Sepsis is both prevented and treated by Vitamin D - many studies

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Summary of Sepsis and Vitamin D

• Sepsis is more likely in those with poor immune systems
  Infants, the elderly, the sick, and those with low vitamin D
• Severe sepsis has been associated with low Vitamin D and poor Vitamin D receptor in many studies
• Loading doses of Vitamin D bypass any poor Vitamin D Receptors
• Vitamin D loading doses have been proven to treat sepsis (RCTs: 2015, 2020, 2021)
    Reduced: ICU stay by 8 days, Hospital stay by 7 days, and readmission rate reduced to 0%
    Note: The fastest way (2 hours) to have a sublingual loading dose of Vitamin D nano-emulsion
• Sepsis is fought by Vitamin D in 9 ways – Feb 2023
• 

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VitaminDWiki recommendations for Vitamin D treatment of sepsis in ICU

1. Fortify the immune system as fast as possible with a Vitamin D Loading dose
   200,000 to 350,000 IU loading doses are often succesful
   • Vitamin D levels can be raised very quickly
   • Note: Injection of Vitamin D into muscle provides a far slower, response
2. Reduce the time to get Vitamin D t the cells by days with sublingual or topical vitamin D
   • The nanoemulsion form of Vitamin D seems particularly fast acting (both topical and sublingual)
   • Vitamin D powder can be poured into a tablespoon of water and swished in mouth for 1 or 2 minutes to get vitamin D into the cells in < 1 hour, vs 30+ hours for oral vitamin D
3. Follow loading dose with maintenance doses of Vitamin D - probably 50,000 IU weekly
   • Note: Many studies incorrectly used no maintenance dosing, just one loading dose
4. Consider reducing sepsis even more by adding Omega-3    magnesium , and/or Glutamine

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People with Sepis have poor guts (Vitamin D less bio-available) - Perplexity AI June 2024

Yes, people with sepsis often experience significant disruptions in their gut health, which can contribute to poor outcomes. Several studies highlight the impact of sepsis on the gut microbiome and intestinal function:

1. Microbiome Disruption: Sepsis can lead to a dysregulated host response to infection, resulting in significant alterations in the gut microbiome. This includes a loss of beneficial microbial species and an increase in pathogenic bacteria, which can exacerbate the condition and lead to further complications such as organ dysfunction and death.
2. Intestinal Failure: Critically ill patients with sepsis often suffer from gut failure, characterized by symptoms such as absent bowel signs, diarrhea, abdominal distension, and poor intestinal motility. These symptoms, when present together, are associated with a higher mortality rate.
3. Gut Permeability: Sepsis induces significant dysfunction in the intestinal barrier, leading to increased permeability. This allows bacteria to translocate from the gut into the bloodstream, perpetuating the inflammatory response and contributing to the severity of sepsis.
4. Mycobiome Dysbiosis: Sepsis and trauma patients often exhibit significant disturbances in their gut fungal communities, with a depletion of commensal fungi and an overgrowth of pathogenic fungi like Candida. This dysbiosis can further compromise gut health and increase the risk of secondary infections.
5. Impact of Antibiotics: The use of antibiotics, while necessary for treating infections, can also disrupt the gut microbiome, leading to a decrease in microbial diversity and the emergence of antibiotic-resistant pathogens. This disruption can worsen the patient's condition and complicate recovery.

Overall, the gut plays a critical role in the pathophysiology of sepsis, and maintaining gut health is essential for improving outcomes in septic patients
Perplexity References

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44+ VitaminDWiki pages with SEPSIS or SEPTIC in the title

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61,100 hits for sepsis "vitamin d" Jan 2024

Google Scholar

• Association between vitamin D status and sepsis in children: A meta-analysis of observational studies June 2020, https://doi.org/10.1016/j.clnu.2019.08.010  PDF from Sci-Hub via VitaminDWiki only 1.13X more likely - low level, did not consider loading dose
• Rapidly Increasing Serum 25(OH)D Boosts the Immune System, against Infections—Sepsis and COVID-19 July 2022, https://doi.org/10.3390/nu14142997 FREE PDF
• Single dose of 150,000 IU of Vitamin D Reduce Sepsis in Children - RCT June 2020 https://doi.org/10.1177/0300060520926890 PDF
  
  Note: loading dose was so tiny that the vitamin D levels were only raised by 6 ng
  
• Novel biomarker for predicting sepsis mortality: vitamin D receptor - Aug 2021 https://doi.org/10.1177/03000605211034733 FREE PDF
• Vitamin D Deficiency: An Underestimated Factor in Sepsis? 2023 - https://doi.org/10.3390/ijms24032924  PDF did not consider loading dose
• 

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Is sepsis treated by "Vitamin d"? - asked https://search.sciphi.ai/ Jan 2024

Vitamin D has emerged as a potential modulator in the immune response to sepsis, a condition characterized by a severe immune reaction to infections 23. Studies have indicated that vitamin D deficiency is not only common in patients with sepsis but is also associated with increased mortality rates 22. Specifically, severe vitamin D deficiency has been linked to higher two-week, four-week, and in-hospital death rates among sepsis patients 21.

Interestingly, vitamin D insufficiency has been shown to correlate with increased severity of sepsis and higher risk of hospitalization 20. On the other hand, vitamin D supplementation during critical illness, including sepsis, has been associated with improved outcomes 19. However, a meta-analysis revealed that early high-dose vitamin D3 did not provide a survival advantage over placebo in critically ill, vitamin D-deficient patients 17. This suggests that while vitamin D may have potential benefits, the optimal dosage and timing of administration remain to be determined.

In summary, the relationship between vitamin D and sepsis is complex, with evidence suggesting that vitamin D deficiency is associated with worse outcomes in sepsis patients. While supplementation may offer benefits, the exact dosage and timing for therapeutic intervention require further investigation.

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Mechanisms of vitamin D in sepsis treatmentDosage and timing of vitamin D supplementation in sepsisClinical trials on vitamin D for sepsisVitamin D receptor activation in immune responseStatins and vitamin D in sepsis management

Vitamin D Deficiency: An Underestimated Factor in Sepsis?
It has been suggested that vitamin D deficiency plays a role in sepsis and septic shock because vitamin-D-related pathways are associated with various immunological, endocrine, and endothelial functions. Previous research has yielded inconclusive results regarding the link between mortality and vitamin D deficiency in sepsis patients.

Vitamin D Supplementation in Sepsis and Critical Illness: Where ...
Large retrospective cohort studies indicate that low serum levels of 25 (OH)D obtained at time points within 1 year prior to ICU admission are associated with higher rates of sepsis, bloodstream infection, and mortality ( 11, 12 ). The reasons for the high rate of vitamin D deficiency in the ICU is likely multifactorial.

Vitamin therapy in sepsis - PMC - National Center for Biotechnol...
Sepsis is associated with a significant degree of morbidity and mortality in children worldwide, and new therapies are needed. 1 Vitamins are essential micronutrients, with key roles in many biological pathways relevant to sepsis, including those leading to anti-inflammatory and antioxidant effects. 2, 3 Furthermore, relative vitamin deficiencie...

Potential benefits of vitamin D for sepsis prophylaxis in critic...
Vitamin D with the effects of immunomodulation and anti-microbes may be an optimal agent to prevent sepsis. Vitamin D deficiency is common in critically ill patients with severe infection and is strongly associated with increased mortality (14, 16). Vitamin D deficiency is an independent risk factor for sepsis, and higher 25-hydroxyvitamin D ...

Vitamin D status was associated with sepsis in critically... : M...
Until the 1980s, its extra-osseous role became research hotspots, studies have found that vitamin D can affect cell proliferation and mutation, hormone secretion regulation and immune regulation, and its role in many acute and chronic diseases has been confirmed and recognized, including infectious diseases, autoimmune diseases, cancer, Type 2 d...

Vitamin D in sepsis: from basic science to clinical impact
The challenges in the field of vitamin D and sepsis may seem daunting, but the basic and clinical data show promise. An interesting connection for future research is the association between vitamin D and the potential role of statins in treating sepsis [].Certain statins have been associated with increasing vitamin D, and although a recent meta-analysis did not support their role in preventing ...

The Correlation between Serum Level of Vitamin D and Outcome of ...
Introduction Sepsis is a clinical syndrome caused by immune response to various infections. Despite the existence of proper antimicrobial and palliative care, due to the high prevalence of multiple organ failure, being affected with sepsis is associated with a high rate of mortality.

Applications of vitamin D in sepsis prevention - PubMed
Vitamin D (VD) is a steroid prohormone that regulates the body's calcium and phosphate levels in bone mineralization. It is also well described as a fat-soluble vitamin playing an important role in immunomodulation, regulation of cytokines, and cell proliferation.

