2507000999
  • Open Access
  • Review
Trauma Induced Acute Redox Imbalance, the Filling Oxidant Sinks, and a Plausible Food as Medicine Solution
  • DuWayne A. Carlson 1, *,   
  • Christopher G. Wilson 2,   
  • Joey P. Johnson 3,   
  • Cheryl A. True 4

Received: 15 May 2025 | Revised: 09 Jul 2025 | Accepted: 16 Jul 2025 | Published: 24 Jul 2025

Abstract

Trauma is a leading cause of death worldwide. While early deaths are most commonly from hemorrhage and direct organ injuries, delayed deaths are mostly caused by the fallout of inflammation, presumably induced by oxidative stress. Increasing evidence shows that many or most of the complications of trauma are also associated with oxidative stress. In this manuscript we review the current literature on trauma associated redox imbalance, bridging the gap between basic science research and clinical practice from a broad perspective. The triple oxidant sink metaphor is presented to give a visual gauge of how redox balance might be achieved. We then introduce a plausible multimodal redox balancing regimen, using food as medicine.

References 

  • 1.
    Sharifi-Rad, M.; Anil Kumar, N.V.; Zucca, P.; et al. Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Front. Physiol. 2020, 11, 552535. https://doi.org/10.3389/fphys.2020.00694.
  • 2.
    Sinenko, S.A.; Starkova, T.Y.; Kuzmin, A.A.; et al. Physiological Signaling Functions of Reactive Oxygen Species in Stem Cells: From Flies to Man. Front. Cell Dev. Biol. 2021, 9, 714370. https://doi.org/10.3389/fcell.2021.714370.
  • 3.
    Chen, X.; Guo, C.; Kong, J. Oxidative stress in neurodegenerative diseases. Neural Regen. Res. 2012, 7, 376–385.
  • 4.
    Holmström, K.M.; Finkel, T. Cellular mechanisms and physiological consequences of redox-dependent signalling. Nat. Rev. Mol. Cell Biol. 2014, 15, 411–421.
  • 5.
    Al-Horani, R.A. A Narrative Review of Exercise-Induced Oxidative Stress: Oxidative DNA Damage Underlined. Open Sports Sci. J. 2022, 15. https://doi.org/10.2174/1875399X-v15-e2202220.
  • 6.
    Domazetovic, V.; Marcucci, G.; Iantomasi, T.; et al. Oxidative stress in bone remodeling: Role of antioxidants. Clin. Cases Miner. Bone Metab. 2017, 14, 209–216.
  • 7.
    Cichoż-Lach, H.; Michalak, A. Oxidative stress as a crucial factor in liver diseases. World J. Gastroenterol. 2014, 20, 8082–8091.
  • 8.
    Guo, J.; Hu, H.; Chen, Z.; et al. Cold Exposure Induces Intestinal Barrier Damage and Endoplasmic Reticulum Stress in the Colon via the SIRT1/Nrf2 Signaling Pathway. Front. Physiol. 2022, 13, 822348. https://doi.org/10.3389/fphys.2022.822348.
  • 9.
    Cooper, J.S.; Phuyal, P.; Shah, N. Oxygen Toxicity. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2023. Available online: http://www.ncbi.nlm.nih.gov/books/NBK430743/ (accessed on 22 October 2023).
  • 10.
    Caliri, A.W.; Tommasi, S.; Besaratinia, A. Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer. Mutat. Res. Mutat. Res. 2021, 787, 108365.
  • 11.
    Dmitrieva, N.I.; Gagarin, A.; Liu, D.; et al. Middle-age high normal serum sodium as a risk factor for accelerated biological aging, chronic diseases, and premature mortality. eBioMedicine 2023, 2, 87. Available online: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00586-2/fulltext (accessed on 6 January 2023).
  • 12.
    Marrugo, D.G.; León-Méndez, D.; Silva, J.P.; et al. Metal fumes: Exposure to heavy metals, their relationship with oxidative stress and their effect on health. Prod. Limpia 2019, 14, 8–20.
  • 13.
    Lunderius-Andersson, C.; Enoksson, M.; Nilsson, G. Mast Cells Respond to Cell Injury through the Recognition of IL-33. Front Immunol. 2012, 3, 82.
  • 14.
    Feinman, R.; Deitch, E.A.; Watkins, A.C.; et al. HIF-1 mediates pathogenic inflammatory responses to intestinal ischemia-reperfusion injury. Am. J. Physiol. Gastrointest. Liver Physiol. 2010, 299, G833–G843.
