Search Results (66)

Lactation imposes substantial metabolic demands on mares, and milk composition is a major determinant of neonatal development. Although β-hydroxy-β-methylbutyrate (HMB) can regulate protein turnover and energy metabolism in several livestock species, its role in the lactation-growth axis of equids remains insufficiently defined. This study evaluated maternal HMB-Ca supplementation in lactating Yili mares, focusing on milk yield measured during a standardized five-session daytime collection schedule, calculated milk-component output during that schedule, foal growth, and day-30 serum and milk metabolomic profiles. Maternal HMB-Ca supplementation was associated with greater milk yield at day 30 and with greater foal average daily gain during early lactation. To reduce over-interpretation of pathway enrichment alone, we performed a structured phenotype-metabolite correlation analysis. First, the day-30 milk-yield endpoint was correlated with serum differential metabolites; second, the serum features showing strong correlations with this endpoint were compared with milk differential metabolites; third, these serum features were related exploratorily to foal body weight and ADG. This analysis identified 26 serum features with |rho| ≥ 0.60 and nominal p < 0.05 for milk yield, 15 of which met FDR q < 0.10. Several of these features showed annotation-level overlap with the milk differential metabolome and exploratory associations with early foal growth traits. These findings support candidate serum-milk-growth metabolic links accompanying improved lactation performance, but they do not establish a causal pathway. Full article

β-hydroxy-β-methylbutyrate (HMB), a bioactive metabolite of leucine, is widely recognized for its anabolic and anti-catabolic effects in skeletal muscle. However, the molecular mechanisms underlying these effects, particularly in relation to circadian regulation, remain incompletely understood. Here, we investigated the impact of HMB on dexamethasone-induced muscle atrophy in C2C12 myotubes, with a focus on anabolic signaling and circadian clock regulation. C2C12 myotubes were treated with HMB or HMB after dexamethasone-induced atrophy. HMB treatment significantly improved cell viability, surface area and fiber diameter by reducing expression of CBL-B, MuRF1 and Atrogin1, key mediators of muscle proteolysis, and increasing myogenin expression compared with atrophic conditions. While HMB did not activate AKT or mTOR, it robustly increased phosphorylation of P70S6K and S6 through a phospholipase D (PLD)-dependent mechanism. HMB restored disrupted circadian clock gene expression induced by dexamethasone, including normalization of expression patterns. HMB also enhanced circadian rhythmic amplitude and advanced phase timing, indicating improved clock robustness. These findings identify circadian regulation as a novel target of HMB action and demonstrate that HMB preserves muscle homeostasis through coordinated modulation of anabolic signaling and intrinsic circadian machinery. This study provides mechanistic insight into how HMB protects against muscle atrophy and highlights circadian regulation as an important contributor to skeletal muscle health. Full article

Background: Oral nutritional supplementation (ONS) is commonly prescribed in malnourished older adults after hip fracture, but formulations are heterogeneous, and their comparative association with mortality remains unclear. We aimed to evaluate whether HMB-containing ONS was associated with lower mortality than non-HMB ONS and to explore whether supplement formulation combined with treatment persistence was associated with differential mortality patterns. Methods: This was a formulation-specific subanalysis of a previously described prospective cohort of older adults with hip fracture and malnutrition or significant nutritional risk. Only patients with known ONS formulation were included (n = 107): 59 received HMB-containing ONS, and 48 received non-HMB ONS, including standard, diabetes-specific, and renal-oriented formulations. Mortality at 3, 6, and 12 months was analyzed using crude comparisons and multivariable logistic regression adjusted for sex, age, and Charlson comorbidity index. A 6-month adjusted Cox model was used as the main time-to-event analysis. Exploratory analyses assessed mortality according to supplement formulation and treatment persistence. Results: Overall mortality was 14.0% at 3 months, 23.4% at 6 months, and 29.9% at 12 months. At 6 months, mortality was lower among patients receiving HMB-containing ONS than among those receiving non-HMB ONS (13.6% vs. 35.4%; p = 0.011), and the association remained significant after adjustment (OR 0.267; 95% CI 0.091–0.784; p = 0.016). Associations at 3 and 12 months were directionally consistent but not statistically significant. In the adjusted Cox model, prescription of HMB-containing ONS was associated with a lower hazard of death within 6 months (HR 0.358; 95% CI 0.145–0.885; p = 0.026). Exploratory analyses showed a 6-month mortality gradient according to formulation and persistence, ranging from 0.0% in patients receiving HMB-ONS for ≥3 months to 41.2% in those receiving non-HMB ONS for <3 months. Conclusions: In this formulation-specific subanalysis of malnourished older adults with hip fracture, an association between HMB-containing ONS and lower 6-month mortality was observed compared with non-HMB ONS. Exploratory findings suggested a clinically relevant mortality gradient according to both supplement formulation and treatment persistence, although these results should be interpreted cautiously. Larger prospective studies are warranted to confirm these findings. Full article

