Open Access
Review
Issue
OCL
Volume 23, Number 1, January-February 2016
Article Number D107
Number of page(s) 6
Section Dossier: Lipids and Brain / Lipides et cerveau
DOI https://doi.org/10.1051/ocl/2015027
Published online 02 October 2015

© M. Ramirez, Published by EDP Sciences, 2015

Licence Creative Commons
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1 Introduction

Carotenoids are a class of naturally occurring pigments that are synthesized by plants and produce the red, orange, and yellow colors of fruits and vegetables.

Carotenoids share a 40 carbon atom backbone and are classified into two subclasses depending on the presence of oxygen in the molecule: xanthophylls (lutein, zeaxanthin (C40H56O2), and β-cryptoxanthin (C40H56O) and carotenes (α-carotene, β-carotene, and lycopene (C40H56)) (see Fig. 1 in Krinsky and Johnson, 2005). The structure of zeaxanthin derives from β-carotene ((3R,3R)-β,β-carotene-3,3-diol. A shift of one double bond in one ionone ring system leads to the structure of lutein ((3R,3R,6R)-β,ε-carotene-3,3-diol) (Dachtler et al., 2001).

They are found in green leafy vegetables and brightly colored fruits. Green vegetables have the highest concentration of lutein particularly kale, spinach parsley, and collards (Alisa Perry and Johnson, 2009; Humphries and Khachik, 2003). Yellow-orange vegetables and fruits are less enriched in xanthophylls and some of them may contain both lutein and zeaxanthin at a ratio close to 1 (Humphries and Khachik, 2003). Some foods increase the amount of carotenoids after cooking. In fact, compared to raw spinach, cooked spinach contained considerably more carotenoids (Alisa Perry and Johnson, 2009). Egg yolk contains lower concentration of xanthophylls than green vegetables but with a higher bioavailability and equal concentrations of lutein and zeaxanthin (Alisa Perry and Johnson, 2009).

From the more than 750 carotenoids in nature, there are only about 40 present in the typical human diet, of which only 20 are found in blood, and from all of them only two accumulate specifically in the retina (Widomska and Subczynski, 2014) and just five in the brain (Johnson et al., 2013; Vishwanathan et al., 2014b). There seems to be a bioselection process of carotenoids.

The absorption of carotenoid like other lipophilic substances is not an easy process. It occurs through the classical pathway of lipid-soluble compounds through the lymph and lipoprotein distribution. A few features of carotenoid absorption process are: (1) mucosal uptake occurs by passive diffusion at pharmacological doses but at dietary doses the preferential route is mediated by cholesterol transporters (Borel, 2012), (2) HDL play an important role in the transport to the retina (Connor et al., 2007) (3) several proteins are involved in carotenoid metabolism in humans, namely carotene oxygenases β,β-carotene-15,15-monooxygenase (BCMO1) and β,β-carotene-9,10-oxygenase (BCDO2), which are involved in carotenoid cleavage; scavenger receptor class B type I (SR-BI), cluster determinant 36 (CD36), and Niemann Pick C1-like 1 (NPC1L1), which are involved in carotenoid uptake by cells; and glutathione S-transferase Pi 1 (GSTP1) and human retinal lutein-binding protein (HR-LBP), which are involved in the transport of xanthophylls in the retina (Borel, 2012). The different nucleotide polymorphisms exhibited by those enzymes condition interindividual differences on the carotenoid metabolism and explain the variability of carotenoid concentration in blood and tissues.

2 What is the function of carotenoids in the eye?

Carotenoids accumulate in the macula. The macula is a yellow spot of about 5 millimetres diameter near the centre of the retina. In its centre is the fovea, a small pit that contains the largest concentration of cone cells in the eye which is responsible for central, high resolution vision. When you look directly at something, the centre part of the image falls on the fovea.

The macular pigment (MP) is composed principally of three isomeric carotenoids, lutein, zeaxanthin, and meso-zeaxanthin. They represent roughly 36, 18, and 18% of the total carotenoid content of the retina. Meso-zeaxanthin, an stereoisomer of zeaxanthin, is not present in the diet or in the blood and it is supposed to be produced from lutein in the retina. Those compounds are not homogenously distributed within the macula: lutein/zeaxanthin ratio reaches a minimum in the central macula where meso-zeaxanthin reaches its highest levels which is approximately 50% of the total zeaxanthin present (Landrum and Bone, 2001).

