The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review
Abstract
:1. Introduction
2. Bioavailability of Vitamin C
3. Physiological Functions of Vitamin C
4. Anti-Carcinogenic Actions of Vitamin C
5. Vitamin C in Cancer Prevention and Therapy—Studies in Humans
5.1. Clinical Trials
5.2. Meta-Analysis and Mendelian Randomization Studies
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Lindblad, M.; Tveden-Nyborg, P.; Lykkesfeldt, J. Regulation of Vitamin C homeostasis during deficiency. Nutrients 2013, 5, 2860–2879. [Google Scholar] [CrossRef] [Green Version]
- Valdes, F. Vitamin C. Actas Dermosifiliogr. 2006, 97, 557–568. [Google Scholar] [CrossRef]
- Beal, T.; Massiot, E.; Arsenault, J.E.; Smith, M.R.; Hijmans, R.J. Global trends in dietary micronutrient supplies and estimated prevalence of inadequate intakes. PLoS ONE 2017, 12, E0175554. [Google Scholar] [CrossRef] [Green Version]
- Mosdol, A.; Erens, B.; Brunner, E.J. Estimated prevalence and predictors of vitamin C deficiency within UK’s low-income population. J. Public Health 2008, 30, 456–460. [Google Scholar] [CrossRef]
- Schleicher, R.L.; Carroll, M.D.; Ford, E.S.; Lacher, D.A. Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003-2004 National Health and Nutrition Examination Survey (NHANES). Am. J. Clin. Nutr. 2009, 90, 1252–1263. [Google Scholar] [CrossRef]
- Gillberg, L.; Ørskov, A.D.; Nasif, A.; Ohtani, H.; Madaj, Z.; Hansen, J.W.; Rapin, N.; Mogensen, J.B.; Liu, M.; Dufva, I.; et al. Vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes. Clin. Epigenetics 2019, 11, 143. [Google Scholar] [CrossRef] [Green Version]
- Levine, M.; Wang, Y.; Katz, A.; Eck, P.; Kwon, O.; Chen, S.; Lee, J.H.; Padayatty, S.J. Ideal vitamin C intake. BioFactors 2001, 15, 71–74. [Google Scholar] [CrossRef]
- Corpe, C.P.; Tu, H.; Eck, P.; Wang, J.; Faulhaber-Walter, R.; Schnermann, J.; Margolis, S.; Padayatty, S.; Sun, H.; Wang, Y.; et al. Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice. J. Clin. Investig. 2010, 120, 1069–1083. [Google Scholar] [CrossRef] [Green Version]
- Villagran, M.; Muñoz, M.; Díaz, F.; Troncoso, C.; Celis-Morales, C.; Mardones, L. Vitamin C in health and disease: A current perspective. Rev. Chil. Nutr. 2019, 46, 800–808. [Google Scholar]
- Levine, M.; Padayatty, S.J.; Espey, M.G. Vitamin C: A concentration-function approach yields pharmacology and therapeutic discoveries. Adv. Nutr. 2011, 2, 78–88. [Google Scholar] [CrossRef] [Green Version]
- Michels, A.J.; Hagen, T.M.; Frei, B. Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function. Annu. Rev. Nutr. 2013, 33, 45–70. [Google Scholar] [CrossRef] [Green Version]
- Frei, B.; England, L.; Ames, B.N. Ascorbate is an outstanding antioxidant in human blood plasma. Proc. Natl. Acad. Sci. USA 1989, 86, 6377–6381. [Google Scholar] [CrossRef] [Green Version]
- Sotiriou, S.; Gispert, S.; Cheng, J.; Wang, Y.; Chen, A.; Hoogstraten-Miller, S.; Miller, G.; Kwon, O.; Levine, M.; Gutentag, S.; et al. Ascorbic-acid transporter Slc23a1 is essential for vitamin C transporter into the brain for perinatal survival. Nat. Med. 2002, 8, 514–517. [Google Scholar] [CrossRef]
- Meister, A. Glutathione-ascorbic acid antioxidant system in animals. J. Biol. Chem. 1994, 269, 9397–9400. [Google Scholar] [CrossRef]
- Camarena, V.; Wang, G. The epigenetic role of vitamin C in health and disease. Cell Mol. Life Sci. 2016, 73, 1645–1658. [Google Scholar] [CrossRef] [Green Version]
