Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population. Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. [The prevention of primary liver cancer by selenium in high risk populations]. Re: Chemoprevention of gastric dysplasia: randomized trial of antioxidant supplements and anti-helicobacter pylori therapy. The effect of folic acid on the development of stomach and other gastrointestinal cancers. Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong. A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study. A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China. No effect of riboflavine, retinol, and zinc on prevalence of precancerous lesions of oesophagus. Randomised double-blind intervention study in high-risk population of China. Effects of long-term vitamin E supplementation on cardiovascular events and cancer: a randomized controlled trial. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. An intervention study to prevent gastric cancer by micro-selenium and large dose of allitridum. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Randomized double-blind factorial trial of three treatments to reduce the prevalence of precancerous gastric lesions.
Epidemiologic evidence indicates that diets high in fruits and vegetables are associated with a reduced risk of several cancers, including cancers of the esophagus and stomach. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian County, China, have one of the world's highest rates of esophageal/gastric cardia cancer and a persistently low intake of several micronutrients.
                We sought to determine if dietary supplementation with specific vitamins and minerals can lower mortality from or incidence of cancer as well as mortality from other diseases in Linxian.
                Individuals of ages 40-69 were recruited in 1985 from four Linxian communes. Mortality and cancer incidence during March 1986-May 1991 were ascertained for 29,584 adults who received daily vitamin and mineral supplementation throughout this period. The subjects were randomly assigned to intervention groups according to a one-half replicate of a 2(4) factorial experimental design. This design enabled testing for the effects of four combinations of nutrients: (A) retinol and zinc; (B) riboflavin and niacin; (C) vitamin C and molybdenum; and (D) beta carotene, vitamin E, and selenium. Doses ranged from one to two times U.S. Recommended Daily Allowances.
                A total of 2127 deaths occurred among trial participants during the intervention period. Cancer was the leading cause of death, with 32% of all deaths due to esophageal or stomach cancer, followed by cerebrovascular disease (25%). Significantly (P = .03) lower total mortality (relative risk [RR] = 0.91; 95% confidence interval [CI] = 0.84-0.99) occurred among those receiving supplementation with beta carotene, vitamin E, and selenium. The reduction was mainly due to lower cancer rates (RR = 0.87; 95% CI = 0.75-1.00), especially stomach cancer (RR = 0.79; 95% CI = 0.64-0.99), with the reduced risk beginning to arise about 1-2 years after the start of supplementation with these vitamins and minerals. No significant effects on mortality rates from all causes were found for supplementation with retinol and zinc, riboflavin and niacin, or vitamin C and molybdenum. Patterns of cancer incidence, on the basis of 1298 cases, generally resembled those for cancer mortality.
                The findings indicate that vitamin and mineral supplementation of the diet of Linxian adults, particularly with the combination of beta carotene, vitamin E, and selenium, may effect a reduction in cancer risk in this population.
                The results on their own are not definitive, but the promising findings should stimulate further research to clarify the potential benefits of micronutrient supplements. Gastric cancer is one of the most common malignancies worldwide. Histopathologic studies have identified a sequence of changes in the gastric mucosa that mark the slow progression from normal tissue to carcinoma. Epidemiologic evidence suggests that a diet rich in fresh fruit and vegetables could be a protective factor against this disease. This effect may be mediated through antioxidant vitamins.
                A randomized, double-blind chemoprevention trial was conducted among 1980 subjects in Tachira State, Venezuela (whose population is at high risk for gastric cancer), to determine the effect of dietary supplementation with vitamin C, vitamin E, and beta-carotene on the progression and regression of precancerous gastric lesions. Subjects were randomly assigned to receive either a combination of vitamin C (750 mg/day), vitamin E (600 mg/day), and beta-carotene (18 mg/day) or placebo for 3 years. Changes in the gastric mucosa were determined by histologic diagnosis based on five biopsies taken from prespecified areas of the stomach at baseline and annually for 3 years. All biopsies were reviewed by a single expert pathologist. Progression rates (and regression rates) were calculated by comparing the first and last available gastroscopies for each subject and dividing the number of subjects whose diagnoses increased (decreased) in severity by the total follow-up time. Overall rate ratios were calculated by Poisson regression, controlling for baseline diagnosis. All statistical tests were two-sided.
