Early Administration of the Lutein/Zeaxanthin in Premature Newborns
Summary
Premature birth is the most common cause of mortality, morbidity and disability. Premature infants have a higher risk of developing damage in the eyes (retinopathy of prematurity ROP), in the central nervous system (intraventricular hemorrhage IVH), in the lungs (bronchial pulmonary dysplasia BPD), in the gut (NEC) and infections. Oxidative stress has been implicated in various capacities, in the etiology of these conditions. Lutein and Zeaxanthin are powerful anti-oxidants and commonly assimilated with different foods. Lutein and Zeaxanthin are present at level of umbilical cord, in the breast milk (particularly in colostrum) and pass the placental barrier. Concerning supplementations, the lutein presents, for its specific characteristics, a high bioavailability after oral administration. In the last few years, there have been more and more studies which have shown that lutein could constitute a valid and important preventive and protective factor against certain diseases related to oxidative stress. The preparations of lutein and zeaxanthin have never pointed out in the human being (included in the term newborn) adverse or toxic effects. This spontaneous / non-commercial pilot study involves the administration of a dietary supplement containing lutein / zeaxanthin, because the healthcare structures need to identify a natural antioxidant product that can reduce the incidence of serious diseases related to oxidative stress in the perinatal period. This study aims to evaluate if the administration of lutein in watery solution will reduce the rate of free radicals in preterm infants.
Timeline
- Start
- 2018-10-11
- Primary completion
- 2019-10-11
- Completion
- 2019-10-11
Publications
- Background Lorenzoni F, Giampietri M, Ferri G, Lunardi S, Madrigali V, Battini L, Boldrini A, Ghirri P. Lutein administration to pregnant women with gestational diabetes mellitus is associated to a decrease of oxidative stress in newborns. Gynecol Endocrinol. 2013 Oct;29(10):901-3. doi: 10.3109/09513590.2013.808329. Epub 2013 Jun 28.
- Background Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.
- Background Gerardi G, Usberti M, Martini G, Albertini A, Sugherini L, Pompella A, Di LD. Plasma total antioxidant capacity in hemodialyzed patients and its relationships to other biomarkers of oxidative stress and lipid peroxidation. Clin Chem Lab Med. 2002 Feb;40(2):104-10. doi: 10.1515/CCLM.2002.019.
- Background Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay. Anal Biochem. 1996 Jul 15;239(1):70-6. doi: 10.1006/abio.1996.0292.
- Background Cohen, J. (1969). Statistical power analysis for the behavioural sciences. New York: Academic Press
- Results Shao A, Hathcock JN. Risk assessment for the carotenoids lutein and lycopene. Regul Toxicol Pharmacol. 2006 Aug;45(3):289-98. doi: 10.1016/j.yrtph.2006.05.007. Epub 2006 Jun 30.
- Results Khachik F, London E, de Moura FF, Johnson M, Steidl S, Detolla L, Shipley S, Sanchez R, Chen XQ, Flaws J, Lutty G, McLeod S, Fowler B. Chronic ingestion of (3R,3'R,6'R)-lutein and (3R,3'R)-zeaxanthin in the female rhesus macaque. Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5476-86. doi: 10.1167/iovs.06-0194.
- Results Khachik F, de Moura FF, Chew EY, Douglass LW, Ferris FL 3rd, Kim J, Thompson DJ. The effect of lutein and zeaxanthin supplementation on metabolites of these carotenoids in the serum of persons aged 60 or older. Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5234-42. doi: 10.1167/iovs.06-0504.
- Results Trevithick-Sutton CC, Foote CS, Collins M, Trevithick JR. The retinal carotenoids zeaxanthin and lutein scavenge superoxide and hydroxyl radicals: a chemiluminescence and ESR study. Mol Vis. 2006 Sep 30;12:1127-35.
- Results Thurmann PA, Schalch W, Aebischer JC, Tenter U, Cohn W. Plasma kinetics of lutein, zeaxanthin, and 3-dehydro-lutein after multiple oral doses of a lutein supplement. Am J Clin Nutr. 2005 Jul;82(1):88-97. doi: 10.1093/ajcn.82.1.88.
- Results Rajendran V, Pu YS, Chen BH. An improved HPLC method for determination of carotenoids in human serum. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Sep 25;824(1-2):99-106. doi: 10.1016/j.jchromb.2005.07.004.
