46th Orthomolecular Medicine Today Conference by Journal of Orthomolecular Medicine

Annual International Conference

2017

syllabus

OMT rthomolecular Medicine Today

April 28 â&#x20AC;&#x201C; 30

toronto Omni King Edward Hotel

International Society for Orthomolecular Medicine

The Annual International Orthomolecular Medicine Today Conference is a continuing education event for MDs, PhDs, Pharmacists, NDs, NPs, RNs, and other health professionals. The Conference is presented by the International Society for Orthomolecular Medicine, which brings together orthomolecular associations established in 20 countries around the world. The 46th Conference will feature leading physicians and researchers presenting sessions on current advances in orthomolecular cardiology, psychiatry, endocrinology and general medicine.

International Society for Orthomolecular Medicine

April 28, 2017 Dear OMT Delegates, Speakers, Exhibitors and Guests Welcome to our 46th Annual International Orthomolecular Medicine Today Conference. We hope these next three days will provide fresh insight and clinical evidence for the advancement of your study and practice in the field of Orthomolecular Medicine. This year we are pleased to bring together 12 speakers, 18 exhibitors and 175 delegates and guests from countries around the world, including Algeria, Canada, Germany, Japan, Mexico, Nigeria, Pakistan, Spain, Sweden, Switzerland, Taiwan, The Netherlands, The United Kingdom and The United States of America. We are celebrating the 23rd anniversary of the founding of the International Society for Orthomolecular Medicine, which now has 21 country members representing over 33,000 individual members. The ISOM was established in 1994 to unite existing societies and to foster the growth of Orthomolecular Medicine internationally through education, communication and advocacy. The year 2017 marks the 50th Anniversary of the Journal of Orthomolecular Medicine, which is now available online, Open Access. We also mark the 14th Anniversary of the Orthomolecular Medicine Hall of Fame, as we induct four pioneers: Osamu Mizukami, MD; Stephen Lawson; James Greenblatt, MD; and Jonathan Prousky, ND, MSc, MA. We thank you for your continued dedication to Orthomolecular Medicine and wish you a most memorable Conference. With best regards,

Atsuo Yanagisawa

Steven Carter

Andrew Cuscianna

President

Founding Director

Program Manager

ISOM Meeting Sunday, April 30 8:30 am â&#x20AC;&#x201C; 10:00 am Please join us to hear reports on activities in education, communication and advocacy from Canada, Japan, Mexico, Spain, Sweden, Algeria, the Netherlands, USA and others among the countries in attendance at the Orthomolecular Medicine Today Conference. Donâ&#x20AC;&#x2122;t miss this opportunity to gain an international perspective on Orthomolecular Medicine.

Contents Conference Schedule...............................................................................................................................................1 Exhibitors.....................................................................................................................................................................2 Exhibitor Floor Plan..................................................................................................................................................3 Speakers’ Biographies..............................................................................................................................................4

Session One • Orthomolecular Medicine John Hoffer, MD, PhD In-hospital Vitamin C Deficiency and High-dose Vitamin C Therapy . ..................................................5 Aileen Burford-Mason, PhD Optimal Nutrition & Chronic Disease Prevention: Clinical Perspective on Laboratory Diagnostics ..........................................................................................15 Ron Hunninghake, MD A Unified Theory of Chronic Illness .................................................................................................................26

Session Two • Orthomolecular Cardiology Joel Kahn, MD Plant Based Reversal of Heart Disease ............................................................................................................40 Jack Wolfson, DO Evidence Based Integrative Cardiology ..........................................................................................................49 Heather Wolfson, DC Give the Body What it Needs and Take Away What it Doesn’t

Session Three • Orthomolecular Endocrinology Jonathan Prousky, ND, MSc, MA Childhood Absence Epilepsy – Putative Complementary Diet and Orthomolecular Treatment Options .......................................................................................................65 Jeffrey Dach, MD & Phyllis Bronson, PhD Debunking Myths about Hormones: Why Bioidenticals Matter ...........................................................75

Session Four • Orthomolecular Psychiatry Osamu Mizukami, MD, PhD Orthomolecular Psychiatry in Japan.................................................................................................................95 James Greenblatt, MD Integrative and Orthomolecular Therapies for ADHD............................................................................ 108 Toru Mizoguchi, MD Distinct Characteristics of Hematological Parameters in Psychiatric Disorders........................... 118

Badge colour code: Red=Speaker/Staff; Silver=Full Delegate; Blue=Sessional Delegate; Green=Exhibitor

Advanced chemistry for progressive practitioners We specialize in intravenous preparations; customizing naturopathic medicines, nutritionals, botanicals, hormones, chelates and other chemistries. Prepared with state-of-the-art equipment and in compliance with USP 795, USP 797 and USP 800. We stay abreast of therapies from leading-edge health scientists from around the world and work with you to deliver the best care possible.

C H E M I S T S Phone: 416-633-3273 Fax: 416-633-8273 info@yorkdownschemists.com

1450 Lodestar Rd. Unit 1, North York, ON M3J 3C1 www.yorkdownschemists.com Accredited by The Ontario College of Pharmacists # 301113

! ! !

1967 - 2017! ! ! Celebrating 50 years of advancing knowledge and the clinical practice of!orthomolecular medicine through research and education! NOW AVAILABLE â&#x20AC;&#x201C; !

â&#x20AC;&#x201C; WWW.ISOM.CA/JOM! !

The Official Journal of the

!!!!!!!!

International Society for Orthomolecular Medicine

Peak-EPA NPN 80073318

Natural lime essential oil flavour

# development of brain, eyes and nerves " # cognitive health healthy mood balance # cardiovascular health " # reduce the pain "

" " ! Improving health and wellnessâ&#x20AC;Śnaturally

" !

Cyto_PeakEPA_8.5x9.8wBleed.indd 1

2016-12-21 11:36 AM

VITAMINC THE PERFECT DELIVERY

1. Helps protect cells from the damage caused by free radicals*

Unlike pills and powders which are not absorbed HIÂ¼ FLHQWO\ /\SR 6SKHULFÂ&#x152; SURGXFWV XVH /LSRVRPDO Encapsulation Technology, so nutrients can enter the bloodstream and cells intact and read to work.

2. Supports a healthy immune system* 3. Supports collagen production for healthier skin, muscles and joints 4. Promotes muscle repair* 5. Supports healthy gums*

6. Supports optimal health* 7. Supports Paleo, Zone and Vegan Diets

% 100 V E G AN

NON

GMO

SUGAR

GLUTEN

FREE

HEXANE

FREE

LivOn

LABS

7 REASONS YOU NEED VITAMIN C

DAIRY

FREE

Cross-Section of a Liposome

LIVON LABS NUTRIENTS ARE PROTECTED BY MICROSCOPIC BUBBLES CALLED LIPOSOMES (LYPO-SPHERICâ&#x201E;¢)

LIPOSOME WALLS ARE MADE OF PHOSPHOLIPIDS, THE SAME MATERIAL THAT MAKES UP OUR CELLS.

PILLS AND POWDERS ARE NOT ABSORBED EFFICIENTLY. LYPO-SPHERICâ&#x201E;¢ PRODUCTS MAXIMIZE ABSORPTION.

www.

.ca

NO BOWEL INTOLERANCE NO VITAMIN C FLUSH YOU ABSORB MORE!

Natureâ&#x20AC;&#x2122;s Source is your best resource for integrative remedies. Natureâ&#x20AC;&#x2122;s Source is your best resource for integrative remedies. Our broad selection of natural health products for professionals is complimented by the in-house expertise of our carefully selected staff. Whether you are a Natural Health Practitioner, Medical Doctor, or Dentist looking for a unique product or want to catch up on the latest in integrative remedies, drop by your local Nature's Source or Nature's Signature today. Grow and promote your practice by tapping into our extensive network of customers with "Wellness Days". Contact us to learn how.

For more about Wellness Days and how to register as a Partner in Health for free, contact Namrata Vaya 416.994.9983 namrata@natures-source.com

+0(" 1+0 (&'# /+ (# -* )+-# +0/ 0.&*$ &/ )&* &* 1+0- ,- !/&!#

!/ CME CREDIT AVAILABLE

! "#)1 &!%&/ *. . Riordan Clinic

The Riordan Clinic IVC Academy is packed with two days of lectures, conversations, and camaraderie with other medical professionals who use high-dose Vitamin C in their practices.

*" *!#- +-$ Chief Medical Officer, Riordan Clinic

Cardiologist and Author

Conference Schedule Friday April 28

4FTTJPO 'PVS t 0SUIPNPMFDVMBS 1TZDIJBUSZ 2:00 pm 0TBNV .J[VLBNJ .% Orthomolecular Psychiatry in Japan

8:00 am Registration 8:30 am Exhibits open

3:00 pm +BNFT (SFFOCMBUU .% Integrative and Orthomolecular Therapies for ADHD

4FTTJPO 0OF t 0SUIPNPMFDVMBS .FEJDJOF 9:00 am

John Hoffer, MD, PhD In-hospital Vitamin C Deficiency and High-dose Vitamin C Therapy

4:00 pm Break - Visit Exhibits 4:30 pm 5PSV .J[PHVDIJ .% Abram Hoffer Memorial Lecture Distinct Characteristics of Hematological Parameters in Psychiatric Disorders

10:00 am Break - Visit Exhibits 10:30 am Aileen Burford-Mason, PhD Dr Rogers Prize Lecture Optimal Nutrition & Chronic Disease Prevention: Clinical Perspective on Laboratory Diagnostics

5:30 pm Exhibits Close

11:30 pm Ron Hunninghake, MD A Unified Theory of Chronic Illness

14th Annual

Orthomolecular Medicine Hall of Fame

12:30 pm Lunch - Visit Exhibits

7:00 pm Reception 7:30 pm Dinner and Induction

4FTTJPO 5XP t 0SUIPNPMFDVMBS $BSEJPMPHZ Evan Shute Memorial Lectures Controversies in Nutriton

Sunday April 30

2:00 pm Joel Kahn, MD Plant Based Reversal of Heart Disease

3:00 pm Break – Visit Exhibits

8:30 am Annual Meeting - International Society for 0SUIPNPMFDVMBS .FEJDJOF

10:00 am Break - Visit Exhibits

3:30 pm Jack Wolfson, DO Evidence Based Integrative Cardiology

10:30 am 0SUIPNPMFDVMBS .FEJDJOF 5PEBZ 'PSVN with OMT Speakers

Heather Wolfson, DC Give the Body What it Needs and Take Away What it Doesn’t

12:00 pm $MPTF 0.5 'PSVN

5:30 pm Exhibits Close

IV Vitamin C Academy

Saturday April 29

3PO )VOOJOHIBLF .% 5PN -FWZ .% +%

9:00 am Jonathan Prousky, ND, MSc, MA Childhood Absence Epilepsy – Putative Complementary Diet and Orthomolecular Treatment Options

1:30 PM

IVC Academy Part 1

3:00 PM

Break

10:00 am Break – Visit Exhibits

3:30 PM

IVC Academy Part 2

5:00 PM

4FTTJPO 5ISFF t 0SUIPNPMFDVMBS &OEPDSJOPMPHZ 10:30 am Jeffrey Dach, MD & Phyllis Bronson, PhD Debunking Myths about Hormones: Why Bioidenticals Matter

Thanks to our generous sponsor

12:30 pm Lunch - Visit Exhibits 1

■

46th Orthomolecular Medicine Today Conference Please Visit Our Exhibitors Acquired Intelligence, Inc. 205 -1095 McKenzie Avenue Victoria, BC V8P 2L5 Canada 250 483 3640 sales@salvestrol.ca www.salvestrol.ca

Helixor 7 - 465 King Street East Toronto, Ontario, M5A 1L6, Canada 877 734 1686 info@helixor.ca www.helixor.com

Nature’s Source Inc. 145 Ceremonial Drive Mississauga, Ontario, L5R 2N2, Canada 866 502 6789 info@natures-source.com www.natures-source.com

College Pharmacy 3505 Austin Bluffs Parkway Colorado Springs, CO 80918 USA 800 888 9358 / 719 262 0022 info@collegepharmacy.com www.collegepharmacy.com

Immundiagnostik AG Stubenwald-Allee 8a D-64625 Bensheim, Germany 49 (0) 6251 70190 0 info@immundiagnostik.com www.immundiagnostik.com

Nutritional Fundamentals for Health 3405 F.X. Tessier Vaudreuil-Dorion, QC J7V 5V5 Canada 866 510 3123 info@nfh.ca www.nfh.ca

Cyto-Matrix Inc. 103 - 300 March Road Ottawa, ON K2K 2E2 Canada 866 783 7504 info@cyto-matrix.com www.cyto-matrix.com

Integrative Therapeutics Nature’s Way of Canada 2 - 10 Brodie Drive Richmond Hill, Ontario, L4B 3K8, Canada 800 665 3414 salescanada@naturesway.com www.integrativepro.com

Pure Encapsulations 490 Elgin Mills Road East Richmond Hill, ON L4C 0L8 Canada 866 856 9954 info@purecaps.ca www.purecaps.ca

Designs for Health Canada 980 South Street Suffield, CT 06078 USA 877 414 9388 canadaorders@designsforhealth.com www.designsforhealth.ca Douglas Laboratories 490 Elgin Mills Road East Richmond Hill, ON L4C 0L8 Canada 866 856 9954 info@douglaslabs.ca www.douglaslabs.ca Genestra Brands 490 Elgin Mills Road East Richmond Hill, ON L4C 0L8 Canada 800 263 5861 sales@seroyal.com www.genestrabrands.ca

LivLong (LivOn Labs) 1203C 16th Street SE High River, AB T1V 2B1 Canada 844 246 5997 info@livlong.ca www.livlong.ca McGuff Medical Canada 74 - 556 Edwards Avenue Richmond Hill, Ontario, L4C 9Y5, Canada 800 958 8121 mmcianswers@mcguff.com www.mcguff.ca Metagenics Canada Inc. 15 - 3250 Ridgeway Drive Mississauga, ON L5L 5Y6 Canada 800 268 6200 brendaparsons@metagenics.com www.metagenics.ca

Smith’s Pharmacy 3463 Yonge Street Toronto, ON M4N 2N3 Canada 416 488 2600 info@smithspharmacy.com www.smithspharmacy.com The Great Plains Laboratory Inc. 11813 West 77th Street Lenexa, KS 66214 USA 800 288 0383 customerservice@gpl4u.com www.greatplainslaboratory.com York Downs Chemists 1 - 1450 Lodestar Road North York, ON M3J 3C1 Canada 416 633 3273 info@yorkdownschemists.com www.yorkdownschemists.com

Thanks to our generous sponsor

■

1 2

■

Nutrition Break

46th Annual International Orthomolecular Medicine Today Conference

Omni King Edward Hotel

Exhibitor Floorplan

Palm Court 16 18

Reception

Vanity Ballroom Foyer X

X Nutrition Break

Entrance to Vanity Ballroom

2017 OMT Exhibitor List 1 2 3 4 5 6 7 8 9

Genestra Brands Douglas Laboratories 1VSF &ODBQTVMBUJPOT $PMMFHF 1IBSNBDZ .D(VGG .FEJDBM $BOBEB Designs for Health Natures Source Inc. Metagenics The Great Plains Laboratory Cyto-Matrix Inc. 3

10 11 12 13 14 15 16 17 18

LivLong (LivOn Labs) Login Canada Nutritional Fundamentals for Health (NFH) Acquired Intelligence / Salvestrol Helixor Immundiagnostik AG York Downs Chemists Integrative Therapeutics 4NJUIhT 1IBSNBDZ

0SUIPNPMFDVMBS .FEJDJOF conceptualized by double Nobel laureate Linus Pauling, is the practice of optimizing health and treating disease by providing, according to individual biochemistry, correct amounts of vitamins, minerals, amino acids, essential fatty acids and other nutrients which are natural to the body’s environment.

Conference Speakers

Phyllis Bronson, PhD, holds a doctorate in biochemistry. Her ongoing research is focused on the science behind bioidentical molecules and ongoing work on mood and emotion. Dr. Bronson works with women who have hormone-based mood disorders, utilizing her original research, along with her medical partner, Chris Martinez, MD. She lives in Aspen, Colorado, and is President of Biochemical Consulting and The Biochemical Research Foundation. Phyllis is the author of Moods, Emoitions and Aging.

Joel Kahn, MD, serves as a Clinical Professor of Medicine at Wayne State University School of Medicine and is the founder of the Kahn Center for Cardiac Longevity. He is the author of 3 bestselling books and The Whole Heart Solution is now a public TV special. He writes for the Huffington Post and other media sites. He was voted the Sexiest Male Vegan over 50 by PETA.org in 2016. He owns GreenSpace Cafe in Ferndale, MI, the largest plant based restaurant and bar between the coasts

Aileen Burford Mason, PhD, is an immunologist, cell biologist and orthomolecular nutritionist with a deep interest in the scientific evidence for nutrition and health. She regularly gives seminars for both professional and lay audiences, and has become known for taking complex nutritional research and translate it into concise, evidence-based guidelines for the safe, effective use of nutritional supplements. She is formerly Assistant Professor in the Department of Pathology in the Faculty of Medicine, University of Toronto, and Director of a cancer research laboratory at The Toronto General Hospital. Dr. Burford-Mason is the author of the best-selling book Eat Well, Age Better. Her new book The Healthy Brain will be published by HarperCollins Canada in the Fall of 2017.

Toru Mizoguchi, MD, graduated in 1990 from Fukushima Medical University, then worked at Yokohama City University Hospital, National Cardiovascular Center. Since 2000, he has incorporated orthomolecular medicine into his practice, having many improved cases for intractable diseases. In 2003, Japan’s first orthomolecular medicine specialized clinic “Shinjuku Mizoguchi Clinic” was established. In addition to his clinical practice, Dr. Mizoguchi lectures for patients and physicians. With his teacher, Dr. Masatoshi Kaneko, was a leader in introducing orthomolecular medicine in to Japan. Today, over 1,300 medical institutions include orthomolecular treatment.

Jeffrey Dach, MD is specialty board-certified in diagnostic and interventional radiology with 25 years experience serving the Memorial Healthcare System in Hollywood, Florida. After retiring from radiology in 2004, Dr Dach returned to clinical medicine and founded TrueMedMD, a clinic in Davie, Florida specializing in bioidentical hormones and natural thyroid. Dr Dach is author of two books, Natural Medicine 101 and Bioidentical Hormones 101, available free online. He serves on the editorial board for Alternative Therapies in Health and Medicine and publishes a monthly free newletter at www.jeffreydachmd.com.

Osamu Mizukami, MD, is the President of Japanese Society for Orthomolecular Medicine, and the Director of Health Promotion Clinic in Tokyo. He graduated from the Hirosaki University School of Medicine in 1973, and since then he has worked as a pioneering integrative internist in Japan. He received a PhD from the Tokyo Medical and Dental University, and a DPH from Loma Linda University. Dr Mizukami started using high-dose IV vitamin C 40 years ago and began to practice orthomolecular psychiatry in 2007. He has published 15 books including Create Health, and High-Dose IV Vitamin C for Cancer Patients.

James Greenblatt, MD, is the Chief Medical Officer of Walden Behavioral Care in Waltham, Massachusetts. He received his medical degree and completed his adult psychiatry residency at George Washington University in Washington, DC, and completed a fellowship in child and adolescent psychiatry at Johns Hopkins Medical School. He maintains a private practice in Waltham, Massachusetts. Dr. Greenblatt is Medical Director of Comprehensive Psychiatric Resources, an orthomolecular treatment center in Boston, Massachusetts and is Assistant Clinical Professor at Tufts University Medical School, Department of Psychiatry.

Jonathan Prousky, ND, MSc,MA, graduated from Bastyr University with a Doctorate in Naturopathic Medicine. He is the Chief Naturopathic Medical Officer at the Canadian College of Naturopathic Medicine and also supervises at the Robert Schad Naturopathic Clinic. He is a passionate advocate for patients who have psychiatric disorders and focuses his clinical practice on optimizing mental and neurological health with nutrition and botanical (plant-based) medicines. He has lectured extensively on various health-related topics throughout North America and is the current editor of the Journal of Orthomolecular Medicine. His clinician-based research primarily involves the neuropsychiatric applications of vitamin B3.

Leonard John Hoffer, MD, PhD, trained in medicine and internal medicine at McGill University in Montreal and obtained a PhD in nutrition from the MIT and completed fellowships in nutritional support (Harvard Medical School) and biochemistry (Brandeis University). He is Professor of Medicine at McGill University, an investigator in the Lady Davis Institute for Medical Research, and Senior Physician in the Division of General Internal Medicine, Jewish General Hospital, Montreal. In addition to his clinical research on vitamin C deficiency and high-dose vitamin C therapy, he has authored chapters on human starvation and nutritional support in textbooks, including upcoming chapters in Scientific American Nutrition and Harrison’s Principles of Internal Medicine. In 2012 he received the Kursheed Jeejeebhoy Award and Plenary Lecture of the Canadian Nutrition Society.

Heather Wolfson, DC, is a chiropractic physician who provides chiropractic and nutritional care to adults and children. She is an incredible mom who home-birthed her two sons, Noah and Brody, and is raising the children in a holistic fashion that includes breast feeding, co-sleeping, and chemical-free living. Dr. Heather is a native of Arizona, loves the outdoors, and is active in animal rights and environmental safety

Ron Hunninghake, MD, completed his medical residency at the Smoky Hill Family Practice Program in Salina, Kansas in 1982. He joined the Riordan Clinic in 1989 as its Medical Director. In addition to his full-time practice as a holistic medical doctor a, Dr. Ron has made multiple trips to Japan, Spain, Ecuador, Columbia, New Zealand, Canada and South Korea to lecture on The Riordan IVC Protocol for Cancer. He has presented more than 400 lectures, including at the OMT, dealing with all facets of nutrition, lifestyle, and optimal health. He has co-authored three books on inflammation, energyboosting supplements, and how to stop pre-diabetes.

Jack Wolfson, DO, is a board-certified cardiologist who grew tired of patients failing to get well (while sometimes feeling worse) using pharmaceuticals and procedures. As a result, he opened Wolfson Integrative Cardiology where he now uses indepth testing and targeted nutrition to prevent and treat cardiovascular disease. He treats the whole person, getting to the cause of the issue, instead of treating only the symptoms. Dr. Wolfson offers practical solutions for heart health in person at his office in Paradise Valley, Arizona. He is the author of the Amazon bestseller, The Paleo Cardiologist.

!"#$%#$!& In-hospital Vitamin C Deficiency and High-dose Vitamin C Therapy

John Hoffer

Presentation Outline

In-Hospital Vitamin C Deficiency and Highdose Vitamin C Therapy

•! DG;+.H=8-I&H?+;2-9?G8.B&=@>&@<8.?J+@& •! •! •! •!

K?8=9?@&5&>-L;?-@;B&>?G-=G-& *BE+M?8=9?@+G?G&5& 4-;+99-@>->&?@8=N-&O+.&2-=:82B&E-+E:-&P&82-&G=8<.=J+@&;+@;-E8&& Q?+;2-9?;=:&?@>?M?><=:?8B&

•! DG;+.H=8-&9-8=H+:?G9&?@&>?G-=G-& •! R@8=N-C&:+GGC&;=8=H+:?G9& •! SBG8-9?;&?@T=99=J+@& •! S-EG?G&

'(&)(&*+,-.&/0&120&34515& 6$!"&7.82+9+:-;<:=.&/->?;?@-&A+>=B&

•! U2B&9=?@G8.-=9&9->?;?@-&?V@+.-G&M?8=9?@&5&

3.?>=BC&DE.?:&6FC&6$!"&

•! S+9-&W+.>G&+O&-@;+<.=V-9-@8&

D;?>&

Q=G-&

0?8&

4-><;J+@&

DG;+.HB:&O.--&.=>?;=:&^

7]?>=J+@&

6#&=@>&\#;=.H+@& 9-8=H+:?8-G&=::& -];.-8->&?@& <.?@-C&?@;:<>?@V& +]=:=8-&

4+H?8=?::-&'C&*+,-.&')(&D&G?9E:-&9-82+>&O+.&E:=G9=&8+8=:&M?8=9?@&5& =@=:BG?G&G<?8=H:-&O+.&.+<J@-&;:?@?;=:&:=H+.=8+.B&<G-(&X<8.&)&6$!YZ&![I%$&&

Transport •! DG;+.H=8-&2?V2:B&;+@;-@8.=8->&?@&82-&JGG<-G&

•! D::&;-::G&<G-&G+>?<9#>-E-@>-@8&SK5A6&8.=@GE+.8-.& •! R@8-GJ@-C&N?>@-BC&:?M-.C&:<@VGC&GN?@&<G-&SK5A!&=@>&SK5A6& •! aE?82-:?=:&JGG<-G&

•! 0-2B>.+=G;+.H?;&=;?>&

•! b'cA&dV:<;+G-&8.=@GE+.8-.e&

1=>=B=_&S)C&'-M?@-&/(&7.=:&0?G(&6$!YZ66I%Y\#`\&

!"#$%#$!& In-hospital Vitamin C Deficiency and High-dose Vitamin C Therapy

John Hoffer

Normal Biochemical Roles

Vitamin C Deficiency

•! 4-><;JM-&;+O=;8+.&?@&2B>.+]B:=J+@&.-=;J+@G&

•! S;<.MB&

•! DG;+.HB:&O.--&.=>?;=:&G;=M-@V-G&2?V2:B&.-=;JM-&O.--& .=>?;=:G&

•! *BE+M?8=9?@+G?G&5&

•! f--EG&;=8=:BJ;&?.+@&?@&.-><;->&G8=8-& •! 1.+#;+::=V-@&8+&;+::=V-@Z&;=8-;2+:=9?@-&GB@82-G?GZ& *R3#!Z&-8;(&

•! 1:=G9=&M?8=9?@&5&;+@;-@8.=J+@&i&!!(%&j9+:k'&=@>& ;+9E=JH:-&;:?@?;=:&GB@>.+9-&W?82&E.+9E8&.-GE+@G-&8+& =EE.+E.?=8-&M?8=9?@&5&82-.=EB& •! 4=.-C&>?=V@+G?G&;+99+@:B&9?GG->& •! 1:=G9=&M?8=9?@&5&i&6F(%&j9+:k'& •! !$l&+O&V-@-.=:&E+E<:=J+@Z&\$l&+O&G9+N-.GZ&Y$l&+O& =;<8-:B&2+GE?8=:?m->&E=J-@8G&

