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CancerPhase 3VITALNCT01169259

Vitamin D and Omega-3 Trial (VITAL)

A Phase 3 study testing vitamin D3 and omega-3 fatty acids (fish oil) in people with Cancer and Cardiovascular Disease, run by Brigham and Women's Hospital at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 50 years and olderHealthy volunteers can take part
Conditions the study is for
Cancer, Cardiovascular Disease
What is being tested?
vitamin D3 and omega-3 fatty acids (fish oil)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
25,871 participants
Where
1 siteUnited States
Study dates
Jul 2010to Mar 2031
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

To be eligible for the study, respondents had to, at study entry,:

  1. be men aged 50 or older or women aged 55 or older;
  2. have no history of cancer (except non-melanoma skin cancer), heart attack, stroke, transient ischemic attack, angina pectoris, coronary-artery bypass grafting, or percutaneous coronary intervention;
  3. have none of the following safety exclusions: history of renal failure or dialysis, hypercalcemia, hypo- or hyperparathyroidism, severe liver disease (cirrhosis), or sarcoidosis or other granulomatous diseases such as active chronic tuberculosis or granulomatosis with polyangiitis (Wegener's);
  4. have no allergy to fish or soy;
  5. have no other serious illness that would preclude participation;
  6. be consuming no more than 800 IU of vitamin D from all supplemental sources combined (individual vitamin D supplements, calcium+vitamin D supplements, medications with vitamin D [e.g., Fosamax Plus D], and multivitamins), or, if taking, willing to decrease or forego such use during the trial;
  7. be consuming no more than 1200 mg/d of calcium from all supplemental sources combined, or, if taking, willing to decrease or forego such use during the trial;
  8. not be taking fish oil supplements, or, if taking, willing to forego their use during the trial

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02215

Other trials in United States

About this study

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.

Read the detailed description

The VITamin D and OmegA-3 TriaL (VITAL) is a randomized clinical trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements in the primary prevention of cancer and cardiovascular disease (CVD). Existing data from laboratory studies, epidemiologic research, small primary prevention trials, and/or large secondary prevention trials strongly suggest that these nutritional agents may reduce risk for cancer or CVD, but large primary prevention trials with adequate dosing in general populations are lacking.

VITAL tested the independent effects of vitamin D and omega-3 fatty acid supplementation on risk for developing cancer and CVD (primary, secondary, and other outcomes are specified in the Outcome Measures section). VITAL also explored (a) whether vitamin D and omega-3 fatty acid supplements exhibit synergistic or additive effects on cancer and CVD risk and (b) whether the effect of each supplement on cancer and CVD risk varies by baseline blood levels or intake of vitamin D and EPA+DHA, race/ethnicity, and body mass index (for vitamin D), as well as age, sex, sunlight exposure, calcium intake, and baseline risk factors for cancer and CVD.

Eligible participants were assigned by chance (like a coin toss) to one of four groups: (1) daily vitamin D and omega-3; (2) daily vitamin D and omega-3 placebo; (3) daily vitamin D placebo and omega-3; or (4) daily vitamin D placebo and omega-3 placebo. Participants had an equal chance of being assigned to any of these four groups and a 3 out of 4 chance of getting at least one active agent.

Participants in all groups took two pills each day -- one softgel that contained either vitamin D or vitamin D placebo and one capsule that contained either omega-3 or omega-3 placebo. Participants received their study pills in convenient calendar packages via U.S. mail.

Participants fill out a short (15-20 minute) questionnaire each year. The questionnaire asks about health; lifestyle habits such as physical exercise, diet, and smoking; use of medications and dietary supplements; family history of illness, and new medical diagnoses. We request consent for medical record review to confirm endpoints. Occasionally, participants may receive a phone call from study staff to collect information or to clarify responses on the questionnaire.

At baseline, 16,954 VITAL participants provided an optional blood sample. Approximately 6,000 of these participants provided a follow-up blood sample during years 1-5 of the trial.

At baseline, year 2, and year 4 of the trial, a subcohort of 1,054 VITAL participants living within driving distance of Boston, Massachusetts received detailed in-clinic health assessments at the Clinical and Translational Science Center (CTSC) of Brigham and Women's Hospital. During CTSC visits, participants had a clinical exam, including measurement of height, weight, other anthropometrics, blood pressure, and physical performance. They also provided fasting blood and urine samples, and underwent 2-hour oral glucose tolerance testing, lung function testing (spirometry), electrocardiograms, bone mineral density testing, 2D-echocardiography, and assessments of thinking and mood.

VITAL is supported by funding from the National Cancer Institute, National Heart, Lung and Blood Institute, Office of Dietary Supplements, National Institute of Neurological Disorders and Stroke, and the National Center for Complementary and Integrative Health. Pharmavite LLC of Northridge, California (vitamin D) and Pronova BioPharma (BASF) of Norway (Omacor® fish oil) donated the study agents, matching placebos, and packaging in the form of calendar packs.

Being tested
vitamin D3, omega-3 fatty acids (fish oil), Vitamin D3 placebo, Fish oil placebo
Keywords
vitamin D3, omega-3 fatty acids, fish oil, cardiovascular disease, cancer, primary prevention
Medical subject headings
Neoplasms, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vitamin D3Dietary supplement

    Also called cholecalciferol

    Vitamin D3 (cholecalciferol), 2000 IU per day.

