Journal List > J Korean Med Sci > v.22(1) > 1020487

Yeom, Jung, and Song: Changes of Terminal Cancer Patients' Health-related Quality of Life after High Dose Vitamin C Administration

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 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.

INTRODUCTION

Numerous studies explored the efficacy of vitamin C in the treatment of cancer, but their mixed findings caused a great deal of controversy. In 1949, Klenner first suggested the possibility of using vitamin C for the treatment of cancer. In 1952, McCormick asserted that vitamin C has been proposed as a chemotherapeutic agent. Hundreds of articles including an array of in vitro, in vivo, cell culture, animal, and human studies have been published on this topic. As a result, it is believed that vitamin C might have anti-cancer effects (1-3).
Twenty-six years ago, Cameron et al. reported that they increased the time of survival of cancer patients and improved their quality of life by administrating high doses of vitamin C (4). As a result, Pauling and Cameron continuously asserted the effect of vitamin C on cancer. However, Moertel et al. (Mayo Clinic) reported that high-dose vitamin C therapy was not effective against advanced cancer (5). This finding is critical because it may prevent clinicians from using vitamin C for cancer patients.
A critical point of both studies (Cameron et al. and Moertel et al.) is that they used a different administration method, intravenous route in the former and oral route of vitamin C in the latter. Oral absorption of vitamin C cannot achieve plasma concentrations comparable to those obtained by intravenous administration. Moreover, it has been recently reported that vitamin C acts as a toxic agent against cancer cells when given intravenously (6).
Unlike most mammals, human and other primates cannot synthesize vitamin C from glucose due to L-gulonolactone oxidase deficiency. Therefore, we must be obtained adequate amounts of this nutrient from foods and supplements. Vitamin C plays a crucial role in the synthesis of L-carnitine from lysine, neurotransmitters synthesis, cytochrome p-450 activity, cholesterol metabolism, detoxification of exogenous compounds and as an antioxidant (7-10). In addition, when given in large doses, vitamin C may function as an ergogenic agent (11). Because the levels of vitamin C in the blood of the cancer patients were significantly decreased compared to healthy persons, cancer patients required larger amounts of vitamin C (12, 13).
Improved health-related quality of life is important as much as a cure of cancer in terminally ill cancer patients who have an estimated survival of less than 6 months. The objective of this study was to examine changes in the quality of life in terminally ill cancer patients after administration of high-doses of vitamin C.

MATERIALS AND METHODS

Study subjects

Outpatients with terminal cancer who were treated in the Department of Family Medicine, Myungji-Hospital, Kwandong University College of Medicine from 1 February 2004 through 31 August 2005, were included in the study. The study included 39 cancer patients (male: 20, female: 19) after excluding those who were undergoing chemotherapy.

Assessment of cancer patients' life-related quality

A written consent was obtained from all patients. They 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 1 week after administration of vitamin C.
Demographic data included sex, age, cancer diagnosis, anti-cancer therapy, recurrence, metastasis and performance status (Eastern Cooperative Oncology Group, ECOG). Quality of life was assessed by the European Organization for Research and Treatment of cancer (EORTC). This was a self-administrated questionnaire (EORTC) that was used to assess the quality of life of the patients. When a patient was unable to self-administer the questionnaire, an interviewer or the patient's caregiver completed the questionnaire after finding out answers from the patient. The Korean version of the European Organization for Research and Treatment of cancer core quality-of-life questionnaire (EORTC QLQ-C30) was used as the questionnaire. It was designed to ask clinical symptoms experienced by the patients during the previous week. The questionnaire consists of 30 items, that comprise a global evaluation of health status and quality of life, five functions (physical, role, emotional, cognitive, and social), three symptoms (fatigue, pain, and nausea/vomiting), and six additional single items (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial impact of the disease and treatment) (14). Scores for each scale on the EORTC QLQ-C30 questionnaire were calculated as suggested by the EORTC Study Group on Quality of Life. All of the scales and single-item measures ranged in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for the global health status/quality of life represents a high quality of life and a high score for a functional scale represents a high/health level of functioning. But a high score for a symptom scale/item represents a high level of symptomatology/problems.

