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Meta-Analysis
. 2017 Jul 31;7(7):CD000254.
doi: 10.1002/14651858.CD000254.pub4.

Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration

Jennifer R Evans  1 , John G Lawrenson
Affiliations
Meta-Analysis

Antioxidant vitamin and mineral supplements for slowing the progression of age-related macular degeneration

Jennifer R Evans et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: It has been proposed that antioxidants may prevent cellular damage in the retina by reacting with free radicals that are produced in the process of light absorption. Higher dietary levels of antioxidant vitamins and minerals may reduce the risk of progression of age-related macular degeneration (AMD).

Objectives: The objective of this review was to assess the effects of antioxidant vitamin or mineral supplementation on the progression of AMD in people with AMD.

Search methods: We searched CENTRAL (2017, Issue 2), MEDLINE Ovid (1946 to March 2017), Embase Ovid (1947 to March 2017), AMED (1985 to March 2017), OpenGrey (System for Information on Grey Literature in Europe, the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 29 March 2017.

Selection criteria: We included randomised controlled trials (RCTs) that compared antioxidant vitamin or mineral supplementation (alone or in combination) to placebo or no intervention, in people with AMD.

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 graded the certainty of the evidence using GRADE.

Main results: We included 19 studies conducted in USA, Europe, China, and Australia. We judged the trials that contributed data to the review to be at low or unclear risk of bias.Nine studies compared multivitamins with placebo (7 studies) or no treatment (2 studies) in people with early and moderate AMD. The duration of supplementation and follow-up ranged from nine months to six years; one trial followed up beyond two years. Most evidence came from the Age-Related Eye Disease Study (AREDS) in the USA. People taking antioxidant vitamins were less likely to progress to late AMD (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 2445 participants; 3 RCTs; moderate-certainty evidence). In people with very early signs of AMD, who are at low risk of progression, this would mean that there would be approximately 4 fewer cases of progression to late AMD for every 1000 people taking vitamins (1 fewer to 6 fewer cases). In people at high risk of progression (i.e. people with moderate AMD) this would correspond to approximately 8 fewer cases of progression for every 100 people taking vitamins (3 fewer to 13 fewer). In one study of 1206 people, there was a lower risk of progression for both neovascular AMD (OR 0.62, 95% CI 0.47 to 0.82; moderate-certainty evidence) and geographic atrophy (OR 0.75, 95% CI 0.51 to 1.10; moderate-certainty evidence) and a lower risk of losing 3 or more lines of visual acuity (OR 0.77, 95% CI 0.62 to 0.96; 1791 participants; moderate-certainty evidence). Low-certainty evidence from one study of 110 people suggested higher quality of life scores (National Eye Institute Visual Function Questionnaire) in treated compared with the non-treated people after 24 months (mean difference (MD) 12.30, 95% CI 4.24 to 20.36). Six studies compared lutein (with or without zeaxanthin) with placebo. The duration of supplementation and follow-up ranged from six months to five years. Most evidence came from the AREDS2 study in the USA. People taking lutein or zeaxanthin may have similar or slightly reduced risk of progression to late AMD (RR 0.94, 95% CI 0.87 to 1.01; 6891 eyes; low-certainty evidence), neovascular AMD (RR 0.92, 95% CI 0.84 to 1.02; 6891 eyes; low-certainty evidence), and geographic atrophy (RR 0.92, 95% CI 0.80 to 1.05; 6891 eyes; low-certainty evidence). A similar risk of progression to visual loss of 15 or more letters was seen in the lutein and control groups (RR 0.98, 95% CI 0.91 to 1.05; 6656 eyes; low-certainty evidence). Quality of life (measured with Visual Function Questionnaire) was similar between groups in one study of 108 participants (MD 1.48, 95% -5.53 to 8.49, moderate-certainty evidence). One study, conducted in Australia, compared vitamin E with placebo. This study randomised 1204 people to vitamin E or placebo, and followed up for four years. Participants were enrolled from the general population; 19% had AMD. The number of late AMD events was low (N = 7) and the estimate of effect was uncertain (RR 1.36, 95% CI 0.31 to 6.05, very low-certainty evidence). There were no data on neovascular AMD or geographic atrophy.There was no evidence of any effect of treatment on visual loss (RR 1.04, 95% CI 0.74 to 1.47, low-certainty evidence). There were no data on quality of life. Five studies compared zinc with placebo. The duration of supplementation and follow-up ranged from six months to seven years. People taking zinc supplements may be less likely to progress to late AMD (OR 0.83, 95% CI 0.70 to 0.98; 3790 participants; 3 RCTs; low-certainty evidence), neovascular AMD (OR 0.76, 95% CI 0.62 to 0.93; 2442 participants; 1 RCT; moderate-certainty evidence), geographic atrophy (OR 0.84, 95% CI 0.64 to 1.10; 2442 participants; 1 RCT; moderate-certainty evidence), or visual loss (OR 0.87, 95% CI 0.75 to 1.00; 3791 participants; 2 RCTs; moderate-certainty evidence). There were no data reported on quality of life.Very low-certainty evidence was available on adverse effects because the included studies were underpowered and adverse effects inconsistently reported.

