Hyperbaric Oxygen, Ozone and Vitamin C: Increasing the Effectiveness of Intravenous Vitamin C as an Anticancer Agent

Article Type: Educational Article
by International Society for Orthomolecular Medicine

, et al. Author(s): Michael J. Gonzalez NMD, DSc, PhD, FANMA, FACN¹; Jorge R. Miranda-Massari PharmD²; Jorge Duconge PhD²; Miguel J. Berdiel MD³

^1,2University of Puerto Rico, Medical Sciences Campus, RECNAC 2 Project, Schools of Public Health and Pharmacy ; ³Pontifical Catholic University, Dept. of Biology

*Correspondence should be addressed to: Dr. Michael J Gonzalez, University of Puerto Rico, Medical Sciences Campus School of Public Health, Department of Human Development, Nutrition Program, GPO Box 365067 San Juan PR 00936-5067; email: [email protected]

Date of Publication: 2017

Hyperbaric Oxygen Therapy plus Vitamin C IVs and Ozone are powerful tools to combat Cancer!

Abstract

Vitamin C has been mentioned as an agent with chemotherapeutic potential since 1952. Physiological concentrations of vitamin C (L-ascorbate or L-ascorbic acid) in the body are controlled through intestinal absorption, tissue accumulation, and renal reabsorption and excretion. Therefore, intravenous administration is used to achieve pharmacologic doses not attainable by other means. In relation to intravenous administration of ascorbate, high-dose intravenous vitamin C (>0.5 g/kg body weight) has several effects: cytotoxicity for cancer cells but not for normal cells; improved quality of life for cancer patients; protection of normal tissues from toxicity caused by chemotherapy; rein¬forcement of the action of radiation and some types of chemotherapy; immune system enhancement; and strengthening of collagen and hyaluronic acid. In this article we discuss important therapeutic variables that the clinician faces that are key for increasing the effectiveness of intravenous vitamin C as an anticancer agent.

JOM Archives, Volume 30, Number 1, 2015

Introduction

After over 60 years of experience with vitamin C and Cancer, what can we say about vitamin C as an anticancer agent? The extensive experience and published papers on vitamin C and cancer demonstrate that the use of high dose, both oral and intrave­nous (IV) vitamin C is remarkably safe. (Murata, Morishige & Yamaguchi, 1982; Drisko, Chapman & Hunter, 2003; Riordan, Casciari, González, et al., 2005; Hoffer, Levine, Assouline, et al., 2008; Stephenson, Levin, Spector, et al., 2013; Fowler, Syed, Knowlson, et al., 2014) Additionally, the vast number of publica­tions confirm that it possesses many thera­peutic benefits.

1. Improves quality of life of cancer patients:

(Yeom, Jung & Song, 2007; Volbracht, Schneider, Leendert et al., 2011; Takahashi, Mizunob & Yanagisawa, 2012)

1. Decreases adverse effects of standard can­cer treatments.
2. Reduces pain.
3. Increases energy.
4. Increases appetite.
5. Reduces many complications of the disease:

(Head, 1998; Mayland, Bennett & Allan, 2005; Ichim, Miney, Braciak, et al., 2011;
Mikirova, Casciari, Rogers, et al., 2012; Mikirova, Hunninghke, 2014; Pohanka, Pejchal, Snopkova, et al., 2012)

1. Resolves ascorbate’s insufficiency in the cancer patient.
2. Combats infections (viral, bacterial, fun­gi).
3. Decreases cancer-associated inflamma­tion.
4. Prevents cancer associated sepsis.
5. Pharmacological doses of vitamin C have shown to have cytostatic or cytotoxic action in cancer cells through a variety of mechanisms:

(Gonzalez, Miranda-Massari, Mora, et al., 2005)

1. Fuel control of malignant cells by glucose antagonism.
2. Electron donor for the energy redox problem present in cancer.
3. Increases hydrogen peroxide formation.
4. Increases collagen formation.
5. Enhances immune parameters (cellular and humoral).
6. Sustains and improves the effect of standard antineoplastic agents.

Discussion

Many patients have shown impressive responses in tumor size reduction, improve­ment in pain control, increased energy lev­els and appetite, in general we can state that most patients improve their quality of life but nevertheless total effectiveness of the use of IV vitamin C as an anticancer agent has not been achieved. Results in some in­stances have been variable. This may be due to a number of direct interacting variables.