Statistical analysis

The EORTC scales scores before and after administration of vitamin C, were compared using the Wilcoxon signed rank-test. A p-value of less than 0.05 is considered statistically significant.

RESULTS

Demographic data

The demographic data (age, sex, cancer diagnosis, anti-cancer therapy, metastasis, performance status) are shown in Table 1. All patients were stage IV, and 12 (30.8%) patients experienced a recurrence of their cancers. No patients were excluded due to side effects of vitamin C.

Quality of life (EORTC)

The quality of life before and after administration of high dose vitamin C, are shown in Table 2. 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 scales, the patients reported significantly higher scores for physical, role, emotional, cognitive, and social function after administration of vitamin C (p<0.005). In symptom scales, the patients reported significantly lower scores for fatigue, nausea/vomiting, pain, sleep disturbance, and appetite loss after administration of vitamin C (p<0.005). The other symptom scales such as dyspnea, constipation, diarrhea, financial impact were not significantly changed after administration of vitamin C.

DISCUSSION

In terminal cancer patients, the quality of life is as important as cure. The treatment for terminal cancer patients was particularly focused on the patient's well-being in addition to the efforts to minimize symptoms. Thus, the ultimate goal of treatment for terminal cancer patients can differ from those pursued in treatments designed to cure.
If terminal cancer patients were concerned about emotional changes and functional impairment and if the patients' quality of life did not improve, the treatment that they underwent should not be considered successful even though it extended their life expectancy. Although investigators are divided in their opinions on whether vitamin C is effective for the treatment of cancers, many of them reported that cancer patients showed improvement in their quality of life.
This study also demonstrated improvement in global health/quality of life in terminal cancer patients after administration of vitamin C along with improvements in all functions (physical, role, emotional, cognitive, and social) and some symptoms (fatigue, nausea/vomiting, pain, sleep disturbance, and appetite loss).
The therapeutic impacts of vitamin C, expected when administered to terminal cancer patients, include anticancer effects, positive impact on the central nervous system and mental ability, pain relief and contribution to energy generation. The anticancer effects of vitamin C boost cytotoxicity of tumor cells, collagen synthesis, antioxidant action, immunity system and low concentration of certain amino acids. First, the mechanism underlying the action of vitamin C in combating cancer cells explains that vitamin C in blood is oxidized to dehydroascorbate acid, which passes freely back and forth through the cell membranes via glucose transport. When dehydroascorbate acid enters cancer cells, glutathione turned the dehydroascorbate back into ascorbic acid (vitamin C), which is not allowed to move out of cancer cells. This ascorbic acid is converted to dehydroascorbate again and produces H2O2, which destroy cancer cells (15). Higher levels of ascorbic acid were observed around cancer cells when compared to normal cells (16). Casciari et al. study reported tumor cells apoptosis occurred in 42.9% of total patients and necrosis in 24.4% when patients' blood level of vitamin C was 11.2 mM. They said apoptosis increased to 57.6% and necrosis to 33.1%, respectively, when patients' blood level of vitamin C rose to 33.7 mM (17). Secondly, an increase in the synthesis of collagen inhibits the growth of cancer cells, leading to apoptosis and necrosis in cancer cells (18). That is, cancer cells releases collagenase and dissove collagen between cells/tissues. This