Antioxidant vitamin supplementation for preventing and slowing the progression of age-related cataract.

The Cochrane database of systematic reviews

Jun 2012

DOI: 10.1002/14651858.CD004567.pub2

Citations:137

Influential Citations:10

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Randomized controlled trials with at least one year of follow-up; adults aged 35 years or older; sex distribution varied (some male-only, one female-only, others mixed); trials conducted in Australia, Finland, India, Italy, the United Kingdom and the United States.

Intervention

High-dose antioxidant regimens tested across nine randomized trials included beta-carotene, vitamin C and vitamin E, alone or in combination. Regimens were above the RDA and administered as daily, alternate-day, or thrice-weekly dosing for 2.1–12 years. Examples: beta-carotene 20 mg/day (ATBC 1998); 50 mg every other day (PHS I 2003; WHS 2004/8); beta-carotene 15 mg (AREDS 2001; APC 2006) in combination regimens with vitamin C 500 mg/day and vitamin E 400 IU/day; vitamin C alone 500 mg/day (PHS II 2010); vitamin E alone regimens included 300–600 IU/day or 500 IU/day or 400 IU/day or 600 IU every other day (PPP 2001; VECAT 2004; WHS 2004/8; AREDS 2001); combinations used AREDS-style triple therapy (beta-carotene 15 mg + vitamin C 500 mg + vitamin E 400 IU daily) or similar dosing (APC 2006; REACT 2002).

Results

No evidence that antioxidant vitamins prevent or slow the incidence, progression, or cataract extraction in age-related cataract. Pooled results show no significant effect for beta-carotene (RR 0.99, 95% CI 0.91–1.08), vitamin C (RR 1.02, 95% CI 0.91–1.14) or vitamin E (RR 0.97, 95% CI 0.91–1.04) on incidence; for cataract extraction, no significant benefit for any vitamin or combination (e.g., vitamin E pooled RR 0.97, 95% CI 0.91–1.04). Adverse effects included hypercarotenodermia in 7–16% of beta-carotene users and epistaxis (~6% with vitamin E in WHS 2004/8). Given lack of benefit and potential harms, high-dose antioxidant supplementation for cataract prevention is not supported; costs and adverse effects should be weighed, and further trials of these vitamins for this purpose are not recommended.

Limitations

Heterogeneity in regimens, endpoints and populations; follow-up duration varied; some trials had incomplete outcome data or masking limitations; most studies conducted in developed countries with older, predominantly healthy populations; several regimens used doses well above RDAs; progression and some safety outcomes were sparse or inconsistently defined across trials.

Abstract

BACKGROUND Age-related cataract is a major cause of visual impairment in the elderly. Oxidative stress has been implicated in its formation and progression. Antioxidant vitamin supplementation has been investigated in this context. OBJECTIVES To assess the effectiveness of antioxidant vitamin supplementation in preventing and slowing the progression of age-related cataract. SEARCH METHODS We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 2), MEDLINE (January 1950 to March 2012), EMBASE (January 1980 to March 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to March 2012), Open Grey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 2 March 2012. We also checked the reference lists of included studies and ongoing trials and contacted investigators to identify eligible randomized trials. SELECTION CRITERIA We included only randomized controlled trials in which supplementation with one or more antioxidant vitamins (beta-carotene, vitamin C and vitamin E) in any form, dosage or combination for at least one year was compared to another antioxidant vitamin or to placebo. DATA COLLECTION AND ANALYSIS Two authors extracted data and assessed trial quality independently. We pooled results for the primary outcomes, i.e., incidence of cataract and incidence of cataract extraction. We did not pool results of the secondary outcomes - progression of cataract and loss of visual acuity, because of differences in definitions of outcomes and data presentation. We pooled results by type of cataract when data were available. We did not perform a sensitivity analysis. MAIN RESULTS Nine trials involving 117,272 individuals of age 35 years or older are included in this review. The trials were conducted in Australia, Finland, India, Italy, the United Kingdom and the United States, with duration of follow-up ranging from 2.1 to 12 years. The doses of antioxidant vitamins were higher than the recommended daily allowance. There was no evidence of effect of antioxidant vitamin supplementation in reducing the risk of cataract, cataract extraction, progression of cataract or in slowing the loss of visual acuity. In the pooled analyses, there was no evidence of effect of beta-carotene supplementation in reducing the risk of cataract (two trials) (relative risk (RR) 0.99, 95% confidence interval (CI) 0.91 to 1.08; n = 57,703) or in reducing the risk of cataract extraction (three trials) (RR 1.00, 95% CI 0.91 to 1.10; n = 86,836) or of vitamin E supplementation in reducing the risk of cataract (three trials) (RR 0.97, 95% CI 0.91 to 1.04; n = 50,059) or of cataract extraction (five trials) (RR 0.98, 95% CI 0.91 to 1.05; n = 83,956). The proportion of participants developing hypercarotenodermia (yellowing of skin) while on beta-carotene ranged from 7.4% to 15.8%. AUTHORS' CONCLUSIONS 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. show less