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Effect of Vitamin C on Cancer Process

Year 2024, , 253 - 262, 01.09.2024
https://doi.org/10.52794/hujpharm.1484625

Abstract

The diverse roles of vitamin C in combatting cancer through its antioxidative and pro-oxidative properties, as well as its immune-boosting functions, are significant. Vitamin C acts as a cofactor for oxygenase enzymes containing iron or copper, aiding in two key processes: firstly, the stimulation of reactive oxygen species production, which selectively targets cancer cells, and secondly, the regulation of cellular metabolism and epigenetic processes involving DNA and histone demethylases, thereby diminishing tumorigenesis. Although various studies highlight the potential effectiveness of vitamin C against different cancer types in laboratory and animal studies, both as a standalone treatment and in combination with traditional chemotherapy and radiation, its role in clinical or non-clinical human studies remains unclear and contentious. Recent papers of randomized clinical trials or observational studies have not yielded conclusive evidence supporting vitamin C’s clinical efficacy in cancer treatment or prevention. In this review, vitamin C usage and its efficacy in cancer therapy approaches have been focused and discussed. In conclusion, it may be speculated that these complexities highlight the need for larger, high-quality randomized clinical trials to provide more definitive understanding of vitamin C’s anticancer potential and to establish appropriate clinical recommendations.

Ethical Statement

Not necessary.

