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Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Other Nutrient Supplementation on Cognitive Function: The AREDS2 Randomized Clinical Trial
Open accessAbstract
IMPORTANCE: Observational data have suggested that high dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer disease. OBJECTIVE: To test the effects of oral supplementation with nutrients on cognitive function. DESIGN, SETTING, AND PARTICIPANTS: In a double-masked randomized clinical trial (the Age-Related Eye Disease Study 2 [AREDS2]), retinal specialists in 82 US academic and community medical centers enrolled and observed participants who were at risk for developing late age-related macular degeneration (AMD) from October 2006 to December 2012. In addition to annual eye examinations, several validated cognitive function tests were administered via telephone by trained personnel at baseline and every 2 years during the 5-year study. INTERVENTIONS: Long-chain polyunsaturated fatty acids (LCPUFAs) (1 g) and/or lutein (10 mg)/zeaxanthin (2 mg) vs placebo were tested in a factorial design. All participants were also given varying combinations of vitamins C, E, beta carotene, and zinc. MAIN OUTCOMES AND MEASURES: The main outcome was the yearly change in composite scores determined from a battery of cognitive function tests from baseline. The analyses, which were adjusted for baseline age, sex, race, history of hypertension, education, cognitive score, and depression score, evaluated the differences in the composite score between the treated vs untreated groups. The composite score provided an overall score for the battery, ranging from -22 to 17, with higher scores representing better function. RESULTS: A total of 89% (3741/4203) of AREDS2 participants consented to the ancillary cognitive function study and 93.6% (3501/3741) underwent cognitive function testing. The mean (SD) age of the participants was 72.7 (7.7) years and 57.5% were women. There were no statistically significant differences in change of scores for participants randomized to receive supplements vs those who were not. The yearly change in the composite cognitive function score was -0.19 (99% CI, -0.25 to -0.13) for participants randomized to receive LCPUFAs vs -0.18 (99% CI, -0.24 to -0.12) for those randomized to no LCPUFAs (difference in yearly change, -0.03 [99% CI, -0.20 to 0.13]; P = .63). Similarly, the yearly change in the composite cognitive function score was -0.18 (99% CI, -0.24 to -0.11) for participants randomized to receive lutein/zeaxanthin vs -0.19 (99% CI, -0.25 to -0.13) for those randomized to not receive lutein/zeaxanthin (difference in yearly change, 0.03 [99% CI, -0.14 to 0.19]; P = .66). Analyses were also conducted to assess for potential interactions between LCPUFAs and lutein/zeaxanthin and none were found to be significant. CONCLUSIONS AND RELEVANCE: Among older persons with AMD, oral supplementation with LCPUFAs or lutein/zeaxanthin had no statistically significant effect on cognitive function. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00345176.
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“In the AREDS2 study, dietary intervention with 350 mg DHA and 650 mg EPA for 5 years did not have a significant effect on cognitive function in 3,501 older adults (mean age 72.7 years) with age-related macular degeneration [74].”
From Role of n-3 long-chain polyunsaturated fatty acids in human nutrition and health: Review of recent studies and recommendations (2021) · cites this paper as [74]
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Citations
Cites
The CES-D Scale: A Self-Report Depression Scale for Research in the General Population
Radloff, L. S. (1977) · Applied Psychological Measurement · doi:10.1177/014662167700100306 · Cited by 53,267
2013 Alzheimer's disease facts and figures
Thies, W. H., & Bleiler, L. (2013) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2013.02.003 · Cited by 3,372
A Standardized Memory Scale for Clinical Use
Wechsler, D. (1945) · The Journal of Psychology · doi:10.1080/00223980.1945.9917223 · Cited by 2,949
Telephone Interview for Cognitive Status
Brandt, J., Spencer, M., & Folstein, M. F. (1988) · PsycTESTS Dataset · doi:10.1037/t28542-000 · Cited by 1,504
Omenn, G. S., Goodman, G. E., Thornquist, M. D., Balmes, J., Cullen, M. R., Glass, A., Keogh, J. P., Meyskens, F. L., Valanis, B., Williams, J. H., et al. (1996) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/88.21.1550 · Cited by 1,255
