Overview of Diet-Gene Interactions and the Example of Xanthophylls

  • Barbara Demmig-Adams
  • William W. AdamsIII
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 698)


This chapter provides an overview of diet-gene interaction and the role of dietary factors in human health and disease. Human master control genes that regulate processes of fundamental importance, such as cell proliferation and the immune response, are introduced and their modulation by nutraceuticals, produced by plants and photosynthetic microbes, is reviewed. Emphasis is placed on antioxidants and polyunsaturated fatty acids as regulators of master control genes. Furthermore, a case study is presented on xanthophylls, a group of carotenoids with multiple health benefits in the protection against eye disease and other chronic diseases, as well as the synergism between xanthophylls and other dietary factors. Lastly, dietary sources of the xanthophylls zeaxanthin and lutein are reviewed and their enhancement via genetic engineering is discussed.


Xanthophyll Cycle Free Radic Biol Master Control Violaxanthin Cycle Chronic Human Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Dalton TD, Shertzer HG, Puga A. Regulation of gene expression by reactive oxygen. Annu Rev Pharmacol Toxicol 1999; 39:67–101.PubMedCrossRefGoogle Scholar
  2. 2.
    Allen RG, Tresini M. Oxidative stress and gene regulation. Free Radic Biol Med 2000; 28:463–499.PubMedCrossRefGoogle Scholar
  3. 3.
    Maher P, Schubert D. Signaling by reactive oxygen species in the nervous system. Cell Mol Life Sci 2000; 57:1287–1305.PubMedCrossRefGoogle Scholar
  4. 4.
    Shackelford RE, Kaufmann WK, Paules RS. Oxidative stress and cell cycle checkpoint function. Free Radic Biol Med 2000; 28:1387–1404.PubMedCrossRefGoogle Scholar
  5. 5.
    Lavrovsky Y, Chatterjee B, Clark RA et al. Role of redox-regulated transcription factors in inflammation, aging and age-related diseases. Exp Gerontol 2000; 35:521–532.PubMedCrossRefGoogle Scholar
  6. 6.
    Janssen-Heiniger YMW, Poynter ME, Baeuerle PA. Recent advances towards understanding redox mechanisms in the activation of nuclear factor kappa B. Free Radic Biol Med 2000; 28:1317–1327.CrossRefGoogle Scholar
  7. 7.
    Nees M, Geoghegan JM, Hyman T et al. Papillomavirus type 16 oncogenes downregulate expression of interferon-responsive genes and upregulate proliferation-associated and NF-kappa B-responsive genes in cervical keratinocytes. J Virol 2001; 75:4283–4296.PubMedCrossRefGoogle Scholar
  8. 8.
    Pande V, Ramos MJ. Nuclear Factor Kappa B: a potential target for anti-HIV chemotherapy. Curr Med Chem 2003; 10:1603–1615.PubMedCrossRefGoogle Scholar
  9. 9.
    Devadas K, Hardegen NJ, Wahl LM et al. Mechanisms for macrophage-mediated HIV-1 induction. J Immunol 2004; 173:6735–6744.PubMedGoogle Scholar
  10. 10.
    Gasparian AV, Fedorova MD, Kisseljove FL. Regulation of matrix metalloproteinase-9 transcription in squamous cell carcinoma of uterine cervix: the role of human papillomavirus gene E2 expression and activation of transcription factor NF-kappa B. Biochemistry-Moscow 2007; 72:848–853.PubMedCrossRefGoogle Scholar
  11. 11.
    Mukerjee R, Sawaya BE, Khalili K et al. Association of p65 and C/EBP beta with HIV-1 LTR modulates transcription of the viral promoter. J Cell Biochem 2007; 100:1210–1216.PubMedCrossRefGoogle Scholar
  12. 12.
    Schreck R, Albermann K, Baeuerle PA. Nuclear factor kappa-B—an oxidative stress-responsive transcription factor of eukaryotic cells (a review). Free Radic Res Comm 1992; 17:221–237.CrossRefGoogle Scholar
  13. 13.
