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Vitamin C and cancer: The irrefutable evidence

Based on the research evidence, Vitamin C should by now have achieved medical respectability both in the prevention and treatment of cancer. Hundreds of research studies published during the past decade alone attest to the monumental research effort mobilized to document the role of Vitamin C in Cancer prevention and treatment.1 Numerous books each replete with hundreds of references, have been published over the years,2-8 documenting the vital role played by Vitamin C in every body system function. For Vitamin C is a potent antioxidant, immune modulator, integral to countless metabolic, endocrine and neurological functions, and an absolute requirement for the synthesis of collagen, vital for skin, bone, muscle and connective tissue.
However, the road to medical respectability has been exceedingly rocky for Vitamin C and especially so for Linus Pauling, twice Nobel Laureate, who has been subjected to a remarkable degree of professional hostility over his championing of Vitamin C. The saga of the battle over twenty years between the research scientist giant Linus Pauling and the medical director of the prestigious Mayo Clinic Charles Moertel is grippingly recounted by Evelleen Richards in Vitamin C and Cancer: Medicine or Politics?,9 a masterly expose of the medical/pharmaceutical establishment in all its powerful workings. This book contains original letters from both combatants, for this battle was played out in full public view in the form of letters to prestigious scientific journals.

The next thing [the judge] is going to say to me is, "Look, I am an educated man and I wouldn't presume to decide between Linus Pauling and the Mayo Clinic. Here is a Nobel prize winning biochemist and here are fifteen doctors from the world's leading something and one tells me yes and the other tells me no, and how the hell as I going to decide? I don't know anything about biochemistry." So he will say, "Look Mr [Attorney], you make a very interesting and persuasive argument, but on the other hand Mr. ______ over here makes a very persuasive argument and I mean isn't this a question for scientists to decide? The history of science for a thousand years is that someone comes up with an idea, the establishment ridicules him, then fifty years later they find he was right and he becomes a saint. That's just life, and Pauling is in the great tradition of outcasts." That's if I had a good judge. The worst is if I had a bad judge. He'd say, "Look, Pauling is not a doctor – these guys are doctors; that's enough for me." That could happen.

An Attorney's Advice to Linus Pauling at the height of the vitamin C and cancer controversy (Linus Pauling Institute) March, 1985)9
To illustrate her point of the political and economic bias intrinsic to the practices of research and medicine, the author also includes a superb comparison of the fast-track acceptance of two other forms of cancer treatment, 5-fluorouracil and interferon, both with inferior clinical effectiveness and higher toxicity than Vitamin C. Highly recommended reading!
Although Linus Pauling appeared to lose his personal battle with the Cancer Establishment during the 1980s, the research evidence has continued to accumulate, until of late the tide seems to have dramatically turned in favour of the efficacy of antioxidants, including Vitamin C, in prevention and treatment. So much so that in a recent Sunday Times supplement about Health Care10, Professor of Biochemistry Anthony Diplock suggested that supplementation was the only way to obtain preventive levels of antioxidant vitamins.

Mechanisms of Vitamin C's Anti-Cancer Abilities
Vitamin C's anti-cancer properties are brought about by a number of modalities of this versatile nutrient:8

1 Scavenges cancer-causing free radicals such as hydrogen peroxide to prevent lipid peroxidation and destruction of cells;
2 Neutralizes carcinogenic chemicals such as nitrosamine and nitrites;
3 Regenerates active vitamin E (another potent antioxidant) in lipid membranes;
4 Enhancement of lymphocyte function and rapid mobilization of phagocytes;
5 Potent anti-viral and anti-bacterial activity;
6 Enhancement of IgA, IgG and IgM antibody levels;
7 Modulation of interferon synthesis;
8 Increases synthesis of prostaglandin PGE1 (anti-inflammatory); inhibits PGE2 (inflammatory);

Protection from Cancer
The epidemiological evidence that Vitamin C affords significant protection is strong.