Background/Objectives: Type 2 diabetes (T2D)-associated sarcopenia is characterized by impaired insulin signaling, lipotoxicity, oxidative stress, and progressive muscle loss. Although liraglutide improves glucose control and reduces lipid burden, its ability to preserve muscle integrity under diabetic lipotoxic conditions remains limited. This study investigated whether β-hydroxy-β-methylbutyrate (HMB) could enhance liraglutide-mediated protection against high-glucose plus free fatty acid (HG+FFA)-induced injury in skeletal muscle cells. Methods: Differentiated C2C12 myotubes were exposed to HG+FFA to establish a sublethal lipotoxic model and treated with liraglutide, HMB, or their combination. Cell viability, lipid accumulation, myotube morphology, insulin signaling, glucose uptake, mitochondrial function, reactive oxygen species (ROS), antioxidant gene expression, and atrophy-related signaling were assessed. Results: HG+FFA induced marked lipid droplet accumulation, impaired insulin signaling, reduced glucose uptake, disrupted mitochondrial membrane potential, increased ROS production, suppressed antioxidant gene expression, and promoted an atrophic phenotype characterized by increased atrogin-1 and MuRF1 and reduced myogenic markers. Liraglutide alone reduced large lipid droplets and partially improved insulin signaling but showed limited efficacy in preserving the myotube phenotype. HMB alone exerted modest effects on lipid accumulation but preserved myotube area. Notably, combined HMB and liraglutide treatment more effectively reduced lipid burden, restored insulin signaling and glucose uptake, attenuated mitochondrial dysfunction and oxidative stress, restored antioxidant gene expression, and preserved MyHC-positive area and myotube diameter while suppressing atrogin-1/MuRF1 activation. These protective effects were largely attenuated by rapamycin, indicating at least partial dependence on mTOR-associated signaling. Conclusions: Overall, HMB and liraglutide exert complementary protective effects against diabetic lipotoxic and atrophic stress, supporting the potential utility of this combination strategy for T2D-associated sarcopenia. Full article

Background: Sarcopenia is associated with adverse surgical outcomes. Recent literature suggested that pre-surgery prehabilitation, nutrition and β-Hydroxy β-methylbutyric acid (HMB) supplementation improve myological and functional outcomes. However, long-term outcomes remain uncertain. Thus, we aimed to analyse findings from the long-term follow-up of surgical patients undergoing oral supplementation and prehabilitation. Methods: A prospective single-centre pilot cohort study was conducted to evaluate the effects of multimodal prehabilitation using high-protein oral nutritional supplementation (HP-ONS) with HMB. Sarcopenic patients between 40 and 90 years old and undergoing gastrointestinal surgery were included from June 2022 to January 2024. Patients were followed up from two to four weeks pre-operatively to six months post-operatively. Paired Wilcoxon signed-rank tests were conducted to evaluate outcomes between time points. Results: 36 patients were included with a median age of 71.5 years (IQR: 55–90), and 50% were male. 12 (33.3%) patients were sarcopenic, while 24 (66.7%) were severely sarcopenic. No significant difference in IMAT% was observed at post-operative six months. Number of chair rise repetitions (Median:15 vs. 11, p < 0.001) and six-min walk test (Median: 387 m vs. 349 m, p = 0.020), mid-arm muscle circumference (Median: 23.7 cm vs. 22.5 cm, p = 0.013), mid-arm muscle area (Median: 44.8 cm² vs. 39.3 cm², p = 0.005), weight (Median: 51.6 kg vs. 50.8 kg, p = 0.023) and BMI (Median: 23.2 kg/m² vs. 21.8 kg/m², p = 0.025) increased significantly at six-months post-operatively from surgery. Conclusions: Our findings suggest that improvements in anthropometric and functional outcomes from prehabilitation may persist beyond the acute recovery period. If supported by future works, multimodal prehabilitation has the potential to optimise postoperative recovery amongst sarcopenic older adult surgical patients. Full article

