Review

Vitamin C and Cancer

  • Received: 18 October 2015 Accepted: 15 December 2015 Published: 27 December 2015
  • Vitamin C or ascorbic acid has been proposed as an anticancer agent, as an intervention to reduce cancer incidence, and also as a medication to reduce cancer treatment-related side effects. While there has been significant basic science research that has evaluated the potential tumoricidal mechanisms of action, clinical studies have been underpowered, retrospective, or poorly designed. Current systematic reviews have suggested that the outcome data from vitamin C therapy is limited. There is an important need for prospective clinical trials and pharmacologic studies to fully evaluate the potential of vitamin C as an anticancer agent.

    Citation: Annekathryn Goodman. Vitamin C and Cancer[J]. AIMS Medical Science, 2016, 3(1): 41-51. doi: 10.3934/medsci.2016.1.41

    Related Papers:

  • Vitamin C or ascorbic acid has been proposed as an anticancer agent, as an intervention to reduce cancer incidence, and also as a medication to reduce cancer treatment-related side effects. While there has been significant basic science research that has evaluated the potential tumoricidal mechanisms of action, clinical studies have been underpowered, retrospective, or poorly designed. Current systematic reviews have suggested that the outcome data from vitamin C therapy is limited. There is an important need for prospective clinical trials and pharmacologic studies to fully evaluate the potential of vitamin C as an anticancer agent.



