To inform this review, a structured literature search of PubMed, Scopus, and Embase was conducted covering the period from 1995 to 2025. Peer-reviewed English-language epidemiologic studies, mechanistic models, and clinical trials evaluating OS, antioxidant status, and asthma outcomes in children—and, when relevant, adults—were included. Throughout this review, findings derived directly from pediatric populations are identified as such. Where pediatric evidence is absent or limited, data from adult studies are presented as a mechanistic context or provisional extrapolations and are explicitly labeled accordingly. Clinical recommendations are grounded exclusively in age-appropriate evidence.

The following subsections organize the mechanistic evidence for antioxidant and nutraceutical interventions according to the three tiers of prevention. Several compounds—including curcumin, quercetin, resveratrol, zinc, selenium, magnesium, and vitamins D and E—appear across multiple tiers because they operate through distinct, stage-specific mechanisms at each level of disease development, reflecting their pleiotropic biological activity rather than redundancy. Primary prevention targets epithelial barrier integrity and damage-associated molecular patterns (DAMPs)-mediated inflammation before sensitization occurs. The epithelial barrier represents the first line of defense; its disruption releases DAMPs that activate the NLRP3 inflammasome, initiating the allergic cascade.

In vitro in murine and human cell models and confirmed in several rodent disease models, it has been shown that Curcumin directly suppresses NLRP3 inflammasome activation through multiple pathways, including NF-κB suppression, reduction of mitochondrial ROS, prevention of potassium efflux, and disruption of inflammasome assembly, thereby preventing DAMP-mediated inflammation and pyroptosis [9]. In epithelial barrier models, curcumin prevents tight junction disruption by upregulating expression of ZO-1, occludin, and claudin-1, and maintaining membrane integrity under oxidative challenge [10].

Quercetin protects epithelial mitochondrial integrity, preventing ROS-mediated NLRP3 activation. In Caco-2 epithelial and alveolar epithelial models, quercetin inhibits caspase-1 activation and IL-1β/IL-18 secretion. It enhances autophagy, which further blocks ROS generation and inflammatory cytokine release [11]. Well-designed human studies with polyphenols are still required to validate the translational relevance of these mechanistic findings.

Zinc is essential for tight junction protein assembly and epithelial barrier integrity. Zinc deficiency compromises barrier function by reducing ZO-1, occludin, and claudin expression. Zinc depletion can promote NLRP3 inflammasome activation through lysosomal disruption [12].

Selenium deficiency reduces GPx activity, increasing epithelial vulnerability to oxidant injury [13]. Selenium is the catalytic core of glutathione peroxidases (GPx, 1–4), which neutralize hydrogen peroxide and lipid peroxides before they damage barrier membranes [14].

Vitamin D strengthens epithelial tight junctions through vitamin D receptor (VDR)-mediated upregulation of claudins and occludin [15], and its antimicrobial peptide induction (cathelicidin) reduces pathogen-mediated barrier disruption [16]. Prenatal vitamin D sufficiency (> 30 ng/mL) associates with reduced childhood wheeze and asthma incidence [17].

Secondary prevention targets antigen-presenting cell (APC) phenotype, Nrf2-mediated antioxidant responses, and prevention of Th2 polarization after initial antigen exposure but before clinical disease manifests.

In the mouse model, Curcumin shifts dendritic cells (DCs) toward tolerogenic phenotypes by reducing CD80/CD86 costimulatory molecule expression [18] and may promote Treg differentiation and increase the production of IL-10 [19]. In human mast cells (HMC-1 line), curcumin inhibited both mRNA expression and the production of thymic stromal lymphopoietin, a key epithelial-derived cytokine that initiates and amplifies type 2 immune responses in allergic diseases [20].