Supporting Institution

None

Project Number

None

Thanks

None

References

  • 1. Iqbal, K., Khan, A., & Khattak, M., M., A., K. (2003). Biological Significance of Ascorbic Acid (Vitamin C) in Human Health - A Review. Pak J Nutr. 3(1), 5–13. https://doi. org/10.3923/PJN.2004.5.13
  • 2. Carr, A. C., & Lykkesfeldt, J. (2021). Discrepancies in global vitamin C recommendations: a review of RDA criteria and underlying health perspectives. Crit Rev Food Sci Nutr. 61(5), 742–755. https://doi.org/10.1080/10408398.2020.1744513
  • 3. Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R. W., Washko, P. W., Dhariwal, K. R., Park, J. B., Lazarev, A., Graumlich, J. F., King, J., & Cantilena, L. R. (1996). Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci. 93(8), 3704– 3709. https://doi.org/10.1073/PNAS.93.8.3704
  • 4. Du, J., Cullen, J. J., & Buettner, G. R. (2012). Ascorbic acid: Chemistry, biology and the treatment of cancer. Biochim Biophys Acta Rev Cancer. 1826(2), 443–457. https://doi. org/10.1016/J.BBCAN.2012.06.003
  • 5. Hulse, J. D., Ellis, S. R., & Henderson, L. M. (1978). Carnitine biosynthesis. beta-Hydroxylation of trimethyllysine by an alpha- ketoglutarate-dependent mitochondrial dioxygenase. J Biol Chem. 253(5), 1654–1659. https://doi.org/10.1016/S0021- 9258(17)34915-3
  • 6. Vissers, M. C. M., Kuiper, C., & Dachs, G. U. (2014). Regulation of the 2-oxoglutarate-dependent dioxygenases and implications for cancer. Biochem Soc Trans. 42(4), 945–951. https://doi.org/10.1042/BST20140118
  • 7. Kontoghiorghes, G. J., Kolnagou, A., Kontoghiorghe, C. N., Mourouzidis, L., Timoshnikov, V. A., & Polyakov, N. E. (2020). Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications. Medicines. 2020, Vol. 7, Page 45, 7(8), 45. https://doi. org/10.3390/MEDICINES7080045
  • 8. Teucher, B., Olivares, M., & Cori, H. (2004). Enhancers of Iron Absorption: Ascorbic Acid and other Organic Acids. Int J Vitam Nutr Res. 74(6), 403–419. https://doi.org/10.1024/0300- 9831.74.6.403
  • 9. Mayland, C. R., Bennett, M. I., & Allan, K. (2005). Vitamin C deficiency in cancer patients. Palliat Med. 19(1), 17–20. https://doi.org/10.1191/0269216305PM970OA
  • 10. Huijskens, M. J. A. J., Wodzig, W. K. W. H., Walczak, M., Germeraad, W. T. V., & Bos, G. M. J. (2016). Ascorbic acid serum levels are reduced in patients with hematological malignancies. Results Immunol. 6, 8–10. https://doi.org/10.1016/J. RINIM.2016.01.001
  • 11. Chambial, S., Dwivedi, S., Shukla, K. K., John, P. J., & Sharma, P. (2013). Vitamin C in disease prevention and cure: An overview. Indian J Clin Biochem. 28(4), 314–328. https://doi. org/10.1007/S12291-013-0375-3
  • 12. Ströhle, A., Wolters, M., & Hahn, A. (2011). Micronutrients at the interface between inflammation and infection - ascorbic acid and calciferol. part 1: General overview with a focus on ascorbic acid. Inflamm Allergy Drug Targets. 10(1), 54–63. https://doi.org/10.2174/187152811794352105
  • 13. Ang, A., Pullar, J. M., Currie, M. J., & Vissers, M. C. M. (2018). Vitamin C and immune cell function in inflammation and cancer. Biochem Soc Trans. 46(5), 1147–1159. https://doi. org/10.1042/BST20180169
  • 14. Agathocleous, M., Meacham, C. E., Burgess, R. J., Piskounova, E., Zhao, Z., Crane, G. M., Cowin, B. L., Bruner, E., Murphy, M. M., Chen, W., Spangrude, G. J., Hu, Z., DeBerardinis, R. J., & Morrison, S. J. (2017). Ascorbate regulates haematopoietic stem cell function and leukaemogenesis. Nature 2017 549:7673, 549 (7673), 476–481. https://doi.org/10.1038/ nature23876
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  • 16. Mastrangelo, D., Pelosi, E., Castelli, G., Lo-Coco, F., & Testa, U. (2018a). Mechanisms of anti-cancer effects of ascorbate: Cytotoxic activity and epigenetic modulation. Blood Cells Mol Dis. 69, 57–64. https://doi.org/10.1016/J.BCMD.2017.09.005
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  • 35. Pavlovic, V., Ciric, M., Petkovic, M., & Golubovic, M. (2023). Vitamin C and epigenetics: A short physiological overview. Open Med. 18(1). https://doi.org/10.1515/MED-2023-0688
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  • 38. Xu, K., Peng, R., Zou, Y., Jiang, X., Sun, Q., & Song, C. (2022). Vitamin C intake and multiple health outcomes: an umbrella review of systematic reviews and meta-analyses. Int J Food Sci Nutr. 73(5), 588–599. https://doi.org/10.1080/0963 7486.2022.2048359
  • 39. Chen, Z., Huang, Y., Cao, D., Qiu, S., Chen, B., Li, J., Bao, Y., Wei, Q., Han, P., & Liu, L. (2022). Vitamin C Intake and Cancers: An Umbrella Review. Front Nutr. 8, 812394. https:// doi.org/10.3389/FNUT.2021.812394