•! A2?G&:+@V#:?M->&O.--&.=>?;=:&?G&=&g.=>?;=:&G=O-&2=M-@h& -=G?:B&;+@M-.8->&8+&DD&+.&0*D&

•! /=.V?@=:&M?8=9?@&5&>-L;?-@;B&&

•! 1:=G9=&M?8=9?@&5&i&6F(%&H<8&n&!!(%&&

•! /=@B&=GE-;8G&+O&@+.9=:&@-<8.+E2?:&O<@;J+@&

Recommended Dietary Allowance: Healthy People

Scurvy

•! S;<.MB&9=B&H-&E.-M-@8->&HB&!$&9Vk>=B&

•! *-@;-&:+@VG8=@>?@V&.-;+99-@>=J+@&82=8&%$&9Vk>=B&?G&-@+<V2&

•! 5<..-@8&.-;+99-@>=J+@&H=G->&+@&JGG<-&G=8<.=J+@&E.?@;?E:-&

•! !$$&9V&E-.&>=B&9+G8:B&G=8<.=8-G&@-<8.+E2?:G&=@>&9+@+@<;:-=.&;-::G& •! 6$$&P&[$$&9V&E-.&>=B&G:?V28:B&O<.82-.&?@;.-=G-G&JGG<-&;+@;-@8.=J+@& •! 5?V=.-o-&G9+N-.G&.-p<?.-&q&[$l&9+.-&82=@&2-=:82B&@+@#G9+N-.G&

•! 5<..-@8&.-;+99-@>=J+@&?V@+.-G&H?+;2-9?;=:&?@>?M?><=:?8B& dSK5A!&=@>&SK5A6&E+:B9+.E2?G9Ge&&

!"##$%&#'()*+,-(.-('/"0$01)*-2"((3'4-1)'56)7"(.0%(-8)*'$(&82.--&-]=9E:-G&O.+9&& U=:8-.G&4U&!"#$%&'"()*+,-&6$$YZ!%6IY[F(&&

Recommended Intake in Disease States

•! X4Q#XDSI&X+&.-;+99-@>=J+@&H-;=<G-&40DG&=.-&O+.& 2-=:82B&E-+E:-&

•! A+&E.-M-@8&;+9E:-]&.-V?+@=:&E=?@&GB@>.+9-&d.-T-]& GB9E=82-J;&>BG8.+E2BeI&[$$&8+&![$$&9V&E-.&>=B& O+.&[$&>=BG&

•! A+&E.-M-@8&;+9E:-]&.-V?+@=:&E=?@&GB@>.+9-&d.-T-]& GB9E=82-J;&>BG8.+E2BeI&[$$&8+&![$$&9V&E-.&>=B&O+.&[$&>=BG& •! '?;289=@&D9&D;=>&7.82+E=->?;&S<.V&6$!!Z&/--@=&a<.&)&7.82+E& S<.V&A.=<9=8+:&6$![Z&52-@&5:?@&)&1=?@&6$!YZ&cE8+0=8-r&6$!"&P&B-G&& •! aM=@?-W&)&7.82+E&A.=<9=&6$![&P&<@E.+M-@&&&

•! A+&E.-M-@8&E+G8+E-.=JM-&E=?@&=@>&9+.E2?@-&.-p<?.-9-@8G&

5+9E:-]&.-V?+@=:&E=?@&GB@>.+9-&

•! 52-@&S(&5:?@&)&1=?@&6$!YZ&\6I!"`#F[&&

2oEIkkWWW(+.82+H<::-8G(;+9kH=G?;#G;?-@;-kY$`[k;+9E:-]#.-V?+@=:#E=?@#GB@>.+9-#;.EG&

In-hospital Vitamin C Deficiency and High-dose Vitamin C Therapy John Hoffer

!"#$%#$!& In-hospital Vitamin C Deficiency and High-dose Vitamin C Therapy

John Hoffer

Sepsis

Except Vitamin C

•! S-EG?G&&?G&=&:?O-#82.-=8-@?@V&+.V=@&>BGO<@;J+@& ;=<G->&HB&=&>BG.-V<:=8->&2+G8&.-GE+@G-&8+& ?@O-;J+@& •! 1=J-@8&>?-G&##&@+8&H-;=<G-&H=;8-.?=&-=8&82-9&<E&##& H<8&O.+9&;?.;<:=8+.B&=@>&+.V=@&O=?:<.-& •! /=@B&82-.=E?-G&2=M-&H--@&>-M-:+E->&=@>&8-G8->&8+& G8=H?:?m-&82-&G-EG?G&GB@>.+9-&H<8&=::&+O&82-9C&G+& O=.C&2=M-&O=?:->&&&

•! /=@B&=@?9=:&G8<>?-G&?@>?;=8-&82=8&2?V2#>+G-& =G;+.H=8-&=o-@<=8-G&9=@B&+O&82-&E=82+:+V?;=:& O-=8<.-G&+O&G-EG?GC&E.+8-;J@V&9?;.+M=G;<:=.& ?@8-V.?8BC&E.-G-.M?@V&H:++>&T+WC&:?9?J@V&:<@V&?@s<.B& =@>&=H@+.9=:&82.+9H+G?GC&=@>&E.-M-@J@V& @-<8.+E2?:&>BGO<@;J+@(&& •! *?V2#>+G-&M?8=9?@&5&9=B&GJ9<:=8-&>-E.-GG->& ;=8-;2+:=9?@-&GB@82-G?G&?@&G-EJ;&G2+;N&d5=..&D5& 5.?8&5=.-&6$![Z!`I%!Fe&&

4-Day Clinical Trial in Septic ICU Patients

!%&Vk>=Bt&

•! F&E=J-@8G&.-;-?M->&G8=@>=.>&R5c&;=.-& •! F&E=J-@8G&.-;-?M->&G8=@>=.>&;=.-&E:<G&=G;+.H=8-&!& V&-M-.B&Y&2&RK& •! F&E=J-@8G&.-;-?M->&G8=@>=.>&;=.-&E:<G&=G;+.H=8-& \([&V&-M-.B&Y&2&RK&

\([&Vk>=Bt&

t&3+.&=&"$&NV&E=J-@8&

S73D& S-p<-@J=:&7.V=@& 3=?:<.-&DGG-GG9-@8&

!"#$%#$!& In-hospital Vitamin C Deficiency and High-dose Vitamin C Therapy

John Hoffer

Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury (CITRIS-ALI)

Fowler, Alpha Alsbury Hite, Duncan R. Martin, Gregory S. Truwit, Jonathon D. Virginia Commonwealth University, Richmond, VA, United States

2oEIkkV.=@8+9-(;+9kV.=@8kXR*kc/!#*'!!YFF[#$6&

Why Does Mainstream Medicine Continue to Ignore Vitamin C? •! /->?;=:&G;2++:&=@>&E+G8#V.=><=8-&9->?;=:&-><;=J+@&P&?@>-->C&82-&-@J.-& =;=>-9?;&9->?;=:&;<:8<.-&P&@-V:-;8G&=@>&>+W@E:=BG&@<8.?J+@C&=@>&:=;NG&=& @<8.?J+@=:&E-.GE-;JM-&

4-E<H:?;=@& S<EE+.8-.G&

•! /->?;=:&;<:8<.-&?G&=&G+;?=:&;+@8.=;8&W?82&.<:-GC&.?V28GC&+H:?V=J+@GC&E.+8-;J+@G& =@>&E.-G<9EJ+@GC&=@>&?8&-];:<>-G&@<8.?J+@&

0-9+;.=J;& S<EE+.8-.G&

•! 5<:8<.-&8.<9EG&G;?-@;-C&8.<9EG&:+V?;&&

&&&

•! K?8=9?@&5&?G&-9+J+@=::B&8=?@8->&HB&?8G&=GG+;?=J+@&W?82&p<=;N&9->?;?@-&& •! R8uG&=:9+G8&?9E+GG?H:-&8+&+H8=?@&=&E:=G9=&M?8=9?@&5&;+@;-@8.=J+@&

1+:?;B&v&E.+E+G->&HB& 4-E<H:?;=@&5+@V.-GG&

4-E<H:?;=@& S<EE+.8-.G&

1+:?;B&v&E.+E+G->&HB& 4-E<H:?;=@&5+@V.-GG&

4-E<H:?;=@& S<EE+.8-.G& S<EE+.8&?8w&

0-9+;.=J;& S<EE+.8-.G&

0-9+;.=J;& S<EE+.8-.G& 7EE+G-&?8w&

!"#$%#$!& In-hospital Vitamin C Deficiency and High-dose Vitamin C Therapy

John Hoffer

Sepsis

Except Vitamin C

4-Day Clinical Trial in Septic ICU Patients

!%&Vk>=Bt&

•! F&E=J-@8G&.-;-?M->&G8=@>=.>&R5c&;=.-& •! F&E=J-@8G&.-;-?M->&G8=@>=.>&;=.-&E:<G&=G;+.H=8-&!& V&-M-.B&Y&2&RK& •! F&E=J-@8G&.-;-?M->&G8=@>=.>&;=.-&E:<G&=G;+.H=8-& \([&V&-M-.B&Y&2&RK&

\([&Vk>=Bt&

t&3+.&=&"$&NV&E=J-@8&

S73D& S-p<-@J=:&7.V=@& 3=?:<.-&DGG-GG9-@8&

!"#$%#$!& In-hospital Vitamin C Deficiency and High-dose Vitamin C Therapy

John Hoffer

Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury (CITRIS-ALI)

Fowler, Alpha Alsbury Hite, Duncan R. Martin, Gregory S. Truwit, Jonathon D. Virginia Commonwealth University, Richmond, VA, United States

2oEIkkV.=@8+9-(;+9kV.=@8kXR*kc/!#*'!!YFF[#$6&

4-E<H:?;=@& S<EE+.8-.G&

•! /->?;=:&;<:8<.-&?G&=&G+;?=:&;+@8.=;8&W?82&.<:-GC&.?V28GC&+H:?V=J+@GC&E.+8-;J+@G& =@>&E.-G<9EJ+@GC&=@>&?8&-];:<>-G&@<8.?J+@&

0-9+;.=J;& S<EE+.8-.G&

•! 5<:8<.-&8.<9EG&G;?-@;-C&8.<9EG&:+V?;&&

&&&

•! K?8=9?@&5&?G&-9+J+@=::B&8=?@8->&HB&?8G&=GG+;?=J+@&W?82&p<=;N&9->?;?@-&& •! R8uG&=:9+G8&?9E+GG?H:-&8+&+H8=?@&=&E:=G9=&M?8=9?@&5&;+@;-@8.=J+@&

1+:?;B&v&E.+E+G->&HB& 4-E<H:?;=@&5+@V.-GG&

4-E<H:?;=@& S<EE+.8-.G&

1+:?;B&v&E.+E+G->&HB& 4-E<H:?;=@&5+@V.-GG&

4-E<H:?;=@& S<EE+.8-.G& S<EE+.8&?8w&

0-9+;.=J;& S<EE+.8-.G&

0-9+;.=J;& S<EE+.8-.G& 7EE+G-&?8w&

!"#$%#$!& In-hospital Vitamin C Deficiency and High-dose Vitamin C Therapy

John Hoffer

R>-@J;=:&E+:?;B&E.+E+G->& HB&0-9+;.=J;&5+@V.-GG&

4-E<H:?;=@& S<EE+.8-.G& 7EE+G-&?8w& &

R>-@J;=:&E+:?;B&E.+E+G->& HB&0-9+;.=J;&5+@V.-GG&

4-E<H:?;=@& S<EE+.8-.G& 7EE+G-&?8w& &

0-9+;.=J;& S<EE+.8-.G& S<EE+.8&?8w&

A.?H=:&:+B=:8B&8.<9EG&G;?-@;-&=@>&:+V?;w&&

The 10 Cognitive Distortions that Help You Avoid Having to Change Your Mind

!(&D::#+.#@+82?@V&82?@N?@V& 6(&7M-.V-@-.=:?m=J+@& \(&/-@8=:&L:8-.& %(&0?Gp<=:?OB?@V&W2=8&;+@8.=>?;8G&B+<.&H?=G&& [(&)<9E?@V&8+&;+@;:<G?+@G&W?82+<8&=>-p<=8-&?@O+.9=J+@& Y(&/=V@?L;=J+@k9?@?9?m=J+@& "(&a9+J+@=:&.-=G+@?@V& F(&S2+<:>k+<V28#8+&.-=G+@?@V& `(&'=H-:?@V&=@>&9?G:=H-:?@V& !$(&1-.G+@=:?m=J+@&dH:=9?@Ve&

5+<:>&=8+.M=G8=J@&?9E.+M-& +<8;+9-G&?@&G-EG?Gy&

/=?@G8.-=9& E2BG?;?=@& x-Gw& &

5+<:>&=G;+.H?;&=;?>&?9E.+M-& +<8;+9-G&?@&G-EG?Gy&

X<8.?J+@=::B& +.?-@8->& E.=;JJ+@-.& X+w&

/=?@G8.-=9& E2BG?;?=@& X+w& &

X<8.?J+@=::B& +.?-@8->& E.=;JJ+@-.& x-Gw&

!"#$%#$!& In-hospital Vitamin C Deficiency and High-dose Vitamin C Therapy

John Hoffer When Will Mainstream Medicine Take Vitamin C Seriously?

When Will Mainstream Medicine Take Vitamin C Seriously?

Ascorbic Acid to Prevent CRPS •! [$$&8+&![$$&9V&E-.&>=B&O+.&[$&>=BG&

•! '?;289=@&D9&D;=>&7.82+E=->?;&S<.V&V<?>-:?@-G&6$!!Z& /--@=&a<.&)&7.82+E&S<.V&A.=<9=8+:&6$![Z&52-@&5:?@&)& 1=?@&6$!YZ&cE8+0=8-r&6$!"&P&B-G&& •! aM=@?-W&)&7.82+E&A.=<9=&6$![&P&<@E.+M-@C&9+.-& .-G-=.;2&@-->->&&&

•! U2-@&G+:?>C&?@;+@8.+M-.JH:-&;:?@?;=:&-M?>-@;-&?G&E<H:?G2->& >-9+@G8.=J@V&?8G&?9E+.8=@;-&?@&=@&?9E+.8=@8&>?G-=G-& •! S-EG?G&=@>&G-.?+<G&?@O-;J+@&=EE-=.G&8+&H-&=@&-=G?-.&;=@>?>=8-&82=@& ;=@;-.& •! U2-@&?8uG&-=GB&8+&9-=G<.-&=&E=J-@8uG&E:=G9=&M?8=9?@&5& ;+@;-@8.=J+@&

•! 1-.;-@8&+O&+.82+E->?;&G<.V-+@G&W2+&E.-G;.?H-& =G;+.H?;&=;?>&?@&=;;+.>=@;-&W?82&82-?.& +.V=@?m=J+@uG&;<..-@8&;:?@?;=:&;=.-&V<?>-:?@-G& •! !!l&&

X<8.&)&6$!YZ&![I%$&&

!"#$%#$!& In-hospital Vitamin C Deficiency and High-dose Vitamin C Therapy

John Hoffer

Practical Advice for Vitamin C Advocates •! f@+W&82-&G;?-@;-&=@>&.-9=?@&G;?-@JL;=::B&:?8-.=8-& •! 5+@G;?+<G:B&8.B&8+&=M+?>&B+<.&+W@&;+V@?JM-&>?G8+.J+@G& •! 0+@u8&V-8&8++&<EG-8&W2-@&+82-.&E-+E:-&9=@?O-G8&82-?.G& •! A.-=8&E=J-@8G&=G&-,-;JM-:B&=@>&;=.-O<::B&=G&B+<&;=@&& •! 5+@J@<-&8+&=>M+;=8-C&-]E:=?@&=@>&?9E.+M-&82-&G+;?=:& ;<:8<.-&+O&gR@8-V.=JM-h&k&g+.82+9+:-;<:=.h&9->?;?@-& •! A+&H-@-L8&?@>?M?><=:&E=J-@8G& •! A+&G<G8=?@&82-&V-G8=:8&W2?:-&=W=?J@V&=&G2?z&?@&9=?@G8.-=9& 9->?;=:&;<:8<.-&&&&

Acknowledgements •! '?@-&4+H?8=?::-& •! 3=.2=>&S=H++2?& •! X<9-.+<G&9->?;=:&G8<>-@8G& •! '+o-&=@>&)+2@&*-;28&/-9+.?=:&3+<@>=J+@& •! /;b?::&c@?M-.G?8B&

!$&

Optimal Nutrition & Chronic Disease Prevention: Clinical Perspective on Laboratory Diagnostics Aileen Burford-Mason, PhD

Unified Theory of Chronic Illness

!"#$%#$&'

Ron Hunninghake, MD

What a “typical” Electron looks like in Super K

Towards a Unified Theory of Chronic Illness ()*'+,**-*./0123'45' 6/-27'428-90:';<92=' (-)=80*'6:-*-9'

Super K Particle Detector in Kamioka Observatory

!"#$%&'()*+,-./)'>!?' 01-2,3(24)'()*+,-./)'>&?''' 01-2,3(24)'256*./)'>@?''

G:29C=)*'H=0*AI)=C'6/0-*'

0=2')7),-(28',.((6)(/'' 0A'B2::'0A'9(2-28'9+49/' ,A-*.'C/2')8)(:1':.68)*'' 7=)D'209/''

)7),-(28%-(.8/;)('/-)9'' -2'42<)'9(2-28/'=$>?''

0.0-*AC'0'' ,28,)8-(.@28':(.*6)8-' 7=)D'-3)'4.-(65'' C)'C/2'68-)(4)4A(.8)'/9.,)E' B51:)8'-A'C/2',:FD0C2''

)7),-(28'(),)6<)(C'

!' 26

Unified Theory of Chronic Illness

!"#$%#$&'

Ron Hunninghake, MD

The Redox Potential Drives Electron Transfer

Redox potentials:

“Favorable Electron Flow”

1.) characterize the free energy cost and direction of reactions involving electron transfer. 2.) the tendency to acquire electrons and thereby be reduced. 3.) the mnemonic “OIL RIG” reminds us that “oxidation is loss, reduction is gain”, where the loss and gain are of electrons. 4.) measured in milliVolts - mV

K2):).-9'H-D2' •! %EL'M-::-)*'N20=A'0.)' •! O=2M-)F9'2P-AC2*92'

•! &EQ'M-::-)*'N20=A'0.)' •! •! •! •! •! •! •!

6;J'0CD)AI/2=2' (-M)A)D2A' 42DM=0*2A' O/)C)AN*C/2A-A' H)P-9';J'=2:20A28' O=)10=N)F9':-72'.=)BA' R*02=)M-9'8)D-*0C2A'

•! JE@'M-::-)*'N20=A'0.)' •! •! •! •!

;J'0CD)AI/2=2' G,10=N)C2A'2D2=.2' R2=)M-9';=.0*2::2A' ST0*)D09/-*2AU'

J' 27

Unified Theory of Chronic Illness

!"#$%#$&'

Ron Hunninghake, MD

So…Which Came First? Ribosom es

So…Which Came First?

DNA

Eukaryot es

Membranes

RNA

Prokaryotes!

Prokaryot es

Ribosomes!

T2PC'V2N'W,2AF)*X' '

Y/-9/'

;(KRTGZZG''

90D2'' [=AC\'

&' 28

Unified Theory of Chronic Illness

!"#$%#$&'

Ron Hunninghake, MD

Carl Woese, in 1977, reported that… ]0::')=.0*-ADA'-*'C/2'B)=:8'9),:8'M2'0==0*.28'

-*C)'C/=22'D0^)='90C2.)=-2A')*'C/2'M0A-A')7')*2')7' C/2-='-*C=092::,:0='AC=,9C,=2A'#''

C/2'=-M)A)D2E'

SR'I/N:).2*2F9'0*0:NA-A'M0A28',I)*'=-M)A)D0:' (TR'A2_,2*92'9/0=09C2=-AF9A'=2`20:A'C/0C':-`-*.' ANAC2DA'=2I=2A2*C')*2')7'C/=22'0M)=-.-*0:':-*2A')7' 82A92*CX'' >-?')+A.,-)(6.3'9)DI=-A-*.'0::'CNI-90:'M09C2=-0a'' >--?'.(,3.).'A.,-)(6.3'D2C/0*).2*-9'M09C2=-0a'' >---?')+(D.(12-)/3'*)B'=2I=2A2*C28'-*'C/2' 9NC)I:0AD-9'9)DI)*2*C')7'2,10=N)F9'92::AEU''

Prokaryotes •! )=.0*-ADA'B-C/),C'0'92::'*,9:2,A' >5TR'b)0CA'-*'C/2'9NC)I:0AD?' •! :091'-**2='D2DM=0*2#M),*8' )=.0*2::2A' •! D-C)9/)*8=-0'0*8')C/2=' )=.0*2::2A'0=2'0MA2*C' •! 9)*A-ACA'I=-D0=-:N')7',*-92::,:0=' M09C2=-0'0*8'M:,2'.=22*'0:.02' •! 36:371'.*.9-.A7)'./' 68*)9)8*)8-',)77/'68'.'32/@7)' )8<6(284)8-'

Eukaryotic Organelles Evolve

Eukaryotes

•! (-M)A)D2A'd''

•! 0*'-**2='D2DM=0*2'2`):`2A'C)' 2*9:)A2'0'92::'*,9:2,A' •! C/2'*,9:2,A'9)*C0-*A'.2*2F9' -*7)=D0F)*'7)='080IC0F)*'C)' 2*`-=)*D2*C0:'9/0::2*.2A'' •! C/2'D0^)='9/0*.2'-*'C/2' 2*`-=)*D2*C'-A')PN.2*'I=):-72=0F)*' •! C)'080IC'0*8'A,=`-`23'C/2'2,10=N)C2' 2`):`2A'D0*N'08`0*928')=.0*2::2A' •! C)':20`2'C/2')920*3'2,10=N)C2A' AI29-0:-c28'C)'M29)D2'I0=C')7' 9)DI:2P3'D,:F92::,:0=')=.0*-ADA'

•! (TR'7)='C=0*A:0F)*')7'5TR'-*7)=D0F)*'

•! G*8)I:0AD-9'=2F9,:,D'd''

•! e=),./e'f'I=)C2-*'AN*C/2A-Aa'' •! eAD))C/e'f':-I-8'AN*C/2A-A'

•! K):.-'0II0=0C,A'd''

•! D2DM=0*2':-12'AC091A'' •! B/2=2'I=)C2-*A'0*8':-I-8A'0=2'I=)92AA28'

•! ZNA)A)D2A'd''

•! D2DM=0*),A'A09'' •! 9)*C0-*-*.'/N8=):NF9'2*cND2A'7)='8-.2AF)*'

Microbes, Oxygen, and Life's Engines

SZ-72'-A'0'9/2D-90:' ANAC2D'90I0M:2')7' 50=B-*-0*'2`):,F)*EU' ''''''''''#'60=:'g0.0*'

E.(-3F/'E<27<68:'E8<6(284)8-G' ''''''''=-M)A)D2A'!'I=)C2-*'AN*C/2A-A' 'I=)C2-*A''!'!"!#$%&"'

T0*)D09/-*2A'

GPC=092::,:0='j'k*C=092::,:0='AI092'

S]0AA2DM:-2A'9)DI)A28':0=.2:N')7'I=)C2-*A' 0*8'*,9:2-9'09-8'C/0C'90==N'),C'C/2' *292AA0=N'7,*9F)*A')7'0::':-`-*.'92::AEU''

Intracellular cytosol

•! Prokaryotic – no intracellular membranes •! Eukaryotic – intracellular membranes

Sh*82=AC0*8-*.'/)B'C/2A2'*0*)D09/-*2A' 7,*9F)*'-A'-DI)=C0*C'M290,A2'C/2-='-*C2=*0:' B)=1-*.A'0::)B',A'C)'A22'/)B'M0A-9' I=)92AA2A'B2=2'9)I-28'0*8'=2I0910.28'-*' 8-i2=2*C'7)=DAEU'

!''H3)'2(6:68'2;'2(:.8)77)/'

Intra-membranous space !!I)-J))8'.8'688)('.8*'2+-)('4)4A(.8)'

Gradient across a membrane

%' 29

Unified Theory of Chronic Illness

!"#$%#$&'

Ron Hunninghake, MD

Endosymbiosis: “Once upon a time…”

R::'92::A'B2=2'I=)10=N)F9'0*8'B2=2'I=2lN'A-DI:2' •! *)'D2DM=0*2#M),*8'*,9:2,A3' •! *)'D-C)9/)*8=-0')='9/:)=)I:0ACA3'' •! A-DI:2='9-=9,:0='AC=0*8A')7'5TRE'

The Oxidative Phosphorylation Organelle •! H/2')8*2/14A62@,'3192-3)/6/' 0AA,D2A'C/0C'D-C)9/)*8=-0'B2=2' )=-.-*0::N'-*82I2*82*C'I=)10=N)F9'92::A' •! gD0::'I=)C)#D-C)9/)*8=-0:'M09C2=-0'B2=2' 0AA-D-:0C28'-*C)'2,10=N)C2A' •! H/2-='9-=9,:0='9/=)D)A)D2A'9)*C0-*28' .2*2A'7)='=28)P'I=)C2-*A'

•! ;`2='D0*N'.2*2=0F)*A3'' •! C/-A'2D2=.28'0A'0'D,C,0::N'M2*2[9-0:'=2:0F)*A/-I''

•! G,10=N)F9'9/=)D)A)D2A'0=2'AC=0-./C'

•! C)'C/2'I)-*C'B/2=2''

•! RC'A)D2'I)-*C':)*.'0.)'-*'2`):,F)*0=N'/-AC)=N' •! A)D2'I=)10=N)C2A'AC0=C28':-`-*.'-*A-82')7':0=.2=' I=)10=N)C2AE'' •! C/2':0=.2='92::'C=-28'C)'20C'C/2'AD0::2=')=.0*-AD'' •! M,C'C/2'AD0::'02=)M-9'I=)10=N)C2'A,=`-`28m''

•! *2-C/2=')=.0*-AD'9),:8':-`2'B-C/),C'C/2')C/2=E'' •! H/2'AD0::2=')=.0*-AD'M290D2'0'D-C)9/)*8=-)*3'' •! 0*8'C)80N'D-C)9/)*8=-0'2P-AC'-*'0::'2,10=N)F9'92::AE'

•! k*'!n%Q'=2A20=9/2=A'`2=-[28'C/0C' D-C)9/)*8=-0'B2=2'C/2'A-C2')7')P-80F`2' I/)AI/)=N:0F)*'-*'2,10=N)C2A'

The metabolic evolution of life on Earth o),='p0A-9'Z-72'4):29,:2A' •! Z-I-8AX''

p-)9)*`2=A-)*')7'o))8'C)'G*2=.N'

•! /N8=)I/)M-9'D):29,:2A'C/0C'D012',I'92::' D2DM=0*2A'

•! 60=MAX''

•! A,.0=A'C/0C'0=2'M,-:8-*.'M:)91A'

•! T,9:2-9'09-8AX''

•! 90==N'C/2'A)qB0=2')7'.2*2F9'-*7)=D0F)*' *292AA0=N'7)='G0=C/':-72'C)'2`):`2'

•! O=)C2-*AX''

•! 0D-*)'09-8A'0=2'C/2'0:I/0M2C'C/0C'7)=D'C/2' B)=8A')7':-72'C/0C'0=2'7,=C/2='9)828'-*C)' A2*C2*92A'

•! o0CA''

!'K:N92=):'!'ON=,`0C2'

•! 60=MA'' !'K:N9):NA-A'!'ON=,`0C2'

•! O=)C2-*'' !!'K:,9)*2).2*2A-A'' !!'K:,9)A2'!'K:N9):NA-A'!'ON=,`0C2'

•! ON=,`0C2''

!'O5+'G*cND2'6)DI:2P''>RZR'82I2*82*C?' '!'R92CN:'6)R''!'6-C=-9'R9-8'6N9:2' 'TR5rsTR5+'!'G:29C=)*'H=0*AI)=C'6/0-*'

''"$$s!''!'&Qr'RHOtA'

@' 30

Unified Theory of Chronic Illness

!"#$%#$&'

Ron Hunninghake, MD

Redox Energy Capture:

The driving force of life's processes are redox reactions involving electron transfer

Life is a chemical system capable of Darwinian evolution Z-72'D2C0M):-c2A'A):0='2*2=.N'`-0'I/)C)AN*C/2A-A'0*8'AC)=2A'-C' 60=M)*'8-)P-82'0*8'B0C2='0=2'9)*`2=C28'-*C)'9)DI:2P'90=M)*' D):29,:2A'###'.:,9)A2' G*2=.N'-A':0C2='=2:20A28'0:)*.'0*'2:29C=)9/2D-90:'.=08-2*C'####'

###'C/2'=28)P'I)C2*F0:'

Mitochondrion

Y/0C'-A'C/2'6)DD)*'52*)D-*0C)=')7'C/2A2'AC2IA]Gu6GOH';TG\'

Pyruva se! !