- Chen, A.A.; Marsit, C.J.; Christensen, B.C.; Houseman, E.A.; McClean, M.D.; Smith, J.F.; Bryan, J.T.; Posner, M.R.; Nelson, H.H.; Kelsey, K.T. Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer. Carcinogenesis 2009, 30, 977–981. [Google Scholar] [CrossRef]
- Cho, M.R.; Han, J.H.; Lee, H.; Park, Y.K.; Kang, M. Purple grape juice supplementation in smokers and antioxidant status according to different types of GST polymorphisms. Clin. Biochem. Nutr. 2015, 56, 49–56. [Google Scholar] [CrossRef] [Green Version]
- Nielsen, C.W.; Rustad, T.; Holdt, S.L. Vitamin C from seaweed: A review assessing seaweed as contributor to daily intake. Foods 2021, 10, 198. [Google Scholar] [CrossRef]
- Hoffer, L.J.; Levine, M.; Assouline, S.; Melnychuk, D.; Padayatty, S.J.; Rosadiuk, K.; Rousseau, C.; Robitaille, L.; Miller, W.H., Jr. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann. Oncol. 2008, 19, 1969–1974. [Google Scholar] [CrossRef]
- Clemetson, C.A.B. Vitamin C; CRC Press: Boca Raton, FL, USA, 1989. [Google Scholar]
- Levine, M.; Wang, Y.; Padayatty, S.J.; Morrow, J. A new recommended dietary allowance of vitamin C for healthy young women. Proc. Natl. Acad. Sci. USA 2001, 98, 9842–9846. [Google Scholar] [CrossRef] [Green Version]
- Monacelli, F.; Acquarone, E.; Giannotti, C.; Borghi, R.; Nencioni, A. Vitamin C, aging and Alzheimer’s disease. Nutrients 2017, 9, 670. [Google Scholar] [CrossRef] [Green Version]
- Kim, K.P.; Shin, K.O.; Park, K.; Yun, H.J.; Mann, S.; Lee, Y.M.; Cho, Y. Vitamin C stimulates epidermal ceramide production by regulating its metabolic enzymes. Biomol. Ther. 2015, 23, 525–530. [Google Scholar] [CrossRef] [Green Version]
- Moser, M.A.; Chun, O.K. Vitamin C and heart health: A review based on findings from epidemiologic studies. Int. J. Mol. Sci. 2016, 17, 1328. [Google Scholar] [CrossRef] [Green Version]
- Ye, Y.; Li, J.; Yuan, Z.; Yuan, Z. Effect of antioxidant vitamin supplementation on cardiovascular outcomes: A meta-analysis of randomized controlled trials. PLoS ONE 2013, 8, e56803. [Google Scholar] [CrossRef] [Green Version]
- Vissers, M.C.M.; Das, A.B. Potential mechanisms of action for vitamin C in cancer: Reviewing the evidence. Front. Physiol. 2018, 9, 809. [Google Scholar] [CrossRef] [Green Version]
- Harris, H.R.; Orsini, N.; Wolk, A. Vitamin C and survival among women with breast cancer: A meta-analysis. Eur. J. Cancer 2014, 50, 1223–1231. [Google Scholar] [CrossRef]
- Pena, E.; Roa, F.J.; Inostroza, E.; Sotomayor, K.; González, M.; Gutierrez-Castro, F.A.; Maurin, M.; Sweet, K.; Labrousse, C.; Gatica, M.; et al. Increased expression of mitochondrial sodium-coupled ascorbic acid transporter-2 (mitSVCT2) as a central feature in breast cancer. Free Radic. Biol. Med. 2019, 135, 283–292. [Google Scholar] [CrossRef]
- Cimmino, L.; Neel, B.G.; Aifantis, I. Vitamin C in stem cell reprogramming and cancer. Trends Cell Biol. 2018, 28, 698–708. [Google Scholar] [CrossRef]
- Lv, H.; Wang, C.; Fang, T.; Li, T.; Lv, G.; Han, Q.; Yang, W.; Wang, H. Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2. NPJ Precis. Oncol. 2018, 2, 1. [Google Scholar] [CrossRef] [Green Version]
- Godoy, A.; Ormazabal, V.; Moraga-Cid, G.; Zuniga, F.A.; Sotomayor, P.; Barra, V.; Vasquez, O.; Montecinos, V.; Mardones, L.; Gúzman, C.; et al. Mechanistic insights and functional determinants of the transport. J. Biol. Chem. 2007, 282, 615–624. [Google Scholar] [CrossRef] [Green Version]
