{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:59:55Z","timestamp":1790279995277,"version":"4.1.0"},"reference-count":83,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds for the Central Non-profit Scientific Institution, Agricultural Information Institute, Chinese Academy of Agricultural Sciences","award":["JBYW-AII-2024-09"],"award-info":[{"award-number":["JBYW-AII-2024-09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Polyphenols are a diverse group of plant-derived bioactives that have been investigated as multi-target candidates for the potential prevention and management of neurodegenerative diseases (NDDs). We conducted an integrated bibliometric and mechanistic scoping review covering 12 polyphenol classes and seven major NDDs using records from PubMed, Embase, the Cochrane Library, and Web of Science (1940\u20132024). Research landscapes and emerging themes were mapped using keyword co-occurrence, clustering analyses, and BERTopic modeling. Mechanistic evidence was synthesized across core pathways, including oxidative stress, neuroinflammation, proteostasis (amyloid\/tau and \u03b1-synuclein), mitochondrial dysfunction, and cholinergic modulation, to link preclinical findings with clinical outcomes. Publication output increased markedly after 2000, with China and the United States contributing the most records. Four persistent hotspots were identified: (1) antioxidant and neuroprotective effects (e.g., resveratrol, curcumin); (2) anti-inflammatory activity and intracellular signaling; (3) cognition, aging, and sex-specific responses in clinical research; and (4) animal models of memory impairment. Clinically investigated interventions include epigallocatechin gallate, Ginkgo biloba extracts, olive\/cocoa polyphenols, and flavonoid-rich mixtures; however, limited bioavailability and heterogeneous trial designs constrain the strength of effect estimates. Advances in delivery systems, computational screening, and precision nutrition may improve translation. Overall, polyphenols show multi-target neuroprotective potential, but larger and more standardized clinical trials are needed to support evidence-based nutritional strategies for NDD prevention and management.<\/jats:p>","DOI":"10.3390\/nu18040602","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:06:16Z","timestamp":1770905176000},"page":"602","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Polyphenols and Neurodegenerative Diseases: Knowledge-Mining Insights, Mechanistic Evidence, and Emerging Nutritional Applications"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6846-3796","authenticated-orcid":false,"given":"Xiaomei","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Agricultural Information, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Agricultural Information, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Agricultural Information, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Agricultural Information, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3343-6889","authenticated-orcid":false,"given":"Yiqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Food Science, Sichuan Agricultural University, Ya\u2019an 625014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Medical Information, Chinese Academy of Medical Sciences, Beijing 100190, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Mei","sequence":"additional","affiliation":[{"name":"Institute of Medical Information, Chinese Academy of Medical Sciences, Beijing 100190, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaihong","family":"Yu","sequence":"additional","affiliation":[{"name":"National Science Library, Chinese Academy of Sciences, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojian","family":"Xian","sequence":"additional","affiliation":[{"name":"Institute of Agricultural Information, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Agricultural Information, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7810-2151","authenticated-orcid":false,"given":"Yingli","family":"Nie","sequence":"additional","affiliation":[{"name":"Institute of Agricultural Information, Chinese Academy of Agricultural Sciences, Beijing 100081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12987-024-00557-1","article-title":"Cellular and molecular mechanisms of the blood\u2013brain barrier dysfunction in neurodegenerative diseases","volume":"21","author":"Chen","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref_2","unstructured":"World Health Organization (2025, December 24). Dementia. Fact Sheet. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/dementia."},{"key":"ref_3","unstructured":"World Health Organization (2025, December 24). Launch of WHO\u2019s Parkinson Disease Technical Brief. Departmental Update. Available online: https:\/\/www.who.int\/news\/item\/14-06-2022-launch-of-who-s-parkinson-disease-technical-brief."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1021\/acsfoodscitech.5c00117","article-title":"Pomegranate punicalagin: A comprehensive review of various in vitro and in vivo biological studies","volume":"5","author":"Maqsood","year":"2025","journal-title":"ACS Food Sci. Technol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1089\/ars.2012.4581","article-title":"Dietary (Poly)phenolics in human health: Structures, bioavailability, and evidence of protective effects against chronic diseases","volume":"18","author":"Spencer","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105390","DOI":"10.1016\/j.tifs.2025.105390","article-title":"Citrus phytochemicals in neurodegenerative diseases: Preclinical evidence and clinical potential","volume":"166","author":"Basha","year":"2025","journal-title":"Trends Food Sci. Technol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"215S","DOI":"10.1093\/ajcn\/81.1.215S","article-title":"Polyphenols: Antioxidants and beyond","volume":"81","author":"Scalbert","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12717","DOI":"10.1021\/acs.jafc.1c04687","article-title":"Sesamol attenuates amyloid peptide accumulation and cognitive deficits in APP\/PS1 mice: The mediating role of the gut\u2013brain axis","volume":"69","author":"Liu","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1136\/jnnp-2012-304792","article-title":"Mediterranean diet improves cognition: The PREDIMED-NAVARRA randomized trial","volume":"84","author":"Clavero","year":"2013","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/S1474-4422(19)30141-3","article-title":"Safety and efficacy of epigallocatechin gallate in multiple system atrophy (PROMESA): A randomised, double-blind, placebo-controlled trial","volume":"18","author":"Levin","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1212\/WNL.0000000000002035","article-title":"A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease","volume":"85","author":"Turner","year":"2015","journal-title":"Neurology"},{"key":"ref_12","first-page":"204","article-title":"A randomized, double-blind, placebo-controlled trial of resveratrol with glucose and malate (RGM) to slow the progression of Alzheimer\u2019s disease: A pilot study","volume":"4","author":"Zhu","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"541","DOI":"10.2174\/156720505774932287","article-title":"A randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimer\u2019s type","volume":"2","author":"Schneider","year":"2005","journal-title":"Curr. Alzheimer Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Grabska-Koby\u0142ecka, I., Szpakowski, P., Kr\u00f3l, A., Ksi\u0105\u017cek-Winiarek, D., Koby\u0142ecki, A., G\u0142\u0105bi\u0144ski, A., and Nowak, D. (2023). Polyphenols and Their Impact on the Prevention of Neurodegenerative Diseases and Development. Nutrients, 15.","DOI":"10.3390\/nu15153454"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jff.2017.11.013","article-title":"Effects of chlorogenic acid against aluminium neurotoxicity in ICR mice through chelation and antioxidant actions","volume":"40","author":"Wang","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_16","first-page":"68","article-title":"Natural flavonoids as potential therapeutics in the management of Alzheimer\u2019s disease: A review","volume":"14","author":"Vo","year":"2024","journal-title":"3 Biotech"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103269","DOI":"10.1016\/j.xpro.2024.103269","article-title":"Protocol for conducting bibliometric analysis in bile acid and related research using CiteSpace and VOSviewer software","volume":"5","author":"Du","year":"2024","journal-title":"STAR Protoc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1007\/s10462-024-11011-x","article-title":"Topic modelling through the bibliometrics lens and its technique","volume":"58","author":"Ogunleye","year":"2025","journal-title":"Artif. Intell. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e14264","DOI":"10.1111\/jfbc.14264","article-title":"Health benefits of polyphenols: A concise review","volume":"46","author":"Rana","year":"2022","journal-title":"J. Food Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"164","DOI":"10.2174\/1874070702115010164","article-title":"Polyphenols: A comprehensive review of their nutritional properties","volume":"15","author":"Ebrahimi","year":"2021","journal-title":"Open Biotechnol. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"293","DOI":"10.22271\/journalofsport.2021.v6.i1e.2236","article-title":"Classifications of polyphenols and their potential application in human health and diseases","volume":"6","author":"Prabhu","year":"2021","journal-title":"Int. J. Physiol. Nutr. Phys. Educ."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Di Meo, F., Valentino, A., Petillo, O., Peluso, G., Filosa, S., and Crispi, S. (2020). Bioactive polyphenols and neuromodulation: Molecular mechanisms in neurodegeneration. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072564"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15164","DOI":"10.1007\/s12035-025-05121-y","article-title":"Polyphenols and exercise in mitochondrial biogenesis","volume":"62","author":"Tu","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jalouli, M., Rahman, M.A., Biswas, P., Rahman, H., Harrath, A.H., Lee, I.-S., Kang, S., Choi, J., Park, M.N., and Kim, B. (2025). Targeting natural antioxidant polyphenols to protect neuroinflammation and neurodegenerative diseases: A comprehensive review. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1492517"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Gentile, M.T., Camerino, I., Ciarmiello, L., Woodrow, P., Muscariello, L., De Chiara, I., and Pacifico, S. (2023). Neuro-Nutraceutical polyphenols: How far are we?. Antioxidants, 12.","DOI":"10.3390\/antiox12030539"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yadav, E., Yadav, P., Khan, M.M.U., Singh, H., and Verma, A. (2022). Resveratrol: A potential therapeutic natural polyphenol for neurodegenerative diseases associated with mitochondrial dysfunction. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.922232"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"431","DOI":"10.2174\/1570159X18666200106155127","article-title":"Neuroprotective polyphenols: A modulatory action on neurotransmitter pathways","volume":"18","author":"Rebas","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Naoi, M., Wu, Y., Shamoto-Nagai, M., and Maruyama, W. (2019). Mitochondria in neuroprotection by phytochemicals: Bioactive polyphenols modulate mitochondrial apoptosis system, function and structure. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102451"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/cns.12971","article-title":"Cholinesterase targeting by polyphenols: A therapeutic approach for the treatment of Alzheimer\u2019s disease","volume":"24","author":"Jabir","year":"2018","journal-title":"CNS Neurosci. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kung, H.-C., Lin, K.-J., Kung, C.-T., and Lin, T.-K. (2021). Oxidative stress, mitochondrial dysfunction, and neuroprotection of polyphenols with respect to resveratrol in Parkinson\u2019s disease. Biomedicines, 9.","DOI":"10.3390\/biomedicines9080918"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Arias-S\u00e1nchez, R.A., Torner, L., and Fenton Navarro, B. (2023). Polyphenols and neurodegenerative diseases: Potential effects and mechanisms of neuroprotection. Molecules, 28.","DOI":"10.3390\/molecules28145415"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-016-0779-0","article-title":"Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer\u2019s disease","volume":"14","author":"Moussa","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jalz.2019.06.1236","article-title":"Can resveratrol reverse cognitive and vestibular dysfunction in late-stage postmenopausal women?","volume":"15","author":"Wong","year":"2019","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s40120-021-00271-2","article-title":"Neuroprotective effect of trans-resveratrol in mild to moderate Alzheimer disease: A randomized, double-blind trial","volume":"10","author":"Gu","year":"2021","journal-title":"Neurol. Ther."},{"key":"ref_35","first-page":"123","article-title":"Neurochemical ameliorating of the hippocampus in dyslipidemic Alzheimer patients following silymarin: A double-blind placebo-controlled randomized clinical trial","volume":"37","author":"Rustamzadeh","year":"2023","journal-title":"Med. J. Islam. Repub. Iran"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1080\/1028415X.2023.2301163","article-title":"Adjunctive silymarin supplementation and its effects on disease severity, oxidative stress, and inflammation in patients with Alzheimer\u2019s disease","volume":"27","author":"Navabi","year":"2024","journal-title":"Nutr. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.3233\/JAD-190757","article-title":"Effect of chlorogenic acids on cognitive function in mild cognitive impairment: A randomized controlled crossover trial","volume":"72","author":"Ochiai","year":"2019","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.3233\/JAD-142958","article-title":"Cognitive effects of soy isoflavones in patients with Alzheimer\u2019s disease","volume":"47","author":"Gleason","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_39","first-page":"707","article-title":"Effects of composite supplement containing astaxanthin and sesamin on cognitive functions in people with mild cognitive impairment: A randomized, double-blind, placebo-controlled trial","volume":"63","author":"Ito","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_40","first-page":"469","article-title":"Genistein in the control of AD progression: From molecular mechanisms to clinical improvement: The GENIAL clinical trial (NCT01982578)","volume":"26","author":"Vina","year":"2022","journal-title":"J. Nutr. Health Aging"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/s12603-018-1028-2","article-title":"A combination of essential fatty acids, Panax ginseng extract, and green tea catechins modifies brain fMRI signals in healthy older adults","volume":"22","author":"Carmichael","year":"2018","journal-title":"J. Nutr. Health Aging"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Baba, Y., Inagaki, S., Nakagawa, S., Kaneko, T., Kobayashi, M., and Takihara, T. (2020). Effect of daily intake of green tea catechins on cognitive function in middle-aged and older subjects: A randomized, placebo-controlled study. Molecules, 25.","DOI":"10.3390\/molecules25184265"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e12155","DOI":"10.1002\/trc2.12155","article-title":"Prevention of cognitive decline in subjective cognitive decline APOE \u03b54 carriers after EGCG and a multimodal intervention (PENSA): Study design","volume":"7","author":"Forcano","year":"2021","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.jalz.2018.06.065","article-title":"Cyanidin-3-glucoside rich black rice extract and cognitive function in subjective cognitive impairment older adults: A double-blind, placebo-controlled, randomized clinical trial","volume":"14","author":"Joo","year":"2018","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jagp.2022.10.002","article-title":"A randomised placebo-controlled study of purified anthocyanins on cognition in individuals at increased risk for dementia","volume":"31","author":"Aarsland","year":"2023","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e16994","DOI":"10.1016\/j.heliyon.2023.e16994","article-title":"The effect of grape seed procyanidins extract on cognitive function in elderly people with mild cognitive impairment: A randomized, double-blind, placebo-controlled clinical trial","volume":"9","author":"Li","year":"2023","journal-title":"Heliyon"},{"key":"ref_47","first-page":"914","article-title":"The efficacy of Ginkgo for elderly people with dementia and age-associated memory impairment: New results of a randomized clinical trial","volume":"63","author":"Kessels","year":"2015","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"483","DOI":"10.2147\/NDT.S120790","article-title":"Efficacy and safety of Ginkgo biloba standardized extract in the treatment of vascular cognitive impairment: A randomized, double-blind, placebo-controlled clinical trial","volume":"13","author":"Demarin","year":"2017","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e12278","DOI":"10.1002\/trc2.12278","article-title":"Olive polyphenols and bioavailable glutathione: Promising results in patients diagnosed with mild Alzheimer\u2019s disease","volume":"8","author":"Marianetti","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.ajcnut.2023.10.031","article-title":"Effect of cocoa extract supplementation on cognitive function: Results from the clinic subcohort of the COSMOS trial","volume":"119","author":"Vyas","year":"2024","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.exger.2016.10.004","article-title":"Examining the impact of grape consumption on brain metabolism and cognitive function in patients with mild decline in cognition: A double-blinded placebo controlled pilot study","volume":"87","author":"Lee","year":"2017","journal-title":"Exp. Gerontol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1080\/1028415X.2017.1287833","article-title":"Enhanced neuronal activation with blueberry supplementation in mild cognitive impairment","volume":"21","author":"Boespflug","year":"2018","journal-title":"Nutr. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Krikorian, R., Skelton, M.R., Summer, S.S., Shidler, M.D., and Sullivan, P.G. (2022). Blueberry supplementation in midlife for dementia risk reduction. Nutrients, 14.","DOI":"10.3390\/nu14081619"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1017\/S0007114516004177","article-title":"Montmorency tart cherries (Prunus cerasus L.) modulate vascular function acutely, in the absence of improvement in cognitive performance","volume":"116","author":"Keane","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jns.2010.08.050","article-title":"Effect of an antioxidant drink on homocysteine levels in Alzheimer\u2019s patients","volume":"299","author":"Albaladejo","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.appet.2018.05.204","article-title":"Chronic consumption of orange juice flavonoids is associated with cognitive benefits: An 8-week randomized double-blind placebo-controlled trial in older adults","volume":"130","author":"Kean","year":"2018","journal-title":"Appetite"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1080\/1028415X.2021.1880312","article-title":"The effects of polyphenols-rich tropical fruit juice on cognitive function and metabolomics profile\u2014A randomized controlled trial in middle-aged women","volume":"25","author":"Rosli","year":"2021","journal-title":"Nutr. Neurosci."},{"key":"ref_58","unstructured":"ClinicalTrials.gov (2025, February 14). Use Muscadine Wine Nutraceuticals to Improve Brain Health, Cognition, and Mental Health, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05541887."},{"key":"ref_59","unstructured":"ClinicalTrials.gov (2025, February 16). The Effectiveness of MIND Diet and Forest Bathing on Stress Reduction, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT06351423."},{"key":"ref_60","unstructured":"ClinicalTrials.gov (2025, February 25). Progression rate of MSA Under EGCG Supplementation as Anti-Aggregation-Approach, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02008721."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s00702-016-1507-8","article-title":"The PROMESA-protocol: Progression rate of multiple system atrophy under EGCG supplementation as anti-aggregation-approach","volume":"123","author":"Levin","year":"2016","journal-title":"J. Neural. Transm."},{"key":"ref_62","unstructured":"International Clinical Trials Registry Platform (ICTRP) (2025, February 24). The Effectiveness of Curcumin on Quality of Life, Severity of Illness, Fatigue and Sleep Quality in Parkinson\u2019s Patients. Available online: https:\/\/trialsearch.who.int\/Trial2.aspx?TrialID=IRCT20101209005352N2."},{"key":"ref_63","unstructured":"International Clinical Trials Registry Platform (ICTRP) (2025, February 24). Effect of Polyphenol Rich Extract of Licorice on Improving Symptoms of Parkinson Disease. Available online: https:\/\/trialsearch.who.int\/Trial2.aspx?TrialID=IRCT20120305009204N3."},{"key":"ref_64","unstructured":"ClinicalTrials.gov (2025, February 16). Can a Flavonoid-Rich Pure Cocoa Reduce Fatigue in People with Parkinson\u2019s (PD)? 2017, Available online: https:\/\/clinicaltrials.gov\/show\/NCT03288155."},{"key":"ref_65","unstructured":"ClinicalTrials.gov (2025, February 16). Role of Saffron and Chamomile in the Management of Parkinson\u2019s Disease, Available online: https:\/\/clinicaltrials.gov\/show\/NCT05696665."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e22800","DOI":"10.1002\/jbt.22800","article-title":"Antioxidative effects of silymarin on the reduction of liver complications of fingolimod in patients with relapsing\u2013remitting multiple sclerosis: A clinical trial study","volume":"35","author":"Ghiasian","year":"2021","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Benlloch, M., Cuerda Ballester, M., Drehmer, E., Platero, J.L., Carrera-Juli\u00e1, S., L\u00f3pez-Rodr\u00edguez, M.M., Ceron, J.J., Tvarijonaviciute, A., Navarro, M.\u00c1., and Moreno, M.L. (2020). Possible reduction of cardiac risk after supplementation with epigallocatechin gallate and increase of ketone bodies in the blood in patients with multiple sclerosis: A pilot study. Nutrients, 12.","DOI":"10.3390\/nu12123792"},{"key":"ref_68","first-page":"789","article-title":"Improvements in gait and balance in patients with multiple sclerosis after treatment with coconut oil and epigallocatechin gallate: A pilot study","volume":"14","year":"2023","journal-title":"Food Funct."