The Function of Lutein in the Brain

“Of the 600 carotenoids identified in nature, only about 25 are found in human serum and tissues, and only lutein and its isomer zeaxanthin preferentially accumulate in the macular region of the retina to form macular pigment. Lutein and zeaxanthin protect the macula from short wavelength blue light and oxidative stress. In infants, lutein and zeaxanthin may also play a role in the maturation of cells in the developing macula. Therefore, lutein may be important for visual de- velopment, maintenance of ocular tissues as well as protection against age-related macular degeneration (AMD), a leading cause of visual impairment and blindness in the United States. Increased intake of lutein is related to a decreased risk of AMD. Similarly, the dietary information from the Age-Related Eye Disease Study (AREDS 1) found that dietary intakes of lutein and zeaxanthin were related to protection against de- veloping AMD. AREDS 2, a multicenter randomized clinical trial, assessed the effects of oral supplemen- tation of lutein and zeaxanthin (10 and 2 mg, respectively), and/or eicosapentaneoic acid (EPA) and docasa- hexaenoic acid (DHA) (650 and 350 mg, respectively) as a treatment for AMD. In secondary analysis, lutein and zeaxanthin supplements on top of the AREDS 1 formula (500 mg vitamin C, 400 IU vitamin E, 15 mg beta-carotene, 80 mg zinc, 2 mg copper) lowered the progression to advanced AMD in persons with low dietary lutein and zeaxanthin.

Scientific evidence is accumulating that lutein may be important for brain function as well. The brain is espe- cially vulnerable to free radical attacks due to its relatively low antioxidant content, high polyunsaturated fatty acid concentrations, and its high metabolic activity. Increased lipid peroxidation and nucleic acidoxidation are found early in Alzheimer’s disease (AD), and increased levels of inflammatory markers and pro-inflammatory cytokines have been found in the central nervous system of individuals with early AD as well as with mild cognitive impairment. If increases in sensitivity to oxidative stress and inflammation in the aging brain lead to cognitive deficits, dietary antioxidant and anti-inflammatory agents may delay the extent of oxidative damage to neural tissues and may have an enormous impact on neural health. Lutein functions as both antioxidant and anti-inflammatory agent. Therefore, intake of this dietary component may be important for neural health across the lifespan.

In a recent study evaluating the carotenoid content in infant brain tissue, lutein, zeaxanthin, beta-crypto- xanthin and beta-carotene were the major carotenoids found in the infant brain tissues. Lutein was the pre- dominant carotenoid, accounting for 59% of total carotenoids. Lutein was higher than all other detected carotenoids in regions of the infant brain that are associated with memory, executive function, vision and hearing. Preterm infants had significantly lower concentrations of lutein in their brain compared to full-term infants despite similarity in postmenstrual age. Brain lutein concentrations were not different between breast-milk-fed and formula-fed term decedents. The data suggested preferential accumulation and maintenance of lutein in the infant brain despite relatively lower intakes among the dietary carotenoids.

Lutein was also found to be the dominant carotenoid in various regions of geriatric brain tissue. On the con- trary, beta-carotene and lycopene were predominant in matched serum, which more closely reflects dietary intake. These findings suggest that although not predominant in the diet, there seems to be a preferential uptake of lutein from the circulation into the brain, similar to what occurs in the macula. In infant brain tis- sue, the relative contribution of lutein to the total carotenoids is twice that found in adults, accounting for more than half the concentration of total carotenoids (4). Therefore, the greater proportion of lutein in the pediatric brain suggests a need for lutein during neural development. The mechanism of a neuroprotective effect of lutein is not known. It has been suggested that lutein’s actions involve decreased oxidative stress, activation of anti-inflammatory pathways and modulation of functional properties of synaptic membranes along with changes in physicochemical and structural features. However, a neuroprotective effect of lutein may not be due to an antioxidant effect alone.

Research has shown that there is an association between macular pigment (MP) density and cognitive func- tion suggesting that lutein and zeaxanthin embedded in neural tissue are capable of influencing cognitive function in the elderly (6, 7). Higher MP densities likely reflect higher brain lutein and zeaxanthin concent- rations which may function in cognition. Among the carotenoids, lutein seems to be the most consistently associated with a range of cognitive measures. A role for lutein in cognitive function was evaluated in a randomized, placebo-controlled double-blind study in healthy elder women who received docasahexaenoic acid (800 mg/d), lutein (12 mg/d), a combination of docasahexaenoic acid and lutein or placebo (8). Fol- lowing supplementation, verbal fluency scores improved significantly in the DHA, lutein, and combined treat- ment groups. Memory scores and rate of learning improved significantly in the combined treatment group, who also displayed a trend toward more efficient learning. Measures of mental processing speed, accuracy and mood were not affected by supplementation. These findings suggest that DHA and lutein supplemen- tation may work together in an additive/synergistic manner to improve cognitive functions in older adults. Although lutein is not an essential nutrient, evidence is accumulating to suggest that lutein is important to optimize neural health. Given this, efforts may be warranted to establish recommended intakes for this dietary component.”