Authors' conclusions: People with AMD may experience some delay in progression of the disease with multivitamin antioxidant vitamin and mineral supplementation. This finding was largely drawn from one large trial, conducted in a relatively well-nourished American population. We do not know the generalisability of these findings to other populations. Although generally regarded as safe, vitamin supplements may have harmful effects. A systematic review of the evidence on harms of vitamin supplements is needed. Supplements containing lutein and zeaxanthin are heavily marketed for people with age-related macular degeneration but our review shows they may have little or no effect on the progression of AMD.

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Conflict of interest statement

None known.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Antioxidant multivitamin and mineral supplement versus placebo, Outcome 1 Progression to late AMD (neovascular AMD or geographic atrophy).
1.2
1.2. Analysis
Comparison 1 Antioxidant multivitamin and mineral supplement versus placebo, Outcome 2 Progression to neovascular AMD.
1.3
1.3. Analysis
Comparison 1 Antioxidant multivitamin and mineral supplement versus placebo, Outcome 3 Progression to geographic atrophy.
1.4
1.4. Analysis
Comparison 1 Antioxidant multivitamin and mineral supplement versus placebo, Outcome 4 Progression to visual loss (loss of 3 or more lines on logMAR chart).
1.5
1.5. Analysis
Comparison 1 Antioxidant multivitamin and mineral supplement versus placebo, Outcome 5 Mean visual acuity.
1.6
1.6. Analysis
Comparison 1 Antioxidant multivitamin and mineral supplement versus placebo, Outcome 6 Quality of life.
2.1
2.1. Analysis
Comparison 2 Lutein and/or zeaxanthin versus placebo, Outcome 1 Progression to late AMD (neovascular AMD and/or geographic atrophy.
2.2
2.2. Analysis
Comparison 2 Lutein and/or zeaxanthin versus placebo, Outcome 2 Progression to neovascular AMD.
2.3
2.3. Analysis
Comparison 2 Lutein and/or zeaxanthin versus placebo, Outcome 3 Progression to geographic atrophy.
2.4
2.4. Analysis
Comparison 2 Lutein and/or zeaxanthin versus placebo, Outcome 4 Progression to visual loss (loss of 3 or more lines on logMAR chart).
2.5
2.5. Analysis
Comparison 2 Lutein and/or zeaxanthin versus placebo, Outcome 5 Distance visual acuity: mean.
2.6
2.6. Analysis
Comparison 2 Lutein and/or zeaxanthin versus placebo, Outcome 6 Visual Function Quality (VFQ).
3.1
3.1. Analysis
Comparison 3 Vitamin E versus placebo, Outcome 1 Progression to late AMD (neovascular AMD and/or geographic atrophy.
3.2
3.2. Analysis
Comparison 3 Vitamin E versus placebo, Outcome 2 Progression to visual loss (loss of 3 or more lines on logMAR chart).
4.1
4.1. Analysis
Comparison 4 Zinc versus placebo, Outcome 1 Progression to late AMD (neovascular AMD or geographic atrophy).
4.2
4.2. Analysis
Comparison 4 Zinc versus placebo, Outcome 2 Progression to neovascular AMD.
4.3
4.3. Analysis
Comparison 4 Zinc versus placebo, Outcome 3 Progression to geographic atrophy.
4.4
4.4. Analysis
Comparison 4 Zinc versus placebo, Outcome 4 Progression to visual loss (loss of 3 or more lines on logMAR chart).
4.5
4.5. Analysis
Comparison 4 Zinc versus placebo, Outcome 5 Distance visual acuity: mean.
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NCT00006202 {published data only}
    1. NCT00006202. Lutein for age‐related macular degeneration [Dose ranging study of lutein supplementation in persons over age 60]. clinicaltrials.gov/ct2/show/NCT00006202 (first received 9 September 2000).
