Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia

Abstract

EGCG (Epigallocatechin-3-gallate) is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract) and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal)] and limited [p.o (oral)] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment.

Paradoxical cardiotoxicity of intraperitoneally-injected epigallocatechin gallate preparation in diabetic mice

“…Mouse maybe a better predictor of EGCG toxicity than rat due to higher bioavailability in both human and mouse compared to rat 25 , 26 . Moreover, i.p route of administration offers a higher bioavailability compared to oral route (poor bioavailability and extensive biotransformation) which allows better investigation of the potential biological activity and toxicity of EGCG as estimated using previous studies 27 , 28 . Moreover, higher EGCG bioavailability has been linked to higher unconjugated EGCG level which is linked to its related toxicity 29 .…”

Alternative Oral Agents in Prophylaxis and Therapy of Uterine Fibroids—An Up-to-Date Review

“…According to the available sources, hepatotoxicity was observed in animal studies with the use of high doses of EGCG. Ramachandran estimated the maximum tolerable dose of EGCG at 67.8 mg/kg orally (in the course of two weeks) [ 91 ].…”

The Effect of Nano-Epigallocatechin-Gallate on Oxidative Stress and Matrix Metalloproteinases in Experimental Diabetes Mellitus

“…in a dose of 2.5 mg/100 g b.w./day as pretreatment, two consecutive days before STZ administration [41]. Intraperitoneal administration was preferred as a method that improves EGCG bioavailability, compared to low bioavailability with oral administration [42].…”