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Nitric oxide-bryan
This document discusses nitric oxide (NO) research presented by Nathan Bryan, Chief Science Officer of Neogenis Labs. It summarizes that NO is an important signaling molecule in the body that plays roles in many physiological systems. However, the body's natural production of NO declines with age. The document proposes strategies for restoring NO levels through dietary sources of nitrates and nitrites, herbal extracts, and supplemental NO donors to promote cardiovascular and overall health. Clinical trials on a supplemental lozenge product showed increased plasma NO markers and benefits such as reduced triglycerides and blood pressure.
Nitric oxide-bryan
- 1. Leading nitric oxideresearch. Changing lives. Nitric Oxide: The Miracle Molecule Nathan S. Bryan, Ph.D. Chief Science Officer for Neogenis Labs Professor of Molecular Medicine at the University of Texas Health Sciences Center at the Houston Institute for Molecular Medicine Disclosure: N.S. Bryan is a paid consultant and Chief Science Officer of Neogenis Labs, Inc. 1 Monday, June 20, 2011
- 2. Leading nitric oxideresearch. Changing lives. Nitric Oxide: Research One of the Most Studied Molecules In Medical History 2 Monday, June 20, 2011
- 3. What is NitricOxide? • A gas with chemical formula NO • A free radical, reacting with the oxygen in air to form nitrogen dioxide • One of the few “signaling” molecules in the body of mammals including humans – Naturally produced in the endothelium – Literally “tells” surrounding muscles to relax – Enhances blood flow through proper dilation 3 Monday, June 20, 2011
- 4. Thousands of Trials& Published Studies Nitric Oxide Molecule of the Year Over 120K Articles On Nitric Oxide 4 Monday, June 20, 2011
- 5.
- 6. Leading nitric oxideresearch. Changing lives. Nitric Oxide: In the body “The discovery of Nitric Oxide and its function is one of the most important in the history of cardiovascular medicine.” The American Heart Association Quoted in The New York Times 6 Monday, June 20, 2011
- 7. Nitric Oxide Cell Proliferation Apoptosis Angiogenesis Tumor cellgrowth Immunology Unspecified immunity Inhibition of viral replication Transplant rejection Cardiovascular System Vasorelaxation Blood cell regulation Myocardial contractility Microvascular permeability Peripheral Nervous System NANC nerve-mediated relaxation Central Nervous System Learning/memory Pain sensitization Epilepsy Neurodegeneration Central BP control Respiratory Tract Bronchodilation Asthma, ARDS Gastrointestinal/ Urogenital Tract Penile erection Pre-term labor 7 Monday, June 20, 2011
- 8. Nitroglycerine, the OriginalNitric Oxide Donor Smooth muscle Endothelium Plaque Adventia Atherosclerosis=plaques reduce blood flow • decreases oxygen supply to the heart • causes angina pectoris or myocardial infarction 8 Monday, June 20, 2011
- 9. Nitroglycerine, the OriginalNitric Oxide Donor Smooth muscle Endothelium Plaque Adventia Nitroglycerine provides NO to the narrow atherosclerotic vessel 9 Monday, June 20, 2011
- 10. Shear stress Thrombocytes MonocytesGranulocytes > anti-atherosclerotic properties Regulation of vascular tone and blood pressure Inhibition of aggregation of thrombocytes and of adhesion of thrombocytes, monocytes and granulocytes at the endothelium Cardiovascular Effects of NO Inhibition of migration and proliferation of smooth muscle cells 10 Monday, June 20, 2011
- 11. Leading nitric oxideresearch. Changing lives. Nitric Oxide: Disease Development “NO plays an important role in the protection against the onset and progression of cardiovascular disease.” 2005, PubMed 11 Monday, June 20, 2011
- 12. Endothelial Dysfunction isthe Enemy Insufficient Nitric Oxide levels = endothelial dysfunction Sufficient Nitric Oxide levels = endothelial cells communicate with surrounding tissues telling them to relax Endothelial Dysfunction = contributor to all major CV diseases 12 Monday, June 20, 2011
