Vitamin D Status Is Associated with Hepcidin and Hemoglobin Concentrations in Children with Inflammatory Bowel Disease

Abstract

BACKGROUND Anemia, iron deficiency and hypovitaminosis D are well-known comorbidities in inflammatory bowel disease (IBD). Epidemiologic studies have linked vitamin D deficiency with increased risk of anemia, and in vitro studies suggest that vitamin D may improve iron recycling through down-regulatory effects on hepcidin and pro-inflammatory cytokines. DESIGN/METHODS We aimed to investigate the association of vitamin D status with inflammation, iron biomarkers, and anemia in pediatric IBD. Cross-sectional data was obtained from N=69 IBD patients aged 5 to <19y. Iron biomarkers [ferritin, soluble transferrin receptor (sTfR)], 25-hydroxyvitamin D (25(OH)D), inflammatory biomarkers [C-reactive protein (CRP), α1-acid glycoprotein (AGP)], hepcidin, and hemoglobin were collected. Iron biomarkers were regression corrected for inflammation. Multivariable logistic/linear models were used to examine the associations of 25(OH)D with inflammation, iron status, hepcidin, and anemia. RESULTS ~ 50% of subjects were inflamed (CRP>5 mg/L or AGP>1 g/L). Iron deficiency prevalence (inflammation-corrected ferritin < 15 μg/L or sTfR > 8.3mg/L) was 67%; anemia was 36%, vitamin D insufficiency (25(OH)D < 30 ng/mL) was 77%. In linear regression models, vitamin D insufficiency was associated with increased hepcidin levels (β(SE)=0.6(0.2), P=0.01) and reduced hemoglobin (β(SE)= −0.9 (0.5), P=0.046), controlling for age, sex, race, insurance status, body mass index-for-age, inflammation, disease diagnosis (ulcerative colitis vs. Crohn’s) and disease duration, compared to 25(OH)D ≥ 30 ng/mL. CONCLUSIONS Our results suggest that concentrations of 25(OH)D ≥ 30 ng/mL are associated with lower hepcidin and higher hemoglobin levels. Further research is needed to clarify the association of vitamin D with inflammation, iron status and anemia in pediatric IBD.

Relationship between vitamin D deficiency and serum ferritin level in healthy women

“…In the present study mean vitamin D3 in the older women group (group II) 11.8 ± 3.5 ng/dL was signi icantly lower than younger women (group I) 35.3 ± 12.2 ng/dL (p-value < 0.001), similar inding observed for ferritin (19.6 ± 13.9 vs. 66.7 ± 52.1, pvalue <0.001), additionally there was signi icant direct correlation between ferritin and vitamin D3 in (SIM et al, 2010) was in agreement with present study in which low vitamin D (<30 ng/dL) associated with elevated Ferritin compared to normal vitamin D (≥30 ng/dL) [364 vs. 189 ng/ml, p-value = 0.01] (SIM et al, 2010;SYED et al, 2017) study, in linear regression models, vitamin D insuf iciency was associated with increased hepcidin levels (β [SE] = 0.6 [0.2], P = 0.01) and reduced hemoglobin (β [SE] = -0.9 [0.5], P = 0.046), suggesting that the concentrations of 25(OH)D ≥30 ng/mL are associated with lower hepcidin and higher hemoglobin levels (SYED et al, 2017) .…”

Measuring Vitamin D Status in Chronic Inflammatory Disorders: How does Chronic Inflammation Affect the Reliability of Vitamin D Metabolites in Patients with IBD?

“…An even stronger correlation with PTH has been observed for 24,25OH2D. However, it might be useful as an indicator of tissue-level 1,25OH2D activity [22,27]. While both parameters could be used to gain a better insight into individual vitamin D status, neither 1,25OH2D nor 24,25OH2D seems to be a better sole marker of vitamin D status than 25OHD.…”

“…Studies have also demonstrated poor vitamin D status to be an independent risk factor for the incidence of colorectal cancer in individuals with IBD [21]. Observational data confirmed low levels of vitamin D to be associated with increased concentrations of hepcidin and thus with anemia, one of the most prevalent extraintestinal complications of IBD [22]. Additionally, vitamin D insufficiency/deficiency has been shown to be associated with poor health-related quality of life (HRQOL) outcomes [23].…”

Rational Management of Iron-Deficiency Anaemia in Inflammatory Bowel Disease

“…Recently, a study in children has shown that supplementation of vitamin D facilitates increased haemoglobin levels. Here plasma concentrations of 25-hydroxyvitamin D (25(OH)D) below 30 ng/mL (i.e., vitamin D deficiency) were associated with increased hepcidin concentrations and reduced haemoglobin concentrations compared with individuals with plasma 25(OH)D concentrations above 30 ng/mL [ 100 ]. Because vitamin D deficiency is frequent in IBD [ 101 ] and because vitamin D has been shown to inhibit hepcidin expression [ 102 ] and to possess important immunologic effects of benefit in the clinical course of patients with IBD [ 103 , 104 , 105 ], normalization of vitamin D is important for elevating the haemoglobin level in these patients.…”