NCT00121589 {published data only}
    1. NCT00121589. Lutein/zeaxanthin and omega‐3 supplementation in persons over age 60. clinicaltrials.gov/ct2/show/NCT00121589 (first received 20 July 2005).
NCT00563979 {published data only}
    1. NCT00563979. Enhancement of macular pigment density by oral lutein supplementation (EMPOLS). clinicaltrials.gov/ct2/show/NCT00563979 (first received 20 July 2005).
NCT00564902 {published data only}
    1. NCT00564902. The zeaxanthin and visual function study (ZVF) [Randomized, double blind, lutein controlled study of zeaxanthin and visual function in atrophic age related macular degeneration patients]. clinicaltrials.gov/ct2/show/NCT00564902 (first received 27 November 2007).
NCT00718653 {published data only}
    1. NCT00718653. Effects of antioxidants on human macular pigments. clinicaltrials.gov/ct2/show/NCT00718653 (first received 17 July 2008).
NCT00800995 {published data only}
    1. NCT00800995. Superoxide Dismutase (SOD) as antioxidant treatment of age related macular degeneration (ARMD) [SOD as antioxidant treatment of ARMD]. clinicaltrials.gov/ct2/show/NCT00800995 (first received 2 December 2008).
NCT00893724 {published data only}
    1. NCT00893724. Supplemental adjuvants for intracellular nutrition and treatment (SAINTS) [The effect of supplemental adjuvants for intracellular nutrition and treatment on diabetic macular edema and neovascular age‐related macular degeneration]. clinicaltrials.gov/ct2/show/NCT00893724 (first received 4 May 2009).
NCT02264938 {published data only}
    1. NCT02264938. Drusen morphology changes in nonexudative age‐related degeneration after oral antioxidants supplementation [Drusen morphology changes in nonexudative age‐related degeneration using spectral domain optical coherence tomography after oral antioxidants supplementation: one‐year results]. clinicaltrials.gov/ct2/show/NCT02264938 (first received 9 October 2014).
Nolan 2006 {published data only}
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Sabour‐Pickett 2014 {published data only}
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Wang 2007 {published data only}
    1. Wang W, Connor SL, Johnson EJ, Klein ML, Hughes S, Connor WE. Effect of dietary lutein and zeaxanthin on plasma carotenoids and their transport in lipoproteins in age‐related macular degeneration. American Journal of Clinical Nutrition 2007;85(3):762‐9. - PubMed
Wenzel 2006 {published data only}
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Wolf‐Schnurrbusch 2015 {published data only}
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References to ongoing studies

NCT01694680 {published data only}
    1. NCT01694680. Intervention trial in early age‐related macular degeneration (I‐TEAM) [Intervention study to assess the effect of daily consumption of a lutein‐enriched‐egg beverage on maintenance of visual function in subjects with early signs of age‐related macular degeneration]. clinicaltrials.gov/ct2/show/NCT01694680 (first received 25 September 2012).
NCT02625376 {published data only}
    1. NCT02625376. Resveratrol for exudative age‐related macular degeneration (AGED) [Influence of resveratrol and resvega versus placebo on incidence of bilateralisation of exudative AMD: a double masked prospective study]. clinicaltrials.gov/ct2/show/NCT02625376 (first received 6 August 2015).

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