In order to consistently improve cancer patient outcomes, it is important to have a comprehensive evaluation of the therapeutic protocol that allows us to identify contrib­uting factors that promote health deteriora­tion and the barriers to achieve total healing. These must be identified and corrected.

These variables include but are not limited to:

1. Cell energy related metabolic derangements. (Hanahan, Weinberg, 2011; Moreno-Sánchez, Rodríguez-Enríquez, Marín-Hernández, et al., 2007; Gonzalez, Miranda-Massari, Duconge, et al., 2012)
2. Toxicities (e.g., tobacco, alcohol, pesti­cides, heavy metals, hydrocarbons, and food nitrosamines). (Xue, Yang & Seng, 2014; Varela-Rey, Woodhoo, Martinez-Chantar, et al., 2013; Alavanja, Ross & Bonner, 2013; Van Maele-Fabry, Hoet & Lison, 2013; Arlt, 2005; Abnet, 2007; Sutandyo, 2010; Liu, Russell, 2008)
3. Medications (i.e., opioids impair im­mune response, increase angiogenesis, and may even act directly on tumor cells to en­courage their growth and spread. There are epidemiologic, animal, and cellular studies that suggest a role of mu opioid receptors on cancer growth and metastasis). (Gach, Wyrebska, Fichna, et al., 2011; Gong, Dong, Ouyang, et al., 2013; Lennon, Moss & Singleton, 2012)
4. Hormonal imbalances/endocrine disruptors. (King, Jiang, Su, et al., 2013; Knower, To, Leung, et al., 2014)
5. Excessive inflammation. (Sethi, Shanmugam, Ramachandran, et al., 2012; Aggarwal, Gehlot, 2009)
6. Infectious agents and the balance of the body flora. (Alibek, Kakpenova & Baiken, 2013; Orlando, Russo, 2013)
7. Excessive psychological stress. (Reiche, Morimoto & Nunes, 2005; Lillberg, Verkasalo, Kaprio, et al., 2003)
8. Excessive exposure to radiation. (Berrington de González, Mahesh, Kim, et al., 2007; Anand, Kunnumakara, Sundaram, et al., 2008)

Ten percent of invasive cancers are re­lated to radiation exposure, including both ionizing radiation and non-ionizing radia­tion

Relevant physiological/cellular variables to consider when improv­ing the effectiveness of IV Vitamin C therapy

1. Level of tissue oxygenation: The level of tissue oxygenation may be the most im­portant limiting factor in the anticancer activity of high dose IV vitamin C. As we are well aware of one of the most impor­tant mechanisms by which vitamin C exerts its anticancer action is by the production of hydrogen peroxide. For this to occur, the presence of sufficient oxygen is a requisite. Limited oxygen availability reduces the chances of the production of hydrogen per­oxide from the conversion of ascorbic acid to dehydroascorbic acid. We propose the utilization of hyperbaric oxygen immediate­ly after IV vitamin C therapy to increase its effectiveness as an anticancer agent, in order to increase the formation of hydrogen per­oxide, and therefore enhance the anticancer effect of IV vitamin C.

In relation to ozone, it is known that vi­tamin C is antagonistic to ozone, although it has been shown that ozone does not to break down vitamin C in the body. Patients taking therapeutic doses of vitamin C either orally or via IV infusion, should take the ozone treatment first, then wait 30 minutes, and then take the vitamin C dose.

