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Overview of the vitamin D axis
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Vitamin D deficiency is common among the general population. It is also observed in up to 76% of critically ill patients. Despite the high prevalence of hypovitaminosis D in critical illness, vitamin D is often overlooked by medical staff as the clinical implications and consequences of vitamin D deficiency in acute contexts remain to be fully unde...
Context in source publication
Context 1
... and nutrition, including dietary supplementa- tion, are the main sources of vitamin D in humans. Solar ultraviolet B radiation infiltrates the skin converting 7- dehydrocholesterol (7-DHC) to pre-vitamin D 3 (pre-D 3 ), which is subsequently converted to vitamin D 3 [4][5][6]. Vitamin D (D 2 and D 3 ) is also found naturally in certain foods (oily fish, mushrooms, egg yolk) and fortified food products, including cereals, cheese, and milk [4,5]. Vita- min D from the skin and diet is then transported to the liver bound to vitamin D-binding protein (VDBP) and albumin, where it is hydroxylated to 25-hydroxyvitamin D (25(OH)D) [4][5][6]. This is used to determine a patient's vitamin D status. 25(OH)D is then metabolized by the enzyme 25-hydroxyvitamin D-1αhydroxylase (CYP27B1) in the kidneys to the active form of vitamin D, 1α,25- dihydroxyvitamin D (1,25(OH) 2 D) [4][5][6], which is then transported to various target cells and tissues where it interacts with intracellular vitamin D receptors (VDRs) to exert transcriptional effects. In addition to the kid- neys, various extra-renal sites (such as macrophages) are reported to contain CYP27B1 permitting direct metabol- ism of 25(OH)D to exert pleotropic effects via autocrine means [7] (Fig. ...
Citations
... According to the most recent consensus statement, vitamin D deficiency is defined as 25-hydroxyvitamin D (25(OH)D) levels less than 12 ng/mL, 25(OH)D levels between 12 and 20 ng/mL define vitamin D insufficiency, while 25(OH)D levels between 20 and 50 ng/mL are considered safe and sufficient for skeletal health [18]. Vitamin D deficiency is highly prevalent in critically ill patients (in around 70 %), and it has been linked to poor outcomes [11,[19][20][21]. Additionally, it is a risk factor for the development of severe infections and sepsis with worse clinical outcomes [8,9,16,21,22]. ...
... Our findings are in accordance with previous data that demonstrate an increased prevalence of hypovitaminosis D in critically ill cases [11,19,20,28]. Evidence also suggests that decreased vitamin D is a risk factor for sepsis and a poor outcome [8,9,13,14,16,20]. ...
... Our findings are in accordance with previous data that demonstrate an increased prevalence of hypovitaminosis D in critically ill cases [11,19,20,28]. Evidence also suggests that decreased vitamin D is a risk factor for sepsis and a poor outcome [8,9,13,14,16,20]. A recent meta-analysis of 8 studies with 1736 cases showed that decreased 25 (OH)D at admission was independently linked to an increased mortality in cases with sepsis [22]. ...
Hypovitaminosis D is highly prevalent in critically ill patients, and it has been suggested to be a risk factor for infections, sepsis and higher mortality. We sought to investigate whether serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) in critically ill patients with new onset sepsis are associated with severity and outcome. We prospectively included 50 consecutive critically ill adult cases with new onset sepsis and 50 healthy controls matched for age and sex. PTH and 25(OH)D were determined in serum via electrochemiluminescence immunoassays at inclusion in the study in all cases and controls, and one week after sepsis onset in cases. Patients had reduced 25(OH)D compared to controls at sepsis onset (7.9 ± 3 vs 24.6 ± 6.7 ng/mL, p < 0.001), whilst PTH was similar (median (range): 34.5 (5.7-218.5) vs 44.2 (14.2-98.1) pg/mL, p = 0.35). In patients, 25(OH)D upon enrollment and one week after did not differ significantly (7.9 ± 3 vs 7 ± 4.3 ng/mL, p = 0.19). All patients presented with hypovitaminosis D (25(OH)D < 20 ng/mL), while 40 patients (80 %) had vitamin D deficiency (25(OH)D < 12 ng/mL) at sepsis onset, including all ten (20 %) nonsurvivors, who died within 28 days from sepsis onset. Patients with sepsis (N = 28) and septic shock (N = 22) as well as survivors (N = 40) and non-survivors (N = 10) had similar 25(OH)D at enrollment (p > 0.05). 25(OH)D was positively correlated with ionized calcium (r = 0.46, p < 0.001) and negatively with PTH (p < 0.05), while inflammatory biomarkers or the severity scores exhibited no correlation with 25(OH)D. Patients with septic shock and nonsurvivors had lower PTH than patients with sepsis and survivors respectively (42.2 ± 42.9 vs 73.4 ± 61.9 pg/mL, p = 0.04, and 18.3 ± 10.7 vs 69.9 ± 58.8 pg/mL, p = 0.001, respectively). C-reactive protein was negatively associated with PTH (r = − 0.44, p = 0.001). In conclusion, vitamin D deficiency was present in 80 % of critically ill patients at sepsis onset, while nonsurvivors exhibited lower PTH than survivors. Additional, larger and multicenter studies are warranted to elucidate the contribution of vitamin D and PTH to the pathogenesis of sepsis and its outcomes.
