EGCG
Epigallocatechin-3-gallate, the principal catechin of green tea
Written by Aaron CuhaReviewed Sep 2026
Also known as: Epigallocatechin gallate, EGCg, Polyphenon E (standardised preparation)
A phase 2 trial of 800 mg EGCG a day in multiple sclerosis was stopped by its data safety monitoring board after 5 of 7 participants on treatment developed abnormal liver function tests, one of them grade III. The largest efficacy trial, 84 young adults with Down's syndrome over twelve months, found no significant difference on 13 of 15 cognitive tests.
Overview
This page covers the isolated molecule and the standardised high-dose preparations built around it. The whole-extract question, including the mouse lifespan test and the weight loss literature, is covered separately on this site under green tea extract, and the two pages are meant to be read together.
EGCG is the catechin that everything else in green tea gets credited to, and at supplemental doses it has produced the most informative safety result in this entire batch. A phase 1 futility study of Polyphenon E, a standardised preparation that is 50 percent EGCG, gave 800 mg of EGCG a day to ten people with multiple sclerosis; one discontinued for grade I liver function abnormalities, and the study rejected its futility endpoint, with brain N-acetyl aspartate adjusted for creatine rising 10 percent. The phase 2 randomised trial that followed enrolled thirteen and was stopped by the data safety monitoring board because 5 of 7 participants taking Polyphenon E had abnormal liver function tests, one grade III, at a median of 20 weeks. Only two people reached the six-month visit, so the neuroprotection endpoint could not be analysed at all. The authors' own classification is Class I evidence that some lots of Polyphenon E have a high risk of hepatotoxicity.
That is an unusually clean statement of a liver signal, and it is worth reading next to what happened on the efficacy side. The TESDAD trial, the largest randomised test of EGCG for a clinical outcome, gave 9 mg/kg per day for twelve months alongside cognitive training to young adults with Down's syndrome. Eighty-four people were analysed. Differences between groups were not significant on 13 of the 15 tests in the trial's own cognitive battery and on eight of nine adaptive skills. Four measures did reach significance, and phase 3 trials were called for.
So the record on the isolated molecule is: a genuine and dose-related hepatotoxicity signal, documented well enough that a safety board acted on it, and an efficacy record that is mostly null tests with a few significant ones inside large batteries.
Mechanism of action
A polyphenolic catechin with a galloyl group that gives it high antioxidant activity in vitro and lets it bind a wide range of proteins non-specifically, which is why the mechanism literature for it is enormous and unfocused. Documented activities include inhibition of DYRK1A, the chromosome 21 kinase that motivated the Down's syndrome trials, NRF2 pathway activation, and effects on laminin receptor signalling. The liver injury mechanism is not established. It is dose-related in trials and more frequent when concentrated preparations are taken fasted. A secondary genetic analysis of a separate one-year trial found that carriers of a UGT1A4 variant had roughly two to three times the rise in alanine aminotransferase of non-carriers, which points at differences in catechin glucuronidation capacity rather than at a single toxic metabolite.
Human evidence
Substantial and unusually informative about harm. The trials that measured liver enzymes found a dose-related signal strong enough to stop one study and to trigger a formal European regulatory opinion. The trials that measured clinical outcomes mostly did not find them.
- Multiple sclerosis phase 2, 800 mg EGCG a day: stopped by the data safety monitoring board, 5 of 7 on treatment with abnormal liver function tests, one grade III, median onset 20 weeks.
- Multiple sclerosis phase 1, same dose, ten people: futility endpoint rejected, brain N-acetyl aspartate adjusted for creatine up 10 percent, one discontinuation for liver enzymes.
- TESDAD, 84 young adults with Down's syndrome, 9 mg/kg per day for 12 months: not significant on 13 of 15 cognitive tests and 8 of 9 adaptive skills; significant on visual recognition memory, two inhibitory control measures and functional academics.
- Minnesota Green Tea Trial, 1,075 women, 843 mg EGCG a day for one year: ALT elevation 6.7 against 0.7 percent, and 1.3 percent with an ALT-related serious adverse event.
- EFSA 2018: supplemental doses at or above 800 mg EGCG a day raise transaminases significantly; brewed tea at usual intakes does not carry the signal.
- No human trial has measured lifespan, mortality or any ageing endpoint with EGCG.
What this does not tell you: The neuroprotection signal in multiple sclerosis rests on ten people in an uncontrolled phase 1 and on a surrogate imaging measure, and the randomised test of it was never completed because the trial was stopped for safety. In TESDAD the significant results sit inside a battery of 24 measures, and the trial itself calls for phase 3 confirmation that has not been reported here. None of this speaks to what happens to a healthy person taking EGCG for years.
Reading the research record
The site publishes a separate entry for green tea extract as a whole, covering the mouse lifespan test, the Gehan reanalysis and the weight loss literature. Nothing on this page contradicts it, and the two share the Minnesota trial and the EFSA opinion deliberately, because those are the two documents that set the dose threshold for the liver signal.
