Central Journal of Human Nutrition & Food Science

Perspective *Corresponding author Jessica Berg, Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74074, and : An Email: Submitted: 28 August 2014 Accepted: 12 October 2014 Overview of Metabolism and Published: 15 October 2014 ISSN: 2333-6706 Eye Health Copyright © 2014 Berg et al. Jessica Berg* and Dingbo Lin OPEN ACCESS Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74074

In 2010, 4.1 million Americans over age 40 were considered visually impaired (i.e. blind or with low vision) [1]. With almost glycemiclow-fiber, indexes low-fat arediets; positively however associated these recommendations with AMD risk, dietarymay be one-third of these visually impaired affected by low vision, or archaic. Recent findings suggest diets that provide foods with high sight in the better eye worse than 20/40 vision despite corrective and supplementation of with omega-3 fatty acids lenses, low vision and vision loss are among the most feared mayfat consumption decrease risk may of AMD significantly [8-10]. increase LUT bioavailability, irreversible diseases among the elderly and can reduce quality of life as well as incur serious economic burdens [1]. Age- Upon ingestion, food is mechanically and enzymatically related eye diseases such as diabetic retinopathy, glaucoma, broken down, are released with help from dietary and age-related (AMD) are the leading causes of visual impairment worldwide and together affect and solubilized into micelles for enterocyte absorption via over 12.4 million Americans aged 40 or older [1]. Vision loss passivelipids, emulsified diffusion or in scavenger the small receptor intestine class and B type incorporated 1(SR-B1)- overtime is largely due to the irreversible loss of retinocytes, and facilitated diffusion. In the enterocyte, carotenoids are packaged subsequent degeneration of the of the eye, leading to AMD into chylomicrons, transported to the liver, repackaged into and other diseases [2]. While treatment is limited, nutritional lipoproteins and transported to extra heptatic tissues through

Considerable research suggests an inverse relationship between carotenoids,interventions polyunsaturated may be beneficial fatty acids, in improving and some eye health. and lipoproteinthe blood [11]. may impair Along with LUT LDL,and ZEA HDL transport has been [12].Although identified as the prevention or delay of progression of AMD and other age- theseacrucial xanthophylls xanthophylls may transporter,accumulate in and hepatic, deficiencies adrenal, adipose in this related degenerative diseases. tissues, as well as others through various transport mechanisms, of greatest interest is the accumulation and macular effect Lutein (LUT) and zeaxanthin (ZEA) are two xanthophyllic of these carotenoids [13]. carotenoids found in dark green and fruits and vegetables associated with retino protective properties. An average U.S. diet LUT and ZEA make up about 80% of the total contains 1-3 mg/day of LUT and ZEA, while ~6 mg/day has been content of the retina, a higher concentrationthan any other associated with lower risks of disease like AMD and [3]. tissue of the human body [13,14]. LUT and ZEA, as well as meso- It is proposed that the retino protective capabilities associated zeaxanthin (meso-ZEA), a LUT metabolite, accumulate as a yellow with these xanthophylls may be due to the unique chemical spot in the macula of the eye, known as the macular pigment. structure and selective retinal accumulation. Hydroxyl groups, This pigment has been suggested to contain antioxidant- large numbers of double bonds, and the polar nature of these like properties, reduce photoreceptor exposure to blue , compounds may contribute to LUT and ZEA’s ability to protect and protect the macula from light –induced oxidative stress against oxidative stress associated with AMD by scavenging free [14,15]. Generally, the ratio of the macular carotenoids varies radicals and transferring energy states [4].Intake of LUT and ZEA in different regions in the eye. Amounts of LUT and ZEA tend to and their selective retinal accumulation may increase macular decrease from the fovea toward the periphery of the eye. In the pigment density which may slow or prevent AMD [5]. LUT fovea for example, less lutein is found compared to zeaxanthin, interests for these reasons. to ZEA is 2:1 [16]. As previously stated, higher intakes of LUT and ZEA are considered recent significant eye health research andin a ZEA1:2ratio; have however been associated in the peripheral with increased retina macular the ratio pigment of LUT eye health is dependent on the digestion, absorption, transport, pigment densities slow or prevent AMD, suggesting an inverse retinalThe uptake,bioavailability and storage and potential of these benefits carotenoids of LUT [6]. and Multiple ZEA on relationshipdensities. Significant between research indicates consumption that and high AMD macular [5]. Although the distribution of the macular pigment may vary, the matrix, processing conditions, and the fat content of the diet [7]. transport governing the status, regulation, and function of these Infactors general, influence carotenoids carotenoid are fat bioavailability soluble compounds including and the follow food carotenoids in the retina remain unclear. lipophilic digestion and absorption pathways. Traditionally, individuals diagnosed with AMD may be instructed to follow The retinal pigment epithelium (RPE) may be a transfer point

