The Plaza Kansas City MO Comprehensive Treatment AutismADHD

The Plaza, Kansas City, MO Comprehensive Treatment Autism/ADHD William Shaw Ph. D The Plaza, Kansas City

Autism: divergent views • Viewpoint one: Autism is a neurological disorder due to primarily genetic causes. • Treatment is behavioral therapy and neuropharmacological therapy.

Autism: divergent views • Viewpoint two : Autism is a systemic disorder in which brain function is also affected due to toxic exposures, nutritional deficiencies, vaccine overuse or vaccine abuse, gastrointestinal dysfunction, food allergies, and genetic vulnerabilities. Treatment is directed to reduce and/or remove toxic chemicals, restore nutritional balance, restore beneficial flora, and remove foods that are not beneficial to the individual. Behavioral therapy helps to recover functions lost during suboptimum physiological state.

Thalidomide Ø Introduced in 1956 as sedative (sleeping pill) and to reduce nausea and vomiting during pregnancy Ø “Completely safe” Ø Withdrawn in 1961 -5 years too late for many children Ø Discovered to be a human teratogen causing absence of limbs or limb malformations in newborns Ø 5000 to 7000 infants effected Ø Resulted in new drug testing rules

The causes of autism • Although autism appears to be multifactorial, could there be a single factor that is much more important than others as in the case of thalidomide? • Autism is more difficult to diagnose since children don’t have missing arms and legs

Symptoms of autism/PDD Pervasive developmental disorder • • Lack of speech: expressive and receptive Stereotypical or odd behavior Social deficits Hyperactivity/hypoactivity Poor focus and concentration Reduced pain and danger perception Poor eye contact

Symptoms Underlying causes • Sleep disturbance • Melatonin, iron deficiency • Eye pain, eye touching • Severe calcium deficiency or poking • Hyperactivity, excessive • GI candida, lead toxicity laughing • Spaced out, no • High concentration of sensitivity to pain, diet opiate peptides from milk high in milk and wheat • Frequent urination of • Oxalate stones in urinary small amounts of urine tract • Head banging, hand • Severe GI pain biting

Symptoms Underlying causes • Bending over sofa with • GI discomfort, pain pressure against stomach • Walking on toes • Excessive drooling • Extremely violent behavior, kicking, screaming, destructive • Looking at things by sideways glance • Oxalate deposits in soles of feet, selenium deficiency • Mercury toxicity • Clostridia overgrowth • Vitamin A deficiency

Comprehensive Biochemical Testing • Organic acid test • for genetic disease, • toxics, and yeast and bacterial • byproducts • Yeast culture and • sensitivity • Cholesterol profile • • Heavy metals • Iron stores-ferritin • • Copper/zinc profile Comprehensive Ig. G food allergies Comprehensive inhalant allergies Immune system deficiencies Amino acids and fatty acids Strep antibodies Vitamin D

Reasons to give supplements for autism, ADHD and PDD • Malabsorption due to lack of digestive enzymes or abnormal gastrointestinal flora • Dietary deficiencies due to special restricted diet • Need for higher than normally recommended nutrients due to abnormal metabolism or inborn errors of metabolism (genetic vulnerability) • Help to detoxify toxic chemicals from environment or infections

Parental Rating of Various Nutrients for Autism compared to drugs

Why is the brain so susceptible to oxidative stress ?

Why the brain is a free-radical target • The brain does not have adequate stores of antioxidants • The brain has so much iron that it leads to significant production of free radicals that cause significant peroxidation of the fats in the cell membrane • The brain has a very limited capacity to regenerate after being damaged.

Why the brain is a free-radical target • The brain has a very high percentage of essential fatty acids, that can be damaged by free radicals • The brain requires a tremendous amount of the total oxygen used in the body, approximately 20% of the total oxygen.

Dolske MC, Spollen J, Mc. Kay S, Lancashire E, Tolbert L. A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry. 1993 Sep; 17(5): 765 -74. • 30 -week double-blind, placebo-controlled trial of the effectiveness of ascorbic acid (8000 mg/70 kg/day) for autistic children • Pacing, rocking, flapping, and whirling behaviors responded especially well to this high dose vitamin C regimen.

