Targeting redox imbalance in pediatric asthma: environmental control, antioxidant strategies, and nutraceutical interventions

Abstract

Oxidative stress-an imbalance between reactive oxygen/nitrogen species and antioxidant defenses-contributes not only to the developmental origins of asthma but also to poor control, airway remodeling, and corticosteroid-resistant inflammation in children. Persistent oxidant exposure, nutritional insufficiency, and mitochondrial dysfunction sustain redox imbalance in pediatric asthma, suggesting potential roles for environmental, dietary, and nutraceutical strategies-defined here as natural bioactive compounds providing health benefits beyond basic nutrition, including polyphenols such as curcumin, quercetin, and resveratrol, and essential minerals such as zinc and selenium-that complement standard therapy. To summarize evidence on preventive and therapeutic approaches that modulate oxidative stress in pediatric asthma, focusing on environmental control, antioxidant-rich dietary patterns, single and multi-component nutraceuticals, and mitochondria-targeted interventions. A structured review of PubMed, Scopus, and Embase (1995–2025) identified peer-reviewed English-language epidemiologic studies, mechanistic models, and clinical trials evaluating oxidative stress, antioxidant status, and asthma outcomes in children and, when relevant, adults. Reference lists of major reviews were screened to identify additional studies. Interventions that reduce exposure to air pollutants and tobacco smoke, combined with antioxidant-rich diets such as high fruit/vegetable intake and Mediterranean-style patterns, are consistently associated with improved lung function, fewer symptoms, and reduced inflammation. Clinical trials of single antioxidants (vitamin D, vitamin E, zinc, selenium, magnesium) show modest, context-dependent benefits, primarily in children with baseline deficiencies. Emerging research suggests that multi-component nutraceuticals-including polyphenols and coordinated micronutrient formulations-may enhance redox balance and improve pulmonary or vascular outcomes, though current evidence is limited by small sample sizes and heterogeneity. Experimental data strongly support mitochondria-targeted mechanisms, but pediatric clinical validation remains sparse. Strategies that reduce oxidative burden or strengthen antioxidant defenses appear biologically plausible adjuncts to standard asthma therapy. Further large, biomarker-guided trials are needed to clarify efficacy, identify responsive phenotypes, and determine the role of multi-component approaches relative to single-nutrient supplementation.

Keywords

oxidative stress / pediatric asthma / nutraceuticals / antioxidants / polyphenol / Mediterranean diet / mitochondrial dysfunction / environmental control

References

[1] Ciencewicki J, Trivedi S, Kleeberger SR. Oxidants and the pathogenesis of lung diseases. J Allergy Clin Immunol. 2008; 122: 456-68; quiz 469.

[2] Li K, Ji X, Tian S, Li J, Tian Y, Ma X, et al. Oxidative stress in asthma pathogenesis: mechanistic insights and implications for airway smooth muscle dysfunction. Cell Tissue Res. 2025; 400: 17-34.

[3] Allam VSRR, Paudel KR, Gupta G, Singh SK, Vishwas S, Gulati M, et al. Nutraceuticals and mitochondrial oxidative stress: bridging the gap in the management of bronchial asthma. Environ Sci Pollut Res. 2022; 29: 62733-54.

[4] Nadeem A, Alshehri S, Al-Harbi NO, Ahmad SF, Albekairi NA, Alqarni SA, et al. Bruton’s tyrosine kinase inhibition suppresses neutrophilic inflammation and restores histone deacetylase 2 expression in myeloid and structural cells in a mixed granulocytic mouse model of asthma. Int Immunopharmacol. 2023; 117: 109920.

[5] Covar RA, Spahn JD, Murphy JR, Szefler SJ; Childhood Asthma Management Program Research Group. Progression of Asthma Measured by Lung Function in the Childhood Asthma Management Program. Am J Respir Crit Care Med. 2004; 170: 234-41.

