Green Tea Extract (EGCG)

Epigallocatechin-3-gallate — a chemopreventive polyphenol with important targeted-therapy interactions

Key Points

• EGCG is the most abundant and biologically active catechin in green tea (Camellia sinensis), studied mainly for chemoprevention rather than treatment of established cancer.
• Best clinical signal is in premalignant conditions: RCT data show reduced progression of high-grade prostate intraepithelial neoplasia and oral leukoplakia.
• EGCG directly binds and inactivates the proteasome inhibitor bortezomib — green tea can abolish bortezomib efficacy and must be avoided in myeloma patients on that drug.
• Modulates CYP and UGT enzymes and can affect levels of drugs like tamoxifen, irinotecan, and some TKIs; also reduces oral bortezomib and can lower plasma levels of nadolol.
• High-dose green tea extract supplements (not brewed tea) have been linked to idiosyncratic hepatotoxicity — a genuine safety concern distinct from drinking tea.
• Cardioprotective and metabolic benefits are relevant to survivorship, but concentrated extract supplements carry risks that brewed tea does not.

Background and Mechanism

Green tea (Camellia sinensis) is rich in catechins, of which **epigallocatechin-3-gallate (EGCG)** is the most abundant and pharmacologically active. EGCG has one of the broadest preclinical anticancer mechanistic profiles of any dietary polyphenol: - **Pro-apoptotic / anti-proliferative:** inhibits EGFR and HER2 receptor signaling, downregulates PI3K/Akt and MAPK pathways, and induces cell-cycle arrest. - **Anti-angiogenic:** suppresses VEGF expression and endothelial proliferation. - **Antioxidant and epigenetic:** scavenges reactive oxygen species and inhibits DNA methyltransferase…

Clinical Evidence

The strongest clinical evidence is in **chemoprevention of premalignant lesions**, not treatment of established cancer. **Prostate:** A double-blind RCT (Bettuzzi et al., Cancer Res 2006; n=60 men with high-grade prostatic intraepithelial neoplasia) found that green tea catechins 600 mg/day reduced progression to prostate cancer over 1 year (3% vs 30% in placebo). A later larger US trial (Kumar et al., 2015) showed a favorable but non-significant trend, tempering the initial enthusiasm. **Oral Leukoplakia:** RCTs of green tea extract have shown improved clinical response and reduced lesion…

Safety, Hepatotoxicity, and Critical Drug Interactions

**The bortezomib interaction is the single most important clinical point.** EGCG directly reacts with the boronic-acid group of bortezomib, forming an inactive complex and abolishing its proteasome-inhibitory (and therefore anti-myeloma) activity in vitro and in animal models (Golden et al., Blood 2009). Any patient receiving bortezomib — and by extension other boronic-acid proteasome inhibitors — should avoid green tea and EGCG supplements entirely. **Hepatotoxicity:** Concentrated green tea extract supplements have been causally linked to idiosyncratic, occasionally fulminant…

Clinical Applications

**Chemoprevention discussions:** For patients with high-grade PIN, oral leukoplakia, or a history of colorectal adenomas, green tea (brewed, or standardized extract with attention to hepatotoxicity risk) is a reasonable evidence-informed option to discuss. **Survivorship:** Regular brewed green tea intake fits within a broadly cardioprotective, anti-inflammatory dietary pattern and is generally safe. **Counseling points:** (1) Absolute avoidance with bortezomib; (2) prefer brewed tea over high-dose extract supplements; (3) if using an extract, take with food, keep EGCG well below 800 mg/day,…