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CompletedNCT01351805VITALUpdated Dec 3, 2025Results posted

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

An interventional study of Fish Oil and Vitamin D in Autoimmune Diseases, Systemic Inflammatory Process and Knee Pain Chronic, sponsored by Brigham and Women's Hospital. Completed at 1 site in United States. Open to participants aged 50 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-12-03.

Sponsored by Brigham and Women's Hospital · Not applicable, Interventional, and Prevention

From the registry’s dates

  • Registered 10 months after the study started (first participant enrolled Jul 2010, registered May 2011).
Phase
Not applicable
Study type
Interventional
Enrollment
25,871
Allocation
Randomized
Ages
50 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • 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
  • systemic inflammation
  • Interleukin-6
  • C-reactive peptide
  • tumor necrosis factor
  • osteoarthritis
03

In context

Autoimmune Diseases

655 studies on the registry are indexed under Autoimmune Diseases; 275 are open to participants now.

This study's enrollment of 25,871 is above the median of 40 across 427 interventional studies indexed under Autoimmune Diseases.

Browse Autoimmune Diseases studies →

Lead sponsor

Brigham and Women's Hospital is the lead sponsor of 1,236 studies on the registry; 224 are open to participants now.

Of its 116 completed or terminated interventional studies of FDA-regulated products, 64 (55%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
50 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes

Eligibility criteria

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.

05

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Factorial assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
25,871 participants (actual)

Study arms

  • Experimental
    Fish Oil

    Subjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]).

    Drug: Fish Oil · Other: placebo pill

  • Experimental
    Vitamin D

    Subjects will receive vitamin D3 (cholecalciferol) 2000 IU a day.

    Dietary Supplement: Vitamin D · Other: placebo pill

  • Placebo comparator
    placebo

    Subjects will receive placebo pill.

    Other: placebo pill

  • Experimental
    Vitamin D and Fish Oil

    Subjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]).

    Drug: Fish Oil · Dietary Supplement: Vitamin D

Interventions

  • DrugFish Oil

    Subjects will receive marine omega-3 fatty acids (465 mg of eicosapentaenoic acid \[EPA\] and 375 mg of docosahexaenoic acid \[DHA\]).

    Also known as: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), marine fatty acids, omega-3 fatty acids, fish oils

  • Dietary supplementVitamin D

    Subjects will receive vitamin D3 (cholecalciferol) 2000 IU a day.

    Also known as: cholecalciferol, vitamin D3

  • Otherplacebo pill

    placebo

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline and 1 year

  2. 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.

    Time frame: Baseline and 1 year

  3. 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.

    Time frame: Baseline and 1 year

  4. 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

    Time frame: 5 years

  5. 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

    Time frame: Baseline and 5 years

Secondary outcomes

  1. Incident Autoimmune Disease

    Development of new autoimmune disease through observational follow-up after trial termination.

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

07

Results

Posted Jan 8, 2021

Participant flow

From the 25871 VITAL participants, we identified 2 main subcohorts: A "systemic inflammation" subcohort of 1561 participants with sufficient blood biomarker assays, balanced by sex, and matched on blood draw season, and a second "knee pain" subcohort including 1,398 participants who returned one knee pain questionnaire and qualified at baseline. Both subcohorts are described below in their respective aims.

Participant flow — Overall Study
MilestoneACTIVE Vitamin D + ACTIVE Omega-3 Fatty AcidsACTIVE Vitamin D + PLACEBO Omega-3 Fatty AcidsPLACEBO Vitamin D + ACTIVE Omega-3 Fatty AcidsPLACEBO Vitamin D + PLACEBO Omega-3 Fatty Acids
Started6463646464706474
Completed6463646464706474
Not completed0000

Outcome measures

PrimarySerum 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.

Time frame:
Baseline and 1 year
Reported as:
Geometric mean · pg/ml
Serum Levels of Biomarkers of Systemic Inflammation: Interleukin-6 (IL-6)
pg/mlActive Vitamin DPlacebo Vitamin DActive n-3 FAPlacebo n-3 FA
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)
Statistical analysis
  • Active Vitamin D vs Placebo Vitamin D · as above · p = 0.02 (IL-6 from baseline to one year: overall % change= 8.19% (95%CI 1.52-15.31).) · Percent change in geometric means: 8.19 · 95% CI 1.52 to 15.31p above adjusted for age, sex, race and n-3 fatty acid randomized treatment group.
  • Active n-3 FA vs Placebo n-3 FA · as above · p = 0.97 (4\. IL-6 from baseline to one year: overall % change= -0.73% (95%CI -6.87 to 5.81).) · Percent change in geometric means: -0.73 · 95% CI -6.87 to 5.81p above adjusted for age, sex, race and vitamin D randomized treatment group.
  • Active Vitamin D vs Placebo Vitamin D vs Active n-3 FA vs Placebo n-3 FA · p for interaction · p = 0.12 (Test of multiplicative interaction between the effects of the two supplements)
PrimarySerum 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.

