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Review

Vitamin C and Cancer: The Role of Vitamin C in Disease Progression and Quality of Life in Cancer Patients

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Pages 1282-1292 | Received 25 Feb 2020, Accepted 23 Jun 2020, Published online: 21 Jul 2020

References

  • Ferlay J, Colombet M, Soerjomataram I, et al. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941–53.
  • Cadeau C, Fournier A, Mesrine S, Clavel-Chapelon F, Fagherazzi G, Boutron-Ruault M-C. Vitamin C supplement intake and postmenopausal breast cancer risk: Interaction with dietary vitamin C. Am J Clin Nutr. 2016;104(1):228–34. doi:10.3945/ajcn.115.126326
  • Chen J, Jiang W, Shao L, Zhong D, Wu Y, Cai J. Association between intake of antioxidants and pancreatic cancer risk: A meta-analysis. Int J Food Sci Nutr. 2016;67(7):744–53. doi:10.1080/09637486.2016.1197892
  • Cao D, Shen K, Li Z, Xu Y, Wu D. Association between vitamin C Intake and the risk of cervical neoplasia: A meta-analysis. Nutr Cancer. 2016;68(1):48–57. doi:10.1080/01635581.2016.1115101
  • Jia L, Jia Q, Shang Y, Dong X, Li L. Vitamin C intake and risk of renal cell carcinoma: A meta-analysis. Sci Rep. 2015;5:17921. doi:10.1038/srep17921
  • Bo Y, Lu Y, Zhao Y, Zhao E, Yuan L, Lu W, Cui L, Lu Q. Association between dietary vitamin C intake and risk of esophageal cancer: A dose-response meta-analysis. Int J Cancer. 2016;138(8):1843–50. doi:10.1002/ijc.29838
  • Bai X-Y, Qu X, Jiang X, Xu Z, Yang Y, Su Q, Wang M, Wu H. Association between dietary vitamin C intake and risk of prostate cancer: A meta-analysis involving 103,658 subjects. J Cancer. 2015;6(9):913–21. doi:10.7150/jca.12162
  • Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: Results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo. 2011;25(6):983–90.
  • Mayland CR, Bennett MI, Allan K. Vitamin C deficiency in cancer patients. Palliat Med. 2005;19(1):17–20. doi:10.1191/0269216305pm970oa
  • Mahdavi R, Faramarzi E, Seyedrezazadeh E, Mohammad- Zadeh M, Pourmoghaddam M. Evaluation of oxidative stress, antioxidant status and serum vitamin C levels in cancer patients. Biol Trace Elem Res. 2009;130(1):1–6. doi:10.1007/s12011-008-8309-2
  • Mikirova N, Casciari J, Riordan N, Hunninghake R. Clinical experience with intravenous administration of ascorbic acid: Achievable levels in blood for different states of inflammation and disease in cancer patients. J Transl Med. 2013;11:191. doi:10.1186/1479-5876-11-191
  • Alexandrescu DT, Dasanu CA, Kauffman CL. Acute scurvy during treatment with interleukin-2. Clin Exp Dermatol. 2009;34(7):811–4. doi:10.1111/j.1365-2230.2008.03052.x
  • Gupta A, Bhatt ML, Misra MK. Lipid peroxidation and antioxidant status in head and neck squamous cell carcinoma patients. Oxid Med Cell Longev. 2009;2(2):68–72. doi:10.4161/oxim.2.2.8160
  • Gan R, Eintracht S, Hoffer LJ. Vitamin C deficiency in a university teaching hospital. J Am Coll Nutr. 2008;27(3):428–33. doi:10.1080/07315724.2008.10719721
  • Fain O. Vitamin C [French]. Rev Prat. 2013;63:1091–6.
