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Lutein and Zeaxanthin Influence Brain Function in Older Adults: A Randomized Controlled Trial

  • Cutter A. Lindbergh (a1), Lisa M. Renzi-Hammond (a1), Billy R. Hammond (a1), Douglas P. Terry (a1), Catherine M. Mewborn (a1), Antonio N. Puente (a1) and L. Stephen Miller (a1) (a2)...

Objectives: The present study constitutes the first randomized controlled trial to investigate the relation of lutein (L) and zeaxanthin (Z) to brain function using functional magnetic resonance imaging (fMRI). It was hypothesized that L and Z supplementation in older adults would enhance neural efficiency (i.e., reduce activation) and cognitive performance on a verbal learning task relative to placebo. Methods: A total of 44 community-dwelling older adults (mean age=72 years) were randomly assigned to receive either placebo or L+Z supplementation (12 mg/daily) for 1 year. Neurocognitive performance was assessed at baseline and post-intervention on an fMRI-adapted task involving learning and recalling word pairs. Imaging contrasts of blood-oxygen-level-dependent (BOLD) signal were created by subtracting active control trials from learning and recall trials. A flexible factorial model was employed to investigate the expected group (placebo vs. supplement) by time (baseline vs. post-intervention) interaction in pre-specified regions-of-interest. Results: L and Z appeared to buffer cognitive decline on the verbal learning task (Cohen’s d=.84). Significant interactions during learning were observed in left dorsolateral prefrontal cortex and anterior cingulate cortex (p < .05, family-wise-error corrected). However, these effects were in the direction of increased rather than decreased BOLD signal. Although the omnibus interaction was not significant during recall, within-group contrasts revealed significant increases in left prefrontal activation in the supplement group only. Conclusions: L and Z supplementation appears to benefit neurocognitive function by enhancing cerebral perfusion, even if consumed for a discrete period of time in late life. (JINS, 2018, 24, 77–90)

Corresponding author
Correspondence and reprint requests to: L. Stephen Miller, Department of Psychology, Psychology Building, University of Georgia, Athens, GA 30602-3013. E-mail:
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Akbaraly, N.T., Faure, H., Gourlet, V., Favier, A., & Berr, C. (2007). Plasma carotenoid levels and cognitive performance in an elderly population: Results of the EVA Study. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 62(3), 308316.
Akbaraly, T.N., Singh-Manoux, A., Marmot, M.G., & Brunner, E.J. (2009). Education attenuates the association between dietary patterns and cognition. Dementia and Geriatric Cognitive Disorders, 27(2), 147154.
Barbey, A.K., Koenigs, M., & Grafman, J. (2013). Dorsolateral prefrontal contributions to human working memory. Cortex, 49(5), 11951205.
Beatty, S., Nolan, J., Kavanagh, H., & O’Donovan, O. (2004). Macular pigment optical density and its relationship with serum and dietary levels of lutein and zeaxanthin. Archives of Biochemistry and Biophysics, 430(1), 7076.
Bernstein, P.S., Khachik, F., Carvalho, L.S., Muir, G.J., Zhao, D.Y., & Katz, N.B. (2001). Identification and quantitation of carotenoids and their metabolites in the tissues of the human eye. Experimental Eye Research, 72(3), 215223.
Bertram, J.S. (1999). Carotenoids and gene regulation. Nutrition Reviews, 57(6), 182191.
Bitner, B.R., Marcano, D.C., Berlin, J.M., Fabian, R.H., Cherian, L., Culver, J.C., & Tour, J.M. (2012). Antioxidant carbon particles improve cerebrovascular dysfunction following traumatic brain injury. ACS Nano, 6(9), 80078014.
Blumenfeld, R.S., Parks, C.M., Yonelinas, A.P., & Ranganath, C. (2011). Putting the pieces together: The role of dorsolateral prefrontal cortex in relational memory encoding. Journal of Cognitive Neuroscience, 23(1), 257265.
