Vitamin D and Autoimmune Rheumatologic Disorders
Introduction
Vitamin D plays an essential role in calcium homeostasis. Vitamin D regulates intestinal absorption of dietary calcium, renal excretion of calcium, and calcium ion flux in bones. In addition to these important metabolic activities, vitamin D also contributes to the regulation of the immune system. In this survey, basic vitamin D physiology will be reviewed, and some of the pitfalls in interpreting vitamin D levels will be highlighted. In addition, the effects of vitamin D on the immune system will be summarized, with a focus on the contributions of vitamin D deficiency to autoimmune disorders.
Section snippets
Sources of vitamin D
Vitamin D may be acquired from three main sources: food, sun exposure, or dietary supplements. However, dietary intake can provide only ∼ 20% of the body's daily requirements of vitamin D [1], [2].
Sun exposure is necessary for humans to maintain adequate vitamin D levels. Vitamin D is synthesized in the skin after ultraviolet B (UVB) radiation induces the conversion of 7-dehydrocholesterol to previtamin D3, which is rapidly converted to vitamin D3 [3]. One minimal erythema dose of UVB radiation
Factors related to vitamin D levels
Interpretation of vitamin D levels is complicated by many factors. Understanding the contributions these factors make is important in interpreting research regarding vitamin D in health and pathologic conditions.
Identifying and treating vitamin D deficiency
Although there is no consensus on optimal levels of vitamin D, most experts define levels of less than 20 ng/ml (50 nmol/L) as vitamin D deficiency, levels from 20–29 ng/ml (50–72 nmol/L) as vitamin D insufficiency, and levels of 30 ng/ml (75 nmol/L) or above as adequate [3], [5]. Levels greater than 150 ng/ml (375 nmol/L) are considered toxic [3], [5].
Recommended treatment for vitamin D deficiency is 2000 IU of vitamin D3 daily or 50,000 IU of vitamin D2 weekly for 8–16 weeks, followed by maintenance
Inadequacy of current guidelines regarding vitamin D
The American Academy of Pediatrics recommends 400 IU of vitamin D daily for every child soon after birth [10]. This recommendation is based on the high prevalence of vitamin D deficiency even among otherwise healthy children. Most over-the-counter multivitamins also contain 400 IU of vitamin D. This dose does not effectively prevent vitamin D deficiency [6]. Besides, most studies that showed benefits of vitamin D in relation to prevention of autoimmune disorders used doses much higher than that.
Vitamin D role in the immune system
1,25-dihydroxyvitamin D [1,25(OH)2D] has many roles in the immune system (Table 1). The overall effect of vitamin D is immunosuppressive [13].
Animal models of vitamin D and autoimmunity
Because of its immunosuppressive activity, the effect of Vitamin D has been investigated in various experimental models of autoimmunity. For example, in the MRL-lpr/lpr mice models of spontaneous lupus, vitamin D supplementation improves longevity and reduces proteinuria, diminishes knee arthritis [14], and prevents dermatological lesions [25]. Administration of 1,25(OH)2D3 prior to the expression of disease can even prevent lupus in these mice models [25].
In the murine model of
Clinical vitamin D deficiency and autoimmune rheumatologic disorders
There are many difficulties in establishing a solid relationship between vitamin D deficiency and autoimmune rheumatologic disorders in humans. Different cut-offs for vitamin D deficiency and insufficiency are used in different studies; some studies are based on the reported intake rather than on serum levels; the rarity of the diseases makes it difficult to obtain large samples of subjects; there are many confounding factors associated with those diseases, as prednisone intake,
Conclusion
A much higher oral vitamin D intake than recommended in current guidelines is safe and necessary to maintain adequate circulating 25(OH)D levels, especially in the absence of UVB radiation of the skin. There is strong evidence of an association between SLE and RA and vitamin D deficiency, although other autoimmune rheumatologic disorders might also have an association. Further studies on the topic are needed to clarify these preliminary findings. In the meantime, if vitamin D deficiency is
Take-home messages
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25(OH)D should be assessed for the evaluation of vitamin D status.
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A much higher oral vitamin D intake than the current guidelines is necessary to maintain adequate circulating 25(OH)D levels in the absence of UVB radiation of the skin.
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Vitamin D has an immunosuppressive effect and it can suppress experimental autoimmunity.
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Repletion of vitamin D may have benefits beyond bone health for patients with certain autoimmune disorders, such as SLE.
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Prevention of hypovitaminosis D may reduce the
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