Vitamin D and sepsis - PMC - National Center for Biotechnology I...
In 2011, the Institute of Medicine issued a publication establishing a serum 25-hydroxyvitamin D (25 (OH)D) concentration of 20ng/mL as an optimal concentration for skeletal health for the US population. 7 In the same year, the Endocrine Society recommended a serum 25 (OH)D concentration of at least 30 ng/mL for optimal health benefits. 3 Using ...

Vitamin therapy in sepsis
One meta-analysis found that vitamin D deficiency was associated with higher rates of sepsis, severity of illness, and length of stay. 89 In contrast, other studies of pediatric sepsis and vitamin ...

Original research: Effects of vitamin D insufficiency on sepsis ...
Measuring a vitamin D level in the ED is important if it will help decrease sepsis severity and improve outcomes. The consequences of vitamin D insufficiency and deficiency are important, especially in sepsis 17 25 because all prevention, evaluation and treatment of sepsis are crucial for reducing morbidity and mortality. Early identification ...

Vitamin D in sepsis: from basic science to clinical impact
PMCID: PMC3580673. DOI: 10.1186/cc11252. The growing basic and clinical investigations into the extraskeletal effects of vitamin D have revealed roles in the functioning of the immune system, generating interesting questions about this nutrient's connections to sepsis. This article briefly reviews the current science of the function of vitamin ...

Frontiers
The effectiveness of vitamin D supplementation for preventing sepsis remains unclear. This retrospective cohort study investigated the effect of vitamin D supplementation on sepsis prophylaxis in critically ill patients with suspected infection.

Full article: Vitamin D and sepsis - Taylor & Francis Online
Vitamin D insufficiency and sepsis are both highly prevalent worldwide problems and this article reviews the emerging science that is defining the intersections of these conditions.

Vitamin D and sepsis: An emerging relationship - PubMed
Vitamin D insufficiency and sepsis are both highly prevalent worldwide problems and this article reviews the emerging science that is defining the intersections of these conditions.

Vitamin D Council
The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med. 2003 Mar 1; 167 (5): 695-701. White, J. H. Vitamin D as an inducer of cathelicidin antimicrobial peptide expression: past, present and future. J Steroid Biochem Mol Biol. 2010 Mar; 121 (1-2): 234-8.

Early High-Dose Vitamin D3 for Critically Ill, Vitamin D–Deficie...
Early administration of high-dose enteral vitamin D 3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D ...

Vitamin D deficiency and clinical outcomes related to septic ......
The controlled thesaurus terms for vitamin D were vitamin D and vitamin D deficiency (VDD). The concept of critical care was covered by critical illness, intensive care, sepsis, and shock.

Nutrients
Vitamin D Supplementation during Intensive Care Unit Stay Is Associated with Improved Outcomes in Critically Ill Patients with Sepsis: A Cohort Study by Boshen Yang 1,†, Yuankang Zhu 2,†, Xinjie Zheng 3, Taixi Li 1, Kaifan Niu 1, Zhixiang Wang 1, Xia Lu 1, Yan Zhang 4,* and Chengxing Shen 1,* 1

Effects of vitamin D insufficiency on sepsis severity and risk o...
Objective To evaluate the association of 25-hydroxyvitamin D (25(OH)D) level on sepsis severity and risk of hospitalisation in emergency department (ED) septic patients when categorised as vitamin D insufficiency according to the level of 25(OH)D<30 ng/mL. Design Cross-sectional observational study. Setting A 900-bed academic tertiary hospital with an ED residency training programme in Bangkok ...

Is there an association between vitamin D deficiency and sepsis ...
Overall, the study findings showed that severe vitamin D deficiency increased sepsis patients' two-week, four-week, and at-hospital death rates, as indicated by higher aHR values than CCI and SOFA ...

Vitamin D Deficiency: An Underestimated Factor in Sepsis? - MDPI
It has been suggested that vitamin D deficiency plays a role in sepsis and septic shock because vitamin-D-related pathways are associated with various immunological, endocrine, and endothelial functions. Previous research has yielded inconclusive results regarding the link between mortality and vitamin D deficiency in sepsis patients.

Vitamin D and sepsis: An emerging relationship - Emory Universit...
suggest that vitamin D has important modulatory effects on the innate immune response to LPS-induced sepsis. While LPS is an important molecule in gram-negative sepsis, vitamin D may also have a role in the sepsis cascade induced by fungal organisms. A study by Khoo et al. treated peripheral blood mononuclear cells (PBMC) with 1,25(OH) 2 D and...

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Sepsis and Vitamin D in adults

See also VitaminDWiki

• ICU Vitamin D injection (300,000 IU) helped - RCT Feb 2021
• Vitamin D for Sepsis prevention – June 2018
• Treatment of neonate sepsis greatly aided by Vitamin D – RCT June 2019
• Urinary sepsis – a single Vitamin D injection reduced hospital days by 40 percent – RCT April 2018

Vitamin D Receptor

• Sepsis is 13 X more likely if poor Vitamin D Receptor – April 2017
• Vitamin D Receptor category listing has 529 items along with related searches

Omega-3

• Sepsis mortality cut in half with Omega-3 – RCT Sept 2017
• Sepsis: 4 fewer days in ICU if add Omega-3 – meta-analysis of 12 RCT – June 2017
• Omega-3 reduced cost of Sepsis by 2900 dollars per patient (12 RCT) – April 2018

Personal note by the founder of VitaminDWiki
My 103-year-old father-in-law got Sepsis in the hospital.
I gave him a loading dose of 200,000 IU of Vitamin D
   Note: loading doses get past the significant Vitamin D receptor barrier
Doctors kicked him out of the ICU after his symptoms went away in a day or so.

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No Consensus on Sepsis and Vitamin D: Type, Amount, When, How Often - July 2023

Should I Supplement Vitamin D in a Patient With Sepsis?
Journal of Acute Medicine 14(1): 1-8, 2024 D01:10.6705/j.jacme.202403_14(l).0001
Vedran Kovacic
Internal Medicine Department, Division of Emergency and Intensive Medicine with Clinical Pharmacology and Toxicology, University Hospital of Split, Spinciceva, Split, Croatia

Sepsis is a potentially fatal organ failure produced by the host’s immune response to infection. It is critical to identify risk factors associated with a poor prognosis in septic patients in order to develop new therapy options. Vitamin D deficiency (25-hydroxyvitamin cholecalciferol < 20 ng/mL) is common in critical and septic patients. Serum vitamin D concentrations are associated with an increased incidence of mortality in critically ill adult patients. In critically ill patients, vitamin D supplementation (a very high vitamin D3 or cholecalciferol loading dosage as a single bolus dose ranging from 400,000 to 540,000 IU) is feasible and safe. Some of the trials and their post-hoc analyses evaluating vitamin D supplementation in severely sick individuals, including septic patients, suggested possible benefits in mortality (reduced 28-day mortality in the range of 8.1%—17.5%), and other outcomes (reduction in hospital length in the range from 9 to 18 days, and decrease in duration of mechanical ventilation in the range from 5 to 10 days). Despite the fact that many studies support the provision of vitamin D to septic patients, there are still many studies that contradict this opinion, and there is still debate about the recommendation to use vitamin D in sepsis. A pragmatic clinical approach in severe sepsis could be supplementation of vitamin D if serum levels are diminished (< 30 ng/ mL).
It appears that a single ultrahigh dose of vitamin D3 (cholecalciferol) could be administered to the septic patient via an enteral tube, followed by daily or monthly maintenance doses.
Parenteral administration ["non-gut: topical, injection (too slow), inhaled, etc.''] might be reserved for a subgroup of septic patients with gastrointestinal, hepatic, or renal dysfunction. Future clinical trials designed exclusively for septic patients are required to assess the potential advantages of vitamin D. Possible impacts of selective activators of vitamin D receptors, such as paricalcitol, should be elucidated in sepsis. This emphasizes the requirement for more study and confirmation of any potential beneficial effects of vitamin D in sepsis.
 Download the PDF from VitaminDWiki

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Vitamin D Deficiency: An Underestimated Factor in Sepsis? – Feb 2023

Int. J. Mol. Sci. 2023, 24(3), 2924; https://doi.org/10.3390/ijms24032924
by Charlotte Delrue 1,Reinhart Speeckaert 2ORCID,Joris R. Delanghe 3ORCID andMarijn M. Speeckaert 1,4,*ORCID
1 Department of Nephrology, Ghent University Hospital, 9000 Ghent, Belgium
2 Department of Dermatology, Ghent University Hospital, 9000 Ghent, Belgium
3 Department of Diagnostic Sciences, Ghent University, 9000 Ghent, Belgium
4 Research Foundation-Flanders (FWO), 1000 Brussels, Belgium