                Median plasma vitamin levels were increased in the treatment group between baseline and 1 year after randomization from 0.43 micromol/L (interquartile range [IQR] = 0.26-0.69) to 2.89 micromol/L (IQR = 1.76-4.22) for beta-carotene, from 26.7 micromol/L (IQR = 23.1-31.2) to 54.9 micromol/L (IQR = 42.8-67.6) for alpha-tocopherol, and from 47.70 micromol/L (IQR = 36.9-58.5) to 61.9 micromol/L (IQR = 52.2-72.7) for vitamin C. Overall progression rates per 100 person-years were 74.3 in the placebo group and 67.8 in the group randomly assigned to vitamins. Overall regression rates were 109.4 in the placebo group and 116.5 in the group randomly assigned to vitamins. There was no statistically significant difference in progression rate (rate ratio = 0.92, 95% confidence interval [CI] = 0.74 to 1.15) or regression rate (rate ratio = 1.09, 95% CI = 0.90 to 1.33) between vitamin and placebo groups.
                Supplementation with antioxidant micronutrients is not an effective tool for gastric cancer control in this high-risk population. The results of this trial are consistent with previous findings on the lack of effect of nutritional supplementation on precancerous gastric lesions. A number of vitamins and minerals have been shown to influence carcinogenesis in experimental animals. In humans, epidemiologic evidence suggests that intake of fruits and vegetables may reduce risk of esophageal and other cancers. Vitamins and minerals in these foods may contribute to the reduced cancer risk. The people of Linxian, China, have persistently low intake of multiple nutrients and exhibit one of the world's highest rates of esophageal/gastric cardia cancer, with an exceptionally high risk of esophageal dysplasia.
                To determine whether supplementation with multiple vitamins and minerals may reduce esophageal/gastric cardia cancer among persons with esophageal dysplasia, we conducted a 6-year prospective intervention trial in Linxian.
                Mortality and cancer incidence were ascertained from May 1985 through May 1991 for 3318 persons with cytologic evidence of esophageal dysplasia who were randomly assigned to receive, throughout that period, daily supplementation with 14 vitamins and 12 minerals or placebo. Doses were typically two to three times U.S. Recommended Daily Allowances. Compliance was assessed by counting unused pills monthly for all trial participants and by assaying nutrient levels in blood collected from samples of individuals randomly selected without replacement every 3 months throughout the trial. Cancers were identified through routine surveillance and by special cytology and endoscopy screenings after 2 1/2 years and 6 years.
                A total of 324 deaths occurred during the 6-year intervention period; 167 occurred in the control (placebo) group and 157 occurred in the supplement group. Cancer was the leading cause of death (54% of all deaths); 18% were due to cerebrovascular diseases and 29% to other causes. Cumulative esophageal/gastric cardia death rates were 8% lower (relative risk [RR] = 0.92; 95% confidence interval [CI] = 0.67-1.28) among individuals receiving supplements rather than placebo, a nonsignificant (P > .10) difference. Risk of total mortality was 7% lower (RR = 0.93; 95% CI = 0.75-1.16; P > .10), total cancer 4% lower (RR = 0.96; 95% CI = 0.71-1.29; P > .10), cerebrovascular disease 38% lower (RR = 0.62; 95% CI = 0.37-1.06; P = .08), and other diseases 12% higher (RR = 1.12; 95% CI = 0.74-1.69; P > .10) among the treated group. Cumulative cancer incidence rates were nearly the same in the two groups.
