Zeaxanthin

Lutein + Zeaxanthin and Omega-3 Fatty Acids for Age-Related Macular Degeneration: The Age-Related Eye Disease Study 2 (AREDS2) Randomized Clinical Trial

Study: This multicenter, randomized, double-blind, placebo-controlled trial (NCT00345176) enrolled 4,203 participants aged 50–85 at risk for advanced age-related macular degeneration (AMD). Participants received lutein (10 mg/day) + zeaxanthin (2 mg/day), omega-3 fatty acids (DHA 350 mg + EPA 650 mg), both, or placebo, added to the original AREDS formulation (vitamins C, E, beta-carotene, zinc, copper). The primary outcome was progression to advanced AMD (neovascular or central geographic atrophy) over 5 years, assessed via fundus photography.

Findings: Lutein + zeaxanthin significantly reduced the risk of progression to advanced AMD by 10% compared to the original AREDS formulation (HR 0.90, 95% CI 0.82–0.99, p=0.02). The effect was more pronounced (18% risk reduction) in those with low dietary lutein intake. No significant benefit was observed for omega-3s. Lutein + zeaxanthin also improved MPOD and was safer than beta-carotene, especially for smokers, as beta-carotene increased lung cancer risk. No serious adverse events were linked to lutein, though minor skin yellowing was reported in some cases.

Link: JAMA - AREDS2

Clinical Effects of Dietary Supplementation of Lutein with High Bio-Accessibility on Macular Pigment Optical Density and Contrast Sensitivity: A Randomized Double-Blind Placebo-Controlled Parallel-Group Comparison Trial

Study: This RCT (Machida et al., 2020) involved 59 healthy adults aged 20–69 in Japan, randomized to receive 12 mg/day lutein or placebo for 16 weeks. Primary outcomes were changes in MPOD, contrast sensitivity, and glare sensitivity, with secondary outcomes including serum lutein levels, assessed at weeks 8 and 16.

Findings: The lutein group showed significantly improved MPOD, contrast sensitivity, and glare sensitivity at week 16 compared to placebo (p<0.05). Serum lutein levels increased significantly at weeks 8 and 16, confirming bioavailability. No adverse events were reported, supporting lutein’s safety at 12 mg/day. The study suggests lutein alone enhances visual function in healthy adults, with effects evident by 16 weeks.

Link: Nutrients - Machida et al., 2020

Clinical Trial of Lutein in Patients with Retinitis Pigmentosa Receiving Vitamin A

Study: This randomized, double-masked, controlled trial (NCT00346333) involved 225 non-smoking adults aged 18–60 with retinitis pigmentosa (RP) receiving vitamin A (15,000 IU/day). Participants were randomized to lutein (12 mg/day) or placebo for 4 years. The primary outcome was the rate of visual field loss (Humphrey Field Analyzer [HFA] 30-2 program), with secondary outcomes including HFA 60-4, combined 30-2/60-4, 30-Hz electroretinogram (ERG) amplitude, and ETDRS visual acuity.

Findings: No significant difference was found in the rate of visual field loss for HFA 30-2 (p=0.66) or other visual outcomes between lutein + vitamin A and placebo + vitamin A groups. However, a prior observational analysis showed higher dietary lutein intake (3.5–13 mg/day) was associated with slower visual field loss (p=0.05). No serious adverse events were reported, confirming safety at 12 mg/day. The study concluded lutein supplementation did not slow visual decline in RP patients on vitamin A.

Link: PMC - Clinical Trial of Lutein in RP

Effect of Dietary Supplementation With Lutein, Zeaxanthin, and ω-3 on Macular Pigment: A Randomized Clinical Trial (LIMPIA)

Study: This RCT (NCT01269697) involved 120 first-generation offspring (aged 18–50) of parents with neovascular AMD, conducted at two French hospitals from 2011–2013. Participants received lutein (10 mg/day), zeaxanthin (2 mg/day), omega-3 fatty acids (DHA 270 mg + EPA 180 mg), and vitamins or placebo for 6 months, with a 6-month follow-up. The primary outcome was MPOD measured by modified Heidelberg Retina Angiograph (HRA) and Visucam 200, with secondary outcomes including visual acuity and serum carotenoid levels.

Findings: No significant change in MPOD was observed after 6 months of supplementation compared to placebo, despite increased plasma lutein and zeaxanthin levels (p<0.001). Visual acuity remained unchanged. The study suggested that MPOD measurement methods or nutrient absorption mechanisms may limit detectable effects in this population. No serious adverse events were reported.

Link: JAMA Ophthalmology - LIMPIA

Dose-Ranging Study of Lutein Supplementation in Persons Aged 60 Years or Older

Study: This RCT (Rosenthal et al., 2006) involved 45 adults aged 60+ with normal vision or early AMD, randomized to receive lutein (3.3, 6.6, or 13 mg/day) or placebo for 4 months, with a 1-month follow-up. Outcomes included serum lutein levels, MPOD, and visual function (e.g., visual acuity, contrast sensitivity).

Findings: All lutein doses significantly increased serum lutein levels and MPOD (p<0.05), with the 13 mg/day group showing the greatest increase. No significant improvements in visual acuity or contrast sensitivity were observed, possibly due to the short duration or healthy baseline vision. No adverse events were reported, supporting lutein’s safety up to 13 mg/day.

Link: IOVS - Rosenthal et al., 2006