- Cho, S.; Chae, J.S.; Shin, H.; Shin, Y.; Kim, Y.; Kil, E.; Byun, H.; Cho, S.; Park, S.; Lee, S.; et al. Enhanced anticancer effect of adding magnesium to vitamin C therapy: Inhibition of hermetic response by SVCT-2 Activation. Transl. Oncol. 2020, 13, 401–409. [Google Scholar] [CrossRef]
- Subramani, T.; Yeap, S.K.; Ho, W.Y.; Ho, C.L.; Omar, A.R.; Aziz, S.A.; Rahman, N.M.A.N.A.; Alitheen, N.B. Vitamin C suppress cell death in MCF-7 human breast cells induced by tamoxifen. J. Cell Mol. Med. 2014, 18, 305–313. [Google Scholar] [CrossRef]
- Schoenfeld, J.D.; Sibenaller, Z.A.; Kapusker, K.A.; Ho, C.L.; Omar, A.R.; Aziz, S.A.; Rahman, N.M.; Alitheen, N.B. O2− and H2O2− mediated disruption of Fe metabolism causes the differential susceptibility of NSCLC and GBM cancer cells to pharmacological ascorbate. Cancer Cell 2017, 31, 487–500. [Google Scholar] [CrossRef] [Green Version]
- Gonzalez, M.J.; Massari, M., Jr.; Duconge, J.; Riordan, N.H.; Ichim, T. Schedule dependence in cancer therapy: Intravenous Vitamin C and the systemic saturation hypothesis. J. Orthomol. Med. 2012, 27, 9–12. [Google Scholar]
- Du, J.; Martin, S.M.; Levine, M.; Wagner, B.; Buettner, G.R.; Wang, S.; Taghiyev, A.T.; Du, C.; Knudston, C.M.; Cullen, J.J. Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer. Clin. Cancer Res. 2010, 16, 509–520. [Google Scholar] [CrossRef] [Green Version]
- Fiorillo, M.; Tóth, F.; Sotgia, F.; Lisanti, M.P. Doxycycline, Azithromycin and Vitamin C (DAV): A potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs). Aging 2019, 11, 2202–2216. [Google Scholar] [CrossRef]
- Yun, J.; Mullarky, E.; Lu, C.; Bosch, K.N.; Kavalier, A.; Rivera, K.; Roper, J.; Chio, I.I.C.; Giannopoulou, E.; Rago, C.; et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 2015, 350, 1391–1396. [Google Scholar] [CrossRef] [Green Version]
- Mandl, J.; Szarka, A.; Bánhegyi, B. Vitamin C: Update on physiology and pharmacology. Br. J. Pharmacol. 2009, 157, 1097–1110. [Google Scholar] [CrossRef] [Green Version]
- Liu, M.; Ohtani, H.; Zho, W.; Ørskov, A.D.; Charlet, J.; Zhang, Y.W.; Shen, H.; Baylin, S.B.; Liang, G.; Grønbæk, K.; et al. Vitamin C increases viral mimicry induced by 5-aza-2′-deoxycytidine. Proc. Natl. Acad. Sci. USA 2016, 113, 10238–10244. [Google Scholar] [CrossRef] [Green Version]
- Pfeifer, G.P.; Kadam, S.; Jin, S.G. 5-hydroxymethylcytosine and its potential roles in development and cancer. Epigenetics Chromatin 2013, 6, 10. [Google Scholar] [CrossRef] [Green Version]
- Gilbert, M.R.; Wang, M.; Aldape, K.D.; Ohtani, H.; Madaj, Z.; Hansen, J.W.; Rapin, N.; Mogensen, J.B.; Liu, M.; Dufva, I.; et al. Dose-dense temozolomide for newly diagnosed glioblastoma: Randomized phase III clinical trial. J. Clin. Oncol. 2013, 31, 4085–4091. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- 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, 285–315. [Google Scholar] [CrossRef]
- 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 1974, 73, 3685–3689. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cameron, E.; Pauling, L. Experimental studies designed to evaluate the management of patients with incurable cancer. Proc. Natl. Acad. Sci. USA 1978, 75, 6252. [Google Scholar] [CrossRef] [Green Version]
- Creagan, E.T.; Fountain, K.S. Symmetrical mental neuropathy in breast cancer. Cancer Treat. Rep. 1978, 62, 178. [Google Scholar]