},{"key":"ref_69","unstructured":"ClinicalTrials.gov (2025, February 18). The Immunomodulatory Effects of Oral Nanocurcumin in Multiple Sclerosis Patients, Available online: https:\/\/clinicaltrials.gov\/show\/NCT03150966."},{"key":"ref_70","unstructured":"ClinicalTrials.gov (2025, February 15). A Trial of Nicotinamide\/Pterostilbene Supplement in ALS: The NO-ALS Extension Study, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05095571."},{"key":"ref_71","unstructured":"ClinicalTrials.gov (2025, February 16). The NO-ALS Study: A Trial of Nicotinamide\/Pterostilbene Supplement in ALS, Available online: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04562831."},{"key":"ref_72","unstructured":"ClinicalTrials.gov (2025, February 17). Impact of the Combined Treatment of Liposomed Polyphenols with G04CB02 on the ALS Patients, Available online: https:\/\/clinicaltrials.gov\/show\/NCT04654689."},{"key":"ref_73","unstructured":"European Union Clinical Trials Register (EUCTR) (2025, February 18). Effects of EGCG (Epigallocatechin Gallate) in Chorea Huntington. Available online: https:\/\/trialsearch.who.int\/Trial2.aspx?TrialID=EUCTR2010-023941-31-DE."},{"key":"ref_74","unstructured":"ClinicalTrials.gov (2025, February 14). Effects of EGCG (Epigallocatechin Gallate) in Huntington\u2019s Disease (ETON-Study), Available online: https:\/\/clinicaltrials.gov\/show\/NCT01357681."},{"key":"ref_75","unstructured":"ClinicalTrials.gov (2025, February 15). Evaluation of the Therapeutic Potential of Resveratrol in Huntington Disease, Available online: http:\/\/clinicaltrials.gov\/show\/nct02336633."},{"key":"ref_76","first-page":"S97","article-title":"Palmitoylethanolamide combined with luteoline in frontotemporal dementia patients (PEA-FTD): A phase 2 randomized clinical trial","volume":"10","author":"Assogna","year":"2023","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Kaluza, M., Ksiazek-Winiarek, D., Szpakowski, P., Czpakowska, J., Fijalkowska, J., and Glabinski, A. (2025). Polyphenols in the Central Nervous System: Cellular Effects and Liposomal Delivery Approaches. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136477"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Fang, S., Zhang, K., Liu, D., Yang, Y., Xi, H., Xie, W., Diao, K., Rao, Z., Wang, D., and Yang, W. (2024). Polyphenol-based polymer nanoparticles for inhibiting amyloid protein aggregation: Recent advances and perspectives. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1408620"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Hu, L., Luo, Y., Yang, J., and Cheng, C. (2025). Botanical Flavonoids: Efficacy, Absorption, Metabolism and Advanced Pharmaceutical Technology for Improving Bioavailability. Molecules, 30.","DOI":"10.3390\/molecules30051184"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5002","DOI":"10.3390\/ijms10115002","article-title":"Methylation of Dietary Flavones Increases Their Metabolic Stability and Chemopreventive Effects","volume":"10","author":"Walle","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1007\/s11095-025-03920-5","article-title":"Metabolic Insights into Drug Absorption: Unveiling Piperine\u2019s Transformative Bioenhancing Potential","volume":"42","author":"Tripathi","year":"2025","journal-title":"Pharm. Res."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Mahdi, L., Graziani, A., Baffy, G., Mitten, E.K., Portincasa, P., and Khalil, M. (2025). Unlocking Polyphenol Efficacy: The Role of Gut Microbiota in Modulating Bioavailability and Health Effects. Nutrients, 17.","DOI":"10.3390\/nu17172793"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s13668-025-00620-9","article-title":"Personalizing Dietary Polyphenols for Health Maintenance and Disease Management: A Nutrigenetic Approach","volume":"14","year":"2025","journal-title":"Curr. Nutr. Rep."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/4\/602\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T14:22:43Z","timestamp":1770906163000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/4\/602"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,12]]},"references-count":83,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["nu18040602"],"URL":"https:\/\/doi.org\/10.3390\/nu18040602","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,12]]}}}