Docosahexaenoic Acid Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Trial
Quinn, J. F., Raman, R., Thomas, R. G., Yurko-Mauro, K., Nelson, E. B., Van Dyck, C., Galvin, J. E., Emond, J., Jack, C. R., Weiner, M., et al. (2010) · JAMA · doi:10.1001/jama.2010.1510 · Cited by 764
Verbal fluency in aging and dementia
Rosen, W. G. (1980) · Journal of Clinical and Experimental Neuropsychology · doi:10.1080/01688638008403788 · Cited by 597
Polyunsaturated Fatty Acids, Antioxidants, and Cognitive Function in Very Old Men
Kalmijn, S., Feskens, E. J. M., Launer, L. J., & Kromhout, D. (1997) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a009029 · Cited by 453
Self-citationThe Age-related Eye Disease Study 2 (AREDS2)
Chew, E. Y., Clemons, T. E., SanGiovanni, J. P., Danis, R. P., Domalpally, A., McBee, W. L., Sperduto, R. D., & Ferris, F. L. (2012) · Ophthalmology · doi:10.1016/j.ophtha.2012.05.027 · Cited by 434
Self-citation
Cited by
Sorted by citations
Artificial Intelligence and Deep Learning in Ophthalmology
Ting, D. S. W., Pasquale, L. R., Peng, L., Campbell, J. P., Lee, A., Raman, R., Tan, G. S. W., Schmetterer, L. F., Keane, P. A., & Wong, T. Y. (2018) · Springer eBooks · doi:10.1007/978-3-030-64573-1_200 · Cited by 1,660
Jomova, K., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2024) · Archives of Toxicology · doi:10.1007/s00204-024-03696-4 · Cited by 1,445
“Age-related Eye Disease Study 2 (AREDS2), conducted for nearly 5 years in 3700 individuals with a mean age of 73 years, did not confirm a positive effect of supplementation with lutein (10 mg/day) or zeaxanthin (2 mg/day) (Chew et al. 2015).”
BackgroundOmega-3 fatty acids for the primary and secondary prevention of cardiovascular disease
Abdelhamid, A. S., Brown, T. J., Brainard, J. S., Biswas, P., Thorpe, G., Moore, H. J., Deane, K. H., AlAbdulghafoor, F. K., Summerbell, C., Worthington, H. V., et al. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003177.pub3 · Cited by 647
Bernstein, P. S., Li, B., Vachali, P. P., Gorusupudi, A., Shyam, R., Henriksen, B. S., & Nolan, J. M. (2015) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.10.003 · Cited by 570
Self-citationEffect of omega-3 fatty acids on cardiovascular outcomes: A systematic review and meta-analysis
Khan, S. U., Lone, A. N., Khan, M. S., Virani, S. S., Blumenthal, R. S., Nasir, K., Miller, M., Michos, E. D., Ballantyne, C. M., Boden, W. E., et al. (2021) · eClinicalMedicine · doi:10.1016/j.eclinm.2021.100997 · Cited by 411
Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease
Abdelhamid, A. S., Brown, T. J., Brainard, J. S., Biswas, P., Thorpe, G., Moore, H. J., Deane, K. H., AlAbdulghafoor, F. K., Summerbell, C., Worthington, H. V., et al. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003177.pub4 · Cited by 419
Docosahexaenoic acid (DHA): An essential nutrient and a nutraceutical for brain health and diseases
Sun, G. Y., Simonyi, Á., Fritsche, K. L., Chuang, D. Y., Hannink, M., Gu, Z., Greenlief, C. M., Yao, J. K., Lee, J. C., & Beversdorf, D. Q. (2017) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2017.03.006 · Cited by 324
Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease
Abdelhamid, A. S., Brown, T. J., Brainard, J. S., Biswas, P., Thorpe, G. C., Moore, H. J., Deane, K. H., Summerbell, C. D., Worthington, H. V., Song, F., et al. (2020) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003177.pub5 · Cited by 295
The Effect of Lutein on Eye and Extra-Eye Health
Buscemi, S., Corleo, D., Di Pace, F., Petroni, M. L., Satriano, A., & Marchesini, G. (2018) · Nutrients · doi:10.3390/nu10091321 · Cited by 260
Nutrients and bioactives in green leafy vegetables and cognitive decline: Prospective study
Morris, M. C., Wang, Y., Barnes, L. L., Bennett, D. A., Dawson-Hughes, B., & Booth, S. L. (2018) · Neurology · doi:10.1212/wnl.0000000000004815 · Cited by 252
“However, no effect of lutein (10 mg)/zeaxanthin (2mg) supplementation on cognitive function was found in the Age-Related Eye Disease Study 2 (AREDS2) trial of older persons at risk of late age-related macular degeneration.(34) The negative trial results should not be interpreted as being inconsistent with the epidemio…”
Effect of nutrition on neurodegenerative diseases. A systematic review
Bianchi, V. E., Herrera, P. F., & Rizzi, L. (2019) · Nutritional Neuroscience · doi:10.1080/1028415x.2019.1681088 · Cited by 268
“Chew, 2015 [107] 3073 risk of mavular degenration.”
