{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:20:44Z","timestamp":1773015644781,"version":"3.50.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p><jats:italic>Ulmus macrocarpa<\/jats:italic> Hance extract (UME) has demonstrated an antilipidemic effect <jats:italic>via<\/jats:italic> upregulation of the adenosine monophosphate-activated protein kinase pathway and regulation of lipid metabolism in both laboratory and animal studies. Therefore, we examined the effects and safety of UME on plasma lipids in adults with untreated high, low-density lipoprotein cholesterol (LDL-C) concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>In the current double-blind placebo-controlled randomized clinical trial, 80 patients with untreated high LDL-C concentrations (130\u2013190 mg\/dl) were randomly allocated to either the \u201cUME group\u201d (received 500 mg UME as two capsules per day) or the \u201cPlacebo group\u201d (received placebo containing cornstarch as two capsules per day) for 12 weeks. The primary outcome was the change in LDL-C concentration within the 12-week treatment period; secondary outcomes included changes in total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol, apolipoprotein A1, and apolipoprotein B (ApoB) concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>UME over 12 weeks led to a greater decrease in LDL-C, TC, and ApoB concentrations than did the placebo as follows: by 18.1 mg\/dl (<jats:italic>P<\/jats:italic> &amp;lt; 0.001); 23.3 mg\/dl (<jats:italic>P<\/jats:italic> &amp;lt; 0.001); 9.3 mg\/dl (<jats:italic>P<\/jats:italic> = 0.018), respectively. When LDL-C, TC, and ApoB concentrations were expressed as a lsmeans percentage of the baseline concentration, they after 12 weeks of UME had greater % differences compared to the placebo as follows: by 11.9% (<jats:italic>P<\/jats:italic> &amp;lt; 0.001); 10.0% (<jats:italic>P<\/jats:italic> &amp;lt; 0.001); 8.6% (<jats:italic>P<\/jats:italic> &amp;lt; 0.05), respectively. However, no significant inter- and intra-group changes in liver enzyme, free fatty acid, anti-inflammatory marker, and fasting glucose concentrations were observed. None of the participants experienced notable adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>UME causes a significant improvement in lipid profiles in adults with untreated high LDL-C concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p>[<jats:ext-link>www.clinicaltrials.gov\/<\/jats:ext-link>], identifier [NCT03773315].<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.1000428","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T04:34:49Z","timestamp":1667277289000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Potential lipid-lowering effects of Ulmus macrocarpa Hance extract in adults with untreated high low-density lipoprotein cholesterol concentrations: A randomized double-blind placebo-controlled trial"],"prefix":"10.3389","volume":"9","author":[{"given":"Ye Li","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Yeoup","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,1]]},"reference":[{"key":"B1","first-page":"S139","article-title":"Epidemiology and management of hyperlipidemia.","volume":"23","author":"Karr","year":"2017","journal-title":"Am J Manag Care."},{"key":"B2","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41569-021-00541-4","article-title":"Global epidemiology of dyslipidaemias.","volume":"18","author":"Pirillo","year":"2021","journal-title":"Nat Rev Cardiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s12944-021-01450-8","article-title":"Cardiovascular RISk prevention (CRISP) in Asia network. Prevalence of plasma lipid disorders with an emphasis on LDL cholesterol in selected countries in the Asia-Pacific region.","volume":"20","author":"Lee","year":"2021","journal-title":"Lipids Health Dis."},{"key":"B4","year":"2022","journal-title":"Noncommunicable Diseases: Risk Factors. The Global Health Observatory."},{"key":"B5","doi-asserted-by":"publisher","first-page":"400","DOI":"10.3389\/fpubh.2020.00400","article-title":"Predictors of the prevalence of dyslipidemia and influencing factors for young health examination cohort: a cross-sectional survey.","volume":"8","author":"Zhang","year":"2020","journal-title":"Front Public Health."},{"key":"B6","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart disease and stroke statistics-2020 update: a report from the American heart association.","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation."},{"key":"B7","first-page":"351","article-title":"Effectiveness of altering serum cholesterol levels without drugs.","volume":"13","author":"Rosenthal","year":"2000","journal-title":"Proc (Bayl Univ Med Cent)."},{"key":"B8","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.arcmed.2017.11.017","article-title":"Optimizing non-pharmacologic management of hypertriglyceridemia.","volume":"48","author":"Byrne","year":"2017","journal-title":"Arch Med Res."},{"key":"B9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.2174\/1871525718666200518093418","article-title":"Managing cardiovascular risk factors without medications: what is the evidence?","volume":"19","author":"Saha","year":"2021","journal-title":"Cardiovasc Hematol Agents Med Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"9883352","DOI":"10.1155\/2021\/9883352","article-title":"Current management guidelines on hyperlipidemia: the silent killer.","volume":"2021","author":"Su","year":"2021","journal-title":"J Lipids."},{"key":"B11","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1001\/jamacardio.2016.4709","article-title":"Statins-almost 30 years of use in the United States and still not quite there.","volume":"2","author":"Harrington","year":"2017","journal-title":"JAMA Cardiol."},{"key":"B12","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1161\/CIRCRESAHA.118.312782","article-title":"Statin toxicity.","volume":"124","author":"Ward","year":"2019","journal-title":"Circ Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s12906-018-2160-6","article-title":"Why people use herbal medicine: insights from a focus-group study in Germany.","volume":"18","author":"Welz","year":"2018","journal-title":"BMC Complement Altern Med."},{"key":"B14","doi-asserted-by":"crossref","first-page":"845","DOI":"10.2459\/JCM.0000000000000970","article-title":"Lipid-lowering nutraceuticals update on scientific evidence.","volume":"21","author":"Derosa","year":"2020","journal-title":"J Cardiovasc Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e0217112","DOI":"10.1371\/journal.pone.0217112","article-title":"Ulmus macrocarpa hance modulates lipid metabolism in hyperlipidemia via activation of AMPK pathway.","volume":"14","author":"Han","year":"2019","journal-title":"PLoS One."},{"key":"B16","doi-asserted-by":"crossref","first-page":"78","DOI":"10.12997\/jla.2019.8.2.78","article-title":"2018 guidelines for the management of dyslipidemia in Korea.","volume":"8","author":"Rhee","year":"2019","journal-title":"J Lipid Atheroscler."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2940","DOI":"10.1093\/eurheartj\/eht295","article-title":"Adherence to cardiovascular therapy: a meta-analysis of prevalence and clinical consequences.","volume":"34","author":"Chowdhury","year":"2013","journal-title":"Eur Heart J."},{"key":"B18","first-page":"532","article-title":"Validity and reliability of Korean version of International physical activity questionnaire (IPAQ) short form.","volume":"28","author":"Oh","year":"2007","journal-title":"J Korean Acad Fam Med."},{"key":"B19","doi-asserted-by":"crossref","first-page":"67","DOI":"10.5142\/JGR.2002.26.2.067","article-title":"The effects on the blood lipid profiles and body fat by long term administration of red ginseng product.","volume":"26","author":"Kim","year":"2002","journal-title":"J Ginseng Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"5690816","DOI":"10.1155\/2018\/5690816","article-title":"Effects of 4-week intervention with Ulmus macrocarpa Hance extract on immune function biomarkers in healthy adults: a randomized controlled trial.","volume":"2018","author":"Cho","year":"2018","journal-title":"Evid Based Complement Alternat Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"5443","DOI":"10.3390\/nu7075230","article-title":"Epigallocatechin gallate: a review of its beneficial properties to prevent metabolic syndrome.","volume":"7","author":"Legeay","year":"2015","journal-title":"Nutrients."},{"key":"B22","doi-asserted-by":"publisher","first-page":"166","DOI":"10.3390\/antiox8060166","article-title":"Effects and mechanisms of tea and its bioactive compounds for the prevention and treatment of cardiovascular diseases: an updated review.","volume":"8","author":"Cao","year":"2019","journal-title":"Antioxidants (Basel)."