The Antioxidants in Prevention of Cataracts Study: effects of antioxidant supplements on cataract progression in South India. Carotenoids in Age-related Maculopathy Italian Study (CARMIS): two-year results of a randomized study. Age-related cataract in a randomized trial of vitamins E and C in men. Vitamin E and age-related cataract in a randomized trial of women. Vitamin E supplementation and cataract: randomized controlled trial. Methodology of the VECAT study: vitamin E intervention in cataract and age-related maculopathy. A randomized trial of beta carotene and age-related cataract in US physicians. Six-year effect of combined vitamin C and E supplementation on atherosclerotic progression: the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) Study. The Roche European American Cataract Trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract.
To determine if antioxidant supplements (beta carotene and vitamins C and E) can decrease the progression of cataract in rural South India.
                The Antioxidants in Prevention of Cataracts (APC) Study was a 5 year, randomised, triple masked, placebo controlled, field based clinical trial to assess the ability of interventional antioxidant supplements to slow cataract progression. The primary outcome variable was change in nuclear opalescence over time. Secondary outcome variables were cortical and posterior subcapsular opacities and nuclear colour changes; best corrected visual acuity change; myopic shift; and failure of treatment. Annual examinations were performed for each subject by three examiners, in a masked fashion. Multivariate modelling using a general estimating equation was used for analysis of results, correcting for multiple measurements over time.
                Initial enrolment was 798 subjects. Treatment groups were comparable at baseline. There was high compliance with follow up and study medications. There was progression in cataracts. There was no significant difference between placebo and active treatment groups for either the primary or secondary outcome variables.
                Antioxidant supplementation with beta carotene, vitamins C and E did not affect cataract progression in a population with a high prevalence of cataract whose diet is generally deficient in antioxidants. The high concentration of carotenoids in the macula, plus evidence linking oxidative stress to age-related macular degeneration (AMD) and carotenoids to antioxidation, generated the hypothesis that higher antioxidant intakes can prevent AMD. The aim of this study was to determine whether nutritional supplementation with a targeted nutritional supplement improves visual acuity and visual function in AMD.
                In this multicenter, prospective open-label randomized study, 145 patients were randomly assigned to 2 different treatment groups. Interventions were lutein (10 mg), zeaxanthin (1 mg), astaxanthin (4 mg; AZYR SIFI, Catania, Italy), and antioxidants/vitamins supplementation formula or no dietary supplementation for 2 years. Primary outcome was mean changes in visual acuity (VA) at 12 and 24 months. Other measures included contrast sensitivity (CS) and National Eye Institute visual function questionnaire (NEI VFQ-25) scores at 12 and 24 months.
                Patients in the treated group showed stabilization of VA with significantly (p=0.003) better VA scores (81.4 ± 7.2) compared to the nontreated group (76.8 ± 8.9) at 24-month follow-up. An improvement in CS (p=0.001) and final mean NEI VFQ-25 composite scores at 12 and 24 months higher in treated group compared to nontreated group were also shown (p<0.001).
                Patients treated with lutein/zeaxanthin and astaxanthin together with other nutrients were more likely to report clinically meaningful stabilization/improvements in VA, CS, and visual function through 24 months compared with nontreated subjects. Further studies are needed with more patients and for longer periods of time. To test whether supplementation with alternate-day vitamin E or daily vitamin C affects the incidence of age-related cataract in a large cohort of men.
                In a randomized, double-masked, placebo-controlled trial, 11,545 apparently healthy US male physicians 50 years or older without a diagnosis of cataract at baseline were randomly assigned to receive 400 IU of vitamin E or placebo on alternate days and 500 mg of vitamin C or placebo daily.
                Incident cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review.
                Long-term use of vitamin E and C supplements has no appreciable effect on cataract.
                After 8 years of treatment and follow-up, 1174 incident cataracts were confirmed. There were 579 cataracts in the vitamin E-treated group and 595 in the vitamin E placebo group (hazard ratio, 0.99; 95% confidence interval, 0.88-1.11). For vitamin C, there were 593 cataracts in the treated group and 581 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.91-1.14).
                Long-term alternate-day use of 400 IU of vitamin E and daily use of 500 mg of vitamin C had no notable beneficial or harmful effect on the risk of cataract.
                clinicaltrials.gov Identifier: NCT00270647. To investigate whether vitamin E supplementation decreases the risk of age-related cataract in women.
                Randomized, double-masked, placebo-controlled trial.
                Thirty-nine thousand eight hundred seventy-six apparently healthy female health professionals aged 45 years or older.
                Participants were assigned randomly to receive either 600 IU natural-source vitamin E on alternate days or placebo and were followed up for presence of cataract for an average of 9.7 years.
