Lutein And Zeaxanthin

Lutein (L) and zeaxanthin (Z) are dietary carotenoids derived from dark green leafy vegetables, orange and yellow fruits that form the macular pigment of the human eyes. The mechanism by which they are involved in the prevention of eye diseases may be due their physical blue light filtration properties and local antioxidant activity. In addition to their protective roles against light-induced oxidative damage, there are increasing evidences that L and Z may also improve normal ocular function by enhancing contrast sensitivity and by reducing glare disability. Studies about L and Z supplementation have indicated that moderate intakes of L and Z are associated with decreased AMD risk and less visual impairment.


Cognitive Function

The relationship between L, a dietary xanthophyll carotenoid, and visual and cognitive health is particularly compelling because L is taken up selectively into eye and brain tissue (1-3). In part, the beneficial effects of L are thought to be attributable to its antioxidant and anti-inflammatory properties. Given that the eye is an extension of the neural system, L is increasingly recognized as having a role in cognitive function (4). A number of recent studies evinced a possible role for L and Z in cognitive function (2,5,6). For instance, one of the investigations conducted as part of the Irish Longitudinal Study on Aging determined that older adults with higher macular pigment optical density (MPOD) had better results in various indices of cognitive function compared to those with lower MPOD(5). Furthermore, several studies have shown cognitive impairment to be related to age-related eye diseases (AREDs) (7,8), suggesting that similar factors may be involved. These observations are in line with the view that vision and cognition are not easily separable. The rationale supporting a role for L in cognitive function is based on the following observations: (1) L is the predominant carotenoid in human brain tissue in early as well as late life (2,3); (2) primate retinal L concentrations, i.e., macular pigment density, are related to brain L concentrations (9); (3) macular pigment density is related to cognitive function in adults (5,6); and (4) L supplementation in adults improves cognitive function (10).



Among the carotenoids, L and Z are the only two that cross the blood-retina barrier to form macular pigment in the eye (11), and L is the dominant carotenoid in human brain tissue (2,3,9,12-14). Furthermore, only L was consistently associated with a wide range of cognitive measures that included executive function, language, learning, and memory, which are all associated with specific brain regions (2). In a double-blinded, placebo-controlled trial of women who received L supplementation (12 mg/d), docosahexaenoic acid supplementation (800 mg/d), or a combination of the two for 4 months, verbal fluency scores improved significantly in all three treatment groups. Memory scores and rates of learning improved significantly in the combined treatment group, who also displayed a trend toward more efficient learning (15). Terry et al. suggested that individuals with less L may have compensatory neural mechanisms to help them to engage in learning and recalling processes (16). Taken together, these observations suggested that L could influence cognitive function. Hoffmann (17) et al. found that supplementation of Z promoted a better long term delayed memory. Neuroprotection How they influence brain function, however, is less clear. One possibility is simply protection from the accumulated effects of oxidative and inflammatory stress (18). Data linking reduced MPOD to dementia (19) and cognitive impairment (20) is consistent with that possibility. Another possibility, more relevant to younger individuals and palliative approaches, is a direct improvement by some type of local interaction with neural cells (the so-called neural efficiency hypothesis) (21). Besides, it has also been suggested that the carotenoids may play a beneficial role by enhancing gap junctional communication in the brain and there is a growing body of evidence that the macular carotenoids may have a favourable effect on neuronal processing (22, 23). These carotenoids have been shown to improve communication through cell-to-cell channels, modulate the dynamic instability of microtubules (structural units of neurons), and prevent degradation of synaptic vesicle proteins (24,25).


Blue light protection

The eye is a major sensory organ that requires special care for a healthy and productive lifestyle. Numerous studies have identified L and Z to be important components for eye health. Their role in human health, in particular the health of eyes, is established from epidemiological, clinical and interventional studies (26,27). They constitute the main MPs found in the yellow spot of the human retina which protect the macula from damage by blue light, improve visual acuity and scavenge harmful reactive oxygen species. They have also been linked with reducing the risk of AMD and ARC. They may also enhance visual performance by decreasing chromatic aberration and enhancing contrast sensitivity (28).



1 Bone, R.A.; Landrum, J.T.; Tarsis, S.L. Preliminary identification of the human macular pigment. Vis. Res. 1985, 25, 1531–1535.

2 Johnson, E.J.; Vishwanathan, R. Relationship between serum and brain carotenoids, α-tocopherol, and retinol concentrations and cognitive performance in the oldest old from the Georgia Centenarian Study. J. Aging Res. 2012, 2013, 214–219.

3 Vishwanathan, R.; Kuchan, M.J.; Sen, S.; Johnson, E.J. Lutein is the predominant carotenoid in infant brain: Preterm infants have decreased concentrations of brain carotenoids. J. Pediatr. Gastroenterol. Nutr. 2014, 59, 659–665

4 Johnson, E.J. A possible role for lutein and zeaxanthin in cognitive function in the elderly. Am. J. Clin. Nutr. 2012, 96, 1161S–1165S

5 Feeney, J.; Finucane, C.; Savva, G.M.; Cronin, H.; Beatty, S.; Nolan, J.M.; Kenny, R.A. Low macular pigment optical density is associated with lower cognitive performance in a large, population-based sample of older adults. Neurobiol. Aging 2013, 34, 2449–2456.

6 Vishwanathan, R.; Iannaccone, A.; Scott, T.M.; Kritchevsky, S.B.; Jennings, B.J.; Carboni, G.; Forma, G.; Satterfield, S.; Harris, T.; Johnson, K.C.; et al. Macular pigment optical density is related to cognitive function in older people. Age Ageing 2014, 43, 271–275.

