Is There a Role for Oral or Intravenous Ascorbate (Vitamin C) in Treating Patients With Cancer? A Systematic Review

Jacobs, Carmel; Hutton, Brian; Ng, Terry L.; Shorr, Risa; Clemons, Mark

doi:10.1634/theoncologist.2014-0381

Cited by 102 publications

(71 citation statements)

References 65 publications

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“…A systematic review found no benefit of supplemental ascorbate (vitamin C) for overall or progression-free survival in cancer patients, most of whom had breast or colorectal cancer (Jacobs et al 2015). Another systematic review examined treatment efficacy and patient survival with the use of any adjuvant antioxidants during chemotherapy or radiotherapy (Yasueda et al 2016).…”

Section: Clinical Trials Of Antioxidants In Cancer Treatmentmentioning

confidence: 99%

Cancer, Oxidative Stress, and Metastasis

Gill

Piskounova

Morrison

2016

Cold Spring Harb Symp Quant Biol

231

164

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Reactive oxygen species (ROS) are highly reactive molecules that arise from a number of cellular sources, including oxidative metabolism in mitochondria. At low levels they can be advantageous to cells, activating signaling pathways that promote proliferation or survival. At higher levels, ROS can damage or kill cells by oxidizing proteins, lipids, and nucleic acids. It was hypothesized that antioxidants might benefit high-risk patients by reducing the rate of ROS-induced mutations and delaying cancer initiation. However, dietary supplementation with antioxidants has generally proven ineffective or detrimental in clinical trials. High ROS levels limit cancer cell survival during certain windows of cancer initiation and progression. During these periods, dietary supplementation with antioxidants may promote cancer cell survival and cancer progression. This raises the possibility that rather than treating cancer patients with antioxidants, they should be treated with pro-oxidants that exacerbate oxidative stress or block metabolic adaptations that confer oxidative stress resistance.

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Section: Clinical Trials Of Antioxidants In Cancer Treatmentmentioning

confidence: 99%

Cancer, Oxidative Stress, and Metastasis

Gill

Piskounova

Morrison

2016

Cold Spring Harb Symp Quant Biol

231

164

View full text Add to dashboard Cite

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“…Ascorbate plays a role in limiting inflammation, regulating cytokine production, and boosting the immune system [2][3][4][5][6][7][8]. It has a variety of properties that have generated interest in using it against cancer [9][10][11][12][13]: it enhances natural killer cell activity [14,15], increases collagen synthesis [16], inhibits capillary tubule formation (angiogenesis) [17,18], reduces inflammation in cancer patients [3], at millimolar concentrations, shows cytotoxicity against cancer cells [19][20][21][22][23][24] and the ability to reduce tumor growth in vivo [25][26][27][28][29][30][31][32][33][34]. Clinical trials to date [35][36][37][38][39][40] indicate that high dose (on the order of ten to 100 grams) intravenous ascorbate therapy can enhance anti-cancer effects of chemotherapy and improve quality of life in cancer patients.…”

Section: Introductionmentioning

confidence: 99%

Gene expression response to ascorbic acid in mice implanted with sarcoma S180 cells

Mikirova¹,

Scimeca²

2016

J Transl Sci

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In recent years, increasing numbers of studies demonstrated that high-dose ascorbate, which can be achieved by intravenous infusion, has cytotoxic effects on cancer cells in vitro and in vivo. There are many hypotheses of anti-cancer mechanisms of high dose ascorbate including a pro-oxidative mechanism, inhibition of angiogenesis and inflammation, enhancement of the anticancer effect of chemotherapy and reduction of chemotherapy-induced side effects. In addition, in recent years there were studies showing that ascorbic acid has effect on gene expression and epigenetic phenomena. In our study we analyzed, by using animal model, the effect of pharmacological concentrations of ascorbic acid on several gene expressions involved in tumorigenesis. To test the effects of ascorbic acid on gene expression, we treated mice with two different concentrations of ascorbic acid after intraperitoneal administration with sarcoma S-180 cells. The injected doses of ascorbic acid were equivalent to 15 g per 70 kg human and 50 g per 70 kg human. Tissue from tumors, liver and kidney was obtained from mice at the end of three weeks of treatment. The gene expression analysis was computed by real time PCR. The results showed significant difference in expression of gene p53 (p<0.02) in tumor tissue between treated and non-treated groups, and reduction of p53 gene expression by size and spreading of tumors. Ascorbate therapy significantly increased expression of NRF2. The experimental data showed that the maximum ascorbate dosage reduced expression of the tumor promoting gene HIF. The dependence of gene expression on the size of tumors was found for P53, HIF and NF-kB. In summary, the results of our study demonstrated that ascorbate therapy had a significant effect on the expression of several genes relevant to the development or inhibition of cancer. Reduced expression of tumor promoting genes as HIF and increased expression of tumor suppression genes such as p53 support the hypothesis that ascorbic acid can act as a potential agent for the suppression of tumor development.

