EGCG Health Benefits and Side Effects
Introduction

The compound (-)-epigallocatechin-3-gallate (EGCG) is the major catechin found in green tea [Camellia
sinensis L. Ktze. (Theaceae)]. This polyphenolic compound and several related catechins are believed to be
responsible for the health benefits associated with the consumption of green tea. Increasing evidence has
suggested that EGCG exhibits anti-inflammatory, anti-oxidant and immunosuppressive effects. [4] The
potential health benefits ascribed to green tea and EGCG include antioxidant effects, cancer
chemoprevention, improving cardiovascular health, enhancing weight loss, protecting the skin from the
damage caused by ionizing radiation, and others. [6]

Research Studies about The Health Benefits of (-)-epigallocatechin-3-gallate (EGCG)


EGCG MAY BENEFIT BONE HEALTH
Researchers from University of Toronto proposed the benefits of epigallocatechin-3-gallate (EGCG)on bone
health. In the study, epigallocatechin-3-gallate (EGCG)at concentrations of 1-5 muM caused a
dose-dependent increase in the number and area of mineralized bone nodules. [1]

EGCG MAY HAVE BENEFITS IN DIABETES
Researchers from University of Dundee, Scotland commented the insulin-like glucose-lowering properties of
epigallocatechin gallate (EGCG) in mammals. EGCG is known to act at least in part by repression of
gluconeogenic genes such as phosphoenolpyruvate carboxykinase. Their study shows EGCG exerts its
insulin mimetic effects at least in part by phosphorylation of the FOXOs through a mechanism that is similar
but not identical to insulin and IGF-1 induced FOXO phosphorylation.

Researchers from other group administrated rats with subtotal nephrectomy plus streptozotocin injection
with(-)-epigallocatechin 3-O-gallate (ECGG). After a 50-day administration period, EGCG treated groups
showed suppressed hyperglycemia, proteinuria, and lipid peroxidation, though there were only weak effects
on the levels of serum creatinine and glycosylated protein. These results suggest that EGCG ameliorates
glucose toxicity and renal injury, thus alleviating renal damage caused by abnormal glucose
metabolism-associated oxidative stress involved in renal lesions of diabetic nephropathy. [8]

EGCG MAY HAVE BENEFITS IN CANCER
There are lots of studies suggesting epigallocatechin gallate (EGCG) or green tea may benefit people at risk
of hormone-related cancers, such as breast and prostate cancers.  Studies using both hormone responsive
and non-responsive cell lines have shown that EGCG induced apoptosis and altered the expression of cell
cycle regulatory proteins that are critical for cell survival and apoptosis. [3]

In a study, pretreatment of HEY and OVCA 433 ovarian carcinoma cell lines with green tea and EGCG
inhibited endothelin-1/ET(A)R expression, endothelin(A)R-mediated COX-1/2 mRNA expression, and COX-2
promoter activity. These effects were associated with a significant reduction in the COX-1/2-derived
prostaglandin E2 (PGE2) production. Thus, EGCG may have benefits in ovarian carcinoma. [12]

Later, Spinella F and co-workers further suggested that EGCG inhibited ovarian cancer cell growth and
induced apoptosis that was associated with a decrease in Bcl-X(L) expression and activation of caspase-3.
Treatment with green tea or EGCG inhibited endothelin A receptor (ET(A)R)/endothelin-1 (ET-1) expression
and reduced the basal and endothelin-1-induced cell proliferation and invasion. [10]

Tan M and co-workers at University of Mississippi proposed the direct administration of EGCG alone or in
combination with thymoquinone can limit PANC-1 cell proliferation in their in vitro studies. [10]

Researchers from Harvard Medical School evaluated the potential health benefits of (-)-
epigallocatechin-3-gallate (EGCG) in multiple myeloma (MM). Basically, they found that EGCG induced both
dose- and time- dependent growth arrest and subsequent apoptotic cell death in multiple myeloma cell lines
including IL-6 dependent cells and primary patient cells; without significant effect on the growth of peripheral
blood mononuclear cells (PBMC) and normal fibroblasts. [11]

Researchers from Soochow University, China, demonstrated the inhibition of EGCG on lung-tumor promotion
and oxidative stress caused by administration of dimethylarsinic acid (DMA(V)) in mice. [A3]