General Aspects of Oxygenation

1. a) Hyperbaric Oxygen: Increases oxygen to tissues.
2. b) Ozone: Increases oxygen. An Italian group postulates that a prolonged cycle of ozonated autohemotherapy may correct tu­mor hypoxia, lead to less aggressive tumor behavior. Improving oxygen levels would be expected to favor the anticancer effect of vi­tamin C. (Bocci, Larini & Micheli, 2005) Ozone therapy has been reported to produce an increase in red blood cell gly­colysis rate. This leads to stimulation of 2, 3 diphosphoglycerate which then allows a rise of the oxygen released to the tissues. Ozone facilitates the Krebs’s cycle by improving the oxidative carboxylation of pyruvate and promoting the synthesis of ATP. There is also an increase in antioxidant enzymes that act as free radical scavengers (such as glutathione peroxidase, catalase and superoxide dismutase). (Ciborowski, Lipska, Godzien, et al., 2012) Vasodilation is also induced by ozone which leads to increased oxygen and nutrients and immune factors available to the cell. (Wayner, Burton, Ingold, et al., 1985) Ozonized autohemotransfusion may be useful to improve both the poor rheological properties of the blood and the oxygen delivery to tissues (Giunta, Coppola, Luongo, et al., 2001) and therefore increase oxygen, immune factors and nutrients that improve healing and tumor response. Animal studies have shown very significant increased survival in advanced head and neck squamous cell carcinomas with the application of ozone. Although the mechanisms for this effect has not been totally elucidated, it is believed that various important immune-modulatory effects in macrophages, polymorphonuclear cells (PMN), NK cells, and cytotoxic T lymphocytes are involved as well as other metabolic modulatory effects. (Schulz, Häussler, Mandic, et al., 2008) Therefore, although at the present time there is no solid evidence that ozone can improve the anticancer activity of vitamin C, given the scope of its biological effects, it might be important to test this combination.

–Increases oxygen metabolism: More oxygen availability activates of the Krebs cycle, increases oxidative decarboxylation of pyruvate and ATP production. The additional supply of oxygen oxidizes the lipid layer of malignant cells and destroys them through cell lysis (apoptosis). Oxygen reacts with the unsaturated fatty acids of the lipid layer in cellular membranes, forming hydroperoxides. Lipid peroxidation products include peroxyl radicals and aldehydes that possess killer cell action.

–Increases circulation: Permits more oxygen, vitamin C and immune factors to be delivered to the tissues.

–Decreases bacteria/viral/fungi load: Microbes are important modulators of the immune system and, if not controlled, they can produce excess inflammation. Since inflammation is known to play a major role in the pathogenesis of cancer, microbial balance can influence tumor progression. This can occur by chronic activation of inflammation, alteration of tumor microenvironment, induction of genotoxic responses, reduction of immune action and metabolic derangements. (Francescone, Hou & Grivennikov, 2014)

1. c) Sodium bicarbonate: May correct tissue acidosis produced by increased fermentation. Sodium bicarbonate also has a specific ability that is, not possessed by other basic compounds to destroy fungi colonies. (Robey, Baggett, Kirkpatrick, et al., 2009; Robey, Martin, 2011)
2. d) Dichloroacetic Acid: May improve mitochondrial function by facilitating oxidative phosphorylation which is lacking in the cancer cell. (Robey, Martin, 2011; Xie, Wang, Yu, et al., 2011)
3. Level of Blood Glucose: (Agus, Vera & Golde, 1999; KC, Cárcamo & Golde, 2005) Excessive blood glucose can compete with vitamin C for the glut receptor sites. It is a good therapeutic approach to provide the high dose IV vitamin C in an empty stomach. Nevertheless we should be aware that sleepiness and hypoglycemia symptoms may arise. Receiving these IVs causes the body to produce insulin because it believes that the blood sugar is spiking. Patients might experience hypoglycemia-like symptoms. If their blood sugar is measured during the infusion of IV vitamin C, the meter reads an enormously high number because the body thinks that the vitamin C is sugar. So having a reduced level of blood sugar seems to be a necessary parameter to increase IV vitamin C’s anti- cancer effectiveness.
4. Physiological Red-Ox balance: (McEligot, Yang & Meyskens, 2005; Gonzalez, Miranda-Massari, 2014) The balance between oxidation and anti-oxidation is believed to be critical in maintaining healthy biological systems. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play important roles in regulation of cell survival. In general, moderate levels of ROS/RNS may function as signals to pro- mote cell proliferation and survival, whereas severe increases of ROS/RNS can induce cell death. Under physiologic conditions, the balance between generation and elimination of ROS/RNS maintains the proper function of redox-sensitive signaling proteins. Normally, the redox homeostasis ensures that the cells respond properly to endogenous and exogenous stimuli. However, when the redox homeostasis is disturbed, oxidative stress may lead to aberrant cell death and contribute to disease development. Redox balance plays a critical role in maintaining the biologic processes under normal conditions. Disruption of redox homeostasis will result in a deregulation of apoptosis associated with various diseases, including cancer, degenerative dis- eases, and aging. In general, ROS at low levels act as signaling molecules that promote cell proliferation, which controls cell division and sustains cell survival. In contrast, a severe increase in ROS can induce cell death. There is continuous demand for exogenous anti- oxidants in order to prevent oxidative stress, representing a disequilibrium redox state in favor of oxidation. However, high doses of isolated reductive compounds may be toxic, owing to pro-oxidative effects at high concentrations or their potential to react with beneficial concentrations of ROS normally present at physiological conditions that are required for optimal cellular functioning. All this said, the physiological Red-Ox state may also influence IV vitamin C effectiveness as an anticancer agent. We do not recommend the concomitant application of agents with anti-oxidative potential (such as glutathione, B-complex vitamins) given at the same time with IV vitamin C since they may interfere with the pro-oxidative activity of vitamin C and reduce its anticancer potential.