Dietary supplements and disease prevention — a global overview
Rautiainen, S., Manson, J. E., Lichtenstein, A. H., & Sesso, H. D. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.54 · Cited by 252
Zinkernagel, M. S., Zysset-Burri, D. C., Keller, I., Berger, L. E., Leichtle, A. B., Largiadèr, C. R., Fiedler, G. M., & Wolf, S. (2017) · Scientific Reports · doi:10.1038/srep40826 · Cited by 229
Geerlings, M. J., de Jong, E. K., & den Hollander, A. I. (2016) · Molecular Immunology · doi:10.1016/j.molimm.2016.11.016 · Cited by 209
Schunck, W., Konkel, A., Fischer, R., & Weylandt, K. H. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.10.016 · Cited by 211
Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease
Abdelhamid, A. S., Martin, N., Bridges, C., Brainard, J. S., Wang, X., Brown, T. J., Hanson, S., Jimoh, F. O., Ajabnoor, S. M., Deane, K. H., et al. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012345.pub2 · Cited by 194
Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications
Xie, S., Xu, S., Deng, W., & Tang, Q. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01378-8 · Cited by 197
Rutjes, A. W., Denton, D. A., Di Nisio, M., Chong, L.-Y., Abraham, R. P., Al-Assaf, A. S., Anderson, J. L., Malik, M. A., Vernooij, R. W., Martínez, G., et al. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011906.pub2 · Cited by 164
Impact of dietary fats on brain functions
Chianese, R., Coccurello, R., Viggiano, A., Scafuro, M., Fiore, M., Coppola, G., Operto, F. F., Fasano, S., Laye, S., Pierantoni, R., et al. (2018) · Current Neuropharmacology · doi:10.2174/1570159x15666171017102547 · Cited by 159
“5 years Cognitive function No effect [284]”
Oulhaj, A., Jernerén, F., Refsum, H., Smith, A. D., & de Jager, C. A. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150777 · Cited by 166
Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease
Abdelhamid, A. S., Martin, N., Bridges, C., Brainard, J. S., Wang, X., Brown, T. J., Hanson, S., Jimoh, F. O., Ajabnoor, S. M., Deane, K. H., et al. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012345.pub3 · Cited by 151
Van Dael, P. (2021) · Nutrition Research and Practice · doi:10.4162/nrp.2021.15.2.137 · Cited by 138
The Pharmacological Effects of Lutein and Zeaxanthin on Visual Disorders and Cognition Diseases
Jia, Y.-P., Sun, L., Yu, H., Liang, L.-P., Li, W., Ding, H., Song, X.-B., & Zhang, L.-J. (2017) · Molecules · doi:10.3390/molecules22040610 · Cited by 146
“Among older persons with AMD, oral supplementation with LCPUFAs or L/Z had no statistically significant effect on cognitive function [107].”
BackgroundSala‐Vila, A., Valls‐Pedret, C., Rajaram, S., Coll‐Padrós, N., Cofán, M., Serra‐Mir, M., Pérez-Heras, A., Roth, I., Freitas-Simoes, T. M., Doménech, M., et al. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqz328 · Cited by 121
Promoting brain health through exercise and diet in older adults: a physiological perspective
Jackson, P. A., Pialoux, V., Corbett, D., Drogos, L. L., Erickson, K. I., Eskes, G. A., & Poulin, M. J. (2015) · The Journal of Physiology · doi:10.1113/jp271270 · Cited by 118
“…and DHA in high quantities (Witte et al. 2014), which may explain the null effects on cognition of a recent 5 year omega-3 PUFA supplementation study in older adults who were at risk for developing age-related macular degeneration (Chew et al. 2015), a possibility that requires further exploration.”
BackgroundOmega-3 fatty acids and cognitive function
Welty, F. K. (2022) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000862 · Cited by 121
Resveratrol ameliorates spatial learning memory impairment induced by Aβ 1–42 in rats
Wang, R., Zhang, Y., Li, J., & Zhang, C. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.08.051 · Cited by 109
“Although a number of therapeutic interventions, including vitamin E (Farina et al., 2012; Dysken et al., 2014), statins (Feldman et al., 2010; Sano et al., 2011) and omega-3 fatty acids (Chew et al., 2015), have been applied, none proved effective when tested in the clinic.”
Patted, P. G., Masareddy, R. S., Patil, A. S., Kanabargi, R., & Bhat, C. T. (2024) · Future Journal of Pharmaceutical Sciences · doi:10.1186/s43094-024-00667-5 · Cited by 126
“…tissues such as the brain, the presence of DHA in phospholipid membranes provides a stabilizing and protective impact that contributes to preserving the integrity of neural tissues and cell membranes, thereby improving cognitive function in conditions of Alzheimer’s disease and dementia [26–28].”
