Vitamin D and the Risk of Autoimmune Diseases Save

The results of the VITAL study (presented at ACR 2021) are now published by BMJ, showing that vitamin D and omega 3 fatty acids reduce the overall risk of autoimmune disease (AID) in a population based intervention trial.

VITAL was a national population trial that originally set out to show whether daily supplementation with 2000 IU/day of vitamin D was compared to omega 3 and placebo daily.  The study enrolled 25 871 adults (12786 men ≥50 years and 13 085 women ≥55 years). Subjects were given Vitamin D (2000 IU/day) or matched placebo, and omega 3 fatty acids (1000 mg/day) or matched placebo. Incident autoimmune diseases (self reported) were assessed after a median of 5.3 years follow-up.

Incident autoimmune diseases reported herein included rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis, and all others.

This report is a sub study of the primary VITAL trial.  At entry to serum vit. D levels were over 30 and roughly 34% of all patients had a family history of autoimmune disease.   The mean age was 67.1 years.

After 5 years of observation, they had 278 (1.1%) confirmed cases of AID and another 457 with probable incident AID.  Thus vitamin D significantly lowered the risk of incident confirmed autoimmune disease (HR 078; 95%CI 0.61, 1.00; p=0.045). Similarly N-3 FA lowered AID risk by 15% (HR 0.85; CI 0.67, 1.09; p0.20) but this was not significant.

Taking both supplements also significantly lowered risk of AID overall (HR 0.69; 0.49, 0.96; p=0.03). But, there was no clear prevention of individual autoimmune diseases like RA, SLE, PMR, etc.  It is unknown if these subtle benefits would apply to a younger population, as most of the benefits seen in this report were in older patients. 

Mechanisms by which vitamin D and omega 3 fatty acids (nutritional supplements) can affect autoimmune disease is based on their role in downregulating inflammation and innate immune responses.  Unfortunately, vitamin D intervention trials have not proven a benefit in SLE patients, yet many still recommend vitamin D supplementation.  Yet, there are trials of omega-3 FA showing antiinflammatory benefits when given in higher doses to patients with rheumatoid arthritis, systemic lupus erythematosus and psoriasis.

Oddly, VITAL study was originally designed to assess the preventative potential of supplements Vitamin D and Omega-3 (n-3) fatty acids on cancer and cardiovascular outcomes, but failed to do so in results previously published in the NEJM. 

While these results are quite novel and encouraging, the prevention event rates were very low, as new onset autoimmune disease in an older population is also low.  One estimate of potential benefit would be the number needed to treat (NNT) which is nearly 400 (number of cases needed to prevent 1 case of rheumatic disease).