A Krebs Elect ronTr ! a

Acetyl Co !

o Gluc

Gaining the Energetic Advantage •! G0=:N'-*'C/2'I/)C)AN*C/2F9'AC0.2')7' D-9=)M-0:':-72')*'G0=C/3'C/2' K:N9):NA-A'

nsp

ort!H 2 0

K71,271/6/'6/'.'/)(6)/'2;'LM',3)46,.7'().,@28/'' •! -*I,C')7'CB)'RHO'D):29,:2A'.2*2=0C2A'7),='RHO'D):29,:2A' •! 0'*2C'.0-*')7'CB)'RHOA' •! HB)'TR5+'D):29,:2A'0=2'I=)8,928'

•! !"#'/)(<)/'./'.8*')7),-(28',.((6)('' •! 7)=')C/2='M-)9/2D-90:'=209F)*A'-*'C/2'92::'

K71,271/6/'6/'.8'.8,6)8-'9.-3J.1''

0CD)AI/2=2'B0A'^,AC'M2.-**-*.'C)' ' M,-:8',I'-CA')PN.2*'9)*92*C=0F)*' ' •! G0=:-2='I=)10=N)F9'92::,:0=' ' D2C0M):-AD'8-8'*)C'=2_,-=2')PN.2*' ' •! k*'C/2)=N3'I=)10=N)C2A'I=)M0M:N',A28' ' .:N9):NA-A'0A'C/2-='D0-*3'-*2<9-2*C' ' 7)=D')7'.:,9)A2'D2C0M):-AD' T2C'2*2=.N'.0-*'I2='.:,9)A2'D):29,:2X' •! K:N9):NA-A'B0A'/0*828'8)B*'0A'C/2' ''(28,928'TR5'''''J'RHO'''''J'ON=,`0C2A' [=AC'AC2I'C)B0=8A'C/2'S2*2=.2F9' 08`0*C0.2U')7'2,10=)9NC2AE'

•! C/0C')99,=A'-*'0:D)AC'0::'92::A3'2,10=N)C2A'0*8'I=)10=N)C2A'0:-12' •! -A'0:A)'1*)B*'0A'72=D2*C0F)*'B/-9/'C012A'I:092'-*'C/2'9NC)I:0AD'' •! .8*'*2)/'82-'()N+6()'251:)8C''

H3)';.-)'2;'-3)'91(+<.-)'9(2*+,)*'*+(68:':71,271/6/'' *)9)8*/'+928'J3)-3)('251:)8'6/'9()/)8-O' P8'-3)'.A/)8,)'2;'251:)8'' •! C/2'IN=,`0C2'90**)C'M2'9)DI:2C2:N')P-8-c28'C)'90=M)*'8-)P-82'' •! A)'`0=-),A'-*C2=D28-0C2'I=)8,9CA'=2A,:C3')/9),6.771'7.,@,'.,6*C'' •! •! •! •!

o)='2P0DI:23'B/2*')PN.2*':2`2:A'0=2':)B3'' A12:2C0:'D,A9:2'92::A'=2:N')*'.:N9):NA-A'' C)'D22C'C/2-='-*C2*A2'2*2=.N'=2_,-=2D2*CA3'' B/-9/'90*'90,A2'0'I2=A)*vA'D,A9:2A'C)'722:'0A'-7'C/2N'0=2'e)*'[=2Ee''

Q6467.(71R'1)./-/'.8*'427*/=/68:7)%,)77)*')+D.(12-)/?' =2C0-*'C/-A'I=-D-F`2'I=272=2*92'7)='.:N9):NF9' D2C0M):-AD'-*'0':)B')PN.2*'2*`-=)*D2*C'

!"#$%#$&'

Unified Theory of Chronic Illness Ron Hunninghake, MD Oxygen Utilization =

Bioconversion of Food to Energy

O.U. ;EhE'f'C/2'2<9-2*9N'MN'B/-9/' 92::A'9)*`2=C')PN.2*#C=0II28' 2:29C=)*A'-*C)'/20C'r'RHO''

60=MA''

ON=,`0C2''

!'K:,9)A2'!'K:N9):NA-A'!'ON=,`0C2'

!!O56'G*cND2' '''' 'ON=,`0C2'52/N8=).2*0A2''''''' 'G*cND2'6)DI:2P''''''''''''' ''' ' '>!"!#$%&%'$%'(?' !'R92CN:'6)R''>)*(+,*'#-.#$%&%'$%'(?' !!'6-C=-9'R9-8'6N9:2'>/0#$%&%'$%'(?' !!'G:29C=)*'H=0*A72='6/0-*'>1!23#4#-5?'

o0CA''

•! o0CA'0*8'60=MA'0=2'8-.2AC283'D2C0M):-c28' 0*8'AC)=28'0A'.:,9)A2'0*8'70lN'09-8A' •! gC)=28'2*2=.N'-A'M=)12*'8)B*'0*8' C=0*A72==28'C)'92::A' •! 42C0M):-C2A'0=2'9)*`2=C28'C)'IN=,`0C2'0*8' R92CN:'6)R' •! R92CN:'6)R'2*C2=A'C/2'V=2M'9N9:2'C)'C=0*A72=' /N8=).2*'0C)DA'C)'TR5r' •! TR5r'=2:20A2A'/N8=).2*'0C)DA'-*'C/2' D-C)9/)*8=-0'C)'I=)8,92'&Q'RHO'D):29,:2A'

!'K:N92=):'!'ON=,`0C2'

O=)C2-*'' !!'K:,9)*2).2*2A-A'' !!'K:,9)A2'!'K:N9):NA-A'!'ON=,`0C2'

''''f'N-2:8A'J'RHOtA'r'!'TR5+'

The Redox Potential Drives Electron

!"#$%&'()*+,-./)'>!?' 01-2,3(24)'()*+,-./)'>&?''' 01-2,3(24)'256*./)'>@?''

Transfer

!!'6;J'r'+J$'

G:29C=)*'H=0*AI)=C'6/0-*'

0=2')7),-(28',.((6)(/'' 0A'B2::'0A'9(2-28'9+49/' ,A-*.'C/2')8)(:1':.68)*'' 7=)D'209/''

)7),-(28%-(.8/;)('/-)9'' -2'42<)'9(2-28/'=$>?''

0.0-*AC'0'' ,28,)8-(.@28':(.*6)8-' 7=)D'-3)'4.-(65'' C)'C/2'68-)(4)4A(.8)'/9.,)E' B51:)8'-A'C/2',:FD0C2''

)7),-(28'(),)6<)(C'

“Favorable Electron Flow”

"' 32

!"#$%#$&'

Unified Theory of Chronic Illness Ron Hunninghake, MD

Oxygen – The Forgotten Nutrient

When… OXYGEN is AVAILABLE

Obvious…but Overlooked

S;PN.2*'hF:-c0F)*U'

Aging? or…the loss of Oxygen Utilization?

Oxidation Plays Many Roles at the Cellular

The Oxygen Paradox o,*9F)*0:'' +NI)P-0' 50D0.2'

Level

“Bad” Oxidation “Good” Oxidation

;J' (2AI-=0F)*'

G*2=.N'

Z-72'

S())'(.*6,.7/X'A2C',I'9/0-*' =209F)*A'B/-9/'90*'80D0.2'92::' D2DM=0*2A3'D-C)9/)*8=-03'0*8' 5TR' #):)8)(.@<)'#6/)./)X'90C0=09CA3' D09,:0='82.2*2=0F)*3'0=C2=N' 8-A20A23'=/2,D0C)-8'0=C/=-FA3' .8*',.8,)('90*'=2A,:C')`2='FD2'

(;g' g-.*0:-*.'

50D0.2'

kDD,*-CN'

Cancer appears to be a maladaptive cellular response to Chronic Injury … setting the stage for … Chronic Illness

P44+86-1X'B/-C2'92::A',A2' /N8=).2*'I2=)P-82'>-*':NA)A)D2A?' C)'0l091'0*8'82AC=)N'-*`08-*.' M09C2=-0'0*8'`-=,A2A' E8)(:1'T)-.A276/4X'D-C)9/)*8=-0' )P-8-c2'>M,=*?'.:,9)A2'C)'=2:20A2' 2*2=.N'B/-9/'-A'AC)=28'0A'RHO'

!"#U'6/'256*6V)*'-2'!"#''

GPC=092::,:0=' ;P-80F`2'' gC=2AA'

6/=)*-9'I/NA-90:'80D0.2'

'''(08-0F)*3'2:29C=)D0.*2F9'[2:8A3'C=0,D03'-==-C0*CA'

6/=)*-9'9/2D-90:'80D0.2'

H=0*A' m' o0CA'm

'''60=9-*).2*A3'C)P-9'9/2D-90:A3'/20`N'D2C0:A3'I2AF9-82A'

6/=)*-9'M-):).-90:'80D0.2'

'''6/=)*-9'-*729F)*'>`-=0:3'M09C2=-0:3'7,*.0:3'0*8s)='I0=0A-F9?'' ''';`2=#09F`2'>)=',*82=#09F`23'-*2i29F`2?'-*b0DD0C)=N'=2AI)*A2'' '''52I:2F)*')7'.=)BC/'w'=2I0-='D):29,:2A3'0*8'=2I0-='92::A'>08,:C'AC2D'92::A?'

6/=)*-9'2D)F)*0:')='D-*8sM)8N'80D0.2'

A' PN.2*'gI29-2 (209F`2'; >(;g?'

+20`N'42C0

:A'

U7./4.'W696*'I6%W.1)('T)4A(.8)'

T6-2,328*(6.'

0A2'k' ,9CA')7'O/ pNI=)8 P-[90F)*' C) :-`2='82

'''gC=2AA3'82I=2AA-)*3'' '''Z)AA')7'D20*-*.3'I,=I)A2:2AA*2AA3'0*8'/,D0*'9)**29C28*2AA'

/C'

'A,*:-.

AA-`2

GP92

!+,7)+/' #!"'

H=0*A' o0CA'mm' R8`0*928

':71,2/17. @28')8*'9( 2*+,-/' >RKGA?'

Q' 33

Unified Theory of Chronic Illness

!"#$%#$&'

Ron Hunninghake, MD

k*C=092::,:0=' ;P-80F`2'' gC=2AA'

!E''+20:C/'' ''d'M0:0*928'=28)P'

4-C)9/)*8=-0:' 42DM=0*2'' SZ2010.2U'-A' 6)*C=)::28'

A' PN.2*'gI29-2 (209F`2'; >(;g?'

W696*'I6%W.1)('' B(:.8)77)'T)4A(.8)/'

T6-2,328*(6.7' I1%9(2*+,-/'2;' B56*.@28'

+20`N' 42C0:A'

(28,9-*.'k*C=092::,:0='4-:-2,'

!+,7)+/' #!"'

;' ;PN.2*'>)IFD0:',F:-c0F)*?' Y0C2=' T,C=-2*CA' R*F)P-80*C'2*cND2A' TR5'0*8'RHO'>2*2=.N?' +20:C/N'Z-72ACN:2'6/)-92A'

gC=2AA3'68X+(1'0*8'82I:2F)*'' R992:2=0C28'0.-*.' 'U22('251:)8'+@76V.@28' 42C0:A'0*8'C)P-*A' O))='7))8sD0:*,C=-F)*' h*/20:C/N'Z-72ACN:2' ' '

Soâ&#x20AC;¦Which Came First?

JE''k*^,=N'' ''d'8-A=,IF)*'

(28,9-*.'k*C=092::,:0='4-:-2,'

;P-8-c-*.'k*C=092::,:0='4-:-2,'

;PN.2*'>)IFD0:',F:-c0F)*?' TR5'0*8'RHO'>2*2=.N?' Y0C2=' T,C=-2*CA' R*F)P-80*C'2*cND2A' +20:C/N'Z-72ACN:2'6/)-92A'

Increasing Oxidative Stress

Decreasing Oxygen Utilization

;P-8-c-*.'k*C=092::,:0='4-:-2,' gC=2AA3'68X+(1'0*8'82I:2F)*'' R992:2=0C28'0.-*.' 'O))=')PN.2*',F:-c0F)*' 42C0:A'0*8'C)P-*A' O))='7))8sD0:*,C=-F)*' h*/20:C/N'Z-72ACN:2' ' '

Mitochondri al

Decay

U22(' BY' \/)'

]22-'' 0.+/)/'

BY'

#),()./)*'

W69271/6/' *),()./)*'

Cascade

#(C'S(.8D' Q3.77)8A)(:)(''

R'829:-*2'-*''

E.(71'B8/)-' Q7))9' *),()./)* T6-2,328*(6.7' #)Z,6)8-' #1/;+8,@28_' $2(428)/'

90,A28'A1'.81' ,24A68.@28')7'C/2'

L`''GE4E;E5'o09C)=A'

#)Z,6)8-'

!+-(6)8-/' '

251:)8'+@76V.@28' ECTCBC#C'

ECBCTC#C'

'H2568/' W2J'

!"#^!"#$'

\8%' 02+97)*'

H31(26*' Q-()//' 68,()./)*'

P8%' [.4)*'

P8;),@28'

U22(' T)-317.@28'

S.,-2(/'H3.-' #),()./)'BY' \@76V.@28'

P/,3)46.'

!2-'' E82+:3' T2<)4)8-'

P8/+768' ])/6/-.8,)'

n' 34

Unified Theory of Chronic Illness Ron Hunninghake, MD

Unified Theory of Chronic Illness

!"#$%#$&'

Ron Hunninghake, MD

Cellular Injury ! Cytokine Signaling

A Cellular Model of

Health and Healing $).7-3'd'6%$78#97,%7:(+:*:# P8X+(1'd'=28)P'$*:6;&<7'# Q6:8.7'd'78*$+<)%#:(6%::# ])9.6('d'0%'%#%8&6%::*7'# $).768:'d'6%$78'6%:(76+<7'#

The relative levels of 174 cytokines in the serum of MXL060330 2.0000

Ratio to control (sam-neg)/(pos-neg)

LC! YC! dC! eC! `C!

''''k7'*,C=-2*C'=2A2=`2A'0=2'-*082_,0C2')='82I:2C28'0*8' C/2'80D0.2'90**)C'M2'=2I0-=283'C/2'9NC)1-*2'A-.*0:-*.' -*C2*A-[2A'C/2'-*b0DD0C)=N'=2AI)*A2'-*'0'82AI2=0C2' 0l2DIC'C)'088=2AA'C/2'D),*F*.')P-80F`2'AC=2AAE'

1.8000 1.6000 1.4000 1.2000 1.0000 0.8000 0.6000 0.4000 0.2000 0.0000

Cytokines

Cytokinesignaling

%E''(28)P'(2I0-='010'S;9).2*2AU' '''k*b0DD0F)*'f'K2*2'GPI=2AA-)*'

Injured Cells = Insufficient Energy

Categories

{')7'g-.*0:A'C)'' jH+(8'2a'$).768:l' R*F#0*.-).2*2A-A'#'L' R*F#k*b0DD0F)*'#'"' 52#5-i2=2*F0F)*'#'L' ;*9).2*2#52R9F`0F)*'#J"' R*F#RI)IC)A-A'#'&&' Y),*8'+20:-*.'#'Jn' 4-C).2*2A-A'5)B*'#'JJ' kDD,*-CN'5)B*'d'!%' 62::'g,=`-`0:'d'&n'' 62::'R9F`0F)*'d'!!''' K:,9)A2'D2C0M):-AD'd'!%''

•!k*^,=28'92::A'90*'*)':)*.2=')I2=0C2''9)DI:2P' 92::,:0='9)*C=):'D29/0*-ADA''

•!Y),*828'92::A'=2.=2AA'C)'.:N9):NF9'D2C0M):-AD'>B-C/' :09F9'09-8'I=)8,9F)*?'

•!60*92='92::A'/0`2'=2.=2AA28'C)'A-*.:2'92::'A,=`-`0:' D29/0*-ADA''

Uncontrolled Replication/ Proliferation

The Shift to Glycolytic Metabolism

Gi29C')7')P-80F)*')*'0'I)I,:0F)*' )7'*)*#90*92=),A3'-*^,=28'92::A'' k* 92 9=20 ::'8 A-* -`- .'' A- ) *'' '

T,DM2=')7'-*^,=28'92::A''

{')7'g-.*0:A'C)'' j$).7'-3)'k2+8*Ol' R*.-).2*2A-A'#'fY' k*b0DD0F)*'#'fg' 5-i2=2*F0F)*'#'`d' ;*9).2*2#R9F`0F)*'#'eh' RI)IC)A-A'#'ed' 60*92=-c0F)*'#'dL' 4-C).2*2A-A'#'iY' kDD,*-CN'hI'd'`e' 6/2D)0l=09C0*C'd'`' 62::'R8/2A-)*'d'Li' RC/2=)A9:2=)A-A'd'Yh'

•!R*'02=)M-9'92::'90*'82=-`2'df'42()'"HUm/' 7=)D'209/'.:,9)A2'D):29,:2E'' •!R*'0*02=)M-9'92::'90*'82=-`2'2871'Y'"HUm/'' •!"8.)(2A6,',)77/'.()')8)(:1'*)Z,6)8-' •!60*92='f'D-C)9/)*8=-0:'8NA7,*9F)*' •!60*92='f'o,*9F)*0:'+NI)P-0' •!6/=)*-9'k::*2AA'f'O))=';PN.2*'hF:-c0F)*'

62 RI ::, )I :0= C)A 'T -A' 29 w' =) ' A-A '''

Z2`2:')7')P-80F`2'AC=2AA''' |'+-912N3'()M2=CAa'=+'>%6#?#1;(6*<7'#@#A;6)*)+B''

!!'

Unified Theory of Chronic Illness Ron Hunninghake, MD

]22-'0.+/)/_'#)-),-'q'02((),-' $2(428)/' Q-()//' S22*/' ''0.8*6*.' *1/():+7.-)*' P8' J3).-o' W6;)' '[.4%'' Q-(+,-+()' 4.@28'

!+-(6)8-/' 46//68:'

I)n)('Q)7;'0.()'

p2+'M2.-*' C)'A22' N),=A2:7'0A'' S6(/-'0.+/)'

#6:)/@<)'

07).8''

*6/2(*)(/'

"*()8.7' ;.@:+)'

•!;l)'Y0=M,=.3'0'!nJ$vA'0'90*92='=2A20=9/2='' •!Y0=M,=.'I,C'828%,.8,)(2+/'3+4.8',)77/'-*'0'O2C=-'8-A/'0*8' *)9(6<)*'-3)4'2;'251:)8E'' •!H3)1'/+(<6<)*GA+-'-+(8)*',.8,)(2+/C'' •!Y0=M,=.'8-A9)`2=28'C/0C'C/2'D2C0M):-AD')7'90*92='92::A'/08' C,=*28'.8.)(2A6,' •!+2'=292-`28'0'T)M2:'O=-c2'7)='C/-A'B)=1'-*'90*92='92::' D2C0M):-ADE''

E42@28/' -256,'

I.7.8,)*'

E8<6(28/'

",@<6-1'

P8;),@28'

E5,)//'

;2,.7'

Cancer Cells are Anaerobic

*6/(+9-)*'

828J327)'

'H2568/'

6C)C'/+:.('

'''6C)C'4)-.7/'

H31(26*' P4A.7.8,)*'

!"#$%#$&'

QCBC"CUC' U.-3J.1/'' H2'I)n)(' U)(/28.7' $).7-3'

Wasting as a Sign of Anaerobic Metabolism 0.8,)('*)97)-)/'8+-(6)8-'()/)(<)/'(.96*71C' 0.,3)56.'>M)8N'B0AF*.?'-A'0'AC=)*.'-*8-90F)*')7' .8.)(2A6,'4)-.A276/4'' (2A,:C'!'2P92AA-`2'0*8'-*2<9-2*C',A2')7'.:,9)A2'' H/-A'B/N'C,D)='92::A'C012',I'=08-)09F`2'C0..28' .:,9)A2'-*'OGH'A90**-*.'

The Healing Factor

Chapter 1 – The Beginnings of Life

Vitamin C Against Disease

•!SR::'I:0*CA')='0*-D0:A'B/-9/'/0`2'2`):`28'-*C)'9)DI:2P' D,:F92::,:0='7)=DA'D012')='*228'0A9)=M-9'09-8E''' •!Y0A'0A9)=M-9'09-8'C/2'AFD,:,A'7)='C/2'2`):,F)*')7' D,:F92::,:0=')=.0*-ADA\''' •!k7'*)C'C/2'AFD,:,A3'-C'92=C0-*:N'-*9=20A28'C/2' M-)9/2D-90:'080IC0M-:-CN'*292AA0=N'7)='A,=`-`0:'-*' 9/0*.-*.'0*8',*70`)=0M:2'2*`-=)*D2*CAEU'

Irwin Stone

!J'

!"#$%#$&'

Unified Theory of Chronic Illness Ron Hunninghake, MD

During its rapid fetal development, the embryo passes through the various evolutionary stages that its species went through in time.

Ontogeny Recapitulates Phylogeny

P8';)-.7'*)<)7294)8-R'./,2(A6,'.,6*',.8'A)'*)-),-)*'<)(1').(71R' J3)8'-3)')4A(12'6/'82-368:'42()'-3.8'.'/3.9)7)//'4.//'2;',)77/C'''

Further evidence for the great antiquity of the ascorbic acidsynthesizing systems may be obtained from the science of embryology.

k*'I:0*CA3'0:A)3'C/2'A228A'/0`2' *)'0A9)=M-9'09-8E' p,C'0'A))*'0A'C/2'I:0*C'2DM=N)' AC0=C'C)'82`2:)I3'0A9)=M-9'09-8'-A'' -DD28-0C2:N'7)=D28E'''

H/,A'0::'C/2'0`0-:0M:2'2`-82*92'I)-*CA'C)' '-3)':().-'.8@N+6-1'2;'' C/2'0A9)=M-9'09-8#AN*C/2A-c-*.'ANAC2DA' -*':-72')*'C/-A'I:0*2CE'

k*'C/2'82`2:)ID2*C')7'C/2'9/-91'2DM=N)3'C/2'9/-912*'2..'-A'82`)-8')7'0A9)=M-9'09-83' A+-'6-',.8'A)'*)-),-)*'68'-3)').(71'A7./-2*)(4'/-.:)'2;'-3)':(2J68:')4A(12C''' ' RC'C/-A'AC0.2'C/2'2DM=N)'-A'^,AC'0'D0AA')7'92::A'' -*'B/-9/'*)'82[*-C2')=.0*A'/0`2'0A'N2C'0II20=28E'' kC'=2A2DM:2A'C/2'D)AC'I=-D-F`2'D,:F92::,:0=')=.0*-ADA'' ##'M)C/'7)AA-:'0*8'I=2A2*C':-`-*.'7)=DAE'''

H/-A'oR6H' :208A'C)'0' C=,:N'.=20C' -DI:-90F)*X'

GLO: nature’s first, major adaptive enzyme •! '' •! H/2'AC=2AA2A')7':-`-*.',*82='B-:8'0*8',*70`)=0M:2'9)*8-F)*A'B2=2' .=20CX'

•! H/2'0*-D0:A'/08'C)'9)*F*,0::N'122I'),C')7'C/2'B0N')7'I=280C)=A'B/-:2'C/2N' A20=9/28'7)='7))8a'' •! C/2N'/08'C)'I=)9=20C2'0*8'C012'90=2')7'C/2-='N),*.a'' •! C/2N'/08'C)'=2A-AC'A,9/'2*`-=)*D2*C0:'AC=2AA2A'0A'/20C3'9):83'=0-*3'0*8'A*)B3'' •! 0*8'C/2'M-):).-90:'AC=2AA2A')7'I0=0A-C2A'0*8'8-A20A2A')7'M09C2=-0:3'7,*.0:3'0*8' `-=0:')=-.-*E'''

+,D0*'2DM=N)A3'' +(#(9%#CB+:(7$%6,+B#:(+0%3'' R6HhRZZy'5;'+RzG'H+G'

•! ''H/2'I=2A2*92')7'0A9)=M-9'09-8#AN*C/2A-c-*.'2*cND2A'9)*72==28' 2*)=D),A'I)B2=A')7'A,=`-`0:E'

W%:+72827.,-28)'256*./)')8V14)O' $+4.8/'0"!'' 4.D)'-3)6('2J8'<6-.468'0O'

“The presence of ascorbic acid-synthesizing enzymes conferred enormous powers of survival.”