  • 15.
    Liguori, I.; Russo, G.; Curcio, F.; et al. Oxidative stress, aging, and diseases. Clin. Interv. Aging. 2018, 13, 757–772.
  • 16.
    Kıvrak, E.G.; Yurt, K.K.; Kaplan, A.A.; et al. Effects of electromagnetic fields exposure on the antioxidant defense system. J. Microsc. Ultrastruct. 2017, 5, 167–176.
  • 17.
    Ghaemi Kerahrodi, J.; Michal, M. The fear-defense system, emotions, and oxidative stress. Redox Biol. 2020, 37, 101588.
  • 18.
    Schiavone, S.; Jaquet, V.; Trabace, L.; et al. Severe Life Stress and Oxidative Stress in the Brain: From Animal Models to Human Pathology. Antioxid. Redox Signal. 2013, 18, 1475–1490.
  • 19.
    Emerson, S.R.; Kurti, S.P.; Harms, C.A.; et al. Magnitude and Timing of the Postprandial Inflammatory Response to a High-Fat Meal in Healthy Adults: A Systematic Review. Adv. Nutr. Bethesda Md. 2017, 8, 213–225.
  • 20.
    Jansen, F.; Yang, X.; Franklin, B.S.; et al. High glucose condition increases NADPH oxidase activity in endothelial microparticles that promote vascular inflammation. Cardiovasc. Res. 2013, 98, 94–106.
  • 21.
    DiNicolantonio, J.J.; Lucan, S.C.; O’Keefe, J.H. The Evidence for Saturated Fat and for Sugar Related to Coronary Heart Disease. Prog. Cardiovasc. Dis. 2016, 58, 464–472.
  • 22.
    Hyperthermia, dehydration, and osmotic stress: Unconventional sources of exercise-induced reactive oxygen species. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2016, 310, R105–R114. https://doi.org/10.1152/ajpregu.00395.2015.
  • 23.
    Wimalawansa, S.J. Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging. Biology 2019, 8, 30.
  • 24.
    Vaccaro, A.; Dor, Y.K.; Nambara, K.; et al. Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut. Cell 2020, 181, 1307–1328.e15.
  • 25.
    Chong, W.C.; Shastri, M.D.; Eri, R. Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Nexus Implicated in Bowel Disease Pathophysiology. Int. J. Mol. Sci. 2017, 18, 771.
  • 26.
    Matés, J.M.; Pérez-Gómez, C.; Núñez de Castro, I. Antioxidant enzymes and human diseases. Clin. Biochem. 1999, 32, 595–603.
  • 27.
    Polonikov, A. Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients. ACS Infect. Dis. 2020, 6, 1558–1562.
  • 28.
    Badawy, M.A.; Yasseen, B.A.; El-Messiery, R.M.; et al. Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality. eLife 2021, 10, e69417.
  • 29.
    Nutrient Data Laboratory (U.S.). USDA Database for the Oxygen Radical Absorbance Capacity (ORAC) of Selected Foods; USDA: Washington, DC, USA, 2010.
  • 30.
    Behl, T.; Kumar, K.; Brisc, C.; et al. Exploring the multifocal role of phytochemicals as immunomodulators. Biomed. Pharmacother. 2021, 133, 110959.
  • 31.
    van de Lagemaat, E.E.; de Groot, L.C.P.G.M.; van den Heuvel, E.G.H.M. Vitamin B12 in Relation to Oxidative Stress: A Systematic Review. Nutrients 2019, 11, 482.
  • 32.
    Heiss, E.; Herhaus, C.; Klimo, K.; et al. Nuclear Factor κB Is a Molecular Target for Sulforaphane-mediated Anti-inflammatory Mechanisms. J. Biol. Chem. 2001, 276, 32008–32015. Available online: https://www.jbc.org/article/S0021-9258(19)31512-1/fulltext (accessed on 23 October 2022).
  • 33.
    Zhang, Z.; Yang, P.; Zhao, J. Ferulic acid mediates prebiotic responses of cereal-derived arabinoxylans on host health. Anim. Nutr. 2021, 9, 31–38.
  • 34.
    Gomez-Cabrera, M.C.; Domenech, E.; Viña, J. Moderate exercise is an antioxidant: Upregulation of antioxidant genes by training. Free Radic. Biol. Med. 2008, 44, 126–131.
