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Vitamin C & Treatment of Cancer. Abstracts and Commentary from the Scientific LiteraturePart I By Gary Null, PhD; Howard Robins, DPM; Mark Tanenbaum, DPM; and Patrick Jennings, Editor. Townsend Letter for Doctors & Patients - May 1997
Why Review the Scientific Literature? Proper basic nutrition is an essential foundation for health, but there is a growing awareness that it's not enough. One has only to consider the high disease rates in our society - infectious diseases are now the third largest killer in the US as well as the first in the world, and our rates of cancer, arthritis, and mental illness are not abating - to realize that we have to go beyond basic nutrition in combating disease.
It is time to look at supplemental nutrients in a serious light, in order to better understand their role in helping our natural immune defenses prevent disease, and in altering the course of disease as well.
People talk about orthodox medicine and alternative medicine as if there's a great divide between the two, but there's really no need for such a dichotomy.
The bottom line in healing and in maintaining health is really the question, What works? and we should feel free to ask it in evaluating the offerings of both realms, and to combine the best of both. After all, the evidence that something works - not the label you give it - is the important factor in evaluating whether a given treatment, or mode of prevention, is of value.
Following is a review of the scientific literature as it pertains to the impact of vitamin C on cancer. The questions, "What works?" and "How might it be applied?" were the motivational ones behind this review. As this one does, each review will include only well-designed studies from peer-reviewed journals. Original journal citations are given, along with capsule descriptions of the original scientific abstracts.
In other words, what follows is not anecdotal evidence; it is scientific evidence. We can now move beyond the stage of allowing quackbusters, apologists for special interest groups, and other adherents of the flat-earth school of intellectual inquiry to maintain that there's no evidence of the disease-fighting value of nutrients. Because, quite simply, there is, and here it is.
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This review article notes that approximately 90 studies have been done on the role of vitamin C in cancer prevention, with most finding statistically significant effects. Protective effects have been shown for cancers of the pancreas, oral cavity, stomach, esophagus, cervix, rectum, breast, and lung.
- G. Block, et al., Epidemiologic Evidence Regarding Vitamin C and Cancer, American Journal of Clinical Nutrition, 54 (6 Suppl), December 1991, p. 1310S-1314S.
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Daily supplementation of lg of vitamin C decreased the amount of chromosome damage induced in lymphocytes by an exposure to bleomycin during the last 5 h of cell culture. The authors suggest a similar assay for genetic instability might be helpful in detecting heterozygotes for chromosome-breakage syndromes and recommend considering dietary and lifestyle factors when interpreting results from this bleomycin assay and related assays for genetic instability.
- H. Pohl and J.A. Reidy, Vitamin C Intake Influences the Bleomycin-induced Chromosome Damage Assay: Implications for Detection of Cancer Susceptibility and Chromosome Breakage Syndromes, Mutat Research, 224(2), October 1989, p. 247-252.
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A ternary antioxidant vitamin mix consisting of ascorbic acid, alpha-tocopherol and lecithin as well as a rosemary extract with carnosic acid and carnosol as the two major active ingredients were shown to exhibit strong antimutagenic effects in Ames tester strain TA102. Ascorbic acid was held responsible for this inhibitory property in the vitamin mix, while carnosic acid was identified as the antimutagenic agent in the rosemary extract. The authors conclude that these antioxidants might exhibit anticarcinogenic properties.
- M. Minnunni, et al., Natural Antioxidants as Inhibitors of Oxygen Species Induced Mutagenicity, Mutat Research, 269(2), October 1992, p. 193-200.
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A mixture of ascorbic acid and cupric sulfate significantly inhibited human mammary tumor growth in mice when administered orally, while the administration of either alone did not. The activity of D-isoascorbic acid was similar to that of ascorbic acid. The authors suggest ascorbic acid's anti-tumor activity was due to its chemical properties rather than the metabolism of ascorbic acid as a vitamin.
- C.S. Tsao. Inhibiting Effect of Ascorbic Acid on the Growth of Human Mammary Tumor Xenografts, American Journal of Clinical Nutrition, 54 (6 Suppl), December 1991, p. 1274S-1280S.
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In this study, vitamin C was shown to decrease kidney tumor incidence by approximately 50% in Syrian hamsters, lower the concentration of diethylstilbesterol-4',4"-quinone, the genotoxic metabolite of diethylstilbestrol, in vitro and in hamsters treated with stilbene, and decreases the levels in hamsters of DES-DNA adducts formed by the quinone metabolite. Noting that estrogens may spawn tumors by their metabolic oxidation to corresponding quionone metabolites, the authors argue that vitmain C may inhibit the formation of tumors by decreasing concentrations of quinone metabolites and their DNA adducts.
- J.G. Liehr, Vitamin C Reduces the Incidence and Severity of Renal Tumors Induced by Estradiol or Diethylstilbestrol, American Journal of Clinical Nutrition, 54 (6 Suppl), December 1991, p. 1256S-1260S.
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This paper reports on the results of two large-scale studies of L-ascorbic acid in the food on tumor-free survival in mice. The first found that increasing ascorbic acid in the diet significantly delayed the development of spontaneous mammary tumors, with the median age at first tumor at 124.9 weeks in the highest-dose ascorbate group and 82.5 week in ad libitum controls. The proportion of mice with tumors was also reduced. The second discovered a significant effect of ascorbate in delaying the onset and reducing the incidence of malignant lesions. Approximately five-times the number of mice developed lesions in the zero-ascorbate as in the high ascorbate group after 20 weeks of administration.
- L. Pauling, Effect of Ascorbic Acid on Incidence of Spontaneous Mammary Tumors and UV-Light-Induced Skin Tumors in Mice, American Journal of Clinical Nutrition, 54 (6 Suppl), December 1991, p. 1252S-1255S.
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Ascorbate stabilizes the normal state of the avian tendon cell by reducing Rous sarcoma virus production and promoting the synthesis of differentiated proteins which allows the virus to coexist within the cell rather than completely take it over.
- R.I. Schwarz, Ascorbate Stabilizes the Differentiated State and Reduces the Ability of Rous Sarcoma Virus to Replicate and to Uniformly Transform Cell Cultures, American Journal of Clinical Nutrition, 54 (6 Suppl), December 1991, p. 1247S-1251S.
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Noting theories that ascorbic acid might lower the risk of gastric cancer by preventing their formation within gastric juice, the authors measured both gastric juice ascorbic and total vitamin C in subjects and found that ascorbic acid is secreted into the gastric lumen so that gastric juices are frequently higher than concentrations in plasma. Gastric pathology affects this secretion, leading to values in gastric juice that are lower than plasma levels.
- C.J. Schorah, et al., Gastric Juice Ascorbic Acid: Effects of Disease and Implications for Gastric Carcinogenesis, American Journal of Clinical Nutrition, 58 (1 Suppl), January 1991, p. 287S-293S.
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This case-control study evaluated the association between specific substances of the diet and invasive cervical cancer in four Latin American countries. Vitamin C was shown to significantly decrease the risk of invasive cervical cancer, as was the case with beta-carotene and other carotenoids. These results are consistent with those from other studies suggesting a protective role for vitamin C in the development of invasive cervical cancer.
- R. Herrero, et al., A Case-Control Study of Nutrient Status and Invasive Cervical Cancer: I. Dietary Indicators, American Journal of Epidemiology, 134 (11), December 1, 1991, p. 1335-1345.