MPOD has been related to a number of visual performance parameters. Namely, MP acts as a natural blue light filter that protects the eye from oxidative damage (Snodderly, 1995). It is also capable of enhancing contrast by adding luminance contrast information to an edge (Liu et al., 2015; Renzi and Hammond, 2010a). It has been related to visual performance and temporal vision (Renzi and Hammond, 2010b) and it is strongly related to improvements in glare disability and photo stress recovery (Stringham and Hammond, 2007).

MPOD can be measured non-invasively by using heterochromatic flicker photometry which is the most widely used MPOD measurement to date and has been validated in elderly subjects. By using this technique, it has been shown that serum lutein response and MPOD response were linearly correlated with lutein doses in healthy subjects (Bone and Landrum, 2010).

Age-related macular degeneration (AMD) is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Societies and it is a multifactorial and complex disease. Early AMD is characterized by a deterioration of the retina that is associated with extracellular deposits forming yellow spots (drusen) and or irregular focal hypopigmentation or hyperpigmentation. The aging retina gradually accumulates fluorescent phototoxic chromophores, generally known as lipofuscin, which leads to apoptosis of retinal pigment epithelial (RPE) cells and the formation of drusen. These changes in turn lead to RPE cellular dysfunction and eventually result in the loss of central vision (Gehrs et al., 2006).

Some epidemiological studies suggest that higher consumption of lutein and zeaxanthin is associated with lower risk of AMD (Whitehead et al., 2006). A recent meta-analysis including 8 randomized clinical trials involving 1176 AMD patients concluded that lutein and zeaxanthin supplementation was a safe strategy to improve visual performance of AMD patients (Liu et al., 2015). In fact, the study by Ma et al. (2012) showed that electroretinogram responses increased after lutein supplementation alone or lutein + zeaxanthin supplementation for up to 6 or 12 months in early AMD patients.

Two recent papers have adressed the question why only human and primates acumulate lutein in the retina (Li et al., 2014; Widomska and Subczynski, 2014). The first one discovered that the enzyme BCO2, also known as BCDO2, the only known mammalian xanthophyll cleavage enzyme, is expressed in both mouse and primate retinas, but that the primate enzyme is not able to cleavage xanthophyll carotenoids (Li et al., 2014). The second paper is a review that indicates the specific properties of macular xanthophylls that could help explain their selective accumulation in the primate retina, namely: (1) high membrane solubility than other carotenoids, (2) transmembrane orientation that enhances their stability in retina membranes, and maximizes their protective action in the eye, (3) location in the most vulnerable regions of photoreceptor outer segment membranes, which play a significant role in enhancing protection of retina against oxidative damage, and (4) high chemical stability (Widomska and Subczynski, 2014).

3 Lutein and zeaxanthin: the function in the brain

The study by Vishwanathan et al. in non-human primates was the first to report that lutein and zeaxanthin in the macular region of the retina are related to brain lutein and zeaxanthin levels. This association was found in the occipital cortex, the primary visual processing area of the brain, in the cerebellum, which is crucial for motor control and some types of learning, and in the pons, a region not associated with visual processing or cognitive function. A significant relationship was found after bivariate analysis that was maintained after adjustment by sex and age, and by sex, age and n-3 fatty acid status. This association also existed in the frontal frontal cortex, which is responsible for several aspects of higher cognitive function, although was only significant after adjusment of the three factors (Vishwanathan et al., 2013).

There have been a number of articles linking lutein in neural tissues to better cognitive performance. Johnson et al. performed a small clinical trial in 60–80 year-old women that were randomized to receive DHA (800 mg/day), lutein (12 mg/day), or a combination of DHA and lutein. Each treatment alone or in combination improved performance in a Verbal fluency test and only the combination of lutein and DHA improved performance in other tests such as Word list, Shopping list and MIR apartment tests sugesting a potential synergistic effect of both nutrients (Johnson et al., 2008).