Introduction: Sarcopenia and frailty are prevalent yet under-recognized contributors to disability, impaired quality of life, and adverse outcomes in chronic obstructive pulmonary disease (COPD). Shared mechanisms, including systemic inflammation, hormonal dysregulation, malnutrition, and physical inactivity, render these syndromes important targets for multimodal intervention. This review summarizes current evidence on exercise-based, nutritional, pharmacological, and adjunctive strategies for their management in COPD. Materials and Methods: This narrative review is based on a structured literature search of PubMed, Scopus, and Embase to identify relevant studies published between January 2000 and May 2025. Eligible publications included randomized controlled trials, meta-analyses, systematic reviews, and observational studies involving adults with COPD and documented sarcopenia and/or frailty. Interventions were categorized by modality, and outcomes included muscle mass, strength, physical performance, quality of life, and hospitalizations. Data were synthesized thematically. Results: Resistance and combined exercise training consistently improved muscle strength and physical function, while endurance training enhanced cardiorespiratory capacity, particularly within pulmonary rehabilitation programs. Nutritional interventions, especially protein, leucine, or β-hydroxy-β-methylbutyrate supplementation, supported gains in lean mass and exercise tolerance. Pharmacological strategies, including anabolic hormones and myostatin inhibitors, showed early promise but require further evaluation regarding safety and long-term efficacy. Adjunctive therapies, such as neuromuscular electrical stimulation and oxygen supplementation, benefited patients unable to participate in conventional exercise training. Conclusions: An integrated, multimodal approach combining structured exercise training and targeted nutritional support should be considered a cornerstone of COPD management to prevent and treat sarcopenia and frailty. Personalized rehabilitation strategies can substantially improve functional outcomes and quality of life, while future research should prioritize biomarker-guided personalization and long-term intervention studies. Full article

Background: Hemodialysis (HD) patients frequently develop muscle wasting and chronic inflammation, conditions associated with functional decline and reduced quality of life (QoL). Nutritional strategies that provide targeted anabolic support without increasing nitrogen load may offer clinical benefits. The aim of this study was to evaluate the possible impact of a food for special medical purposes (FFSMP), composed of free-form branched-chain amino acids, β-hydroxy-β-methylbutyrate, and zinc, on muscle mass and strength, laboratory parameters, physical performance (PP), and QoL in HD patients. Methods: in this randomized double-blind crossover study, 24 adult HD patients received the FFSMP (10 g/day; two sachets) supplementation or placebo for 12 weeks, separated by an 8-week wash-out (protocol code RS 29.23). Measured outcomes included quadriceps rectus femoris thickness (QRFT) muscle, body composition analysis, inflammatory markers, oxidative stress indices, other routine biochemical parameters, PP, and QoL (SF-36 questionnaire). Results: FFSMP supplementation resulted in significant increases in QRFT and in fat-free mass percentage. Reductions in oxidative stress and inflammatory biomarkers were observed. Routine biochemical parameters remained stable, with the exception of a decrease in pre-dialysis urea. Functional performance measures did not differ between treatment periods. Improvements were noted in selected SF-36 domains, specifically energy/fatigue and general health. No major adverse events occurred during the study. Conclusions: In HD patients, this FFSMP produced favorable changes in markers of muscle mass and systemic inflammation without affecting short-term physical performance. These findings support the potential clinical utility of targeted amino acid supplementation in this patient population, highlighting the need for larger, longer-term trials. Full article

Background: Ulcerative colitis (UC) is characterized by chronic mucosal inflammation, oxidative stress, and disruption of intestinal metabolic homeostasis. Immunomodulatory nutrients such as arginine, glutamine, and β-hydroxy β-methylbutyrate (HMB) have shown potential benefits; however, their combined molecular effects on UC remain insufficiently defined. Objective: To investigate the individual and combined effects of arginine, glutamine, and HMB on inflammatory and metabolic gene expression, oxidative stress markers, and histopathological outcomes in a dextran sulfate sodium (DSS)-induced colitis model. Methods: Female Sprague Dawley rats were assigned to six groups: control, DSS, DSS + arginine, DSS + glutamine, DSS + HMB, and DSS + mixture. Colitis was induced using 3% DSS. Colon tissues were examined histologically, serum MDA, MPO, and GSH levels were quantified, and mRNA expression of IL6, IL10, COX2, NOS2, ARG2, CCR1, and ALDH4A1 was measured by RT-qPCR. Pathway enrichment analyses were performed to interpret cytokine and metabolic network regulation. Results: DSS induced severe mucosal injury, elevated MDA and MPO, reduced GSH, and significantly increased IL6, COX2, NOS2, ARG2, and CCR1 expression. Glutamine demonstrated the strongest anti-inflammatory and antioxidant effects by decreasing IL6 and COX2 and restoring GSH. Arginine primarily modulated nitric oxide–related pathways, whereas HMB increased ALDH4A1 expression and metabolic adaptation. The combination treatment produced more balanced modulation across inflammatory, chemokine, and metabolic pathways, consistent with enrichment results highlighting cytokine signaling and amino acid metabolism. Histopathological improvement was greatest in the mixture group. Conclusions: Arginine, glutamine, and HMB ameliorate DSS-induced colitis through coordinated regulation of cytokine networks, oxidative stress responses, and metabolic pathways. Their combined use yields broader and more harmonized therapeutic effects than individual administration, supporting their potential as targeted immunonutritional strategies for UC. Rather than targeting a single inflammatory mediator, this study was designed to test whether combined immunonutrient supplementation could promote coordinated regulation of cytokine signaling, oxidative stress responses, and metabolic adaptation, thereby facilitating mucosal repair in experimental colitis. Full article

