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
"In sum, there is little evidence to support the idea that, within the wide range of doses bordered by deficiency and toxicity, modulating preformed vitamin A intake will have any substantial cancer-preventive effect." (International Agency for Research on Cancer)
There is insufficient evidence that vitamin A is effective in treating or preventing cancer.
High doses of vitamin A may be toxic. (See Toxicity/ Risks section below)
Description/ Source/ Components
"Vitamin A is one of a group of substances that have similar structures and biological activities and that are known collectively as retinoids." (Kaegi)
"It cannot be synthesized in the body and must therefore be taken in with food as either vitamin A alcohol (retinol) and its esters or beta carotene (a pro vitamin split in the intestine to vitamin A)" (Bollag)
"Natural preformed vitamin A is found only in foods from animal sources." (Willett)
"Vitamin A is necessary for normal growth, bone development, vision and reproduction and for the maintenance of the integrity of the skin and mucous membranes. A deficiency in vitamin A, rare in developed countries, can lead to night blindness, dermatoses and decreased resistance to infection." (Kaegi)
"Unlike beta-carotene, vitamin A is not an antioxidant, so its benefits relate to its possible roles in reversing tumor development and boosting immune function." (McDonald)
Because vitamin A is a fat-soluble vitamin, oral supplements should be taken with food that contains at least a little fat. (Kaegi)
Preformed vitamin A is found in natural sources such as milk, cheese, yogurt, "fish liver oils, liver, egg yolk, butter, cream..." (Ontario)
The recommended adult daily intake of vitamin A is 800-1000 Retinol Equivalents (RE). 1 RE = 3.33 IU's. (Health and Welfare Canada)
History
"Vitamin A was first discovered in 1913 as a fat-soluble substance required for normal nutrition." (Loescher)
"The association of vitamin A and cancer was initially reported in 1926 when rats, fed a vitamin A-deficient diet, developed gastric carcinomas." (Loescher)
"The first investigation showing a relationship between vitamin A and human cancer was performed in 1941 by Abelsetal who found low plasma vitamin A levels in patients with gastrointestinal cancer." (Loescher)
Proponent/ Advocate Claims - Use in Preventing Cancer
Proponents claim that "vitamin A has the potential to reverse precancerous lesions..." (McDowell)
"Moon and colleagues "conducted a randomized, double-blind, controlled trial to examine the efficacy of retinol supplementation on the incidence of first new nonmelanoma skin cancer in moderate-risk subjects." They concluded that "daily supplementation with 25,000 IU of retinol was effective in preventing SCC [squamous cell carcinoma], although it did not prevent BCC [basal cell carcinoma]." (Moon)
de Klerk and colleagues compared rates of disease and death in subjects randomly assigned to beta-carotene or retinol. They concluded that "the findings of significantly lower rates of mesothelioma among subjects assigned to retinol requires further investigation." (de Klerk)
Intervention trials were conducted in Kerala, India, involving fishermen who chewed tobacco--containing betel quids daily before and throughout the study period. "Administration of vitamin A (60 mg/wk) for 6-mo resulted in complete remission of leukoplakias in 57% and a reduction of micronucleated cells in 96% of tobacco-chewers. After withdrawal of vitamin A, oral leukoplakias reappeared and frequency of micronuclei in oral mucosa increased." (Stich)
"Studies that use animal models have shown that retinoids (including vitamin A) can act in promotion-progression phase of carcinogenesis and block the development of invasive carcinoma at several epithelial sites, including the head and neck and lung." (Lippman)
Professional Evaluation/ Critique - Use in Preventing Cancer
"There is evidence suggesting lack of cancer-preventive activity of preformed vitamin A for cancers at the following sites: upper aerodigestive tract, lung, breast (among postmenopausal women), colorectal, bladder, prostate and stomach. There is inadequate evidence with respect to possible cancer-preventive activity of preformed vitamin A at all other sites and for second primary cancers of the lung." (International Agency for Research on Cancer)
"The observed effects of preformed vitamin A on cell and organ culture, on animal models, in dietary observational epidemiological studies, and in human intervention studies was reviewed in the meeting. In summary, there is little evidence that vitamin A intake has any substantial cancer-preventive effects. (Giovannucci)" (Vainio)
"Vitamin A (retinol) and its active metabolites are essential for cell differentiation, visual function, physiologic growth, and reproduction, yet despite numerous studies, no consistent association with cancer risk has been established." (Olson)
The World Cancer Research Fund and the American Institute for Cancer Research summarizes that high dietary retinol intake possibly has no relationship with the risk of breast, cervical, lung, and stomach cancers. (World Cancer Research Fund)
"...a recently reported large study involving smokers receiving beta-carotene and vitamin A reported the unexpected finding of an increased risk of lung cancer. (Omenn)" (Kaegi)
For the present, the data presented by Pastorino et al. (see under Proponent/ Advocate Claims) are promising, however, they are not conclusive. Further studies will be needed. (Lippman)
"Some studies show an inverse relationship between serum retinol and the risk of prostate cancer, while others indicate a positive association, particularly in men over the age of 70 years. Some of this discrepancy may be explained by the fact that vitamin A comes from both plant sources (carotenoids) and animal sources (vitamin A), so that a link with dietary fat may be a confounding variable." (Olson)
