Palermo, CM, JI Martin Hernando, SD Dertinger, AS Kende and TA Gasiewicz. 2003. Identification of Potential Aryl Hydrocarbon Receptor Antagonists in Green Tea. Chemical Research in Toxicology 16:865-872.

Many signs have pointed to green tea's beneficial impact for health, including multiple studies with animals and hints that green tea drinkers and people living in green tea growing areas are less likely to develop cancer.

In this new study, Palermo and his colleagues probe deeply into one of the mechanisms suggested by previous research for how green tea might have beneficial effects. This suggestion is that plant compounds in green tea interfere with a specific molecular action of dioxin, preventing it from turning on genes that are involved in causing cancer.

Reported in this publication in Chemical Research in Toxicology, their results confirm this earlier work and identify the specific plant compounds most likely to be responsible for green tea's action at suppressing gene activation.

The scientists remain uncertain about whether their findings reveal the way green tea has beneficial health effects, however. Their results indicate that the concentrations of the active compounds required to work against dioxin via this mechanism are high compared to the levels reached in people's blood after drinking green tea.

A number of chemical contaminants cause their damaging effects through the molecular pathway that green tea shuts down, including dioxins, some PCBs, and some polycyclic aromatic hydrocarbons among others, contaminants that are virtually ubiquitous. Hence this line of research offers some promising possibilities for preventing diseases. Given how much remains to be learned and confirmed about this, however, long-term prospects for developing chemical treatments to prevent diseases shouldn't diminish efforts to reduce and eliminate exposures in the first place.

What did they do? Palermo et al. experimented with mouse cells that had been altered genetically to make it possible to measure when and how much a specific gene was turned on via a pathway known to be activated by dioxin and related compounds, a pathway that begins with dioxin binding with the Ah (aryl hydrocarbon) receptor. The techniques they used are standard, widely employed for this type of research.

They first exposed the mouse cells to dioxin, and then added varying amounts of green tea extract (made by brewing Lipton Green Tea for 20-30 minutes). This round of research confirmed the extract's ability to suppress dioxin gene activation (see part one, below).

They then used some tools out of analytical chemistry to separate the crude extract into different components, as the crude is a complex mixture of multiple plant compounds. That separation then allowed them to confirm the identity of the components.

For the next round of experiments, they bought commercial versions of the identified components and performed a series of experiments with these pure substances, and mixtures thereof. The experiments again looked at whether or not different concentrations of the compounds interfered with dioxin-mediated gene activation.

What did they find?
Part one: Work with the Lipton green tea extract showed that as the concentration of the extract was increased, gene activation decreased.

The graph to the right compares the percent of dioxin-induced gene activation without green tea extract (GTE), the left-most point on the curve, with what happens as GTE is increased from 0 to 100 µg/ml. Between 10 and 100 µg/ml, gene activation starts to drop sharply. GTE clearly suppresses gene activation by dioxin at higher levels. Polyphenon 100 is a commercially-available mixture of green tea extracts.

Part two: The separation analysis revealed that the principal constituents of their green tea extract were a series of plant compounds called catechins, including EGCG (epigallocatechin-3-gallate), EGC (epigallocatechin) and ECG (epicatechin-3-gallate). EGCG was the most abundant catechin in the extract, amounting to 50%-80% of the total.

When they tested effect of the different components of green tea extract, 4 of 5 showed a substantial impact (graph to left). Of those 4, however, only two reached high enough concentrations in green tea extract to be likely to play a role in green tea's overall effect, EGCG and EGC (The data on relative abundance in extract are not shown).

Part three: The research team conducted a series of additional tests in an effort to eliminate other interpretations of how plant compounds from green tea extract reduced dioxin's impact on gene expression. Each of these tests provided support for the theory that green tea extracts, in the experimental system they used, interfered with the chain of molecular events that allow dioxin to activate genes by interacting with the Ah receptor.

What does it mean? Most of these results provide support for the idea that people drinking green tea may benefit from the plant compounds' inteference with gene activation via the Ah receptor. That pathway is one of the main molecular mechanisms for toxic effects of dioxin and related compounds.

The principal argument against this conclusion is that the concentrations of the compounds necessary to cause a reduction in gene activation are much higher than what can be measured in people's blood after drinking green tea. Note in the graphs above that the percentage of gene activation does not begin to fall until concentrations are between 10 and 100 µg/ml. Direct measurements in people's blood, in contrast, typically are less than one-tenth this amount.

In evaluating that argument, Palermo et al. pointed to two considerations

• First, green tea is a complex mixture of many components, only a few of which they tested in these experiments. Additive and synergistic effects might dramatically alter the impact of low levels of the plant compounds. Mixtures are proving important for many toxicological analyses.
• Second, an impact through the Ah receptor is only one of many possible biochemical routes by which green tea might have health benefits. Their results provide biochemical support for one pathway, but in no way exclude other possibilities.

In sum, this study adds to a growing body of evidence indicating that drinking green tea brings significant health benefits. It suggests that additional work will further refine what we understand about exactly how green tea has that effect, and this deeper knowledge may point to treatments that prevent cancers even in the face of continuing exposures to dioxins and related compounds.

Given how far we are from certainty about these findings, however, continued investments in exposure reduction remain vitally important.