Lutein-containing supplementation was associated with improved macular pigment optical density and best-corrected visual acuity in patients with age-related macular degeneration, with the clearest benefits observed in early-stage disease, according to a systematic review and meta-analysis.
The researchers analyzed nine randomized, placebo-controlled trials including 860 patients with age-related macular degeneration (AMD). Eligible studies evaluated oral lutein alone or in combination with zeaxanthin or epilutein and reported preintervention and postintervention measures of macular pigment optical density (MPOD) and best-corrected visual acuity (BCVA). Supplementation lasted 2 to 24 months, and lutein doses ranged from 2 mg/day to 20 mg/day.
Across the included trials, lutein-containing supplementation was associated with statistically significant improvements in MPOD and BCVA compared with placebo. In subgroup analyses, improvements in both outcomes were statistically significant among patients with early-stage AMD but not among those with late-stage disease or mixed-stage populations.
When analyzed by regimen, lutein monotherapy was associated with improvements in both MPOD and BCVA, whereas combination formulations improved MPOD but did not show a statistically significant association with BCVA. The researchers cautioned that this difference may reflect smaller sample sizes in combination groups and should not be interpreted as evidence of superiority for monotherapy.
The pooled effects were statistically significant, with moderate-to-large effect sizes, although the clinical significance of these standardized differences—particularly for BCVA—remains uncertain. The researchers noted that observed BCVA changes in early-stage AMD likely reflect preservation of function rather than true improvements in visual acuity.
Secondary analyses also favored supplementation. Contrast sensitivity improved at several spatial frequencies, and serum lutein concentrations increased, suggesting systemic absorption. Meta-regression analyses suggested that longer supplementation duration and greater cumulative lutein exposure were associated with larger changes in MPOD and BCVA, although these analyses cannot establish an optimal dose or prove a causal dose-response relationship.
The findings add to existing evidence from the Age-Related Eye Disease Study 2 (AREDS2), which found that substituting lutein and zeaxanthin for beta-carotene in the AREDS formulation was associated with reduced progression risk, although effects versus no supplementation have been more variable. The AREDS2 formulation—10 mg lutein and 2 mg zeaxanthin daily—remains the primary clinical reference for supplementation.
The researchers noted several limitations, including substantial heterogeneity across trials, differences in dosing and measurement methods, and follow-up limited to 2 to 24 months. Funnel plot asymmetry and Egger testing suggested potential publication bias for MPOD outcomes, raising the possibility that the magnitude of the pooled structural effect may be overestimated. They also emphasized that AMD is a chronic disease requiring longer follow-up to assess effects on progression and long-term vision outcomes.
“Lutein-based supplementation is associated with measurable structural and functional visual benefits in early-stage AMD,” wrote lead study author Wei-Xiang Wang, of Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and colleagues. “Treatment effects appear dose- and duration-dependent, while evidence in late-stage AMD remains limited.”
The researchers reported no conflicts of interest and no external funding.
Source: Journal of Ophthalmology