{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T12:20:29Z","timestamp":1784031629853,"version":"3.55.0"},"reference-count":32,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T00:00:00Z","timestamp":1696032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BYHEALTH","award":["TY0191119"],"award-info":[{"award-number":["TY0191119"]}]},{"name":"BYHEALTH","award":["lzujbky-2023-40"],"award-info":[{"award-number":["lzujbky-2023-40"]}]},{"name":"BYHEALTH","award":["21JR7RA507"],"award-info":[{"award-number":["21JR7RA507"]}]},{"name":"BYHEALTH","award":["21JR7RA425"],"award-info":[{"award-number":["21JR7RA425"]}]},{"name":"the Fundamental Research Funds for the Central Universities","award":["TY0191119"],"award-info":[{"award-number":["TY0191119"]}]},{"name":"the Fundamental Research Funds for the Central Universities","award":["lzujbky-2023-40"],"award-info":[{"award-number":["lzujbky-2023-40"]}]},{"name":"the Fundamental Research Funds for the Central Universities","award":["21JR7RA507"],"award-info":[{"award-number":["21JR7RA507"]}]},{"name":"the Fundamental Research Funds for the Central Universities","award":["21JR7RA425"],"award-info":[{"award-number":["21JR7RA425"]}]},{"name":"the Gansu Province Science Foundation for Youths","award":["TY0191119"],"award-info":[{"award-number":["TY0191119"]}]},{"name":"the Gansu Province Science Foundation for Youths","award":["lzujbky-2023-40"],"award-info":[{"award-number":["lzujbky-2023-40"]}]},{"name":"the Gansu Province Science Foundation for Youths","award":["21JR7RA507"],"award-info":[{"award-number":["21JR7RA507"]}]},{"name":"the Gansu Province Science Foundation for Youths","award":["21JR7RA425"],"award-info":[{"award-number":["21JR7RA425"]}]},{"name":"the Gansu Province Science Foundation for Youths","award":["TY0191119"],"award-info":[{"award-number":["TY0191119"]}]},{"name":"the Gansu Province Science Foundation for Youths","award":["lzujbky-2023-40"],"award-info":[{"award-number":["lzujbky-2023-40"]}]},{"name":"the Gansu Province Science Foundation for Youths","award":["21JR7RA507"],"award-info":[{"award-number":["21JR7RA507"]}]},{"name":"the Gansu Province Science Foundation for Youths","award":["21JR7RA425"],"award-info":[{"award-number":["21JR7RA425"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Dyslipidemia, a condition implying high cardiovascular risks, has been widely studied on its potential nutrition interventions, including functional foods. This study aims to examine the effect of nattokinase monascus supplements (NMSs) on cardiovascular biomarkers and carotid intima-media thickness (CIMT) in patients with dyslipidemia. A total of 113 eligible subjects were randomly assigned to receive either NMSs or a placebo (55 and 58, respectively). After a 120-day intervention, there were significant mean absolute changes in total cholesterol (TC), low-density cholesterol (LDL-C), non-high-density cholesterol (non-HDL-C), and low-density cholesterol to high-density cholesterol ratio (LDL-C to HDL-C ratio), with values of \u22120.52 (95% CI: \u22120.51 to \u22120.54) mmol\/L, \u22120.43 (95% CI: \u22120.45 to \u22120.41) mmol\/L, \u22120.52 (95% CI: \u22120.52 to \u22120.52) mmol\/L, and \u22120.29 (95% CI: \u22120.30 to \u22120.28) mmol\/L, respectively, between the two groups. However, no significant differences were found in triglycerides (TGs), high-density cholesterol (HDL-C), and CIMT. Furthermore, the results for lipids and CIMT remained essentially unchanged after adjusting for various confounding factors using the analysis of covariance model. There were no significant differences in coagulation, liver function, renal function, or other indicators. No intervention-related adverse events, such as mouth ulcers, drooling, and stomach pain, were reported. The study results demonstrate that NMSs can ameliorate lipid levels (TC, LDL-C, non-HDL-C, and the LDL-C to HDL-C ratio) without the occurrence of adverse events. However, it did not significantly affect serum TG, HDL-C, and CIMT.<\/jats:p>","DOI":"10.3390\/nu15194239","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T04:28:08Z","timestamp":1696220888000},"page":"4239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Effect of Nattokinase-Monascus Supplements on Dyslipidemia: A Four-Month Randomized, Double-Blind, Placebo-Controlled Clinical Trial"],"prefix":"10.3390","volume":"15","author":[{"given":"Xiaoming","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejiao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinli","family":"Mahe","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianwen","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxia","family":"Li","sequence":"additional","affiliation":[{"name":"BYHEALTH Institute of Nutrition & Health, No.3 Kehui 3rd Street, No.99 Kexue Avenue Central, Huangpu District, Guangzhou 