                No substantial short-term beneficial effect on incidence or mortality for this type of cancer occurred following daily supplementation with multiple vitamins and minerals among adults with precancerous lesions of the esophagus.
                Although no statistically significant short-term benefits were observed, longer follow-up should be more informative about the effectiveness of this 6-year supplementation on cancer and other diseases among individuals with esophageal dysplasia. To determine whether a nutritional supplement of selenium will decrease the incidence of cancer.
                A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial.
                Seven dermatology clinics in the eastern United States.
                A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years.
                Oral administration of 200 microg of selenium per day or placebo.
                The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers.
                After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR; 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred.
                Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the effect of daily beta-carotene (30 mg) and retinyl palmitate (25,000 IU) on the incidence of lung cancer, other cancers, and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure. CARET was stopped ahead of schedule in January 1996 because participants who were randomly assigned to receive the active intervention were found to have a 28% increase in incidence of lung cancer, a 17% increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group.
                After the intervention ended, CARET participants returned the study vitamins to their study center and provided a final blood sample. They continue to be followed annually by telephone and mail self-report. Self-reported cancer endpoints were confirmed by review of pathology reports, and death endpoints were confirmed by review of death certificates. All statistical tests were two-sided.
                With follow-up through December 31, 2001, the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 (95% confidence interval [CI] = 0.97 to 1.31) and 1.08 (95% CI = 0.99 to 1.17), respectively. Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up. By contrast, the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped. During the post-intervention phase, females had larger relative risks of lung cancer mortality (1.33 versus 1.14; P = .36), cardiovascular disease mortality (1.44 versus 0.93; P = .03), and all-cause mortality (1.37 versus 0.98; P = .001) than males.
                The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant. Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females, and cardiovascular disease mortality primarily to females and to former smokers. To study the preventive effects of selenium on primary liver cancer.
                After screening of blood samples in 18,000 males from 20 to 65 years-old in Qidong, Jiangsu province (a high risk area for liver cancer), 2,065 cases of HBsAg positive, AFP negative and normal liver function (normal ALT values) were found. The subjects were randomly divided into two groups, based on their residence areas; 1,112 subjects (experimental group) received one tablet of sodium selenite (0.5 mg Se) every day and 953 subjects (control group) received one placebo tablet every day.
                During three years of intervention and follow up, the blood selenium concentration and glutathione peroxidase activity of the subjects in the experimental group were increased and had significant difference as compared with those of the control group (P < 0.01). At the same time, the prevalence rate of micronucleus cells in peripheral blood lymphocytes in the experimental group was significantly lower than that of the control group (P < 0.01), and the incidence of new liver cancer in the experimental group (3 057.55/10(6), 34 cases out of 1,112 subjects) was significantly lower than the control group (5 981.11/10(6); 57 cases out of 953 subjects) (P < 0.01).
                The results confirms that selenium supplementation in general populations lived in high risk is effective in the prevention of liver cancer and the using of selenium tablets is simple and feasible. nan To evaluate the roles of folic acid and beta-carotene in the chemoprevention of gastric and other gastrointestinal (GI) cancers.
                In a randomized, double-blind, placebo-controlled trial, a total of 216 patients with atrophic gastritis were randomly assigned to one of the four groups: (1) folate (FA, 20 mg per day plus vitamin B(12) 1 mg, intramuscularly, per month for one year, then 20 mg two times a week plus 1 mg per three months for the next year); (2) natural beta-carotene (N-betaC, 30 mg per day for first year, then 30 mg two times a week for the next); (3) synthetic beta-carotene (S-betaC, administered as in N-betaC); and (4) placebo. Follow-ups continued from 1994 to 2001.
