drugset / Trial / NCT01169259
Vitamin D and Omega-3 Trial (VITAL)
Phase 3
Active not recruiting
25871 enrolled
Brigham and Women's Hospital
BASF · collabNational Cancer Institute (NCI) · collabNational Center for Complementary and Integrative Health (NCCIH) · collabNational Heart, Lung, and Blood Institute (NHLBI) · collabNational Institute of Neurological Disorders and Stroke (NINDS) · collabOffice of Dietary Supplements (ODS) · collabPharmavite LLC · collabPronova BioPharma · collab
RandomizedFactorialTriple-blindPrevention
Summary
The VITamin D and OmegA-3 TriaL (VITAL) is a randomized clinical trial in 25,871 U.S. men and women investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (Omacor® fish oil, 1 gram) reduces the risk of developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses. The 5-year intervention phase (study pill-taking, median 5.3 years) has ended; post-intervention observational follow-up of study participants is ongoing.
Timeline
- Start
- 2010-07
- Primary completion
- 2018-11-10
- Completion
- 2026-05
Publications
- Background Bassuk SS, Manson JE, Lee IM, Cook NR, Christen WG, Bubes VY, Gordon DS, Copeland T, Friedenberg G, D'Agostino DM, Ridge CY, MacFadyen JG, Kalan K, Buring JE. Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL). Contemp Clin Trials. 2016 Mar;47:235-43. doi: 10.1016/j.cct.2015.12.022. Epub 2016 Jan 6.
- Background Pradhan AD, Manson JE. Update on the Vitamin D and OmegA-3 trial (VITAL). J Steroid Biochem Mol Biol. 2016 Jan;155(Pt B):252-6. doi: 10.1016/j.jsbmb.2015.04.006. Epub 2015 Apr 9.
- Background Manson JE, Bassuk SS, Lee IM, Cook NR, Albert MA, Gordon D, Zaharris E, Macfadyen JG, Danielson E, Lin J, Zhang SM, Buring JE. The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials. 2012 Jan;33(1):159-71. doi: 10.1016/j.cct.2011.09.009. Epub 2011 Oct 2.
- Background Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Gordon D, Copeland T, D'Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE; VITAL Research Group. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med. 2019 Jan 3;380(1):33-44. doi: 10.1056/NEJMoa1809944. Epub 2018 Nov 10.
- Background Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Albert CM, Gordon D, Copeland T, D'Agostino D, Friedenberg G, Ridge C, Bubes V, Giovannucci EL, Willett WC, Buring JE; VITAL Research Group. Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. N Engl J Med. 2019 Jan 3;380(1):23-32. doi: 10.1056/NEJMoa1811403. Epub 2018 Nov 10.
- Background Song M, Lee IM, Manson JE, Buring JE, Dushkes R, Gordon D, Walter J, Wu K, Chan AT, Ogino S, Fuchs CS, Meyerhardt JA, Giovannucci EL; VITAL Research Group. Effect of Supplementation With Marine omega-3 Fatty Acid on Risk of Colorectal Adenomas and Serrated Polyps in the US General Population: A Prespecified Ancillary Study of a Randomized Clinical Trial. JAMA Oncol. 2020 Jan 1;6(1):108-115. doi: 10.1001/jamaoncol.2019.4587.
- Background Song M, Lee IM, Manson JE, Buring JE, Dushkes R, Gordon D, Walter J, Wu K, Chan AT, Ogino S, Fuchs CS, Meyerhardt JA, Giovannucci EL. No Association Between Vitamin D Supplementation and Risk of Colorectal Adenomas or Serrated Polyps in a Randomized Trial. Clin Gastroenterol Hepatol. 2021 Jan;19(1):128-135.e6. doi: 10.1016/j.cgh.2020.02.013. Epub 2020 Feb 13.
- Hamaya R, Cook NR, Sesso HD, Buring JE, Manson JE. A Bayesian analysis of the VITAL trial: effects of omega-3 fatty acid supplementation on cardiovascular events. Am J Clin Nutr. 2025 May;121(5):1046-1053. doi: 10.1016/j.ajcnut.2025.02.028. Epub 2025 Mar 1.
- Digvijaya, Mittal S, Mittal P, Singh R, Gupta S, Singh T, Khan R, Alzobaidi N, Alhalmi A. Vitamin D Fortification: A Promising Approach to Overcome Drug Resistance and Tolerance in Therapeutic Interventions. Scientifica (Cairo). 2024 Nov 22;2024:9978076. doi: 10.1155/2024/9978076. eCollection 2024.