Vitamin D is an important immune modulator that is linked to infection susceptibility. It has been suggested that vitamin D deficiency plays a role in sepsis and septic shock because vitamin-D-related pathways are associated with various immunological, endocrine, and endothelial functions. Previous research has yielded inconclusive results regarding the link between mortality and vitamin D deficiency in sepsis patients. In patients with sepsis and severe vitamin D deficiency, an adequate vitamin D concentration may reduce mortality. Randomized controlled trials to assess the influence of vitamin D supplementation on clinical outcomes in sepsis patients with vitamin D deficiency are uncommon. We will provide an overview of the current knowledge about the relationship between vitamin D and sepsis in this review, as well as consider the potential value of vitamin D supplementation in this situation.
 Download the PDF from VitaminDWiki

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Sepsis strongly associated with both low vitamin D and poor Vitamin D Receptors - Jan 2022

Lower vitamin D levels and VDR FokI variants are associated with susceptibility to sepsis: a hospital-based case-control study.
Biomarkers. 2022 Jan 9;1-8. doi: 10.1080/1354750X.2021.2024598
Xinyue Yang 1, Jin Ru 1, Zhengchao Li 1, Xingpeng Jiang 1, Chuming Fan 1

Background: Vitamin D deficiency has been associated with increased sepsis incidence and mortality in various populations. Vitamin D exerts its effect through vitamin receptors (VDR), and various single nucleotide polymorphisms have been reported to affect the expression and structure of the VDR. In the present study, we investigated the possible role of vitamin D deficiency and VDR polymorphisms in susceptibility to sepsis.

Methods: 576 sepsis patients and 421 healthy controls were enrolled in the present study. Plasma vitamin D levels in patients and healthy controls were quantified by ELISA. Genetic variants in the VDR (FokI, TaqI, BsmI, and ApaI) were genotyped by TaqMan assay.

Results: Reduced serum Vitamin D level was observed in subjects with sepsis compared to healthy controls (p ≤ 0.0001). Further, subjects with septic shock had diminished 25(OH) vitamin D compared to severe sepsis cases (p ≤ 0.0001). FokI variants and minor alleles were more prevalent in sepsis patients compared to healthy controls (Ff: p ≤ 0.0001, χ2 =17.39; ff: p=0.001, χ2 =10.79; f: p ≤ 0.0001, χ2 =23.51).
Furthermore, combined plasma levels of 25(OH) vitamin D and FokI polymorphism revealed a significant role in a predisposition to sepsis and septic shock. However, the prevalence of other VDR polymorphisms (TaqI, BsmI, and ApaI) was comparable among different clinical categories.

Conclusions: Low 25(OH) vitamin D levels and FokI mutants are associated with an increased risk of sepsis and septic shock in a Chinese cohort. Clinical significanceLower levels of 25-OH vitamin D are highly prevalent in Sepsis patients. Subjects harboring VDR FokI variants are predisposed to susceptibility to sepsis in the studied cohort.
- - - - -
See also VitaminDWiki Vitamin D Receptor

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Micronutrients in Sepsis and COVID-19 (mostly Vitamin D)- April 2021

 Download the PDF from VitaminDWiki

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Sepsis death 1.9 X higher risk if <10 ng of Vitamin D - meta-analysis March 2020

BMC Infect Dis, 20 (1), 189 2020 Mar 4, DOI: 10.1186/s12879-020-4879-1
Serum 25-Hydroxyvitamin D and the Risk of Mortality in Adult Patients With Sepsis: A Meta-Analysis
Yuye Li 1, Shifang Ding 2
 Download the PDF from VitaminDWiki

Background: Vitamin D deficiency has been related to the risk of sepsis. However, previous studies showed inconsistent results regarding the association between serum 25-hydroxyvitamin D (25 (OH) D) and mortality risk in septic patients. We aimed to evaluate the relationship between serum 25 (OH) D at admission and mortality risk in adult patients in a meta-analysis.

Methods: Follow-up studies that provided data of multivariate-adjusted relative risk (RR) between serum 25 (OH) D and mortality risk in septic patients were retrieved via systematic search of PubMed and Embase databases. A random effect model was used to pool the results.

Results: Eight studies with 1736 patients were included. Results of the overall meta-analysis showed that lower 25 (OH) D at admission was independently associated with increased risk or (of?) mortality (adjusted RR: 1.93, p < 0.001; I2 = 63%) in patients with sepsis.
Exploring subgroup association showed that patients with severe vitamin D deficiency (25 (OH) D < 10 ng/ml) were significantly associated with higher mortality risk (adjusted RR: 1.92, p < 0.001), but the associations were not significant for vitamin D insufficiency (25 (OH) D 20~30 ng/ml) or deficiency (25 (OH) D 10~20 ng/ml). Further analyses showed that the association between lower serum 25 (OH) D and higher mortality risk were consistent in studies that applied different diagnostic criteria for sepsis (systemic inflammatory response syndrome, Sepsis-2.0, or Sepsis-3.0), short-term (within 1 month) and long-term studies (3~12 months), and in prospective and retrospective studies.

Conclusions: Severe vitamin D deficiency may be independently associated with increased mortality in adult patients with sepsis. Large-scale prospective studies are needed to validate our findings.

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200,000 and 400,000 IU of vitamin D reduced septic shock, length of stay - RCT June 2015

Effect of Cholecalciferol Supplementation on Vitamin D Status and Cathelicidin Levels in Sepsis: A Randomized, Placebo-Controlled Trial.
Critical Care Medicine, Post Author Corrections: June 17, 2015, doi: 10.1097/CCM.0000000000001148
Quraishi, Sadeq A. MD, MHA, MMSc; De Pascale, Gennaro MD; Needleman, Joseph S. BS, BA; Nakazawa, Harumasa MD, Ph.D.; Kaneki, Masao MD, Ph.D.; Bajwa, Ednan K. MD, MPH; Camargo, Carlos A. Jr MD, DrPH; Bhan, Ishir MD, MPH
Quraishi, Sadeq A., MD SQURAISHI at PARTNERS.ORG

	Placebo	200,000 IU	400,000 IU	p
ICU LOS	12 days	4 days	3 days	0.83
Hospital LOS	21 days	13 days	14 days	0.03
30-day readmission	20%	0%	0%	< 0.001
30 days still alive	70%	70%	80%	0.18

Objectives: To compare changes in vitamin D status and cathelicidin (LL-37) levels in septic ICU patients treated with placebo versus cholecalciferol.
Design: Randomized, placebo-controlled trial.
Setting: Medical and surgical ICUs of a single teaching hospital in Boston, MA.
Patients: Thirty adult ICU patients.
Interventions: Placebo (n = 10) versus 200,000 IU cholecalciferol (n = 10) versus 400,000 IU cholecalciferol (n = 10) within 24 hours of new-onset severe sepsis or septic shock.

Measurements and Main Results: Blood samples were obtained at baseline (day 1) and on days 3, 5, and 7 to assess total 25-hydroxyvitamin D, as well as vitamin D-binding protein and albumin to calculate bioavailable 25-hydroxyvitamin D. Plasma LL-37 and high-sensitivity C-reactive protein levels were also measured. At baseline, median (interquartile range) plasma 25-hydroxyvitamin D was 17 ng/mL (13-22 ng/mL) and peaked by day 5 in both intervention groups.
Groups were compared using Kruskal-Wallis tests. Relative to the baseline, on day 5, the median change in biomarkers for
placebo,
200,000 IU cholecalciferol, and
400,000 IU cholecalciferol groups, respectively,
were as follows:

• 1) total 25-hydroxyvitamin D, 3% (-3% to 8%), 49% (30-82%), and 69% (55-106%) (p < 0.001);
• 2) bioavailable 25-hydroxyvitamin D, 4% (-8% to 7%), 45% (40-70%), and 96% (58-136%) (p < 0.01); and
• 3) LL-37: -17% (-9% to -23%), 4% (-10% to 14%), and 30% (23-48%) (p = 0.04).
  Change in high-sensitivity C-reactive protein levels did not differ between groups.

A positive correlation was observed between bioavailable 25-hydroxyvitamin D and LL-37 (Spearman rho = 0.44; p = 0.03) but not for total 25-hydroxyvitamin D and LL-37.