Quercetin activates the SIRT1/Nrf2/HO-1 signaling axis and reduces OS markers in OVA-induced asthma models. Treatment with quercetin decreases eosinophilia, Th2 cytokines (IL-4, IL-5, IL-13), and airway inflammation while alleviating asthma through inhibition of ferroptosis [21]. Additionally, quercetin has been shown to improve Th1/Th2 balance by suppressing GATA-3 and increasing T-bet expression, thereby reducing allergic airway inflammation and hyperresponsiveness [22]. In allergic rhinitis models, quercetin also restores Treg/Th17 balance by inactivating the NF-κB pathway [23].

In cell model, resveratrol inhibits hypoxia-inducible factor 1-alpha protein accumulation and reduces NF-κB activity through SIRT1-mediated mechanisms [24] and in mice this suppresses the glycolytic pathway in immune cells, particularly reducing the upregulation of glycolytic enzymes and lactate production that drive Th17 cell differentiation, thereby shifting the immune balance toward a less inflammatory phenotype [25].

Zinc regulates DC maturation and promotes tolerogenic DC phenotypes characterized by reduced MHC-II expression and increased expression of immunosuppressive markers enhancing FoxP3+ regulatory T cell development and skewing the immune balance toward Treg expansion while reducing Th17 differentiation [26]. Zinc deficiency impairs DC tolerogenic function, favoring immunogenic responses, as demonstrated by increased MHC class II and costimulatory molecule expression and enhanced T cell activation capacity [27] and causes a shift from Th1 cellular immunity to Th2 humoral responses, impairing cell-mediated immune function and increasing allergy development [12].

Magnesium functions as a natural antagonist of L-type calcium channels in immune cells [28], thereby modulating intracellular calcium concentrations that are critical for immune cell activation and signaling [29]. Through this calcium channel antagonism, magnesium regulates calcium influx, which serves as a key priming signal for immune cells. Elevated intracellular calcium concentrations trigger leukocyte and macrophage activation, stimulate the release of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and promote the production of ROS [30]. By antagonizing calcium channels, magnesium thus exerts control over these calcium-dependent immune and inflammatory processes.

Vitamin D promotes Treg differentiation through VDR-mediated FOXP3 induction in cells [31]. In human studies, vitamin D supplementation consistently increases Treg frequency and IL-10 levels but had had no significant effect on serum IgE, blood eosinophils or fractional exhaled nitric oxide (FeNO) [32].

Vitamin E (α-tocopherol) functions as a lipid-soluble antioxidant that terminates lipid peroxidation chain reactions in cell membranes by scavenging peroxyl radicals [33]. In animal and human models under normal and disease conditions, it has been shown that Vitamin E supplementation, particularly α-tocopherol, enhances T cell-mediated immune responses primarily by reducing prostaglandin E2 (PGE2) production in macrophages [34]. This mechanism has been particularly well-documented in aged individuals, where macrophages produce elevated levels of PGE2 due to increased cyclooxygenase (COX) activity. Vitamin E reduces COX activity through post-translational mechanisms rather than by affecting COX2 gene expression or protein synthesis. PGE2 acts as an immunosuppressive lipid mediator that inhibits T cell proliferation and IL-2 secretion; by lowering PGE2 levels, vitamin E restores T cell function [34].

