Potential Benefit of High Dose of Vitamin C for Cancer Patients

Transcription

1 Potential Benefit of High Dose of Vitamin C for Cancer Patients By Dr Yuen Raymond C F MBBS, MMed Sc,MMed OM, FAMS Occupational Physician, 365 Cancer Prevention Society Medical Consultant, Family Physician, Hosanna Clinic. Dear Colleague, I am writing as fellow of Occupational Medicine and Medical Consultant of 365 Cancer Prevention Society (formally known as CareCancer Society) to draw your interest in the latest medical nutrition researches about high dose intravenous vitamin C (IVC). Recent article written by Ana Sandoiu Monday 13 March 2017 published in Medical News Today titled Vitamin C can target and kill cancer stem cells, study shows suggests the beneficial effect of high dose IVC help cancer patients. The research focused on the bioenergetic processes of Cancer Stem Cells (CSCs), which enable the cells to live and multiply. The study aimed to disrupt the CSCs' metabolism and ultimately prevent their growth. Of all the substances tested, the team found that actinonin and FK866 were the most effective. However, the natural products were also found to prevent the formation of CSCs, and vitamin C was 10 times more effective than the experimental drug 2-DG. Additionally, the study revealed that ascorbic acid works by inhibiting glycolysis - the process by which glucose is broken down within the cell's mitochondria and turned into energy for the cell's proliferation. Dr. Michael P. Lisanti, professor of translational medicine at the University of Salford, comments on the findings: "We have been looking at how to target cancer stem cells with a range of natural substances including silibinin (milk thistle) and CAPE, a honey-bee derivative, but by far the most exciting are the results with vitamin C. Vitamin C is cheap, natural, nontoxic and readily available so to have it as a potential weapon in the fight against cancer would be a significant step." "This is further evidence that vitamin C and other nontoxic compounds may have a role to play in the fight against cancer," says the study's lead author. 1

2 "Our results indicate it is a promising agent for clinical trials, and as an add-on to more conventional therapies, to prevent tumor recurrence, further disease progression, and metastasis," Bonuccelli adds. Vitamin C has been shown to be a potent, nontoxic, anticancer agent by Nobel Prize winner Linus Pauling. This is the first study providing evidence that ascorbic acid can specifically target and neutralize CSCs. High Dose Vitamin C makes Conventional Cancer Treatment more Effective More recent studies have examined the combined effect of high-dose vitamin C and conventional cancer treatment. Some of this research showed that patients who received the combined treatment had a slower progression of the disease, while others have suggested that the side effects of chemotherapy were less pronounced among those who also took high doses of vitamin C (references). To obtain a high dose in these studies, vitamin C is usually administered using intravenous infusion. Vitamin C has a short half-life of only 2 hours in the human body, which is why it must be administered in high doses as a treatment. The theory that malignant cells produce a hyaluronidase enzyme, which helps the cancer grow by free-radical spread and that vitamin C seemed to inhibit this. This seems to have been confirmed - the speed of breast cancer spread is believed to be about free radical damage and is drastically reduced by vitamin C (Malins: Nat Ac Sciences vol 93, March 1996). Intravenous vitamin C uses ascorbate and acts as a pro-drug to deliver H2O2 to the tissues and eliminate free radicals and kill cancer cells. Riordan at his Arizona Clinic took the view that intravenous vitamin C works as a pro-oxidant in much the same way as some chemotherapy agents and this brings about cancer cell death because large doses build up hydrogen peroxide in cancer cells. One study in 2008 seemed to show that an oxidised version of vitamin C could interfere with antineoplastic cancer drugs in laboratory experiments - so the word went out that you definitely should not take antioxidants if you are having chemotherapy. But Riordan s research seems to say clearly that you should take vitamin C with chemotherapy. In 1999 Gotlieb went further. With Kedar Prasad, Professor of Radiology at the University of Colorado, Denver, they showed that high dose vitamin C, as well as other antioxidants, can protect healthy cells, which regulate their uptake levels during treatment. Whereas Prasad is quite clear, cancer cells cannot regulate uptake and this aids their death. 2

