The role of your cancer health professional is to create an environment of openness and trust, and to help in making informed decisions about alternative/ complementary therapies. Collaboration will improve the safe integration of all therapies during your experience with cancer. The "Summary" and "Professional Evaluation/ Critique" sections of this Unconventional Therapies manual are cited directly from the medical literature, and are intended to help in the objective evaluation of alternative/ complementary therapies.

Summary

Use in Preventing Cancer:

Overall, it appears that the intake of vitamin C, certainly at the level of the RNI (Recommended Nutrient Intake) and possibly at supplement levels, is safe. The presentation of new findings, some of which are controversial, make it difficult for the scientific community to reach a consensus on the recommended level of antioxidants that would most likely achieve the goal of preventing disease in humans, and specifically cancer. At the present time, it is suggested that making changes in diet and lifestyle, including the consumption of more fruits and vegetables that are high in vitamin C and other antioxidants confers benefits well in excess of simply adding supplements to an existing diet.

Use in Treating Cancer:

"Some preliminary clinical data indicate that vitamin C may improve the survival of cancer patients. However, most of the studies were either anecdotal reports or uncontrolled case series, and therefore the results, although suggestive, are not conclusive." (Kaegi)

"...it can be concluded that high-dose vitamin C therapy is not effective against advanced malignant disease regardless of whether the patient has had any prior chemotherapy." (Moertel)

There is a lack of research to support the use of vitamin C in the treatment of cancer in humans. Researchers theorize that too much antioxidant (such as vitamin C) may interfere with chemotherapy and radiation, thereby leaving cancerous cells alive. Some chemotherapy and radiation therapy work by inducing apoptosis [programmed cell death] and in theory, use of antioxidant vitamins in these patients could potentially interfere with the benefits of treatment.

"Although moderate dietary levels of ascorbate often reach 250-1000 mg [milligrams] or more daily and appear beneficial, our data caution against sustained megadoses of ascorbate (Vitamin C) for treatment of patients with AIDS and cancer." (Eylar)

Description/ Source/ Components

More than 80% of the vitamin C in Western diets comes from foods of vegetable/fruit origin, chiefly citrus fruits, green vegetables, peppers, tomatoes, berries, and potatoes (Jacob 1994). Because some loss of vitamin C occurs with storage and in cooking, the best food sources are fruits and vegetables, preferably acidic, fresh and when necessary, rapidly cooked in very little water and served immediately. Cooking methods such as steaming and using the microwave will result in less vitamin C loss. Organically grown produce is the same as non-organic produce in fiber and vitamin content (Canadian Cancer Society). Growing organic foods may be protective of the environment but doesn't provide much of a nutritional advantage. Washing all fruits and vegetables under clean, running tap water will ensure clean, healthy produce.

Recommendations by the National Cancer Institute and Canada's Food Guide include the ingestion of a minimum of five servings of fruits and vegetables daily (Lachance). The vitamin C content of these five servings equates to approximately 200 mg [milligrams]. This value may be a useful estimate of optimal vitamin C ingestion based on food-consumption patterns which have demonstrated a protective effect for cancer.

* One Serving of Fruit or Vegetable Can Include:

• 1 medium orange
• 1/2 cup frozen carrots
• 1 cup tossed green salad
• 1/2 cup apple juice

** Dark Green and Orange Vegetables and Orange Fruits Include:

• Carrots
• Cantaloupe
• Sweet potato (yam)
• All citrus fruit
• Broccoli
• Mangoes
• Brussel sprouts
• Papaya
• Spinach
• Strawberries
• Swiss chard
• Asparagus

Vitamin C content of selected foods* (Nutritionist IV Diet Analysis)

RNI (Recommended Nutrient Intake)*:

The current Recommended Nutrient Intake (Health and Welfare Canada) in Canada is:

• Males: 40 mg (Age 25-74)
• Females: 30 mg (Age 25-74)

For smokers the recommended vitamin C intake is 50% higher.

• Males: 60 mg (Age 25-74)
• Females: 45 mg (Age 25-74)

Supplements on the market today generally contain 100, 250, 500 or 1000 mg [milligrams] of vitamin C per tablet. Vitamin C crystals are also available in some drug stores and health food stores. Prices vary greatly, with generic and store brands generally being 1/2 to 1/3 the cost of name brands. Timed-release tablets are formulated to be released slowly in the body over an 8-hour period and are most often 1000 mg/tablet.