BackgroundDeane, K. H., Jimoh, F. O., Biswas, P., O'Brien, A. T., Hanson, S., Abdelhamid, A. S., Fox, C., & Hooper, L. (2019) · The British Journal of Psychiatry · doi:10.1192/bjp.2019.234 · Cited by 108
Zysset-Burri, D. C., Keller, I., Berger, L. E., Largiadèr, C. R., Wittwer, M., Wolf, S., & Zinkernagel, M. S. (2020) · npj Genomic Medicine · doi:10.1038/s41525-020-00141-0 · Cited by 94
Nrf2 Is an Attractive Therapeutic Target for Retinal Diseases
Nakagami, Y. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/7469326 · Cited by 100
“Drusen deposits, which are initially formed by oxidized lipids, have been shown to be associated with AMD, along with laminar deposits in Bruch’s membrane [5, 6].”
BackgroundInfluentialMancinelli, A. C., Mattioli, S., Twining, C. W., Bosco, A. D., Donoghue, A. M., Arsi, K., Angelucci, E., Chiattelli, D., & Castellini, C. (2022) · Nutrients · doi:10.3390/nu14091969 · Cited by 97
“Accordingly, a lower concentration of DHA was found in the serum of patients affected by AD as compared to healthy people [50], suggesting that n-3 LC-PUFA could represent a preventative strategy against AD, especially when consumed in the early stage of the disease [51].”
BackgroundWood, A. H. R., Chappell, H. F., & Zulyniak, M. A. (2021) · European Journal of Nutrition · doi:10.1007/s00394-021-02655-4 · Cited by 95
Computer-Aided Diagnosis in Ophthalmology
Kazi, K. S. L. (2024) · Advances in healthcare information systems and administration book series · doi:10.4018/979-8-3693-3661-8.ch006 · Cited by 92
Bioactive nutrients - Time for tolerable upper intake levels to address safety
Yates, A. A., Erdman, J. W., Shao, A. E., Dolan, L. C., & Griffiths, J. C. (2017) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2017.01.002 · Cited by 81
“More recently the AREDS2 trial was completed where some subjects received 10 mg/ day of lutein plus 2 mg/day of zeaxanthin for 5 years (Chew et al., 2015) with no adverse events from the lutein-zeaxanthin supplement reported.”
BackgroundEffects of lutein supplementation in age-related macular degeneration
Feng, L., Nie, K., Jiang, H., & Fan, W. (2019) · PLoS ONE · doi:10.1371/journal.pone.0227048 · Cited by 79
Microbiota and Ocular Diseases
Xue, W., Li, J. J., Zou, Y., Zou, B., & Wei, L. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.759333 · Cited by 81
“Oral supplements, antioxidants, minerals, and a diet containing carotenoids have been found in the Age-Related Eye Disease Studies (AREDS and AREDS2) to reduce the risk of AMD progression (Chew et al., 2015).”
BackgroundD’Cunha, N. M., Georgousopoulou, E. N., Dadigamuwage, L., Kellett, J., Panagiotakos, D. B., Thomas, J., McKune, A. J., Mellor, D. D., & Naumovski, N. (2018) · British Journal of Nutrition · doi:10.1017/s0007114517003452 · Cited by 68
“Chew et al.((40)) n-3 FA, Lutein and zeaxanthin USA 2×2 factorial, double-blind, placebocontrolled RCT Inclusion criteria: individuals at high risk of AMD Exclusion: previous ocular disease or retinal surgery procedure, previous supplementation with 2mg or more of lutein and/or 500mg of n-3 for 1 year or more n 3741 (…”
BackgroundMethodInfluentialBrainard, J. S., Jimoh, F. O., Deane, K. H., Biswas, P., Donaldson, D. H., Maas, K., Abdelhamid, A. S., Hooper, L., Ajabnoor, S. M., AlAbdulghafoor, F., et al. (2020) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2020.02.022 · Cited by 70
Jernerén, F., Cederholm, T., Refsum, H., Smith, A. D., Turner, C., Palmblad, J. E. W., Eriksdotter, M., Hjorth, E., Irving, G. F., Wahlund, L., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-181148 · Cited by 66
Acute EPA-induced learning and memory impairment in mice is prevented by DHA
Liu, J.-H., Wang, Q., You, Q.-L., Li, Z.-L., Hu, N.-Y., Wang, Y., Jin, Z.-L., Li, S.-J., Li, X.-W., Yang, J.-M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19255-1 · Cited by 77
Alex, A., Abbott, K. A., McEvoy, M., Schofield, P. W., & Garg, M. L. (2019) · Nutrition Reviews · doi:10.1093/nutrit/nuz073 · Cited by 66
Role of antioxidants and a nutrient rich diet in Alzheimer's disease
Veurink, G., Perry, G. L., & Singh, S. K. (2020) · Open Biology · doi:10.1098/rsob.200084 · Cited by 69
Danthiir, V., Hosking, D. E., Nettelbeck, T., Vincent, A. D., Wilson, C. J., O’Callaghan, N. J., Calvaresi, E., Clifton, P. M., & Wittert, G. (2018) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqx077 · Cited by 61
Zinc in Cognitive Impairment and Aging
Sun, R., Wang, J., Feng, J., & Cao, B. (2022) · Biomolecules · doi:10.3390/biom12071000 · Cited by 70
Feeney, J., O’Leary, N., Moran, R., O’Halloran, A. M., Nolan, J. M., Beatty, S., Young, I. S., & Kenny, R. A. (2017) · The Journals of Gerontology Series A · doi:10.1093/gerona/glw330 · Cited by 61
“Results from studies investigating the effects of supplementation or increasing dietary intake of lutein and zeaxanthin on cognition in a healthy elderly population have been contradictory, with some showing a beneficial effect on cognitive performance (19,20), and others finding no effect (21,22).”