Tertiary interventions address established chronic asthma through mechanisms targeting persistent inflammation, OS, airway remodeling, and steroid responsiveness. In established asthma models, curcumin reduces airway hyperresponsiveness, eosinophilic infiltration, and mucus hypersecretion through Nrf2/HO-1 pathway activation [35]. Its metabolite tetrahydrocurcumin reduces IL-4Rα/Jak1/STAT6 pathway activity [36]. Curcumin acts at a post-translational level by maintaining both histone deacetylase-2 (HDAC2) activity and expression, thereby reversing steroid insensitivity induced by either cigarette smoke extract or OS in monocytes [37]. Curcumin may therefore have the potential to reverse steroid resistance, which is common in patients with chronic obstructive pulmonary disease (COPD) and asthma. In experimental asthma, quercetin mitigates ferroptosis-related airway inflammation, reducing iron overload, M1 proinflammatory macrophage polarization, lipid peroxidation marker malondialdehyde, and distorted mitochondria morphological changes in the lung tissues [38]. In lung injury models, quercetin protects alveolar epithelial cells by inhibiting ferroptosis via the SIRT1/Nrf2/GPx4 pathway [39]. In the allergic rhinitis mouse model, quercetin improves Th1/Th2 and Treg/Th17 imbalance and reduces IgE, IL-17, TGF-β, IL-6, TNF-α, and eosinophilic inflammation [23]. In preclinical airway inflammation and lung injury models, resveratrol has been shown to attenuate endoplasmic reticulum (ER) stress and to reduce apoptosis of epithelial or other airway-relevant cells [40]. It also enhances antioxidant defense systems (including Nrf2 activation and preservation of superoxide dismutase (SOD)/GPx activities) that may interrupt the ROS ↔ ER-stress vicious cycle [41]. In airway disease contexts, resveratrol ameliorates bronchial inflammation, airway hyperresponsiveness, and remodeling in murine models of asthma [42]. Moreover, although GC resistance is a major issue in severe asthma and resveratrol has been shown to improve GC-insensitivity in COPD airway cells through SIRT1–GR signaling [43], direct evidence in steroid-resistant asthma models or patients is lacking. Thus, while resveratrol holds promise as an adjunctive therapy to reduce ER stress and enhance GC responsiveness in airway diseases, further studies are needed to confirm these effects in chronic asthma, especially in the context of steroid resistance. A meta-analysis documented that asthma patients had lower selenium and zinc levels in serum or plasma compared with healthy controls [44], which, together with low vitamin D levels, may be associated with airway inflammation and poor asthma control [45]. Chronic inflammation is associated with depletion of zinc stores, which impairs the function of Cu/Zn-SOD1 and diminishes antioxidant defenses, thereby perpetuating oxidative damage [46].

Selenium is essential for GPx synthesis and activity, which protects against oxidative damage by catalyzing the reduction of hydrogen and lipid hydroperoxides [47]. In this context, asthmatic patients often demonstrate selenium deficiency and reduced GPx activity, suggesting impaired antioxidant capacity in chronically inflamed airways [48]. A study comparing 103 asthmatic patients with 103 healthy controls found approximately two-fold lower serum selenium levels in asthmatic subjects (p < 0.001), with selenium deficiency showing significant inverse correlation with inhaler usage (β = –0.226; p < 0.001) and asthma severity (β = –0.644; p < 0.001). These findings suggest that selenium deficiency may impair antioxidant defenses and contribute to asthma pathophysiology, indicating potential therapeutic benefits of selenium supplementation [49]. In 2,432 eligible adults with asthma, all-cause mortality dropped by 10% for every additional 10 units of blood selenium (μg/L) up to 200 μg/L and then increased with a U-shaped correlation [50].

Magnesium supplementation in CD4⁺ T cells, isolated from the blood of the acute asthmatic patients, decreases the secretion of Th2 cytokines (IL-4, IL-5, IL-13) while potentially supporting a more balanced Th1/Th2 cytokine profile [51].

Mitochondrial dysfunction represents a pathogenic mechanism operative across all three prevention tiers described above. It is therefore addressed here as a unifying cross-cutting theme, with specific clinical evidence reviewed further in Antioxidant nutraceuticals in asthma: insights from human studies section and Synergistic antioxidant framework: rationale for multicomponent nutraceutical therapy in asthma section. Mitochondrial dysfunction is increasingly recognized as an important pathogenic mechanism in asthma, contributing to OS, impaired cellular bioenergetics, and dysregulated inflammatory responses [52]. Structural and functional mitochondrial abnormalities promote excessive generation of mitochondrial ROS (mtROS), activation of redox-sensitive pathways such as the NLRP3 inflammasome, and the persistence of pro-inflammatory and metabolically altered cellular states within the airways [53]. A growing body of preclinical work suggests that several antioxidants and nutraceutical compounds exert direct mitochondrial-protective effects, including restoration of mitochondrial membrane potential, modulation of respiratory chain activity, and reduction of mtROS [3]. However, these findings derive largely from experimental models, and mitochondrial-targeted antioxidant strategies have only been modestly validated in clinical trials.