Competing Interests

The authors declare that they have no competing interests.

References

Abnet, C.C., (2007) Carcinogenic Food Contaminants, Cancer Investigation, 25(3) 189-96.

Aggarwal, B.B., Gehlot, P., (2009) Inflammation and Cancer: How Friendly is the Relationship for Cancer Patients?, Current Opinion in Pharmacology, 9(4) 351-369.

Agus, D.B., Vera, J.C. & Golde, D.W., (1999) Stromal Cell Oxidation: A Mechanism by which Tumors Obtain Vitamin C, Cancer Research, 59(18) 4555-4558.

Alavanja, M.C., Ross, M.K. & Bonner, M.R., (2013) Increased Cancer Burden Among Pesticide Applicators and Others Due to Pesticide Exposure, CA: A Cancer Journal for Clinicians, 63(2) 120-142.

Alibek, K., Kakpenova, A. & Baiken, Y., (2013) Role of Infectious Agents in the Carcinogenesis of Brain and Head and Neck Cancers, Infectious Agents and Cancer, 8(7)

Anand, P., Kunnumakara, A.B., Sundaram, C., et al., (2008) Cancer is a Preventable Disease that Requires Major Lifestyle Changes, Pharmaceutical Research, 25(9) 2097-2116.

Arlt, V.M., (2005) 3-Nitrobenzanthrone, A Potential Human Cancer Hazard in Diesel Exhaust and Urban Air Pollution: A Review of the Evidence, Mutagenesis, 20(6) 399-410.

Berrington de González, A., Mahesh, M., Kim, K., et al., (2007) Projected Cancer Risks from Computed Tomographic Scans Performed in the United States, Archives of Internal Medicine, 169(22) 2071-2077.

Bocci, V., Larini, A. & Micheli, V. (2005) Restoration of Normoxia by Ozone Therapy May Control Neoplastic Growth: A Review and a Working Hypothesis, Journal of Alternative Complementary Medicine, 11(2) 257-265.

Ciborowski, M., Lipska, A., Godzien, J., et al., (2012) Combination of LC-MS- and GC-MS-based Metabolomics to Study the Effect of Ozonated Autohemotherapy on Human Blood, Journal of Proteome Research, 11(12) 6231-6241.

Drisko, J.A., Chapman, J. & Hunter, V.J., (2003) The Use of Antioxidants with First-Line Chemotherapy in Two Cases of Ovarian Cancer, Journal of the American College of Nutrition, 22(2) 118-123.

Francescone, R., Hou, V. & Grivennikov, S.I., (2014) Microbiome, Inflammation, and Cancer, Cancer Journal, 20(3) 181-189.

Fowler, A.A. 3rd, Syed, A.A., Knowlson, S., et al., (2014) Phase I Safety Trial of Intravenous Ascorbic Acid in Patients with Severe Sepsis, Journal of Translational Medicine, 12(32).

Gach, K., Wyrebska, A., Fichna, J., et al., (2011) The Role of Morphine in Regulation of Cancer Cell Growth, Naunyn Schmiedeberg’s Archives of Pharmacology, 384(3) 221-30.

Giunta, R., Coppola, A., Luongo, C., et al,. (2001) Ozonized Autohemotransfusion Improves Hemorheological Parameters and Oxygen Delivery to Tissues in Patients with Peripheral Occlusive Arterial Disease, Annals of Hematology, 80(12) 745-748.