- Qian F, Guo Y, Li C, Liu Y, Luttmann-Gibson H, Gomelskaya N, Demler OV, Cook NR, Lee IM, Buring JE, Larsen J, Boring J, McPhaul MJ, Manson JE, Pradhan AD, Mora S. Biomarkers of glucose-insulin homeostasis and incident type 2 diabetes and cardiovascular disease: results from the Vitamin D and Omega-3 trial. Cardiovasc Diabetol. 2024 Nov 2;23(1):393. doi: 10.1186/s12933-024-02470-1.
- Camargo CA Jr, Schaumberg DA, Friedenberg G, Dushkes R, Glynn RJ, Gold DR, Mora S, Lee IM, Buring JE, Manson JE. Effect of Daily Vitamin D Supplementation on Risk of Upper Respiratory Infection in Older Adults: A Randomized Controlled Trial. Clin Infect Dis. 2024 May 15;78(5):1162-1169. doi: 10.1093/cid/ciad770.
- Vyas CM, Kang JH, Mischoulon D, Cook NR, Reynolds Iii CF, Chang G, Mora S, De Vivo I, Manson JE, Okereke OI. Apolipoprotein E and Its Association With Cognitive Change and Modification of Treatment Effects of Vitamin D3 and Omega-3s on Cognitive Change: Results From the In-Clinic Subset of a Randomized Clinical Trial. J Gerontol A Biol Sci Med Sci. 2024 Mar 1;79(3):glad260. doi: 10.1093/gerona/glad260.
- Soens MA, Sesso HD, Manson JE, Fields KG, Buring JE, Lee IM, Cook NR, Kim E, Bubes V, Dushkes R, Serhan CN, Rathmell JP. The effect of vitamin D and omega-3 fatty acid supplementation on pain prevalence and severity in older adults: a large-scale ancillary study of the VITamin D and OmegA-3 triaL (VITAL). Pain. 2024 Mar 1;165(3):635-643. doi: 10.1097/j.pain.0000000000003044. Epub 2023 Oct 25.
- Tikkanen JT, Soliman EZ, Pester J, Danik JS, Gomelskya N, Copeland T, Lee IM, Buring JE, Manson JE, Cook NR, Albert CM. A randomized clinical trial of omega-3 fatty acid and vitamin D supplementation on electrocardiographic risk profiles. Sci Rep. 2023 Jul 15;13(1):11454. doi: 10.1038/s41598-023-38344-x.
- Vyas CM, Mischoulon D, Chang G, Reynolds CF 3rd, Cook NR, Weinberg A, Copeland T, Bubes V, Bradwin G, Lee IM, Buring JE, Mora S, Rifai N, Manson JE, Okereke OI. Relation of serum BDNF to major depression and exploration of mechanistic roles of serum BDNF in a study of vitamin D3 and omega-3 supplements for late-life depression prevention. J Psychiatr Res. 2023 Jul;163:357-364. doi: 10.1016/j.jpsychires.2023.05.069. Epub 2023 May 26.
- Vyas CM, Sadreyev RI, Gatchel JR, Kang JH, Reynolds CF, Mischoulon D, Chang G, Hazra A, Manson JE, Blacker D, De Vivo I, Okereke OI. Pilot Study of Second-Generation DNA Methylation Epigenetic Markers in Relation to Cognitive and Neuropsychiatric Symptoms in Older Adults. J Alzheimers Dis. 2023;93(4):1563-1575. doi: 10.3233/JAD-230093.
- Hlatky MA, Gonzalez PE, Manson JE, Buring JE, Lee IM, Cook NR, Mora S, Bubes V, Stone NJ. Statin-Associated Muscle Symptoms Among New Statin Users Randomly Assigned to Vitamin D or Placebo. JAMA Cardiol. 2023 Jan 1;8(1):74-80. doi: 10.1001/jamacardio.2022.4250.
- Bassuk SS, Manson JE; VITAL Research Group. Marine omega-3 fatty acid supplementation and prevention of cardiovascular disease: update on the randomized trial evidence. Cardiovasc Res. 2023 Jun 13;119(6):1297-1309. doi: 10.1093/cvr/cvac172.