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2,974 men participating in the third examination of the prospective Basel Study in 1971-1973 were measured for plasma antioxidant vitamins A, C, and E, and carotene. Low mean plasma levels of carotene adjusted for cholesterol and of vitamin C was associated with overall mortality from cancer. Lower mean vitamin C levels were found to increase the risks of stomach cancer and gastrointestinal cancer in older subjects. In light of these results for vitamin C, in combination with those of the other vitamins studied, the authors conclude that low levels of antioxidants are associated with an increased risk of mortality from numerous cancers.
- H.B. Stahelin, et al., Plasma Antioxidant Vitamins and Subsequent Cancer Mortality in the 12-year Follow-up of the Prospective Basel Study, American Journal of Epidemiology, 133(8), April 15, 1991, p. 766-775.
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Inverse relationships were found between intake of carotenoids, vitamin E, and vitamin C and the incidence of lung cancer among nonsmokers in a 20 year follow-up study of 4,538 initially cancer-free Finnnish men. The authors suggest that increased intake of these nutrients may protect against the development of lung cancer among nonsmokers.
- P. Knekt, et al., Dietary Antioxidants and the Risk of Lung Cancer, American Journal of Epidemiology, 134(5), September 1, 1991, p. 471-479.
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NAC administered in doses from 0.1 to 10 mmol/L reduced the number of mutagenic-induced breaks per cell in a range from 23% to 73%. In a dose range from 0.01 to 1 mmol/L, ascorbic acid reduced chromosomal breakage by 21% to 58%. These results illustrate NAC and ascorbic acid's protective effects mediated in vitro against mutagen-induced chromosomal damage. The difference in occurrence of head and neck cancer between population with varying diets may be explained by related in vivo phenomenon.
- Z. Trizna, et al., Effects of N-acetyl-L-cysteine and Ascorbic Acid on Mutagen-induced Chromosomal Sensitivity in Patients with Head and Neck Cancers, American Journal of Surgery 162(4), October 1991, p. 294-298.
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One hundred fifty-eight samples from 139 lung-cancer patients were examined with respect to levels of plasma and buffy-coat vitamin C. Diet dependent hypovitaminosis C tended to be present in the majority of samples and proved capable of being increased by oral supplementatiom Assays demonstrated that tumors had a greater vitamin C content than normal lung tissue.
- H.M. Anthony and C.J. Schorah, Severe Hypovitaminosis C in Lung-Cancer Patients: The Utilization of Vitamin C in Surgical Repair and Lymphocyte-Related Host Resistance, British Journal of Cancer, 46(3), Sept. 1982, p. 354-367.
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Beta carotene and ascorbic acid were shown to persistently protect against colorectal cancer in this case-controlled study of 828 patients with colon cancer and 498 patients with rectal cancer in Northern Italy.
- M. Ferraroni, et al., Selected Micronutrient Intake and the Risk of Colorectal Cancer, British Journal of Cancer, 70(6), December 1994, p. 1150-1155.
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Vitamin C supplement use was shown to be inversely related to bladder and colon cancer in women in an 8 year follow-up study beginning in 1981 of 11,580 residents of a retirement community initially free from cancer.
- A. Shibata, et al., Intake of Vegetables, Fruits, Beta Carotene, Vitamin C and Vitamin Supplements and Cancer Incidence Among the Elderly: A Prospective Study, British Journal of Cancer (1992 Oct) 66(4), Oct. 1992, p. 673-679.
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This double-blind, placebo-controlled study examined the relationship between ascorbic acid and large bowel adenomas. 3 g/day of ascorbic acid reduced polyp area in the treatment group at nine months of follow-up and resulted in a trend toward the decrease in both area and number of rectal polyps midway through the trial.
- H.J. Bussey, et al., A Randomized Trial of Ascorbic Acid in Polyposis Coli, Cancer, 50(7), October 1, 1982, p. 1434-1439.
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Human neoplastic cell lines MCF-7 (breast carcinoma), KB (oral epidermal carcinoma), and AN3-CA (endometrial adenocarcinoma) were studied relative to the effects of in vivo administration either in combination or alone of sodium ascorbate (vitamin C) and 2-methyl-1,4-napthoquinone (vitamin K3). When administered separately, vitamin C or K3 showed a growth inhibiting effect but only at high concentrations (5.10(3) mumol/1 and 10(5) nmol/l, respectively). When administered in combination, both vitamins showed a synergistic inhibition of cell growth at 10 to 50 times lower concentrations. The addition of catalase to the culture medium containing vitamins C and K3 totally suppressed this tumor cell growth inhibitory effect. The authors argue this suggests an excessive production of hydrogen peroxide as being implied in mechanisms responsible for the tumor cell growth inhibitory effects.
- V. Noto, et al., Effects of Sodium Ascorbate (Vitamin C) and 2-methyl-1,4-Naphthoquinone (Vitamin K3) Treatment on Human Tumor Cell Growth in Vitro. I. Synergism of Combined Vitamin C and K3 Action, Cancer, 63(5), March 2, 1989, p. 901-906.
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In this hospital based, case-control study of lung cancer, a strong protective effect for squamous and small cell carcinoma was associated with dietary vitamin C intake based on data obtained from food frequency questionnaires.
- E.T. Fontham, et al., Dietary Vitamins A and C and Lung Cancer Risk in Louisiana, Cancer, 62(10), November 15, 1988, p. 2267-2273.
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The effects of 6-hydroxydopamine (6-OHDA) and H202 on metabolic parameters critical for cell survival were examined in cells with low and high ferritin content in the presence and absence of ascorbate in this study. Human neuroblastoma SKN-SH cells were pretreated with 100 microM FeSO4 and 10 microM desferrioxamine, respectively, for 24 hours yielding cells with different ferritin contents. The most pronounced effects were in ferritin-rich cells and in the presence of ascorbic acid. Using isolated CCC PM2 DNA, 6-OHDA and ascorbic acid caused strand breaks that were prevented in the presence of mannitol or desferrithiocine. H202-mediated strand breaks were observed only in the presence of ascorbic acid. The authors suggest their data along with the results of previous studies, suggests that high dosages of ascorbic acid continuously applied may be an effective new approach in neuroblastoma therapy.
- G. Bruchelt, et al., Ascorbic Acid Enhances the Effects of 6-Hydroxdopamine and H202 on Iron-Dependent DNA Strand Breaks and Related Processes in the Neuroblastoma Cell Line SK-N-SH, Cancer Research, 51(22), November 15, 1991, p. 6066-6072.
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This study involving patients with acute nonlymphocytic leukemia found that the numbers of leukemic bone marrow cell colonies grown in culture were decreased 21% of control in 7/28 patients by adding 0.3 milliM of L-ascorbic acid to the culture medium. Concentrations of L-ascorbic acid as low as 0.1 milliM was capable of suppressing the leukemic cell colony in cultures of both leukemic and normal marrow cells. However, 1 milliM of L-ascorbic acid was required for suppression of normal myeloid colonies. Based on their results, the authors argue that the achieved suppression was a specific effect of L-ascorbic acid and was not due to its oxidation-reduction potential or pH change since normal hemopoietic cells were not suppressed while leukemic cells were selectively affected at an L-ascorbic acid concentration attainable in vivo.