The KEY to Survival

•!SR*-D0:A'C/0C'B2=2'0M:2'C)'9)I2'B-C/'C/2A2'AC=2AA2A'' •!MN'I=)8,9-*.')IFD0:'0D),*CA')7'0A9)=M-9'09-8'B-C/-*'C/2-='M)8-2A'' •!B2=2'D)=2'=2A-AC0*C'C)'2*`-=)*D2*C0:'2PC=2D2A')7'/20C'0*8'9):83'' •!M2l2='0M:2'C)'[./C')i'-*729F)*A'0*8'8-A20A23'' •!M2l2='0M:2'C)'=29)`2='7=)D'I/NA-90:'C=0,D03'' •!0*8'M2l2='I=2I0=28'C)'8)'-C'=2I20C28:NEU'

•! ST)=D0::N3'0'D0DD0:' 2_,-II28'C)'AN*C/2A-c2'-CA' )B*'0A9)=M-9'09-8'B-::' I=)8,92'-C'-*'`0=-0M:2' 0D),*CA'82I2*8-*.',I)*' C/2'AC=2AA2A'C/2'0*-D0:'-A' ,*82=.)-*.E''' •! H/2A2'0*-D0:A'/0`2'0' 7228M091'D29/0*-AD'' •! C/0C'I=)8,92A'D)=2'B/2*' C/2'0*-D0:'*228A'D)=2EU'

K)0C' 4),A2' 5).' 60C' g_,-==2:' o:N'

R'.)0C')7'"$'1.' >!@%'I),*8A?' AN*C/2A-c2A' !&3$$$'D.')7' 0A9)=M0C2'80-:NE' H/2')C/2='0*-D0:A' 0=2'C/2'A0D23' I=)I)=F)*0:'C)' C/2-='B2-./CE|'

H/2'M-.'08`0*C0.2A')`2='/,D0*AX' !E';`2=0::'50-:N'5)A2' JE';*'5G4RT5'AN*C/2A-A'd'`0=-2A' 099)=8-*.'C)'C/2')=.0*-ADtA'TGG5'0C'C/0C' D)D2*Cm' |()*+,-')*.'/01)20*'('MN'O0,:-*.'0*8'60D2=)*'

!&' 38

!"#$%#$&'

Unified Theory of Chronic Illness Ron Hunninghake, MD

Mitochondri al

Decay

U22(' BY' \/)'

]22-'' 0.+/)/'

BY'

#),()./)*'

W69271/6/' *),()./)*'

Cascade

#(C'S(.8D' Q3.77)8A)(:)(''

R'829:-*2'-*''

E.(71'B8/)-' Q7))9' *),()./)* T6-2,328*(6.7' #)Z,6)8-' #1/;+8,@28_' $2(428)/'

L`''GE4E;E5'o09C)=A'

!+-(6)8-/' '

251:)8'+@76V.@28' ECTCBC#C' 90,A28'A1'.81' ,24A68.@28')7'C/2'

#)Z,6)8-'

'H2568/' W2J'

!"#^!"#$'

\8%' 02+97)*'

U22('

S.,-2(/'H3.-' #),()./)'BY' \@76V.@28'

68,()./)*'

P8%' [.4)*'

0)77+7.('' $19256.'6/' ])/27<)*'

"*)N+.-)' BcP#"HPB!'2;' !"#$'-2'!"#'

62::A'=2A,D2'RG(;pk6'

P/,3)46.'

!2-'' E82+:3' T2<)4)8-'

k*b0DD0C)=N';P-80F)*' -A'hI=2.,:0C28''

T6-2,328*(6.7' #),.1'01,7)' 028-(277)*'

k*9=20A28' D-C)9/)*8=-0:' (GORk('

H31(26*' Q-()//'

P8;),@28'

T)-317.@28'

62::'g-.*0:-*.'H,=*28';*'

ECBCTC#C'

k*9=20A28'I=)8,9F)*')7' 0*F)P-80*C'2*cND2A'

P8/+768' ])/6/-.8,)'

V=2MA'9N9:2'AI228A',IX'

-*9=20A-*.'RHO''

Orthos

The Therapeutic Continuum

'''''''''''g9-2*F[9' ''''''''''''''g)9-2C0:' '''''''''';=.0*-c0F)*A' ''''''''''''428-90:' ''''''''''6)#Z20=*-*.' ''''''''''6:-*-90:' '''''''O2=A)*0:'''''''''''O2=A)*0:'6/)-92A' ''''''''''Y-::-*.*2AA'C)'H(y' ''''6)*92IC,0:' ''62::,:0=' ''''''''''62::A'R80IF*.' 4):29,:0=' ''''''''''G:29C=)*A'M2-*.'' ''''''''''''''G:29C=)*A' ' '

]62(*.8'07686,' www.riordanclinic.org jp2+',.8F-'A):68'-2'7).(8'J3.-'12+'-368D' 12+'.7().*1'D82JCl'' ' ' ' %'E96,-)-+/'

!%' 39

Plant Based Reversal of Heart Disease

17-04-01

Joel Kahn, MD

Heart Disease deaths: no joke

The end of heart disease 2016 Joel Kahn MD, FACC Professor, Wayne State University School of Medicine www.drjoelkahn.com Kahn Center for cardiac longevity GreenSpace Cafe

1 40

Plant Based Reversal of Heart Disease Joel Kahn, MD

17-04-01

Early researchers of diet-health

Actual causes of death:

REDUCTION OF MORTALITY RATE IN CORONARY DISEASE BY A LOW CHOLESTEROL-LOW FAT DIET.

Lester Morrison, MD

(1951) AM. HEART J. 42: 538-545.

•! •!

•!

PRITIKIN LIFESTYLE PROGRAM Morrison low-fat diet results

•! •! •! •! •! Barnard et al. Arch Intern Med 1991;151:1389-1394.

Plant Based Reversal of Heart Disease Joel Kahn, MD

17-04-01

Early researchers of diet-health

Processed Food as Poison: artery damage in minutes lasting hours

Original Ornish Plan No calorie restriction! Fats (<10%)

2) Moderate exercise! 3) Stress reduction! 4) Smoking cessation!

Nonfat dairy products – yogurt, cheese, egg whites Nonfat products – cereal, soups, tofu, crackers, egg beaters Whole grain – corn, rice, oats, wheat, etc

Beans and legumes

Fruits

Vegetables

Excluded All oils All meats Olives Avocados Nuts – seeds High or low fat products Sugar – syrup – honey Alcohol

CP1095424-1

Plant Based Reversal of Heart Disease Joel Kahn, MD

17-04-01

Ornish: The Lifestyle Heart Trial •! •! •! •! JAMA 1998;280(23):2001-2007, Lancet 1990;336:129-33

Lifestyle Heart Trial 1-Year Results Variable

Experimental

Control

LDL mg/dl

95 ± 60

157 ± 45 .0072

HDL mg/dl

37 ± 15

51 ± 15

Progression

18%

53%

Regression ! stenosis

82%

42%

-2.2%

+3.4%

.001

Plant Based Reversal of Heart Disease Joel Kahn, MD

17-04-01

PROSTATE CANCER LIFESTYLE TRIAL •!

•!

ORNISH D, J UROL. 2005 SEP;174(3):1065-70

•! •! •! •! •! RNA SAMPLES TAKEN BEFORE THE INTERVENTION COMPARED WITH

RNA SAMPLES TAKEN 3 MONTHS INTO IT, SHOWED 48 GENES HAD UP-REGULATED AND 453 HAD DOWN-REGULATED. EPIGENETICS

A STRATEGY TO ARREST AND REVERSE CORONARY ARTERY DISEASE: A 12-YEAR LONGITUDINAL STUDY OF A SINGLE PHYSICIAN S PRACTICE Caldwell B. Esselstyn, Jr., MD

foods to be Included •! •! •! •!

Plant Based Reversal of Heart Disease Joel Kahn, MD

Excluded

17-04-01

Diet – 11% fat – plant based Cholesterol lowering medication Unstructured exercise

•! •! •! •! •!

Patients Followed 12 Years •! 49 coronary events during 8 years prior to study

•! None in compliant patients during 12 years

Plant Based Reversal of Heart Disease Joel Kahn, MD

17-04-01

Fuhrman, Singer, 2015 AJLM

Beyond Nutrition: Reversing atherosclerosis

Plant Based Reversal of Heart Disease Joel Kahn, MD

Are you doing 5/5 daily? Heart Attacks Drop 85% •! •! •! •! •!

17-04-01

Early detection of America s #1 killer

•! •!

Tools of the heart attack prevention specialist

What is your Coronary artery calcium score?

Heart disease is reversible

Yellow vs. red

Plant Based Reversal of Heart Disease Joel Kahn, MD

Chelation and Vitamins

17-04-01

HOW OLD ARE YOUR ARTERIES? person

Canary in the Bedroom

Session - Cardiology Evidence Based Two Integrative Cardiology Drs Jack and Heather Wolfson Give the Body What it Needs and Take Away What it Doesnâ&#x20AC;&#x2122;t

Jack Wolfson, DO & Heather Wolfson, DC

Fighting Healthy

!& 49

Session Two - Cardiology DrsBased Jack and Heather Wolfson Evidence Integrative Cardiology

Give the Body What it Needs and Take Away What it Doesnâ&#x20AC;&#x2122;t Jack Wolfson, DO & Heather Wolfson, DC

Over 300 references

D.O. 1996- Midwestern Univ.

Internal Medicine 96-99

Cardiology 1999-2002

Chief fellow

Senior partner of a large cardiology group, 2002-2012

Chairman of Dept. of Medicine

Director of Cardiac Rehab

Phoenix Top Doc 2011

Top Holistic MD 2012,14-16

'& 50

Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesn’t Jack Wolfson, DO & Heather Wolfson, DC

Knock Knock…. It’s Dr. Heather Wolfson

CDC Vaccine Schedule 2016

!"##$%"&'%()) *)+,'#-./,-)0')1,-"23)45-6) 7".)2')8"9-)$2)8"%."2',6) )*+,--.../010/234-45006789-+5:87;9-13.7<3519-+5:87;#48:#90)#$#=>:9/+1?&

(& 51

& Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesnâ&#x20AC;&#x2122;t

Jack Wolfson, DO & Heather Wolfson, DC

Infant Mortality More Vaccines = Higher Infant Mortality

#58 .../065/234-<6@:5:>-+A@<605B379-;)8#.3:<1#?50;@33C-:57C3:18:'$D!:57C/);E<&

)*+9,--.../70@6/7<E/76)/234-+E0-5:B0<89-FGH(!"$$"I-&

Cardiologist Goes Rogue

J78&G6<<637&K;87;9&F8:&L85:& M&G6<<637&N>+599&KA:28:689&

%& 52

Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesnâ&#x20AC;&#x2122;t Jack Wolfson, DO & Heather Wolfson, DC

F:890:6+B379&O6<<81&& 67&;)8&P/K/Q&'$!%&RS878:60T&

U)8&H8<<&G8E@:578&

Cholesterol and Sex Hormones

Low Vitamin D Is Linked to Everything

The Sun Converts Cholesterol into Vitamin D )*+,--.../<6?88V;879637/03E-G525W678-'$!(-X-U)8# J48:<33C81#YE+3:;5708#3?#Z6;5E67#[#\808+;3:9-F528#$'&

I& 53

& Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesnâ&#x20AC;&#x2122;t

Jack Wolfson, DO & Heather Wolfson, DC

Vitamin D Supplementation Lowers BP

High Vitamin D is Linked to Longer Telomeres!

Z6;5E67&[&KA++<8E87;9&]3.8:&G3:;5<6;>&N>&"^,& !X&\HU_9#&I"Q$$$&+5B87;9&

Vitamin D Receptors (VDR) are located in: Cardiovascular: Endothelial cells, smooth muscle cells, myocytes

Endocrine: Parathyroid, thyroid, pancreatic beta cells

Immune: Thymus, bone marrow, macrophages, B cells, T cells

Exocrine: Parotid gland, sebaceous gland

Gastrointestinal: Esophagus, stomach, small intestine, colon, rectum Respiratory: Lung alveolar cells Hepatic: Liver parenchyma cells Renal: Proximal and distal tubules, collecting duct

CNS Brain neurons, astrocytes, microglia Musculoskeletal: Osteoblasts, osteocytes, chondrocytes, striated muscle Connective Tissue: Fibroblasts, stroma Reproductive: Testis, ovary, placenta, uterus, endometrium, yolk sac, breast&

The Lower the Latitude, The Lower the Cholesterol

Could Sunshine Lower Cholesterol?

Vitamin D

=& 54

Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesnâ&#x20AC;&#x2122;t Jack Wolfson, DO & Heather Wolfson, DC More Sunshine = Lower Risk of Cardiac Death

What Is Your Caveman Cholesterol?

Meta-analysis on saturated fat and heart disease

:;<3<<<)=-'=>-& 0"2/,"2-.)?"2)$@)%'2)"@@'#$"2-.)A$25)"%) $%#,-"@-.),$@9)'?)5-",2).$@-"@-&

`E8:&a/&H<67&bA;:6B37&'$!$&

"& 55

Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesnâ&#x20AC;&#x2122;t Jack Wolfson, DO & Heather Wolfson, DC K8487;)&[5>&`1487B9;9& +-@#'B!-C-2",$"%)7"@)25-)D'A-@2)E$@9)F?)8',2">$26)$%)25$@)1,'/=)

Paleo Lowers Inflammation JAMA Intern Med.!2013;173(13):1230-1238. &

Omega-3 Supplements Saves Lives

High Omega-3 Levels Live Longest

#&!&2:5E-15>&

)*+9,--.../70@6/7<E/76)/234-+A@E81-'"(D""(%&

)*+9,--.../70@6/7<E/76)/234-+A@E81-!!X("DXI&

Berberine

K+608&P+&L3A:&H)3<89;8:3<&bAE@8:9& S6728:& N<50C&0AE67&& J:82573& H8<8:>&9881& U)>E8&& S5:<60&& UA:E8:60&& H5+8:9&

It is found in such plants as barberry, tree turmeric, Oregon grape, goldenseal, yellowroot, Amur cork, Chinese goldthread, prickly poppy, and California poppy. Berberine is usually found in the roots, rhizomes, stems, and bark.& https://www.thedrswolfson.com/10-spices-heart-health/&

X& 56

Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesnâ&#x20AC;&#x2122;t

Jack Wolfson, DO & Heather Wolfson, DC Berberine Increases LDL receptors

G-,H-,$%-)*#&I"2-@)*8+J)

Berberine , Lipids and Blood Sugar TC dropped by 18%

Berberine and Cancer

LDL dropped by 21% 20% reduction in FBS Hgb A1C from 7.5 to 6.6

J Clin Endocrinol Metab. 2008 Jul;93(7):2559-65.&

Leaky Gut Syndrome

The 10 Health Commandments &

1.! Get responsible Paleo 2.! Get sunshine 3.! Get sleep 4.! Get active 5.! Get hydrated 6.! Get chiropractic care 7.! Get rid of stress 8.! Get away from toxins 9.! Get grounded 10.! Get quality supplements

D& 57

& Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesn’t

Jack Wolfson, DO & Heather Wolfson, DC Vibrant- Wheat Zoomer

Vibrant- Wheat Wheat Zoomer VibrantZoomer

Zonulin Levels Are Higher in Patients with Coronary Artery Disease

K'%/>$%)#'%2,'>@) 25-)&C52)L/%#&'%)

)*+,--.../70@6/7<E/76)/234-+E0-5:B0<89-FGH(%IXI!!-c2A:8-O!-&

The higher the LPS…the higher the heart attack risk

Leaky Gut is Linked to Heart Failure

)*+9,--.../70@6/7<E/76)/234-+A@E81-!"=$!I%!&

!$& 58

Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesnâ&#x20AC;&#x2122;t Jack Wolfson, DO & Heather Wolfson, DC Wheat and the Leaky Gut

Decreased Melatonin and Leaky Gut

Leaky Gut and Parkinsonâ&#x20AC;&#x2122;s Disease

Stress and the Leaky Gut

Gluten-free Diet Resolves Neurologic Symptoms in Celiac and Non-Celiac Patients

Celiac Patients Have a Higher Risk of:

& 7-",2)"M"#93)@2,'9-3)"%.)#",.$'I"@#/>",).-"25)H6)N<O)

!!& 59

Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesn’t Jack Wolfson, DO & Heather Wolfson, DC

Leaky Gut Protocol NP! RP! :P! UP! ;P! ZP! [P! \P!

Butyrate Reduces Plaque

+">-')Q>-"%@-)R)@#''=@)=-,)."6) 1/2)S/->)R)#"=@)RT)=-,)."6) 1/2)E-="$,)N)2-"@=''%)=-,)."6) 8VD4W)U)#"=@)=-,)."6) FX-C")Y7*)N)#"=)=-,)."6) 1/2)S>',"):<)H$>>$'%3)N)#"=)=-,)."6) 1/2)05$->.)R)#"=@)RT)=-,)."6) G-,H-)N)#"=)RT)=-,)."6)

"&L85:&J<1&N3>&.6;)&b56<&F6d72&

Butyrate Lowers Inflammation

I’ll just pop a Lipitor and eat whatever I want!

!'& 60

Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesnâ&#x20AC;&#x2122;t Jack Wolfson, DO & Heather Wolfson, DC

K;5B7&N878c;9i&

PROSPER Trial

K;:3C8&[85;),&$/I^&49&$/X^&

5800 patients 50% women Aged 70-82 History of, or risk factors for vascular disease Pravastatin or placebo 3.2 year follow-up

%/'^&49/&(/(^& H3:375:>&f85:;&[698598&[85;),&%/'^&49&(/(^& $/I^&49/&$/X^&

H5708:&[85;),&(/!^&49&%/$^&

U3;5<&G3:;5<6;>g//b3&[6h8:8708&

U)8&]5708;&'$$'e&(=$,!='(#!=($& &

n'I$Q$$$Q$$$Q$$$&

)*+,--.../78jE/3:2-136-?A<<!$/!$I=bkaG35!=!I==%l;m5:B0<8&

!(& 61

Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesnâ&#x20AC;&#x2122;t Jack Wolfson, DO & Heather Wolfson, DC Chiropractic Care Lowers Blood Pressure

Low HRV Means Higher MI Risk )*+9,--.../70@6/7<E/76)/234-+A@E81-!D=D%(%I&

17/1 0

Chiropractic Improves HRV )*+9,--.../70@6/7<E/76)/234-+A@E81-!==D$(X$&

Just Say NO!!!!!

Case Study Z<)6]')X">-)A$25)5T)'?)Q*Y])^04_8W)"%.)@2-%2)2')D*Y) ) 02'=)D$=$2',) ) +">-')^/2,$&'%)"%.)+">-')D$?-@26>-3)#5$,'=,"#&#)#",-) "%.)-I$.-%#-BH"@-.)@/==>-X-%2@)

!%& 62

Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesnâ&#x20AC;&#x2122;t Jack Wolfson, DO & Heather Wolfson, DC

K+85C&L3A:&U:A;)&

3 Months Later

!I& 63

Evidence Based Integrative Cardiology Give the Body What it Needs and Take Away What it Doesn’t Jack Wolfson, DO & Heather Wolfson, DC Are you living the Wellness lifestyle?

“ The person who is not master of himself, can never be master of others.” - The Devil

Text PALEO to

42828

Over 300 references

!=& 64

Childhood Absence Epilepsy – Putative Complementary Diet and Orthomolecular Treatment Options Jonathan Prousky, ND, MSc, MA After this presentation you will be able to:! •! Distinguish between generalized and focal epilepsy! •! Understand some of the comorbidity that affects patients with childhood absence epilepsy! •! Recognize the morbidity and mortality risks of epilepsy in general! •! Know the limits of anti-epileptic medication! •! Describe the different dietary approaches for childhood absence epilepsy! •! Apply evidence-informed orthomolecular treatments for childhood absence epilepsy and other types of seizures!

Childhood Absence Epilepsy Putative complementary diet and orthomolecular treatment options! !

Dr. Jonathan E. Prousky, ND, MSc, MA, RP (Qualifying)!

What is epilepsy?!

Different types explained!

•! The disease of epilepsy is marked by repeated, but intermittent episodes of seizure activity “in which synchronous activity of nerve cells increases so that a gigantic hyperpolarization of neurons spreads over a large area in an atypical and abnormal manner” (Banich & Compton, 2011, p. 491). !

•! Two major classes:! 1.! Partial (or focal) seizures! 2.! Generalized seizures! a)! Grand mal seizures! b)! Petit mal (a.k.a., absence) seizures!

Different types explained !

Childhood Absence Epilepsy (CAE)! •! Involves the entire body when seizure activity is present, and accounts for 10-17% of all childhood-onset epilepsy cases (Berg et al, 2000; Jallon, Loiseau, & Loiseau, 2001). !

Childhood Absence Epilepsy – Putative Complementary Diet and Orthomolecular Treatment Options Jonathan Prousky, ND, MSc, MA CAE! !

CAE! ! •! Many patients also exhibit other clinical manifestations, such as mild clonic jerks (e.g., of the eyelids or corner of the mouth), atonic components (e.g., relaxation of grip and dropping of the arms), tonic muscular contractions (e.g., arching of the trunk), automatisms (e.g., aimless walking or lip licking), and even autonomic components like pallor, sweating, and less commonly, urinary incontinence (Panayiotopoulos, 1999). !

•! If one were to observe a child having absence seizures, there would be an “abrupt and brief impairment of consciousness, with interruptions of the ongoing activity, and usually unresponsiveness” lasting anywhere from several to twenty seconds, which is then followed by a sudden “resumption of the preabsence activity” as though it had never been interrupted (Panayiotopoulos, 1999, p. 351).!

CAE! !

CAE!

•! This form of epilepsy is often thought to be rather benign, but yet the remission rates are variable, and affected children can experience cognitive deﬁcits and long-term psychosocial difﬁculties (Bouma, Westendorp, Dijk, Peters, & Brouwer, 1996; Wirrell et al, 1997; Pavone et al, 2001). !

•! A study identiﬁed some of the general psychosocial problems encountered by children with CAE such as social isolation and low self-esteem, but these children also experienced higher rates of comorbid psychiatric symptoms, such as anxiety (nervousness and thought rumination) and depression (sadness and crying) (Vega et al, 2011). !

Epilepsy-Related Mortality! !

•! A population-based cohort study that followed patients for 40 years demonstrated that being diagnosed with epilepsy during childhood was associated with a substantial risk of epilepsy-related death that persisted into adulthood (Sillanpää & Shinnar, 2010). !

•!

The risk of death can also be ascertained by looking at the hazard ratio (HR), which (based on this study) refers to the probability of dying from epilepsy compared to deaths among individuals without epilepsy. !

Childhood Absence Epilepsy – Putative Complementary Diet and Orthomolecular Treatment Options Jonathan Prousky, ND, MSc, MA

Epilepsy-Related Mortality!

•! For epilepsy-related deaths among subjects did not achieve a 5-year terminal remission, the HR was determined to be 6.4 (95% CI, 2.2 to 18.8). ! •! A diagnosis of epilepsy in childhood presents serious threats to an individual’s overall mortality especially if the disease remains poorly controlled or resistant to treatment.!

•! For instance, among subjects that did not achieve a 5-year terminal remission, the HR for sudden, unexplained deaths was determined to be 5.2 (95% CI, 1.4 to 18.5). !

CAE - Treatment outcomes from ! !

! anti-seizure medication

•! The most widely regarded study on the treatment for CAE evaluated the most commonly prescribed antiseizure medications for efﬁcacy - i.e., ethosuximide (ES), valproic acid (VA), and lamotrigine (LT) - in a double-blind, randomized, controlled clinical trial (Glauser et al, 2010).!

•! Subjects (n=453; median age: 7 years and 5 months; age range: 2.5-13 years old) were randomized to one of these treatments over a 16-week period (sometimes, up to 20 weeks). ! •! All the subjects had CAE of new onset. Doses of all medications were increased every 1-2 weeks over the study period until the subjects became seizurefree, or adverse effects limited the prescribed dose. ! !

CAE - Treatment outcomes from ! !

CAE - Treatment outcomes from anti-seizure medication ! !

! anti-seizure medication

•! ES group details:! –! Lack of seizure control in 14% ([22/154]*100);! –! Intolerable adverse effects in 24% ([37/154]*100); ! –! Adverse psychological effects in 8% ([12/154]*100); ! –! Attentional problems in 33% ([35/106]*100);! –! Overall treatment failure 47% ([73/154]*100); and ! –! Seizure-free 53% ([81/154]*100).!

•! VA group details:! –! Lack of seizure control in 12% ([18/146]*100); ! –! Intolerable adverse effects in 24% ([35/146]*100); ! –! Adverse psychological effects in 14% ([20/146]*100); ! –! Attentional problems in 49% ([52/106]*100);! –! Overall treatment failure 42% ([61/146]*100); and ! –! Seizure-free 58% ([85/146]*100).!

! *Treatment failure=persistence of CAE at week 16 or week 20, a generalized tonic-clonic seizure at any time, excessive drug-related systemic toxicity, an increase in body mass index by 3.0 from baseline, and/or withdrawal initiated by physician or parent.!

Childhood Absence Epilepsy – Putative Complementary Diet and Orthomolecular Treatment Options Jonathan Prousky, ND, MSc, MA CAE - Treatment outcomes from anti-seizure medication ! !

CAE - Treatment outcomes from anti-seizure medication ! !

•! LT group details:! –! Lack of seizure control in 47% ([69/146]*100); ! –! Intolerable adverse effects in 17% ([25/146]*100);! –! Adverse psychological effects in 6% ([9/146]*100);! –! Attentional problems in 24% ([25/104]*100);! –! Overall treatment failure 71% ([103/146]*100); and ! –! Seizure-free 29% ([43/146]*100).!

•! As can be ascertained, some 50% of the subjects (i.e., 209 of the 446 children) became seizure-free during the study period. ! •! Treatment failure occurred in 42-71% of subjects (depending on the anti-seizure medication taken), which meant that a fairly large percentage of subjects failed to achieve complete remission of their seizures during the study.! !

CAE - Treatment outcomes from anti-seizure medication ! !

General treatment outcomes from anti-seizure medication ! ! •!! Treatment failures from the aforementioned studies were much larger when compared to the inefﬁcacy of anti-seizure

•! In a follow-up study (Glauser et al, 2012), patients were followed for 12 months. The freedom-fromfailure rates for ES, VA, and LT were 45%, 44%, and 21%, respectively. !

medications in general that fail to control seizures in about 30% of patients due to pharmacoresistance (Wahab, 2010).! •! Even when treatment is initiated early (as in CAE), there is no guarantee of long-term remission despite the fact that most patients with epilepsy are treated with anti-seizure medication for the duration of their lives (Wahab, 2010). !

Complementary Dietary Interventions for CAE!

•! Ketogenic diet (KD) - 90% fat, 8% protein, and 2% carbohydrates, and modiﬁed Atkins diet (MAD) - 64% fat, 30% protein, and 6% carbohydrates (Kossoff et al, 2013).! •! Paleolithic KD has been the subject of a case report (Clemens et al, 2013).! •! The KD has been compared to the MAD among patients with CAE (Groomes et al, 2011).!

•! Historical review (n=133; Groomes et al, 2011) demonstrated the following results from the KD: ! –! A total of 69% ([92/133]*100) had a greater than 50% reduction in seizures from the diet;! –! A total of 34% ([45/133]*100) became seizure-free for some period of time on the diet; ! –! It took between 3 days and 3 months to respond to the diet; and! –! The diet was continued for 9 weeks, and as long as 3 years among some patients.!

Childhood Absence Epilepsy – Putative Complementary Diet and Orthomolecular Treatment Options Jonathan Prousky, ND, MSc, MA Complementary Dietary Interventions for CAE!

