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

Objective. In the 5.3-year randomized, 2 x 2 factorial, double-blind, placebo-controlled Vitamin D and Omega-3 Trial (VITAL), vitamin D supplementation reduced autoimmune disease (AD) incidence (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.61-0.99). Omega-3 (n-3) fatty acid supplementation showed a statistically nonsignificant reduction (HR 0.85, 95% CI 0.67-1.08). We aimed to confirm further AD cases arising during and after randomization and assess sustained effects with two years of postintervention observation. Methods. Of the 12,786 men aged >= 50 and 13,085 women aged >= 55 initially randomized, we observed surviving and willing participants for two more years. We continued to confirm annual participant-reported new AD by medical record review. Cox models calculated HRs for all confirmed incident AD, (and secondary endpoints, including probable cases, and individual ADs), during the observational and randomized periods. Results. A total of 21,592 participants (83.5%) were observed for two more years; 514 participants developed incident confirmed AD (236 since prior report), of whom 255 had been randomized to vitamin D versus 259 to vitamin D placebo (HR 0.98 [95% CI 0.83-1.17] at 7 years). AD was confirmed in 234 participants initially randomized to n-3 fatty acids versus 280 randomized to its placebo (HR 0.83 [95% CI 0.70-0.99] at 7 years). Of newly confirmed cases, 65 had onset during randomization; their inclusion changed randomized results as follows: HR 0.85 (95% CI 0.70-1.04) for vitamin D and HR 0.87 (95% CI 0.71-1.06) for n-3 fatty acids. Conclusion. Two years after trial termination, the protective effects of 2000 IU/day of vitamin D dissipated, but 1,000 mg/day of n-3 fatty acids had a sustained effect in reducing AD incidence.