  • 35.
    Mohr, A.E.; McEvoy, C.; Sears, D.D.; et al. Impact of intermittent fasting regimens on circulating markers of oxidative stress in overweight and obese humans: A systematic review of randomized controlled trials. Adv. Redox Res. 2021, 3, 100026.
  • 36.
    Calabrese, V.; Cornelius, C.; Dinkova-Kostova, A.T.; et al. Cellular Stress Responses, The Hormesis Paradigm, and Vitagenes: Novel Targets for Therapeutic Intervention in Neurodegenerative Disorders. Antioxid. Redox Signal. 2010, 13, 1763–1811.
  • 37.
    Calabrese, V.; Cornelius, C.; Dinkova-Kostova, A.T.; et al. Vitagenes, cellular stress response, and acetylcarnitine: Relevance to hormesis. BioFactors Oxf. Engl. 2009, 35, 146–160.
  • 38.
    Bellot, G.L.; Dong, X.; Lahiri, A.; et al. MnSOD is implicated in accelerated wound healing upon Negative Pressure Wound Therapy (NPWT): A case in point for MnSOD mimetics as adjuvants for wound management. Redox Biol. 2018, 20, 307–320.
  • 39.
    Ngo, V.; Duennwald, M.L. Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease. Antioxidants 2022, 11, 2345.
  • 40.
    Carlson, D.; Wilson, C. Redox Imbalance Theory of Disease, The Triple Oxidant Sink, and The Antioxidant Lifestyle. Int. J. Dis. Reversal Prev. 2024, 6, 23.
  • 41.
    Leimkühler, M.; Bourgonje, A.R.; van Goor, H.; et al. Oxidative Stress Predicts Post-Surgery Complications in Gastrointestinal Cancer Patients. Ann. Surg. Oncol. 2022, 29, 4540–4547.
  • 42.
    Dekker, A.B.E.; Krijnen, P.; Schipper, I.B. Predictive value of cytokines for developing complications after polytrauma. World J. Crit. Care Med. 2016, 5, 187–200.
  • 43.
    Moisejevs, G.; Bormane, E.; Trumpika, D.; et al. Glutathione Reductase Is Associated with the Clinical Outcome of Septic Shock in the Patients Treated Using Continuous Veno-Venous Haemofiltration. Medicina 2021, 57, 689.
  • 44.
    Ayala, J.C.; Grismaldo, A.; Sequeda-Castañeda, L.G.; et al. Oxidative Stress in ICU Patients: ROS as Mortality Long-Term Predictor. Antioxidants 2021, 10, 1912.
  • 45.
    Servia, L.; Serrano, J.C.E.; Pamplona, R.; et al. Location-dependent effects of trauma on oxidative stress in humans. PLoS ONE 2018, 13, e0205519.
  • 46.
    Liguori, I.; Russo, G.; Curcio, F.; et al. Oxidative stress, aging, and diseases. Clin. Interv. Aging. 2018, 13, 757–772.
  • 47.
    Victorino, G.P.; Chong, T.J.; Pal, J.D. Trauma in the Elderly Patient. Arch. Surg. 2003, 138, 1093–1098.
  • 48.
    Resnick, S.; Inaba, K.; Okoye, O.; et al. Impact of Smoking on Trauma Patients. Turk. J. Trauma. Emerg. Surg. 2014, 20 248–252.
  • 49.
    He, K.; Hemmila, M.R.; Cain-Nielsen, A.H.; et al. Complications and resource utilization in trauma patients with diabetes. PLoS ONE 2019, 14, e0221414.
  • 50.
    Pugachev, A.; Gershevich, V.; Korzhuk, M.; et al. Treatment of Patients with A Chest Trauma Suffering COPD. In A41 Chronic Obstructive Pulmonary Disease Exacerbations: Epidemiology and Outcomes; American Thoracic Society International Conference Abstracts; American Thoracic Society: New York, NY, USA, 2010. p. A1514. Available online: https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A1514 (accessed on 27 October 2023).
  • 51.
    Ferraris, V.A.; Ferraris, S.P.; Saha, S.P. The relationship between mortality and preexisting cardiac disease in 5971 trauma patients. J. Trauma Acute Care Surg. 2010, 69, 645–652.
  • 52.
    Kelley, N.; Jeltema, D.; Duan, Y.; et al. The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation. Int. J. Mol. Sci. 2019, 20, 3328.
  • 53.
