{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:46:14Z","timestamp":1792215974778,"version":"4.4.0"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The safety of aspartame, a widely consumed low-calorie artificial sweetener, for human consumption has recently been heavily debated. Published research has demonstrated that aspartame\u2019s breakdown products\u2014aspartic acid, phenylalanine, and methanol\u2014are associated with potential neurotoxicity and possible carcinogenic and metabolic effects in animal models. For this scoping review, existing literature on neurocognitive effects of aspartame was gathered and analyzed. A search of 3 literature databases (Embase, Ovid MEDLINE, and Web of Science) yielded 170 peer-reviewed, full-text articles. After consideration of exclusion criteria, 29 articles were selected for inclusion. After reviewing the findings, indications of aspartame\u2019s potential neurotoxic effects were demonstrated: multiple experimental studies revealed histopathological changes, such as elevated oxidative stress markers and neuronal loss, in various brain regions of animal models after exposure to aspartame. Additional studies showed memory and learning impairments in animal models, as well as behavioral dysfunction and mood disorders indicative of depression and anxiety in both animal and human models, illustrated by processes such as the downregulation of gamma aminobutyric acid signaling and upregulation of glutamate signaling in the amygdala. Notably, many of these studies investigated aspartame\u2019s impact not only at or above the Food and Drug Administration (FDA)\u2013approved level, but below it as well. Two studies also indicated that populations with preexisting neurocognitive deficits, such as individuals with parkinsonism or preexisting metabolic conditions such as diabetes may have an increased vulnerability to neurocognitive harm when consuming aspartame. Interestingly, several agents were found to ameliorate aspartame\u2019s neurocognitive impacts, such as Pimpinella anisum oil and vitamin\u2009E. These negative neurocognitive effects and their potential mitigators demonstrate the necessity for further research into aspartame\u2019s possible impacts on health and safety at current FDA-approved levels, with additional consideration of certain populations at higher risk for neurocognitive injury.<\/jats:p>","DOI":"10.1093\/nutrit\/nuaf103","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T09:06:50Z","timestamp":1747818410000},"page":"1026-1038","source":"Crossref","is-referenced-by-count":9,"title":["Aspartame and Its Potential Neurocognitive Effects in Humans"],"prefix":"10.1093","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2946-1993","authenticated-orcid":false,"given":"Maiah N","family":"Fogel","sequence":"first","affiliation":[{"name":"Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University , Fort Lauderdale, FL 33328,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6674-5889","authenticated-orcid":false,"given":"Alena","family":"Khalil","sequence":"additional","affiliation":[{"name":"Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University , Fort Lauderdale, FL 33328,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0208-2862","authenticated-orcid":false,"given":"Sheikh F","family":"Khaled","sequence":"additional","affiliation":[{"name":"Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University , Fort Lauderdale, FL 33328,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6321-9899","authenticated-orcid":false,"given":"Elizette M","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University , Fort Lauderdale, FL 33328,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0758-8893","authenticated-orcid":false,"given":"Keaton M","family":"Payne","sequence":"additional","affiliation":[{"name":"Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University , Fort Lauderdale, FL 33328,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6925-5041","authenticated-orcid":false,"given":"Jesse R","family":"Blount","sequence":"additional","affiliation":[{"name":"Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University , Fort Lauderdale, FL 33328,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2672-8967","authenticated-orcid":false,"given":"Madison","family":"Petschke","sequence":"additional","affiliation":[{"name":"Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University , Fort Lauderdale, FL 33328,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5164-8683","authenticated-orcid":false,"given":"Roshan Ara","family":"Nizamuddin","sequence":"additional","affiliation":[{"name":"Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University , Fort Lauderdale, FL 33328,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8164-8017","authenticated-orcid":false,"given":"Faige","family":"Jeidel","sequence":"additional","affiliation":[{"name":"Dr. Kiran C. 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