... 4 Severe burn injuries disturb immune and physiological responses, including inflammation, immunosuppression, reduced plasma levels of vitamin D and its carrier proteins (hypoalbuminemia), and calcium homeostasis derangements. 4,7,8 Clinical studies have established an association between low circulating vitamin D levels and adverse outcomes in burn patients, including increased susceptibility to infections, sepsis, pneumonia, prolonged hospital stays, recurrent ICU admissions, delayed wound healing, organ failure, escalated treatment costs, and higher mortality rates. 7,9,10 On the other hand, vitamin D is a hormone known for its role in calcium homeostasis. ...
... 4,7,8 Clinical studies have established an association between low circulating vitamin D levels and adverse outcomes in burn patients, including increased susceptibility to infections, sepsis, pneumonia, prolonged hospital stays, recurrent ICU admissions, delayed wound healing, organ failure, escalated treatment costs, and higher mortality rates. 7,9,10 On the other hand, vitamin D is a hormone known for its role in calcium homeostasis. 11 Calcium derangement is associated with complications of severe trauma (including hypothermia, coagulopathy, and acidosis) and poorer outcomes in trauma patients. ...
In the ongoing challenge to reduce burn‐associated mortality rates, this study explores the predictive capacity of clinical factors in burn patients, focusing on vitamin D, calcium, and serum albumin levels during hospitalisation in cases with Pseudomonas aeruginosa infection. Our research involves a comprehensive analysis of 100 burn patients, encompassing crucial clinical parameters such as the burn severity index, serum albumin, vitamin D, and calcium levels at admission. Data were meticulously entered into IBM Statistics SPSS software version 28 and subjected to statistical analysis. The study reveals an average patient age of 39.75 years and a notable 34% mortality rate. Additionally, the average lengths of hospital and intensive care unit (ICU) stays are determined to be 11.33 and 7.79 days, respectively. Significantly, a correlation between calcium and albumin variables and treatment outcomes is established, showcasing their potential to predict variable changes in patient mortality rates. Furthermore, a noteworthy association is observed between serum calcium levels and the duration of ICU hospitalisation. In conclusion, albumin and calcium variables emerge as sensitive and specific indicators for predicting outcomes in burn patients. Importantly, the independence of these factors from the physician's experience and diagnosis reduces human error and thus increases the accuracy of mortality prediction in this patient population.
... 6 Vitamin D deficiency is frequent in critically ill patients, including those who have suffered burns. 7,8 A clinical study recently reported that most burn patients (79.6%) had vitamin D deficiency at admission. 9 Severe burn damage can cause a decrease in vitamin D and the proteins that carry it. ...
... 7 This is of concern because vitamin D has wide-ranging biological effects on the body and may affect short-term and long-term outcomes in these patients. 7 Vitamin D stimulates wound healing and enhances immunity through vitamin D receptors in B and T lymphocytes, monocytes and macrophages. 8 In addition, vitamin D levels are associated with the biomechanical properties of hypertrophic scars. ...
... 8 The literature on hypovitaminosis D and its clinical consequences in adult burn patients is limited. 7 However, some studies have shown that low vitamin D levels in critically ill patients can be associated with negative outcomes such as infection and sepsis, increased length of hospitalization, wound healing time, organ failure and increased mortality risk. 7,[9][10][11][12][13][14][15][16][17] Some studies also reported no association between vitamin D deficiency and outcomes such as length of hospitalization, sepsis and mortality. ...