Of note is the Georgia Centenarian Study, a population-based multidisciplinary study conducted in 44 counties in northern Georgia (USA) from 2001 to 2009. It was designed to identify and isolate longevity genes, neuropathology, functional capacity, and adaptational characteristics of centenarians. It represents a unique opportunity to link cognitive findings with compositional analyses of the brain in humans. We can realize that while β-carotene was the major carotenoid in serum, lutein and zeaxanthin account for almost 50% of carotenoids in the brain. If serum represents the actual intake, this means that there is a preferential uptake of lutein and zeaxanthin in the brain as it happens in the retina (Johnson et al., 2013). Moreover, total carotenoids content was inversely associated to a global cognitive deterioration scale (Johnson et al., 2013) and particularly lutein and/or zeaxanthin levels in several areas of the brain, such as temporal, occipital, and frontal cortices as well as cerebellum were correlated to different cognition measures such as retention, global cognition or intelligence quotient (Johnson, 2012).

Other studies have correlated MOPD with cognitive outcomes in aging. Fenney et al. studied the relationship between MP and cognitive function in 4453 adults aged 50 years as part of the Irish Longitudinal Study on Aging. Lower MPOD was associated with poorer performance on the mini-mental state examination and on the Montreal cognitive assessment. Individuals with lower MPOD also had poorer prospective memory, took longer time to complete a trail-making task, and had slower and more variable reaction times on a choice reaction time task (Feeney et al., 2013). MPOD levels were significantly associated with better global cognition, verbal learning and fluency, recall, processing speed and perceptual speed in older adults from the age-related maculopathy ancillary study of the Health Aging and Body Composition Study (Vishwanathan et al., 2014a). Finally, in subjects with mild cognitive impairment, MPOD was related to cognition including the composite score on the mini-mental state examination, visual-spatial and constructional abilities, language ability, attention, and the total scale on the repeatable battery for the assessment of neuropsychological status (Renzi et al., 2014).

4 The role of lutein on infant nutrition

According to Horton et al. and in contrast to the carotenoid composition of plasma in other studies, where β-carotene was the most abundant, lutein + zeaxanthin and beta-cryptoxanthin were the major carotenoid in maternal plasma during gestation. The concentration of total carotenoid in mother plasma tended to increase during gestation, and after birth, carotenoid in cord plasma decreased sharply (Horton et al., 2013).

Although the fovea started to develop in the utero, it begins postnatal life at a relatively immature stage and develops more rapidly after birth. In fact, the future fovea is identifiable at 22 weeks of gestation and 1 week after birth, there is only a shallow foveal depression (Hendrickson and Yuodelis, 1984). Both pigments lutein and zeaxhanthin were detected in prenatal eyes (approximately at 20 weeks of gestation) but did not form a visible yellow spot. Generally they were not easily discernible until about 6 months after birth (Bone et al., 1988) but the human fovea reaches maturity between 15 and 45 months of age (Hendrickson and Yuodelis, 1984). However, cone density probably increases further with age until 13 years of age (Hendrickson, 1992). Moreover, lutein and zeaxanthin are transfer from vitreous to retina and lens during fetal development (Panova et al., 2007). The lutein/zeaxanthin ratio change with age being lutein the predominant in infants and zeaxanthin the predominant in adults (Bone et al., 1988).

Carotenoids are present in human milk with higher concentration in colostrum than in transitional and mature milk. The most important ones are β-carotene and lycopene. Lutein concentrations in human milk range from approximately 3–237 mg/L (Bettler et al., 2010; Canfield et al., 2003; Jewell et al., 2004; Tacken et al., 2009). Taken together lutein and zeaxanthin account for 28% of total (Song et al., 2012). In colostrum the carotenoid pattern resembled those of plasma and the low-density lipoprotein fraction. In mature milk it was similar to the pattern found in the high density lipoprotein fraction. Based on these observations a selective mechanism might be responsible for the transfer of these components in milk involving different lipoprotein fractions at specific times of lactation (Schweigert et al., 2004).

At birth, infants might have around 50 μg/L of lutein and zeaxanthin in plasma. After one month of formula feeding the level decreased while in breast-fed infant increased (Bettler et al., 2010).

