Fasting, Systemic Epigallocatechin-3-Gallate Exposure, and Hepatotoxicity

Green tea (Camellia sinensis) contains bioactive catechins, particularly epigallocatechin-3-gallate (EGCG), but traditional infusions and concentrated green tea extracts differ in EGCG content, dosing pattern, product matrix, systemic exposure, and safety. This structured narrative review evaluates how fasting affects EGCG pharmacokinetics and the relevance of increased systemic exposure to hepatotoxicity. Its distinctive contribution is not a further summary of green tea safety but an explicit appraisal of the evidence chain that is generally assumed to connect the two: each link is assessed separately, and the steps that are demonstrated in humans are separated from those that rest on biological inference. Standardized catechin preparations or purified EGCG taken after an overnight fast produce substantially higher peak plasma concentrations and total systemic exposure than when taken with food, although the two randomized within-subject comparisons that establish this effect were small, differed in dose and formulation, and assessed neither hepatic exposure nor liver injury. Evidence linking high EGCG exposure to prooxidant effects, mitochondrial dysfunction, and hepatocellular injury derives mainly from cellular and animal models at concentrations that exceed reported human peak plasma concentrations by roughly one order of magnitude; in mice, caloric restriction renders otherwise non-hepatotoxic EGCG doses hepatotoxic. In humans these outcomes must be kept apart. High-dose, long-term extract use raises serum aminotransferases in a susceptible minority, a laboratory abnormality demonstrated in controlled trials; hepatic adverse events cluster among catechin-rich bolus preparations rather than brewed beverages; and clinically apparent liver injury, documented in registry cases and associated with HLA-B*35:01, is idiosyncratic rather than dose-determined. Progression from the laboratory abnormality to clinically apparent injury has not been established. Fasting therefore increases systemic EGCG exposure, particularly from concentrated preparations, but has not been established as an independent cause of hepatotoxicity in humans. Treating fasting as an exposure-modifying condition rather than a hepatotoxic factor and nutritional state as a graded variable rather than a single category clarifies which precautions are evidence-based and which research questions remain genuinely open. Safety assessments should consider product type, dose, bolus administration, fed or fasting state, concomitant exposures, and individual susceptibility.