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Wang","sequence":"additional","affiliation":[{"name":"BYHEALTH Institute of Nutrition & Health, No.3 Kehui 3rd Street, No.99 Kexue Avenue Central, Huangpu District, Guangzhou 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Lanzhou University Second Hospital, Lanzhou 730030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1856-0324","authenticated-orcid":false,"given":"Lipeng","family":"Jing","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mollace, R., Macri, R., Tavernese, A., Gliozzi, M., Musolino, V., Carresi, C., Maiuolo, J., Fini, M., Volterrani, M., and Mollace, V. (2022). Comparative Effect of Bergamot Polyphenolic Fraction and Red Yeast Rice Extract in Rats Fed a Hyperlipidemic Diet: Role of Antioxidant Properties and PCSK9 Expression. Nutrients, 14.","DOI":"10.3390\/nu14030477"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1056\/NEJMra1806939","article-title":"Lipid Management for the Prevention of Atherosclerotic Cardiovascular Disease","volume":"381","author":"Michos","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/S0140-6736(10)62038-7","article-title":"National, regional, and global trends in serum total cholesterol since 1980: Systematic analysis of health examination surveys and epidemiological studies with 321 country-years and 3.0 million participants","volume":"377","author":"Farzadfar","year":"2011","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Luna-Castillo, K.P., Olivares-Ochoa, X.C., Hernandez-Ruiz, R.G., Llamas-Covarrubias, I.M., Rodriguez-Reyes, S.C., Betancourt-Nunez, A., Vizmanos, B., Martinez-Lopez, E., Munoz-Valle, J.F., and Marquez-Sandoval, F. (2022). The Effect of Dietary Interventions on Hypertriglyceridemia: From Public Health to Molecular Nutrition Evidence. Nutrients, 14.","DOI":"10.3390\/nu14051104"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yu, S., Yang, H., Guo, X., Zhang, X., Zheng, L., and Sun, Y. (2015). Prevalence of dyslipidemia and associated factors among the hypertensive population from rural Northeast China. BMC Public Health, 15.","DOI":"10.1186\/s12889-015-2486-7"},{"key":"ref_6","first-page":"e1082","article-title":"2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"139","author":"Grundy","year":"2019","journal-title":"Circulation"},{"key":"ref_7","first-page":"757","article-title":"Safety and efficacy of statin therapy. Nature reviews","volume":"15","author":"Adhyaru","year":"2018","journal-title":"Cardiology"},{"key":"ref_8","first-page":"1622","article-title":"Muscle-related adverse effects of statins","volume":"130","author":"Julkunen","year":"2014","journal-title":"Duodecim"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.jacc.2020.11.056","article-title":"Red Yeast Rice for Hypercholesterolemia: JACC Focus Seminar","volume":"77","author":"Cicero","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yang, Y., Lan, G., Tian, X., He, L., Li, C., Zeng, X., and Wang, X. (2021). Effect of Fermentation Parameters on Natto and Its Thrombolytic Property. Foods, 10.","DOI":"10.3390\/foods10112547"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/ajcn\/53.3.665","article-title":"Milk- and soy-protein ingestion: Acute effect on serum uric acid concentration","volume":"53","author":"Garrel","year":"1991","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1142\/S0192415X19500150","article-title":"A Randomized Clinical Efficacy Trial of Red Yeast Rice (Monascus pilosus) Against Hyperlipidemia","volume":"47","author":"Wang","year":"2019","journal-title":"Am. J. Chin. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1007\/s00253-007-1256-6","article-title":"Biologically active components and nutraceuticals in the Monascus-fermented rice: A review","volume":"77","author":"Lin","year":"2008","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS), Younes, M., Aggett, P., Aguilar, F., Crebelli, R., Dusemund, B., Filipic, M., Frutos, M.J., Galtier, P., and Gott, D. (2018). Scientific opinion on the safety of monacolins in red yeast rice. EFSA J. Eur. Food Saf. Auth., 16, e05368.","DOI":"10.2903\/j.efsa.2018.5368"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3109\/14017431003624123","article-title":"HypoCol (red yeast rice) lowers plasma cholesterol\u2014A randomized placebo controlled study","volume":"44","author":"Bogsrud","year":"2010","journal-title":"Scand. Cardiovasc. J. SCJ"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11883-010-0145-0","article-title":"The role of red yeast rice for the physician","volume":"13","author":"Gordon","year":"2011","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_17","first-page":"264","article-title":"Effectiveness and safety of red yeast rice predominated by monacolin K beta-hydroxy acid form for hyperlipidemia treatment and management","volume":"42","author":"Benjian","year":"2022","journal-title":"J. Tradit. Chin. Med. Chung I Tsa Chih