                A total of 7 new cases of gastrointestinal cancers were diagnosed with 3 stomach, 1 colon and 1 esophageal cancers occurring in the placebo group; 1 stomach cancer in both of the N-betaC and S-betaC groups, and no cancer occurring in FA group. In terms of GI cancers, there was a significant reduction in the FA group, compared with the placebo group (P = 0.04). A similar trend was observed in both N-betaC and S-betaC groups (P = 0.07 - 0.08). Taken together, the three intervention groups displayed a highly significant decrease in occurrence (P = 0.004, vs placebo), and a lower risk for GI cancers (OR = 0.12; 95% confidence interval, 0.03 - 0.51). For development of gastric cancer, any one of the three active-treated groups did not reach statistically significant reduction. The FA group showed obvious improvement of the gastric mucosal lesions with more patients displaying lesions reversed or stable atrophy and inflammation (P = 0.04), reversed intestinal metaplasia (P = 0.06) at the end of follow-up, and reversed displasia (P = 0.017) at 12 months. Two cases of false jaundice were found in beta-carotene groups with no influence on administration, and no side-effects were reported in FA group.
                This trial revealed the interventional effect of folic acid on the development of GI cancers, a similar effect of beta-carotene was also detected. Also, folic acid may be of use to treat atrophic gastritis by preventing or reversing the precancerous lesions. In the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, alpha-tocopherol supplementation decreased prostate cancer incidence, whereas beta-carotene increased the risk of lung cancer and total mortality. Postintervention follow-up provides information regarding duration of the intervention effects and may reveal potential late effects of these antioxidants.
                To analyze postintervention effects of alpha-tocopherol and beta-carotene on cancer incidence and total and cause-specific mortality.
                Postintervention follow-up assessment of cancer incidence and cause-specific mortality (6 years [May 1, 1993-April 30, 1999]) and total mortality (8 years [May 1, 1993-April 30, 2001]) of 25 563 men. In the ATBC Study, 29 133 male smokers aged 50 to 69 years received alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5 to 8 years. End point information was obtained from the Finnish Cancer Registry and the Register of Causes of Death. Cancer cases were confirmed through medical record review.
                Site-specific cancer incidence and total and cause-specific mortality and calendar time-specific risk for lung cancer incidence and total mortality.
                Overall posttrial relative risk (RR) for lung cancer incidence (n = 1037) was 1.06 (95% confidence interval [CI], 0.94-1.20) among recipients of beta-carotene compared with nonrecipients. For prostate cancer incidence (n = 672), the RR was 0.88 (95% CI, 0.76-1.03) for participants receiving alpha-tocopherol compared with nonrecipients. No late preventive effects on other cancers were observed for either supplement. There were 7261 individuals who died by April 30, 2001, during the posttrial follow-up period; the RR was 1.01 (95% CI, 0.96-1.05) for alpha-tocopherol recipients vs nonrecipients and 1.07 (95% CI, 1.02-1.12) for beta-carotene recipients vs nonrecipients. Regarding duration of intervention effects and potential late effects, the excess risk for beta-carotene recipients was no longer evident 4 to 6 years after ending the intervention and was primarily due to cardiovascular diseases.
                The beneficial and adverse effects of supplemental alpha-tocopherol and beta-carotene disappeared during postintervention follow-up. The preventive effects of alpha-tocopherol on prostate cancer require confirmation in other trials. Smokers should avoid beta-carotene supplementation. High rates of hepatitis B virus (HBV) infection and primary liver cancer (PLC) are present in Qidong county. Epidemiological surveys demonstrated an inverse association between selenium (Se) level and regional cancer incidence, as well as HBV infection. Four-year animal studies showed that dietary supplement of Se reduced the HBV infection by 77.2% and liver precancerous lesion by 75.8% of ducks, caused by exposure to natural environmental etiologic factors. An intervention trial was undertaken among the general population of 130,471. Individuals in five townships were involved for observation of the preventive effect of Se. The 8-yr follow-up data showed reduced PLC incidence by 35.1% in selenized table salt supplemented vs the nonsupplemented population. On withdrawal of Se from the treated group, PLC incidence rate began to increase. However, the inhibitory response to HBV was sustained during the 3-yr cessation of treatment. The clinical study among 226 Hepatitis B Surface Antigen (HBsAg)-positive persons provided either 200 micrograms of Se in the form of selenized yeast tablet or an identical placebo of yeast tablet daily for 4 yr showed that 7 of 113 subjects were diagnosed as having PLC in the placebo group, whereas no incidence of PLC was found in 113 subjects supplemented with Se. Again on cessation of treatment, PLC developed at a rate comparable to that in the control group, demonstrating that a continuous intake of Se is essential to sustain the chemopreventive effect. Randomized trials have largely failed to support an effect of antioxidant vitamins on the risk of cardiovascular disease (CVD). Few trials have examined interactions among antioxidants, and, to our knowledge, no previous trial has examined the individual effect of ascorbic acid (vitamin C) on CVD.
