VITAMIN E, BETA CAROTENE, SELENIUM SUPPLEMENTS REDUCED CANCER MORTALITY

VITAMIN E, BETA CAROTENE, SELENIUM SUPPLEMENTS REDUCED CANCER MORTALITY and incidence in a study of Chinese villagers conducted by William Blot, PhD, National Cancer Institute, et al. Published in the Sept. 15 issue of the Journal of the National Cancer Institute, the study found that the relative risk of mortality from stomach cancer in subjects taking a daily regimen of vitamin E, beta carotene and selenium during the five years of the trial was 21% below that for subjects on placebo. In addition, the incidence of stomach cancer among those taking vitamin E, beta carotene and selenium supplements dropped 16% compared to placebo. The study was conducted in the Linxian area of China where the esophageal and gastric cardia cancer rate is "one of the world's highest," the researchers reported. "The decrease in cancer mortality among those receiving beta carotene, vitamin E and selenium was more pronounced for stomach and other cancers than for esophageal cancers, but differences between [relative risks] were not significant," the researchers said. Esophageal cancer rates decreased 4% among study subjects taking vitamin E, beta carotene and selenium, and rates of other non-stomach, non-esophageal cancers decreased 20%. "This is the first randomized trial to show a significant reduction of cancer in a population supplemented with vitamins and minerals," Blot declared at a Sept. 14 press conference in Washington, D.C. Blot is chief of the biostatistics branch in NCI's Division of Cancer Etiology. Investigators from the National Institutes of Health worked with Chinese health officials to enroll 29,584 Linxian adults aged 40-69. Participants in the double-blind, placebo-controlled, randomized trial received a supply of daily supplements each month from 1986 to 1991. The oral tablets distributed were one of eight possible combinations of four specific vitamin and mineral supplement groups: retinol and zinc; riboflavin and niacin; vitamin C and molybdenum; and beta carotene, selenium and vitamin E. Nutrient doses ranged from one to two times the U.S. Recommended Daily Allowance. NIH funded the trial with approximately $ 10 mil. over eight years. The researchers found that the other three vitamin/mineral combinations produced "no significant reduction" in cancer rates. Blot speculated at the press conference that the other combinations might be more effective if administered earlier in the life of the patient. Riboflavin and niacin supplements came close to showing a beneficial effect; people who took daily riboflavin and niacin supplements exhibited a 14% decrease in esophageal cancer incidence and a 10% decrease in esophageal cancer mortality than the placebo population. However, those reductions "were of borderline statistical significance," the researchers concluded. A total of 2,127 deaths occurred among trial participants. "Cancer was the leading cause of death," the study points out, "with 32% of all deaths due to esophageal or stomach cancer, followed by cerebrovascular disease (25%)." "The mechanisms by which beta carotene, vitamin E, or selenium inhibit cancer development are not clear," Blot, et al. explained, "but might involve their antioxidant properties." These nutrients, 11 especially beta carotene, can quench free radicals and protect against oxidative damage to DNA. The nutrients also inhibit the endogenous formation of N-nitroso compounds, some of which are potent carcinogens in animal experiments and are suspected risk factors for stomach and esophageal cancers in human populations." The investigators cautioned against extrapolating the study results to the U.S. population. The findings "don't automatically translate to the situation in the U.S., in part because the people in Linxian had considerably lower nutritional status," Blot pointed out at the press conference. "The findings," Blot explained, "can be looked at as providing another piece [of] the puzzle regarding possible agents that might lower cancer risk and strengthen our growing knowledge of the relationship between nutrition and cancer." NCI's Division of Cancer Prevention and Control Director Peter Greenwald, MD, added that the study findings increase the "need for further emphasis on nutrition research . . . across the board." To that end, Greenwald recommended "a special focus of research" on nutrition and supplement bioavailability in certain groups, such as women and the elderly. The researchers pointed out in the study that interventional trials involving "beta carotene, vitamin E and/or selenium and assessing cancer end points" are under way in the U.S. and Finland. "Although the numbers of esophageal or stomach cancers likely to arise in these trials will be considerably smaller than in Linxian, evaluation of the effects of supplementation on these cancers should be possible," they noted. In addition, the Linxian participants will continue to be evaluated in order to monitor the "persistence" of the lowered mortality in the dietary supplement groups. The effect of multivitamins on esophageal dysplasia was the subject of a smaller, concurrent study, also published in the Sept. 15 Journal of the National Cancer Institute. The same researchers evaluated cancer incidence and mortality in 3,318 Linxian participants with esophageal dysplasia who received a multivitamin or placebo for six years. A total of 324 deaths occurred during the six-year study period, with 167 occurring in the placebo group and 157 occurring in the supplement group. Cancer was the leading cause of death (54% of all deaths), followed by cerebrovascular diseases (18%) and other causes (29%). "Cumulative esophageal/gastric cardia death rates were 8% lower among individuals receiving supplements rather than placebo, a nonsignificant difference," the study says. In the treated population, the risk of total mortality was 7% lower, risk of total cancer was 4% lower, risk of cerebrovascular disease was 38% lower, and the risk of other disease was 12% higher. While "no statistically significant short-term benefits were observed" with daily multivitamin supplementation, the investigators observed that "longer follow-up should be more informative about the effectiveness of this six-year supplementation on cancer and other diseases among individuals with esophageal dysplasia."