Cite this article: Berg J, Lin D (2014) Lutein and Zeaxanthin: An Overview of Metabolism and Eye Health. J Hum Nutr Food Sci 2(4): 1048. Berg et al. (2014) Email: Central of LUT and ZEA from the blood to the neural retina portion of 5. Carpentier S, Knaus M, Suh M. Associations between lutein, zeaxanthin, and age-related macular degeneration: an overview. Crit Rev Food Sci the eye, using specific xanthophyll-binding proteins (XBP) for 6. Nutr.Yonova-Doing 2009; 49: E, 313-326. Hysi PG, Venturini C, Williams KM, Nag A, Beatty S, et ZEAretinal uptake uptake is ambiguous. and macular Glutathione concentration S-transferase [17]. Many (GSTP1), XBPs al. Candidate gene study of macular response to supplemental lutein locatedhave been in identified; the macula however preferentially the exact interacts mechanism with of ZEALUT and meso-ZEA, while more the steroidogenic acute regulatory 7. andCastenmiller zeaxanthin. JJ, Exp West Eye Res. CE. 2013; Bioavailability 115: 172-177. and bioconversion of domain 3 (StARD3) is partly responsible for retinal uptake of LUT [18,19]. Some research suggests that cell lines similar to RPE 8. carotenoids.Chiu CJ, Milton Annu RC, Rev Gensler Nutr. G, 1998; Taylor 18: A. 19-38. Association between dietary are involved in LUT and ZEA uptake and are entirely dependent glycemic index and age-related macular degeneration in nondiabetic on SR-B1 transporters [17]. Different research indicates that participants in the Age-Related Eye Disease Study. Am J Clin Nutr. cleavage of double bonds forming apo-carotenoid metabolites, 9. 2007;Roodenburg 86: 180-188. AJ, Leenen R, van het Hof KH, Weststrate JA, Tijburg LB. whichcarotene may cleavage have important oxygenases metabolic (CCOs) roles mediate that differ site-specific from the Amount of fat in the diet affects bioavailability of lutein esters but not original compound [20]. Mein and associates demonstrated that of alpha-, beta-carotene, and E in humans. Am J Clin xanthophyllic cleavage enzyme carotene-9’10’-monooxygenase, 10. Nutr.Chong 2000; EW, 71: Kreis 1187-1193. AJ, Wong TY, Simpson JA, Guymer RH. Dietary BCO2), a CCO highly expressed in the RPE, cleave LUT and ZEA (CMO2, also known as β,β-Carotene-9’,10’-dioxygenase 2 or related macular degeneration: a systematic review and meta-analysis. at the 9,10 and 9’,10’ double bonds in ferrets [20]. No apo- omega-3 and fish intake in the primary prevention of age- this BCO2 cleavage, however other LUT and ZEA metabolites 11. ArchYonekura Ophthalmol. L, Nagao 2008; A. Intestinal 126: 826-833. absorption of dietary carotenoids. Mol have.carotenoid The metabolites functional purpose in the RPE of these have been metabolites identified remains from 12. NutrWang Food Y, Connor Res. 2007; SL, Wang 51: 107-115. W, Johnson EJ, Connor WE. The selective aforementioned meso-ZEA [21]. retention of lutein, meso-zeaxanthin and zeaxanthin in the retina of elusive but includes: 3’-epilutein, 3-OH-β, ε-caroten-3’-one and Most recently, BCO2 is suggested as the underlying reason 13. chicksKaplan fed LA, a Lau xanthophyll-free JM, Stein EA. Carotenoid diet. Exp Eye composition, Res. 2007; 84:concentrations, 591-598. for human retinal accumulation of LUT and ZEA because of the and relationships in various human organs. Clin Physiol Biochem. enzyme inactivity or loss of enzymatic function [22], likely due to excess amino acid residues, GKAA. It is suggested that because 14. 