Green Tea as a Pro-oxidant: Too Much of a Good Thing?

Is too much green tea harmful for you? (Photo by tornado_twister)

I was browsing through the latest studies on green tea and came across a paper saying EGCG, one of the green tea polyphenols, increases protein cross-linking (link). I was intrigued, because this was the first time I'd heard of such an effect. The abstract also mentions that there's increasing evidence EGCG can generate reactive oxygen species and break DNA strands in biological systems. In effect, it says that the antioxidant is actually a pro-oxidant.

I looked up some of the references and indeed, even green tea's polyphenols (at least EGCG, possibly some others) have oxidative effects under certain in vitro conditions. For example, in human whole blood lymphocytes, EGCG either suppresses or induces DNA strand breakage, depending on the concentration.

In concentrations between 0.01-10 μM (micromoles/L), strand breakage decreases, but once the concetration gets higher than 1000 μM, it increases instead. In purified blood lymphocytes, concentrations of 1-100 μM induce and concentrations of 0.01-0.1 μM suppress DNA strand breakage.

Sounds an awfully lot like hormesis, doesn't it? As with everything, the dose makes the poison. The interesting part, of course, is whether drinking green tea can cause similar harmful effects in real life.

Luckily, one study looked at the effect of green tea on DNA strand breaks in rats (link). The smaller dose (which according to the authors is equivalent to one desiliter of green tea in humans) had no effect, but the larger dose (equivalent to half a liter) significantly reduced strand breaks.

Half a liter of green tea, equal to about three cups, increase total plasma antioxidant capacity only moderately. When only EGCG is taken into account, the results vary somewhat from study to study, but concentrations rarely exceed 1 μM (link). Also, plasma antioxidant activity has a plateau, which suggests that the absorption mechanism of green tea polyphenols becomes saturated after a certain point:

To make the tea used in the study, 500 ml of boiling water was poured on 20 grams of green tea leaves (8-10 tea bags), and the tea was then allowed to infuse for 10 minutes. That makes for a very strong tea, much stronger than the ones used in the other studies. The volunteers drank 300-400 ml of the tea, after which blood samples were collected at different time intervals

In this study, there was no difference between those who drank 300 and 400 ml of the tea. Even then, the increase in antioxidant activity was only 4% at the peak. Thus, it seems unlikely that harmful levels could be reached by simply drinking plenty of green tea. In one Asian population, 10 cups of green tea daily reduced total mortality compared to those who drank less green tea and/or smoked.

Theoretically at least, extracts and supplements could be a different matter, because they often contain a higher percentage of EGCG than green tea and come with things that increase absorption. For example, piperine increases plasma levels of EGCG.

One green tea extract containing 40% EGCG resulted in a peak  of 0.8 μg/mL in human subjects; when the same extract was complexed with phospholipids, the peak was 1.9 μg/mL. If my calculations are correct (which they often aren't; please correct me if I'm wrong), then these would be ~1.75 μM and ~4.14 μM, respectively. Again, in whole blood lymphocytes concentrations between 0.01-10 μM, strand breakage was decreased, and it took concentrations higher than 1000 μM to increase strand breakage.

All in all, it appears that green tea in reasonable quantities (at least up to 10 cups) does not cause it to act as an oxidant in vivo. It's unknown what a much higher amount would do, assuming you could somehow bring yourself to drink 50 cups. I haven't seen any human studies on such amounts. But if the plateau effect is indeed true, then you might not be able to reach high plasma levels of EGCG no matter how much you drink.

With supplements, the situation is different. Piperine and phospholipids make reaching higher plasma values possible, which can be a good thing or a bad thing, depending on what you're using the supplements for. Some conditions require higher doses than others, so you'll have to judge the proper approach on a case by case basis. However, since EGCG does have the potential of being a pro-oxidant in vitro and is toxic to the liver in very high amounts, be careful not to overdo it with green tea supplements.

For more information on green tea and health, see these posts:

Green Tea Protects from the Psychological Effects of Stress in Rats
Tea, Coffee and Cocoa: All Good for Your Teeth
Green Tea and Capsaicin Reduce Hunger and Calorie Intake
Green Tea Catechin Reverses the Effect of DHT in Prostate Cancer Cells