[6] Larkin EK, Gao YT, Gebretsadik T, Hartman TJ, Wu P, Wen W, et al. New Risk Factors for Adult-Onset Incident Asthma. A Nested Case-Control Study of Host Antioxidant Defense. Am J Respir Crit Care Med. 2015; 191: 45-53.

[7] Oakley RH, Jewell CM, Yudt MR, Bofetiado DM, Cidlowski JA. The Dominant Negative Activity of the Human Glucocorticoid Receptor β Isoform. J Biol Chem. 1999; 274: 27857-66.

[8] Lewis BW, Ford ML, Rogers LK, Britt RD Jr. Oxidative Stress Promotes Corticosteroid Insensitivity in Asthma and COPD. Antioxidants. 2021; 10: 1335.

[9] Moon DO. Curcumin as a Dual Modulator of Pyroptosis: Mechanistic Insights and Therapeutic Potential. Int J Mol Sci. 2025; 26: 7590.

[10] Ghosh SS, He H, Wang J, Gehr TW, Ghosh S. Curcumin-mediated regulation of intestinal barrier function: The mechanism underlying its beneficial effects. Tissue Barriers. 2018; 6: e1425085.

[11] Xue Y, Du M, Zhu MJ. Quercetin suppresses NLRP3 inflammasome activation in epithelial cells triggered by Escherichia coli O157:H7. Free Radic Biol Med. 2017; 108: 760-9.

[12] Maywald M, Rink L. Zinc Deficiency and Zinc Supplementation in Allergic Diseases. Biomolecules. 2024; 14: 863.

[13] Coursin DB, Cihla HP. Pulmonary effects of short term selenium deficiency. Thorax. 1996; 51: 479-83.

[14] Ursini F, Bindoli A. The role of selenium peroxidases in the protection against oxidative damage of membranes. Chem Phys Lipids. 1987; 44: 255-76.

[15] Chen Y, Zhang J, Ge X, Du J, Deb DK, Li YC. Vitamin D Receptor Inhibits Nuclear Factor κB Activation by Interacting with IκB Kinase β Protein. J Biol Chem. 2013; 288: 19450-8.

[16] Gombart AF, Borregaard N, Koeffler HP. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D₃ . FASEB J. 2005; 19: 1067-77.

[17] Wolsk HM, Chawes BL, Litonjua AA, Hollis BW, Waage J, Stokholm J, et al. Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials. PLOS ONE. 2017; 12: e0186657.

[18] Cong Y, Wang L, Konrad A, Schoeb T, Elson CO. Curcumin induces the tolerogenic dendritic cell that promotes differentiation of intestine-protective regulatory T cells. Eur J Immunol. 2009; 39: 3134-46.

[19] Chai YS, Chen YQ, Lin SH, Xie K, Wang CJ, Yang YZ, et al. Curcumin regulates the differentiation of naïve CD4+T cells and activates IL-10 immune modulation against acute lung injury in mice. Biomed Pharmacother. 2020; 125: 109946.

[20] Moon PD, Jeong HJ, Kim HM. Down-regulation of thymic stromal lymphopoietin by curcumin. Pharmacol Rep. 2013; 65: 525-31.

[21] Sun B, Cai F, Yu L, An R, Wei B, Li M. Quercetin inhibits ferroptosis through the SIRT1/Nrf2/HO-1 signaling pathway and alleviates asthma disease. Transl Pediatr. 2024; 13: 1747-59.

[22] Park HJ, Lee CM, Jung ID, Lee JS, Jeong YI, Chang JH, et al. Quercetin regulates Th1/Th2 balance in a murine model of asthma. Int Immunopharmacol. 2009; 9: 261-7.

[23] Ke X, Chen Z, Wang X, Kang H, Hong S. Quercetin improves the imbalance of Th1/Th2 cells and Treg/Th17 cells to attenuate allergic rhinitis. Autoimmunity. 2023; 56: 2189133.

[24] Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, et al. Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004; 23: 2369-80.