  • 40. Fu, Y., Xu, F., Jiang, L., Miao, Z., Liang, X., Yang, J., Larsson, S. C., & Zheng, J. S. (2021). Circulating vitamin C concentration and risk of cancers: a Mendelian randomization study. BMC Med. 19(1), 1–14. https://doi.org/10.1186/S12916-021- 02041-1/FIGURES/5
  • 41. Yin, L., Yan, H., Chen, K., Ji, Z., Zhang, X., Ji, G., & Zhang, B. (2022). Diet-Derived Circulating Antioxidants and Risk of Digestive System Tumors: A Mendelian Randomization Study. Nutrients. 14(16), 3274. https://doi.org/10.3390/ NU14163274/S1
  • 42. Zhao, H., & Jin, X. (2022). Causal associations between dietary antioxidant vitamin intake and lung cancer: A Mendelian randomization study. Front Nutr. 9, 965911. https://doi. org/10.3389/FNUT.2022.965911
  • 43. Larsson, S. C., Mason, A. M., Vithayathil, M., Carter, P., Kar, S., Zheng, J. S., & Burgess, S. (2022). Circulating vitamin C and digestive system cancers: Mendelian randomization study. Clin Nutr. 41(9), 2031–2035. https://doi.org/10.1016/J. CLNU.2022.07.040
  • 44. Abdel-Latif, M., Babar, M., Kelleher, D., & Reynolds, J. (2019). A pilot study of the impact of Vitamin C supplementation with neoadjuvant chemoradiation on regulators of inflammation and carcinogenesis in esophageal cancer patients. J Cancer Res Cell Ther. 15(1), 185–191. https://doi.org/10.4103/ JCRT.JCRT_763_16
  • 45. Furqan, M., Abu-Hejleh, T., Stephens, L. M., Hartwig, S. M., Mott, S. L., Pulliam, C. F., Petronek, M., Henrich, J. B., Fath, M. A., Houtman, J. C., Varga, S. M., Bodeker, K. L., Bossler, A. D., Bellizzi, A. M., Zhang, J., Monga, V., Mani, H., Ivanovic, M., Smith, B. J., Allen, B. G. (2022). Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer. Redox Biol. 53, 102318. https://doi.org/10.1016/J.REDOX.2022.102318
  • 46. Hoppe, C., Freuding, M., Büntzel, J., Münstedt, K., & Hübner, J. (2021). Clinical efficacy and safety of oral and intravenous vitamin C use in patients with malignant diseases. J Cancer Res Clin Oncol. 147(10), 3025–3042. https://doi.org/10.1007/ S00432-021-03759-4/FIGURES/2
  • 47. 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(4), 285–315. https://doi.org/10.1016/0009-2797(74)90019- 2
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  • 49. 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 U S A. 73(10), 3685–3689. https://doi.org/10.1073/PNAS.73.10.3685
  • 50. Carr, A. C. (2019). Vitamin C administration in the critically ill: A summary of recent meta-analyses. Crit Care. 23(1), 1–3. https://doi.org/10.1186/S13054-019-2538-Y/TABLES/1
  • 51. Levine, M., Padayatty, S. J., & Espey, M. G. (2011). Vitamin C: A Concentration-Function Approach Yields Pharmacology and Therapeutic Discoveries. Adv Nutr. 2(2), 78–88. https:// doi.org/10.3945/AN.110.000109
  • 52. Rasmussen, K. D., & Helin, K. (2016). Role of TET enzymes in DNA methylation, development, and cancer. Genes Dev. 30(7), 733–750. https://doi.org/10.1101/GAD.276568.115
  • 53. van Gorkom, G. N. Y., Lookermans, E. L., Van Elssen, C. H. M. J., & Bos, G. M. J. (2019). The Effect of Vitamin C (Ascorbic Acid) in the Treatment of Patients with Cancer: A Systematic Review. Nutrients. 2019, Vol. 11, Page 977, 11(5), 977. https://doi.org/10.3390/NU11050977
  • 54. Wang, F., He, M. M., Xiao, J., Zhang, Y. Q., Yuan, X. L., Fang, W. J., Zhang, Y., Wang, W., Hu, X. H., Ma, Z. G., Yao, Y. C., Zhuang, Z. X., Zhou, F. X., Ying, J. E., Yuan, Y., Zou, Q. F., Guo, Z. Q., Wu, X. Y., Jin, Y., Xu, R. H. (2022). A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study). Clin Cancer Res.28(19), 4232–4239. https://doi.org/10.1158/1078-0432.CCR-22- 0655/707466/AM/A-RANDOMIZED-OPEN-LABELMULTICENTER- PHASE-3-STUDY
  • 55. van Gorkom, G. N. Y., Boerenkamp, L. S., Gijsbers, B. L. M. G., van Ojik, H. H., Wodzig, W. K. W. H., Wieten, L., Van Elssen, C. H. M. J., & Bos, G. M. J. (2022). No Effect of Vitamin C Administration on Neutrophil Recovery in Autologous Stem Cell Transplantation for Myeloma or Lymphoma: A Blinded, Randomized Placebo-Controlled Trial. Nutrients. 2022, Vol. 14, Page 4784, 14(22), 4784. https://doi.org/10.3390/ NU14224784
  • 56. Park, J. Y., Baek, J. W., Yu, J., Kim, C. S., Bae, J., & Kim, Y. K. (2023). Vitamin C and catheter-related bladder discomfort after transurethral resection of bladder tumor: A doubleblind, randomized, placebo-controlled study. J Clin Anesth. 89, 111191. https://doi.org/10.1016/J.JCLINANE.2023.111191
  • 57. Gillberg, L., Ørskov, A. D., Nasif, A., Ohtani, H., Madaj, Z., Hansen, J. W., Rapin, N., Mogensen, J. B., Liu, M., Dufva, I. H., Lykkesfeldt, J., Hajkova, P., Jones, P. A., & Grønbæk, K. (2019). Oral vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes. Clin Epigenetics. 11(1), 1–11. https://doi.org/10.1186/S13148-019-0739-5/ FIGURES/4