Evaluating complications and mortality risks in burn patients is crucial for effective treatment planning and improving survival rates. This study investigated the relationship between the serum vitamin D level and the clinical outcomes of adult burns patients. This was a prospective cohort of adult patients hospitalized due to thermal burns at a burn centre in the north of Iran. Based on the level of 25 hydroxyvitamin D measured upon admission, patients were divided into two groups of patients with sufficient 25 hydroxyvitamin D level and insufficient 25 hydroxyvitamin D level. Descriptive statistics were used for baseline demographics. Univariate analysis was conducted using Mann–Whitney U, Chi‐square, independent samples, and Fisher's exact tests. A multivariate logistic regression was performed to adjust for the effects of confounding variables. Statistical analyses were conducted using SPSS 28.0 software. A total of 220 patients were included in the study. The average total body surface area burned was 30.52 ± 9.34. Patients with insufficient vitamin D levels had longer hospital stays (12.53 vs. 11.45) and longer stays in the intensive care unit (ICU) (3.32 vs. 2.40) than those with appropriate vitamin D levels. Participants with insufficient vitamin D levels exhibited a numerically higher incidence of infections than those with adequate levels ( p < 0.05). The multivariate regression found that vitamin D deficiency levels were associated with increased infection rates and prolonged hospital stay. This study suggests that vitamin D deficiency is a significant risk factor for adverse clinical outcomes in burn patients. Further research is needed to confirm these associations and to explore potential interventions to optimize vitamin D status in this patient population.
... Vitamin D plays a vital role in the immune system through its receptors on various immune cells, including activated CD4 and CD8 T cells, B cells, macrophages, neutrophils, and dendritic cells. Vitamin D also regulates the production of immunoglobulins [12]. ...
Background & objective
Patients in the intensive care unit have a high prevalence of vitamin D deficiency (VDD). In the present study, clinical outcomes in the ICU were analyzed with vitamin D status.
Materials and methods
In this prospective, multicenter study, sampling was conducted on seven ICUs in three hospitals. Within the first 24 h of ICU admission, patient’s serum vitamin D levels were measured, and their disease severity was monitored using the scores of acute physiologic assessment and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), and the modified Nutrition Risk in Critically ill (mNUTRIC) score.
Results
A total of 236 patients were enrolled in this study, of which 163 (69.1%) had lower vitamin D levels than 20 ng/ml upon ICU admission. The patients with VDD had higher APACHE II scores)P = 0.02), SOFA scores (P < 0.001), and mNUTRIC scores (P = 0.01). Patients with sufficient levels of vitamin D (> 30 ng/ml) had a shorter stay at ICU (P < 0.001). VDD was independently associated with 28-day mortality (OR: 4.83; 95% CI: 1.63–14.27; P = 0.004).
Conclusion
The data showed that VDD was common among the critically ill and was related to a more severe course of illness and a higher mortality rate.
... 59 In addition, vitamin D has numerous beneficial effects in the immune system, generally suppressing pro-inflammatory cytokines and stimulating anti-inflammatory cytokines in cells expressing the vitamin D receptor (VDR). 60 Vitamin D also has anti-inflammatory activities in skin, and deficiency has been associated with several cutaneous inflammatory diseases. 61 Vitamin D has demonstrated anti-fibrotic activities in many cells and tissues, including lung, liver, kidney and skin. ...
... 73,111 This is consistent with epidemiological evidence of associations between vitamin D deficiency and immune-related diseases and disorders, including type 1 diabetes, multiple sclerosis, psoriasis, rosacea, rheumatoid arthritis, respiratory infections, cardiovascular disease, systemic lupus erythematosus, inflammatory bowel disease and sepsis, in addition to keloid disorder. 60,73,89,91,108,110,[112][113][114] Given the widely accepted role of both local and systemic inflammation in keloid disorder, 4 it is reasonable to speculate that vitamin D deficiency may contribute to a proinflammatory state that is permissive to, or actively promotes, development of keloids. ...
Keloids are disfiguring fibroproliferative lesions that can occur in susceptible individuals following any skin injury. They are extremely challenging to treat, with relatively low response rates to current therapies and high rates of recurrence after treatment. Although several distinct genetic loci have been associated with keloid formation in different populations, there has been no single causative gene yet identified and the molecular mechanisms guiding keloid development are incompletely understood. Further, although it is well known that keloids are more commonly observed in populations with dark skin pigmentation, the basis for increased keloid risk in skin of color is not yet known. Because individuals with dark skin pigmentation are at higher risk for vitamin D deficiency, the role of vitamin D in keloid pathology has gained interest in the keloid research community. A limited number of studies have found lower serum vitamin D levels in patients with keloids, and reduced expression of the vitamin D receptor (VDR) in keloid lesions compared with uninjured skin. Vitamin D has documented anti-inflammatory, anti-proliferative, and pro-differentiation activities, suggesting it may have a therapeutic role in suppression of keloid fibrosis. Here we review the evidence supporting a role for vitamin D and VDR in keloid pathology. This article is protected by copyright. All rights reserved.
