Abstract
Vitamin C (ascorbic acid) is an essential water-soluble nutrient that primarily exerts its effect on a host defense mechanisms and immune homeostasis and is the most important physiological antioxidant. Stable intake of vitamin C is essential for life in humans because the body does not synthesize it. Even the numerous studies have demonstrated that vitamin C supplementation stimulates the immune system, prevents DNA damage and significantly decreases the risk of a wide range of pathologies; the potential protective mechanisms are still largely unknown. This review summarizes the recently known facts about the role of vitamin C on the selected cells of the immune system and potential molecular mechanisms involved. Further, in this review, many new data about the positive effects of vitamin C on the immune system, potential toxicological effects, vitamin C supplementation in disease development, as well as some proposed mechanisms of vitamin C activity, are discussed.
Similar content being viewed by others
References
McGregor GP, Biesalski HK. Rationale and impact of vitamin c in clinical nutrition. Curr Opin Clin NutrMetab Care 2006; 9: 697–703
Kannak K, Jain SK. Oxidative stress and apoptosis. Pathophysiology 2000; 7: 153–163
Babusyte A, Jeroch J, Stakauskas R, Salakuskas R. (2009). The production of reactive oxygen species in peripheral blood neutrophilis modulated by airway mucous. Cent Eur J Med, 4, 245–252
Cayir K, Kardeniz A, Yildirim A, Kalkan Y, Karakoc A, Keles M, Tekin SB. (2009). Protective effect of L-karnitine against cisplatin-induced liver and kidney oxidant injury in rats. Cent Eur J Med, 4, 184–191
Cekic S, Pavlovic D, Sarac M, Kamenov B, Dimic A, Pavlovic V. The effect of vitamin C on-amiodarone induced toxicity in rat thymocytes. Cent Eur J Med, DOI: 10.2478/s11536-010-0050-5
Mayne ST. Antioxidant nutrients and chronic disease: use of biomarkers of exposure and oxidative stress status in epidemiologic research. J Nutr 2003; 133: 933S–940S
Berger TM, Polidori MC, Dabbagh A, Evans PJ, Halliwell B, Morrow JB, Roberts LJ, Frei B. Antioxidant activity of vitamin C in iron-overloaded human plasma. J Biol Chem 1997; 272: 15656–15660
Hediger DA. New view at C. Nat Med. 2002; 8: 445–446
Savini I, Rossi A, Pierro C, Avigliano L, Catani MV. SVCT1 and SVCT2: key proteins for vitamin C uptake. Amino Acids, 2008; 34: 347–355
Hornig D. Distribution of ascorbic acid, metabolites and analogues in man and animals. Ann NY Acad Sci 1975; 258: 103–118
Rumsey SC, Daruwala R, Al-Hasani H, Zarnowski MJ, Simpson IA, Levine M. Dehydroascorbic acid transport by GLUT4 in Xenopus oocytes and isolated rat adipocytes. J Biol Chem, 2000; 275: 28246–28253
Rumsey SC, Kwon O, Xu GW, Burant CF, Simpson I, Levine M. Glucose transporter isoforms GLUT1 and GLUT3 transport dehydroascorbic acid. J Biol Chem, 1997; 272: 18982–18989
May JM. Ascorbate function and metabolism in the human erythrocyte. Front Biosci 1998; 3: 1–10
Nualart FJ, Rivas CI, Montecinos VP, Godoy AS, Guaiquil VH, Golde DW, Vera JC. Recycling of vitamin C by a bystander effect. J Biol Chem 2003; 278: 10128–10133
Schorah CJ, Downing C, Piripitsi A, Gllivan L, Al-Haaza AH, Sanderson MJ, Bodenham A. Total vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in plasma of critically ill patients. Am J Clin Nutr 1996; 63: 760–765
Parkin J, Cohen B. An overview on the immune system. Lancet 2001; 357: 1777–1789