Gong, L., Dong, C., Ouyang, W., et al., (2013) Regulatory T cells: A Possible Promising Approach to Cancer Recurrence Induced by Morphine, Medical Hypotheses, 80(3) 308-310.

Gonzalez, M.J. and Miranda-Massari, J.R., (2014), Springer Briefs in Cancer Research: New Insights on Vitamin C and Cancer, New York, NY: Springer

Gonzalez, M.J., Miranda-Massari, J.R., Duconge, J., et al., (2012) The Bio-Energetic Theory of Carcinogenesis, Medical Hypotheses, 79(4) 433-439.

Gonzalez, M.J., Miranda-Massari, J.R., Mora, E.M., et al., (2005) A Orthomolecular Oncology Review: Ascorbic Acid and Cancer 25 Years Later, Integrative Cancer Therapies, 4(1) 32-44.

Hanahan, D., Weinberg, R.A., (2011) Hallmarks of Cancer: The Next Generation, Cell, 144(5) 646-674.

Head, K.A.,(1998) Ascorbic Acid in the Prevention and Treatment of Cancer, Alternative Medicine Review, 3(3) 174-186.

Hoffer, L.J., Levine, M., Assouline, S., et al., (2008) Phase I Clinical Trial of IV Ascorbic Acid in Advanced Malignancy, Annals of Oncology, 19(11), 1969-1974

Ichim, T.E., Minev, B., Braciak, T., et al., (2011) Intravenous Ascorbic Acid to Prevent and Treat Cancer-Associated Sepsis? Journal of Translational Medicine, 9(25).

KC S., Cárcamo, J.M. & Golde, D.W., (2005) Vitamin C Enters Mitochondria Via Facilitative Glucose Transporter 1 (Glut1) and Confers Mitochondrial Protection Against Oxidative Injury, FASEB Journal, 19, 1657- 1667.

King, B., Jiang, Y., Su, X., et al., (2013) Weight Control, Endocrine Hormones and Cancer Prevention, Experimental Biology and Medicine, 238(5) 502-508.

Knower, K.C., To, S.Q., Leung, Y.K., et al., (2014) Endocrine Disruption of The Epigenome: A Breast Cancer Link, Endocrine-Related Cancer, 21(2) T33-T55.

Lennon, F.E., Moss, J. & Singleton, P.A., (2012) The μ-Opioid Receptor in Cancer Progression: Is There a Direct Effect?, Anesthesiology, 116, 940-945

Lillberg, K., Verkasalo, P.K., Kaprio, J., et al., (2003) Stressful Life Events and Risk of Breast Cancer in 10,808 Women: A Cohort Study, American Journal of Epidemiology, 157(5) 415-423

Liu, C., Russell, R.M., (2008) Nutrition and Gastric Cancer Risk: An Update, Nutrition Reviews, 66(5) 237-249.

Mayland, C.R., Bennett, M.I. & Allan, K., (2005) Vitamin C Deficiency in Cancer Patients, Palliative Medicine, 19(1) 17-20.

McEligot, A.J., Yang, S. & Meyskens, F.L., (2005) Redox Regulation by Intrinsic Species and Extrinsic Nutrients in Normal and Cancer Cells, Annual Reviews Nutrition, 25, 261-295.

Mikirova, N., Casciari, J., Rogers, A., et al., (2012) Effect of High-Dose Intravenous Vitamin C on Inflammation in Cancer Patients, Journal of Translational Medicine, 10(189).

Mikirova, N., Hunninghake, R. (2014) Effect of High Dose Vitamin C on Epstein-Barr Viral Infection, Medical Science Monitor, 20, 725-732.

Moreno-Sánchez, R., Rodríguez-Enríquez, S., Marín-Hernández, A., et al., (2007) Energy Metabolism in Tumor Cells, FEBS J, 274(6) 1393- 418.

Murata, A., Morishige, F. & Yamaguchi, H., (1982) Prolongation of Survival Times of Terminal Cancer Patients by Administration of Large Doses of Ascorbate, International Journal for Vitamin Nutrition Research, Supplement, 23, 103-113.

Orlando, A., Russo, F., (2013) Intestinal Microbiota, Probiotics and Human Gastrointestinal Cancers, Journal of Gastrointestinal Cancer, 44(4) 121-131.