                The Women's Antioxidant Cardiovascular Study tested the effects of ascorbic acid (500 mg/d), vitamin E (600 IU every other day), and beta carotene (50 mg every other day) on the combined outcome of myocardial infarction, stroke, coronary revascularization, or CVD death among 8171 female health professionals at increased risk in a 2 x 2 x 2 factorial design. Participants were 40 years or older with a history of CVD or 3 or more CVD risk factors and were followed up for a mean duration of 9.4 years, from 1995-1996 to 2005.
                A total of 1450 women experienced 1 or more CVD outcomes. There was no overall effect of ascorbic acid (relative risk [RR], 1.02; 95% CI, 0.92-1.13 [P = .71]), vitamin E (RR, 0.94; 95% CI, 0.85-1.04 [P = .23]), or beta carotene (RR, 1.02; 95% CI, 0.92-1.13 [P = .71]) on the primary combined end point or on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD death. A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior CVD (RR, 0.89; 95% CI, 0.79-1.00 [P = .04]; P value for interaction, .07). There were no significant interactions between agents for the primary end point, but those randomized to both active ascorbic acid and vitamin E experienced fewer strokes (P value for interaction, .03).
                There were no overall effects of ascorbic acid, vitamin E, or beta carotene on cardiovascular events among women at high risk for CVD. The purpose of this study was to evaluate the effect of selenium (Se) in the prevention of human primary liver cancer. Three intervention trials were conducted among the residents at high risk to primary liver cancer (PLC) in Qidong county, Jiang-su province, the People's Republic of China. This area has the second highest rate of PLC in China. One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite (Se-salt) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt. The second trial was undertaken among hepatitis B virus surface antigen carriers (HBVsAg+) receiving supplement of 200 micrograms Se in form of selenized yeast (Se-yeast) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast (200 micrograms of Se daily) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly. A randomised double-blind intervention trial was carried out in Huixian, Henan Province, People's Republic of China, to determine whether combined treatment with retinol, riboflavine, and zinc could lower the prevalence of precancerous lesions of the oesophagus. 610 subjects in the age group 35-64 were randomised to receive once a week the active treatment (15 mg [50 000 IU] retinol, 200 mg riboflavine, and 50 mg zinc) or placebo. Both at entry to the study and at the end of the treatment, 13.5 months later, the subjects were examined, with an emphasis on signs of vitamin A and riboflavine deficiences, and riboflavine, retinol, beta-carotene, and zinc levels were measured. Compliance was excellent. The final examination, on 567 (93%) subjects, included oesophagoscopy and at least two biopsies. The intervention did not affect the prevalence of oesophageal lesions: after one year, the prevalence of oesophagitis with or without atrophy or dysplasia was 45.3% in the placebo group and 48.9% in the vitamin/zinc treated group. Experimental and epidemiological data suggest that vitamin E supplementation may prevent cancer and cardiovascular events. Clinical trials have generally failed to confirm benefits, possibly due to their relatively short duration.
