{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:19:28Z","timestamp":1785435568802,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI23\/01554"],"award-info":[{"award-number":["PI23\/01554"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PI23\/01554"],"award-info":[{"award-number":["PI23\/01554"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Foundation of the Spanish Society of Endocrinology"},{"name":"Vegenat Healthcare\u00ae"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Chronic inflammation and metabolic dysregulation of heart failure (HF) often result in sarcopenia. The combined effect of Mediterranean diet (MD) and omega-3 polyunsaturated fatty acids on the advanced lipidomic profile of HF patients remains poorly defined. Objective: Our objective was to analyze the specific effects of a MD plus omega-3-enriched oral nutritional supplements (MD+ONS) versus MD alone on the metabolic lipid profile of patients with HF, stratified by sarcopenia status. Methods: In this prospective, open-label, randomized controlled trial, 38 patients with HF were assigned to MD alone or MD+ONS (24 weeks). Advanced lipoprotein profiling (triglycerides, cholesterol, particle size, and concentration for VLDL, LDL, and HDL subclasses) was performed using 2D 1H-NMR spectroscopy. Results: At baseline, NT-proBNP levels correlated positively with \u03c96\/\u03c97\u03c99 fatty acids and IDL-TG (p &lt; 0.05). Over 24 weeks, VLDL-C, VLDL-TG, and VLDL-P significantly decreased in the whole cohort (p &lt; 0.001). However, stratified analysis revealed that in patients with sarcopenia, these reductions were primarily driven in the MD group (p &lt; 0.01). Conversely, in patients without sarcopenia, the MD+ONS group showed significant reductions in VLDL-TG, VLDL-P, and VLDL-Z (p &lt; 0.05). Regarding intermediate lipoproteins, IDL-C significantly increased in the MD group (p &lt; 0.05) but not in the MD+ONS group. In the LDL fraction, total LDL-P and small LDL-P decreased in the MD group (p &lt; 0.05), while medium LDL-P increased across both groups (p &lt; 0.01). Total HDL-P decreased (p &lt; 0.05), yet large HDL-P significantly increased in the whole cohort and the MD group (p &lt; 0.05). No significant changes were observed in structural lipids or total fatty acid families. Conclusions: MD+ONS induces lipidomic shifts that are significantly modulated by baseline sarcopenia. The intervention appears to stabilize VLDL and IDL levels in patients with sarcopenia compared to diet alone, while promoting a more favorable VLDL reduction in individuals without sarcopenia, suggesting that early nutritional support for improving body composition is a critical determinant of the metabolic response to specific interventions in patients with HF.<\/jats:p>","DOI":"10.3390\/nu18132159","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T09:34:11Z","timestamp":1783071251000},"page":"2159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolomic Lipid Profile Changes in Patients with Heart Failure Undergoing Oral Nutritional Supplements Enriched with the Omega-3 (n-3) Polyunsaturated Fatty Acids and Mediterranean Diet"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1437-9878","authenticated-orcid":false,"given":"Aura D.","family":"Herrera-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 C\u00f3rdoba, Spain"},{"name":"Endocrinology and Nutrition Service, Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n","family":"Mu\u00f1oz Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 C\u00f3rdoba, Spain"},{"name":"Endocrinology and Nutrition Service, Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6160-5044","authenticated-orcid":false,"given":"Jos\u00e9","family":"L\u00f3pez Aguilera","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 C\u00f3rdoba, Spain"},{"name":"Cardiology Service, Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Crespin","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 C\u00f3rdoba, Spain"},{"name":"Cardiology Service, Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda \u00c1ngeles","family":"G\u00e1lvez Moreno","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 C\u00f3rdoba, Spain"},{"name":"Endocrinology and Nutrition Service, Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Molina Puerta","sequence":"additional","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), 14004 C\u00f3rdoba, Spain"},{"name":"Endocrinology and Nutrition Service, Reina Sofia University