Topics

Impact of Vitamin D Supplementation on Hepcidin Levels and Transfusion Requirements in Surgical and Septic Patients

2016-12-26 23:17:32 | BioPortfolio

Summary

Acute inflammation induced by surgery and sepsis is complicated by the development of iron-restricted anemia due to the up-regulation of hepcidin. Excess hepcidin causes intracellular sequestration of iron, decreasing its availability for erythropoiesis. Hepcidin might be a potential target to reduce transfusion requirements in surgical and sepsis patients. Vitamin D supplementation might constitute a novel strategy to modulate the hepcidin-ferroportin-iron axis. Up to now, there are no data regarding the possibility that by using vitamin D supplementation in surgical and septic shock patients, the physicians could ameliorate anemia and, hence, reduce transfusion requirements. Aim: to conduct a randomised controlled trial to determine the impact of high-dose vitamin D enteral supplementation on serum hepcidin levels and transfusion requirements after major abdominal surgery and in septic shock patients.

Description

Patient blood management has become an important concept for the perioperative care of the surgical patients and in septic patients, aiming to improve outcomes. Hepcidin might be a potential target to reduce transfusion requirements after major abdominal surgery and in patients with sepsis. Major surgery and sepsis induce complex immune dysregulations, characterised by a pro-inflammatory state (the postoperative acute-phase reaction). Excess hepcidin values in acute inflammatory conditions might represent an exaggerated response that leads to iron-sequestration anemia, a functional iron deficiency anemia. Vitamin D supplementation might constitute a novel strategy to modulate the hepcidin-ferroportin-iron axis in surgery and sepsis-induced acute inflammation. Thus, vitamin D might impact hepcidin values and might reduce transfusion requirements.

I. Inflammation-induced regulation of the hepcidin-ferroportin-iron axis

Surgery and sepsis are associated with iron-restricted anemia. After major abdominal surgery and sepsis, a prototypical inflammatory syndrome, often complicated by the development of anemia, appears. Inflammatory cytokines (like interleukin 6) released during acute infection alter iron metabolism by inducing excess synthesis of hepcidin. Anemia after major abdominal surgery and sepsis may be the expression of impaired erythropoiesis as a result of hepcidin up-regulation. Hepcidin plays a role in the development of anemia, together with the inhibition of erythropoietin production, a decreased lifespan of erythrocytes, and a blunted erythropoietic response. Functional iron deficiency is increasingly recognised as a cause of anemia in the general surgical patient and in patients with sepsis.

Iron is a two-faced element. First, iron is essential for living as it is incorporated in the "breathing" molecule haemoglobin and in the mitochondrial respiratory chain. On the other hand, iron is detrimental due to the generation of oxidative stress and its availability for the growing of bacteria. Low serum iron level is considered detrimental as it leads to anemia and low tissue oxygen delivery. Iron deficiency and anemia are associated with poor outcomes in surgical and septic patients. Also, transfusion is associated with immune suppression and other adverse reactions. Thus, other approaches to the correction of anemia are advocated, even though not yet included in the clinical practice.

Hepcidin is the master regulator of iron metabolism and hence, a modulator of anemia in states of inflammation. Hepcidin is an acute phase protein synthetised in the liver and which acts as an hyposideremia inducing hormone. It binds to ferroportin (an iron exporter) and prevents the release of iron from the cells: prevents the absorption of dietary iron from enterocytes and prevents iron release from macrophages, where it is stored. Thus, the effect of hepcidin would be iron sequestration, lowering the serum iron concentrations. The beneficial result would be a low availability of iron for bacterial growth (thus, a direct antimicrobial effect) and less oxidative stress. The detrimental result is the limited possibility for the synthesis of new haemoglobin molecules and the occurrence of anemia. The up-regulation of hepcidin, as a pro-inflammatory biomarker, characterises both acute and chronic inflammatory conditions. The induction of hepcidin synthesis may be the cause for the iron-restricted erythropoiesis in the surgical population and in patients with sepsis. The induction of hepcidin synthesis may contribute to the development of anemia, which is detrimental for tissue oxygenation and might increase transfusion requirements and the aggravation of immune suppression after blood transfusion. In animal models of anemia due to inflammation, hepcidin knockout mice had milder anemia and faster recovery.

Excess values of the iron regulating hormone hepcidin causes intracellular sequestration of iron and might decrease the availability of iron for erythropoiesis, leading to the anemia frequently encountered in inflammatory conditions. Anemia is not only very frequent among critically ill patients, but is associated with increased transfusion rates and worse outcomes. Anemia may impair oxygen delivery to peripheral tissues and impose transfusion, which itself carries the risk of further immune suppression. Recent data has emphasised the need to restrict transfusions as much as possible, as transfusion is associated with increased morbidity and mortality. Instead, alternative methods to improve anemia and ameliorate tissue oxygen delivery might be beneficial.

II. Vitamin D down-regulates hepcidin expression

Vitamin D is a hormone promoting bone health, which also has a wide range of cellular activities including the differentiation of hematopoietic cells and down-regulation of inflammatory cytokines. Vitamin D has anti-inflammatory and immune-regulating properties and the maintenance of adequate vitamin D status may play a role in managing inflammation and immunity. Vitamin D supplementation in patients with chronic inflammatory conditions like chronic kidney disease improves the values of circulating markers of inflammation and immunity. Recently, it has been highlighted that in certain conditions, like chronic kidney disease, the administration of vitamin D reduces serum hepcidin values and transfusion requirements.

Up to now, there are no data regarding the possibility that by using vitamin D supplementation in surgical or septic shock patients, the physicians could target the hepcidin-ferroportin-iron axis to prevent the occurrence of anemia and, hence, reduce transfusion requirements. Oral vitamin D supplementation lowers hepcidin values and might increase erythropoiesis and decrease inflammation.