Resveratrol (RES), a natural polyphenol, and β-hydroxy-β-methylbutyric acid (HMB), a key metabolite of leucine, are emerging as potent feed additives in animal production. This study investigated the individual and combined effects of dietary RES and HMB on gut microbiota, metabolic profiles, and meat quality in Tibetan sheep. A total of 120 two-month-old male lambs were randomly assigned to four experimental groups: control (C, basal diet, n = 6), RES (basal diet + 1.5 g/d RES, n = 6), HMB (basal diet + 1.25 g/d HMB, n = 6), and RES-HMB (basal diet + 1.5 g/d RES + 1.25 g/d HMB, n = 6), with 16S rDNA sequencing and LC-MS/MS analyses performed on rumen fluid and longissimus lumborum (LL). Meat quality improved significantly in all supplemented groups, the RES-HMB co-administration exhibited the most pronounced effects, suggesting a synergistic interaction. These improvements were linked to the activation of amino acid (AA) and unsaturated fatty acid biosynthesis pathways, leading to increased levels of AAs and polyunsaturated fatty acids (PUFAs). Concurrently, dietary RES and HMB supplementation enriched the relative abundance of beneficial gut microbiota, notably Christensenellaceae_R-7_group and Solibacillus, which further promoted the production of short-chain fatty acids, AAs, and PUFAs. The study highlights the role of rumen microbiota in regulating muscle metabolism and meat quality, offering a new scientific basis of strategies for using green feed additives in Tibetan sheep. Full article

Background/Objectives: Resistance training (RT) is a key strategy to counteract age-related declines in muscle strength and physical function. β-hydroxy-β-methylbutyrate (HMB) has been proposed as a complementary supplement to enhance these adaptations. However, the additional effects of RT plus HMB (RT+HMB) compared with RT alone remain unclear. This systematic review and meta-analysis evaluated the effects of RT+HMB versus RT alone on body composition, muscle quality (MQ), and physical function in older adults. Methods: Following PRISMA guidelines (PROSPERO: CRD420251144810), six databases (PubMed, Scopus, Cochrane Library, CINAHL, Web of Science, and ScienceDirect) were searched up to July 2025. Randomized controlled trials comparing RT+HMB with RT alone were included. Methodological quality was assessed with the PEDro scale and risk of bias using Cochrane RoB 2. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. Results: Ten trials (n = 596) met inclusion criteria. RT+HMB produced modest and borderline significant improvements in handgrip strength (SMD 0.24; 95% CI 0.00–0.48; p = 0.05) and moderate benefits in Short Physical Performance Battery (SPPB) scores (SMD 0.54; 95% CI 0.12–0.95; p = 0.01). No significant effects were observed for gait speed, appendicular lean mass, MQ, fat mass, or body weight (p > 0.05). Five trials (50%) were rated at high risk of bias, limiting confidence in pooled estimates. Conclusions: HMB supplementation combined with RT may yield modest improvements in functional performance, particularly handgrip strength and overall physical function, without statically significant effects in body composition and MQ. Further high-quality RCTs are warranted to confirm its clinical relevance. Full article