    Chen F, Shi XL. NF-kappa B, A pivotal transcription factor in silica-induced diseases. Mol Cell Biochem 2002; 234:169–176.PubMedCrossRefGoogle Scholar
  14. 14.
    Flaherty DM, Monick MM, Carter AB et al. Oxidant-mediated increases in redox factor-1 nuclear protein and activator protein-1 DNA binding in asbestos-treated macrophages. J Immunol 2002; 168:5675–5681.PubMedGoogle Scholar
  15. 15.
    Valko M, Morris H, Cronin MTD. Metals, toxicity and oxidative stress. Curr Med Chem 2005; 12:1161–1208.PubMedCrossRefGoogle Scholar
  16. 16.
    Hirano F, Tanaka H, Miura T et al. Inhibition of NF-kappa B-dependent transcription of human immunodeficiency virus 1 promoter by a phosphodiester compound of vitamin C and vitamin E, EPC-K1. Immunopharmacology 1998; 39:31–38.PubMedCrossRefGoogle Scholar
  17. 17.
    Garland M, Fawzi W. Antioxidants and progression of human immunodeficiency virus (HIV) disease. Nutr Res 1999; 19:1259–1276.CrossRefGoogle Scholar
  18. 18.
    Guiliano A. The Role of nutrients in the prevention of cervical dysplasia and cancer. Nutrition 2000; 16:570–573.CrossRefGoogle Scholar
  19. 19.
    Beniston RG, Campo MS. Quercetin elevates p27 (Kip1) and arrests both primary and HPV16 E6/E7 transformed human keratinocytes in G1. Oncogene 2003; 22:5504–5514.PubMedCrossRefGoogle Scholar
  20. 20.
    Kaiser JD, Campa AM, Ondercin JP et al. Micronutrient supplementation increases CD4 count in HIV-infected individuals on highly active antiretroviral therapy: A prospective, double-blinded, placebo-controlled trial. J Acquir Immune Defic Syndr 2006; 42:523–528.PubMedCrossRefGoogle Scholar
  21. 21.
    Yaqoob P. Fatty acids as gatekeepers of immune cell regulation. Trends Immunol 2003; 24:639–645.PubMedCrossRefGoogle Scholar
  22. 22.
    Lapillonne A, Clarke SD, Heird WC. Polyunsaturated fatty acids and gene expression. Curr Opin Clin Nutr Metab Care 2004; 7:151–156.PubMedCrossRefGoogle Scholar
  23. 23.
    Simopoulos AP. Omega-6/omega-3 essential fatty acid ratio and chronic disease. Food Rev Int 2004; 20:77–90.CrossRefGoogle Scholar
  24. 24.
    Simopoulos AP. Omega-3 fatty acids and cancer. Indoor Built Environ 2003; 12:405–412.CrossRefGoogle Scholar
  25. 25.
    Simopoulos AP. The omega-6/omega-3 fatty acid ratio, genetic variation and cardiovascular disease. Asia Pac J Clin Nutr 2008; 17:131–134.PubMedGoogle Scholar
  26. 26.
    Haag M, Dippenaar NG. Dietary fats, fatty acids and insulin resistance: short review of a multifaceted connection. Med Sci Mon 2005; 11:RA359–RA367.Google Scholar
  27. 27.
    Blaschke F, Takata Y, Caglayan E et al. Obesity, peroxisome proliferator-activated receptor and atherosclerosis in type 2 diabetes. Arteroscler Thromb Vasc Biol 2006; 26:28–40.CrossRefGoogle Scholar
  28. 28.
    Richardson AJ, Ross MA. Fatty acid metabolism in neurodevelopmental disorder: a new perspective on associations between attention-deficit/hyperactivity disorder, dyslexia, dyspraxia and the autistic spectrum. Prostaglandins Leukot Essent Fatty Acids 2000; 63:1–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Young G, Conquer J. Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev 2004; 45:1–28.CrossRefGoogle Scholar
  30. 30.