... Vitamin D deficiency [defined as 25(OH)D levels below 20 ng/ml] is common and occurs in nearly half of the normal population and in about 70% of all intensive care patients (20,21). Burn patients are particularly affected (22,23). Vitamin D deficiency can be caused by low seasonal sun exposure or high air pollution (1), vegan diet (24), using sunscreen, staying indoors, wearing concealing clothing and reduced endogenous vitamin D production efficiency from solar UVB in older age. ...
Many critically ill patients are vitamin D and vitamin C deficient and the current international guidelines state that hypovitaminoses should be compensated. However, uncertainty about optimal dosage, timing and indication exists in clinical routine, mainly due to the conflicting evidence. This narrative review discusses both micronutrients with regards to pathophysiology, clinical evidence of benefits, potential risks, and guideline recommendations. Evidence generated from the most recent clinical trials are summarized and discussed. In addition, pragmatic tips for the application of these vitamins in the clinical routine are given. The supplementations of vitamin D and C represent cost-effective and simple interventions with excellent safety profiles. Regarding vitamin D, critically ill individuals require a loading dose to improve 25(OH)D levels within a few days, followed by a daily or weekly maintenance dose, usually higher doses than healthy individuals are needed. For vitamin C, dosages of 100–200 mg/d are recommended for patients receiving parenteral nutrition, but needs may be as high as 2–3 g/d in acutely ill patients.
... However, burn injuries, particularly large area burn injuries, represent a complex process. Beyond massive fluid loss, the body is under a pathological condition involving excessive inflammation, hypermetabolism and an acute immune response (5,6). Early treatment is key to improving prognosis and can decrease systemic inflammatory response syndrome, sepsis, multiple organ failure and other life-threatening conditions in patients (7). ...
The pathophysiological mechanisms, especially the roles of immune cells, underlying early stages of severe burn injury have not yet been fully clarified. Here, we analyzed circulating neutrophils (PMNs) in healthy donors and early burned patients by single-cell RNA sequencing to provide a comprehensive transcriptional landscape of PMNs in heterogeneity and functional multiplicity. Circulating PMNs in the healthy donors and burned groups were divided into five subgroups (G3, G4, G5a, G5b, G5c) with different functions. The dominant subsets of PMNs in homeostasis and burn injury significantly differed between groups. In addition, cells in the same subpopulation had the same core identity markers but performed different functions in healthy and burned states. Under burned conditions, PMN activation was very evident and accompanied by clear degranulation and metabolic abnormalities. Interestingly, was found that PMN activation, degranulation, chemotaxis, phagocytosis and reactive oxygen species (ROS) production in burned patients significantly differed between day 1 and days 2 or 3, thus providing a theoretical basis for PMN interventions in early burn stages. Significantly, previously undescribed transcription factors were also identified, including ZNF-787, ZNF-467, ZNF-189, ZNF-770, ZNF-262. In conclusion, this study conducted for the first time a detailed analysis of the heterogeneity and functional multiplicity of PMNs in early stages of severe burn injuries. Our findings attempted to clarify the influence of PMN heterogeneity on the pathophysiology and related mechanisms of burn injuries, which can provide new ideas for further research in burn intervention.
... Neutrophil dysfunction, release of immature granulocytes, and a decreased number and disturbed expression of CD14+/HLA-DR+ monocytes have also been observed [10,11]. Conversely, up to 3 years after the burn, there may be a simultaneous increase in the level of granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 10 (IL-10) and other cytokines [12]. We can distinguish three zones in burns, which were described by Jackson ( Figure 2) [13]. ...
In the literature, burns are understood as traumatic events accompanied by increased morbidity and mortality among affected patients. Their characteristic feature is the formation of swelling and redness at the site of the burn, which indicates the development of inflammation. This reaction is not only important in the healing process of wounds but is also responsible for stimulating the patient’s innate immune system. As a result of the loss of the protective ability of the epidermis, microbes which include bacteria, fungi, and viruses have easier access to the system, which can result in infections. However, the patient is still able to overcome the infections that occur through a cascade of cytokines and growth factors stimulated by inflammation. Long-term inflammation also has negative consequences for the body, which may result in multi-organ failure or lead to fibrosis and scarring of the skin. The innate immune response to burns is not only immediate, but also severe and prolonged, and some people with burn shock may also experience immunosuppression accompanied by an increased susceptibility to fatal infections. This immunosuppression includes apoptosis-induced lymphopenia, decreased interleukin 2 (IL-2) secretion, neutrophil storm, impaired phagocytosis, and decreased monocyte human leukocyte antigen-DR. This is why it is important to understand how the immune system works in people with burns and during infections of wounds by microorganisms. The aim of this study was to characterize the molecular pathways of cell signaling of the immune system of people affected by burns, taking into account the role of microbial infections.