- Results During A, Dawson HD, Harrison EH. Carotenoid transport is decreased and expression of the lipid transporters SR-BI, NPC1L1, and ABCA1 is downregulated in Caco-2 cells treated with ezetimibe. J Nutr. 2005 Oct;135(10):2305-12. doi: 10.1093/jn/135.10.2305.
- Results Reboul E, Abou L, Mikail C, Ghiringhelli O, Andre M, Portugal H, Jourdheuil-Rahmani D, Amiot MJ, Lairon D, Borel P. Lutein transport by Caco-2 TC-7 cells occurs partly by a facilitated process involving the scavenger receptor class B type I (SR-BI). Biochem J. 2005 Apr 15;387(Pt 2):455-61. doi: 10.1042/BJ20040554.
- Results Lutein and zeaxanthin. Monograph. Altern Med Rev. 2005 Jun;10(2):128-35. No abstract available.
- Results Krinsky NI, Landrum JT, Bone RA. Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu Rev Nutr. 2003;23:171-201. doi: 10.1146/annurev.nutr.23.011702.073307. Epub 2003 Feb 27.
- Results Tyssandier V, Reboul E, Dumas JF, Bouteloup-Demange C, Armand M, Marcand J, Sallas M, Borel P. Processing of vegetable-borne carotenoids in the human stomach and duodenum. Am J Physiol Gastrointest Liver Physiol. 2003 Jun;284(6):G913-23. doi: 10.1152/ajpgi.00410.2002. Epub 2003 Jan 10.
- Results Cardinault N, Gorrand JM, Tyssandier V, Grolier P, Rock E, Borel P. Short-term supplementation with lutein affects biomarkers of lutein status similarly in young and elderly subjects. Exp Gerontol. 2003 May;38(5):573-82. doi: 10.1016/s0531-5565(03)00039-1.
- Results Krinsky NI. Possible biologic mechanisms for a protective role of xanthophylls. J Nutr. 2002 Mar;132(3):540S-542S. doi: 10.1093/jn/132.3.540S.
- Results Granado F, Olmedilla B, Blanco I. Nutritional and clinical relevance of lutein in human health. Br J Nutr. 2003 Sep;90(3):487-502. doi: 10.1079/bjn2003927.
- Results Giuseppe Buonocore, Monica Tei, Serafina Perrone. Lutein as protective agent against neonatal oxidative stress. Journal of Pediatric and Neonatal Individualized Medicine 2014;3(2):e030244.
- Results Perrone S, Tei M, Longini M, Santacroce A, Turrisi G, Proietti F, Felici C, Picardi A, Bazzini F, Vasarri P, Buonocore G. Lipid and protein oxidation in newborn infants after lutein administration. Oxid Med Cell Longev. 2014;2014:781454. doi: 10.1155/2014/781454. Epub 2014 Apr 30.
- Results Perrone S, Longini M, Marzocchi B, Picardi A, Bellieni CV, Proietti F, Rodriguez A, Turrisi G, Buonocore G. Effects of lutein on oxidative stress in the term newborn: a pilot study. Neonatology. 2010;97(1):36-40. doi: 10.1159/000227291. Epub 2009 Jul 7.
- Results Shoji H, Koletzko B. Oxidative stress and antioxidant protection in the perinatal period. Curr Opin Clin Nutr Metab Care. 2007 May;10(3):324-8. doi: 10.1097/MCO.0b013e3280a94f6d.
- Results Fokkelman K, Haase E, Stevens J, Idikio H, Korbutt G, Bigam D, Cheung PY. Tissue-specific changes in glutathione content of hypoxic newborn pigs reoxygenated with 21% or 100% oxygen. Eur J Pharmacol. 2007 May 7;562(1-2):132-7. doi: 10.1016/j.ejphar.2007.01.057. Epub 2007 Feb 8.
- Results Franco MC, Akamine EH, Reboucas N, Carvalho MH, Tostes RC, Nigro D, Fortes ZB. Long-term effects of intrauterine malnutrition on vascular function in female offspring: implications of oxidative stress. Life Sci. 2007 Jan 30;80(8):709-15. doi: 10.1016/j.lfs.2006.10.028. Epub 2006 Nov 11.
- Results Mercer JS, Erickson-Owens DA, Graves B, Haley MM. Evidence-based practices for the fetal to newborn transition. J Midwifery Womens Health. 2007 May-Jun;52(3):262-72. doi: 10.1016/j.jmwh.2007.01.005.