- C.H.J. Park, et al., Growth Suppression of Human Leukemic Cells in Vitro by L-Ascorbic Acid, Cancer Research, 40(4), 1980, p. 1062-1065.
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This in vitro study on the effects of L-ascorbic acid (LAA) on the growth of human leukemic colony-forming cells (L-CFC) demonstrated that L-CFC growth suppression by LAA is observed in one-sixth of leukemic patients, L-CFC enhancement in one-third of patients, and that L-CFC growth enhancement is a significant discovery with a biological mechanism as the basis.
- C.H. Park, Biologial Nature of the Effect of Ascorbic Acids on the Growth of Human Leukemic Cells, Cancer Research, 45(8), August 1985, p. 3969-3973.
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Eighty-one patients with premalignant lesions of the oral cavity were given 30 mg of beta-carotene, 1000 mg of ascorbic acid, and 800 IU of alpha tocopherol daily for nine months, 55.6% experienced either complete or partial clinical resolution of their lesions. Based on these findings, the authors recommend the use of antioxidant supplements as a treatment for oral premalignant lesions.
- G. Kaugars, et al., Serum and Tissue Antioxidant Levels in Supplemented Patients with Premalignant Oral Lesions (Meeting abstract), FASEB Journal, 7(4), 1993, A519.
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This study examined levels of vitamin C and ascorbic acid in the gastric juice of 77 patients suffering from dyspepsia. Gastric concentrations of vitamin C and ascorbic acid were significantly lower in chronic gastritis patients and patients with hypochlorhydia were found to have particularly low levels of ascorbic acid concentrations.
- G.M. Sobala, et al., Ascorbic Acid in the Human Stomach, Gastroenterology, 97(2), August 1989, p. 357-368.
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In this placebo-controlled study, vitamin supplementation was examined in relation to its effects on cell kinetics in uninvolved rectal mucosa patients with colorectal adenomas. Vitamins A, C, and E were administered to 20 subjects 6 months after complete polypectomy. Results indicate that supplementation was successful in reducing abnormalities in cell kinetics that may indicate a precancerous condition.
- G.M. Paganelli, et al., Effect of Vitamin A, C and E Supplementation on Rectal Cell Proliferation in Patients with Colorectal Adenomas, Journal of the National Cancer Institute, 84(1), January 1, 1992, p. 47-51.
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In this case-control study of 117 in situ cervical patients, plasma vitamin C was found to reduce the risk of cancer by 60%.
- K. E. Brock, et al., Nutrients in Diet and Plasma and Risk of in Situ Cervical Cancer, Journal of the National Cancer Institute, 80(8), June 15, 1988, p. 580-585.
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This case-control study of 419 colon and rectal cancer patients found that dietary vitamin C intake resulted in reduced risk of rectal cancer in women.
- J.D. Potter and A.J. McMichael, Diet and Cancer of the Colon and Rectum: A Case-Control Study, Journal of the National Cancer Institute, 76(4), April 1986, p. 557-569.
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Noting that the use of ascorbate to treat cancer began in 1971, this case-control study involved over 300 patients with cancer who received 2.5 g of vitamin C four times a day in combination with standard surgical treatment and radiotherapy (a few cases of chemotherapy). Two hundred sixty-six patients with incurable cancer were found to benefit significantly from the vitamin C therapy which was shown to have significant benefits for those suffering from cancer of the stomach and colon, while there was a similar trend for those with cancer of the bladder. Based on their results, the authors conclude that ascorbate in high doses can improve survival in certain types of cancer.
- L. Moffat, et al., High Dose Ascorbate Therapy and Cancer, NFCR Cancer Research Association Symposium, (2), 1983, p. 243-256.
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This review article on the effects of vitamins A, C, E, and selenium on cancer cites research pointing to ascorbic acid's ability to prevent formation of nitrosamine and other N-nitroso compounds. Studies also show supplementation with vitamin C can inhibit skin, nose, kidney, lung and tracheal cancer.
- D.F. Birt, Update on the Effects of Vitamins A, C, and E and Selenium on Carcinogenesis, Proc Soc Exp Biol Med, 183(3), December 1986, p. 311-320.
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The administration of ascorbic acid (0.1-20 micrograms/ml for the first week) was found to suppress X-ray induced transformation of C3H1OT1/2 cells in a concentration-dependent manner after irradiation. Cells initiated by radiation remained vulnerable to ascorbic acid up until the moment of morphological phenotype expression. Based on these findings, the authors postulate that expression of the neoplastically transformed phenotype is promoted by reactive oxygen species and peroxy radicals generated in cells during the whole assay period and they suggest their data might be helpful as a guide for chemopreventive efforts against radiation carcinogenesis.
- M. Yasukawa, et al., Radiation-induced Neoplastic Transformation of C3HlOT1/2 Cells is Suppressed by Ascorbic Acid, Radiation Research, 120(3), December 1989 p. 456-467.
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This study found that pretreatment of tumor target cells in vitro with a combination of interferon and ascorbate resulted in a 71% increase in growth inhibition of target cells compared to inhibition with interferon by itself. Administration of ascorbate alone showed minimal effect on tumor target cell growth in human monocytes.
- M .J. Skeen, et al., Synergy of Interferon and Ascorbic Acid in Stimulating Human Monocyte Cytostasis Against Tumor Target Cells, Rev Latinoam Oncology Clin, 13(4), 1981, p. 9-14.
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Vitamin C (85 mg/kg) ingestion has been shown to result in a reduction in DNA single strand breaks induced by ionizing radiation in human lymphocytes, as indicated by a significant decrease in overall comet length in both unirradiated control and the dose response to ionizing radiation damage. The effect was found to persist for up to six hours.
- C. F. Arlett, et al., The Modulation of DNA Damage in Human Lymphocytes by Dietary Vitamin C Supplementation, Molecular Mechanisms in Radiation Mutagenesis and Carcinogenesis April 19-22, 1993, Doorwerth, The Netherlands.
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Patients with oral leukoplakia were administered 30 mg of beta-carotene, 1000 mg of ascorbic acid, and 800 IU of alpha-tocopherol per day for 9 months. 55.6% of the 81 patients who completed the study showed either partial or complete clinical resolution of their oral lesions.
- G. Kaugars, et al., The Role of Antioxidants in the Treatment of Oral Leukoplakia, CCPC-93: Second International Cancer Chemo Prevention Conf., April 28-30, 1993, Berlin, Germany, p. 65.
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Twenty-four lung cancer and 35 bladder cancer patients were treated with doses of 5 g/day of ascorbic acid. Results suggest that such high doses are useful in correcting low haematic levels of vitamin C and in increasing the defense reactions in patient suffering from these types of cancer.
- A.M. Greco, et al., Study of Blood Vitamin C in Lung and Bladder Cancer Patients Before and After Treatment with Ascorbic Acid: A Preliminary Report, Acta Vitaminol Enzymol, 4(1-2), 1982, p. 155-162.
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This review article points out that vitamin C's role in preventing cancer has been discussed in the literature for over 50 years and cites studies which suggest that foods rich in vitamin C are associated with lower risks of stomach cancer and cancer of the esophagus. Ascorbic acid had been demonstrated to interact with a number of tumor-inducing compounds, such as precursors of N-nitroso compounds to prevent tumors. Animal and in vivo studies have also shown ascorbic acid disrupts tumor promotion. Based on a review of the existing evidence, the authors conclude that vitamin C can inhibit the formation of some types of cancer.
