VITAMIN D. Christina Nieuwoudt RD(SA) CCSSA/SASPEN 2018

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1 VITAMIN D Christina Nieuwoudt RD(SA) CCSSA/SASPEN

2 OBJECTIVES Why is it in the spotlight? Vit D and acute illness If it has a role how much should we give? Future 2

3 Why is it in the spotlight? FUNCTIONS Vit D and calcium homeostasis Discovered in 1920s different scientists including Nobel Prize for Chemistry winner 1928 Adolf Windaus anti-rachitic substance BUT acts via pleiotropic cell-specific genomic and non-genomic pathways (VDR) Muscle Lung Heart Kidney Immune system 3

4 Vitamin D receptor (VDR) Discovered in 1974 Actions of the vitamin D hormone 1,25(OH)2D3 are mediated by the vitamin D receptor (VDR), a ligand-activated transcription factor that functions to control gene expression. Following ligand(small molecules that transmit signals in cells) activation, the VDR binds directly to specific sequences located near promoters and recruits a variety of coregulatory complexes that perform the additional functions required to modify transcriptional output. Many target genes identified 4

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7 VITAMIN D 7

8 Deficiency Optimal tissue levels Initial depletion & compensation Metabolic Oxidative damage to membranes/dna Impairment of biochemical function Functional defects: non-specific Immunological Cognitive Work capacity CLINICAL DISEASE 8

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10 1 billion individuals worldwide, nearly 15% of the world s population, are vitamin D deficient or insufficient (less than 20 ng/ml or between ng/ml, respectively). Causes: Insufficient UVB exposure caused by sunscreen use, time of day exposed to the sun, season, latitude, skin pigmentation and clothing Vitamin D3 supplements are superior to D2 for raising 25(OH)D in individuals. Supplementing with 50,000 IU per week or 6,000 IU per day is sufficient for eliminating vitamin D deficiency (>30 ng/ml). 10

11 VIT D LEVELS OF 116 PATIENTS Admitted to ICU in Life Groenkloof Hospital, Pretoria Jan July % 40.5% 25% Deficient <12ng/ml Insufficient 12-20ng/ml Sufficient >20ng/ml 11

12 Vit D and acute illness DEFINITION: (CRITICALLY ILL PATIENTS) Patients at high risk for actual or potential life-threatening health problems They are highly vulnerable Unstable Complex Thereby requiring intense and vigilant nursing care in addition to medical and or surgical care

13 Vit D and acute illness Sepsis = Mitochondrial dysfunction Impaired autophagy in sepsis = mortality Vit D upregulates NOD2 NUCLEOTIDE-BINDING OLIGOMERIZATION DOMAIN PROTEIN 2 linked to autophagy Autophagy regulates innate immunity via inhibition of mitochondrial DNA (mtdna) release by the inflammasone Circulating mtdna predictor of mortality in ICU patients Vit D-mediated pathways may link autophagic and inflammasone processes Litonjua et al

14 Innate immunity Innate immune system first line of defense in protection from pathogenic microbes and host-derived signals of cellular distress. A way these danger signals trigger inflammation is through activation of inflammasomes, multiprotein complexes that assemble in the cytosol after exposure to pathogenassociated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) result in the activation of caspase-1 and subsequent cleavage of proinflammatory cytokines IL-1β and IL-18. ( 14

15 Cathelicidins & β-defensins Vitamin D is essential for the production cathelicidins and β-defensins, potent groups of antimicrobial peptides which provide innate defenses against pathogens, maintain the structural integrity of various epithelial barriers aid in wound re-epithelialization. In the ICU patient population, a significant positive correlation exists between 25(OH)D serum levels and cathelicidin production and associations between cathelicidin and outcomes (sepsis and mortality) 15

16 Vit D deficiency and critical illness Association with important clinical outcomes: LOS Readmission rates Sepsis Increased risk of acute respiratory failure Han et al

17 Vit D and lung function 17

18 Vit D pleitropic effect Immune function of lung Alveolar capillary barrier function 18

19 In monocytes & macrophages pathogens bind to cell surface tolllike receptors 25 (OH)D converted to 1,25 (OH)2 D3 Upregulates mrna expression of hcap-18 to be cleaved to IL-37 antimicrobial peptide 19

20 Evidence suggests supplementation with Vit D3 decrease susceptibility/enhance recovery to infections influenza, recurrent pneumonia & TB Pilot study to evaluate the safety and efficacy of two doses of vitamin D3, 250,000 or 500,000 IU given in divided doses over 5 consecutive days to increase plasma 25(OH)D concentrations to the sufficient range (>30 ng/ml) to increase plasma IL-37 in adult ventilated patients requiring intensive care. 20

21 Outcome There was a difference in hospital LOS between groups; Placebo: 36 ± 19 days compared to 250,000 IU group: 25 ± 14 days compared to 500,000 IU group :18 ± 11 days, (p = 0.03) with no statistical differences in ICU LOS or duration of mechanical ventilation 21

22 Limitations Small sample size Differences in comorbidities Low rate of infections Steroid use not considered 22

23 Summary No clinical guidelines for dosing High-dose vitamin D may have multifactorial effects that could contribute directly or indirectly to hospital LOS, including salutary effects, via improved 25(OH)D levels on respiratory or other skeletal muscle function, by modulation of the proinflammatory milieu, and by regulation of immune functions Additional studies needed 23

24 Vit D and wound healing 24

25 Pressure injuries are a common medical condition used as indicator of quality of care in hospitals USA between 1 million and 2.5 million individuals in pressure-related injuries Painful, might be life-threatening; costly HAPI cost U$ per injury (2006) 25

26 What has this got to do with critical illness? Specific risk factors for HAPI prolonged periods of immobility increased severity of disease, anemia, hemodynamic instability, impaired immunity, medical comorbidities, malnutrition 26

27 Unexplored factor is Vit D status Central role in Immune function Epithelial cell integrity Wound healing Possible modifiable role in HAPIs in critically ill 27

28 Cohort of 402 Controlling for BMI, cumulative caloric deficit, NUTRIC score, and ICU LOS. Each unit increment in 25(OH)D was associated with 11% reduced odds of HAPI formation (odds ratio 0.89; 95% CI ). Patients with 25(OH)D <20 ng/ml were >2 times as likely to develop a HAPI (OR 2.51; 95% CI ) compared with patients with levels 20 ng/ml. 28

29 Conclusion Optimizing Vit D status of critically ill patients Cost effective intervention to reduce risk of HAPI RCTs needed to confirm 29

30 If it has a role how much should we give? Up to U daily safe 30

31 FUTURE 31

32 Preiser 2018 presentation 32

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