Sepsis is a severe illness. It is caused by a bacterial infection that begins anywhere in the body and moves to the blood. The bloodstream is soon overwhelmed by bacteria.
Each year in the United States, more than one million people are diagnosed with sepsis. About 200,000 people die. Many deaths are noted in the Southeast United States. Nearly 60% of sepsis cases are associated with respiratory infections.
A number of risk factors are associated with sepsis:
- Hospitalization and surgery: It is easy for bacterial infections to spread within a hospital. Surgery allows bacteria to have direct contact with the blood.
- Respiratory infections and smoking: Both of these damage the lining of the lungs. Then bacteria can more easily make contact with the blood.
Poorer outcomes may occur in those who are:
- Obese or smoke
- Premature, low birth-weight infants (They have poorly developed immune systems.)
Sunlight exposure and risk
There is a lot of evidence that solar ultraviolet-B (UVB) light reduces the risk of sepsis:
- Sepsis rates are highest in the winter/spring and lowest in the summer/fall.
- African-Americans have higher hospitalization rates for sepsis than white Americans. Overall, African-Americans have lower vitamin D blood levels than white Americans (16 ng/mL [40 nmol/L] vs 26 ng/mL [65 nmol/L]).
People with cancer and other diseases associated with low vitamin D blood levels have higher rates of sepsis.
Vitamin D and sepsis
Vitamin D levels
Vitamin D has been found to lower bacteria infection rates, as seen in two studies:
- At Emory University (Atlanta), patients with sepsis or in an intensive care unit (ICU) had lower vitamin D blood levels than healthy controls. Mean blood cathelicidin levels were significantly lower in critically subjects compared to healthy controls. Cathelicidin is a protein that fights infections.
- In Tennessee, patients in an ICU had similar vitamin D levels as healthy controls. Those with lower vitamin D levels had poorer outcomes. 53% of those who died in the ICU or shortly thereafter had vitamin D levels below 20 ng/ml (50 nmol/l) compared to 28% of those who survived.
How vitamin D works
Vitamin D fights bacterial infections by producing proteins called cathelicidin and defensins. They can be considered antiseptic molecules.
There are no reported studies showing that higher vitamin D levels reduce the risk of sepsis. However, vitamin D reduces the risk of other diseases. Therefore, high vitamin D blood levels (40 ng/mL [100 nmol/L]) may reduce the risk of sepsis.
Those planning for a hospital stay should consider increasing their vitamin D blood levels to this amount. Take 10,000–50,000 international units (IU) (250-1250 mcg)/day of vitamin D for a few days to quickly bring the levels up. After that, reduce the intake to 1000–5000 IU (25-125 mcg)/day. It would be worthwhile to have vitamin D levels measured before going to the hospital.
There are no reported studies of using vitamin D to treat sepsis. However, it takes 1–2 days for the body to make cathelicidin after vitamin D from oral intake or UVB. Thus, vitamin D may a secondary way to treat sepsis in conjunction with antibiotics.
This evidence summary was written by:
William B. Grant, Ph.D.
Sunlight, Nutrition, and Health Research Center (SUNARC)
P.O. Box 641603
San Francisco, CA 94164-1603, USA
Complete bibliography of research used in this summary
The research we have cited in our summary is listed below, with links to PubMed abstracts and full-text for those who wish to explore further.
- Barnato, A. E. Alexander, S. L. Linde-Zwirble, W. T. Angus, D. C. Racial variation in the incidence, care, and outcomes of severe sepsis: analysis of population, patient, and hospital characteristics. Am J Respir Crit Care Med. 2008 Feb 1; 177 (3): 279-84.
- Blanco, J. Muriel-Bombin, A. Sagredo, V. Taboada, F. Gandia, F. Tamayo, L. Collado, J. Garcia-Labattut, A. Carriedo, D. Valledor, M. De Frutos, M. Lopez, M. J. Caballero, A. Guerra, J. Alvarez, B. Mayo, A. Villar, J. Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study. Crit Care. 2008; 12 (6): R158.
- Cirioni, O. Ghiselli, R. Tomasinsig, L. Orlando, F. Silvestri, C. Skerlavaj, B. Riva, A. Rocchi, M. Saba, V. Zanetti, M. Scalise, G. Giacometti, A. Efficacy of LL-37 and granulocyte colony-stimulating factor in a neutropenic murine sepsis due to Pseudomonas aeruginosa. Shock. 2008 Oct; 30 (4): 443-8.
