Green tea extract (GTE) does not appear to protect against colorectal adenoma recurrence, according to a study from Germany.
Preclinical, epidemiologic, and small clinical studies have suggested that GTE and its major active component, epigallocatechin gallate (EGCG), have antineoplastic effects in the colon and rectum.
But the new study found no statistically significant difference in adenoma recurrence in people who took GTE, standardized to 150 mg EGCG, twice daily for 3 years, relative to those who took matching placebo.
However, there was a suggestion of possible benefit in men but not women, which requires further study, Thomas Seufferlein, MD, with Ulm University Hospital, Baden-Württemberg, Germany, and colleagues write.
Their study was published online in The American Journal of Gastroenterology.
Largest trial to date
The MIRACLE trial (Minimizing the Risk of Metachronous Adenomas of the Colorectum With Green Tea Extract) included 879 adults aged 50-80 years. Participants had undergone removal of one or more histologically confirmed colorectal adenomas within 6 months prior to recruitment during colonoscopy, and there were no remaining colorectal adenomas.
There were 432 patients in the GTE group and 447 in the placebo group. Baseline characteristics were well balanced between the groups, and overall adherence to the study protocol was good.
After 3 years, adenomas were detected in 55.7% of participants in the placebo group and in 51.1% of those in the GTE group in the modified intention-to-treat population. This absolute difference of 4.6% in favor of GTE was not statistically significant.
The per protocol analysis also did not show a significant effect of GTE on new adenoma formation in the whole study population.
However, a preplanned subgroup analysis revealed a significant difference in the adenoma recurrence rate in favor of GTE in men but not women.
In men, GTE intake was associated with a significant 12.4% relative and 7.5% absolute reduction of metachronous adenomas, they report.
This potential gender-specific difference in chemoprevention “warrants further investigations,” the study team writes.
The safety profile of GTE as taken in this trial was good, with only grade 1/2 elevations in liver enzymes in the GTE group, compared with the placebo group. However, because the follow-up period was limited to 3 years, the long-term safety of GTE cannot be determined.
The researchers write that, to their knowledge, this study is the largest randomized trial to date of the effect of GTE on adenoma recurrence in a colorectal cancer screening population consisting of White patients.
Caveats and cautionary notes
Reached for comment, David Johnson, MD, professor of medicine and chief of gastroenterology at the Eastern Virginia School of Medicine, Norfolk, noted that “although the study showed no significant differences, the time horizon to show benefit may be longer than the 3-year duration of the study.”
“There are also methodologic issues with the readjustment of the target sample size, which may have led to a type II error, related to underpowering of the sample size,” said Dr. Johnson, who wasn’t involved in the study.
The researchers write that the study initially generated “great interest” and that many centers applied to participate. However, “quite a few” centers did not meet their promised recruitment targets and had to be replaced. Therefore, the statistical analysis plan had to be modified, and the number of participants had to be reduced over the course of the trial, they note.
Dr. Johnson also cautioned that while green tea is a popular drink, “there is strong evidence that green tea extract, found in many herbal and dietary supplements, is among the leading causes listed for drug-induced liver injury, including acute liver failure, urgent liver transplantation, and death.”
The study was fully funded by a grant from German Cancer Aid. The investigators and Dr. Johnson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.