- Shenoy, N.; Creagan, E.; Witzig, T.; Levine, M. Ascorbic acid in cancer treatment: Let the phoenix fly. Cancer Cell 2018, 34, 700–706. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hercberg, S.; Galan, P.; Preziosi, P.; Bertrais, S.; Mennen, L.; Malvy, D.; Roussel, A.; Favier, A.; Briançon, S. The SU.VI.MAX Study: A randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch. Intern. Med. 2004, 164, 2335–2342. [Google Scholar] [CrossRef] [Green Version]
- Gaziano, J.M.; Glynn, R.J.; Christen, W.G.; Kurth, T.; Belanger, C.; MacFadyen, J.; Bubes, V.; Manson, J.E.; Sesso, H.D.; Buring, J.E. Vitamins E and C in the prevention of prostate and total cancer in men: The Physicians’ Health Study II randomized controlled trial. JAMA 2009, 301, 52–62. [Google Scholar] [CrossRef] [Green Version]
- Wang, L.; Sesso, H.D.; Glynn, R.J.; Christen, W.G.; Christen, W.G.; Bubes, V.; Manson, J.E.; Buring, J.E.; Gaziano, J.M. Vitamin E and C supplementation and risk of cancer in men: Posttrial follow-up in the Physicians’ Health Study II randomized trial. Am. J. Clin. Nutr. 2014, 100, 915–923. [Google Scholar] [CrossRef] [Green Version]
- Gaziano, J.M.; Sesso, H.D.; Christen, G.; Bubes, V.; Smith, J.P.; MacFadyen, J.; Schvartz, M.; Manson, J.E.; Glynn, R.J.; Buring, J.E. Multivitamins in the prevention of cancer in men: The Physicians’ Health Study II randomized controlled trial. JAMA 2012, 308, 1871–1880. [Google Scholar] [CrossRef]
- Nielsen, T.K.; Højgaard, M.; Andersen, J.T.; Jørgensen, N.R.; Zerahn, B.; Kristensen, B.; Henriksen, T.; Lykkesfeldt, J.; Mikines, K.J.; Puolsen, H.E. Weekly ascorbic acid infusion in castration-resistant prostate cancer patients: A single-arm phase II trial. Transl. Androl. Urol. 2017, 6, 517–528. [Google Scholar] [CrossRef] [Green Version]
- Nielsen, T.K.; Højgaard, M.; Andersen, J.T.; Pulsen, H.E.; Lykkesfeldt, J.; Mikines, K.; Poulsen, H.E.; Lykkesfeldt, J.; Mikines, K.J. Elimination of ascorbic acid after high-dose infusion in prostate cancer patients: A pharmacokinetic evaluation. Basic Clin. Pharmacol. Toxicol. 2015, 116, 343–348. [Google Scholar] [CrossRef] [PubMed]
- Hoffer, L.J.; Robitaille, L.; Zakarian, R.; Melnychuk, D.; Kavan, P.; Agulnik, J.; Cohen, V.; Small, D.; Miller, W.H. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: A phase I-II clinical trial. PLoS ONE 2015, 10, e0120228. [Google Scholar] [CrossRef]
- Bahlis, N.J.; McCafferty-Grad, J.; Jordan-McMurry, I.; Neil, J.; Reis, I.; Kharfan-Dabaja, M.; Eckman, J.; Goodman, M.; Fernandez, H.F.; Boise, L.H. Feasibility and correlates of arsenic trioxide combined with ascorbic acid-mediated depletion of intracellular glutathione for the treatment of relapsed/refractory multiple myeloma. Clin. Cancer Res. 2002, 8, 3658–3668. [Google Scholar] [PubMed]
- Welsh, J.L.; Wagner, B.A.; van’t Erve, T.J.; Zehr, P.S.; Berg, D.J.; Halfdanarson, T.R.; Yee, N.S.; Bodeker, K.L.; Du, J.; Roberts, L.J., 2nd; 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, 765–775. [Google Scholar] [CrossRef] [Green Version]
- Polireddy, K.; Dong, R.; Reed, G.; Yu, J.; Chen, P.; Williamson, S.; Violet, P.; Pessetto, Z.; Godwin, A.K.; Fan, F.; et al. High dose parenteral ascorbate inhibited pancreatic cancer growth and metastasis: Mechanisms and a phase I/IIa study. Sci. Rep. 2017, 7, 17188. [Google Scholar] [CrossRef] [Green Version]
- Monti, D.A.; Mitchell, E.; Bazzan, A.J.; Littman, S.; Zabrecky, G.; Yeo, C.J.; Pillai, M.V.; Newberg, A.B.; Deshmukh, S.; Levine, M. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS ONE 2012, 7, e29794. [Google Scholar] [CrossRef]