[25] Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, et al. Control of TH17/Treg Balance by Hypoxia-Inducible Factor 1. Cell. 2011; 146: 772-84.

[26] George MM, Subramanian Vignesh K, Landero Figueroa JA, Caruso JA, Deepe GS Jr. Zinc Induces Dendritic Cell Tolerogenic Phenotype and Skews Regulatory T Cell-Th17 Balance. J Immunol. 2016; 197: 1864-76.

[27] Kitamura H, Morikawa H, Kamon H, Iguchi M, Hojyo S, Fukada T, et al. Toll-like receptor-mediated regulation of zinc homeostasis influences dendritic cell function. Nat Immunol. 2006; 7: 971-7.

[28] Levine BS, Coburn JW. Magnesium, the Mimic/Antagonist of Calcium. N Engl J Med. 1984; 310: 1253-5.

[29] Tam M, Gómez S, González-Gross M, Marcos A. Possible roles of magnesium on the immune system. Eur J Clin Nutr. 2003; 57: 1193-7.

[30] Nielsen FH. Magnesium deficiency and increased inflammation: current perspectives. J Inflamm Res. 2018; 11: 25-34.

[31] Kang SW, Kim SH, Lee N, Lee WW, Hwang KA, Shin MS, et al. 1,25-Dihyroxyvitamin D3 Promotes FOXP3 Expression via Binding to Vitamin D Response Elements in Its Conserved Noncoding Sequence Region. J Immunol. 2012; 188: 5276-82.

[32] El Abd A, Dasari H, Dodin P, Trottier H, Ducharme FM. The effects of vitamin D supplementation on inflammatory biomarkers in patients with asthma: a systematic review and meta-analysis of randomized controlled trials. Front Immunol. 2024; 15: 1335968.

[33] Wang X, Quinn PJ. Vitamin E and its function in membranes. Prog Lipid Res. 1999; 38: 309-36.

[34] Lee GY, Han SN. The Role of Vitamin E in Immunity. Nutrients. 2018; 10: 1614.

[35] Zhu T, Chen Z, Chen G, Wang D, Tang S, Deng H, et al. Curcumin Attenuates Asthmatic Airway Inflammation and Mucus Hypersecretion Involving a PPAR γ-Dependent NF-κB Signaling Pathway In Vivo and In Vitro. Mediat Inflamm. 2019; 2019: 4927430.

[36] Chen BL, Chen YQ, Ma BH, Yu SF, Li LY, Zeng QX, et al. Tetrahydrocurcumin, a major metabolite of curcumin, ameliorates allergic airway inflammation by attenuating Th2 response and suppressing the IL-4Rα-Jak1-STAT6 and Jagged1/Jagged2-Notch1/Notch2 pathways in asthmatic mice. Clin Exp Allergy. 2018; 48: 1494-508.

[37] Meja KK, Rajendrasozhan S, Adenuga D, Biswas SK, Sundar IK, Spooner G, et al. Curcumin Restores Corticosteroid Function in Monocytes Exposed to Oxidants by Maintaining HDAC2. Am J Respir Cell Mol Biol. 2008; 39: 312-23.

[38] Wang Y, Wan R, Peng W, Zhao X, Bai W, Hu C. Quercetin alleviates ferroptosis accompanied by reducing M1 macrophage polarization during neutrophilic airway inflammation. Eur J Pharmacol. 2023; 938: 175407.

[39] Deng S, Li J, Li L, Lin S, Yang Y, Liu T, et al. Quercetin alleviates lipopolysaccharideinduced acute lung injury by inhibiting ferroptosis via the Sirt1/Nrf2/Gpx4 pathway. Int J Mol Med. 2023; 52: e52.

[40] Cao Q, Gu L, Wang L, Sun G, Ying T, Su H, et al. Resveratrol alleviates endoplasmic reticulum stress-induced cell death and improves functional prognosis after traumatic brain injury in mice. J Appl Biomed. 2024; 22: 99-106.