- Results Kopsell DA, Lefsrud MG, Kopsell DE, Wenzel AJ, Gerweck C, Curran-Celentano J. Spinach cultigen variation for tissue carotenoid concentrations influences human serum carotenoid levels and macular pigment optical density following a 12-week dietary intervention. J Agric Food Chem. 2006 Oct 18;54(21):7998-8005. doi: 10.1021/jf0614802.
- Results Fanaris, Bel BO, Guidettic E et al. Ruolo della Luteina nella prevenzione delle patologie oculari nel neonato. Rivista Italiana di Medicina Pediatrica 2006;numero speciale:51-53
- Results Kvansakul J, Rodriguez-Carmona M, Edgar DF, Barker FM, Kopcke W, Schalch W, Barbur JL. Supplementation with the carotenoids lutein or zeaxanthin improves human visual performance. Ophthalmic Physiol Opt. 2006 Jul;26(4):362-71. doi: 10.1111/j.1475-1313.2006.00387.x.
- Results Rodriguez-Carmona M, Kvansakul J, Harlow JA, Kopcke W, Schalch W, Barbur JL. The effects of supplementation with lutein and/or zeaxanthin on human macular pigment density and colour vision. Ophthalmic Physiol Opt. 2006 Mar;26(2):137-47. doi: 10.1111/j.1475-1313.2006.00386.x.
- Results Provis JM, Penfold PL, Cornish EE, Sandercoe TM, Madigan MC. Anatomy and development of the macula: specialisation and the vulnerability to macular degeneration. Clin Exp Optom. 2005 Sep;88(5):269-81. doi: 10.1111/j.1444-0938.2005.tb06711.x.
- Results Yanoff M and Duker i.S (2005) "Ophthalmology" Edizione italiana ed 2003 ristampa 2005, Antonio Delfino Editore medicina-scienze, volume 1, cap 1.3
- Results Santosa S, Jones PJ. Oxidative stress in ocular disease: does lutein play a protective role? CMAJ. 2005 Oct 11;173(8):861-2. doi: 10.1503/cmaj.1031425. No abstract available.
- Results van Leeuwen R, Boekhoorn S, Vingerling JR, Witteman JC, Klaver CC, Hofman A, de Jong PT. Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA. 2005 Dec 28;294(24):3101-7. doi: 10.1001/jama.294.24.3101.
- Results Schweigert FJ, Bathe K, Chen F, Buscher U, Dudenhausen JW. Effect of the stage of lactation in humans on carotenoid levels in milk, blood plasma and plasma lipoprotein fractions. Eur J Nutr. 2004 Feb;43(1):39-44. doi: 10.1007/s00394-004-0439-5. Epub 2004 Jan 6.
- Results Jewell VC, Mayes CB, Tubman TR, Northrop-Clewes CA, Thurnham DI. A comparison of lutein and zeaxanthin concentrations in formula and human milk samples from Northern Ireland mothers. Eur J Clin Nutr. 2004 Jan;58(1):90-7. doi: 10.1038/sj.ejcn.1601753.
- Results Nolan J, O'Donovan O, Kavanagh H, Stack J, Harrison M, Muldoon A, Mellerio J, Beatty S. Macular pigment and percentage of body fat. Invest Ophthalmol Vis Sci. 2004 Nov;45(11):3940-50. doi: 10.1167/iovs.04-0273.
- Results Richer S, Stiles W, Statkute L, Pulido J, Frankowski J, Rudy D, Pei K, Tsipursky M, Nyland J. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry. 2004 Apr;75(4):216-30. doi: 10.1016/s1529-1839(04)70049-4.
- Results Vento M, Asensi M, Sastre J, Lloret A, Garcia-Sala F, Vina J. Oxidative stress in asphyxiated term infants resuscitated with 100% oxygen. J Pediatr. 2003 Mar;142(3):240-6. doi: 10.1067/mpd.2003.91.
- Results Broekmans WM, Berendschot TT, Klopping-Ketelaars IA, de Vries AJ, Goldbohm RA, Tijburg LB, Kardinaal AF, van Poppel G. Macular pigment density in relation to serum and adipose tissue concentrations of lutein and serum concentrations of zeaxanthin. Am J Clin Nutr. 2002 Sep;76(3):595-603. doi: 10.1093/ajcn/76.3.595.