                To evaluate whether long-term supplementation with vitamin E decreases the risk of cancer, cancer death, and major cardiovascular events.
                A randomized, double-blind, placebo-controlled international trial (the initial Heart Outcomes Prevention Evaluation [HOPE] trial conducted between December 21, 1993, and April 15, 1999) of patients at least 55 years old with vascular disease or diabetes mellitus was extended (HOPE-The Ongoing Outcomes [HOPE-TOO]) between April 16, 1999, and May 26, 2003. Of the initial 267 HOPE centers that had enrolled 9541 patients, 174 centers participated in the HOPE-TOO trial. Of 7030 patients enrolled at these centers, 916 were deceased at the beginning of the extension, 1382 refused participation, 3994 continued to take the study intervention, and 738 agreed to passive follow-up. Median duration of follow-up was 7.0 years.
                Daily dose of natural source vitamin E (400 IU) or matching placebo.
                Primary outcomes included cancer incidence, cancer deaths, and major cardiovascular events (myocardial infarction, stroke, and cardiovascular death). Secondary outcomes included heart failure, unstable angina, and revascularizations.
                Among all HOPE patients, there were no significant differences in the primary analysis: for cancer incidence, there were 552 patients (11.6%) in the vitamin E group vs 586 (12.3%) in the placebo group (relative risk [RR], 0.94; 95% confidence interval [CI], 0.84-1.06; P = .30); for cancer deaths, 156 (3.3%) vs 178 (3.7%), respectively (RR, 0.88; 95% CI, 0.71-1.09; P = .24); and for major cardiovascular events, 1022 (21.5%) vs 985 (20.6%), respectively (RR, 1.04; 95% CI, 0.96-1.14; P = .34). Patients in the vitamin E group had a higher risk of heart failure (RR, 1.13; 95% CI, 1.01-1.26; P = .03) and hospitalization for heart failure (RR, 1.21; 95% CI, 1.00-1.47; P = .045). Similarly, among patients enrolled at the centers participating in the HOPE-TOO trial, there were no differences in cancer incidence, cancer deaths, and major cardiovascular events, but higher rates of heart failure and hospitalizations for heart failure.
                In patients with vascular disease or diabetes mellitus, long-term vitamin E supplementation does not prevent cancer or major cardiovascular events and may increase the risk for heart failure. Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease, and earlier basic research suggested plausible mechanisms. Because large randomized trials of long duration were necessary to test this hypothesis directly, we conducted a trial of beta carotene supplementation.
                In a randomized, double-blind, placebo-controlled trial of beta carotene (50 mg on alternate days), we enrolled 22,071 male physicians, 40 to 84 years of age, in the United States; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982. By December 31, 1995, the scheduled end of the study, fewer than 1 percent had been lost to follow-up, and compliance was 78 percent in the group that received beta carotene.
                Among 11,036 physicians randomly assigned to receive beta carotene and 11,035 assigned to receive placebo, there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease, or in overall mortality. In the beta carotene group, 1273 men had any malignant neoplasm (except nonmelanoma skin cancer), as compared with 1293 in the placebo group (relative risk, 0.98; 95 percent confidence interval, 0.91 to 1.06). There were also no significant differences in the number of cases of lung cancer (82 in the beta carotene group vs. 88 in the placebo group); the number of deaths from cancer (386 vs. 380), deaths from any cause (979 vs. 968), or deaths from cardiovascular disease (338 vs. 313); the number of men with myocardial infarction (468 vs. 489); the number with stroke (367 vs. 382); or the number with any one of the previous three end points (967 vs. 972). Among current and former smokers, there were also no significant early or late differences in any of these end points.
                In this trial among healthy men, 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms, cardiovascular disease, or death from all causes. Basic research provides plausible mechanisms and observational studies suggest that apparently healthy persons, who self-select for high intakes of vitamin E through diet or supplements, have decreased risks of cardiovascular disease and cancer. Randomized trials do not generally support benefits of vitamin E, but there are few trials of long duration among initially healthy persons.