Blumenfeld, R.S., & Ranganath, C. (2006). Dorsolateral prefrontal cortex promotes long-term memory formation through its role in working memory organization. The Journal of Neuroscience, 26(3), 916925.
Boespflug, E.L., McNamara, R.K., Eliassen, J.C., Schidler, M.D., & Krikorian, R. (2016). Fish oil supplementation increases event-related posterior cingulate activation in older adults with subjective memory impairment. The Journal of Nutrition, Health and Aging, 20(2), 161169.
Bokov, A., Chaudhuri, A., & Richardson, A. (2004). The role of oxidative damage and stress in aging. Mechanisms of Ageing and Development, 125(10–11), 811826.
Bone, R.A., Landrum, J.T., & Tarsis, S.L. (1985). Preliminary identification of the human macular pigment. Vision Research, 25(11), 15311535.
Bookheimer, S.Y., Renner, B.A., Ekstrom, A., Li, Z., Henning, S.M., Brown, J.A., & Small, G.W. (2013). Pomegranate juice augments memory and fMRI activity in middle-aged and older adults with mild memory complaints. Evidence-Based Complementary and Alternative Medicine.
Bookheimer, S.Y., Strojwas, M.H., Cohen, M.S., Saunders, A.M., Pericak-Vance, M.A., Mazziotta, J.C., &&Small, G.W. (2000). Patterns of brain activation in people at risk for Alzheimer’s disease. The New England Journal of Medicine, 343(7), 450456.
Braskie, M.N., Small, G.W., & Bookheimer, S.Y. (2009). Entorhinal cortex structure and functional MRI response during an associative verbal memory task. Human Brain Mapping, 30(12), 39813992.
Brickman, A.M., Khan, U.A., Provenzano, F.A., Yeung, L.K., Suzuki, W., Schroeter, H., & Small, S.A. (2014). Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults. Nature Neuroscience, 17(12), 17981803.
Britton, G., Liaaen-Jensen, S., & Pfander, H. (2004). Carotenoids: Handbook. Basel, Switzerland: Springer.
Butterfield, D.A., Bader Lange, M.L., & Sultana, R. (2010). Involvements of the lipid peroxidation product, HNE, in the pathogenesis and progression of Alzheimer’s disease. Biochimica et Biophysica Acta, 1801(8), 924929.
Cabeza, R., & Nyberg, L. (2000). Imaging Cognition II: An empirical review of 275 PET and fMRI studies. Journal of Cognitive Neuroscience, 12(1), 147.
Clément, F., & Belleville, S. (2009). Test–retest reliability of fMRI verbal episodic memory paradigms in healthy older adults and in persons with mild cognitive impairment. Human Brain Mapping, 30(12), 40334047.
Craft, N.E., Haitema, T.B., Garnett, K.M., Fitch, K.A., & Dorey, C.K. (2004). Carotenoid, tocopherol, and retinol concentrations in elderly human brain. The Journal of Nutrition, Health and Aging, 8(3), 156162.
D’Esposito, M., Deouell, L.Y., & Gazzaley, A. (2003). Alterations in the BOLD fMRI signal with ageing and disease: A challenge for neuroimaging. Nature Reviews Neuroscience, 4(11), 863872.
Erdman, J.W., Smith, J.W., Kuchan, M.J., Mohn, E.S., Johnson, E.J., Rubakhin, S.S., & Neuringer, M. (2015). Lutein and brain function. Foods, 4(4), 547564.
Faul, F., Erdfelder, E., Buchner, A., & Lang, A.-G. (2009). Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses. Behavior Research Methods, 41, 11491160.
Faul, F., Erdfelder, E., Lang, A.-G., & Buchner, A. (2007). G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior Research Methods, 39, 175191.
Feart, C., Letenneur, L., Helmer, C., Samieri, C., Schalch, W., Etheve, S., & Barberger-Gateau, P. (2015). Plasma carotenoids are inversely associated with dementia risk in an elderly French cohort. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 71(5), 683688.