- 13. RISK FACTORS Hyperlipidemia Arterial hypertension Smoking Age(45 males: 55 females) Plasma NO concentrations reflect the degree of endothelial dysfunction in humans. Kleinbongard et al FRBM 2006 Plasma NO & Endothelial Dysfunction 13 Monday, June 20, 2011
- 14. Nitric Oxide Production& Aging Gerhard et al Hypertension 1996 Celermajer et al JACC 1994 Taddei et al Hypertension 2001 Egashira et al Circulation 1993 Adults over 40 make far less Nitric Oxide than their bodies need 14 Monday, June 20, 2011
- 15. L-Arg L-Arg Arginase ADMA NOS Uncoupling Reduced Oxygen Reduced Cofactor+ Substrate Oxidative Stress Antioxidants NO2 NO3 Oxidation Bacterial Reduction NO O2 -٠۰ ONOO- Disease BH4 Ca/Cam FAD+ FMN NADPH O2 Heme iron GSH Mitochondria XO NADPH oxidase Urea Cycle L-Arg Health Diet The Complex L-arginine Pathway 15 Monday, June 20, 2011
- 16. How the roadfrom promising scientific breakthrough to real-world remedy has become all but a dead end. “From 1996 to 1999, the U.S. food and Drug Administration approved 157 new drugs. In the comparable period a decade later—that is, from 2006 to 2009—the agency approved 74. Not among them were any cures, or even meaningfully effective treatments, for Alzheimer’s disease, lung or pancreatic cancer, Parkinson’s disease, Huntington’s disease, or a host of other afflictions that destroy lives.” Newsweek, May 15, 2010 The Current Environment 16 Monday, June 20, 2011
- 17. Co-factor or SubstrateSupplementation L-Arginine Ascorbic Acid Folic Acid Tetrahydrobiopterin (BH4) Nitrosothiols Nitrite/Nitrate Nitro-fatty acids Nitroglycerin/organic nitrates NO hybrid drugs (NO-NSAIDS) Require Functional NOS System NOS-Independent Sources of NO Ways to enhance NO availability 17 Monday, June 20, 2011
- 18. Dietary nitrate israpidly absorbed into the bloodstream, where it mixes with endogenous nitrate from the NOS/NO pathway. A large portion of nitrate is taken up by the salivary glands, secreted with saliva and reduced to nitrite by symbiotic bacteria in the oral cavity. Salivary-derived nitrite is further reduced to NO and other biologically active nitrogen oxides in the acidic stomach. Remaining nitrite is rapidly absorbed and accumulates in tissues, where it serves to regulate cellular functions via reduction to NO or possibly by direct reactions with protein and lipids. NO and nitrite are ultimately oxidized to nitrate, which again enters the enterosalivary circulation or is excreted in urine. Human Nitrogen Cycle 18 Monday, June 20, 2011
- 19. Bryan et alPNAS (2007) Comparing mice on a low nitrite diet and mice receiving supplemental nitrite 19 Monday, June 20, 2011
- 20. Bryan et alPNAS (2007) Heart attack injury is reversed 20 Monday, June 20, 2011
- 21. * * * Bryan et al,FRBM 2008 Steady state levels of NOx affected both By diet and NOS 21 Monday, June 20, 2011
- 22. Bryan et al,FRBM 2008 Nitrite Reverses MIR injury in eNOS-/- mice 22 Monday, June 20, 2011
- 23. LDL LDL Endothelium Vessel Lumen Intima Monocyte Modified LDL Macrophage TCells Neutrophils Smooth Muscles Proliferation Foam cells LESION Atherogenesis 23 Monday, June 20, 2011
- 24. Stokes, et al.AJP 2009 High fat diet induces microvascular inflammation that is inhibited by nitrite supplementation 24 Monday, June 20, 2011
- 25. High Fat Diet NitritePre-Clinical Trial Actual artery with high fat diet & endothelial dysfunction 25 Monday, June 20, 2011
- 26. High Fat Diet+ Nitrite Nitrite Pre-Clinical Trial Same artery after nitrite treatment, improved blood flow 26 Monday, June 20, 2011
- 27. Stokes, et al.AJP 2009 High fat diet causes endothelial dysfunction and reversed by supplemental nitrite 27 Monday, June 20, 2011
- 28. Stokes, et al.AJP 2009 High fat diet causes increase in CRP and reversed by nitrite 28 Monday, June 20, 2011
- 29.