Time frame:
Baseline and 1 year
Reported as:
Geometric mean · mg/L
Serum Levels of Biomarkers of Systemic Inflammation: C-reactive Protein (CRP)
mg/LActive Vitamin DPlacebo Vitamin DActive n-3 FAPlacebo n-3 FA
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)
Statistical analysis
  • Active Vitamin D vs Placebo Vitamin D · as above · p = 0.16 (3\. HsCRP from baseline to one year: overall % change= 7.12% (95%CI -1.81-16.78).) · Percent change in geometric means: 7.12 · 95% CI -1.81 to 16.87p above adjusted for age, sex, race and n-3 fatty acid randomized treatment group.
  • Active n-3 FA vs Placebo n-3 FA · as above · p = 0.44 (6\. HsCRP from baseline to one year: overall % change= -3.89% (95%CI -11.92-4.86).) · Percent change in geometric means: -3.89 · 95% CI -11.92 to 4.86p above adjusted for age, sex, race and vitamin D randomized treatment group.
  • Active Vitamin D vs Placebo Vitamin D vs Active n-3 FA vs Placebo n-3 FA · P for interaction · p = 0.38
PrimarySerum 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.

Time frame:
Baseline and 1 year
Reported as:
Geometric mean · pg/ml
Serum Levels of Biomarkers of Systemic Inflammation: Tumor Necrosis Factor-receptor 2 (TNFR2)
pg/mlActive Vitamin DPlacebo Vitamin DActive n-3 FAPlacebo n-3 FA
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)
Statistical analysis
  • Active Vitamin D vs Placebo Vitamin D · as above · p = 0.57 (2\. TNFR2 from baseline to one year: overall % change= 0.63% (95%CI -1.03 to 2.31).) · Percent change in geometric means: 0.63 · 95% CI -1.03 to 2.31p above adjusted for age, sex, race and n-3 fatty acid randomized treatment group.
  • Active n-3 FA vs Placebo n-3 FA · as above · p = 0.13 (5\. TNFR2 from baseline to one year: overall % change= -1.27% (95%CI -2.89 to 0.39).) · Percent change in geometric means: -1.27 · 95% CI -2.89 to 0.39p above adjusted for age, sex, race and vitamin D randomized treatment group.
  • Active Vitamin D vs Placebo Vitamin D vs Active n-3 FA vs Placebo n-3 FA · P for interaction · p = 0.74
PrimaryIncident 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

Time frame:
5 years
Reported as:
Count of participants · Participants
Incident Autoimmune Diseases
ParticipantsActive Vitamin DPlacebo Vitamin DActive n-3 FAPlacebo n-3 FA
Incident Autoimmune Diseases123155130148
Statistical analysis
  • Active Vitamin D vs Placebo Vitamin D · Regression, Cox · p = 0.05 · Cox proportional hazard: 0.78 · 95% CI 0.61 to 0.99
  • Active n-3 FA vs Placebo n-3 FA · Regression, Cox · p = 0.19 · Cox proportional hazard: 0.85 · 95% CI 0.67 to 1.08
  • Active Vitamin D vs Placebo Vitamin D vs Active n-3 FA vs Placebo n-3 FA · P for interaction · p = 0.20p multiplicative interaction between effects of vitamin D and n-3 fa supplements
PrimarySeverity 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