Conclusions: High-dose cholecalciferol supplementation rapidly and safely improves 25-hydroxyvitamin D and bioavailable 25-hydroxyvitamin D levels in patients with severe sepsis or septic shock. Changes in bioavailable 25-hydroxyvitamin D are associated with concomitant increases in circulating LL-37 levels. Larger trials are needed to verify these findings and to assess whether optimizing vitamin D status improves sepsis-related clinical outcomes.

 Download the PDF from VitaminDWiki

Notes by VitaminDWiki

1. Dr. Quraishi has another another Clinical Trial using 400,000 IU followed by 25,000 IU weekly - due 2022
2. Dr. Quraishi has co-authored a chapter Vitamin D, Hospital-Acquired Infections and Mortality in Critically Ill Patients: Emerging Evidence
   The publisher wants $31 for the chapter, https://doi.org/10.1007/978-3-319-51908-1_15. References, however, are free.
    Download the PDF from Sci-Hub via VitaminDWiki
3. LL-37 is an antimicrobial peptide - click to see the full image
   
4. 400,000 IU increases vitamin D levels by >40 ng in healthy individuals in a few days
   But Vitamin D levels increased only about 15 ng for those with sepsis.
   
   Suspect those with Sepsis need more than 400,000 IU
5. Injection should also be considered - as it totally skips over any digestion problems which might be associated with Sepsis
6. See also: Overview Loading of vitamin D, which is widely used to improve ICU outcomes

201 citations of this study (as of July 2024)

Google Scholar

• Update on vitamin D role in severe infections and sepsis - Jan 2024 FREEPDF
• Vitamin D Deficiency: An Underestimated Factor in Sepsis? Feb 2023 https://doi.org/10.3390/ijms24032924 FREE PDF
• Vitamin D Supplementation in Critically Ill Patients: A Meta-Analysis of Randomized Controlled Trials - April 2022 PDF
• Vitamin D and acute and severe illness – a mechanistic and pharmacokinetic perspective Aug 2021 PDF
• Importance of vitamin D in critically ill children with subgroup analyses of sepsis and respiratory tract infections: a systematic review and meta-analysis - Dec 2019 FREE PDF
• 18 fewer hospital days if given 500,000 IU of vitamin D while ventilated in ICU – RCT June 2016 in VitaminDWiki
• Vitamin D loading doses reduce ICU mortality by 30 percent – meta-analysis April 2017 in VitaminDWiki

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12 X more likely to recover from Septic Shock in 24 hours if you have a higher level of vitamin D (> 10 ng?) - 2017

Effect of Severe Vitamin D Deficiency at Admission on Shock Reversal in Children With Septic Shock.
J Intensive Care Med. 2017 Jan 1:885066617699802. Doi 10.1177/0885066617699802

OBJECTIVES:
To evaluate the association of severe vitamin D deficiency with clinically important outcomes in children with septic shock.
METHODS:
We enrolled children ≤17 years with septic shock prospectively over a period of 6 months. We estimated 25-hydroxyvitamin D [25 (OH) D] levels at admission and 72 hours. Severe deficiency was defined as serum 25 (OH) <10 ng/mL. We performed univariate and multivariate analyses to evaluate the association with clinically important outcomes.
RESULTS:
Forty-three children were enrolled in the study. The prevalence of severe vitamin D deficiency was 72% and 69% at admission and 72 hours, respectively. On univariate analysis, severe vitamin D deficiency at admission was associated with lower rates of shock reversal, 74% (23) versus 25% (3); relative risk (95% confidence interval CI): 2.9 (1.09-8.08), at 24 hours and greater need for fluid boluses (75 vs 59 mL/kg).
On multivariate analysis, nonresolution of shock at 24 hours was significantly associated with severe vitamin D deficiency after adjusting for other key baseline and clinical variables, adjusted odds ratio (95% CI): 12 (2.01-87.01); 0.01.
CONCLUSION:
The prevalence of severe vitamin D deficiency is high in children with septic shock admitted to the pediatric intensive care unit. Severe vitamin D deficiency at admission seems to be associated with lower rates of shock reversal at 24 hours of ICU stay. Our study provides preliminary data for planning interventional studies in children with septic shock and severe vitamin D deficiency.
 Download the PDF from Sci-Hub via VitaminDWiki

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Sepsis injection of 300,000 IU of vitamin D helped in a small RCT - Feb 2017

Reduced length of stay and deaths - not statistically significant, too small of a trial, should have used oral instead of slow injection
Effect of vitamin D3 on the severity and prognosis of patients with sepsis: a prospective randomized double-blind placebo study
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2017 Feb;29(2):106-110. doi 10.3760/cma.j.issn.2095-4352.2017.02.003.
[Article in Chinese]
Ding F1, Zang B, Fu J, Ji K.

OBJECTIVE:
To observe the relationship between vitamin D3 and the severity as well as prognosis in patients with sepsis and to explore whether exogenous vitamin D3 can improve the prognosis in patients with sepsis.

METHODS:
A prospective randomized double-blind placebo study was conducted. Fifty-seven patients with sepsis admitted to the intensive care unit (ICU) of Shengjing Hospital, Affiliated with China Medical University, from March to November 2015 were enrolled. Twenty patients with systemic inflammatory response syndrome (SIRS) and 20 healthy volunteers with a normal physical examination as control were enrolled during the same time. Patients with sepsis were divided into a general sepsis group and a severe sepsis group (including septic shock) according to the criteria for the diagnosis of severe sepsis and septic shock in 2012. According to the diagnostic criteria established by the American Endocrine Society, and on the basis of 25-hydroxy vitamin D3 [25(OH)D3], sepsis patients with deficiency [25(OH)D3 20-30 μg/L] or insufficiency [25(OH)D3 < 20 μg/L] of vitamin D were divided into D3 treatment group (supplemented 300 kU vitamin D3) and placebo group (injected 1 mL physiological saline). 28th day was set as the endpoint, and the patients with sepsis were divided into a survival group and a death group. The levels of serum 25(OH)D3 in each group were measured by the electrochemical luminescence method, and the difference in 25(OH)D3 levels among patients with different severity, gender, and age were recorded. Procalcitonin (PCT), C-reactive protein (CRP), blood routine, liver and kidney function, electrolytes and arterial blood gas analysis, acute physiology, and chronic health evaluation II (APACHE II) and sequential organ failure score (SOFA), duration of mechanical ventilation, and length of ICU stay of patients with sepsis were observed. Multivariate Cox proportional hazard regression analysis was used to analyze the risk factors of prognosis in patients with sepsis.

RESULTS:
(1) In 57 patients with sepsis, there were 15 patients in the general sepsis group, 42 in the severe sepsis group, 29 in D3 treatment group, and 28 in the placebo group; 8 patients died within 28 days with a mortality rate of 14.04%. (2) The levels of serum 25(OH)D3 in sepsis group and SIRS group were significantly lower than those in healthy control group [μg/L: 3.92 (< 3.00, 11.22), 6.99 (3.51, 9.77) vs. 17.25 (13.48, 22.50), both P < 0.01], but there was no significant difference in the serum 25(OH)D3 level between sepsis group and SIRS group as well as patients with different degrees of sepsis. The serum 25(OH)D3 level in female patients with sepsis (n = 24) was significantly lower than that in males (n = 33), and the difference was statistically significant [μg/L: <3.00 (<3.00, 3.87) vs. 11.96 (5.14, 17.29), Z = -4.020, P = 0.000]. There was no significant difference in serum 25(OH)D3 level between the young (age <60 years old, n = 30) and the old (age ≥ 60 years old, n = 27) patients with sepsis [μg/L: 4.54 (<3.00, 9.88) vs. 3.00 (<3.00, 15.08), Z = -0.601, P = 0.548]. (3) In patients with sepsis, there was no significant difference in the duration of mechanical ventilation [hours: 41.00 (7.50, 82.50) vs. 67.00 (4.75, 127.75)], length of ICU stay (days: 5.48±4.08 vs. 6.68±4.87) and 28-day mortality (10.34% vs. 17.86%) between D3 treatment group and placebo group (all P > 0.05). It was shown by Kaplan-Meier survival curve analysis that there was no significance in the 28-day accumulated survived rate between the two groups' [log-rank test: χ 2 = 0.222, P = 0.638]. It was shown by multivariate Cox regression analysis that APACHE II score [relative risk (RR) = 8.487,</strong> 95% confidence interval (95%CI) = 1.506-47.835, P = 0.015|relative risk (RR) = 8.487,][relative risk (RR) = 8.487,</strong> 95% confidence interval (95%CI) = 1.506-47.835, P = 0.015| 95% confidence interval (95%CI) = 1.506-47.835, P = 0.015] and 25(OH)D3 < 20 μg/L (RR = 0.088, 95%CI = 0.013-0.592, P = 0.012) were the risk factors of prognosis in patients with sepsis.

