Epigallocatechin-3-gallate (EGCG) for clinical trials: more pitfalls than promises?

Abstract

Epigallocatechin-3-gallate (EGCG), the main and most significant polyphenol in green tea, has shown numerous health promoting effects acting through different pathways, as antioxidant, anti-inflammatory and anti-atherogenic agent, showing gene expression activity, functioning through growth factor-mediated pathways, the mitogen-activated protein kinase-dependent pathway, the ubiquitin/proteasome degradation pathway, as well as eliciting an amyloid protein remodeling activity. However, epidemiological inferences are sometimes conflicting and in vitro and in vivo studies may seem discrepant. Current knowledge on how to enhance bioavailability could be the answer to some of these issues. Furthermore, dose levels, administration frequency and potential side effects remain to be examined.

Keywords: bioavailability; epigallocatechin-3-gallate; green tea.

Figures

Figure 1

Chemical structure of EGCG. Some currently documented structure-function relationships are depicted in this figure. The pyrogallol-type structure on the B-ring induces apoptosis and possesses strong antioxidative activity undergoing autooxidation to form reactive oxygen species [10,11]. The galloyl moiety (D-ring, gallate group) is the critical structure in the inhibition of fatty-acid synthase leading to cytotoxicity in human cancer cells [12]. Both components B and D contribute to the exertion of biological activities related to the cell-surface 67 kDa laminin receptor [13,14]. EGCG molecular docking fractions for amyloid remodeling activity are still not known.

Figure 2

Factors influencing EGCG bioavailability: Factors enhancing plasma levels of EGCG are listed to the left, those that diminish bioavailability can be found on the right. Most of these factors are easily modifiable.

Figure 3

Single assessments of plasma levels of EGCG [6] available from 2008 on, measured 2 h after ingestion, depicted together with assessments of serum free light chains: Kappa, Lambda and K/L ratio, as well as international normalized ratio (INR) and interventricular septum thickness (IVS). EGCG assessments were undertaken 2 h after ingestion, referring to expected peak plasma levels [17,25]. (A) Therapy with oral melphalan plus high-dose dexamethasone until August 2006. No further conventional chemotherapy administered later on. (B) September 2006: start 1.5–2 L/day green tea (GT). (C) June 2008: Start 150 mg EGCG t.i.d. instead of GT, because of oral fluid intake restriction due to progressive renal failure. (D) October 2008: dosage change to 450 mg EGCG t.i.d. + 200 mg vitamin C + 20 mg piperine each time. (E) December 2008: start continuous ambulatory peritoneal dialysis (CAPD); EGCG plasma levels decreased significantly, at the same time high EGCG levels were found in CAPD lavage fluid. (F) July 2009: transurethral prostatectomy with further decrease EGCG levels. (G) Dosage correction to 900 mg EGCG t.i.d. + 200 mg vitamin C + 20 mg piperine. (H) November 2009: second transurethral prostatectomy and concurrent peritonitis. Further dosage correction with 450 mg EGCG t.i.d. + 200 mg vitamin C + 10 mg piperine. (I) April 2011: final dosage optimizing with 600 mg EGCG t.i.d. + 200 mg vitamin C + 1000 mg omega-3 fatty acids from salmon each time. No significant changes in FCL or INR were observed across the timeline. A significant decrease in IVS thickness under EGCG therapy could be documented.