- B.E. Glatthaar, et al., The Role of Ascorbic Acid in Carcinogenesis, Adv Exp Med. Biol, 206, 1986, p. 357-377.
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The administration of flavone, quercetin, and fisetin either alone, or in combination with ascorbic acid, were studied for their effects on the growth of human squamous cell carcinoma cell line (HTB 43) in vitro. When combined with ascorbic acid (2 micrograms/ml) fisetin and quercetin (2 micrograms/ml of either) impaired cell growth in 72 hours significantly. Ascorbic acid administered alone had no effect, nor did it when in combination with flavone.
- C. Kandaswami, et al., Ascorbic Acid-enhanced Antiproliferative Effect of Flavonoids on Squamous Cell Carcinoma in Vitro, Anticancer Drugs, 4(1), February 1993, p. 91-96.
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This review article on the relationship between vitamin C, vitamin E, and cancer cites studies which suggest that the consumption of foods containing vitamin C is related to a reduced risk of esophageal and stomach cancer. Supplementation with vitamin C has been shown to inhibit nerve, lung, kidney, and skin cancer. Studies have also shown vitamin C is capable of inhibiting tumor cell growth and carcinogen-induced DNA damage. In vitro and animal studies have demonstrated that vitamin C inhibits the formation of carcinogenic nitrosamines.
- L.H. Chen, et al., Vitamin C, Vitamin E and Cancer, Anticancer Research, 8(4), July-August 1988, p. 739-748.
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Previous research has shown ascorbic acid to be cytotoxic to neuroblastoma cells in vitro and in vivo. In this study, ascorbic acid proved to be more cytotoxic than Dehydroascorbic acid in neuroblastoma SK-NSH cells. It was also discovered that uptake of [14C] ascorbic acid and [14C] Dehydroascorbic acid was impaired by gluthathione and diethiothreitol. [14C] Dehydroascorbic acid was partially reduced to [14C] ascorbic acid once inside the cell. The authors argue that their results add support to previous beliefs that ascorbic acid acts as a pro-oxidant inside neuroblastoma cells and they recommend the use of ascorbic acid in treating neuroblastoma.
- S.L. Baader, et al., Uptake and Cytotoxicity of Ascorbic Acid and Dehydroascorbic Acid in Neuroblastoma (SK-N-SH) and Neuroectodermal (SK-N-LO) Cells, Anticancer, 14(1A), January-February 1994 p. 221-227.
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L-ascorbate and its oxidative product dehydroascorbate have been shown to be lethal or cytoxic to fast-growing malignant cells while being less toxic to nonmalignant cells. Similar effects were seen with D-ascorbate and D-isoascorbate. Additional studies on the viability of treated cells have found that the effect on cell growth was a result of ascorbate's direct killing action rather than being cytostatic in nature.
- P.Y. Leung, et al., Cytotoxic Effect of Ascorbate and its Derivatives on Cultured Malignant and Nonmalignant Cell Lines Anticancer Research, 13(2), March-April 1993, p. 475-480.
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Noting the radioprotective effect of ascorbic acid on patients with head and neck cancer, this paper recommends the oral administration of ascorbic acid for patient suffering from these conditions.
- R. Garcia-Alejo Hernandez, et al., Radioprotective Effect of Ascorbic Acid on Oral Structures in Patients with Cancer of the Head and Neck, Av Odontoestomatol, 5(7), September 1989, p. 469-472.
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This study found that doses of 2mM of ascorbic acid had a strong cytotoxic effect on neuroblastoma, osteosarcoma, rhabdomyosarcoma and retinoblastoma cells cultured in vitro. Ascorbic acid administered at 0.2 2mM continue to be cytotoxic for neuroblastoma, osteosarcoma and retinoblastoma cells, but stimulates the growth of rhabdomyosarcoma cells.
- M. A. Medina, et al., Ascorbic Acid is Cytotoxic for Pediatric Tumor Cells Cultured in Vitro, Biochem Mol Biol Int, 34(5), November 1994, p. 871-874.
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In this case-control study of 723 gastric cancer patients, significant protective effects were found between ascorbic acid and the risk of developing the disease.
- C. La Vecchia, et al., Selected Micronutrient Intake and the Risk of Gastric Cancer, Cancer Epidemiol Biomarkers Prevention, 3(5), July-August 1994, p. 393-398.
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An inverse association was found between dietary vitamin C and cervical intraepithelial neoplasia (CIN) in this case-control study of biopsy confirmed CIN patients.
- J. VanEenwyk, et al., Folate, Vitamin C, and Cervical Intraepithelial Neoplasia, Cancer Epidemiol Biomarkers Prevention, 1(2), January-February 1992, p. 119-124.
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This study examined the effects of nitric oxide and ascorbate on the control human brain tumor cells. Results indicated that combining nitroprusside and ascorbate may be an effective approach for treating brain tumors.
- Y.S. Lee and R.D. Wurster, Potentiation of Anti-Proliferative Effect of Nitroprusside by Ascorbate in Human Brain Tumor Cells Cancer Letters, 78(1-3), April 1, 1994, p. 19-23.
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This study found that the cytotoxic effects of ascorbic acid on two sensitive lymphocyte tumor and cell lines were time and dose dependent. The authors suggest that the existence of lymphocyte lines with differing sensitivities to ascorbic acid might be considered a useful model in the study of vitamin C's action on cancer cells.
- T.L. Kao, et al., Inhibitory Effects of Ascorbic Acid on Growth of Leukemic and Lymphoma Cell Lines, Cancer Letters, 70(1-2), June 15, 1993, p. 101-106.
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This study found vitamin C to have a distinct inhibitory effect on the mutational specificity of 6 antineoplastic drugs. Such results, the authors argue, are significant with respect to the clinical prevention of tumors.
- Z.Z. Zhao and M.T. Huang, A Study of Vitamin Inhibition on the Mutagenicity of the Antineoplastic Drugs, Chung Hua Yu Fang I Nsuch Tsa Chih, 26(5), September 1992, p. 291-293.
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Noting that DES or estradiol-treated male Syrian hamsters supplemented with vitamin C have been shown to inhibit renal carcinogenesis, the effects of administered vitamin C on a series of biochemical markers of kidney carcinogenesis was studied. Results indicate that vitamin C inhibits estrogen-induced carcinogenesis by decreasing concentrations of estrogen quinone metabolites and their DNA adducts.
- J.G. Liehr, et al., Mechanism of Inhibition of Estrogen-Induced Renal Carcinogenesis in Male Syrian Hamsters by Vitamin C, Carcinogenesis, 10(11), November 1989, p. 1983-1988.
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Forty-three patients were treated with oral supplementation of vitamin C. Treatment with vitamin C in patients with normal gastric mucosa resulted in elevation of intragastric ascorbate levels in all cases. Vitamin C supplementation decreased gastric mucosal DNA damage in 28 of the 43 patients which suggests that it may provide a protective role against the onset of gastric cancer.
- G.W. Dyke, et al., Effect of Vitamin C Suppelmentation on Gastric Mucosal DNA Damage, Carcinogenesis, 15(2), p. 291-295.
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Noting that chromium metal salts are thought to be human carcinogens, and that lead chromate has been shown to be tumorigenic genotoxic and clastogenic; this study demonstrated that a nontoxic dose of vitamin C blocked uptake of ionic chromium and eliminated the clastogenic activity of particles in cells treated with lead chromate particles.