3 Whilst he is actually against high doses of vitamin C because of possible toxicity in the liver, he believes C, E or beta-carotene is highly protective. UCLA confirmed this theory in 2004, and MD Anderson has also stated that people should take their antioxidants during radiotherapy and chemotherapy. Indeed, MD Anderson has gone further and in clinical trials has shown vitamin C and vitamin K3 enhance the effects of Bladder Cancer drugs. Other US research shows that vitamin E enhances the effects of Tamoxifen. In fact, women taking vitamin E need 25 per cent less Tamoxifen. Then in 2014 researchers (Assistant Professor Qi Chen and Dr. Jeanne Drisco) at the University of Kansas Medical Centre showed in several studies (in vitro, in mouse models, and in human ovarian cancer patients) that IVC kills cancer cells without harming healthy cells. They went further and showed how High Dose vitamin C enhanced the effects of two drugs - carboplatin and paclitaxel. 27 patients with Grade 3 and Grade 4 Ovarian Cancer were treated. Patients were monitored for 5 years and experienced fewer side-effects from the toxicity of the drugs. High Dose IVC inhibits cancer cells growth Research by the University of Iowa over the past four decades has shown that high doses in laboratory experiments are successful at inhibiting and killing cancer cells, but that ingesting vitamin C never achieves these levels because the body regulates the plasma levels on ingestion; whereas injecting the vitamin C intravenously allows the same high doses used in lab experiments to reach the tumours. A new clinical trial studies the effect of giving between 800 and 1,000 times the daily-recommended dose of vitamin C to patients with brain and lung cancer. The new research was led by scientists at the University of Iowa in Iowa City, and the results were published in the journal Cancer Cell. The High Dose vitamin C also endures longer; normal vitamin C is watersoluble and so is destroyed in the body after approximately 2 hours. In a safety check, patients with brain cancer on chemo- or radiotherapy saw no significant side effects after 9 months usage. The work was conducted by Bryan Allen author of the paper and Assistant Professor of Radiation Oncology and the University of Iowa, and Professors Douglas Spitz and Garry Buettner. In this first Clinical Trial phase, patients with glioblastoma (GBM) brain cancer survived on average months compared with those only receiving conventional treatment who on average survive months. Similar findings occurred with NSCLC patients. In 2017, the University of Iowa announced the results of the first stage of their 3

4 three phase clinical trials announcing that IVC increased the survival times for people with brain cancer and non-small cell lung cancer; and that no sideeffects were noted from High Dose vitamin C, which was effective on its own or in enhancing both chemotherapy and radiotherapy. Vitamin C passes human safety trial 4

5 As part of the human safety trial, 11 patients with brain cancer who were undergoing standard chemotherapy and radiation therapy were also administered three weekly intravenous infusions of vitamin C for 2 months, and then two weekly infusions for 7 months. Each infusion raised the patients' blood levels of vitamin C to 20,000 micromoles (μm). The average level of vitamin C in adults is approximately 70 μm. Overall, the treatment was tolerated well. The team noted very few minor side effects, such as dry mouth or rare and brief episodes of high blood pressure. This safety test was the first phase of a series of clinical trials that will investigate whether high-dose vitamin C can effectively increase the lifespan and quality of life for patients that are being treated with chemotherapy and radiation therapy. For now, the data from the phase I trial show that patients with glioblastoma survived for 4 to 6 months longer than the average survival time noticed in patients who undergo conventional treatment alone. Specifically, patients who also received high doses of ascorbic acid survived for 18 to 22 months compared with 14 to 16 months, which is the typical survival rate for glioblastoma. For the upcoming phase II of the clinical trials, the scientists will examine the effects of vitamin C in participants with stage 4 lung cancer as well as in those with highly aggressive brain tumors, such as glioblastoma. How vitamin C weakens cancer cells The mechanism that might explain the potential efficacy of vitamin C in treating lung and brain cancer relates to the cancer cells' metabolism. As a consequence of the faulty metabolism that occurs inside the cancer cells' mitochondria, these cells produce abnormally high levels of so-called redox active iron molecules. These molecules react with vitamin C and form hydrogen peroxide and hydrogen peroxide-derived free radicals. Scientists think that these free radicals drive cancer cell death by damaging the cells' DNA. The free radicals are also thought to weaken the cancer cells and make them more vulnerable to radiation therapy and chemotherapy. "This paper reveals a metabolic frailty in cancer cells that is based on their own production of oxidizing agents that allows us to utilize existing redox active compounds, like vitamin C, to sensitize cancer cells to radiation [therapy] and chemotherapy." Garry Buettner, study co-author 5

