{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:43:37Z","timestamp":1792788217770,"version":"4.5.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T00:00:00Z","timestamp":1605139200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T00:00:00Z","timestamp":1605139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HighTide","award":["N.A."],"award-info":[{"award-number":["N.A."]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Lipids Health Dis"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Reduction in elevated serum cholesterol concentrations is important in the management of individuals at risk of atherosclerotic cardiovascular disease (ASCVD), such as myocardial infarction and thrombotic stroke. Although HMGCoA reductase inhibitors (\u201cstatins\u201d) are frequently used for this purpose, a significant proportion of patients remain at increased residual risk of ASCVD as they do not adequately address some of the associated co-morbidities such as diabetes and fatty liver disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A double-blind, randomized, placebo-controlled, dose ranging study was carried out that compared three doses of berberine ursodeoxycholate (BUDCA) to placebo in a cohort of subjects with a history of hypercholesterolemia and serum LDL cholesterol levels above 2.59\u2009mmol\/L (&gt;\u200999.9\u2009mg\/dL). BUDCA was administered in two divided doses each day for 28\u2009days. The primary endpoints of the study were safety and tolerability of this new compound, as well as its effect in lowering serum lipid and lipoprotein concentrations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 50 subjects were enrolled into three dose cohorts in this study. BUDCA was generally well tolerated, even at doses of 2000\u2009mg per day (the highest dose group); there were no significant adverse effects reported and this highest dose was associated with significant reductions in LDL cholesterol. By day 28 and with the highest dose of BUDCA, there were significant reductions in the serum concentrations of total cholesterol by 8.2% (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0004) and LDL cholesterol by 10.4% (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0006), but no significant changes in triglyceride and HDL cholesterol concentrations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BUDCA is a new single molecular entity that has a significant but modest effect in safely lowering serum LDL-cholesterol concentrations in individuals with a history of hypercholesterolemia. It has a potential use for treating hypercholesterolemia in individuals who cannot take statins, and possibly as adjunctive to other agents, such as ezetimibe or bempedoic acid.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      The study was registered on\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">Clinicaltrials.gov<\/jats:ext-link>\n                      (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03381287?term=NCT03381287&amp;draw=2&amp;rank=1\">NCT03381287<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12944-020-01406-4","type":"journal-article","created":{"date-parts":[[2020,11,12]],"date-time":"2020-11-12T05:02:50Z","timestamp":1605157370000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Pharmacokinetics and pharmacodynamics of HTD1801 (berberine ursodeoxycholate, BUDCA) in patients with hyperlipidemia"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6075-9305","authenticated-orcid":false,"given":"Adrian M.","family":"Di Bisceglie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald F.","family":"Watts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Lavin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,12]]},"reference":[{"key":"1406_CR1","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1016\/j.pop.2012.11.003","volume":"40","author":"RH Nelson","year":"2013","unstructured":"Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care. 2013;40:1995\u2013211.","journal-title":"Prim Care"},{"key":"1406_CR2","unstructured":"National Cholesterol Education Program, National Heart, Lung, and blood institute, National Institute of health (2002). Third report of the National Cholesterol Education Program Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). (report no. 02-5215). Retrieved from: http:\/\/circ.ahajournals.org\/content\/106\/25\/3143."},{"key":"1406_CR3","unstructured":"Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC\/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology\/American Heart Association task force on clinical practice guidelines. J am Coll Cardiol 2019;[Epub ahead of print]."