Low serum 25(OH)D concentrations may explain the findings regarding IL-6, hyperglycemia and glucose control in septic patients
William B. Grant, Sunlight, Nutrition and Health Research Center
14 May 2012
The paper by Nakamura et al. [1] reported correlations between interleukin-6 (IL-6) level, hyperglycemia, and glucose control and outcomes of septic patients. Those with failed glucose control had poorer survival rates than those with successful glucose control. Those with failed glucose control had higher IL-6 levels and much higher rates of septic shock.
The findings are consistent with lower 25-hydroxyvitamin D [25(OH)D] concentrations for those with failed glucose control. Vitamin D shifts cytokine production from T-helper 1 (Th1) to Th2 types, which includes reducing IL-6 levels [2]. Serum 25(OH)D concentrations have been found inversely correlated with glucose concentrations [3]. However, treatment with vitamin D seems to be able to increase insulin secretion but may have little impact on glucose control [4]. Thus, the effects of vitamin D deficiency may act over an extended period to reduce glucose control. More importantly, serum 25(OH)D concentrations have been found inversely associated with sepsis [5] and those with lower serum 25(OH)D concentrations have poorer survival with sepsis and other conditions in intensive care units [6-8]. The mechanism whereby vitamin D reduces risk and severity of sepsis is through induction of cathelicidin (LL-37) by the 1,25-dihydroxyvitmin D metabolite [2]. Cathelicidin is considered an antisepsis molecule [9].
The 25(OH)D concentration required for optimal health is at least 40 ng/ml (100 nmol/l) [10]. Based on the link between low serum 25(OH)D concentration and sepsis, increasing serum 25(OH)D concentrations for those diagnosed with sepsis may be beneficial. According to one paper, ¿Theoretically, pharmacological doses of vitamin D (2,000 IU per kg per day for three days) may produce enough of the naturally occurring antibiotic cathelicidin to cure common viral respiratory infections, such as influenza and the common cold, but such a theory awaits further science.¿ [10]. Vitamin D3 is much more effective than is vitamin D2 [11]. Vitamin D3 can now be prescribed in 50,000 IU doses [12].
While the evidence presented in this comment supports use of vitamin D in treating those with sepsis, such treatment should still be considered experimental and should be done in conjunction with standard medical practice.
References
1. Nakamura M, Oda S, Sadahiro T, Watanabe E, Abe R, Nakada T, Morita Y, Hirasawa H. Correlation between high blood interleukin-6 level, hyperglycemia and glucose control in septic patients. Critical Care 2012, 16:R58 (11 April 2012)
2. Khoo AL, Chai LY, Koenen HJ, Oosting M, Steinmeyer A, Zuegel U, Joosten I, Netea MG, van der Ven AJ. Vitamin D(3) down-regulates proinflammatory cytokine response to Mycobacterium tuberculosis through pattern recognition receptors while inducing protective cathelicidin production. Cytokine. 2011 Aug;55(2):294-300.
3. Hirani V. Relationship between vitamin D and hyperglycemia in older people from a nationally representative population survey. J Am Geriatr Soc. 2011;59:1786-1792.
4. Thomas GN, Scragg R, Jiang CQ, Chan W, Marz W, Pilz S, Kim HC, Tomlinson B, Bosch J, Lam TH, Cheung BM, Cheng KK. Hyperglycaemia and vitamin d: a systematic overview. Curr Diabetes Rev. 2012;8:18-31.
5. Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, 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;7:28.
6. Ginde AA, Camargo CA Jr, Shapiro NI. Vitamin D insufficiency and sepsis severity in emergency department patients with suspected infection. Acad Emerg Med. 2011;18:551-554.
7. Youssef DA, El Abbassi AM, Cutchins DC, Chhabra S, Peiris AN. Vitamin D deficiency: implications for acute care in the elderly and in patients with chronic illness. Geriatr Gerontol Int. 2011;11:395-407.
8. Flynn L, Zimmerman LH, McNorton K, Dolman M, Tyburski J, Baylor A, Wilson R, Dolman H. Effects of vitamin D deficiency in critically ill surgical patients. Am J Surg. 2012;203:379-382; discussion 382.
9. Mookherjee N, Rehaume LM, Hancock RE. Cathelicidins and functional analogues as antisepsis molecules. Expert Opin Ther Targets. 2007;11:993-1004.
10. Cannell JJ, Hollis BW. Use of vitamin D in clinical practice. Altern Med Rev. 2008;13:6-20.
11. Heaney RP, Recker RR, Grote J, Horst RL, Armas LA. Vitamin D3 Is more potent than vitamin D2 in humans. J Clin Endocrinol Metab. 2011;96:E447-E452.
12. Cannell J. Bio-Tech 50,000 IU D3 now available for prescription. 28 Feb. 2012. http://www.vitamindcouncil.org/bio-tech-50000-iu-d3-now-available-for-prescription/
Competing interests
I receive funding from the UV Foundation (McLean, VA), Bio-Tech Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), and the Vitamin D Society (Canada).