BackgroundResultAbdullah, L. I., Evans, J. E., Emmerich, T., Crynen, G. C., Shackleton, B., Keegan, A. P., Luis, C. A., Tai, L. M., LaDu, M. J., MULLAN, M. J., et al. (2017) · Aging · doi:10.18632/aging.101203 · Cited by 63
Solfrizzi, V., Agosti, P., Lozupone, M., Custodero, C., Schilardi, A., Valiani, V., Sardone, R., Dibello, V., Lena, L. D., Lamanna, A., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179940 · Cited by 63
Lindbergh, C. A., Mewborn, C. M., Hammond, B. R., Renzi‐Hammond, L. M., Curran‐Celentano, J., & Miller, L. S. (2016) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617716000850 · Cited by 61
Beydoun, M. A., Beydoun, H. A., Kuczmarski, M. F., Weiss, J., Hossain, S. A., Canas, J. A., Evans, M. K., & Zonderman, A. B. (2022) · Neurology · doi:10.1212/wnl.0000000000200289 · Cited by 59
“Nevertheless, a recent randomized controlled trial of >3,000 participants with age-related macular degeneration (AREDS2 study) showed that supplementation with omega-3 fatty acids and lutein/zeaxanthin had no significant effect on cognitive function.(30)”
BackgroundOxidative Stress and Microglial Response in Retinitis Pigmentosa
Murakami, Y., Nakabeppu, Y., & Sonoda, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197170 · Cited by 57
A Comprehensive Review of Eggs, Choline, and Lutein on Cognition Across the Life-span
Wallace, T. C. (2018) · Journal of the American College of Nutrition · doi:10.1080/07315724.2017.1423248 · Cited by 53
Lipophilic antioxidants in neurodegenerative diseases
Chang, K., Cheng, M., Chiang, M.-C., & Chen, C. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.06.031 · Cited by 59
Cederholm, T. (2016) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000350 · Cited by 59
Acyl-CoA synthetases as regulators of brain phospholipid acyl-chain diversity
Fernandez, R. F., & Ellis, J. M. (2020) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2020.102175 · Cited by 53
Zinc Therapy in Early Alzheimer’s Disease: Safety and Potential Therapeutic Efficacy
Squitti, R., Pal, A., Picozza, M., Avan, A., Ventriglia, M., Rongioletti, M. C. A., & Hoogenraad, T. U. (2020) · Biomolecules · doi:10.3390/biom10081164 · Cited by 62
Prevention of cognitive impairment: scientific guidance and windows of opportunity
Gorelick, P. B. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14113 · Cited by 49
“Other select interventional studies that focused mainly on a single intervention (e.g., exercise or oral supplementation with nutrients) have not resulted in significant improvements in cognition (Chew et al. 2015; Sink et al. 2015).”
BackgroundLopresti, A. L., Smith, S. J., & Drummond, P. D. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.843512 · Cited by 48
“However, in a large 5-year study on older-age adults with intermediate or advanced age-related macular degeneration, lutein and zeaxanthin supplementation did not change cognitive function as measured by several telephone-administered cognitive tasks (24).”