6 Co-senior author Douglas Spitz also comments on the significance of the findings: "This is a significant example of how knowing details of potential mechanisms and the basic science of redox active compounds in cancer versus normal cells can be leveraged clinically in cancer therapy," he explains. "Here, we verified convincingly that increased redox active metal ions in cancer cells were responsible for this differential sensitivity of cancer versus normal cells to very high doses of vitamin C." If the approach proves effective in future clinical trials as well, the new treatment could also be significantly less costly than the standard treatment. To put this into perspective, 9 months of intravenous vitamin C treatment as part of the phase II trial currently costs less than one dose of chemotherapy. "The majority of cancer patients we work with are excited to participate in clinical trials that could benefit future patient outcomes down the line. Results look promising but we are not going to know if this approach really improves therapy response until we complete these phase II trials." Bryan Allen, cosenior author. High dose vitamin C works on its own or with chemo- and radiotherapy The researchers believe they are closer to showing exactly how high dose vitamin C works. Cancer cells have faulty biochemistry, and their mitochondria produce high levels of labile iron, or redox-active iron molecules. The vitamin C reacts with these molecules and produces hydrogen peroxide-derived free radicals, which sensitize the cancer cells, damaging them so that the chemoand radiotherapy kill more of them. The vitamin C on its own seemed also to pre-sensitize cancer cells and lead to their death, without the presence of chemotherapy or radiotherapy. Similar observations have been made in research in recent years with both exercise and Hyperbaric Oxygen. High Dose of vitamin C has both oxidant and anti oxidant effect to control inflammation and suppress cancer growth As noted by Dr. Hunninghake from the Riordan Clinic, conventional cancer therapies, such as certain chemotherapy and radiation treatments, work by increasing cell oxidation to kill off cancer cells. In the process, however, the control mechanisms for cell death are also damaged, including the p53 gene, which suppresses tumor formation. Certain therapy-resistant cells survive this treatment, and other cells are left with less control over the formation of cancer. 6

7 In addition to IVC s oxidant effect, high doses also act as an antioxidant. Many conventional doctors worry about the antioxidant effect of IVC for patients undergoing chemotherapy and radiation treatment, but this seems largely unfounded given recent research. The antioxidant effect of IVC, a bit less strong than its oxidant effect, helps control inflammation and therefore inhibits cancer cell replication. Dr. Hunninghake also notes that his team has documented seven ways by which IVC helps fight cancer. These seven areas are: 1. Self-sufficiency of growth signals 2. Insensitivity to antigrowth signals 3. Evasion of apoptosis (cell death) 4. Unlimited proliferation potential 5. Enhanced angiogenesis (blood-vessel supply to the tumor) 6. Tissue invasion and metastasis 7. Inflammatory microenvironment In general, Vitamin C together with chemotherapy medicines has been shown in the scientific journals to: Reverse chemotherapy resistant cancer cells Increase the delivery of chemotherapy into cancer cells (helps to overcome drug resistance) Make the tumour cell membrane more permeable (enhanced drug delivery) Stabilize p53 genes, Bax, decrease Bcl-2 and telomerase activity (decreases drug resistance) Inhibit translocation of NF-kappaB and AP-1 (decreases drug resistance) Inhibit Nrf2-mediated gene expression (decreases drug resistance) Activate the MLH1, c-abl, and p73 signalling cascade (enhanced drug killing effect) Note: it is important to also highlight that, on its own, Vitamin C in particular by intravenous injection also has chemotherapeutic effects and possesses supportive properties for the rest of the body (unlike standard chemotherapy agents). The researched chemotherapy agents used together with Vitamin C showing a positive effect have included the following: Arsenic Trioxide Cisplatinum (platinum-based) 7