- Chandra A, Picard MH, Huang S, Gupta DK, Agusala K, Buring JE, Lee IM, Cook NR, Manson JE, Thadhani RI, Wang TJ. Impact of Vitamin D3 Versus Placebo on Cardiac Structure and Function: A Randomized Clinical Trial. J Am Heart Assoc. 2022 Nov;11(21):e025008. doi: 10.1161/JAHA.121.025008. Epub 2022 Oct 26.
- Orkaby AR, Dushkes R, Ward R, Djousse L, Buring JE, Lee IM, Cook NR, LeBoff MS, Okereke OI, Copeland T, Manson JE. Effect of Vitamin D3 and Omega-3 Fatty Acid Supplementation on Risk of Frailty: An Ancillary Study of a Randomized Clinical Trial. JAMA Netw Open. 2022 Sep 1;5(9):e2231206. doi: 10.1001/jamanetworkopen.2022.31206.
- Djousse L, Cook NR, Kim E, Walter J, Al-Ramady OT, Luttmann-Gibson H, Albert CM, Mora S, Buring JE, Gaziano JM, Manson JE. Diabetes Mellitus, Race, and Effects of Omega-3 Fatty Acids on Incidence of Heart Failure Hospitalization. JACC Heart Fail. 2022 Apr;10(4):227-234. doi: 10.1016/j.jchf.2021.12.006. Epub 2022 Mar 9.
- Hahn J, Cook NR, Alexander EK, Friedman S, Walter J, Bubes V, Kotler G, Lee IM, Manson JE, Costenbader KH. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ. 2022 Jan 26;376:e066452. doi: 10.1136/bmj-2021-066452.
- Okereke OI, Vyas CM, Mischoulon D, Chang G, Cook NR, Weinberg A, Bubes V, Copeland T, Friedenberg G, Lee IM, Buring JE, Reynolds CF 3rd, Manson JE. Effect of Long-term Supplementation With Marine Omega-3 Fatty Acids vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA. 2021 Dec 21;326(23):2385-2394. doi: 10.1001/jama.2021.21187.
- Kang JH, Vyas CM, Okereke OI, Ogata S, Albert M, Lee IM, D'Agostino D, Buring JE, Cook NR, Grodstein F, Manson JE. Effect of vitamin D on cognitive decline: results from two ancillary studies of the VITAL randomized trial. Sci Rep. 2021 Dec 1;11(1):23253. doi: 10.1038/s41598-021-02485-8.
- Markland AD, Vaughan C, Huang A, Kim E, Bubes VY, Tangpricha V, Buring J, Lee IM, Cook N, Manson JE, Grodstein F. Effect of vitamin D supplementation on urinary incontinence in older women: ancillary findings from a randomized trial. Am J Obstet Gynecol. 2022 Apr;226(4):535.e1-535.e12. doi: 10.1016/j.ajog.2021.10.017. Epub 2021 Oct 19.
- Best CM, Zelnick LR, Thummel KE, Hsu S, Limonte C, Thadhani R, Sesso HD, Manson JE, Buring JE, Mora S, Lee IM, Cook NR, Friedenberg G, Luttmann-Gibson H, de Boer IH, Hoofnagle AN. Serum Vitamin D: Correlates of Baseline Concentration and Response to Supplementation in VITAL-DKD. J Clin Endocrinol Metab. 2022 Jan 18;107(2):525-537. doi: 10.1210/clinem/dgab693.
- Bassuk SS, Chandler PD, Buring JE, Manson JE; VITAL Research Group. The VITamin D and OmegA-3 TriaL (VITAL): Do Results Differ by Sex or Race/Ethnicity? Am J Lifestyle Med. 2020 Dec 24;15(4):372-391. doi: 10.1177/1559827620972035. eCollection 2021 Jul-Aug.
- Albert CM, Cook NR, Pester J, Moorthy MV, Ridge C, Danik JS, Gencer B, Siddiqi HK, Ng C, Gibson H, Mora S, Buring JE, Manson JE. Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation: A Randomized Clinical Trial. JAMA. 2021 Mar 16;325(11):1061-1073. doi: 10.1001/jama.2021.1489.
- Chou SH, Murata EM, Yu C, Danik J, Kotler G, Cook NR, Bubes V, Mora S, Chandler PD, Tobias DK, Copeland T, Buring JE, Manson JE, LeBoff MS. Effects of Vitamin D3 Supplementation on Body Composition in the VITamin D and OmegA-3 TriaL (VITAL). J Clin Endocrinol Metab. 2021 Apr 23;106(5):1377-1388. doi: 10.1210/clinem/dgaa981.