EGCG MAY HAVE BENEFITS IN INFLAMMATIONS

HEPATITIS
Researchers pretreated mice with (-)-Epigallocatechin-3-gallate (EGCG) before concanavalin A injection,
and then measured alanine aminotransferase (ALT) levels in plasma, inflammatory infiltration and
hepatocyte apoptosis in liver. They found that mice pretreated with EGCG exhibited much less increased
ALT levels in plasma, reduced inflammatory infiltration and hepatocyte apoptosis in liver compared with
control mice pretreated with vehicle solutions.[4]

ARTHRITIS
Ahmed S and colleagues at University of Michigan Medical School found that EGCG was nontoxic to RA
synovial fibroblasts and  treatment with EGCG may be of potential benefits in inhibiting joint destruction in
rheumatoid arthritis. [6]

EGCG MAY HAVE BENEFITS IN NEURONAL DISORDER
Huntington's disease is a progressive neurodegenerative disorder for which only symptomatic treatments of
limited effectiveness are available. Preventing early misfolding steps and thereby aggregation of the
polyglutamine (polyQ)-containing protein huntingtin (htt) in neurons of patients may represent an attractive
therapeutic strategy to postpone the onset and progression of such disease. Here, researchers
demonstrated that polyphenol (-)-epigallocatechin-3-gallate (EGCG) potently inhibits the aggregation of
mutant htt exon 1 protein in a dose-dependent manner. [5]

Individuals with partial HSA21 trisomies and mice with partial MMU16 trisomies containing an extra copy of
the DYRK1A gene present various alterations in brain morphogenesis. They present also learning
impairments modeling those encountered in Down syndrome. Researchers from Université Paris Diderot,
France, claimed that green tea extract-epigallocatechin gallate (EGCG) is a specific and safe DYRK1A
inhibitor. [A2]


EGCG MAY HAVE BENEFITS IN ANXIETY
Vignes M and co-workers at University of Montpellier II, France observed that (-)-epigallocatechin gallate
(EGCG) reversed GABA(A) receptor negative modulator methyl beta-carboline-3-carboxylate (beta-CCM)
inhibition on GABA currents in a concentration dependent manner. Behavioral tests in mice indicated that
EGCG exerted both anxiolytic and amnesic effects just like the benzodiazepine drug, chlordiazepoxide. [7]

EGCG MAY HAVE BENEFITS IN FUNGAL DISEASES
Japanese compared the antifungal activities of epigallocatechin 3-O-gallate (EGCG)with six antifungal
agents, amphotericin B (AMPH), fluconazole (FLCZ), flucytosin (5FC), itraconazole (ITCZ), micafungin
(MCFG), and miconazole (MCZ)and concluded that EGCG has a comparable antifungal actvities on some
strains than some of these antifugal agents. [9]

Recent Findings:

Researchers from University of Bari, Italy, demonstrated the vaso-relaxation in ophthalmic arteries with
endothelium-intact via the activation of the NO/cGMP signalling pathway via NO-mediated relaxant
responses. [A1]

Researchers from Wuhan University demonstrated EGCG has a strong effect against influenza A H1 N1
virus in vitro and in vivo, in a dose-dependent manner. {A5].

Do not overdose yourself with green tea (extracts). Researchers from University of Science and
Technology of China, Hefei, Anhui, reported EGCG has pro-oxidant effects at high concentration. In their
study, EGCG caused a rapid elevation of intracellular free calcium levels in a dose-dependent way.
Exposure to EGCG dose- and time-dependently increased the production of reactive oxygen species (ROS)
and reduced mitochondrial membrane potential as well as the Bcl-2/Bax expression ratio. EGCG induced
hippocampal neuron death through the mitochondrion-dependent pathway.
I am not sure what side
effects we'll have, if we overdose ourselves with green tea (or its extracts) for a prolonged
period of time. [A4]

Are there any side effects or interactions of EGCG?

Green tea is generally free of side effects. However, large amounts of green tea consumption may lead to
insomnia, anxiety, and other symptoms caused by the caffeine content. It may also inhibit iron absorption.

