Effectiveness of a Comprehensive Program Including a Novel Concentrated High-Protein, High-Calorie Oral Nutritional Supplement to Enhance Nutritional and Morphofunctional Recovery in Malnourished Patients with Cancer: The ONAVIDA Study

Background/Objectives: Malnutrition in cancer adversely affects treatment outcomes and survival. Early intervention through oral nutritional supplements (ONSs) and dietary counseling can improve outcomes. This study evaluated the evolution of nutritional and morphofunctional parameters over three months in malnourished patients with cancer undergoing a comprehensive nutritional support program comprising dietary counseling, physical activity, and a novel concentrated high-protein, high-calorie ONS (cHPHC-ONS) with a high intrinsic leucine content. Methods: A prospective, observational, multicenter cohort study was conducted across 18 public hospitals in Spain. Two hundred thirty malnourished patients with cancer were enrolled: 147 naïve (no ONS treatment in the last three months) and 83 non-naïve (who transitioned to cHPHC-ONS after inadequate response to initial ONSs). Nutritional status was assessed using Global Leadership Initiative on Malnutrition (GLIM) criteria and morphofunctional parameters via bioelectrical impedance analysis, nutritional ultrasound, handgrip strength, the Timed Up and Go (TUG) test, and analysis of biochemical parameters. Results: After three months, 23.8% achieved normal GLIM nutritional status (p < 0.0001), with a greater improvement seen in non-naïve patients (28.4%, p < 0.0001). Weight loss ceased in 42.6% (p < 0.0001). and inflammation resolved for 10.3% (p = 0.0015). Non-naïve patients experienced a significant increase in fat-free mass index (p = 0.0159), appendicular skeletal muscle index (p = 0.0248), and rectus femoris cross-sectional area (p = 0.0016). Muscle strength increased significantly by +1.7 kg (p = 0.0025), and TUG test time decreased by 1.13 s (p = 0.0003) overall. Conclusions: The comprehensive nutritional support program—including a novel cHPHC-ONS, along with dietary and physical activity guidance—significantly improved the nutritional and morphofunctional status of malnourished patients with cancer, with benefits particularly evident in non-naïve individuals. Limitations: Observational design, no control group, short follow-up, and unadjusted non-multivariable comparisons, limiting causal inference.