    加载中
    [1] Padayatty SJ, Katz A, Wang Y, et al. (2003) Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 22: 18-35. doi: 10.1080/07315724.2003.10719272
    [2] Peterkofsky B (1991) Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy. Am J Clin Nutr 54: 1135S-1140S.
    [3] McCormick WJ (1959) Cancer: a collagen disease, secondary to a nutritional deficiency. Arch Pediatr 76: 166-171.
    [4] Cameron E, Rotman D (1972) Ascorbic acid, cell proliferation, and cancer. Lancet 1: 542.
    [5] Cameron E, Pauling L (1976) Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proc Natl Acad Sci USA 73: 3685-3689. doi: 10.1073/pnas.73.10.3685
    [6] Jacobs C, Hutton B, Ng T, et al. (2015) Is there a role for oral or intravenous ascorbate (vitamin C) in treating patients with cancer? A systematic review. The Oncologist 20: 210-223.
    [7] Levine M, Espey MG, Chen Q (2009) Losing and finding a way at C: new promise for pharmacologic ascorbate in cancer treatment. Free Radic Biol Med 47: 27-29. doi: 10.1016/j.freeradbiomed.2009.04.001
    [8] Parrow NL, Leshin JA, Levine M (2013) Parenteral ascorbate as a cancer therapeutic: a reassessment based on pharmacokinetics. Antioxidants Redox Signal 19: 2141-2156. doi: 10.1089/ars.2013.5372
    [9] Chen Q, Polireddy K, Chen P, et al. (2015) The unpaved journey of vitamin C in cancer treatment. Can J Physiol Pharmacol 27: 1-9.
    [10] Rebouche CJ (1991) Ascorbic acid and carnitine biosynthesis. Am J Clin Nutr 54: 1147S-1152S.
    [11] Eipper BA, Stoffers DA, Mains RE (1992) The biosynthesis of neuropeptides: peptide alpha-amidation. Annu Rev Neurosci 15: 57-85.
    [12] Venturelli S, Sinnberg TW, Niessner H, et al. (2015) Molecular mechanisms of pharmacological doses of ascorbate on cancer cells. Wien Med Wochenschr 165: 251-257. doi: 10.1007/s10354-015-0356-7
    [13] Ranzato E, Biffo S, Burlando B (2011) Selective ascorbate toxicity in malignant mesothelioma: a redox Trojan mechanism. Am J Respir Cell Mol Biol 44: 108-117.
    [14] Gonzalez MJ, Miranda-Massari JR (2014) New insights on vitamin C and cancer. Springer Brief Cancer Res.
    [15] Oreopoulos DG, Lindeman RD, VanderJagt DJ, et al. (1993) Renal excretion of ascorbic acid: effect of age and sex. J Am Coll Nutr 12: 537-542. doi: 10.1080/07315724.1993.10718349
    [16] Stephenson CM, Levin RD, Spector T, et al. (2013) Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. Cancer Chemoth Pharmacol 72: 139-146. doi: 10.1007/s00280-013-2179-9
    [17] Murata A, Morishige F, Yamaguchi H (1982) Prolongation of survival times of terminal cancer patients by administration of large doses of ascorbate. Int J Vitam Nutr Res Suppl 23:103-113.
    [18] Padayatty SJ, Sun H, Wang Y, et al. (2004) Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med 140: 533-537.
    [19] Fritz H, Flower G, Weeks L, et al. (2014) Intravenous vitamin C and cancer: A systematic review. Integr Cancer Ther 13: 280-300. doi: 10.1177/1534735414534463
    [20] McCarty MF, Contreras F (2014) Increasing superoxide production and the labile iron pool in tumor cells may sensitize them to extracellular ascorbate. Frontiers Oncology 4: 249.
    [21] Chen Q, Espey MG, Krishna MC, et al. (2005) Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci USA 102: 13604-13910.
    [22] Knowles HJ, Raval RR, Harris AL,et al. (2003) Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells. Cancer Res 63:1764-1768.
    [23] Uetaki M, Tabata S, Nakasuka F, et al. (2015) Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress. Sci Report 5: 13896. doi: 10.1038/srep13896
    [24] Sinnberg T, Noor S, Venturelli S, et al. (2014) The ROS-induced cytotoxicity of ascorbate is attenuated by hypoxia and HIF-1alpha in the NCI60 cancer cell lines. J Cell Mol Med 18: 530-541. doi: 10.1111/jcmm.12207
    [25] Mastrangelo D, Massai L, Lo Cocco F, et al. (2015) Cytotoxic effects of high concentrations of sodium ascorbate on human myeloid cell lines. Ann Hematol 94: 1807-1816. doi: 10.1007/s00277-015-2464-2
    [26] Pichler V, Göschi S, Schreiber-Brynzak E, et al. (2015) Influence of reducing agents on the cytotoxic activity of platinum (IV) complexes: induction of G2/M arrest, apoptosis and oxidative stress in A2780 and cisplatin resistant A2780cis cell lines. Metallomics 7: 1078-1090.
    [27] Chtourou Y, Aouey B, Kebieche M, et al. (2015) Protective role of naringin against cisplatin induced oxidative stress, inflammatory response and apoptosis in rat striatum via suppressing ROS-mediated NF-kB and P53 signalling pathways. Chem Biol Interact 239: 76-86. doi: 10.1016/j.cbi.2015.06.036
    [28] Gerhardt T, Jones R, Park J, et al. (2015) Effects of antioxidants and pro-oxidants on cytotoxicity of dihydroartemisinin to Molt-4 human leukemia cells. Anticancer Res 35: 1867-1871.
    [29] Harada S, Ehara S, Ishi K, et al. (2015) Targeted concurrent chemotherapy, by using improved microcapsules that release carboplatin in response to radiation, improves detectability by computed tomography as well as antitumor activity while reducing adverse effect in vivo. Biomed Pharmacother 70: 196-205. doi: 10.1016/j.biopha.2015.01.006
    [30] Cortés-Jofré M, Rueda JR, Corsini-Muñoz G, et al. (2012) Drugs for preventing lung cancer in healthy people. Cochrane Database Syst Rev 10: CD002141.
    [31] Luo J, Shen L, Zheng D (2014) Association between vitamin C intake and lung cancer: a dose-response meta-analysis. Sci Rep 4: 6161.
    [32] Stratton J, Godwin M (2011) The effect of supplemental vitamins and minerals on the development of prostate cancer: a systematic review and meta-analysis. Fam Pract 28: 243-252. doi: 10.1093/fampra/cmq115
    [33] Xu X, Yu E, Liu L, et al. (2013) Dietary intake of vitamins A, C, and E and the risk of colorectal adenoma: a meta-analysis of observational studies. Eur J Cancer Prev 22: 529-539.