Time frame:
Baseline and 5 years
Reported as:
Mean · WOMAC units on a scale
Severity of Knee Pain in Subsample With Chronic, Frequent Knee Pain at Baseline- With n-3 FA & Vitamin D
WOMAC units on a scaleActive n-3 FAPlacebo n-3 FAActive Vitamin DPlacebo Vitamin D
Baseline mean WOMAC Pain36.5 ± 0.735.4 ± 0.735.4 ± 0.736.5 ± 0.7
Follow Up mean WOMAC pain33.6 ± 0.933.7 ± 0.932.7 ± 0.934.6 ± 0.9
Statistical analysis
  • Active n-3 FA vs Placebo n-3 FA · Mixed Models Analysis · p = 0.77 (Repeated measures model with unstructured variance to assess effect of treatment on WOMAC Pain adjusting for age, sex, and other treatment. Linear time by treatment interaction term assessed change in WOMAC Pain over time in treatment vs placebo.)Repeated measures model with censoring for total knee replacement.
  • Active Vitamin D vs Placebo Vitamin D · Mixed Models Analysis · p = 0.41 (Repeated measures model with unstructured variance to assess effect of treatment on WOMAC Pain adjusting for age, sex, and other treatment. Linear time by treatment interaction term assessed change in WOMAC Pain over time in treatment vs placebo.)Linear time by treatment interaction (comparing change in WOMAC pain over time in two randomized groups)
  • Active n-3 FA vs Placebo n-3 FA vs Placebo Vitamin D · Regression, Linear · p = 0.42 · Mean difference (net): -1.5
  • Placebo n-3 FA vs Active Vitamin D vs Placebo Vitamin D · Regression, Linear · p = 0.18 · Mean difference (net): -2.5
  • Active n-3 FA vs Placebo n-3 FA vs Active Vitamin D · Regression, Linear · p = 0.84 · Mean difference (net): 0.39
  • Active n-3 FA vs Placebo n-3 FA vs Placebo Vitamin D · Regression, Linear · p = 0.76 · Mean difference (net): -0.55
SecondaryIncident Autoimmune Disease

Development of new autoimmune disease through observational follow-up after trial termination.

Time frame:
extension of follow-up through 2 years post trial closure, up to 7 years
Reported as:
Count of participants · Participants
Incident Autoimmune Disease
ParticipantsActive Vitamin DPlacebo Vitamin DActive n-3 FAPlacebo n-3 FA
Incident Autoimmune Disease255259234280
Statistical analysis
  • Active Vitamin D vs Placebo Vitamin D vs Active n-3 FA vs Placebo n-3 FA · Regression, Cox · p = <0.05 (HR with 95%CI) · Hazard ratio (hr): 1.0

Adverse events

Collected over 5 years. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Active Vitamin D/ Active Omega-3 Fatty Acids241/6,463 (3.7%)791/6,463 (12.2%)5,101/6,463 (78.9%)
Active Vitamin D/ Active Omega-3 Placebo244/6,464 (3.8%)782/6,464 (12.1%)5,027/6,464 (77.8%)
Active Omega-3 Fatty Acids, Placebo Vitamin D252/6,470 (3.9%)822/6,470 (12.7%)5,037/6,470 (77.9%)
Omega-3 Fatty Acids Placebo/ Placebo Vitamin D241/6,474 (3.7%)837/6,474 (12.9%)5,101/6,474 (78.8%)
Most frequent serious events
Showing 10 of 11
Most frequent serious events
EventActive Vitamin D/ Active Omega-3 Fatty AcidsActive Vitamin D/ Active Omega-3 PlaceboActive Omega-3 Fatty Acids, Placebo Vitamin DOmega-3 Fatty Acids Placebo/ Placebo Vitamin D
Invasive cancer of any typeNeoplasms benign, malignant and unspecified (incl cysts and polyps)408/6463385/6464412/6470412/6474
Major cardiovascular eventVascular disorders186/6463210/6464200/6470209/6474
Gastrointestinal bleedingBlood and lymphatic system disorders170/6463171/6464200/6470203/6474
Prostate cancer (in men)Neoplasms benign, malignant and unspecified (incl cysts and polyps)109/646383/6464110/6470109/6474
Myocardial infarctionVascular disorders72/646397/646473/6470103/6474
Death from cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)75/646379/646493/647094/6474
StrokeVascular disorders66/646375/646482/647067/6474
Death from cardiovascular causesVascular disorders74/646378/646468/647070/6474
HypercalcemiaEndocrine disorders77/646370/646474/647069/6474
Breast cancer (in women)Neoplasms benign, malignant and unspecified (incl cysts and polyps)60/646364/646457/647065/6474
Most frequent other events
Showing 10 of 13
Most frequent other events
EventActive Vitamin D/ Active Omega-3 Fatty AcidsActive Vitamin D/ Active Omega-3 PlaceboActive Omega-3 Fatty Acids, Placebo Vitamin DOmega-3 Fatty Acids Placebo/ Placebo Vitamin D
DiarrheaGastrointestinal disorders2781/64632730/64642818/64702850/6474
ConstipationGastrointestinal disorders2567/64632566/64642617/64702545/6474
Stomach upset or painGastrointestinal disorders2439/64632421/64642448/64702422/6474
NauseaGastrointestinal disorders1748/64631771/64641810/64701779/6474
Easy bruisingBlood and lymphatic system disorders1737/64631697/64641706/64701702/6474
Skin rashSkin and subcutaneous tissue disorders1629/64631639/64641702/64701728/6474
Bad taste in mouthGeneral disorders1109/64631086/64641131/64701159/6474
Increased burpingGastrointestinal disorders1107/64631061/64641110/64701097/6474
Blood in urineBlood and lymphatic system disorders469/6463442/6464450/6470432/6474
Frequent nosebleedsBlood and lymphatic system disorders224/6463242/6464241/6470249/6474