* An analysis by G Block, University of California, of 90 epidemiological studies which examined the role of vitamin C or vitamin-C-rich foods showed that the vast majority found statistically significant protective effects. Evidence was "strong" for cancers of the esophagus, oral cavity, stomach, and pancreas; "substantial" for cervical, rectal and breast cancers as well as recent evidence for the role of Vitamin C in lung cancer.11
* The 12-year mortality follow-up of 3000 participants of the ground-breaking Basel Study showed that overall cancer mortality was associated with low mean plasma levels of carotene and Vitamin C; stomach and gastrointestinal cancer victims had lower Vitamin C levels. It was concluded that low plasma levels of all major essential antioxidants was associated with an increased risk of subsequent cancer mortality;12
* Enstrom et al from University of California examined the relation between vitamin C intake and mortality with some 12,000 adults in the US, followed for a median of 10 years. Those with the highest Vitamin C intakes had the lowest standardized mortality ratios for all cancers; the inverse relationship between Vitamin C and cancer death was stronger in males than in females;13
* Reed et al, Wexham Park Hospital, Slough, studied the ability of Vitamin C to reduce the nitrosation of foods in 62 patients at high-risk of gastric cancer. Treatment with 1g Vitamin C four times daily resulted in a reduction in nitrate-reducing bacteria and in nitrite and N-nitroso concentrations, demonstrating that Vitamin C reduces cancer-causing nitrite and N-nitroso compounds of gastric juices;14
* Howe et al, University of Toronto conducted a combined analysis of 12 case-control studies of diet and breast cancer which showed a consistent and statistically significant inverse association between Vitamin C intake and breast cancer risk. They postulated that if these dietary associations represented causality, that dietary modification could prevent 24% of breast cancers for postmenopausal and 16% for premenopausal North American women.15
* Chen et al, Chinese Academy of Preventive Medicine, Beijing, China studied the sex-specific mortality rates for selected cancer sites (including oesophagus, stomach, liver, lung, colorectal, breast and cervix) and indicators of antioxidant status (including beta-carotene, alpha-tocopherol, ascorbic acid, selenium, glutathione peroxidase, catalase, superoxide dismutase, iron, copper, zinc, total cholesterol and lipid peroxide) in a study of 65 rural counties in China. The simple correlational and multivariate analyses showed that plasma levels of dietary antioxidants were consistently inversely correlated with cancer mortality rates. Vitamin C was most strongly inversely associated with most cancers; selenium with oesophageal and stomach cancer, and beta-carotene particularly with stomach cancer.16

Treatment in Cancer
The evidence for Vitamin C's positive clinical ability to treat cancer is also growing:

* Lupulescu, Wayne State University, Detroit studying the inhibition of cancer cell metabolism and proliferation by Vitamin C upon rat tumour (basal and squamous) cells at the ultrastructural and cell surface level, revealed cell cytolyis (disintegration), disorganization, mitochondrial alterations, cell membrane disruption and increased collagen synthesis.17
* Kessler and Husemann, University of Erlangen-Nurnberg, Germany determined that Vitamin C protects against liver cancer in rats caused by nitrosamine in drinking water. Vitamin C reduced rate of liver cancer from 90% to 68% when Vitamin C was administered alternately, and 55% when administered together with the nitrosamine carcinogen.18
* Cameron, Linus Pauling Institute, California described a protocol for cancer patients involving an initial course of intravenous Vitamin C, followed by a maintenance oral dose to be continued indefinitely thereafter.19
* Paganelli and colleagues, University of Bologna, Italy studied the preventive effects of Vitamins A, C and E on patients with colon cancer (colorectal adenomas). Following surgery, 20 patients were given Vitamins A, C and E for 6 months; 21 adenoma patients were given placebos. Cells taken from biopsies before and during the 6 months were evaluated for cell proliferation criteria. While there were no statistically significant in cell parameters in the placebo group, in patients receiving vitamins, there was a statistically significant decrease in labelling in cells near the mucosal surface, a biomarker of proliferation and cancer risk. The findings suggest that Vitamins A, C and E reduce cell abnormalities associated with a precancerous condition.20
* Tsao, Linus Pauling Institute, California determined that Vitamin C and cupric sulfate significantly inhibited the growth of human breast tumour fragments implanted in mice. Furthermore since the activity of D-isoascorbic, the inactive Vitamin C isomer, was similar to vitamin C, this suggested that Vitamin C's antitumour activity was due not to its metabolism as a vitamin, but rather to its chemical properties.21
* Poydock, Mercyhurst College, Pennsylvania studied the effect of Vitamins C and B-12 upon the survival of mice with cancers and leukemias. Whereas all the control mice had died by day 19, more than 50% of the mice given Vitamins C and B-12 were alive after 60 days. Cell division (mitoses) was inhibition in leukemia cells. The combination of Vitamins B-12 and C forms cobalt ascorbate; cobalt ascorbate plus Vitamin C inhibits tumour cells.22
* Liehr, University of Texas, Galveston investigated Vitamin C's ability to decrease by 50% estrogen-induced tumour growth in hamster kidneys. Vitamin C lowers the concentration of toxic hormonal metabolites (quinones) and DNA levels of diethylstilbestrol, which may also inhibit free radicals generated between estrogens and their quinones.23
* Pauling, Linus Pauling Institute, studied the effects of Vitamin C upon tumour-free survival in mice. One study on spontaneous mammamy tumours demonstrated that increased levels of dietary Vitamin C resulted in a highly significant delay before the appearance of the first tumour, 82.5 in the controls, as compared to 124.9 weeks in the high Vitaminc C group. A second study demonstrated that Vitamin C decreased the incidence and delayed the onset of skin lesions caused by ultraviolet irradiation. At 20 weeks, five times more mice in the control groups had developed malignant lesions than in the high Vitamin C group.24
* Kandarker and Reade, University of Melbourne, Australia determined that topically applied Vitamin C delayed the progression cancerous cell changes caused by carcinogen (4-nitroquinoline-1-oxide) in oral mucosal cells in rats.25
* Ramesha and colleagues, University College, Delhi, India demonstrated that while breast tumor incidence in rats was reduced to between 46-57% by single applications of selenium (S), magnesium (M), Vitamin C (C) and Vitamin A (A), in combinations of twos tumour incidences were further reduced to between 25.9-31.8%. When all four nutrients were given, tumour incidence was reduced to only 12%.26

