Autoimmune DiseasesVITALNCT01351805

Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Knee Pain

A study testing Fish Oil and Vitamin D in people with Autoimmune Diseases and Systemic Inflammatory Process, run by Brigham and Women's Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 50 years and olderHealthy volunteers can take part
Conditions the study is for: Autoimmune Diseases, Systemic Inflammatory Process, Knee Pain Chronic
What is being tested?: Fish Oil and Vitamin D
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 Feb 2025
Phase: Interventional
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

As for the parent trial, VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259). Individuals with chronic, frequent knee pain at study baseline will be followed as a subcohort. Trial enrollment complete.

Trial locations and contacts

1 site in 1 country.

United States1 site

Brigham and Women's Hospital
Boston, Massachusetts, 02115

Other trials in United States

About this study

The VITamin D and OmegA-3 TriaL (VITAL; NCT 01169259) 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. This ancillary study is being conducted among VITAL participants and will examine whether vitamin D or fish oil have effects upon A) autoimmune disease incidence, B) biomarkers of systemic inflammation, and C) chronic knee pain. Blood samples at baseline and in follow-up will be collected in a randomly selected subcohort of 1500 individuals and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein, interleukin-6, and tumor necrosis factor-receptor 2. Approximately 1300 individuals with chronic, frequent knee pain will be followed with annual questionnaires to evaluate the effects of the supplements on chronic knee pain.

Conditions: Autoimmune Diseases, Systemic Inflammatory Process, Knee Pain Chronic, Osteoarthritis, Rheumatoid Arthritis
Being tested: Fish Oil, Vitamin D, placebo pill
Keywords: vitamin D, omega-3 fatty acid, fish oil, prevention, trial, autoimmune disease, rheumatoid arthritis, psoriasis, systemic inflammation, Interleukin-6, C-reactive peptide, tumor necrosis factor, osteoarthritis
Medical subject headings: Autoimmune Diseases, Osteoarthritis, Arthritis, Rheumatoid, Psoriasis

What participants receive

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

Fish OilDrug
Also called eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), marine fatty acids, omega-3 fatty acids
Subjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
Vitamin DDietary supplement
Also called cholecalciferol, vitamin D3
Subjects will receive vitamin D3 (cholecalciferol) 2000 IU a day.
placebo pillOther
placebo

Study groups in NCT01351805
Study group	Role	What they receive
Fish Oil	Experimental	Subjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]). Receives: Drug: Fish Oil; Other: placebo pill
Vitamin D	Experimental	Subjects will receive vitamin D3 (cholecalciferol) 2000 IU a day. Receives: Dietary Supplement: Vitamin D; Other: placebo pill
placebo	Placebo comparator	Subjects will receive placebo pill. Receives: Other: placebo pill
Vitamin D and Fish Oil	Experimental	Subjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]). Receives: Drug: Fish Oil; Dietary Supplement: Vitamin D