Hospital, 14004 C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nrcardio.2017.51","article-title":"Muscle wasting and cachexia in heart failure: Mechanisms and therapies","volume":"14","author":"Ebner","year":"2017","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1159\/000338166","article-title":"Inflammatory cytokines in heart failure: Mediators and markers","volume":"122","author":"Gullestad","year":"2012","journal-title":"Cardiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1002\/ejhf.1304","article-title":"Comparison of sarcopenia and cachexia in men with chronic heart failure: Results from the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF)","volume":"20","author":"Emami","year":"2018","journal-title":"Eur. J. Heart Fail."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1093\/eurheartj\/ehs381","article-title":"Muscle wasting in patients with chronic heart failure: Results from the studies investigating co-morbidities aggravating heart failure (SICA-HF)","volume":"34","author":"Fulster","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1007\/s11897-012-0090-z","article-title":"Skeletal muscle abnormalities in chronic heart failure","volume":"9","author":"Georgiadou","year":"2012","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1002\/ehf2.14667","article-title":"Sarcopenia prognosis using dual-energy X-ray absorptiometry and prediction model in older patients with heart failure","volume":"11","author":"Saito","year":"2024","journal-title":"ESC Heart Fail."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Benitez-Velasco, A., Alzas-Teomiro, C., Zurera G\u00f3mez, C., Mu\u00f1oz Jim\u00e9nez, C., L\u00f3pez Aguilera, J., Crespin, M., Vallejo-Casas, J.A., G\u00e1lvez-Moreno, M., Molina Puerta, M.J., and Herrera-Mart\u00ednez, A.D. (2024). Differences in the Evaluation of Malnutrition and Body Composition Using Bioelectrical Impedance Analysis, Nutritional Ultrasound, and Dual-Energy X-ray Absorptiometry in Patients with Heart Failure. Nutrients, 16.","DOI":"10.3390\/nu16101535"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1097\/HCR.0000000000000872","article-title":"Association of Sarcopenia and Oxygen Uptake Efficiency Slope in Male Patients with Heart Failure","volume":"44","author":"Bispo","year":"2024","journal-title":"J. Cardiopulm. Rehabil. Prev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1002\/ejhf.750","article-title":"Mediterranean diet and risk of heart failure: Results from the PREDIMED randomized controlled trial","volume":"19","author":"Papadaki","year":"2017","journal-title":"Eur. J. Heart Fail."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/ehf2.12237","article-title":"Muscle wasting and sarcopenia in heart failure and beyond: Update 2017","volume":"4","author":"Springer","year":"2017","journal-title":"ESC Heart Fail."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/ejhf.481","article-title":"Adherence to a Mediterranean diet is associated with reduced risk of heart failure in men","volume":"18","author":"Tektonidis","year":"2016","journal-title":"Eur. J. Heart Fail."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.amjmed.2014.10.014","article-title":"The Mediterranean diet, its components, and cardiovascular disease","volume":"128","author":"Widmer","year":"2015","journal-title":"Am. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Herrera-Mart\u00ednez, A.D., Mu\u00f1oz Jim\u00e9nez, C., L\u00f3pez Aguilera, J., Crespin, M.C., Manzano Garc\u00eda, G., G\u00e1lvez Moreno, M., Cala\u00f1as Continente, A., and Molina Puerta, M.J. (2023). Mediterranean Diet, Vitamin D, and Hypercaloric, Hyperproteic Oral Supplements for Treating Sarcopenia in Patients with Heart Failure\u2014A Randomized Clinical Trial. Nutrients, 16.","DOI":"10.3390\/nu16010110"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e4","DOI":"10.1161\/CIR.0000000000001110","article-title":"Complementary and Alternative Medicines in the Management of Heart Failure: A Scientific Statement From the American Heart Association","volume":"147","author":"Chow","year":"2023","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1111\/joim.13442","article-title":"Changes in eicosapentaenoic acid and docosahexaenoic acid and risk of cardiovascular events and atrial fibrillation: A secondary analysis of the OMEMI trial","volume":"291","author":"Myhre","year":"2022","journal-title":"J. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1194\/jlr.D050120","article-title":"Liposcale: A novel advanced lipoprotein test based on 2D diffusion-ordered 1H NMR spectroscopy","volume":"56","author":"Mallol","year":"2015","journal-title":"J. Lipid Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.cll.2006.07.006","article-title":"Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy","volume":"26","author":"Jeyarajah","year":"2006","journal-title":"Clin. Lab. Med."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Girona, J., Guardiola, M., Barroso, E., Garc\u00eda-Altares, M., Ibarretxe, D., Plana, N., Ribalta, J., Amig\u00f3, N., Correig, X., and V\u00e1zquez-Carrera, M. (2025). GDF15 Circulating Levels Are Associated with Metabolic-Associated Liver Injury and Atherosclerotic Cardiovascular Disease. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26052039"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Herrera-Mart\u00ednez, A.D., Jim\u00e9nez, C.M., Romo, A.N., Aguilera, J.L., Crespin, M.C., Baena, B.T., Casado-D\u00edaz, A., Moreno, M.G., Puerta, M.J.M., and Roger, A.J. (2024). Nutritional Support Reduces Circulating Cytokines in Patients with Heart Failure. Nutrients, 16.","DOI":"10.3390\/nu16111637"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1177\/2047487314536694","article-title":"No effect of n-3 fatty acids supplementation on NT-proBNP after myocardial infarction: The Alpha Omega Trial","volume":"22","author":"Hoogeveen","year":"2015","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"10645","DOI":"10.1038\/s41598-024-61440-5","article-title":"A combined observational and Mendelian randomization investigation reveals NMR-measured analytes to be risk factors of major cardiovascular diseases","volume":"14","author":"Zheng","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lundgren, M., Ridefelt, P., Svensson, M.K., Hagstr\u00f6m, E., Cars, T., and Larsson, A. (2025). NT-proBNP and its correlation to left ventricular ejection fraction and heart failure\u2014The DEMONSTRATE database. Ann. Clin. Biochem., 45632251403397.","DOI":"10.1177\/00045632251403397"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1017\/S0954422420000049","article-title":"Nutraceutical support in heart failure: A position paper of the International Lipid Expert Panel (ILEP)","volume":"33","author":"Cicero","year":"2020","journal-title":"Nutr. Res. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1016\/j.jacl.2019.09.012","article-title":"Impact on cardiometabolic risk of a weight loss intervention with higher protein from lean red meat: Combined results of 2 randomized controlled trials in obese middle-aged and older adults","volume":"13","author":"Connelly","year":"2019","journal-title":"J. Clin. Lipidol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s43044-024-00484-4","article-title":"Prognostic factors in patients with heart failure and sarcopenia: An observational retrospective study","volume":"76","author":"Imamura","year":"2024","journal-title":"Egypt. Heart J."},{"key":"ref_26","first-page":"864","article-title":"H-magnetic resonance spectroscopy lipoprotein profile in patients with chronic heart failure versus matched controls","volume":"75","author":"Teis","year":"2022","journal-title":"Rev. Esp. Cardiol. Engl. Ed."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jacl.2011.02.001","article-title":"Clinical implications of discordance between low-density lipoprotein cholesterol and particle number","volume":"5","author":"Otvos","year":"2011","journal-title":"J. Clin. Lipidol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106458","DOI":"10.1016\/j.cct.2021.106458","article-title":"Omega-3 supplementation and heart failure: A meta-analysis of 12 trials including 81,364 participants","volume":"107","author":"Barbarawi","year":"2021","journal-title":"Contemp. Clin. Trials"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ding, M., and Rexrode, K.M. (2020). A Review of Lipidomics of Cardiovascular Disease Highlights the Importance of Isolating Lipoproteins. Metabolites, 10.","DOI":"10.3390\/metabo10040163"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/13\/2159\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T10:35:57Z","timestamp":1783074957000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/13\/2159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":29,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["nu18132159"],"URL":"https:\/\/doi.org\/10.3390\/nu18132159","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]}}}