- Cirioni, O. Giacometti, A. Ghiselli, R. Bergnach, C. Orlando, F. Silvestri, C. Mocchegiani, F. Licci, A. Skerlavaj, B. Rocchi, M. Saba, V. Zanetti, M. Scalise, G. LL-37 protects rats against lethal sepsis caused by gram-negative bacteria. Antimicrob Agents Chemother. 2006 May; 50 (5): 1672-9.
- Danai, P. A. Moss, M. Mannino, D. M. Martin, G. S. The epidemiology of sepsis in patients with malignancy. Chest. 2006 Jun; 129 (6): 1432-40.
- Danai, P. A. Sinha, S. Moss, M. Haber, M. J. Martin, G. S. Seasonal variation in the epidemiology of sepsis. Crit Care Med. 2007 Feb; 35 (2): 410-5.
- Dombrovskiy, V. Y. Martin, A. A. Sunderram, J. Paz, H. L. Facing the challenge: decreasing case fatality rates in severe sepsis despite increasing hospitalizations. Crit Care Med. 2005 Nov; 33 (11): 2555-62.
- Dombrovskiy, V. Y. Martin, A. A. Sunderram, J. Paz, H. L. Occurrence and outcomes of sepsis: influence of race. Crit Care Med. 2007 Mar; 35 (3): 763-8.
- Dombrovskiy, V. Y. Martin, A. A. Sunderram, J. Paz, H. L. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med. 2007 May; 35 (5): 1244-50.
- Downey, L. C. Smith, P. B. Benjamin, D. K., Jr. Risk factors and prevention of late-onset sepsis in premature infants. Early Hum Dev. Jul; 86 Suppl 17-12.
- Esper, A. M. Martin, G. S. Extending international sepsis epidemiology: the impact of organ dysfunction. Crit Care. 2009; 13 (1): 120.
- Esper, A. M. Moss, M. Lewis, C. A. Nisbet, R. Mannino, D. M. Martin, G. S. The role of infection and comorbidity: Factors that influence disparities in sepsis. Crit Care Med. 2006 Oct; 34 (10): 2576-82.
- Esper, A. M. Moss, M. Martin, G. S. The effect of diabetes mellitus on organ dysfunction with sepsis: an epidemiological study. Crit Care. 2009; 13 (1): R18.
- Fukumoto, K. Nagaoka, I. Yamataka, A. Kobayashi, H. Yanai, T. Kato, Y. Miyano, T. Effect of antibacterial cathelicidin peptide CAP18/LL-37 on sepsis in neonatal rats. Pediatr Surg Int. 2005 Jan; 21 (1): 20-4.
- Giacometti, A. Cirioni, O. Ghiselli, R. Bergnach, C. Orlando, F. D’Amato, G. Mocchegiani, F. Silvestri, C. Del Prete, M. S. Skerlavaj, B. Saba, V. Zanetti, M. Scalise, G. The antimicrobial peptide BMAP-28 reduces lethality in mouse models of staphylococcal sepsis. Crit Care Med. 2004 Dec; 32 (12): 2485-90.
- Giacometti, A. Cirioni, O. Ghiselli, R. Mocchegiani, F. D’Amato, G. Circo, R. Orlando, F. Skerlavaj, B. Silvestri, C. Saba, V. Zanetti, M. Scalise, G. Cathelicidin peptide sheep myeloid antimicrobial peptide-29 prevents endotoxin-induced mortality in rat models of septic shock. Am J Respir Crit Care Med. 2004 Jan 15; 169 (2): 187-94.
- Ginde, A. A. Liu, M. C. Camargo, C. A., Jr. Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. Arch Intern Med. 2009 Mar 23; 169 (6): 626-32.
- Gombart, A. F. The vitamin D-antimicrobial peptide pathway and its role in protection against infection. Future Microbiol. 2009 Nov; 41151-65.
- Grant, W. B. Vitamin D supplementation could reduce risk of sepsis in infants. World J Pediatr. 2010 May; 6 (2): 185; author reply 185-6.
- Grant, W. B. Vitamin D supplementation of mother and infant could reduce risk of sepsis in premature infants. Early Hum Dev. 2010 Feb; 86 (2): 133.