With regards to the level of carotenoids in the brain, there was an interesting study by Vishwanathan et al. (2014b) that provided the first data on the distribution of carotenoids in the infant brain and compare concentrations in preterm and term infant. The study was done on pre-existing voluntarily donated samples that were obtained from a federally-funded brain tissue bank. Brain tissue samples were from healthy infants who died during the first year of life from SIDS (sudden infant death symdrome) or other conditions. There were 30 subjects, 22 term and 8 preterms. The results showed that the major carotenoids detected in the infant brain were lutein (0–181.7 pmol/g), zeaxanthin (0–33.94 pmol/g), cryptoxanthin (0–35.29 pmol/g), and β-carotene (0–88.19 pmol/g). Lutein was the predominant carotenoid in all the brain areas evaluated being the higher content in auditory and occipital cortex. Infants born preterm had significantly lower concentrations of lutein and zeaxanthin compared with term infants in most of the brain regions analyzed. If on average the total content of carotenoids in term infants was between 50–60 pmol/g, in preterm infant was about 20 pmol/g, sugesting a potential deficiency in infant born before term.

Moreover, if the average of the 5 regions is considered, lutein account for more than 59% of total carotenoids in the brain, followed by β-carotene (16%), zeaxanthin (13%), β-criptoxanthin (7%), and lycopene (5%). If this distribution is compared to the dietary intake pattern, which predominantly was enriched in β-carotene (43%) and lycopene (23%), according to the National Health and Nutrition Examination Survey (NHANES, 1988–1994), it seems that there is a preferential accumulation of xanthophylls on the brain likely due to their chemical properties mentioned above (Widomska and Subczynski, 2014). If the percentual composition of carotenoids in infant brains is compared to that found in the Georgia centenarian study, the percentage of lutein decreases with age (from 59 to 34%).

5 Is there a translation to functionality?

There have been a number of clinical studies testing lutein supplementation in infants. One of them dealed with serum concentration of lutein supplemented infants in comparison to breast fed infants (Bettler et al., 2010). Another one was focus on the supplementation of the mother throught lactation and how it affected breast milk levels and maternal and infant plasma levels (Sherry et al., 2014). Capeding et al. addressed safety, tolerance and growth (Capeding et al., 2010). There have been three papers suggesting a potential influence of lutein supplementation on the prevention on the retinopathy of prematurity (Dani et al., 2012; Manzoni et al., 2013; Romagnoli et al., 2011). The first one did not showed any effect of lutein/zeaxanthin supplementation. The second one found lower incidence of necrotizong enterocholitis, bronchopulmonary dysplasia and retinopathy of prematurity (ROP) in the carotenoid supplemented group although the differences did not reach statistical significance. Noteworthy, the progression rate from early ROP stages to threshold ROP was decreased by 50%. Romagnoli et al. did not find conclusive results but pointed out that supplementation with antioxidant substances might have beneficial effects noticeable only on larger samples of high risk neonates or at very high dosages.

The study by Henriksen et al. showed that infant serum zeaxanthin levels but not lutein correlated with MPOD and that mother serum zeaxanthin levels correlated with infant MPOD (Henriksen et al., 2013). A randomized controlled multicenter study in preterm infants fed diets with and without added lutein, lycopene and beta-carotene showed that supplemented infants had lower plasma C-reactive protein pointing out that carotenoid supplementation may decrease inflammation. Moreover, the supplemented group showed greater rod photoreceptor sensitivity and plasma lutein levels correlated with full field electroretinogram-saturated response amplitude in rod photoreceptors suggesting protective effects of lutein on the health and maturation of preterm retina (Rubin et al., 2011). There was another study in which infants were supplemented at birth with only two doses of lutein (0.28 mg) within 6 h after birth and at 36 h of life and the generation of free radical-induced damage at birth was reduced by lutein (Perrone et al., 2014).

Despite those studies showing a beneficial effect on different outcomes after birth, so far there have not been any randomized clinical trials testing the effect of lutein supplementation on cognitive development in infants. There was only one showing that an intervention with lutein and zeaxanthin increased temporal processing speed in young healthy subjects (18–32 years) showing that carotenoid supplementation not only prevents diseases but it also optimizes function throughout life (Bovier and Hammond, 2014). Nonetheless, the potential role of lutein on the functionality of the brain during this stage of life comes from indirect evidences. For instance, lutein has also been shown to enhance gap junctional communication (Stahl and Sies, 2001), which may be important for the development of the brain and visual proceesing (Johnson, 2014).