Back to the Real World of Oncology Practice
We have not yet arrived at the stage where everyone is prescribed preventive doses, and all cancer patients are prescribed massive doses of cancer-fighting antioxidant supplements. However, the nauseatingly repetitive statements "there is no scientific basis for the efficacy of Vitamin C" or "there is not enough research to demonstrate clinical efficacy" will continue to sound progressively more hollow as the mass of research data grows into higher mountains of proof.

Vitamin C Shields Cells

Sure they're tasty, but there's another reason that you might want to down a glass of freshly squeezed orange juice, slice a red pepper over your green salad and nibble a handful of fragrant strawberries. You'll be getting lots of vitamin C, potentially potent protection against cancer.

"Approximately 90 population studies have examined the role of vitamin C-rich foods in cancer prevention, and the vast majority have found statistically significant protective effects," reports researcher Gladys Block, Ph.D., of the University of California, Berkeley. "Evidence is strong for cancers of the esophagus, oral cavity, stomach and pancreas. There is also substantial evidence of a protective effect against cancers of the cervix, rectum and breast."

One review that looked at the results of several population studies found that women with the lowest risk of breast cancer were getting about 300 milligrams of vitamin C a day, the equivalent of about 4½ oranges or about three cups of orange juice. Their risk was reduced by about 30 percent.

In a study from Latin America, an area with one of the highest rates of cervical cancer in the world, women who got more than 314 milligrams of vitamin C a day had 31 percent less risk of developing cervical cancer than women whose intakes were under 153 milligrams a day.

And in a study from New Orleans, people getting at least 140 milligrams of vitamin C in their diets (about two oranges' worth) every day were only half as likely to develop lung cancer as those getting less than 90 milligrams a day.

"Vitamin C is a potent antioxidant," explains Balz Frei, Ph.D., associate professor of medicine and biochemistry at Boston University School of Medicine.

What's an antioxidant?

"Vitamin C," explains Dr. Frei, "along with certain other nutrients, has the ability to neutralize free radicals, harmful molecules in the body that can be produced during chemical reactions that involve oxygen."

Free radicals steal electrons from your body's healthy molecules to balance themselves, and in the process, they can harm a cell's membrane and genetic material. Antioxidant nutrients such as vitamin C offer free radicals their own electrons and so save cells from oxidative damage. "Free radical damage can occur as the result of normal body processes as we age and can also be the result of exposure to cancer-promoting chemicals," Dr. Frei explains.

Vitamin C helps prevent mouth, throat, stomach and intestinal cancers by neutralizing cancer-promoting nitrosamines. Nitrosamines are produced during the digestion of nitrites and nitrates. Nitrites are preservatives found in especially high concentrations in meats such as hot dogs and ham, while nitrates are naturally present in vegetables.

Vitamin Chelps maintain a healthy immune system, an additional cancer-fighting talent. Plus it may help build up vitamin E, another anti-cancer nutrient, to proper fighting form.