What is being measured

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

Serum Levels of Biomarkers of Systemic Inflammation: Interleukin-6 (IL-6)
In a subsample of the randomized trial population across the four arms, blood samples at baseline and in follow-up were collected and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-receptor 2 (TNFR2). We tested whether either or both supplements were associated with a decrease in the biomarkers of systemic inflammation (blood biomarker levels among those receiving supplements vs. placebo). We also tested whether there were interactions between the two supplements in their effects on changes in the IL-6 serum biomarker of systemic inflammation.
Measured: Baseline and 1 year
Serum Levels of Biomarkers of Systemic Inflammation: C-reactive Protein (CRP)
In a subsample of the randomized trial population across the four arms, blood samples at baseline and in follow-up were collected and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-receptor 2 (TNFR2). We tested whether either or both supplements were associated with a decrease in the biomarkers of systemic inflammation (blood biomarker levels among those receiving supplements vs. placebo). We also tested whether there were interactions between the two supplements in their effects on changes in the CRP serum biomarker of systemic inflammation.
Measured: Baseline and 1 year
Serum Levels of Biomarkers of Systemic Inflammation: Tumor Necrosis Factor-receptor 2 (TNFR2)
In a subsample of the randomized trial population across the four arms, blood samples at baseline and in follow-up were collected and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-receptor 2 (TNFR2). We tested whether either or both supplements were associated with a decrease in the biomarkers of systemic inflammation (blood biomarker levels among those receiving supplements vs. placebo). We also tested whether there were interactions between the two supplements in their effects on changes in the TNFR2 serum biomarker of systemic inflammation.
Measured: Baseline and 1 year
Incident Autoimmune Diseases
All participants were followed for the development of new autoimmune diseases, including, but not limited to, rheumatoid arthritis, psoriasis, autoimmune thyroid disease, inflammatory bowel disease and polymyalgia rheumatica. The primary endpoint was all incident autoimmune disease confirmed by extensive medical record review. Participants self-reported all incident autoimmune diseases from baseline through follow-up. We used Cox proportional hazards models to test the effects of vitamin D and n-3 fatty acids upon autoimmune disease incidence.
We compared the separate main effects of vitamin D or n-3 fatty acid supplement assignment on AD incidence using Cox regression models. To account for randomization stratification and study design, we additionally adjusted for age, sex, self-reported race, and randomization to the other supplement. Person-time was counted until diagnosis of a new confirmed AD, death, or the end of the trial. We also test interactions between the two supplements
Measured: 5 years
Severity of Knee Pain in Subsample With Chronic, Frequent Knee Pain at Baseline- With n-3 FA & Vitamin D
Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Pain was the primary outcome on a scale of 0-100 with 100= worst pain.
Subsample of VITAL participants with chronic, frequent knee pain at trial baseline were followed with annual WOMAC questionnaires to test for change in severity of chronic knee pain in those taking Omega-3 fish oil (n-3 FA) supplements compared to those taking placebo and for those taking Vitamin D supplements compared to those taking placebo. We tested whether n-3 FA supplements and Vitamin D are associated with reduced levels of WOMAC knee pain at the end of the trial (comparing knee pain outcomes in those receiving supplements to placebo). We will also test whether there were multiplicative interactions between the two supplements for the outcome of knee pain severity by WOMAC-Pain index
Measured: Baseline and 5 years

Secondary outcomes (1)

Incident Autoimmune Disease
Development of new autoimmune disease through observational follow-up after trial termination.
Measured: extension of follow-up through 2 years post trial closure, up to 7 years

Timeline

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

Jul 2010Feb 2025

First posted11 May 2011 (estimated)
Study startJul 2010
Primary completion10 Nov 2018
Study completionFeb 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Autoimmune DiseasesStudies of the same condition, open and under way.
More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 N/A
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: NCT01351805
Sponsor's protocol ID: R01AR059086
Other IDs: R01AR059086
Acronym: VITAL
Status last verified: Nov 2025
First submitted: 4 May 2011
Last updated: 3 Dec 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Oakes EG, Vlasakov I, Kotler G, Bubes V, Mora S, Tatituri R, Cook NR, Manson JE, Costenbader KH. Joint effects of one year of marine omega-3 fatty acid supplementation and participant dietary fish intake upon circulating lipid mediators of inflammation resolution in a randomized controlled trial. Nutrition. 2024 Jul;123:112413. doi: 10.1016/j.nut.2024.112413. Epub 2024 Feb 28.
PubMed 38518540
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
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.
PubMed 31699704
MacFarlane LA, Cook NR, Kim E, Lee IM, Iversen MD, Gordon D, Buring JE, Katz JN, Manson JE, Costenbader KH. The Effects of Vitamin D and Marine Omega-3 Fatty Acid Supplementation on Chronic Knee Pain in Older US Adults: Results From a Randomized Trial. Arthritis Rheumatol. 2020 Nov;72(11):1836-1844. doi: 10.1002/art.41416. Epub 2020 Oct 3.
PubMed 32583982
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.
PubMed 35082139