  • Emri S, Kilickap S, Kadilar C, Halil MG, Akay H, Besler T. Serum levels of alpha-tocopherol, vitamin C, beta-carotene, and retinol in malignant pleural mesothelioma. Asian Pac J Cancer Prev. 2012;13(7):3025–9. doi:10.7314/APJCP.2012.13.7.3025
  • Mehdi WA, Zainulabdeen JA, Mehde AA. Investigation of the antioxidant status in multiple myeloma patients: Effects of therapy. Asian Pac J Cancer Prev. 2013;14(6):3663–7. doi:10.7314/apjcp.2013.14.6.3663
  • Yeom CH, Jung GC, Song KJ. Changes of terminal cancer patients’ health-related quality of life after high dose vitamin C administration. J Korean Med Sci. 2007;22(1):7–11. doi:10.3346/jkms.2007.22.1.7
  • Carr AC, Vissers MD, Cook JS. The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life. Front Oncol. 2014;4:283. doi:10.3389/fonc.2014.00283
  • Takahashi H, Mizuno H, Yanagisawa A. High-dose intravenous vitamin C improves quality of life in cancer patients. Personalized Medicine Universe. 2012;1(1):49–53. doi:10.1016/j.pmu.2012.05.008
  • Mikirova N, Casciari J, Rogers A, Taylor P. Effect of high-dose intravenous vitamin C on inflammation in cancer patients. J Transl Med. 2012;10:189. doi:10.1186/1479-5876-10-189
  • Esme H, Cemek M, Sezer M, Saglam H, Demir A, Melek H, Unlu M. High levels of oxidative stress in patients with advanced lung cancer. Respirology. 2008;13(1):112–6. doi:10.1111/j.1440-1843.2007.01212.x
  • Yalcin O, Karatas F, Erulas FA, Ozdemir E. The levels of glutathione peroxidase, vitamin A, E, C and lipid peroxidation in patients with transitional cell carcinoma of the bladder. BJU Int. 2004;93(6):863–6.
  • Akinloye O, Adaramoye O, Kareem O. Changes in antioxidant status and lipid peroxidation in Nigerian patients with prostate carcinoma. Pol Arch Med Wewn. 2009;119(9):526–32. doi:10.20452/pamw.759
  • Chen Q, Espey MG, Sun AY, Pooput C, Kirk KL, Krishna MC, Khosh DB, Drisko J, Levine M. Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci USA. 2008;105(32):11105–9. doi:10.1073/pnas.0804226105
  • Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E, Levine M. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a prodrug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci USA. 2005;102(38):13604–9. doi:10.1073/pnas.0506390102
  • Chen Q, Espey MG, Sun AY, Lee J-H, Krishna MC, Shacter E, Choyke PL, Pooput C, Kirk KL, Buettner GR, et al. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci USA. 2007;104(21):8749–54. doi:10.1073/pnas.0702854104
  • Lee SJ, Jeong J-H, Lee IH, Lee J, Jung JH, Park HY, Lee DH, Chae YS. Effect of high-dose vitamin C combined with anti-cancer treatment on breast cancer cells. Anticancer Res. 2019;39(2):751–8. doi:10.21873/anticanres.13172
  • Welsh JL, Wagner BA, van’t Erve TJ, Zehr PS, Berg DJ, Halfdanarson TR, Yee NS, Bodeker KL, Du J, Roberts LJ, et al. Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): Results from a phase I clinical trial. Cancer Chemother Pharmacol. 2013;71(3):765–75. doi:10.1007/s00280-013-2070-8
  • Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, Rosadiuk K, Rousseau C, Robitaille L, Miller WH. Phase I clinical trial of I.V. ascorbic acid in advanced malignancy. Ann Oncol. 2008;19(11):1969–74. [Erratum in: Ann Oncol 2008;19:2095]. doi:10.1093/annonc/mdn377
  • Stephenson CM, Levin RD, Spector T, Lis CG. Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. Cancer Chemother Pharmacol. 2013;72(1):139–46. doi:10.1007/s00280-013-2179-9
  • Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med. 2014;6(222):222ra18. doi:10.1126/scitranslmed.3007154
  • Monti DA, Mitchell E, Bazzan AJ, Littman S, Zabrecky G, Yeo CJ, Pillai MV, Newberg AB, Deshmukh S, Levine M, et al. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One. 2012;7(1):e29794. doi:10.1371/journal.pone.0029794
  • Cui Y, Shikany JM, Liu S, Shagufta Y, Rohan TE. Selected antioxidants and risk of hormone receptor-defined invasive breast cancers among postmenopausal women in the Women's Health Initiative Observational Study. Am J Clin Nutr. 2008;87(4):1009–18. doi:10.1093/ajcn/87.4.1009
  • Zhang S, Hunter DJ, Forman MR, Rosner BA, Speizer FE, Colditz GA, Manson JE, Hankinson SE, Willett WC. Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst. 1999;91(6):547–56. doi:10.1093/jnci/91.6.547
  • Roswall N, Olsen A, Christensen J, Dragsted LO, Overvad K, et al. Micronutrient intake and breast cancer characteristics among postmenopausal women. Eur J Cancer Prev. 2010;19:360–5.