Curcumin appears to support healthier mitochondrial function in several experimental models. It helps cells produce new, well-functioning mitochondria, improves the activity of key energy-producing enzymes, and reduces the amount of harmful OS generated inside the mitochondria. Many of these benefits seem to involve activation of the SIRT1–PGC-1α pathway, which is one of the body’s main regulators of mitochondrial quality and energy metabolism and its ability to induce the expression of antioxidant enzymes via Nrf2 [54]. However, curcumin also acts through other cellular mechanisms, and its mitochondrial effects have not yet been confirmed in clinical studies, especially in children.

Quercetin exerts a range of dose- and context-dependent effects on mitochondrial structure and function. At physiologically relevant concentrations, quercetin has been shown in several cell and animal models to activate the SIRT1/PGC-1α pathway, increase the expression of nuclear regulators of mitochondrial biogenesis (PGC-1α, NRF-1, TFAM), and elevate surrogate markers of mitochondrial content such as mtDNA copy number, cytochrome c. In parallel, quercetin can enhance respiratory capacity and ATP generation under conditions of oxidative or inflammatory stress, thereby supporting cellular energy metabolism and stress resilience [55].

Resveratrol is a natural polyphenol that activates the NAD⁺-dependent deacetylase SIRT1, leading to the deacetylation and activation of PGC-1α, a central regulator of mitochondrial biogenesis. Through this pathway, resveratrol can enhance mitochondrial gene expression, support mitochondrial function, and improve cellular resistance to metabolic and OS [56].

Zinc is an essential cofactor for numerous metalloproteins and contributes to maintaining cellular redox balance and antioxidant defenses. Altered zinc homeostasis—whether deficiency or excess—can disrupt intracellular signaling, promote OS, and impair organelle function, including that of mitochondria. Although zinc imbalance is linked to increased ROS production and to mitochondrial and ER stress in chronic disease contexts, the precise zinc-dependent molecular mechanisms within mitochondrial respiratory pathways, and their relevance to respiratory-disease models, remain insufficiently defined and require further investigation [57].

GPx4 is the principal enzyme known to reduce phospholipid hydroperoxides in biological membranes, and by doing so, contributes to the preservation of mitochondrial inner-membrane integrity and function under OS. Because GPx4 is a selenium-dependent GPx that defends against lipid-peroxide–driven ferroptosis, it is hypothesized that selenium-GPx4 pathways may be relevant in chronic inflammatory disease, though dedicated studies in that domain remain limited [58]. Magnesium is fundamental to mitochondrial bioenergetics: it forms complexes with ATP (Mg-ATP), acts as a cofactor for multiple Krebs-cycle and oxidative-phosphorylation enzymes, and its deficiency impairs mitochondrial energy production [59]. It is therefore plausible that magnesium deficiency might contribute to cellular energy deficits in chronic asthma, although direct mechanistic studies in asthma are lacking. In summary, several antioxidants and minerals act on overlapping pathways that support mitochondrial function and reduce inflammation. Table 2 summarizes shared convergent mechanisms, highlighting where each compound contributes within this common network. Although these effects are primarily derived from cell and animal models, the underlying pathways are conserved across species, making it biologically plausible that similar mechanisms operate in humans. The mechanisms underlying redox imbalance in pediatric asthma, driven by ROS/reactive nitrogen species (RNS) from inflammatory cells and environmental pollutants, along with key targets for antioxidant therapies, are depicted in Figure 1.

The dietary studies reviewed below are discussed in the context of their capacity to modulate OS and antioxidant status. Where evidence derives from adult cohorts, this is explicitly noted; pediatric data are prioritized and presented first.