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 3 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Knee Pain
ClinicalTrials.gov ID: NCT01351805
Acronym / sponsor ID: VITAL / R01AR059086
Conditions: Autoimmune Diseases, Systemic Inflammatory Process, Knee Pain Chronic, Osteoarthritis, Rheumatoid Arthritis
Keywords: vitamin D, omega-3 fatty acid, fish oil, prevention, trial, autoimmune disease, rheumatoid arthritis, psoriasis
Study type: Interventional
Recruitment status: Completed
Enrolment: 25,871 participants (actual)
Lead sponsor: Brigham and Women's HospitalUniversity, hospital or other
Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Study start: Jul 2010 (actual)
Primary completion: 10 Nov 2018 (actual)
Study completion: Feb 2025 (actual)
First posted: 11 May 2011 (estimated)
Results: Posted 8 Jan 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Factorial
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Fish Oil	Experimental	Drug: Fish Oil, Other: placebo pillSubjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).
Vitamin D	Experimental	Dietary Supplement: Vitamin D, Other: placebo pillSubjects will receive vitamin D3 (cholecalciferol) 2000 IU a day.
placebo	Placebo comparator	Other: placebo pillSubjects will receive placebo pill.
Vitamin D and Fish Oil	Experimental	Drug: Fish Oil, Dietary Supplement: Vitamin DSubjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).

Who may qualify

Ages: 50 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Fish OilAlso: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), marine fatty acids, omega-3 fatty acidsSubjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid [EPA] and 375 mg of docosahexaenoic acid [DHA]).	Drug	Fish Oil, Vitamin D and Fish Oil
Vitamin DAlso: cholecalciferol, vitamin D3Subjects will receive vitamin D3 (cholecalciferol) 2000 IU a day.	Dietary supplement	Vitamin D, Vitamin D and Fish Oil
placebo pillplacebo	Other	Fish Oil, Vitamin D, placebo

Primary outcome

Serum Levels of Biomarkers of Systemic Inflammation: Interleukin-6 (IL-6)
Time frame: Baseline and 1 year
In a subsample of the randomized trial population across the four arms, blood samples at baseline and in follow-up were collected and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-receptor 2 (TNFR2). We tested whether either or both supplements were associated with a decrease in the biomarkers of systemic inflammation (blood biomarker levels among those receiving supplements vs. placebo). We also tested whether there were interactions between the two supplements in their effects on changes in the IL-6 serum biomarker of systemic inflammation.
Serum Levels of Biomarkers of Systemic Inflammation: C-reactive Protein (CRP)
Time frame: Baseline and 1 year
In a subsample of the randomized trial population across the four arms, blood samples at baseline and in follow-up were collected and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-receptor 2 (TNFR2). We tested whether either or both supplements were associated with a decrease in the biomarkers of systemic inflammation (blood biomarker levels among those receiving supplements vs. placebo). We also tested whether there were interactions between the two supplements in their effects on changes in the CRP serum biomarker of systemic inflammation.
Serum Levels of Biomarkers of Systemic Inflammation: Tumor Necrosis Factor-receptor 2 (TNFR2)
Time frame: Baseline and 1 year
In a subsample of the randomized trial population across the four arms, blood samples at baseline and in follow-up were collected and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-receptor 2 (TNFR2). We tested whether either or both supplements were associated with a decrease in the biomarkers of systemic inflammation (blood biomarker levels among those receiving supplements vs. placebo). We also tested whether there were interactions between the two supplements in their effects on changes in the TNFR2 serum biomarker of systemic inflammation.
Incident Autoimmune Diseases
Time frame: 5 years
All participants were followed for the development of new autoimmune diseases, including, but not limited to, rheumatoid arthritis, psoriasis, autoimmune thyroid disease, inflammatory bowel disease and polymyalgia rheumatica. The primary endpoint was all incident autoimmune disease confirmed by extensive medical record review. Participants self-reported all incident autoimmune diseases from baseline through follow-up. We used Cox proportional hazards models to test the effects of vitamin D and n-3 fatty acids upon autoimmune disease incidence. We compared the separate main effects of vitamin D or n-3 fatty acid supplement assignment on AD incidence using Cox regression models. To account for randomization stratification and study design, we additionally adjusted for age, sex, self-reported race, and randomization to the other supplement. Person-time was counted until diagnosis of a new confirmed AD, death, or the end of the trial. We also test interactions between the two supplements
Severity of Knee Pain in Subsample With Chronic, Frequent Knee Pain at Baseline- With n-3 FA & Vitamin D
Time frame: Baseline and 5 years
Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Pain was the primary outcome on a scale of 0-100 with 100= worst pain. Subsample of VITAL participants with chronic, frequent knee pain at trial baseline were followed with annual WOMAC questionnaires to test for change in severity of chronic knee pain in those taking Omega-3 fish oil (n-3 FA) supplements compared to those taking placebo and for those taking Vitamin D supplements compared to those taking placebo. We tested whether n-3 FA supplements and Vitamin D are associated with reduced levels of WOMAC knee pain at the end of the trial (comparing knee pain outcomes in those receiving supplements to placebo). We will also test whether there were multiplicative interactions between the two supplements for the outcome of knee pain severity by WOMAC-Pain index

