This document summarizes research on potential biological causes and treatments for autism spectrum disorders and other neurodevelopmental conditions. It discusses intestinal and immune system abnormalities, nutritional deficiencies, toxic metals, and the rationale for treating these factors through dietary changes and supplements. Specific treatments mentioned include gluten/casein-free diets, probiotics, sulfur supplements, chelation therapy, and targeting yeast, parasites, and Clostridia overgrowth. Concerns about mercury in vaccines and their relationship to autism prevalence are also outlined.
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2008-03 Louisville Autism Lecture
1. Biomedical Treatments for Neurodevelopmental, Autoimmune and other Chronic Disorders David Berger, MD Medical Director Wholistic Pediatrics Tampa, FL (813) 960-3415 www.wholisticpeds.com
8. Robert Cade, MD, Professor, University of Florida Medical School “ A gluten and casein free diet resulted in significant improvement in 81% of children with autism within three months.”
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10. DPP-IV Dipeptidyl Peptidase IV, carboxypeptidase A, and aminopeptidase are some of the main enzymes that brake down the opiate peptides. Some of the enzymes are zinc dependent, and it’s activity can be inhibited by mercury, among other things. A first generation enzyme containing DPP-IV is available from Kirkman Labs. Although for most children it can not serve as a sole replacement for the C/G free diet, giving it with these foods allow some children to take c/g foods with out negative reactions, and it can be administered in cases of accidental exposure
11. Dr. Lewis’ book is the essential starting point for a gluten and casein free diet.
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15. Autism Speaks Launches Pediatrician Outreach Initiative to Increase Awareness about the Diagnosis and Treatment of Gastrointestinal Problems Consensus Statement Developed by Expert Panel Includes Recommendations for Care Specific to Children with Autism February 28, 2007
35. Immunity is complex and impacts every system in the body. It isn’t surprising that it effects child behavior and development.
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41. The developing fetus and young children are thought to be disproportionately affected by mercury exposure, because many aspects of development, particularly brain maturation, can be disturbed by the presence of mercury. Minimizing mercury exposure is, therefore, essential to optimal child health ….. Mercury in all of its forms is toxic to the fetus and children, and efforts should be made to reduce exposure to the extent possible to pregnant women and children as well as the general population . _______________________________________________________________ Vaccine inserts would typically say “0.01% thimerosal as a preservative”, which to anyone would sound like an extremely small amount. When called to testify in front of the Institute of Medicine, an independent group formed by our government to monitor safety issues, Dr. Neil Halsey of Johns Hopkins University, and head of the vaccine recommendation committee that reports to the CDC, went on record as saying “No one ever did the math…. No one knows what dose of mercury, if any, from vaccines is safe. We can say there is no evidence of harm but the truth is no one has looked” MERCURY Statement: Pediatrics 2001 Jul, American Academy of Pediatrics: Committee on Environmental Health.
61. Antonio After Chelation with DMSA Has bad gas during the DMSA days, and is moody, then this goes away when the DMSA is finished. Doing better and better in speech therapy If he does not want to do things he cries. Teachers are reporting improvements seen on a month-to-month basis More hand gesturing In a more advanced class. The mimicry behavior has stopped. At this point language is the major barrier, behaviors and stemming are under control
69. Biochemistry 101 Enzymes – the keys to life A + B 0 C 0 D A & B are substrates, the ingredients being “mixed” together 0 is the enzyme, the catalyst that makes the reaction proceed. C & D are products made by the reaction, which can then go on to be substrates (ingredients) in other reactions Some enzyme reactions can go both directions
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76. SAM SAH MTase SAHH Homocysteine B6 THF MS CBS MB12 Protein synthesis BHMT Choline Betaine Overview of The Methylation / Transsulfuration Pathway THF: tetrahydrofolate Betaine:TMG 5-CH 3 THF Methylation of DNA, RNA, proteins, membrane phospholipids, creatine, neurotransmittors Cystathionine Cysteine Glutathione Methionine Adenosine AK ADA Inosine AMP MAT B6 MTHFR
78. SAM SAH MTase SAHH Homocysteine THF MS MB12 Protein synthesis The Methionine Cycle: Remethylation of Homocysteine THF: tetrahydrofolate 5-CH 3 THF Methylation of DNA, RNA, proteins, histones, membrane phospholipids, neurotransmitters Methionine Adenosine AK ADA Inosine AMP MAT