... The role of the vitamin D (VITD) is of great interest in lung disease, this includes not only VITD itself but also VITD receptor and VITD-binding protein (Chishimba et al., 2010). In fact, VITD deficiency has been suggested to alter SARS-CoV-2 susceptibility and the course of the disease (Pizzini et al., 2020), and this must not be ignored since VITD insufficiency and deficiency are common in the general population (Al-Tarrah et al., 2018). ...
... Through the VITD axis, probiotics can regulate both innate and adaptive immune systems and thus help to maintain mucosal barrier integrity and suppress gut mucosal inflammation (Li et al., 2015). All of this can be done by decreasing Th1 and Th17 T cells and proinflammatory cytokines, such as IL-1, IL-6, IL-8, IFN-γ, and TNFα (Del Pinto et al., 2017), favoring at the same time Th2 and Treg differentiation (Al-Tarrah et al., 2018), downregulating T-cell-driven IgG production, inhibiting DC differentiation, and helping maintain self-tolerance, while enhancing protective innate immune responses (Del Pinto et al., 2017). ...
Nowadays, respiratory infections are one of the main causes of death worldwide. It was always thought that the respiratory tract was devoid of its microbiota, but it was a few years ago when this changed. It has not only been described but also the pulmonary microbial community is altered in the context of various respiratory disorders. Despite the lack of knowledge about its role in health and disease, there is evidence indicating that the use of probiotics may have beneficial effects during respiratory disorders since they can modulate the immune system both directly and indirectly.
... Einnig má nefna skort á D-vítamíni, sem getur orðið alvarlegur, einkum hjá börnum, þar sem bruni á húð truflar D-vítamínframleiðslu húðarinnar. 17 Sýnt hefur verið fram á marktaek neikvaeð tengsl milli heilsutengdra lífsgaeða og fullþykktarbruna, fjölda skurðaðgerða og atvinnuleysis í kjölfar slyss allt að 16 árum eftir brunaslysið. 11 Rannsókn á saenskum brunasjúklingum leiddi í ljós að 30% þátttakenda höfðu langvinna verki tveimur til 7 árum eftir slysið og hafði sá hópur einnig lakari heilsutengd lífsgaeði heldur en þeir sem ekki höfðu langvinna verki. ...
Objectives:
The aim of the study was to assess the long-term effects of burn injury on the health-related quality of life of adult burn survivors in Iceland and to validate the translated Icelandic version of the Burn Specific Health Scale-Brief (BSHS-B).
Materials and methods:
The participants of this descriptive cross-sectional study were all burn survivors, 18 years or older, admitted to hospital for 24 hours or more because of skin burn during a 15 years period (N=196). They completed questionnaire about their health (BSHS-B), health related quality of life (EQ-5D-5) and additional questions on burn-related symptoms and their burn experience.
Results:
Response rate was 34% (N=66). Men were 77%, mean age 45.7 years (sf=18.3 and range 18-82 years), mean age when burned was 34.0 (sf=20,1, range 1-75), median time from burn accident was 11.5 years (range 1-44 years) and 32% had been burned when under 18 years of age. Burn-specific health was 4.4-4.0 (median) and health on the EQ5D-5vas scale was 80 (median, range 10-100). Those who lost a body part or had skin transplantation had more negative body image and needed more selfcare than others (p<). A significant proportion of participants reported physical and psychosocial symptoms such as itch (48%), persistent pain (37%), anxiety/depression (29%) and negative self-image (37%). Majority (67%) believed they did not get enough information, follow-up, or support after discharge from hospital. The Icelandic version of the Burn Specific Health Scale-Brief (BSHS-B) was reliable, but more research is needed to establish its validity.
Conclusion:
These findings suggest that most Icelandic burn survivors report acceptable health and health-related quality of life. The study identified a subgroup of survivors that experience persistent physical and psychosocial symptoms. Team approach with holistic support after discharge, for a prolonged period of time aiming at preventing physical and psychiatric morbidity, is recommended.