[41] Shahcheraghi SH, Salemi F, Small S, Syed S, Salari F, Alam W, et al. Resveratrol regulates inflammation and improves oxidative stress via Nrf2 signaling pathway: Therapeutic and biotechnological prospects. Phytother Res. 2023; 37: 1590-605.

[42] Lee HY, Kim IK, Yoon HK, Kwon SS, Rhee CK, Lee SY. Inhibitory Effects of Resveratrol on Airway Remodeling by Transforming Growth Factor-β/Smad Signaling Pathway in Chronic Asthma Model. Allergy Asthma Immunol Res. 2017; 9: 25-34.

[43] Xie J, Che S, Liu J, Long X. SIRT1: potential target in glucocorticoid-resistant diseases. Front Immunol. 2025; 16: 1514745.

[44] Chen M, Sun Y, Wu Y. Lower circulating zinc and selenium levels are associated with an increased risk of asthma: evidence from a meta-analysis. Public Health Nutr. 2019; 23: 1555-62.

[45] Srivastava S, Tiwari V, Singh S, Karoli R, Bhattacharya P, Gupta N. Low Serum Levels of Zinc, Selenium, and Vitamin D3 Are Biomarkers of Airway Inflammation and Poor Asthma Control: A Two-Centre Study. Cureus. 2023; 15: e41082.

[46] Homma K, Fujisawa T, Tsuburaya N, Yamaguchi N, Kadowaki H, Takeda K, et al. SOD1 as a Molecular Switch for Initiating the Homeostatic ER Stress Response under Zinc Deficiency. Mol Cell. 2013; 52: 75-86.

[47] Rayman MP. The importance of selenium to human health. Lancet. 2000; 356: 233-41.

[48] Qujeq D, Hidari B, Bijani K, Shirdel H. Glutathione Peroxidase Activity and Serum Selenium Concentration in Intrinsic Asthmatic Patients. Clin Chem Lab Med. 2003; 41: 200-2.

[49] Girdhar N, Kansal H, Garg K, Sharma S, Prabhu KS, Chopra V, et al. Correlation of Serum Selenium in Asthma Patients with Severity of the Disorder. Biol Trace Elem Res. 2022; 200: 4949-54.

[50] Liao J, Wen J, Wei C, Zhuang R, Giri M, Guo S. Association between blood heavy metal element and all-cause mortality in asthmatic adults: a cohort study. Sci Rep. 2024; 14: 20457.

[51] Liang RY, Wu W, Huang J, Jiang SP, Lin Y. Magnesium Affects the Cytokine Secretion of CD4⁺T Lymphocytes in Acute Asthma. J Asthma. 2012; 49: 1012-5.

[52] Zhou WC, Qu J, Xie SY, Sun Y, Yao HW. Mitochondrial Dysfunction in Chronic Respiratory Diseases: Implications for the Pathogenesis and Potential Therapeutics. Oxidative Med Cell Longev. 2021; 2021: 5188306.

[53] Zhao W, Fang H, Wang T, Yao C. Identification of mitochondria-related biomarkers in childhood allergic asthma. BMC Med Genom. 2024; 17: 141.

[54] Avendaño-Briseño KA, Escutia-Martínez J, Hernández-Cruz EY, Pedraza-Chaverri J. Antioxidant Effect of Curcumin and Its Impact on Mitochondria: Evidence from Biological Models. J Xenobiotics. 2025; 15: 139.

[55] de Oliveira MR, Nabavi SM, Braidy N, Setzer WN, Ahmed T, Nabavi SF. Quercetin and the mitochondria: A mechanistic view. Biotechnol Adv. 2016; 34: 532-49.

[56] Palabiyik AA, Palabiyik E. Pharmacological approaches to enhance mitochondrial biogenesis: focus on PGC-1Α, AMPK, and SIRT1 in cellular health. Mol Biol Rep. 2025; 52: 270.

