{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T05:45:45Z","timestamp":1785908745348,"version":"3.56.0"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Heart failure (HF) is associated with disease-related malnutrition, all of which contribute to impaired functional capacity and adverse outcomes. Nutritional strategies combining Mediterranean diet (MD) patterns with oral nutritional supplements (ONS) have shown clinical and anti-inflammatory benefits in HF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To evaluate the impact of MD combined with hypercaloric, hyperproteic, omega-3\u2013enriched ONS vs. MD alone on targeted metabolomic profiles related to energy metabolism, skeletal muscle metabolism, and amino acid handling in patients with HF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study is a secondary analysis of a prospective, randomized, open-label clinical trial including patients with chronic HF. Participants were randomized to receive either MD alone or MD plus two hypercaloric, hyperproteic, omega-3\u2013enriched ONS for 24 weeks. Targeted metabolomic profiling was performed using proton nuclear magnetic resonance, assessing glycoproteins, energy metabolism\u2013related metabolites, muscle-related metabolites, and amino acid metabolism\u2013related metabolites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty-eight patients were included, of whom 65.8% presented sarcopenia. Glycoprotein fraction levels significantly decreased over time in the whole cohort, without differences between intervention groups. In energy metabolism\u2013related parameters, glucose and pyruvate significantly decreased in the DM\u2013only group, whereas glycerol levels showed a trend toward increase in the intervention group, reaching statistical significance in patients without sarcopenia. Regarding muscle-related metabolites, leucine levels significantly increased in the intervention group, while isoleucine decreased in the control group (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05). In patients with sarcopenia, the intervention was associated with increases in valine and leucine (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05), whereas no significant muscle-related metabolomic changes were observed in non-sarcopenic patients. In amino acid metabolism, threonine decreased in the control group, while glycine significantly increased in sarcopenic patients receiving combined nutritional support (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05). Baseline NT-proBNP levels positively correlated with inflammatory glycoproteins and inversely correlated with glycine and proline. Multivariate analysis showed that baseline isoleucine levels were independently associated with mortality after adjustment for age, sex, type 2 diabetes, NT-proBNP levels, left ventricular ejection fraction, and body mass index, baseline isoleucine and valine remained independently associated with mortality (OR 0.77, 95% CI 0.591\u20130.9998; OR 0.95, 95% CI 0.907\u20130.999).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with HF, nutritional support combining MD with hypercaloric, hyperproteic, omega-3\u2013enriched ONS was associated with distinct metabolomic adaptations, particularly affecting branched-chain amino acid profiles in patients with sarcopenia. These findings suggest a potential role for comprehensive nutritional strategies in modulating systemic and muscle-related metabolic pathways linked to functional status and prognosis in high-risk HF populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1880396","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:56:07Z","timestamp":1785905767000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic energy metabolism changes in patients with heart failure receiving specific oral nutritional supplements in combination with Mediterranean diet"],"prefix":"10.3389","volume":"13","author":[{"given":"Aura D.","family":"Herrera-Mart\u00ednez","sequence":"first","affiliation":[{"name":"Maimonides Institute for Biomedical Research of Cordoba (IMIBIC)","place":["C\u00f3rdoba, Spain"]},{"name":"Endocrinology and Nutrition Service, Reina Sofia University 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Spain"]},{"name":"Cardiology Service, Reina Sof\u00eda University Hospital","place":["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)","place":["C\u00f3rdoba, Spain"]},{"name":"Endocrinology and Nutrition Service, Reina Sofia University Hospital","place":["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)","place":["C\u00f3rdoba, Spain"]},{"name":"Endocrinology and Nutrition Service, Reina Sofia University Hospital","place":["C\u00f3rdoba, 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