Эпигаллокатехин и рак
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- METHODS/DESIGN
- DISCUSSION
- Дизайн и установка
- Design and setting
- Определение дозы
- Побочные эффекты и противопоказания
- Dose determination
- Side effects and contraindications
Protocol for minimizing the risk of metachronous adenomas of the colorectum with green tea extract (MIRACLE): a randomised controlled trial of green tea extract versus placebo for nutriprevention of metachronous colon adenomas in the elderly population.Stingl JC1, Ettrich T, Muche R, Wiedom M, Brockmöller J, Seeringer A, Seufferlein T.
Prevention of colorectal cancer is a major health care issue. People who have undergone colonoscopy screening and had colorectal polyps removed have a higher risk of being diagnosed with polyps again compared to the normal population. Therefore, it would be ideal to find appropriate means that effectively help to prevent the reoccurrence of polyps after polypectomy. So far, pharmaceutical chemoprevention with NSAIDs including aspirin has been shown to be effective but not gained general acceptance due to side effects. Nutraceuticals such as polyphenols from tea plants have demonstrated remarkable therapeutic and preventive effects in molecular, epidemiological and clinical trials. However, placebo-controlled trials demonstrating the efficacy of nutraceuticals for the (secondary) prevention of colorectal polyps as precursors for colorectal cancer are missing. METHODS/DESIGN:We present the design of a randomized, placebo controlled, multicentre trial to investigate the effect of diet supplementation with green tea extract containing 300 mg epigallocatechin gallate (EGCG), the major polyphenol in green tea, on the recurrence of colon adenomas. Patients who have undergone polypectomy for colonic polyps will be randomized to receive either green tea extract containing 150 mg EGCG two times daily or a placebo over the course of three years. After a one month run-in period in which all patients will receive the active intervention, 2534 patients will be randomized, and 2028 patients are expected to complete the whole study course. Incidence, number and histology of adenoma at endpoint colonoscopy at three years will be compared in both groups. DISCUSSION:The beneficial safety profile of decaffeinated green tea extract, the quantifiable and known active content EGCG, and the accumulating evidence of its cancer preventive potential require, in our view, a validation of this compound for the nutriprevention of colorectal adenoma. Good accessibility and low costs might render this neutraceutical a top candidate for wider use as food supplement in colon cancer prevention. Дизайн и установкаСудебная образом проспективное рандомизированное контролируемое дизайн сравнивая два раза суточная доза зеленого чая экстракт, содержащий 150 мг EGCG дополнение к плацебо. Пациенты будут рандомизированы после verum выполнения-в течение одного месяца получить либо экстракт зеленого чая, содержащий 150 мг EGCG два раза в день или плацебо в течение трех лет. Design and settingThe trial follows a prospective randomized controlled design comparing the twice daily intake of green tea extract containing 150 mg EGCG supplement to a placebo. Patients will be randomized after a verum run-in period of one month to receive either green tea extract containing 150 mg EGCG two times daily or placebo over the course of three years. Определение дозыПрименение зеленого чая экстракт, стандартизированный по два раза в день в дозе 150 мг EGCG было решено, обзор существующей литературы по клинической долговременной профилактики исследования и обоснование, что nutriprevention исследование должно включать дозах, соответствующих питательных использовать зеленый чай, для которых существует, по крайней мере, некоторые эпидемиологические данные для рака-профилактическое действие. Простой расчет показывает, что в суточной дозе 300 мг EGCG соответствует нормальному потребление зеленого чая: одну чашку зеленый чай заваривается примерно 2 г чайного листа. Листья чая имеют катехина, около 10%. Если чай заваривается в течение 10 мин, около 80% катехинов будет распущен. Количество EGCG составляет около 50% катехинов. Это означает, что одна чашка зеленого чая будет содержать около 80 мг EGCG, и такое же количество других растворенных катехины. Таким образом, 300 мг будет соответствовать 4 чашки чая, заваренного с помощью этого метода. На практике, чай может быть заварен более короткий срок, в результате чего снижают концентрацию катехинов. Таким образом, суточная доза применяемых в данном исследовании, безусловно, лежит в диапазоне 4-7 чашек чая в день, который до сих пор физиологической дозы. Чек с литературой показывает, что во всех существующих долгосрочных исследований, аналогичных дозах были даны (см. таблицу table11).
A simple calculation shows that a daily dose of 300 mg EGCG corresponds to a normal intake of green tea: one cup of green tea is brewed with approximately 2 g of tea leaves. Tea leaves have a catechin content of about 10%. If the tea is brewed for 10 min, about 80% of the catechins will have dissolved. The amount of EGCG is about 50% of the catechins. This means that one cup of this green tea would contain about 80 mg EGCG, and the same amount of other dissolved catechins. Thus, 300 mg would correspond to 4 cups of tea brewed with this method. In practice, tea may be brewed with a shorter duration, which would result in a lower concentration of catechins. Thus, the daily dose applied in this study certainly lies within the range of 4-7 cups of tea per day, which is still a physiological dose. A check with the literature reveals that in all existing long term studies, similar doses have been given (see table table11). Side effects and contraindicationsThere are no known common side effects of green tea extract. A systematic review performed in 2008 by the United States Pharmacopeia, case reports and animal pharmacology/toxicology studies from 1966 to 2007 showed no clear evidence for EGCG-related toxicity, specifically liver enzyme elevation in a common dose range of up to 800 mg [28]. A total of 216 case reports on green tea products were analyzed, including 34 reports concerning liver damage. Twenty-seven reports pertaining to liver damage were categorized as possible causality and seven as probable causality [28]. Consumption of concentrated green tea extract on an empty stomach is more likely to lead to adverse effects than consumption in the fed state, since up to five-fold higher plasma concentrations have been observed with empty stomach compared to the fed state [29-31]. In our study, liver enzyme parameters will be tested prior to enrollment, after the one month run-in period and after 4, 12, 20 and 36 months, respectively. An increase of liver enzymes by 2.5-fold above the upper normal value will lead to discontinuation of the study medication. Participants will be urged to take the capsules at breakfast and dinner. There are no known contraindications for the intake of green tea extract. Nevertheless, we will test for hepatotoxicity after one month of EGCG intake. жүктеу/скачать 1.88 Mb. Достарыңызбен бөлісу:
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