https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891800
Introduction
Lutein and zeaxanthin are fat-soluble nutrients forming part of the carotenoid family. Lutein is found in dark green leafy vegetables such as kale and spinach and in egg yolks and corn (1). Zeaxanthin is more prominently found in yellow and orange foods such as egg yolks, corn, orange capsicums, tangerines, persimmons, mandarins, and oranges (2, 3). In the body, lutein and zeaxanthin are found in eye, brain, breast and adipose tissue. Although lutein is not the major carotenoid in our diet, it is the carotenoid of the highest concentration in human brain tissue (4, 5). In fact, lutein and zeaxanthin account for 66 to 77% of the total carotenoid concentration in human brain tissue (6). Lutein and zeaxanthin have been identified in the hippocampus, cerebellum, and frontal, occipital, and temporal cortices (5, 7–9); and due to their powerful antioxidant and anti-inflammatory properties (10, 11), interest in their neuroprotective effects is increasing.
Studies examining the relationship between the dietary intake of carotenoids, including lutein and zeaxanthin, have demonstrated a generally positive relationship between lutein and zeaxanthin intake and cognitive health. For example, a higher dietary intake of lutein and/or zeaxanthin was associated with a lower risk of experiencing moderate-to-poor cognitive function in middle-aged women (12), better immediate and delayed word recall in older adults (13), and higher scores on several cognitive-based measures in adults over the age of 60 years (14). Moreover, higher plasma concentrations of lutein and/or zeaxanthin were associated with better cognitive function in older adults (15, 16), visual-spatial functioning in older adults (17), and relational memory performance in young and middle-aged adults (18). Macular pigment optical density (MPOD), which provide a measure of lutein and zeaxanthin concentration in the brain (8, 19), was also associated with better cognitive performance in older-age adults (16), adults with mild cognitive impairment (20), and in adults with age-related macular degeneration (21). However, despite these findings, results from randomized controlled trials have been inconsistent. For example, 12 months of supplementation with 10 mg of lutein and 2 mg of zeaxanthin were associated with improvements in complex attention and cognitive flexibility in community-dwelling older adults (22), buffered cognitive decline on a verbal learning task in older adults (22), and increased spatial memory in young, healthy adults (23). In this latter study, participants who experienced increases in MPOD, irrespective of group allocation, experienced improvements in visual memory, complex attention, and reasoning ability. However, in a large 5-year study on older-age adults with intermediate or advanced age-related macular degeneration, lutein and zeaxanthin supplementation did not change cognitive function as measured by several telephone-administered cognitive tasks (24). These inconsistent findings are likely due to differences in the population recruited, outcome measures used, and treatment duration. Exposure to dietary sources of lutein and zeaxanthin are also likely to confound results as it is challenging to conduct clinical trials on nutrients that are found in everyday foods and may be consumed by participants daily. The finding by Renzi-Hammond et al. (23) where improvements in cognitive performance occurred in participants who experienced increases in MPOD, irrespective of group allocation, suggests increases in brain concentration of lutein and zeaxanthin (either via dietary sources or supplementation) are necessary for improvements in cognition to be realized.
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