Victor VM, Guayerbas N, De la Fuente M. Changes in the antioxidant content of mononuclear leukocytes from mice with endotoxin-induced oxidative stress. Mol Cell Biochem 2002; 229: 107–111
Brennan LA, Morris GM, Wasson GR, Hannigan BM, Barnett YA. The effect of vitamin C or vitamin E supplementation on basal and H2O2-induced DNA damage in human lymphocytes. Br J Nutr 2000; 84: 195–202
Packer L, Landvik S. Vitamin E: introduction to biochemistry and health benefits. Ann N Y Acad Sci 1989; 570: 1–6
Schwager J, Schulze J. Modulation of interleukin production by ascorbic acid. Vet Immunol Immunopathol 1998; 64: 45–57
Pavlovic V, Pavlovic D, Kocic G, Sokolovic D, Sarac M, Jovic Z. Ascorbic acid modulates monosodium glutamate induced cytotoxicity in rat thymus. Bratisl Lek Listy, 2009; 110: 205–209
Wu CC, Doriarajan T, Lin TL. Effect of ascorbic acid supplementation on the immune response of chickens vaccinated and challenged with infectious bursal disease virus. Vet Immunol Immunopathol 2000; 74: 145–152
Carbonell LF, Nadal JA, Llanos C, Hernindez I, Nava E, Diaz J. Depletion of liver glutathione potentiates the oxidative stress and decreases nitric oxide synthesis in a rat endotoxin shock model. Crit Care Med 2000; 28: 2002–2006
Pavlovic V, Cekic S, Bojanic V, Stojiljkovic N, Rankovic G. Ascorbic acid modulates spontaneous thymocyte apoptosis. Acta Medica Medianae 2005; 44: 21–23
Perez-Cruz I, Carcamo JM, Golde DW. Vitamin C inhibits FAS-induced apoptosis in monocytes and U937 cells. Blood 2003; 102: 336–343
Vojdani A, Bazargan M, Vojdani E, Wright J. New evidence for antioxidant properties of Vitamin C. Cancer Detect Prev 2000; 24: 508–523
Campbell JD, Cole M, Bunditrutavorn B, Vella AT. Ascorbic acid is a potent inhibitor of various forms of T cell apoptosis. Cell Immunol 1999; 194: 1–5
Tan PH, Sagoo P, Chan C, Yates JB, Campbell J, Beutelspacher SC, Foxwell BM, Lombardi G, George AJ. Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells. J Immunol 2005; 174: 7633–7644
Fang JC, Kinlay S, Beltrame J, Hikiti H, Wainstein M, Behrendt D, Suh J, Frei B, Mudge GH, Selwyn AP, Ganz P. Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomized trial. Lancet 2002; 359: 1108–1113
Vissers MCM, Hamptom MB. The role of oxidants and vitamin C on neutrophil apoptosis and clearance. Biochem Soc Trans 2004; 32: 499–501
Goldschmidt MC. Reduced bactericidal activity in neutrophils from scorbutic animals and the effect of ascorbic acid on these target bacteria in vivo and in vitro. Am J Clin Nutr 1991; 54: 1214S–1220S
Wang Y, Russo TA, Kwon O, Chanock S, Rumsey SC, Levine M. Ascorbate recycling in human neutrophils: induction by bacteria. Proc. Natl. Acad. Sci. USA 1997; 94: 13816–13819
Savill J. Apoptosis in resolution of inflammation. J Leukoc Biol 1997; 61: 375–380
Maianski NA, Maianski AN, Kuijpers TW, Roos D. Apoptosis of neutrophils. Acta Haematol 2004; 111: 56–66
Savill J, Haslett C. Granulocyte clearance by apoptosis in the resolution of inflammation. Semin Cell Biol 1995; 6: 385–393
Mecklenburgh KI, Walmsley SR, Cowburn AS, Wiesener M, Reed BJ, Upton PD, Deighton J, Greening AP, Chilvers ER. Involvement of a ferroprotein sensor in hypoxia-mediated inhibition of neutrophil apoptosis. Blood 2002; 100: 3008–3016
Walmsley SR, Print C, Farahi N, Peyssonnaux C, Johnson RS, Cramer T, Sobolewski A, Condliffe AM, Cowburn AS, Johnson N, Chilvers ER. Hypoxia-induced neutrophil survival is mediated by HIF-1-dependent NF-B activity. J Exp Med 2005; 201: 105–115