A cross-sectional study of children found lower antioxidant intake and lower total antioxidant status (TAS) in those with asthma vs. controls [60] (pediatric study). In a study of asthmatic children exposed to Mexico City air pollution, it was found that a higher intake of fruits and vegetables and greater adherence to a Mediterranean-style diet are associated with lower airway inflammation (reduced IL-8) and better lung function (higher FEV₁ and FVC). These dietary patterns also appear to buffer the harmful effects of ozone, suggesting that nutrition plays a meaningful protective role in polluted environments [61] (pediatric study). A randomized, double-blind, placebo-controlled 16-week trial investigated whether combining fruit and vegetable concentrates, fish oil, and probiotics could improve asthma control in school-aged children. Among 192 asthmatic participants, the supplement group showed significantly better pulmonary function—higher FEV₁, FVC, and FEV₁/FVC ratio—as well as reduced use of short-acting bronchodilators and inhaled corticosteroids compared with placebo [62] (pediatric randomized controlled trial [RCT]). In a pediatric trial, increasing fruit/vegetable intake by ~3.5 servings/day, plasma carotenoids rose, and airway reactance improved, although exacerbation rates did not significantly change [63] (pediatric trial). One recent RCT in children with mild-to-moderate asthma (aged 4–15 years) compared usual care vs. usual care + an antioxidant-rich diet (tomato juice + mixed fruit juice) for 8 weeks. The intervention arm showed improved Asthma Control Test (ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores and increased serum lycopene, β-carotene, and ascorbic acid levels compared to control [64] (pediatric RCT). In adults with asthma (NHANES cohort, n ≈ 4,698), higher Composite Dietary Antioxidant Index and lower dietary inflammatory index were significantly associated with lower all-cause mortality in subjects with asthma [65] (adult cohort, NHANES). Another cross-sectional study in severe asthma patients (n = 44) found that lower antioxidant intake and lower plasma TAS correlated with poorer asthma control and longer disease duration [66] (adult study). In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control [67] (adult study).

Beyond their individual health benefits, antioxidant-rich dietary patterns—characterized by high consumption of fruits, vegetables, legumes, whole grains, and reduced reliance on animal-source foods—align closely with dietary frameworks associated with lower environmental impact. Plant-dominant diets generate substantially fewer greenhouse gas emissions, require less land and water, and contribute less to biodiversity loss compared with Western meat-heavy dietary patterns [68]. This convergence suggests that dietary recommendations aimed at reducing oxidative burden in children with asthma may simultaneously contribute to planetary health goals. The concept of “co-benefits”—whereby individual nutritional interventions also reduce environmental pollutant load and climate-related stressors (e.g., increased ground-level ozone, wildfire smoke, and aeroallergen exposure associated with climate change)—provides an additional rationale for promoting antioxidant-rich dietary patterns as part of comprehensive asthma management strategies [69].

It is important to distinguish between two distinct clinical contexts for magnesium in asthma. Intravenous magnesium is an established evidence-based intervention for acute severe asthma in children [69, 70], producing rapid bronchodilation through calcium antagonism in airway smooth muscle [71]—this is an acute rescue therapy and is not the subject of this review. By contrast, oral magnesium supplementation (300 mg/day for 2 months) as a long-term adjunctive strategy in children with moderate persistent asthma led to fewer exacerbations, reduced need for inhaled salbutamol, and significantly reduced bronchial hyperreactivity compared with placebo, providing additional benefit beyond inhaled corticosteroids [68] (pediatric RCT). Oral magnesium supplementation appears beneficial and safe in children with moderate to severe asthma [72].

Selenium supplementation in established asthma may reduce inflammatory markers [70] and may improve lung function [71].

Zinc supplementation represents a plausible adjunct to restore antioxidant capacity and modulate immune-effector cell activity in chronic airway disease, through mechanisms detailed in the Redefining asthma treatment: biological plausibility of integrating environmental and antioxidant strategies section. However, direct clinical evidence in asthma remains limited, and further targeted studies are required to confirm these effects in airway-specific inflammation [72–75] (clinical evidence largely from adult or mixed populations).