8 Cyclophosphamide (Cytoxan) Doxorubicin (Adriamycin) Dacarbazine (DTIC) Gemcitabine (Gemzar) Interferon-alpha 2b Imatinib (Gleevec) Mitomycin C Paclitaxel (Taxol) Etoposide 5-FU (fluorouracil) Tamoxifen Vincristine (Oncovin) (Article by Dr. Walter Lemmo, Vancouver, BC Enhancing chemotherapy effectiveness with simple Vitamin C.) The benefit and efficacy of high dose f vitamin c injection for cancer patients is getting clearer nowadays with the latest medical researches. Most of the developed countries like USA, UK, Australia, New Zealand, Japan, China and neighboring city like Thailand, Hong Kong recognized the importance of using high doses of vitamin C injection for patients and is readily available to their citizens. Singapore being the medical hub for SE Asia may lose out to our neighbors if we do not catch up with the latest medical nutrition research. I have seen a stage 4 lung patient went to Hong Kong successfully treated his cancer by the oncologist ( Dr Tsao Shiu Ying) who use combination of high dose vitamin C and radiation therapy. ( Attached : Reporting a Case of Vocal Cord Palsy Due to Lung Cancer Treated by Intravenous Vitamin C & Radiotherapy: Implications ) 8

9 J have also documented few cases of high dose vitamin C in cancer patients here, most of them tolerated well with the high doses of vitamin C well with minimal side effects (see reference). I hope that oncologists in Singapore are more open to try high dose of vitamin for their cancer patients to see the benefits themselves. For terminal cancer patients, strong medications like chemotherapy drugs and morphine are frequently use, and it is worth to try this non toxic vitamin C which is documented to improve cancer patients quality of life, reduce inflammation markers (CRP), prolong cancer patients survival, enhance chemotherapy, radiation therapy killing effects and speed up surgical wound healing. All are documented in peel-reviewed journals (attached for your references). Thanks for your reading and I look forward to your favorably action to the encourage the use of high dose vitamin C in Singapore. Regards, Dr Yuen Chuen Fong Raymond Hosanna Clinic MBBS, MMedSc, MMed OM, FAMS 9

10 This summary (National Cancer Institute on High Dose Vitamin C Review) contains the following key information: 1. High Tolerance of Vit C in Clinical Trials Vitamin C is an essential nutrient with redox functions at normal physiologic concentrations. High-dose vitamin C has been studied as a treatment for cancer patients since the 1970s. Laboratory studies have reported that high-dose vitamin C has redox properties and decreased cell proliferation in prostate, pancreatic, hepatocellular, colon, mesothelioma, and neuroblastoma cell lines. Two studies of high-dose vitamin C in cancer patients reported improved quality of life and decreases in cancer-related side effects. Studies of vitamin C combined with other drugs in animal models have shown mixed results. Intravenous vitamin C has been generally well tolerated in clinical trials. 2. Clinical Studies of Vitamin C Used Alone: Intravenous (IV) vitamin C was studied in patients with breast cancer who were treated with adjuvant chemotherapy and radiation therapy. The study found that patients who received IV vitamin C had better quality of life and fewer side effects than those who did not. A study of IV vitamin C and high doses of vitamin C taken by mouth was done in patients with cancer that could not be cured. Vitamin C was shown to be a safe and effective therapy to improve quality of life in these patients, including physical, mental, and emotional functions, symptoms of fatigue, nausea and vomiting, pain, and appetite loss. Vitamin C has been shown to be safe when given to healthy volunteers and cancer patients at doses up to 1.5 g/kg, while screening out patients with certain risk factors who should avoid vitamin C. Studies have also shown that Vitamin C levels in the blood are higher when taken by IV than when taken by mouth, and last for more than 4 hours. 3. Studies of Vitamin C combined with other drugs Studies of vitamin C combined with other drugs have shown mixed results: In a small study of 14 patients with advanced pancreatic cancer, IV vitamin C was given along with chemotherapy and treatment with a targeted therapy. Patients had very few bad side effects from the vitamin C treatment. The nine patients who completed the treatment had stable disease as shown by imaging studies. In another small study of 9 patients with advanced pancreatic cancer, patients were 10

