Urolithins urinary excretion kinetics in Costa Rican volunteers after acute consumption of a blackberry ( Rubus adenotrichos )-based drink

Abstract

Background

Tropical mountain blackberry, widely consumed in Costa Rica, is rich in ellagitannins (ETs) such as ellagic acid (EA), which are metabolized by the intestinal microbiota into urolithins after ingestion.

Objective

This study aimed to characterize the urinary excretion kinetics of urolithins in healthy Costa Rican volunteers following the intake of a blackberry-based drink, thereby contributing to the biopharmaceutical understanding of these compounds.

Methods

Fifteen healthy non-smoking male volunteers (aged 18–35 years) consumed 500 ml of water and, on a separate day, 500 ml of a blackberry-based drink (33.3%) at breakfast. Urine samples were collected at 0–6 h, 6–12 h, and 12–24 h intervals and analyzed using Ultra-Performance Liquid Chromatography coupled to Mass Spectrometry (UPLC/ESI-Q-TOF-MS). Targeted metabolomic analysis was performed to detect urolithins and related metabolites. Participants were classified according to urolithin production capacity (metabotypes A/B). All volunteers produced either one or both urolithins.

Results

In the first 6 h, significant differences in metabolomic profiles were observed, although not attributable to urolithins; instead, a presumed decrease in glucuronidated hydroxyprogesterone (HPG) and tetrahydroxycortisone (THC) metabolites was identified. Between 6–12 h, urolithins A (UA) and C (UC) were identified as the main contributors to group differences. In the 12–24 h fraction, increased excretion of UA, UC, and urolithin B (UB) was observed. Quantitatively, UA was detected in 73% of participants, UC in 60%, and UB in 47%.

Conclusions

The observed reduction in metabolites putatively identified as HPG and THC may indicate, though not confirm, potential hypolipidemic or hormone-related anticancer effects of ET-rich foods. The delayed appearance of UA and UC (6–12 h) could reflect slower gastric emptying and intestinal transit, while the presence of UB up to 24 h may indicate enterohepatic recirculation of UA conjugates. These findings provide new evidence on the metabolic fate of blackberry-derived ETs, highlight plausible biomarkers of consumption, and support the functional potential of berry-based foods in human health.