Most experts believe that the average daily intake of vitamin C, 109 milligrams for men and 77 milligrams for women, isn't enough to provide optimum cancer protection. Although vitamin Csupplements can easily boost your intake, eating vitamin C-rich foods such as citrus fruits and other tropical fruits, broccoli and brussels sprouts provides additional cancer protection with nutrients such as folate(the naturally occurring form of folic acid), beta-carotene, bioflavonoidsand fiber. In fact, evidence of anti-cancer activity is considerably stronger for vitamin C-rich fruits and vegetables than for vitamin C itself.

The amounts of vitamin C supplementation that doctors recommend to optimize the potential for cancer protection vary widely, from 50 to 5,000 milligrams or more a day. Most, however, stay within 250 to 1,000 milligrams a day, taken in two or three divided doses.

Prescriptions for Healing
If you have cancer, you should be under a doctor's care. The high doses of vitamins and minerals recommended here should be taken only under knowledgeable medical supervision and are not substitutes for standard cancer treatment.

Some doctors recommend these nutrients, in a range of amounts, as part of a program to prevent or treat cancer.

Prevention

Vitamin C (ascorbic acid)--has a chemotherapeutic effect on many cancers, promotes collagen production, sequestering the tumor, and reduces the toxicity of conventional therapies
Linus Pauling, winner of the Nobel Prize for chemistry in 1954 and the Nobel Prize for Peace in 1963, believed strongly that vitamin C could play an important role in cancer treatment. Dr. Pauling suggested 10 grams of vitamin C a day for patients with advanced cancer for whom conventional treatments had ceased to be of benefit (Cameron et al. 1993). Over an 8-year period, 500 patients with varying stages and types of cancer were treated with vitamin C therapy. Those receiving 10 grams of vitamin C a day improved their state of well-being, as measured by increased appetite and mental alertness, as well as a decreased need for pain-killing drugs. A retrospective analysis showed that those using vitamin C lived considerably longer than those not supplemented.

Various clinics are using intravenous vitamin C and with positive results. Dr. Hugh Riordan, recognized as a world authority on this procedure, practices from Wichita, KS, at the Center for the Improvement of Human Functioning International. Dr. Riordan's vitamin C story began in 1984 when he treated his first cancer patient; a 70-year-old renal cell carcinoma patient with metastasis to the lung and liver, using injectable vitamin C. Renal cell carcinoma has only a 5% response rate.

The initial treatment began with 15 grams of vitamin C administered intravenously 2 times a week; showing excellent tolerance, the vitamin C dosage was increased to 30 grams twice weekly. Within 6 weeks, the patient showed a favorable response to treatment and at the 12-week interval was pronounced tumor-free. The patient lived 14 additional years and died of congestive heart failure with no evidence of tumors.

In light of the favorable initial response to intravenous (IV) vitamin C, ascorbic acid was investigated. Vitamin C is preferentially toxic to tumor cells, that is, it kills tumor cells but not normal cells.

In low doses, vitamin C assumes the nature of an antioxidant; in high dosages, vitamin C changes roles and becomes a prooxidant, inducing peroxide production. Tumor cells have a relative catalase deficiency, an enzyme necessary to detoxify hydrogen peroxide to water and oxygen. A 10- to 100-fold difference in catalase concentrations exists between tumor cells and normal cells. Without the protection of catalase, peroxide accumulates in cancerous cells, along with aldehydes (toxic byproducts of the reaction), causing death to malignant cells. On the other hand, normal, healthy tissues have the protection of the detoxification enzyme and are spared destruction by peroxide and aldehyde. Vitamin C, a virtually nontoxic nutrient (Bowie et al. 2000), could cause a transient diarrhea if not absorbed properly.

Vitamin C is safe compared to standard chemotherapeutics and has an ability to preserve immune function. Many patients succumb, not because of cancer, but rather from a post-chemotherapeutic toxicity, resulting from a damaged immune system. Vitamin C protects the immune system. Vitamin C is preferentially toxic to many types of cancer cells, including 20 different melanoma cell lines. Ovarian cell lines are more susceptible to vitamin C-induced toxicity than pancreatic cells. Breast cancer appears to be one of the most responsive cancers to IV vitamin C.

Much higher concentrations of vitamin C are required to kill cancer cells than originally thought, about 600 mg/dL. Also, as the density of the cells increases, the efficacy of vitamin C decreases. It is extremely difficult to reach vitamin C concentrations greater than 200 mg/dL even when administered intravenously (Riordan et al. 2000). To increase the sensitivity of tumor cells to vitamin C, other approaches need to be employed.

