Cocoa colonic phenolic metabolites are related to HDL-cholesterol raising effects and methylxanthine metabolites and insoluble dietary fibre to anti-inflammatory and hypoglycemic effects in humans

Abstract

Background In many cocoa intervention studies, health outcomes are related to cocoa components without taking into account the bioavailability of the main bioactive components: phenolic compounds and methylxanthines. Methods The present work associates the results of bioavailability and randomised controlled crossover studies in humans carried out with similar cocoa products, so that the main phenol and methylxanthine metabolites observed in plasma and urine are associated to the health effects observed in the chronic studies. We outstand that doses of cocoa and consumption rate used are realistic. In the bioavailability study, a conventional (CC) and a methylxanthine-polyphenol rich (MPC) cocoa product were used, whereas in the chronic study a dietary fibre-rich (DFC) and a polyphenol-rich (PC) product were studied in healthy and cardiovascular risk subjects. Results and Discussion The main phenolic metabolites formed after CC and MPC intake, 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-sulfate, 3′-methyl-epicatechin-5-sulfate, 4-hydroxy-5-(4′-hydroxyphenyl)valeric acid-sulfate, 5-phenyl-γ-valerolactone--sulfate and 5-(4′-hydroxyphenyl)-γ-valerolactone-3′-glucuronide, may contribute to the changes in cholesterol (and indirectly HDL-cholesterol) observed after the regular intake of both DFC and PC, in healthy and cardiovascular risk subjects, whereas 7-methylxanthine (the main cocoa methylxanthine metabolite) and theobromine, together with its content in insoluble dietary fibre, may be responsible for the decrease of IL-1β and hypoglycemic effects observed with DFC. With both phenolic and methylxanthine metabolites a strong dose–response effect was observed. Conclusion After the regular consumption of both DFC and PC, positive changes were observed in volunteer’s lipid profile, which may be related to the long-lasting presence of colonic phenolic metabolites in blood. In contrast, the anti-inflammatory and hypoglycemic effects were only observed with DFC, and these may be related to methylxanthine metabolites, and it is likely that insoluble dietary fibre may have also played a role.

From Cocoa to Chocolate: Effect of Processing on Flavanols and Methylxanthines and Their Mechanisms of Action

“…On the other hand, the results show that the regular consumption of a theobromine/flavanols-rich cocoa product may contribute to the changes in cholesterol (and indirectly the HDL cholesterol) observed after the regular intake in healthy and cardiovascular risk subjects. The data also suggest that theobromine and 7-methylxanthine (the main theobromine metabolite), together with its content in insoluble dietary fiber, may be responsible for the decrease in IL-1β and the hypoglycemic effects observed [218]. In a study from last year, theobromine protected against the glutamate toxicity-induced GABAergic decline in the brain of rats with transient global cerebral ischemia injury.…”

Investigating the Underlying Mechanisms of Ardisia japonica Extract’s Anti-Blood-Stasis Effect via Metabolomics and Network Pharmacology

“…Mannose has been proven to be an analgesic drug that can prevent LPS-induced lung injury [25], and D-mannose depletion may help prevent the onset of inflammation [26]. 7-methylxanthine nucleoside has been shown to significantly reduce IL-1 levels in the plasma and blood glucose levels in patients with hyperglycemia [27]. The concentration of 7-methylxanthine nucleoside in the AJH groups is higher than that in the MOD group, which may help reduce inflammatory reactions in blood stasis rats.…”

A Comprehensive Analysis of Microflora and Metabolites in the Development of Ulcerative Colitis into Colorectal Cancer Based on the Lung–Gut Correlation Theory

“…In purine metabolism, we detected a decreased content of 3-methylxanthine in the UC group and an even lower content in the CRC group. Methylxanthine was involved in numerous regulatory roles, such as increasing the blood circulation, dilating the blood vessels, improving the airflow, reducing inflammation, and preventing chronic obstructive pulmonary disease, which is highly applicable to the treatment of respiratory diseases [33,34]. Thus, the reduced concentration of 3-methylxanthine could be associated with pulmonary disease caused by intestinal diseases.…”