- Grad, J.M.; Bahlis, N.J.; Reis, I.; Oshiro, M.M.; Dalton, W.S.; Boise, L.H. Ascorbic acid enhances arsenic trioxide-induced cytotoxicity in multiple myeloma cells. Blood 2001, 98, 805–813. [Google Scholar] [CrossRef] [Green Version]
- Freitas, B.d.J.; Lloret, G.R.; Visacri, M.V.; Tuan, B.T.; Amaral, L.S.; Baldini, D.; de Sousa, V.M.; de Castro, L.L.; Aguiar, J.R.S.; Pincinato, E.; et al. High 15-F2t-isoprostane levels in patients with a previous history of melanoma skin cancer: The effects of supplementary antioxidant therapy. Biomed. Res. Int. 2015, 2015, 963569. [Google Scholar] [CrossRef] [Green Version]
- Munoz-Montesino, C.; Roa, F.J.; Pena, E.; Gonzalez, M.; Sotomayor, K.; Inostroza, E.; Munoz, C.A.; Gonzalez, I.; Maldonado, M.; Soliz, C.; et al. Mitochondrial ascorbic acid transport is mediated by a low-affinity form of the sodium-coupled ascorbic acid transporter-2. Free Radic. Biol. Med. 2014, 70, 241–254. [Google Scholar] [CrossRef]
- Huijskens, M.J.; Walczak, M.; Sarkar, S.; Atrafi, F.; Senden-Gijsbers, B.L.; Tilanus, M.G.; Bos, G.M.; Wieten, L.; Germeraad, W.T.V. Ascorbic acid promotes proliferation of natural killer cell populations in culture systems applicable for natural killer cell therapy. Cytotherapy 2015, 17, 613–620. [Google Scholar] [CrossRef] [PubMed]
- Lee, B.; Oh, S.W.; Myung, S.K. Efficacy of Vitamin C supplements in prevention of cancer: A meta-analysis of randomized controlled trials. Korean J. Fam. Med. 2015, 36, 278–285. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aune, D.; Keum, N.; Giovannucci, E.; Fadnes, L.T.; Boffetta, P.; Greenwood, D.C.; Tonstad, S.; Vatten, L.J.; Riboli, E.; Norat, T. Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: A systematic review and dose-response meta-analysis of prospective studies. Am. J. Clin. Nutr. 2018, 108, 1069–1091. [Google Scholar] [CrossRef] [PubMed]
- van Gorkom, G.N.Y.; Lookermans, E.L.; Van Elssen, C.H.M.J.; Bos, G.M.J. The Effect of Vitamin C (Ascorbic Acid) in the treatment of patients with cancer: A Systematic Review. Nutrients 2019, 11, 977. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stratton, J.; Godwin, M. The effect of supplemental vitamins and minerals on the development of prostate cancer: A systematic review and meta-analysis. Fam. Pract. 2011, 28, 243–252. [Google Scholar] [CrossRef] [Green Version]
- Jiang, L.; Yang, K.H.; Tian, J.H.; Guan, Q.L.; Yao, N.; Cao, N.; Mi, D.H.; Wu, J.; Ma, B.; Yang, S.H. Efficacy of antioxidant vitamins and selenium supplement in prostate cancer prevention: A meta-analysis of randomized controlled trials. Nutr. Cancer 2010, 62, 719–727. [Google Scholar] [CrossRef]
- Bai, X.; Qu, X.; Jiang, X.; Xu, Z.; Yang, Y.; Su, Q.; Wang, M.; Wu, H. Association between dietary vitamin v Intake and risk of Prostate cancer: A meta-analysis involving 103,658 Subjects. J. Cancer 2015, 6, 913–921. [Google Scholar] [CrossRef]
- Cho, E.; Hunter, D.J.; Spiegelman, D.; Albanes, D.; Beeson, W.L.; van den Brandt, P.A.; Colditz, G.A.; Feskanich, D.; Folsom, A.R.; Fraser, G.E.; et al. Intakes of vitamins A, C and E and folate and multivitamins and lung cancer: A pooled analysis of 8 prospective studies. Int. J. Cancer 2006, 118, 970–978. [Google Scholar] [CrossRef] [Green Version]
- Luo, J.; Shen, L.; Zheng, D. Association between vitamin C intake and lung cancer: A dose-response meta-analysis. Sci. Rep. 2014, 4, 6161. [Google Scholar] [CrossRef]
