{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T17:30:18Z","timestamp":1777915818212,"version":"3.51.4"},"reference-count":48,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100008347","name":"Bezmialem Vak\u0131f \u00dcniversitesi","doi-asserted-by":"publisher","award":["20220202E"],"award-info":[{"award-number":["20220202E"]}],"id":[{"id":"10.13039\/501100008347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Nutr Health"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aspartame, a widely used artificial sweetener, is metabolized into phenylalanine, aspartic acid, and methanol. Previous studies have suggested that these metabolites may exert detrimental effects on the human body, particularly through alterations gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aimed to investigate the effects of long-term aspartame consumption on global DNA methylation levels in different tissues in order to evaluate the potential epigenetic mechanisms associated with low- and high-dose aspartame exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eighteen adult\n                      <jats:italic toggle=\"yes\">Long Evans<\/jats:italic>\n                      rats were divided into three groups: control (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20096), low-dose aspartame (50\u2005mg\/kg,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20096), and high-dose aspartame (250\u2005mg\/kg,\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20096). Aspartame was administered daily via drinking water for 10 weeks. At the end of the 10\n                      <jats:sup>th<\/jats:sup>\n                      week, the rats were sacrificed under anesthesia, and pancreas, liver, kidney, testis, and brain tissues were collected to determine global DNA methylation levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High-dose aspartame consumption significantly increased the global 5-mC levels in the liver, kidney, and pancreas compared with the low-dose and control groups. No significant change was observed in global 5-mC levels in the testis. Interestingly, low-dose aspartame exposure increased the global 5-mC levels in the brain cortex, whereas high-dose aspartame did not produce a significant change.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The present study provides the first\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      evidence suggesting that prolonged exposure to high doses of aspartame may regulate gene expression by altering global DNA methylation levels in the liver, kidney, and pancreatic tissues.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02601060261443466","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T14:30:17Z","timestamp":1776781817000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term aspartame consumption affects global levels of DNA methylation in different types of rat tissues"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3698-4367","authenticated-orcid":false,"given":"Ali Kaan","family":"Sadic","sequence":"first","affiliation":[{"name":"Bezmialem Vakif University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9689-3111","authenticated-orcid":false,"given":"Seda","family":"Susgun","sequence":"additional","affiliation":[{"name":"Bezmialem Vakif University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8553-659X","authenticated-orcid":false,"given":"Damla","family":"Alkhalidi","sequence":"additional","affiliation":[{"name":"Bezmialem Vakif University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4512-8764","authenticated-orcid":false,"given":"Emrah","family":"Yucesan","sequence":"additional","affiliation":[{"name":"Istanbul University-Cerrahpasa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3837-250X","authenticated-orcid":false,"given":"Fahri","family":"Akbas","sequence":"additional","affiliation":[{"name":"Bezmialem Vakif University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9462-0862","authenticated-orcid":false,"given":"Birsen","family":"Elibol","sequence":"additional","affiliation":[{"name":"Istanbul Medeniyet University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41936-021-00244-9"},{"key":"e_1_3_2_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1091581814537087"},{"key":"e_1_3_2_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00092"},{"key":"e_1_3_2_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-018-3935-5"},{"key":"e_1_3_2_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0394632015586134"},{"key":"e_1_3_2_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.9b02284"},{"issue":"5","key":"e_1_3_2_8_1","first-page":"339","article-title":"Nephrotoxic effect of aspartame as an artificial sweetener: a brief review","volume":"11","author":"Ardalan MR","year":"2017","unstructured":"Ardalan MR, Tabibi H, Ebrahimzadeh Attari V, et al. 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