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C -Carotene & Vitamin E
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The carotenoids are plant pigments that protect plant cells from damage and were thought to have an antioxidant role in human tissues -Carotene is a carotenoid found in high concentrations in human tissues; its importance as an antioxidant is controversial Several randomized studies have evaluated the effect of carotene and vitamin E on the prevention of cancer in highrisk populations The ATBC Cancer Prevention Study randomized 29,000 Finnish male smokers to receive -carotene, vitamin E, both agents, or neither agent for an average of 6 years A minimal (2%) and statistically insignificant reduction in the incidence of lung cancer was seen in the men who received vitamin E In contrast, there was a statistically significant 18% higher incidence of lung cancer in the group taking -carotene Vitamin E supplementation reduced prostate cancer incidence by 34% and colorectal cancer by 16%, though only the reduction in prostate cancer incidence was statistically significant Men in the control group with higher levels of vitamin E or -carotene before the study was initiated developed fewer lung cancers, suggesting that other components of foods high in these vitamins may be responsible for the protective effects noted in epidemiologic studies
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vitamin content of a diet high in vegetables In addition, intake of -carotene is a marker of increased fruit and vegetable consumption The balanced mixture of antioxidants found in a diet rich in fruit and vegetables may be more important and more effective in reducing cancer risk than carotene supplementation Other micronutrients such as vitamin E may prove more promising The Women s Health Study, begun in 1992, is a randomized, double-blind, placebo-controlled trial testing the risks and benefits of vitamin E, -carotene, and aspirin in the primary prevention of cancer and cardiovascular disease in 40,000 healthy female health professionals in the United States Results are expected in the next few years
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The Beta-Carotene and Retinol Efficacy Trial (CARET), a lung cancer chemoprevention study targeting high-risk populations, randomized a total of 18,000 smokers, nonsmokers, and workers with extensive occupational exposure to asbestos to receive either a combination of 30 mg/d of -carotene (as an antioxidant) and 25,000 international units/d of retinol (vitamin A as a tumor suppressor) or placebo With an average of 4 years and 73,000 person-years of follow-up, the combination of -carotene and vitamin A had no benefit on the incidence of lung cancer In fact, the active treatment group had a 28% higher incidence of lung cancer than the placebo group, and the mortality from all causes and the rate of death from cardiovascular disease were higher by 17% and 26%, respectively On the basis of these results, this study was stopped early The Physician s Health Study randomized 22,000 US male physicians to receive -carotene (50 mg on alternate days) or placebo The physicians were treated for an average of 12 years; 11% were current smokers and 39% were former smokers at the beginning of the study In this trial, no evidence either of benefit or of increased risk for cancer was found, with a much longer follow-up than either of the two other studies There were no differences in the overall incidence of malignant neoplasms, cardiovascular disease, or overall mortality in the group as a whole or in the smokers One additional randomized study that found a positive effect of -carotene supplementation evaluated a poorly nourished population group rather than the well-nourished populations described above Linxian, China, is an area with one of the world s highest rates of esophageal and stomach cancers and a habitually low intake of several nutrients In nearly 30,000 participants from the general population, the mortality rates from cancer were substantially lower among those who received daily supplementation with a combination of -carotene, -tocopherol, and selenium over a 5-year period A marked reduction in the cancer death rate (13%) was observed in the supplemented group, largely due to a 21% decrease in stomach cancer mortality Over 85% of cancers arose in the esophagus or stomach, but 31 deaths were caused by lung cancer The risk of death from lung cancer was reduced by 45% among those receiving supplements, though the numbers were very small (11 versus 20 lung cancer deaths), and only 30% were cigarette smokers A second study evaluated the effect of supplements, including -carotene, on prevention of esophageal and gastric cancers in over 3300 people with esophageal dysplasia Although esophageal cancer mortality and total cancer mortality were not significantly lower in the supplemented group, the incidence of mortality due to stomach cancer was higher On repeat endoscopy comparing results 2 and 6 years after randomization, dysplasia had resolved in about two-thirds of patients in both arms at 6 years These findings emphasize the need for placebocontrolled trials in the area of cancer prevention The NCI is currently collaborating with agencies in China to pursue further chemoprevention studies in this unique population In summary, there is no evidence to support the use of carotene in the primary prevention of cancer in well-nourished populations The major criticism of the large studies conducted to date is that increasing one type of vitamin even one stereoisomer of a vitamin does not reflect the
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