- Gandini, S.; Merzenich, H.; Robertson, C.; Boyle, P. Meta-analysis of studies on breast cancer risk and diet: The role of fruit and vegetable consumption and the intake of associated micronutrients. Eur. J. Cancer 2000, 36, 636–646. [Google Scholar] [CrossRef]
- Hu, F.; Jiang, C.; Wang, Y.B.; Zhang, W.; Lin, C.; Wang, F.; Li, D.; Sun, D.; Wang, T.; Pang, D.; et al. Retinol, vitamins A, C, and E and breast cancer risk: A meta-analysis and meta-regression. Cancer Causes Control 2011, 22, 1383–1396. [Google Scholar] [CrossRef]
- Hu, F.; Wu, Z.; Li, G.; Teng, C.; Liu, Y.; Wag, F.; Zhao, Y.; Pang, D. The plasma level of retinol, vitamins A, C and α-tocopherol could reduce breast cancer risk? A meta-analysis and meta-regression. J. Cancer Res Clin. Oncol. 2015, 141, 601–614. [Google Scholar] [CrossRef] [PubMed]
- Zhang, D.; Xu, P.; Li, Y.; Wei, B.; Yang, S.; Zheng, Y.; Lyu, L.; Deng, Y.; Zhai, Z.; Li, N. Association of vitamin C intake with breast cancer risk and mortality: A meta-analysis of observational studies. Aging 2020, 12, 18415–18435. [Google Scholar] [CrossRef] [PubMed]
- Fu, Y.; Xu, F.; Jiang, L.; Miao, Z.; Liang, X.; Yang, J.; Larsson, S.C.; Zheng, J.S. Circulating vitamin C concentration and risk of cancers: A Mendelian randomization study. BMC Med. 2021, 19, 171. [Google Scholar] [CrossRef]
Code | N° Subjects | Cancer Type | Finding | Ref. |
---|---|---|---|---|
NCT0272428 | 12,741 | all | ↓incidence in men (7,5 yr.) | Hercber et al. [48] |
NCT00270647 | 14,641 | all | ↓re-incidence in men (11 yr.) | Gaziano et al. [49] |
Eudra-CT2019-004074-25/ NCT01080352 | 20 | prostate | Media-severe side effects | Nielsen et al. [52] |
NCT0105062 | 14 | all | ↓symptoms/progression (43%) | Hoffer et al. [54] |
NCT00006021 | 22 | myeloma | ↓progression (50%) | Bahlis et al. [55] |
NCT01515046/ NCT01049880 | 9 | pancreas | ↑survival (12 mo.) | Welsh et al. [56] |
NCT01364805 | 14 | pancreas | ↓metastasis and cell proliferation | Polireddy et al. [57] |
NCT00954525 | 14 | pancreas | ↓tumor size | Monti et al. [58] |
N° Subjects | Cancer Type | Finding | Ref. |
---|---|---|---|
62,619 | all | No effect in incidence | Lee et al. [63] |
32,631 | all | ↓incidence | Aune et al. [64] |
5074 | all | No effect in incidence | Van Gorkom et al. [65] |
265,932 | prostate | No effect in incidence | Stratton et al. [66] |
165,056 | prostate | No effect in incidence | Jiang et al. [67] |
103,658 | prostate | ↓incidence | Bai et al. [68] |
430,281 | lung | No effect in incidence | Cho et al. [69] |
8938 | lung | ↓incidence | Lou et al. [70] |
278,847 475,234 | breast breast | ↓incidence No effect in incidence | Gandini et al. [71] Fulan et al. [72] |
908 | breast | ↓incidence | Hu et al. [73] |
17,296 17,067 | breast breast | ↓mortality No effect in mortality | Harris et al. [27] Zhang et al. [74] |
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Villagran, M.; Ferreira, J.; Martorell, M.; Mardones, L. The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review. Antioxidants 2021, 10, 1894. https://doi.org/10.3390/antiox10121894
Villagran M, Ferreira J, Martorell M, Mardones L. The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review. Antioxidants. 2021; 10(12):1894. https://doi.org/10.3390/antiox10121894
Chicago/Turabian StyleVillagran, Marcelo, Jorge Ferreira, Miquel Martorell, and Lorena Mardones. 2021. "The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review" Antioxidants 10, no. 12: 1894. https://doi.org/10.3390/antiox10121894