Nutrients and Alzheimer’s Disease

Dementia. https://www.who.int/news-room/fact-sheets/detail/dementia.

What is Alzheimer’s Disease? https://www.cdc.gov/aging/aginginfo/alzheimers.htm (2023).

What Causes Alzheimer’s Disease? https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-causes-alzheimers-disease (2024).

How is Alzheimer’s Disease Treated?. https://www.nia.nih.gov/health/alzheimers-treatment/how-alzheimers-disease-treated.

Petersson, S. D. & Philippou, E. Mediterranean Diet, Cognitive Function, and Dementia: A Systematic Review of the Evidence. Adv. Nutr. 7, (2016).

Bloom, G. S. Amyloid-β and Tau: The Trigger and Bullet in Alzheimer Disease Pathogenesis. JAMA Neurol. 71, 505–508 (2014).

van Dyck, C. H. et al. Lecanemab in Early Alzheimer’s Disease. N. Engl. J. Med. 388, 9–21 (2023).

Danysz, W. & Parsons, C. G. Alzheimer’s disease, β-amyloid, glutamate, NMDA receptors and memantine – searching for the connections. Br. J. Pharmacol. 167, 324–352 (2012).

Berti, V. et al. Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults. Neurology 90, e1789–e1798 (2018).

David Smith, A. et al. Homocysteine and Dementia: An International Consensus Statement. J. Alzheimers. Dis. 62, 561 (2018).

Fratoni, V. & Brandi, M. L. B Vitamins, Homocysteine and Bone Health. Nutrients 7, 2176 (2015).

Ganguly, P. & Alam, S. F. Role of homocysteine in the development of cardiovascular disease. Nutr. J. 14, 1–10 (2015).

Homocysteine-methionine cycle is a metabolic sensor system controlling methylation-regulated pathological signaling. Redox Biology 28, 101322 (2020).

Vitamin B6s inhibit oxidative stress caused by Alzheimer’s disease-related CuII-β-amyloid complexes—cooperative action of phospho-moiety. Bioorg. Med. Chem. Lett. 21, 6430–6432 (2011).

Martínez, Y. et al. The role of methionine on metabolism, oxidative stress, and diseases. Amino Acids 49, 2091–2098 (2017).

Iskusnykh, I. Y., Zakharova, A. A. & Pathak, D. Glutathione in Brain Disorders and Aging. Molecules 27, (2022).

Alzheimer’s disease pathogenesis: Is there a role for folate? Mech. Ageing Dev. 174, 86–94 (2018).

Critical levels of brain atrophy associated with homocysteine and cognitive decline. Neurobiol. Aging 35, S35–S39 (2014).

de Jager, C. A., Oulhaj, A., Jacoby, R., Refsum, H. & David Smith, A. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int. J. Geriatr. Psychiatry 27, 592–600 (2012).

Meng, H. et al. The relationship between cognitive impairment and homocysteine in a B12 and folate deficient population in China: A cross-sectional study. Medicine 98, e17970 (2019).

Wang, Q., Zhao, J., Chang, H., Liu, X. & Zhu, R. Homocysteine and Folic Acid: Risk Factors for Alzheimer’s Disease—An Updated Meta-Analysis. Front. Aging Neurosci. 13, 665114 (2021).

O’Brien, R. J. & Wong, P. C. Amyloid Precursor Protein Processing and Alzheimer’s Disease. Annu. Rev. Neurosci. 34, 185 (2011).

Seshadri, S. et al. Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer’s Disease. (2002) doi:10.1056/NEJMoa011613.

Chen, H. et al. Folic Acid Supplementation Mitigates Alzheimer’s Disease by Reducing Inflammation: A Randomized Controlled Trial. Mediators Inflamm. 2016, 5912146 (2016).

An, Y. et al. Dietary intakes and biomarker patterns of folate, vitamin B6, and vitamin B12 can be associated with cognitive impairment by hypermethylation of redox-related genes NUDT15 and TXNRD1. Clin. Epigenetics 11, 1–19 (2019).

Lloret, A., Esteve, D., Monllor, P., Cervera-Ferri, A. & Lloret, A. The Effectiveness of Vitamin E Treatment in Alzheimer’s Disease. Int. J. Mol. Sci. 20, 879 (2019).

Grimm, M. O. W., Mett, J. & Hartmann, T. The Impact of Vitamin E and Other Fat-Soluble Vitamins on Alzheimer´s Disease. Int. J. Mol. Sci. 17, 1785 (2016).

Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radical Biology and Medicine 72, 76–90 (2014).

