Whey proteins revisited: from an amino acid source to therapeutic potential-a narrative review.

Abstract

Whey proteins are well-established sources of indispensable amino acids, but their relevance to clinical nutrition may also depend on rapid digestion, leucine availability, sulfur-containing amino acids, and bioactive fractions. Previous reviews have commonly focused on sports nutrition, muscle protein synthesis, individual metabolic outcomes, or food-derived peptides, with less emphasis on how these characteristics may inform the formulation of Foods for Special Medical Purposes (FSMPs). This narrative review integrates clinical, preclinical, and mechanistic literature identified in PubMed, Scopus, and Web of Science, with emphasis on muscle metabolism, glycemic regulation, antioxidant and immunomodulatory pathways, wound healing, gut microbiota, and experimental protein-lipid complexes. The most consistent human evidence supports rapid postprandial aminoacidemia, stimulation of muscle protein synthesis, and acute modulation of postprandial glycemia. Evidence for improvements in muscle-related outcomes is also available for selected older or malnourished populations, although whey protein has frequently been administered as part of a multinutrient formulation. Antioxidant, immunomodulatory, wound-healing, microbiota-related, and anticancer-related effects remain supported mainly by mechanistic, in vitro, animal, or limited clinical evidence. Whey proteins should be considered high-quality protein sources with potentially relevant biofunctional properties rather than established therapeutic agents. Their use in FSMPs should be tailored to the target population, required protein and leucine delivery, tolerance, processing characteristics, and overall formulation. Comparative randomized trials are needed to define formulation-specific effects, dose-response relationships, long-term efficacy, and safety.

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