Theobromine, caffeine, and theophylline metabolites in human plasma and urine after consumption of soluble cocoa products with different methylxanthine contents

摘要

© 2014 Elsevier Ltd. The health promoting properties of cocoa products and their excellent acceptance by consumers turn cocoa into an important product for enrichment with bioactive components, such as methylxanthines (MX), adding potential health properties to cocoa products. The present work aimed at studying the bioavailability of methylxanthines in two soluble cocoa products, one containing methylxanthines naturally occurring in cocoa (CC) and a product enriched in methylxanthines (CC-MX). A crossover, randomized, controlled, single-blind study was carried out in 13 healthy subjects who consumed realistic doses of the two cocoa products in milk. CC provided 84.45. mg of theobromine (TB) and 9.9. mg of caffeine (CF), while CC-MX provided 177. mg. TB, 75.75. mg CF and 3.25. mg theophylline (TP). In each intervention, blood samples were collected at baseline (t. =. 0) and 0.5, 1, 2, 3, 4, 6 and 8. h after drinking the beverages. Urine was collected at different time intervals (baseline (-. 2-0. h), 0-4, 4-8, 8-12 and 12-24. h).TB, CF, TP and paraxanthine (PX) together with two monomethylxanthines (3-MX and 7-MX) were identified and quantified in plasma by HPLC-DAD. These metabolites together with 1-MX and different mono-, di- and tri-methyluric (MU) acids (1-MU, 1,3-MU, 1,7-MU, 3,7-MU and 1,3,7-MU) involved in the biotransformation of the ingested methylxanthines were detected by LC-QTOF and quantified by LC-DAD, with 7-MX and TB as the major urinary metabolites. The maximum concentration (Cmax) and area under curve (AUC) values of all metabolites were significantly higher after the intake of CC-MX, showing a dose-dependent response. In conclusion, cocoa methylxanthines show high bioavailability and rapid excretion, with a direct relationship existing between the amount of methylxanthine consumed and the metabolites quantified in biological fluids.