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“…Jacobs és mtsai a témában 1946 és 2014 között megjelent közlemények metaanalízisét végezték el, átte-kintésük alapján nem áll rendelkezésre elegendő bizonyí-ték, hogy a C-vitamin-pótlás segítené a kemoterápia hatékonyságát vagy csökkentené toxicitását daganatos betegekben [11].…”

Section: A C-vitamin Daganatellenes Hatásaunclassified

Antioxidánsok – antioxidánssokk: tények és kérdések, 2015

2015

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Az elmúlt években nagy jelentőséget tulajdonítottak az antioxidáns-kezelésnek az oxidatív stresszel összefüggő betegségek megelőzésében, illetve kezelésében. A kezdeti sikerek után azonban bizonyos antioxidánsok nem kívánt hatásairól, toxicitásáról, prooxidáns tulajdonságáról számoltak be (CARET, ATBC vizsgálat). A későbbi metaanalízi-sek eredményei sem támasztották alá az antioxidáns-pótlás alkalmazását az elsődleges és a másodlagos megelőzésben. A szerzők áttekintik az antioxidánsok prooxidáns tulajdonságait, valamint a jelátviteli folyamatokban, a sejtműködés befolyásolásában betöltött szerepüket. Az antioxidánsok kombinált alkalmazása előnyösebb, amelynek lehetséges magyarázatát összegzik a szerzők. Orv. Hetil., 2015, 156(47), 1884-1887.Kulcsszavak: oxidatív stressz, antioxidánsstressz, antioxidáns vitaminok, prooxidáns, jelátviteli folyamatok Antioxidants -antioxidative stress: Facts and questions, 2015In the past years great importance has been attributed to antioxidant therapy in the prevention and treatment of disorders developed in connection with oxidative stress. After initial success, undesirable effects, toxicities, and prooxidant effects of antioxidants were reported [CARET, ATBC study]. In addition, metaanalyses failed to confi rm the role of antioxidant supplementation in the primary and secondary prevention. The authors review the prooxidant effects of antioxidants, and their role in cell signalling and cell process modulation. Finally, the authors summarize possible explanations why combined use of antiooxidants is more favourable. ÖSSZEFOGLALÓ KÖZLEMÉNYRövidítések AP-1 = aktivátor protein-1; HIF-1α = hipoxia indukálta faktor-1α; IGF-IR = inzulinszerű növekedési faktor receptor; NF-κB = nuclear factor kappa-B; PK = proteinkináz; RARE = retinsav; TET = ten-eleven translocation methylcytosine; TGF-α = transzformáló növekedési faktor-α Az utóbbi években kiemelkedő szerepet tulajdonítottak az antioxidáns-kezelésnek a kóros szabad gyökös reakciókkal összefüggő betegségek megelőzésében, illetve kezelésében [1,2]. Legelőször az ATBC, illetve CARET vizsgálatban számoltak be az antioxidánsok nem kívánt hatásairól (retinol, β-karotin-kezelések a tüdőtumor előfordulását növelték) [3]. Későbbi áttekintések sem igazolták a napi ajánlott táplálkozási bevitelt meghaladó mennyiségű ("supra-nutritional") antioxidáns-pótlás hatásosságát az elsődleges és másodlagos megelőzésben [4,5]. C-vitaminA C-vitamin vízoldékony antioxidáns, elektrondonor tulajdonsága révén redukálószer [6]. Számos enzim kofaktora (prolil-, lizilhidroxiláz), szerepet játszik a koleszterinmetabolizmusban, a citokróm P450 működésében, a neurotranszmitterek, valamint a karnitin szintézisében [6]. Az aszkorbát epigenomikai folyamatokat befolyásol a DNS-és a hisztondemetiláció szabályozásával, mivel esszenciális kofaktora a TET (ten-eleven translocation methylcytosine) dioxigenázoknak, valamint a Jmjc domént tartalmazó hisztondemetilázoknak [7].Kis koncentrációban a C-vitamin redukálja az átmene-ti fémionokat, elősegíti a fémkatalízist a Fenton-...

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Is There a Role for Oral or Intravenous Ascorbate (Vitamin C) in Treating Patients With Cancer? A Systematic Review

Cited by 102 publications

References 65 publications

Cancer, Oxidative Stress, and Metastasis

Cancer, Oxidative Stress, and Metastasis

Gene expression response to ascorbic acid in mice implanted with sarcoma S180 cells

Antioxidánsok – antioxidánssokk: tények és kérdések, 2015

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