Possible Controversy over Dietary Polyphenols:  Benefits vs Risks - Chemical Research in Toxicology

>Our laboratory has found two lines of evidence that suggest
that EGCG can induce oxidative stress in vivo. First, intraperitoneal
administration of EGCG resulted in the formation of
two cysteine conjugates of EGCG (EGCG-2¢-cysteine and
EGCG-2¢¢-cysteine) (17). These compounds were only formed
at toxic doses of EGCG (200 and 400 mg/kg ip), and we propose
that they arise from the formation of an EGCG quinone (Figure
1), which then reacts with the sulfhydryl group on cysteine and
likely other cysteine-containing molecules such as glutathione.
Second, treatment of lung tumor-bearing nude mice with either
daily injections of 40 mg/kg ip EGCG for 40 days resulted in
increased expression of phosphorylated histone 2AX (a marker
of DNA damage) and metallothionein (a marker of response to
oxidative stress) in the liver and tumors relative to vehicletreated
mice (Hou et al., unpublished results).

200 and 400 mg/kg are pretty high doses! Using the mouse to human dosage translation of (D*3)/37, that gives us 16mg/kg and 32mg/kg. That would be the equivalent of myself taking 1.3-2.6 grams of epigallocatechin gallate. Much higher than what most people take. I take at most 400mg.

___________________________________________________

>Despite several human studies that showed no toxicity of tea
polyphenol preparations and that the major adverse effects
associated with consumption of high doses of tea preparations
are due to gastrointestinal irritation, there have been a number
of recent case reports of hepatotoxicity related to the consumption
of high doses of tea-based dietary supplements (10-29 mg/
kg/day po) (18). In nearly all cases (eight out of nine), patients
presented with elevated serum alanine aminotransferase (ALT)
and bilirubin levels. In two of nine cases, periportal and portal
inflammation were observed. All cases resolved following
cessation of supplement consumption. A causative role for the
green tea preparations is suggested by the fact that reinjury was
observed following rechallenge with the same preparations. The
authors of these reports, however, could not conclusively rule
out the involvement of potentially hepatotoxic pharmaceutical
agents such as acetaminophen or other dietary supplements.

Again, these are really high doses, and they did not control for other hepatotoxic substances.

_____________________________________________________

Although there have been no reports of toxicity in human volunteers enrolled in intervention studies, careful monitoring of liver and kidney function is required until the risk of toxic events associated with tea catechins is established in humans.

I'm not trying to discount the possibility of increased reactive oxygen species or hepatotoxicity. However, I am not seeing conclusive evidence of it at reasonable therapeutic doses, yet.