    Duan, J.; Gao, S.; Tu, S.; et al. Pathophysiology and Therapeutic Potential of NADPH Oxidases in Ischemic Stroke-Induced Oxidative Stress. Oxid. Med. Cell Longev. 2021, 2021, 6631805.
  • 54.
    Lord, J.M.; Midwinter, M.J.; Chen, Y.F.; et al. The systemic immune response to trauma: An overview of pathophysiology and treatment. Lancet Lond. Engl. 2014, 384, 1455–1465.
  • 55.
    Rao, R. Oxidative Stress-Induced Disruption of Epithelial and Endothelial Tight Junctions. Front. Biosci. J. Virtual Libr. 2008, 13, 7210–7226.
  • 56.
    Nadatani, Y.; Watanabe, T.; Shimada, S.; et al. Microbiome and intestinal ischemia/reperfusion injury. J. Clin. Biochem. Nutr. 2018, 63, 26–32.
  • 57.
    Hernández-Reséndiz, S.; Muñoz-Vega, M.; Contreras, W.E.; et al. Responses of Endothelial Cells Towards Ischemic Conditioning Following Acute Myocardial Infarction. Cond. Med. 2018, 1, 247. Available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191189/ (accessed on 29 March 2023).
  • 58.
    Chelombitko, M.A.; Fedorov, A.V.; Ilyinskaya, O.P.; et al. Role of Reactive Oxygen Species in Mast Cell Degranulation. Biochemistry 2016, 81, 1564–1577.
  • 59.
    Bortolotti, P.; Faure, E.; Kipnis, E. Inflammasomes in Tissue Damages and Immune Disorders after Trauma. Front. Immunol. 2018, 9, 1900. https://doi.org/10.3389/fimmu.2018.01900.
  • 60.
    Brito, G.M.C.; Fontenele, A.M.M.; Carneiro, E.C.R.L.; et al. Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Nondialysis Chronic Kidney Patients. Int. J. Inflamm. 2021, 2021, 6678960.
  • 61.
    Amer, S.A.; Albeladi, O.A.; Elshabrawy, A.M.; et al. Role of neutrophil to lymphocyte ratio as a prognostic indicator for COVID-19. Health Sci. Rep. 2021, 4, e442.
  • 62.
    Xu, J.; Li, S.; Lui, K.Y.; et al. The neutrophil-to-lymphocyte ratio: A potential predictor of poor prognosis in adult patients with trauma and traumatic brain injury. Front. Surg. 2022, 9, 917172. https://doi.org/10.3389/fsurg.2022.917172.
  • 63.
    Sørensen, O.E.; Borregaard, N. Neutrophil extracellular traps—The dark side of neutrophils. J. Clin. Investig. 2016, 126, 1612–1620.
  • 64.
    White, N.J.; Wang, Y.; Fu, X.; et al. Post-translational oxidative modification of fibrinogen is associated with coagulopathy after traumatic injury. Free Radic. Biol. Med. 2016, 96, 181–189.
  • 65.
    Oxidative Stress and Platelet Dysfunction. Available online: https://austinpublishinggroup.com/thrombosis-haemostasis/fulltext/thrombosis-v2-id1017.php (accessed on 2 October 2022).
  • 66.
    Dayal, S.; Gu, S.X.; Hutchins, R.D.; et al. Deficiency of Superoxide Dismutase Impairs Protein C Activation and Enhances Susceptibility to Experimental Thrombosis. Arterioscler. Thromb. Vasc. Biol. 2015, 35, 1798–1804.
  • 67.
    Perler, B.A.; Tohmeh, A.G.; Bulkley, G.B. Inhibition of the compartment syndrome by the ablation of free radical-mediated reperfusion injury. Surgery 1990, 108, 40–47.
  • 68.
    Lawendy, A.R.; Bihari, A.; Sanders, D.W.; et al. Contribution of inflammation to cellular injury in compartment syndrome in an experimental rodent model. Bone Jt. J. 2015, 97, 539–543.
  • 69.
    Tharayil, A.M.; Ganaw, A.; Abdulrahman, S.; et al. Abdominal Compartment Syndrome: What Is New? Intensive Care. IntechOpen 2017. Available online: https://www.intechopen.com/state.item.id (accessed on 28 January 2023).
  • 70.
    Leng, Y.; Zhang, K.; Fan, J.; et al. Effect of Acute, Slightly Increased Intra-Abdominal Pressure on Intestinal Permeability and Oxidative Stress in a Rat Model. PLoS ONE 2014, 9, e109350.