BackgroundMedicinal plants and natural products as neuroprotective agents in age-related macular degeneration
Bosch‐Morell, F., Villagrasa, V., Ortega, T., Acero, N., Mingarro, D. M., González‐Rosende, M. E., Castillo, E., Sanahuja, M. A., Soriano, P., & Martínez‐Solís, I. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.284978 · Cited by 47
Walia, V., Kaushik, D., Mittal, V., Kumar, K., Verma, R., Parashar, J., Akter, R., Rahman, M. H., Bhatia, S., Al-Harrasi, A., et al. (2022) · Molecular Neurobiology · doi:10.1007/s12035-021-02617-1 · Cited by 47
A Review of the Role of the Intestinal Microbiota in Age-Related Macular Degeneration
Lin, P., McClintic, S. M., Nadeem, U., & Skondra, D. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10102072 · Cited by 48
“While analysis of the role of nutritional factors is notoriously difficult, an oral supplement containing the carotenoids lutein and zeaxanthin, or beta-carotene (original formulation), minerals, and antioxidants was found by the Age-Related Eye Disease Studies (AREDS and AREDS2) to reduce the risk of AMD progression…”
BackgroundRangel-Huerta, Ó. D., & Gil, Á. (2017) · Nutrition Reviews · doi:10.1093/nutrit/nux064 · Cited by 52
Zhou, X., Wang, S., Ding, X., Li, Q., Mao, Y., Chen, L., Li, W., & Ying, C. (2017) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2017.06.001 · Cited by 45
Dietary total antioxidant capacity in relation to depression and anxiety in Iranian adults
Milajerdi, A., Keshteli, A. H., Afshar, H., Esmaillzadeh, A., & Adibi, P. (2018) · Nutrition · doi:10.1016/j.nut.2018.11.017 · Cited by 47
Mazereeuw, G., Herrmann, N., OH, P. I., David, W. L., Wang, C. T., Kiss, A., & Lanctôt, K. L. (2016) · Journal of Clinical Psychopharmacology · doi:10.1097/jcp.0000000000000565 · Cited by 47
Modulation of innate immunity of patients with Alzheimer's disease by omega‐3 fatty acids
Fiala, M., Kooij, G., Wagner, K. M., Hammock, B. D., & Pellegrini, M. A. (2017) · The FASEB Journal · doi:10.1096/fj.201700065r · Cited by 44
Andriambelo, B., Stiffel, M., Roke, K., & Plourde, M. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101835 · Cited by 49
Yu, M., Yan, W., & Beight, C. D. (2018) · Nutrients · doi:10.3390/nu10070842 · Cited by 43
The Potential Uses of Omega-3 Fatty Acids in Dermatology: A Review
Thomsen, B. J., Chow, E. Y., & Sapijaszko, M. (2020) · Journal of Cutaneous Medicine and Surgery · doi:10.1177/1203475420929925 · Cited by 46
Unified theory of Alzheimer’s disease (UTAD): implications for prevention and curative therapy
Nehls, M. (2016) · Journal of Molecular Psychiatry · doi:10.1186/s40303-016-0018-8 · Cited by 41
“Another reason for the increase of n-6 PUFAs in our modern diet results from the intense consumption of meat and high fat milk products.”
BackgroundInfluentialSuh, S. W., Lim, E., Burm, S.-Y., Lee, H., Bae, J. B., Han, J. W., & Kim, K. W. (2024) · BMC Medicine · doi:10.1186/s12916-024-03296-0 · Cited by 50
Enriched Brain Omega-3 Polyunsaturated Fatty Acids Confer Neuroprotection against Microinfarction
Luo, C., Ren, H., Yao, X., Shi, Z., Liang, F., Kang, J. X., Wan, J., Pei, Z., Su, K., & Su, H. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.05.028 · Cited by 43
“A large clinical trial with 4000 patients included showed that ω-3 PUFAs supplements did not slow cognitive decline in older people [8].”
BackgroundKeenan, T. D. L., Agrón, E., Mares, J. A., Clemons, T. E., van Asten, F., Swaroop, A., & Chew, E. Y. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12077 · Cited by 41
Self-citationNon-Enzymatic Antioxidants against Alzheimer’s Disease: Prevention, Diagnosis and Therapy
Varesi, A., Campagnoli, L. I. M., Carrara, A., Pola, I., Floris, E., Ricevuti, G., Chirumbolo, S., & Pascale, A. (2023) · Antioxidants · doi:10.3390/antiox12010180 · Cited by 51
“Nevertheless, results from the “Age-Related Eye Disease Study 2” (AREDS2) randomized trial report no significant benefits of lutein and zeaxanthin supplementation in terms of cognitive performance among individuals with a high risk of AMD development [75].”