1990;Handelman 8: 1-10. GJ, Snodderly DM, Adler AJ, Russett MD, Dratz EA. Measurement of carotenoids in human and monkey . Methods carotenoidshuman BCO2 may has a be weaker the grounds binding behindaffinity thefor carotenoids human enzyme’s when 15. Enzymol.Cho E, Hankinson 1992; 213: SE, 220-230. Rosner B, Willett WC, Colditz GA. Prospective losscompared of function. to mouse This BCO2; loss this of enzymatic inability to function capture therefore macular study of lutein/zeaxanthin intake and risk of age-related macular prevents xanthophyllic cleavage and facilitates the unique retinal accumulation of LUT and ZEA in humans [22]. 16. degeneration.Bone RA, Landrum Am J Clin JT, Nutr. Fernandez 2008; 87: L, 1837-1843. Tarsis SL. Analysis of the macular pigment by HPLC: retinal distribution and age study. Invest Although the functions of macular xanthophylls as preventers of AMD are promising, links between LUT and ZEA and diabetic retinopathy and other degenerative eye diseases 17. Ophthalmol Vis Sci. 1988; 29: 843-849. taken up compared with beta-carotene by retinal cells via a SRBI- are less established. Future investigations should consider During A, Doraiswamy S, Harrison EH. Xanthophylls are preferentially the mechanisms of transport and regulation of LUT and ZEA in the retina, the non-xanthophyllic role of human BCO2, as 18. dependent mechanism. J Lipid Res. 2008; 49: 1715-1724. as a lutein-binding protein in the macula of the primate retina. well as identifying the function of these potentially biologically Li B, Vachali P, Frederick JM, Bernstein PS. Identification of StARD3 important apo-carotenoid metabolites. 19. Biochemistry.Bhosale P, Larson 2011; AJ, 50: Frederick 2541-2549. JM, Southwick K, Thulin CD, Bernstein Refe rences PS, et al. glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein in 1. Prevent Blindness America, . Vision problems Identification and characterization of a Pi isoform of in the U. S. : Prevalence of adult vision impairment and age-related 20. the macula of the . J Biol Chem. 2004; 279: 49447-49454. 2012. formation of apo-carotenoids from the xanthophyll carotenoids eye disease in America. Bethesda, MD: National Institutes of Health; lutein,Mein JR, zeaxanthin Dolnikowski and GG, β-cryptoxanthin Ernst H, Russell byRM, ferret Wang carotene-9’,10’- XD. Enzymatic 2. Stringham JM, Hammond BR Jr. Dietary lutein and zeaxanthin: possible

21. monooxygenase.Bernstein PS, Khachik Arch F,Biochem Carvalho Biophys. LS, Muir 2011; GJ, Zhao 506: DY, 109-121. Katz NB, et al. 3. effectsSeddon on JM, visual Ajani function. UA, Sperduto Nutr Rev.RD, 2005;Hiller R,63: Blair 59-64. N, Burton TC, et al. Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA. Identification and quantitation of carotenoids and their metabolites in 22. theLi B, tissues Vachali of PP, the Gorusupudi human eye. A, Exp Shen Eye Z, SharifzadehRes. 2001; 72: H, Besch215-223. BM, Nelson K. Inactivity of human β,β-carotene-9’,10’-dioxygenase (BCO2) 4. 1994;Koushan 272: K, 1413-1420. Rusovici R, Li W, Ferguson LR, Chalam KV. The role of underlies retinal accumulation of the human macular carotenoid

lutein in eye-related disease. Nutrients. 2013; 5: 1823-1839. pigment. Proc Natl Acad Sci U S A. 2014; 111: 10173-10178. Cite this article Berg J, Lin D (2014) Lutein and Zeaxanthin: An Overview of Metabolism and Eye Health. J Hum Nutr Food Sci 2(4): 1048.

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