Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration.

The Cochrane database of systematic reviews

Jul 2017

DOI: 10.1002/14651858.CD000253.pub4

Citations:65

Influential Citations:3

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Five randomized controlled trials conducted in Australia, USA, and Finland. Participants included Finnish male smokers (ATBC), US male physicians (PHS I and PHS II), US female health professionals (WHS), and mixed-sex populations (VECAT); study designs were randomized controlled trials (some with 2x2 factorial designs; some double-blind/double-masked). Follow-up ranged about 4–12 years.

Intervention

ATBC 1998: alpha-tocopherol 50 mg/day; beta-carotene 20 mg/day; alpha-tocopherol + beta-carotene; duration 5–8 years. VECAT 2002: vitamin E 500 IU/day; duration 4 years. PHS I 2007: beta-carotene 50 mg every other day; duration 12 years. PHS II 2012: vitamin C 500 mg/day; vitamin E 400 IU every other day; Centrum Silver multivitamin; beta-carotene arm discontinued in 2003; duration 11 years. WHS 2010: vitamin E 600 IU every other day; duration 10 years.

Results

Across five large randomized trials, antioxidant vitamin/mineral supplements did not reduce the risk of developing AMD. Vitamin E alone or with beta-carotene did not reduce any AMD or late AMD; Vitamin C did not reduce any AMD or late AMD; Multivitamin may increase risk of any AMD. There is no evidence for lutein/zeaxanthin in these healthy populations. Adverse events were inconsistently reported. These findings do not support using these supplements for AMD prevention; individuals with AMD should refer to reviews on progression rather than prevention.

Limitations

Very few late AMD events leading to imprecision; outcome ascertainment varied (self-report vs graded imaging); some trials had overlapping populations; generalizability limited (predominantly male or health-professional cohorts); adverse-event reporting for eye outcomes was sparse.

Abstract

BACKGROUND There is inconclusive evidence from observational studies to suggest that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C, and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD). OBJECTIVES To determine whether or not taking antioxidant vitamin or mineral supplements, or both, prevent the development of AMD. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 29 March 2017), Embase Ovid (1947 to 29 March 2017), AMED (Allied and Complementary Medicine Database) (1985 to 29 March 2017), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/); searched 29 March 2017, the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 29 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 29 March 2017 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 29 March 2017. We did not use any date or language restrictions in the electronic searches for trials. SELECTION CRITERIA We included all randomised controlled trials (RCTs) comparing an antioxidant vitamin or mineral supplement (alone or in combination) to control. DATA COLLECTION AND ANALYSIS Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5; the other author checked the data entry. We pooled data using a fixed-effect model. We graded the certainty of the evidence using GRADE. MAIN RESULTS We included a total of five RCTs in this review with data available for 76,756 people. The trials were conducted in Australia, Finland, and the USA, and investigated vitamin C, vitamin E, beta-carotene, and multivitamin supplements. All trials were judged to be at low risk of bias.Four studies reported the comparison of vitamin E with placebo. Average treatment and follow-up duration ranged from 4 to 10 years. Data were available for a total of 55,614 participants. There was evidence that vitamin E supplements do not prevent the development of any AMD (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.06; high-certainty evidence), and may slightly increase the risk of late AMD (RR 1.22, 95% CI 0.89 to 1.67; moderate-certainty evidence) compared with placebo. Only one study (941 participants) reported data separately for neovascular AMD and geographic atrophy. There were 10 cases of neovascular AMD (RR 3.62, 95% CI 0.77 to 16.95; very low-certainty evidence), and four cases of geographic atrophy (RR 2.71, 95% CI 0.28 to 26.0; very low-certainty evidence). Two trials reported similar numbers of adverse events in the vitamin E and placebo groups. Another trial reported excess of haemorrhagic strokes in the vitamin E group (39 versus 23 events, hazard ratio 1.74, 95% CI 1.04 to 2.91, low-certainty evidence).Two studies reported the comparison of beta-carotene with placebo. These studies took place in Finland and the USA. Both trials enrolled men only. Average treatment and follow-up duration was 6 years and 12 years. Data were available for a total of 22,083 participants. There was evidence that beta-carotene supplements did not prevent any AMD (RR 1.00, 95% CI 0.88 to 1.14; high-certainty evidence) nor have an important effect on late AMD (RR 0.90, 95% CI 0.65 to 1.24; moderate-certainty evidence). Only one study (941 participants) reported data separately for neovascular AMD and geographic atrophy. There were 10 cases of neovascular AMD (RR 0.61, 95% CI 0.17 to 2.15; very low-certainty evidence) and 4 cases of geographic atrophy (RR 0.31 95% CI 0.03 to 2.93; very low-certainty evidence). Beta-carotene was associated with increased risk of lung cancer in people who smoked.One study reported the comparison of vitamin C with placebo, and multivitamin (Centrum Silver) versus placebo. This was a study in men in the USA with average treatment duration and follow-up of 8 years for vitamin C and 11 years for multivitamin. Data were available for a total of 14,236 participants. AMD was assessed by self-report followed by medical record review. There was evidence that vitamin C supplementation did not prevent any AMD (RR 0.96, 95% CI 0.79 to 1.18; high-certainty evidence) or late AMD (RR 0.94, 0.61 to 1.46; moderate-certainty evidence). There was a slight increased risk of any AMD (RR 1.21, 95% CI 1.02 to 1.43; moderate-certainty evidence) and late AMD (RR 1.22, 95% CI 0.88 to 1.69; moderate-certainty evidence) in the multivitamin group. Neovascular AMD and geographic atrophy were not reported separately. Adverse effects were not reported but there was possible increased risk of skin rashes in the multivitamin group.Adverse effects were not consistently reported in these eye studies, but there is evidence from other large studies that beta-carotene increases the risk of lung cancer in people who smoke or who have been exposed to asbestos.None of the studies reported quality of life or resource use and costs. AUTHORS' CONCLUSIONS Taking vitamin E or beta-carotene supplements will not prevent or delay the onset of AMD. The same probably applies to vitamin C and the multivitamin (Centrum Silver) investigated in the one trial reported to date. There is no evidence with respect to other antioxidant supplements, such as lutein and zeaxanthin. Although generally regarded as safe, vitamin supplements may have harmful effects, and clear evidence of benefit is needed before they can be recommended. People with AMD should see the related Cochrane Review on antioxidant vitamin and mineral supplements for slowing the progression of AMD, written by the same review team. show less