabolism, are produced in excess in certain disease states, including heart disease. 氧化损伤,或氧化应激,出现在被称为自由基的高活性分子攻击和破坏细胞蛋白质,脂类(脂肪)和脱氧核糖核酸时。这些被称为正常代谢副产品的自由基,在一些疾病状态时产生过剩,这些疾病包括心脏病。 Epidemiological data and animal studies suggested that antioxidant compounds like vitamin E, vitamin C and beta-carotene might offer some protection against heart attack in individuals at risk. 流行病学资料及动物实验表明抗氧化物如维生素e ,维生素c和β -胡萝卜素可能会为处于心脏病危险状态下的个人提供一些保护。 But subsequent controlled clinical trials of vitamin E -- which showed little to no benefit from the vitamin -- stymied that hope. 但后来的维生素e对照临床试验显示,几乎很少从维生素中收益的,这一结果使希望成为泡影。 "Multiple human trials looking at the effect of vitamin E supplementation on coronary events and atherosclerosis have all failed," said Jack Roberts, M.D., the T. Edwin Rogers Professor of Pharmacology, professor of Medicine, and lead author on the study. "许多种盼望着维生素e对冠心病事件及动脉粥样硬化的人体试验都失败了, "杰克。罗伯茨博士说,这位药理学教授同时也是医学教授,主导了这项研究。"We're talking about trials that examined quite high doses," added Jason Morrow, M.D., F. Tremaine Billings Professor of Medicine & Pharmacology and chief of the Division of Clinical Pharmacology. "Short of a couple of studies, there was no benefit in terms of prevention of cardiovascular events and deaths." "我们正在对审查相当高的剂量进行讨论, " 医学与药理学的教授同时担负者临床药理主管的Jason Morrow补充说, "简短的两项研究表明,没有人受惠于心血管事件和死亡的预防中" 。 These results caused many to discount vitamin E supplementation as a cardioprotective treatment, but Morrow and Roberts suspected that the studies had been poorly designed. All of the trials simply gave a dose of vitamin E and looked for end points such as heart attack occurrence. But Morrow and Roberts found a critical piece of information missing. 这些结果导致许多人不在用维生素e治疗心脏病,但Morrow and Roberts怀疑该研究已设计欠佳。所有的实验都是给予一定剂量的维生素e,并且寻找终点如心脏病发生。但Morrow and Roberts发现了一个缺失关键信息。
"All of these studies were designed in a way that they never assessed the ability of the dose of vitamin E tested to effectively reduce oxidant stress," Morrow said. "所有这些研究都遵循同一种方式,他们从来没有评估过实验剂量维生素e降低氧化应激的能力", Morrow说。Without determining whether the dose of vitamin E given was exerting sufficient antioxidant effects, the previous clinical trial results were flawed, the researchers said. 研究人员说,先前的临床试验结果存在缺陷,即给定剂量的维生素e是否施加足够的抗氧化作用没有被确定。In the new study, Morrow and Roberts determined the optimum antioxidant dose of vitamin E using an assay they developed to measure compounds formed by oxidative stress processes, called F2-isoprostanes. This measure, said Roberts, "has been independently validated as the best measure of oxidative stress status in vivo." 在一项新的研究中,Morrow and Roberts通过测定维生素E的剂量来测定在氧化应激过程形成的化合物的量,确定了维生素e最佳抗氧化剂量, 既所谓的F2-isoprostanes。Robert说,这种测定方法已被独立的验证,在体内氧化应激状态下最好的测定方法。" The researchers first determined how long it took for a very high dose of vitamin E -- 3200 IU/day -- to suppress oxidative stress in individuals at risk for cardiovascular disease. 研究人员用大剂量的维生素e(3200IU每天)来抑制危险个体中的氧化应激,从而控制心血管疾病,并首次确定这种方法能维持多长时间。 