CONCLUSIONS:
The serum 25(OH)D3 level in ICU patients with sepsis was lower than that in healthy people, but there was no significant difference between patients with sepsis and SIRS. The serum 25(OH)D3 level in sepsis patients was related to gender, and the level of the female was lower than that of the male but was not related to age. Exogenous vitamin D3 supplementation cannot improve the prognosis of ICU patients with sepsis. APACHE II score and 25(OH)D3 < 20 μg/L were risk factors for the prognosis in ICU patients with sepsis.

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Two Meta-analyses of ICU and Vitamin D - April and May 2017

• Vitamin D loading doses reduce ICU mortality by 30 percent – meta-analysis April 2017
  The two studies, which shared an analysis of 5 Randomized Controlled Trials, came up with different conclusions
  some ICU mortality problems were due to sepsis

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High dose + maint. dose Vitamin D reduce mortality – large RCT 2014

Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial.
JAMA. 2014 Oct 15;312(15):1520-30. doi: 10.1001/jama.2014.13204.
Amrein K1, Schnedl C1, Holl A2, Riedl R3, Christopher KB4, Pachler C5, Urbanic Purkart T6, Waltensdorfer A5, Münch A5, Warnkross H1, Stojakovic T7, Bisping E8, Toller W5, Smolle KH9, Berghold A3, Pieber TR1, Dobnig H10.

IMPORTANCE:
Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal.
OBJECTIVE:
To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs.
DESIGN, SETTING, AND PARTICIPANTS:
A randomized double-blind, placebo-controlled, single-center trial conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3 (n = 249) or a placebo (n = 243).
INTERVENTIONS:
Vitamin D3 or placebo was given orally or via nasogastric tube once at a dose of 540,000 IU, followed by monthly maintenance doses of 90,000 IU for 5 months.
MAIN OUTCOMES AND MEASURES:
The primary outcome was the hospital length of stay. Secondary outcomes included, among others, length of ICU stay, the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7, hospital mortality, and 6-month mortality. A predefined severe vitamin D deficiency (≤12 ng/mL) subgroup analysis was specified before data unblinding and analysis.
RESULTS:
A total of 475 patients were included in the final analysis (237 in the vitamin D3 group and 238 in the placebo group). The median (IQR) length of hospital stay was not significantly different between groups (20.1 days IQR, 11.1-33.3 for vitamin D3 vs. 19.3 days IQR, 11.1-34.9 for placebo; P = .98). Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28.3% 95% CI, 22.6%-34.5% for vitamin D3 vs. 35.3% 95% CI, 29.2%-41.7% for placebo; hazard ratio HR, 0.81 95% CI, 0.58-1.11; P = .18; 6-month mortality: 35.0% 95% CI, 29.0%-41.5% for vitamin D3 vs. 42.9% 95% CI, 36.5%-49.4% for placebo; HR, 0.78 95% CI, 0.58-1.04; P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D3 vs 19.0 days (IQR, 11.6-33.8) for placebo.
Hospital mortality was significantly lower, with 28 deaths among 98 patients (28.6% 95% CI, 19.9%-38.6%) for vitamin D3 compared with 47 deaths among 102 patients (46.1% 95% CI, 36.2%-56.2%) for placebo (HR, 0.56 95% CI, 0.35-0.90, P for interaction = .04), but not 6-month mortality (34.7% 95% CI, 25.4%-45.0% for vitamin D3 vs. 50.0% 95% CI, 39.9%-60.1% for placebo; HR, 0.60 95% CI, 0.39-0.93, P for interaction = .12).
CONCLUSIONS AND RELEVANCE:
Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis-generating and requires further study.
 Download the PDF from VitaminDWiki

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The only people who died of sepsis in the hospital were vitamin D deficient – April 2017

Correlation of serum vitamin D level with mortality in patients with sepsis
Indian Journal of Critical Care Magazine 2017 Vol 21, # 4, page: 199- 204 DOI: 10.4103/ijccm.IJCCM_192_16
Prakash Vipul1, Consul Shuchi2, Agarwal Avinash1, Gutch Manish1, Kumar Sukriti1, Prakash Ved1
1 Department of Medicine, King George's Medical College, Lucknow, Uttar Pradesh, India
2 Department of OBG, King George's Medical College, Lucknow, Uttar Pradesh, India

Hospital Stay (Table 8)

	Deficiency	Insufficiency	Normal
<7 days	48 %	18 %	34 %
7-14 days	87 %	7 %	7 %
>14 days	73 %	6 %	21 %
Died	100 %	0 %	0%

Note by VitaminDWiki: The study does not seem to define the levels for Deficiency, etc.

Background: Sepsis is the leading cause of mortality in the critically ill. Recently, it has been found in many studies that many trace elements and nutrients do have an effect on the human body and, if supplemented, can improve the prognosis in patients with sepsis.

Aim and Objectives: Primary objective: Whether low Vitamin D is associated with mortality. Secondary objective: To find out the association between low Vitamin D levels and morbidity in terms of length of hospital and Intensive Care Unit (ICU) stay.

Subjects and Methods: Following ethical approval, consent will be sought from either the patient or assent from a near relative. Successive patients admitted to the medical emergency and ICU at tertiary care health center who fulfill the following criteria for sepsis within a 24 h time window were included in the study.

Results: Among 88 patients evaluated in our study, 15 patients (18.2%) were found to have adequate Vitamin D levels and seven patients (8%) were found insufficient, and the rest 52 patients (73.9%), were found deficient in Vitamin D. Age of the patients ranged between 18 and 82 years with mean (±standard deviation) 45.02 ± 17.69 years. Mean Vitamin D level was found to be significantly higher among patients with positive outcomes than those with unfavorable outcomes (expiry) (t = 2.075, P = 0.04). On comparison of the length of hospital stay (morbidity) with Vitamin D levels, we found a statistically significant inverse relation between Vitamin D levels and length of hospital stay.

Conclusion: Vitamin D deficiency leads to increased risk of mortality in the critically ill along with prolonged hospital stay.
 Download the PDF from VitaminDWiki

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Sepsis death in women 1.8X more likely if very low vitamin D Nov 2018

• ;Prospective Association of Serum Vitamin D Level with Sepsis-Mortality in Postmenopausal Women: Results From the Women’s Health Initiative free PDF

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Review of vitamin monotherapy for Sepsis: Vitamin C or Vitamin D - July 2021

Vitamin therapy in sepsis
 Download the PDF from VitaminDWiki

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Meta-analysis concludes: Sepsis 1.8 X more likely if low vitamin D - June 2015

A significant association between vitamin D deficiency and sepsis: a systematic review and meta-analysis.
BMC Anesthesiol. 2015 Jun 4;15(1):84. doi 10.1186/s12871-015-0063-3.
Upala S1,2, Sanguankeo A3,4, Permpalung N5.

BACKGROUND: A number of observational studies have found an association between low vitamin D levels and the risk of sepsis. We conducted a systematic review and meta-analysis to determine the overall estimate of risk.

METHODS: This was a systematic review and meta-analysis conducted by online searches (CENTRAL, PubMed/MEDLINE, and EMBASE) registered in PROSPERO (CRD42014014767). The primary outcome was the incidence, prevalence, relative risk, or odds ratio of having sepsis or bloodstream infection between patients with vitamin D deficiency and controls.

RESULTS: The initial search yielded 647 articles. Twenty-one articles underwent full-length review, and data were extracted from 10 observational studies. The pooled odds ratio of sepsis in participants with vitamin D deficiency was 1.78 (95 % confidence interval CI = 1.55 to 2.03, p < 0.01) compared with controls in studies that reported participant numbers and was 1.45 (95 % CI = 1.26 to 1.66, p < 0.01) in studies that reported an adjusted odds ratio of vitamin D deficiency for developing sepsis. Statistical between-study heterogeneity was low (I(2) = 0 % and 5 %, respectively). The standardized mean difference of 25-hydroxyvitamin D levels in patients with sepsis and controls was -0.24 (95 % CI = -0.49 to 0.00, p = 0.05) and lower in the sepsis group compared with non-sepsis or control participants. The statistical between-study heterogeneity (I(2)) was 0 %.

CONCLUSION: Vitamin D deficiency was associated with an increased susceptibility to sepsis.

 Download the PDF from VitaminDWiki

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Vitamin D - a new hope for septic shock - July 2013

Is vitamin D supplementation a new hope for the therapy of septic shock?
Endocr Regul. 2013 Jul;47(3):133-6.
Yılmaz H, Sahiner E, Darcin T, Celik HT, Bilgic MA, Akcay A.

