Table 2Summary of the evidence on the effects of nutritional supplements for age-related macular degeneration

OutcomeTreatmentPopulationEffect*GRADE ClassificationComment
Functional vision lossCarotenoidsEarly AMD(∼)LowSingle study (N=90) found a small increase in visual acuity after 12 months, but the improvement was not clinically significant (i.e. <15 letters).12
AntioxidantsCategories 3-4 AMD(+)ModerateEvidence of benefit from 1 large multicenter trial10 and one smaller trial.11 4 small trials found neutral effects on functional vision loss.12-15
AntioxidantsCategory 2 AMD(∼)LowNo evidence of benefit after 7 years of treatment in 1 large multicenter trial that included 1,063 Category 2 subjects.10
Omega-3 fatty acidsEarly AMD (94% in Categories 1- 2)(∼)Very LowOne study found evidence of slowed visual acuity loss but not to a clinically significant degree. Very few subjects in this study (6.4%) had Categories 3-4 AMD.16
Quality of lifeCarotenoidsAMD(∼)LowNo significant findings on night driving in one study (N=90).12
AntioxidantsN/A(0)N/ANo evidence.
Omega-3 fatty acidsN/A(0)N/ANo evidence.
MortalityBeta-caroteneSmokers(−)ModerateHigh-dose beta carotene (20 to 30 mg/day) was linked with increased mortality in 2 large trials in smokers and asbestos workers.25, 26
Vitamin EGeneral population(−)HighHigh-dose vitamin E (>=400 IU/day) was associated with a slight increase in mortality in a meta-analysis of 11 trials.19
Lung cancerBeta-caroteneSmokers(−)ModerateHigh-dose beta carotene (20 to 30 mg/day) was linked with increased lung cancer incidence among smokers in a meta-analysis of 4 large trials.21 No increase in lung cancer was observed among former and non-smokers.
Prostate cancerVitamin EGeneral population(−)LowHigh-dose vitamin E (400 IU/day) was associated with an increase in prostate cancer in one study.31
Gastrointestinal cancersAntioxidantsGeneral population(∼)HighSupplements had no effect on incidence of gastrointestinal cancers in a meta-analysis of 12 good-quality trials.23
Congestive heart failureVitamin EDM, CVD, or post-infarction(−)LowVitamin E (300-400 IU/day) was linked with increased CHF hospitalization in 2 trials of high-risk patients.34, 35
Urinary tract infections (UTIs)ZincAMD(−)LowZinc (80 mg/day) was associated with more UTIs and hospital admissions due to genitourinary causes compared with non-zinc treated subjects in one large study.42
Yellowing of the skinBeta-carotene LuteinAMD and general population(−)HighTransient yellowing of the skin was frequently reported in trials of beta carotene24 and in two trials of lutein44
Gastrointestinal (GI) symptomsAntioxidantsAMD(−)HighGI symptoms were the most common adverse effect that led to withdrawal from studies, according to a systematic review of 10 RCTs of antioxidant supplements for AMD.18

GRADE = Grades of Recommendation, Assessment, Development, and Evaluation; ICU = intensive care unit; RCT = randomized controlled trial; AMD = age-related macular degeneration; CHF = congestive heart failure.


Effect: (+) benefit; (−) harm; (∼) mixed findings/no effect; (0) no evidence.

GRADE Classification: high = further research is very unlikely to change our confidence on the estimate of effect; moderate = further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; low = further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; very low = any estimate of effect is very uncertain.

Trials of antioxidants included treatment with antioxidants alone or combined with carotenoids or other supplements.


Cover of Nutritional Supplements for Age-Related Macular Degeneration: A Systematic Review
Nutritional Supplements for Age-Related Macular Degeneration: A Systematic Review [Internet].
Kansagara D, Gleitsmann K, Gillingham M, et al.
Washington (DC): Department of Veterans Affairs (US); 2012 Jan.

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