Vissers M, Vilkie R. Ascorbate deficiency results in impaired neutrophil apoptosis and clearance and is associated with up-regulation of hypoxia inducible factor 1. J Lek Biol 2007; 81: 1236–1244
Churg A, Wright JL. Proteases and emphysema. Curr Opin Pulm Med 2005; 11: 153–159
Ferrón-Celma I, Mansilla A, Hassan L, Garcia-Navarro A, Comino AM, Bueno P, Ferrón JA. Effect of vitamin C administration on neutrophil apoptosis in septic patients after abdominal surgery. J Surg Res 2009; 153: 224–230
Winterbourn CC, Vissers MC. Changes in ascorbate levels on stimulation of human neutrophils. Biochim Biophys Acta 1983; 763: 175–179
Rajan G, Sleigh JW. Lymphocyte counts and the development of nosocomial sepsis. Intensive Care Med 1997; 23: 1187
Hotchkiss RS, Swanson PE, Freeman BD, Freeman BD, Tinsley KW, Cobb JP, Matuschak GM, Buchman TG, Karl IE. Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction. Crit Care Med 1999; 27: 1230–1251
Bergman M, Salman H, Djaldetti M, Fish L, Punsky I, Bessler H. In vitro immune response of human peripheral blood cells to vitamin C and E. J Nutr Biochem 2004; 15: 45–50
de-la-Fuente M, Ferrandez MD, Burgos MS, Soler A, Prieto A, Miquel J. Immune function in aged women is improved by ingestion of vitamin C and E. Can J Physiol Pharmacol 1998; 76: 373–380
Ndiweni N, Finch JM. Effects of in vitro supplementation with alpha-tocopherol and selenium on bovine neutrophil functions: implications for resistance to mastitis. Vet Immunol Immunopathol 1996; 51: 67–78
Andreasen CB, Frank DE. The effect of ascorbic acid on in vitro heterophil function. Avian Dis 1999; 43: 656–663
Goode HF, Cowley HC, Walker BE, Howdle PD Webster NR. Decreased antioxidant status and increased lipid peroxidation in patients with septic shock and secondary organ dysfunction. Crit Care Med 1995; 23: 646–651
Schorah CJ, Downing C, Piripitsi A, Gallivan L, Al-Haaza AH, Sanderson MJ, Bodenham A. Total vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in plasma of critically ill patients. Am J Clin Nutr 1996; 63: 760–765
Menon M, Maramag C, Malhorta RK, Seethalakshmi L. Effect of vitamin C on androgen independent prostate cancer cells (PC3 and Mat-Ly-Lu) in vitro: Involvement of reactive oxygen species-effect on cell number, viability and DNA synthesis. Cancer Biochem Biophys 1998; 16: 17–30
Maramag C, Menon M, Balaji KC, Reddy PG, Laxmanan S. Effect of vitamin C on prostate cancer cells in vitro: effect on cell number, viability, and DNA synthesis. Prostate 1997; 32: 188–195
Lee SH, Oe T, Blair IA. Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins. Science 2001; 292: 2083–2089
Seppanen M, Henttinen T, Lin L, Punnomen J, Grenman S, Punnonen R, Vihko KK. Inhibitory effects of cytokines on ovarian and endometrial carcinoma cells in vitro with special reference to induction of specific transcriptional regulators. Oncol Res 1998; 10: 575–589
Hartel C, Strunk T, Bucsky P, Schultz C. Effects of vitamin c on intracytoplasmatic cytokine production in human whole blood monocytes and lymphocytes. Cytokine 2004; 27: 101–106
Baeuerle PA, Henkel T. Function and activation of NFkB in the immune system. Annu Rev Immunol 1994; 12: 141–179
MacDonald J, Galley HF, Webster NR. Oxidative stress and gene expression in sepsis. Br J Anaesth 2003; 90: 221–232
Los M, Schenk H, Hexel K, Baeuerle PA, Droge W, Schulze-Osthoff K. IL-2 gene expression and NFkappa B activation through CD28 requires reactive oxygen production by 5-lipoxygenase. EMBO J 1995; 14: 3731–3740