Thus, although selenium or zinc supplementation is a plausible adjunct to restore antioxidant capacity and modulate immune-effector cell activity in chronic airway disease, further targeted studies are required to confirm these effects in airway-specific inflammation and mast cell-driven pathology. In established asthma, meta-analysis showed that vitamin D supplementation reduces the rate of exacerbations requiring systemic corticosteroids by approximately 25–30%, with benefits primarily observed in patients with baseline vitamin D insufficiency (25-hydroxyvitamin D < 30 ng/mL) (meta-analysis, mixed pediatric/adult populations) [72, 73].

Vitamin D enhances GR function and reduces corticosteroid resistance through anti-inflammatory mechanisms (mechanistic data—see Redefining asthma treatment: biological plausibility of integrating environmental and antioxidant strategies section) [74]. An 8-week double-blind RCT in children with moderate asthma demonstrated that 50 mg/day vitamin E improved FEV₁ and FEV₁/FVC, suggesting enhanced airway function (pediatric RCT) [75]. In an umbrella review of meta-analyses, there was consistent evidence of a beneficial association between circulating α-tocopherol levels and asthma or wheeze in children in both randomized and observational evidence (pediatric umbrella review) [76]. A randomized study of pomegranate extract (500 mg/day for 8 weeks) in adults with persistent allergic asthma found improved symptoms (day and night breath shortness) and reduced neutrophil and eosinophil counts in the intervention group vs control (adult RCT) [77].

The following combination studies are reviewed with explicit distinction between pediatric and adult populations, focusing on clinical outcomes including airway inflammation markers, lung function, and exacerbation rates. A small-scale pediatric study examined supplementation of a nutraceutical combination (curcumin, resveratrol, soy phospholipids, zinc, selenium, vitamin D) in children with asthma and found a reduction in FeNO over 4 weeks [78]. Importantly, this effect emerged at the end of the high-altitude residency, when FeNO values had already reached a stable plateau from allergen avoidance, indicating that antioxidant supplementation conferred an additional benefit beyond allergen reduction. No significant change in FeNO was observed in the control group, reinforcing that the reduction was attributable to the nutraceutical intervention. In a randomized placebo-controlled design, a multi-component supplementation containing curcumin, resveratrol, zinc, magnesium, selenium, and vitamin D significantly improved endothelial function in obese children [79]. This finding is relevant beyond obesity, because children with asthma also show early vascular abnormalities, including increased carotid artery intima-media thickness, arterial stiffness, and reduced distensibility, indicative of subclinical cardiovascular dysfunction [80]. Since asthma and obesity share systemic inflammation and OS as central mechanisms of endothelial injury, those results suggest that targeted antioxidant and anti-inflammatory supplementation could represent a promising supportive strategy to counteract vascular impairment in asthmatic children as well. Future studies are warranted to evaluate whether similar multi-nutrient interventions may mitigate the endothelial dysfunction documented in pediatric asthma. In a placebo-controlled trial, the combination of beta-glucan extracted from the mushroom Pleurotus ostreatus with vitamin C improved asthma control, reduced respiratory infections, and lowered exacerbations in children with perennial asthma [81]. One observational study assessed the relationship between self-reported antioxidant supplement use and plasma antioxidant status in asthmatic children. The study found significant positive associations between regular supplementation with vitamin A, E, selenium and β-carotene and multiple biomarkers of redox balance in asthmatics with improved total antioxidant capacity, compared to non-supplemented asthmatic children but not in healthy controls, suggesting disease-specific effects [82]. A review of plant-based antioxidants in asthma identified nine randomized trials, though with variable quality and heterogeneity in agents and outcomes. Despite these limitations, the review indicated that plant-based antioxidants could have adjuvant beneficial effects in the management of asthma inflammatory markers, which may help improve asthma-related clinical outcomes [83]. Furthermore, it has been suggested that an approach optimizing multiple micronutrients may have significant short- and even long-term benefits in relation to their multiple and synergic effects (Table 3) [84, 85]. A summary of the key clinical studies organized by intervention type (dietary, single-nutrient, multicomponent), population, study design, intervention, and key findings is reported in Table 4.