- J.P. Wise, et al., Inhibition of Lead Chromate Clastogenesis by Ascorbate: Relationship to Particle Dissolution and Uptake, Carcinogenesis, 14(3), March 1993, P. 429-434.
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This study found a positive relationship between human exposure to nitrosamines and the risk of esophageal cancer mortality. Vitamin C reduced the amount of gastric N-nitroxamines in the stomach and thus may be considered of potential value in the prevention of esophageal cancer.
- W.X. Yang, Exposure Level of N-nitrosamines in the Gastric Juice and its Inhibition by Vitamin C in High Risk Areas of Esophageal Cancer, Chung Hua Chung Liu Tsa Chih, 14(6), November 1992, p. 407-410.
Part II
By Gary Null, PhD; Howard Robins, DPM; Mark Tanenbaum, DPM; and Patrick Jennings, Editor The Townsend Letter for Doctors and Patients - June 1997
This study found that ascorbic acid administered in drinking water (0.3%) inhibited the promoting effect of estradiol dipropionate on the 1,2-dimethylhydrazine-induced uterine sarcogenesis in CBA mice.
- L.S. Trukhanova. Modifying Effect of Ascorbic Acid and Sodium Ascorbate on Uterine Carcomogenesis Induced by 1,2 dimethylhydrazine in CBA Mice. Eksp Onkol, 10(5), 1988, p. 65-66.
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This study found that ascorbic acid intake affects in vivo N-ethyl-N-nitrosourea (ENU) mutagenicity in rats. The authors suggest that previously reported antioxidant inhibitory effects on carcinogenesis could be partially mediated by its effects on mutagenesis.
- A. Aidoo, et. al. Ascorbic Acid (Vitamin C) Modulates the Mutagenic Effects Produced by an Alkylating Agent in VivoEnviron Mol Mutagen, 24(3), 1994, p. 220-228.
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This case-control, population-based study found Vitamin C intake, attenuated by age, level of education, and lifetime cigarette use, offers protective effects against developing cervical cancer.
- M.L. Slattery, et. al. Dietary Vitamins A, C, and E and Selenium as Risk Factors for Cervical Cancer Epidemiology, 1(1), January 1990, p. 8-15.
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This paper reports the discovery of a new malignant human T-cell line-labeled PFI-285 in a boy with malignant lymphoma. One of the striking characteristics of this new T-cell line was its sensitivity to ascorbic acid, evidenced by the fact that concentrations as low as 50 mumuol/l resulted in cell death within hours.
- J. Helgestad, et. al. Characterization of a New Malignant Human T-cell Line (PFI-285) Sensitive to Ascorbic Acid European Journal of Haematology, 44(l), January 1990, p. 9-17.
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This study found that oral administration of vitamin C can retard the onset of N-nitrosodiethylamine-induced liver cancer in rats.
- H. Kessler, et. al. Potential Protective Effect of Vitamin C on Carcinogenesis Caused by Nitrosamine in Drinking Water: An Experimental Study on Wistar Rats European Journal of Surgery and Oncology, 18(3), June 1992, p. 275-281.
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The survival rate of mice bearing P388 leukemia and Ehrlich carcinoma was increased after treatment with a mixture of vitamins C and B12. All the mice receiving the vitamins outlived the control group. At the termination of the experiment 30 days later, 50% of the treated mice appeared normal and healthy, whereas the remainder showed signs of tumor distention.
- M.E. Poydock, et. al. Influence of Vitamins C and B12 on the Survival Rate of Mice Bearing Ascites Tumor Exp Cell Biol, 50(2), 1982, p. 88-91.
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This study found that a daily dose of 50 mg/kg of vitamin C in combination with methylcholanthrene (MCA) over 9 months significantly reduced MCA-induced squamous cell carcinomas in mice and basal cell carcinomas in rats over a period of nine months. The authors conclude that vitamin C's antineoplastic effects are the result of increasing autophagic and cytolytic activity, increased collagen synthesis, and cell membrane disruption.
- A. Lupulescu. Ultrastructure and Cell Surface Studies of Cancer Cells Following Vitamin C Administration Exp Toxicol Pathol, 44(l), March 1992, p. 3-9.
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This study found that vitamin C reduced the incidence of DMBA-induced epithelial tumor in the hamster cheek pouch.
- P.D. Potdar, et. al. Modulation by Vitamin C of Tumor Incidence and Inhibition in Oral Carcinogenesis Funct Dev Morphol, 2(3), 1992, p. 167-172.
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Previous studies have found that nitrosation can be decreased by the administration of ascorbic acid in vivo and that vitamin C-rich foods are inversely related to gastric cancer. This study treated 62 high risk patients for gastric cancer with 1 gr of ascorbic acid taken 4 times a day for four weeks. Results found that ascorbic acid given in high doses can reduce the intragastric formation of nitrite and N-nitroso compounds.
- P.I. Reed, et. al. Effect of Ascorbic Acid on the Intragastric Environment in Patients at Increased Risk of Developing Gastric Cancer LARC Sci Publ, (105), 1991, p. 139-142.
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1000 mg/kg of ascorbic acid in combination with mitomycin and 5-fluorouracil significantly inhibited tumor growth in mice implanted with Lewis lung carcinoma cells relative to mice treated with mitomycin and 5-fluorouracil in the absence of ascorbic acid or animal that received only ascorbic acid alone.
- K Nakano, et. al. Antitumor Activity of Ascorbic Acid in Combination with Antitumor Agents Against Lewis Lung Carcinoma In Vivo, 2(3-4), May-August 1988, p. 247-252.
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This study found that 1 or 5 g/liter of ascorbic acid in the drinking water significantly inhibited the growth of human mammary tumor fragments implanted beneath the renal capsule of immunocompetent mice. Mice fed a diet including 50 g/kg ascorbic acid and 18 or 90 mg/liter of cupric sulfate in the drinking water also experienced inhibited tumor growth. The authors conclude ascorbic acid contains specific oxidation and degradation products that serve as antineoplastic agents for human mammary carcinoma. - C.S. Tsao, et. al. In Vivo Antineoplastic Activity of Ascorbic Acid for Human Mammary Tumor In Vivo, 2(2), March-April 1988, p. 147-150.
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This study found that administration of 500 mg/kg of L-ascorbic acid to athymic nude mice bearing human mammary carcinoma inhibited tumor cell growth. Treatment with L-ascorbic acid was also found to induce cellular DNA strand breaks and DNA crosslinks. When L-ascorbic acid was removed from cell cultures, researchers witnessed an immediate onset of spontaneous repair of single or double stranded DNA breaks. Reintroduction of L-ascorbic acid reversed this process.
- K. Pavelic, et. al. Antimetabolic Activity of L-ascorbic Acid in Human and Animal tumors International Journal of Biochemistry, 21(8), 1989, p. 931-935
This population-based dietary study found inverse relationship between vitamin-C consumption in women and the risk of developing cancer in the lower urinary tract.
- A.M. Nomura, et. al. Dietary Factors in Cancer of the Lower Urinary Tract International Journal of Cancer, 48(2), May 10, 1991, p. 199-205
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An inverse relationship was found in this population-based case-control study between the intake of vitamin C and invasive cervical cancer.