Eur Child Adolesc Psychiatry. 2006 May 13; Treatment of ADHD with French maritime pine bark extract, Pycnogenol. • Results of double-blind placebo study show that 1 -month Pycnogenol administration caused a significant reduction of hyperactivity, improves attention and visual-motor coordination and concentration of children with ADHD. • In the placebo group no positive effects were found. • One month after termination of Pycnogenol a relapse of symptoms was noted.

The plasma zinc/serum copper ratio as a biomarker in children with autism spectrum disorders. Scott Faber et al Biomarkers March 11, 2009 The Children's Institute, Pittsburgh, PA, USA • A retrospective review of plasma zinc, serum copper and zinc/copper was performed on data from 230 children with autistic disorder, pervasive developmental disorder-NOS and Asperger's syndrome. • The entire cohort's mean zinc level was 77. 2 mcg/dl; mean copper level was 131. 5 mcg/dl, and mean Zn/Cu was. 608, which was below the 0. 7 cut-off of the lowest 2. 5% of healthy children. • The plasma zinc/serum copper ratio may be a biomarker of heavy metal, particularly mercury, toxicity in children with ASDs.

Destruction of vitamin C by free copper or iron ions without SOD Ascorbate (Vitamin C) Cu Cu Cu Free copper has as much SOD activity as SOD Dehydroascorbate

Zinc deficiency

Severe zinc deficiency Physical symptoms • Skin rash • Poor appetite • Frequent infections • Nail white spots

Children With Autism: Effect of Iron Supplementation on Sleep and Ferritin. J. Pediatr Neurol. 2006. 11. 004. Cara F. Dosman MD, • 33 children with autism in study. • 77% had restless sleep at baseline, which improved significantly with iron therapy, • 69% of preschoolers and 35% of school-aged children had insufficient dietary iron intake. • Mean ferritin increased significantly (16 μg/L to 29 μg/L), as did mean corpuscular volume and hemoglobin, suggesting that low ferritin in this patient group resulted from insufficient iron intake.

Need for calcium and/or vitamin D supplementation in autism • Because of milk and dairy restriction many children with autism or ADHD may be calcium deficient and may also be vitamin D deficient due to lack of milk and or not enough sun exposure • Most children after 2 years of age need 1000 mg per calcium

Need for calcium and/or vitamin D supplementation in autism • Need for calcium in autism is critically needed for strong bones and teeth • Special need in autism due to eye poking behavior associated with calcium deficiency, milk-free diet • Over 20 children with autism have poked out own eyes.

Cannell JJ. Autism and vitamin D. Med Hypotheses 2008; 70: 750 -759. • Children with rickets have hypotonia, decreased activity, developmental motor delay, listlessness, failure to thrive, and other autistic • Children with the Williams syndrome , some of whom have greatly elevated calcitriol levels for several months in early infancy, have remarkable sociability, overfriendliness, empathy, and willingness to initiate social interaction, strikingly the opposite phenotype of autism. • A placebo controlled three-month study of 20 autistic children found multivitamins with low doses of vitamin D (150 units or 3. 75 mcg) significantly improved sleep and gastrointestinal problems

Recommended daily doses of essential minerals; more needed in deficiency Age in yrs Amount of calcium Amount of magnesium Amount of zinc 1 -4 800 mg 100 mg 2. 5 mg 5 -10 800 -1000 mg 200 mg 5 mg >10 800 -1200 mg 350 -450 15 mg

J Am Coll Nutr. 2002 Feb; 21(1): 14 -21. Lithium: occurrence, dietary intakes, nutritional essentiality. Schrauzer GN. • Low lithium intakes from water supplies were associated with increased rates of suicides, rape, homicides and the arrest rates for drug use and other crimes. • The available experimental evidence now appears to be sufficient to accept lithium as essential; a provisional RDA for a 70 kg adult of 1, 000 micrograms/day is suggested.

Toxic Metals and Essential Minerals in the Hair of Children with Autism and their Mothers J. B. Adams 1; C. E. Holloway 1; F. George 2; D. Quig 3 • The levels of 39 toxic metals and essential minerals in hair samples were determined for children with autism spectrum disorders and a subset of their mothers compared to controls. • Iodine levels were 45% lower in the children with autism (p=0. 005). • Lithium levels were 30% lower (p=0. 04) in the younger children with autism. The mothers of young children with autism had especially low levels of lithium.