Feeney, J., Finucane, C., Savva, G.M., Cronin, H., Beatty, S., Nolan, J.M., &&Kenny, R.A. (2013). Low macular pigment optical density is associated with lower cognitive performance in a large, population-based sample of older adults. Neurobiology of Aging, 34(11), 24492456.
Fleck, M.S., Daselaar, S.M., Dobbins, I.G., & Cabeza, R. (2006). Role of prefrontal and anterior cingulate regions in decision-making processes shared by memory and nonmemory tasks. Cerebral Cortex, 16(11), 16231630.
Gasquoine, P.G. (2013). Localization of function in anterior cingulate cortex: From psychosurgery to functional neuroimaging. Neuroscience and Biobehavioral Reviews, 37(3), 340348.
Goekoop, R., Rombouts, S.A., Jonker, C., Hibbel, A., Knol, D.L., Truyen, L., & Scheltens, P. (2004). Challenging the cholinergic system in mild cognitive impairment: A pharmacological fMRI study. NeuroImage, 23(4), 14501459.
Hammond, B.R., Johnson, E.J., Russell, R.M., Krinsky, N.I., Yeum, K.J., Edwards, R.B., &&Snodderly, D.M. (1997). Dietary modification of human macular pigment density. Investigative Ophthalmology and Visual Science, 38(9), 17951801.
Hammond, B.R., Wooten, B.R., & Smollon, B. (2005). Assessment of the validity of in vivo methods of measuring human macular pigment optical density. Optometry and Vision Science, 82(5), 387404.
Hassevoort, K.M., Khazoum, S.E., Walker, J.A., Barnett, S.M., Raine, L.B., Hammond, B.R., & Cohen, N.J. (2017). Macular carotenoids, aerobic fitness, and central adiposity are associated differentially with hippocampal-dependent relational memory in preadolescent children. The Journal of Pediatrics. doi: 10.1016/j.jpeds.2017.01.016
Heneka, M.T., Carson, M.J., El Khoury, J., Landreth, G.E., Brosseron, F., Feinstein, D.L., & Kummer, M.P. (2015). Neuroinflammation in Alzheimer’s disease. The Lancet: Neurology, 14(4), 388405.
Huang, S., Du, F., Shih, Y.Y.I., Shen, Q., Gonzalez-Lima, F., & Duong, T.Q. (2013). Methylene blue potentiates stimulus-evoked fMRI responses and cerebral oxygen consumption during normoxia and hypoxia. NeuroImage, 72, 237242.
Johnson, E.J. (2012). A possible role for lutein and zeaxanthin in cognitive function in the elderly. The American Journal of Clinical Nutrition, 96(5), 11611165.
Johnson, E.J. (2014). Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan. Nutrition Reviews, 72(9), 605612.
Johnson, E.J., McDonald, K., Caldarella, S.M., Chung, H., Troen, A.M., & Snodderly, D.M. (2008). Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women. Nutritional Neuroscience, 11(2), 7583.
Johnson, E.J., Vishwanathan, R., Johnson, M.A., Hausman, D.B., Davey, A., Scott, T.M., & Poon, L.W. (2013). Relationship between serum and brain carotenoids, α-tocopherol, and retinol concentrations and cognitive performance in the oldest old from the Georgia Centenarian Study. Journal of Aging Research.
Kang, J.H., Ascherio, A., & Grodstein, F. (2005). Fruit and vegetable consumption and cognitive decline in aging women. Annals of Neurology, 57(5), 713720.
Kelly, D., Coen, R.F., Akuffo, K.O., Beatty, S., Dennison, J., Moran, R., & Nolan, J.M. (2015). Cognitive function and its relationship with macular pigment optical density and serum concentrations of its constituent carotenoids. Journal of Alzheimer’s Disease, 48(1), 261277.
Kesse-Guyot, E., Andreeva, V.A., Ducros, V., Jeandel, C., Julia, C., Hercberg, S., && Galan, P. (2014). Carotenoid-rich dietary patterns during midlife and subsequent cognitive function. The British Journal of Nutrition, 111(5), 915923.
