Vitamin C, Vitamin D, and Zinc in Respiratory Health: Mechanistic Pathways and Clinical Evidence

Abstract Respiratory diseases- including upper respiratory tract infections (URTI), influenza, coronavirus disease 2019 (COVID-19), asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), pulmonary fibrosis, and Post-COVID-19 Syndrome (Long COVID) - constitute a continuum of acute and chronic disorders characterized by oxidative stress, immune dysregulation, epithelial and endothelial barrier dysfunction, and extracellular matrix (ECM) remodeling. Nutritional modulation provides a multi-dimensional strategy to address these overlapping pathological axes. This paper synthesizes mechanistic, translational, and clinical evidence on vitamin C, vitamin D, and zinc as core modulators of respiratory resilience, together with their synergistic interactions with quercetin, bromelain, elderberry (Sambucus nigra), mulberry leaf (Morus alba), and fish cardiac arterial bulb-derived elastin peptides (FCAB-EPs). Vitamin C functions as a redox regulator and collagen cofactor, enhancing endothelial stability, leukocyte function, and fibrotic restraint. Vitamin D, via vitamin D receptor (VDR) signaling, induces antimicrobial peptides (LL-37, β-defensins), rebalances Th1/Th17–Treg immune axes, and stabilizes tight-junction integrity. Zinc orchestrates antiviral restriction (RNA polymerase inhibition), immune maturation, metallothionein-mediated antioxidant defense, and epithelial restitution. Synergistic nutrient partners extend these effects into targeted mechanistic domains: - Quercetin enhances intracellular zinc uptake as a zinc ionophore, complements vitamin C in redox control, and attenuates NLRP3 inflammasome activation. - Bromelain lowers mucus viscosity, modulates bradykinin-mediated edema, and reduces airway obstruction, complementing zinc’s barrier repair and vitamin D’s junctional stability. - Elderberry polyphenols inhibit viral entry via hemagglutinin binding interference and reduce pro-inflammatory cytokines, synergizing with zinc’s replication inhibition and vitamin D’s antimicrobial priming. - Mulberry leaf bio-actives restrain metaflammation by reducing glycemia-driven NF-κB activation and oxidative stress, integrating with zinc and vitamin D in immune–barrier regulation. - Fish cardiac arterial bulb–derived elastin peptides (FCAB-EPs) provide structural substrates and signaling cues for elastic fiber regeneration, ECM remodeling, and compliance restoration, complementing zinc’s anti-fibrotic regulation and vitamin C’s collagen stabilization. Collectively, these interactions establish a systems-level, multi-nutrient defense and repair framework, spanning antiviral containment, immune homeostasis, mucus and edema resolution, metabolic-inflammatory modulation, and elastic tissue regeneration. Clinical and translational data suggest that such strategies hold promise not only in reducing incidence and severity of acute infections (URTI, influenza, COVID-19) but also in stabilizing chronic airway disorders (asthma, COPD), improving outcomes in critical illness (ARDS), restraining fibrotic progression, and supporting rehabilitation in Long COVID. This integrative approach redefines nutritional interventions as multi-targeted, mechanistically coherent adjuncts in respiratory medicine.