},{"key":"1406_CR4","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1161\/CIRCULATIONAHA.105.169404","volume":"112","author":"SM Grundy","year":"2005","unstructured":"Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and Management of the Metabolic Syndrome: an American Heart Association\/National Heart, Lung, and Blood Institute scientific statement. Circulation. 2005;112:2735\u201352.","journal-title":"Circulation."},{"key":"1406_CR5","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1053\/j.gastro.2019.11.312","volume":"158","author":"M Eslam","year":"2020","unstructured":"Eslam M, Sanyal AJ, George J, et al. MAFLD: A Consensus-Driven Proposed Nomenclature for Metabolic Associated Fatty Liver Disease. Gastroenterology. 2020;158:1999\u20132014 e1.","journal-title":"Gastroenterology"},{"key":"1406_CR6","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1093\/eurheartj\/ehv043","volume":"36","author":"ES Stroes","year":"2015","unstructured":"Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al. Statin-associated muscle symptoms: impact on statin therapy\u2014European atherosclerosis society consensus panel statement on assessment, Aetiology and Management. Eur Heart J. 2015;36:1012\u201322.","journal-title":"Eur Heart J"},{"key":"1406_CR7","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1016\/j.jacc.2017.07.752","volume":"70","author":"RS Rosenson","year":"2017","unstructured":"Rosenson RS, Baker S, Banach M, Borow KM, Braun LT, Bruckert E, et al. Optimizing cholesterol treatment in patients with muscle complaints. J Am Coll Cardiol. 2017;70:1290\u2013301.","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"1406_CR8","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1161\/CIRCRESAHA.118.312782","volume":"124","author":"NC Ward","year":"2019","unstructured":"Ward NC, Watts GF, Eckel RH. Statin toxicity. Circ Res. 2019;124(2):328\u201350.","journal-title":"Circ Res"},{"key":"1406_CR9","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1002\/clc.22862","volume":"41","author":"NC Ward","year":"2018","unstructured":"Ward NC, Pang J, Ryan JDM, Watts GF. Nutraceuticals in the management of patients with statin-associated muscle symptoms, with a note on real-world experience. Clin Cardiol. 2018;41:159\u201365.","journal-title":"Clin Cardiol"},{"key":"1406_CR10","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1186\/s12872-016-0241-3","volume":"16","author":"S Mitchell","year":"2016","unstructured":"Mitchell S, Roso S, Samuel M, Pladevall-Vila M. Unmet need in the hyperlipidemia population with high risk of cardiovascular disease: a targeted literature review of observational studies. BMC Cardiovasc Disord. 2016;16:74.","journal-title":"BMC Cardiovasc Disord"},{"key":"1406_CR11","doi-asserted-by":"crossref","first-page":"289264","DOI":"10.1155\/2014\/289264","volume":"2014","author":"Z Li","year":"2014","unstructured":"Li Z, Geng Y-N, Jiang J-D, et al. Antioxidant and anti-inflammatory activities of Berberine in the treatment of diabetes mellitus. Evid Based Complement Alternat Med. 2014;2014:289264.","journal-title":"Evid Based Complement Alternat Med"},{"key":"1406_CR12","doi-asserted-by":"publisher","first-page":"RA164","DOI":"10.12659\/MSM.881842","volume":"17","author":"J Han","year":"2011","unstructured":"Han J, Lin H, Huang W. Modulating gut microbiota as an anti-diabetic mechanism of Berberine. Med Sci Monit. 2011;17:RA164\u20137.","journal-title":"Med Sci Monit"},{"key":"1406_CR13","doi-asserted-by":"publisher","first-page":"e42529","DOI":"10.1371\/journal.pone.0042529","volume":"7","author":"X Zhang","year":"2012","unstructured":"Zhang X, Zhao Y, Zhang M, et al. Structural changes of gut microbiota during Berberine-mediated prevention of obesity and insulin. PLoS One. 2012;7:e42529.","journal-title":"PLoS One"},{"key":"1406_CR14","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1038\/nm1135","volume":"10","author":"W Kong","year":"2004","unstructured":"Kong W, Wei J, Abidi P, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004;10:1344\u201351.","journal-title":"Nat Med"},{"key":"1406_CR15","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.pharmthera.2020.107496","volume":"209","author":"W-J Kong","year":"2020","unstructured":"Kong W-J, Vernieri C, Foini M, et al. Berberine in the treatment of metabolism-related chronic diseases: a drug cloud (dCloud) effect to target multifactorial disorders. Pharmacol Ther. 2020;209:1074\u201396.","journal-title":"Pharmacol Ther"},{"issue":"Suppl 204","key":"1406_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/00365529409103618","volume":"29","author":"AF Hofmann","year":"1994","unstructured":"Hofmann AF. Pharmacology of ursodeoxycholic acid, an enterohepatic drug. Scan J Gastroenterol. 