Recently, our group has shown that lutein was able to stimulate the differentiation of human stem cells into neural cells in vitro simulating the process of brain development and maturation (Kuchan et al., 2013). In particular, treatment of human stem cells with lutein (1 μM) alone for 6–9 days resulted in increased SOX1 and PAX6 expression compared with vehicle (3.8- and 3.1-fold, respectively). PAX6 and SOX1 are neuroepithelial transcription factors and well-accepted protein markers for neural progenitor cells. PAX6 (paired-box protein) is a transcription factor that acts at the molecular level in the signaling and formation of the central nervous system (Manuel et al., 2015). SOX1 (sex-determining region Y-box 1) is another transcription factor involved in the early central nervous system development and maintenance of neural progenitor cells identity (Pevny et al., 1998).

6 Conclusions and final remarks

It seems like the research around the influence of xanthophylls, particularly lutein, follows a paralelism with the research supporting the foundation for the addition of docosahexaenoic acid (DHA) to infant formulas. Firstly, in the eighties it was extensively described that DHA was present in human milk (Harris et al., 1984). Concomitantly, the importance of this fatty acid for the retina and the brain was also shown (Connor and Neuringer, 1988; Connor et al., 1990). As it happens with lutein, it was reported that plasma DHA levels of formula fed infants were lower than breast-fed infants (Innis et al., 1997) and thereafter in postmortem analyses, that formula fed infants had lowers level of DHA in the brain (Farquharson et al., 1995). Currently, there are many evidences of the role of DHA on the retina and on the brain at molecular and signaling levels (Bazan et al., 2011). Despite this, there are two differences: on the one hand, there is always some DHA in tissues however it was reported that a few infants had no detectable levels of carotenoids (Vishwanathan et al., 2014b). On the other hand, DHA can be synthetized from alpha-linolenic acid while lutein can not be synthetized and must be taken with the diet.

All these scientific evidences and reasoning point out a potential conditionally essential role of lutein in infant nutrition and may support its inclusion on infant formula composition.

