{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T20:00:40Z","timestamp":1794427240350,"version":"4.9.1"},"reference-count":193,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"S&T Project of Yangjiang","award":["SDZX2020012"],"award-info":[{"award-number":["SDZX2020012"]}]},{"name":"Guangdong Provincial Key Laboratory of Intelligent Food Manufacturing","award":["2022B1212010015"],"award-info":[{"award-number":["2022B1212010015"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172348"],"award-info":[{"award-number":["32172348"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31972205"],"award-info":[{"award-number":["31972205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Science and Technology projects of Xinjiang Uygur Autonomous Regions","award":["2022A02002-4"],"award-info":[{"award-number":["2022A02002-4"]}]},{"name":"S&T Project of China-Singapore International Joint Research Institute","award":["201-A022005"],"award-info":[{"award-number":["201-A022005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) remains a major public health challenge. Observational associations between dietary patterns and reduced dementia risk have prompted investigations of dietary bioactives (DBs) as cognitive nutraceuticals. Methods: This critical narrative review examines interventional trials for nine prominent DBs relevant to AD: docosahexaenoic acid (DHA), curcumin, resveratrol, epigallocatechin gallate (EGCG), nicotinamide riboside (NR), tricaprilin, vitamin E (\u03b1-tocopherol), cannabinoids, and NIC5-15 (D-pinitol). Trials were identified through ClinicalTrials.gov (search date: December 2024) and supplemented by PubMed searches for published results. Data were extracted on trial phase, design, cognitive\/functional endpoints, biomarker outcomes, and development status. Findings are synthesized qualitatively; no formal meta-analysis or risk of bias assessment was conducted. Results: None of the nine bioactives demonstrated consistent cognitive efficacy in AD. Phase III trials of DHA, curcumin, and tricaprilin did not meet primary cognitive endpoints. Resveratrol reduced CSF A\u03b240 without cognitive benefit. Cannabinoids improved behavioral symptoms but showed no measurable cognitive effects. High-dose vitamin E slowed functional decline, while cognition remained unchanged. In contrast, trials in preclinical or at-risk populations reported preliminary cognitive signals for EGCG and biomarker engagement for NR, suggesting potential for early intervention. Conclusions: Current clinical evidence does not support high-dose DBs supplementation as an effective treatment for AD. Predominantly negative late-phase findings highlight limitations, with potential contributors including limited bioavailability, late intervention, insufficient target engagement, and biological heterogeneity. Future research may benefit from early biomarker-defined populations, optimized formulations, multi-nutrient or dietary approaches, and precision nutrition strategies considering genetic risk and baseline nutrient status. DBs may be better positioned for prevention or early-stage intervention rather than late-stage therapy.<\/jats:p>","DOI":"10.3390\/nu18060907","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T16:27:51Z","timestamp":1773332871000},"page":"907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dietary Bioactives in Alzheimer\u2019s Disease: A Critical Appraisal of Clinical Trials and Future Nutritional Strategies"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1484-8286","authenticated-orcid":false,"given":"Ankita","family":"Kumari","sequence":"first","affiliation":[{"name":"School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China"},{"name":"Guangdong Key Laboratory of Food Intelligent Manufacturing, Foshan University, Foshan 528225, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-An","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China"},{"name":"Guangdong Key Laboratory of Food Intelligent Manufacturing, Foshan University, Foshan 528225, China"},{"name":"School of Food Science and Engineering, Foshan University, Foshan 528225, China"},{"name":"Overseas Expertise Introduction Centre for Discipline Innovation of Food Nutrition and Human Health (111 Centre), Guangzhou 510640, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","article-title":"Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: An analysis for the Global Burden of Disease Study 2019","volume":"7","author":"Nichols","year":"2022","journal-title":"Lancet Public Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"32725","DOI":"10.1038\/s41598-025-17055-5","article-title":"The long-term neuroprotective effect of MIND and Mediterranean diet on patients with Alzheimer\u2019s disease","volume":"15","author":"Liu","year":"2025","journal-title":"Sci. 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