Nutritional supplementation is widely used in resistance training, yet assessment of “hypertrophy” is often confounded by body-composition surrogates. This narrative review, anchored in mechanistic plausibility, integrates trials reporting morphology-direct outcomes (ultrasound/MRI). Across 46 eligible trials, protein/essential amino acids (EAA) showed consistent benefits when daily intake was <1.6 g·kg⁻¹·day⁻¹ or when per-meal leucine provision was <2–3 g; effects plateaued once intakes exceeded ~2.0 g·kg⁻¹·day⁻¹. Creatine monohydrate (3–5 g·day⁻¹, with or without loading) produced measurable increases in muscle thickness or cross-sectional area in interventions lasting ≥8–12 weeks, mediated by enhanced training volume and quality. β-hydroxy-β-methylbutyrate (HMB, 3 g·day⁻¹) demonstrated conditional utility during high training stress or caloric deficit, but was largely neutral in well-fed, resistance-trained cohorts. Adjuncts such as omega-3 fatty acids (1–2 g·day⁻¹), citrulline (6–8 g pre-exercise), and collagen (10–15 g·day⁻¹ plus vitamin C) primarily facilitated training tolerance, recovery, or connective-tissue adaptation, rather than driving hypertrophy directly. A tiered model is proposed: protein/EAA as the foundation, creatine as amplifier, HMB as conditional agent, and adjuncts as facilitators. Methodological heterogeneity, short intervention length, and inconsistent imaging protocols remain limiting factors, underscoring the need for standardized ultrasound/MRI and adequately powered, preregistered trials. Full article

Background/Objectives: Malnutrition in hospitalized older adults is associated with increased healthcare utilization, prolonged hospitalizations, and higher readmission rates. Specialized oral nutritional supplements enriched with β-hydroxy-β-methylbutyrate (HMB-ONS) have shown benefits in preserving muscle mass, improving functional outcomes, and reducing readmission rates, yet real-world data on their effectiveness remain limited. This study evaluated the association between HMB-ONS use and hospital readmission rates, as well as healthcare costs, in patients with malnutrition or at risk of malnutrition. Methods: This retrospective study analyzed electronic medical records (2015–2021) of hospitalized patients at risk of malnutrition at two tertiary care hospitals in Israel. Patients receiving HMB-ONS during hospitalization were compared with those receiving standard ONS (S-ONS). Propensity score matching (PSM) was employed to reduce potential confounding due to differences in observable characteristics. Primary outcomes were readmission rates at 1-, 3-, and 6-month post-discharge. A cost analysis estimated per-patient hospitalization costs and financial savings from reduced readmissions. Results: Of 391,838 hospitalizations, 16,751 patients met the inclusion criteria. Patients with malnutrition or at risk of malnutrition who received HMB-ONS during hospitalization were PSM-matched to those who received S-ONS (n = 1440, 53.5% female, average age of 78.25 (±15.62) years). Patients who received HMB-ONS had significantly lower odds of readmission compared with those receiving S-ONS at 1 month (OR = 0.698; 95% CI: 0.548–0.888; p = 0.0034), 3 months (OR = 0.772; 95% CI: 0.623–0.958; p = 0.0187), and 6 months (OR = 0.780; 95% CI: 0.633–0.961; p = 0.0195). Based on these differences, the economic analysis estimated net cost savings of EUR 387.61 (USD 403.29) per patient for HMB-ONS versus S-ONS. Conclusions: HMB-ONS was associated with significantly lower readmission rates and healthcare costs compared to S-ONS in patients with malnutrition or at risk of malnutrition. These findings may support the use of specialized nutritional interventions to improve clinical outcomes and optimize hospital resource utilization in patients with malnutrition or at risk of malnutrition. Full article

Anabolic resistance, consisting of a diminished ability of aging muscle to respond to anabolic stimuli such as exercise and protein intake, is a key contributor to age-related declines in muscle mass. However, diseases and lifestyle factors associated with aging, including insulin resistance states, overweight/obesity, persistent inflammation and specifically—as a focus herein—physical inactivity and inadequate dietary protein-intake habits, might interact with chronological impairments in muscle anabolism. In this context, master athletes, as individuals who have engaged in lifelong structured exercise, including regular training and sports participation, offer a valuable model for studying processes of chronological vs. inactivity-related aging. While these lifelong exercisers may present improved body composition parameters and other potential benefits in terms of muscle mass and function, it remains unclear whether exercise practice throughout life can prevent the development of anabolic resistance associated with aging. Albeit limited, evidence has indicated that even in lifelong-trained older individuals there is a blunted post-exercise muscle anabolic response compared to younger athletes. However, there is a paucity of data to systematically understand the differences in postprandial anabolic response to varying protein doses in older vs. young athletes. In lieu of the above, it seems reasonable that master athletes may benefit from increasing protein intake closer to the upper limit of current recommendations (1.6–2.0 g/kg/day). In addition, supplementing their diet with ingredients that have established anabolic potential, including branched chain amino acids (BCAAs) such as leucine, the leucine metabolite β-hydroxy-β-methylbutyrate (HMB), and n3-polyunsaturated fatty acids (n3-PUFA), may potentiate the anabolic response to protein and exercise. Full article

