1. Abstract Introduction Experimental Discussion Conclusions References and Acknowledgements * Results The Effect of Green Tea on Weight Loss and Cardiovascular Health Ryan Albert, Allyson Angles, Ann Bui, Michael Dail, Laura Hunter Ford, Ruta Patel, William Wolanski Class of 2013, School of Pharmacy, Virginia Commonwealth University Because green tea is classified as a dietary supplement, the FDA does not regulate the efficacy of these claims. In order for a claim to be made, they must be identified and these claims must be assessed based on evidence on the product. The FTC controls the advertising of green tea. The manufacturers are responsible for the safety of these products before they are marketed and the FDA monitors this by voluntary ADR reporting. Based on current literature, there do not appear to be any significant side effects or toxicity risks associated with regular green tea consumption. The only negative side effects reported have been trouble sleeping primarily due to the caffeine content present which is approximately 30-60 mg in 6-8 ounces of tea. This can be avoided by the use of a caffeine-free product. Polyphenols accounts for several of the beneficial effects of green tea due to its potent antioxidant properties. Alkaloids present in green tea, such as caffeine, theobromine, and theophylline, provide for its stimulatory effects. The phenols present in green tea are classified as catechins. The primary, and most studied, polyphenol in green tea is (-)-epigallocatechin gallate (EGCG) with lesser amounts of catechin, epicatechin, gallocatechin, gallocatechin gallate (GCG), and epicatechin gallate (ECG). Green tea catechins provide cardiovascular benefits through their antioxidant properties by inhibiting LDL oxidation, reducing TBARS formation, cellular oxidation, superoxide production, and smooth muscle cell proliferation. They have been shown to prolong lag time, inhibit formation of oxidized cholesterol and decrease lioleic acid and arachdonic acid concentrations. The elevation of plasma cholesterol has been shown to be a major risk factor for the development of heart disease. An inverse association has been identified between the consumption of green tea and the plasma concentration of cholesterol which is a major risk factor in the development of heart disease. Animal studies have found that green tea exhibits a hypocholesterolemic effect. The purified tea catechins, (-)-epicatechin gallate and (-)-epigallocatechin gallate, have been correlated with a decrease in plasma cholesterol due to dietary-induced hypercholesterolemia. This study primarily focuses on the effects of EGCG and its effect on weight loss and cardiovascular health. Whether by the mechanism s discussed or other reasons, green tea decreases cellular cholesterol levels and up-regulates the expression of LDL-receptors. In response to a decreased cholesterol level, the sterol-regulated element binding protein (SREBP-1) is activated, enters the nucleus of the cell, and promotes the transcription and translation of the LDL-receptor gene. This promotion increases cellular representation of the receptor and an increase in cholesterol uptake from the plasma via the hepatocytes of the liver. Ingestion of green tea results in a peak plasma concentration within 2 to 4 hours. Based on a recent study provided by Arbita, EGCG shows the lowest bioavailability based on the average peak plasma concentrations after a single measured dose. EGC had the highest bioavailability followed by ECG. EGCG shows a difference in the bioavailability between the different green tea catechins which is also influenced by the dosing schedule. There are two major mechanisms that describe the role of green tea and the lowering of plasma cholesterol levels, both of which indicate that green tea plays a role in the metabolism and handling of cholesterol once consumed. The first mechanism highlights an intracellular approach in which green tea affects plasma cholesterol levels by decreasing cellular concentrations of cholesterol, wherein more is absorbed by the hepatocytes and metabolized versus being available to circulate in the plasma. In a study performed in hepatocytes, green tea decreased the cell cholesterol concentration by 30% and increased the conversion of the sterol-regulated element binding protein (SREBP-1) from the inactive precursor form to the active transcription-factor form. Consistent with this, the mRNA of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol synthesis, was