    Wainwright PE. Dietary essential fatty acids and brain function: a developmental perspective on mechanisms. Proc Nutr Soc 2002; 61:61–69.PubMedCrossRefGoogle Scholar
  31. 31.
    Warner K, Knowlton S. Frying quality and oxidative stability of high-oleic corn oils. J Am Oil Chem Soc 1997; 74:1317–1322.CrossRefGoogle Scholar
  32. 32.
    Forster VA. Genetically modified crop approvals and planted acreages. Crop Biotechnol 2002; 829:17–22.CrossRefGoogle Scholar
  33. 33.
    Liu Q, Singh SP, Green AG. High-stearic and high-oleic cottonseed oils produced by hairpin RNA-mediated posttranscriptional gene silencing. Plant Physiol 2002; 129:1732–1743.PubMedCrossRefGoogle Scholar
  34. 34.
    Liu Q, Singh S, Green A. High-oleic and high-stearic cottonseed oils: Nutritionally improved cooking oils developed using gene silencing. J Am Coll Nutr 2002; 21:205S–211S.PubMedGoogle Scholar
  35. 35.
    Smith SA, King RE, Min DB. Oxidative and thermal stabilities of genetically modified high oleic sunflower oil. Food Chem 2007; 102:1208–1213.CrossRefGoogle Scholar
  36. 36.
    Tran E, Demmig-Adams B. Vitamins and minerals: Powerful medicine or potent toxins? Nutr Food Sci 2007; 37:50–60.CrossRefGoogle Scholar
  37. 37.
    Ellinger S, Ellinger J, Stehle P. Tomatoes, tomato products and lycopene in the prevention and treatment of prostate cancer: do we have the evidence from intervention studies? Curr Opin Clin Nutr Metab Care 2006; 9:722–727.PubMedCrossRefGoogle Scholar
  38. 38.
    Mares-Perlman JA, Millen AE, Ficek TL et al. The body of evidence to support a protective role for lutein and zeaxanthin in delaying chronic disease. Overview. J Nutr 2002; 132:518S–524S.Google Scholar
  39. 39.
    Seddon JM, Ajani UA, Sperduto RD et al. Dietary carotenoids, vitamin A, vitamin C and vitamin E and advanced age-related macular degeneration. J Am Med Assoc 1994; 272:1413–1420.CrossRefGoogle Scholar
  40. 40.
    Chasan-Taber L Willett WC, Seddon JM et al. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. Am J Clin Nutr 1999; 70:509–516.PubMedGoogle Scholar
  41. 41.
    Brown L, Rimm EB, Seddon JM et al. A prospective study of carotenoid intake and risk of cataract extraction in US men. Am J Clin Nutr 1999; 70:517–524.PubMedGoogle Scholar
  42. 42.
    Demmig-Adams B, Adams WW III. The role of xanthophyll cycle carotenoids in the protection of photosynthesis. Trends Plant Sci 1996; 1:21–26.CrossRefGoogle Scholar
  43. 43.
    Demmig-Adams B, Adams WW III. Photoprotection in an ecological context: the remarkable complexity of thermal dissipation. New Phytol 2006; 172:11–21. <doi: 10.1111/j.l469-8137.2006.01835PubMedCrossRefGoogle Scholar
  44. 44.
    Demmig-Adams B, Adams WW III. Antioxidants in photosynthesis and human nutrition. Science 2002; 298:2149–2153.PubMedCrossRefGoogle Scholar
  45. 45.
    Külheim C, Agren J, Jansson S. Rapid regulation of light harvesting and plant fitness in the field. Science 2002; 297:91–93.PubMedCrossRefGoogle Scholar
  46. 46.
    Holt NE, Zigmantas D, Valkunas L et al. Carotenoid cation formation and the regulation of photosynthetic light harvesting. Science 2005; 307:433–436.PubMedCrossRefGoogle Scholar
  47. 47.