To their surprise, it took 16 weeks for this dose -- which is more than 100 times the recommended daily intake and about four times higher than doses used in most previous clinical studies -- to maximally suppress F2-isoprostane formation. 令人吃惊的是,这种剂量最大限度的抑制F2-isoprostane的形利用了16个星期的时间,这种剂量是日建议用量的100倍,并且高出了先前临床研究用量的4倍。 In another group with similar cardiovascular risk factors, the researchers administered varying doses (0, 100, 200, 400, 800, 1600, and 3200 IU/day) over the 16-week period to find the minimum effective dose. 在具有类似心血管危险因素的另一个实验组中,研究者在16周的时间里,通过给不同的剂量( 0 , 100 , 200 , 400 , 800 , 1600 , 3200IU每天)来找出最低有效剂量。 They found that it was necessary to give at least 1600 IU per day to cause a significant reduction in oxidative stress -- twice that used in some of the previous clinical trials. 他们发现,有必要每天至少给予16000IU才能有效的减少氧化应激的损害,是先前临床实验用药的两倍。"It was clear that large doses -- and doses in excess of what all clinical studies had used -- were necessary," Morrow said. "很显然,大剂量用药和剂量超过临床研究所用的是必要的, " Morrow说。"Even with this massive dose of vitamin E, you only observe a 50 percent reduction in F2- isoprostanes," added Roberts. "So in my opinion, vitamin E is not the spiffy antioxidant everybody thinks it is -- it's a pretty poor antioxidant." "即使在这种应用大剂量维生素e的情况下 ,你只观察F2- isoprostanes 减少了50 % ,”Roberts补充说: "所以我认为,维生素e并不是向每个人想象的那样具有很强的抗氧化作用,它是一种效果比较弱的抗氧化剂。" Because the long-term safety of such high doses is unknown, "we are not touting taking vitamin E in large doses," Morrow said. "We are saying that, in the design of clinical trials, one needs to have good surrogate biochemical markers." 因为如此高剂量用药的长期安全性还不确定,所以我们还不敢大剂量的应用维生素e,我们的意思是说,在临床实验的设计中,你首先要找准市场。” Morrow如是说。 整理如下 心脏病患者应用维生素e 与其剂量有关据科学日报报道——一项来自Vanderbilt University医学中心的最新研究表明,剂量的不足可能是导致维他命E不能预防心脏病的发作的原因。 结果发表在年初公布在网上“自由基生物学和医学”,表明这些早期的研究都有一个根本缺陷-剂量使用不够高,从而未达到明显抗氧化作用。事实上,没有研究证明维生素e可视为一种抗氧化药物,研究者报告。 氧化损伤,或氧化应激,出现在被称为自由基的高活性分子攻击和破坏细胞蛋白质,脂类(脂肪)和脱氧核糖核酸时。这些被称为正常代谢副产品的自由基,在一些疾病状态时产生过剩,这些疾病包括心脏病。 流行病学资料及动物实验表明抗氧化物如维生素e ,维生素c和β -胡萝卜素可能会为处于心脏病危险状态下的个人提供一些保护。 但后来的维生素e对照临床试验显示,几乎很少从维生素中收益的,这一结果使希望成为泡影。 "许多种盼望着维生素e对冠心病事件及动脉粥样硬化的人体试验都失败了, "杰克。罗伯茨博士说,这位药理学教授同时也是医学教授,主导了这项研究。 "我们正在对审查相当高的剂量进行讨论, " 医学与药理学的教授同时担负者临床药理主管的Jason Morrow补充说, "简短的两项研究表明,没有人受惠于心血管事件和死亡的预防中" 。 这些结果导致许多人不在用维生素e治疗心脏病,但Morrow and Roberts怀疑该研究已设计欠佳。所有的实验都是给予一定剂量的维生素e,并且寻找终点如心脏病发生。但Morrow and Roberts发现了一个缺失关键信息。 "所有这些研究都遵循同一种方式,他们从来没有评估过实验剂量维生素e降低氧化应激的能力", Morrow说。 研究人员说,先前的临床试验结果存在缺陷,即给定剂量的维生素e是否施加足够的抗氧化作用没有被确定。 在一项新的研究中,Morrow and Roberts通过测定维生素E的剂量来测定在氧化应激过程形成的化合物的量,确定了维生素e最佳抗氧化剂量, 既所谓的F2-isoprostanes。Robert说,这种测定方法已被独立的验证,在体内氧化应激状态下最好的测定方法。" 研究人员用大剂量的维生素e(3200IU每天)来抑制危险个体中的氧化应激,从而控制心血管疾病,并首次确定这种方法能维持多长时间。 令人吃惊的是,这种剂量最大限度的抑制F2-isoprostane的形利用了16个星期的时间,这种剂量是日建议用量的100倍,并且高出了先前临床研究用量的4倍。 在具有类似心血管危险因素的另一个实验组中,研究者在16周的时间里,通过给不同的剂量( 0 , 100 , 200 , 400 , 800 , 1600 , 3200IU每天)来找出最低有效剂量。 他们发现,有必要每天至少给予16000IU才能有效的减少氧化应激的损害,是先前临床实验用药的两倍。 "很显然,大剂量用药和剂量超过临床研究所用的是必要的, " Morrow说。 "即使在这种应用大剂量维生素e的情况下 ,你只观察F2- isoprostanes 减少了50 % ,”Roberts补充说: "所以我认为,维生素e并不是向每个人想象的那样具有很强的抗氧化作用,它是一种效果比较弱的抗氧化剂。"因为如此高剂量用药的长期安全性还不确定,所以我们还不敢大剂量的应用维生素e,我们的意思是说,在临床实验的设计中,你首先要找准市场。” Morrow如是说。
转自丁香园 |