  • Rohan TE, Howe GR, Friedenreich CM, Jain M, Miller AB. Dietary fiber, vitamins A, C, and E, and risk of breast cancer: A cohort study. Cancer Causes Control. 1993;4(1):29–37. doi:10.1007/BF00051711
  • Kushi LH, Fee RM, Sellers TA, Zheng W, Folsom AR. Intake of vitamins A, C, and E and postmenopausal breast cancer. The Iowa Women's Health Study. Am J Epidemiol. 1996;144(2):165–74. doi:10.1093/oxfordjournals.aje.a008904
  • Lin J, Cook NR, Albert C, Zaharris E, Gaziano JM, Van Denburgh M, Buring JE, Manson JE. Vitamins C and E and beta carotene supplementation and cancer risk: A randomized controlled trial. J Natl Cancer Inst. 2009;101(1):14–23. doi:10.1093/jnci/djn438
  • Cameron E, Campbell A. The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem Biol Interact. 1974;9(4):285–315. doi:10.1016/0009-2797(74)90019-2
  • Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA. 1976;73(10):3685–9. doi:10.1073/pnas.73.10.3685
  • Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: Reevaluation of prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA. 1978;75(9):4538–42. doi:10.1073/pnas.75.9.4538
  • Benade L, Howard T, Burk D. Synergistic killing of Ehrlich ascites carcinoma cells by ascorbate and 3-amino-1,2,4,-triazole. Oncology. 1969;23(1):33–43. doi:10.1159/000224465
  • Bram S, Froussard P, Guichard M, Jasmin C, Augery Y, Sinoussi-Barre F, Wray W. Vitamin C preferential toxicity for malignant melanoma cells. Nature. 1980;284(5757):629–31. doi:10.1038/284629a0
  • Leung PY, Miyashita K, Young M, Tsao CS. Cytotoxic effect of ascorbate and its derivatives on cultured malignant and nonmalignant cell lines. Anticancer Res. 1993;13(2):475–80.
  • Casciari JJ, Riordan NH, Schmidt TL, Meng XL, Jackson JA, Riordan HD. Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours. Br J Cancer. 2001;84(11):1544–50. doi:10.1054/bjoc.2001.1814
  • Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, et al. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci U S A. 2005;102(38):13604–9.
  • Sullivan GG, Chen Q, Chen P, Chapman J, Levine M, et al. Prospective randomized phase I/IIa pilot trial to assess safety and benefit administering high-dose intravenous ascorbate in combination with chemotherapy in newly diagnosed advanced stage III or Stage IV ovarian cancer. Conference abstract of the Society of Integrative Oncology; 2011 November; Cleveland, OH.
  • Riordan HD, Riordan NH, Jackson JA, Casciari JJ, Hunninghake R, González MJ, Mora EM, Miranda-Massari JR, Rosario N, Rivera A, et al. Intravenous vitamin C as a chemotherapy agent: A report on clinical cases. P R Health Sci J. 2004;23(2):115–8.
