Vitamin D Deficiency and RA Activity

  • Nobody would argue that rheumatoid arthritis is associated with pain. In fact, pain, tenderness, and swelling of the joints are some of the primary indications of disease activity. Nobody likes to hurt, and reducing pain and associated tissue damage are goals of RA treatment.


    Pain is often the brain’s way of telling us that something isn’t right; it can be an early warning signal of sorts. “Get your hands away from the fire before you seriously get burned!” The sensation of pain may indicate that we need to make a change in some way, e.g., physically, emotionally, spiritually.  


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    Pain also may be an indication that our body needs something it isn’t getting. For example, if I am not drinking enough water and begin to become dehydrated, I might get a headache, feel weak or dizzy, and have an upset stomach. And then there are times when nothing is wrong but you still feel pain, perhaps due to a malfunctioning nervous system that gets confused and sends misleading messages to/from the brain.


    Several factors can influence how we perceive pain. One such factor is vitamin D deficiency, which is measured by the 25(OH)D test. A recent study found that vitamin D deficiency was associated with higher pain intensity levels and lower quality of life in patients with widespread pain when compared with a control group. Researchers also found that lower vitamin D levels correlated with abnormal results from nerve conduction studies (Kuru, 2014).


    Changes in vitamin D levels in the blood have been associated with inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, lupus, multiple sclerosis, atherosclerosis, or asthma (Wöbke, 2014). A 2012 meta-analysis, which included eight studies investigating the association between vitamin D and RA activity in 2,885 RA patients and 1,084 controls, revealed that the available evidence indicates that lower vitamin D levels are indeed associated with more RA disease activity as measured by DAS28 (disease activity score in 28 joints) (Song, 2012). Subsequent studies have found the same (Kostoglou-Athanassiou, 2012; Abourazzak, 2014; Hong, 2014).


    Disease activity in RA is assessed by objective and subjective tests that are combined to produce the DAS28. Since studies have shown that vitamin D levels can influence pain perception, as well as DAS28 scores, it may be difficult to determine whether vitamin D deficiency is influencing objective disease activity or subjective pain perception. To try to answer this question, another team of researchers compared vitamin D levels with disease activity in 176 RA patients, calculating the DAS28 both with and without the patient’s rating of their symptoms on the visual analog scale (VAS), and analyzing each component of the DAS28 separately.


    In this study, the overall mean DAS28 score was 3.66 (SE ± 0.11), but dropped to 3.43 (SE ± 0.10) when the VAS was omitted. The mean vitamin D level at 39.42 nmol/L (SE ± 1.55) was deficient (i.e., less than 50 nmol/L). Although no significant correlation was seen between vitamin D and DAS28 scores with or without the inclusion of VAS, there was a significant inverse relationship between vitamin D levels and the VAS itself (p = 0.013). The higher mean DAS28 score in vitamin D-deficient patients was explained by the higher VAS scores (Higgins, 2013).


    Why is this important?

    Researchers emphasize that the VAS component of the DAS28, assessing the patient’s perception of symptoms including pain, is inversely related to vitamin D, with lower levels producing higher VAS values. Although there was no overall correlation between vitamin D levels and DAS28 in this study, the results suggest that patients (and clinicians) may believe that their disease is worse, or not responding to disease-modifying treatment, when they actually have a correctable vitamin D deficiency.


    Note: Laboratories in the United States generally report 25(OH)D levels as nanograms per milliter (ng/mL), while labs in other countries use nanomoles per liter (nmol/L). To convert ng/mL to nmol/L, multiply by 2.5. Some drugs can interfere with the absorption of vitamin D.

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    Shortly after my own RA diagnosis, it was discovered that my 25(OH)D level was 7.6 ng/mL. I was experiencing widespread achy pain and my bones literally hurt. After years of D3 supplementation, my levels have stayed in the 70-76 ng/mL range, and I experience much less pain. How much of that is due to Rituxan and methotrexate or to more desirable vitamin D levels, I can’t really know for sure.  



    Abourazzak FE, Talbi S, Aradoini N, Berrada K, Keita S, Hazry T. 25-hydroxy vitamin D and its relationship with clinical and laboratory parameters in patients with rheumatoid arthritis. Clin Rheumatol. 2014 Jun 13. [Epub ahead of print]

    Higgins MJ, Mackie SL, Thalayasingam N, et al. The effect of vitamin D levels on the assessment of disease activity in rheumatoid arthritis. Clin Rheumatol. 2013 Jun;32(6):863-7. doi: 10.1007/s10067-013-2174-x. Epub 2013 Jan 23.

    Hong Q, Xu J, Xu S, Lian L, Zhang M, Ding C. Associations between serum 25-hydroxyvitamin D and disease activity, inflammatory cytokines and bone loss in patients with rheumatoid arthritis. Rheumatology (Oxford). 2014 Jun 6. pii: keu173. [Epub ahead of print]

    Kostoglou-Athanassiou I, Athanassiou P, Lyraki A, Raftakis I, Antoniadis C. Vitamin D and rheumatoid arthritis. Ther Adv Endocrinol Metab. 2012 Dec;3(6):181-7. doi: 10.1177/2042018812471070. 

    Kuru P, Akyuz G, Yagci I, Giray E. Hypovitaminosis D in widespread pain: its effect on pain perception, quality of life and nerve conduction studies. Rheumatol Int. 2014 Aug 2. [Epub ahead of print]

    Song GG, Bae SC, Lee YH. Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis. Clin Rheumatol. 2012 Dec;31(12):1733-9. doi: 10.1007/s10067-012-2080-7. Epub 2012 Sep 2.

    Wöbke TK, Sorg BL, Steinhilber D. Vitamin D in inflammatory diseases. Front Physiol. 2014 Jul 2;5:244. doi: 10.3389/fphys.2014.00244. eCollection 2014.


    Craig SM, Yu F, Curtis JR, et al. Vitamin D status and its associations with disease activity and severity in African Americans with recent-onset rheumatoid arthritis. J Rheumatol. 2010 Feb;37(2):275-81. doi: 10.3899/jrheum.090705. Epub 2009 Dec 23.

    Gopinath K, Danda D. Supplementation of 1,25 dihydroxy vitamin D3 in patients with treatment naive early rheumatoid arthritis: a randomised controlled trial. Int J Rheum Dis. 2011 Oct;14(4):332-9. doi: 10.1111/j.1756-185X.2011.01684.x.

  • Haque UJ, Bartlett SJ. Relationships among vitamin D, disease activity, pain and disability in rheumatoid arthritis. Clin Exp Rheumatol. 2010 Sep-Oct;28(5):745-7. Epub 2010 Oct 22.

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    Harari M, Dramsdahl E, Shany S, et al. Increased vitamin D serum levels correlate with clinical improvement of rheumatic diseases after Dead Sea climatotherapy. Isr Med Assoc J. 2011 Apr;13(4):212-5.

    Lisa Emrich is author of the blog Brass and Ivory: Life with MS and RA and founder of the Carnival of MS Bloggers.


Published On: August 15, 2014