},{"key":"B23","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1177\/02601060211073236","article-title":"Potential therapeutic effects of green tea on obese lipid profile - a systematic review.","volume":"28","author":"Mac\u00eado","year":"2022","journal-title":"Nutr Health."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2090","DOI":"10.1248\/bpb.31.2090","article-title":"Antihypertensive, vasorelaxant, and antioxidant effect of root bark of Ulmus macrocarpa.","volume":"31","author":"Oh","year":"2008","journal-title":"Biol Pharm Bull."},{"key":"B25","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.jep.2018.11.042","article-title":"Ulmus macrocarpa Hance improves benign prostatic hyperplasia by regulating prostatic cell apoptosis.","volume":"233","author":"Rho","year":"2019","journal-title":"J Ethnopharmacol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3389\/fphar.2020.00004","article-title":"Synergistic effect of Rubus crataegifolius and Ulmus macrocarpa against Helicobacter pylori clinical isolates and gastritis.","volume":"11","author":"Park","year":"2020","journal-title":"Front Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.3390\/ijms18061200","article-title":"Ulmus macrocarpa Hance extracts attenuated H2O2 and UVB-induced skin photo-aging by activating antioxidant enzymes and inhibiting MAPK pathways.","volume":"18","author":"Choi","year":"2017","journal-title":"Int J Mol Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"726","DOI":"10.3892\/mmr.2013.1581","article-title":"Extract of Ulmus macrocarpa Hance prevents thrombus formation through antiplatelet activity.","volume":"8","author":"Yang","year":"2013","journal-title":"Mol Med Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1007\/s12275-021-1329-8","article-title":"Ulmus macrocarpa Hance extract modulates intestinal microbiota in healthy adults: a randomized, placebo-controlled clinical trial.","volume":"59","author":"Kim","year":"2021","journal-title":"J Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"822","DOI":"10.7326\/M20-4648","article-title":"Management of dyslipidemia for cardiovascular disease risk reduction: synopsis of the 2020 updated U.S. department of veterans affairs and U.S. department of defense clinical practice guideline.","volume":"173","author":"O\u2019Malley","year":"2020","journal-title":"Ann Intern Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1001\/jamacardio.2019.3780","article-title":"Apolipoprotein B particles and cardiovascular disease: a narrative review.","volume":"4","author":"Sniderman","year":"2019","journal-title":"JAMA Cardiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.2174\/0929867327666200427092114","article-title":"Regulation of apolipoprotein B by natural products and nutraceuticals: a comprehensive review.","volume":"28","author":"Bagherniya","year":"2021","journal-title":"Curr Med Chem."},{"key":"B33","first-page":"542","article-title":"Study of in vivo serum lipid regulation with Ulmus macrocarpa Hance extract in rats.","volume":"30","author":"Hwang","year":"2020","journal-title":"J Life Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.jnutbio.2006.05.007","article-title":"Isoflavone-poor soy protein alters the lipid metabolism of rats by SREBP-mediated down-regulation of hepatic genes.","volume":"18","author":"Shukla","year":"2007","journal-title":"J Nutr Biochem."},{"key":"B35","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2217\/clp.10.15","article-title":"Apolipoprotein B: not just a biomarker but a causal factor in hepatic endoplasmic reticulum stress and insulin resistance.","volume":"5","author":"Su","year":"2010","journal-title":"Clin Lipidol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"3","DOI":"10.4082\/kjfm.18.0015","article-title":"Cigarette smoking in South Korea: a narrative review.","volume":"41","author":"Gunter","year":"2020","journal-title":"Korean J Fam Med."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.1000428\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T04:35:01Z","timestamp":1667277301000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.1000428\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,1]]},"references-count":36,"alternative-id":["10.3389\/fmed.2022.1000428"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.1000428","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,1]]},"article-number":"1000428"}}