History

An association between vitamin C and cancer was found by McCormick in 1959. (Loescher)

"The claim that vitamin C is useful in the treatment of cancer [has been] made by Dr. Linus Pauling, PhD., since the early 1970s." (CA)

Proponent/ Advocate Claims - Use in Preventing Cancer

Numerous mechanisms have been proposed whereby vitamin C may act on cancer cells (Lupulescu).

1. as an antioxidant and scavenger of free radicals;
2. by acting together with vitamin E in lipid peroxidation;
3. by blocking the formation of carcinogenic nitrosamines from nitrates in the stomach;
4. by stimulating immune system activity (phagocytosis, detoxification and chemotaxis);
5. by exerting antibacterial and antiviral actions;
6. by protecting against carcinogen-induced chromosomal breakage;
7. by preventing carcinogen-induced transformation and progression of normal cells to cancerous cells, and in some cases reversing the transformed cells back to a normal state.

The evidence which links increased intakes of fruits and vegetables with decreased risk of most types of cancer comes from consistent epidemiological evidence (Flagg).

Fruits and vegetables contain a large number of constituents including vitamin C, which may contribute to cancer prevention. The evidence appears most convincing for the protective effect of vitamin C from dietary sources against cancers of the stomach, esophagus, oral cavity and pharynx (Flagg).

In a comprehensive review of vitamin C and cancer risk, Block (Block) found that 18 of 20 studies of cancers at these sites showed significant associations between a diet low in vitamin C and increased risk of cancer. At least in the stomach, the protective effect may be attributed to the ability of vitamin C to block the formation of nitrosamines, which can form in the stomach with the ingestion of high amounts of salted, pickled or cured foods (Yamanaka).

For cancers of other sites including lung, rectum, cervix, colon and breast, the association is not as strong but epidemiological data indicates a diet high in vitamin C may reduce the risk of cancer at several sites in the body (Bendich).

"There is some epidemiologic evidence that populations whose dietary intake of vitamin C is high have a decreased risk of some types of cancer. (Merill) This may be due to the antioxidant function of the vitamin or its ability to block the formation of N-nitrosamines, which are formed in the stomach following the ingestion of certain foods. The strongest epidemiologic finding has been the association between high intakes of foods rich in vitamin C and a reduced risk of stomach cancer. (Sauberlich) There is weaker evidence that high levels of vitamin C are associated with a decrease risk of cervical cancer in smokers. (Merill)" (Kaegi)

Professional Evaluation/ Critique - Use in Preventing Cancer

The relationship between diet and cancer is believed to be strong. When considering changes in diet and possible supplementation of individual nutrients, it is extremely important to remember the following relationship, which is based on the results of numerous epidemiological studies:

High correlation ----------------------------------->----------------------------------------- Low Correlation

Overall diet ------------>------------- Particular Food ------------->------------ Individual Nutrients

(Adapted from: Helzlsouer et al, 1994)

The relationship between many types of cancer and overall diet tends to be very strong. [However, the relationship between particular nutrients and cancer is less clear.] This phenomenon is very likely due to the fact that we do not as yet know all of the important nutrients that are found in food (Helzlsouer). For example, an overall diet rich in fruits and vegetables is protective against cancer. Fruits and vegetables are a good source of individual nutrients (including fiber, antioxidants, vitamins, minerals and phytochemicals) which, alone, have not reproduced the same beneficial effects. The protective effect may be strongest when all these components are consumed as part of the diet.

While epidemiological studies reveal associations, intervention studies are designed to determine a cause and effect relationship (Rautalahti). The results of a large-scale intervention study on antioxidants and cancer risk has recently been published. The study, conducted in Linxian, China, involved 29,584 adults who received several mixtures of vitamins and minerals for 5 years. The group receiving 120 mg [milligrams] of vitamin C showed no significant reduction in risk of cancer. (Blot)

For cancers of the ovary and prostate, none of the studies reviewed showed an effect of vitamin C in preventing cancer. (Bendich)

"A double-blind, placebo-controlled, randomized, factorial study using a daily oral administration of [vitamin C] was conducted in 141 women with... minor squamous atypia or cervical intraepithelial neoplasia (CIN) I... The currently available evidence from this and other trials suggests that high doses of [vitamin C] are unlikely to increase the regression or decrease the progression of minor atypia and CIN I." (Mackerras)

Although no dietary advice can guarantee the prevention of cancer, recommendations by the Canadian Cancer Society (Canadian Cancer Society) to lower risk include:

1. A lower fat diet
2. A diet rich in whole grain foods, fruits & vegetables
3. Less alcohol
4. Maintaining a healthy weight
5. Cooking methods that avoid the charring or deep browning of foods
6. Limit consumption of salt & nitrite preserved and real smoked foods

Proponent/ Advocate Claims - Use in Treating Cancer

Many chemotherapy agents have immune suppressive qualities that can result in infectious complications. It has been hypothesized that high doses of vitamin C could be preferentially toxic to tumor cells without having immune suppressive qualities. This potential demonstrates the need to investigate their use as a chemotherapeutic agent. To date, unlike the numerous studies on cancer prevention, relatively little work has been done in regards to the use of vitamin C in the treatment of cancer. In Japan, use of vitamin C in humans, not as a primary anticancer drug but as a means of counteracting the toxicity of some cancer treatments has shown some promise. In animal studies, vitamin C blocks the oxidative damage to heart muscle that often occurs as a side effect of the anticancer drug, adriamycin (Barinaga). In New York, Stuart Marcus and Peter Wiernick at the Montefiore Medical Center found that patients undergoing Interleukin-2 cancer treatment had vitamin C levels drop to levels low enough to cause scurvy. This may contribute to the treatment's toxicity (Barinaga).

The use of vitamin C as a tumor cytotoxic chemotherapeutic agent has been proposed. To date, studies have demonstrated that vitamin C can be infused at a high enough rate to maintain blood levels of vitamin C proven high enough to kill tumor cells in a test tube (Riordan). The next step in this research will be to determine if these infusion levels of vitamin C are able to make a significant impact on tumor burden in patients with cancer.

"Megadose vitamin C therapy for cancer may be administered either intravenously or orally. (Cameron 1979) (Riordon) Proponents advise that it can be given concurrently with chemotherapy. (Cameron 1974) They claim that megadose vitamin C therapy improves the well-being and quality of life of cancer patient and that it may result in improved survival." (Kaegi)

"In laboratory experiments, vitamin C has been shown to have a range of effects that could be beneficial to cancer patients, including tumour regression, the inhibition of tumour growth and increased survival of animals with implanted tumours as well as promotion of cell differentiation and stabilization of gene transcription." (Kaegi)

"Proponents criticized the design of both studies [showing negative results for vitamin C as a treatment for cancer (see Professional Evaluation / Critique - (Moertel),(Creagan))], specifically the focus on patients with advanced disease and limited life expectancy, the route of administration (oral rather than intravenous), the sudden withdrawal of vitamin C in some cases and patient selection criteria." (Kaegi)

Professional Evaluation/ Critique - Use in Treating Cancer

"Some preliminary clinical data indicate that vitamin C may improve the survival of cancer patients. However, most of the studies were either anecdotal reports or uncontrolled case series, and therefore the results, although suggestive, are not conclusive." (Kaegi)

At the University of Pennsylvania in Philadelphia, John E. Biaglow and colleagues suggest that antioxidants interfere with the ability of radiation and chemotherapy to kill cancer cells. By recommending that patients stop taking antioxidant vitamins a few days prior to radiation they hope to improve the kill rate of the radicals generated by the radiation or drug treatment (Adler).

This line of thinking is supported by recent work in the expanding field of research in apoptosis. Apoptosis is the pre-programmed death of cells in the body [the end of the life cycle of cells], including those cells that are on the way to becoming cancerous. Oxidation reactions appear to initiate apoptosis and move it along (Holzman). Researchers theorize that too much antioxidant may interfere with the process and leave the precancerous cells alive. Some chemotherapy drugs work by inducing apoptosis and in theory, use of antioxidant vitamins in these patients could potentially interfere with treatment.

Use of vitamins may not be without risk. Water soluble vitamins in megadoses may in some cases be tumor promoters. Because the exploration of megadoses of vitamin C as a therapeutic agent is in its infancy, the use of large dose vitamin therapy for prevention and treatment of cancer requires a fuller understanding of all the anticancer mechanisms involved before concrete recommendations can be made.

