Vitamin D and Marine n‐3 Fatty Acids for Autoimmune Disease Prevention: Outcomes Two Years After Completion of a Double‐Blind, Placebo‐Controlled Trial

Abstract

ObjectiveIn the 5.3 year randomized, 2 x 2 factorial, double‐blind, placebo‐controlled VITamin D and OmegA‐3 TriaL (VITAL), vitamin D supplementationreduced autoimmune disease (AD) incidence (hazard ratio [HR] 0.78, 95% confidence interval 0.61‐0.99). Omega‐3(n‐3) fatty acid supplementation showed a statistically non‐significant reduction (HR 0.85, 0.67‐1.08). We aimed to confirm further AD cases arising during and after randomization and assess sustained effects with 2 years of post‐intervention observation.MethodsOf the 12,786 men ≥ age 50 and 13,085 women ≥ age 55 initially randomized, we followed surviving and willing participants for 2 more years. We continued to confirm annual participant‐reported new AD by medical record review. Cox models calculated HRs for all confirmed AD, and for secondary endpoints, confirmed and probable cases, and individual ADs, including the observational period and during randomized time.Results21,592 participants (83.5%) were followed observationally for two more years. 514 participants had incident confirmed AD (236 since prior report). 255 had been randomized to vitamin D vs. 259 to vitamin D placebo: HR 0.98 (0.83‐1.17) at 7 years. AD was confirmed in 234 participants initially randomized to n‐3 fatty acids vs. 280 randomized to its placebo: HR 0.83 (0.70‐0.99) at 7 years. Of newly confirmed cases, 65 had onset during randomization; their inclusion changed randomized results to: HR 0.85 (0.70‐1.04) for vitamin D and HR 0.87 (0.71‐1.06) for n‐3 fatty acids.ConclusionsTwo years after trial termination, vitamin D 2000 IU/day's protective effects dissipated, but 1000 mg/day n‐3 fatty acids had a sustained effect in reducing AD incidence.