- Results Gossage CP, Deyhim M, Yamini S, Douglass LW, Moser-Veillon PB. Carotenoid composition of human milk during the first month postpartum and the response to beta-carotene supplementation. Am J Clin Nutr. 2002 Jul;76(1):193-7. doi: 10.1093/ajcn/76.1.193.
- Results Jewell VC, Northrop-Clewes CA, Tubman R, Thurnham DI. Nutritional factors and visual function in premature infants. Proc Nutr Soc. 2001 May;60(2):171-8. doi: 10.1079/pns200089.
- Results Vento M, Asensi M, Sastre J, Garcia-Sala F, Pallardo FV, Vina J. Resuscitation with room air instead of 100% oxygen prevents oxidative stress in moderately asphyxiated term neonates. Pediatrics. 2001 Apr;107(4):642-7. doi: 10.1542/peds.107.4.642.
- Results Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001 Oct;119(10):1417-36. doi: 10.1001/archopht.119.10.1417.
- Results Sommerburg O, Meissner K, Nelle M, Lenhartz H, Leichsenring M. Carotenoid supply in breast-fed and formula-fed neonates. Eur J Pediatr. 2000 Jan-Feb;159(1-2):86-90. doi: 10.1007/pl00013811.
- Results Kiely M, Cogan PF, Kearney PJ, Morrissey PA. Concentrations of tocopherols and carotenoids in maternal and cord blood plasma. Eur J Clin Nutr. 1999 Sep;53(9):711-5. doi: 10.1038/sj.ejcn.1600838.
- Results Yeum KJ, Ferland G, Patry J, Russell RM. Relationship of plasma carotenoids, retinol and tocopherols in mothers and newborn infants. J Am Coll Nutr. 1998 Oct;17(5):442-7. doi: 10.1080/07315724.1998.10718791.
- Results Oostenbrug GS, Mensink RP, Al MD, van Houwelingen AC, Hornstra G. Maternal and neonatal plasma antioxidant levels in normal pregnancy, and the relationship with fatty acid unsaturation. Br J Nutr. 1998 Jul;80(1):67-73. doi: 10.1017/s0007114598001780.
- Results Bonn D. Keeping the stork at bay until the time is right. Lancet. 1998 Feb 21;351(9102):576. doi: 10.1016/S0140-6736(05)78569-X. No abstract available.
- Results Sommerburg O, Keunen JE, Bird AC, van Kuijk FJ. Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes. Br J Ophthalmol. 1998 Aug;82(8):907-10. doi: 10.1136/bjo.82.8.907.
- Results Jackson JG, Eric L, Lien A, Sharon J, White B, Nicholas J, Bruns C, Charles F, Kuhlman A. Major carotenoids in mature human milk: longitudinal and diurnal patterns. The Journal of Nutritional Biochemistry 1998 Jan;9(1):2-7.
- Results Khachik F, Spangler CJ, Smith JC Jr, Canfield LM, Steck A, Pfander H. Identification, quantification, and relative concentrations of carotenoids and their metabolites in human milk and serum. Anal Chem. 1997 May 15;69(10):1873-81. doi: 10.1021/ac961085i.
- Results Landrum JT, Bone RA, Joa H, Kilburn MD, Moore LL, Sprague KE. A one year study of the macular pigment: the effect of 140 days of a lutein supplement. Exp Eye Res. 1997 Jul;65(1):57-62. doi: 10.1006/exer.1997.0309.
- Results Leung AK, Siu TO, Chiu AS, Robson WL, Larsen TE. Serum carotene concentrations in normal infants and children. Clin Pediatr (Phila). 1990 Oct;29(10):575-8; discussion 579-80. doi: 10.1177/000992289002901004.
- Results Nakamura H, Lee Y, Uetani Y, Kitsunezuka Y, Shimabuku R, Matsuo T. Effects of phototherapy on serum unbound bilirubin i icteric newborn infants. Biol Neonate. 1981;39(5-6):295-9. doi: 10.1159/000241451.
- Results Alberti A, Bolognini L, Macciantelli D, et al. The radical cation of N,N-dimethyl-para-phenylendiamine: a possible indicator of oxidative stress in biological samples. Res Chem Intermed 2000; 26:253-267
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Lutein | Other / unclassified | 0.5 mg | Oral |
| Subject | Zeaxanthin | Small molecule | 0.05 mg | Oral |
Indications
No indication recorded.