                To test whether vitamin E supplementation decreases risks of cardiovascular disease and cancer among healthy women.
                In the Women's Health Study conducted between 1992 and 2004, 39 876 apparently healthy US women aged at least 45 years were randomly assigned to receive vitamin E or placebo and aspirin or placebo, using a 2 x 2 factorial design, and were followed up for an average of 10.1 years.
                Administration of 600 IU of natural-source vitamin E on alternate days.
                Primary outcomes were a composite end point of first major cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and total invasive cancer.
                During follow-up, there were 482 major cardiovascular events in the vitamin E group and 517 in the placebo group, a nonsignificant 7% risk reduction (relative risk [RR], 0.93; 95% confidence interval [CI], 0.82-1.05; P = .26). There were no significant effects on the incidences of myocardial infarction (RR, 1.01; 95% CI, 0.82-1.23; P = .96) or stroke (RR, 0.98; 95% CI, 0.82-1.17; P = .82), as well as ischemic or hemorrhagic stroke. For cardiovascular death, there was a significant 24% reduction (RR, 0.76; 95% CI, 0.59-0.98; P = .03). There was no significant effect on the incidences of total cancer (1437 cases in the vitamin E group and 1428 in the placebo group; RR, 1.01; 95% CI, 0.94-1.08; P = .87) or breast (RR, 1.00; 95% CI, 0.90-1.12; P = .95), lung (RR, 1.09; 95% CI, 0.83-1.44; P = .52), or colon cancers (RR, 1.00; 95% CI, 0.77-1.31; P = .99). Cancer deaths also did not differ significantly between groups. There was no significant effect of vitamin E on total mortality (636 in the vitamin E group and 615 in the placebo group; RR, 1.04; 95% CI, 0.93-1.16; P = .53).
                The data from this large trial indicated that 600 IU of natural-source vitamin E taken every other day provided no overall benefit for major cardiovascular events or cancer, did not affect total mortality, and decreased cardiovascular mortality in healthy women. These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women. People have more and more concerned about allitridum as studies have shown that taking more raw garlic associated with a lower risk for cancers of the alimentary system. In the present study, we tried to examine whether a large dose of allitridum and a microdose of selenium prevent gastric cancer.
                A double-blind intervention study was performed on the participants aged (35 - 74) years, who had matched at least one of the following criteria: (1) a medical history of stomach disorder, (2) a family history of tumour, or (3) smoking and/or alcohol consumption. A total of 2,526 and 2,507 persons were randomly enrolled into intervention group and control group respectively from 288 natural villages of seven communities in Qixia County, Shandong Province, China. Each person of the intervention group orally took 200 mg synthetic allitridum every day and 100 microg selenium every other day for one month of each year during November 1989 to December 1991. At the same time, people in control group were given 2 placebo capsules containing corn oid with the identical appearance to that in the intervention group.
                For all subjects the large dose of allitridum was accepted and no harmful side effects were found during the study. In the first follow-up five years (1992 - 1997) after stopping the intervention, the morbidity rates of malignant tumours in the intervention group declined by 22%, in contrast to the control group, declined by 47.3%. After adjusting for age, gender, and other potential confounders, relative risks (RRs) for all tumours and gastric cancer of the whole population were 0.67 (95% CL: 0.43 - 1.03) and 0.48 (95% CL: 0.21 - 1.06), respectively, and for male group they were 0.51 (95% CL: 0.30 - 0.85) and 0.36 (95% CL: 0.14 - 0.92), respectively. No signigicantly protective effect was found for the female subgroup.
                The present study proves that large doses of allitridum and microdorse of selenium may effectively prevent gastric cancer, especially in men. It has been suggested that a low dietary intake of antioxidant vitamins and minerals increases the incidence rate of cardiovascular disease and cancer. To date, however, the published results of randomized, placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficial effect. We tested the efficacy of nutritional doses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population.