1 secondary outcome

Incident Autoimmune Disease
Time frame: extension of follow-up through 2 years post trial closure, up to 7 years

Results and safety

Results posted to the registry on 8 Jan 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ACTIVE Vitamin D + ACTIVE Omega-3 Fatty Acids	6,463	6,463
ACTIVE Vitamin D + PLACEBO Omega-3 Fatty Acids	6,464	6,464
PLACEBO Vitamin D + ACTIVE Omega-3 Fatty Acids	6,470	6,470
PLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids	6,474	6,474

Primary outcome: Serum Levels of Biomarkers of Systemic Inflammation: Interleukin-6 (IL-6)

Time frame: Baseline and 1 year. Geometric mean (95% Confidence Interval). Unit: pg/ml

Measure	Active Vitamin D n = 784	Placebo Vitamin D n = 777	Active n-3 FA n = 784	Placebo n-3 FA n = 777
Baseline ln (IL-6) pg/ml, geometric mean (95% Cl)	1.71 (1.65 to 1.78)	1.68 (1.61 to 1.74)	1.69 (1.63 to 1.75)	1.70 (1.63 to 1.77)
Year 1 ln (IL-6) pg/mL, geometric mean (95% CI)	1.80 (1.73 to 1.87)	1.63 (1.57 to 1.69)	1.70 (1.64 to 1.77)	1.72 (1.66 to 1.79)

Active Vitamin D vs Placebo Vitamin D: Percent change in geometric means: 8.19 (95% CI 1.52 to 15.31), p = 0.02, as above
Active n-3 FA vs Placebo n-3 FA: Percent change in geometric means: -0.73 (95% CI -6.87 to 5.81), p = 0.97, as above
Active Vitamin D vs Placebo Vitamin D vs Active n-3 FA vs Placebo n-3 FA: p = 0.12, p for interaction

Population analysed: Subsample of the VITAL trial participants at baseline and one year.

Primary outcome: Serum Levels of Biomarkers of Systemic Inflammation: C-reactive Protein (CRP)

Time frame: Baseline and 1 year. Geometric mean (95% Confidence Interval). Unit: mg/L

Measure	Active Vitamin D n = 784	Placebo Vitamin D n = 777	Active n-3 FA n = 784	Placebo n-3 FA n = 777
Baseline ln (hsCRP) mg/L, geometric mean (95% Cl)	1.48 (1.40 to 1.57)	1.51 (1.43 to 1.60)	1.57 (1.49 to 1.66)	1.43 (1.35 to 1.51)
Year 1 ln (hsCRP) mg/L, geometric mean (95% CI)	1.62 (1.53 to 1.71)	1.54 (1.46 to 1.63)	1.63 (1.54 to 1.72)	1.53 (1.45 to 1.62)

Active Vitamin D vs Placebo Vitamin D: Percent change in geometric means: 7.12 (95% CI -1.81 to 16.87), p = 0.16, as above
Active n-3 FA vs Placebo n-3 FA: Percent change in geometric means: -3.89 (95% CI -11.92 to 4.86), p = 0.44, as above
Active Vitamin D vs Placebo Vitamin D vs Active n-3 FA vs Placebo n-3 FA: p = 0.38, P for interaction

Population analysed: Subsample of the VITAL trial participants at baseline and one year.

Primary outcome: Serum Levels of Biomarkers of Systemic Inflammation: Tumor Necrosis Factor-receptor 2 (TNFR2)

Time frame: Baseline and 1 year. Geometric mean (95% Confidence Interval). Unit: pg/ml

Measure	Active Vitamin D n = 784	Placebo Vitamin D n = 777	Active n-3 FA n = 784	Placebo n-3 FA n = 777
Baseline ln (TNFR2) pg/ml, geometric mean (95% Cl)	2546.5 (2508.6 to 2584.9)	2525.4 (2482.7 to 2568.9)	2571.3 (2528.1 to 2615.2)	2500.9 (2463.6 to 2538.8)
Year 1 ln (TNFR2) pg/mL, geometric mean (95% CI)	2604.7 (2565.2 to 2644.7)	2567.9 (2523.9 to 2612.7)	2605.3 (2561.4 to 2649.9)	2567.3 (2527.7 to 2607.6)