What if water is too pure?

Hair elements test profile –autism-

Clinical usefulness of high dose vitamin-B-6 in autism • V. E. Bonisch, reported in 1968 that 12 of 16 autistic children had shown considerable behavioral improvement on high dosage levels (100 mg to 600 mg per day) of vitamin B 6. • Three of Bonisch's patients spoke for the first time after vitamin B 6 was administered in this open clinical trial.

Improvements in autism noted with vitamin B-6 megadose • • Better eye contact Less self-stimulatory behavior More interest in the world around them Fewer tantrums More speech Some children spoke for first time Less aggressive behavior

Benefits of different fats in autism and ADHD

What are omega-3 and 6 fatty acids

Vancassel S, et al Plasma fatty acid levels in autistic children. Prostaglandins Leukot Essent Fatty Acids 2001; 65(1): 1 -7. • Total omega-3 fatty acids 20% lower than control group with mental retardation • One omega-3 fatty acid (DHA) was 23% lower than control group • This deficiency has also been found in schizophrenia, attention deficit, and Rett’s syndrome • 20% of dry weight of brain is polyunsaturated fatty acids

JG Bell et al Prostaglandins Leukot Essent Fatty Acids. 2004 Oct; 71(4): 201 -4. Essential fatty acids and phospholipase A 2 in autistic spectrum disorders. • • • Benefits of omega-3 supplementation Less aggression Less hyperactivity Improvements in sleep Improvements in speech and behavior • Improved ability of the child to concentrate

High cholesterol in children is associated with decreased mortality Child mortality rate in different countries 57. 5% of ASD children are below this value (<160) Serum cholesterol mg/d. L

The Great Plains Laboratory cholesterol study Of children with autistic spectrum disorder Low cholesterol 57. 5% Cholesterol in children with Extremely low autistic spectrum disorder cholesterol 17. 5%

Other new reports of cholesterol supplements in autism-Case 1 • Neurologist: • Marked reduction in anxiety in 17 year old girl with autism. • In addition, the girl had normal menstrual periods for the first time.

Other new reports of cholesterol supplements in autism-Case 2 • A woman called to say that her son is significantly less aggressive when on just one capsule (250 mg) of Cholesterol. • He stopped head banging and being aggressive toward others. In addition, after a couple of months on the product, her son started to spell for the first time. • She stopped it for one week and his aggressiveness came back so she is a believer.

Other new reports of cholesterol supplements in autism-Case 3 • I wanted to let you know that my son’s cholesterol went up 20 points to 131 after taking cholesterol supplements for a month. He is improving wonderfully. However, the proof is in way more than the numbers. Babbling is back and he is watching my lips when I talk to him. He understands and follows verbal commands. He learned to give himself a drink from a cup (I used to give him a bottle) during the first month on sonic, two weeks ago he learned to climb stairs and yesterday he fed himself with a spoon. Best of all, he is happy now! He smiles and laughs -- with people!!! At 12 months of age my son would be best described as catatonic, rather than autistic -- he was extremely severe.

Other new reports of cholesterol supplements in autism-Case 4 • My son's cholesterol number came back at 106, the lowest our DAN's office had seen. We have been on cholesterol supplementation for 2 days and my son has been making great eye contact and been very interested in connecting with me. I haven't done anything else new in a while so I am pretty excited that this might be doing something.

Other new reports of cholesterol supplements in autism-Case 5 • “Cholesterol supplementation raised my son's cholesterol level from 117 to 159. • We have to give him 5 capsules/day to maintain that cholesterol level but we had a dramatic decrease in his aggression at school overnight when we started it. • His teachers and therapists all asked us what we were doing. • He is allergic to eggs, but we couldn't have given him enough eggs to make a difference anyway. It was a amazing for us. ”

Dosing of eggs or cholesterol • Determine total cholesterol • If 160 or more, the patient doesn’t need more cholesterol • Subtract patient’s cholesterol from 160 mg/d. L, then divide by 10 to determine daily dose of cholesterol in 250 mg capsules or eggs • If patient’s cholesterol is 100, 160 -100=60 • 60/10=6=number of eggs or 250 mg cholesterol capsules per day • One average egg=250 mg cholesterol