  • Abdel-Latif MM, Raouf AA, Sabra K, Kelleher D, Reynolds JV. Vitamin C enhances chemosensitization of esophageal cancer cells in vitro. J Chemother. 2005;17(5):539–49. doi:10.1179/joc.2005.17.5.539
  • Kurbacher CM, Wagner U, Kolster B, Andreotti PE, Krebs D, Bruckner HW. Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett. 1996;103(2):183–9. doi:10.1016/0304-3835(96)04212-7
  • Prasad KN, Sinha PK, Ramanujam M, Sakamoto A. Sodium ascorbate potentiates the growth inhibitory effect of certain agents on neuroblastoma cells in culture. Proc Natl Acad Sci USA. 1979;76(2):829–32. doi:10.1073/pnas.76.2.829
  • Reddy VG, Khanna N, Singh N. Vitamin C augments chemotherapeutic response of cervical carcinoma HeLa cells by stabilizing P53. Biochem Biophys Res Commun. 2001;282(2):409–15. doi:10.1006/bbrc.2001.4593
  • Taper HS, de Gerlache J, Lans M, Roberfroid M. Non-toxic potentiation of cancer chemotherapy by combined C and K3 vitamin pre-treatment. Int J Cancer. 1987;40(4):575–9. doi:10.1002/ijc.2910400424
  • Wells WW, Rocque PA, Xu DP, Meyer EB, Charamella LJ, Dimitrov NV. Ascorbic acid and cell survival of Adriamycin resistant and sensitive MCF-7 breast tumor cells. Free Radic Biol Med. 1995;18(4):699–708. doi:10.1016/0891-5849(94)00188-p
  • Verrax J, Calderon PB. Pharmacologic concentrations of ascorbate are achieved by parenteral administration and exhibit antitumoral effects. Free Radic Biol Med. 2009;47(1):32–40. doi:10.1016/j.freeradbiomed.2009.02.016
  • Frömberg A, Gutsch D, Schulze D, Vollbracht C, Weiss G, Czubayko F, Aigner A. Ascorbate exerts anti-proliferative effects through cell cycle inhibition and sensitizes tumor cells towards cytostatic drugs. Cancer Chemother Pharmacol. 2011;67(5):1157–66. doi:10.1007/s00280-010-1418-6
  • Martinotti S, Ranzato E, Burlando B. In vitro screening of synergistic ascorbate-drug combinations for the treatment of malignant mesothelioma. Toxicol In Vitro. 2011;25(8):1568–74. doi:10.1016/j.tiv.2011.05.023
  • Espey MG, Chen P, Chalmers B, Drisko J, Sun AY, Levine M, Chen Q. Pharmacologic ascorbate synergizes with gemcitabine in preclinical models of pancreatic cancer. Free Radic Biol Med. 2011;50(11):1610–9. doi:10.1016/j.freeradbiomed.2011.03.007
  • Prasad KN, Hernandez C, Edwards-Prasad J, Nelson J, Borus T, Robinson WA. Modification of the effect of tamoxifen, cis-platin, DTIC, and interferon-alpha 2b on human melanoma cells in culture by a mixture of vitamins. Nutr Cancer. 1994;22(3):233–45. doi:10.1080/01635589409514349
  • Pathak AK, Singh N, Khanna N, Reddy VG, Prasad KN, Kochupillai V. Potentiation of the effect of paclitaxel and carboplatin by antioxidant mixture on human lung cancer h520 cells. J Am Coll Nutr. 2002;21(5):416–21. doi:10.1080/07315724.2002.10719244
  • Bannerman B, Xu L, Jones M, Tsu C, Yu J, Hales P, Monbaliu J, Fleming P, Dick L, Manfredi M, et al. Preclinical evaluation of the antitumor activity of bortezomib in combination with vitamin C or with epigallocatechin gallate, a component of green tea. Cancer Chemother Pharmacol. 2011;68(5):1145–54. doi:10.1007/s00280-011-1591-2
