Vadim Ivanov, M.D., Ph.D. Micronutrients in controlling INFLAMMATION Webinar June 12, 2012

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1 Vadim Ivanov, M.D., Ph.D. Micronutrients in controlling INFLAMMATION Webinar June 12, 2012

2 1. What is Inflammation? 2. Acute and Chronic Inflammation 3. Role of Chronic Inflammation in Modern Human Diseases 4. Beneficial Micronutrients in Chronic Inflammation 5. Molecular Mechanisms of Inflammation 6. Research on Micronutrients and Inflammation at Dr Rath Research Institute

3 Inflammation is a reaction of organism to irritation, injury, or infection.

5 Acute inflammation Pain Redness Immobility Swelling Heat

7 Inflammatory Cytokines

8 Outcomes of Acute Inflammation 1. Resolution

9 Outcomes of Acute Inflammation 2. Fibrosis

10 Outcomes of Acute Inflammation 3. Abscess formation Acute Appendicitis

11 Outcomes of Acute Inflammation 4. Chronic inflammation

12 Role of Chronic Inflammation in Modern Human Diseases a. Cardiovascular Disease b. Cancer c. Chronic Infections d. Arthritis e. Allergy f. Alzheimer g. Parkinson h. Multiple Sclerosis

13 Beneficial Micronutrients and Food Products in Chronic Inflammation 1. Vitamins A, B, C, D, E 2. Protein Proline, Lysine, Arginine 3. Fats and Oils Omega-3 and Monounsaturated Fatty Acids 4. Phytochemicals Green Tea, Citrus, Ginger, Pomegranate, Chokeberry, Cabbage, Turmeric, Walnut

14 Inflammation in Cardiovascular Disease Macrophage Lipids Smooth Muscle Cell Accumulation Deposition Proliferation

16 Inflammatory Cytokines

17 Micronutrients decrease inflammatory response of human aorta smooth muscle cells Inhibition of Cytokines Secretion Pro-IL1beta 89% IL-1beta 87% Caspase-1 63% IL-1alpha 55% IL-6 70% Ivanov et al., Research Communications in Pharmacology and Toxicology, 2004, 9:3-16

18 MCP-1 secretion % Micronutrients Decrease Secretion of Monocyte Chemoattractant Protein (MCP-1) MCP-1 Decrease 43% Control TNFa TNFa+NS 100 mcg/ml

19 Role of COX-2 in Inflammation

20 PGE-2 secretion pcg/ml Regulation by PG-E2 production by Nutrient Mixture 1400 PG-E2 Secretion p<0.001 vs LPS Control 10 mcg/ml LPS LPS+NM Ivanov V. et al., International Journal of Molecular Medicine. 2008;22(6):

21 PG-E2 formation, pg/ml Inhibition of COX-2 Activity by Nutrients COX-2 Activity p<0.05 for a trend Nutrient Mixture mcg/ml Ivanov V. et al., International Journal of Molecular Medicine. 2008;22(6):

22 Regulation of Inflammation (cytokines release) by PG-E2 signaling Activation (NFkb) COX-2 gene expression Synthesis of COX-2 enzyme PG-E2 Production by COX-2 from Arachidonic Acid Induction of Cytokine Release by PG-E2

23 Phosphorylated p65 increase, % INFLAMMATION Regulation by PG-E2 signaling Activation (NFkb) COX-2 gene expression p<0.05 vs Synthesis of COX- 2 enzyme PG-E2 Production LPS LPS + EFC Ivanov V. et al., International Journal of Molecular Medicine. 2008;22(6):

COX-2 RNA relative to B- Actin INFLAMMATION Regulation by PG-E2 signaling Activation (NFkb) COX-2 gene expression Synthesis of COX- 2 enzyme PG-E2 Production 0.

24 COX-2 RNA relative to B- Actin INFLAMMATION Regulation by PG-E2 signaling Activation (NFkb) COX-2 gene expression Synthesis of COX- 2 enzyme PG-E2 Production p=0.02 vs LPS Control LPS LPS+Nutrient Mixture Ivanov V. et al., International Journal of Molecular Medicine. 2008;22(6):

25 COPX2/bActin Ratio, % of LPS INFLAMMATION Regulation by PG-E2 signaling Activation (NFkb) COX-2 gene expression Synthesis of COX- 2 enzyme PG-E2 Production p<0.005 vs LPS 0 Control LPS LPS+NM Ivanov V. et al., International Journal of Molecular Medicine. 2008;22(6):

26 PGE-2 secretion pcg/ml INFLAMMATION Regulation by PG-E2 signaling Activation (NFkb) COX-2 gene expression PG-E2 Secretion Synthesis of COX-2 enzyme PG-E2 Production p<0.001 vs LPS Control 10 mcg/ml LPS LPS+NM Nutrient Mixture Regulates PG-E2 Production by Both: Direct Inhibition of COX-2 Activity Inhibition of COX-2 Synthesis Ivanov V. et al., International Journal of Molecular Medicine. 2008;22(6):

27 CONCLUSIONS Micronutrients can effectively control pathological processes involved in the development and maintaining of chronic inflammation by multiple molecular actions

Depression, omega 3 fatty acid therapy 13

Depression, omega 3 fatty acid therapy 13 Subject Index Adhesion molecules fish oil effects 12, 13 omega 3 fatty acid desaturase transfection effects on expression in endothelial cells 31 Alzheimer s disease (AD), omega 6 fatty acid/omega 3 fatty