- X Varreault, et. al. A Case-Control Study of Diet and Invasive Cervical Cancer International Journal of Cancer, 43(6), June 15,1989, p. 1050-1054.
This study found that guinea pigs fed high vitamin C diets experienced a significantly less mutagenic effect after being injected with K2Cr2O7 than those fed a vitamin C-deficient diet. Vitamin C-deficient animals also suffered greater mutagenic and toxic effects from hexavalent chromium. High vitamin C-guinea pigs experienced no mutagenic effects in the bone marrow or changes in microsomal enzymes in the liver following exposure to bichromate. In interpreting their results, the authors suggest that vitamin C's protective effects likely consist in the enhanced extracellular and intracellular reduction of hexavalent chromium in the less toxic and less mutagenic trivalent chromium.
- E. Ginter, et. al. Vitamin C Lowers Mutagenic and Toxic Effect of Hexavalent Chromium in Guinea Pigs International Journal of Vitamin and Nutritional Research, 59(2),1989, p. 161-166.
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In this study, ascorbic acid deficiencies in guinea pig were found to change leukocyte morphology and significantly interfere with the bactericidal effectiveness of circulating leukocytes against ingested, cell-associated, and extracellular bacterial cells of Actinomyces viscosus. Adding vitamin C can reverse this activity.
- M.C. Goldschmidt, at. al.. The Effect of Ascorbic Acid Deficiency on Leukocyte Phagocytosis and Killing of Actinomyces Viscosus International Journal of Vitamin and Nutrition Research, 58(3), 1988, p. 326-334.
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This review article points out the importance of vitamin C, as well as vitamins A and E, as regulators of cancer cell differentiation, cell regression, membrane biogenesis, DNA, RNA, protein, and collagen synthesis, as well as transformation of precancer cells into cancer cells. Vitamins C, A, and E can reverse the cancer cell to the normal phenotype and possess cytotoxic and cytostatic effects.
- A. Lupulescu The Role of Vitamins A, Beta-carotene, E and C in Cancer Cell Biology International Journal of Vitamin and Nutrition Research, 64(1),1994, p. 3-14.
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This study found that mice consuming distilled water suffered from tumor growth after being injected with Ehrlich ascites tumor cells at a rate significantly faster than those consuming 0.1% ascorbic acid in distilled water.
- F.A. Towfik et. al. The Influence of Ascorbic Acid on the Growth of Solid Tumors in.Mice and on Tumor Control by X-Irradiation International Journal of Vitamin and Nutrition Research Suppl.,23, 1982, p. 257-263.
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This comprehenesive review article cites numerous studies supporting ascorbic acid's protective effects against cancer and recommend that it be used in treatment. Clinical trials over the last ten years are summarized, with the majority of them supporting this view. The authors predict that supplemental ascorbate will soon secure an established place in all full-scale therapeutic programs for cancer.
- E. Cameron Vitamin C and Cancer, An Overview International Journal of Vitamin and Nutrition Research Suppl., 23, 1982, p. 115-127.
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This study reported on two sets of Japanese clinical trials involving the use of supplemental ascorbate to treat terminal cancer patients. The first trial found average survival time of high ascorbate patients was 246 compared to 43 days for low ascorbate patients. Results of the second trial were similar, with high ascorbate patients surviving an average of 115 days compared to 48 days for those in the low ascorbate group.
- A. Murata, et. al. Prolongation of Survival Times of Terminal Cancer Patients by Administration of Large Doses of Ascorbate International Journal of Vitamin and Nutrition Research Suppl., 23,1982, p. 103-113.
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This study demonstrated the effectiveness of ascorbic acid as a blocking agent in vivo and in vitro to N-Nitroso compounds, which can lead to cancer of the stomach.
- S.R. Tannenbaum Preventive Action of Vitamin C on Nitrosamine Formation International Journal of Vitamin and Nutrition Research Suppl, 30, 1989, p. 109-113.
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Ascorbic acid and dehydroascorbic acid have both been shown to favor ATP C+ cell multiplication in vitro at low doses and inhibit it at high doses. Ascorbic acid was found to be more effective in determining both sets of effects than dehydroascorbic acid. Fractioned rather than single administration of both substances proved to the most efficient method for inhibiting cell multiplication.
- F.S. Liotti, et. al. Effects of Ascorbic and Dehydroascorbic Acid on the Multiplication of Tumor Ascites Cells in Vitro Journal of Cancer Research and Clinical Oncology, 108(2),1984, p. 230-232.
In this study, the oral administration of 525 mg/day of vitamin C greatly inhibited benzo(a)pyrene-induced local malignant tumors in rats relative to controls.
- G. Kallistratos and E. Fasske Inhibition of Benzo(a)pyrene Carcinogenesis in Rats with Vitamin C Journal of Cancer Research and Clinical Oncology, 97(l),1980, p. 91-96.
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This study found that catecholamine-positive neuroblastoma cell line SK-N-SH was inhibited by high doses of ascorbic acid as were LS cells and catecholamine-negative SK-N-LO, albeit to a smaller extent.
- S.L. Baader, et. al. Ascorbic-acid-mediated Iron Release from Cellular Ferritin and its Relation to the Formation of DNA Strand Breaks in Neuroblastoma Cells Journal of Cancer Research and Clinical Oncology, 120(7), 1994, p. 415-421.
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This study examined the effects of vitamin C on the efficacy and adverse effects of drug 864T in Ehrlich ascites carcinoma (EAC) cells in vivo. Results demonstrated that vitamin C both potentiates the anticancer effect of 864T as well as helps to counteract the drug's adverse effects.
- M.M. el-Merzabani MM, et. al. Potentiation of therapeutic Effect of Methanesulphonate and Protection Against its Organ Cytotoxicity by Vitamin C in Ehrlich Ascites Carcinoma Bearing Mice Journal of Pharm Belg, 44(2), March-April 1989, p. 109-116.
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This study documents the case of one patient given large doses of ascorbic acid with indomethacin who consequently experienced a slow tumor resolution that has continued for 14 months. Similar effects were seen in a second patient receiving the same treatment.
- W.R. Waddell and R.E. Gerner Indomethacin and Ascorbate Inhibit Desmoid Tumors Journal of Surg Oncol, 15(l), 1980, p. 85-90.
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This comparative study of normal and malignant conditions in humans and in mice found that serum levels of vitamin C were lower in all human malignant cases relative to controls. With respect to mice, results showed that vitamin C and vitamin A supplementation administered at the start of tumor development reduced both tumor take and rate of growth and prolonged host survival relative to controls.
- J. Ghosh and S. Das Evaluation of Vitamin A and C Status in Normal and Malignant Conditions and Their Possible Role in Cancer Prevention Japanese Journal of Cancer Research, 76(12), December 1995, p. 1174-1178.
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This study compared 294 incurable patients treated with supplemental ascorbate with 1,532 untreated patients who served as controls over a 4.5 year period. The median survival time of the ascorbate group was 343 days compared to 180 days for the controls.
E. Cameron and A. Campbell Innovation vs. Quality Control: An 'Unpublishable' Clinical Trial on Supplemental Ascorbate in Incurable Cancer Medical Hypotheses, 36(3), November 1991, p. 185-189.
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Noting that previous studies have found ascorbic acid and its salts to be toxic to tumor cells in vitro and in vivo, this study presents data showing that ascorbic acid plasma levels can be sustained above levels toxic to tumor cells in vitro. The authors argue that ascorbic acid's cytotoxic properties should qualify it for consideration as a chemotherapeutic agent.