Gugliandolo, A., Bramanti, P. & Mazzon, E. Role of Vitamin E in the Treatment of Alzheimer’s Disease: Evidence from Animal Models. Int. J. Mol. Sci. 18, 2504 (2017).

Pizzino, G. et al. Oxidative Stress: Harms and Benefits for Human Health. Oxid. Med. Cell. Longev. 2017, (2017).

Alfadda, A. A. & Sallam, R. M. Reactive Oxygen Species in Health and Disease. Biomed Res. Int. 2012, 936486 (2012).

Snezhkina, A. V. et al. ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells. Oxid. Med. Cell. Longev. 2019, (2019).

Sharifi-Rad, M. et al. Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases. Front. Physiol. 11, 552535 (2020).

Zhao, Y. & Zhao, B. Oxidative Stress and the Pathogenesis of Alzheimer′s Disease. Oxid. Med. Cell. Longev. 2013, 316523 (2013).

Ansari, M. A. & Scheff, S. W. Oxidative Stress in the Progression of Alzheimer Disease in the Frontal Cortex. J. Neuropathol. Exp. Neurol. 69, 155–167 (2010).

Oxidative stress, protein modification and Alzheimer disease. Brain Res. Bull. 133, 88–96 (2017).

The role of antioxidants in the chemistry of oxidative stress: A review. Eur. J. Med. Chem. 97, 55–74 (2015).

Barrera, G. Oxidative Stress and Lipid Peroxidation Products in Cancer Progression and Therapy. International Scholarly Research Notices 2012, 137289 (2012).

Huang, W., Zhang, X. & Chen, W. Role of oxidative stress in Alzheimer’s disease (Review). Biomedical Reports 4, 519–522 (2016).

Rango, M. & Bresolin, N. Brain Mitochondria, Aging, and Parkinson’s Disease. Genes 9, 250 (2018).

Emerging roles of oxidative stress in brain aging and Alzheimer’s disease. Neurobiol. Aging 107, 86–95 (2021).

Lobo, V., Patil, A., Phatak, A. & Chandra, N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn. Rev. 4, 118 (2010).

Multiple signaling events in amyloid β-induced, oxidative stress-dependent neuronal apoptosis. Free Radical Biology and Medicine 35, 45–58 (2003).

Relation of the tocopherol forms to incident Alzheimer disease and to cognitive change. Am. J. Clin. Nutr. 81, 508–514 (2005).

Tocopherols and tocotrienols plasma levels are associated with cognitive impairment. Neurobiol. Aging 33, 2282–2290 (2012).

da Silva, S. L. et al. Plasma nutrient status of patients with Alzheimer’s disease: Systematic review and meta-analysis. Alzheimers. Dement. 10, 485–502 (2014).

Dysken, M. W. et al. Effect of Vitamin E and Memantine on Functional Decline in Alzheimer Disease: The TEAM-AD VA Cooperative Randomized Trial. JAMA 311, 33–44 (2014).

Catharine Ross, A., Taylor, C. L., Yaktine, A. L. & Del Valle, H. B. Dietary Reference Intakes for Calcium and Vitamin D. (2011) doi:10.17226/13050.

Catharine Ross, A., Taylor, C. L., Yaktine, A. L. & Del Valle, H. B. Overview of Vitamin D. in Dietary Reference Intakes for Calcium and Vitamin D (National Academies Press (US), 2011).

Banerjee, A. et al. Vitamin D and Alzheimer’s Disease: Neurocognition to Therapeutics. International Journal of Alzheimer’s Disease 2015, 192747 (2015).

Zong, L., Chu, P., Huang, P., Guo, Y. & Lv, Y. Effect of vitamin D on the learning and memory ability of FGR rat and NMDA receptor expression in hippocampus. Exp. Ther. Med. 14, 581–586 (2017).

Vitamin D and the brain: Key questions for future research. J. Steroid Biochem. Mol. Biol. 148, 305–309 (2015).

Behl, T. et al. Understanding the role of ‘sunshine vitamin D’ in Parkinson"s disease: A review. Front. Pharmacol. 13, 993033 (2022).

The vitamin D receptor in dopamine neurons; its presence in human substantia nigra and its ontogenesis in rat midbrain. Neuroscience 236, 77–87 (2013).

Vitamin D and the risk of dementia and Alzheimer disease. Neurology https://www.neurology.org/doi/10.1212/WNL.0000000000000755.

