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

JAMA Ophthalmol. 2017 Nov 1;135(11):1259-1266. doi: 10.1001/jamaophthalmol.2017.3398.


Importance: Nutritional uptake of lutein, zeaxanthin, and ω-3 polyunsaturated fatty acids may increase macular pigment optical density (MPOD) and thereby protect against the development of age-related macular degeneration (AMD).

Objectives: To estimate the efficiency of dietary supplementation containing lutein, zeaxanthin, ω-3 polyunsaturated fatty acids, and vitamins to increase the density of macular pigment in first-generation offspring of parents with neovascular AMD.

Design, setting, and participants: This study was a randomized clinical trial (Lutein Influence on Macula of Persons Issued From AMD Parents [LIMPIA]) with a 6-month treatment period, followed by a 6-month follow-up period. Analyses were based on the intent-to-treat principle. The setting was 2 university hospitals in France (at Bordeaux and Dijon) from January 2011 (first participant first visit) to February 2013 (last participant last visit). The analysis was conducted from January to November 2016. Participants were 120 individuals free of any retinal ocular disease. They were first-generation offspring of parents with neovascular AMD.

Interventions: Participants were randomized in a 1:1 ratio to receive either 2 daily dietary supplementation capsules or placebo for 6 months.

Main outcomes and measures: The primary assessment criterion was the evolution of MPOD after 6 months of supplementation (value of both eligible eyes) measured using the modified MPD-Visucam 200 (Carl Zeiss Meditec) and the modified Heidelberg Retina Angiograph (Heidelberg Engineering) (HRA) at 0.98° eccentricity. The statistical analysis was adjusted for hospital and for risk factors.

Results: Overall, 120 participants (60 in each group) were included, and 239 eyes were analyzed (119 in the lutein plus zeaxanthin [L + Z] group and 120 in the placebo group). Their mean (SD) age was 56.7 (6.6) years, and 71.7% (n = 86) were female. A statistically significant increase in plasma lutein and zeaxanthin was shown in the L + Z group after 3 months and 6 months of treatment compared with the placebo group. However, the difference between groups in the evolution of MPOD measured by HRA 0.98° eccentricity between 6 months and baseline was 0.036 (95% CI, -0.037 to 0.110) (P = .33).

Conclusions and relevance: Among first-generation offspring of parents with neovascular AMD in the LIMPIA trial, MPOD as measured with the modified HRA and the MPD-Visucam was not modified after 6 months of lutein and zeaxanthin dietary supplementation despite plasma levels showing continuous exposure to lutein and zeaxanthin. Further research is necessary to understand the mechanism of absorption and metabolism of these nutrients in the macula, the best way to measure MPOD, and the clinical benefit for the patients.

Trial registration: clinicaltrials.gov Identifier: NCT01269697.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Dietary Supplements
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / pharmacokinetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Lutein / administration & dosage
  • Lutein / pharmacokinetics*
  • Macula Lutea / drug effects*
  • Macula Lutea / metabolism
  • Macula Lutea / pathology
  • Macular Pigment / metabolism*
  • Male
  • Middle Aged
  • Ophthalmoscopy
  • Retrospective Studies
  • Treatment Outcome
  • Visual Acuity
  • Vitamins / administration & dosage
  • Wet Macular Degeneration / diagnosis
  • Wet Macular Degeneration / drug therapy*
  • Wet Macular Degeneration / metabolism
  • Zeaxanthins / administration & dosage
  • Zeaxanthins / pharmacokinetics*


  • Fatty Acids, Omega-3
  • Macular Pigment
  • Vitamins
  • Zeaxanthins
  • Lutein

Associated data

  • ClinicalTrials.gov/NCT01269697