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Lutein and Zeaxanthin: an Overview of Metabolism and Eye Health Central Journal of Human Nutrition & Food Science Perspective *Corresponding author Jessica Berg, Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74074, Lutein and Zeaxanthin: 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 xanthophylls 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, carotenoids are released with help from dietary and age-related macular degeneration (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, emulsifieddiffusion 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 retina 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 vitaminseye health. and lipoproteinthe blood [11]. may impairAlong withLUT LDL,and ZEAHDL transport has been [12].Although identified as the prevention or delay of progression of AMD and other age- theseacrucial xanthophylls xanthophylls may transporter,accumulate inand hepatic, deficiencies adrenal, adiposein this related degenerative diseases. tissues, as well as others through various transport mechanisms, of greatest interest is the retinal accumulation and macular effect Lutein (LUT) and zeaxanthin (ZEA) are two xanthophyllic of these carotenoids [13]. carotenoids found in dark green and yellow fruits and vegetables associated with retino protective properties. An average U.S. diet LUT and ZEA make up about 80% of the total carotenoid 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 cataracts [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 light, 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. Significantbetween xanthophyllresearch indicates consumption that andhigh AMDmacular [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 fatbioavailability 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-carotene, beta-carotene, and vitamin 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 fatty acid 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 metabolitesfunctional purposein the RPE of thesehave beenmetabolites 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 retinas. Methods carotenoidshuman BCO2 may has abe weaker the grounds binding behindaffinity thefor carotenoidshuman 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 thisof enzymaticinability tofunction capture therefore macular study of
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