{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:01:04Z","timestamp":1790402464984,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":75,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["P30MH090333"],"award-info":[{"award-number":["P30MH090333"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R56MH091448"],"award-info":[{"award-number":["R56MH091448"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG036755"],"award-info":[{"award-number":["R01AG036755"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR059086"],"award-info":[{"award-number":["R01AR059086"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR060574"],"award-info":[{"award-number":["R01AR060574"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001102"],"award-info":[{"award-number":["UL1TR001102"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Vitamin D3 and omega\u20103 supplementation may slow outcomes related to Alzheimer's disease and related dementias (ADRD), with variation by sex or race, but their effects on ADRD\u2010associated biomarkers are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>In this secondary analysis of a randomized clinical trial (RCT), we included 929 participants from the in\u2010clinic subcohort of the VITamin D and OmegA\u20103 TriaL \u2013 a completed, placebo\u2010controlled, 2\u00d72 factorial trial testing vitamin D3 (2000 IU\/day) and omega\u20103s (1\u00a0g\/day) for cardiovascular disease and cancer prevention. Plasma ADRD biomarkers were assayed at baseline and 2\u2010 and\/or 4\u2010year follow\u2010up. Study outcomes were longitudinal change in four ADRD biomarkers: N\u2010terminal tau fragment (NT1), amyloid beta (A\u03b2)40:42, neurofilament\u2010light (NfL), and glial fibrillary acidic protein (GFAP). Repeated\u2010measures models were used, with sex and race were pre\u2010specified effect modifiers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The sample mean (SD) age was 65.0 (6.6) years; 49.2% were female, and 8.2% were Black adults. Neither vitamin D3 nor omega\u20103s, compared to placebo, significantly reduced ADRD biomarkers over 4 years. Pre\u2010specified subgroup analyses suggested potential interactions by sex and race. Vitamin D3 supplementation resulted in a reduction in NT1 among males (\u22122.7%) but not females (\n                      <jats:italic>p<\/jats:italic>\n                      \u2010interaction = 0.08). Among Black participants, vitamin D3 supplementation resulted in a 16.2% reduction in NfL levels [95% CI: \u221230.5% to 1.1%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2010interaction = 0.06], while omega\u20103 supplementation showed a 12.4% reduction in GFAP levels [95% CI: \u221221.5% to \u22122.2%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2010interaction = 0.049].\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>In this secondary analysis of a RCT, neither vitamin D3 nor omega\u20103s significantly reduced selected plasma ADRD biomarkers over 4 years. Potential differences were observed by sex and race in reductions of ADRD biomarkers in response to these supplements; however, these analyses were uncorrected for multiple hypothesis testing and should be interpreted cautiously as hypothesis\u2010generating signals requiring replication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov identifiers: c (VITAL); NCT01696435 (VITAL\u2010DEP).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70312","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:11:47Z","timestamp":1789449107000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of long\u2010term daily supplementation with vitamin D3 and marine omega\u20103 fatty acids on change in ADRD biomarkers: A secondary analysis of a randomized clinical trial"],"prefix":"10.1002","volume":"12","author":[{"given":"Chirag M.","family":"Vyas","sequence":"first","affiliation":[{"name":"Department of Psychiatry Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth L.","family":"Ostaszewski","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases Department of Neurology Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirah K.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Ann Romney Center for Neurologic Diseases Department of Neurology Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy R.","family":"Cook","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Epidemiology Harvard T.H. Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae H.","family":"Kang","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mischoulon","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles F.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Psychiatry UPMC and University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R.","family":"Gatchel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn E.","family":"Manson","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine Department of Medicine Brigham and Women's Hospital and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Epidemiology Harvard T.H. 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