Kanser sürecinde vitamin C'nin etkisi

Year 2024, , 253 - 262, 01.09.2024
https://doi.org/10.52794/hujpharm.1484625

Abstract

The diverse roles of vitamin C in combatting cancer through its antioxidative and pro-oxidative properties, as well as its immune-boosting functions, are significant. Vitamin C acts as a cofactor for oxygenase enzymes containing iron or copper, aiding in two key processes: firstly, the stimulation of reactive oxygen species production, which selectively targets cancer cells, and secondly, the regulation of cellular metabolism and epigenetic processes involving DNA and histone demethylases, thereby diminishing tumorigenesis. Although various studies highlight the potential effectiveness of vitamin C against different cancer types in laboratory and animal studies, both as a standalone treatment and in combination with traditional chemotherapy and radiation, its role in clinical or non-clinical human studies remains unclear and contentious. Recent papers of randomized clinical trials or observational studies have not yielded conclusive evidence supporting vitamin C's clinical efficacy in cancer treatment or prevention. In this review, vitamin C usage in cancer therapy and its efficacy in cancer therapy approaches have been focused and discussed. In conclusion, it may be speculated that these complexities highlight the need for larger, high-quality randomized clinical trials to provide more definitive understanding of vitamin C's anticancer potential and to establish appropriate clinical recommendations.

Ethical Statement

Gerekli değil.

Supporting Institution

None.

Project Number

None

Thanks

None.

