High doses of green tea extract are associated with dozens of cases reported since 1999 in the Drug-Induced Liver Injury Network, according to studies in the Annals of Internal Medicine and the European Journal of Clinical Pharmacology , noted Herbert Bonkovsky, the chief of hepatology at Wake Forest University School of Medicine.
In particular, epigallocatchin gallate (EGCG) – the most abundant, active and toxic catechin in green tea – appears to be the culprit when it is highly concentrated in extracts, Bonkovsky explained at a May 4 workshop on liver injury from herbal and dietary supplements hosted by the National Institutes of Diabetics and Digestive and Kidney Diseases and the American Association for the Study of Liver Disease.
For support, Bonkovsky pointed to an analysis that found a catechin was in 51% of the 97 different herbal and dietary supplements associated with liver damage cases listed in the Drug-Induced Liver Injury Network database.
He acknowledged that the mere presence of catachins in the supplements does not establish a causal connection, but noted they were a primary and concentrated ingredient in many of the cases.
He also pointed to a case on which he worked that involved a middle-aged woman who suffered liver damage while taking a weight loss supplement with 383.3 mg of green tea extract per each three capsule serving. The connection between her condition and the supplement was not made during her first hospital admission, but it was when she was readmitted a year later after she resumed taking the supplement.
“I consider this about as strong of evidence as we get in the field, mainly because it was a positive re-challenge of acute hepatitis due to the same dietary supplement,” he said.
In addition, data from experimental mouse models “establish beyond a reasonable doubt that EGCG is an intrinsic hepatotoxin,” Bonkovsky said. He noted the models showed evidence of acute liver injury and necrosis in mice within 24-48 hours of being exposed to high doses of EGCE.
A mechanism of action
While the connection between liver damage and high amounts of EGCE are clear to Bonkovsky, he acknowledged that mechanism of action remains elusive, although recent research is “beginning to give us some clues.”
For example, he pointed to research published in 2014 that showed EGCG binds and inhibits respiratory complexes in swelling, but not normal rat hepatic mitochondria.
Additional research based on mice and human genetic analysis suggest people may be more susceptible to liver damage from high doses of green tea extract if they have an over representation of certain genes, including period circadian clock 3, mitofusin 2 and vacuolar protein sorting 13 homolog 7.
These discoveries are worth additional research, he added.
The good news
While these developments are bleak for supplements with high doses of green tea extract, those with low or moderate levels appear to be safe, according to the research. And certainly drinking several cups of regular green tea daily is fine, Bonkovsky said.
He also acknowledged recent studies that support the efficacy of moderate doses to improve fat oxidation, body composition and performance. A study in January’s Journal of the International Society of Sports Nutrition found healthy active men who took green tea extract equal to about six or seven cups of tea per day experienced a 25% increase in fat oxidation, compared to no change in the men who took the placebo.
This study followed a previous mouse study published in 2014 that found green tea extract and exercise can reduce body mass almost 30%, abdominal fat almost 40% and improve fasting blood sugar and insulin levels.
The juxtaposition of these findings and the dangers detected in research focused on high doses suggest that, as is the case with most things, moderation is the key, Bonkovsky concluded.