79. SAM SAH MTase SAHH Homocysteine THF MS B12 Protein synthesis The Methionine Cycle: Remethylation of Homocysteine THF: tetrahydrofolate 5-CH 3 THF Methylation of DNA, RNA, proteins, histones, membrane phospholipids, neurotransmitters Methionine Adenosine AK ADA Inosine AMP MAT
80. SAM SAH MTase SAHH Homocysteine THF MS B12 Protein synthesis BHMT Choline Betaine The Methionine Cycle: Remethylation of Homocysteine Betaine: TMG 5-CH 3 THF Methylation of DNA, RNA, proteins, histones, membrane phospholipids, neurotransmitters Methionine Adenosine AK ADA Inosine AMP MAT
81. SAM SAH MTase SAHH Homocysteine B6 THF MS CBS B12 Protein synthesis BHMT Choline Betaine Methionine Transsulfuration to Cysteine and Glutathione Transsulfuration Pathway THF: tetrahydrofolate 5-CH 3 THF Methylation of DNA, RNA, proteins, membrane phospholipids, creatine, neurotransmittors Cystathionine Cysteine Glutathione Methionine Adenosine AK ADA Inosine AMP MAT B6
82. SAM SAH MTase SAHH Homocysteine B6 THF MS CBS B12 Protein synthesis BHMT Choline Betaine Effect of Oxidative Stress on Methionine Transsulfuration THF: tetrahydrofolate 5-CH 3 THF Methylation of DNA, RNA, proteins, membrane phospholipids, creatine, neurotransmittors Cystathionine Cysteine GSH GSSG Methionine Adenosine ( AK and/or ADA) MAT B6
83. Neurotoxicity of Thimerosal in Human Brain Cells is Associated with Glutathione Depletion: Protective Effect of Cysteine or Glutathione Supplementation S. Jill James, William Slikker, Elizabeth New, Stefanie Jernigan, Stepan Melnyk Department of Pediatrics University of Arkansas for Medical Sciences Little Rock, AR
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85. 0 2.5 5 10 20 VIABILITY OF GLIOBLASTOMA AND NEUROBLASTOMA CELLS WITH INCREASING DOSE OF THIMEROSAL Viability (MTT OD) Glioblastoma Cells Neuroblastoma Cells ( 48 hr Exposure ) ( 3 hr Exposure ) 0 2.5 5 10 20 0 2.5 5 10 20 M Thimerosal M Thimerosal
86. Control Thimerosal +GSH + Cystine +NAC + Methionine O.D. (Viability) Viability of Glioblastoma cells exposed to 15 M Thimerasol in the presence of GSH-ester, Cystine, N-acetylcysteine (NAC), or Methionine
87. Control Thimerosal +GSH + Cystine +NAC + Methionine O.D. (Viability) Viability of Neuroblastoma cells exposed to 15 M Thimerosal Pretreated with 100 M GSH-ester, Cystine, N-acetylcysteine (NAC), or Methionine
88. Methyl-B12, Folinic Acid, and Betaine Supplementation in 8 Children with Autism Injectible Methyl-B12 (75 µg/Kg b.i.d.) was given to the 8 children who had been taking folinic and and betaine supplements for 3-4 months Plasma thiol profile was repeated in the 8 children after 4 weeks of combined folinic acid, betaine, and methyl B12
89. Control Before Folinic Folinic Betaine Betaine Me-B12 Methionine S-Adenosylmethionine S-Adenosylhomocysteine Adenosine Control Before Folinic Folinic Betaine Betaine Me-B12 Control Before Folinic Folinic Betaine Betaine Me-B12 Control Before Folinic Folinic Betaine Betaine Me-B12 Transmethyation Metabolites after addition of Methyl-B12 to Folinic Acid and Betaine Supplementation in 8 Autistic Children
90. Control Before Folinic Folinic Betaine Betaine Me-B12 Control Before Folinic Folinic Betaine Betaine Me-B12 Control Before Folinic Folinic Betaine Betaine Me-B12 Control Before Folinic Folinic Betaine Betaine Me-B12 Homocysteine Cysteine Cystinyl-Glycine Total Glutathione tGSH) Transsulfuration Metabolites after addition of Methyl-B12 to Folinic Acid and Betaine Supplementation in 8 Autistic Children
91. Total Glutathione (tGSH) Control Before Folinic Folinic Betaine Betaine Me-B12 Oxidized Glutathione (fGSSG) GSH/GSSG Ratio Glutathione Redox Potential after addition of Methyl-B12 to Folinic Acid and Betaine Supplementation in 8 Autistic Children Control Before Folinic Folinic Betaine Betaine Me-B12 Control Folinic Folinic Before Betaine Betaine Me-B12
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93. JAMES A. NEUBRANDER, M.D., F.A.A.E.M. EDISON, N.J. 08837 OPEN CLINICAL TRIAL METHYLCOBALAMIN STUDY
94. OPEN CLINICAL TRIAL METHYLCOBALAMIN STUDY Total number of children included in the data: 85 • 71 males •14 females • 84% males •16 % females 51 males responded 12 females responded 74.1 % of the children responded positively!
95. OPEN CLINICAL TRIAL METHYLCOBALAMIN STUDY THE TOP TEN Symptoms Parents Reported Were Helped Most Often Language 71% Awareness 65% Cognition 52% Engagement 43% Eye Contact 37% Better Behavior 35% More Focused 35% Understanding 35% Vocalization 35% Trying“New Things” 33%
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103. Elevated Male Hormones/Androgens The enzyme that converts DHEA to DHEA-S (storage hormone) is sulfotransferase, which is glutathione dependant. When this enzyme is not working, there is a build up of DHEA which then gets sent to androstenedione and then testosterone
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106. Armanini D et al. N Engl J Med 1999;341:1158 Serum Hormone Concentrations in Seven Men Given Licorice for Seven Days
123. Before After Mild HBO SPECT Scans in a 4 year old autistic child after 10 dives mHBOT at 1.3 atm and 24% oxygen Heuser et al., 2002 Best Publications; 2002:109-15
124. HBOT 1.3 ATA, 24% Oxygen: 4 year old child Before and after 40 dives