Active Vitamin D vs Placebo Vitamin D: Percent change in geometric means: 0.63 (95% CI -1.03 to 2.31), p = 0.57, as above
Active n-3 FA vs Placebo n-3 FA: Percent change in geometric means: -1.27 (95% CI -2.89 to 0.39), p = 0.13, as above
Active Vitamin D vs Placebo Vitamin D vs Active n-3 FA vs Placebo n-3 FA: p = 0.74, P for interaction

Population analysed: Subsample of the VITAL trial participants at baseline and one year.

Primary outcome: Incident Autoimmune Diseases

Time frame: 5 years. Count of participants. Unit: Participants

Measure	Active Vitamin D n = 12927	Placebo Vitamin D n = 12944	Active n-3 FA n = 12933	Placebo n-3 FA n = 12938
Value	123	155	130	148

Active Vitamin D vs Placebo Vitamin D: Cox Proportional Hazard: 0.78 (95% CI 0.61 to 0.99), p = 0.05, Regression, Cox
Active n-3 FA vs Placebo n-3 FA: Cox Proportional Hazard: 0.85 (95% CI 0.67 to 1.08), p = 0.19, Regression, Cox
Active Vitamin D vs Placebo Vitamin D vs Active n-3 FA vs Placebo n-3 FA: p = 0.20, P for interaction

Population analysed: All participants in VITAL followed for the development of new autoimmune diseases, including, but not limited to, rheumatoid arthritis, psoriasis, autoimmune thyroid disease, inflammatory bowel disease and polymyalgia rheumatica. Categorized by vitamin D (active/placebo) and n-3 (active/placebo)

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 5 years. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Active Vitamin D/ Active Omega-3 Fatty Acids	791 of 6,463 (12.2%)	5,101 of 6,463 (78.9%)	241 of 6,463
Active Vitamin D/ Active Omega-3 Placebo	782 of 6,464 (12.1%)	5,027 of 6,464 (77.8%)	244 of 6,464
Active Omega-3 Fatty Acids, Placebo Vitamin D	822 of 6,470 (12.7%)	5,037 of 6,470 (77.9%)	252 of 6,470
Omega-3 Fatty Acids Placebo/ Placebo Vitamin D	837 of 6,474 (12.9%)	5,101 of 6,474 (78.8%)	241 of 6,474

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 38518540Oakes EG, Vlasakov I, Kotler G, Bubes V, Mora S, Tatituri R, Cook NR, Manson JE, Costenbader KH. Joint effects of one year of marine omega-3 fatty acid supplementation and participant dietary fish intake upon circulating lipid mediators of inflammation resolution in a randomized controlled trial. Nutrition. 2024 Jul;123:112413. doi: 10.1016/j.nut.2024.112413. Epub 2024 Feb 28.
Results publication: PubMed 38272846Costenbader 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.
Results publication: PubMed 31699704Costenbader 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.
Results publication: PubMed 32583982MacFarlane LA, Cook NR, Kim E, Lee IM, Iversen MD, Gordon D, Buring JE, Katz JN, Manson JE, Costenbader KH. The Effects of Vitamin D and Marine Omega-3 Fatty Acid Supplementation on Chronic Knee Pain in Older US Adults: Results From a Randomized Trial. Arthritis Rheumatol. 2020 Nov;72(11):1836-1844. doi: 10.1002/art.41416. Epub 2020 Oct 3.
Results publication: PubMed 35082139Hahn 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.
Welcome to the VITAL Study WebsiteLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Karen H Costenbader, MD, MPH principal investigator

Brigham and Women's Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Fish Oil and Vitamin D in people with Autoimmune Diseases and Systemic Inflammatory Process, 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: finished, as of the sponsor's last update on 3 Dec 2025. 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jan 2021). 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?

Serum Levels of Biomarkers of Systemic Inflammation: Interleukin-6 (IL-6) (time frame: Baseline and 1 year). The study lists 5 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 NCT01351805, which also lists 5 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 3 Dec 2025.