  • omega-3 fatty acids (fish oil)Drug

    Omacor, one 1-gram capsule per day. Each capsule of Omacor contains 840 milligrams of marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).

  • Vitamin D3 placeboDietary supplement

    Vitamin D placebo

  • Fish oil placeboDietary supplement

    Fish oil placebo

Study groups in NCT01169259
Study groupRoleWhat they receive
Vitamin D + fish oilActive comparatorNot described
Receives: Dietary Supplement: vitamin D3; Drug: omega-3 fatty acids (fish oil)
Vitamin D + fish oil placeboActive comparatorNot described
Receives: Dietary Supplement: vitamin D3; Dietary Supplement: Fish oil placebo
Vitamin D placebo + fish oilActive comparatorNot described
Receives: Drug: omega-3 fatty acids (fish oil); Dietary Supplement: Vitamin D3 placebo
Vitamin D placebo + fish oil placeboPlacebo comparatorNot described
Receives: Dietary Supplement: Vitamin D3 placebo; Dietary Supplement: Fish oil placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Invasive Cancer of Any Type

    Number of participants with invasive cancer of any type

    Measured: 5 years

  2. Number of Participants With a Major Cardiovascular Event

    Major cardiovascular event = a composite endpoint of myocardial infarction, stroke, and death from cardiovascular causes

    Measured: 5 years

Secondary outcomes (11)

  1. Number of Participants Who Died From Invasive Cancer of Any Type

    Number of participants who died from invasive cancer of any type

    Measured: 5 years

  2. Number of Female Participants With Breast Cancer

    Number of female participants with breast cancer

    Measured: 5 years

  3. Number of Male Participants With Prostate Cancer

    Number of male participants with prostate cancer

    Measured: 5 years

  4. Number of Participants With Colorectal Cancer

    Number of participants with colorectal cancer

    Measured: 5 years

  5. Number of Participants With Cardiovascular Event in Expanded Composite Cardiovascular Endpoint

    Expanded composite cardiovascular endpoint = a composite endpoint of myocardial infarction, stroke, death from cardiovascular causes, and coronary revascularization (coronary artery bypass grafting or percutaneous coronary intervention)

    Measured: 5 years

  6. Number of Participants With Myocardial Infarction

    Number of participants with myocardial infarction

    Measured: 5 years

  7. Number of Participants With Stroke

    Number of participants with stroke

    Measured: 5 years

  8. Number of Participants Who Died From Cardiovascular Causes

    Number of participants who died from cardiovascular causes

    Measured: 5 years

  9. Number of Participants Who Died From Any Cause

    Number of participants who died from any cause

    Measured: 5 years

  10. Number of Participants With Invasive Cancer of Any Type, Excluding First 2 Years of Follow-up

    Number of participants with invasive cancer of any type, excluding first 2 years of follow-up

    Measured: 5 years, excluding first 2 years of follow-up

  11. Number of Participants With a Major Cardiovascular Event, Excluding First 2 Years of Follow-up

    Major cardiovascular event = a composite endpoint of myocardial infarction, stroke, and death from cardiovascular causes; excluding first 2 years of follow-up

    Measured: 5 years, excluding first 2 years of follow-up

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2010 (estimated)
  2. Study startJul 2010
  3. Primary completion10 Nov 2018
  4. Study completionMar 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Factorial
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
25,871 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01169259
Sponsor's protocol ID
2009P-001217
Other IDs
U01CA138962, R01CA138962
Acronym
VITAL
Status last verified
Jul 2026
First submitted
13 Jan 2010
Last updated
16 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
Individual data sharing
Yes: Researchers who are interested in collaborating on research that uses VITAL data should visit the "For VITAL Investigators" section of the VITAL website, www.vitalstudy.org.

Publications

  • 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.

    PubMed 26767629

  • 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.

    PubMed 25864623

  • 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.

    PubMed 21986389

  • 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.

    PubMed 30415629

  • 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.

    PubMed 30415637

  • 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.

    PubMed 31750855

  • 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.

    PubMed 32062040

  • Cho HL, Li C, Manson JE, Cook NR, Lee IM, Buring JE, Berliner N. Effect of vitamin D and omega-3 fatty acid supplementation on anemia incidence among older adults: the VITAL trial. Blood Red Cells Iron. 2025 Dec;1(3):100032. doi: 10.1016/j.brci.2025.100032. Epub 2025 Dec 9.

    PubMed 42630947

  • 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.

    PubMed 40032221

  • 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.

    PubMed 39618688

  • 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.

    PubMed 39488682

  • Costenbader KH, Cook NR, Lee IM, Hahn J, Walter J, Bubes V, Kotler G, Yang N, Friedman S, Alexander EK, Manson JE. Vitamin D and Marine n-3 Fatty Acids for Autoimmune Disease Prevention: Outcomes Two Years After Completion of a Double-Blind, Placebo-Controlled Trial. Arthritis Rheumatol. 2024 Jun;76(6):973-983. doi: 10.1002/art.42811. Epub 2024 Feb 20.

    PubMed 38272846

  • 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.

    PubMed 38113446

  • 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.

    PubMed 37952113

  • 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.

    PubMed 37878483

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing vitamin D3 and omega-3 fatty acids (fish oil) in people with Cancer and Cardiovascular Disease, run by Brigham and Women's Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Invasive Cancer of Any Type (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01169259, which also lists 40 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2026.

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