Among all food-derived bioactive compounds examined for ocular disease, lutein and zeaxanthin stand out as the only nutraceuticals with consistent clinical validation — specifically increasing macular pigment optical density and slowing progression to advanced age-related macular degeneration (AMD). By contrast, polyphenols including curcumin, resveratrol, and flavonoids demonstrate mechanistically plausible anti-inflammatory and anti-angiogenic effects via Nrf2 antioxidant pathways and NF-κB inhibition, but their clinical evidence remains sparse, heterogeneous, and largely confined to cell and animal models.
The gap between preclinical promise and clinical proof is a defining problem in nutraceutical ophthalmology — and this review crystallizes it sharply. Lutein and zeaxanthin's advantage isn't accidental: they physically accumulate in the macula, giving them a measurable pharmacodynamic footprint that other polyphenols simply lack. Curcumin and resveratrol face compounding obstacles — poor oral bioavailability, rapid metabolism, and ill-defined therapeutic dosing windows — that preclinical models routinely ignore. The AREDS2 trial already established carotenoid supplementation as standard-of-care adjunct for intermediate AMD, giving lutein/zeaxanthin a clinical foundation no other dietary compound in this space currently matches.
For adults concerned with long-term visual health, the actionable takeaway is narrow: consistent dietary or supplemental lutein and zeaxanthin intake has genuine clinical backing. The rest of the nutraceutical pipeline, however promising mechanistically, requires rigorous randomized trials before therapeutic recommendations are warranted. This is a confirmatory synthesis, not a paradigm shift.
