Vitamin D and Disease Prevention: Worth Another Look? | MedPage Today https://www.medpagetoday.com/meetingcoverage/acr/95529?xid=nl_mp...

Vitamin D and Disease Prevention: Worth
 

Another Look?
— Incidence of autoimmune disease decreased by 25-30% with dietary
supplements
by Nancy Walsh, Contributing Writer, MedPage Today
November 8, 2021
The use of vitamin D and omega-3 fatty acid supplementation was associated with a
decreased likelihood of autoimmune disease in an ancillary analysis of a large randomized
trial.

During 5 years of follow-up in a cohort of almost 17,000 adults, there were 123 incident
cases of autoimmune disease among those who were taking vitamin D supplements daily,
while there were 155 among those on placebo, for a hazard ratio of 0.78 (95% CI 0.61-1.00,
P=0.045), reported Karen Costenbader, MD, of Brigham and Women's Hospital in Boston.

"I don't have to convince this audience of the burden of autoimmune diseases. These
diseases affect 5% to 8% of the population, or 15 to 20 million Americans. They are among
the top 10 causes of death among women under 65 in the U.S. and the second most
common cause of chronic illness," she said in a plenary session at the 2021 virtual annual
meeting of the American College of Rheumatology.

There currently is no means of preventing autoimmune diseases, which include conditions

such as rheumatoid arthritis, polymyalgia rheumatica, and psoriasis.

Vitamin D is a pleiotropic hormone with wide regulatory actions. It binds to the nuclear
vitamin D receptor and regulates an array of genes involved in innate and adaptive
immune responses, she explained.

Ecological observations have demonstrated that autoimmune diseases such as

inflammatory bowel disease, multiple sclerosis, and type 1 diabetes are more prevalent at
northern latitudes where vitamin D levels typically are lower. In previous observational
studies, high residential ultraviolet exposures have been associated with lower risks of
Crohn's disease, and also with decreased rates of rheumatoid arthritis. However, no

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Vitamin D and Disease Prevention: Worth Another Look? | MedPage Today https://www.medpagetoday.com/meetingcoverage/acr/95529?xid=nl_mp...

prospective trial has tested the effects of supplementation with vitamin D and the
 
incidence of autoimmune disease over time.

Omega 3 fatty acids are abundant in fish. These compounds suppress the biosynthesis of
inflammatory arachidonic acid-derived eicosanoids and regulate the inflammatory
transcription factors nuclear factor kappa B and peroxisome proliferator activated receptor.
Previous studies have found that higher intake of omega-3 fatty acids was associated with
a lower incidence of rheumatoid arthritis and a decreased prevalence of seropositivity. To
date, no prospective study has evaluated the effects of daily use of omega 3 fatty acids on
the incidence of autoimmune disease.

To address these knowledge gaps, Costenbader's group analyzed data from the vitamin D
and omega 3 (VITAL) trial, which included almost 26,000 men ages 50 and older and women
55 and older.

The primary analysis of VITAL was for the incidence of cancer and cardiovascular disease;
no decrease in risk was observed for those conditions.

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In this ancillary study, the outcome of interest was the incidence of all autoimmune
diseases among the 16,956 participants who had undergone assays for 25 (OH) vitamin D
and had plasma omega-3 index measurements.

First, participants were randomized to vitamin D, 2,000 IU/day (n=12,937) or placebo

(n=12,937), and then in a 2 × 2 factorial design they were again randomized to omega 3
fatty acids, 1 g/day (n=6,468) or placebo (n=6,469) in the active vitamin D arm and to
omega 3 fatty acids, 1 g/day (n=6,468) or placebo (n=6,469) in the placebo group of the
vitamin D randomization arm.

Median follow-up was 5.3 years.

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Vitamin D and Disease Prevention: Worth Another Look? | MedPage Today https://www.medpagetoday.com/meetingcoverage/acr/95529?xid=nl_mp...

Participants' mean age was 67, and the groups were well matched on factors such as
 
demographics, vitamin D levels and intake, and family history.

The cumulative incidence curves for vitamin D supplementation versus placebo begin to
diverge after 2 to 3 years of follow-up, "which makes sense biologically and supports long-
term use," she said.

For omega-3 supplementation, there were 130 confirmed cases of autoimmune disease in
the active treatment group and 148 cases in the placebo group (HR 0.85, 95% CI 0.67-1.09,
P=0.20). In an additional analysis comparing patients who had initially been randomized to
the vitamin D placebo arm, there were 67 confirmed cases in the re-randomized omega-3
supplementation group and 88 in the placebo group (HR 0.74, 95% CI 0.54-1.03, P=0.07). In
that analysis, there were 63 cases in the vitamin D plus omega-3 group and 88 cases in the
placebo/placebo arm, for a hazard ratio of 0.69 (95% CI 0.49-0.96, P=0.03).

There were no significant differences in adverse events between the active and placebo
groups.

"Supplementation for 5 years with vitamin D3 and/or omega-3 fatty acids reduced incident
autoimmune disease by 25% to 30% in older adults versus those who received neither
supplement," she concluded.

"The clinical importance of these findings is high, given that these are well tolerated,
nontoxic supplements and that there are no other effective therapies to reduce the
incidence of autoimmune diseases," she commented.

Nancy Walsh earned a BA in English literature from Salve Regina College in Newport, R.I.

Disclosures

Costenbader reported financial relationships with Neutrolis, Merck, Exagen, Gilead, and AstraZeneca.

Primary Source
American College of Rheumatology
Source Reference: Hahn J, et al "Vitamin D and marine n-3 fatty acid supplementation and prevention of autoimmune disease
in the VITAL randomized controlled trial" ACR 2021; abstract 0957.

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