III. Vitamin D supplementation in the critically ill. Safety profile

The therapeutic potential of vitamin D is a topic of intense interest. A high prevalence of low vitamin D levels has been confirmed in patients who are critically ill. Vitamin D deficiency is associated with higher infection rates, 30-day mortality and in-hospital mortality in adult critically ill patients. During critical illness, vitamin D supplementation has a favorable safety profile and a possible mechanism of vitamin D supplementation in inducing bactericidal pleiotropic effects has been suggested. To improve vitamin D status, high-dose vitamin D is required in the critically ill, as they display a blunted response to supplementation. Recent evidence suggests that treatment of vitamin-D deficient critically ill patients may improve outcomes and mortality, possibly through enhancing innate immunity and the inhibition of proinflammatory cytokines. Further clinical trials to explore the effects of vitamin D supplementation on the up-regulation process of proinflammatory cytokines are needed.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Conditions

Systemic Inflammatory Response Syndrome

Intervention

enteral supplementation with vitamin D, blood collection 3mL

Location

Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca
Cluj-napoca
Cluj
Romania
400012

Status

Not yet recruiting

Source

Iuliu Hatieganu University of Medicine and Pharmacy

Results (where available)

View Results

Links

Published on BioPortfolio: 2016-12-26T23:17:32-0500

Clinical Trials [4533 Associated Clinical Trials listed on BioPortfolio]

Effect of Vitamin D Supplementation on Inflammatory Markers

Previous studies have shown that improving vitamin D status among the elderly may lead to an improvement in some inflammatory markers, especially with patients with type 2 diabetes. The ai...

Effect of Enteral Genistein Supplementation in Sepsis

To evaluate effects of genistein supplementation to enteral nutrition on inflammatory cytokines and morbidity in patients with sepsis

Vitamin C Supplementation Intervention

This study is to test a low-cost, simple vitamin C supplementation intervention, that is, comparing placebo to 500 mg/day vitamin C and 1 gram/day vitamin C daily to assess feasibility and...

Optimizing Vitamin D Nutrition in Healthy Adults

The purpose of this study is to determine the average dosage of oral vitamin D supplementation to maintain optimal vitamin D levels in the body and to see if there are differences in the r...

Vitamin D Supplementation Requirement in Obese Subjects

Vitamin D deficiency is common in obese patients. Most of vitamin D supplementation studies were done with non-obese subjects. This study looks at vitamin D supplementation requirements ...

PubMed Articles [16988 Associated PubMed Articles listed on BioPortfolio]

Effect of vitamin D supplementation on clinical outcome and biochemical profile in South Indian population with vitamin D-deficient chronic urticaria- a randomized double-blind placebo controlled trial.

Chronic urticaria (CU) is a debilitating inflammatory skin disease. Prior studies have shown reduced concentrations of vitamin D in CU and there are limited reports of potential beneficial role for vi...

Randomized clinical trials of oral vitamin D supplementation in need of a paradigm change: The vitamin D autacoid paradigm.

Epidemiological studies highlight the negative correlation between vitamin D levels and the incidence of many non-skeletal diseases including inflammatory diseases, cancer, and metabolic and neurologi...

Variable Genomic and Metabolomic Responses to Varying Doses of Vitamin D Supplementation.

To assess the impact of vitamin D supplementation on genomic and metabolomic profiles and relate them to the individual's responsiveness to varying doses of vitamin D Patients and Methods: Healthy adu...

Genetic Variations in VDR could Modulate the Efficacy of Vitamin D3 Supplementation on Inflammatory Markers and Total Antioxidant Capacity among Breast Cancer Women: A Randomized Double Blind Controlled Trial.

Low levels of vitamin D are found in a great part of breast cancer women. Study subjects using vitaminD3 supplement had lower rates of cancers and fewer markers of inflammation. Additionally, recent s...

Four months vitamin D supplementation to vitamin D insufficient individuals does not improve muscular strength: A randomized controlled trial.

The inconsistent results on the effects of vitamin D on muscle strength reported by intervention trials may partly be explained by inclusion of vitamin D sufficient individuals. The main objective was...

Medical and Biotech [MESH] Definitions

A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.

Development of a library collection, including the determination and coordination of selection policy, assessment of needs of users and potential users, collection use studies, collection evaluation, identification of collection needs, selection of materials, planning for resource sharing, collection maintenance and weeding, and budgeting.

Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes.

A systemic inflammatory response to a variety of clinical insults, characterized by two or more of the following conditions: (1) fever >38 degrees C or HYPOTHERMIA <36 degrees C; (2) TACHYCARDIA >90 beat/minute; (3) tachypnea >24 breaths/minute; (4) LEUKOCYTOSIS >12,000 cells/cubic mm or 10% immature forms. While usually related to infection, SIRS can also be associated with noninfectious insults such as TRAUMA; BURNS; or PANCREATITIS. If infection is involved, a patient with SIRS is said to have SEPSIS.

A condition characterized by the presence of ENDOTOXINS in the blood. On lysis, the outer cell wall of gram-negative bacteria enters the systemic circulation and initiates a pathophysiologic cascade of pro-inflammatory mediators.

More From BioPortfolio on "Impact of Vitamin D Supplementation on Hepcidin Levels and Transfusion Requirements in Surgical and Septic Patients"

Quick Search

Relevant Topics

Surgical treatments
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...

Sepsis, septicaemia and blood poisoning
Septicaemia (another name for blood poisoning) refers to a bacterial infection of the blood, whereas sepsis can also be caused by viral or fungal infections.  Sepsis is not just limited to the blood and can affect the whole body, including the organ...

Blood
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...


Searches Linking to this Trial