{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:40:08Z","timestamp":1785775208533,"version":"3.56.0"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"20","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,10,15]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The trans intestinal cholesterol excretion (TICE) pathway is a potential therapeutic target to reduce plasma low\u2010density lipoprotein (LDL) cholesterol levels. TICE encompasses the direct excretion of cholesterol by enterocytes into feces. In mice, TICE has been shown to be stimulated by a hydrophilic bile acid pool, resulting in increased fecal neutral sterol loss and reduced plasma cholesterol levels. We investigated whether treatment with a hydrophilic bile acid, ursodeoxycholic acid (UDCA), would increase fecal neutral sterols in humans as a proxy for TICE.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We performed a randomized, double\u2010blind, placebo\u2010controlled, cross\u2010over trial in 20 male participants aged &gt;18\u2009years, with plasma LDL cholesterol levels \u22652.6\u2009mmol\/L. After a run\u2010in period of ezetimibe 20\u2009mg once daily for 3\u2009weeks, patients were randomized to UDCA 600\u2009mg or placebo orally once daily for 2\u2009weeks. After a 3\u2009week washout, patients underwent the alternate treatment. At baseline, mean (SD) age, body mass index, and plasma LDL cholesterol were 59\u00b111.3\u2009years, 26.4\u00b13.1\u2009kg\/m\n              <jats:sup>2<\/jats:sup>\n              , and 3.9\u00b10.8\u2009mmol\/L, respectively. After UDCA treatment, the plasma bile acid hydrophobicity index was reduced compared with placebo (\u2212118.7% versus +2.3%,\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). The fecal neutral sterols did not change (\u22125.8% versus +18.8%,\n              <jats:italic>P<\/jats:italic>\n              =0.51) and treatment with UDCA increased LDL cholesterol with 0.39\u2009mmol\/L (+8.1% versus \u22123.64%,\n              <jats:italic>P<\/jats:italic>\n              =0.002) when compared with placebo.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">UDCA in combination with ezetimibe increased plasma bile acid hydrophilicity in healthy subjects with LDL cholesterol levels &gt;2.6\u2009mmol\/L but did not result in increased fecal neutral sterols or decreased LDL cholesterol. This suggests that TICE is not stimulated by an increase in the hydrophilicity of the bile acid pool in humans.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.035259","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T16:07:34Z","timestamp":1728403654000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Ursodeoxycholic Acid for Trans Intestinal Cholesterol Excretion Stimulation: A Randomized Placebo Controlled Crossover Study"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7182-2886","authenticated-orcid":false,"given":"Reindert F.","family":"Oostveen","sequence":"first","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam Cardiovascular Sciences Amsterdam UMC, University of Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam Cardiovascular Sciences Amsterdam UMC, University of Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merel L.","family":"Hartgers","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam Cardiovascular Sciences Amsterdam UMC, University of Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma C. E.","family":"Meessen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Amsterdam UMC, University of Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1761-9494","authenticated-orcid":false,"given":"Aldo","family":"Grefhorst","sequence":"additional","affiliation":[{"name":"Department of Experimental Vascular Medicine Amsterdam UMC, University of Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8145-1676","authenticated-orcid":false,"given":"G. Kees","family":"Hovingh","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam Cardiovascular Sciences Amsterdam UMC, University of Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2518-737X","authenticated-orcid":false,"given":"Folkert","family":"Kuipers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Medical Center Groningen, University of Groningen The Netherlands"},{"name":"European Research Institute for the Biology of Ageing (ERIBA) University Medical Center Groningen, University of Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7584-7677","authenticated-orcid":false,"given":"Erik S. G.","family":"Stroes","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam Cardiovascular Sciences Amsterdam UMC, University of Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9942-1854","authenticated-orcid":false,"given":"Albert K.","family":"Groen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Amsterdam UMC, University of Amsterdam The Netherlands"},{"name":"Department of Experimental Vascular Medicine Amsterdam UMC, University of Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8043-951X","authenticated-orcid":false,"given":"Laurens F.","family":"Reeskamp","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Amsterdam Cardiovascular Sciences Amsterdam UMC, University of Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.11.005"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.13985"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehx144"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI105587"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.12.037"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.07.035"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.10.001"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M008128"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(83)80003-1"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(86)90708-0"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/18.6.499"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.07.009"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30778"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)38331-0"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(19)31871-2"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.034"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M200478-JLR200"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-019-1041-4"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1980.tb00040.x"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(80)90567-3"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.124.035259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T03:10:51Z","timestamp":1729048251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.124.035259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,15]]},"references-count":20,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2024,10,15]]}},"alternative-id":["10.1161\/JAHA.124.035259"],"URL":"https:\/\/doi.org\/10.1161\/jaha.124.035259","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,15]]},"assertion":[{"value":"2024-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e035259"}}