Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial.
Level 2 - randomized trial
Large individual double-blind randomized controlled trial (2x2 factorial design)
PubMed 35082139 · doi:10.1136/bmj-2021-066452
What was done
The nationwide VITAL randomized, double-blind, placebo-controlled trial with a 2x2 factorial design enrolled 25,871 US participants (12,786 men aged 50 and older, 13,085 women aged 55 and older; mean age 67.1 years; 18,046 non-Hispanic white, 5,106 black, 2,152 other). Participants received vitamin D3 (2000 IU/day) or matched placebo, and marine omega-3 fatty acids (1000 mg/day) or matched placebo. Participants self-reported incident autoimmune diseases over a median of 5.3 years of follow-up, which were confirmed by extensive medical record review. The primary endpoint was total confirmed incident autoimmune diseases (including rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and others) analyzed with Cox proportional hazards models.
What was found
In the vitamin D arm, 123 participants in the treatment group versus 155 in the placebo group developed confirmed autoimmune disease (hazard ratio 0.78, 95% confidence interval 0.61 to 0.99, P=0.05), a 22% reduction. In the omega-3 arm, 130 participants in the treatment group versus 148 in the placebo group developed confirmed autoimmune disease (HR 0.85, 95% CI 0.67 to 1.08, P=0.19). Compared with the reference arm of double placebo (88 confirmed cases), confirmed autoimmune disease occurred in 63 participants receiving vitamin D plus omega-3 (HR 0.69, 95% CI 0.49 to 0.96), 60 receiving only vitamin D (HR 0.68, 95% CI 0.48 to 0.94), and 67 receiving only omega-3 (HR 0.74, 95% CI 0.54 to 1.03).
Why it matters
This trial demonstrates that long-term supplementation with 2000 IU/day of vitamin D reduces the incidence of autoimmune diseases in older adults.
Limits
The study was restricted to older adults (men ≥50 and women ≥55), precluding direct generalization to younger populations where many autoimmune conditions first manifest. Ascertainment relied on participant self-reporting prior to medical record confirmation. Only a single fixed dose of each supplement was evaluated.
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