    Ahn TK, Avenson TJ, Ballottari M et al. Architecture of a charge-transfer state regulating light harvesting in a plant antenna protein. Science 2008; 320:794–797.PubMedCrossRefGoogle Scholar
  48. 48.
    Pogson BJ, Niyogi KK, Björkman O et al. Altered xanthophyll compositions adversely affect chlorophyll accumulation and nonphotochemical quenching in Arabidopsis mutants. Proc Natl Acad Sci USA 1998; 95:13324–13329.PubMedCrossRefGoogle Scholar
  49. 49.
    Havaux M, Niyogi KK. The violaxanthin cycle protects plants from photooxidative damage by more than one mechanism. Proc Natl Acad Sci USA 1999; 96:8762–8767.PubMedCrossRefGoogle Scholar
  50. 50.
    Havaux M, Dall’Osto L, Cuine S et al. The effect of zeaxanthin as the only xanthophyll on the structure and function of the photosynthetic apparatus in Arabidopsis thaliana. J Biol Chem 2004; 279:13878–13888.PubMedCrossRefGoogle Scholar
  51. 51.
    Sajilata MG, Singhal RS, Kamat MY. The carotenoid pigment zeaxanthin—A review. Compr Rev Food Sci Food Saf 2008; 7:29–49.CrossRefGoogle Scholar
  52. 52.
    Thomson LR, Toyoda Y, Langner A et al. Elevated retinal zeaxanthin and prevention of light-induced photoreceptor cell death in quail. Investig Ophthalmol Vis Sci 2002; 43:3538–3549.Google Scholar
  53. 53.
    Thomson LR, Toyoda Y, Delori FC et al. Long term dietary supplementation with zeaxanthin reduces photoreceptor death in light-damaged Japanese quail. Exp Eye Res 2002; 75:529–542.PubMedCrossRefGoogle Scholar
  54. 54.
    Sumatran VN, Zhang R, Lee DS et al. Differential regulation of apoptosis in normal versus transformed mammary epithelium by lutein and retinoic acid. Canc Epidemiol Biomarkers Prev 2000; 9:257–263.Google Scholar
  55. 55.
    Müller K, Carpenter KLH, Challis IR et al. Carotenoids induce apoptosis in the T-lymphoblast cell line Jurkat E6.1. Free Radic Res 2002; 36:791–802.PubMedCrossRefGoogle Scholar
  56. 56.
    Chew BP, Brown CM, Park JS et al. Dietary lutein inhibits mouse mammary tumor growth by regulating angiogenesis and apoptosis. Anticancer Res 2003; 23:3333–3339.PubMedGoogle Scholar
  57. 57.
    Chitchumroonchokchai C, Bomser JA, Glamm JE et al. Xanthophylls and α-tocopherol decrease UVB-induced lipid peroxidation and stress signalling in human lens epithelial cells. J Nutr 2004; 134:3225–3232.PubMedGoogle Scholar
  58. 58.
    Wrona M, Korytowksi W, Ròzanowska M et al. Cooperation of antioxidants in protection against photosensitized oxidation. Free Radic Biol Med 2003; 35:1319–1329.PubMedCrossRefGoogle Scholar
  59. 59.
    Wrona M, Ròzanowska M, Sarna T. Zeaxanthin in combination with ascorbic acid or alpha-tocopherol protects APRE-19 cells against photosensitized peroxidation of lipids. Free Radic Biol Med 2004; 36:1094–1101.PubMedCrossRefGoogle Scholar
  60. 60.
    Youdim KA, Spencer JPE, Schroeter H et al. Dietary flavonoids as potential neuroprotectants. Biol Chem 2002; 383:503–519.PubMedCrossRefGoogle Scholar
  61. 61.
    Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Canc 2003; 3:768–780.CrossRefGoogle Scholar
  62. 62.
    Seo T, Blaner WS, Deckelbaum RJ. Omega-3 fatty acids: molecular approaches to optimal biological outcomes. Curr Opin Lipidol 2005; 16:11–18.PubMedCrossRefGoogle Scholar
  63. 63.