Critical Care
Low serum 25(OH)D concentrations may explain the findings regarding IL-6, hyperglycemia and glucose control in septic patients
14 May 2012
The paper by Nakamura et al. [1] reported correlations between interleukin-6 (IL-6) level, hyperglycemia, and glucose control and outcomes of septic patients. Those with failed glucose control had poorer survival rates than those with successful glucose control. Those with failed glucose control had higher IL-6 levels and much higher rates of septic shock.
The findings are consistent with lower 25-hydroxyvitamin D [25(OH)D] concentrations for those with failed glucose control. Vitamin D shifts cytokine production from T-helper 1 (Th1) to Th2 types, which includes reducing IL-6 levels [2]. Serum 25(OH)D concentrations have been found inversely correlated with glucose concentrations [3]. However, treatment with vitamin D seems to be able to increase insulin secretion but may have little impact on glucose control [4]. Thus, the effects of vitamin D deficiency may act over an extended period to reduce glucose control. More importantly, serum 25(OH)D concentrations have been found inversely associated with sepsis [5] and those with lower serum 25(OH)D concentrations have poorer survival with sepsis and other conditions in intensive care units [6-8]. The mechanism whereby vitamin D reduces risk and severity of sepsis is through induction of cathelicidin (LL-37) by the 1,25-dihydroxyvitmin D metabolite [2]. Cathelicidin is considered an antisepsis molecule [9].
The 25(OH)D concentration required for optimal health is at least 40 ng/ml (100 nmol/l) [10]. Based on the link between low serum 25(OH)D concentration and sepsis, increasing serum 25(OH)D concentrations for those diagnosed with sepsis may be beneficial. According to one paper, ¿Theoretically, pharmacological doses of vitamin D (2,000 IU per kg per day for three days) may produce enough of the naturally occurring antibiotic cathelicidin to cure common viral respiratory infections, such as influenza and the common cold, but such a theory awaits further science.¿ [10]. Vitamin D3 is much more effective than is vitamin D2 [11]. Vitamin D3 can now be prescribed in 50,000 IU doses [12].
While the evidence presented in this comment supports use of vitamin D in treating those with sepsis, such treatment should still be considered experimental and should be done in conjunction with standard medical practice.
References
1. Nakamura M, Oda S, Sadahiro T, Watanabe E, Abe R, Nakada T, Morita Y, Hirasawa H. Correlation between high blood interleukin-6 level, hyperglycemia and glucose control in septic patients. Critical Care 2012, 16:R58 (11 April 2012)
2. Khoo AL, Chai LY, Koenen HJ, Oosting M, Steinmeyer A, Zuegel U, Joosten I, Netea MG, van der Ven AJ. Vitamin D(3) down-regulates proinflammatory cytokine response to Mycobacterium tuberculosis through pattern recognition receptors while inducing protective cathelicidin production. Cytokine. 2011 Aug;55(2):294-300.
3. Hirani V. Relationship between vitamin D and hyperglycemia in older people from a nationally representative population survey. J Am Geriatr Soc. 2011;59:1786-1792.
4. Thomas GN, Scragg R, Jiang CQ, Chan W, Marz W, Pilz S, Kim HC, Tomlinson B, Bosch J, Lam TH, Cheung BM, Cheng KK. Hyperglycaemia and vitamin d: a systematic overview. Curr Diabetes Rev. 2012;8:18-31.
5. Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, 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;7:28.
6. Ginde AA, Camargo CA Jr, Shapiro NI. Vitamin D insufficiency and sepsis severity in emergency department patients with suspected infection. Acad Emerg Med. 2011;18:551-554.
7. Youssef DA, El Abbassi AM, Cutchins DC, Chhabra S, Peiris AN. Vitamin D deficiency: implications for acute care in the elderly and in patients with chronic illness. Geriatr Gerontol Int. 2011;11:395-407.
8. Flynn L, Zimmerman LH, McNorton K, Dolman M, Tyburski J, Baylor A, Wilson R, Dolman H. Effects of vitamin D deficiency in critically ill surgical patients. Am J Surg. 2012;203:379-382; discussion 382.
9. Mookherjee N, Rehaume LM, Hancock RE. Cathelicidins and functional analogues as antisepsis molecules. Expert Opin Ther Targets. 2007;11:993-1004.
10. Cannell JJ, Hollis BW. Use of vitamin D in clinical practice. Altern Med Rev. 2008;13:6-20.
11. Heaney RP, Recker RR, Grote J, Horst RL, Armas LA. Vitamin D3 Is more potent than vitamin D2 in humans. J Clin Endocrinol Metab. 2011;96:E447-E452.
12. Cannell J. Bio-Tech 50,000 IU D3 now available for prescription. 28 Feb. 2012. http://www.vitamindcouncil.org/bio-tech-50000-iu-d3-now-available-for-prescription/
Competing interests
I receive funding from the UV Foundation (McLean, VA), Bio-Tech Pharmacal (Fayetteville, AR), the Vitamin D Council (San Luis Obispo, CA), and the Vitamin D Society (Canada).