What this page adds is the isolated-molecule picture, and the reason it matters is that people take EGCG capsules at doses no tea drinker reaches. The trial stopped by its safety board is the single most useful fact available about this compound, and it has a detail that supplement buyers should sit with: the phase 1 and phase 2 participants took capsules from different manufacturing lots with similar EGCG content but different levels of minor catechins, and the investigators could not explain the difference in liver injury by EGCG plasma levels. Whatever caused it, it was not captured by the number on the label.
A surrogate endpoint is a measurement that stands in for the thing you care about, on the assumption that moving it moves the outcome. That assumption has failed often enough to be treated as a claim rather than a given. Homocysteine is the canonical case: it predicts cardiovascular disease strongly in observational data, it can be lowered reliably by several cheap interventions, and when trials lowered it and then counted heart attacks, the events did not fall. The lesson is not that markers are worthless. It is that a trial reporting a marker has answered a smaller question than the one the buyer is asking, and the page should say which question was answered.
The evidence, charted
Fig. 1 · evidence composition
3of 4 citations (75%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 3 distinct years, 2015 to 2018, counted from the citation list on this page. The newest citation on file is from 2018, more than five years ago; the published record may have gone quiet.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four jurisdictions shown. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Human2015
Polyphenon E, non-futile at neuroprotection in multiple sclerosis but unpredictably hepatotoxic: Phase I single group and phase II randomized placebo-controlled studies.
Phase 1: ten people with multiple sclerosis on 800 mg EGCG a day for six months, one discontinued for grade I liver function abnormalities, futility endpoint rejected with N-acetyl aspartate adjusted for creatine up 10 percent. Phase 2: thirteen enrolled, twelve started, and the data safety monitoring board stopped the study because 5 of 7 on Polyphenon E had abnormal liver function tests, one grade III, at a median of 20 weeks. Only two reached the six-month visit so the efficacy endpoint could not be analysed. Authors classify this as Class I evidence that some lots carry a high risk of hepatotoxicity. NIH funded; the manufacturer supplied drug and placebo and reviewed the manuscript.
Journal of the Neurological Sciences - Human2016
Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial.
87 adults aged 16 to 34 with Down's syndrome randomised to EGCG 9 mg/kg per day or placebo, both with cognitive training, for 12 months; 84 analysed. Differences were not significant on 13 of the 15 tests in the trial battery and on 8 of 9 adaptive skills. Significant gains appeared in visual recognition memory (6.23 percentage points), inhibitory control, and the ABAS-II functional academics score (5.49). No difference in adverse effects between groups. Registered as NCT01699711.
Lancet Neurology - Human2015
The safety of green tea extract supplementation in postmenopausal women at risk for breast cancer: results of the Minnesota Green Tea Trial.
1,075 postmenopausal women randomised to an extract delivering 843 mg EGCG a day or placebo for one year. Alanine aminotransferase elevation in 36 women on extract (6.7 percent) against 4 on placebo (0.7 percent), p < 0.001, with 1.3 percent having an ALT-related serious adverse event. Overall adverse event rates were similar, 75.6 against 72.8 percent, with more nausea and skin events on extract. US National Cancer Institute funded.
Food and Chemical Toxicology - Review2018
Scientific opinion on the safety of green tea catechins.
European Food Safety Authority panel opinion. Catechins from traditionally brewed green tea are safe at reported intakes, while interventional trials show that supplemental doses at or above 800 mg EGCG a day produce a statistically significant increase in serum transaminases compared with control. Supplements provide between 5 and 1,000 mg EGCG a day; high-level tea drinkers reach up to 866 mg a day.
EFSA Journal
Frequently asked questions
How much EGCG is too much?
The European Food Safety Authority set the threshold at 800 mg a day from supplements, above which interventional trials show a statistically significant rise in liver transaminases. Brewed green tea at normal intakes does not carry that signal; EFSA estimates typical drinkers get 90 to 300 mg a day and heavy drinkers up to 866 mg. The multiple sclerosis trial that was stopped for liver injury used exactly 800 mg a day.
Why was the multiple sclerosis trial stopped?
The data safety monitoring board halted it because 5 of the 7 participants taking Polyphenon E developed abnormal liver function tests, one of them grade III, at a median of 20 weeks. Only two people reached the six-month visit, so the trial could not answer its own efficacy question. The authors classified it as Class I evidence that some lots carry a high risk of hepatotoxicity.
Did EGCG improve cognition in Down's syndrome?
Partly, and less than the headlines suggested. In 84 young adults over twelve months, differences were not significant on 13 of the trial's 15 cognitive tests and on eight of nine adaptive skills. Visual recognition memory, two inhibitory control measures and one adaptive behaviour score did improve significantly. The authors called for phase 3 trials to confirm it.
Is EGCG an anti-ageing compound?
No human trial has measured any ageing endpoint with it. The lifespan evidence concerns whole green tea extract in mice and is covered on this site's green tea extract entry, where the protocol log-rank test found no effect in either sex and a later reanalysis found a 7 percent female median gain confined to midlife.
Is taking it with food safer?
The pattern in the case report literature and in the US Pharmacopeia's review of green tea products is that concentrated preparations taken on an empty stomach are more likely to cause harm than the same product taken fed. That is an observation about risk pattern, not a demonstrated protective measure, and it does not remove the dose threshold.