[57] Bui HB, Inaba K. Structures, Mechanisms, and Physiological Functions of Zinc Transporters in Different Biological Kingdoms. Int J Mol Sci. 2024; 25: 3045.

[58] Lee J, Roh JL. Selenium and selenoproteins: key regulators of ferroptosis and therapeutic targets in cancer. J Mol Med. 2025; 103: 899-911.

[59] Nam K, Thodika ARA, Tischlik S, Phoeurk C, Nagy TM, Schierholz L, et al. Magnesium induced structural reorganization in the active site of adenylate kinase. Sci Adv. 2024; 10: eado5504.

[60] Luo L, Chen G, Zhou Y, Xiang Y, Peng J. Dietary intake, antioxidants, minerals and vitamins in relation to childhood asthma: a Mendelian randomization study. Front Nutr. 2024; 11: 1401881.

[61] Romieu I, Barraza-Villarreal A, Escamilla-Núñez C, Texcalac-Sangrador JL, Hernandez-Cadena L, Díaz-Sánchez D, et al. Dietary intake, lung function and airway inflammation in Mexico City school children exposed to air pollutants. Respir Res. 2009; 10: 122.

[62] Lee SC, Yang YH, Chuang SY, Huang SY, Pan WH. Reduced medication use and improved pulmonary function with supplements containing vegetable and fruit concentrate, fish oil and probiotics in asthmatic school children: a randomised controlled trial. Br J Nutr. 2012; 110: 145-55.

[63] Berthon BS, McLoughlin RF, Jensen ME, Hosseini B, Williams EJ, Baines KJ, et al. The effects of increasing fruit and vegetable intake in children with asthma: A randomized controlled trial. Clin Exp Allergy. 2021; 51: 1144-56.

[64] Songnuy T, Ninla-Aesong P, Thairach P, Thok-Ngaen J. Effectiveness of an antioxidant-rich diet on childhood asthma outcomes: A randomized controlled trial. BMC Nutr. 2025; 11: 89.

[65] Zhang H, Huang L, Guo Y. Dietary antioxidant and inflammatory potential in asthmatic patients and its association with all-cause mortality. Nutr J. 2024; 23: 95.

[66] Terzi M, Bulut İ, Yakut T, Güneş FE. Exploring the link between nutritional status and total antioxidant status in patients with severe asthma: a cross-sectional study. BMC Pulm Med. 2025; 25: 216.

[67] Bime C, Wei CY, Holbrook J, Smith LJ, Wise RA. Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial. Prim Care Respir J. 2012; 21: 398-404.

[68] Willett W, Rockström J, Loken B, Springmann M, Lang T, Vermeulen S, et al. Food in the Anthropocene: the EAT-Lancet Commission on healthy diets from sustainable food systems. Lancet. 2019; 393: 447-92.

[69] Romanello M, Walawender M, Hsu SC, Moskeland A, Palmeiro-Silva Y, Scamman D, et al. The 2025 report of the Lancet Countdown on health and climate change: climate change action offers a lifeline. Lancet. 2025; 406: 2804-57.

[70] Allam MF, Lucane RA. Selenium supplementation for asthma. Cochrane Database Syst Rev. 2004; 2004: CD003538.

[71] Gazdik F, Kadrabova J, Gazdikova K. Decreased consumption of corticosteroids after selenium supplementation in corticoid-dependent asthmatics. Bratisl Lek Listy. 2002; 103: 22-5.

[72] Jolliffe DA, Greenberg L, Hooper RL, Griffiths CJ, Camargo CA Jr, Kerley CP, et al. Vitamin D supplementation to prevent asthma exacerbations: a systematic review and meta-analysis of individual participant data. Lancet Respir Med. 2017; 5: 881-90.

[73] Wang M, Liu M, Wang C, Xiao Y, An T, Zou M, et al. Association between vitamin D status and asthma control: A meta-analysis of randomized trials. Respir Med. 2019; 150: 85-94.