On September 18, 2006, I found more than 500 scientific articles related to the health benefits of
epigallocatechin gallate.  I summarized only a few interesting of the most recent articles to demonstrate its
potential health benefits. Moreover, most of the studies are either in animals or in vitro.
--------------------


References [1] Vali B, et al, Epigallocatechin-3-gallate increases the formation of mineralized bone nodules
by human osteoblast-like cells. J Nutr Biochem. 2006 Sep 7[2] Anton S,et al, Epigallocatechin gallate
(EGCG) mimics insulin action on the transcription factor FOXO1a and elicits cellular responses in the
presence and absence of insulin.Cell Signal. 2006 Jul 25[3] Stuart EC et al, Role of epigallocatechin gallate
(EGCG) in the treatment of breast and prostate cancer.Life Sci. 2006 Aug 5 [4] Wang Y et al,
(-)-Epigallocatechin-3-gallate protects mice from concanavalin A-induced hepatitis through suppressing
immune-mediated liver injury.Clin Exp Immunol. 2006 Sep;145(3):485-92.[5] Ehrnhoefer DE, et al, Green tea
(-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in
Huntington's disease models.Hum Mol Genet. 2006 Sep 15;15(18):2743-51. Epub 2006 Aug 7.[6] Nagle DG
et al, Epigallocatechin-3-gallate (EGCG): Chemical and biomedical perspectives.Phytochemistry. 2006
Sep;67(17):1849-55. Epub 2006 Jul 31. [6] Ahmed S et al, Regulation of interleukin-1beta-induced
chemokine production and matrix metalloproteinase 2 activation by epigallocatechin-3-gallate in rheumatoid
arthritis synovial fibroblasts.Arthritis Rheum. 2006 Aug;54(8):2393-401. [7] Vignes M et al, Anxiolytic
properties of green tea polyphenol (-)-epigallocatechin gallate (EGCG). Brain Res. 2006 Jul 19. [8] Yamabe
N, et al, Therapeutic Potential of (-)-Epigallocatechin 3-O-gallate on Renal Damage in Diabetic Nephropathy
Model Rats.J Pharmacol Exp Ther. 2006 Jul 11. [9] Park BJ, et al, Antifungal susceptibility of epigallocatechin
3-O-gallate (EGCg) on clinical isolates of pathogenic yeasts.Biochem Biophys Res Commun. 2006 Aug
25;347(2):401-5. Epub 2006 Jun 15.[10] Spinella F et al, Green tea polyphenol epigallocatechin-3-gallate
inhibits the endothelin axis and downstream signaling pathways in ovarian carcinoma.Mol Cancer Ther. 2006
Jun;5(6):1483-92.[10] Tan M, et al, Effects of (-)epigallocatechin gallate and thymoquinone on proliferation
of a PANC-1 cell line in culture.Biomed Sci Instrum. 2006;42:363-71. [11] Shammas MA, et al, Specific killing
of multiple myeloma cells by (-)- epigallocatechin-3-gallate extracted from green tea: biological activity and
therapeutic implications.Blood. 2006 Jun 29. [12]Spinella F, et al, Antitumor effect of green tea polyphenol
epigallocatechin-3-gallate in ovarian carcinoma cells: evidence for the endothelin-1 as a potential target.Exp
Biol Med (Maywood). 2006 Jun;231(6):1123-7. [A1] Romano MR, Lograno MD. Epigallocatechin-3-gallate
relaxes the isolated bovine ophthalmic artery: Involvement of phosphoinositide 3-kinase-Akt-nitric
oxide/cGMP signalling pathway. Eur J Pharmacol. 2009 Feb 26. [A2] Guedj F, Sébrié C, Rivals I, Ledru A,
Paly E, Bizot JC, Smith D, Rubin E, Gillet B, Arbones M, Delabar JM. Green tea polyphenols rescue of brain
defects induced by overexpression of DYRK1A. PLoS ONE. 2009;4(2):e4606. Epub 2009 Feb 26.[A3] An Y,
Li Z, Wang S, Wang Z. Inhibition of (-)epigallocatechin gallate on dimethylarsinic acid promoting lung
tumorigenesis through the induction of oxidative stress in mice Wei Sheng Yan Jiu. 2008 Nov;37(6):748-50
[A4] Yin ST, Tang ML, Deng HM, Xing TR, Chen JT, Wang HL, Ruan DY. Epigallocatechin-3-gallate induced
primary cultures of rat hippocampal neurons death linked to calcium overload and oxidative stress. Naunyn
Schmiedebergs Arch Pharmacol. 2009 Feb 17. A5 Xiao X, Yang ZQ, Shi LQ, Liu J, Chen W. Antiviral effect of
epigallocatechin gallate (EGCG) on influenza A virus Zhongguo Zhong Yao Za Zhi. 2008
Nov;33(22):2678-82.
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