High-dose vitamin D 3 reduces circulating hepcidin concentrations: A pilot, randomized, double-blind, placebo-controlled trial in healthy adults

Smith, Ellen M. Lavoie; Alvarez, Jessica A.; Kearns, Malcolm D.; Li, Hao; Sloan, John H.; Konrad, Robert J.; Ziegler, Thomas R.; Zughaier, Susu M.; Tangpricha, Vin

doi:10.1016/j.clnu.2016.06.015

Cited by 92 publications

(106 citation statements)

References 31 publications

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“…Cholecalciferol was the main form of vitamin D that were supplemented in these studies. The duration of supplementation with vitamin D also varied from 3 h to 6 months [40][41][42][43][44][45][46][47][48][49][50][51][52][53].…”

Section: Study Characteristicsmentioning

confidence: 99%

The effect of vitamin D supplementation on hemoglobin concentration: a systematic review and meta-analysis

Arabi

Ranjbar

Bahrami

et al. 2020

Nutr J

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Aims: The purpose of this review was to investigate the effect of vitamin D supplements on hemoglobin concentration in subjects aged 17.5-68 years old; using randomized controlled trials (RCTs). Methods: Relevant RCT studies were identified from January 2000 to January 2019 by using MeSH terms in PubMed, Embase, Cochrane Library, Clinical trials, Scopus databases and gray literature. The studies were reviewed systematically, and quality assessments were evaluated by the guidelines of the Cochrane risk of bias. The effect of vitamin D supplements (n = 14) on hemoglobin concentration was considered as primary outcome, while its effects on the levels of ferritin, transferrin saturation and iron status were derived as secondary outcomes. In total, 1385 subjects with age range of 17.5 to 68 years old were examined for 3 h to 6 months; Mean (standard deviation) or median interquartile changes in the hemoglobin concentration in each treatment group was recorded for metaanalysis. Results: Fourteen RCTs met the inclusion criteria. Current study findings propose that vitamin D supplementation leads to a non-significant reduction in hemoglobin levels in subjects (17.

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Section: Study Characteristicsmentioning

confidence: 99%

The effect of vitamin D supplementation on hemoglobin concentration: a systematic review and meta-analysis

Arabi

Ranjbar

Bahrami

et al. 2020

Nutr J

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“…Moreover, recent studies from our group also found that treatment with high-dose vitamin D reduced circulating hepcidin concentrations in healthy adults (23) and increased hemoglobin concentrations in critically ill adults (24). The anti-inflammatory and hepcidin-lowering effects of vitamin D may therefore increase iron bioavailability for erythropoiesis and hemoglobin synthesis, possibly improving anemia in individuals with vitamin D insufficiency.…”

Section: Introductionmentioning

confidence: 67%

“…This group subsequently identified a vitamin D response element on the HAMP gene, lending strong biological plausibility the association between vitamin D and hepcidin. Furthermore,, treatment with high-dose vitamin D has been found to significantly reduced circulating hepcidin concentrations among healthy adults (23). The results from the current study suggest that an inverse association between vitamin D status and hepcidin may exist in the pediatric IBD population as well.…”

Section: Discussionmentioning

confidence: 99%

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

Syed

Michalski

Tangpricha

et al. 2017

Inflammatory Bowel Diseases

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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.

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“…It has been reported that locally-activated 25D inhibits the production of inflammatory cytokines including IL-6 and TNF-α, and that inflammatory cytokines may serve to directly induce hepcidin production [12,15,16,30,31]. Alternatively, a recent study published by Smith et al reported that high dose vitamin D3 supplementation reduced plasma hepcidin concentrations in healthy adults without change in plasma cytokine concentration, suggesting that vitamin D may play a role in the regulation of the hepcidin-iron axis independently of changes in pro-inflammatory cytokines [32]. There is accumulating evidence that nutritional 25D deficiency is a risk factor for anemia in both healthy people and in those with kidney disease, and hepcidin upregulation is likely a key mediator of anemia [33–35].…”

Section: Discussionmentioning

confidence: 99%

Pilot study of the effect of cholecalciferol supplementation on hepcidin in children with chronic kidney disease: Results of the D-fense Trial

et al. 2016

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Background Hepcidin is a key mediator of the anemia of chronic kidney disease (CKD). There is emerging evidence that 25-hydroxyvitamin D (25D) regulates hepcidin production. Methods A randomized controlled trial of daily vitamin D supplementation for 12 weeks testing the effects of 4000 vs. 400 IU of cholecalciferol on serum hepcidin levels in children with non-dialysis CKD recruited at a tertiary care children’s hospital. Hepcidin was quantified using a validated competitive enzyme-linked immunosorbent assay. 25D levels were measured using the chemiluminescence Liaison 25(OH)D assay system. Co-variables included hemoglobin, C-reactive protein, ferritin, and serum calcium and phosphorus for safety monitoring. Results Thirty-four subjects were randomized; 26.5% female, mean (SD) age 10.9 (5.8) years, 23.5% African American, mean (SD) baseline glomerular filtration rate was 60 (17.6) ml/min/1.73m2, and mean (SD) baseline 25D level was 29.7 (11.5) ng/ml. Fifty percent of subjects were 25D deficient at baseline. There were no significant differences in baseline characteristics between the intervention and controls. Treatment with 4000 IU cholecalciferol was not associated with a significant change in hepcidin level at 4 or 12 weeks, and multivariable generalized estimating equation regression demonstrated no significant difference in change in hepcidin over the treatment period in either arm. Median CRP decreased significantly at 12 weeks in the intervention group. Conclusions These results do not suggest that daily nutritional vitamin D supplementation modifies serum hepcidin levels in children with CKD. Further study will be required to determine whether supplementation may be effective in children with more advanced CKD or on dialysis.

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High-dose vitamin D 3 reduces circulating hepcidin concentrations: A pilot, randomized, double-blind, placebo-controlled trial in healthy adults

Cited by 92 publications

References 31 publications

The effect of vitamin D supplementation on hemoglobin concentration: a systematic review and meta-analysis

The effect of vitamin D supplementation on hemoglobin concentration: a systematic review and meta-analysis

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

Pilot study of the effect of cholecalciferol supplementation on hepcidin in children with chronic kidney disease: Results of the D-fense Trial

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