大剂量维生素C在肿瘤患者应用的安全性观察
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摘要
目的观察大剂量维生素C静脉滴注治疗晚期恶性肿瘤的安全性,为临床合理用药提供参考。方法收集航空总医院2016年4月至2017年6月应用大剂量维生素C治疗晚期恶性肿瘤的患者共计21例,分别记录这21例肿瘤患者在应用大剂量维生素C治疗前、治疗后可能存在的恶心、食欲下降、腹胀、腹泻、腹痛、头晕等症状,以及前后两组的血糖、电解质(血Na~+、K~+及Cl~-)和肝肾功能(谷丙转氨酶、谷草转氨酶、总胆红素、尿素、肌酐和尿酸)等参数,然后以配对检验方法比较这些患者在大剂量维生素C治疗后上述临床症状和血液生物化学参数有无明确的统计学差异。结果在应用大剂量维生素C静脉滴注治疗恶性肿瘤的过程中,患者血糖、电解质以及肝肾功能等未见明显变化,1例患者诉食欲下降,1例患者诉恶心、腹胀加重,1例患者出现下肢水肿,但是再次使用维生素C时未见类似症状及表现,未见腹泻、腹痛、头晕等症状。结论应用大剂量维生素C治疗晚期恶性肿瘤患者尚未发现明确的不良反应,安全性良好。
Objective To observe the safety of high-dose vitamin C intravenous infusion in the treatment of advanced malignant tumors, and to provide reference for clinical rational use of vitamin C. Methods from April 2016 to June 2017, 21 patients with advanced malignant tumor were treated with high dose vitamin C in aviation general hospital, chinese medical sciences university. The symptoms of nausea, loss of appetite, abdominal distention, diarrhea, abdominal pain, dizziness, blood glucose, electrolytes(blood Na~+, K~+, Cl~-) and liver and kidney function(alanine aminotransferase, aspartate aminotransferase, total bilirubin, urea, creatinine and Uric acid) were recorded in 21 patients with tumor before and after high dose vitamin C treatment. The paired test was then used to compare these patients' clinical symptoms and blood biochemical parameters after high-dose vitamin C treatment. Results there were no significant changes in blood glucose, electrolytes, liver and kidney function in patients with malignant tumor treated with high dose vitamin C intravenous drip. One patient complained of loss of appetite, one patient complained of nausea and abdominal distention, and one patient suffered from lower limb edema. However, no similar symptoms and manifestations were found when vitamin C was used again, and no diarrhea, abdominal pain, dizziness and other symptoms was observed. Conclusions High-dose vitamin C has not been found in the treatment of advanced malignant tumor patients with adverse reactions and the security is good.
Objective To observe the safety of high-dose vitamin C intravenous infusion in the treatment of advanced malignant tumors, and to provide reference for clinical rational use of vitamin C. Methods from April 2016 to June 2017, 21 patients with advanced malignant tumor were treated with high dose vitamin C in aviation general hospital, chinese medical sciences university. The symptoms of nausea, loss of appetite, abdominal distention, diarrhea, abdominal pain, dizziness, blood glucose, electrolytes(blood Na~+, K~+, Cl~-) and liver and kidney function(alanine aminotransferase, aspartate aminotransferase, total bilirubin, urea, creatinine and Uric acid) were recorded in 21 patients with tumor before and after high dose vitamin C treatment. The paired test was then used to compare these patients' clinical symptoms and blood biochemical parameters after high-dose vitamin C treatment. Results there were no significant changes in blood glucose, electrolytes, liver and kidney function in patients with malignant tumor treated with high dose vitamin C intravenous drip. One patient complained of loss of appetite, one patient complained of nausea and abdominal distention, and one patient suffered from lower limb edema. However, no similar symptoms and manifestations were found when vitamin C was used again, and no diarrhea, abdominal pain, dizziness and other symptoms was observed. Conclusions High-dose vitamin C has not been found in the treatment of advanced malignant tumor patients with adverse reactions and the security is good.
引文
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24.Chen Qi,Espey Michael Graham,Krishna Murali C,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):13604-13609.
25.Rees DC,Kelsey H,Richards JD.Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenasedeficiency.BMJ.1993;306(6881):841-842.
26.Verrax J,Calderon PB.The controversial place of vitamin C in cancer treatment.Biochem Pharmacol.2008;76(12):1644-1652.
27.Institute of Medicine(US)Panel on Dietary Antioxidants and Related Compounds.Dietary reference intakes for vitamin C,vitamin E,selenium,and carotenoids.Washington,DC:The National Academies Press.(US);2000.
28.Ou J,Zhu X,Lu Y,et al.The safety and pharmacokinetics of high dose intravenous ascorbic acid synergy with modulated electrohyperthermia in Chinese patients with stage III-IV non-small cell lung cancer.Eur J Pharm Sci.2017;109:412-418.
