Vitamin D: Unclear Link With Autoimmune Diseases

It's that time of year when the clock has been turned back, days are shorter, and less time is spent outside in bright sunlight. It's also the time when vitamin D levels naturally decline.

Vitamin D lies at the center of a "chicken versus egg" debate in the face of conflicting evidence over its association with autoimmune rheumatologic diseases. The biologically active form of vitamin D is a hormone that regulates cell growth and differentiation, immune function, and inflammatory processes. Macrophages and immune (T and B) cells express a vitamin D receptor (VDR) that responds to vitamin D.

One school of thought claims a link between low levels of vitamin D and some autoimmune diseases. Adorini and Penna¹ maintained that the vitamin D system enhances natural immunity and suppresses adaptive immunity (T and B lymphocyte functions). They noted that evidence indicates a significant association between vitamin D deficiency and an uptick in some autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus. Patients with these disorders often worsen during winter or spring, times when levels of vitamin D in the body are low.²

According to a contrary school of thought, giving vitamin D worsens autoimmune diseases. Central to this theory is the concept that autoimmune diseases are caused by persistent pathogens, such as bacteria and viruses.

Albert and colleagues³ suggested that vitamin D may suppress inflammation in the short term but worsen disease symptoms over time by inactivating VDR. Besides being active in calcium metabolism, VDR transcribes hundreds of genes and controls the innate immune response by expressing the bulk of the body's antimicrobial peptides, natural antimicrobials that target bacteria. By deactivating VDR and the immune response, vitamin D reduces inflammation caused by these bacteria but allows them to propagate long-term. The team's research shows that in patients with autoimmune disease, vitamin D levels are naturally down-regulated in response to VDR dysregulation by chronic pathogens. In this scenario, supplementation with extra vitamin D can slow the ability of the immune system to deal with the bacteria underlying the autoimmune disease.

More research needs to be done. In the interim, however, patients might err on the side of not exceeding the recommended daily amount of vitamin D: 400 IU/d for infants up to age 1 year, 600 IU/d for persons aged 1 to 70 years, and 800 IU/d for persons older than 70 years.

References:

1. Adorini L, Penna G. Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol. 2008;4:404-412.

2. Cutolo M, Pizzorni C, Sulli A. Vitamin D endocrine system involvement in autoimmune rheumatic diseases. Autoimmun Rev. 2011;11:84-87.

3. Albert PJ, Proal AD, Marshall TG. Vitamin D: the alternative hypothesis. Autoimmun Rev. 2009;8:639-644.