{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:57:49Z","timestamp":1792162669800,"version":"4.4.0"},"reference-count":58,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T00:00:00Z","timestamp":1600300800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy and Competitivity","award":["AGL2010-18269 and AGL2015-69986-R"],"award-info":[{"award-number":["AGL2010-18269 and AGL2015-69986-R"]}]},{"name":"JAE Program","award":["JAEPre097"],"award-info":[{"award-number":["JAEPre097"]}]},{"name":"CSIC and European Social Fund"},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"crossref","award":["BES2008-007138"],"award-info":[{"award-number":["BES2008-007138"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>The main phenolic metabolites formed after CC and MPC intake, 5-(4\u2032-hydroxyphenyl)-\u03b3-valerolactone-3\u2032-sulfate, 3\u2032-methyl-epicatechin-5-sulfate, 4-hydroxy-5-(4\u2032-hydroxyphenyl)valeric acid-sulfate, 5-phenyl-\u03b3-valerolactone--sulfate and 5-(4\u2032-hydroxyphenyl)-\u03b3-valerolactone-3\u2032-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-1\u03b2 and hypoglycemic effects observed with DFC. With both phenolic and methylxanthine metabolites a strong dose\u2013response effect was observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>After the regular consumption of both DFC and PC, positive changes were observed in volunteer\u2019s 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.9953","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T04:01:10Z","timestamp":1600315270000},"page":"e9953","source":"Crossref","is-referenced-by-count":14,"title":["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 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