Background Strong biologic rationale supports both vitamin D and marine omega-3 (n-3) fatty acids for prevention of autoimmune disease (AD). Within the randomized, double-blind, placebo-controlled VITamin D and OmegA-3 TriaL (VITAL), we tested the effects of these supplements on AD incidence. We previously reported results after 5.3 years of randomized follow-up showing overall protective effects for vitamin D on AD incidence (HR 0.78, 95% CI 0.61-0.99) and suggestive results for n-3 fatty acids (HR 0.85, 95%CI 0.67-1.08)¹.

Objectives We aimed to test effects of these supplements with two more years of post-intervention follow-up in VITAL.

Methods VITAL enrolled and randomized men and women (age ≥50 and ≥55 years, respectively) in a 2-by-2 factorial design to vitamin D₃ (2000 IU/d) and/or n-3 fatty acids (1000 mg/d) or placebo and followed for median 5.3 years. Here, we followed participants for another 2 years of observation to assess for sustained effects. Incident AD diagnoses were reported by participants annually and confirmed by medical record review by expert physicians using existing classification criteria. The primary endpoint was total incident AD, including rheumatoid arthritis (RA), polymyalgia rheumatica (PMR), autoimmune thyroid disease (AITD), psoriasis, and all others. Pre-specified secondary endpoints included individual common AD; and probable AD. Cox models calcuated hazard ratios (HR) for incident ADs.

Results Of 25,871 participants randomized, 71% self-reported non-Hispanic Whites, 20% Black, 9% other racial/ethnic groups, 51% women, mean age was 67.1 years. During 7.5 years median follow-up, confirmed AD was diagnosed in 156 participants in vitamin D arm vs 198 in vitamin D placebo arm, HR 0.79 (0.64-0.97). Incident AD was confirmed in 167 participants in n-3 fatty acid arm and 187 in n-3 fatty acid placebo arm, HR 0.89 (0.72-1.10). For vitamin D, HRs trended toward reduction for RA 0.67 (0.37- 1.21), PMR 0.69 (0.46-1.03) and psoriasis 0.57 (0.33-0.99). For n-3 fatty acids, HRs trended toward reduction for RA 0.55 (0.30-1.10) and AITD 0.61 (0.33-1.12). Vitamin D’s effect on AD incidence was stronger in those with body mass index (BMI) < 25 (HR 0.65, 0.44-0.96) than ≥ 25 kg/m² (p interaction 0.01).

Conclusion Supplementation for 5.3 years with 2000 IU/day vitamin D (compared to placebo), followed by 2 years of observational follow-up, significantly reduced overall incident AD by 21% in older adults. HRs for RA, PMR and psoriasis trended toward reduction with vitamin D, with stronger effect in those with normal BMI. Supplementation with 1000 mg/day n-3 fatty acids did not significantly reduce total AD.

References [1]Hahn J et al, BMJ, 2022 Jan 26;376: e066452.

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Disclosure of Interests Karen Costenbader Consultant of: Astra Zeneca, Glaxo Smith Kline, Neutrolis, Grant/research support from: Merck, Exagen, Gilead, Nancy Cook: None declared, I-min Lee: None declared, Jill Hahn: None declared, Joseph Walter: None declared, Vadim Bubes: None declared, Gregory Kotler: None declared, Nicole Yang: None declared, Sonia Friedman: None declared, Erik Alexander: None declared, JoAnn Manson: None declared.