TPN and lipid RCT of 57 patients TPN with lipid vs TPN without lipid TPN associated with increased infectious complications * * * * Battistella FD, et al. J Trauma 1997; 43:52.
Data Needed 1. New TPN trials with glucose control 2. New trials withholding lipids or utilizing Omega -3 lipids 3. Omega-3 lipid administration as a separate pharmacologic supplement
Outline Topics for Research in Clinical Nutrition! Glucose Control/Caloric Intake! Proper delivery of TPN! Pharmaconutrients! Pharmaconutrients: : Omega-3 Fats - the age of nutrigenomics is upon us! Pharamaconutrients: : Glutamine! Pharamaconutrients: Arginine! Perioperative Nutritional Intervention
Modulating inflammatory and oxidative stress with nutrients: The effect of aging
Aging is associated with an increase in signs of inflammation and oxidatative stress and reduction in cell mediated immunity Increased cytokine production Loss of muscle and bone Increased blood lipids Inflammatory & Oxidative Increased amount of disease with an inflammatory component in its cause. Increased Stress Impaired cell mediated immunity
Increase in fasting plasma triglycerides and C-Reactive protein with age in healthy Caucasian men Fasting triglyceride Fasting C-reactive protein 1.8 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 3 2.5 2 1.5 1 0.5 0 Age group 18-29 30-49 50-84 18-29 30-49 50-84 n=132 75 85 n=132 75 85 Significant effect of age grouping p<0.0001 Kruskal-Wallis Test
IL-1-511 pro-inflammatory SNP (T) related to 3-year mortality in elderly male geriatric patients 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 Cumulative Proportion Surviving 1,0 Non-infl (CC) Pro-infl (CT+TT) P=0.02 0,0 0 5 10 15 20 25 30 35 40 Months Cederholm et al J. Intern Med 2007; 262: 215-223
Investigation of whether the genotype for pro-inflammatory cytokines influences the outcome of hospitalised elderly subjects.
Subjects 79 patients consecutively admitted to two geriatric wards were studied 83±7 years, 68% females Chronic illness/exacerbation, infections, fall trauma Median hospital stay 11 (6-16 25th-75th perc) days
TNF!-308 pro-inflammatory SNP (A2) improves survival in elderly female geriatric patients 1,0 Cumulative Proportion Surviving 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 TNF12 Pro-infl (A1A2) Non-infl (A1A1) TNF11 P=0.056 0,1 0,0 0 5 10 15 20 25 30 35 40 Months Grimble et al Clin Nutr 2003;22:S39
IL-6-174 pro-inflammatory genotype (GG) improves 3-year survival in elderly female geriatric patients 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 Cumulative Proportion Surviving 1,0 Non-infl (CC+CG) Pro-infl (GG) P=0.02 P=0.056 0,1 0,0 0 5 10 15 20 25 30 35 40 Months Grimble et al Clin Nutr 2003;22:S39
TNF"+252 pro-inflammatory genotype (B22) decreases 3- year survival in elderly male geriatric patients 1,0 Cumulative Proportion Surviving 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 TNFB22 Non-infl (B11, B12) Pro-infl (B22) P=0.04 Grimble et al Clin Nutr 2003;22:S39 0,0 0 5 10 15 20 25 30 35 40 Months
IL-1-511 pro-inflammatory SNP (T) decreases 3-year survival in elderly male geriatric patients 0,9 0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 Cumulative Proportion Surviving 1,0 Non-infl (CC) Pro-infl (CT+TT) P=0.02 Grimble et al Clin Nutr 2003;22:S39 0,0 0 5 10 15 20 25 30 35 40 Months
Modulating inflammatory and oxidative stress with nutrients. The effect of aging.
Trauma/infection/burns Pro-inflammatory cytokines Immune system activation T and B cells
Trauma/infection/burns Pro-inflammatory cytokines Immune system activation T and B cells Oxidants Pathogen killing Tissue damage Hostile environment
Trauma/infection/burns Pro-inflammatory cytokines Immune system activation T and B cells Oxidants Pathogen killing Tissue damage Nutrient release from host tissues Hostile environment Appetite loss
Trauma/infection/burns Pro-inflammatory cytokines Immune system activation Immunonutrition T and B cells Oxidants Antioxidant defence Glucose Pathogen killing Hostile environment Tissue damage - Nutrient release from host tissues Appetite loss Sulphur amino acids Glutamine Glutathione synthesis Antioxidant defences strengthened
Trauma/infection/burns Pro-inflammatory cytokines Oxidants Antioxidant defence Immune system activation - Feedback systems IL10, Heat shock proteins Glucose Immunonutrition T and B cells Pathogen killing Hostile environment Tissue damage - Nutrient release from host tissues Appetite loss Sulphur amino acids Glutamine Glutathione synthesis Antioxidant defences strengthened
Take home messages "Inflammatory and oxidative stress increase with aging. "Plasma lipids and endothelial dysfunction increase with age. "The lipid lowering, anti-inflammatory effects of fish oil are more likely to occur in old than young subjects. "These effects in old subjects are more likely in individuals with a pro-inflammatory genotype.