Alpha-lipoic acid, a water- and lipid-soluble antioxidant that recycles vitamin, enhances the toxic effect of ascorbic acid. Lipoic acid decreases the dose of vitamin C required to kill tumor cells from 700 to 120 mg/dL (Riordan et al. 2000). Vitamin C toxicity is further enhanced by 1000 mcg of vitamin B12, which forms cobalt ascorbate, a benign but cancer-cell-toxic agent. Vitamin K, selenium, quercetin, niacinamide, biotin, and grape seed extract are also regarded as potentiation factors.

The goal is to achieve and maintain 400 mg/dL of vitamin C in the plasma. At this concentration, every cancer cell line so far tested has been found to be sensitive to vitamin C. After reaching an ascorbic acid peak, as occurs during infusion, the level returns to near baseline levels 24 hours after the IV infusion.

Vitamin C has an ability to increase collagen production. Vitamin C is required for the hydroxylation of proline, which in turn is required for collagen production. Vitamin C has the ability to inhibit enzymes that degrade or break down the extracellular matrix. Vitamin C dramatically increased the collagen within tumor cells, an act that tended to immobilize the cells

Vitamin C (supported by lipoic acid) has been used as a cancer therapy. It is strongly advised that patients contact a physician trained in administering infusions and monitoring progress. By giving vitamin C intravenously, doctors can achieve a blood saturation that far exceeds that attained by administering vitamin C orally (200% versus 2%). A high dose of vitamin C is critical to achieve tumor cell kill.

A Hickman line allows large doses of vitamin C to be self-administered at home on a daily to weekly basis over a period of months, modulating down or up in frequency according to response. Otherwise the treatment can be administered as an outpatient. Contraindications to vitamin C therapy are few but include individuals with kidney failure and on dialysis, as well as those with hemochromatosis. Also, physicians should screen patients for a red blood cell glucose-6 phosphate dehydrogenase deficiency, a rare condition whose presence can lead to a hemolytic crisis involving red blood cell breakdown.

Large doses of vitamin C should be reached gradually to establish tolerance. For example, 15 grams for one or two sessions and then 50 grams to 100 grams if necessary. The exact dose is determined by the individual's plasma saturation immediately after an infusion. The therapy should not be stopped abruptly because a rebound effect could result in scurvy. Patients should allow weeks or even months to wean off the treatment, with oral vitamin C therapy used on the days between infusions.

A 10-year research project using high dose IV vitamin C has been completed. While a number of orthomolecular physicians are using IV vitamin C therapy, it is recommended that Dr. Riordan's protocol become the backbone of the therapy. Instructions are available to physicians upon request from the center (Riordan et al. 2003).

Center for the Improvement of Human Functioning
3100 North Hillside Avenue
Wichita, KS 67219
(316) 682-3100

Other chemotherapeutic credits awarded to vitamin C:

Vitamin C prolongs the lives of animals undergoing conventional cancer treatment by protecting normal cells against chemotherapy-induced toxicity; in tandem, vitamin C increases the cytotoxicity targeted at the cancer (Antunes et al. 1998; Giri et al. 1998). When 5-FU was administered together with vitamin C, the tumor cell kill rate was boosted from 38 to 95.5%. X-ray therapy decreased cancer growth 72%, but adding vitamin C to the regime decreased cancer growth by 98.2%. Full spectrum antioxidants rather than isolated nutrients are suggested (Prasad et al. 1999; Moss 2000).
Infection: Heliobacter pylori increases the risk of developing stomach cancer (Uemura et al. 2001), as well as pancreatic cancer (Stolzenberg-Solomon et al. 2001). High doses of vitamin C inhibit the growth of H. pylori, both in vitro and in vivo (Zhang et al. 1997). A study showed vitamin C levels to be consistently low in individuals with the H. pylori infection (The Analyst 2002).
Frequent intake of vitamin C from food and supplement sources was associated with a protective effect against multiple myeloma, particularly among Caucasians. African Americans benefited less from ascorbic acid intake (Brown et al. 2001).
NF-kB is a central mediator of altered gene expression during inflammation and is implicated in cancer. Vitamin C inhibited the activation of NF-kB by multiple stimuli, including IL-1 and TNF-alpha (Bowie et al. 2000).
It should be re-emphasized that oral vitamin C does not bestow equal benefits compared to intravenous vitamin C. If a patient with a solid tumor elects to use oral vitamin C, ascorbic acid buffered with sodium may produce better results. If the cancer is blood-borne (leukemia, lymphoma, or myeloma), ascorbic acid crystals buffered with calcium appears to offer greater efficacy. The majority of the patients use 6-12 grams a day. Food sources of vitamin C are berries, citrus fruits, papayas, and pineapple, as well as tomatoes, broccoli, Brussels sprouts, dandelion and mustard greens, peas, red peppers, and spinach.