"The objective of this study was to examine the effect of retinol and isotretinoin on the incidence of nonmelanoma skin cancer in high-risk subjects... There were no differences between those who received retinol, isotretinoin, or the placebo, with regard to the time to first occurrence or to the total number of tumors noted. No beneficial effects were noted with regard to the prevention of nonmelanoma skin cancer with either retinol or isotretinoin." (Levine)
Proponent/ Advocate Claims - Use in Treating Cancer
"The anticancer effects of retinoids are thought to be due to inhibition of cell proliferation and promotion of cell differentiation. Recently, progress has been made in establishing a possible mechanism of action at the cellular level. For example, the presence of retinoid receptors has been reported, and one study using breast cancer cells showed that retinoids attaching to these receptors influence gene expression and cell proliferation. (Baumann)" (Kaegi)
"Daily oral administration of high-dose vitamin A is effective in reducing the number of new primary tumors related to tobacco consumption and may improve the disease-free interval in patients curatively resected for Stage I lung cancer." (Pastorino)
"Some animal studies have shown the ability of vitamin A, beta-carotene and other retinoids to enhance the immune system, to retard tumor growth and to decrease the size of established tumors." (Kaegi)
"There is also a decrease in metastases if retinoids are used as adjuvant treatment after removal of the primary tumor." (Spencer)
"In Pastorino's lung trial,... the average annual second primary tumor rate was 4.8% in the control arm versus 3.1% in the treatment arm, a reduction of 35%. In the head and neck trial, the annual second primary tumor rate was 6.8% (control) versus 3.1% (treatment), a reduction of 54%." (Lippman)
Professional Evaluation/ Critique - Use in Treating Cancer
"Although a vitamin A derivative, all trans-retinoic acid induces a high initial rate of complete remission in acute promyelocytic leukaemia patients, disease relapse is generally the case." (van der Weyden)
In a study involving two hundred forty patients with a histologically confirmed diagnosis of primary melanoma that was greater than 0.75-mm thickness in vertical height, patients were divided into two groups. One group received 100,000 IU of vitamin A orally daily for 18 months. The other group was randomized to observation alone. At the end of the study, "there was no difference in disease-free survival or overall survival between the two groups." (Meyskens)
Toxicity/ Risks
"Serious toxic effects from taking vitamin A supplements are relatively rare, but side effects such as headache, irritability, drowsiness, dizziness, itchiness, desquamation and perioral dermatitis may occur. Megadoses may cause liver damage." (Kaegi)
"Preformed vitamin A is not excreted from the body; doses may accumulate in the body and liver causing potentially harmful toxicity, including hemotoxicity." (McDowell)
"Signs and symptoms of vitamin A toxicity include: blurred vision, bone/joint pain, diarrhea, fatigue, hair loss, nausea, headache, hypercarotenemia (yellow discoloration of skin from excess beta carotene; harmless, reverses with discontinuation of vitamin A), irregular menses, liver enlargement, rashes, scaly skin, vomiting, swelling, and fluid accumulation." (McDowell)
Patients who received vitamin A experienced various kinds of toxicity: emotional/personality change, rash, nausea, gastrointestinal distress, thrombocytopenia, fatigue, bone/joint pain, conjunctivitis, insomnia, and impotence. (Meyskens)
"High doses of vitamin A have a potent teratogenic effect [tendency to produce anomalies of formation of the fetus] and are therefore contra-indicated during pregnancy... This high teratogenic potency justifies a strict limitation of such a prescription in women susceptible to become pregnant." (Guillonneau)
"...a recently reported large study involving smokers receiving beta-carotene and vitamin A reported the unexpected finding of an increased risk of lung cancer. (Omenn)" (Kaegi)
"High dietary intake of retinol seems to be associated with osteoporosis." (Melhus)
"When given high doses or on a long-term basis (as with cancer therapy or self-medication), retinoids are potentially toxic. In adults, a single vitamin A dose of 2 million IU can cause acute toxicities of increased intracranial pressure within 8 to 12 hours, and cutaneous desquamation in a few days. Adults receiving 50,000 IU daily for longer than 18 months or 500,000 IU daily for two months can develop retinoid toxicity." (Loescher)
"Vitamin A toxicity may be difficult to recognize clinically until the patient is quite ill." (Clinical)
"Doses of vitamin A only slightly in excess of the RDA produce neurological toxicity in some cases." (Snodgrass)
According to Dr. Byers, Chief of the Chronic Disease Prevention Branch in the Division of Nutrition at the Centers for Disease Control (CDC), "at this time doses of either vitamin A or beta carotene far in excess of what one would normally intake from diet are probably not a good idea until specific vitamin formulations for health benefits are known... Supplements do not seem to have a role in prevention of cancer, heart disease, or obesity at this point." (McDowell)
Vitamin A is expressed as either RE (retinol equivalents) or IU (international units): Acute toxicity may occur at 90,000-300,000 RE (single dose). Chronic toxicity may occur at 3,600-15,000 RE/day in children and >10,000 RE/d in adults. >7,500 RE/d in pregnancy can lead to congenital malformations. (Note: 1 IU of vitamin A = 1/1.33 RE) Guidelines for "upper safe limits" (USL) for all vitamins and minerals is currently under revision as a joint undertaking between USA and Canada national dietetic organizations. (British)
Costs
Ninety 10,000 IU capsules of vitamin A cost approximately $4. (Ontario)
References
Baumann KH, Clarke R. Effects of all-trans retinoic acid on proliferation and gene expression of human breast cancer cells in vitro [abstract 1643]. Proc Annu Meet Am Assoc Cancer Res 1994;35:275.