You Are What You Eat Dietary!-6 FA Membrane phospholipids Dietary!-3 FA Arachidonic acid Eicosapentaenoic acid Docosahexaenoic acid lipoxygenase cyclooxygenase lipoxygenase Leukotrienes (4 series) Proinflammatory Cell adhesive Chemotactic Prostanoids & Thromboxanes (2 series) Aggregates platelets Immunosuppressive Prostanoids & Thromboxanes (3 series) Antiaggregatory Non-immunosuppressive Leukotrienes (5 series) Anti-inflammatory Nonadhesive
Enteral Nutrition With Eicosapentaenoic Acid (EPA),!-Linonenic Acid (GLA) and Antioxidants in Critical Illness: : A Meta- Analysis Evaluation of Outcome Data Pontes-Arruda A, DeMichele S, Seth A and Singer P Crit Care Med 34 (12 Suppl 1): A95, 2006
Enteral Nutrition With Eicosapentaenoic Acid (EPA),!-Linonenic Acid (GLA) and Antioxidants in Critical Illness: : A Meta- Analysis Evaluation of Outcome Data Pontes-Arruda A, DeMichele S, Seth A and Singer P Crit Care Med 34 (12 Suppl 1): A95, 2006
Study name Statistics for each study Std diff in means and 95% CI Std diff Standard Lower Upper Relative in means error Variance limit limit Z-Value p-value weight Pontes-Arruda et al, 2006 0.845 0.206 0.042 0.441 1.249 4.100 0.0000 33.19 Singer et al, 2006 0.198 0.206 0.042-0.206 0.601 0.960 0.3368 33.29 Gadek et al, 1999 0.482 0.205 0.042 0.080 0.884 2.349 0.0188 33.52 Fixed effects 0.508 0.119 0.014 0.275 0.740 4.276 0.0000-1.00-0.50 0.00 0.50 1.00 MORE ICU-FREE DAYS p < 0.0001 Favors Control Favors EPA+GLA Pontes-Arruda et al. Crit Care Med 34:A95, 2006
Study name Statistics for each study Std diff in means and 95% CI Pontes-Arruda et al, 2006 Std diff Standard Lower Upper Relative in means error Variance limit limit Z-Value p-value weight 0.933 0.208 0.043 0.525 1.340 4.485 0.0000 32.85 Singer et al, 2006 0.242 0.206 0.042-0.161 0.646 1.176 0.2395 33.46 Gadek et al, 1999 0.501 0.205 0.042 0.099 0.904 2.442 0.0146 33.69 Fixed effects 0.556 0.119 0.014 0.323 0.790 4.669 0.0000-1.00-0.50 0.00 0.50 1.00 Favors Control Favors EPA+GLA MORE VENTILATOR-FREE DAYS p < 0.0001 Pontes-Arruda et al. Crit Care Med 34:A95, 2006
Study name Statistics for each study Odds ratio and 95% CI Odds Lower Upper Relative ratio limit limit Z-Valuep-Value weight Pontes-Arruda et al, 2006 0.143 0.058 0.353-4.213 0.0000 63.85 Gadek et al, 1999 0.223 0.067 0.742-2.445 0.0145 36.15 Fixed effects 0.167 0.081 0.345-4.837 0.0000 0.1 0.2 0.5 1 2 5 10 Favors EPA+GLA Favors Control 83% LESS ORGAN FAILURES p < 0.0001 Pontes-Arruda et al. Crit Care Med 34:A95, 2006
28-Days All Cause Mortality Study name Statistics for each study Odds ratio and 95% CI Odds Lower Upper Relative Oxepa ratio limit limit Z-Valuep-Value weight (n/n) Control (n/n) Pontes-Arruda et al, 2006 0.448 0.201 0.995-1.973 0.049 42.01 18/55 25/48 Singer et al, 2006 0.295 0.126 0.695-2.793 0.005 36.61 Gadek et al, 1999 0.563 0.184 1.725-1.006 0.315 21.38 13/46 28/49 6/51 9/47 Fixed effects 0.404 0.241 0.678-3.434 0.001 0.1 0.2 0.5 1 2 5 10 60% Reduction p = 0.001 FAVORS EPA/GLA FAVORS CONTROL ITT Mortality (All 411 Patients) 49% Reduction p = 0.002 (OR 0.514 95%CI: 0.335-0.788) Pontes-Arruda et al. Crit Care Med 34:A95, 2006
Would Parenteral Omega-3 lipids have even better effects??