Study: Effect of EGCG on the liver function in women of childbearing age

reference

Siblini H, al-Hendy A, Segars J, et al. Evaluation of the hepatic security of Epigallocatechingallat (EGCG) in women of childbearing age.Nutrients. 2023; 15 (2): 320.

Study goal

To find out whether the daily administration of 720 mg epigallocatechingallat (EGCG) on women over the duration of their menstrual cycle (at least 30–35 days) would have an impact on their liver enzymes or overall picture.

Key to take away

There was no evidence that EGCG had an impact on the results of serum tests used to identify acute liver oxicity reaction (alanintranaminase (old), aspartat transformaminase (AST) or overall bilder tubin).

design

Interventional, randomized, controlled study

Participant

39 women of childbearing age (18–40 years) took part in the study, either with or without uterine myoma. The ethnic groups included 59 % white, 12.8 % black, 20.5 % Asians and 2.6 % native islanders, with 2 participants (or 5.1 %) rejected an answer. 36 women completed the study, two broke off the study voluntarily and a follow -up examination.

Participants were divided into three arms: Arm 1 contained EGCG only (n=16), Arm 2 contained EGCG + clomiphene citrate (n=11), and Arm 3 contained EGCG + letrozole (n=12).

Exclusion criteria included hormonal contraception, alcohol consumption (more than 14 drinks per week), and liver disease (historical or current). Twelve of the subjects had a diagnosis of uterine fibroids; 2 were diagnosed with endometriosis.

intervention

After the first intake, all subjects started intervention. The intervention consisted of 4 capsules with 400 mg green tea-over-the-fed extract (GTE) with 45 % (180 mg) EGCG, which were taken for breakfast once a day during the entire study. Between cycle days 2 and 5, arms received 2 and 3 5 daysClomiphene citrate(100 mg/day) or letrozole (2.5 mg/day).

Evaluated study parameters

Each subject in this study had a total of five visits, including the intake visit. Liver function (serum ALT, AST, direct/total bilirubin) and folic acid were measured at screening and at visits 1, 2, and 4. The study assessed adverse events and endometrial thickness using midcycle pelvic ultrasound.

Primary end point that the study should rate

Change in AST/ALT/total and direct bilirubin

Most important knowledge

There was no evidence of elevation in liver function tests that were considered significant (based on ALT or AST ≥ 3 × upper limit of normal (ULN) or bilirubin ≥ 2 × ULN). There were no differences within any arm or between arms.

transparency

This study was funded by several grants listed as “Eunice Kennedy Shriver Institute of Child Health and Human Development (Nichd), R01 HD100365 (Johns Hopkins University), R01 HD100367 (University of Chicago and University of Illinois Chicago), R01 HD100369 (Yale University). " None of the authors have disclosed conflicts of interest.

Effects on practice

The first obvious limitation of this study is the time period over which these women were followed. This is not clear from the study, but it appears to be as little as 30 days and even 35 to 40 days. The study was designed to capture an acute liver toxicity event, as researchers only detected elevations in ALT and AST at three times the upper limit of normal and total bilirubin at two times the upper limit of normal. Many other studies with significantly better study designs and more participants have shown that longer-term follow-up is necessary to evaluate liver-related data.

The Minnesota Green Tea Trial is one such study. This was a controlled, randomized study involving 1,021 women who took 843 mg of EGCG or placebo daily for 12 months.¹

All of these individuals had normal baseline ALT/AST values. After 12 months, serum ALT increased by 5.4 U/L and AST increased by 3.8 U/L in the GTE arm of the study, significantly higher than in the placebo arm (both).P<0.001). Overall, 26 (5.1%) treated subjects demonstrated moderate or severe abnormalities in liver function tests.Seven out of twelve (58%) had experience serious adverse events related to ALT elevations.The probability relationship for the development of liver dysfunction was 7.0 (P=0.0002; 95% CI: 2.4-20.3) compared to placebo. The rise-fall pattern of liver enzyme levels followed a challenge-dechallenge-rechallenge cycle of GTE consumption, with no evidence present in the first 30 days of the study. However, in all these casesGTE could not be identified as the sole cause of an increase in liver enzymes, since they were all related to an simultaneous infection, taking new medication, alcohol consumption or a self -reported medical history with increased liver enzymes.