Khachik, F., Beecher, G.R., Goli, M.B., & Lusby, W.R. (1991). Separation, identification, and quantification of carotenoids in fruits, vegetables and human plasma by high performance liquid chromatography. Pure and Applied Chemistry, 63(1), 7180.
Krinsky, N.I., Mayne, S.T., & Sies, H. (2004). Carotenoids in Health and Disease. Boca Raton, FL: CRC Press.
Kvansakul, J., Rodriguez-Carmona, M., Edgar, D.F., Barker, F.M., Koëpcke, W., Schalch, W., && Barbur, J.L. (2006). Supplementation with the carotenoids lutein or zeaxanthin improves human visual performance. Ophthalmic and Physiological Optics, 26(4), 362371.
Landrum, J.T., Bone, R.A., Joa, H., Kilburn, M.D., Moore, L.L., & Sprague, K.E. (1997). A one year study of the macular pigment: The effect of 140 days of a lutein supplement. Experimental Eye Research, 65(1), 5762.
Lazar, N. (2008). The statistical analysis of functional MRI data. New York, NY: Springer.
Lee, Y., Kim, J., & Back, J.H. (2009). The influence of multiple lifestyle behaviors on cognitive function in older persons living in the community. Preventive Medicine, 48(1), 8690.
Lindbergh, C.A., Mewborn, C., Hammond, B.R., Renzi-Hammond, L.M., Curran-Celentano, J.M., & Miller, L.S. (2016). The relationship of lutein and zeaxanthin levels to neurocognitive functioning: An fMRI study of older adults. Journal of the International Neuropsychological Society, 22, 112. doi: 10.1017/S1355617716000850
Ma, L., Dou, H.-L., Wu, Y.-Q., Huang, Y.-M., Huang, Y.-B., Xu, X.-R., & Lin, X.-M. (2012). Lutein and zeaxanthin intake and the risk of age-related macular degeneration: A systematic review and meta-analysis. British Journal of Nutrition, 107(3), 350359.
Ma, L., Lin, X.M., Zou, Z.Y., Xu, X.R., Li, Y., & Xu, R. (2009). A 12-week lutein supplementation improves visual function in Chinese people with long-term computer display light exposure. British Journal of Nutrition, 102(2), 186190.
MacDonald, A.W., Cohen, J.D., Stenger, V.A., & Carter, C.S. (2000). Dissociating the role of the dorsolateral prefrontal and anterior cingulate cortex in cognitive control. Science, 288(5472), 18351838.
Maci, S., Fonseca, B., & Zhu, Y. (2016). The role of lutein in brain health and function. Nutrafoods, 15, 179188. doi: 10.17470/nf-016-1014-3
Maldjian, J.A., Laurienti, P.J., & Burdette, J.H. (2004). Precentral gyrus discrepancy in electronic versions of the Talairach Atlas. NeuroImage, 21(1), 450455.
Maldjian, J.A., Laurienti, P.J., Burdette, J.B., & Kraft, R.A. (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage, 19, 12331239.
Malinow, M.R., Feeney-Burns, L., Peterson, L.H., Klein, M.L., & Neuringer, M. (1980). Diet-related macular anomalies in monkeys. Investigative Ophthalmology and Visual Science, 19(8), 857863.
Mares, J.A., LaRowe, T.L., Snodderly, D.M., Moeller, S.M., Gruber, M.J., Klein, M.L., & Chappell, R.J. (2006). Predictors of optical density of lutein and zeaxanthin in retinas of older women in the Carotenoids in Age-Related Eye Disease Study, an ancillary study of the Women’s Health Initiative. The American Journal of Clinical Nutrition, 84(5), 11071122.
Mazereeuw, G., Lanctôt, K.L., Chau, S.A., Swardfager, W., & Herrmann, N. (2012). Effects of omega-3 fatty acids on cognitive performance: A meta-analysis. Neurobiology of Aging, 33(7), 1729.
Mikkilä, V., Räsänen, L., Raitakari, O.T., Pietinen, P., & Viikari, J. (2005). Consistent dietary patterns identified from childhood to adulthood: The Cardiovascular Risk in Young Finns Study. British Journal of Nutrition, 93(6), 923931.