- 30. 0.25mg/kg Nitrite in BreastMilk is Absent in Formula 30 Monday, June 20, 2011
- 31. Nitrite is Enrichedin Colostrum and Declines as Gut Bacteria Colonize 31 Monday, June 20, 2011
- 32. Traditional Chinese Medicine(TCM) has been used as a main stream of medical care throughout Asia for centuries. But it is still considered an alternative medical system in the western world. Mostly because of a lack of understanding of their mechanisms of action and/or the active compounds. Many cardiovascular diseases are characterized by a NO insufficiency. There are a number of published reports on the association of TCM and NO- related effects in cardiovascular field. However, their mechanism of action is far from clear. Traditional Chinese Medicine 32 Monday, June 20, 2011
- 33. Tang et alFRBM 2009 Traditional Chinese Medicines for CVD 33 Monday, June 20, 2011
- 34. Kinetics of NOFormation From Herbs 34 Monday, June 20, 2011
- 35. Endothelial Impact ofSelect Herbs 35 Monday, June 20, 2011
- 36. NO3 - NO2 - NO OXIDATION REDUCTION Probiotics Herbs with reductive capacity Beet,artichoke, etc Oxygen, ceruloplasmin Oxyheme proteins L-arginine Using Natural Product Chemistry 36 Monday, June 20, 2011
- 37. Leading nitric oxideresearch. Changing lives. Nitric Oxide: Restoration 37 Monday, June 20, 2011
- 38. Tibetans live at4200 meter above sea level. The low barometric pressure causes lower arterial oxygen content and subjects the highlanders to chronic hypoxia. Study: Can Nitric Oxide be Naturally Restored? 38 Monday, June 20, 2011
- 39. Erzurum et al. PNAS(2007) Results: Increased Blood Flow 39 Monday, June 20, 2011
- 40. Because of increasedNO production Erzurum et al. PNAS (2007) 40 Monday, June 20, 2011
- 41. Leading nitric oxideresearch. Changing lives. Nitric Oxide: Restoration 41 Monday, June 20, 2011
- 42. Leading nitric oxideresearch. Changing lives. Nitric Oxide: Restoration Over 40 L-arginine cannot be converted 42 Monday, June 20, 2011
- 43. Naturally Restoring NitricOxide Production 43 Monday, June 20, 2011
- 44. Strong & sustainedNitric Oxide activity Neo40 Daily Clinical Trial Results 44 Monday, June 20, 2011
- 45. 30-day regimen increased plasmanitrite and nitrate in patients Neo40 Daily Clinical Trial Results 45 Monday, June 20, 2011
- 46. Significant reduction inpatients with elevated triglycerides Neo40 Daily Clinical Trial Results 46 Monday, June 20, 2011
- 47. Neo40 Daily ClinicalTrial Results Modest reduction in blood pressure 47 Monday, June 20, 2011
- 48. Dosing & Protocol ObjectiveDose Routine Prevention, improved absorption of dietary nutrients & supplements 1 lozenge per day, dissolve on tongue Early in the morning on empty stomach Therapeutic, history of CV disease or current risk factors 1 lozenge, 2X per day, dissolve on tongue Early in the morning on empty stomach, ½ before dinner on empty stomach. At least 2 hours before bed. For exercise enhancement 1 lozenge 15-30 minutes before exercise 48 Monday, June 20, 2011
- 49.