  • Perrone G, Hideshima T, Ikeda H, Okawa Y, Calabrese E, Gorgun G, Santo L, Cirstea D, Raje N, Chauhan D, et al. Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Leukemia. 2009;23(9):1679–86. doi:10.1038/leu.2009.83
  • Chen AA, Marsit CJ, Christensen BC, Houseman EA, McClean MD, Smith JF, Bryan JT, Posner MR, Nelson HH, Kelsey KT, et al. Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer. Carcinogenesis. 2009;30(6):977–81. doi:10.1093/carcin/bgp076
  • Erichsen HC, Peters U, Eck P, Welch R, Schoen RE, Yeager M, Levine M, Hayes RB, Chanock S. Genetic variation in sodium-dependent vitamin C transporters SLC23A1 and SLC23A2 and risk of advanced colorectal adenoma. Nutr Cancer. 2008;60(5):652–9. doi:10.1080/01635580802033110
  • Wright ME, Andreotti G, Lissowska J, Yeager M, Zatonski W, Chanock SJ, Chow W-H, Hou L. Genetic variation in sodium-dependent ascorbic acid transporters and risk of gastric cancer in Poland. Eur J Cancer. 2009;45(10):1824–30. doi:10.1016/j.ejca.2009.01.027
  • Park J-H, Davis KR, Lee G, Jung M, Jung Y, Park J, Yi S-Y, Lee M-A, Lee S, Yeom C-H, et al. Ascorbic acid alleviates toxicity of paclitaxel without interfering with the anticancer efficacy in mice. Nutr Res. 2012;32(11):873–83. doi:10.1016/j.nutres.2012.09.011
  • An SH, Kang JH, Kim DH, Lee MS. Vitamin C increases the apoptosis via up-regulation p53 during cisplatin treatment in human colon cancer cells. BMB Rep. 2011;44(3):211–6. doi:10.5483/BMBRep.2011.44.3.211
  • Levine M, Padayatty SJ, Espey MG. Vitamin C: A concentration- function approach yields pharmacology and therapeutic discoveries. Adv Nutr. 2011;2(2):78–88. doi:10.3945/an.110.000109
  • Kimoto E, Tanaka H, Gyotoku J, Morishige F, Pauling L. Enhancement of antitumor activity of ascorbate against Ehrlich ascites tumor cells by the copper:glycylglycylhistidine complex. Cancer Res. 1983;43(2):824–8.
  • Ranzato E, Biffo S, Burlando B. Selective ascorbate toxicity in malignant mesothelioma: A redox Trojan mechanism. Am J Respir Cell Mol Biol. 2011;44(1):108–17. doi:10.1165/rcmb.2009-0340OC
  • 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(3):188–95. doi:10.1002/(SICI)1097-0045(19970801)32:3<188::AID-PROS5>3.0.CO;2-H
  • Hong S-W, Lee S-H, Moon J-H, Hwang JJ, Kim DE, Ko E, Kim H-S, Cho IJ, Kang JS, Kim DJ, et al. SVCT-2 in breast cancer acts as an indicator for L-ascorbate treatment. Oncogene. 2013;32(12):1508–17. doi:10.1038/onc.2012.176
  • Hong S-W, Jin D-H, Hahm E-S, Yim S-H, Lim J-S, Kim K-I, Yang Y, Lee S-S, Kang J-S, Lee W-J, et al. Ascorbate (vitamin C) induces cell death through the apoptosis-inducing factor in human breast cancer cells. Oncol Rep. 2007;18(4):811–5. doi:10.3892/or.18.4.811
  • Bhat SH, Azmi AS, Hanif S, Hadi SM. Ascorbic acid mobilizes endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: A putative mechanism for anticancer properties. Int J Biochem Cell Biol. 2006;38(12):2074–81. doi:10.1016/j.biocel.2006.05.017
  • Park S, Han S-S, Park CH, Hahm E-R, Lee SJ, Park HK, Lee S-H, Kim WS, Jung CW, Park K, et al. L-Ascorbic acid induces apoptosis in acute myeloid leukemia cells via hydrogen peroxide-mediated mechanisms. Int J Biochem Cell Biol. 2004;36(11):2180–95. doi:10.1016/j.biocel.2004.04.005
