Vitamin D Deficiency Associated with Disease Activity in RA

Patient Expert

Rheumatoid arthritis is a relatively common autoimmune disease for which the cause is still unknown.   Researchers are investigating the contributing factors for developing disease, including the impact of vitamin D.   Vitamin D deficiency has been implicated in the development of autoimmune disease such as type I diabetes and multiple sclerosis.

Vitamin D is a fat-soluble hormone which is synthesized in the body as sunlight (ultraviolet light UVB) reaches exposed skin.   Vitamin D is found naturally in very few foods, such as fatty fish, and is available as a dietary supplement in over-the-counter and prescription form.   Many people do not produce enough vitamin D from UVB exposure nor get enough from food or supplementation.   As RA patients might avoid sun exposure due to photosensitivity, they may be especially susceptible to vitamin D deficiency.   Vitamin D is essential for calcium absorption in the gut and for bone growth and mineralization (preventing osteoporosis).

Reduced vitamin D intake has been linked to increased risk of developing RA and vitamin D deficiency has been found to be associated with disease activity and musculoskeletal pain in patients with RA.   In a recent study, researchers evaluated vitamin D status in 44 patients with RA and looked for any relationship between vitamin D serum levels and disease activity.   A control group of 44 persons was evaluated as well.

Vitamin D circulates in the body in two forms.   The liver converts vitamin D to 25-hydroxyvitamin D3 [25(OH)D3], also known as calcidiol.   The kidneys convert calcidiol to activated vitamin D, also known as 1,25-dihydroxyvitamin D [1,25(OH)2D] or calcitriol.   When measuring vitamin D levels in the blood, the recommended test measures serum concentration of 25(OH)D3, reported as nanomoles per liter (nmol/L) and/or nanograms per milliter (ng/mL).

Persons who have serum concentrations of 25(OH)D3 less than 12 ng/mL are considered deficient in vitamin D.   Levels between 12 and 20 ng/mL are considered inadequate in healthy persons.   Greater than 20 ng/mL is considered adequate in healthy persons.   According to NIH, levels greater than 50 ng/mL may cause undesirable adverse effects.   However, some rheumatologists (including my own) recommend serum concentrations between 50-80 ng/mL in patients diagnosed with autoimmune disease.

[My 25(OH)D3 level was 76 ng/mL the last time it was tested after years of monitored vitamin D supplementation, whereas it had been 7.6 ng/mL shortly after my RA diagnosis when I wasn't taking supplements and was experiencing more pain.]

In the study, levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and parathyroid hormone were also measured.   Disease activity was assessed using the 28-joint Disease Activity Score (DAS28).   What was observed is that 25(OH)D3 levels were low in the RA patients compared with healthy controls, 15.26 ± 1.07 ng/ml and 25.8 ± 1.6 ng/ml, respectively.   Results from the additional blood tests were elevated in the RA group with parathyroid hormone levels at 71.08 ± 7.02 pg/ml (normal values 10.0-65.0 pg/ml), CRP at 7.6 ± 1.57 mg/litre (normal values < 3 mg/litre) and ESR at 38.0 ± 4.6 mm/h.   The DAS28 index was 4.26 ± 0.26 in the RA group.

Levels of 25(OH)D3 were found to be negatively correlated with disease activity, meaning that patients with lower levels of vitamin D experienced more disease activity as measured by DAS28.   Levels of 25(OH)D3 were also found to be negatively correlated to CRP and ESR.   Elevated levels of CRP and ESR, as well as DAS28 scores, are associated with disease severity in RA.   Researchers suggest that vitamin D supplementation may be needed not only for the prevention of osteoporosis but also for pain relief in patients with RA.

Results from prior studies have been mixed with associations found between vitamin D deficiency and RA disease activity, while some studies have shown no such association.   Further research is warranted.

The take away message is that patients with RA should talk to their rheumatologists about getting tested for vitamin D deficiency and discuss recommendations for possible supplementation.

Kostoglou-Athanassiou I, et al. Vitamin D and rheumatoid arthritis. Ther Adv Endocrinol Metab 2012;3(6):181-187. DOI: 10.1177/2042018812471070

Dietary Supplement Fact Sheet: Vitamin D.   Office of Dietary Supplements at National Institutes of Health. Accessed at