Can we save lives with more vitamin C?

Transcription

1 ANZICS NZ 5/4/2017 Can we save lives with more vitamin C? Anitra Carr, PhD Sir Charles Hercus Health Research Fellow Department of Pathology University of Otago, Christchurch, NZ

2 Human vitamin C requirement Glucose Glucuronic acid Vitamin C is synthesised from glucose in plants and the livers of most animals except: humans, primates, guinea pigs, fruit bats, teleost fish, some birds Glucuronolactone Gulonolactone Ascorbic Acid Gulo enzyme Vitamin: vital for life

3 Vitamin C uptake & excretion Intestinal uptake Renal excretion & reabsorption Linblad et al. Nutrients, 2013.

4 Vitamin C levels in the body Very high (200x) Adrenals, pituitary, retina High (100x) Brain, white blood cells, pancreas, liver, spleen Medium (10x) Skeletal & heart muscle

5 Functions of vitamin C Enzyme cofactor Protein 3 structure Epigenetic regulation Mitochondrial energy production Hormone & neurotransmitter synthesis Metabolic regulation

6 Vitamin C intake and plasma levels Adapted from: Levine et al, PNAS 1996.

7 Vitamin C deficiency in hospital patients Adapted from: McGregor & Biesalki, Curr Opin Clin Nutr Metab Care, Gan et al, J Am Coll Nutr, 2006.

8 Vitamin C and the critically ill High performance liquid chromatography with electrochemical detection (HPLC-ECD) Study cohort (n) Vitamin C (µm) Adequate (%) Marginal (%) Deficient (%) > 50 µm < 23 µm < 11 µm University students (139) 58 ± Middle aged people (389) 44 ± Sepsis patients (17) 23 ± Septic shock patients (24) 15 ±

9 Observational Study Vitamin C levels in the critically ill Cohort: 24 ICU patients with severe sepsis/septic shock 17 ICU patients without sepsis (trauma/surgery) Measures: vitamin C status, inflammatory biomarkers (e.g. CRP), leukocyte enzyme myeloperoxidase, blood cell counts and diffs, patient outcomes (length of stay, mortality, etc). Status: recruitment completed, still analysing patient samples.

10 Vitamin C levels in the critically ill Patients: 24 severe sepsis, 16 trauma/surgical Plasma vitamin C C-reactive protein

11 Vitamin C depletion in the critically ill Patient: failed kidney transplant (receiving ~180 mg/d vitamin C) Plasma vitamin C C-reactive protein

12 Vitamin C levels in the critically ill Enteral = 64% (~103 mg/d) TPN = 7% (~265 mg/d) Both = 10%, Neither = 19% Estimated vitamin C Measured vitamin C absorption, haemodilution, dialysis, excretion, turnover/requirement

13 Vitamin C requirement in critical illness Adapted from: Long et al, J Surg Res, AMA Nutrition Advisory Group: 100 mg/d vitamin C

14 IV vitamin C and organ failure Patients: 24 with severe sepsis IV Vitamin C: 0, 50, 200 mg/kg/d Patients: 94 with severe sepsis IV vitamin C: 0 or 6 g/d (+ B vitamin) Fowler et al, J Tranls Med, Marik et al, Chest, 2016.

15 IV vitamin C and lung dysfunction Patient with ARDS (enterovirus/rhinovirus) Vitamin C: 200 mg/kg/d Fowler et al, World J Crit Care Med, Patient with ARDS (Gram positive cocci) Vitamin C: 200 mg/kg/d Bharara et al, Case Rep Crit Care, 2016.

16 Vitamin C and vasopressor synthesis L-Tyrosine L-DOPA Glycine-extended precursor Enzyme + vitamin C Hydroxylated intermediate Dopamine Enzyme + vitamin C Noradrenaline Vasopressin Adrenaline Carr et al, Crit Care, 2015.

17 IV vitamin C and vasopressor requirements Patients: 28 septic shock IV vitamin C: 0 or 100 mg/kg/d Adapted from: Zabet et al, J Res Pharm Pract, Patients: 94 with severe sepsis IV Vitamin C: 0 or 6 g/d (+ B vitamin) Adapted from: Marik et al, Chest, 2016.

18 IV vitamin C and vasopressor requirements * Patients: 40 severely burned IV vitamin C: 0 or 66 mg/kg/h Tanaka et al, Arch Surg, * * Khan et al, J Burn Care, 2011.

19 IV vitamin C and mortality Patients: 28 with septic shock IV vitamin C: 0 or 100 mg/kg/d Marik et al, Chest, Patients: 94 with severe sepsis IV Vitamin C: 0 or 6 g/d (+ B vitamin) Adapted from: Zabet et al, J Res Pharm Pract, 2016.

20 Intervention Study Vitamin C administration in septic shock Study aim To carry out a pilot RCT to assess the effects of adjunctive vitamin C administration in patients with septic shock Patients: 40 patients with septic shock: 20 placebo infusion 20 intravenous vitamin C (100 mg/kg/d for 4 d)

21 Functions of vitamin C Enzyme cofactor Protein 3 structure Epigenetic regulation Mitochondrial energy production Hormone & neurotransmitter synthesis Metabolic regulation

22 Thank you! Questions?