Repeated High Dose of Galloylated Catecins after Meals Does Not Cause Liver Damage in Healthy, Adult Japanese Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial

摘要

Galloylated catechins exert various physiological functions. However, their overconsumption may be harmful. Hepatotoxicity is associated with overconsumption in the form of supplements. Therefore, to evaluate the safety of high dose of galloylated catechin in the form of supplements for short intake period, we conducted a randomized, double-blind, placebo-controlled trial in Japanese healthy subjects receiving galloylated catechin 2837 mg/day ((-)-epigallocatechin gallate 1939 mg/day) for 4 weeks. Sixty subjects were divided into two groups that received either the galloylated catechin-containing supplements or placebo in three split doses after each meal, for 4 weeks. There were no significant differences between the groups regarding liver function-related parameters. Compared with those at the basal state, aspartate aminotransferase and alanine transferase levels were significantly increased in the galloylated catechin group at 2 weeks (p < 0.001, respectively). However, these changes were transient, within reference ranges, and within physiological fluctuations. Furthermore, the medical interviews and examination of subjective and objective symptoms showed no side effects indicating liver damage and no clinical problems were observed in the physical examinations, hematological examinations, blood biochemistry tests, urinalysis, subjective symptoms, and medical interviews. That is, this study did not identify hepatotoxicity and any side effects of galloylated catechin-containing supplements. Our study reports the highest galloylated catechins levels per day as a dose of (-)-epigallocatechin gallate consumed without side effects after repeated intake to date. This finding is important for the safety of supplements containing high dose of galloylated catechins and for further effective utilization in the future.