Vitamin D is mainly known for its traditional role in bone mineralization and calcium homeostasis. Recent studies have shown that vitamin D receptors (VDR) are present in almost all the tissues and cells in the human body. In addition, several studies have revealed that vitamin D is important in immunomodulation, regulation of inflammation and cytokines, cell proliferation, cell differentiation, apoptosis, angiogenesis, muscle strength, and muscle contraction. Patients with sepsis have a high mortality rate and high deficiency in vitamin D. In addition, septic patients have decreased vitamin D binding-protein (DBP) levels which further exacerbate the vitamin D deficiency. The role of vitamin D treatment in sepsis syndrome has been evaluated in an animal model of sepsis where 1,25-dihydroxy vitamin D3 1,25(OH)2D3 administration was associated with improved blood coagulation parameters in sepsis associated with disseminated intravascular coagulation.

Vitamin D treatment in vitro has also been demonstrated to modulate levels of the systemic inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6), as well as inhibit the lipopolysaccharide (LPS)-induced activation and vasodilation of vascular endothelium.

Vitamin D may enhance the induction of the antimicrobial peptides, cathelicidin, and b-defensin, which have been described on mucosal and epithelial surfaces as acting as the body's first line of defense against viral and bacterial pathogens.

Vitamin D supplementation may divert attention from relatively simple, natural, and low-cost methods of preventing severe sepsis and septic shock.

Further prospective, randomized, and controlled clinical trials of adjunctive vitamin D therapy in patients who are vitamin D deficient are needed in the management of human sepsis syndrome.

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Sepsis and Vitamin D in children

VitaminDWiki

• Sepsis in infants 4.8 X more likely if poor vitamin D receptor – March 2018
• Sepsis in first year of life is much more likely if preterm (low Vitamin D) – May 2017
• Treatment of neonate sepsis greatly aided by Vitamin D – RCT June 2019
• 3X less Septic Shock in children with sepsis getting 150,000 IU of Vitamin D - RCT June 2020
• Septic children have low Vitamin D (54 studies, ignored Vitamin D Receptor) – meta-analysis April 2019
• Infant sepsis strongly associated with low vitamin D – Aug 2014

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Role of Vitamin D and Parathyroid Hormone Levels In Prediction of Late Onset Sepsis among Preterm Infants - June 2024

10.21608/ANJ.2024.276513.1087 PDF behind paywall
"Conclusion: Preterm neonates with low vitamin D levels are more likely to develop sepsis with more disease severity, higher mortality, and higher duration of hospital admission also, a percentage of critically ill neonates have vitamin D deficiency"

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Neonatal Sepsis 4.7 X more likely if mother was Vitamin D insufficient - Feb 2020

Is Lower Vitamin D Level Associated With Increased Risk of Neonatal Sepsis? A Prospective Cohort Study
Indian J Pediatr, 2020 Feb 13, DOI: 10.1007/s12098-020-03188-0
Chinmay Kumar Behera 1, Jagdish Prasad Sahoo 2, Saumya Darshana Patra 3, Pratap Kumar Jena 4

Objective: To evaluate the effect of maternal/ neonatal vitamin D levels on culture-positive neonatal sepsis.

Methods: This prospective cohort study was conducted in the NICU of a tertiary care teaching hospital in Odisha, Eastern India, from January 2015 through December 2016. Forty (40) neonates with culture-positive sepsis were included in the study group. Forty (40) healthy neonates admitted for evaluation of neonatal jaundice who are similar in gender, gestational age, postnatal age, and without any clinical signs of sepsis were recruited as the control group after informed consent. Vitamin D level (25 OH D) was assessed in the neonates and their mothers in both groups.

Results: Neonatal 25 OH vitamin D level in the study group (12.71 ± 2.82 ng/ml) was significantly lower than in the control group (25.46 ± 7.02 ng/ml). The Odds ratio was 273 (95% CI 30.39-2451.6) for culture-positive sepsis in neonates with vitamin D deficiency/insufficiency. Mothers of septic neonates had significantly lower 25 OH vitamin D levels (20.92 ± 3.92 ng/ml) than the mothers of healthy neonates in the control group (27.31 ± 6.83 ng/ml). The Odds ratio was 4.71 (95% CI 1.69-13.1) for culture-positive sepsis in babies born to mothers with vitamin D deficiency/insufficiency.

Conclusions: Neonates with vitamin D deficiency/insufficiency are at higher risk for developing sepsis than those with sufficient vitamin D levels. Lower vitamin D levels in mothers are also associated with an increased risk of sepsis in neonates.

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Most Sepsis children also have a chronic disease (both low vitamin D) – Aug 2018

Children with Chronic Disease Bear the Highest Burden of Pediatric Sepsis
The Journal of Pediatrics, Volume 199, August 2018, Pages 194-199.e1, https://doi.org/10.1016/j.jpeds.2018.03.056
Andrew J.ProutMD, MPH12 Victor B.TalisaBS13 Joseph A.CarcilloMD2 Florian B.MayrMD, MPH124 Derek C.Angus MD12 Christopher W.SeymourMD12 Chung-Chou H.ChangPhD56SachinYendeMD, MS124

Objective
To describe the contemporary epidemiology of pediatric sepsis in children with chronic disease and the contribution of chronic diseases to mortality. We examined the incidence and hospital mortality of pediatric sepsis in a nationally representative sample and described the contribution of chronic diseases to hospital mortality.

Study design
We analyzed the 2013 Nationwide Readmissions Database using a retrospective cohort design. We included non-neonatal patients <19 years of age hospitalized with sepsis. We examined patient characteristics, the distribution of chronic disease, and the estimated national incidence and described hospital mortality. We used mixed-effects logistic regression to explore the association between chronic diseases and hospital mortality.

Results
A total of 16 387 admissions, representing 14 243 unique patients, were for sepsis. The national incidence was 0.72 cases per 1000 per year (54 060 cases annually). Most (68.6%) had a chronic disease. The in-hospital mortality was 3.7% overall—0.7% for previously healthy patients and 5.1% for patients with chronic disease. In multivariable analysis,

• oncologic,
• hematologic,
• metabolic,
• neurologic,
• cardiac and
• renal disease, and
• solid organ transplantation

were associated with increased in-hospital mortality.

Conclusions
More than 2 of 3 children admitted with sepsis have ≥1 chronic disease, and these patients have a higher in-hospital mortality than previously healthy patients. The burden of sepsis in hospitalized children is greatest in pediatric patients with chronic disease.

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Sepsis in infants 8X higher if less than 30 ng of vitamin D (India) – June 2021

Vitamin D Levels and Early Onset Sepsis in Newborns
Balveer Jeengar, Sunil Gothwal, Kailash Kumar Meena, ...
https://doi.org/10.1177/09732179211019905

Aim: To find out the association between vitamin D level and early onset neonatal sepsis (EONS).

Methods: This case-control study was conducted at a tertiary care center in Northern India from June 2018 to May 2019. Neonates with culture-proven EONS were included as cases and neonates without EONS were enrolled as control. 25OH-D levels were evaluated with other routine blood samples. Statistical analysis was done by using an unpaired t-test and chi-square test.

Results: Sixty-two infants were enrolled in each group; baseline characteristics were comparable in both groups. The risk of EONS increased 8 times in neonates with 25OH-D level <30 ng/mL (odds ratio = 8.2; 95% confidence interval CI: 3.08-21.82; P = .000). The 25OH-D level was significantly lower in the EONS group than the control group. The optimal cut-off for 25OH-D was 25 ng/mL to predict EONS with a sensitivity and specificity of 88.7% and 79%, respectively (area under the curve: 0.84; 95% CI: 0.76-0.92; P = .000).

Conclusions: Vitamin D insufficiency is significantly associated with EONS. Vitamin D deficiency significantly increases the risk of EONS. Maternal vitamin D supplementation may improve neonatal vitamin D levels and may decrease the risk of EONS. Further studies, including maternal vitamin D levels, are required for implementation.

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A small amount of vitamin D helped children with Sepsis - May 2020 RCT

150,000 IU only raised vitamin D levels to 22ng,
but even this small increase reduced shock, ventilation, and days in PICU
 Download the PDF from VitaminDWiki

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Sepsis 72 or more hours after birth: 1.7 X higher risk if low Vitamin D - Nov 2018

Association of vitamin D deficiency with an increased risk of late-onset neonatal sepsis.
Paediatr Int Child Health. 2018 Aug;38(3):193-197. doi 10.1080/20469047.2018.1477388. Epub 2018 Jul 13.
Dhandai R1, Jajoo M1, Singh A1, Mandal A2, Jain R1.