Baseline characteristics

In this 2x2 factorial design trial, the primary analyses were: all active vitamin D vs. all placebo vitamin D and all active omega-3 fatty acids vs. all placebo omega-3 fatty acids.

Age, Categorical
Age, Categorical(Participants)ACTIVE Vitamin D + ACTIVE Omega-3 Fatty AcidsACTIVE Vitamin D + PLACEBO Omega-3 Fatty AcidsPLACEBO Vitamin D + ACTIVE Omega-3 Fatty AcidsPLACEBO Vitamin D + PLACEBO Omega-3 Fatty AcidsTotal
<=18 years00000
Between 18 and 65 years24582462246124679848
>=65 years400540024009400716023
Age, Continuous
Age, Continuous(Years)ACTIVE Vitamin D + ACTIVE Omega-3 Fatty AcidsACTIVE Vitamin D + PLACEBO Omega-3 Fatty AcidsPLACEBO Vitamin D + ACTIVE Omega-3 Fatty AcidsPLACEBO Vitamin D + PLACEBO Omega-3 Fatty AcidsTotal
Mean67.1 ± 7.167.1 ± 7.067.2 ± 7.167.1 ± 7.167.1 ± 7.1
Sex/Gender, Customized
Sex/Gender, Customized(Participants)ACTIVE Vitamin D + ACTIVE Omega-3 Fatty AcidsACTIVE Vitamin D + PLACEBO Omega-3 Fatty AcidsPLACEBO Vitamin D + ACTIVE Omega-3 Fatty AcidsPLACEBO Vitamin D + PLACEBO Omega-3 Fatty AcidsTotal
Female327632713271326713085
Male318731933199320712786
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)ACTIVE Vitamin D + ACTIVE Omega-3 Fatty AcidsACTIVE Vitamin D + PLACEBO Omega-3 Fatty AcidsPLACEBO Vitamin D + ACTIVE Omega-3 Fatty AcidsPLACEBO Vitamin D + PLACEBO Omega-3 Fatty AcidsTotal
Non-Hispanic white451544984529450418046
African American12781275127112825106
Hispanic (not African American)2462702452521013
Asian/Pacific Islander1028698102388
Native American/ Alaskan Native62565852228
Other/ unknown126133123141523
Region of Enrollment
Region of Enrollment(participants)ACTIVE Vitamin D + ACTIVE Omega-3 Fatty AcidsACTIVE Vitamin D + PLACEBO Omega-3 Fatty AcidsPLACEBO Vitamin D + ACTIVE Omega-3 Fatty AcidsPLACEBO Vitamin D + PLACEBO Omega-3 Fatty AcidsTotal
United States646364646470647425871
08

Study locations

1 site
  • Brigham and Women's Hospital
    Boston, Massachusetts 02115, United States
09

References and documents

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 ↗

Study documents

  • Protocol and statistical analysis plan · Nov 9, 2009

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 3, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01351805
Lead sponsor
Brigham and Women's Hospital
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Responsible party
Karen H. Costenbader (Associate Physician, Brigham and Women's Hospital) — Principal investigator
First posted
May 11, 2011
Start date
Jul 2010
Primary completion
Nov 10, 2018
Completion
Feb 2025
Results posted
Jan 8, 2021
Last update
Dec 3, 2025

Study contacts

Karen H Costenbader, MD, MPH
principal investigator · Brigham and Women's Hospital

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

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