Rheumatoid arthritis is the most common autoimmune disease found in about 1% of adults worldwide. Rheumatoid arthritis is caused by neutrophils, macrophages, T cells, B cells and dendritic cells infiltrating the synovium of joints and causing inflammation, it causes damage to bone and disability. Finally, it induces systemic complications such as cardiovascular and cardiopulmonary dysfunction, and reduces life expectancy by about 3–10 years (Alamanos and Drosos, 2005; Picerno et al., 2015). Rheumatoid arthritis is 2 to 3 times more common in females than males (Alamanos and Drosos, 2005). Although the pathogenesis of rheumatoid arthritis has not yet been elucidated, it is known that the interaction of genetic and environmental factors influences congenital and adaptive immunity, resulting in systemic inflammation (Picerno et al., 2015).

Vitamin D not only plays a major role in the regulation of bone mineral homeostasis but also plays a role in cell function such as cell proliferation, differentiation, apoptosis, and angiogenesis (Abourazzak et al., 2015).

Recently, appropriate level of vitamin D has been reported to reduce the risk of some chronic inflammatory or autoimmune conditions such as various cancers, infectious diseases, type 1 diabetes, multiple sclerosis, and autoimmune rheumatic disease (Agmon-Levin et al., 2013). Calcitriol or 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), an endogenous serum-active metabolite of vitamin D, is a kind of steroid hormone produced by cholesterol. Therefore, calcitriol has immunomodulatory properties such as glucocorticoid and gonadal hormones (Cutolo et al., 2011).

There are reports that low vitamin D intake is associated with the development of rheumatoid arthritis, or low serum vitamin D level is associated with disease activity or physical disability in rheumatoid arthritis (Haque and Bartlett 2010; Kerr et al., 2011; Merlino et al., 2004; Rossini et al., 2010). On the other hand, there are reports that vitamin D levels in patients with inflammatory joint disease are not related to arthritis activity (Braun-Moscovici et al., 2011; Craig et al., 2010).

The purpose of this study was to investigate the effect of vitamin D levels on the prevalence of rheumatoid arthritis in Korean adult women and to investigate the association of vitamin D levels with pain level and quality of life in Korean adult women with rheumatoid arthritis using the Korean National Health and Nutrition Examination Survey (KNHANES) from the Korea Centers for Disease Control and Prevention (2015).

Vitamin D levels in the body are most important to be produced by exposure to sunlight, which affects sun exposure, including skin pigmentation, clothing style, use of sunscreen, physical activity, and age. However, in case of inadequate exposure to sunlight increases the importance of food intake. And vitamin D levels are also affected by obesity, calcium, and parathyroid hormone (Lips et al., 2014). Obesity has been reported to reduce vitamin D (Derdemezis et al., 2011), and increasing age also reduces vitamin D, leading to a reduction in vitamin D to about 1/4 of that of younger adults (Holick et al., 2007).

However, in this study, postmenopausal period female with higher body mass index and higher age showed higher levels of vitamin D than fertile period female. Meta-analysis of vitamin D levels showed that there were differences according to age and region. Children and adolescent vitamin D levels were lower in the Asia/Pacific region than adults and elderly, however, children and adolescent vitamin D levels were higher in the Middle East/Africa region than adults and elderly (Hilger et al., 2014). Moreover, in Korea’s previous study, serum vitamin D levels were the lowest in the 20s and gradually increased with age up to 60s in both sexes (Nah et al., 2015). In industrialized countries, relatively younger women tend to use clothing or sunscreen agents, to reduce exposure to sunlight. In addition, the higher proportion of indoor occupation then undeveloped country may have reduced vitamin D in young cases (Nah et al., 2015). The elderly can maintain a sufficient level of vitamin D when exposed to the appropriate amount of ultraviolet light. Therefore, postmenopausal period female with higher occupation rate of occupations with a lot of outdoor activities such as agriculture and a higher rate of participation in outdoor activities such as sports may have a relatively long exposure time to sunlight (Lips et al., 2014).

The immune function of vitamin D is mediated by the vitamin D receptor. Vitamin D inhibits proliferation of activated B lymphocytes expressing vitamin D receptors and inhibits proliferation and differentiation of T cells. Vitamin D also has been shown to inhibit the production of interleukin (IL)-2, interferon gamma of T helper (Th) 1 cells and to inhibit the production of IL-17 of Th17 cells. Therefore, vitamin D has been reported to inhibit the proinflammatory response (Abourazzak et al., 2015). However, in this study, there was no significant difference in the odds ratio of rheumatoid arthritis according to the level of vitamin D. There have been some preclinical studies that suggest that vitamin D may be helpful in the treatment of Th17 mediated inflammatory diseases such as rheumatoid arthritis (Abourazzak et al., 2015).