    [34] Papaioannou D, Cooper KL, Carroll C, et al. (2011) Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis. Colorectal Dis 13: 1085-1099. doi: 10.1111/j.1463-1318.2010.02289.x
    [35] Fulan H, Changxing J, Baina WY, et al. (2011) Retinol, vitamins A, C, and E and breast cancer risk: a meta-analysis and meta-regression. Cancer Causes Control 22: 1383-1396. doi: 10.1007/s10552-011-9811-y
    [36] Fan H, Kou J, Han D, et al. (2015) Association between vitamin C intake and the risk of pancreatic cancer: a meta-analysis of observational studies. Sci Rep 5:13973. doi: 10.1038/srep13973
    [37] Bo Y, Lu Y, Zhao Y, et al (2015). Association between dietary vitamin C intake and risk of esophageal cancer: a dose-response meta-analysis. Int J Cancer. doi: 10.1002/ijc.29838. doi: 10.1002/ijc.29838
    [38] Creagan ET, Moertel CG, O'Fallon JR, et al. (1979) Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med 301: 687-690.
    [39] Hoffer LJ (2001) Proof versus plausibility: rules of engagement for the struggle to evaluate alternative cancer therapies. CMAJ 164: 351-353.
    [40] Wilson MK, Baguley BC, Wall C, et al. (2014) Review of high-dose intravenous vitamin C as an anticancer agent. Asia Pac J Clin Oncol 10: 22-37.
    [41] Itoh H, Ikeda S, Oohata Y, et al. (1988) Treatment of desmoid tumors in Gardner’s syndrome. Report of a case. Dis Colon Rectum 31: 459-461. doi: 10.1007/BF02552617
    [42] Berenson JR, Yellin O, Woytowitz D, et al. (2009) Bortezomib, ascorbic acid and melphalan (BAM) therapy for patients with newly diagnosed multiple myeloma: an effective and well-tolerated frontline regimen. Eur J Haematol 82: 433-439. doi: 10.1111/j.1600-0609.2009.01244.x
    [43] Seo MS, Kim JK, Shim JY (2015) High-dose vitamin C promotes regression of multiple pulmonary metastases originating from hepatocellular carcinoma.Yonsei Med J 56: 1449-1452.
    [44] Moertel CG, Fleming TR, Creagan ET, et al. (1985) High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy: a randomized double-blind comparison. N Engl J Med 312:137-141. doi: 10.1056/NEJM198501173120301
    [45] Goel SAS, Mandal A, Singhal K, et al. (1999) Emerging role of ascorbic acid in the management of advanced breast carcinoma as a chemosensitizer. Asian J Surg 22: 333-336.
    [46] Li X, Sun WJ (2015) The clinical activity of arsenic trioxide, ascorbic acid, ifosfamide and prednisone combination therapy I patients with relapsed and refractory multiple myeloma. Onco Targets Ther 8: 775-781.
    [47] Ma Y, Chapman J, Levine M, et al. (2014) High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med 6: 222-218.
    [48] Harris HR, Orsini N, Wolk A (2014) Vitamin C and survival among women with breast cancer: a meta-analysis. Eur J Cancer 50: 1223-1231. doi: 10.1016/j.ejca.2014.02.013
    [49] Welsh JL, Wagner BA, van't Erve TJ, et al. (2013) 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 71: 765-775. doi: 10.1007/s00280-013-2070-8
    [50] Cameron E, Campbell A (1974) The orthomolecular treatment of cancer II clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem Biol Interact 9: 285-315.
    [51] Yeom CH, Jung GC, Song KJ (2007) Changes of terminal cancer patients’ health-related quality of life after high dose vitamin C administration. J Korean Med Sci 22: 7-11.
    [52] Vollbracht C, Schneider B, Leendert V, et al. (2011) 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 25: 983-990.
    [53] Günes-Bayir A, Kiziltan HS (2015) Palliative vitamin C application in patients with radiotherapy-resistant bone metastases: a retrospective study. Nutr Cancer 67: 921-925. doi: 10.1080/01635581.2015.1055366
    [54] Carr AC, Vissers MCM, Cook JS (2014) The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life. Frontiers Oncology 4: 283.
    [55] Riordan NH, Riordan HD, Meng X, et al. (1995) Intravenous ascorbate as a tumor cytotoxic chemotherapeutic agent. Med Hypotheses 44: 207-213. doi: 10.1016/0306-9877(95)90137-X
    [56] Molassiotis A, Fernadez-Ortega P, Pud D, et al. (2005) Use of complementary and alternative medicine in cancer patients: a European survey. Ann Oncol 16: 655-663.
    [57] Padayatty SJ, Sun AY, et al. (2010) Vitamin C: Intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One 5: e11414.
    [58] Bjørklund G (2015) The Adjuvant Nutritional Intervention in Cancer (ANICA) Trial. Nutr Cancer 16:1-4.
    [59] Lawton JM, Conway LT, Crosson JT, et al. (1985) Acute oxalate nephropathy after massive ascorbic acid administration. Arch Intern Med 145: 950-951. doi: 10.1001/archinte.1985.00360050220044
    [60] McAllister CJ, Scowden EB, Dewberry FL, et al. (1984) Renal failure secondary to massive infusion of vitamin C. JAMA 252: 1684.
    [61] Rees DC, Kelsey H, Richards JD (1993) Acute haemolysis induced by high dose ascorbic acid in glucose-6- phosphate dehydrogenase deficiency. BMJ 306: 841-842.
    [62] Hoffer LJ, Levine M, Assouline S, et al. (2008) Phase I clinical trial of I.V. ascorbic acid in advanced malignancy. Ann Oncol 19: 1969-1974.
    [63] Monti DA, Mitchell E, Bazzan AJ, et al. (2012) Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One 7: e29794. doi: 10.1371/journal.pone.0029794
    [64] Nielsen TK, Højgaard M, Andersen JT, et al (2015) Elimination of ascorbic acid after high-dose infusion in prostate cancer patients: a pharmacokinetic evaluation. Basic Clin Pharmacol Toxicol 116: 343-348. doi: 10.1111/bcpt.12323
    [65] Sterne JA, Gavaghan D, Egger M (2000) Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol 53: 1119-1129. doi: 10.1016/S0895-4356(00)00242-0
  • Reader Comments
  • © 2016 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(5013) PDF downloads(1357) Cited by(2)

Article outline

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog