{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:25:54Z","timestamp":1791923154744,"version":"4.3.4"},"reference-count":33,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003668","name":"Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries","doi-asserted-by":"publisher","award":["321030051HD030"],"award-info":[{"award-number":["321030051HD030"]}],"id":[{"id":"10.13039\/501100003668","id-type":"DOI","asserted-by":"publisher"}]},{"award":["321030051HD030"],"award-info":[{"award-number":["321030051HD030"]}],"id":[{"id":"https:\/\/ror.org\/00c25dn03","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00354524"],"award-info":[{"award-number":["RS-2024-00354524"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2024-00354524"],"award-info":[{"award-number":["RS-2024-00354524"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: The Mediterranean diet is widely recognized for its cardiovascular and metabolic benefits, including weight reduction; however, the metabolic mechanisms underlying these effects remain incompletely understood. This study investigated whether changes in circulating polyamines are associated with metabolic improvements following a Mediterranean diet intervention, particularly in breast cancer survivors. Methods: This exploratory secondary analysis used stored paired serum samples from a previously reported 8-week controlled intervention conducted in three groups: Group A (breast cancer survivors following a Mediterranean diet alone, n = 21), Group B (breast cancer survivors following a Mediterranean diet combined with naltrexone\/bupropion, n = 23), and Group C (non-cancer participants receiving the combined intervention, n = 28). Paired polyamine data were available for 16, 9, and 16 participants, respectively. Breast cancer survivors were randomized to Groups A and B, whereas Group C was enrolled as a non-randomized active comparison group. Serum metabolic profiles were analyzed using liquid chromatography\u2013mass spectrometry-based untargeted metabolomics, and nine polyamines were quantified using targeted analysis. An exploratory indirect-effect analysis examined associations between changes in serum polyamines and clinical outcomes, including body composition and lipid parameters. Results: Body weight, fat mass, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) decreased significantly within all three groups after the 8-week intervention (median changes: \u22121.9 to \u22122.8 kg, \u22121.9 to \u22122.8 kg, and \u22120.3 to \u22120.7, respectively). LDL cholesterol decreased significantly only within the two groups receiving naltrexone\/bupropion (median changes: \u221220.6 and \u221210.1 mg\/dL). However, between-group differences in these changes were not statistically significant. N-acetylspermine increased nominally in all groups (p &lt; 0.01), whereas spermine increased only in the Mediterranean diet alone group (p = 0.015). Conclusions: Mediterranean diet-related metabolic improvements were accompanied by changes in circulating polyamines. Spermine and N-acetylspermine may represent candidate metabolic response markers associated with nutritional and pharmacological interventions in breast cancer survivorship.<\/jats:p>","DOI":"10.3390\/nu18101621","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T12:30:51Z","timestamp":1779280251000},"page":"1621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Circulating Polyamines and Metabolic Changes Following a Mediterranean Diet with or Without Naltrexone\/Bupropion in Breast Cancer Survivors: An Exploratory Secondary Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8233-9272","authenticated-orcid":false,"given":"Won-Jun","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Medicine, Graduate School, Yonsei University, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1258-5363","authenticated-orcid":false,"given":"Yu Ra","family":"Lee","sequence":"additional","affiliation":[{"name":"Food Functionality Research Division, Korea Food Research Institute, Wanju-gun 55365, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1411-1938","authenticated-orcid":false,"given":"Yae-Ji","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Computing, Yonsei University, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9021-3856","authenticated-orcid":false,"given":"Yu-Jin","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3645-2282","authenticated-orcid":false,"given":"A-Ra","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Yonsei University College of Medicine, Yong-in Severance Hospital, Yong-in 16995, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7412-8977","authenticated-orcid":false,"given":"Jeongae","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Advanced Molecular Recognition, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2666-4249","authenticated-orcid":false,"given":"Ji Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref_1","unstructured":"Ministry of Data and Statistics (Republic of Korea) (2025, September 24). 2020 Annual Report on the Causes of Death Statistics, Available online: https:\/\/www.kostat.go.kr."},{"key":"ref_2","unstructured":"National Cancer Information Center (2025, September 24). 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