Carcamo JM, Pedraza A, Borquez-Ojeda O, Golde DW. Vitamin C suppresses TNFa-induced NFkB activation by inhibiting IkBa phosphorylation. Biochemistry 2002; 41: 12995–13002
Bowie AG, O’Neill LAJ. Vitamin C inhibits NF-kB activation by TNF via the activation of p38 mitogenactivated protein kinase. J Immunol 2000; 165: 7180–7188
Carcamo JM, Borquez-Ojeda O, Golde DW. Vitamin C inhibits granulocyte macrophage-colonystimulating factor-induced signaling pathways. Blood 2002; 99: 3205–3212
Kodama M, Kodama T. Vitamin C and the genesis of autoimmune disease and allergy. In Vivo 1995; 9: 231–238
Tak PP, Zvaifler NJ, Green DR, Firestein GS. Rheumatoid arthritis and p53: how oxidative stress might alter the course of inflammatory diseases. Immunol Today 2000; 21:78–82
Du WD, Yuan ZR, Sun J, Tang JX, Cheng AQ, Shen DM, Huang CJ, Song XH, Yu XF, Zheng SB. Therapeutic efficacy of high-dose vitamin C on acute pancreatitis and its potential mechanisms. World J Gastroenterol 2003; 9: 2565–2569
Lefer DJ, Granger DN. Oxidative stress and cardiac disease. Am J Med 2000; 109: 315–323
Cuzzocrea S, Riley DP, Caputi AP, Salvemini D. Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury. Pharmacol Rev 2001; 53: 135–159
Hamuy R, Berman B. Treatment of herpes simplex virus infections with topical antiviral agents. Eur J Dermatol 1998; 8: 310–319
Anderson R, Oosthuizen R, Maritz R, Theron A, Van Rensburg AJ. The effects of increasing weekly doses of ascorbate on certain cellular and humoral immune functions in normal volunteers. Am J Clin Nutr 1980; 33: 71–76
Hume R, Weyers E: Changes in leukocyte ascorbic acid during the common cold. Scot Med J 1973; 18: 3–7
Douglas RM, Hemila H. Vitamin C for preventing and treating the common cold. Plos Med 2005; 2: 503–504
Field CJ, Johnson LR, Schley PD. Nutrients and their role in host resistance to infection. J Leuk Biol 2002; 71: 16–32
Anderson R, Smit MJ, Joone GK, van Staden AM. Vitamin C and cellular immune functions. Protection against hypochlorous acid-mediated inactivation of glyceraldehyde-3-phosphate dehydrogenase and ATP generation in human leukocytes as a possible mechanism of ascorbatemediated immunostimulation. Ann N Y Acad Sci 1990; 587:34–48
Saitoh Y, Ouchida R, Kayasuga A, Miwa N. Anti-Apoptotic Defense of bcl-2 Gene Against Hydroperoxide-Induced Cytotoxicity Together With Suppressed Lipid Peroxidation, Enhanced Ascorbate Uptake, and Upregulated Bcl-2 Protein. J Cell Biochem 2003; 89: 321–334
Hildeman DA, Mitchell T, Aronow B, Wojciechowski S, Kappler J, Marrack P. Control of Bcl-2 expression by reactive oxygen species. Proc Natl Acad Sci 2003; 100: 15035–15040
Pavlovic V, Cekic S, Sokolovic D, Djindjic B. Modulatory effect of monosodium glutamate on rat thymocyte proliferation and apoptosis. Bratisl Lek Listy 2006; 107: 185–191
Pavlovic V, Cekic S, Kocic G, Sokolovic D, Zivkovic V. Effect of monosodium glutamate on apoptosis and Bcl-2/Bax protein level in rat thymocyte culture. Physiol Res 2007; 56: 619–626
Pavlovic V, Pavlovic D, Kocic G, Sokolovic D, Jevtovic-Stoimenov T, Cekic S, Velickovic D. Effect of monosodium glutamate on oxidative stress and apoptosis in rat thymus. Mol Cell Biochem 2007; 303: 161–166
Pavlovic V, Cekic S: The effect of monosodium glutamate on the apoptosis of rat thymocytes and Bcl-2 expression. Arch Med Sci 2006; 2: 28–31
Saitoh Y, Ouchida R, Kayasuga A, Miwa N. (2003). Anti-Apoptotic Defense of bcl-2 Gene Against Hydroperoxide-Induced Cytotoxicity Together With Suppressed Lipid Peroxidation, Enhanced Ascorbate Uptake, and Upregulated Bcl-2 Protein. J Cell Biochem, 89, 321–334