  • 71.
    Floyd, R.A.; Hensley, K. Oxidative stress in brain aging: Implications for therapeutics of neurodegenerative diseases. Neurobiol. Aging 2002, 23, 795–807.
  • 72.
    Fesharaki-Zadeh, A. Oxidative Stress in Traumatic Brain Injury. Int. J. Mol. Sci. 2022, 23, 13000.
  • 73.
    Soeters, P.B.; Wolfe, R.R.; Shenkin, A. Hypoalbuminemia: Pathogenesis and Clinical Significance. JPEN J. Parenter. Enteral Nutr. 2019, 43, 181–193.
  • 74.
    Bissinger, R.; Bhuyan, A.A.M.; Qadri, S.M.; et al. Oxidative stress, eryptosis and anemia: A pivotal mechanistic nexus in systemic diseases. FEBS J. 2019, 286, 826–854.
  • 75.
    Gonçalves, A.C.; Alves, R.; Baldeiras, I.; et al. Oxidative Stress Parameters Can Predict the Response to Erythropoiesis-Stimulating Agents in Myelodysplastic Syndrome Patients. Front. Cell Dev. Biol. 2021, 9, 701328. https://doi.org/10.3389/fcell.2021.701328.
  • 76.
    Miller, M.W.; Sadeh, N. Traumatic stress, oxidative stress and post-traumatic stress disorder: Neurodegeneration and the accelerated-aging hypothesis. Mol. Psychiatry 2014, 19, 1156–1162.
  • 77.
    Bai, X.C.; Lu, D.; Bai, J.; et al. Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB. Biochem. Biophys. Res. Commun. 2004, 314, 197–207.
  • 78.
    Wang, G.; Yang, F.; Zhou, W.; et al. The initiation of oxidative stress and therapeutic strategies in wound healing. Biomed. Pharmacother. 2023, 157, 114004.
  • 79.
    Kawahito, S.; Kitahata, H.; Oshita, S. Problems associated with glucose toxicity: Role of hyperglycemia-induced oxidative stress. World J. Gastroenterol. WJG 2009, 15, 4137–4142.
  • 80.
    Freeman, T.A.; Parvizi, J.; Dela Valle, C.J.; et al. Mast cells and hypoxia drive tissue metaplasia and heterotopic ossification in idiopathic arthrofibrosis after total knee arthroplasty. Fibrogenesis Tissue Repair 2010, 3, 17. Available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940819/ (accessed on 21 October 2009).
  • 81.
    Ziskoven, C.; Jäger, M.; Zilkens, C.; et al. Oxidative stress in secondary osteoarthritis: From cartilage destruction to clinical presentation? Orthop. Rev. 2010, 2, e23.
  • 82.
    Song, Y.; Hao, D.; Jiang, H.; et al. Nrf2 Regulates CHI3L1 to Suppress Inflammation and Improve Post-Traumatic Osteoarthritis. J. Inflamm. Res. 2021, 14, 4079–4088.
  • 83.
    Guo, T.Z.; Wei, T.; Huang, T.T.; et al. Oxidative Stress Contributes to Fracture/Cast-Induced Inflammation and Pain in a Rat Model of Complex Regional Pain Syndrome. J. Pain 2018, 19, 1147–1156.
  • 84.
    Taha, R.; Blaise, G.A. Update on the pathogenesis of complex regional pain syndrome: Role of oxidative stress. Can. J. Anaesth. J. Can. Anesth. 2012, 59, 875–881.
  • 85.
    Lopez, M.G.; Hughes, C.G.; DeMatteo, A.; et al. Intraoperative oxidative damage and delirium following cardiac surgery. Anesthesiology 2020, 132, 551–561.
  • 86.
    Li, Q.H.; Yu, L.; Yu, Z.W.; et al. Relation of postoperative serum S100A12 levels to delirium and cognitive dysfunction occurring after hip fracture surgery in elderly patients. Brain Behav. 2019, 9, e01176.
  • 87.
    Davis, G.; Fayfman, M.; Reyes-Umpierrez, D.; et al. Stress hyperglycemia in general surgery: Why should we care? J. Diabetes Complicat. 2018, 32, 305–309.
  • 88.
    Campbell, T.C. Untold nutrition. Nutr. Cancer 2014, 66, 1077–1082.
  • 89.
