{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:35:07Z","timestamp":1790602507290,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T00:00:00Z","timestamp":1619481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Appropriate monitoring and control of modifiable risk factors, such as the level of low-density lipoprotein cholesterol (LDL-C) and other types of dyslipidemia, have an important role in the prevention of cardiovascular diseases (CVD). Recently, various nutraceuticals with lipid-lowering effects have gained attention. In addition to the plant-derived bioactive compounds, recent studies suggested that plant cells are able to release small lipoproteic structures named extracellular vesicles (EVs). The interaction between EVs and mammalian cells could lead to beneficial effects through anti-inflammatory and antioxidant activities. The present study aimed to assess the safety of the new patented plant-based product citraVes\u2122, containing extracellular vesicles (EVs) from Citrus limon (L.) Osbeck juice, and to investigate its ability to modulate different CV risk factors in healthy subjects. A cohort of 20 healthy volunteers was recruited in a prospective open-label study. All participants received the supplement in a spray-dried formulation at a stable dose of 1000 mg\/day for 3 months. Anthropometric and hematobiochemical parameters were analyzed at the baseline and after the follow-up period of 1 and 3 months. We observed that the supplement has an effect on two key factors of cardiometabolic risk in healthy subjects. A significant change in waist circumference was found in women after 4 (85.4 [79.9, 91.0] cm, p &lt; 0.005) and 12 (85.0 [80.0, 90.0] cm, p &lt; 0.0005) weeks, when compared to the baseline value (87.6 [81.7, 93.6] cm). No difference was found in men (baseline: 100.3 [95.4, 105.2] cm; 4 weeks: 102.0 [95.7, 108.3] cm; 12 weeks: 100.0 [95.3, 104.7] cm). The level of LDL-C was significantly lower at 12 weeks versus 4 weeks (p = 0.0064). Our study evaluated, for the first time, the effects of a natural product containing plant-derived EVs on modifiable risk factors in healthy volunteers. The results support the use of EV extracts to manage cardiometabolic risk factors successfully.<\/jats:p>","DOI":"10.3390\/metabo11050276","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T21:18:20Z","timestamp":1619558300000},"page":"276","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Preliminary Results of CitraVes\u2122 Effects on Low Density Lipoprotein Cholesterol and Waist Circumference in Healthy Subjects after 12 Weeks: A Pilot Open-Label Study"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5413-1303","authenticated-orcid":false,"given":"Stefania","family":"Raimondo","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D), Section of Biology and Genetics, University of Palermo, 90133 Palermo, Italy"},{"name":"Navhetec s.r.l, Via Elvira ed Enzo Sellerio, 90141 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9572-9651","authenticated-orcid":false,"given":"Dragana","family":"Nikolic","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D), Section of Biology and Genetics, University of Palermo, 90133 Palermo, Italy"},{"name":"Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3037-835X","authenticated-orcid":false,"given":"Alice","family":"Conigliaro","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D), Section of Biology and Genetics, University of Palermo, 90133 Palermo, Italy"},{"name":"Navhetec s.r.l, Via Elvira ed Enzo Sellerio, 90141 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7843-5969","authenticated-orcid":false,"given":"Gianluca","family":"Giavaresi","sequence":"additional","affiliation":[{"name":"IRCSS Istituto Ortopedico Rizzoli, SC Scienze e Tecnologie Chirurgiche-SS Piattaforma Scienze Omiche per Ortopedia Personalizzata, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna","family":"Lo Sasso","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D), Section of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine, University-Hospital \u201cP. Giaccone\u201d of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaria Vincenza","family":"Giglio","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D), Section of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Chianetta","sequence":"additional","affiliation":[{"name":"Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9843-0428","authenticated-orcid":false,"given":"Mauro","family":"Manno","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, National Research Council of Italy, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuele","family":"Raccosta","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, National Research Council of Italy, 90146 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Corleone","sequence":"additional","affiliation":[{"name":"Navhetec s.r.l, Via Elvira ed Enzo Sellerio, 90141 Palermo, Italy"},{"name":"Agrumaria Corleone s.p.a., Via S. 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Brancaccio, 90124 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Citarrella","sequence":"additional","affiliation":[{"name":"Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-8504","authenticated-orcid":false,"given":"Manfredi","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"De Leo","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D), Section of Biology and Genetics, University of Palermo, 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6120-9041","authenticated-orcid":false,"given":"Marcello","family":"Ciaccio","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D), Section of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, 90127 Palermo, Italy"},{"name":"Department of Laboratory Medicine, University-Hospital \u201cP. 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