Padayatty, S.J., Sun, A.Y., Chen, Q., et al., (2010) Vitamin C: Intravenous Use by Complementary and Alternative Medicine Practitioners and Adverse Effects. PLoS ONE, 5(7): e11414. doi:10.1371/journal.pone.0011414

Pohanka, M., Pejchal, J., Snopkova, S., et al., (2012) Ascorbic Acid: An Old Player With a Broad Impact on Body Physiology Including Oxidative Stress Suppression and Immunomodulation: A Review, Mini Reviews in Medicinal Chemistry, 12(1) 35-43.

Reiche, E.M., Morimoto, H.K. & Nunes, S.M. (2005) Stress and Depression-Induced Immune Dysfunction: Implications for the Development and Progression of Cancer, International Review of Psychiatry, 17(6) 515-527.

Riordan, H.D., Casciari, J.J., González, M.J., et al., (2005) A Pilot Clinical Study of Continuous Intravenous Ascorbate in Terminal Cancer Patients, Puerto Rico Health Sciences Journal, 24(4), 269-276

Robey, I.F., Baggett, B.K., Kirkpatrick, N.D., et al., (2009) Bicarbonate Increases Tumor pH and Inhibits Spontaneous Metastases, Cancer Research, 69(6) 2260- 2268.

Robey, I.F., Martin, N.K., (2011) Bicarbonate and Dichloroacetate: Evaluating pH Altering Therapies in a Mouse Model for Metastatic Breast Cancer, BMC Cancer, 11, 235.

Schulz, S., Häussler, U., Mandic, R., et al., (2008) Treatment with Ozone/Oxygen-Pneumoperitoneum Results in Complete Remission of Rabbit Squamous Cell Carcinomas, International Journal of Cancer, 122(10) 2360-2367.

Sethi, G., Shanmugam, M.K., Ramachandran, L., et al., (2012) Multifaceted Link Between Cancer and Inflammation, Bioscience Reports, 32(1) 1-15.
Stephenson, C.M., Levin, R.D., Spector, T., et al., (2013) Phase I Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of High-Dose Intravenous Ascorbic Acid in Patients with Advanced Cancer, Cancer Chemotherapy and Pharmacology, 72(1) 139-146.

Sutandyo, N., (2010) Nutritional Carcinogenesis, Acta Medica Indonesiana, 42(1) 36-42.

Takahashi, H., Mizunob, H. & Yanagisawa, A., (2012) High-Dose Intravenous Vitamin C Improves Quality of Life in Cancer Patients, Person Med Univ, 1(_) 49–53.

Van Maele-Fabry, G., Hoet, P. & Lison, D., (2013) Parental Occupational Exposure to Pesticides as Risk Factor for Brain Tumors in Children and Young Adults: A Systematic Review and Meta-Analysis, Environment International, 56, 19-31.

Varela-Rey, M., Woodhoo, A., Martinez-Chantar, M.L., et al., (2013) Alcohol, DNA Methylation, and Cancer, Alcohol Research, 35(1) 25-35.

Vollbracht, C., Schneider, B., Leendert, V., et al., (2011) 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 Germany, In Vivo, 25(6), 983-990

Wayner, D.D.M., Burton, G.W., Ingold, K.U., Locke, S., (1985) Quantitative Measurement of the Total, Peroxyl Radical-Trapping Antioxidant Capability of Human Blood Plasma by Controlled Peroxidation: The Important Contribution Made by Plasma Proteins, FEBS, 187(1) 33-37.

Xie, J., Wang, B.S., Yu, D.H., et al., (2011) Dichloroacetate Shifts the Metabolism from Glycolysis to Glucose Oxidation and Exhibits Synergistic Growth Inhibition with Cisplatin in HeLa Cells, International Journal of Oncology, 38(2) 409-417.

Xue, J., Yang, S. & Seng, S., (2014) Mechanisms of Cancer Induction by Tobacco-Specific NNK and NNN,
Cancers (Basel), 6(2) 1138-1156.

Yeom, C.H., Jung, G.C. & Song, K.J., (2007) Changes of Terminal Cancer Patients’ Health-Related Quality of Life After High Dose Vitamin C Administration, Journal of Korean Medical Science, 22(1) 7