References

  • Alisa Perry HR, Johnson EJ. 2009. Xanthophyll (lutein, zeaxanthin) content in fruits, vegetables and corn and egg products. J. Food Compost. Anal. 22: 9–15. [CrossRef] [PubMed] [Google Scholar]
  • Bazan NG, Molina MF, Gordon WC. 2011. Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuroinflammation, macular degeneration, Alzheimer’s, and other neurodegenerative diseases. Annu. Rev. Nutr. 31: 321–351. [CrossRef] [PubMed] [Google Scholar]
  • Bettler J, Zimmer JP, Neuringer M, DeRusso PA. 2010. Serum lutein concentrations in healthy term infants fed human milk or infant formula with lutein. Eur. J. Nutr. 49: 45–51. [CrossRef] [PubMed] [Google Scholar]
  • Bone RA, Landrum JT, Fernandez L, Tarsis SL. 1988. Analysis of the macular pigment by HPLC: retinal distribution and age study. Invest. Ophthalmol. Vis. Sci. 29: 843–849. [PubMed] [Google Scholar]
  • Bone RA, Landrum JT. 2010. Dose-dependent response of serum lutein and macular pigment optical density to supplementation with lutein esters. Arch. Biochem. Biophys. 504: 50–55. [CrossRef] [PubMed] [Google Scholar]
  • Borel P. 2012. Genetic variations involved in interindividual variability in carotenoid status. Mol. Nutr. Food. Res. 56: 228–240. [CrossRef] [PubMed] [Google Scholar]
  • Bovier ER, Hammond BR. 2014. A randomized placebo-controlled study on the effects of lutein and zeaxanthin on visual processing speed in young healthy subjects. Arch. Biochem. Biophys. 572: 54–57. [CrossRef] [PubMed] [Google Scholar]
  • Canfield LM, Clandinin MT, Davies DP, et al. 2003. Multinational study of major breast milk carotenoids of healthy mothers. Eur. J. Nutr. 42: 133–141. [PubMed] [Google Scholar]
  • Capeding R, Gepanayao CP, Calimon N, et al. 2010. Lutein-fortified infant formula fed to healthy term infants: evaluation of growth effects and safety. Nutr. J. 9: 22. [CrossRef] [PubMed] [Google Scholar]
  • Connor WE, Neuringer M. 1988. The effects of n-3 fatty acid deficiency and repletion upon the fatty acid composition and function of the brain and retina. Prog. Clin. Biol. Res. 282: 275–294. [PubMed] [Google Scholar]
  • Connor WE, Neuringer M, Lin DS. 1990. Dietary effects on brain fatty acid composition: the reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys. J. Lipid Res. 31: 237–247. [PubMed] [Google Scholar]
  • Connor WE, Duell PB, Kean R, Wang Y. 2007. The prime role of HDL to transport lutein into the retina: evidence from HDL-deficient WHAM chicks having a mutant ABCA1 transporter. Invest. Ophthalmol. Vis. Sci. 48: 4226–4231. [CrossRef] [PubMed] [Google Scholar]
  • Dachtler M, Glaser T, Kohler K, Albert K. 2001. Combined HPLC-MS and HPLC-NMR on-line coupling for the separation and determination of lutein and zeaxanthin stereoisomers in spinach and in retina. Anal. Chem. 73: 667–674. [CrossRef] [PubMed] [Google Scholar]
  • Dani C, Lori I, Favelli F, et al. 2012. Lutein and zeaxanthin supplementation in preterm infants to prevent retinopathy of prematurity: a randomized controlled study. J. Matern. Fetal Neonatal Med. 25: 523–527. [CrossRef] [PubMed] [Google Scholar]
  • Farquharson J, Jamieson EC, Abbasi KA, Patrick WJ, Logan RW, Cockburn F. 1995. Effect of diet on the fatty acid composition of the major phospholipids of infant cerebral cortex. Arch. Dis. Child. 72: 198–203. [CrossRef] [PubMed] [Google Scholar]
  • Feeney J, Finucane C, Savva GM, et al. 2013. Low macular pigment optical density is associated with lower cognitive performance in a large, population-based sample of older adults. Neurobiol. Aging 34: 2449–2456. [CrossRef] [PubMed] [Google Scholar]
  • Gehrs KM, Anderson DH, Johnson LV, Hageman GS. 2006. Age-related macular degeneration-emerging pathogenetic and therapeutic concepts. Ann. Med. 38: 450–471. [CrossRef] [PubMed] [Google Scholar]
  • Harris WS, Connor WE, Lindsey S. 1984. Will dietary omega-3 fatty acids change the composition of human milk? Am. J. Clin. Nutr. 40: 780–785. [PubMed] [Google Scholar]
  • Hendrickson A. 1992. A morphological comparison of foveal development in man and monkey. Eye (Lond.) 6: 136–144. [CrossRef] [Google Scholar]