Complementary Dietary Interventions for CAE!

•! Johns Hopkins study (n=21) as reported by Groomes et al (2011) demonstrated favourable results from either the KD (n=8) or MAD (n=13). ! •! With respect to the KD, a total of 25% ([2/8]*100) became seizurefree. ! •! With respect to the MAD diet:! –! A total of 15% ([2/13]*100) became seizure free, with a total of 31% ([4/13]*100) demonstrating greater than 90% reduction in seizures (i.e., meaning that a total of 46% of patients on the diet had an excellent clinical response);! –! A total of 46% ([6/13]*100) of patients experienced greater than 50% reduction in seizures; and! –! A total of 8% ([1/13]*100) of patients showed no improvement from the diet.!

•! Overall, it took between 1-3 months to respond to these diets, with greater improvements happening the longer the diet was maintained. Patients did better at 3 months compared to 1 month.! •! The more medicated the patients were, the less they beneﬁted from either diet. ! •! Children that demonstrate a greater than 50% seizure response from either the KD or MAD are encouraged to remain on the diet for at least 2 years.!

Complementary Dietary Interventions for CAE!

Complementary Dietary Interventions for CAE

•! With respect to the Paleolithic KD, the efﬁcacy of the diet was documented in 7 year-old girl with CAE (Clemens et al, 2013). The patient was having approximately 50 seizures daily prior to the dietary changes. The patient’s diet was complemented with vitamin D3 (2,000 IU/day), and omega-3 essential fatty acids (500 mg/day). It took 6 weeks for the child to become seizure-free on this diet, and this result was maintained for 20 months (i.e., before the paper was published). !

•! Possible mechanisms of action?! !

Complementary Orthomolecular Interventions for CAE!

Complementary Orthomolecular

! Interventions for CAE!

•! First-line treatments: Gamma-aminobutyric acid (GABA) and phosphatidylserine (PS).! One of the ﬁrst reports discussed results from the chronic oral administration of GABA among several patients under the subheading, “Anticonvulsant Effects of GABA in Man” (Tower, 1960, p. 568). The complete report involved a total of 11 patients that were given a regular daily schedule of oral GABA, and were followed for 3 months, and some for as long as 2 years. !

•! The ﬁrst case involved a 14-year-old girl with petit maltype seizures. For 7 months the patient had been treated with adequate doses of anti-seizure medications (i.e., trimethadione and diphenylhydantoin), but still experienced 300-500 seizures per month (mean: 402±68 seizures per month). The patient was given oral GABA only (2 mM/ kg 4 times daily or 0.8 g/kg daily), there was a “prompt and dramatic reduction of seizure frequency essentially to zero within 2 months” (p. 568).!

•!

! !

Childhood Absence Epilepsy – Putative Complementary Diet 17-04-01 and Orthomolecular Treatment Options Jonathan Prousky, ND, MSc, MA Figure 1. Monthly seizure record of J.D., 14-year-old female. Petit mal (PM) seizure frequency for the 7-month control period (C) while on trimethadione (TD) and diphenylhydantoin (D) had a mean value (M) of 402 (±68). Standard deviation of mean value indicated by length of the box (Tower, 1960, p. 569). Reprinted with permission from: Tower, D. B. (1960). The administration of gamma-aminobutyric acid to man: Systemic effects and anticonvulsant action. In Inhibition in the nervous system and gamma-aminobutyric acid (pp. 562-578). New York, NY: Pergamon Press, Inc.!

! Figure 2. Electroencephalographic records of patient J. D. (Fig. 1) at the start of hyperventilation (samples on left) and at the end of 3 min of hyperventilation (sample on the right). Record A taken before second trial of GABA (see Fig. 1) when frequency of seizures was 200-300 per month. Record B taken at the end of ! month 18 (see Fig. 1) while on oral GABA 2mM/kg 4 times daily. Seizure frequency at this time was less than 40/month. Electrode placements, instrument calibrations and other conditions were the same for both recordings. Time and calibration scales given ! between lower records. Electrode leads given between upper records (abbreviations: R=right; L=left; F=frontal; C=central; P=parietal; O=occipital – all in the midlateral ! plane – T=temporal (ear); and V=mid-vertex) (Tower, 1960, p. 570). Reprinted with permission from: Tower, D. B. (1960). The administration of gamma-aminobutyric acid to man: Systemic effects and anticonvulsant action. In Inhibition in the nervous system and gamma-aminobutyric acid (pp. 562-578). New York, NY: Pergamon Press, Inc.!

Figure 3. Seizure frequencies for three patients during control (C) periods and periods on oral GABA 2 mM/kg 4 times daily. Observation periods in months (m) indicated below each bar. For two patients on the left seizures are plotted as mean frequency per month for each period with the standard deviations indicated by the central line atop each bar. For patient M. B. on the right seizure are plotted as total number for the entire respective observation periods. (Abbreviations: Seizure types: PM= petit mal; Gn=nocturnal generalized or major; G=generalized or major; M=minor or petit mal; medications during control periods: A=L-asparagine; PD=paramethadione; MB=mephobarbital/Mebaral; MY=Mysoline). (Tower, 1960, p. 571). Reprinted with permission from: Tower, D. B. (1960). The administration of gamma-aminobutyric acid to man: Systemic effects and anticonvulsant action. In Inhibition in the nervous system and gamma-aminobutyric acid (pp. 562-578). New York, NY: Pergamon Press, Inc.! !

GABA and PS!

! •! A study by Loeb et al (1987) assessed the combined oral administration of GABA and PS among 42 patients with drugresistant epilepsy. Four patients were on 1 medication, 30 patients were on 2 medications, and 8 patients were on 3 medications.! •! The group included patients with various types of seizures (i.e., complex partial seizures, simple partial seizures, and absence seizures).!

Childhood Absence Epilepsy – Putative Complementary Diet and 17-04-01 Orthomolecular Treatment Options Jonathan Prousky, ND, MSc, MA GABA and PS!

GABA and PS!

•! The study was comprised of three different trials - denoted as A, B, and C (Loeb et al, 1987).! •! The results showed signiﬁcant clinical improvements, with 10 patients from the 34 (29.4%) having a demonstrable drop in seizure frequency (expressed as mean number of seizures per month ± SD) of 50% or more. ! •! A total of 12 patients with absence seizures (AS) were analyzed separately to determine their response to treatment. When Trials A, B, and C were combined, the results demonstrated a statistically signiﬁcant drop in the mean numbers of seizures per month during the reference period (29±18) and treatment period (12±13). !

•! Loeb et al (1987) concluded:! “There remains a pressing need for studies concerning the effect of GABA and phosphatidylserine on subjects suffering from absence seizures” (p. 212).!

GABA and PS! •! Possible mechanisms of action?! •! Case: Six-Year-Old Girl with CAE! !

What about the treatment of seizures of all types?! •!

Here are some examples! •! Manganese deﬁciency! –! 12-year-old boy with seizures had a poor response to anti-seizure medications.! –! Blood manganese level was half the normal value.! –! Manganese supplementation (20 mg/day) resulted in fewer seizures (Sampson, 1977).!

There are published reports showing benefits when individual orthomolecules are administered, especially when deficiencies were identified and treated.!

! !

Childhood Absence Epilepsy – Putative Complementary Diet and 17-04-01 Orthomolecular Treatment Options Jonathan Prousky, ND, MSc, MA Here are some examples!

Here are some examples!

•! Manganese deﬁciency! –! There are reports showing a relationship between low manganese levels and seizure activity. From Papavasiliou et al (1979): “...most of those with frequent seizures had manganese levels falling below the lowest control level, suggesting a relationship between manganese tissue levels and high seizure activity” (p. 1466).! –! From Dupont & Tanaka (1985): “Highly signiﬁcant was the lower mean blood manganese found in the convulsive disorder group as compared to the reference group. There was also a slight trend in the convulsive group for blood manganese to decrease from 1 to 22 years of age” (p.246).!

•! Vitamin D deficiency! –! In Holló, Clemens, Kamondi, Lakatos, and Sz!cs (2012), the adults had a disease duration ranging from 10 to 42 years, and all were considered to be pharmacoresistant. When the deficient 25(OH)D levels (defined as <30 ng/ mL or <75 nmol/L) were normalized from vitamin D3 supplementation, 10 patients experienced decreased seizure frequency during the 90-day observation period, with 5 having a marked seizure reduction of "50%.

! !

Here are some examples!

•! Vitamin E! –! Najafi et al (2016): “This double-blind, placebo-controlled trial was carried out on 65 epileptic patients with chronic antiepileptic intake. The subjects received 400 IU/day of Vitamin E or placebo for 6 months. Seizure frequency, electroencephalogram (EEG), and redox state markers were measured monthly through the study” (p.1).! –! “Vitamin E administration also caused a significant decrease in the frequency of seizures (P < 0.001) and improved EEG findings (P = 0.001). Of 32 patients in case group, the positive EEG decreased in 16 patients (50%) whereas among 33 patients in control group only 4 patients (12.1%) showed decreased positive EEG” (p. 1).!

•! Vitamin B3 ! –! Hoffer (1962) reported that niacin can reduce the amount of anti-seizure medication needed while still affording adequate seizure control. Hoffer’s report noted beneﬁcial effects from 3 g of niacin given to 6 epileptics who were having difﬁculty with control. Their anticonvulsants resulted in too much sedation. With niacin, the amount of anticonvulsant could as a rule be halved. ! !

Here are some examples!

•! Vitamin B3! –! As I suggested in my prior publication (Prousky, 2014), niacinamide is preferred because the cutaneous ﬂushing seldom happens, and because this form inﬂuences the GABA system, and has therapeutic effects similar to that of benzodiazepine medications commonly used to suppress seizure activity. ! ! !

•! Combined Treatment! –! Wright (1997) reported on a case of a 25-year-old male who had been taking phenytoin (100 mg QID) and phenobarbital (60 mg BID) for 22 years. He would have a grand mal seizure if he forgot to take his medications.! –! The patient’s energy was low and he reported problems in thinking clearly. His diet consisted of hamburgers, french fries, milkshakes, doughnuts, candy, pizza, chicken, cheese, bread, apples, bananas, and occasional salads. ! –! A healthier diet was likely advocated, but the report was not clear about any speciﬁc dietary changes. ! ! !

Childhood Absence Epilepsy – Putative Complementary Diet and 17-04-01 Orthomolecular Treatment Options Jonathan Prousky, ND, MSc, MA Here are some examples!

Here are some examples!

•! Combined Treatment Continued! –! Laboratory testing work-up consisted of mononuclear cell magnesium, white cell manganese and zinc, red blood cell copper, and hair selenium. Both magnesium and manganese were found to be low. ! –! Since his medications interfered with the absorption and/ or metabolism of folate and vitamin B12, he was given a few injections of vitamin B12 and folate and then recommended to take 2,000 mcg of vitamin B12 and 5 mg folic acid daily. !

•! Combined Treatment Continued! –! He was also placed on vitamin B6 (100 mg BID), calcium (600 mg QD), magnesium citrate (300 mg elemental magnesium QD), manganese citrate (50 mg elemental manganese QD), and also took a multiple vitamin-mineral containing 400 IU of both vitamins D and E, and a larger than usual amount of the B-complex vitamins. ! –! Since he observed that the injections of vitamin B12 and folate helped to keep him "mentally clearer" compared to the oral supplements, he learned to give himself injections of these two nutrients. !

! !

Here are some examples!

Transdiagnostic Orthomolecular Approach to Epilepsy 1.0!

•! Combined Treatment Continued! –! A trial of dimethylglycine was unsuccessful, but a trial of taurine 1,500 mg twice daily between meals was effective. ! –! Over the next 18 months, he was able to eliminate phenobarbital and reduce his phenytoin (100 mg TID) while maintaining complete seizure control. He also noted improvement in energy and mental clarity ! ! !

Transdiagnostic orthomolecular approach to epilepsy 1.0! Intervention!

Suggested daily therapeutic dose range!

Chromium picolinate !

200-600 mcg (in suspected hypoglycemia-associated seizures)!

GABA!

400-3,000 mg!

Magnesium!

200-600 mg (or more aggressively, 5-30 mg/kg)!

Manganese!

15-30 mg!

Phosphatidylserine!

200-500 mg!

Taurine!

100-1,500 mg (or more aggressively, up to 8,000 mg)!

Vitamin B3!

500-2,500 mg (as niacinamide)!

Vitamin B6!

60-200 mg (consider pyridoxal phosphate - the more potent form - at a dose of 7-38 mg/kg)!

Vitamin D3!

Optimal daily doses to maintain a 25(OH) D level "30 ng/mL ("75 nmol/L)!

Vitamin E (alpha-tocopherol)!

400 IU!

Zinc!

10-80 mg (consider adding 1-2 mg of copper if high doses of zinc, i.e., at or above 80 mg are taken long-term)!

17-04-01 Childhood Absence Epilepsy – Putative Complementary Diet and Orthomolecular Treatment Options

Jonathan Prousky, ND, MSc, MA References! ! Banich, M.T., & Compton, R.J. (2013). Generalized cognitive disorders. In Cognitive neuroscience (3rd ed., Int ed., pp. 466-497). United Kingdom: Wadsworth Cengage Learning.! ! Berg, A. T., Shinnar, S., Levy, S. R., Testa, F. M., Smith-Rapaport, S., & Beckerman, B. (2000). How Well Can Epilepsy Syndromes Be Identiﬁed at Diagnosis? A Reassessment 2 Years After Initial Diagnosis. Epilepsia, 41(10), 1269-1275.! ! Bouma, P., Westendorp, R. G., Dijk, J. G., Peters, A. C., & Brouwer, O. F. (1996). The outcome of absence epilepsy: A meta-analysis. Neurology, 47(3), 802-808. ! ! Clemens, Z., Kelemen, A., Fogarasi, A., & Toth, C. (2013). Childhood absence epilepsy successfully treated with the Paleolithic ketogenic diet. Neurology and Therapy, 2(1), 71-76.! ! Dupont, C., & Tanaka, Y. (1985). Blood manganese levels in children with convulsive disorder. Biochemical Medicine, 33(2), 246-255.!

References!

References! Loeb, C., Benassi, E., Bo, G. P., Cocito, L., Maffini, M., & Scotto, P. (1987). Preliminary investigation of the effect of GABA and phosphatidylserine in epileptic patients. Epilepsy Research, 1(3), 209-212.! ! Najafi, M., Mehvari, J., Motlagh, F., Ghazvini, M. A., Naeini, A., & Zare, M. (2016). Effects of Vitamin E on seizure frequency, electroencephalogram findings, and oxidative stress status of refractory epileptic patients. Advanced Biomedical Research, 5(1), 36. ! ! Panayiotopoulos, C. P. (1999). Typical absence seizures and their treatment. Archives of Disease in Childhood, 81(4), 351-355.! ! Papavasiliou, P. S., Kutt, H., Miller, S. T., Rosal, V., Wang, Y. Y., & Aronson, R. B. (1979). Seizure disorders and trace metals: Manganese tissue levels in treated epileptics. Neurology, 29(11), 1466-1466.! ! Pavone, P., Bianchini, R., Trifiletti, R., Incorpora, G., Pavone, A., & Parano, E. (2001). Neuropsychological assessment in children with absence epilepsy. Neurology, 56(8), 1047-1051. !

Glauser, T. A., Cnaan, A., Shinnar, S., Hirtz, D. G., Dlugos, D., … Adamson, P. C [on behalf of the Childhood Absence Epilepsy Study Group]. (2016). Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: Initial monotherapy outcomes at 12 months. Epilepsia, 54(1), 141-155.! ! Glauser, T. A., Cnaan, A., Shinnar, S., Hirtz, D. G., Dlugos, D., … Adamson, P. C [on behalf of the Childhood Absence Epilepsy Study Group]. (2010). Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. New England Journal of Medicine, 362(9), 790-799.! ! Groomes, L. B., Pyzik, P. L., Turner, Z., Dorward, J. L., Goode, V. H., & Kossoff, E. H. (2011). Do patients with absence epilepsy respond to ketogenic diets? Journal of Child Neurology, 26(2), 160-165.! ! Holló, A., Clemens, Z., Kamondi, A., Lakatos, P., & Sz!cs, A. (2012). Correction of vitamin D deﬁciency improves seizure control in epilepsy: A pilot study. Epilepsy & Behavior, 24(1), 131-133. ! ! Jallon, P., Loiseau, P., & Loiseau, J. (2001). Newly diagnosed unprovoked epileptic seizures: Presentation at diagnosis in CAROLE study. Epilepsia, 42(4), 464-475.! ! Kossoff, E. H., Cervenka, M. C., Henry, B. J., Haney, C. A., & Turner, Z. (2013). A decade of the modiﬁed Atkins diet (2003-2013): Results, insights, and future directions. Epilepsy & Behavior, 29 (2013), 437-442.!

References! !

References! Tower, D. B. (1960). The administration of gamma-aminobutyric acid to man: Systemic effects and anticonvulsant action. In Inhibition in the nervous system and gamma-aminobutyric acid (pp. 562-578). New York, NY: Pergamon Press, Inc.! ! Vega, C., Guo, J., Killory, B., Danielson, N., Vestal, M., Berman, R., . . . Spann, M. N. (2011). Symptoms of anxiety and depression in childhood absence epilepsy. Epilepsia, 52(8), 1528-1167. ! ! Wahab, A. (2010). Difficulties in treatment and management of epilepsy and challenges in new drug development. Pharmaceuticals, 3(7), 2090-2110.! ! Wirrell, E. C., Camfield, C. S., Camfield, P. R., Dooley, J. M., Gordon, K. E., Smith, B. (1997). Long-term psychosocial outcome in typical absence epilepsy: Sometimes a wolf in sheeps’ clothing. Archives of Pediatrics & Adolescent Medicine,151(2), 152-158.! ! Wright, J. V. (1997). Seizure disorder (epilepsy). Nutrition & Healing, 4(4), 1-2, & 9.!

Prousky, J. (2016). Childhood absence epilepsy: Putative complementary diet and orthomolecular treatment options; with an addendum to an earlier report. Journal of Orthomolecular Medicine, 32(2), 97-116.! ! Prousky, J. (2014). The adjunctive treatment of epilepsy with orthomolecular substances. Journal of Orthomolecular Medicine, 29(4), 167-175.! ! Sampson, P. (1977). Low manganese level may trigger epilepsy. Journal of the American Medical Association, 238, 1805.! ! Sillanpää, M., & Shinnar, S. (2010). Long-Term Mortality in Childhood-Onset Epilepsy. New England Journal of Medicine, 363(26), 2522-2529.!

Debunking Myths about Hormones: Why Bioidenticals Matter!"#$%#$!& Jeffrey Dach, MD & Phyllis Bronson, PhD

'()*+,+-./0-1(&2.34/45.& 6+(+5)+&78(4-&9$!"& :4+43.5;/1-&<+(,+5.=&153&& >((+(=&45&2+3.(5&6*?(+43+-+@?& &

7&C4B.(.5)&U.(=8./;J.&

A.B(.?&C1/*&2C& "%D$&E(4F5&G+13&H04).&!I$& C1J4.K&LM&NN$9!& ID%#"I9#%OON& PPPQR.B(.?31/*,3Q/+,&

&H-43.=&7J14-1S-.&7)T&!"#$%%&'()'*+,-!.+/-0.1

6*.&V5W+(,1;+5&X1(& 7@145=)&& :4+43.5;/1-&<+(,+5.=& & &

V5W+(,1;+5&X1(& C./.8;+5&#&Y1,+0Z1@.&

Y+5/.8)=&<1J.&S..5&6(15=W.((.3&W(+,&24-4)1(?&)+&Y4J4-415&7B14(=Q&& &H-43.=&7J14-1S-.&1)T1111111!"#$%%&'()'*+,-!.+/-0.1

6./*54[0.=&+W&C>Y>U6V'\K&& 1&L0531,.5)1-&G.[04(.,.5)& W+(&V5W+(,1;+5&X1(W1(.& ! " ]C./.8;+5&4=&^Q&4=&1&W0531,.5)1-&(.[04(.,.5)& W+(&=0//.==W0-&45W+(,1;+5&P1(W1(.Q_&`<0)/*45=+5K9$$!Oa& ! " E*+=)P(4;5@&7(;/-.=&45&2.34/1-&M4).(1)0(.& ! " H..345@&2.34/1-&H)034.=&P4)*&U(+#V530=)(?&:41=Q& ! " H..345@&U(+#V530=)(?&7(;/-.=&45&)*.&2.341Q& ! " Y+5W0=.&6.(,45+-+@?&P*.5&:.5.b/41-Q& ! " C.5?45@&>J43.5/.&+W&<1(,Q&&&

!"#$%#$!& Debunking Myths about Hormones: Why Bioidenticals Matter

Jeffrey Dach, MD & Phyllis Bronson, PhD

C./.8;+5&J=Q&G.1-4)?& !C " ./.8;+5#&<+(,+5.=&Y10=.& Y15/.(&153&<.1()&C4=.1=.&

! "UQ&V5*4S4)=&C2:7&4530/.3&,+3.-&+W& S(.1=)&/15/.(&45&,4/.K&C(&A1S1(1&`!a&& ! "V5&J4)(+&=)03?&c&U&V5*4S4)=&6P+&:(.1=)& Y15/.(&Y.--&M45.=K&C(&L+(,S?&`9a&& ! G1Rd0,1(&=*+P.3&1&8(+)./;J.&.B./)& +W&/+,S45.3&.=)(+@.5&153& 8(+@.=).(+5.&45&154,1-&,+3.-=&+W& S(.1=)&/15/.(Q`N#Da&

!G " .1-4)?&#&H?5)*.;/&<+(,+5.=& Y10=.&Y15/.(&153&<.1()&C4=.1=.&

! ! ! !

! "Y*-.S+P=d4K&G+P15&6QK&.)&1-Q&& & e>=)(+@.5&8-0=&U(+@.=;5&153&:(.1=)& Y15/.(&V5/43.5/.&153&2+()1-4)?&45& U+=),.5+810=1-&X+,.5Qe&& & A727&N$%Q!D&`9$!$aT&!Of%#!OI9Q&

"V5/(.1=.3&S(.1=)&/15/.(&& "V5/(.1=.3&/+(+51(?&*.1()&34=.1=.& "V5/(.1=.3&=)(+d.& "V5/(.1=.3&80-,+51(?&.,S+-0=&

:(.1=)&Y15/.(&

2!3'40567819:;:1<=>=1

Debunking Myths about Hormones: Why Bioidenticals Matter!"#$%#$!& Jeffrey Dach, MD & Phyllis Bronson, PhD

>=)(+@.5&&

U(.J.5;5@&:(.1=)&Y15/.(&& 45&U1;.5)=&& 61d45@&:4+43.5;/1-&<+(,+5.=&

X*1)&4=&)*.&>J43.5/.&k&

! " U(+@.=).(+5.&U-0=&>=)(+@.5&`L(.5/*&Y+*+()K9$$fa& ! " H/(..545@&21,,+@(18*?&7&C4=188+45),.5)&c

! "U(.J.5)=&:(.1=)&Y15/.(&

`>==.(,15&9$$Ia&

! " V+345.&6.=;5@&153&H088-.,.5)1;+5&V+3+(1-#`7/.J.=K&

! "U(.J.5)=&Y+(+51(?&7().(?&C4=.1=.&

L051*1=*4KY155K&&>=d45K&H*(4J1=)1J1K&g.5h0(4a&

! " H.-.540,&6.=;5@&153&H088-.,.5)1;+5&&

!U " (.J.5)=&'=).+1()*(4;=& ! "G.30/.=&7--&Y10=.&2+()1-4)?&

`Y-1(dK!IIOa&`:-.?=K9$$fa&

! CV2KC4453+-.2.)*15.K&VNY&`6*+,8=+5K&9$!Oa`L1(.=K9$!%a& ! " g4)1,45&CN&c&'8;,4i.Q`E1(-153K&9$$Oa& ! " 7J+43&j.5+#>=)(+@.5=&`C1J4=K!IINa&

"Y+(+51(?&7().(?&C4=.1=.&<1i1(3&G1;+& "D$#DI&?(=^^^^$QDI& "O$#OI&?(=^^^^!Q$& ""$#"I&?(=^^^^!Q$O&

! ! ! !

"7--#Y10=.&2+()1-4)?&<1i1(3&G1;+& "D$#DI&?(=^^^^$Q"N& "O$#OI&?(=^^^^!Q$%& ""$#"I&?(=^^^^!Q!9&

! " A727Q&9$!!mN$D`!NaT!N$D#!N!%&

M1Y(+4lK&9$!!&A727&

! ! ! !

"6+)1-&2?+/1(341-&V5W1(/;+5& "D$#DI&?(=^^^^$QD%& "O$#OI&?(=^^^^!Q$D& ""$#"I&?(=^^^^!Q9N&

Debunking Myths about Hormones: Why Bioidenticals Matter!"#$%#$!& Jeffrey Dach, MD & Phyllis Bronson, PhD

! ! ! !