References

  • 1. Iqbal, K., Khan, A., & Khattak, M., M., A., K. (2003). Biological Significance of Ascorbic Acid (Vitamin C) in Human Health - A Review. Pak J Nutr. 3(1), 5–13. https://doi. org/10.3923/PJN.2004.5.13
  • 2. Carr, A. C., & Lykkesfeldt, J. (2021). Discrepancies in global vitamin C recommendations: a review of RDA criteria and underlying health perspectives. Crit Rev Food Sci Nutr. 61(5), 742–755. https://doi.org/10.1080/10408398.2020.1744513
  • 3. Levine, M., Conry-Cantilena, C., Wang, Y., Welch, R. W., Washko, P. W., Dhariwal, K. R., Park, J. B., Lazarev, A., Graumlich, J. F., King, J., & Cantilena, L. R. (1996). Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci. 93(8), 3704– 3709. https://doi.org/10.1073/PNAS.93.8.3704
  • 4. Du, J., Cullen, J. J., & Buettner, G. R. (2012). Ascorbic acid: Chemistry, biology and the treatment of cancer. Biochim Biophys Acta Rev Cancer. 1826(2), 443–457. https://doi. org/10.1016/J.BBCAN.2012.06.003
  • 5. Hulse, J. D., Ellis, S. R., & Henderson, L. M. (1978). Carnitine biosynthesis. beta-Hydroxylation of trimethyllysine by an alpha- ketoglutarate-dependent mitochondrial dioxygenase. J Biol Chem. 253(5), 1654–1659. https://doi.org/10.1016/S0021- 9258(17)34915-3
  • 6. Vissers, M. C. M., Kuiper, C., & Dachs, G. U. (2014). Regulation of the 2-oxoglutarate-dependent dioxygenases and implications for cancer. Biochem Soc Trans. 42(4), 945–951. https://doi.org/10.1042/BST20140118
  • 7. Kontoghiorghes, G. J., Kolnagou, A., Kontoghiorghe, C. N., Mourouzidis, L., Timoshnikov, V. A., & Polyakov, N. E. (2020). Trying to Solve the Puzzle of the Interaction of Ascorbic Acid and Iron: Redox, Chelation and Therapeutic Implications. Medicines. 2020, Vol. 7, Page 45, 7(8), 45. https://doi. org/10.3390/MEDICINES7080045
  • 8. Teucher, B., Olivares, M., & Cori, H. (2004). Enhancers of Iron Absorption: Ascorbic Acid and other Organic Acids. Int J Vitam Nutr Res. 74(6), 403–419. https://doi.org/10.1024/0300- 9831.74.6.403
  • 9. Mayland, C. R., Bennett, M. I., & Allan, K. (2005). Vitamin C deficiency in cancer patients. Palliat Med. 19(1), 17–20. https://doi.org/10.1191/0269216305PM970OA
  • 10. Huijskens, M. J. A. J., Wodzig, W. K. W. H., Walczak, M., Germeraad, W. T. V., & Bos, G. M. J. (2016). Ascorbic acid serum levels are reduced in patients with hematological malignancies. Results Immunol. 6, 8–10. https://doi.org/10.1016/J. RINIM.2016.01.001
  • 11. Chambial, S., Dwivedi, S., Shukla, K. K., John, P. J., & Sharma, P. (2013). Vitamin C in disease prevention and cure: An overview. Indian J Clin Biochem. 28(4), 314–328. https://doi. org/10.1007/S12291-013-0375-3
  • 12. Ströhle, A., Wolters, M., & Hahn, A. (2011). Micronutrients at the interface between inflammation and infection - ascorbic acid and calciferol. part 1: General overview with a focus on ascorbic acid. Inflamm Allergy Drug Targets. 10(1), 54–63. https://doi.org/10.2174/187152811794352105
  • 13. Ang, A., Pullar, J. M., Currie, M. J., & Vissers, M. C. M. (2018). Vitamin C and immune cell function in inflammation and cancer. Biochem Soc Trans. 46(5), 1147–1159. https://doi. org/10.1042/BST20180169
  • 14. Agathocleous, M., Meacham, C. E., Burgess, R. J., Piskounova, E., Zhao, Z., Crane, G. M., Cowin, B. L., Bruner, E., Murphy, M. M., Chen, W., Spangrude, G. J., Hu, Z., DeBerardinis, R. J., & Morrison, S. J. (2017). Ascorbate regulates haematopoietic stem cell function and leukaemogenesis. Nature 2017 549:7673, 549 (7673), 476–481. https://doi.org/10.1038/ nature23876
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There are 57 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Toxicology, Clinical Pharmacy and Pharmacy Practice, Clinical Pharmacology and Therapeutics
Journal Section Review Articles
Authors

Omnia Abdo Mahmoud Hemdan 0009-0004-4064-2478

Gözde Girgin 0000-0002-7051-0490

Terken Baydar 0000-0002-5497-9600

Project Number None
Publication Date September 1, 2024
Submission Date May 15, 2024
Acceptance Date August 13, 2024
Published in Issue Year 2024

Cite

Vancouver Abdo Mahmoud Hemdan O, Girgin G, Baydar T. Effect of Vitamin C on Cancer Process. HUJPHARM. 2024;44(3):253-62.