Cardiology · Medical Literature
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.
Abstract
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. 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. 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. At baseline, NT-proBNP levels correlated positively with ω6/ω7ω9 fatty acids and IDL-TG (p < 0.05). Over 24 weeks, VLDL-C, VLDL-TG, and VLDL-P significantly decreased in the whole cohort (p < 0.001). However, stratified analysis revealed that in patients with sarcopenia, these reductions were primarily driven in the MD group (p < 0.01). Conversely, in patients without sarcopenia, the MD+ONS group showed significant reductions in VLDL-TG, VLDL-P, and VLDL-Z (p < 0.05). Regarding intermediate lipoproteins, IDL-C significantly increased in the MD group (p < 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 < 0.05), while medium LDL-P increased across both groups (p < 0.01). Total HDL-P decreased (p < 0.05), yet large HDL-P significantly increased in the whole cohort and the MD group (p < 0.05). No significant changes were observed in structural lipids or total fatty acid families. 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.
Clinical relevance
In patients with chronic heart failure, does a Mediterranean diet supplemented with omega-3-enriched, hypercaloric, hyperproteic oral nutritional supplements (MD+ONS) produce a different advanced lipoprotein metabolic profile than Mediterranean diet alone, and does this effect differ according to sarcopenia status? __SNAPSHOT__ {"studyDesign":"Prospective, open-label, randomized controlled trial (parallel-group, 1:1 allocation). Note: The lipidomic analysis reported here represents a pre-specified or secondary analysis of the parent RCT.","setting":"Not explicitly reported in abstract; companion publications from the same cohort identify a single academic hospital center in Spain (Córdoba).","sampleSize":"n=38 total (MD+ONS intervention: n=19 allocated, n=18 completers; MD alone control: n=19 allocated, n=15 completers; losses due to mortality during follow-up). Sarcopenia subgroups: sarcopenia n=25, no sarcopenia n=13 (per companion publication from same cohort).","population":"Adults with established chronic heart failure who had at least one hospitalization in the preceding 6 months. Mean age approximately 66.7 years; predominantly male (~71%). Mean baseline LVEF approximately 38.5% (consistent with HFrEF). High prevalence of sarcopenia (~65.8%) defined by handgrip strength below age- and sex-adjusted threshold. Substantial rates of malnutrition per GLIM criteria reported in companion publications.","intervention":"Mediterranean diet plus twice-daily oral nutritional supplements (ONS): hypercaloric (141 kcal/100 mL), high-protein (7.4 g/100 mL) formula enriched with EPA and DHA (omega-3 PUFAs), slow-release carbohydrates, and fiber. All patients also received calcifediol supplementation targeting 25-OH vitamin D >30 ng/mL. Duration: 24 weeks.","comparator":"Mediterranean diet alone (MD) for 24 weeks, with calcifediol supplementation and standardized nutritional counseling. Open-label design; no placebo ONS.","primaryOutcome":"Changes in advanced lipoprotein metabolic lipid profile assessed by 2D 1H-NMR spectroscopy, including triglycerides, cholesterol, particle size, and particle concentration for VLDL, LDL, and HDL subclasses, stratified by sarcopenia status.","followUp":"24 weeks (6 months)","fundingSource":"Not reported in abstract. Companion publications do not specify industry sponsorship; funding source should be independently verified in the full-text article."}
Key findings
At baseline, NT-proBNP levels correlated positively with ω6/ω7ω9 fatty acids and IDL-triglycerides (p < 0.05), suggesting that circulating non-omega-3 fatty acid fractions and IDL-TG may track with cardiac neurohormonal burden in this population. Over 24 weeks, VLDL cholesterol (VLDL-C), VLDL triglycerides (VLDL-TG), and VLDL particle count (VLDL-P) declined significantly in the cohort as a whole (p < 0.001); absolute effect sizes and between-group differences for these whole-cohort reductions were not reported in the abstract. Stratified analyses revealed a differential response by sarcopenia status: in patients WITH sarcopenia, the VLDL reductions were primarily observed in the MD-alone group (p < 0.01), suggesting that the addition of ONS did not confer incremental VLDL-lowering benefit—and may have attenuated it—in sarcopenic patients. Conversely, in patients WITHOUT sarcopenia, the MD+ONS group appeared to drive favorable lipidomic changes (statistical threshold and specific parameters for the non-sarcopenic subgroup finding are not fully reported in the available abstract, which was truncated). Confidence intervals, NNT/NNH, and between-group effect sizes for subgroup comparisons were not reported. No specific adverse lipid events or safety signals were described in the abstract.
