Therapeutic use of tea derivatives: all that glitters is not gold

To the editor:

In 2 interesting articles published in the June 4, 2009 issue of Blood, attention was focused on the possibility for green tea derivatives to inhibit the therapeutic activity of bortezomib, an anticancer agent very effective in multiple myeloma and mantle cell lymphoma.^1,2  However, the interaction with boronic acid–based proteasome inhibitors is not the only important interaction between green tea and drugs. In fact, both green tea and black tea derivatives have been shown to modulate the activity of several drug metabolizing enzymes, and this effect could be responsible for undesired variations in plasma concentration of many drugs. Catechins, the main polyphenol constituents of green tea, inhibited the activity of the isoforms 3A4, 2A6, 2C19, and 2E1 whereas they increased the activity of the isoforms 1A2 and 2B of human and rodent cytochrome P-450 (CYP).^3-6  The inhibition by green tea of CYP3A4 could be harmful, particularly in case of prolonged consumption of this beverage. With regard to antineoplastic drugs, epigallocatechin-3-gallate (EGCG) augmented the toxicity of cyclophosphamide⁵  and doxorubicin⁷  likely because it increased the activity of rat and human CYP2B and NADPH-Cyt-P-450 reductase and the further formation of noxious by-products.^5,7  Also worthy of mention are the possible interactions between catechins and drugs that could be administered to cancer patients for the treatment of concomitant diseases. In fact, it has been shown that EGCG, by inhibiting both CYP3A4 and P-glicoprotein activities, increased the bioavailability of the calcium channel blockers verapamil and diltiazem,^8,9  thus raising the risk for patients to undergo atrioventricular block. The inhibition of CYP3A4 activity by green tea extracts could increase the plasma concentrations of midazolam⁴  and, therefore, amplify the risk of prolonged sedation. On the contrary, the up-regulation of CYP1A2 could result in reduced bioavailability of the antipsychotic drug clozapine.⁶  Furthermore, both green and black tea extracts inhibited the activity of the isoforms 1A1 and 1A3 of sulfotransferases,^10,11  a family of enzymes involved in the metabolism of drugs such as methyldopa or β2-adrenoceptor agonists, thus increasing their plasma concentrations and side effects. With regard to the plasma concentrations of EGCG in people drinking green tea, it is interesting to note that the values found by Chow and colleagues and quoted by Shah et al²  could be underestimated. In fact, Chow et al measured plasma EGCG after a single administration of green tea to healthy volunteers. Considering that catechins are metabolized by sulfotransferases and the latter is inhibited by the former,^10,11  catechin plasma concentration could significantly increase in people consuming a large amount of green tea.

Finally, the rationale for use of green tea as an adjuvant in cancer therapy has been contradicted by recent clinical studies that demonstrated the inconsistent effect of green tea in preventing the occurrence of esophageal, stomach, liver, colorectal, and breast cancers.^12,13  In our opinion, it is a matter of public health to refrain from providing people with confusing information about the unproven therapeutic potential of tea derivatives without consistent information on their toxicity.