                Age-related cataract defined as an incident, age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report and confirmed by medical record review.
                There was no significant difference between the vitamin E and placebo groups in the incidence of cataract (1159 vs. 1217 cases; relative risk [RR], 0.96; 95% confidence interval [CI], 0.88-1.04). In subgroup analyses of subtypes, there were no significant effects of vitamin E on the incidence of nuclear (1056 vs. 1127 cases; RR, 0.94; 95% CI, 0.87-1.02), cortical (426 vs. 461 cases; RR, 0.93; 95% CI, 0.81-1.06), or posterior subcapsular cataract (357 vs. 359 cases; RR, 1.00; 95% CI, 0.86-1.16). Results were similar for extraction of cataract and subtypes. There was no modification of the lack of effect of vitamin E on cataract by baseline categories of age, cigarette smoking, multivitamin use, or several other possible risk factors for cataract.
                These data from a large trial of apparently healthy female health professionals with 9.7 years of treatment and follow-up indicate that 600 IU natural-source vitamin E taken every other day provides no benefit for age-related cataract or subtypes. To determine whether treatment with vitamin E (500 IU daily) reduces either the incidence or rate of progression of age-related cataracts.
                A prospective, randomized, double-masked, placebo-controlled clinical trial entitled the Vitamin E, Cataract and Age-Related Maculopathy Trial.
                Of 1906 screened volunteers, 1193 eligible subjects with early or no cataract, aged 55 to 80 years, were enrolled and followed up for 4 years.
                Subjects were assigned randomly to receive either 500 IU of natural vitamin E in soybean oil encapsulated in gelatin or a placebo with an identical appearance.
                The incidence and progression rates of age-related cataract were assessed annually with both clinical lens opacity gradings and computerized analysis of Scheimpflug and retroillumination digital lens images obtained with a Nidek EAS-1000 lens camera. The analysis was undertaken using data from the eye with the more advanced opacity for each type of cataract separately and for any cataract changes in each individual.
                Overall, 87% of the study population completed the 4 years of follow-up, with 74% of the vitamin E group and 76% of the placebo group continuing on their randomized treatment allocation throughout this time. For cortical cataract, the 4-year cumulative incidence rate was 4.5% among those randomized to vitamin E and 4.8% among those randomized to placebo (P = 0.87). For nuclear cataract, the corresponding rates were 12.9% and 12.1% (P = 0.77). For posterior subcapsular cataract, the rates were 1.7% and 3.5% (P = 0.08), whereas for any of these forms of cataract, they were 17.1% and 16.7%, respectively. Progression of cortical cataract was seen in 16.7% of the vitamin E group and 18.4% of the placebo group (P = 0.76). Corresponding rates for nuclear cataract were 11.4% and 11.9% (P = 0.84), whereas those of any cataract were 16.5% and 16.7%, respectively. There was no difference in the rate of cataract extraction between the 2 groups (P = 0.87). Lens characteristics of the participants withdrawn from the randomized medications were not different from those who continued.
                Vitamin E given for 4 years at a dose of 500 IU daily did not reduce the incidence of or progression of nuclear, cortical, or posterior subcapsular cataracts. These findings do not support the use of vitamin E to prevent the development or to slow the progression of age-related cataracts. Cataract is the leading cause of blindness in the world today, while age-related macular degeneration is responsible for the majority of new cases of visual impairment in the Western world. There is a growing body of evidence suggesting a role for antioxidant therapy to prevent the progression of these conditions. A 4-year prospective, randomised, controlled trial of an antioxidant versus placebo in a population of healthy volunteers aged 55-80 years at enrolment is described. This paper outlines the primary aims of the Vitamin E, Cataract and Age-related Macular Degeneration (VECAT) Study, the methodology, and the recruitment rates. Additional data on the toxicity and non-ocular effects of vitamin E will also be collected. Standardised clinical grading of macular and lens features, and comparison of serial macular photographs and digital lens photographs will form the basis for assessment of primary study outcomes. Information collected in this study will assist in the assessment of the potential value of antioxidants in preventing the enormous burden imposed on developed communities by age-related eye disease. In addition, important data on prevalence and progression rates of cataract and macular degeneration will be collected. To examine the development of age-related cataract in a trial of beta carotene supplementation in men.
                Randomized, double-masked, placebo-controlled trial.
                Male US physicians aged 40 to 84 years (n = 22 071) were randomly assigned to receive either beta carotene (50 mg on alternate days) or placebo for 12 years.
                Age-related cataract and extraction of age-related cataract, defined as an incident, age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review.