Banerjee S, Chattopadhyay R, Ghosh A, Koley H, Panda K, Roy S, Chattopadhyay D, Chatterjee IB. Cellular and molecular mechanisms of cigarette smoke-induced lung damage and prevention by vitamin C. J Inflamm (Lond). 2008 Nov 11; 5:21
Pavlovic V, Sarac M. The role of ascorbic acid and monosodium glutamate in rat thymocyte apoptosis. Bratisl lek Listy 2010; 111: 357–360
Heuser G, Vojdani A. Enhancement of natural killer cell activity and T and B cell function by buffered vitamin C in patients exposed to toxic chemicals: the role of protein kinase-C. Immunopharmacol Immunotoxicol 1997; 19: 291–312
Wolf G. Uptake of ascorbic acid by human neutrophils. Nutr Rev 1993; 51: 337–338
Pavlovic V, Cekic S, Rankovic G, Stojiljkovic N. Antioxidant and pro-oxidant effect of ascorbic acid. Acta Medica Medianae 2005; 44: 65–68
Pavlovic Z, Pavlovic V. The effect of ascorbic acid on pathohistological tumor characteristics and phenotype characteristics of lymphocytes during the development of experimental mammary carcinoma in mice. Acta Medica Medianae 2005; 44: 23–31
Pavlovic Z, Pavlovic V, Pavlovic Z. The effect of ascorbic acid on development of experimental mammary carcinoma in mice. Acta Medica Medianae 2004; 43: 5–9
Auer BL, Auer D, Rodgers AL. Relative hyperoxaluria, crystalluria and haematuria after megadose ingestion of vitamin C. Eur J Clin Invest 1998; 28: 695–700
Wandzilak TR, D’Andre SD, Davis PA, Williams HE. Effect of high dose vitamin C on urinary oxalate levels. J Urol 1994; 151: 834–837
Deruelle F, Baron B. Vitamin C: is supplementation necessary for optimal health? J Altern Complement Med 2008; 14: 1291–1298
Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Intake of vitamins B6 and C and the risk of kidney stones in women. J Am Soc Nephrol 1999; 10: 840–845
Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A prospective study of the intake of vitamins C and B6, and the risk of kidney stones in men. J Urol 1996; 155: 1847–1851
Gerster H. No contribution of ascorbic acid to renal calcium oxalate stones. Ann Nutr Metab 1997; 41: 269–282
Lee SH, Yoon YC, Jang YY, Song JH, Han ES, Lee CS. Effect of iron and ascorbate on cyclosporine-induced oxidative damage of kidney mitochondria and microsomes. Pharmacol Res 2001; 43: 161–171
Rehman A, Collis CS, Yang M, Halliwell B. The effects of iron and vitamin C cosupplementation on oxidative damage to DNA in healthy volunteers. Biochem Biophys Res Commun 1998; 246: 293–298
Premkumar K, Bowlus CL. Ascorbic acid reduces the frequency of iron induced micronuclei in bone marrow cells of mice. Mutat Res 2003; 542: 99–103
Carr A, Frei B. Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans. Am J Clin Nutr 1999; 69: 1086–1107
Gomez-Cabrera MC, Domenech E, Romagnoli M, Arduini A, Borras C, Pallardo FV, Sastre J, Vina J. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr 2008; 87: 142–149
Deruelle F, Baron B. Vitamin C: Supplementation necessary for optimal health? J Altern Complement Med 2008; 14: 1291–1298
Rose RC, Bode AM. Biology of free radical scavengers: An evaluation of ascorbate. FASEB J. 1993; 7: 1135–1142
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Pavlovic, V., Sarac, M. A short overview of vitamin C and selected cells of the immune system. cent.eur.j.med 6, 1–10 (2011). https://doi.org/10.2478/s11536-010-0066-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.2478/s11536-010-0066-x