2.Lv H,Wang C,Fang T,et al.Vitamin C preferentially kills cancer stem cells in hepatocellular carcinoma via SVCT-2.NPJ Precis Oncol.2018;2(1):1.
3.Carr AC,Cook J.Intravenous vitamin c for cancer therapyidentifying the current gaps in our knowledge.Front Physiol.2018;9:1182.
4.Baillie N,Carr AC,Peng S.The use of intravenous vitamin C as a supportive therapy for a patient with glioblastoma multiforme.Antioxidants(Basel).2018;7(9).pii:E115.
5.Rees MJ,Strach MC,Burbury K,et al.Massive oxidative haemolysis and renal failure caused by high dose vitamin C.Med JAust.2018;209(6):248-249.
6.Squires VR.The role of food,agriculture,forestry and fisheries in human nutrition-volume IV.EOLSS Publications.Australia;2009;121.
7.Chambial S1,Dwivedi S1,Shukla KK,et al.Vitamin C in disease prevention and cure:An overview.Ind J Clin Biochem.2013;28(4):314-328.
8.Hughes DA.Effects of dietary antioxidants on the immune function of middle-aged adults.Proc Nutr Soc.1999;58(1):79-84.
9.Del Rio M,Ruedas G,Medina S,et al.Improvement by several antioxidants of macrophage function in vitro.Life Sci.1998;63(10):871-881.
10.Jeng KC,Yang CS,Siu WY,et al.Supplementation with vitamins C and E enhances cytokine production by peripheral blood mononuclear cells in healthy adults.Am J Clin Nutr.1996;64(6):960-965.
11.Chan SW,Reade PC.The role of ascorbic acid in oral cancer and carcinogenesis.Oral Dis.1998;4(2):120-129.
12.Bruchelt G,Baader L,Reith AG,et al.Rationale for the use of ascorbic acid in neuroblastoma therapy.In:Schwab M,editor.Human Neuroblastoma,1993;34-40.
13.Fujinaga S,Sakagami H,Kuribayashi N,et al.Possible role of hydrogen peroxide in apoptosis induction by ascorbic acid in human myelogenous leukemic cell lines.Showa University Journal of Medical Sciences,1994;6(2):135-144.
14.Monti DA,Mitchell E,Bazzan A J,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.
15.Cieslak JA,Cullen JJ.Treatment of pancreatic cancer with pharmacological ascorbate.Curr Pharm Biotechnol.2015;16(9):759-770.
16.Hoffer LJ,Robitaille L,Zakarian R,et al.High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer:a phase I-II clinical trial.PLoS One.2015;10(4):e0120228.
17.Harris HR,Bergkvist L,Wolk A.Vitamin C intake and breast cancer mortality in a cohort of Swedish women.Br J Cancer.2013;109(1):257-264.
18.Harris HR,Orsini N,Wolk A.Vitamin C and survival among women with breast cancer:a meta-analysis.Eur J Cancer.2014;50(7):1223-1231.
19.Koh WS,Lee SJ,Lee H,et al.Differential effects and transport kinetics of ascorbate derivatives in leukemic cell lines.Anticancer Res.1998;18(4A):2487-2493.
20.Padayatty SJ,Sun H,Wang Y,et al.Vitamin C pharmacokinetics:implications for oral and intravenous use.Ann Intern Med.2004;140(7):533-537.
21.Graumlich JF,Ludden TM,Conry-Cantilena C,et al.Pharmacokinetic model of ascorbic acid in healthy male volunteers during depletion and repletion.Pharm Res.1997;14(9):1133-1139.
22.Padayatty SJ,Riordan HD,Hewitt SM,et al.Intravenously administered vitamin C as cancer therapy:three cases.CMAJ.2006;174(7):937-942.
23.Chen Q,Espey MG,Sun AY,et al.Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo.Proc Natl Acad Sci U S A.2007;104(21):8749-8754.
24.Chen Qi,Espey Michael Graham,Krishna Murali C,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):13604-13609.
25.Rees DC,Kelsey H,Richards JD.Acute haemolysis induced by high dose ascorbic acid in glucose-6-phosphate dehydrogenasedeficiency.BMJ.1993;306(6881):841-842.
26.Verrax J,Calderon PB.The controversial place of vitamin C in cancer treatment.Biochem Pharmacol.2008;76(12):1644-1652.
27.Institute of Medicine(US)Panel on Dietary Antioxidants and Related Compounds.Dietary reference intakes for vitamin C,vitamin E,selenium,and carotenoids.Washington,DC:The National Academies Press.(US);2000.
28.Ou J,Zhu X,Lu Y,et al.The safety and pharmacokinetics of high dose intravenous ascorbic acid synergy with modulated electrohyperthermia in Chinese patients with stage III-IV non-small cell lung cancer.Eur J Pharm Sci.2017;109:412-418.