. "4 Review of Potential Indicators of Adequacy and Selection of Indicators: Calcium and Vitamin D." Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press, 2011.
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DRI Dietary Reference Intakes Calcium Vitamin D
inflammation in the lungs, pericardium, pleura, and sclera, as well as nodular lesions under the skin. This progressive disease can result in chronic pain, loss of function, and eventual disability.
Biological plausibility In experimental studies, Tetlow and Wooley (1999) found that the VDR was strongly expressed in cells associated with rheumatoid lesions, including macrophages, synovial fibroblasts, and chondrocytes, but weakly or not at all in normal articular cartilage tissue, suggesting an up-regulation of VDR-mediated activity in tissues affected by RA. Smith et al. (1999) found that cultured human synovial fibroblasts, but not human articular chondrocytes, when treated with the inflammatory cytokine, interleukin 1 (IL-1), followed by calcitriol, indicated inhibition of expression of the matrix metalloproteinases associated with RA. In a mouse model of RA, treatment with calcitriol decreased arthritis symptoms induced by injection with bovine collagen and halted the progression of arthritis after arthritic lesions were apparent (Cantorna et al., 1998). Together, this evidence is suggestive of an immunomodulatory role for vitamin D in expression of arthritic changes in some, but not all, cell types associated with RA.
Systematic reviews and meta-analyses The AHRQ systematic reviews found no RCTs for immune function clinical outcomes related to RA and no evidence that RA was related to vitamin D. No meta-analyses were identified for this indicator.
Additional evidence from randomized controlled trials No RCTs were identified for an effect of vitamin D and/or calcium on risk for RA.
Observational studies A number of studies have been conducted to determine whether serum 25OHD level and incidence of RA are associated. In a prospective cohort study, a small subset of subjects from the Iowa Women’s Health Study were followed to determine if dietary vitamin D intake (primary outcome) and/or calcium intake (secondary outcome) were associated with incident RA (Merlino et al., 2004). No significant associations were found for dietary (not supplemented) vitamin D intake and risk for RA, although the association was significant for daily supplemental intakes of 400 IU or more compared with less than 400 IU. No association was found between calcium intake and risk for incident RA. A cross–sectional analysis of women with RA living in Brazil, found a significant correlation between higher mean serum calcium level and normal BMD compared with calcium levels in women with osteopenia, although no significant difference was found between calcium and vitamin D intake and BMD (Sarkis et al., 2009).
With no large prospective cohort studies and no clinical trials to support a relationship between vitamin D and/or calcium and RA, along with a paucity of other observational evidence, the committee could not conclude that either vitamin D or calcium is related to risk for RA.