- N.H. Riordan, et. al. Intravenous Ascorbate as a Tumor Cytotoxic Chemotherapeutic Agent Medical Hypotheses, 44(3), March 1995, p. 207-213.
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This article examined the results and methodology of a controversial case-control study involving the treatment of 100 incurable patients with 10g a day of vitamin C. The study has received criticism for not being conducted on a randomized, double-blind basis (out of ethical considerations). Instead, test cases were studied against historical controls. Results found that patients receiving vitamin C outlived controls by an average of 255 days (671%). This author considers the various criticisms the study has received, yet concludes that vitamin C is likely to have increased survival time, an average of 100% in cancer patients who had failed to respond to previous treatments.
- M. Jaffey Vitamin C and Cancer: Examination of the Value of Leven Trial Results Using Broad Inductive Reasoning Medical Hypotheses, 8(l), 1982, p. 49-84.
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This paper reports on the case of a 42 year-old man suffering from reticulum cell sarcoma who experienced two complete spontaneous regressions following the intravenous administration of high doses of ascorbate in 1975.
- A. Campbell, et. al. Reticulum Cell Sarcoma: Two Complete Spontaneous Regressions, in Response to High-Dose Ascorbic Acid Therapy. A Report on Subsequent Progress Oncology (1991) 48(6), 1991, p. 495-497.
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This study looked at vitamin C's effects on methylcholanthrene-induced local malignant sarcomas in mice. Results found that doses of 6, 25 and 35 mg/day of vitamin C five times weekly for 20 weeks offered significant prevention against the induction of sarcomas relative to controls.
- M. Abdel-Galil. Preventive Effect of Vitamin C (L-ascorbic acid) on Methylcholanthrene-induced Soft Tissue Sarcomas in Mice Oncology, 43(5), 1986, p. 335-337.
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This 12-year mortality follow-up study reports that vitamin C is inversely associated with overall mortality from cancer and cadiovascular disease.
- M. Eichholzer, et. al. Inverse Correlation Between Essential Antioxidants in Plasma and Subsequent Risk to Develop Cancer, Ischemic Heart Disease and Stroke Respectively: 12-Year Follow-up of the Prospective Basel Study EX3, 62, 1992, p. 398-410.
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This double-blind, randomized, crossover study found that ascorbic acid significantly reduced muscle soreness in subjects following strenuous use of posterior calf muscles relative to subjects taking a lactose placebo.
- M. Kaminski and R. Boal An Effect of Ascorbic Acid on Delayed-onset Muscle Soreness Pain, 50(3), September 1992, p. 317-321.
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This review article cites immunological studies documenting ascorbic acid's ability to induce immunity in mice against certain types of cancer. The authors argue that ascorbate works as an effective thiolprive in oxygenated cancer tissues which is primarily responsible for its immunological effects.
- F.E. Knock, et. al. Ascorbic Acid as a Thiolprive: Ability to Induce Immunity Against Some Cancers in Mice Physiol Chem Phys, 13(4), 1981, p. 325-333.
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This study found that combinations of vitamin C and cisplatin lead to the regression of Dalton's lymphoma tumor activity in mice, which resulted in significantly increased host survival.
- S.B. Prasad, et. al. Use of Subtherapeutical Dose of Cisplatin and Vitamin C Against Murine Dalton's Lymphoma Pol J Pharmacol Pharm, 44(4), July-August 1992, p. 383-391.
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This study found that the administration of 8g/day over 810 days before starting chemotherapy with cytostatics decreased p-hydroxyphenyl lactic acid (pHPLA) excretion in leukemia patients. Mice given 5 mg, 2x1wk, sc, 5wk of pHPLA with 250 mg/100 ml of ascorbic acid were also found to experience a reduction in the incidences of hepatoma, leukemia and bladder cancer. Based on those results, the authors argue that pHPLA carcinogenesis is inhibited by ascorbic acid.
- M.O. Raushenbakh, et. al. Effect of Ascorbic Acid on Formation and Leukemogenic Activity of P-Hydroxyphenyllactic Acid. Probl Gematol Pereliv Krovi, 27(7), 1982, p.3-6.
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This study showed that treatment with vitamin C and chlorophyllin significantly reduced cytotoxicity and the rate of 6-sulfooxymethyl benzo[a]pyrene (SMBP) induced mutagenicity in animal and bacterial cell cultures.
- A.S. Chung and Y.S. Cho Antimutagenicity of Vitamin C and Chlorophyllin on 6-sulfooxymethyl benzolalpyrene in Salmonella Typhimurium and V79 Cell Line Proceedings of the Annual Meeting of the American Association of Cancer Researchers, 36, 1995, A755.
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Rat liver carcinogenesis was found to be inhibited by vitamin C and vitamin E derivatives in this study when administered at concentrations of 0.01, 0.05 or 0.10% for 12 weeks. Among the four vitamin derivatives administered, 20-octadecylascorbic acid (CV3611) proved to be the most effective.
- D. Nakae, et. al. Inhibitory Effects of Vitamin C and E Derivatives on Rat Liver Carcinogenesis Induced by a Choline-Deficient L-Amino Acid (CDAA)-Defined Diet Proceedings of the Annual Meeting of the American Association of Cancer Researchers, 34, 1993, A729.
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In this study, Metha tumor cell proliferation was found to be inhibited in vitro after simultaneous exposure to diethyldithiocarbamate (DDC (1 to approx 2x10(-7) and ascorbic acid (1 to approx 5xl0(-5)M). The two substances were able to inhibit tumor proliferation at slightly lower doses when cells were pretreated at 370C for one hour. In a mouse injected with 2 million tumor cells, 25 mg or 50 mg of ascorbic acid and 10 mg of DDC was also observed to inhibit tumor growth.
- H. Mashiba and K Matsunaga. Inhibition of Metha Tumor Cell Proliferation in Vitro and Tumor Inhibiton of Metha Tumor Cell Proliferation in Vitro and Tumor Growth in Combined Use of Diethyldithiocarbamate with Ascorbic Acid Proceedings of the Annual Meeting of the American Association of Cancer Researchers, 33, 1992, A2649.
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This study of ultraviolet light-induced malignant skin tumors and other lesions in hairless mice found that animals fed a standard diet including L-ascorbic acid experienced significantly less malignant lesions as well as significant delays in those that did develop relevant to controls.
- W.B. Dunham, et. al. Effects of Intake of L-ascorbic Acid on the Incidence of Dermal Neoplasms Induced in Mice by Ultraviolet Light Proceedings of the National Academy of Sciences, 79(23), December 1982, p. 7532-7536.
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This study found that vitamin C prevented cigarette smoke-induced leukocyte adhesion to micro and macrovascular endothelium and leukocyte-platelet aggregate formation in mice.
- H.A. Lehr, et. al. Vitamin C Prevents Cigarette Smoke-Induced Leukocyte Aggregation and Adhesion to Endothelium in Vivo Proceedings of the National Academy of Sciences, 91(16), August 2, 1994, p. 7688-7692.
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Percentages of L-ascorbic acid contained in food ranging from 0.076% to 8.3% were studied for their effects on spontaneous mammary tumors in mice. Results showed that as ascorbic acid dosages were increased, significant decreases occurred in the first-order appearance tumors after lag time detection by palpation when compared to controls.