! "C(&753(.1&>4=.5n=&818.(&(.W.(=&)+&<+(,+5.=& 0=.3&45&X<V&9$$9&1=&U(+@.=).(+5.&

"V5J1=4J.&:(.1=)&Y15/.(&<1i1(3&G1;+& "D$#DI&?(=^^^^$Qf$& "O$#OI&?(=^^^^$Q"N& ""$#"I&?(=^^^^$Qf!&

! "6*.&H)03?&C43&\+)&o=.&U(+@.=).(+5.Q& ! "X<V&9$$9&H)03?&0=.3&U(.,8(+p&`U(.,1(45p& 153&2.3(+l?#U(+@.=).(+5.a& ! " >4=.5K&753(.1&]<+(,+5.&)*.(18?&153&)*.&(4=d&+W&S(.1=)&/15/.(&45& :GY7!&,0)1;+5&/1((4.(=Q_&A\YVQ9$$fQ

X1(&:.)P..5&U1).5).3&C(0@=&153& '()*+,+-./0-1(&2.34/45.& ! "2145=)(.1,& 2.34/45.&4=&:1=.3& +5&H?5)*.;/1--?& 7-).(.3&U1).5).3& C(0@=Q& ! ">l/-03.=&\1)0(1-& H0S=)15/.=&P*4/*& Y155+)&S.& U1).5).3&

U(+@.=;5=&7(.&2+5=).(&<+(,+5.=&

7q.(&X<V&9$$9&

! "Y*.,4/1--?& 7-).(45@&1&\1)0(1-& H0S=)15/.&Y(.1).=& 1&2+5=).(& ! "U1).5)=&G.[04(.& 7-).(45@&)*.& Y*.,4/1-&H)(0/)0(.& +W&1&\1)0(1-& H0S=)15/.&

?0.'@1:4,@+0@1A!'1 B*@A!'C-1D0).0@'1B!8#1

Debunking Myths about Hormones: Why Bioidenticals Matter!"#$%#$!& Jeffrey Dach, MD & Phyllis Bronson, PhD

7S153+545@&H?5)*.;/&<+(,+5.=& Y+5=.[0.5/.=&+W&9$$9&X<V&H)03?&

X+,.5&153&C+/)+(=&7J+43&>=)(+@.5& &

! "U+=)&2.5+810=.&<G6&o=.&C(+8=&45&<1-W& 99r&)+&!9rQ&&`H8(1@0.K&9$!9a&& ! ""#I&r&G.30/;+5&V5&:(.1=)&Y15/.(&G1).=&45& oH&153&Y15131&45&9$$NQ`G1J345&9$$"a`E-1==K9$$"a& ! "Y+0()&Y-14,=&c&U(.,8(+p&Y10=.=&:(.1=)& Y15/.(K&&Ubi.(&H.h-.=&!$K$$$&Y1=.=&W+(&& !Q"&:4--4+5&C+--1(=Q&`6+(+5)+&H)1(&9$!%a&

2+()1-4)?&6+--&+W&>=)(+@.5&7J+4315/.& & ]'J.(&!$&?.1(=K&& D$K$$$&U+=)#2.5+810=1-&X+,.5&& C4.3&U(.,1)0(.-?&& :./10=.&+W&7J+4315/.&+W&>=)(+@.5&6*.(18?Q_& & `U*4-48&2Q&H1((.-K&2C&&s1-.&9$!Na&

>=)(+@.5&7J+4315/.&Y(.1).=& o55./.==1(?&H0B.(45@&

2.5+810=1-&7()*(4;=&c&& >=)(+@.5&C.b/4.5/?&

! " 6*.&,.34/1-&=?=).,&W14-=&,.5+810=1-&P+,.5&Q&& ! " ]G.-0/)15/.&)+&)(.1)&,.5+810=1-&=?,8)+,=&*1=& 3.(14-.3&153&W(1@,.5).3&)*.&/-454/1-&/1(.&+W& ,43-4W.&P+,.5K&/(.1;5@&1&-1(@.&153&

055./.==1(?&S0(3.5&+W&=0B.(45@Q_& & &

! " `A+755&215=+5&45&\>A2&>34)+(41-&9$!Oa&

>=)(+@.5&6*.(18?&U(.J.5)=& 2.5+810=1-&'=).+1()*(4;=&

G.W0@..=&>=/18.&W(+,&2+3.(5& >53+/(45+-+@?&

! " ]>=)(+@.5&G./.8)+(=&*1J.&S..5&43.5;b.3&45& 1(;/0-1(&/*+53(+/?).=&45&154,1-=&153&*0,15=Q_&&& ! " :./10=.&+W&`S.5.b/41-a&.B./)=&+W&.=)(+@.5&+5& 1(;/0-1(&/1(;-1@.^C(&615d+&13J4=.=^>=)(+@.5& )*.(18?&W+(&,145)14545@&/1(;-1@.&*.1-)*&45& 8+=),.5+810=1-&P+,.5Q_& ! " !%&754,1-&H)034.=&Y+5b(,&Y1(;-1@.&C.=)(0/;+5& 7q.(&'J1(4./)+,?K&U(.J.5;+5&P4)*&>=)(+@.5Q&& ! " `615d+K&&Y-4,1/).(4/Q&9$$f&L.Sm!!`!aT%#!OQ&a

Debunking Myths about Hormones: Why Bioidenticals Matter!"#$%#$!& Jeffrey Dach, MD & Phyllis Bronson, PhD

>((+(=&45&6*?(+43&>53+/(45+-+@?& 6%&2+5+)*.(18?&153&6H<& ! "G.-415/.&+5&6H<&'5-?&)+&2+54)+(&6(.1),.5)Q&Q`:415/+&9$!Oa& ! "6H<&H088(.==4+5&,1?&S.&5..3.3&W+(&73.[01).& 6(.1),.5)Q`V)+&9$!9a& ! "G.-415/.&+W&6%&'5-?#2+5+)*.(18?&`M.J+&+(& H?5)*+43a&&`E0--+K9$!!a& ! "\C6&c\1)0(1-&C.==4/1).3&6*?(+43&:.h.(&Y*+4/.Q&

& >((+(=&45&2+3.(5& 6*?(+43&>53+/(45+-+@?&

! " `<+15@K&9$!Na&

! "H*+().(&<1-W&M4W.#,1d.=&\C6&=1W.(&/*+4/.Q& ! "\C6&Y+,S45.=&6N&153&6%&#&,+(.&(+S0=)&W+(&8++(& /+5J.().(=Q&

<U7&&153&6H<&

6H<&H088(.==4+5&c&M1/d&+W&<1(,&

! "6H<& o5(.-41S-.&45& <?8+)*1-1,4/& C?=W05/;+5K& Y*(+54/& L1;@0.K& L4S(+,?1-@41& U1;.5)=&&

6(<&

6*?(+43&Y15/.(&U)=Q&&

6NK6%&

6H<&

•" M+5@#6.(,&H)03?&`"&?.1(=a&45&Y15/.(&U)=Q& •" 6%&6*.(18?&153&6H<&H088(.==4+5&Q& •" \+&>J43.5/.&+W&M+P.(&:+5.&245.(1-&C.5=4)?&

6%&

! " `6.4).-S10,K&<+-)+(WK& Hd455.(a&

•" `Y*.5&9$$%a&

6H<&H088(.==4+5&c&M1/d&+W&<1(,&

6*?(+43&\+30-.&&U)=Q&&

U+=)&2.5+810=1-&X+,.5& •" :4+43.5;/1-&<+(,+5.&U(+@(1,K&g4)&t9K&g4)&CK& Y1-/40,&.)/Q&&&&

•" 6(.1).3&P4)*&6H<&=088(.==4+5K&&

\+&4--&>B./)=Q&

•" :+5.&C.5=4)?&V,8(+J.=&.J.5&P4)*&=088(.==.3&6H<&Q `H/*5.43.(&!II%a&

•" `E*1(4SK&!If"a&

Debunking Myths about Hormones: Why Bioidenticals Matter!"#$%#$!& Jeffrey Dach, MD & Phyllis Bronson, PhD

6*.&6*?(+43&\+30-.&>843.,4/&&

6*?(+43&Y15/.(&& V5/43.5/.&153&2+()1-4)?&

C(&Y(+515T&e6*?(+43&\+30-.=T&& V=&V)&64,.&)+&60(5&'B&)*.&oH&21/*45.=k_&&

! " `C1J4.=&153&X.-/*K&9$!%a&

>((+(=&45&6*?(+43&>53+/(45+-+@?&& 6*.&6*?(+43&\+30-.&>843.,4/&& &

6*?(+43&Y15/.(&&>843.,4/& & ]\+)&15&>843.,4/&+W&C4=.1=.&S0)&& G1)*.(&15&>843.,4/&+W&C41@5+=4=Q_& &

! "C(&Y(+515&G134+-+@?&9$$f&T&& 60(5&'B&)*.&o-)(1=+053&21/*45.=&c&H6'U&oH& H/(..545@Q& ! "s+05@&P+,.5&P4)*&/-454/1--?&45=4@54b/15)&=,1--& )*?(+43&/15/.(=&1(.&S.45@&)(.1).3&P4)*& )*?(+43./)+,?&153&V#!N!&(134+#1S-1;+5Q& ! "6.=)&153&H088-.,.5)&P4)*&V+345.Q&

! " `C1J4.=&153&X.-/*K&9$!%a&

>((+(=&45&6*?(+43&>53+/(45+-+@?& 6*?(+43&153&U(.@515/?&

>((+(=&45&6*?(+43&>53+/(45+-+@?& V@5+(45@&73(.51-&L1;@0.& ! "<?8+)*?(+43K&& s.)&Y155+)&6+-.(1).&6*?(+43&2.3=Q& ! "6.=;5@#&& M+P&72&H.(0,&Y+(;=+-&M+PK&& M+P&H1-4J1(?&Y+(;=+-&72&`M1031)K&!Iffa& ! "73(.51-&H088+()&P4)*&<YK&g4)&YK&:DK& 7318)+@.5=Q&`Y-.1(.K&9$$!a&

! "V@5+(45@T&21).(51-&75;#6*?(+43&75;S+34.=&

153&H0S/-454/1-&<?8+)*?(+434=,&& 7==+/&Pu&V5/(.1=.3&24=/1((41@.K&&U(.J.5).3&P4)*& 6*?(+l45.Q&`\.@(+K&9$$Oa&

! "V@5+(45@&T&21).(51-&V+345.&C.b/4.5/?&

7==+/41).3&P4)*&G.30/.3&>30/1;+51-&'0)/+,.& 45&'B=8(45@Q&`<?5.=K&9$!Na&

Debunking Myths about Hormones: Why Bioidenticals Matter!"#$%#$!& Jeffrey Dach, MD & Phyllis Bronson, PhD >((+(=&45&6*?(+43&>53+/(45+-+@?&

H1-4J1(?&Y+(;=+-&73(.51-&L1;@0.&

V@5+(45@&<.1-)*&G4=d=& +W&<?8+)*?(+434=,&

! "<?8+)*?(+434=,&#&V5/(.1=.=&G4=d&+W&& Y+(+51(?&7().(?&C4=.1=.&153&& 2?+/1(341-&V5W1(/;+5#&<05)&H)03?#&`7=J+-3&:Rv(5& 9$$fa&

\+(,1-&

! "<?8+)*?(+434=,&c&C.8(.==.=&V,,05.& H?=).,K&V5/(.1=.=&G4=d&W+(&V5W./;+5&153& Y15/.(&& `L(4/dK&9$$Ia&`H/*+.5W.-3K&!IIDa&`U.((+h1&9$!%a&

L-1)&M45.&

>((+(=&45&6*?(+43&>53+/(45+-+@?& <1=*4,+)+=n& & ! "V@5+(45@&70)+#4,,054)?&45&<1=*4,+)+=&&

>((+(=&c&<1=*4,+)+=n&& 70)+#V,,05.&6*?(+43&C4=.1=.& ! "!a&V@5+(45@&H.-.540,&c&G.30/.=&15;S+3?&-.J.-=Q& `C(0).-K&9$!Na& ! "9a&V@5+(45@&6H<&H088(.==4+5&P4)*&6*?(+l45.&+(& \C6Q`G45d&!IIIa`U13S.(@K9$$!a& ! "Na&V@5+(45@&V+345.&##&=)1()&-+P&3+=.&99D&,/@&#& V,8+()15)&W+(&/*4-3&S.1(45@&1@.=&)+&8(.J.5)&-+P& Vw&45&S1S?Q& ! "%a&V+345.&P4--&H088(.==&6*?(+43&L05/;+5Q`C1?15K&!IIOa& ! "Da&V@5+(45@&E-0).5&L(..&C4.)&`<134)*4&9$$"a& ! "Oa&V@5+(45@&MC\&#&&M+P&C+=.&\1-)(.l+5.& ! ""a&C.1-45@&P4)*&<1=*4#)+l4/+=4=&&&L-0/)01;5@& )*?(+43&W05/;+5`7-i1*(154&9$$Da&

! ! ! ! ! !

>((+(=& E(1J.=n&<?8.(6*?(+434=,&

"V@5+(45@&6H<&H088(.==4+5&P4)*&6*?(+l45.&+(&\C6& "V@5+(45@&H.-.540,&6.=;5@&153&H088-.,.5)1;+5& "V@5+(45@&153&L.1(&+W&V+345.&H088-.,.5)1;+5Q& "V@5+(45@&G+-.&+W&X*.1)&E-0).5Q& "V@5+(45@&M+P&C+=.&\1-)(.l+5.&`MC\a& "'8;,4i.&g4)1,45&CN&

>((+(=&c&& 6+l4/&20-;5+30-1(&E+4).(&153&& 70)+5+,+0=&\+30-.&

! "G.-?45@&'5T&2.)*4,1i+-.K&G134+1/;J.&V+345.K& H0(@.(?&1=&'5-?&6(.1),.5)&#&\+)&)*.&'5-?&'8;+5=Q& ! "V+345.&6(.1)=&E(1J.=Q&`X1()+W=d?K&!I"$a& ! "M4)*40,&Y1(S+51).&6(.1)=&<?8.()*?(+434=,&`:+.*,K&

! "V+345.&Y+5)(1#V534/1).3& ! "V+345.&Y10=.=&6*?(+)+l4/+=4=&153& 6*?(+43&H)+(,Q&

!If$a&`6.,8-.K&!I"9a&

! "20=)&C4B.(.5;1).&E(1J.=n&W(+,&6+l4/&70)+5+,+0=& 6*?(+43&\+30-.K&153&6+l4/#\+30-1(&E+4).(#&V+345.& Y+5)(1#V534/1).3#&/10=.=&6*?(+)+l4/+=4=K&6*?(+43& H)+(,Q&o=.&6HV&153&6:#VVK&V,1@45@&PuoH&153&V#!N!Q&

Debunking Myths about Hormones: Why Bioidenticals Matter!"#$%#$!& Jeffrey Dach, MD & Phyllis Bronson, PhD

>((+(=& :4()*&Y+5)(+-&U4--=&W+(&UY'H&

Y(4,451-&>((+(=&45&>53+/(45+-+@?&& HHGVn=&W+(&2.5+810=1-&H?,8)+,=&

! "Y.5)(1-&L.1)0(.&+W&UY'H&c&M1/d&+W&'J0-1;+5& ! ":YUn=&V530/.&Y*.,4/1-&Y1=)(1;+5K&H088(.==& 'J0-1;+5&L0()*.(Q& ! "6(.1),.5)&+W&UY'H&=*+0-3&S.&)+&G.=)1()&'J0-1;+5& ! "Y?/-4/&U(+@.=).(+5.&!%&+5&!%&+BQ& ! "2.y+(,45u:.(S.(45.& ! "2?+#V5+=4)+-&

! "\+)&+5-?&4=&)*4=&15&>GG'GK&)*4=&4=&Y(4,451-&7S0=.&+W& X+,.5&xx& ! "6*.(.&1(.&5+&:4+43.5;/1-&<+(,+5.=&45&HHGV&C(0@=& & &

! "6*?(+43&xxx&

:4+43.5;/1-&<+(,+5.=& & :4+43.5;/1-&<+(,+5.=& Y-454/1-&788(+1/*.=& &

! "V5W+(,1;+5&X1(&1@145=)&\1)0(1-&H0S=)15/.=& ! "E*+=)P(4;5@&45&)*.&2.34/1-&M4).(1)0(.&S?&C(0@& V530=)(?&c&`H.5Q&E(1==-.?K&9$!$a& ! "6*.&>J43.5/.&E1,.&##&eV)z=&5+)&.J43.5/.&05-.==&4)=& 1&(153+,4i.3&8-1/.S+&/+5)(+--.3&)(41-e& ! "V,8+()15/.&153&H1W.)?&+W&:4+43.5;/1-&<+(,+5.=&#& 1h1/*&)+&50/-.1(&(./.8)+(=&P*4/*&/+5)(+-&8(+).45& =?5)*.=4=&5..3.3&W+(&;==0.&(.@.5.(1;+5Q&

:4+43.5;/1-&<+(,+5.=& U+=)#2.5+810=.& <.1-)*&G4=d=&+W&>=)(+@.5&C.b/4.5/?&

:4+43.5;/1-&<+(,+5.=&&& U+=)#2.5+810=.& 6.=)+=).(+5.&W+(&X+,.5&

! ! ! ! ! !

! "V,8(+J.=&20=/-.&6+5.K&20=/-.&21==K&:+5.& C.5=4)?&`J15&E..-&9$$Ia& ! "V,8(+J.=&M4S43+&V,8(+J.=&2++3K&>5.(@?&K& 2+;J1;+5K&75;3.8(.==15)&`C1J4=K&9$$fa&`E-+3=)1)K&9$$Na& ! "G.-4.J.=&C(?&>?.&H?53(+,.#&>?.&M43&C.-4J.(?& H?=).,Q`H0--4J15&9$$9a&

"V5/(.1=.3&2+()1-4)?&1q.(&<?=).(./)+,?& "Y1(;-1@.&M+==&153&'=).+1()*(4;=&153&CAC& "Y+(+51(?&7().(?&C4=.1=.&V5/(.1=.3& "M+==&+W&20=/-.&153&:+5.&C.5=4)?&#&'=).+8+(+=4=& "C.8(.==4+5K&75l4.)?&153&2++3&34=)0(S15/.& ":(.1=)&Y15/.(&V5/(.1=.3&xxxx&

Debunking Myths about Hormones: Why Bioidenticals Matter!"#$%#$!& Jeffrey Dach, MD & Phyllis Bronson, PhD

:4+43.5;/1-&<+(,+5.=&c& Y*1--.5@45@&Y1=.=& &

:4+43.5;/1-&<+(,+5.=&c& Y*1--.5@45@&Y1=.=& & ! "6*.&s+05@&UY'H&U1;.5)&#&&&

! "6*.&s+05@&73+-.=/.5)&L.,1-.&c*1=&5+)&=)1().3& +J0-1;5@K&+(&*1=&4((.@0-1(&/?/-.=Q& ! "6?84/1--?K&U)Q&*1=&05341@5+=.3&-+P&)*?(+43& /+534;+5Q&&V5&=84).&+W&5+(,1-&)*?(+43&-1S=Q&& GjT&6*?(+43&2.3=Q&`\C6K&M.J+)*?(+l45.a& ! "U(+@.=).(+5.&3.b/4.5/?Q&&& GlT&U(+@.=).(+5.&!%&+5&!%&+BQ&&& ! "'J1(415&W05/;+5&(./+J.(=&P4)*&)*?(+43& ,.34/1;+5Q&&

! ! ! ! !

:4+43.5;/1-&<+(,+5.=&& Y*1--.5@45@&Y1=.=&

75+J0-1;+5K&>-.J1).3&6.=)+=).(+5.K&'S.=4)?K& V5=0-45&G.=4=)15/.&& "Y?/-4/&U(+@.=).(+5.&& "2?+#45+=4)+-K&& "2.y+(,45K&:.(S.(45.&&.)/Q& "V+345.& "21?&/+#.l4=)&P4)*&<1=4,+)+=&&

:4+43.5;/1-&<+(,+5.=&c& Y*1--.5@45@&Y1=.=& & ! "6*.&U+=)&2.5+810=1-&'S.=.&2.)1S+-4/&

! "6*.&Y?/-45@&L.,1-.&P4)*&U2H&c&GlT&Y?/-4/& U(+@.=).(+5.&C1?=&!9#9O& ! "6*.&U.(4#2.5+810=1-&U1;.5)&#&21==4J.&HP45@=&45& >=)(+@.5&M.J.-=K&\+&8(+@.=).(+5.&8(+30/;+5Q&GlT& U(+@.=).(+5.&9f&+5&9&+BQ&&733&>=)(+@.5&-1).(& 1q.(&8+=)#,.5+810=1-&=?,8)+,=&=)1()Q& ! "6*.&>53+,.)(4+=4=&U1;.5)&c&GlT&H088(.==& 'J0-1;+5&P4)*&U(+@.=).(+5.&

H?53(+,.&U1;.5)&#&<+(,+5.&G.8-1/.,.5)&21?& X+(=.5&X.4@*)&E145&#&21?&X+(=.5=&Y+5)(+-&+W& :-++3&H0@1(#&X+(=.5&6(4@-?/.(43.,41Q& & ! "6*.&U+=)&2.5+810=1-&:-..345@&U1;.5)&c&& \..3=&U.-J4/&H+5+@(1,&153&U.-J4/&>l1,&P4)*&':u E?5&c&M++d&W+(&L4S(+43=K&73.5+#,?+,1)+=4=K& >53+,.)(41-&Y7&.)/Q&

:4+43.5;/1-&<+(,+5.=&c& s+05@&21-.=&#&M+P&6.=)+=).(+5.&

:4+43.5;/1-&<+(,+5.=&c& Y*1--.5@45@&Y1=.=&

! "7J+43&6.=)+=).(+5.&c&H088(.==.=&6&8(+30/;+5Q& ! "6(?&Y-+,48*.5.&#&:-+/d=&>=)(+@.5&G./.8)+(=&45& <?8+)*1-1,0=Q&N#O&,+5)*=&)*.5&=)+8Q& ! "73J.(=.&>B./)=&>?.&H?,8)+,=Q& ! "V5/(.1=.=&M<K&LH<K&153&6.=)+=).(+5.& ! "M++d&W+(&<U7&3?=W05/;+5&30.&)+&3(0@=&`+841).=K& ./=)1=?aK&-.1d?&@0)K&:!9&3.b/4.5/?&.)/Q& ! "21?&1-=+&0=.&<YE&`M<&151-+@a&

U+=)#<?=).(./)+,?&U1;.5)& ! "6?84/1--?&*1=&M+P&).=)+=).(+5.&153&M+P&M4S43+Q& ! "V5/(.1=.3&2+()1-4)?&7==+/41).3&P4)*&'J1(./)+,?&& ! "o5-.==&E4J.5&<G6Q&

!$&

Debunking Myths about Hormones: Why Bioidenticals Matter!"#$%#$!& Jeffrey Dach, MD & Phyllis Bronson, PhD

:4+43.5;/1-&<+(,+5.=&c& 7@45@&21-.=&#&M+P&6.=)+=).(+5.&

:4+43.5;/1-&<+(,+5.=&c& 7@45@&21-.=&#&M+P&6.=)+=).(+5.& ! "6.=)+=).(+5.&153&)*.&U(+=)1).&c&C+.=&\'6&Y10=.& U(+=)1).&Y7^L+--+P&UH7& ! "U+=)&#6(.1).3&U(+=)1).&Y7K&UH7{$&K&,1?&)(.1)& P4)*&6.=)+=).(+5.Q& ! "6.=)+=).(+5.&153&Y1(34+J1=0-1(&C4=.1=.& `8(.J.5;J.&+(&5+)a&H)1;5=&153&Y1-/40,&H/+(.& ! "6.=)+=).(+5.&:.5.b/41-&W+(&)*.&C41S.;/&21-.& ! "<E<&<0,15&E(+P)*&<+(,+5.&153&H.(,+(*.-45& `<1=&)*.&W13&.53.3ka&&

! "HjT&M+==&+W&20=/-.&6+5.K&>C&>(./;-.&C?=W05/;+5K& L1;@0.& ! "GlT&6(15=3.(,1-&6K&45R./)1S-.&6#/?84+51).K&& ! "7(+,1)1=.&45*4S4)+(=K&C<6&45*4S4)+(=& ! "<YE&45R./)1S-.&`M<&151-+@a&

E.|5@&'B&:13&C(0@=&

<?8+/*-+(*?3(41K&M.1d?&E0)K&& E-0).5&H.5=4;J4)?#&& >1(-?&70)+#V,,05.&C4=.1=.&

! "!a&:4=8*+=8*+51).=&W+(&'=).+8.541u'=).+8+(+=4=& ! "9a&H)1;5&C(0@=&45&X+,.5&153&>-3.(-?&cY7Y&H/+(.& ! "Na&HHGV=K&:.5i+=&153&153&7)?84/1-&75;8=?/*+;/=&# Y*./d&W+(&26<LG& ! "%a&UUV&75)#7/43&3(0@=&& ! "Da&E.|5@&X+,.5&'LL&:4()*&Y+5)(+-&U4--=&153& H?5)*.;/&<+(,+5.=& ! "Oa&E.|5@&t43=&+B&7CC&7C<C&C(0@=&# 7,8*.)1,45.=#&Y*./d&W+(&26<LG& ! ""a&L-+0(+[045+-+5.=&153&7Y*4--.=&6.53+5& G08)0(.& ! "fa&7/.)1,45+8*.5&153&M4J.(&6+l4/4)?&

! "M1S&81h.(5#&M+P&:!9K&M+P&L.K&M+P&H.K&M+P& ,45.(1-=K&M+P&6(4@-?/.(43.=K&<14(&M+==K&20=/-.& /(1,845@&1)&54@*)Q& ! "Y*(+54/&M+P&E(13.&>53+)+l.,41&c&Y+(+51(?& 7().(?&Y1-/40,&H/+(.& ! "6.=;5@&W+(&L++3&H.5=4;J4;.=&#&&7MY76K&Y?(.lK& >5).(+-1S=& ! "E-0).5&L(..&C4.)#&+)*.(=&C14(?K&>@@K&H+?&.)/Q&

H/(..545@&6.=)=& ! ! ! ! ! !

:4+43.5;/1-&<+(,+5.=& U(.J.5;5@&:(.1=)&Y15/.(&

":!9&3.b/4.5/?&c&H.(0,&:!9&153&227&& "H.-.540,&C.b/4.5/?&& "V+345.&C.b/4.5/?&c&=8+)&0(45.&4+345.&& "26<LG&,0)1;+5=& "V(+5&L.((4;5#&<.,+/*(+,1)+=4=& "M+P&:!9K&M+P&L.((4;5K&M+P&6(4@-?/.(43.=K& .-.J1).3&ML6n=T&81h.(5&=0@@.=)=&E-0).5&H.5=Q&

! "7J+43&H?5)*.;/&<+(,+5.=& ! "V+345.&H088-.,.5)1;+5&#&<4@*&C+=.&V+345.&153& :(+,45.&C.)+l&P4)*&H.1&H1-)& ! "G+-.&+W&H/(..545@&21,,+@(18*?&#&N$&?.1(& 51;+51-&,+()1-4)?&31)1&=*+P=&5+&S.5.b)Q&C(& M10(1&>==.(,15&A727& ! ":4+43.5;/1-&<+(,+5.=&W+(&:(.1=)&Y15/.(& H0(J4J+(=&`s.=&+(&\+ka&

!!&

Debunking Myths about Hormones: Why Bioidenticals Matter!"#$%#$!& Jeffrey Dach, MD & Phyllis Bronson, PhD

:4+43.5;/1-&<+(,+5.=& U(.J.5;5@&<.1()&C4=.1=.& ! ! ! ! ! ! ! !

:4+43.5;/1-&<+(,+5.=& U(.J.5;5@&70)+#V,,05.&C4=.1=.& &

">=)(+@.5&U(.J.5)=&Y7C&45&X+,.5& "6.=)+=).(+5.&U(.J.5)=&Y7C&45&21-.=&& "Y*+-.=).(+-&6*.+(?&J=Q&MUH&6*.+(?&+W&Y7C& "G+-.&+W&E-0).5K&\H7VCHK&M.1d?&E0)&153&M+P&-.J.-& .53+)+l.,41K&MUH& "G+-.&+W&6*?(+43&'8;,4i1;+5&#&&<05)&=)03?& "G+-.&+W&:-++3&C+51;+5#&G.30/.&L.((4;5&M.J.-& XV--41,&C1J4=&2C&6(1/d&s+0(&U-1[0.&U(+@(1,& "Y1-/40,&H/+(.K&H)1;5=&J=Q&7@.3&E1(-4/&153&g4)&t9&

! ! ! !

