Does vitamin D play a part in the onset of rheumatoid arthritis and could vitamin D supplementation help prevent and treat the disease?

Low serum vitamin D levels are common in sufferers of the painful condition rheumatoid arthritis. This condition is caused by inflammation. Vitamin D has beneficial immunomodulatory effects, so even low dose supplementation could enable the dose of conventional rheumatoid arthritis therapies to be reduced, with the consequent benefit of a reduction in side effects. A very recent trial supports this hypothesis.

In synovial human bone joints, there is a layer of very thin tissue between the joint capsule and joint cavity called the synovium or synovial membrane. When healthy, the synovium secretes synovial fluid to lubricate and cushion the joint. The disease rheumatoid arthritis (RA) leads to inflammation of the synovium, eventually resulting in destruction of surrounding cartilage and bone, causing severe pain and immobility. There is a wide range of risk factors for the disease: genetic, environmental (such as alcohol intake and smoking) and dietary.

The active form of vitamin D, 1,25-dihydroxyvitamin D, has potent antiproliferative, antibacterial and anti-inflammatory properties. In a new review, Jeffrey et al. examine the potential for the use of vitamin D in the treatment and prevention of rheumatoid arthritis (1). Humans obtain their vitamin D either from dietary sources or from exposure to UV light. It is converted to the metabolically active form in the body by specific cytochrome P450 enzymes.

An early link was made between RA and vitamin D status when it was discovered that lymphocytes from patients with rheumatoid arthritis produced specific receptors for 1,25 (OH)2D. There is a wide array of potential anti-inflammatory actions from 1,25 (OH)2D including innate antibacterial responses (in neutrophils and monocytes), effects on antigen presentation by dendritic cells, and modulation of T-cell and B-cell phenotype and function.

It has been shown that vitamin D can restore the imbalance in TH17 and TREG cells that occurs during RA. It is also negatively correlated with serum levels of the inflammatory interleukins IL-23 and IL-17 common in RA patients. It has also been shown that 1,25 (OH)2D can reduce the accumulation of senescent T cells. This happens in RA patients because of their reduced ability to express telomerase. Telomerase deficiency is thought to have potential as a preclinical marker for RA. It seems reasonable to suppose that vitamin D may be able to reduce the risk of onset of RA and delay its progression through increasing telomerase activity.

At present, the data linking low vitamin D status to risk of onset of RA is not clear. However, it is clear that patients with early RA often exhibit severe serum vitamin D deficiency (˂ 10 ng/mL).

In a very recent study (2), a high dose intervention of vitamin D (60,000 IU per week for the first six weeks, thereafter 60,000 IU per month) was given to a cohort of RA patients (n=73), average age 49 years, for three months. The patients were already being treated with disease-modifying antirheumatic drugs (DMARDs), and have been identified as having a low serum vitamin D level (˂ 20 ng/mL) as well as a Disease Activity Score of 28 joints/C-reactive protein (DAS28-CRP) of more than 2.6 . After the intervention, the average serum vitamin D levels had increased almost six-fold to 57.2 ng/mL. There was also a significant improvement in the state of the joints, as the mean DAS28-CRP score reduced from a baseline of 3.68 to 3.08 at the end of the intervention.

Whilst there is clearly much work in the area that needs to be done, it is clear that vitamin D can have benefits to RA patients through its immunomodulatory effects. It seems possible that the use of low dose vitamin D supplementation on RA patients may enable a reduction in the dose of conventional therapies, with a consequent reduction of the side effects from those treatments.

1. Jeffery L. E., Raza K. and Hewison M. (2015), “Vitamin D in rheumatoid arthritis—towards clinical application”, Nature Reviews Rheumatology 2015, doi.org/10.1038/nrrheum.2015.140.
2. Chandrashekara S. and Patted A., “Role of Vitamin D supplementation in improving disease activity in rheumatoid arthritis: An exploratory study”, Int J Rheum Dis 2015, Oct 20th, DOI: 10.1111/1756-185X.12770.