[74] Zhang Y, Leung DY, Goleva E. Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma. J Allergy Clin Immunol. 2014; 133: 1744-52.e1.

[75] Ghaffari J, Farid Hossiani R, Khalilian A, Nahanmoghadam N, Salehifar E, Rafatpanah H. Vitamin e supplementation, lung functions and clinical manifestations in children with moderate asthma: a randomized double blind placebo-controlled trial. Iran J Allergy Asthma Immunol. 2014; 13: 98-103.

[76] Xiong Z, Liu L, Jian Z, Ma Y, Li H, Jin X, et al. Vitamin E and Multiple Health Outcomes: An Umbrella Review of Meta-Analyses. Nutrients. 2023; 15: 3301.

[77] Hosseini SA, Shateri Z, Abolnezhadian F, Maraghi E, Haddadzadeh Shoushtari M, Zilaee M. Does pomegranate extract supplementation improve the clinical symptoms of patients with allergic asthma? A double-blind, randomized, placebo-controlled trial. Front Pharmacol. 2023; 14: 1109966.

[78] Tenero L, Piazza M, Zanoni L, Bodini A, Peroni D, Piacentini GL. Antioxidant supplementation and exhaled nitric oxide in children with asthma. Allergy Asthma Proc. 2016; 37: e8-13.

[79] Pecoraro L, Zoller T, Atkinson RL, Nisi F, Antoniazzi F, Cavarzere P, et al. Correction: Supportive treatment of vascular dysfunction in pediatric subjects with obesity: the OBELIX study. Nutr Diabetes. 2022; 12: 5.

[80] Karakaya Z, Cavkaytar Ö, Tosun Ö, Arga M. Subclinical cardiovascular dysfunction in children and adolescents with asthma. J Asthma. 2020; 59: 451-61.

[81] Jesenak M, Hrubisko M, Chudek J, Bystron J, Rennerova Z, Diamant Z, et al. Beneficial effects of pleuran on asthma control and respiratory tract-infection frequency in children with perennial asthma. Sci Rep. 2025; 15: 7146.

[82] Fabian E, Pölöskey P, Kósa L, Elmadfa I, Réthy LA. Nutritional supplements and plasma antioxidants in childhood asthma. Wien klin Wochenschr. 2013; 125: 309-15.

[83] Ajaz M, Singh I, Vugic L, Jani R, Rathnayake H, Diyapaththugama S, et al. The interplay of plant-based antioxidants, inflammation, and clinical outcomes in asthma: A systematic review. Respir Med. 2025; 236: 107918.

[84] Buonsenso D, Di Gennaro L, De Rose C, Morello R, D'Ilario F, Zampino G, et al. Long-Term Outcomes of Pediatric Infections: From Traditional Infectious Diseases to Long Covid. Future Microbiol. 2022; 17: 551-71.

[85] Bush A, Buonsenso D, Peroni D, Piazza M, Piacentini G, Boner AL. Early-life respiratory infection: How do we react to this red flag? Pediatr Pulmonol. 2024; 59: 1817-9.

[86] Gombart AF, Pierre A, Maggini S. A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection. Nutrients. 2020; 12: 236.

[87] Hansdottir S, Monick MM. Vitamin D Effects on Lung Immunity and Respiratory Diseases. Vitam Horm. 2011; 86: 217-37.

[88] Shea MK, Barger K, Booth SL, Matuszek G, Cushman M, Benjamin EJ, et al. Vitamin K status, cardiovascular disease, and all-cause mortality: a participant-level meta-analysis of 3 US cohorts. Am J Clin Nutr. 2020; 111: 1170-7.

[89] Ohsaki Y, Shirakawa H, Miura A, Giriwono PE, Sato S, Ohashi A, et al. Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor κB through the repression of IKKα/β phosphorylation. J Nutr Biochem. 2010; 21: 1120-6.

