Vitamin D and Autoimmune Disease Study

In observational studies, vitamin D has been inconsistently associated with reduced risk of several autoimmune diseases, and a large randomized, controlled trial has been lacking.

Supplementation with vitamin D and fish oil-derived omega-3 fatty acids may prevent autoimmune diseases, suggests a large prospective randomized trial. A nationwide randomized trial by Jill Hahn and team revealed that supplementation for 5 years with vitamin D3 and/or n-3 fatty acids reduced incident autoimmune disease by 25-30% in older adults than those who received neither supplement. The effect of vitamin D3 appeared to be stronger after 2 years of supplementation.

The findings of the study were presented at the meeting of The American College of Rheumatology.

Objective of the Study

The objective of the study was to test both vitamin D3 and n-3 fatty acids for the prevention of autoimmune disease within a large nationwide randomized, controlled trial.

Study Design

The study was a nationwide randomized, double-blind, placebo-controlled trial, enrolling men at least 50 years and women at least 55 years of age in a two-by-two factorial design. Randomization to vitamin D3 (2000 IU/d) and/or n-3 fatty acids (1000 mg/d) or placebo occurred from November 2011 to March 2014, and treatment continued through December 2017. The effects tested of vitamin D3 and n-3 fatty acids were upon autoimmune disease incidence. The primary endpoint was total incident autoimmune diseases, including rheumatoid arthritis, polymyalgia rheumatica, and all others. Pre-specified secondary endpoints included individual most common autoimmune diseases; and probable autoimmune disease. Results were displayed in cumulative incidence curves and Cox regression models calculated hazard ratios (HR) of incident autoimmune diseases.

Results of the Study

• A total of 25,871 participants were randomized: 71% self-reported non-Hispanic Whites, 20% Black, and 9% other racial/ethnic groups, 51% women, mean age 67.1 years.
• During median follow-up of 5.3 years, confirmed autoimmune disease was diagnosed in 117 participants in the vitamin D3 group and 150 in the placebo group (HR 0.78, 95% confidence interval 0.61-1.00, p=0.04).
• Excluding the first 2 years in pre-specified analyses of the primary endpoint, the HR for vitamin D3 was 0.61 (0.43 – 0.86; 137 cases).
• Confirmed autoimmune disease was diagnosed in 123 participants in the n-3 fatty acids group and 144 in the placebo group (HR 0.85 (0.67-1.09). Excluding the first 2 years, the HR for the primary endpoint was 0.90 (0.64-1.26).

Hahn and team concluded that "Supplementation for 5 years with vitamin D3 and/or n-3 fatty acids reduced incident autoimmune disease by 25-30% in older adults vs. those who received neither supplement. The effect of vitamin D3 appeared stronger after 2 years of supplementation."

Reference

Hahn J, Cook N, Alexander E, Friedman S, Bubes V, Walter J, Kotler G, Lee I, Manson J, Costenbader K. Vitamin D and Marine n-3 Fatty Acid Supplementation and Prevention of Autoimmune Disease in the VITAL Randomized Controlled Trial [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10).