ResultSala-Vila, A., Satizabal, C. L., Tintle, N., Melo van Lent, D., Vasan, R. S., Beiser, A. S., Seshadri, S., & Harris, W. S. (2022) · Nutrients · doi:10.3390/nu14122408 · Cited by 40
van Asten, F., Simmons, M., Singhal, A., Keenan, T. D. L., Ratnapriya, R., Agrón, E., Clemons, T. E., Swaroop, A., Lu, Z., & Chew, E. Y. (2017) · Ophthalmology · doi:10.1016/j.ophtha.2017.09.023 · Cited by 38
Self-citationCognitive function in patients with coronary artery disease: A literature review
Burkauskas, J., Lang, P., Bunevičius, A., Neverauskas, J., Bučiūtė-Jankauskienė, M., & Mickuvienė, N. (2018) · Journal of International Medical Research · doi:10.1177/0300060517751452 · Cited by 43
Kuszewski, J. C., Wong, R. H. X., & Howe, P. R. C. (2017) · Nutrients · doi:10.3390/nu9050487 · Cited by 39
Therapeutic Opportunities for Food Supplements in Neurodegenerative Disease and Depression
Businaro, R., Vauzour, D., Sarris, J. J., Münch, G. W., Gyengési, E., Brogelli, L., & Zuzarte, P. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.669846 · Cited by 42
Nerve Growth Factor-Based Therapy in Alzheimer’s Disease and Age-Related Macular Degeneration
Amadoro, G., Latina, V., Balzamino, B. O., Squitti, R., Varano, M., Calissano, P., & Micera, A. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.735928 · Cited by 44
Screening for Impaired Visual Acuity in Older Adults
Chou, R., Bougatsos, C., Jungbauer, R., Grusing, S., Blazina, I., Selph, S., Jonas, D. E., & Tehrani, S. (2022) · JAMA · doi:10.1001/jama.2022.6381 · Cited by 36
The Emerging Role of Gut Microbiota in Age-Related Macular Degeneration
Xiao, J. F., Zhang, J. Y., Luo, W., He, P. C., & Skondra, D. (2023) · American Journal Of Pathology · doi:10.1016/j.ajpath.2023.04.006 · Cited by 37
“53 e 55 Although the protective mechanisms of these compounds are not completely understood, their impact on the intestinal microbiome and interactions with speci fi c microbiota may be essential to their bioavailability and bene fi cial effects.”
BackgroundImpact of a high-fat diet on the fatty acid composition of the retina
Albouery, M., Buteau, B., Gregoire, S., Martine, L., Gambert, S., Bron, A. M., Acar, N., Chassaing, B., & Bringer, M.-A. (2020) · Experimental Eye Research · doi:10.1016/j.exer.2020.108059 · Cited by 35
Role of nutraceuticals in cognition during aging and related disorders
Singh, P., Sivanandam, T. M., Konar, A., & Thakur, M. K. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104928 · Cited by 37
Microglia and modifiable life factors: Potential contributions to cognitive resilience in aging
Duggan, M. R., & Parikh, V. (2021) · Behavioural Brain Research · doi:10.1016/j.bbr.2021.113207 · Cited by 38
Lenin, R. R., Koh, Y., Zhang, Z., Yeo, Y., Parikh, B. H., Seah, I. Y. J., Wong, W., & Su, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24108763 · Cited by 33
“NCT00345176 was a controlled randomised clinical trial, where the participants were evaluated to have high risk of progression to late AMD [75].”
BackgroundDietary Lutein and Cognitive Function in Adults: A Meta-Analysis of Randomized Controlled Trials
Li, J., & Abdel‐Aal, E. M. (2021) · Molecules · doi:10.3390/molecules26195794 · Cited by 38
“[43] and small sample size of the other two studies [39,45].”
BackgroundMethodResultInfluentialSantos, F. M., Ciordia, S., Mesquita, J., Sousa, J. P. C., Paradela, A., Tomaz, C. T., & Passarinha, L. A. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04670-y · Cited by 38
Diabetes, Edentulism, and Cognitive Decline: A 12-Year Prospective Analysis
Wu, B., Luo, H., Tan, C., Qi, X., Sloan, F. A., Kamer, A. R., Schwartz, M. D., Martinez, M., & Plassman, B. L. (2023) · Journal of Dental Research · doi:10.1177/00220345231155825 · Cited by 33
“…to changes in dietary intake and diversity (De Marchi et al. 2008); DM-related impaired glucose tolerance and insulin sensitivity (Ojo and Brooke 2015) could partially contribute to a nutritional deficiency—all of which are risk factors for cognitive impairment and dementia (Chew et al. 2015).”
