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Housekeeping Audio Audio can be heard directly through your computer speakers Questions (Q&A) Please e-mail your questions to clientservices2@PERQUE.com. Dr. Jaffe will answer questions within 24 hours. 2
Dr. Russell Jaffe, MD, Ph.D., CCN FASCP, FACN, FACAAI, FOCIS, FAMLI, FRSM Fellow, Health Studies Collegium Director, PERQUE Integrative Health & ELISA/ACT Biotechnologies, LLC 3
What is Methylation?Complex biological process: fuel for the bodyTransfer or donation of one carbon methylgroup (-CH3) to other molecules• Methyl donors• Methyl acceptors• Methyl carriers/factors 4
What is Methylation? Methylation acceptors need methyl carriers and donorsMethyl acceptors: nucleic acids/DNA, RNA, Proteins,Phospholipids, Bile salts, Biological aminesMethyl carriers: Vitamins B6, B12,folate, magnesiumascorbateMethyl donors: methionine, S-adenosylmethionine(SAMe), betaine (trimethylglycine). 5
Methylation in the bodyMagnesiumAscorbateMagnesiumAscorbate 6
Methylation deficitsDeficiency of methylation factors and donors Impaired protection Reduced detoxification Lack of mitochondrial energy 7
Clinical manifestations of hyperhomocysteinemia • Cardiovascular health coronary artery disease, renovascular hypertension, thrombotic and embolic events (stroke). • CNS effects: Vascular dementia, increased risk of multiple brain infarcts and Alzheimer’s senility. • Bone Health: strong link with bone mineral density, bone blood flowBoers GHJ, et al. Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. New Engl J Med 1985; 313:709-715.Refsum H, Nurk E, etal The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease. JNutr. 2006 Jun; 136(6 Suppl): 1731S-1740SNeetu Tyagi, Thomas P Vacek, John T Fleming, et al. Hyperhomocysteinemia decreases bone blood flow. Vascular Health and Risk Management,January 2011 8Volume 2011:7 Pg 31 – 35. (DOI: http://dx.doi.org/10.2147/VHRM.S15844)
Clinical manifestations of hyperhomocysteinemia • Cancer: both increased and decreased DNA methylation involved • Other • Chronic Fatigue Syndrome/ Fibromyalgia/muscle pain • PMS symptomsKim YI, et al. Global DNA Hypomethylation increases progressively in cervical dysplasia and carcinoma Cancer 1994; 74:893-899.Regland B, et al. Homocysteinosis in the central nervous system in patients with fibromyalgia/chronic fatique syndrome. Abstr Intern ConfHomocysteine Metabol 1995; Dromoland Castle, County Clare, Ireland, July 2-6.Cooney C, et al. Methyl magic: maximum health through methylation. Andrew McMeel Publishing, Kansas City, Missouri, 1999. 9
Cardiovascular EpigeneticsAndrea Baccarelli, Michiel Rienstra Emelia J. Benjamin. Cardiovascular Epigenetics Basic Concepts and Results From Animaland Human Studies. Circulation: Cardiovascular Genetics. 2010; 3: 567-573. 10
Cardiovascular Epigenetics DNA methylation Primary regulator of inflammation Homocysteine C-Reactive protein atherosclerosis, hypertension, and diabetesAndrea Baccarelli, Michiel Rienstra Emelia J. Benjamin.Cardiovascular Epigenetics Basic Concepts and Results From Animaland Human Studies. Circulation: Cardiovascular Genetics. 2010; 3:567-573. 11
Effect of Homocysteine Levels on Survival in CHD <6 mol/L <9 mol/L 9-15 mol/L 16X 4X 15-20 mol/L >20 mol/L 12
Healthy Methylation B6, B12, folates Difference in Five-Year Mortality Risk 1000% R e la t iv e R is k (in % ) 800% The Difference in Senility Risk 600% 200% S e n ility R is k (in % ) 400% 100% 200% 0% 0% <6.5 6.5-9 9. - 12. 12. - 15 >15 <6.5 >15 Relative Risk of Senility in Relation to Relative Risk at Different Homocysteine Levels Homocysteine LevelsArch Chem. 2004;50:3-32. and Arch Intern Med 2003;163:1933-1937. Schroecksnadel K, et. al. Hyperhomocysteinemia and immune activation. Clin Chem Lab Med 2003; 41(11):1438-1443.NEJM. 2002;346:476-483.
Methylation and autism • Vitamin insufficiency • Increased oxidative stress • Reduced capacity for energy transport, sulfation & detoxificationAdams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, Gehn E, Loresto M, Mitchell J, Atwood S, Barnhouse S, Lee W.Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutr Metab(Lond). 2011 Jun 8;8(1):34. 15
DNA methylation and immune systemDNA methylation patternshave relevance in immunefunction.Restoring methylation canstrengthen immunesystem-related therapies Suarez-Alvarez B, Rodriguez RM, Fraga MF, López-Larrea C.DNA methylation: a promising landscape for immune system-related diseases.Trends Genet. 2012 Oct;28(10):506-14. Epub 2012 Jul 21. 16
Overloaded Immune System means: • Chronic illness • Inflammation = Repair deficits • Increase in digestive remnants • Chronic, degenerative, autoimmune illnessJaffe R. Immune Defense and Repair Systems in Biologic Medicine: Clinical Relevance of Biological Response Modifiers inAutoimmunity: Diagnosis, Treatment, Tests, and Interpretation (Part I). Townsend Letter for Doctors and Patients 2009; Oct: 82-89. 17
Healthy Immune Responses • No allergies = tolerance • Neutralizes infections & allergens • Repairs us from daily damage • Deletes cancer cellsWhite blood cell recycles pathogens 18
Allergy Laboratory TestsType I AllergiesRAST or skin testsDelayed AllergiesLymphocyte responseassay needed to tell‘good’ from ‘bad’e.g. LRA by ELISA/ACTcovers all delayedpathways 19
Predictive Lab Tests with Healthy Goal values• Homocysteine <6 µmol/L for methylation, detox• CRP <0.5 mg/dl for repair deficit inflammation• Oxidative stress antioxidant sufficiency: Goal Oxidized LDL/HDL & 8-oxo-guanine absent• LRA by ELISA/ACT delayed allergy functional tests and treatment plans 20
Immune System: Enhance; Stop Burden Hospitable host to pathogens = Tolerance lost Allergens provoke symptoms: Overload of Foreign Reactive Antigens Repair deferred…defense 1st Only Functional tests can identify causes of immune overload… go by results 21
Physiology 1st approachImmune System: Reset, Renew, Repair, & Restore Tolerance Comprehensive Plan: • Lower burden by substituting reactives • Bioavailable nutritional supplements • Life long health the Alkaline Way Health Studies Collegium, The Joy of Food The Alkaline Way Guide, 18th ed. 2009-2010 22
To Your Health “Health is more than the absence of disease. Health is the fullest physical, mental, and spiritual expression attainable by each individual."Russ Jaffe paraphrasingHippocrates, Galen, Huang Ti, & WHO 24
Health Studies Collegium Questions WelcomeYou have been watching apre-recorded presentationPlease email us your questions toclientservices2@PERQUE.com and Dr.Jaffe will respond to them within 24hours. 25