  • Hendrickson AE, Yuodelis C. 1984. The morphological development of the human fovea. Ophthalmology 91: 603–612. [CrossRef] [PubMed] [Google Scholar]
  • Henriksen BS, Chan G, Hoffman RO, et al. 2013. Interrelationships between maternal carotenoid status and newborn infant macular pigment optical density and carotenoid status. Invest. Ophthalmol. Vis. Sci. 54: 5568–5578. [CrossRef] [PubMed] [Google Scholar]
  • Horton DK, Adetona O, Aguilar-Villalobos M, et al. 2013. Changes in the concentrations of biochemical indicators of diet and nutritional status of pregnant women across pregnancy trimesters in Trujillo, Peru, 2004-2005. Nutr. J. 12: 80. [CrossRef] [PubMed] [Google Scholar]
  • Humphries JM, Khachik F. 2003. Distribution of lutein, zeaxanthin, and related geometrical isomers in fruit, vegetables, wheat, and pasta products. J. Agric. Food. Chem. 51: 1322–1327. [CrossRef] [PubMed] [Google Scholar]
  • Innis SM, Akrabawi SS, Diersen-Schade DA, Dobson MV, Guy DG. 1997. Visual acuity and blood lipids in term infants fed human milk or formulae. Lipids 32: 63–72. [CrossRef] [PubMed] [Google Scholar]
  • Jewell VC, Mayes CB, Tubman TR, Northrop-Clewes CA, Thurnham DI. 2004. A comparison of lutein and zeaxanthin concentrations in formula and human milk samples from Northern Ireland mothers. Eur. J. Clin. Nutr. 58: 90–97. [CrossRef] [PubMed] [Google Scholar]
  • Johnson EJ. 2012. A possible role for lutein and zeaxanthin in cognitive function in the elderly. Am. J. Clin. Nutr. 96: 1161S–1165S. [CrossRef] [PubMed] [Google Scholar]
  • Johnson EJ. 2014. Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan. Nutr. Rev. 72: 605–612. [CrossRef] [PubMed] [Google Scholar]
  • Johnson EJ, McDonald K, Caldarella SM, Chung HY, Troen AM, Snodderly DM. 2008. Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutr. Neurosci. 11: 75–83. [CrossRef] [PubMed] [Google Scholar]
  • Johnson EJ, Vishwanathan R, Johnson MA, et al. 2013. Relationship between Serum and Brain Carotenoids, alpha-Tocopherol, and Retinol Concentrations and Cognitive Performance in the Oldest Old from the Georgia Centenarian Study. J. Aging Res. 2013: 951786. [CrossRef] [PubMed] [Google Scholar]
  • Krinsky NI, Johnson EJ. 2005. Carotenoid actions and their relation to health and disease. Mol. Aspects Med. 26: 459–516. [CrossRef] [PubMed] [Google Scholar]
  • Kuchan M, Wang F, Geng Y, Feng B, Lai C. 2013. Lutein Stimulates the Differentiation of Human Stem Cells to Neural Progenitor Cells In Vitro. Presented at Advances and Controversies in Clinical Nutrition, Washington, DC. Abstract No. 23. [Google Scholar]
  • Landrum JT, Bone RA. 2001. Lutein, zeaxanthin, and the macular pigment. Arch. Biochem. Biophys. 385: 28–40. [CrossRef] [PubMed] [Google Scholar]
  • Li B, Vachali PP, Gorusupudi A, et al. 2014. Inactivity of human beta,beta-carotene-9′,10′-dioxygenase (BCO2) underlies retinal accumulation of the human macular carotenoid pigment. Proc. Natl. Acad. Sci. USA 111: 10173–10178. [CrossRef] [Google Scholar]
  • Liu R, Wang T, Zhang B, Qin L, Wu C, Li Q, Ma L. 2015. Lutein and zeaxanthin supplementation and association with visual function in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 56: 252–258. [CrossRef] [PubMed] [Google Scholar]
  • Ma L, Dou HL, Huang YM, et al. 2012. Improvement of retinal function in early age-related macular degeneration after lutein and zeaxanthin supplementation: a randomized, double-masked, placebo-controlled trial. Am. J. Ophthalmol. 154: 625–634 e1. [CrossRef] [PubMed] [Google Scholar]
  • Manuel MN, Mi D, Mason JO, Price DJ. 2015. Regulation of cerebral cortical neurogenesis by the Pax6 transcription factor. Front. Cell. Neurosci. 9: 70. [PubMed] [Google Scholar]
  • Manzoni P, Guardione R, Bonetti P, et al. 2013. Lutein and zeaxanthin supplementation in preterm very low-birth-weight neonates in neonatal intensive care units: a multicenter randomized controlled trial. Am. J. Perinatol. 30: 25–32. [PubMed] [Google Scholar]
  • Panova IG, Tatikolov AS, Sukhikh GT. 2007. Correlation between the content of albumin and carotenoids in human vitreous body during prenatal development. Bull. Exp. Biol. Med. 144: 681–683. [CrossRef] [PubMed] [Google Scholar]
