{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:36:22Z","timestamp":1785861382491,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Metabolic syndrome (MetS) patients have impaired hypothalamic regulatory functions involved in food intake and energy expenditure and suffer from a state of meta-inflammation. Pre-clinical studies demonstrated that ultramicronized palmitoylethanolamide (PEA) acts both on the adipose tissue and the central nervous system, while hydroxytyrosol (HTyr) counteracts several types of dysmetabolism. Objectives: The aim of our randomized crossover double-blind placebo-controlled pilot study was to evaluate the potential effects of a food supplement (FS) containing a co-micronized formulation of PEA and rutin along with HTyr, combined with a tailored calorie-controlled Mediterranean diet, in patients with MetS. Methods: Nineteen patients were enrolled and block-randomized to an eight-week MD together with the FS or placebo. After a two-week washout period, the treatments were reversed. Data on laboratory parameters and those detected by capillary sampling, anthropometry, body composition analysis, ultrasound examination, blood pressure monitoring, the 36-Item Short-Form Health Survey questionnaire, handgrip strength test, and physical performance tests were collected at each time point (protocol code R.S. 262.22, registered on 20 December 2022). Results: At the end of the study, patients supplemented with the FS showed a significant reduction in body weight, body mass index, fat mass, and inflammation biomarkers (CRP and ESR), compared to placebo-supplemented patients. In contrast, the fat-free mass, phase angle, and body cell mass were increased in FS compared to placebo patients. Conclusions: Although preliminary, the results of our clinical study suggest that co-micronized PEA\u2013rutin and HTyr may be of help against adiposopathy in patients with MetS.<\/jats:p>","DOI":"10.3390\/nu17030413","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T12:24:09Z","timestamp":1737635049000},"page":"413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Effects of a Food Supplement, Based on Co-Micronized Palmitoylethanolamide (PEA)\u2013Rutin and Hydroxytyrosol, in Metabolic Syndrome Patients: Preliminary Results"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-8904-4399","authenticated-orcid":false,"given":"Kevin","family":"Cornali","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, PhD School in Biochemistry and Molecular Biology, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8118-1330","authenticated-orcid":false,"given":"Manuela","family":"Di Lauro","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5854-2086","authenticated-orcid":false,"given":"Giulia","family":"Marrone","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Masci","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3501-6894","authenticated-orcid":false,"given":"Giulia","family":"Montalto","sequence":"additional","affiliation":[{"name":"School of Specialization in Nephrology, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Giovannelli","sequence":"additional","affiliation":[{"name":"Unit of Laboratory Medicine, University Hospital Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7176-1980","authenticated-orcid":false,"given":"Carlo","family":"Schievano","sequence":"additional","affiliation":[{"name":"Innovative Statistical Research, 35100 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfredi","family":"Tesauro","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3463-0268","authenticated-orcid":false,"given":"Massimo","family":"Pieri","sequence":"additional","affiliation":[{"name":"Unit of Laboratory Medicine, University Hospital Tor Vergata, 00133 Rome, Italy"},{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Bernardini","sequence":"additional","affiliation":[{"name":"Unit of Laboratory Medicine, University Hospital Tor Vergata, 00133 Rome, Italy"},{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1310-3730","authenticated-orcid":false,"given":"Annalisa","family":"Noce","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"UOSD Nephrology and Dialysis, Policlinico Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11906-018-0812-z","article-title":"The Global Epidemic of the Metabolic Syndrome","volume":"20","author":"Saklayen","year":"2018","journal-title":"Curr. 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