[90] Merra G, Dominici F, Gualtieri P, Capacci A, Cenname G, Esposito E, et al. Role of vitamin K2 in bone-vascular crosstalk. Int J Vitam Nutr Res. 2024; 94: 143-52.

[91] Hoekstra WG. Biochemical function of selenium and its relation to vitamin E. Fed Proc. 1975; 34: 2083-9.

[92] Jiang J, Mehrabi Nasab E, Athari SM, Athari SS. Effects of vitamin E and selenium on allergic rhinitis and asthma pathophysiology. Respir Physiol Neurobiol. 2021; 286: 103614.

[93] Pazos M, Andersen ML, Medina I, Skibsted LH. Efficiency of Natural Phenolic Compounds Regenerating α-Tocopherol from α-Tocopheroxyl Radical. J Agric Food Chem. 2007; 55: 3661-6.

[94] Prasad AS. Zinc in human health: effect of zinc on immune cells. Mol Med. 2008; 14: 353-7.

[95] Zeng C, Li H, Lei GH. The effect of oral magnesium supplementation on serum C-reactive protein. Eur J Clin Nutr. 2015; 69: 408.

[96] Halliwell B. The antioxidant paradox. Lancet. 2000; 355: 1179-80.

[97] Podmore ID, Griffiths HR, Herbert KE, Mistry N, Mistry P, Lunec J. Vitamin C exhibits pro-oxidant properties. Nature. 1998; 392: 559.

[98] Son TG, Camandola S, Mattson MP. Hormetic Dietary Phytochemicals. NeuroMolecular Med. 2008; 10: 236-46.

[99] Kawamoto EM, Scavone C, Camarini R. Physiological aspects of hormesis. Prog Brain Res. 2025; 295: 1-7.

[100] Bellezza I, Giambanco I, Minelli A, Donato R. Nrf2-Keap1 signaling in oxidative and reductive stress. Biochim Biophys Acta (BBA)-Mol Cell Res. 2018; 1865: 721-33.

[101] Duarte TL, Jones GD. Vitamin C modulation of H2O2-induced damage and iron homeostasis in human cells. Free Radic Biol Med. 2007; 43: 1165-75.

[102] Chaudière J, Ferrari-Iliou R. Intracellular Antioxidants: from Chemical to Biochemical Mechanisms. Food Chem Toxicol. 1999; 37: 949-62.

[103] Münzel T, Gori T, Bruno RM, Taddei S. Is oxidative stress a therapeutic target in cardiovascular disease? Eur Heart J. 2010; 31: 2741-8.

[104] Schmidt HH, Stocker R, Vollbracht C, Paulsen G, Riley D, Daiber A, et al. Antioxidants in Translational Medicine. Antioxid Redox Signal. 2015; 23: 1130-43.

[105] Khaw KT, Bingham S, Welch A, Luben R, Wareham N, Oakes S, et al. Relation between plasma ascorbic acid and mortality in men and women in EPIC-Norfolk prospective study: a prospective population study. Lancet. 2001; 357: 657-63.

[106] Ames BN. Prolonging healthy aging: Longevity vitamins and proteins. Proc Natl Acad Sci. 2018; 115: 10836-44.

[107] Semba RD. The Historical Evolution of Thought Regarding Multiple Micronutrient Nutrition. J Nutr. 2012; 142: 143S-56S.

[108] Bhardwaj RL, Parashar A, Parewa HP, Vyas L. An Alarming Decline in the Nutritional Quality of Foods: The Biggest Challenge for Future Generations’ Health. Foods. 2024; 13: 877.

[109] Temkin AM, Subramaniam V, Friedman A, Fleury E, de Montagnac D, Campbell C, et al. A cumulative dietary pesticide exposure score based on produce consumption is associated with urinary pesticide biomarkers in a U.S. biomonitoring cohort. Int J Hyg Environ Health. 2025; 270: 114654.