1994;29(Suppl 204):1\u201315.","journal-title":"Scan J Gastroenterol"},{"key":"1406_CR17","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/S2468-1253(19)30343-7","volume":"5","author":"RA Shah","year":"2020","unstructured":"Shah RA, Kowdley KV. Current and potential treatments for primary biliary cholangitis. Lancet Gastroenterol Hepatol. 2020;5:306\u201315.","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"1406_CR18","doi-asserted-by":"crossref","unstructured":"Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology 2018;0:0. aasld.org (accessed August 6th 2020).","DOI":"10.1002\/hep.30145"},{"key":"1406_CR19","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1002\/lt.25496","volume":"25","author":"J Mallea","year":"2019","unstructured":"Mallea J, Bolan C, Cortese C, Harnois D. Cystic fibrosis-associated liver disease in lung transplant recipients. Liver Transpl. 2019;25:1265\u201375.","journal-title":"Liver Transpl"},{"key":"1406_CR20","doi-asserted-by":"crossref","unstructured":"Poupon RE, Ouguerram K, Chr\u00e9tien Y, Verneau C, Eschw\u00e8ge E, Magot T, Poupon R. Cholesterol-lowering effect of ursodeoxycholic acid in patients with primary biliary cirrhosis. Hepatology. 1993:577\u201382.","DOI":"10.1002\/hep.1840170408"},{"key":"1406_CR21","unstructured":"Liu L, Bai R, Li Y, Yu M, Fu X. HTD1801 a novel treatment for NAFLD\/NASH and primary sclerosing cholangitis (PSC). Hepatology. 2019;70:1261A\u20132A."},{"key":"1406_CR22","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1002\/jcph.1409","volume":"59","author":"S Lee","year":"2019","unstructured":"Lee S, Yoon S, Chung H, Ji SC, Yoon SH, Yu KS, Cho JY, Chung JY. Pharmacokinetics of Ursodeoxycholic acid in elderly volunteers compared with younger adults in a Korean population. J Clin Pharmacol. 2019;59:1085\u201392.","journal-title":"J Clin Pharmacol"},{"key":"1406_CR23","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1177\/2047487319864671","volume":"27","author":"CM Ballantyne","year":"2020","unstructured":"Ballantyne CM, Laufs U, Ray KK, et al. Bempedoic acid plus ezetimibe fixed-dose combination in patients with hypercholesterolemia and high CVD risk treated with maximally tolerated statin therapy. Eur J Prevent Cardiol. 2020;27:593\u2013603.","journal-title":"Eur J Prevent Cardiol"}],"container-title":["Lipids in Health and Disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12944-020-01406-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12944-020-01406-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12944-020-01406-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T04:43:35Z","timestamp":1723869815000},"score":1,"resource":{"primary":{"URL":"https:\/\/lipidworld.biomedcentral.com\/articles\/10.1186\/s12944-020-01406-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,12]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1406"],"URL":"https:\/\/doi.org\/10.1186\/s12944-020-01406-4","relation":{},"ISSN":["1476-511X"],"issn-type":[{"value":"1476-511X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,12]]},"assertion":[{"value":"13 August 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was registered on Clinicaltrials.gov (NCT03381287) and the study was conducted in accordance with the International Council for Harmonisation tripartite guideline on the ethical principles of Good Clinical Practice (ICHE6). The study was approved by Independent Ethics Committees (IECs) at each of the participating institutions and all subjects gave written informed consent to participate.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors of the manuscript have read and agreed to its content and are accountable for all aspects of the accuracy and integrity of the manuscript in accordance with ICMJE criteria.This article is original, has not already been published in a journal, and is not currently under consideration by another journal.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The following authors have potentially competing interests:AMD is a consultant to HighTide and Chief Medical Officer.GFW: Research grants and consultancy fees from Amgen, Sanofi, Regeneron, Arrowhead and Novartis.PL: Consultant to HighTide.LL, MY, RB: employees of HighTide Therapeutics.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"239"}}