11 given chemotherapy in treatment cycles of once per week for 3 weeks along with IV vitamin C twice per week for 4 weeks. These patients had disease that did not progress for a period of months. The combined treatment was well tolerated and no serious side effects were reported. In a 2014 study of 27 patients with advanced ovarian cancer, treatment with chemotherapy alone was compared to chemotherapy along with IV vitamin C. Patients who received IV vitamin C along with chemotherapy had fewer serious side effects from the chemotherapy. Patients with acute myeloid leukemia, refractory metastatic colorectal cancer, or metastatic melanoma treated with IV vitamin C combined with other drugs had serious side effects and the disease got worse. Another prospective cohort studies indicate that higher intakes of vitamin C from either diet or supplements are associated with a reduced risk of cardiovascular disease (CVD), including coronary heart disease and stroke. Observational prospective cohort studies report no or modest inverse associations between vitamin C intake and the risk of developing a given type of cancer. Randomized controlled trials have shown no effect of vitamin C supplementation on cancer outcomes. Prospective cohort studies indicate that higher blood levels of vitamin C are associated with lower risk of death from all-causes, cancer, and CVD. Pharmacological doses of Vit C administered intravenously are generally safe and well tolerated in cancer patients. References Dr Yuen Vitamin C Article (Abstract) Effects of High Doses of Vitamin C on Cancer Patients in Singapore Nine Cases Introduction. Intravenous high-dose vitamin C therapy is widely used in naturopathic and integrative oncology; however, a study reviewing its effects has never been performed in Singapore. This article serves to document administration of supportive vitamin C therapy for cancer patients in Singapore. Methods. The clinical response of 9 cancer patients of differing stages to the regular administration of large doses ( g/d) of intravenous vitamin C (IVC; ascorbic acid) is outlined. Tumor pathology and patient health were verified by doctors who do not practice vitamin C treatment. Results. Cases suggesting survival beyond prognosis, improvement in quality of life, safe co administration with and improved tolerance of conventional therapy, and deterioration in clinical condition following withdrawal of vitamin C therapy are documented clinically. Some patients experience the Jarisch-Herxheimer reaction the release of 11

12 endotoxin from microorganism death resulting in pimples, fever, and body odor for a few hours after the therapy, but these are resolved quickly with no lasting effects. Conclusion. Randomized trials of IVC therapy are recommended because it has minimal side effects and has shown promising results. References for intravenous vitamin C on Quality of life 1) The Effect of Intravenous Vitamin C on Cancer- and Chemotherapy- Related Fatigue and Quality of Life Anitra C. Carr,1,* Margreet C. M. Vissers,1 and John S. Cook2. Cancer patients commonly experience a number of symptoms of disease progression and the side effects of radiation therapy and adjuvant chemotherapy, which adversely impact on their quality of life (QOL). Fatigue is one of the most common and debilitating symptom reported by cancer patients and can affect QOL more than pain. Several recent studies have indicated that intravenous (IV) vitamin C alleviates a number of cancer- and chemotherapy-related symptoms, such as fatigue, insomnia, and loss of appetite, nausea, and pain. Improvements in physical, role, cognitive, emotional, and social functioning, as well as an improvement in overall health, were also observed. In this mini review, we briefly cover the methods commonly used to assess health-related QOL in cancer patients, and describe the few recent studies examining the effects of IV vitamin C on cancer- and chemotherapy-related QOL. We discuss potential mechanisms that might explain an improvement in QOL and also considerations for future studies. 2) J Korean Med Sci Feb; 22(1): Changes of terminal cancer patients' health-related quality of life after high dose vitamin C administration. Yeom CH1, Jung GC, Song KJ. Abstract Over the years there has been a great deal of controversy on the effect of vitamin C on cancer. To investigate the effects of vitamin C on cancer patients' health-related quality of life, we prospectively studied 39 terminal cancer patients. All patients were given an intravenous administration of 10 g vitamin C twice with a 3-day interval and an oral intake of 4 g vitamin C daily for a week. And then we investigated demographic data and assessed changes in patients' quality of life after administration of vitamin C. Quality of life was assessed with EORTC QLQ-C30. In the global health/quality of life scale, health score improved from 36+/-18 to 55+/-16 after administration of vitamin C (p=0.001). In functional scale, the patients reported significantly higher scores for physical, role, emotional, and cognitive function after administration of vitamin C (p<0.05). In symptom scale, the patients reported significantly lower scores for fatigue, nausea/vomiting, pain, and appetite loss 12