Motivated by the claims of Pauling and Cameron, investigators at the Mayo Clinic conducted a placebo-controlled double-blind study:

"One hundred and fifty patients with advanced cancer participated in a controlled double-blind study to evaluate the effects of high-dose vitamin C on symptoms and survival... The two groups showed no appreciable difference in changes in symptoms, performance status, appetite or weight. The median survival for all patients was about seven weeks, and the survival curves essentially overlapped. In this selected group of patients, we were unable to show a therapeutic benefit of high-dose vitamin C treatment." (Creagan)

This trial was criticized by Pauling on the grounds that the cytotoxic chemotherapy given to the large majority of patients before study entry might have inhibited the ability of vitamin C to stimulate host defenses. (Pauling 1980)

This criticism persuaded Moertel to conduct a second study:

"In a double-blind study 100 patients with advanced colorectal cancer were randomly assigned to treatment with either high-dose vitamin C (10 g daily) or placebo. Overall, these patients were in very good general condition, with minimal symptoms. None had received any previous treatment with cytotoxic drugs. Vitamin C therapy showed no advantage over placebo therapy with regard to either the interval between the beginning of treatment and disease progression or patient survival. Among patients with measurable disease, none had objective improvement. On the basis of this and our previous randomized study, it can be concluded that high-dose vitamin C therapy is not effective against advanced malignant disease regardless of whether the patient has had any prior chemotherapy." (Moertel)

"This study indicates that... L-ascorbic acid [enhances the growth of human leukemic colony forming cells (L-CFC) in one third of the patients with acute non-lymphocytic leukemia]... and that L-CFC growth enhancement is a clearly significant finding with a biological mechanism as the basis" (Park)

Toxicity/ Risks

Several reviews (Diplock) (Levine) have concluded that vitamin C has little toxicity. Even when consumed at very high levels of intake (10,000 -20,000 mg/d) for long periods of time, adverse effects have not been convincingly demonstrated. At usual dietary intakes (30-180 mg [milligrams]) vitamin C is approximately 90% absorbed (Jacob 1994). Absorption falls to 50% with a dose of 1500 mg [milligrams] and to 16% with a dose of 12,000 mg [milligrams].

High doses of vitamin C, however, can interfere with certain laboratory tests for glucose, uric acid, creatinine and inorganic phosphate and can interfere with the detection of occult blood in feces. Clinicians are advised to discuss these possibilities with patients and suggest discontinuation of the supplement several days prior to testing.

Ingestion of vitamin C is known to enhance the absorption of non-heme iron from foods consumed at the same meal (Levine). Recent evidence suggests that high body iron stores are associated with increasing risk for cancer and heart disease. Studies have demonstrated, however, that in individuals with normal iron status large doses of vitamin C do not result in excessive iron accumulation (Herbert 1996). It appears that only those patients with inherited iron overload disease, hemochromatosis, or other genetic diseases of the blood, such as thalassemia and sideroblastic anemia be advised not to consume vitamin C supplements due to this concern.

"Vitamin C may interfere with the absorption or activity of a number of agents, including anticoagulants, iron, vitamin B₁₂, and vitamin E. Effects of vitamin C on the absorption or excretion of chemotherapeutic drugs are possible, but reports of such effects were not found. High doses of vitamin C during pregnancy may cause subsequent vitamin C deficiency in newborns. (Sauberlich)_(Bendich)" (Kaegi)

"Since oxidative DNA damage has been suggested as a risk factor for the development of cancer, the implications of increased levels in well-nourished subjects after iron/ascorbate supplementation are disturbing in view of the frequent use of dietary supplements containing both iron salts and ascorbate." (Rehman)

"Excess vitamin C is excreted in the urine. Side effects are uncommon, [but include] nausea, diarrhea, kidney stone formation." (Cassileth)

"The suppressive effect of ascorbate [on the immune system] appears irreversible, since removal of ascorbate after 18 hours did not restore the mitogenic response [T-cell proliferation]. Although moderate dietary levels of ascorbate often reach 250-1000 mg [milligrams] or more daily and appear beneficial, our data caution against sustained megadoses of ascorbate for treatment of patients with AIDS and cancer." (Eylar)

References

Adler T Power foods: looking at how nutrients may fight cancer.

Barinaga M. Vitamin C gets a little respect. Science 1991;254:374-376.

Bendich A, Langseth L. The health effects of vitamin C supplementation: a review. Journal of the American College of Nutrition 1995;4:124-136.

Block G. Vitamin C status and cancer: epidemiologic evidence of reduced risk. Annals of the New York Academy of Science 1992;669:280-290.

Blot W, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, disease-specific mortality in the general population. Journal of the National Cancer Institute 1993;85:1483-91.

CA (Anonymous). Questionable methods of cancer management: 'nutritional' therapies. CA: a Cancer Journal for Clinicians 1993 Sept/Oct;43(5):309-319.

