Supplemental Retinal Carotenoids Enhance Memory in Healthy Individuals with Low Levels of Macular Pigment in A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

J Alzheimers Dis. 2018;61(3):947-961. doi: 10.3233/JAD-170713.


Background: There is a biologically plausible rationale whereby the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), which are collectively referred to as macular pigment (MP) in the central retina (macula), support the maintenance of cognition via their antioxidant and anti-inflammatory properties.

Objective: To investigate the impact of supplemental L, Z, and MZ on memory, executive function, and verbal fluency among healthy individuals with low MP levels.

Methods: In this double-blind, placebo-controlled, randomized clinical trial, subjects (n = 91; mean±SD age = 45.42±12.40; % male = 51.6) consumed a daily formulation of 10 mg L, 10 mg MZ, and 2 mg Z (n = 45) or placebo (n = 46) for 12 months. Cognitive domains assessed included verbal and visual learning, immediate and delayed memory, executive function, and verbal fluency. MP and serum carotenoid concentrations of L, Z, and MZ were also measured.

Results: Following 12-month supplementation, individuals in the active group exhibited statistically significant improvements in memory when compared to the placebo group (paired associated learning [PAL] memory score [rANOVA, p = 0.009]; PAL errors [rANOVA, p = 0.017]). Furthermore, the observed reduction in the number of errors made in the PAL task among those in the intervention group was positively and significantly related to observed increases in MP volume (p = 0.005) and observed increases in serum concentrations of L (p = 0.009).

Conclusion: This randomized, double-blind, placebo-controlled clinical trial demonstrates a memory-enhancing effect of daily supplementation with L, Z, and MZ in healthy subjects with low MP at baseline. The implications of these findings for intellectual performance throughout life, and for risk of cognitive decline in later life, warrant further study.

Keywords: Brain; CANTAB; carotenoids; cognitive function; episodic memory; lutein; macular pigment; meso-zeaxanthin; paired associated learning; zeaxanthin.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cognition
  • Dietary Supplements / analysis*
  • Double-Blind Method
  • Executive Function
  • Female
  • Healthy Volunteers
  • Humans
  • Lutein / administration & dosage
  • Lutein / pharmacology*
  • Macular Pigment / physiology*
  • Male
  • Memory, Episodic*
  • Middle Aged
  • Retina / drug effects*
  • Retina / physiology
  • Vision Tests
  • Zeaxanthins / administration & dosage
  • Zeaxanthins / pharmacology


  • Macular Pigment
  • Zeaxanthins
  • meso-zeaxanthin
  • Lutein