Iron Deficiency in Inflammatory Bowel Disease Is Associated With Low Levels of Vitamin D Modulating Serum Hepcidin and Intestinal Ceruloplasmin Expression

Abstract

INTRODUCTION: Iron deficiency and vitamin D deficiency are common comorbidities in inflammatory bowel disease (IBD). Accumulating evidence indicates that active 1,25-dihydroxyvitamin D (1,25(OH)D) may enhance iron absorption by suppressing hepcidin. We investigated the influence of vitamin D on iron metabolism in patients with IBD and on the expression of genes facilitating intestinal epithelial iron absorption. METHODS: Iron parameters and serum levels of 25-hydroxyvitamin D (25(OH)D), 1,25(OH)D, and hepcidin were measured in 104 adult patients with IBD (67 with Crohn's disease and 37 with ulcerative colitis). Genes involved in iron absorption were tested for induction by 1,25(OH)D in Caco-2 cells, which resemble the small intestinal epithelium. RESULTS: In multiple regression models controlling for age, sex, body mass index, smoking status, disease activity, and C-reactive protein levels, low 25(OH)D levels were associated with iron deficiency in patients with IBD (β [SE] = −0.064 [0.030], P = 0.029). Vitamin D sufficiency was associated with increased levels of ferritin (β [SE] = 0.25 [0.11], P = 0.024) and transferrin saturation (β [SE] = 8.41 [4.07], P = 0.044). Higher 1,25(OH)D:25(OH)D ratios were associated with lower hepcidin levels (β [SE] = −4.31 [1.67], P = 0.012). Especially in Crohn's disease, increased 1,25(OH)D correlated with higher transferrin saturation (β [SE] = 0.43 [0.18], P = 0.027). Furthermore, 1,25(OH)D strongly induced the expression of the ferroxidase ceruloplasmin in Caco-2 cells. DISCUSSION: Low vitamin D levels in IBD correlate with iron deficiency. Vitamin D may ameliorate iron deficiency, potentially by downregulating hepcidin and upregulating ceruloplasmin, enhancing intestinal iron absorption.

Evaluation of plasma levels of iron, copper, zinc, selenium and some transporter proteins in patients with IBD compared to IBS

“…Ceruloplasmin as an acute-phase plasma protein that elevated plasma level of ceruloplasmin can be observed in in ammation, trauma, or infection. Ceruloplasmin is a ferroxidase with important function in Fe metabolism via converting Fe2 + to Fe3+, and inhibition of ferrous ion-mediated production of ROS [35]. In our study IBS patients have increase in ceruloplasmin level in comparison with control and IBD patients, however the observation was not signi cant.…”

Association of Vitamin D in Different Trimester with Hemoglobin during Pregnancy

“…In addition, hepcidin was also recognized as a key role in the association between VD and Hb. Increased hepcidin could inhibit enterocytes to absorb iron and lead to anemia, but VD could suppress the expression of hepcidin mRNA and enhance iron absorption by regulating the iron-hepcidin-ferroportin axis in monocytes [14,17]. However, one RCT from England reported that VD supplementation (1000 IU/day) from the first trimester had no effect on hepcidin in the third trimester [27].…”

“…As Ellen et al summarized, epidemiological studies have linked VD deficiency to an increased risk of anemia in various healthy and diseased populations [10][11][12][13]. In terms of biological mechanisms, VD affects hemoglobin concentration by regulating erythropoiesis, immune cells, and hepcidin production [14][15][16][17]. However, evidence for such an association in pregnant women remains scarce and contradictory.…”

Recent advances in ferroptosis and therapeutic strategies for glioblastoma

“…Iron is a vital element for the survival of organisms. It is indispensable for the metabolism of many substances in the body [ (Dutt et al, 2022); (Stallhofer et al, 2022)]. Iron in the digestive tract is mainly absorbed in the duodenum and upper jejunum in the form of Fe 2+ (Karaskova et al, 2021).…”