- L. Pauling, et. al. Effect of Dietary Ascorbic Acid on the Incidence of Spontaneous Mammary Tumors in RIII Mice Proceedings of the National Academy of Sciences, 82(15), August 1985, p. 5185-5189.
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In this study, 6-deoxy-6-bromo-ascorbic acid (6-Br-AA) in concentrations 10(-1) to 10(-8)M and incubated for periods of 2, 18, 24 and 72 hours was found to greatly inhibit the growth and DNA synthesis of melanoma cells in mice and was confirmed by in vivo experiments. Mice given 9 mg of 6-Br-AA three times daily for 16 days experienced tumor-suppressing effects on solid melanoma.
- M. Osmak, et. al. 6-Deoxy-6-bromo-ascorbic Acid Inhibits Growth of Mouse Melanoma Cells Res Exp Med (Berl), 190(6), 1990, p. 443-449.
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In this seven year follow-up study of 2,974 men, average vitamin C levels were found to be lower in stomach cancer death cases relative to controls.
- H.B. Stahelin. Vitamins and Cancer: results of a Basel Study. Soz Praventivmed, 34(2), 1989, p. 75-77.
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This study found that ascorbic acid incubation in cultured stomach cancer surgery specimens resulted in a 50-90% increase in the rate of 5-fluorouracil incorproation into RNA of 5-fluorouracil-sensitive stomach tumors and in an approximately 50% increase of the rate of 5-fluorouracil resistant tumors.
- M.P. Shlemkevich. Effect of Ascorbic Acid on In Vitro (6-3H)-5-Fluorouracil Incorporation into RNA of Stomach Cancer Tissue, Normal Gastric Mucosa, and Normal Small Intestine Mucosal. Vopr Med Khim, 29(l), 1983, p. 17-19.
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This study demonstrated that a 3% solution of ascorbic acid in drinking water added to estradiol propionate (carcinogen) decreased the incidence of uterine sarcoma tumors in mice by 35%.
- L.S. Trukhanova, et. al. The Inhibitory Effect of Ascorbic Acid on the Estrogen-Stimulated Promotion of Uterine Sarcoma Development in Mice. Vopr Onkol, 36(5), 1990, p. 563-567.
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This study showed that injections of ascorbic acid before onset and at the start of tumor development decreased blood and urine 3-oxyanthranilic acid-antigen levels down to its eventual elimination from the body in rats and mice. Such activity was found to prevent the subsequent development of hepatoma.
- T.A. Korosteleva, et. al. Effects of the Administration of Ascorbic Acid on 3-OAA-antigen Levels Formed During Chemical epatocarcinogenesis] Vopr Onkol, 35(12), 1989, p. 1455-1461.
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In this randomized study, postoperative treatment of 95 stomach cancer patients with vitamins C, E and A following, resulted in a decreased rate of postoperative complications from 30.9% to 1.9%.
V.N. Sukolinskii and T.S. Morozkina. Prevention of Postoperative Complications in Patients with Stomach Cancer Using an Antioxidant Complex. Vopr Onkol, 35(10), 1989, p. 1242-1245
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This study found that cancer patients suffered from a decreased level of ascorbic acid relative to non-cancer patients in addition to showing that such decreases correlated with an increase in blood concentrations of malonic and pyruvic acids. When cancer patients were given 1.5 g of ascorbic acid daily over a period of 7 days, blood levels of ascorbic acid returned to almost normal and lactate and pyruvate levels exhibited a decrease. In addition to these changes, ascorbic acid deficiencies were found to result in an increased risk of postoperative complications. This risk was decreased by increasing the levels of ascorbic acid in the blood of deficient patients.
- E.G. Gorozhanskaia, et. al. The Role of Ascorbic Acid in the Combined Preoperative Preparation of Cancer Patients. Vopr Onkol, 35(4), 1989, p. 436-441.
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This study showed that mice treated with doses of 1.5, 0.25, and 0.025% of ascorbic acid in drinking water all experienced decreases in the frequency of N-nitroso compound induced tumors.
- N.L. Vlasenko, et. al. Effect of Different Doses of Ascorbic Acid on the Induction of Tumors with N-Nitroso Compound Precursors in Mice. Vopr Onkol, 34(7), 1988, p. 839-843.
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Doses of 0.3, 0.75 or 1.5% of ascorbic acid administered in drinking water inhibited the growth of 1,2 dimethylhydrazine and estradiol-dipropionate induced uterine sarcomas in mice.
- L.S. Trukhanova. Effect of Ascorbic Acid on the Induction of Uterine Sarcomas in Mice. Vopr Onkol, 33(11), 1987, p. 53-57.
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The effect of high doses of ascorbic acid (100 mg/kg daily) on tyrosine metabolism and clinical course of acute lymphoblastic leukemia was studied in nine children. Ascorbic acid administration was shown to prevent or to considerably lower the excretion of a blastogenic metabolite of tyrosine-phydroxyphenylpyruvic acid. The treatment improved clinical blood count indexes, prevented hemorrhage and was followed by an earlier onset of complete remission after chemotherapy. Although chemotherapy suppressed p-hydroxyphenylpyruvic acid excretion, its level was inordinately high as late as on day 12. It is concluded that although the effects of ascorbic acid and cytostatic drugs on p-hydroxyphenylpyruvate hydroxylase level are similar, that of ascorbic acid is more specific and is followed by a complete recovery of tyrosine metabolism.
- V.N. Baikova, et. al. The Effect of Large Doses of Ascorbic Acid on Tyrosine Metabolism and Hemoblastosis Course in Children. Vopr Onkol, 28(9), 1982, p. 28-34.
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This case-control study of diet and breast cancer in 2 Chinese populations found a strong inverse association between breast cancer and the intake of vitamin C, carotene, and crude fiber.
- J.M. Yuan, et. al. Diet and Breast Cancer in Shanghai and Tianjin, China British Journal of Cancer, 71, 1995, p. 1353-1358.
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This review article looked at 12 case-control studies on the relationship between breast cancer and diet. The most consistently significant inverse association found was between vitamin C and breast cancer risk.
- G.R. Howe, et. al. Dietary Factors and the Risk of Breast Cancer: Combined Analysis of 12 Case-Controlled Studies Journal of the National Cancer Institute, 82, 1992, p. 561-569.
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This review article cites results from several studies documenting the protective effects of vitamin C in reducing the risk of cervical cancer. One, in particular, found that women with the highest levels of dietary vitamin C decreased their chances of developing cervical cancer by 4-5 times compared to those with the lowest levels.
- J. VanEenwyk. The Role of Vitamins in the Development of Cervical Cancer The Nutrition Report, 11(l), January 1993, p. 1-8
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Dietary vitamin C was found to be protective against cervical intraiepithehal neoplasia in this case-control study.
- C.F. Amburgey, et. al. Undernutrition as a Risk Factor for Cervical Intraepithelial Neoplasia: A Case-control Analysis Nutrition and Cancer, 20(l), 1993, p. 51-60.
Townsend Letter for Doctors and Patients - June 1997
P.O. Box 918 Planetarium Station New York, New York 10024 USA 646-505-4660
Gary Null, PhD, award-winning investigative reporter has authored 50 books on health and nutrition, as well as numerous articles published in leading magazines. Dr. Null holds a PhD in human nutrition and public health science from the Union Graduate School.
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