  • Vuyyuri SB, Rinkinen J, Worden E, Shim H, Lee S, Davis KR. Ascorbic acid and a cytostatic inhibitor of glycolysis synergistically induce apoptosis in non-small cell lung cancer cells. PLoS One. 2013;8(6):e67081. doi:10.1371/journal.pone.0067081
  • Chen P, Yu J, Chalmers B, Drisko J, Yang J, Li B, Chen Q. Pharmacological ascorbate induces cytotoxicity in prostate cancer cells through ATP depletion and induction of autophagy. Anticancer Drugs. 2012;23(4):437–44. doi:10.1097/CAD.0b013e32834fd01f
  • Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang S-h, Taghiyev AF, Du C, Knudson CM, Cullen JJ, et al. Mechanisms of ascorbateinduced cytotoxicity in pancreatic cancer. Clin Cancer Res. 2010;16(2):509–20. doi:10.1158/1078-0432.CCR-09-1713
  • Kim JE, Kang JS, Lee WJ. Vitamin C induces apoptosis in human colon cancer cell line, HCT-8 via the modulation of calcium influx in endoplasmic reticulum and the dissociation of bad from 14-3-3β. Immune Netw. 2012;12(5):189–95. doi:10.4110/in.2012.12.5.189
  • Kuiper C, Molenaar IGM, Dachs GU, Currie MJ, Sykes PH, Vissers MCM. Low ascorbate levels are associated with increased hypoxia-inducible factor-1 activity and an aggressive tumor phenotype in endometrial cancer. Cancer Res. 2010;70(14):5749–58. doi:10.1158/0008-5472.CAN-10-0263
  • Kim J, Lee S-D, Chang B, Jin D-H, Jung S-I, Park M-Y, Han Y, Yang Y, Il Kim K, Lim J-S, et al. Enhanced antitumor activity of vitamin C via p53 in cancer cells. Free Radic Biol Med. 2012;53(8):1607–15. doi:10.1016/j.freeradbiomed.2012.07.079
  • Pollard HB, Levine MA, Eidelman O, Pollard M. Pharmacological ascorbic acid suppresses syngeneic tumor growth and metastases in hormone-refractory prostate cancer. In Vivo. 2010;24(3):249–55.
  • Kim HN, Kim H, Kong JM, Bae S, Kim YS, Lee N, Cho BJ, Lee SK, Kim H-R, Hwang Y-i, et al. Vitamin C down-regulates VEGF production in B16F10 murine melanoma cells via the suppression of p42/44 MAPK activation. J Cell Biochem. 2011;112(3):894–901. doi:10.1002/jcb.22997
  • Mikirova NA, Casciari JJ, Riordan NH. Ascorbate inhibition of angiogenesis in aortic rings ex vivo and subcutaneous Matrigel plugs in vivo. J Angiogenes Res. 2010;2:2. doi:10.1186/2040-2384-2-2
  • Lee SK, Kang JS, Jung DJ, Hur DY, Kim JE, Hahm E, Bae S, Kim HW, Kim D, Cho BJ, et al. Vitamin C suppresses proliferation of the human melanoma cell SK-MEL-2 through the inhibition of cyclooxygenase-2 (COX-2) expression and the modulation of insulin-like growth factor II (IGF-II) production. J Cell Physiol. 2008;216(1):180–8. doi:10.1002/jcp.21391
  • Yeom C-H, Lee G, Park J-H, Yu J, Park S, Yi S-Y, Lee HR, Hong YS, Yang J, Lee S, et al. High dose concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis. J Transl Med. 2009;7:70. doi:10.1186/1479-5876-7-70
  • Carcamo JM, Pedraza A, Borquez-Ojeda O, Golde DW. Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation. Biochemistry. 2002;41(43):12995–3002. doi:10.1021/bi0263210
  • Son EW, Mo SJ, Rhee DK, Pyo S. Vitamin C blocks TNF-α-induced NF-kB activation and ICAM-1 expression in human neuroblastoma cells . Arch Pharm Res. 2004;27(10):1073–9. doi:10.1007/BF02975434
  • Oberley TD, Oberley LW. Antioxidant enzyme levels in cancer. Histol Histopathol. 1997;12(2):525–35.
