The Impact of Vitamin D Supplementation on the IFNγ-IP10 Axis in Women with Hashimoto’s Thyroiditis Treated with Levothyroxine: A Double-blind Randomized Placebo-controlled Trial

Abstract

Hashimoto's thyroiditis (HT) results from chemoattraction of inflammatory cells toward the thyroid gland by inducing the production of interferon-gamma (IFNγ)-induced protein 10 (IP10) by T helper (Th) 1 cells. Vitamin D may suppress the IFNγ-IP10 axis, but this new function of vitamin D has not yet been investigated in HT patients.
 In an intervention and control group, patients received 50000 IU cholecalciferol or placebo every week for three months, respectively. The CD4+ T cells of 40 patients were isolated, and the mRNA expression levels of vitamin D receptor (VDR), peroxisome proliferator-activated receptors (PPAR)-α, and PPAR-γ genes were determined by real-time PCR. ELISA method was used to determine serum levels of vitamin D, tumor necrosis factor-alpha (TNF-α), IFN-γ, and IP10.
 Vitamin D levels in the intervention group were significantly higher than in the placebo group after supplementation. PPAR-α and PPAR-γ gene expression levels did not differ significantly between the two groups. The serum levels of IP10, IFNγ, and TNF-α decreased significantly in the vitamin D group, as well as in the placebo group. 
 During this study, vitamin D levels significantly increased in the intervention group and inflammatory factors decreased. Based on the similar results obtained in the placebo group, further studies with larger sample sizes and longer intervention times are recommended.

Autoimmune Thyroiditis and Vitamin D

“…In fact, in the recent decade, several studies have demonstrated a significant reduction in TPOAb and/or TgAb in adult patients diagnosed with autoimmune thyroiditis after vitamin D supplementation in different populations ( Table 1 ): Greece [ 29 ], India [ 55 , 56 ], Turkey [ 57 ], Iran [ 58 , 59 ], Poland [ 54 , 60 ], and Canada [ 61 ]. The dose used in vitamin D supplementation has been highly variable, ranging from 1000 to 4000 IU/daily for 1–6 months [ 29 , 54 , 57 , 60 ]; or with weekly doses between 50,000 and 60,000 IU for 2–3 months [ 55 , 56 , 58 , 59 ]. In addition, some researchers have recently reported that vitamin D supplementation may influence other immunological markers.…”

“…In addition, some researchers have recently reported that vitamin D supplementation may influence other immunological markers. Supplementation with 50.00 IU of vitamin D weekly for 3 months in adult patients with TH resulted in beneficial immunological effects through a significant decrease in the Th17/Treg ratio and inflammatory factors, such as IFN-γ and TNF-α, as well as a significant decrease in IL-10 (pro-inflammatory cytokine) [ 59 , 62 ]. The wide variety of both doses and duration of vitamin D supplementation makes it risky to establish and, consequently, recommend an optimal vitamin D regimen in patients with HT.…”

Impact of Vitamin D on Immunopathology of Hashimoto’s Thyroiditis: From Theory to Practice

“…Besides antibody levels, several researchers explored how vitamin D supplementation can affect other immunological markers. Robat-Jazi et al [ 119 ] supplemented 40 HT female patients with 50,000 IU of 25(OH)D weekly for 3 months. At the baseline and follow-up, they assessed the serum levels of inflammatory factors, such as TNF-α, IFN-γ, and the chemokine CXCL10 (or IP10, interferon gamma-induced protein 10).…”

Do Dietary Supplements Affect Inflammation, Oxidative Stress, and Antioxidant Status in Adults with Hypothyroidism or Hashimoto’s Disease?—A Systematic Review of Controlled Trials

“…The characteristics of the studies included in this review are presented in Table 1. Most of the papers identified were published after 2010 (except Karanikas et al [26] and Xiang et al [27]), and seven of them were published in the last 3 years [28][29][30][31][32][33][34]. Fourteen studies were conducted in Asia (seven in China [27,29,32,[34][35][36][37], six in Iran [28,30,31,33,38,39], and one in India [40]), seven in Europe (three in Italy [41][42][43], one each in Austria [26], Germany [44], Poland [45], and Romania [46]), and one in South America (Brazil [47]).…”

“…Most of the papers identified were published after 2010 (except Karanikas et al [26] and Xiang et al [27]), and seven of them were published in the last 3 years [28][29][30][31][32][33][34]. Fourteen studies were conducted in Asia (seven in China [27,29,32,[34][35][36][37], six in Iran [28,30,31,33,38,39], and one in India [40]), seven in Europe (three in Italy [41][42][43], one each in Austria [26], Germany [44], Poland [45], and Romania [46]), and one in South America (Brazil [47]). The sizes of groups in the studies varied (15-183 subjects), but usually the number in the intervention groups did not exceed 50 people (except in three studies [32,35,37]), and the smallest intervention group consisted of 15 people [42].…”