13 after administration of vitamin C (p<0.005). The other function and symptom scales were not significantly changed after administration of vitamin C. In terminal cancer patients, the quality of life is as important as cure. Although there is still controversy regarding anticancer effects of vitamin C, the use of vitamin C is considered a safe and effective therapy to improve the quality of life of terminal cancer patients. 3) 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 Aim: The aim of the study was to evaluate under praxis conditions the safety and efficacy of intravenous (i.v.) vitamin C administration in the first postoperative year of women with breast cancer. Results: Comparison of control and study groups revealed that i.v. vitamin C administration resulted in a significant reduction of complaints induced by the disease and chemo-/radiotherapy, in particular of nausea, loss of appetite, fatigue, depression, sleep disorders, dizziness and haemorrhagic diathesis. After adjustment for age and baseline conditions (intensity score before adjuvant therapy, chemotherapy, radiotherapy), the overall intensity score of symptoms during adjuvant therapy and aftercare was nearly twice as high in the control group compared to the study group. No side effects of the i.v. Vitamin C administration was documented. Discussion: Oxidative stress and vitamin C deficiency play an important role in the etiology of adverse effects of guideline-based adjuvant chemo- /radiotherapy. Restoring ant oxidative capacity by complementary i.v. Vitamin C administration helps to prevent or reduce disease-, or therapy-induced complaints in breast cancer patients. Conclusion: Complementary treatment of breast cancer patients with i.v. Vitamin C was shown to be a well-tolerated optimization of standard tumourdestructive therapies, reducing quality of life-related side effects. References for Cancer patients are deficiency of vitamins supplements. 4) Vitamin C deficiency in cancer patients Catriona R Mayland St Gemma's Hospice, Leeds Michael I Bennett St Gemma's Hospice, Harrogate Road, Leeds Keith Allan Department of Clinical Biochemistry, Leeds Teaching Hospitals, Leeds Conclusion: Vitamin C deficiency is common in patients with advanced cancer and the most important factors determining plasma levels 13

14 are dietary intake and markers of the inflammatory response. Patients with low plasma concentrations of vitamin C have a shorter survival. 5) Epidemiologic evidence regarding vitamin C and cancer. Am J Clin Nutr December 1991 Vol. 54 no S-1314S G Block Public Health Nutrition Program, School of Public Health, University of California, Berkeley Abstract Approximately 90 epidemiologic studies have examined the role of vitamin C or vitamin-c-rich foods in cancer prevention, and the vast majorities have found statistically significant protective effects. Evidence is strong for cancers of the esophagus, oral cavity, stomach, and pancreas. There is also substantial evidence of a protective effect in cancers of the cervix, rectum, and breast. Even in lung cancer, for which carotenoids show a consistent protective effect, there is recent evidence of a role for vitamin C. Vitamin C is an important antioxidant and free radical scavenger in plasma and acts to regenerate active vitamin E in lipid membranes. Although several different factors in fruits and vegetables probably act jointly, the epidemiologic and biochemical evidence indicate an important role for vitamin C. 6) Severe hypovitaminosis C in lung-cancer patients: the utilization of vitamin C in surgical repair and lymphocyte-related host resistance H M Anthony and C J Schorah Abstract Plasma and buffy-coat vitamin C were estimated in 158 samples from 139 lung-cancer patients, at all stages of the disease. Most samples showed hypovitaminosis C in both estimations. Vitamin C is necessary for phagocytosis and for the expression of cellmediated immunity. In view of the increasing circumstantial evidence that immune mechanisms exert some measure of control on tumour extension and metastasis in man, the effect of supplementation with vitamin C in lungcancer patients on survival should be tested in a clinical trial. References: Vitamin C enhanced Chemo sensitivity and reduces side effects. 7) High-dose parenteral ascorbate enhanced chemo sensitivity of ovarian cancer and reduced toxicity of chemotherapy. Ma Y1, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. 14