  • Davies KJ. The broad spectrum of responses to oxidants in proliferating cells: A new paradigm for oxidative stress. IUBMB Life. 1999;48(1):41–7. doi:10.1080/713803463
  • Robitaille L, Mamer OA, Miller WH, Levine M, Assouline S, Melnychuk D, Rousseau C, Hoffer LJ. Oxalic acid excretion after intravenous ascorbic acid administration. Metab Clin Exp. 2009;58(2):263–9. doi:10.1016/j.metabol.2008.09.023
  • Riordan HD, Casciari JJ, González MJ, Riordan NH, Miranda-Massari JR, Taylor P, Jackson JA. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. P R Health Sci J. 2005;24(4):269–76.
  • Auer BL, Auer D, Rodgers AL. Relative hyperoxaluria, crystalluria and haematuria after megadose ingestion of vitamin C. Eur J Clin Invest. 1998;28(9):695–700. doi:10.1046/j.1365-2362.1998.00349.x
  • Mashour S, Turner JF, Jr, Merrell R. Acute renal failure, oxalosis, and vitamin C supplementation: A case report and review of the literature. Chest. 2000;118(2):561–3. doi:10.1378/chest.118.2.561
  • 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;10:840–5.
  • Gerster H. No contribution of ascorbic acid to renal calcium oxalate stones. Ann Nutr Metab. 1997;41(5):269–82. doi:10.1159/000177954
  • Mehta JB, Singhal SB, Mehta BC. Ascorbic-acid-induced haemolysis in g-6-pd deficiency. Lancet. 1990;336(8720):944. doi:10.1016/0140-6736(90)92317-b
  • Rees DC, Kelsey H, Richards JD. Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenase deficiency. BMJ. 1993;306(6881):841–2. doi:10.1136/bmj.306.6881.841
  • Braunstein EM. Glucose 6-phosphate dehydrogenase deficiency. In: Lichtin AE, editors. Merck manual: professional edition. 19th ed. Kenilworth, NJ: Merck Sharp and Dohme Corp; 2018. [accessed 2016 January 8]. http://www.merckmanuals.com/professional/hematology_and_oncology/anemias_caused_by_hemolysis/glucose-6-phosphate_dehydrogenase_g6pd_deficiency.html.
  • Rosenthal G. Interaction of ascorbic acid and warfarin. JAMA. 1971;215(10):1671.
  • Padayatty SJ, Sun AY, Chen Q, Espey MG, Drisko J, Levine M. Vitamin C: Intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One. 2010;5(7):e11414doi:10.1371/journal.pone.0011414
  • Buettner GR, Jurkiewicz BA. Catalytic metals, ascorbate and free radicals: Combinations to avoid. Radiat Res. 1996;145(5):532–41. doi:10.2307/3579271
  • McCarty MF, Barroso-Aranda J, Contreras F. Oxidative stress therapy for solid tumors - a proposal. Med Hypotheses. 2010;74(6):1052–4. doi:10.1016/j.mehy.2009.12.029
  • Szatrowski TP, Nathan CF. Production of large amounts of hydrogen peroxide by human tumor cells. Cancer Res. 1991;51(3):794–8.

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