However, in clinical studies and research results, many cases were not. In cross-sectional studies, there was no difference in the activity of arthritis, C-reactive protein, and erythrocyte sedimentation rate according to serum vitamin D levels in patients with inflammatory arthritis such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis (Braun-Moscovici et al., 2011). Preclinical rheumatoid arthritis may be caused by a subclinical inflammatory process as well as a decrease in vitamin D levels due to reduced sun exposure due to decreased physical activity and changes in dietary intake. However, it is unclear whether low levels of vitamin D increase the risk of rheumatoid arthritis or whether inflammatory conditions due to preclinical rheumatoid arthritis lower vitamin D levels (Hiraki et al., 2014).

Moreover, in Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHS II) cohort studies confirmed the relationship between the incidence of rheumatoid arthritis and vitamin D intake. There was no significant association between the incidence of rheumatoid arthritis and in NHS II, even with an intake of 400 IU/day or more of vitamin D, resulted in an increase in rheumatoid arthritis (Costenbader et al., 2008). A randomized double-blind placebo-controlled study of vitamin D in patients with rheumatoid arthritis for 12 months showed that vitamin D treatment was not effective in improving parathyroid hormone, bone mineral density, disease activity and cytokines in patients with rheumatoid arthritis (Hansen et al., 2014).

Although there was no statistically significant difference between the two groups, fertile period female group had higher odds ratios of rheumatoid arthritis at lower vitamin D levels, whereas postmenopausal period female group showed lower odds ratios of rheumatoid arthritis at lower levels of vitamin D, in this study. The incidence of rheumatoid arthritis is high in case of nulliparity or when there was no experience of oral contraceptive use (Doran et al., 2004), or when breastfeeding is not performed after first birth (Brennan and Silman, 1994) Thus, female hormone changes have been reported to affect the risk of rheumatoid arthritis. Interactions between the endocrine system and the immune system are the basis for causing differences in the development of autoimmune diseases in women of childbearing and postmenopausal age. Diseases, induced by B cells, peak at reproductive years in women due to the effects of serum estrogens and their metabolites synthesized by the endocrine system. After that, the role of endocrine system decreases with age. When women become older and the majority of estrogen is made at a peripheral aromatase, the immune and inflammatory responses of men and women become similar (Cutolo et al., 2014). Calcitriol (1,25(OH)2D3) inhibits the expression of aromatase, an enzyme that catalyzes the production of estrogen at the periphery, using androgen under normal conditions (Cutolo et al., 2014). The high prevalence of autoimmune rheumatoid disease in women is due to a decrease in the down regulation of aromatase due to the deficiency of calcitriol (1,25(OH)2D3), leading to an increase in estrogen production in the periphery, which increases the risk and severity of rheumatoid arthritis (Krishnan et al., 2010).

The present study showed that the relationship between vitamin D levels and pain was statistically significant in postmenopausal period rheumatoid arthritis female group. However, there was no significant difference in linear trend between pain and vitamin D level. Severe deficiency of vitamin D (<10 ng/mL) is associated with symptoms such as musculoskeletal pain and symptomatic improvement in vitamin D supplementation has been reported (Haque and Bartlett, 2010). However, a randomized, double-blind, placebo-controlled study reported no significant trends in patients’ self-reported health status and visual pain rating (VAS), which were reported to be significantly worse in the vitamin-supplemented group (Hansen et al., 2014).

In the present study, there was no difference in quality of life according to the level of vitamin D. In some studies, univariate analysis showed an inverse correlation with increased functional impairment at low vitamin D levels. However, there was no significant difference in multivariate analysis (Abourazzak et al., 2015). The limitations of this study are that despite the data for many years, the actual number of patients with rheumatoid arthritis is not large enough, and seasonal effects, sun exposure time, use of drugs, such as disease modifying antirheumatic drugs or glucocorticoids, were not controlled.

The current recommendation for vitamin D supplements focuses on bone mineral density and fracture, and the Korean Society of Bone Metabolism (2015) recommends a daily intake of 800 IU of vitamin D. Although vitamin D has not been statistically associated with the development of rheumatoid arthritis, it has been reported that vitamin D may be an appropriate adjuvant therapy for patients with rheumatoid arthritis due to its low cost and harmless (Dehghan et al., 2014).

The results of this study showed that there was no difference in the incidence of rheumatoid arthritis according to the level of vitamin D in Korean adult women and that there was no difference in pain and quality of life when rheumatoid arthritis occurred. However, it is necessary to clarify the relationship through a large-scale cohort study that reflects the results of recently reported genome studies. Considering the effect of vitamin D supply on bone density and fracture, and the low price, vitamin D administration with effectiveness analysis is also needed.