                The Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study is a randomized, double-blind, placebo-controlled primary prevention trial. A total of 13 017 French adults (7876 women aged 35-60 years and 5141 men aged 45-60 years) were included. All participants took a single daily capsule of a combination of 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 mug of selenium, and 20 mg of zinc, or a placebo. Median follow-up time was 7.5 years.
                No major differences were detected between the groups in total cancer incidence (267 [4.1%] for the study group vs 295 [4.5%] for the placebo group), ischemic cardiovascular disease incidence (134 [2.1%] vs 137[2.1%]), or all-cause mortality (76 [1.2%] vs 98 [1.5%]). However, a significant interaction between sex and group effects on cancer incidence was found (P = .004). Sex-stratified analysis showed a protective effect of antioxidants in men (relative risk, 0.69 [95% confidence interval [CI], 0.53-0.91]) but not in women (relative risk, 1.04 [95% CI, 0.85-1.29]). A similar trend was observed for all-cause mortality (relative risk, 0.63 [95% CI, 0.42-0.93] in men vs 1.03 [95% CI, 0.64-1.63] in women; P = .11 for interaction).
                After 7.5 years, low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women. Supplementation may be effective in men only because of their lower baseline status of certain antioxidants, especially of beta carotene. Randomized trials have yielded mixed results on the effects of treatment for Helicobacter pylori and little information on the effects of vitamins or garlic supplements on precancerous gastric lesions. We conducted a randomized trial to test the effects of one-time H. pylori treatment and long-term vitamin or garlic supplements in reducing the prevalence of advanced precancerous gastric lesions.
                Most of the adults aged 35-64 years in 13 randomly selected villages in Linqu County, Shandong Province, China, were identified and given baseline endoscopies in 1994. In 1995, 3365 eligible subjects were randomly assigned in a factorial design to three interventions or placebos: amoxicillin and omeprazole for 2 weeks in 1995 (H. pylori treatment); vitamin C, vitamin E, and selenium for 7.3 years (vitamin supplement); and aged garlic extract and steam-distilled garlic oil for 7.3 years (garlic supplement). Subjects underwent endoscopies with biopsies in 1999 and 2003, and the prevalence of precancerous gastric lesions was determined by histopathologic examination of seven standard biopsy sites. The 3365 eligible randomized subjects represented 93.5% of those with baseline endoscopy and included all baseline histologic categories except gastric cancer. Only 0.18% had normal gastric mucosa. Logistic regression was used to estimate the intervention effects on the odds of advanced precancerous gastric lesions, and t-tests were used to assess effects on histologic severity. All statistical tests were two-sided.
                H. pylori treatment resulted in statistically significant decreases in the combined prevalence of severe chronic atrophic gastritis, intestinal metaplasia, dysplasia, or gastric cancer in 1999 (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.62 to 0.95) and in 2003 (OR = 0.60; 95% CI = 0.47 to 0.75), and had favorable effects on the average histopathologic severity and on progression and regression of precancerous gastric lesions in 2003. H. pylori treatment did not reduce the combined prevalence of dysplasia or gastric cancer. However, fewer subjects receiving H. pylori treatment (19/1130; 1.7%) than receiving placebo (27/1128; 2.4%) developed gastric cancer (adjusted P = .14). No statistically significant favorable effects were seen for garlic or vitamin supplements.
                H. pylori treatment reduces the prevalence of precancerous gastric lesions and may reduce gastric cancer incidence, but further data are needed to prove the latter point. Long-term vitamin or garlic supplementation had no beneficial effects on the prevalence of precancerous gastric lesions or on gastric cancer incidence.
We could not find convincing evidence that antioxidant supplements prevent gastrointestinal cancers. On the contrary, antioxidant supplements seem to increase overall mortality. The potential cancer preventive effect of selenium should be tested in adequately conducted randomised trials.