Vitamin D, fish oil: protective against autoimmune diseases?

In the postintervention results of the VITAL* trial, vitamin D and marine omega-3 fatty acids (n-3 FAs) continued to demonstrate a protective effect against autoimmune diseases in older adults.

“We previously reported a protective effect of vitamin D on the incidence of autoimmune disease (hazard ratio [HR], 0.78) after 5 years of randomized follow-up, as well as a [nonsignificant but] suggestive protective effect of n-3 FAs on the incidence of autoimmune disease (HR, 0.85),” said Dr Karen Costenbader from Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts, US, at EULAR 2022.

In the current four-arm factorial analysis, at 7.3 years, the effect of vitamin D declined, as reflected by the HRs for confirmed (0.97; p=0.78) and confirmed + probable incident autoimmune diseases (0.95; p=0.45). There was no decline seen with n-3 FAs, as the HRs were “very close to the original HR”, said Costenbader, and were similar for both confirmed and confirmed + probable cases (0.87 for both). [EULAR 2022, abstract OP0038]

“[A]lthough the reduction of the protective effects at 2 years after discontinuation was lower ... all intervention arms had sustained lower incidence autoimmune disease than did placebo/placebo arm,” Costenbader explained.

For individual autoimmune diseases, while both supplements seemed rather protective against rheumatoid arthritis, the reductions were not as significant, be it with vitamin D (HR, 0.83; p=0.45 [confirmed] and HR, 0.79; p=0.31 [confirmed + probable]) or n-3 FAs (HR, 0.64; p=0.08 and HR, 0.75; p=0.21, respectively). No significant reductions were seen as well in the incidence of polymyalgia rheumatica across all evaluated groups (HRs ranging from 0.81 to 0.92).

Strong biologic rationale

“[There is a] strong biologic rationale to study vitamin D and n-3 FAs for the prevention of autoimmune diseases,” said Costenbader. Vitamin D regulates genes involved in inflammation and innate and adaptive immune responses, while n-3 FAs suppress biosynthesis of inflammatory arachidonic acid-derived eicosanoids. “[N-3 FAs] lead to synthesis of specialized pro-resolving mediators, which is thought to have a role in resolving inflammation,” she added.

The team initially randomized >25,000 older adults (mean age 67.1 years, 51 percent female) 1:1 to receive daily vitamin D 2,000 IU or placebo. They were then rerandomized to receive daily n-3 FAs 1,000 mg or placebo. Participants were followed for a median 5.3 years. Another 2 years of post-intervention observation without trial supplements ensued to evaluate for sustained effects.

During the 2-year extension period, 196 new confirmed incident autoimmune disease cases were identified, bringing the total number of cases up to 474. There were 287 new confirmed + probable autoimmune disease cases, jumping from 457 to 744.

Despite the large cohort and the extension phase that allowed for the identification of more cases and evaluation of prolonged effects after discontinuation, the population was not high-risk or deficient. “The effects may be greater [in such individuals],” Costenbader pointed out. “[Also, the participants were] older adults, so the prevention of other autoimmune diseases in younger populations remains to be proven.”

“[Nonetheless, the] clinical importance of these findings is high, given that these are well-tolerated, nontoxic supplements, and that there are no other known effective therapies to reduce the incidence of autoimmune diseases,” said Costenbader.