BACKGROUND: Vitamin D deficiency in mothers and neonates is being recognized increasingly as a leading cause of many adverse health effects in the newborn infant, including sepsis.

METHODS:
A prospective observational study was conducted at a tertiary care Paediatric teaching hospital in northern India to assess vitamin D deficiency as a possible risk factor for late-onset sepsis (LOS) in term and late preterm neonates and also to examine the correlation between maternal and infant vitamin D levels during the neonatal period. Late-onset sepsis (LOS) was defined as the development of signs and symptoms of severe sepsis after 72 h of life and a positive sepsis screen. All term and late preterm neonates admitted with LOS between September 2015 and February 2016 who had not been previously admitted for >48 h and had not been prescribed antibiotics or vitamin D were included in the study. Matched controls were recruited from otherwise healthy neonates admitted with physiological hyperbilirubinemia. Serum 25(OH) vitamin D was assessed in neonates in both groups and their mothers.

RESULTS:
A total of 421 neonates were admitted to the neonatal intensive care unit during the study period, 120 of whom satisfied the inclusion criteria, and 60 were recruited as cases. Sixty neonates were recruited as controls who were similar in gender, gestational age, age at admission, and anthropometry. The study group had significantly lower mean (SD) vitamin D levels, 15.37 ng/ml (10.0), than the control group, 21.37 ng/ml (9.53) (p = 0.001). The odds ratio was 1.7 (95% CI 0.52-5.51) for LOS in vitamin D-deficient neonates. Mothers of septic neonates also had significantly lower mean (SD) vitamin D levels, 17.87 (11.89), than the mothers of non-septic neonates, 23.65 ng/ml (9.55) (p = 0.004). Maternal vitamin D levels strongly correlated to neonatal vitamin D levels in both groups.

CONCLUSION: Neonates with vitamin D deficiency are at greater risk of LOS than those with sufficient vitamin D levels

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Infants with sepsis have very low Vitamin D levels – Aug 2014

Lower vitamin D levels are associated with an increased risk of early-onset neonatal sepsis in term infants
Journal of Perinatology (2015) 35, 39-45;doi:10.1038/jp.2014.146; published online 7 August 2014
M Cetinkaya1, F Cekmez2, G Buyukkale1, T Erener-Ercan1, F Demir1, T Tunc2, FN Aydin3 and G Aydemir2
OBJECTIVE: To evaluate the effect of vitamin D levels on early-onset sepsis (EOS) in term infants.

STUDY DESIGN: Fifty term infants with clinical and laboratory findings of EOS (study group) and 50 healthy infants with no signs of clinical/laboratory infection (control group) were enrolled. Blood was drawn at the time of admission during the first 3 postnatal days of life in both groups for measurement of 25-hydroxyvitamin D (25-OHD) levels.

RESULT: Maternal and neonatal 25-OHD levels (22.2/8.6 ng ml-1, respectively) in the study group were significantly lower than those of the control group (36.2/19 ng ml-1, respectively, P < 0.001). A positive correlation was detected between maternal and neonatal 25-OHD levels. Severe vitamin D deficiency was significantly more common in the sepsis group.

CONCLUSION: Lower maternal and neonatal 25-OHD levels are associated with EOS. These data suggest that adequate vitamin D supplementation during pregnancy may be helpful in preventing EOS in term neonates.

 Download the PDF from VitaminDWiki

Clipped from PDF

• “ The incidence of neonatal sepsis varies between 1 and 8 neonates per 1000 live births.
• Sepsis accounts for more than 25% of neonatal deaths worldwide

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Neonatal Sepsis 4.8 X more likely if poor Vitamin D receptor – June 2018

• Neonatal Sepsis 4.8 X more likely if poor Vitamin D receptor – June 2018

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Neonates are 1.7 X more likely to get Sepsis if they low vitamin D, mothers had low levels as well - July 2018

Association of vitamin D deficiency with an increased risk of late-onset neonatal sepsis.
doi: 10.1080/20469047.2018.147738

Background Vitamin D deficiency in mothers and neonates is being recognized increasingly as a leading cause of many adverse health effects in the newborn infant, including sepsis.

Methods A prospective observational study was conducted at a tertiary care Paediatric teaching hospital in northern India to assess vitamin D deficiency as a possible risk factor for late-onset sepsis (LOS) in term and late preterm neonates and also to examine the correlation between maternal and infant vitamin D levels during the neonatal period. Late-onset sepsis (LOS) was defined as the development of signs and symptoms of severe sepsis after 72 h of life and a positive sepsis screen. All term and late preterm neonates admitted with LOS between September 2015 and February 2016 who had not been previously admitted for >48 h and had not been prescribed antibiotics or vitamin D were included in the study. Matched controls were recruited from otherwise healthy neonates admitted with physiological hyperbilirubinemia. Serum 25(OH) vitamin D was assessed in neonates in both groups and their mothers.

Results A total of 421 neonates were admitted to the neonatal intensive care unit during the study period, 120 of whom satisfied the inclusion criteria, and 60 were recruited as cases. Sixty neonates were recruited as controls who were similar in gender, gestational age, age at admission, and anthropometry. The study group had significantly lower mean (SD) vitamin D levels, 15.37 ng/ml (10.0), than the control group, 21.37 ng/ml (9.53) (p = 0.001). The odds ratio was 1.7 (95% CI 0.52-5.51) for LOS in vitamin D-deficient neonates. Mothers of septic neonates also had significantly lower mean (SD) vitamin D levels, 17.87 (11.89), than the mothers of non-septic neonates, 23.65 ng/ml (9.55) (p = 0.004). Maternal vitamin D levels strongly correlated to neonatal vitamin D levels in both groups.

Conclusion Neonates with vitamin D deficiency are at greater risk of LOS than those with sufficient vitamin D levels.

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Sepsis in general

A Silent Killer Slate April 2016

• There is no easy way to diagnose sepsis. The good news is you probably don’t have it, but here’s how to ask your doctor if you’re worried.
• Between 16% and 49 % who get Sepsis will die.
• Until recently, the CDC failed to even mention sepsis in its A–Z index of medical terms
• Sepsis costs the U.S. more than $20 billion per year
•  Download "Surviving Sepsis 2012" PDF from VitaminDWiki
  referenced by Wikipedia
• Morality increase 7.6% for EVERY HOUR of Sepsis June 2006
• Septic Shock - Medical dictionary has the following chart

• Developing a New Definition and Assessing New Clinical Criteria for Septic Shock Feb 2017
  For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)
  The word VITAMIN does not occur once in the following PDF
   Download the PDF from VitaminDWiki

The first World Sepsis congress was held Sept 2016

Sepsis is an orphan disease - it affects so many parts of the body that no single medical profession focuses on it
Medicine.Net has a great Sepsis description
Source: http://www.medicinenet.com/script/main/art.asp?articlekey=97492
Medical Authors: Charles Patrick Davis, MD, Ph.D., Medical Editor: Melissa Conrad Stöppler, MD

Sepsis (blood poisoning) facts
Sepsis is a potentially life-threatening medical condition that's associated with an infection; the infection's signs and symptoms must fulfill a minimum of two criteria of a systemic inflammatory response syndrome (SIRS).
Blood poisoning is a nonmedical term that usually refers to a medical condition known as sepsis.
The major SIRS criteria are an increased heart rate, fever, and increased respiratory rate; the young and the elderly may show other early signs and symptoms of sepsis sometimes before exhibiting SIRS criteria.
The majority of cases of sepsis are due to bacterial infection.
Sepsis is treated with hospitalization, intravenous antibiotics, and therapy to support any organ dysfunction.
Prevention of infections and early diagnosis and treatment of sepsis are the best ways to prevent sepsis or reduce the problems sepsis causes.
The prognosis depends on the severity of sepsis as well as the underlying health status of the patient; in general, the elderly have the worst prognosis.

What is sepsis?
Sepsis is a potentially dangerous or life-threatening medical condition found in association with a known or suspected infection (usually caused by but not limited to bacteria) whose signs and symptoms fulfill at least two of the following criteria of a systemic inflammatory response syndrome (SIRS):

• elevated heart rate (tachycardia) >90 beats per minute at rest
• body temperature either high (>100.4 F or 38 C) or low (<96.8 F or 36 C)
• increased respiratory rate of >20 breaths per minute or a reduced PaCO2 (partial pressure of carbon dioxide in arterial blood level)
• abnormal white blood cell count (>12,000 cells/µL or <4,000 cells/µL or >10% bands an immature type of white blood cell)

Patients who meet the above criteria have sepsis and are also termed septic. These criteria described above were proposed by several medical societies and may continue to be modified by other medical groups. For example, pediatric groups use the same four criteria listed above but modify the values for each to make the SIRS criteria for children. Other groups want to add criteria, but currently, this is the most widely accepted definition.