Cameron E, Pauling L. Ascorbic acid as a therapeutic agent in cancer. J Int Acad Prev Med 1979;5:8-29.

Cameron E, Campbell A. The orthomolecular treatment of cancer: II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem Biol Interact 1974;9:285-315.

Canadian Cancer Society. Healthy eating: reducing your risk of cancer. 1992.

Cassileth BR. Alternative medicine handbook: the complete reference guide to alternative and complementary therapies. New York: W.W.Norton & Co., 1998:67,74.

Creagan ET, et al. Failure of high dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer: a controlled trial. N Engl J Med 1979;301:687-90.

Diplock AT. Safety of antioxidant vitamins and _-carotene. American Journal of Clinical Nutrition 1995;62(Suppl):1510S-1516S.

Eylar E, et al. Sustained levels of ascorbic acid are toxic and immunosuppressive for human T cells. Puerto Rico Health Sciences Journal 1996;15:21-6.

Flagg EW, et al. Epidemiological studies of antioxidants and cancer in humans. Journal of the American College of Nutrition 1995;14:419-27.

Health and Welfare Canada. Nutrition Recommendations: The Report of the Scientific Review Committee. Ottawa: Supply and Services Canada. 1990.

Helzlsouer KJ, et al. Summary of the round table discussion on strategies for cancer prevention: diet, food, additives, supplements and drugs. Cancer Research (Supplement) 1994;54:2044S-51S.

Herbert V, Shaw S, Jayatilleke E. Vitamin C-driven free radical generation from iron. Journal of Nutrition 1996;126:1213S-20S.

Holzman D. Do antioxidants promote cancer? Alternative & Complementary Therapies June 1997.

Jacob RA. Vitamin C. In Modern Nutrition in Health and Disease. Edited by M.E. Shils, J.A. Olson, M. Shike. Lea & Febiger, Philadelphia, 1994.

Kaegi E, on behalf of the Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. Unconventional therapies to cancer: 5. Vitamins A, C, and E. Canadian Medical Association 1998; 158:1483-88.

Lachance PA, Langseth L, eds. Proceedings of the Rutgers Workshop on the future of the recommended dietary allowances. New Brunswick, NJ; Cook College Continuing Education, 1993.

Levine M, et al. Determination of optimal vitamin C requirements in humans. American Journal of Clinical Nutrition 1995;62(Suppl):1347S-1356S.

Loescher LJ, Sauer KA. Vitamin therapy for advanced cancer. Oncology Nursing Forum 1984 Nov/Dec;11(6):38-45.

Lupulescu A. The role of vitamins A, _-carotene, E and C in cancer cell biology. International Journal of Vitamin Nutrition Research 1993;63:3-14.

Makerras D, et al. Randomized double-blind trial of beta-carotene and vitamin C in women with minor cervical abnormalities. Br J Cancer 1999;79:1448-53.

Merill AH, et al. Vitamins and cancer. In: Alfin-Slater RB, Kritchevsky D, editors. Cancer and Nutrition. New York: Plenum Press, 1991:261-320.

Moertel CG, et al. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy: a randomized double-blind comparison. N Engl J Med 1985;312:137-41.

Nutritionist IV Diet Analysis, Version 4.1, Copyright 1995, First Data Bank Division, The Hearst Corporation.

Park CH. Biological nature of the effect of ascorbic acid on the growth of leukemic cells. Cancer Research 1995;45:3969-3973.

Pauling L. Vitamin C therapy of advanced cancer. N Engl J Med 1980;302:694.

Rautalahti M, Huttunen J. Antioxidants and carcinogenesis. Annals of Medicine 1993;25:435-441.

Rehman A, et al. The effects of iron and vitamin C co-supplementation on oxidative damage to DNA in healthy volunteers. Biochem Biophys Res Commun 1998;246:293-8.

Riordan NH, et al. Intravenous ascorbate as a tumor cytotoxic chemotherapeutic agent. Medical Hypotheses 1995;44:207-213.

Sauberlich HE. Pharmacology of vitamin C. Annu Rev Nutr 1994;14:371-91.

Yamanaka WK. Vitamin C and cancer: how convincing a connection? Postgraduate Medicine 1985; 78:47-53.

Note: original material in this section (not in quotations) was authored by: Raylene Reimer, RDN, PhD
BC Cancer Agency, Nutrition Services

Revised February 2000