Allicin bioavailability of garlic products

描述（由申请人提供）：大蒜素负责几乎所有在动物中观察到的生大蒜的几种公认的药理活性。为了能够进行盲法、安慰剂对照的临床试验，大蒜粉补充剂已被普遍使用。然而，在设计这类补品时必须非常小心。自20世纪40年代以来，人们就知道大蒜素不存在于生大蒜中，而是在大蒜细胞被破坏时，如被压碎，蒜氨酸酶对蒜素的酶促作用会迅速形成蒜素。因此，大蒜粉不含大蒜素。它们含有蒜素和不同水平的蒜氨酸酶，只有当蒜氨酸酶不被低胃pH值（低于pH 3.5无活性）抑制时，蒜素才能在体内形成。胃的pH值在1.5到5之间，取决于饮食条件。因此，对补充剂中大蒜素形成的信心只能通过测量此类产品中大蒜素的实际生物利用度来实现。在过去的30年里，用大蒜补充剂（主要是大蒜粉片）对几种心血管危险因素进行了近100项临床试验。对于每一种效果，试验结果都存在很大的冲突，但这些试验中没有一个使用了大蒜素生物利用度已经确定的补充剂。因此，这些试验的结果都不能应用于大蒜本身。目的：本研究的主要目的是确定各种常见的大蒜粉补充剂和大蒜食品中大蒜素的人类生物利用度。具体目标包括确定大蒜片剂和胶囊在膳食条件下影响胃pH值(高蛋白，低蛋白；补充剂的食用时间，用餐开始，用餐结束),(b)关于补充剂的蒜氨酸酶活性和分解时间，(c)与估计其生物利用度的标准体外方法进行比较，(d)来自煮熟的（煮，炸，烤）大蒜，(e)来自商业大蒜食品（腌制等）。设计：通过比较呼吸中丙烯基甲基硫醚（大蒜素的主要代谢物）32小时浓度曲线下的面积与食用已知大蒜素浓度的均质生大蒜后发现的AUC32来确定补充剂/食品中大蒜素的生物利用度。在计划的40个测试中，每个测试12个科目。公共卫生相关性：这项研究将为临床研究人员提供必要的理解，以确定在临床试验中应该使用哪种类型的补充剂，应该以何种方式食用，以及如何将结果推断到碾碎的生大蒜，所有这些都是确定大蒜或大蒜补充剂是否有益于健康所必需的。它还将允许对过去的临床试验进行重新评估。它将为制造商提供补充剂设计的正确标准。它将让消费者意识到大蒜食品与大蒜补充剂的区别。这是可以用大蒜产品进行的最重要的健康研究。相关性：这项研究将为临床研究人员提供必要的理解，以确定在临床试验中应该使用哪种类型的补充剂，应该以何种方式食用，以及如何将结果推断为碾碎的生大蒜，所有这些都是确定大蒜或大蒜补充剂是否有益于健康所必需的。它还将允许对过去的临床试验进行重新评估。它将为制造商提供补充剂设计的正确标准。它将让消费者意识到大蒜食品与大蒜补充剂的区别。这是可以用大蒜产品进行的最重要的健康研究。

DESCRIPTION (provided by applicant): Allicin is responsible for nearly all of each of the several well established pharmacological activities of raw garlic observed in animals. To be able to conduct blinded, placebo-controlled clinical trials, garlic powder supplements have been commonly used. However, much care must be taken in the design of such supplements. It has been known since the 1940s that allicin is not present in raw garlic, but that it is rapidly formed by the enzymatic action of alliinase on alliin when garlic cells are disrupted, such as by crushing. Hence, garlic powders do not contain allicin. They contain alliin and widely varying levels of alliinase, from which allicin can be formed in the body only if alliinase is not inhibited by low gastric pH (inactive below pH 3.5). Gastric pH ranges from 1.5 to 5, depending upon meal conditions. Hence, confidence in allicin formation from supplements can only be achieved by measuring the actual bioavailability of allicin from such products. In the past 30 years, nearly 100 clinical trials have been conducted with garlic supplements, mainly garlic powder tablets, on several cardiovascular risk factors. For every effect there have been substantial conflicts in the trial results, yet not one of these trials has used a supplement for which allicin bioavailability has been determined. Hence, none of the results of these trials can be applied to garlic itself. Objectives: The primary objective of this research is to determine the problematic, and hitherto unknown, human bioavailability of allicin from a variety of commonly consumed garlic powder supplements and garlic foods. Specific aims include determining the bioavailability of allicin (a) from garlic tablets and capsules under meal conditions that will affect the gastric pH (high protein, low protein; timing of supplement consumption, start of meal, end of meal), (b) with respect to the alliinase activity and disintegration time of the supplements, (c) compared to a standard in vitro method for estimating its bioavailability, (d) from cooked (boiled, fried, roasted) garlic, and (e) from commercial garlic foods (pickled, etc.). Design: The bioavailability of allicin from a supplement/food will be determined by comparing the area under the 32-hour concentration curve of breath allyl methyl sulfide (the main metabolite of allicin) to the AUC32 found after consuming homogenized raw garlic of known allicin concentration. Twelve subjects will be tested for each of the 40 planned tests. PUBLIC HEALTH RELEVANCE: This study will provide clinical researchers with the understanding needed to determine what type of supplement should be used in a clinical trial and in what manner it should be consumed, as well as how the results can be extrapolated to crushed raw garlic, all of which are necessary to establish whether or not garlic or garlic supplements can have a health benefit. It will also permit re-evaluation of the clinical trials of the past. It will provide manufacturers a correct standard for the design of supplements. It will provide consumers an awareness of how garlic foods might compare to garlic supplements. This is the most important health research that can be conducted with garlic products. Relevance: This study will provide clinical researchers with the understanding needed to determine what type of supplement should be used in a clinical trial and in what manner it should be consumed, as well as how the results can be extrapolated to crushed raw garlic, all of which are necessary to establish whether or not garlic or garlic supplements can have a health benefit. It will also permit re-evaluation of the clinical trials of the past. It will provide manufacturers a correct standard for the design of supplements. It will provide consumers an awareness of how garlic foods might compare to garlic supplements. This is the most important health research that can be conducted with garlic products.