Some References

1. Nutrition and Cancer Database is a comprehensive compilation of published scientific research, with Abstracts. 1993. For information, contact the Bristol Cancer Help Centre (0272) 743 216.
2. Cameron E. Hyaluranidase and Cancer. Pergamon Press. 1966.
3. Pauling L. Vitamin C and the Common Cold. W.H. Freeman and Co. 1970.
4. Stone I. The Healing Factor: Vitamin C against Disease. Grosset and Dunlap. 1972.
5. Cameron E and Pauling L. Cancer and Vitamin C. The Linus Pauling Institute of Science and Medicine. 1979.
6. Cheraskin E. The Vitamin C Connection. Harper & Row. 1983.
7. Pauling L. How to Live Longer and Feel Better. W.H. Freeman & Co. 1986.
8. Goodman S. Vitamin C – The Master Nutrient. Keats. 1991.
9. Richards E. Vitamin C and Cancer: Medicine or Politics. MacMillan. 1991.
10. Stacey S. A glass a day can keep the doctor away. Preventive Medicine. The Sunday Times. 24 October 1993.
11. Block G. Epidemiologic evidence regarding vitamin C and cancer. Am J Clin Nutr; 54(6 Suppl):1310S-1314S. 1991.
12. Stahelin HB et al. Plasma antioxidant vitamins and subsequent cancer mortality in the 12-year follow-up of the prospective Basel Study. Am J Epidemiol; 133(8):766-75. 1991.
13. Enstrom JE et al. Vitamin C intake and mortality among a sample of the United States population. Epidemiology: 3(3):194-202. 1992.
14. Reed PT et al. Effect of ascorbic acid on the intragastric environment in patients at increased risk of developing gastric cancer; IARC Sci Publ; 105:139-42. 1991.
15. Howe GR et al. Dietary factors and risk of breast cancer: combined analysis of 12 case-control studies: J Natl Cancer Inst: 82(7):561-9. 1990.
16. Chen et al. Antioxidant status and cancer mortality in China. Int J epidemiol: 21(4):625-35. 1992.
17. Lupulescu A. Ultrastructure and cell surface studies of cancer cells following Vitamin C administration. Exp Toxicol Pathol; 44(1):3-9). 1992.
18. Kessler H et al. Potential protective effect of Vitamin C on carcinogenesis caused by nitrosamine in drinking water: an experimental study on Wistar rats. Eur J Surg Oncol; 18(3):275-81. 1992.
19. Cameron E. Protocol for the use of Vitamin C in the treatment of cancer. Med Hypotheses; 36(3):190-4. 1991.
20. Paganelli GM et al. Effect of Vitamin A, C and E supplementation on rectal cell proliferation in patients with colorectal adenomas. J Natl Cancer Inst; 84(1):47-41. 1992.
21. Tsao CS. Inhibiting effect of ascorbic acid on the growth of human mammary tumor xenografts. Am J Clin Nutr; 54 (6 Suppl): 1274S-1280S). 1991.
22. Poydock ME. Effect of combined ascorbic acid and B-12 on survival of mice with implanted Ehrlich carcinoma and L1210 leukemia. Am J Clin Nutr; 54( 6 Suppl): 1261S-1265S). 1991.
23. Liehr JG. Vitamin C reduces the incidence and severity of renal tumors induced by estradiol or diethylstilbestrol; Am J CLin Nutr; 54 (6 Suppl): 1256S-1260S). 1991.
24. Pauling L. Effect of ascorbic acid on incidence of spontaneous mammary tumors and UV-light-induced skin tumors in mice. Am J Clin Nutr; 54(6 Suppl): 1252S-1255S. 1991.
25. Kandarker SV. The effect of topical vitamin C on palatal oral mucosal carcinogenesis using 4-nitroquinoline-1-oxide. J Biol Buccale; 19(3): 199-204. 1991.
26. Ramesha A et al. Chemoprevention of 7, 12-dimethylbenz[a]anthracene- induced mammary carcinogenesis in rat by the combined actions of selenium, magnesium, ascorbic acid and retinyl acetate. Jpn J Cancer Res; 81(12): 1239-46. 1990.