Min, J., & Min, K. (2014). Serum lycopene, lutein and zeaxanthin, and the risk of Alzheimer’s disease mortality in older adults. Dementia and Geriatric Cognitive Disorders, 37(3-4), 246256.
Morris, M.C., Evans, D.A., Tangney, C.C., Bienias, J.L., & Wilson, R.S. (2006). Associations of vegetable and fruit consumption with age-related cognitive change. Neurology, 67(8), 13701376.
Murray, I.J., Makridaki, M., van der Veen, R.L., Carden, D., Parry, N.R., & Berendschot, T.T. (2013). Lutein supplementation over a one-year period in early AMD might have a mild beneficial effect on visual acuity: The CLEAR Study. Investigative Ophthalmology & Visual Science, 54(3), 17811788.
Niendam, T.A., Laird, A.R., Ray, K.L., Dean, Y.M., Glahn, D.C., & Carter, C.S. (2012). Meta-analytic evidence for a superordinate cognitive control network subserving diverse executive functions. Cognitive, Affective, and Behavioral Neuroscience, 12(2), 241268.
Nolan, J.M., Loskutova, E., Howard, A.N., Moran, R., Mulcahy, R., Stack, J., & Thurnham, D.I. (2014). Macular pigment, visual function, and macular disease among subjects with Alzheimer’s disease: An exploratory study. Journal of Alzheimer’s Disease, 42(4), 11911202.
Nolan, J.M., Stack, J., Mellerio, J., Godhinio, M., O’Donovan, O., Neelam, K., && Beatty, S. (2006). Monthly consistency of macular pigment optical density and serum concentrations of lutein and zeaxanthin. Current Eye Research, 31(2), 199213.
Nyberg, L., Lövdén, M., Riklund, K., Lindenberger, U., & Bäckman, L. (2012). Memory aging and brain maintenance. Trends in Cognitive Sciences, 16(5), 292305.
Park, D.C., & Reuter-Lorenz, P. (2009). The adaptive brain: Aging and neurocognitive scaffolding. Annual Review of Psychology, 60, 173196.
Presley, T.D., Morgan, A.R., Bechtold, E., Clodfelter, W., Dove, R.W., Jennings, J.M., & Miller, G.D. (2011). Acute effect of a high nitrate diet on brain perfusion in older adults. Nitric Oxide: Biology and Chemistry, 24(1), 3442.
Renzi, L.M., Dengler, M.J., Puente, A., Miller, L.S., & Hammond, B.R. (2014). Relationships between macular pigment optical density and cognitive function in unimpaired and mildly cognitively impaired older adults. Neurobiology of Aging, 35(7), 16951699.
Renzi, L.M., & Hammond, B.R. (2010). The relation between the macular carotenoids, lutein and zeaxanthin, and temporal vision. Ophthalmic and Physiological Optics, 30(4), 351357.
Renzi, L., Iannaccone, A., Johnson, E., & Kritchevsky, S. (2008). The relation between serum xanthophylls, fatty acids, macular pigment and cognitive function in the Health ABC Study. FASEB Journal, 22, 877.5. doi: 10.1096/fj.1530-6860
Reuter-Lorenz, P.A., & Park, D.C. (2014). How does it STAC up? Revisiting the Scaffolding Theory of Aging and Cognition. Neuropsychology Review, 24(3), 355370.
Rorden, C. (2007). DCM2NII (Computer software).
Rosano, C., Marsland, A.L., & Gianaros, P.J. (2012). Maintaining brain health by monitoring inflammatory processes: A mechanism to promote successful aging. Aging and Disease, 3(1), 1633.
Ruitenberg, A., den Heijer, T., Bakker, S.L., van Swieten, J.C., Koudstaal, P.J., Hofman, A., &&Breteler, M. (2005). Cerebral hypoperfusion and clinical onset of dementia: The Rotterdam Study. Annals of Neurology, 57(6), 789794.