                There was no difference between the beta carotene and placebo groups in the overall incidence of cataract (998 cases vs 1017 cases; relative risk [RR], 1.00; 95% confidence interval [CI], 0.91-1.09) or cataract extraction (584 vs 593; RR, 1.00; 95% CI, 0.89-1.12). In subgroup analyses, the effect of beta carotene supplementation appeared to be modified by smoking status at baseline (P =.02). Among current smokers, there were 108 cases of cataract in the beta carotene group and 133 in the placebo group (RR, 0.74; 95% CI, 0.57-0.95). Among current nonsmokers, there was no significant difference in the number of cases in the 2 treatment groups (884 vs 881; RR, 1.03; 95% CI, 0.94-1.13). The results for cataract extraction appeared to be similarly modified by baseline smoking status (P =.05).
                Randomized trial data from a large population of healthy men indicate no overall benefit or harm of 12 years of beta carotene supplementation on cataract or cataract extraction. However, among current smokers at baseline, beta carotene appeared to attenuate their excess risk of cataract by about one fourth. Self-selected supplementation of vitamin E has been associated with reduced coronary events and atherosclerotic progression, but the evidence from clinical trials is controversial. In the first 3 years of the ASAP trial, the supplementation with 136 IU of vitamin E plus 250 mg of slow-release vitamin C twice daily slowed down the progression of carotid atherosclerosis in men but not women. This article examines the 6-year effect of supplementation on common carotid artery (CCA) intima-media thickness (IMT).
                The subjects were 520 smoking and nonsmoking men and postmenopausal women aged 45 to 69 years with serum cholesterol > or =5.0 mmol/L (193 mg/dL), 440 (84.6%) of whom completed the study. Atherosclerotic progression was assessed ultrasonographically. In covariance analysis in both sexes, supplementation reduced the main study outcome, the slope of mean CCA-IMT, by 26% (95% CI, 5 to 46, P=0.014), in men by 33% (95% CI, 4 to 62, P=0.024) and in women by 14% (not significant). In both sexes combined, the average annual increase of the mean CCA-IMT was 0.014 mm in the unsupplemented and 0.010 mm in the supplemented group (25% treatment effect, 95% CI, 2 to 49, P=0.034). In men, this treatment effect was 37% (95 CI, 4 to 69, P=0.028). The effect was larger in subjects with either low baseline plasma vitamin C levels or CCA plaques. Vitamin E had no effect on HDL cholesterol.
                These data replicate our 3-year findings confirming that the supplementation with combination of vitamin E and slow-release vitamin C slows down atherosclerotic progression in hypercholesterolemic persons. Funding surgery worldwide for age-related cataract (ARC), a leading cause of blindness, is a huge economic burden. Non-surgical means of slowing ARC progression could benefit patients and reduce this burden.
                To determine if a mixture of oral antioxidant micronutrients [mg/day] (beta-carotene [18], vitamin C [750], and vitamin E [600]) would modify progression of ARC.
                REACT was a multi-centered, prospective, double-masked, randomized, placebo-controlled, 3-year trial.
                Consecutive adult American and English outpatients with early ARC were recruited.
                Four-hundred-and-forty-five patients were eligible; 297 were randomized; 231 (78%) were followed for two years; 158 (53%) were followed for three years; 36 (12%) were followed for four years. Twelve patients died during the trial (9 on vitamins; 3 on placebo (p = 0.07)). There were no serious safety issues.
                After a three-month placebo run-in, patients were randomized by clinical center to the vitamin or placebo groups and followed every four months.
                Cataract severity was documented with serial digital retroillumination imagery of the lens; progression was quantified by image analysis assessing increased area of opacity. This measure of area, 'increase % pixels opaque' (IPO), was the main outcome measure.
                There were no statistically significant differences between the treatment groups at baseline. The characteristics of dropouts and the mean follow-up times by treatment group were the same. After two years of treatment, there was a small positive treatment effect in U.S. patients (p = 0.0001); after three years a positive effect was apparent (p = 0.048) in both the U.S. and the U.K. groups. The positive effect in the U.S. group was even greater after three years: (IPO = 0.389 (vitamin) vs. IPO = 2.517 (placebo); p = 0.0001). There was no statistically significant benefit of treatment in the U.K. group. In spite of nearly perfect randomization into treatment groups, the U.S. and U.K. cohorts differed significantly.
                Daily use of the afore-mentioned micronutrients for three years produced a small deceleration in progression of ARC.
There is no evidence from RCTs that supplementation with antioxidant vitamins (beta-carotene, vitamin C or vitamin E) prevents or slows the progression of age-related cataract. We do not recommend any further studies to examine the role of antioxidant vitamins beta-carotene, vitamin C and vitamin E in preventing or slowing the progression of age-related cataract. Costs and adverse effects should be weighed carefully with unproven benefits before recommending their intake above recommended daily allowances.