  • Perrone S, Tei M, Longini M, et al. 2014. Lipid and protein oxidation in newborn infants after lutein administration. Oxid. Med. Cell. Longev. 2014: 781454. [CrossRef] [PubMed] [Google Scholar]
  • Pevny LH, Sockanathan S, Placzek M, Lovell-Badge R. 1998. A role for SOX1 in neural determination. Development 125: 1967–1978. [PubMed] [Google Scholar]
  • Renzi LM, Hammond BR. 2010a. The effect of macular pigment on heterochromatic luminance contrast. Exp. Eye Res. 91: 896–900. [CrossRef] [PubMed] [Google Scholar]
  • Renzi LM, Hammond BR, Jr. 2010b. The relation between the macular carotenoids, lutein and zeaxanthin, and temporal vision. Ophthalmic Physiol. Opt. 30: 351–357. [CrossRef] [PubMed] [Google Scholar]
  • Renzi LM, Dengler MJ, Puente A, Miller LS, Hammond BR, Jr. 2014. Relationships between macular pigment optical density and cognitive function in unimpaired and mildly cognitively impaired older adults. Neurobiol. Aging 35: 1695–1699. [CrossRef] [PubMed] [Google Scholar]
  • Romagnoli C, Giannantonio C, Cota F, et al. 2011. A prospective, randomized, double blind study comparing lutein to placebo for reducing occurrence and severity of retinopathy of prematurity. J. Matern. Fetal Neonatal Med. 24: 147–150. [CrossRef] [PubMed] [Google Scholar]
  • Rubin LP, Chan GM, Barrett-Reis BM, et al. 2011. Effect of carotenoid supplementation on plasma carotenoids, inflammation and visual development in preterm infants. J. Perinatol. 32: 418–424. [CrossRef] [PubMed] [Google Scholar]
  • Schweigert FJ, Bathe K, Chen F, Buscher U, Dudenhausen JW. 2004. Effect of the stage of lactation in humans on carotenoid levels in milk, blood plasma and plasma lipoprotein fractions. Eur. J. Nutr. 43: 39–44. [CrossRef] [PubMed] [Google Scholar]
  • Sherry CL, Oliver JS, Renzi LM, Marriage BJ. 2014. Lutein supplementation increases breast milk and plasma lutein concentrations in lactating women and infant plasma concentrations but does not affect other carotenoids. J. Nutr. 144: 1256–1263. [CrossRef] [PubMed] [Google Scholar]
  • Snodderly DM. 1995. Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. Am. J. Clin. Nutr. 62: 1448S–1461S. [PubMed] [Google Scholar]
  • Song BJ, Jouni ZE, Ferruzzi MG. 2012. Assessment of phytochemical content in human milk during different stages of lactation. Nutrition 29: 195–202. [CrossRef] [PubMed] [Google Scholar]
  • Stahl W, Sies H. 2001. Effects of carotenoids and retinoids on gap junctional communication. Biofactors 15: 95–98. [CrossRef] [PubMed] [Google Scholar]
  • Stringham JM, Hammond BR, Jr. 2007. The glare hypothesis of macular pigment function. Optom. Vis. Sci. 84: 859–864. [CrossRef] [PubMed] [Google Scholar]
  • Tacken KJ, Vogelsang A, van Lingen RA, Slootstra J, Dikkeschei BD, van Zoeren-Grobben D. 2009. Loss of triglycerides and carotenoids in human milk after processing. Arch. Dis. Child Fetal Neonatal Ed. 94: F447–F450. [CrossRef] [PubMed] [Google Scholar]
  • Vishwanathan R, Neuringer M, Snodderly DM, Schalch W, Johnson EJ. 2013. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates. Nutr. Neurosci. 16: 21–29. [CrossRef] [PubMed] [Google Scholar]
  • Vishwanathan R, Iannaccone A, Scott TM, et al. 2014a. Macular pigment optical density is related to cognitive function in older people. Age Ageing 43: 271–275. [CrossRef] [PubMed] [Google Scholar]
  • Vishwanathan R, Kuchan MJ, Sen S, Johnson EJ. 2014b. Lutein and preterm infants with decreased concentrations of brain carotenoids. J. Pediatr. Gastroenterol. Nutr. 59: 659–665. [CrossRef] [PubMed] [Google Scholar]
  • Whitehead AJ, Mares JA, Danis RP. 2006. Macular pigment: a review of current knowledge. Arch. Ophthalmol. 124: 1038–1045. [CrossRef] [PubMed] [Google Scholar]
  • Widomska J, Subczynski WK. 2014. Why has Nature Chosen Lutein and Zeaxanthin to Protect the Retina? J. Clin. Exp. Ophthalmol. 5: 326. [CrossRef] [PubMed] [Google Scholar]

Cite this article as: Maria Ramirez. Why lutein is important for the eye and the brain. OCL 2016, 23(1) D107.

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