Dietary interventions for AMD:what do we know and what do wenot know?Jennifer R Evans,1 John G Lawrenson2

Dietary supplements are marketed topeople worried about their eyes, andrecommended by eye healthcare profes-sionals for people who have signs ofage-related macular degeneration (AMD).But how much do we actually know aboutwhich dietary interventions prevent orslow down the progression of AMD? Andwhat do we know about the adverseeffects of supplements? This article sum-marises the Cochrane reviews on nutri-tional supplementation in AMD.

There are three relevant reviews on TheCochrane Library.1–3 Overall the reviewsinclude a total of 16 trials. Two reviewsfocus on the role of antioxidant supple-mentation in the prevention1 and progres-sion2 of AMD and one review focuses onthe role of omega 3 fatty acid (ω-3) sup-plementation.3 The reviews are slightlydifferent in scope: the antioxidant reviewsare restricted to dietary supplements (pillscontaining vitamin/mineral supplementsalone or in combination); the ω-3 reviewalso considers dietary sources, forexample, fish consumption. All threereviews focus on intervention studies, spe-cifically experimental studies where parti-cipants have been randomly allocated todietary supplement or placebo/nointervention.

The Cochrane review on antioxidantvitamin and mineral supplements toprevent AMD includes four trials.1 Thesearches for trials were last done inJanuary 2012. This review provides highquality evidence that people aged 40 yearsand above in the general population areunlikely to prevent the development ofAMD by taking vitamin E or β-carotenesupplements. By ‘high quality’ evidence,we mean that further research is unlikelyto change the conclusions of the review.4

The included trials were large (enrollingbetween 1000 and 40 000 participants),

conducted so as to avoid bias, and wereconsistent with each other. The reviewdoes not tell us about the role of com-monly marketed multivitamin combina-tions or about the effect of lutein orzeaxanthin supplements on the preventionof AMD. We do not know whether or notthe general population should take thesemultivitamin or lutein/zeaxanthin supple-ments to prevent the development ofAMD in later life.In contrast, the Cochrane review on

antioxidant vitamin and mineral supple-ments to slow down the progression ofAMD (searches done August 2012)includes at least one large trial (Age-Related Eye Disease Study (AREDS)5)which found that a multivitamin combin-ation slowed down the progression ofAMD.2 AREDS was large, well designedand well reported, and found a statistic-ally significant effect on progression toadvanced AMD. People with AMDi whotook the AREDS formulaii had a 32%reduced odds (99% CI 7% to 51%) ofprogression to advanced AMD over anaverage of 6.3 years of follow-up. If weassume that on average approximately300 in every 1000 people with AMD willexperience progression to advanced AMDthen this study suggests that fewer people(on average 226 per 1000) will experiencesuch progression if they take the AREDSformula.The Cochrane review includes a total of

12 other trials. These other trials aresmaller and of shorter duration and inves-tigate a heterogeneous group of supple-ments. Overall these smaller trials do notprovide evidence of any benefit of supple-mentation. So although this review findssome evidence of benefit for people withAMD of supplementation with a specificcombination of antioxidant vitamins andzinc, overall the evidence is graded as

‘moderate’. The majority of participantswere enrolled in the largest and longestduration trial, which demonstrated abenefit but there were no other publishedtrials investigating the same formulationwith which to compare the results. So it isdifficult to assess the consistency of thisfinding with the data available. Furtherresearch may change the estimate ofeffect. This review did not find convincingevidence that lutein and zeaxanthinslowed down the progression of AMD butcurrent included trials (three trials, 246participants) were not reported in such away as to enable their meaningful inclu-sion in the review. One further trial hassince been published and will be includedin the next update of the review.6

The ω-3 review was completed recently;searches were done in April 2012. No eli-gible trials were identified but there areongoing trials that will be published in thenear future and the review will beupdated when data from these trialsbecome available. AREDS2, for example,is investigating the role of lutein/zeax-anthin and ω-3 fatty acids on progressionto advanced AMD (http://www.areds2.org/, accessed 29 November 2012).

