**5. Conclusions**

*Vitamin D Deficiency*

recommended.

tinal tract [128].

adult populations.

disease [131].

**3.5 Vitamin D and inflammatory bowel disease**

**3.7 Vitamin D deficiency and systemic sclerosis**

may contribute to the risk of multiple sclerosis [62, 63, 75, 119, 120]. Moreover, several genetic studies in multiple sclerosis patients have shown that diverse abnormalities in vitamin D metabolism are related to the risk of the disease. It appears that vitamin D deficiency may interact with genetic and environmental protective and risk factors, such as the allele HLA BRB1\*1501, infections, obesity, smoking, and sexual hormones and may modulate the risk of the disease [63, 74, 80]. Thus, vitamin D deficiency may be a risk modulating factor for the development of multiple sclerosis. Vitamin D acts as an immunomodulatory factor affecting T and B lymphocytes, and it may exert neuroprotector and neurotrophic actions within the central nervous system. Several studies have shown that vitamin D supplementation exerts multiple beneficial immunomodulatory effects in multiple sclerosis [121–124]. On the contrary, a Cochrane review states that there appears to be no benefit from vitamin D supplementation in patients with multiple sclerosis; however, the level of evidence is very low [125]. Nevertheless, it should be noted that robust statistical models used in association studies have already predicted a favorable vitamin D effect reducing relapses by 50–70% [121]. There is little doubt that vitamin D exerts a beneficial action on multiple sclerosis, the inflammatory component in particular, less so the degenerative. Until more information becomes available, vitamin D supplementation of multiple sclerosis patients, using a moderate physiological dose essentially correcting their vitamin insufficiency, is

Vitamin D deficiency has been observed in patients with inflammatory bowel disease, Crohn's disease, and ulcerative colitis [126]. It was found to be related to disease activity in Crohn's disease and ulcerative colitis. Vitamin D supports the integrity of the intestinal barrier and is related to microbiota homeostasis in this cohort of patients [127, 128]. Thus, vitamin D may contribute to the prevention of inflammatory bowel disease by supporting the integrity of the intestinal barrier, contributing to bacterial homeostasis and ameliorating disease progression via anti-inflammatory action. Vitamin D deficiency in inflammatory bowel disease is aggravated by decreased absorption of the vitamin via the gastrointes-

Studies have observed an association between autoimmune Hashimoto's thyroiditis and low vitamin D levels [79, 129]. These studies have not observed low vitamin D levels in patients with Graves' disease. A meta-analysis of 26 observational studies confirmed an association between vitamin D deficiency and autoimmune Hashimoto's thyroiditis [130]. The aforementioned meta-analysis found that although there was heterogeneity between the results of the various studies performed all over the globe, studies had similar results in populations from different countries and also in populations in different age ranges, in particular pediatric and

Systemic sclerosis is a chronic, inflammatory, fibrotic disorder thought to be related to autoimmune etiology. Vitamin D deficiency has been observed in patients with systemic sclerosis [86, 131], especially in patients with the diffuse type of the

**3.6 Vitamin D deficiency and autoimmune Hashimoto's thyroiditis**

**234**

It appears that vitamin D is a potent immunomodulator. It has multiple and diverse effects on the immune system. In particular, it potentiates the innate immune response enhancing the production of cathelicidin from human macrophages, monocytes, and keratinocytes, thus enhancing and potentiating the immune response against external pathogens. It affects the adaptive immune response shifting the phenotype of the adaptive immune response toward a more tolerogenic phenotype. Vitamin D deficiency is related to various autoimmune disorders. Vitamin D deficiency appears to be related to the development of RA and correlates with disease severity. Vitamin D deficiency is observed in patients with SLE. It was found to be related to disease severity and activity in some but not all studies. Vitamin D deficiency is observed in patients with multiple sclerosis, and vitamin D administration may ameliorate disease severity. Vitamin D deficiency is also observed in patients with inflammatory bowel disease, Crohn's disease, and ulcerative colitis, and it is related to disease activity. Vitamin D contributes to the integrity of the intestinal barrier and bacterial homeostasis. In addition, vitamin D absorption is decreased making supplementation important. Vitamin D deficiency is also observed in patients with autoimmune Hashimoto's thyroiditis. Vitamin D deficiency is found in patients with systemic sclerosis, especially the diffuse form of the disease. It appears that optimal levels of vitamin D are important for immune function and for the prevention of autoimmunity in the human organism.