    Bjelakovic, G.; Nikolova, D.; Gluud, C. Antioxidant supplements and mortality. Curr. Opin. Clin. Nutr. Metab. Care 2014, 17, 40–44.
  • 90.
    Macpherson, H.; Pipingas, A.; Pase, M.P. Multivitamin-multimineral supplementation and mortality: A meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 2013, 97, 437–444.
  • 91.
    Antioxidant Supplements: What You Need to Know. NCCIH. Available online: https://www.nccih.nih.gov/health/antioxidant-supplements-what-you-need-to-know (accessed on 3 November 2023).
  • 92.
    Lonn, E.; Bosch, J.; Yusuf, S.; et al. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: A randomized controlled trial. JAMA 2005, 293, 1338–1347.
  • 93.
    Jain, M.; Chandel, N.S. Rethinking Antioxidants in the Intensive Care Unit. Am. J. Respir. Crit. Care Med. 2013, 188, 1283–1285.
  • 94.
    Bouayed, J.; Bohn, T. Exogenous antioxidants—Double-edged swords in cellular redox state. Oxid. Med. Cell Longev. 2010, 3, 228–237.
  • 95.
    Gontero, P.; Marra, G.; Soria, F.; et al. A randomized double-blind placebo controlled phase I-II study on clinical and molecular effects of dietary supplements in men with precancerous prostatic lesions. Chemoprevention or “chemopromotion”? A RCT on Dietary Supplements in PCa Chemoprevention. Prostate 2015, 75, 1177–1186.
  • 96.
    Lock, M.; Loblaw, A. Vitamin E might increase risk of death. Can. Fam. Physician 2005, 51, 829–831.
  • 97.
    Haynes, R.; Jiang, L.; Hopewell, J.C.; et al. HPS2-THRIVE randomized placebo-controlled trial in 25673 high-risk patients of ER niacin/laropiprant: Trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur. Heart J. 2013, 34, 1279–1291.
  • 98.
    null null. Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy. N. Engl. J. Med. 2011, 365, 2255–2267.
  • 99.
    Ingles, D.P.; Cruz Rodriguez, J.B.; Garcia, H. Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment. Curr. Cardiol. Rep. 2020, 22, 22.
  • 100.
    Chen, F.; Du, M.; Blumberg, J.B.; et al. Association Between Dietary Supplement Use, Nutrient Intake, and Mortality Among US Adults: A Cohort Study. Ann. Intern. Med. 2019, 170, 604–613.
  • 101.
    Podmore, I.D.; Griffiths, H.R.; Herbert, K.E.; et al. Vitamin C exhibits pro-oxidant properties. Nature 1998, 392, 559.
  • 102.
    Heyland, D.; Muscedere, J.; Wischmeyer, P.E.; et al. A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients. N. Engl. J. Med. 2013, 368, 1489–1497.
  • 103.
    Gudivada, K.K.; Kumar, A.; Shariff, M.; et al. Antioxidant micronutrient supplementation in critically ill adults: A systematic review with meta-analysis and trial sequential analysis. Clin. Nutr. 2021, 40, 740–750.
  • 104.
    Ornish, D.; Scherwitz, L.W.; Billings, J.H.; et al. Intensive Lifestyle Changes for Reversal of Coronary Heart Disease. JAMA 1998, 280, 2001–2007.
  • 105.
    Esselstyn, C.B. A plant-based diet and coronary artery disease: A mandate for effective therapy. J. Geriatr. Cardiol. 2017, 14, 317–320.
  • 106.
    Bansal, S.; Connolly, M.; Harder, T. Impact of a Whole-Foods, Plant-Based Nutrition Intervention on Patients Living with Chronic Disease in an Underserved Community. Am. J. Lifestyle Med. 2021, 16, 382–389.
  • 107.
    Liu, R.H. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am. J. Clin. Nutr. 2003, 78, 517S–520S.
  • 108.
    Liu, R.H. Potential synergy of phytochemicals in cancer prevention: Mechanism of action. J. Nutr. 2004, 134, 3479S–3485S.
  • 109.
    Wang, S.; Meckling, K.A.; Marcone, M.F.; et al. Synergistic, additive, and antagonistic effects of food mixtures on total antioxidant capacities. J. Agric. Food Chem. 2011, 59, 960–968.
  • 110.