β-Hydroxy-β-methylbutyrate (HMB), a natural metabolite derived from the essential amino acid leucine, is primarily recognised for its anabolic and anti-catabolic effects on skeletal muscle tissue. Recent studies indicate that HMB may also play a role in influencing the structural organisation of extracellular matrix (ECM) components, particularly collagen, which is crucial for maintaining the mechanical integrity of connective tissues. In this investigation, bovine type I collagen was polymerised in the presence of two concentrations of HMB (0.025 M and 0.25 M) to explore its potential function as a molecular modulator of fibrillogenesis. The morphology of the resulting collagen fibres and their molecular architecture were examined using atomic force microscopy (AFM) and Fourier-transform infrared (FTIR) spectroscopy. The findings demonstrated that lower levels of HMB facilitated the formation of more regular and well-organised fibrillar structures, exhibiting increased D-band periodicity and enhanced stabilisation of the native collagen triple helix, as indicated by Amide I and III band profiles. Conversely, higher concentrations of HMB led to significant disruption of fibril morphology and alterations in secondary structure, suggesting that HMB interferes with the self-assembly of collagen monomers. These structural changes are consistent with a non-covalent influence on interchain interactions and fibril organisation, to which hydrogen bonding and short-range electrostatics may contribute. Collectively, the results highlight the potential of HMB as a small-molecule regulator for soft-tissue matrix engineering, extending its consideration beyond metabolic supplementation towards controllable, materials-oriented modulation of ECM structure. Full article

Background/Objective: We compared healthcare utilization and cost outcomes for patients before and after they underwent a nutrition care intervention that included daily consumption of specialized or standard oral nutritional supplements (ONS) as part of a multimodal program. We sought to determine whether this nutritional intervention was associated with reduced use of healthcare resources and lowered costs. Methods: This retrospective analysis included adult patients who were referred to the medical nutrition office with malnutrition or its risk. We followed outcomes for patients who had received nutritional interventions (3–6 months) that included diet and exercise recommendations as well as a specialized ONS enriched with β-hydroxy-β-methylbutyrate (HMB-ONS) or a standard ONS (S-ONS). We reviewed hospital records for resource utilization data—hospital (re)admissions, number of days in the hospital, patient visits to the emergency department (ED), and visits to general practitioners (GP) and specialty physician clinics. We compared healthcare utilization for intervals up to 12 months before and after the initiation of the nutrition care intervention. We also examined healthcare utilization and costs as well as changes in oncology treatment following initiations of the nutrition care intervention for a subgroup of cancer patients. Results: Over a 12-month period following the start of nutritional intervention with ONS, the patients had lower healthcare resource use and costs. With daily use of S-ONS or HMB-ONS for up to 6 months, the patients’ healthcare utilization was significantly reduced at 3-, 6-, and 12-month time points for hospital admissions, ED visits, GP visits, and specialty visits (all p < 0.001). Overall, ONS use was associated with reduced patient healthcare costs by half (EUR 27,024.80 to EUR 13,349.60, p < 0.001). Significant clinical predictors of higher use of healthcare resources and costs were older age, having positive indications of malnutrition, exhibiting a greater Charlson Comorbidity Index (CCI), and having been hospitalized for oncology surgery. Regression analysis revealed that ONS intervention was associated with lower total healthcare costs (β_Post-ONS = −0.504), and that patients receiving HMB-ONS (β_ONS-HMB = −0.583) had a greater reduction in costs than did patients receiving S-ONS in the 12 months after nutritional intervention. Patients with cancer who received HMB-ONS were less likely than those receiving S-ONS to need suspension or dose reduction in oncology drug treatment due to failure or intolerance of the treatment drug. Conclusions: multimodal programs including ONS improve health economic outcomes for patients with poor nutritional status due to disease. Health economic outcome improvements included lower healthcare resource use, lower healthcare costs, and, for patients being treated for cancer, a reduced likelihood of treatment failure. The use of ONS enriched with HMB provided advantages over standard ONS, both in health outcomes and cost-of-care reductions. Full article