6*15d&s+0&c&75?&w0.=;+5=k&

"M+P&C+=.&\1-)(.l+5.& "E-0).5&H.5=4;J4)?#M.1d?&E0)&2+-./0-1(&24,4/(?& "'8;,4i45@&g4)1,45&C&153&:!9& ":4+43.5;/1-&<+(,+5.=&:.5.b/41-&W+(&70)+# V,,05.&C4=.1=.&

H)(1).@4.=&+W&V5W+(,1;+5&X1(W1(.&& ! " !Q&Y+5/.1-,.5)&&153&&Y1,+0Z1@.K&&+(&=).1-)*Q& `<4345@&+(&C.5?45@&C(0@&73J.(=.&.B./)=a& ! " 9Q&C./.8;+5&153&24,4/(?&K&4Q.Q&)*.&45=.(;+5&+W& 45).5;+51--?&,4=-.1345@&45W+(,1;+5m& `E*+=)P(4;5@&2.34/1-&1(;/-.=K&H..345@&2.34/1-& H)034.=a& ! " NQ&C4=(08;+5&&153&&C.=)(0/;+5}K&&4Q.Q&&)*.&& 45=.(;+5&&+W&&45W+(,1;+5&&P*4/*&&8(+30/.=&&1& 3?=W05/;+5&&&45=43.&&&)*.&&&+88+5.5)n=&&&=?=).,m& `Y+5W0=45@&6.(,45+-+@4.=&W+(&<+(,+5.=a&&

E)F';'+;G1HIJ=1K)8L@1M0,+1BF8A'1>N=%>O=1G,P8'Q1R31SSS>I11 OJITHO<TIUUS111111111111111111111111111111111111111555/&'()'*+,-!.+/-0.1 B38+'61:P,83,43'1,A$11!"#$%%&'()'*+,-!.+/-0.1

! " t+88K&Y1(-+&9$$D&

<U7&&153&6H<& ! "6H<&o5(.-41S-.&45& <?8+)*1-1,4/& C?=W05/;+5K& Y*(+54/&L1;@0.K& L4S(+,?1-@41& U1;.5)=&&

! " `6.4).-S10,K&<+-)+(WK&Hd455.(a&

!9&

Debunking Myths about Hormones: Why Bioidenticals Matter17-04-01 Jeffrey Dach, MD & Phyllis Bronson, PhD

17-04-01 Debunking Myths about Hormones: Why Bioidenticals Matter

Jeffrey Dach, MD & Phyllis Bronson, PhD

Debunking Myths about Hormones: Why Bioidenticals Matter17-04-01 Jeffrey Dach, MD & Phyllis Bronson, PhD

Orthomolecular Psychiatry in Japan Osamu Mizukami , MD Facts in Mental Disorders Autism, ADHD, Schizophrenia, Dementia Ultimate Target of Treatment

Orthomolecular Psychiatry in Japan

Osamu Mizukami, M.D., Ph.D.,Dr.P.H. Health Promotion Clinic

Conventional Treatment of Orthomolecular Psychiatry since Dr. Abram Hoffer

From Conventional to Today (2002-2017) Orthomolecular

Medication

Orthomolecular Neurotransmitter

Genome （Nutrigenomics）

Brain Mapping Cytokines

Source#http://www.myvmc.com/news/lifestyle-holds-key-to-predicting-womens-brain-health/

Psychiatric Care in Japan

Legacy “Hope for Schizophrenia” Dr. Abram Hoffer, M.D., Ph.D.

!!Antipsychotics were used since more than 60 years

!! Paradigm of Medication and Nutritional approach

!!Treatment and finding the cause are completely separated

!! Schizophrenia, Hope for Cure

!!Conventional medicine only focuses to suppress symptoms Cure disease is not in the scope, not even thought

!! Possibility of Curative Therapy

Reference: Physicians' Desk Reference

!! Another Pathway for Hope

Orthomolecular Psychiatry in Japan

Osamu Mizukami , MD

Psychiatrists in Japan Conventional Physicians

Orthomolecular Physicians

!!Medication for the rest of your life

!!Medication is temporally, use during acute phase and importance to reduce

!!Disease remains for a lifetime

Struggles of Japanese Orthomolecular Physicians !!Stories from Conventional Psychiatrists contradict with Orthomolecular concept and perturb families who listen in between.

!!Disease may be curable, need to find the root cause

!!Specialized inpatient facilities put a lid on mental disorders, Hide from Society

!!Treatment is mainly diets and nutritional supplements

!!Less care on side effects

!!Effects – Health and longevity

!!Vitamin therapy not acknowledged as treatment options. Most of Japanese doctors believe only medication is the treatment.

(per Dr. Hoffer)

Concept of Psychiatry !!Psychiatry doctors in Japan consider Schizophrenia cannot be improved to the extent of cure. !!Pharmaceutical drugs, only treatment and if drugs do not work, no other way.

Causes of Schizophrenia seen in Japan

!!Lots of psychiatry doctors in Japan tend to effect the treatment to extreme that usage of drug volume is heavy burden for patients.

Japanese Diet

Lifestyle change in past 50-60 years !!Junk foods, convenient stores !!Vending machines (soda drinks) ! excess sugar intake !!Preservatives：Foods, cosmetics !!Food additives：Thousands of new chemicals created in the past 50 years – bodies do not have the ability to e x c r e t e t h e m !!Use of antibiotics in livestock !!Foods：Raw fish, fried foods, dairy foods, Gluten !!Cooking utensils: Microwave, aluminum foil, plastic wrap !!Radiation: X-ray, Fukushima, various contamination !!Foods: Pesticides, herbicides, insecticides Destroy the whole ecological system from basis !!Air: Dioxin, emission (BTX), ultraviolet !! Heavy Metals: amalgam, foods, water, vaccines, fish

Past !!Lots of Enzyme & Fermented !!Lots of vegetables ! vitamins, minerals !!Fish, beans, brown rice, Soy ! High in good proteins, hepatic detoxification Phase 1 & 2 !!Nutrients played a major role in regulation and expression of genes

Today !!Refined !!Junk and fast convenient food with preservatives !!Food additives !!Lack of good air in cities !!Excess sugar intake !!No nutrients

Orthomolecular Psychiatry in Japan Osamu Mizukami , MD

Nutritional Approach for Schizophrenia Private Study

Abstract

（１）Hiroyuki Abe. M.D.

We provided 27 patients with schizophrenia, Orthomolecular Treatment based Dr. Hoffer’s Protocol

（２）Osamu Mizukami, M.D.

The nutritional protocol was the treatment based on orthomolecular medicine.

（３) Ken Kitahara, Director

The results show improvement among the patients hence we have decided to produce a short file to report to Dr. Hoffer.

Kudan Medical Clinic

Health Promotion Clinic

Japanese Society for Orthomolecular Medicine (JSOM)

Details of Participants

Applied Orthomolecular program

Age: 18∼50 years old（Average age 30.4 years old)

•! Vitamin B3

Gender: 21 males and 6 females Total 27 patients with schizophrenia

•! Vitamin C

3000mg

(Dosage varies depending on the symptoms according to Dr. Hoffer)

3000mg

•! Zinc

30mg

•! Magnesium

250mg

•! Fish oil EPA

1500mg

•! 5HTP

Varies on patient

•! Pyridoxal 5 Phosphate •! ALA

50mg

1000~2000mg (depend on patient)

•! Folic acid, Folate

5000~10,000mcg

Improvements in symptoms with Orthomolecular approach

Clinical Tests provided to patients with Schizophrenia

Number of cases

Proportion (%)

１ HOD（Hoffer-Osmond diagnostic test）: Basis of Evaluation

Improvement range (�) - 5 stages

２ Heavy metals（hair）

50> 50~<65

３ Allergy test（IgG foods)

65~<80

15%

４ Biochemical testing（liver, kidneys, fats, anemia … etc）

80~<95

15%

95<

22%

Total

100%

44%

Orthomolecular Psychiatry in Japan

Osamu Mizukami , MD

Summary

Improvements in severity (HOD testing)

Severity

Improvement range (�50%)

# of cases

Severe

50>

50~<65

65~<80

80~<95

The nutritional treatment based on orthomolecular medicine for schizophrenia correlates with the improvements in their symptoms.

Proportion (%)

95<

Moderate

74% 11%

Mild

15%

Total

Therefore, it is an effective treatment for improvement of schizophrenia.

100%

Japanese Society for Orthomolecular Medicine and Defeat Autism Now! Concluded partnership agreement with DAN! For exchange of info

Biomedical Treatment for Autism Conclusion Autism should be positively treated Orthomolecular as Core of treatment

Current Approach for Autism in Japan

Current Approach for Autism in Japan •! Clinical study ! Not much abnormal results found on brain EEG

•! Medical practice ! Mostly seen as pediatric psychiatry

•! Diagnostic approach ! Behavior observation

•! Coping strategy ! Medication for Schizophrenia

•! The most acknowledged treatment in Japan ! Use of psychotropic drug, risperidone

•! Most of doctors do not believe possibility of cure for the problem •! No Consideration for Nutrition, Orthomolecular approach ! Use of psychotropic drug, risperidone

Orthomolecular Psychiatry in Japan Osamu Mizukami , MD

Comparison of Healthcare System in Japan and the U.S. Japan and US •! Autism is psychiatric disorder = Treatment is only medication

Why is there is no concept for treatment of Autism in Japan?

•! The root causes are not specified yet •! There is no consensus on the Government side, medical community, insurance and treatment protocol for the disease •! Do not know when the treatment will be enacted

Comparison of Complementary and Integrative Medicine for Autism in Japan vs U.S.

Comparison of Available Supports for Autism in Japan and the US

U.S.

"""""Japan •! None

"""""Japan

(Complementary & Integrative medicine)

•! Education

•! Many healthcare options which are not designated by government •! Variety of alternative treatments are available for the difficult diseases which cannot be cured by conventional medicine •! These treatments are also approved by the government （The systems differ for each state）

What we have learned from U.S. & Canada on Biomedical Approach

•! Education •! ABA、RDI •! Hyperbaric oxygen therapy •! Homeopathy •! Music therapy •! Vision therapy •! Exercise therapy •! Others

What we have learned from US & Canada on Biomedical Approach •! The key is to know what is going on

•! Verify the root cause based on the Biomedical tests, Functional Medicine

•! Intervention of biomedical treatment to the test results which are scientifically authenticated

•! According to the test results, intervene complementary and integrative approaches ! Starting from Sleep disturbance, hyperactivity, selfinjury, violence, digestive problems, detoxification, infection.

•! Biomedical testing provided by U.S. Labs are almost non existing in Japan

•! Major task is recover speech and social compatibility. •! Basic approach by nutritional treatment

Orthomolecular Psychiatry in Japan

Osamu Mizukami , MD

We strongly Recommend Treatment at young age as possible •! There is a possibility to develop other serious diseases with growth. Intervention of treatment in the early age can help them develop to full potential – Young brain responds to the treatment well and parents can manage children’s medical conditions whereas the management will be difficult when they grew up. •! The cost doubles since the designated disability insurance do not cover enough （double negative factor）

Factors for development of Autism in children in Japan

Causal factors for Autism Multifaceted factors ! Genetics

! Imbalance in zinc and copper

! Harmful substance from mother ! Major GI issues ! Oxidative stress ! Vaccination

! Casein & Gluten

Psychotropic Substance Doesn’t Work

! Lowered immune function ! Chronic inflammation

Due to the Multifaceted Factors

! Mercury ! Hepatic detoxification ! Environmental pollution

Japanese Tendency in IgG delayed Food Allergy

Particularity of Children in Japan from today’s Nutrients and Diets •! •! •! •! •! •!

•! Food allergy testing identifies food intolerance and high sensitivity which leading to immune response.

Lack of quality protein and quality fat intake from Diet Tendency of over intake of low quality Carb Too high sugar diet Condition of gut, weak absorption capacity Very low diversity of Gut Flora Digestive ability of stomach acid and pancreatic enzyme

•! From the test results, elimination of wheat and dairy foods are recommended. •! There is very high prevalence of allergy to Egg white and york. •! Prevalence of allergy to Soy is not common.

100

Orthomolecular Psychiatry in Japan Osamu Mizukami , MD

Frequent problems requiring imminent solution

•! Sleep disorder（sleep onset, arousal at midnight, day-night reversal）

•! Hyperactivity and agitation > Good response with Orthomolecular therapy

•! As seen in Mental Disorders, often problems in neurodegenerative disease start here

•! Too much of Excitatory neuro system is activated •! Low level of serotonin and deficiency of inhibitory neurotransmitter and hormone

•! Often children show deficiency in protein from diet which leading to serious deficiency of Amino Acids.

•! Nutritional and Orthomolecular approach is very effective

•! Nutritional and Orthomolecular approach with Melatonin, 5HTP, Amino Acdis are useful.

Foods

Very challenging symptoms Avoid

•! Loss of interest •! Obsessiveness •! Monology •! Speech disability •! Problems in conversations, understanding social communications

•! Glutamine, glutamic acid, MSM •! Pesticides, preservatives, food coloring, flavoring •! Gluten, casein（wheat, milk） •! Sugar, excess intake of carbohydrate •! Junk foods, trans fat salad oil

Most of children in Japan showing problem in this area

Encourage •! High quality protein diet •! High quality fats ! Tissues in brain Fish oils (Omega 3), Animal fats •! Whole foods ! No refined, no processed, no additives

Immune conditions very often affected by LGS •!

Leaky Gut Syndrome High prevalence in Japan

•! •! •!

101

Gut health compromised （70% of immune and neurotransmitter generated） Balance of good bacteria and bad bacteria is reversed Inflammation（inability of breaking down gluten and casein） Generation of morphine lowering brain function

Orthomolecular Psychiatry in Japan

Osamu Mizukami , MD

Gastrointestinal Test

("/-!(-*-&6

•! Treatment for Autism：First thing to do is to treat gut •! Strong correlation in microbiome and brain neurons •! Nutrient absorption

(&' ,8 ++ 1(-,

$"/$1-/6 *&

216/ 1$ -1 *

102

Orthomolecular Psychiatry in Japan

Osamu Mizukami , MD

Eliminate Inhibitory Factors in children

Detoxification of Toxins •! •! •!

•! Bad bacteria in gut, virus •! Toxic substances in vaccines MMR, DPT, thimerosal, aluminum •! Detoxification of aluminum (especially in Females) •! Chelation（mercury, lead, cadmium, arsenic…etc）

Hepatic detoxification Capacity compromised Heavy metals, PCB, pesticides, BTX, insecticides Low function of detoxification and glutathione deficiency

Heavy Metal, problem in Japan •!

•!

Toxic & essential elements in Hair (Screening test)

Heavy metals from mothers •! Mercury •! Contact lens fluid（thimerosal） •! Vaccines that mothers had •! Fish consumption in Japan (Tuna)

•! Japanese parents very interested to check the excretion of induced toxins in the past few month •! Appropriate screening for living environment •! We find high numbers of Arsenic, Mercury from most of patients and population •! In essential element paragraph, we see lots of very high Copper and often low level of essential minerals as Magnesium, Zinc, chromium etc.

Heavy metals from environment •! Coal fired power generation •! Chlorination releases 50 tons of mercury annually •! 1,000 times of lead accumulation in bones after industrialization •! Heavy metals from vaccines •! Thimerosal, aluminium •! Lots of newborns have toxic level of mercury

Study with Dr. Amy Yasko Protocol

Patient M. A.

Total Support Program

•! !"#$%

•!Step One:

•! &'$%(%)$"*+%,#-%

Preparation therapy for Detoxification program

•! .$/$*$%&01+12%3"4"/5,*6%7,7%/$*3"#6%"'*$++5/$

•!Step Two: Therapy to remove heavy metals through treatment of chronic virus infection due to low Immune function and Vaccination

103

Orthomolecular Psychiatry in Japan

Osamu Mizukami , MD

!0$/3 1(-, (, $1-5 -% $+ *$ 21(0+ 1($,1 â&#x20AC;¢!8$7-$72)%95:4%;$<"#$%=45#-*$7% â&#x20AC;¢!%>?2*$1,7%,@%45'4%&#0<570<

Patient M. S. â&#x20AC;¢! ;$<"#$% â&#x20AC;¢! &'$%A%)$"*+%,#-% â&#x20AC;¢! B,7%/$*3"#6%2,/$*57'%/"*5,0+%&.C%+)<D:,<+

104

Orthomolecular Psychiatry in Japan

Osamu Mizukami , MD

Methylation Pathway Support â&#x20AC;¢! SAMe

100~200mg/day

â&#x20AC;¢! B6 Complex

25mg P5P+ Vitamin Bs

â&#x20AC;¢! 5 MTHF

200~400mcg

â&#x20AC;¢! Adenosyl/Hydroxy B12

4,000mcg ~ Higher/day

â&#x20AC;¢! Methyl B12

5,000mcg ~ Higher/day

21/(&$,-+("0 $1'6* 1(-, 1'4 6 -+-76&-20 Mutation

/$ )#-4, -% 21 1(-,0 , $1'6* 1(-, 1'4 6 +-,& . ,$0$ .-.2* 1(-,

21/(&$,-+("0 $1'6* 1(-, 1'4 6 $1$/-76&-20 Mutation

Total screened" Number + U.S.A (heterozygous) for mutation

Percent + (heterozygous) for mutation

Total screened" Number + JAPAN (heterozygous) for mutation

MTHFR A1298C

3266

1380

42%

243

40%

3265

1424

44%

243

100

41%

CBS C699T

3264

1259

36%

243

32%

CBS A360A

2650

1384

53%

243

153

63%

MTRR A66G

3265

1573

48%

243

112

46%

MTRR K350A

3086

702

23%

243

18%

MTRR H595Y

3087

599

19%

243

18%

MTR A2756G

3261

979

30%

243

33%

Percent ++ (homozygous) for mutation

Total screened" Number ++ -JAPAN (homozygous) for mutation

Percent ++ (homozygous) for mutation

MTHFR A1298C

3266

363

11%

243

11%

MTHFR C677T

3265

371

11%

243

10%

CBS C699T

3264

355

11%

243

11%

CBS A360A

2650

243

MTRR A66G

3265

896

27%

243

17%

MTRR K350A

3086

243

MTRR H595Y

3087

243

MTR A2756G

3261

161

243

NutriGenomics Conclusion

Percent + (heterozygous) for mutation

MTHFR C677T

Total screened" Number ++ * -U.S.A (homozygous) for mutation

Specificity of Individual DNA SNiPs and Biochemical Reaction Different Reactions to Medications and Natural Substances Necessity for Tailor-Made Treatment

105

Orthomolecular Psychiatry in Japan Osamu Mizukami , MD Direct overlook into the Brain Function

New Protocol, Direct Overlook of Brain

1. EEG plus computerized analysis of brain function

2. Attention Circuit Brain Especially, monitors frontal lobe (Fp1, Fp2) and occipital lobe â&#x20AC;&#x192;

Edelfo, Neurorecovery Center

3. Cognitive Activity P300 Tests cognitive function, decision-making, imagination skills 4. Coherence Analysis Evaluates the function of brain in transforming signals evenly spread through the brain.

â&#x20AC;˘!Brain Mapping, EEG â&#x20AC;˘!Functional Brain Assessment â&#x20AC;˘!Cytokines, activation of Stem cells, Neuro Genesis â&#x20AC;˘!Still Orthomolecular treatment at the basic core of the treatment

5. Emotion Process Evaluates how brain reacts to emotions such as happiness, laugh, sadness, fear, wonder, anger or neutral status 6. Visual Space Memory Evaluates cognitive function and memory function 7. Mental Flexibility Evaluates creative skills, imagination skills, and mental flexibility 8. Flash Visual Evoke Potential Evaluates severity of diseases

Treatments

â&#x20AC;˘! Introduction of neurotrophic factor

â&#x20AC;˘! Production of serotonin

" Brain derived neurotrophic factor

â&#x20AC;˘! Fragments of protein amino acids

â&#x20AC;˘! Production of Dopamine

â&#x20AC;˘! Precursors of cytokine which induces traffic of neurons for recovery

" Glia cell derived neurotrophic factor

â&#x20AC;˘! Production of glutamate " Fibroblast growth factor

â&#x20AC;˘! Production of GABA " Granulocyte colony-stimulatory factor

â&#x20AC;˘! Production of neurons, glutamate " Stem cell factor

â&#x20AC;˘! Progenitor to produce neuroblast " Fibroblast growth factor Hepatocyte growth factor Brain derived neurotrophic factor

1($,1 *$ &$ â&#x20AC;˘! 61-)(,$0 # & # " ! ! & &" ! ' !"! " " &" ! # ! ! ! " â&#x20AC;˘! 61-)(,$0 & 1'$/ %" " ! " # ! ! " ! & !" # " " ! "# ! ! " ! â&#x20AC;˘! $"10 !!# " # ! ! # " $ " $ !! ! " !

! $ " ! ' " ! $ " ! % ! ! " " ! ! " " ! " " ! " " " " " $ #! !"# & " " # # # " "" " " !" Subject: YUJI KUNIHIRA, Age: 10 EEG file: ATENCIONSEĂ&#x2018;AL-4.avg Recorded : 11:30:40 10-Nov-2016 Rate - 500 Hz, HPF - 0.5 Hz, LPF - 30 Hz, Notch - 50 Hz

*ATENCIONSEĂ&#x2018;AL-4.avg ATENCIONSEĂ&#x2018;AL-3.avg 12500.00

ATENSEĂ&#x2018;ALGROUP.avg

Neuroscan SCAN 4.3 Printed : 17:54:04 10-Nov-2016

!"#$%&'(#)*+,-

10000.00

!V^2

7500.00 5000.00 2500.00 0.00 0.0

106

250.0

500.0

750.0

1000.0

Orthomolecular Psychiatry in Japan Osamu Mizukami , MD

1($,1 *$ &$

! $ " ! ' " $ " " & " " "% /($1 * "$,1/ * /$&(-, " !" " !

! $ " ! ' " $ " " & " " "% $+.-/ * ,1$/(-/ /(&'1 /$&(-, " !" " !

" ! "

Subject: YUJI KUNIHIRA, Age: 8 EEG file: 1-P3TARGERCOH52.coh Recorded : 01:32:04 24-Nov-2014 Rate - 500 Hz, HPF - 0.5 Hz, LPF - 30 Hz, Notch - 50 Hz

Neuroscan SCAN 4.3 Printed : 17:36:20 10-Nov-2016

Subject: YUJI KUNIHIRA, Age: 10 EEG file: 4-P3TARGERCOH52.coh Recorded : 11:24:48 10-Nov-2016 Rate - 500 Hz, HPF - 0.5 Hz, LPF - 30 Hz, Notch - 50 Hz

Neuroscan SCAN 4.3 Printed : 17:35:45 10-Nov-2016

Severity

# of Patient

Mild

â&#x20AC;&#x192;

Moderate

Moderate to Severe

9 2 15

Subject: YUJI KUNIHIRA, Age: 10 EEG file: 4-P3TARGERCOH52.coh Recorded : 11:24:48 10-Nov-2016 Rate - 500 Hz, HPF - 0.5 Hz, LPF - 30 Hz, Notch - 50 Hz

Neuroscan SCAN 4.3 Printed : 17:37:33 10-Nov-2016

Nutraceuticals, Orthomolecular remain at the Core Augmentation Therapy

Sampleï¼&#x161;15

Total

Neuroscan SCAN 4.3 Printed : 17:37:05 10-Nov-2016

New Paradigm

Effects of Treatment

Severe

" ! "

Subject: YUJI KUNIHIRA, Age: 8 EEG file: 1-P3TARGERCOH52.coh Recorded : 01:32:04 24-Nov-2014 Rate - 500 Hz, HPF - 0.5 Hz, LPF - 30 Hz, Notch - 50 Hz

Nutrition + Supplementation

Others*

[ã&#x192;&#x2018;ã&#x192;¼ã&#x201A;»ã&#x192;³ ã&#x192;&#x2020;ã&#x192;¼ã&#x201A;¸] Not Improved [ã&#x192;&#x2018;ã&#x192;¼ã&#x201A;»ã&#x192;³ ã&#x192;&#x2020;ã&#x192;¼ã&#x201A;¸]

Improvedâ&#x20AC;&#x192; [ã&#x192;&#x2018;ã&#x192;¼ã&#x201A;»ã&#x192;³ ã&#x192;&#x2020;ã&#x192;¼ã&#x201A;¸]

Others*ï¼&#x161;Patients whose symptoms were already improved before the treatment from Edelfo

Thank you The continued importance of lifestyle modification and orthomolecular medicine is reaffirmed.

107

Phytochemicals in the Treatment of ADHD

!"#$%#$!&

James Greenblatt, MD

Diary of a Young Psychiatrist

Phytochemicals in the treatment of ADHD

NO DRUGS!

DRUGS!

46th Orthomolecular Medicine Today Conference April 29, 2017

James Greenblatt, MD

Chief Medical Officer, Walden Behavioral Care

The Evolution of ADHD !! !! !! !! !! !! !! !! !! !! !!

Fidgety Philip

Defective Moral Control (1902) Restlessness Syndrome (1920s) Post-Encephalitic Behavior Disorder (1920s-1930s) Brain Injured Child (1940s) Minimal Brain Damage (1950s) Minimal Brain Dysfunction (1960sâ&#x20AC;&#x201C;1970s) Hyperactive Child Syndrome or Hyperkinetic Reaction of Childhood (1960s) Attention Deficit Disorder with or without Hyperactivity (1980) Attention Deficit Hyperactivity Disorder & Undifferentiated Attention Deficit Disorder (1987) Attention Deficit Hyperactivity Disorder & Attention Deficit Disorder (1993) ADHD (2013) â&#x20AC;&#x201C; DSM V

Hoffmann - 1846 Thome & Jacobs.Eur Psychiatry. 2004 Aug;19(5):303-6.

Prevalence

Developmental Consequences of ADHD !! Low self esteem

ADHD is the most common psychiatric disorder of childhood

!! Poor peer relations !! School failure

6.4 million children, or 11% of children aged 4-17, have been diagnosed with ADHD nationwide

!! Strained family relations

41% increase from 2003 to 2011

For children with ADHD, at least 15% will continue to meet full ADHD diagnostic criteria and an additional 50% will continue to have ADHD symptoms These individuals are more likely to experience social, educational, emotional, and cognitive challenges

Visser. J Am Acad Child Adolesc Psychiatry. 2014 Jan;53(1):34-46.e2.

Agnew-Blais. JAMA Psychiatry. 2016 May 18.

108

Phytochemicals in the Treatment of ADHD

!"#$%#$!&

James Greenblatt, MD

Economic Burden Of Chronic Conditions (2010 U.S. Dollars)

Consequences of Adult ADHD

Emotional Impairments

Generalized anxiety disorder: $139-$155.5 billion

Behavioral Impairments Work

Self Esteem

Relationships

Major depression: $124 billion Asthma: $20.4 billion

Drug Abuse

Divorce

ADHD: $143-$266 billion

Financial

Global Differences

Doshi. J Am Acad Child Adolesc Psychiatry. 2012 Oct;51(10):990-1002.e2.