means that these enzymes dissolve basement membranes, an organization of collagen and extracellular matrices, enabling cancer cells to infiltrate and destroy adjacent normal tissues. An increase in collagen synthesis due to vitamin C would however increase membrane mechanical integrity and cohesion and eventually prevent the growth of cancer cells. Thirdly, antioxidant properties of vitamin C inhibit cancer growth induced by free radicals (3, 19). It is however an interesting fact that vitamin C is taken up in oxidized form by cancer cells. Fourthly, vitamin C enhances the immune system by elevating the production of infection-fighting white blood cells and interferon levels, so cancer cells are suppressed or eliminated (20, 21). Last, the vitamin C can change the levels of certain amino acids in body fluids and may deplete the bioavailability of lysine and cyteine, 2 amino acids that required for rapidly growing tumors (22, 23).
The impact of vitamin C on the central nervous system and mental ability is based on the following mechanisms: First, increased c-AMP enables vitamin C to block phosphodiesterase, so the breakdown of c-AMP can be prevented (24). An increase in blood c-AMP levels therefore boosts mental ability. Secondly, vitamin C also prevents the formation of toxic neurotransmitters. Vitamin C deficiency triggers the oxidation of adrenalin and noradrenalin, and adrenochrome and noradrenochrome are generated, respectively, and their toxic effects pose various problems (25).
The impact of vitamin C on pain relief is explained by various mechanisms (26). First, vitamin C has anti-inflammatory effects by stimulating c-AMP production, which in turn elevates production of steroid in the ACTH. Secondly, vitamin C works to help decrease blood calcium levels and enhances calcium uptake in bone. As a result, bone pain is relieved (27).
It was recently discovered that vitamin C also supports the body's energy generation (28). The mechanism of ergogenic activity of vitamin C is probably due to vitamin C's oxidation reduction potential, capable of providing necessary electrons to the electron transport system in the mitochondria for increased energy production.
Since Szent-Gyorgyi reported the efficacy of vitamin C for the first time in 1928, studies in the same area have continued and anticancer effects of vitamin C are still under debate. While Cameron et al. suggested beneficial effects of vitamin C on the treatment of cancer (4), the Mayo Clinic study reported no anticancer effects of vitamin C (5). Investigators cited the different administration method as the reason for such opposite results. The former used intravenous vitamin C administration at a dose of 10 g and subsequent oral administration, whereas the latter used oral administration only. Padayatty et al. proved that it was difficult to increase vitamin C level to more than 220 M/L in blood through oral administration and that blood levels of vitamin C that are required for combating cancer could be achieved through intravenous adminstration (6). Their findings provided the scientific basis for using intravenous administration in cancer patients.
Vitamin C is a water-soluble and remarkably nontoxic at high levels. Nevertheless, this treatment should be administered with caution to patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency (29). When given high doses of vitamin C, these patients may have the risk of developing hemolysis. Before applying vitamin C therapy, patients should be screened for this deficiency.
Although there is still controversy regarding anticancer effects of vitamin C, the use of vitamin C is considered the safe and effective therapy to improve the quality of life in terminal cancer patients. The further study is required to compare effects of vitamin C in between placebo and vitamin C group in terminal cancer patients with well-designed experimental strategy.

