TABLE 3.
Systematic reviews of risk assessment associated with flavan-3-ol intake1
| Author (year) | Study characteristics | Dose range | Key findings |
|---|---|---|---|
| Hu et al. (2018) (45) | Systematic review of human intervention studies of green tea and green tea extract preparations | Green tea: 96.3 to 1343 mg/d | Catechin-rich green tea preparations resulted in hepatic adverse events in a dose-dependent manner when ingested in large bolus doses, but not when consumed as brewed green tea or extracts in beverages or as part of food |
| 104 studies monitored and reported adverse events | Green tea extracts and purified EGCG: 29.5 to 4000 mg/d | Suggested safe intake level of 338 mg EGCG/d for green tea preparations ingested as a bolus dose | |
| 53 studies examined brewed green tea or green tea extract delivered in beverage form. Remaining studies examined green tea preparations administered as a solid dosage via capsules | An Observed Safe Level (OSL) of 704 mg EGCG/d for preparations in beverage form | ||
| Yates et al. (2017) (46) | Risk assessment using basic principles to establish an EGCG upper limit as described in the FAO/WHO Technical Report | Human intervention studies: 100 to 1600 mg/d EGCG | None of the studies in healthy or diseased patients reported adverse liver effects of EGCG at doses <600 mg/d |
| There were 10 animal studies, 27 human interventions, and 22 case reports | Higher doses (>600 mg/d) were associated with an elevation in liver enzyme activity within the normal range, whereas levels >800 mg/d were associated with liver enzyme activity above the normal range | ||
| An overall average incidence of liver injury from consuming EGCG over ∼10 y is 0.0036 in 10,000 persons from case studies, where no dose–response information was derived | |||
| Oketch-Rabah et al. (2020) (47) | US Pharmacopeia systematic review of 204 human clinical research studies and 127 animal studies of green tea extracts | Human cases reviewed involved use of green tea extracts from 500 to 3000 mg/d (∼250 to 1800 mg/d EGCG) | Green tea extracts can contain hepatotoxic solvent residues, pesticide residues, pyrrolizidine alkaloids, and elemental impurities, but no evidence of their involvement in green tea extract–induced liver injury was found |
| 51 published case report articles reporting 75 individual cases associated with green tea extract intake | Animal and human data indicate repeated oral consumption of bolus doses during fasting significantly increases bioavailability of catechins (specifically EGCG) | ||
| Published adverse event case reports associate hepatotoxicity with EGCG intake amounts from 140 to 1000 mg/d with substantial interindividual variability | |||
| Statement: US Pharmacopeia recommended a cautionary label requirement in its Powdered Decaffeinated Green Tea Extract monograph that reads as follows: Do not take on an empty stomach. Do not use if you have a liver problem and discontinue use and consult a healthcare practitioner if you develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes) |
1
EGCG, epigallocatechin gallate.