- Chandler PD, Chen WY, Ajala ON, Hazra A, Cook N, Bubes V, Lee IM, Giovannucci EL, Willett W, Buring JE, Manson JE; VITAL Research Group. Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial. JAMA Netw Open. 2020 Nov 2;3(11):e2025850. doi: 10.1001/jamanetworkopen.2020.25850.
- Okereke OI, Reynolds CF 3rd, Mischoulon D, Chang G, Vyas CM, Cook NR, Weinberg A, Bubes V, Copeland T, Friedenberg G, Lee IM, Buring JE, Manson JE. Effect of Long-term Vitamin D3 Supplementation vs Placebo on Risk of Depression or Clinically Relevant Depressive Symptoms and on Change in Mood Scores: A Randomized Clinical Trial. JAMA. 2020 Aug 4;324(5):471-480. doi: 10.1001/jama.2020.10224.
- Farukhi ZM, Demler OV, Caulfield MP, Kulkarni K, Wohlgemuth J, Cobble M, Luttmann-Gibson H, Li C, Nelson JR, Cook NR, Buring JE, Krauss RM, Manson JE, Mora S. Comparison of nonfasting and fasting lipoprotein subfractions and size in 15,397 apparently healthy individuals: An analysis from the VITamin D and OmegA-3 TriaL. J Clin Lipidol. 2020 Mar-Apr;14(2):241-251. doi: 10.1016/j.jacl.2020.02.005. Epub 2020 Feb 21.
- LeBoff MS, Chou SH, Murata EM, Donlon CM, Cook NR, Mora S, Lee IM, Kotler G, Bubes V, Buring JE, Manson JE. Effects of Supplemental Vitamin D on Bone Health Outcomes in Women and Men in the VITamin D and OmegA-3 TriaL (VITAL). J Bone Miner Res. 2020 May;35(5):883-893. doi: 10.1002/jbmr.3958. Epub 2020 Jan 30.
- Manson JE, Bassuk SS, Cook NR, Lee IM, Mora S, Albert CM, Buring JE; VITAL Research Group. Vitamin D, Marine n-3 Fatty Acids, and Primary Prevention of Cardiovascular Disease Current Evidence. Circ Res. 2020 Jan 3;126(1):112-128. doi: 10.1161/CIRCRESAHA.119.314541. Epub 2020 Jan 2.
- Manson JE, Bassuk SS, Buring JE; VITAL Research Group. Principal results of the VITamin D and OmegA-3 TriaL (VITAL) and updated meta-analyses of relevant vitamin D trials. J Steroid Biochem Mol Biol. 2020 Apr;198:105522. doi: 10.1016/j.jsbmb.2019.105522. Epub 2019 Nov 13.
- Costenbader KH, MacFarlane LA, Lee IM, Buring JE, Mora S, Bubes V, Kotler G, Camargo CA Jr, Manson JE, Cook NR. Effects of One Year of Vitamin D and Marine Omega-3 Fatty Acid Supplementation on Biomarkers of Systemic Inflammation in Older US Adults. Clin Chem. 2019 Dec;65(12):1508-1521. doi: 10.1373/clinchem.2019.306902. Epub 2019 Nov 7.
- Luttmann-Gibson H, Mora S, Camargo CA, Cook NR, Demler OV, Ghoshal A, Wohlgemuth J, Kulkarni K, Larsen J, Prentice J, Cobble M, Bubes V, Li C, Friedenberg G, Lee IM, Buring JE, Manson JE. Serum 25-hydroxyvitamin D in the VITamin D and OmegA-3 TriaL (VITAL): Clinical and demographic characteristics associated with baseline and change with randomized vitamin D treatment. Contemp Clin Trials. 2019 Dec;87:105854. doi: 10.1016/j.cct.2019.105854. Epub 2019 Oct 24.
- Okereke OI, Reynolds CF 3rd, Mischoulon D, Chang G, Cook NR, Copeland T, Friedenberg G, Buring JE, Manson JE. The VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention (VITAL-DEP): Rationale and design of a large-scale ancillary study evaluating vitamin D and marine omega-3 fatty acid supplements for prevention of late-life depression. Contemp Clin Trials. 2018 May;68:133-145. doi: 10.1016/j.cct.2018.02.017. Epub 2018 Mar 8.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Cholecalciferol | Other / unclassified | 2000 iu | — |
| Comparator | Omega-3 fatty acids | Unknown | 1 g | — |