7 Ong, S.Y.; Cheung, C.Y.; Li, X.; Lamoureux, E.L.; Ikram, M.K.; Ding, J.; Cheng, C.Y.; Haaland, B.A.; Saw, S.M.; Venketasubramanian, N.; et al. Visual impairment, age-related eye diseases, and cognitive function: The Singapore Malay Eye study. Arch. Ophthalmol. 2012, 130, 895–900.

8 Rogers, M.A.M.; Langa, K.M. Untreated poor vision: A contributing factor to late-life dementia. Am. J. Epidemiol. 2010, 171, 728–735.

9 Vishwanathan, R.; Neuringer, M.; Snodderly, D.M.; Schalch, W.; Johnson, E.J. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates. Nutr. Neurosci. 2013, 16, 21–29.

10 Johnson, E.J.; McDonald, K.; Caldarella, S.M.; Chung, H.Y.; Troen, A.M.; Snodderly, D.M. Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutr. Neurosci. 2015, 11, 75–83

11 Snodderly, D.M. Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. Am. J. Clin. Nutr. 1995, 62, 1448S–1461S

12 Devore, E.E.; Grodstein, F.; van Rooij, F.J.; Hofman, A.; Stampfer, M.J.; Witteman, J.C.; Breteler, M.M. Dietary antioxidants and long-term risk of dementia. Arch. Neurol. 2010, 67, 819–825.

13 Lindbergh, C.; Terry, D.; Mewborn, C.; Renzi-Hammond, L.; Hammond, B.; Miller, S. Aging and dementia-1lutein and zeaxanthin supplementation improves neurocognitive function in older adults as measured using functional magnetic resonance imaging: A randomized controlled trial. Natl. Acad. Neuropsychol. 2016, 31, 574.

14 Kuchan, M.; Wang, F.; Geng, Y.; Feng, B.; Lai, C. Lutein stimulates the differentiation of human stem cells to neural progenitor cells in vitro. In Presented at Advances and Controversies in Clinical Nutrition, Washington, DC, USA, 5–7 December 2013

15 Johnson, E.J.; McDonald, K.; Caldarella, S.M.; Chung, H.Y.; Troen, A.M.; Snodderly, D.M. Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutr. Neurosci. 2015, 11, 75–83

16 Terry, D.; Duda, B.; Mewborn, C.; Lindbergh, C.; Bovier, E.; Shon, D.; Puente, A.; Chu, K.; Washington, T.; Stapley, L.; et al. Brain activity associated with verbal learning and recall in older adults and its relationship to lutein and zeaxanthin concentrations. Arch. Clin. Neuropsychol. 2014, 29, 506.

17 Hoffmann, K.; Richer, S.; Wrobel, J.; Chen, E.; Podella, C. A prospective study of neuro-cognitive enhancement with carotenoids in elderly adult males with early age related macular degeneration. Ophthalmol. Res. Int. J. 2015, 4, 1–8.

18 Fatani, A.J.; Parmar, M.Y.; Abuohashish, H.M.; Ahmed, M.M.; Al-Rejaie, S.S. Protective effect of lutein supplementation on oxidative stress and inflammatory progression in cerebral cortex of streptozotocin-induced diabetes in rats. Neurochem. J. 2016, 10, 69–76.

19 Nolan, J.M.; Loskutova, E.; Howard, A.N.; Moran, R.; Mulcahy, R.; Stack, J.; Bolger, M.; Dennison, J.; Akuffo, K.O.; Owens, N. Macular pigment, visual function, and macular disease among subjects with Alzheimer’s disease: An exploratory study. J. Alzheimer’s Dis. 2014, 42, 1191–2002.

20 Renzi, L.M.; Dengler, M.J.; Puente, A.; Miller, L.S.; Hammond, B.R. Relationships between macular pigment optical density and cognitive function in unimpaired and mildly cognitively impaired older adults. Neurobiol. Aging 2014, 35, 1695–1699

21 Zimmer, J.P.; Hammond, B.R., Jr. Possible influences of lutein and zeaxanthin on the developing retina. Clin. Ophthalmol. 2007, 1, 25–35.

22 Renzi, L.M.; Bovier, E.R.; Hammond, B.R., Jr. A role for the macular carotenoids in visual motor response. Nutr. Neurosci. 2013, 16, 262–268.

23 Crabtree, D.V.; Ojima, I.; Geng, X.; Adler, A.J. Tubulins in the primate retina: evidence that xanthophylls may be endogenous ligands for the paclitaxel-binding site. Bioorg. Med. Chem. 2001, 9, 1967–1976.

24 Ozawa, Y.; Sasaki, M.; Takahashi, N.; Kamoshita, M.; Miyake, S.; Tsubota, K. Neuroprotective effects of lutein in the retina. Curr. Pharm. Des. 2012, 18, 51–56

25 Johnson, E.J. Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan. Nutr. Rev. 2014, 72, 605–612

26 Bernstein, P.S. The role of lutein and zeaxanthin in protection against age-related macular degeneration. Acta Hortic. 2015, 1106, 153–160

27 Renzi, L.M.; Hammond, B.R. The relation between the macular carotenoids, lutein and zeaxanthin, and temporal vision. Ophthalmic Physiol. Opt. 2010, 30, 351–357

28 Renzi, L.M.; Hammond, B.R. The effect of macular pigment on heterochromatic luminance contrast. Exp. Eye Res. 2010, 91, 896–900