    Maccarrone M, Bari M, Gasperi V et al. The photoreceptor protector zeaxanthin induces cell death in neuroblastoma cells. Anticancer Res 2005; 25:3871–3876.PubMedGoogle Scholar
  64. 64.
    Yamamoto HY. Biochemistry of the violaxanthin cycle in higher plants. Pure Appl Chem 1979; 51:639–648.CrossRefGoogle Scholar
  65. 65.
    Demmig-Adams B. Linking the xanthophyll cycle with photoprotective energy dissipation. Photosynth Res 2003; 76:73–80.PubMedCrossRefGoogle Scholar
  66. 66.
    Landrum JT, Bone RA. Lutein, zeaxanthin and the macular pigment. Arch Biochem Biophys 2001; 385:28–40.PubMedCrossRefGoogle Scholar
  67. 67.
    Niyogi KK. Safety valves for photosynthesis. Curr Opin Plant Biol 2000; 3:455–460.PubMedCrossRefGoogle Scholar
  68. 68.
    Dharmapuri S, Rosati C, Pallara P et al. Metabolic engineering of xanthophyll content in tomato fruits. FEBS Lett 2002; 519:30–34.PubMedCrossRefGoogle Scholar
  69. 69.
    Romer S, Lubeck J, Kauder F et al. Genetic engineering of a zeaxanthin-rich potato by antisense inactivation and cosuppression of carotenoid epoxidation. Metab Eng 2002; 4:263–272.PubMedCrossRefGoogle Scholar
  70. 70.
    Albrecht M, Misawa N, Sandmann G. Metabolic engineering of the terpenoid biosynthetic pathway of Escherichia coli for production of the carotenoids beta-carotene and zeaxanthin. Biotechnol Lett 1999; 21:791–795.CrossRefGoogle Scholar
  71. 71.
    de Oliveira GPR, Rodriguez-Amaya DB. Processed and prepared corn products as sources of lutein and zeaxanthin: Compositional variation in the food chain. J Food Sci 2007; 72:S079–S085.PubMedCrossRefGoogle Scholar
  72. 72.
    Daicker B, Schiedt K, Adnet JJ et al. Canthaxanthin retinophathy—an investigation by light and electron-microscopy and physicochemical analysis. Graefes Arch Clin Exp Ophthalmol 1987; 225:189–197.PubMedCrossRefGoogle Scholar
  73. 73.
    Stewart G. Investigating the effect of diet on nutrient concentration in eggs: How your breakfast might be healthier than you think. Inquiry (The University of New Hampshire) 2007: <
  74. 74.
    Wang YM, Conner SL, Wang W et al. The selective retention of lutein, meso-zeaxanthin and zeaxanthin in the retina of chicks fed a xanthophyll-free diet. Exp Eye Res 2007; 84:591–598.PubMedCrossRefGoogle Scholar
  75. 75.
    McGraw KJ, Beebee MD, Hill GE et al. Lutein-based plumage coloration in songbirds is a consequence of selective pigment incorporation into feathers. Comp Biochem Physiol B Biochem Mol Biol 2003; 135:689–696.PubMedCrossRefGoogle Scholar
  76. 76.
    Moller AP, Biard C, Blount JD et al. Carotenoid-dependent signals: Indicators of foraging efficiency, immunocompetence or detoxification ability? Avian Poultry Biol Rev 2000; 11:137–159.Google Scholar
  77. 77.
    Kim HW, Chew BP, Wong TS et al. Dietary lutein stimulates immune response in the canine. Vet Immunol Immunopathol 2000; 74:315–327.PubMedCrossRefGoogle Scholar
  78. 78.
    Kim HW, Chew BP, Wong TS et al. Modulation of humoral and cell-mediated immune responses by dietary lutein in cats. Vet Immunol Immunopathol 2000; 74:331–341.CrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Barbara Demmig-Adams
    • 1
  • William W. AdamsIII
  1. 1.Department of Ecology and Evolutionary BiologyUniversity of ColoradoBoulderUSA

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