also increased by green tea. Figure 2 represents a dose-dependent effect of freshly brewed green tea in intracellular total and free cholesterol concentrations. Both the total and free cholesterol concentrations showed a marked decrease. As evidenced in vitro and in vivo studies green tea’s catechins, mainly EGCG, inhibit the intestinal absorption of dietary lipids. Studies in vitro indicate these catechins interfere with the emulsification, digestion, and micellar solubilization of lipids which are critical steps involved in the intestinal absorption of dietary fat, cholesterol, and other lipids. Figure 3 signifies a dose-dependent effect of freshly brewed green tea on the LDL receptor binding activity. The data suggests an up-regulation of the LDL receptor was triggered by the binding of the catechins (particularly EGCG). Figure 4 presents a dose-dependent correlation of EGCG and fat mass in subjects of a clinical trial. A positive relationship is apparent in the decrease of fat mass based on the relative dose of EGCG administered adding to the further proof of the beneficial aspects of green tea. Materials: Fresh green tea leaves HepG2 cell cultures LDL receptor protein Methods: Green Tea : Fresh green tea leaves were used in each experiment. Green tea leaves were boiled in adequate volumes of water for an appropriate time and then filtered to remove particulate matter. Study 1: HepG2 cell cultures were assayed for LDL receptor binding observations. Study 2: Total and free cholesterol plasma levels were measured in mice after increasing stepwise dosing of green tea extract from 0-200 µL. Study 3: Test subjects administered green tea extract were monitored for fat mass reduction. Figure 1: Division of subject population within similar studies. Figure 2: A dose-dependent effect of freshly brewed green tea in intracellular total and free cholesterol concentrations. A decrease of both the total and free cholesterol concentrations was noticed HepG2 cells in mice. Figure 3: A dose-dependent effect of freshly brewed green tea on the LDL receptor binding activity. The data suggests an up-regulation of the LDL receptors was triggered by their interaction with catechins. Figure 4: A dose-dependent correlation of EGCG and fat mass in subjects of a clinical trial showed a positive relationship in the decrease of fat mass based on the relative EGCG doses. Green tea ( Camellia sinensis ), native to eastern Asia, is cultivated in approximately 30 countries worldwide. The leaves are consumed traditionally as a beverage which is believed to be rivaled in popularity only by water. Although extensive clinical studies are lacking, it has been shown to exhibit strong antioxidant activity and primarily can be used as a cardio-protective agent as well as having a calming capacity and as an anticancer agent. Arpita, Basu, Edralin A Lucas. (2007). Mechanisms and Effects of Green Tea on Cardiovascular Health. Nutrition Reviews,1 65(8), 361-75. Green tea as inhibitor of the intestinal absorption of lipids.pdf Green Tea Upregulates the Low-Density Lipoprotein Receptor.pdf Green tea Health benefits.pdf Green Tea (-)-Epigallocatechin-3-Gallate Reduces Body Weight with Regulation of Multiple Genes Expression in Adipose Tissue of Diet-Induced Obese Mice.pdf Group 2 would like to acknowledge the course coordinator of Pharmacognosy MEDC 553, Dr. Y. Zhang and all faculty members in collaboration of the course’s instruction. Also, the articles published by the authors of the above references were invaluable in this presentation. The use of green tea has been popular for many years due to its useful effects on weight loss and cardiovascular health. Inconsistent data has been presented regarding the exact mechanisms and efficacy of green tea on these two areas. It was found that catechins of green tea have cardiovascular benefits through their antioxidant properties by inhibiting LDL oxidation, cellular oxidation and superoxide production, and inhibiting smooth muscle cells proliferation. The results indicate a dose-dependent relationship regarding the benefits of green tea in lowering overall total and free cholesterol leading to an overall lowering of fat mass in the body. Also, an up-regulation of LDL receptors was observed relative to the dosing of the primary catechin, EGCG. Even though positive results were observed in this study, more studies need to be conducted in order to have a concrete conclusion of its clinical benefits due to controversial results in the past.