- 50. The First &Only Saliva Test for NO Simple to use Instant, easy-to-read results 50 Monday, June 20, 2011
- 51. Testing Protocol Baseline Neo40Daily Test 1 Test 2 Repeat every week 1 test on empty stomach 1 lozenge on empty stomach 15 minutes later 2-3 hours later 51 Monday, June 20, 2011
- 52. Neo40 Daily Benefits BenefitHow it works Energy Circulation Sexual function Circulation Sleep Circulation Workout – pre & post Circulation Mental acuity Circulation Absorption of nutrients Circulation Blood flow to extremities Circulation 52 Monday, June 20, 2011
- 53. Chapter 3 NOtrition: NO-BoostingFoods and Supplements Go For the Greens “There’s a scientific revolution in progress, and it’s happening on your plate.” 53 Monday, June 20, 2011
- 54. Rich source ofnitrate (beet root, artichokes, etc) Contain the active nitrate and nitrite reductase, antioxidants and polyphenols that can generate nitrite and NO NO From Plants & Botanicals 54 Monday, June 20, 2011
- 55. H. Garg, Master’sThesis Western Menu Mediterranean Menu Breakfast Bagel w/ Cream Cheese Toast w/ Jam and Butter Black Coffee (12 oz) Cappuccino (Espresso+Milk) AM Snack Carrot Nut Muffin Yogurt (Strawberry) Diet Coke (12 oz) Carrot Juice (12 oz) Lunch Big Mac Mediterranean Wrap Large French Fries Garden Vegetable Soup Diet Coke (12 oz) Mineral Water (12 oz) PM Snack Snickers Trail Mix Black Coffee (12 oz) Orange Juice (12 oz) Dinner Cheese Pizza (4 slices) Salmon (Smoked) Diet Coke (12 oz) Red Wine (12 oz) Daily NO Intake Varies By Diet 55 Monday, June 20, 2011
- 56. The NO Contentof Beverages 56 Monday, June 20, 2011
- 57. The Ultimate NitricOxide Index Kale 6825 Swiss Chard 2055 Arugula 1452 Spinach 1123 Chicory 938 Wild Radish 814 Bok Choy 775 Collard Greens 697 Beets 632 Chinese Cabbage 499 Le>uce 388 Cabbage 312 Mustard greens 226 Cauliflower, Raw 167 Parsley 150 Kohlrabi 136 Carrot 127 Broccoli 122 57 Monday, June 20, 2011
- 58. Current paradigm forNO production through L-arginine is complex and inefficient, especially in the aging population Strategies to restore NO production/homeostasis will have a profound impact on public health Utilizing activity from natural products can overcome our inherent inefficiencies and provide an essential source of bioactive NO Rational design of NO rich herbs may provide a natural, cost effective and over the counter product for conditions related to NO insufficiency to improve health, performance and prevent disease. Recognizing foods rich in NO potential may provide information into the health benefits of certain foods/diets (Nitric Oxide Index) Conclusions 58 Monday, June 20, 2011
- 59. The University ofTexas Health Sciences Center at Houston Harsha Garg Yaoping Tang, M.D. Ferid Murad, M.D., Ph.D. Pamela Berens, M.D. Albert Einstein College of Medicine David Lefer, Ph.D. John Elrod, Ph.D. Mark Duranski John Calvert, Ph.D. Susheel Gundewar M.D. LSU Health Sciences Center at Shreveport Karen Stokes, Ph.D. Tammy Dugas, Ph.D. D. Neil Granger, Ph.D. Cleveland Clinic & Case Western Cynthia Beall S.C. Erzurum Dennis Steuhr J. Tejero Acknowledgements 59 Monday, June 20, 2011
- 60. www.destechpub.com ISBN: 978-1-932078-84-8, September 2009 238pages, 6x9, hardcover Price: $149.50 60 Monday, June 20, 2011
- 61.
- 62. Book Highlights: Restoring nitricoxide production in the body thereby combating: • High blood pressure • Heart attack • Stroke • Diabetes • Arthritis • Kidney disease • Memory loss • Osteoporosis 62 Monday, June 20, 2011