{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,15]],"date-time":"2026-11-15T12:03:13Z","timestamp":1794744193223,"version":"4.9.1"},"reference-count":39,"publisher":"BMJ","license":[{"start":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T00:00:00Z","timestamp":1643155200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ"],"accepted":{"date-parts":[[2021,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate whether vitamin D and marine derived long chain omega 3 fatty acids reduce autoimmune disease risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Vitamin D and omega 3 trial (VITAL), a nationwide, randomized, double blind, placebo controlled trial with a two-by-two factorial design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Nationwide in the United States.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>25\u2009871 participants, consisting of 12\u2009786 men \u226550 years and 13\u2009085 women \u226555 years at enrollment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions<\/jats:title>\n                    <jats:p>Vitamin D (2000 IU\/day) or matched placebo, and omega 3 fatty acids (1000 mg\/day) or matched placebo. Participants self-reported all incident autoimmune diseases from baseline to a median of 5.3 years of follow-up; these diseases were confirmed by extensive medical record review. Cox proportional hazard models were used to test the effects of vitamin D and omega 3 fatty acids on autoimmune disease incidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measures<\/jats:title>\n                    <jats:p>The primary endpoint was all incident autoimmune diseases confirmed by medical record review: rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>25\u2009871 participants were enrolled and followed for a median of 5.3 years. 18\u2009046 self-identified as non-Hispanic white, 5106 as black, and 2152 as other racial and ethnic groups. The mean age was 67.1 years. For the vitamin D arm, 123 participants in the treatment group and 155 in the placebo group had a confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05). In the omega 3 fatty acids arm, 130 participants in the treatment group and 148 in the placebo group had a confirmed autoimmune disease (0.85, 0.67 to 1.08, P=0.19). Compared with the reference arm (vitamin D placebo and omega 3 fatty acid placebo; 88 with confirmed autoimmune disease), 63 participants who received vitamin D and omega 3 fatty acids (0.69, 0.49 to 0.96), 60 who received only vitamin D (0.68, 0.48 to 0.94), and 67 who received only omega 3 fatty acids (0.74, 0.54 to 1.03) had confirmed autoimmune disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Vitamin D supplementation for five years, with or without omega 3 fatty acids, reduced autoimmune disease by 22%, while omega 3 fatty acid supplementation with or without vitamin D reduced the autoimmune disease rate by 15% (not statistically significant). Both treatment arms showed larger effects than the reference arm (vitamin D placebo and omega 3 fatty acid placebo).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT01351805\">NCT01351805<\/jats:ext-link>\n                      and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT01169259\">NCT01169259<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmj-2021-066452","type":"journal-article","created":{"date-parts":[[2022,1,26]],"date-time":"2022-01-26T20:00:13Z","timestamp":1643227213000},"page":"e066452","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":330,"title":["Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial"],"prefix":"10.1136","volume":"376","clinical-trial-number":[{"clinical-trial-number":"nct01351805","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01169259","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01351805","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Jill","family":"Hahn","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA"},{"name":"Division of Rheumatology, Inflammation and Immunity, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"},{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy R","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA"},{"name":"Division of Preventive Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik K","family":"Alexander","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Friedman","sequence":"additional","affiliation":[{"name":"Center for Crohn\u2019s and Colitis, Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Walter","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Bubes","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Kotler","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. 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