BackgroundMao, D., Tao, B., Sheng, S., Jin, H. Z., Chen, W., Gao, H., Deng, J., Li, Z., Chen, F., Chan, S., et al. (2023) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.64.12.32 · Cited by 32
Thoene, M. K., Anderson‐Berry, A., Ormer, M. V., Furtado, J. D., Soliman, G. A., Goldner, W. S., & Hanson, C. (2019) · Nutrients · doi:10.3390/nu11010134 · Cited by 30
Dietary Interventions to Prevent or Delay Alzheimer’s Disease: What the Evidence Shows
Bartochowski, Z., Conway, J., Wallach, Y., Chakkamparambil, B., Alakkassery, S., & Grossberg, G. T. (2020) · Current Nutrition Reports · doi:10.1007/s13668-020-00333-1 · Cited by 31
Rôżanowska, M., Czuba-Pełech, B., Landrum, J. T., & Różanowski, B. (2021) · Antioxidants · doi:10.3390/antiox10050753 · Cited by 30
Controversies in omega-3 efficacy and novel concepts for application
Radcliffe, J., Thomas, J., Bramley, A. L., Kouris‐Blazos, A., Radford, B. E., Scholey, A. B., Pipingas, A., Thomas, C., & Itsiopoulos, C. (2016) · Journal of Nutrition & Intermediary Metabolism · doi:10.1016/j.jnim.2016.05.002 · Cited by 27
Malik, A., Ramadan, A., Vemuri, B., Siddiq, W., Amangurbanova, M., Ali, A., & Welty, F. K. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa420 · Cited by 26
Rivier, C. A., Renedo, D. B., de Havenon, A., Sunmonu, N. A., Gill, T. M., Payabvash, S., Sheth, K. N., & Falcone, G. J. (2023) · Neurology · doi:10.1212/wnl.0000000000208010 · Cited by 26
A Review of the Impact of Alterations in Gut Microbiome on the Immunopathogenesis of Ocular Diseases
Bu, Y., Chan, Y. K., Wong, H. L., Poon, S. H. L., Lo, A., Shih, K. C., & Tong, L. H. T. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10204694 · Cited by 27
Zhang, J. Y., Xie, B., Barba, H., Nadeem, U., Movahedan, A., Deng, N., Spedale, M., D’Souza, M., Luo, W., Leone, V., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179676 · Cited by 24
Carotenoid Supplementation for Alleviating the Symptoms of Alzheimer’s Disease
Flieger, J., Forma, A., Flieger, W., Flieger, M., Gawlik, P. J., Dzierżyński, E., Maciejewski, R., Teresiński, G., & Baj, J. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168982 · Cited by 30
“…supplementation with long-chain polyun-saturated fatty acids (LCPUFAs) (1 g) and/or lutein (10 mg)/zeaxanthin (2 mg) on cognitive function was reported in another double-blind, randomized clinical trial [306]. group, carotenes such as β -carotene and α -carotene, or apocarotenoid cis configuration.”
BackgroundAhmad, N., Hussain, A., Khan, S., Korma, S. A., Hussain, G., Aadil, R. M., Siddique, R., Ali, A., Shabbir, U., Haq, A. U., et al. (2021) · Food Science & Nutrition · doi:10.1002/fsn3.2236 · Cited by 23
“The National Institute of the United States recommended 650 mg of fish fatty acids daily (Chew et al., 2015).”
Background
Metadata
- Authors
- Chew, E. Y., Clemons, T. E., Agrón, E., Launer, L. J., Grodstein, F., & Bernstein, P. S.
- Affiliations
- National Institutes of Health (US)
- Emmes (United States) (US)
- Brigham and Women's Hospital (US)
- University of Utah (US)
- Corresponding author
- Chew, Emily Y.
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2015-08-25
- Volume
- 314
- Issue
- 8
- Pages
- 791
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC5369607
- OpenAlex
- W2164097888
- Cited by
- 191
- References
- 29
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 16 · 2023: 17 · 2022: 19 · 2021: 22 · 2020: 24 · 2019: 9 · 2018: 18 · 2017: 19 · 2016: 17 · 2015: 9
- FWCI
- 20.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 EY999999)
- U.S. Public Health Service (HHS-N-260-2005-00007-C)
- National Eye Institute (ZIAEY000485, N01-EY-5-0007)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- omega-3 fatty acids, long-chain polyunsaturated fatty acids, lutein, zeaxanthin, cognitive function, age-related macular degeneration, AREDS2, dietary supplementation, vitamin E, vitamin C, beta-carotene, zinc, cognitive decline, Alzheimer's disease risk, macular pigment, older adults
- MeSH terms
- Aged, Aged, 80 and over, Algorithms, Ascorbic Acid, Cognition, Copper, Docosahexaenoic Acids, Double-Blind Method, Female, Hispanic or Latino, Humans, Macular Degeneration, Male, Middle Aged, Neuropsychological Tests, Time Factors, Vitamins, Lutein, Zinc Oxide, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Outcome Assessment, Health Care, beta Carotene, Dietary Supplements, Racial Groups, Medication Adherence, Lost to Follow-Up, Zeaxanthins
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