    Einer, C.; Leitzinger, C.; Lichtmannegger, J.; et al. A High-Calorie Diet Aggravates Mitochondrial Dysfunction and Triggers Severe Liver Damage in Wilson Disease Rats. Cell Mol. Gastroenterol. Hepatol. 2018, 7, 571–596.
  • 111.
    Hernández-Aguilera, A.; Rull, A.; Rodríguez-Gallego, E.; et al. Mitochondrial Dysfunction: A Basic Mechanism in Inflammation-Related Non-Communicable Diseases and Therapeutic Opportunities. Mediat. Inflamm. 2013, 2013, 135698.
  • 112.
    Hübner, M.; Mantziari, S.; Demartines, N.; et al. Postoperative Albumin Drop Is a Marker for Surgical Stress and a Predictor for Clinical Outcome: A Pilot Study. Gastroenterol. Res. Pract. 2016, 2016, 8743187.
  • 113.
    Liu, L.; Xie, K.; Yin, M.; et al. Serum potassium, albumin and vitamin B12 as potential oxidative stress markers of fungal peritonitis. Ann. Med. 2021, 53, 2132–2141.
  • 114.
    Casey, L. Hope and Healing: Type 2 Diabetes Remission with Lifestyle Medicine. Am. Coll. Lifestyle Med. 2023. Available online: https://lifestylemedicine.org/articles/type-2-diabetes-remission-with-lifestyle-medicine/ (accessed on 21 April 2025).
  • 115.
    Percival, S.S.; Vanden Heuvel, J.P.; Nieves, C.J.; et al. Bioavailability of herbs and spices in humans as determined by ex vivo inflammatory suppression and DNA strand breaks. J. Am. Coll. Nutr. 2012, 31, 288–294.
  • 116.
    Lu, Q.; Summanen, P.H.; Lee, R.; et al. Prebiotic Potential and Chemical Composition of Seven Culinary Spice Extracts. J. Food Sci. 2017, 82, 1807–1813.
  • 117.
    Gut Microbial Modulation by Culinary Herbs and Spices | Elsevier Enhanced Reader. Available online: https://reader.elsevier.com/reader/sd/pii/S0308814622032484?token=9FCAF3B54B201EE12984EF64F732F2814E5880280BEAA0D401FDD7B3DA5943A413C8CABDC54A9D1E105835DC41456AE9&originRegion=us-east-1&originCreation=20230110222333 (accessed on 10 January 2023).
  • 118.
    Meyer, M.; Kesic, M.J.; Clarke, J.; et al. Sulforaphane induces SLPI secretion in the nasal mucosa. Respir. Med. 2013, 107, 472–475.
  • 119.
    Yang, L.; Palliyaguru, D.L.; Kensler, T.W. Frugal Chemoprevention: Targeting Nrf2 with Foods Rich in Sulforaphane. Semin. Oncol. 2016, 43, 146–153.
  • 120.
    Yagishita, Y.; Fahey, J.W.; Dinkova-Kostova, A.T.; et al. Broccoli or Sulforaphane: Is It the Source or Dose That Matters? Molecules 2019, 24, 3593.
  • 121.
    Sedlak, T.W.; Nucifora, L.G.; Koga, M.; et al. Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study. Mol. Neuropsychiatry 2018, 3, 214–222.
  • 122.
    Gan, N.; Wu, Y.C.; Brunet, M.; et al. Sulforaphane Activates Heat Shock Response and Enhances Proteasome Activity through Up-regulation of Hsp27. J. Biol. Chem. 2010, 285, 35528–35536.
  • 123.
    Maheshwari, S.; Kumar, V.; Bhadauria, G.; et al. Immunomodulatory potential of phytochemicals and other bioactive compounds of fruits: A review. Food Front. 2022, 3, 221–238.
  • 124.
    Liu, X.F.; Shao, J.H.; Liao, Y.T.; et al. Regulation of short-chain fatty acids in the immune system. Front. Immunol. 2023, 14, 1186892.
  • 125.
    Nielsen, S.J.J.; Trak-Fellermeier, M.A.; Joshipura, K. The Association between Dietary Fiber Intake and CRP levels, US Adults, 2007–2010. FASEB J. 2017, 31, 648.8–648.8.
  • 126.
    Bouayed, M.Z.; Laaribi, I.; Chatar, C.E.M.; et al. C-Reactive Protein (CRP): A poor prognostic biomarker in COVID-19. Front. Immunol. 2022, 13, 1040024. https://doi.org/10.3389/fimmu.2022.1040024.
  • 127.