Although ‘generally regarded as safe’vitamin and mineral supplements mayhave harmful effects. In the past few yearsthere have been reports of adverse effectsin particular subgroups of the population.β-Carotene supplementation has beenassociated with an increased risk of lungcancer in people who smoke or who havebeen exposed to asbestos,7 and vitamin Ehas been associated with an increased riskof heart failure in people with diabetes.8

A Cochrane review of vitamin andmineral supplements and mortality con-cluded that ‘Beta-carotene and vitamin Eseem to increase mortality, and so mayhigher doses of vitamin A. Antioxidantsupplements need to be considered asmedicinal products and should undergosufficient evaluation before marketing’.9

The Cochrane reviews do not provideinformation on the role of diet and thedevelopment or progression of AMD.There is a considerable literature on dietand AMD drawn from observationalstudies, not all of it consistent. The roleof diet may be complex, and it may bedietary patterns or healthy lifestyles,rather than individual nutrients that areimportant.10 Randomised controlled trialsmay not be a feasible study design formeasuring the effects of diet which meansthat conclusions will be based on observa-tional studies. This can be problematicbecause people who choose, or haveaccess to, a relatively high dietary intake

1Clinical Research Department, International Centre forEye Health, London School of Hygiene and TropicalMedicine, London, UK; 2Division of Optometry andVisual Science, City University, London, UK

Correspondence to Dr Jennifer R Evans, ClinicalResearch Department, International Centre for EyeHealth, London School of Hygiene and TropicalMedicine, London WC1E 7HT, UK;jennifer.evans@lshtm.ac.uk

iAMD was defined as extensive small drusen,intermediate drusen, large drusen, non-centralgeographic atrophy, or pigment abnormalitiesin one or both eyes, or advanced AMD/visionloss due to AMD in one eye.iiAREDS formula (per day): vitamin C (500 g),vitamin E (400 IU), β-carotene (15 mg), zincoxide (80 mg).

Evans JR, et al. Br J Ophthalmol September 2013 Vol 97 No 9 1089

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of vitamins (or ω-3 fatty acids) differ inmany other ways from people who eatless of these nutrients. In addition (as fortrials), there may be problems with select-ive publication of promising results. Thereis a need for a critical systematic review ofthe evidence for an association betweendiet and AMD that includes explicitassessment of the quality of the evidenceusing the GRADE approach.4

This is the first in a series of short articles summarisingthe results of Cochrane reviews.

Contributors JE and JL made substantialcontributions to conception and design, acquisition ofdata, or analysis and interpretation of data of theCochrane reviews on which this summary is based. JEdrafted this summary and JL revised it critically forimportant intellectual content. Both JE and JL approvedthe version to be published.

Funding This research received no specific grant fromany funding agency in the public, commercial or not-for-profit sectors.

Competing interests None.

Provenance and peer review Not commissioned;externally peer reviewed.

To cite Evans JR, Lawrenson JG. Br J Ophthalmol2013;97:1089–1090.

Published Online First 9 March 2013

Br J Ophthalmol 2013;97:1089–1090.doi:10.1136/bjophthalmol-2013-303134

REFERENCES1 Evans JR, Lawrenson JG. Antioxidant vitamin and

mineral supplements for preventing age-relatedmacular degeneration. Cochrane Database Syst Rev2012(6):CD000253.

2 Evans JR, Lawrenson JG. Antioxidant vitamin andmineral supplements for slowing the progression ofage-related macular degeneration. CochraneDatabase Syst Rev 2012(11):CD000254.

3 Lawrenson JG, Evans JR. Omega 3 fatty acids forpreventing or slowing the progression of age-relatedmacular degeneration. Cochrane Database Syst Rev2012(11):CD010015.

4 Guyatt GH, Oxman AD, Vist GE, et al. GRADE: anemerging consensus on rating quality of evidenceand strength of recommendations. BMJ2008;336:924–6.

5 Age-Related Eye Disease Study Research G. Arandomized, placebo-controlled, clinical trial ofhigh-dose supplementation with vitamins C and E,beta carotene, and zinc for age-related maculardegeneration and vision loss: AREDS report no. 8.Arch Ophthalmol 2001;119:1417–36.

6 Beatty S, Chakravarthy U, Nolan JM, et al. Secondaryoutcomes in a clinical trial of carotenoids withcoantioxidants versus placebo in early age-relatedmacular degeneration. Ophthalmology 2012.Published Online First: Epub Date. doi:10.1016/j.ophtha.2012.08.040

7 Omenn GS. Chemoprevention of lung cancers:lessons from CARET, the beta-carotene and retinolefficacy trial, and prospects for the future. EurJ Cancer Prev 2007;16:184–91.

8 Lonn E, Bosch J, Yusuf S, et al. Effects of long-termvitamin E supplementation on cardiovascular eventsand cancer: a randomized controlled trial. JAMA2005;293:1338–47.

9 Bjelakovic G, Nikolova D, Gluud LL, et al.Antioxidant supplements for prevention of mortalityin healthy participants and patients with variousdiseases. Cochrane Database Syst Rev 2012(3):CD007176.

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know and what do we not know?Dietary interventions for AMD: what do we

Jennifer R Evans and John G Lawrenson

doi: 10.1136/bjophthalmol-2013-3031342013

2013 97: 1089-1090 originally published online March 9,Br J Ophthalmol 

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