medwireNews: Findings from the VITAL trial suggest that vitamin D supplementation, with or without omega-3 fatty acids, may warrant further investigation as a strategy to reduce the risk for autoimmune diseases including rheumatoid arthritis (RA) and polymyalgia rheumatica (PMR).
“The clinical importance of this trial is high because these are well tolerated, non-toxic supplements, and other effective treatments to reduce the incidence of autoimmune diseases are lacking,” write the investigators in The BMJ.
Karen Costenbader (Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA) and co-investigators explain that VITAL was a trial designed to examine the impact of vitamin D and omega-3 supplementation on cancer and cardiovascular disease risk in men aged at least 50 years and women aged at least 55 years. Autoimmune disease incidence was a prespecified endpoint of an ancillary study.
In the two-by-two factorial design trial, 25,871 participants (average age 67.1 years, 51% women) were randomly assigned to receive daily supplements of vitamin D (cholecalciferol; 2000 IU/day) and/or omega-3 fatty acids (1 g/day as a fish oil capsule containing 460 mg eicosapentaenoic acid and 380 mg docosahexaenoic acid), or matched placebo for each supplement. These people were sent annual questionnaires to ask about whether they had experienced new-onset physician-diagnosed RA, PMR, psoriasis, inflammatory bowel disease, or another autoimmune disease (with space to specify which).
During a median 5.3 years of follow-up, 0.95% of the 12,927 participants given vitamin D developed an autoimmune disease, compared with 1.20% of the 12,944 given placebo, translating into a significant 22% lower risk in the vitamin D arm.
There were also numerically lower rates of autoimmune disease among people given omega-3 fatty acids versus placebo (1.01 vs 1.14%), but the between-group difference did not reach statistical significance.
The team then evaluated the efficacy of different combinations of supplements in a model adjusting for age, sex, and race, finding that people taking both vitamin D and omega-3 fatty acids (hazard ratio [HR]=0.69) or vitamin D alone (HR=0.68), but not omega-3 alone, had a significantly lower autoimmunity risk than those given placebo.
When the individual autoimmune diseases were analyzed separately, the researchers say there was a trend toward reduced risk favoring supplementation for “almost all diseases”, but there were no significant between-group differences, which they say could be due to “the small numbers of participants with individual diseases.”
Subgroup analyses also suggested that people with a lower BMI “seem to benefit more from vitamin D treatment,” while those with a family history of autoimmunity may be more likely to benefit from omega-3 than those without.
Costenbader et al say that participants will be followed up “in an extension study to test the time course of this autoimmune disease reduction effect.”
They recommend that future studies could test vitamin D and omega-3 fatty acid supplementation “in younger populations, and those with high autoimmune disease risk.”
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