U.S. versus France

Global Variation in Prevalence and Treatment

In France it is illegal to prescribe stimulants to children under age 6 In contrast, the AAP recommends medications for children as young as 4

â&#x20AC;˘! 11% of children aged 4-17 have ADHD diagnosis â&#x20AC;˘! 6% taking medication

A review of national insurance data from 2008-2014 for children under 6 found over 75% received medication for treatment

<.5% of children diagnosed and medicated for ADHD

Visser. MMWR Morb Mortal Wkly Rep. 2016 May 6;65(17):443-50. Subcommittee on ADHD. Pediatrics. 2011 Nov;128(5):1007-22.

Wedge. 2012. Why French Kids Don't Have ADHD. Psychology Today.

Finally Focused

Phenylalanine

Dopamine degradation

Reuptake

MAO

Tyrosine

COM T

5-MTHF

Is there a need to get something?

Is there a need to avoid something?

L-DOPA

P5P Zinc

Dopamine

Dopamine Nutrients Vitamins Minerals Fatty acids Amino acids Hormones Light Love Nature Positive Feedback

Toxins Elementary (lead, mercury, etc.) Biologic (plants, germs, etc.) Synthetic (mostly petrochemical) Pesticides

Allergens Food Pollen Dust Dander Chemicals Mold Germs

Dopamine

Cognitive function* Mental sharpness* Alertness* Dopamine receptor

Autoimmune Celiac Disease

Genetics and Epigenetics

109

Phytochemicals in the Treatment of ADHD

!"#$%#$!&

James Greenblatt, MD

Oligomeric Proanthocyanidins – OPC’s

OPCs: History

OPCs are a type of polyphenol, a compound that plants produce to protect themselves from environmental harm

1534: Quebec Native Americans cured the crew of French explorer Jacques Cartier of scurvy by feeding them tea from the needles and bark of certain pine trees

Oftentimes the polyphenol is a plant pigment: –! –! –! –!

1947: Dr. Jack Masquelier of France read Cartier’s journal

the blue in blueberry the red in grapes the green in green tea the dark brown in dark chocolate

red wine

Knowing pine bark contained only a small amount of vitamin C, he isolated OPCs from peanut skin

ginkgo biloba peanut skin cranberries plums

Passwater, RA. (1991). Pycnogenol (proanthocyanidins). Whole Foods. Carper, J. (1998). Miracle cures. New York, NY: HarperPerennial. pp.221-236.

OPC’s – A fad?

Benefits of OPCs for ADHD •! •! •! •! •! •! •! •!

General calming effect Improved cooperation with teachers and parents Increased mental alertness and ability to remain focused Less impulsiveness Decreased aggressiveness Improved grades Less disruptive behavior Decreased restlessness

Synchronicity

OPCs

OPC’s

Clinical psychologist suffered from ADHD into adulthood

6 year old with ADHD

Could not take ADHD medication because he would lose his pilot’s license

Developed a tic and increased aggression on Ritalin

OPC Supplements Started

On Pycnogenol, patient stopped being argumentative, was more obedient, and able to complete schoolwork, handwriting improved

Increased attention, increased focus, decreased emotional reactivity, elevated mood Daily Dose Required Carper, J. (1998). Miracle cures. New York, NY: HarperPerennial. pp. 221-236.

110

Phytochemicals in the Treatment of ADHD

!"#$%#$!&

James Greenblatt, MD

Academic Journals

Brain Waves

10-year-old boy with ADHD Significant improvement in symptoms with Pycnogenol, stopped his physical altercations at school Within 2 weeks of stopping Pycnogenol he became hyperactive and impulsive, evident by numerous issues at school Improvement in symptoms when Pycnogenol was reinstated Heimann. J Am Acad Child Adolesc Psychiatry. 1999 Apr;38(4):357-8.

ADHD EEGs

An abnormal pattern of cortical activity is consistently seen in ADHD patients

EEGs obtained from 25 children (aged 6-11), 25 adolescents (aged 13-17), and 25 adults (aged 20-42) diagnosed with ADHD and compared with age-matched controls

Increased slow-wave activity (theta, unfocused)

ADHD group showed significantly more theta activity than controls

Decreased fast-wave activity (beta, concentrated)

Controls showed a higher level of beta activity than ADHD group

Theta/beta ratio has been shown to be predictive of an ADHD diagnosis across the lifespan

increased theta/beta ratio Bresnahan. Biol Psychiatry. 1999 Dec 15;46(12):1690-7.

Bresnahan. Biol Psychiatry. 1999 Dec 15;46(12):1690-7.

Neurofeedback

Neurofeedback vs. MPH

Neurofeedback, also called EEG biofeedback, enables a person to alter his or her brain waves

91 children with ADHD, mean age 10.5 years

In 2012 the American Academy of Pediatrics designated neurofeedback as â&#x20AC;&#x153;Level 1 - Best Support,â&#x20AC;? the highest level of support, as an intervention for attention and hyperactivity behavioral problems

NF caused a significant improvement in attention and hyperactivity symptoms, based on parental reports

Randomized to either 30 sessions of beta/theta neurofeedback, MPH (20-60 mg/d), or both

Neurofeedback was as effective as methylphenidate at treating ADHD symptoms Duric. BMC Psychiatry. 2012 Aug 10;12:107.

111

Phytochemicals in the Treatment of ADHD

!"#$%#$!&

James Greenblatt, MD

Neurofeedback vs. MPH

Neurofeedback

23 children with ADHD aged 7-14

104 children aged 7-11 randomized to neurofeedback, cognitive training, or a control condition over 5 months

NF children had quicker and

Randomized to 40 theta/beta training sessions or Improvements methylphenidate (1 mg/kg/day) were still

NF group compared to controls had improvedin attention, greater improvements executive functioning, and classroom motor/verbal off-task ADHD symptoms, which behavior

seen at 2-month and 6-

Both treatments led to afollow similar reduction ADHD month ups in inNF functional impairment and in primary ADHD symptoms

remained at the 6-month

group

follow-up Stimulant medication dosage significantly increased for children in the cognitive training and control conditions, but not for those in the NF condition

Only neurofeedback group improved significantly in academic performance Meisel . Biol Psychol. 2013 Sep;94(1):12-21.

Steiner. J Dev Behav Pediatr. 2014 Jan;35(1):18-27. Steiner. Pediatrics. 2014 Mar;133(3):483-92.

Joel Lubar, PhD

13 year old with ADHD

Dr. Lubar was responsible for developing the use of EEG Biofeedback -Neurofeedback as a treatment modality for Attention Deficit Hyperactivity Disorder, starting with his controlled studies in the mid-1970's

“So Prove It…”

13 year old with ADHD

OPC and ADHD

112

Phytochemicals in the Treatment of ADHD

!"#$%#$!&

James Greenblatt, MD

OPC and ADHD

Teacher Rating Scale

Theta/Beta Ratioâ&#x20AC;&#x2122;s

OPCs for ADHD Decreases Theta waves

Theta/beta ratio has been shown to be predictive of an ADHD diagnosis across the lifespan

Improve Theta/Beta Ratio

Support antioxidant activity (e.g. GSH)

OPC

Moderate catecholamine levels Help maintain blood brain barrier Decrease Copper

Neurofeedback

Acts as an antihistamine

113

Phytochemicals in the Treatment of ADHD

!"#$%#$!&

James Greenblatt, MD

Poisoned City

Lead and ADHD Risk

In April 2014, the city of Flint, Michigan changed its water supply from Lake Huron to the Flint River

2,195 children aged 7-9 who did not have ADHD at baseline were followed for 2 years

The aging Flint water distribution system contains a high percentage of lead pipes and lead plumbing which led to high lead levels in the water supply

The risk of ADHD symptoms increased with increasing blood lead levels even in quite low concentrations

No Safe Lead Children with blood lead levels in the highest Levels quartile (>2.17 Âľg/dL) were 155% more likely to be diagnosed with ADHD

Hanna-Attisha. Am J Public Health. 2016 Feb;106(2):283-90.

Choi. Psychiatry Res. 2016 Feb 28;236:42-6.

Beyond Flint

Sample of Copper Results November 2016

The action level for copper is 1.3 mg/L

Tested 300 Schools Majority had increased Lead or Copper

!"#$ !"#$ .!%$#/+# 0#8#/9 %:.;:/<=>/ <!$0/#$ .!%$#/+# />$=?*!/0>8#$ .>%#.. .>/<;#!0>% #99#D />$B>.E GH:/+" 9>;#$9#= .>%#.. %#9=5>$>H<? 5.!+E9=>/#

%"&'!("$)!*+, %&'()*+,,-() 0)123124*%&'()*5677-() %&'()*+,,-()

-,./%! 010 0120 0103 4124 0)123124*%&'()*5677-() 514 %&'()*+,,-() 613 >'@() 413 5&'@),,A*B&6C(' 5143 0)123124*%&'()*5677-() 710 >'@() 5185 +-&FF),,A*B&6C(' 5174 +-&FF),,A*B&6C(' 513 0)123124*%&'()*5677-() 5169 +-&FF),,A*B&6C(' 9103 %&'()*+,,-() 51867 %&'()*+,,-() 015

Massachusetts Department of Environmental Protection

Attention and Memory

Dopamine Synthesis

606 adolescents aged 13-17 with normal copper levels

Phenylalanine Tyrosine Tyrosine Hydroxylase

Iron Folate (5-MTHF)

L-DOPA

Amino Acid Decarboxylase

Higher blood copper was associated with lower sustained attention on a Continuous Performance Test and worse short-term memory on a Digit Span Test

AADC

Vitamin B6 (P5P) Zinc

Dopamine Dopamine Beta-hydroxylase

Copper concentrations regarded as normal may actually affect cognition

Copper Vitamin C

Norepinephrine Kicinski. Int J Hyg Environ Health.!2015 Jan;218(1):139-46.

114

Phytochemicals in the Treatment of ADHD

!"#$%#$!&

James Greenblatt, MD

Broad Based Micronutrients

Copper, Zinc, and OPCâ&#x20AC;&#x2122;s 65 ADHD children aged 6-14 randomized to 1 mg/ kg/day OPC or placebo for 4 weeks

RCT of 80 adults with ADHD

with Broadfollowed by 8 weeks ofCaution micronutrients or placebo an 8 week open-label phase Based Nutrient

Compared to controls at baseline, ADHD children had lower Zn level, higher Cu/Zn ratio, and higher Cu level

Formulas

OPC administration significantly decreased Cu levels and Cu/Zn ratio

Lower baseline copper levels were associated with better response to treatment Rucklidge. Prog Neuropsychopharmacol Biol Psychiatry. 2014 Apr;50:163-71

Viktorinova. Biomed Pharmacother. 2009 Oct 20.

Think Zinc

Zinc in ADHD Zinc levels predict stimulant response Serum zinc levels low in ADHD Zinc effective as supplement to stimulant Zinc effective in reducing hyperactive and impulsive behavior Arnold LE et al. Does hair zinc predict amphetamine improvement of ADD/hyperactivity? Int J Neurosci. 1990:50 (1-2):103-7. Bekaroglu M et al. Relationships between serum-free fatty acids and zinc and ADHD. J. Child Psychol Psychiatry 1996;37:225-227. Akhondzadeh S et al. Zinc sulfate as an adjunct to methylphenidate for the treatment of attention deficit hyperactivity disorder in children: A double blind and randomized trial. BMC Psychiatry 2004, 4:9. Bilici M, Yildirim F, Kandil S, et al. Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:181-90.

Zinc for ADHD

OPCs : Blood Brain Barrier

OPCs have a strong affinity for collagenelastin crosslinks in the tight junctions of the BBB

OPCs protect the brain and maintain regulatory mechanisms within the BBB Akhondzadah,s BMC Psychiatry 2004 Apr 8;4:9.

Robert. Pathol Biol (Paris). 2001 May;49(4):298-304; He. Phytother Res. 2009 Jul;23(7):933-7.

115

Phytochemicals in the Treatment of ADHD

!"#$%#$!&

James Greenblatt, MD

“Leaky Brain”

OPCs and Allergies

RCT food challenge on 16 children # ingestion of reactive foods impaired sustained concentration compared to placebo

OPCs inhibit histidine decarboxylase from binding to collagen microfibrils, moderating the production and release of immune activating molecules from mast cells.*

Topographic EEG mapping has shown that intake of reactive foods directly increases brain electrical activity in the fronto-temporal areas of the brain In a 2009 study, children who followed a restricted diet exhibited a 70% reduction in ADHD symptoms after 9 weeks

OPCs act as Antihistamines

-./012&!""#!$$%&'()#!,,%3"'4)56%*'#+2& 7890:2&*+&#,)#-%./01&)#!,,"3!)*4"56))"#*!2& ;<911</2&*+&#23/$.#!.4$%56#-5(63/01&()#7889:!'#,2&&

OPC and Antioxidant Status

OPC’s Effect on Glutathione

RCT on 61 children aged 6-14 with ADHD

RCT on 43 children aged 6-14 with ADHD

Pycnogenol (1 mg/kg/d) or placebo administered for 1 month, no other psychotropic drugs or antioxidants

OPC (1 mg/kg/d) or placebo administered for 1 month

At baseline ADHD children had significantly increased DNA damage vs. controls

OPCs promote a healthy glutathione (reduced:oxidized) ratio

OPCs reduced DNA damage, normalizes antioxidant status, and improves attention Chovanová. Free Radic Res. 2006 Sep;40(9):1003-10.

OPCs Effect on Urinary Catecholamines

Dvo!áková. Redox Rep. 2006;11(4):163-72.

OPCs and Attention

RCT study on 57 children aged 6-14 with ADHD

53 healthy students aged 18-27 given 100 mg/d Pycnogenol for 8 weeks

At baseline, concentrations of catecholamines were higher in urine of ADHD patients vs. controls

Supplementation significantly improved sustained attention, memory, alertness, executive functions, and mood

Noradrenaline concentrations positively correlated with degree of hyperactivity

Students taking Pycnogenol had higher test scores on university exams than the control group

Adrenaline and noradrenaline concentrations positively correlated with levels of oxidized glutathione

Levels of anxiety decreased by 17%

OPC improves cognitive function, attention, and mental performance

OPCs inhibits oxidative stress by normalizing catecholamine levels Dvo!áková. Nutr Neurosci. 2007 Jun-Aug;10(3-4):151-7.

Luzzi. Panminerva Med. 2011 Sep;53(3 Suppl 1):75-82.

116

Phytochemicals in the Treatment of ADHD

!"#$%#$!&

James Greenblatt, MD

Beyond Pycnogenol

Blueberries and Brain Function

Double-blind RCT with 26 adults, mean age 68 years

Blueberry group vs. placebo group had

–! Increases in brain activity in brain areas related to the cognitive tests –! Improvements in grey matter perfusion in the parietal and occipital lobes –! Improvement in working memory

Consumed either 1 oz blueberry concentrate providing 387 mg anthocyanidins or placebo (synthetic blackcurrant and apple cordial) once a day for 12 weeks

Completed cognitive function tests while undergoing fMRI scans at baseline and after 12 weeks

Blueberry concentrate increases brain activation in areas associated with memory and executive function

Bowtell. Appl Physiol Nutr Metab. 2017 Mar 1.

Integrative Medicine for Mental Health Once neurotransmitters are synthesized, their activity and stability can be influenced by specific phytochemicals* Reuptake balance* •! Rhodiola rosea •! Green tea

Reuptake (inactivation)

Neurotransmitter

Enzyme modulation* •! Curcuminoids •! Quercetin

Plus-Minus Plan Is there a need to get something?

Nutrients Vitamins Minerals Fatty acids Amino acids Hormones Light Love Nature Positive Feedback

THANK YOU Finallyfocusedbook.com

Is there a need to avoid something?

Toxins Elementary (lead, mercury, etc.) Biologic (plants, germs, etc.) Synthetic (mostly petrochemical) Pesticides

Degradation (inactivation)

JamesGreenblattmd.com

Allergens Food Pollen Dust Dander Chemicals Mold Germs

Jgreenblatt@waldenbehavioralcare.com

Autoimmune Celiac Disease

117

!$&

17-04-01 Distinct Characteristics of Hematological Parameters in Psychiatric Disorders

Toru Mizoguchi , MD

Female 30 yo •! Chief Complaint

Applying Blood Test Data into Clinical Practice

–! Dizziness, fatigue, anxiety

•! Medical History –! Feb. 1995 give birth to son –! Jun. 1998 give birth to daughter

qIntroduction to the "Kaneko Methodology"q

•! Clinical History

the 46th Orthomolecular Medicine TodayJConference in Toronto, April 28 - 30

–! Oct. 19,1998JSudden dizziness, nausea and vomiting –! Cephalic MRI and other tests showed no abnormalities

Test Results

Initial Screening Test Data WBC

4400

7.4

RBC

429

AST

Hct

40.2

ALT

11 278

MCV

93.7

LDH

MCH

30.3

!GTP

MCHC

32.3

ALP

PLT

33.3

BUN

13.9

CRP

0.0

CRE

0.8

•! Blood Test –! AnemiaJN/A –! Inflammation N/A –! Hepatic FunctionJNAA –! Renal Function NAA

•! Diagnostic Imaging Test –! MRIJNAA –! Brain WaveJNAA

NAA = No Apparent Abnormalities

GOtolaryngologist --> Meniere's Disease GPsychiatrist --> postpartum depression

Lifetime Mentor •! Dr. Masatoshi Kaneko

I had a strong conviction… she was not suffering from depression!!

–! Came to USA in the 1970's as a student –! Researched at Linus Pauling Institute –! Introduced Orthomolecular Medicine to Japan –! First Japanese to be inducted into the Hall of Fame

Reason??

118

17-04-01 Distinct Characteristics of Hematological Parameters in Psychiatric Disorders

Toru Mizoguchi , MD

WBC

4400

7.4

RBC

429

AST

Hct

40.2

ALT

MCV

93.7

LDH

278

MCH

30.3

!GTP

MCHC

32.3

ALP

PLT

33.3

BUN

13.9

CRP

0.0

CRE

0.8

Todayâ&#x20AC;&#x2122;s Contents â&#x20AC;˘! Introduction to Orthomolecular Medicine (Kaneko Method) â&#x20AC;˘! Interpretation of Blood Test Data â&#x20AC;&#x201C;! AST, ALT, LDH, BUN â&#x20AC;Śand the relation with psychiatric symptoms â&#x20AC;Śand the relation with nutritional deficiency

â&#x20AC;&#x201C;! Progress of patients

742 9./8 *'9' 7 '3+04 <4:1* '*;/8+C N Lack of B Vitamins, Iron and Zinc

Orthomolecular in Japan

Introduction in Medical Journals

â&#x20AC;˘! 1980â&#x20AC;&#x2122;s

â&#x20AC;˘! Nov. 2003 Issue

â&#x20AC;&#x201C;! Dr. Kaneko starts small seminars to general public â&#x20AC;&#x201C;! Domestic production of therapeutic dietary supplements â&#x20AC;&#x201C;! Show dramatic clinical improvement

â&#x20AC;˘! Orthomolecular featured in a medical journal (internal medicine)

â&#x20AC;˘! 1990â&#x20AC;&#x2122;s â&#x20AC;&#x201C;! Examination on understanding clinical condition and therapeutic effect â&#x20AC;˘! Orthomolecular Interpretation of blood tests â&#x20AC;˘! Increasing numbers of cooperative Medical institutions for blood withdrawal

!!Editor in chief !!Member of editorial board

20â&#x20AC;&#x2122;sJFemaleJSchizophrenia

Initial Screening Data

History â&#x20AC;˘! Diagnosed with depression at 17yoK 22yo â&#x20AC;˘! Diagnosed with schizophrenia at 22yo (hospitalized) Symptoms â&#x20AC;˘! Irritation appears even if medication is missed once. Demanding for medication â&#x20AC;˘! Exhaustion and depression â&#x20AC;˘! Strong anxiety

119

!+,+7+3)+ !'3-+

Initial Screening

#49'1 749+/3

"# #

q q

+77/9/3 +24-14(/3 +:9745./1

q q J

>25.4)>9+

q J

Distinct Characteristics of Hematological Parameters in Psychiatric Disorders Toru Mizoguchi , MD

120

Distinct Characteristics of Hematological Parameters in Psychiatric Disorders Toru Mizoguchi , MD

121

Distinct Characteristics of Hematological Parameters in Psychiatric Disorders Toru Mizoguchi , MD

122

17-04-01 Distinct Characteristics of Hematological Parameters in Psychiatric Disorders

Toru Mizoguchi , MD

Applying to Psychiatry

Neurotransmitters & Vitamin B6

LSymptoms related to low ALT, BUN, LDHM

JJJ â&#x20AC;˘! PhenylalanineJ# DopamineJ â&#x20AC;˘! DopamineJJJ#J Noradrenaline â&#x20AC;˘! GlutamineJJJ#J Glutamic Acid â&#x20AC;˘! TryptophanJJ #JSerotonin â&#x20AC;˘! Glutamic Acid #J GABA

B! ">259428 */7+)91> 7+1'9+* 94 14< % [ /')/3 749+/3 2+9'(41/82 â&#x20AC;&#x201C;! â&#x20AC;&#x201C;! â&#x20AC;&#x201C;! â&#x20AC;&#x201C;!

Fatigue, muscle stiffness Depression, lack of concentration Sensitive to any stimulus Sleep troubleâ&#x20AC;Śsleep rhythm, increase dreams

â&#x20AC;˘! Gluconeogenesis sympathetically dependent symptoms â&#x20AC;&#x201C;! Irritation, impatience, aggressiveness

JDDeficiency in VB6 will result in multiple complaints

20â&#x20AC;&#x2122;sJFemaleJSchizophrenia

Initial Screening Data

!+,+7+3)+ !'3-+

Initial Screening

#49'1 749+/3 "# # $ +77/9/3 +24-14(/3 +:9745./1 >25.4)>9+

q q

q q J

q J

Difference in Data Interpretation

Progress in Test Data

Orthomolecular Interpretation Nutritional Status â&#x20AC;˘! Deficiency in VB[ NAA â&#x20AC;˘! Zinc Deficiency Hepatic Function NAA â&#x20AC;˘! Low Protein Renal Function NAA metabolism Anemia NAA â&#x20AC;˘! Very Low Iron Store Ferritin Level within â&#x20AC;˘! Tense Sympathetic reference range nervous system F F â&#x20AC;˘! Medication only â&#x20AC;˘! Nutritional approach

Normal Interpretation â&#x20AC;˘! â&#x20AC;˘! â&#x20AC;˘! â&#x20AC;˘! â&#x20AC;˘!

Reference Range

Initial Screening

3 months later

7 months later

123

+77/9/3

(

+:9745./1

>25.4)>9+

17-04-01 Distinct Characteristics of Hematological Parameters in Psychiatric Disorders

Toru Mizoguchi , MD Change in Symptoms and Medication Initial Screening 3 months later NStrong fatigue Naniety Ndepression Nacne

Glucose-Alanine cycle

Nable to do Nno symptoms household chores (shopping, cooking, cleaning) Nimprovement in acne

NRisperdalJ5mg NSeroquelJ750mg NRohypnol NLevotomin

NRisperdal 0.5mg NSeroquelJ50mg

Glucose

Blood Sugar

glycolysis

Circulating Blood

LDH

Lactic Acid

Circulating Blood

Pyruvate ALT

ALT

Alanine

ALT, LDH and Glucose Metabolism

Hepatic

â&#x20AC;˘! Gluconeogenesis is the major factor in blood sugar modulation after 2hrs of food intake

Glucose

â&#x20AC;&#x201C;! Glucose Alanine CycleJGJALT (lead role) â&#x20AC;&#x201C;! Cori CycleJGJLDH (lead role)

Gluconeogenesis

Pyruvate

Glucose Gluconeogenesis

Pyruvate

Cori Cycle

Glucose

Blood Sugar

glycolysis

Nno medications

Musculoskeletal

Hepatic

Musculoskeletal

7 months later

â&#x20AC;˘! ALT, LDH and unidentified symptoms

Pyruvate

â&#x20AC;&#x201C;! Increased involvement of sympathetic nervous in gluconeogenesis â&#x20AC;&#x201C;! Relation with unidentified symptoms

LDH

Lactic Acid

â&#x20AC;˘! Relation with Nocturnal hypoglycemia, afternoon drowsiness

Dysglycemia

The high-affinity niacin receptor HM74A is decreased in the anterior cingulate cortex of individuals with schizophrenia

Dysglycemia â&#x20AC;&#x201C; The Common Factor in Mental Disorders Patrick Holford 38thJISOM Conference

Christine L. Miller a, , Jeannette R. Dulay b

B! 489 58>)./'97/) 8>259428 '7+ )':8+* (> >8-1>)+2/' B!&'73/3- 43 /3)7+'8+ /39'0+ /3 8:-'78

Brain Research Bulletin 2008 Dear Toru .45+ >4: .';+ ' ;+7> /39+7+89/3- 9/2+ /3 %'3)4:;+7 <./). '2 8477> </11 349 (+ '(1+ 94 '99+3* '3* .45+ >4: )'3 8.'7+ 842+ 4, >4:7 ;+7> -44* ,/3*/3-8 </9. 842+ 4, 9.+ 49.+7 *4)9478 '9 9.+ 2++9/3- 440 :5 #./8 /8 , /11+78 ;+7> /25479'39 5'5+7 43 3/')/3 7+)+59478 /3 ,.+ (7'/3 (7'2

124

17-04-01 Distinct Characteristics of Hematological Parameters in Psychiatric Disorders

Toru Mizoguchi , MD

Enhanced carbonyl stress in a subpopulation of schizophrenia.

Arai M, Yuzawa H,et al Arch Gen Psychiatry. 2010 Jun;67(6):589-97.

Various factors are involved in the pathogenesis of schizophrenia. Accumulation of advanced glycation end products, including pentosidine, results from carbonyl stress, a state featuring an increase in reactive carbonyl compounds (RCOs) and their attendant protein modifications. Vitamin B(6) is known to detoxify RCOs, including advanced glycation end products. Glyoxalase I (GLO1) is one of the enzymes required for the cellular detoxification of RCOs. A)! Concentration of pentosidine was higher in schizophrenia group than control B)! Blood Vitamin B6 was lower in schizophrenia group than control

Dr. Hoffer’s Message

Lactic Acid Detoxification system

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

Carbonyl compounds (toxic) capture Pyridoxamine

(form of Vitamin B6)

Suppression of production

Advanced Glycation End (AGEs) Products (Pentosidine, etc.) Renal Dysfunction, Arteriosclerosis Alzheimer, Schizophrenia

Conclusion •! About the history of Japanese Orthomolecular •! Understand nutritional status from blood test •! Evidence is finally catching up with Orthomolecular medicine in which Dr. Hoffer proposed •! With the lead of Dr. Yanagisawa, Japan will keep on spreading Orthomolecular to the world

125