SanGiovanni, J.P., & Neuringer, M. (2012). The putative role of lutein and zeaxanthin as protective agents against age-related macular degeneration: Promise of molecular genetics for guiding mechanistic and translational research in the field. The American Journal of Clinical Nutrition, 96(5), 12231233. doi:
Saykin, A.J., Wishart, H.A., Rabin, L.A., Flashman, L.A., McHugh, T.L., Mamourian, A.C., &&Santulli, R.B. (2004). Cholinergic enhancement of frontal lobe activity in mild cognitive impairment. Brain, 127(7), 15741583.
Shenhav, A., Botvinick, M.M., & Cohen, J.D. (2013). The expected value of control: An integrative theory of anterior cingulate cortex function. Neuron, 79(2), 217240.
Stahl, W., & Sies, H. (2001). Effects of carotenoids and retinoids on gap junctional communication. Biofactors, 15(2–4), 95.
Stringham, J.M., & Hammond, B.R. (2008). Macular pigment and visual performance under glare conditions. Optometry & Vision Science, 85(2), 8288.
Stringham, J.M., Hammond, B.R., Nolan, J.M., Wooten, B.R., Mammen, A., Smollon, W., && Snodderly, D.M. (2008). The utility of using customized heterochromatic flicker photometry (cHFP) to measure macular pigment in patients with age-related macular degeneration. Experimental Eye Research, 87(5), 445453.
Vishwanathan, R., Iannaccone, A., Scott, T.M., Kritchevsky, S.B., Jennings, B.J., Carboni, G., & Johnson, E.J. (2014). Macular pigment optical density is related to cognitive function in older people. Age and Ageing, 43(2), 271275.
Vishwanathan, R., Neuringer, M., Snodderly, D.M., Schalch, W., & Johnson, E.J. (2013). Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates. Nutritional Neuroscience, 16(1), 2129.
Vishwanathan, R., Schalch, W., & Johnson, E.J. (2016). Macular pigment carotenoids in the retina and occipital cortex are related in humans. Nutritional Neuroscience, 19(3), 95101.
Wechsler, D. (2001). Wechsler Test of Adult Reading: WTAR. San Antonio, TX: Psychological Corporation.
Wechsler, D. (2009). The Wechsler Memory Scale-Fourth Edition (WMS-IV). San Antonio, TX: Pearson Assessments.
Weigert, G., Kaya, S., Pemp, B., Sacu, S., Lasta, M., Werkmeister, R.M., & Schmetterer, L. (2011). Effects of lutein supplementation on macular pigment optical density and visual acuity in patients with age-related macular degeneration. Investigative Ophthalmology & Visual Science, 52(11), 81748178.
Weissman, D.H., Gopalakrishnan, A., Hazlett, C.J., & Woldorff, M.G. (2005). Dorsal anterior cingulate cortex resolves conflict from distracting stimuli by boosting attention toward relevant events. Cerebral Cortex, 15(2), 229237.
Widomska, J., & Subczynski, W.K. (2014). Why has nature chosen lutein and zeaxanthin to protect the retina? Journal of Clinical and Experimental Ophthalmology, 5(1).
Wilkinson, D., & Halligan, P. (2004). The relevance of behavioural measures for functional-imaging studies of cognition. Nature Reviews Neuroscience, 5(1), 6773.
Yagi, A., Fujimoto, K., Michihiro, K., Goh, B., Tsi, D., & Nagai, H. (2009). The effect of lutein supplementation on visual fatigue: A psychophysiological analysis. Applied Ergonomics, 40(6), 10471054.
Yesavage, J.A., Brink, T.L., Rose, T.L., Lum, O., Huang, V., Adey, M., & Leirer, V.O. (1983). Development and validation of a geriatric depression screening scale: A preliminary report. Journal of Psychiatric Research, 17(1), 3749.
Zamroziewicz, M.K., & Barbey, A.K. (2016). Nutritional cognitive neuroscience: Innovations for healthy brain aging. Frontiers in Neuroscience, 10, 110. doi: 10.3389/fnins.2016.00240
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