Figures and Tables

Table 1
Demographic data
jkms-22-7-i001
Table 2
Change of terminal cancer patients' health-related quality of life (EORTC) after high dose vitamin C adminstration
jkms-22-7-i002

Notes

This research was supported by Huons Co. Ltd.

References

1. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK, Levine M. Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr. 2003. 22:18–35.
crossref
2. Tamayo C, Richardson MA. Vitamin C as a cancer treatment: state of the science and recommendation for research. Altern Ther Health Med. 2003. 9:94–101.
3. Gonzalez MJ, Miranda-Massari JR, Mora EM, Guzman A, Riordan NH, Riordan HD, Casciari JJ, Jackson JA, Roman-Franco A. Orthomolecular oncology review: ascorbic acid and cancer 25 years later. Integrative Cancer Therapies. 2005. 4:32–44.
4. Cameron E, Pauling L, Leibovitz B. Ascorbic acid and cancer: a review. Cancer Res. 1979. 39:663–681.
5. Moertel CG, Fleming TR, Creagan ET, Rubin J, O'Connell MJ, Ames MM. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. A randomized double-blind comparison. N Engl J Med. 1985. 312:137–141.
6. Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, Wesley RA, Levine M. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med. 2004. 140:533–537.
crossref
7. Levine M. New concepts in the biology and biochemistry of ascorbic acid. N Engl J Med. 1986. 314:892–902.
crossref
8. Sies H, Stahl W, Sundquist AR. Antioxidant functions of vitamins. Ann N Y Acad Sci. 1992. 669:7–20.
crossref
9. Leibovitz B, Mueller J. Carnitine. J Optimal Nutr. 1993. 2:90–109.
10. Block G. Vitamin C and cancer prevention: the epidemiologic evidence. Am J Clin Nutr. 1991. 53:270S–282S.
crossref
11. Komarova SV, Ataullakhanov FI, Globus RK. Bioenergetics and mitochondrial transmembrane potential during differentiation of cultured osteoblasts. Am J Physiol Cell Physiol. 2000. 279:C1220–C1229.
crossref
12. Khanzode SS, Muddeshwar MG, Khanzode SD, Dakhale GN. Antioxidant enzymes and lipid peroxidation in different stages of breast cancer. Free Radic Res. 2004. 38:81–85.
crossref
13. Lee JG, Chung HW, Lee KH, Ahn HS. Antioxidant vitamins and lipid peroxidation in patients with cervical intraepithelial neoplasia. J Korean Med Sci. 2005. 20:267–272.
crossref
14. Yun YH, Park YS, Lee ES, Bang SM, Heo DS, Park SY, You CH, West K. Validation of the Korean version of the EORTC QLQ-C30. Qual Life Res. 2004. 13:863–868.
crossref
15. Agus DB, Vera JC, Golde DW. Stromal cell oxidation: a mechanism by which tumors obtain vitamin C. Cancer Res. 1999. 59:4555–4558.
16. Langemann H, Torhorst J, Kabiersch A, Krenger W, Honegger CC. Quantitive determination of water and lipid soluble antioxidants in neoplastic and non-neoplastic human breast tissue. Int J Cancer. 1989. 43:1169–1173.
17. Casciari JJ, Riordan NH, Schmidt TL, Meng XL, Jackson JA, Riordan HD. Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours. Br J Cancer. 2001. 84:1544–1550.
crossref
18. Henson DE, Block G, Levine M. Ascorbic acid: biologic functions and relation to cancer. J Natl Cancer Inst. 1991. 83:547–550.
crossref
19. Do MH, Lee SS, Jung PJ, Lee HY. Intake of dietary fat and vitamin in relation to breast cancer risk in Korean women: a case-control study. J Korean Med Sci. 2003. 18:534–540.
crossref
20. Cameron E, Pauling L. Vitamin C and the immune system. Cancer and vitamin C. 1990. 2nd ed. USA: Camino Book;108–111.
21. Basu TK. Hanck A, Ritzel G, editors. Possible role of vitamin C in cancer therapy. Vitamin C: Recent Advances and aspects in virus disease, Cancer and in lipid metabolism. 1979. Hans Huber;95–102.
22. Tsao CS, Miyashita K. Effects of high intake of ascorbic acid on plasma levels of amino acids. IRCS Med Sci. 1984. 12:1052–1053.
23. Tsao CS, Miyashita K. Effects of large intake of ascorbic acid on urinary excretion of amino acids and related compounds. IRCS Med Sci. 1985. 13:855–856.
24. Lewin S. The link between ascorbate and c-AMP and c-GMP. Vitamin C: Its molecular biology and medical potential. 1976. London: Academic Press;93–98.
25. Lewin S. Activity of ascorbate in the adrenals. Vitamin C: Its molecular biology and medical potential. 1976. London: Academic Press;98–101.
26. Jensen NH. Reduced pain from osteoarthritis in hip joint or knee joint during treatment with calcium ascorbate. Ugeskr Laeger. 2003. 165:2563–2566.
27. Lewin S. Maintenance of physiological actions by c-AMP and c-GMP. Vitamin C: Its molecular biology and medical potential. 1976. London: Academic Press;92–93.
28. Luo G, Xie ZZ, Liu FY, Zhang GB. Effect of vitamin C on mitochondrial function and ATP content in hypoxic rats. Zhongguo Yao Li Xue Bao. 1998. 19:351–355.
29. Rivers JM. Safety of high-level vitamin C ingestion. In: Third conference on AA. Ann NY Acad Sci. 1987. 498:445–454.
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