Supplements to Slow Progression of Age-Related Macular Degeneration

Do antioxidant vitamin and mineral supplements slow the progression of age-related macular degeneration (ARMD)?

Use of antioxidant vitamin or zinc supplements may delay progression of ARMD compared with placebo. (Strength of Recommendation [SOR]: A, systematic review and meta-analysis.) The addition of docosahexaenoic acid (DHA), lutein, zeaxan-thin, resveratrol, and hydroxytyrosol to the supplements used in the original Age-Related Eye Disease Study (AREDS) provided no significant improvement in visual acuity for patients with unilateral wet ARMD. (SOR: B, multicenter randomized controlled trial [RCT].) Adding lutein and zeaxanthin to the original AREDS supplement formulation may delay progression of ARMD compared with placebo. (SOR: B, prospective cohort study.)

In 2023, a systematic review and meta-analysis of 26 RCTs (N = 11,952) compared various antioxidant vitamin and mineral supplements with placebo or no intervention for their ability to slow disease progression in adults 65 to 75 years of age with ARMD.¹ The review included participants who had ARMD in one or both eyes and compared outcomes of ARMD progression in groups given vitamin or mineral supplements, alone or in combination, with placebo or no intervention. The supplements included multivitamins and single-component formulations of lutein, vitamin E, and zinc. The length of intervention and follow-up ranged from 6 months to 5 years.

A fixed-effect model was used to pool data from 14 studies in the meta-analysis. However, pooled data were not reported because there was significant variation across the different studies, with an I² value greater than 50% indicating inconsistency with results.

Three studies (n = 2,445) found that patients taking anti-oxidant vitamin supplements were less likely to progress to late-stage ARMD (odds ratio [OR] = 0.72; 95% CI, 0.58-0.9). Three studies that compared zinc supplementation with placebo also found a decrease in progression to late-stage ARMD (OR = 0.83; 95% CI, 0.7–0.98). No significant difference was shown with lutein-zeaxanthin supplementation compared with placebo (relative risk [RR] = 0.94; 95% CI, 0.87–1.01). The risk of progression was higher in one study that compared vitamin E with placebo, although it was not significant (RR = 1.36; 95% CI, 0.31–6.05). An increased risk of lung cancer with beta-carotene supplementation was noted, mostly in former smokers. Many of the trials were unable to detect rare adverse effects due to small sample size. The review also was limited by the heterogeneity of studies compared.

A 2021 multicenter RCT (N = 109) compared the original AREDS supplement plus manganese and selenium with the AREDS formulation with added DHA, lutein, zeaxanthin, resveratrol, and hydroxytyrosol for slowing disease progression in patients with unilateral wet ARMD.² The patients were 50 years or older, were from Spain or Portugal, and had unilateral exudative ARMD. Participants were a mean age of 77 years and the sex distribution was even between men and women.

Using a 1: 1 ratio, patients were randomized to a control or intervention group for 12 months. The control group received the original AREDS supplement, manganese, and selenium. The intervention group received the AREDS formulation without beta carotene but with added DHA, lutein, zeaxanthin, resveratrol, and hydroxytyrosol. The primary outcome was best-corrected visual acuity evaluated at baseline and 6 and 12 months. At 12 months there was no significant difference in visual acuity between the groups, with an estimated treatment difference of −1.63 (95% CI, −0.83 to 4.09). The most common adverse effect was cataract development or progression. This study was limited by a short follow-up period for visual acuity assessment and was underpowered to detect the primary outcome.