Vitamin D, omega 3 fatty acid supplements lower risk of autoimmune disease

Five-year supplementation with vitamin D, regardless of the presence of omega 3 fatty acids, results in a 22-percent decrease in autoimmune disease, while omega 3 fatty acid supplementation, with or without vitamin D, leads to a 15-percent reduction in autoimmune disease, results of a study have shown.

“This study of more than 25,000 older adults in the US provides evidence that daily supplementation with 2,000 IU/day vitamin D or a combination of vitamin D and omega 3 fatty acids for 5 years reduces autoimmune disease incidence, with more pronounced effects found after 2 years of supplementation,” the researchers said.

“Autoimmune diseases are a group of heterogeneous conditions with similar underlying pathogenetic mechanisms and together are associated with considerable morbidity and mortality,” they added.

A total of 25,871 participants (mean age 67.1 years, 18,046 non-Hispanic White, 5,106 Black, 2,152 other racial/ethnic groups) were included in Vitamin D and Omega 3 Trial (VITAL), a nationwide, randomized, double-blind, placebo-controlled trial with a two-by-two factorial design. Of these, 12,786 were men aged ≥50 years and 13,085 were women aged ≥55 years at enrolment.

Participants were assigned to receive vitamin D (2,000 IU/day) or matched placebo and omega 3 fatty acids (1,000 mg/day) or matched placebo. All incident autoimmune diseases from baseline to a median follow-up of 5.3 years were self-reported. The researchers confirmed these diseases through an extensive medical record review. They tested the effects of both supplements on autoimmune disease incidence using Cox proportional hazard models.

Incidence of autoimmune disease

In the vitamin D arm, 123 participants on intervention and 155 on placebo had a confirmed autoimmune disease (hazard ratio [HR], 0.78, 95 percent confidence interval [CI], 0.61‒0.99; p=0.05). In the omega 3 fatty acids arm, 130 on treatment and 148 on placebo were diagnosed with the disease (HR, 0.85, 95 percent CI, 0.67‒1.08; p=0.19). [BMJ 2022;376:e066452]

Compared with the reference arm (both placebo groups: 88 with confirmed autoimmune disease), 63 participants who received both vitamin D and omega 3 fatty acids (HR, 0.69, 95 percent CI, 0.49‒0.96), 60 who received vitamin D only (HR, 0.68, 95 percent CI, 0.48‒0.94), and 67 who received omega 3 fatty acids only (HR, 0.74, 95 percent CI, 0.54‒1.03) had an autoimmune disease.

“The clinical importance of these findings is high because these are well tolerated, nontoxic supplements, and other effective treatments to reduce the incidence of autoimmune diseases are lacking,” the researchers said. “Additionally, we saw consistent results across autoimmune diseases and increasing effects with time.”

Several mechanisms could potentially explain how these supplements might reduce the incidence of autoimmune disease. For instance, the vitamin D metabolite 1,25-dihydroxyvitamin D controls an array of genes that are involved in inflammation as well as acquired and innate immune responses. [Endocr Rev 2019;40:1109-1151]

The addition of these metabolites to CD4+ T cells also inhibits inflammatory IL-6, an important factor stimulating T helper 17 cells, which play a role in the development of autoimmune disease. Moreover, 1,25-dihydroxyvitamin D could increase the production of anti-inflammatory regulatory T cells. [Immunol Cell Biol 2007;85:83-84; PLoS One 2019;14:e0222313]

“We are continuing to follow participants for 2 years in an extension study to test the time course of this autoimmune disease reduction effect,” the researchers said. “Further trials could test these interventions in younger populations, and those with high autoimmune disease risk.”