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Increasing evidence suggests that cholesterol-lowering and inflammation-lowering nutraceuticals are useful in the management of moderate hypercholesterolemia. Here, we describe the study protocol of a clinical trial aimed to evaluate the cholesterol and inflammatory lowering effect of an innovative dietary supplement (BruMeChol\u2122, Mivell S.r.l., Italy), composed of a mixture of extracts of bergamot and olive fruits in association with vitamin K2 in subjects with mild hypercholesterolemia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The study was planned as a randomized, double-blind, placebo-controlled, parallel group clinical trial for 12\u2009weeks at the Cardiology Unit of the IRCCS INRCA of Ancona, Italy. A total of 125 subjects (age \u2265\u200940\u2009years) with mild hypercholesterolemia (total serum cholesterol levels \u2265\u2009200 and \u2264\u2009250\u2009mg\/dl) will be recruited. Intervention arm participants will take one capsule of dietary supplement two times a day, 15\u2009min before the main meal. Control arm participants will receive one capsule of placebo in the same way. The dietary supplement capsule contains the following ingredients: phytosterols, flavonoid-rich extract of bergamot fruit (<jats:italic>Citrus bergamia<\/jats:italic>), flavonoid-rich extract of olive fruit (<jats:italic>Olea europaea<\/jats:italic>), and vitamin K2. Participants will undergo a medical evaluation and chemical-clinical examinations, which include lipid profile, glycemia, biomarkers of renal, liver and cardiac\/muscular functions, interleukins (IL 6, IL-32, IL-37, and IL-38), and innovative mediators of inflammation such as inflamma-miRs (miR-21 and miR-146a), at baseline, and after 6 and 12\u2009weeks of treatment. The decrease in total cholesterol levels and inflammatory biomarkers will be the primary and secondary endpoints of the study.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>This protocol study, planned to verify the effects of BruMeChol\u2122 dietary supplementation in subjects with mild hypercholesterolemia, could also contribute to new study designs for next large-scale multicenter clinical trials.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>Australian New Zealand Clinical Trials Registry: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.anzctr.org.au\/Trial\/Registration\/TrialReview.aspx?id=376807&amp;isReview=true\">ACTRN12619000170123<\/jats:ext-link>. Retrospectively registered on 5 February 2019<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-020-04551-4","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T10:02:58Z","timestamp":1594029778000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Effects of a novel nutraceutical combination (BruMeChol\u2122) in subjects with mild hypercholesterolemia: study protocol of a randomized, double-blind, controlled trial"],"prefix":"10.1186","volume":"21","author":[{"given":"Anna Rita","family":"Bonfigli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1936-6139","authenticated-orcid":false,"given":"Olga","family":"Protic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiola","family":"Olivieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Montesanto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gelsomina","family":"Malatesta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raffaele","family":"Di Pillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Antonicelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,6]]},"reference":[{"issue":"3","key":"4551_CR1","first-page":"e86","volume":"16","author":"GA Nichols","year":"2010","unstructured":"Nichols GA, Bell TJ, Pedula KL, O'Keeffe-Rosetti M. 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