Habib, A. M., Nagi, K., Thillaiappan, N. B., Sukumaran, V. & Akhtar, S. Vitamin D and Its Potential Interplay With Pain Signaling Pathways. Front. Immunol. 11, 523854 (2020).

Papuć, E. & Rejdak, K. The role of myelin damage in Alzheimer’s disease pathology. Arch. Med. Sci. 16, 345 (2020).

Chabas, J.-F. et al. Cholecalciferol (Vitamin D3) Improves Myelination and Recovery after Nerve Injury. PLoS One 8, e65034 (2013).

Inadequate supply of vitamins and DHA in the elderly: Implications for brain aging and Alzheimer-type dementia. Nutrition 31, 261–275 (2015).

Vitamin D, cognition, and dementia. Neurology https://www.neurology.org/doi/10.1212/WNL.0b013e31826c197f.

Llewellyn, D. J. et al. Vitamin D and Risk of Cognitive Decline in Elderly Persons. Arch. Intern. Med. 170, 1135–1141 (2010).

Vitamin D deficiency exacerbates Alzheimer-like pathologies by reducing antioxidant capacity. Free Radical Biology and Medicine 161, 139–149 (2020).

Ma, T. et al. GPX4-independent ferroptosis—a new strategy in disease’s therapy. Cell Death Discovery 8, 1–8 (2022).

Liu, J., Xia, X. & Huang, P. xCT: A Critical Molecule That Links Cancer Metabolism to Redox Signaling. Mol. Ther. 28, 2358 (2020).

Wang, R. & Hemachandra Reddy, P. Role of glutamate and NMDA receptors in Alzheimer’s disease. J. Alzheimers. Dis. 57, 1041 (2017).

Institute of Medicine (US) Forum on Neuroscience & Disorders, N. S. Overview of the Glutamatergic System. in Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary (National Academies Press (US), 2011).

Ghahremani, M. et al. Vitamin D supplementation and incident dementia: Effects of sex, APOE, and baseline cognitive status. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring 15, e12404 (2023).

Maoka, T. Carotenoids as natural functional pigments. J. Nat. Med. 74, 1 (2020).

Vitamin A and Carotenoids. https://ods.od.nih.gov/factsheets/VitaminA-Consumer/.

Loskutova, E., Nolan, J., Howard, A. & Beatty, S. Macular Pigment and Its Contribution to Vision. Nutrients 5, 1962 (2013).

Carotenoids in human nutrition and health. Arch. Biochem. Biophys. 652, 18–26 (2018).

Young, A. J. & Lowe, G. L. Carotenoids-Antioxidant Properties. Antioxidants (Basel) 7, (2018).

Dorey, C. K., Gierhart, D., Fitch, K. A., Crandell, I. & Craft, N. E. Low Xanthophylls, Retinol, Lycopene, and Tocopherols in Grey and White Matter of Brains with Alzheimer’s Disease. J. Alzheimers. Dis. 94, 1–17 (2023).

Hammond, B. R. et al. Effects of Lutein/Zeaxanthin Supplementation on the Cognitive Function of Community Dwelling Older Adults: A Randomized, Double-Masked, Placebo-Controlled Trial. Front. Aging Neurosci. 9, 243556 (2017).

Mozaffarieh, M., Sacu, S. & Wedrich, A. The role of the carotenoids, lutein and zeaxanthin, in protecting against age-related macular degeneration: a review based on controversial evidence. Nutr. J. 2, 20 (2003).

Pandey, K. B. & Rizvi, S. I. Plant polyphenols as dietary antioxidants in human health and disease. Oxid. Med. Cell. Longev. 2, 270 (2009).

Abbas, M. et al. Natural polyphenols: An overview. Int. J. Food Prop. (2017) doi:10.1080/10942912.2016.1220393.

Antioxidant properties of natural polyphenols and their therapeutic potentials for Alzheimer’s disease. Brain Res. Bull. 87, 144–153 (2012).

Zwolak, I. Epigallocatechin Gallate for Management of Heavy Metal-Induced Oxidative Stress: Mechanisms of Action, Efficacy, and Concerns. Int. J. Mol. Sci. 22, (2021).

Weinreb, O., Amit, T., Mandel, S. & Youdim, M. B. H. Neuroprotective molecular mechanisms of (−)-epigallocatechin-3-gallate: a reflective outcome of its antioxidant, iron chelating and neuritogenic properties. Genes Nutr. 4, 283 (2009).

Fernandes, L., Cardim-Pires, T. R., Foguel, D. & Palhano, F. L. Green Tea Polyphenol Epigallocatechin-Gallate in Amyloid Aggregation and Neurodegenerative Diseases. Front. Neurosci. 15, 718188 (2021).