Bollag W. Vitamin A and the retinoids: from nutrition to pharmacology in dermatology and oncology. Lancet 1983;1(8329):860-863.
British Columbia Dietitians' and Nutritionists' Manual of Nutritional Care, 4th ed., 1992. Appendix G: Adverse effects of large doses of vitamins and minerals:542-545.
Clinical Oncology Alert (Anonymous). What harm can a little vitamin A do? Clinical Oncology Alert 1995 Mar:22.
de Klerk NH, et al. Vitamin A and cancer prevention II: comparison of the effects of retinol and beta-carotene. Int J Cancer 1998;75:362-67.
Giovannucci E, et al. Epidemiologic characteristics of prostate cancer. Cancer 1995;75:1766-77.
Guillonneau M, Jacqz-Aigrain E. Teratogenic effects of vitamin A and its derivatives [French]. Archives de Pediatrie 1997;4:867-74.
Health and Welfare Canada. Nutrition recommendations. The Report of the Scientific Review Committee 1990.
International Agency for Research on Cancer. World Health Organization. IARC handbook of cancer prevention: vitamin A. Lyon, France: IARC, 1998:202-3.
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.
Levine N, et al. Trial of retinol and isotretinoin in skin cancer prevention: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Group. Cancer Epidemiol Biomarkers Prev 1997;6:957-61.
Lippman SM, Hong WK. Not yet standard: retinoids versus second primary tumors. Journal of Clinical Oncology 1993 July;11(7):1204-1207.
Loescher LJ, Sauer KA. Vitamin therapy for advanced cancer. Oncology Nursing Forum 1984 Nov/Dec;11(6):38-45.
McDonald A, et al. Complete book of vitamins and minerals. Publications International, Ltd., 1996;94-5.
McDowell B. Vitamin A and beta carotene: broad therapeutic applications. Alternative & Complementary Therapies 1995 January/February:67-75.
Melhus H, et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med 1998;129:770-78.
Meyskens FL, et al. Randomized trial of vitamin A versus observation as adjuvant therapy in high-risk primary malignant melanoma: a SouthWest Oncology Group study. Journal of Clinical Oncology 1994 Oct;12(10):2060-2065.
Moon TE, et al. Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev 1997;6:949-56.
Olson KB, Pienta KJ. Vitamins A and E: further clues for prostate cancer prevention. J Natl Cancer Inst 1998;90:414-5.
Omenn GS, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334:1150-5.
Ontario Breast Cancer Information Exchange Project. Guide to unconventional cancer therapies. 1st ed. Toronto: Ontario Breast Cancer Information Exchange Project, 1994:253-256.
Pastorino U, et al. Adjuvant treatment of Stage I lung cancer with high-dose vitamin A. J Clin Oncol 1993 July;11(7):1216-1222.
Snodgrass SR. Vitamin neurotoxicity. Molecular neurobiology 1992;6(1):41-73.
Spencer JW, Jacobs JJ. Complementary/alternative medicine: an evidence based approach. Toronto: Mosley, 1999:133-4.
Stich HF, et al. Remission of precancerous lesions in the oral cavity of tobacco chewers and maintenance of the protective effect of B-carotene or vitamin A. American Journal of Clinical Nutrition 1991;53:298S-304S.
Vainio H, Rautalahti M. An international evaluation of the cancer preventive potential of vitamin A. Cancer Epidemiol Biomarkers Prev 1999;8:107-9.
van der Weyden MB, Curtis DJ, Szer J. Vitamin therapy for acute leukaemia. Australian & New Zealand Journal of Medicine 1992 Oct;22(5):446-448.
Willett WC, et al. Diet and cancer - an overview. (Part 1) New England Journal of Medicine 1984;310:633-638 ; Part 2 NEJM 1984;310:697-703
World Cancer Research Fund in Association with American Institute for Cancer Research. Food, nutrition and th-e prevention of cancer: a global perspective. World Cancer Research Fund/American Institute for Cancer Research, 1997;142,157,276,307.
Revised February 2000