Ying Wen Pan"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.atherosclerosis.2015.04.004","article-title":"Traditional Chinese lipid-lowering agent red yeast rice results in significant LDL reduction but safety is uncertain\u2014A systematic review and meta-analysis","volume":"240","author":"Gerards","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1001\/jama.2016.13985","article-title":"Association Between Lowering LDL-C and Cardiovascular Risk Reduction Among Different Therapeutic Interventions: A Systematic Review and Meta-analysis","volume":"316","author":"Silverman","year":"2016","journal-title":"JAMA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/ajcn\/69.2.231","article-title":"Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement","volume":"69","author":"Heber","year":"1999","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e1801157","DOI":"10.1002\/mnfr.201801157","article-title":"EPA + DHA, but not ALA, Improved Lipids and Inflammation Status in Hypercholesterolemic Adults: A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"63","author":"Zhou","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Authors\/Task Force Members, Catapano, A.L., Graham, I., De Backer, G., Wiklund, O., Chapman, M.J., Drexel, H., Hoes, A.W., Jennings, C.S., and Landmesser, U. (2016). 2016 ESC\/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis, 253, 281\u2013344.","DOI":"10.1016\/j.atherosclerosis.2016.08.018"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1001\/jama.2020.5685","article-title":"Lipids and Lipoproteins in 2020","volume":"324","author":"Ference","year":"2020","journal-title":"JAMA"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Li, Y., Jiang, L., Jia, Z., Xin, W., Yang, S., Yang, Q., and Wang, L. (2014). A meta-analysis of red yeast rice: An effective and relatively safe alternative approach for dyslipidemia. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098611"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Verhoeven, V., Lopez Hartmann, M., Remmen, R., Wens, J., Apers, S., and Van Royen, P. (2013). Red yeast rice lowers cholesterol in physicians\u2014A double blind, placebo controlled randomized trial. BMC Complement. Altern. Med., 13.","DOI":"10.1186\/1472-6882-13-178"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3845","DOI":"10.1039\/C8FO00415C","article-title":"The short-term supplementation of monacolin K improves the lipid and metabolic patterns of hypertensive and hypercholesterolemic subjects at low cardiovascular risk","volume":"9","author":"Mazza","year":"2018","journal-title":"Food Funct."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s12944-018-0775-8","article-title":"LDL-cholesterol lowering effect of a new dietary supplement: An open label, controlled, randomized, cross-over clinical trial in patients with mild-to-moderate hypercholesterolemia","volume":"17","author":"Magno","year":"2018","journal-title":"Lipids Health Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.2147\/DDDT.S128623","article-title":"Effect of a food supplement containing berberine, monacolin K, hydroxytyrosol and coenzyme Q(10) on lipid levels: A randomized, double-blind, placebo controlled study","volume":"11","author":"Scandiani","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_29","first-page":"310","article-title":"Combined nattokinase with red yeast rice but not nattokinase alone has potent effects on blood lipids in human subjects with hyperlipidemia","volume":"18","author":"Yang","year":"2009","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"215","DOI":"10.4103\/0366-6999.173500","article-title":"Carotid Intima-media Thickness Measurements: Relations with Atherosclerosis, Risk of Cardiovascular Disease and Application in Randomized Controlled Trials","volume":"129","author":"Bots","year":"2016","journal-title":"Chin. Med. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3233\/CH-211147","article-title":"Nattokinase atherothrombotic prevention study: A randomized controlled trial","volume":"78","author":"Hodis","year":"2021","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40001-019-0370-0","article-title":"Influence of blood glucose fluctuation, C-peptide level and conventional risk factors on carotid artery intima-media thickness in Chinese Han patients with type 2 diabetes mellitus","volume":"24","author":"Liu","year":"2019","journal-title":"Eur. J. Med. Res."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/19\/4239\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:03:20Z","timestamp":1760130200000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/19\/4239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,30]]},"references-count":32,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["nu15194239"],"URL":"https:\/\/doi.org\/10.3390\/nu15194239","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,30]]}}}