    Clark, A.; Mach, N. The Crosstalk between the Gut Microbiota and Mitochondria during Exercise. Front. Physiol. 2017, 8, 319. https://doi.org/10.3389/fphys.2017.00319/full.
  • 128.
    Imdad, S.; Lim, W.; Kim, J.H.; et al. Intertwined Relationship of Mitochondrial Metabolism, Gut Microbiome and Exercise Potential. Int. J. Mol. Sci. 2022, 23, 2679.
  • 129.
    Liu, T.; Li, J.; Liu, Y.; et al. Short-Chain Fatty Acids Suppress Lipopolysaccharide-Induced Production of Nitric Oxide and Proinflammatory Cytokines Through Inhibition of NF-κB Pathway in RAW264.7 Cells. Inflammation 2012, 35, 1676–1684.
  • 130.
    Jackson, D.N.; Theiss, A.L. Gut bacteria signaling to mitochondria in intestinal inflammation and cancer. Gut Microbes 2020, 11, 285–304.
  • 131.
    Pisoschi, A.M.; Iordache, F.; Stanca, L.; et al. Antioxidant, Anti-inflammatory, and Immunomodulatory Roles of Nonvitamin Antioxidants in Anti-SARS-CoV-2 Therapy. J. Med. Chem. 2022, 65, 12562–12593.
  • 132.
    Chen, R.; Kang, R.; Tang, D. The mechanism of HMGB1 secretion and release. Exp. Mol. Med. 2022, 54, 91–102.
  • 133.
    Li, M.; van Esch, B.C.A.M.; Henricks, P.A.J.; et al. Time and Concentration Dependent Effects of Short Chain Fatty Acids on Lipopolysaccharide- or Tumor Necrosis Factor α-Induced Endothelial Activation. Front. Pharmacol. 2018, 9, 233.
  • 134.
    Muzio, G.; Barrera, G.; Pizzimenti, S. Peroxisome Proliferator-Activated Receptors (PPARs) and Oxidative Stress in Physiological Conditions and in Cancer. Antioxidants 2021, 10, 1734.
  • 135.
    Cotogni, P.; Trombetta, A.; Muzio, G.; et al. Polyunsaturated Fatty Acids and Cytokines: Their Relationship in Acute Lung Injury. Diet. Nutr. Crit. Care 2015, 12, 929–942.
  • 136.
    Kaya, M.O.; Pamukçu, E.; Yakar, B. The role of vitamin D deficiency on COVID-19: A systematic review and meta-analysis of observational studies. Epidemiol. Health 2021, 43, e2021074.
  • 137.
    Oh, E.S.; Petersen, K.S.; Kris-Etherton, P.M.; et al. Spices in a High-Saturated-Fat, High-Carbohydrate Meal Reduce Postprandial Proinflammatory Cytokine Secretion in Men with Overweight or Obesity: A 3-Period, Crossover, Randomized Controlled Trial. J. Nutr. 2020, 150, 1600–1609.
  • 138.
    Burmeister, D.M.; Johnson, T.R.; Lai, Z.; et al. The Gut Microbiome Distinguishes Mortality in Trauma Patients Upon Admission to the Emergency Department. J. Trauma. Acute Care Surg. 2020, 88, 579–587.
  • 139.
    Mohammadi, Z.; Abdollahzad, H.; Rezaeian, S.; et al. The Association of Dietary Total Antioxidant Capacity with Inflammatory Biomarkers and Anthropometric Indices in Patients Who Candidate for Coronary Artery Bypass Graft Surgery: A Cross-sectional Study. Clin. Nutr. Res. 2021, 10, 353–363.
  • 140.
    Mittal, M.; Siddiqui, M.R.; Tran, K.; et al. Reactive Oxygen Species in Inflammation and Tissue Injury. Antioxid. Redox Signal. 2014, 20, 1126.
  • 141.
    Yang, D.; Elner, S.G.; Bian, Z.M.; et al. Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells. Exp. Eye Res. 2007, 85, 462–472.
Share this article:
How to Cite
A. Carlson, D.; G. Wilson, C.; P. Johnson, J.; A. True, C. Trauma Induced Acute Redox Imbalance, the Filling Oxidant Sinks, and a Plausible Food as Medicine Solution. Food as Medicine 2025, 1 (1), 3. https://doi.org/10.53941/fm.2025.100003.
RIS
BibTex
Copyright & License
article copyright Image
Copyright (c) 2025 by the authors.