15 Sci Transl Med Feb 5;6(222):222ra18. doi: /scitranslmed Abstract Ascorbate (vitamin C) was an early, unorthodox therapy for cancer, with an outstanding safety profile and anecdotal clinical benefit. Because oral ascorbate was ineffective in two cancer clinical trials, ascorbate was abandoned by conventional oncology but continued to be used in complementary and alternative medicine. Recent studies provide rationale for reexamining ascorbate treatment. Because of marked pharmacokinetic differences, intravenous, but not oral, ascorbate produces millimolar concentrations both in blood and in tissues, killing cancer cells without harming normal tissues. In the interstitial fluid surrounding tumor cells, millimolar concentrations of ascorbate exert local pro-oxidant effects by mediating hydrogen peroxide (H(2)O(2)) formation, which kills cancer cells. We investigated downstream mechanisms of ascorbate-induced cell death. Data show that millimolar ascorbate, acting as a pro-oxidant, induced DNA damage and depleted cellular adenosine triphosphate (ATP), activated the ataxia telangiectasia mutated (ATM)/adenosine monophosphate-activated protein kinase (AMPK) pathway, and resulted in mammalian target of rapamycin (mtor) inhibition and death in ovarian cancer cells. The combination of parenteral ascorbate with the conventional chemotherapeutic agents carboplatin and paclitaxel synergistically inhibited ovarian cancer in mouse models and reduced chemotherapy-associated toxicity in patients with ovarian cancer. On the basis of its potential benefit and minimal toxicity, examination of intravenous ascorbate in combination with standard chemotherapy is justified in larger clinical trials. 8) The use of antioxidant therapies during chemotherapy Jeanne A Drisko, Julia Chapman, Verda J Hunter DOI: Conclusions Currently, evidence is growing that antioxidants may provide some benefit when combined with certain types of chemotherapy. Because of the potential for positive benefits, a randomized controlled trial evaluating the safety and efficacy of adding antioxidants to chemotherapy in newly diagnosed ovarian cancer is underway at the University of Kansas Medical Center. 9) Relief from cancer chemotherapy side effects with pharmacologic vitamin Relief from cancer chemotherapy side effects with pharmacologic vitamin C New Zealand Medical journal 24th January 2014, Volume 127 Number 1388 Anitra C Carr, Margreet C M Vissers, John Cook Research has shown that fatigue has a constant presence following chemotherapy and also increases incrementally with consecutive cycles of chemotherapy.2 A retrospective, multicentre, epidemiological cohort study 15

16 has indicated that intravenous vitamin C administration improves quality of life, including fatigue, in breast cancer patients during chemo-/radiotherapy and aftercare.10 Our case report supports the findings of Vollbracht et al10 and extends these by further investigating the effects of intravenous vitamin C on the multidimensional aspects of fatigue. Following pharmacologic vitamin C administration there were dramatic decreases in chemotherapy-related fatigue and other symptoms, as well as increased functioning and overall health. It is not possible to rule out a placebo effect, particularly as this effect tends to be more prevalent with measures of subjective symptoms.11 However, based on the varied functions of vitamin C in the body,4 it is plausible that vitamin C contributed to some of the observed quality of life effects and similar findings have recently been reported.12 Overall, our report has shown that pharmacologic vitamin C may be considered for patients experiencing side effects from chemotherapy. Furthermore, based on our prospective findings and others12 and the retrospective findings of Vollbracht et al,10 a double-blind placebo-control study of the efficacy of intravenous vitamin C on chemotherapy-related quality of life and fatigue appears warranted. 16

17 17

18 18

19 19

20 20

21 21

22 22

23 23

24 24

25 25

26 26

27 27

28 28

29 29

30 30

31 31

32 32

33 33