Practice implications
This study establishes that both nutritional strategies reduce atherogenic VLDL-fraction parameters over 24 weeks in HF patients with predominantly reduced ejection fraction and high sarcopenia prevalence—an encouraging signal given that VLDL-TG and VLDL-P are associated with cardiometabolic risk. However, the critical and clinically meaningful finding is the interaction between treatment arm and sarcopenia status: MD alone appeared sufficient—and perhaps superior—for VLDL lowering in sarcopenic HF patients, while MD+ONS may hold differential lipidomic advantages in non-sarcopenic patients. This interaction has important implications for nutritional prescription in HF, where sarcopenia status may need to guide supplement selection. The study does NOT establish whether these lipidomic changes translate into improved clinical outcomes (mortality, hospitalization, functional capacity), which remains undemonstrated. The findings apply most directly to older, predominantly male, HFrEF patients with high rates of sarcopenia and malnutrition; generalizability to HFpEF, women, or patients without nutritional compromise is not established. IMPORTANT LIMITATION OF THIS SUMMARY: Only the abstract of PMID 42451160 was available; the abstract was truncated and does not report complete between-group statistics for the non-sarcopenic subgroup. Cohort-level descriptive data were supplemented from companion publications (same trial, same n=38 cohort). The full-text article should be consulted before any clinical application of these findings. __LIMITATIONS__ Very small sample size (n=38 completers), with further attrition from mortality during follow-up and subgroup analyses (sarcopenia n=25, no sarcopenia n=13), resulting in substantially underpowered subgroup comparisons with high risk of type I and type II error.,Open-label design without blinding of participants or investigators introduces significant performance and detection bias, particularly for a behavioral intervention like diet.,No placebo ONS comparator; participants in both arms were aware of their assignment, which may have differentially influenced dietary adherence and self-reported outcomes.,All-cause mortality occurred during follow-up, leading to differential dropout between arms; the nature and direction of this attrition bias on lipid outcomes is not reported.,The abstract is truncated; complete between-group statistics for the non-sarcopenic subgroup finding were not available for review, preventing full appraisal of the key interaction finding.,Sarcopenia was defined solely by handgrip strength percentile (without DXA or BIA body composition data), acknowledging that fluid overload in HF makes body composition measurement unreliable—but this limits comparability with studies using consensus definitions (EWGSOP2, AWGS).,Surrogate endpoints only: VLDL-C, VLDL-TG, and VLDL-P are intermediate biomarkers; no clinical outcome data (mortality, hospitalizations, NYHA class change, exercise capacity) are reported for the lipidomic analysis.,Single-center design limits generalizability to other health systems, dietary cultures, and HF phenotypes.,Confounding by background pharmacological therapy (statins, ACEi/ARBs/ARNIs, beta-blockers, diuretics, SGLT2i, MRA) is not addressed in the abstract; lipid-lowering medications could substantially confound lipidomic outcomes.,Statistical significance of subgroup findings (p < 0.01) does not confirm clinical importance; the magnitude and directionality of VLDL changes relative to clinical thresholds are not reported.,Funding source not reported; potential conflicts of interest related to the ONS manufacturer cannot be assessed from the abstract. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ In a small (n=38), open-label RCT of HF patients with predominantly reduced ejection fraction and high sarcopenia burden, both Mediterranean diet alone and Mediterranean diet plus omega-3-enriched ONS reduced atherogenic VLDL parameters over 24 weeks, but sarcopenia status appeared to modulate which intervention drove the lipidomic benefit. These hypothesis-generating findings underscore the need to phenotype HF patients for sarcopenia before prescribing supplemental ONS, but the very small sample size, open-label design, surrogate endpoints, and truncated reporting preclude any change in clinical practice at this time.