During this USP check from 2020, 25 different pesticides were found in green tea extract samples.

In 2018, Hu et al. a review of adverse side effects of green tea from 159 human intervention studies. Based on the 48 clinical trials that specifically examined liver injury, the incidence of hepatotoxicity was approximately 4.9%, calculated from elevated liver function biomarkers in 111 events in 2,269 subjects who consumed green tea preparations (including green tea, GTE, or individual catechins).²So this is clearly a problem, at least as far as some preparations examined.

In the study currently certified, it was found that this limited security study was initiated by a review of the United States Pharmacopeia (USP) from 2016, which was appointed a prescribed "warning identification declaration" for all manufacturers of powdered decaffeinated green tea extract and consequences in 2020 by a"Expert committee for hepatotoxicity of green tea extract."³ The committee found that there were some concerns and stated: "Published case reports of adverse events have associated hepatotoxicity with EGCG intake levels ranging from 140 mg to∼1000 mg/day and considerable inter -individual variability in susceptibility, possibly due to genetic factors. ”

The committee reviewed 331 relevant articles, including clinical studies, preclinical animal studies, and 75 cases of human hepatologic toxicity from green tea, catechins, polyphenols (i.e., EGCG), and green tea extract. The toxicology studies revealed contamination problems(solvent residues, pesticide residues, pyrrolizidine alkaloids and elemental impurities) or problems with the high EGCG concentrations in the final products.

Reviewers identified several potential sources of hepatotoxicity. First, alcohols or solvents (acetone or ethyl acetate) may be used to extract the catechins from green tea, resulting in residues in the final product. Secondly, the decaffeination process can use solvents – chloroform or dichloromethane, both of which can be present in the finished product. Third, the extraction process may increase the content of catechins, pesticide residues, toxic metals or pyrrolizidine alkaloids in the powdered extract.

A green tea extract, Exolise – an 80% ethanolic dry extract standardized to 25% EGCG catechins – reportedly caused liver damage and was banned in France and Spain in 2003. Both articles referenced are not available in English, so I was unable to access them to determine whether the injury may be due to high levels of catechins or impurities in the finished product.

Green tea as well as white and black tea have been shown to contain considerable organophosphate and organochlor pesticides, including DDE (dichlordiphenyldichlorethylene), the metabolites and the human fat storage form of DDT (Dichlordiphenyltrichlorethane). During this USP check from 2020, 25 different pesticides were found in green tea extract samples. There was no indication of whether one of them was grown under the editions of the USDA-Bio certification. While pesticide residues logically provide cause for concern, there were no cases of acute hepatotoxicity by GTE, which could be attributed directly to pesticide contamination. A pesticide contamination of green and black tea often occurs, and researchers assume that the extraction of the tea leaves for the production of GTE also extracts/concentrated.⁴

In the 2020 review study, several studies were identified in which the enrichment of hepatotoxic metals was found in green tea leaves, including arsenic, cadmium, chrome, copper, lead, mercury and manganese. Since none of the case studies have been searched for in the presumed products according to the presence of these metals, there is no information about metal contamination in reported cases of liver damage.

PPyrrolizidine alkaloids (PAS) are often found as contaminants in green tea, since neighboring plants with high concentrations of these alkaloids are harvested together. According to the review of 2020, it is unlikely that PAS will be the cause of events related to green tea hepatotoxicity.It is known that PAS cause a hepatic sinusob construction syndrome (also called hepatic venous closure disease) and not the hepatocellular damage that is observed in cases in connection with the GTE intake.

Despite the inconsistencies of the above studies, using organic green tea extracts and whole leaves tested for contaminants (metals, pesticides) seems to be a wise decision. And a conscientious doctor may want to ask the manufacturer for the actual data for this batch of products. If the manufacturer cannot provide transparency (related to the finished product, not the raw material), it may be wise to choose one that can.