- Grant, W. B . Solar ultraviolet-B irradiance and vitamin D may reduce the risk of septicemia. Dermato-Endocrinology. 2009 January/February; 1 (1): 37-42.
- Hatherill, M. Sepsis predisposition in children with human immunodeficiency virus. Pediatr Crit Care Med. 2005 May; 6 (3 Suppl): S92-8.
- Huttunen, R. Laine, J. Lumio, J. Vuento, R. Syrjanen, J. Obesity and smoking are factors associated with poor prognosis in patients with bacteraemia. BMC Infect Dis. 2007; 713.
- Jeng, L. Yamshchikov, A. V. Judd, S. E. Blumberg, H. M. Martin, G. S. Ziegler, T. R. Tangpricha, V. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J Transl Med. 2009 Apr 23; 7 (1): 28.
- Lee, P. Eisman, J. A. Center, J. R. Vitamin D deficiency in critically ill patients. N Engl J Med. 2009 Apr 30; 360 (18): 1912-4.
- Lee, P. Nair, P. Eisman, J. A. Center, J. R. Vitamin D deficiency in the intensive care unit: an invisible accomplice to morbidity and mortality?. Intensive Care Med. 2009 Dec; 35 (12): 2028-32.
- Liu, P. T. Schenk, M. Walker, V. P. Dempsey, P. W. Kanchanapoomi, M. Wheelwright, M. Vazirnia, A. Zhang, X. Steinmeyer, A. Zugel, U. Hollis, B. W. Cheng, G. Modlin, R. L. Convergence of IL-1beta and VDR activation pathways in human TLR2/1-induced antimicrobial responses. PLoS One. 2009; 4 (6): e5810.
- Liu, P. T. Stenger, S. Li, H. Wenzel, L. Tan, B. H. Krutzik, S. R. Ochoa, M. T. Schauber, J. Wu, K. Meinken, C. Kamen, D. L. Wagner, M. Bals, R. Steinmeyer, A. Zugel, U. Gallo, R. L. Eisenberg, D. Hewison, M. Hollis, B. W. Adams, J. S. Bloom, B. R. Modlin, R. L. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006 Mar 24; 311 (5768): 1770-3.
- Liu, P. T. Stenger, S. Tang, D. H. Modlin, R. L. Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol. 2007 Aug 15; 179 (4): 2060-3.
- Martin, G. S. Mannino, D. M. Eaton, S. Moss, M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003 Apr 17; 348 (16): 1546-54.
- Mayr, F. B. Yende, S. Linde-Zwirble, W. T. Peck-Palmer, O. M. Barnato, A. E. Weissfeld, L. A. Angus, D. C. Infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis. JAMA. 2010 Jun 23; 303 (24): 2495-503.
- Moller, S. Laigaard, F. Olgaard, K. Hemmingsen, C. Effect of 1,25-dihydroxy-vitamin D3 in experimental sepsis. Int J Med Sci. 2007 Jul; 4 (4): 190-5.
- Mookherjee, N. Rehaume, L. M. Hancock, R. E. Cathelicidins and functional analogues as antisepsis molecules. Expert Opin Ther Targets. 2007 Aug; 11 (8): 993-1004.
- Olsen, M. A. Krauss, M. Agniel, D. Schootman, M. Gentry, C. N. Yan, Y. Damiano, R. J., Jr. Fraser, V. J. Mortality associated with bloodstream infection after coronary artery bypass surgery. Clin Infect Dis. 2008 May 15; 46 (10): 1537-46.
- Peric, M. Koglin, S. Dombrowski, Y. Gross, K. Bradac, E. Buchau, A. Steinmeyer, A. Zugel, U. Ruzicka, T. Schauber, J. Vitamin D analogs differentially control antimicrobial peptide/”alarmin” expression in psoriasis. PLoS One. 2009 Jul; 4 (7): e6340.
- Sreeramoju, P. V. Tolentino, J. Garcia-Houchins, S. Weber, S. G. Predictive factors for the development of central line-associated bloodstream infection due to gram-negative bacteria in intensive care unit patients after surgery. Infect Control Hosp Epidemiol. 2008 Jan; 29 (1): 51-6.
- Watson, R. S. Carcillo, J. A. Linde-Zwirble, W. T. Clermont, G. Lidicker, J. Angus, D. C. 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.