The Haber–Weiss reaction and mechanisms of toxicity. Toxicology 149, 43–50 (2000).

Flora, S. J. S. & Pachauri, V. Chelation in Metal Intoxication. Int. J. Environ. Res. Public Health 7, 2745 (2010).

Chronic green tea consumption prevents age-related changes in rat hippocampal formation. Neurobiol. Aging 32, 707–717 (2011).

Cordiano, R. et al. Malondialdehyde as a Potential Oxidative Stress Marker for Allergy-Oriented Diseases: An Update. Molecules 28, 5979 (2023).

Bao, J. et al. Epigallocatechin-3-gallate Alleviates Cognitive Deficits in APP/PS1 Mice. Current Medical Science 40, 18–27 (2020).

John, A. & Reddy, P. H. Synaptic basis of Alzheimer’s disease: Focus on synaptic amyloid beta, P-tau and mitochondria. Ageing Res. Rev. 65, 101208 (2021).

Green Tea Consumption and the Risk of Incident Dementia in Elderly Japanese: The Ohsaki Cohort 2006 Study. Am. J. Geriatr. Psychiatry 24, 881–889 (2016).

Green tea supplementation produces better neuroprotective effects than red and black tea in Alzheimer-like rat model. Food Res. Int. 100, 442–448 (2017).

Park, J., Park, R., Jang, M. & Park, Y.-I. Therapeutic Potential of EGCG, a Green Tea Polyphenol, for Treatment of Coronavirus Diseases. Life 11, (2021).

Early Vitamin E supplementation in young but not aged mice reduces Aβ levels and amyloid deposition in a transgenic model of Alzheimer’s disease. http://dx.doi.org/10.1096/fj.03-0961fje doi:10.1096/fj.03-0961fje.

Sun, Y. et al. Extra cup of tea intake associated with increased risk of Alzheimer’s disease: Genetic insights from Mendelian randomization. Front. Nutr. 10, 1052281 (2023).

Folate. https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/.

Vitamin B6. https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/.

Watanabe, F. & Bito, T. Vitamin B sources and microbial interaction. Exp. Biol. Med. 243, 148–158 (2018).

Dietrich, M. et al. Does gamma-tocopherol play a role in the primary prevention of heart disease and cancer? A review. J. Am. Coll. Nutr. 25, 292–299 (2006).

Borel, P., Caillaud, D. & Cano, N. J. Vitamin D bioavailability: state of the art. Crit. Rev. Food Sci. Nutr. 55, 1193–1205 (2015).

Meléndez-Martínez, A. J. et al. A comprehensive review on carotenoids in foods and feeds: status quo, applications, patents, and research needs. Crit. Rev. Food Sci. Nutr. (2022) doi:10.1080/10408398.2020.1867959.

Guasch-Ferré, M., Merino, J., Sun, Q., Fitó, M. & Salas-Salvadó, J. Dietary Polyphenols, Mediterranean Diet, Prediabetes, and Type 2 Diabetes: A Narrative Review of the Evidence. Oxid. Med. Cell. Longev. 2017, (2017).

MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimers. Dement. 11, 1007–1014 (2015).

Aridi, Y. S., Walker, J. L. & Wright, O. R. L. The Association between the Mediterranean Dietary Pattern and Cognitive Health: A Systematic Review. Nutrients 9, 674 (2017).

The Mediterranean Diet, its Components, and Cardiovascular Disease. Am. J. Med. 128, 229–238 (2015).

Mediterranean diet: The role of long-chain ω-3 fatty acids in fish; polyphenols in fruits, vegetables, cereals, coffee, tea, cacao and wine; probiotics and vitamins in prevention of stroke, age-related cognitive decline, and Alzheimer disease. Rev. Neurol. 175, 724–741 (2019).

Zhang, R. et al. The Difference in Nutrient Intakes between Chinese and Mediterranean, Japanese and American Diets. Nutrients 7, 4661–4688 (2015).

García-Montero, C. et al. Nutritional Components in Western Diet Versus Mediterranean Diet at the Gut Microbiota–Immune System Interplay. Implications for Health and Disease. Nutrients 13, 699 (2021).

Clemente-Suárez, V. J., Beltrán-Velasco, A. I., Redondo-Flórez, L., Martín-Rodríguez, A. & Tornero-Aguilera, J. F. Global Impacts of Western Diet and Its Effects on Metabolism and Health: A Narrative Review. Nutrients 15, (2023).