Vitamin D With or Without Omega 3 Fatty Acids Reduces Risk of Autoimmune Disease

Brown bottle of vitamin D and fish oil capsules spilling onto wooden surface

The VITamin D and OmegA-3 TriaL (VITAL), conducted at Brigham and Women’s Hospital, was the first randomized, controlled trial to investigate whether supplementation with vitamin D and/or marine-derived, long-chain omega 3 fatty acid (here abbreviated “fatty acids”) supplementation can reduce the risk of autoimmune disease.

Karen H. Costenbader, MD, MPH, director of the Lupus Program in the Division of Rheumatology, Inflammation and Immunity, Jill Hahn, ScD, a research fellow in the division, and colleagues reported in The BMJ that fatty acids alone did not reduce the risk of incident (new onset) autoimmune disease. However, vitamin D or a combination of vitamin D and fatty acids was protective, with effects being more pronounced after two years of supplementation.


Men ≥50 years old and women ≥55 were recruited nationwide for this randomized, double-blind, placebo-controlled trial. 25,871 people successfully completed a three-month placebo run-in period (demonstrating they would adhere well to a supplementation regimen). They were randomly assigned to one of four regimens for five years:

  • Vitamin D (cholecalciferol; 2000 IU/day) + fatty acids (1 g/day as a liquid-filled capsule containing 460 mg eicosapentanoic acid [EPA] and 380 mg docosahexaenoic acid [DHA])
  • Vitamin D + fatty acid placebo
  • Fatty acids + vitamin D placebo
  • Vitamin D placebo + fatty acid placebo

Randomization occurred between November 2011 and March 2014, and supplementation ended in December 2017. 51% of participants were women, the mean age was 67, and the cohort’s racial/ethnic makeup was 71% non-Hispanic white, 20% Black, and 9% other groups.

Participants completed health history questionnaires six months and one year after randomization, then annually. The form inquired about rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, and psoriasis; all other autoimmune diseases were grouped together.

A participant who reported an autoimmune disease was asked to allow investigators to examine their medical records to confirm the diagnosis. These researchers were blinded to the regimen assigned.

Participants were said to have “probable” autoimmune disease if confirmatory tests had not been completed or documentation was otherwise insufficient.

Confirmed Disease

The primary endpoint was the incidence of confirmed autoimmune disease:

  • Vitamin D arm—Patients who used vitamin D had a 22% reduced risk of any confirmed autoimmune disease compared with those who used placebo alone (p=0.05)
  • Fatty acids arm—15% reduced risk, not statistically significant

The cumulative incidence of confirmed autoimmune disease over the five years of the trial was lower in all three supplementation groups than in the dual placebo group:

  • Vitamin D + fatty acids—31% reduced risk
  • Vitamin D + fatty acid placebo—32% reduced risk
  • Fatty acids + vitamin D placebo—26% reduced risk

Secondary Endpoints

The effect of supplementation on the incidence of confirmed plus probable autoimmune disease was:

  • Vitamin D—15% reduction, not statistically significant
  • Fatty acids—18% reduction (p=0.04)

When only the last three years of supplementation were considered, the effects were:

  • Vitamin D—39% reduction in confirmed disease (P=0.005) and 31% reduction in confirmed + probable disease (P=0.007)
  • Fatty acids—10% reduction in confirmed disease and 6% reduction in confirmed + probable disease; neither was statistically significant

Analyses of individual autoimmune diseases favored supplementation with either vitamin D or fatty acids, but no result for any particular disease was statistically significant.

Follow-up Continues

Given the latency of autoimmune disease onset, a longer period of follow-up may clarify these results and shed light on what happens after supplement discontinuation. A two-year observational study after trial termination is ongoing.

VITAL also investigated the effect of vitamin D and fatty acid supplementation on the risks of cancer and cardiovascular disease, and several other disease outcomes.

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