What causes sepsis?
The majority of cases of sepsis are due to bacterial infections, some are due to fungal infections, and very few are due to other causes of infection or agents that may cause SIRS. The infectious agents, usually bacteria, begin infecting almost any organ location or implanted device (for example, skin, lung, gastrointestinal tract, surgical site, intravenous catheter, etc.). The infecting agents or their toxins (or both) then spread directly or indirectly into the bloodstream. This allows them to spread to almost any other organ system. SIRS criteria result as the body tries to counteract the damage done by these blood-borne agents.

Common bacterial causes of sepsis are gram-negative bacilli (for example, E. coli, P. aeruginosa, E. corrodes, and Haemophilus influenza in neonates). Other bacteria also causing sepsis are S. aureus, Streptococcus species, Enterococcus species, and Neisseria; however, there are large numbers of bacterial genera that have been known to cause sepsis. Candida species are some of the most frequent fungi that cause sepsis. In general, a person with sepsis can be contagious, so precautions such as hand washing, sterile gloves, masks, and clothing coverage should be considered depending on the patient's infection source.
What are the risk factors for sepsis?

• The very young and the elderly are at greatest risk
• People in an intensive-care unit
• People with weakened or compromised immune systems
• People with devices such as IV catheters, breathing tubes, or other devices
• People with extensive burns
• People with severe trauma

What is the treatment for sepsis?
In almost every case of sepsis, patients need to be hospitalized, treated with appropriate intravenous antibiotics, and given therapy to support any organ dysfunction. Sepsis can quickly cause organ damage and death; therapy should not be delayed as statistics suggest as high as a 7% mortality increase per hour if antibiotics are delayed in severe sepsis. Most cases of sepsis are treated in an intensive-care unit (ICU) of the hospital.

Physicians agree that the faster the patient with sepsis is diagnosed and treated, the better the prognosis and fewer complications, if any, for the patient.
Sepsis mortality decreased by 15 percent if conventionally treated within 3 hours - May 2017
Time to Treatment and Mortality during Mandated Emergency Care for Sepsis - NEJM

 Download the PDF from VitaminDWiki

Sepsis is an equal opportunity Killer

it contains 45 additional Sepsis charts

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Is Sepsis Responsible for 20% of Deaths Worldwide?: Asked Chat-GPT Jan 2, 2024

ChatGPT: I did a quick search and here's what I discovered.

Yes, sepsis is responsible for a significant portion of deaths worldwide. According to the World Health Organization (WHO), it was estimated that in 2017 there were 48.9 million cases and 11 million sepsis-related deaths worldwide, which accounted for almost 20% of all global deaths. This means that sepsis causes 1 in 5 deaths globally WHO   WHO   CidRap The burden of sepsis varies by country, with mortality rates ranging from 15% to more than 50%. Notably, approximately 85% of all sepsis-related deaths occur in low- and middle-income countries (LMICs) Lancet.

A study involving collaborators from the University of Pittsburgh and University of Washington further supports these findings, estimating that sepsis was at least partially responsible for roughly 11 million global deaths in 2017 out of a total of 56 million deaths, which aligns with the assessment that sepsis accounts for about 20% of worldwide deaths ACDIS

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Sepsis overlaps with Systemic Inflammatory Response Syndrome

Medscape Aug 2016

Sepsis is the 3rd leading cause of UK hospital deaths

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Sepsis incidence and mortality are higher than many other health problems

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Severe sepsis increased 3.5X in a decade.

Should we track sepsis trends using administrative data? March 2016

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Subtile Signs of Sepsis - Pintrest -2018

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Sepsis Myths and Facts

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I nearly died from sepsis – and ignorance of this condition is killing millions. July 2018

• The author was in a Sepsis coma for 3 months.
• "Sepsis affects more than 30m people a year worldwide and kills an estimated 6m people, of whom nearly 2m are children."
• "Of those who do survive, 40% will have post-sepsis syndrome, which leaves them with lasting physical and mental symptoms."
• "Surveys suggest that only 40% of people in Australia have heard of sepsis, and only one-third of this group are able to identify a single symptom. Figures are even lower in Brazil, where only 14% of the public know what it is"

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Sepsis treatment other than Vitamin D

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FLCCC: Sepsis at home: Melatonin, Vit. C, Zinc, Quercetin, Curcumin, Pre & Probiotics: - Sept 2023

SEPSIS CARE - A GUIDE TO INPATIENT AND OUTPATIENT TREATMENT

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Vitamin C perhaps reduces Sepsis

• Sepsis death was prevented in 85% by intravenous vitamin C, vitamin B1, and hydrocortisone LEF Sept 2018
  •  Download the PDF from VitaminDWiki
  • 3 clinical trials are underway to confirm
• Vitamin C Lowers Mortality in Severe Sepsis Mercola Oct 2019
  • "Sepsis Is the Costliest Condition Treated in the US"
  • "In 2017, news emerged about a critical care physician who claimed to have discovered a simple and inexpensive way to treat sepsis using an intravenous (IV) cocktail of vitamin C and thiamine (vitamin B1) in combination with the steroid hydrocortisone"
  • "giving septic patients this simple IV cocktail for two days reduced mortality from 40% percent to 8.5%"
• Sepsis mortality reduced 4X with Intravenous Vitamin C, Thiamine, and hydrocortisone - March 2017 (without any Vitamin D)
  • Around ten million lives per year could be saved from Sepsis using $60 treatment of intravenous Vitamin C, Vitamin B and hydrocortisone
  • "The global burden of sepsis is estimated as 15 to 19 million cases annually with a mortality rate approaching 60% in low-income countries."
  •  Download the PDF from VitaminDWiki
  • They injected all Sepsis patients for 6 months and compared results from patients in the previous 6 months.
  • 
• Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure - The CITRIS-ALI Randomized Clinical Trial - JAMA Oct 2019 - doi:10.1001/jama.2019.11825
  • "Among patients with sepsis and ARDS, high-dose vitamin C infusion compared with placebo did not significantly reduce organ failure scores at 96 hours or improve biomarker levels at 168 hours."

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Update on Vitamin cocktail (without Vitamin D) - May 2018

• Medscape Getting wider test
  • 19 of 47 sepsis patients died previously
  • 4 out of 47 who got the treatment died
• "Sevransky's study plans to involve at least 500 and up to 2,000 patients at multiple hospitals for about a year and a half. The plan is to wrap up work in December 2019"
• Beth Israel Deaconess Medical Center study involves about 200 patients
• "Similar studies are underway in New Jersey, Slovenia, China, Australia, and Qatar"
• Vitamin C "...dose being studied is about 1.5 grams intravenously, every 6 hours for 4 days"
  "In a follow-up paper in April, Marik wrote that vitamin C lowers oxidative stress and inflammation, and it helps stop blood vessels from dilating, which helps maintain blood pressure. People who have sepsis often don't have enough vitamins C and B1, and those vitamins appear to combine with the steroid hydrocortisone to boost the effects."
• Many references at the end of the article

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Sepsis best treated by Thiamine (B1) - Vitamin D, Selenium, etc. also considered - literature review July 2018

A review of micronutrients in sepsis: the role of thiamine, l-carnitine, vitamin C, selenium and vitamin D.
Nutr Res Rev. 2018 Jul 9:1-10. Doi 10.1017/S0954422418000124. _available at sci-hub
Belsky JB1, Wira CR1, Jacob V1, Sather JE1, Lee PJ2.

Sepsis is defined as the dysregulated host response to an infection resulting in life-threatening organ dysfunction. The metabolic demand from inefficiencies in anaerobic metabolism, mitochondrial and cellular dysfunction, increased cellular turnover, and free-radical damage result in the increased focus of micronutrients in sepsis, as they play a pivotal role in these processes. In the present review, we will evaluate the potential role of micronutrients in sepsis, specifically, thiamine, l-carnitine, vitamin C, Se, and vitamin D. Each micronutrient will be reviewed in a similar fashion, discussing its major role in normal physiology, suspected role in sepsis, use as a biomarker, discussion of the major basic science and human studies, and conclusion statement. Based on the currently available data, we conclude that thiamine may be considered in all septic patients at risk for thiamine deficiency and l-carnitine and vitamin C to those in septic shock. Clinical trials are currently underway, which may provide greater insight into the role of micronutrients in sepsis and validate standard utilization.
A portion of the table from Sci-Hub

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Additional cost-effective uses of Vitamin D in medical emergencies (beyond Sepsis)

Items in both VitaminDWiki categories: Cost savings with Vitamin D and Trauma and surgery

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