Abnormal Gastrointestinal Flora in autism

Candida Overgrowth of Esophagus

Normal Intestine ** **

After Antibiotics

Stool Yeast and Urine Organic Acids in Child With Ig. A Deficiency and Autism before therapy arabinose in urine* *mmol/mol creatinine 341 after therapy with antifungals 51 normal range 0 -115 Candida parapsilosis stool 4+ none detected 0 -1+

Symptoms Improved by Antifungal • Increased focus and concentration • Improved receptive and expressive language • Reduced bowel symptoms • Increased eye contact and socialization • Reduced self-stimulatory behavior • Reduced aggressive and self-abusive • • behaviors Reduced Candida symptoms such as thrush Reduced skin rashes

Prescription Antifungals • Nystatin-Mycostatin-very little toxicity • Amphotericin B • Fluconazole-Diflucan • Itraconazole-Sporanox • Ketoconazole-Nizoral • Terbinafine-Lamisil

Over the Counter Antifungals • Caprylic Acid, • • caprylates MCT oil Coconut oil Garlic Oregano • Aloe vera (oral) • Goldenseal • Pau d’arco • Grapefruit seed • • extract Tanalbit Candex (cellulase enzymes)

Candida defense formula • • • Biotin Zinc undecylenate Oregano leaf extract Pau d’arco Sodium caprylate Berberine Cinammon bark extract Ginger root Grapefruit seed extract

Side Effects Associated with the Yeast “die-off” Reaction • Lethargy(tiredness) • Fever • Increased stereotypical behavior • Increased hyperactivity • Nausea, vomiting • Alka-Seltzer Gold neutralizes some of the toxic acids produced

Clostridia Bacteria and Autism

Endoscopy of Colon of Patient with Mild Clostridium Difficile Overgrowth

Endoscopy of Colon of Patient with Severe Clostridium Difficile Overgrowth- pseudomembranous Colitis

J Child Neurol 2000 Jul; 15(7): 429 -35 Short-term Benefit from Oral Vancomycin Treatment of Regressive-onset Autism Sandler RH, Finegold SM, Bolte ER, Buchanan CP, Maxwell AP, Vaisanen ML, Nelson, MN, Wexler HM 11 children with regressive-onset autism were recruited for an intervention trial using vancomycin. • A clinical psychologist blinded to treatment status. . noted improvement in 8 of 10 children studied. • “…these results indicate that a possible gut florabrain connection warrants further investigation”

Properties of Clostridia Bacteria • • • Strict anaerobe-dies when exposed to oxygen Causes tetanus, diarrhea, and botulism (food poisoning) Forms spores that are highly resistant to heat and antibiotics About 100 species of Clostridia in GI tract Controlled by vancomycin, metronidazole, and Lactobacillus acidophilus GG

HPHPA (MMOL/MOL CREATININE) 2000. 00 1800. 00 1600. 00 1400. 00 1200. 00 1000. 00 800. 00 Male control infants 600. 00 N = 211 N = 30 400. 00 200. 00 Control Males 2 -13 yr Autistic males 2 -13 yr N = 14 0. 00 CONTROL MALE INFANTS CONTROL MALE CHILDREN 2 - 13 YRS AUTISTIC MALES 2 - 13 YRS

Structure of 3 -(3 -hydroxyphenyl)3 -hydroxypropionic acid CHOHCH 2 COOH HO

phenylalanine NH phenylalanine hydroxylase CH 2 CHCOOH NH 2 HO microbial NH 2 CH 2 CHCOOH HO microbial m- tyrosine HO tyrosine hydroxylase HO 3, 4 -dihydroxyphenylalanine DOPA) norepinephrine 3 -hydroxyphenylpropionic acid human beta-oxidation CHOHCH 2 COOH HO dopamine phenylpropionic acid microbial CH 2 COOH NH 2 CH 2 CH 2 COOH microbial CH 2 CHCOOH tyrosine hydroxylase 2 HO CH 2 CHCOOH HO NH 2 DOPA analog 3 -(3 -hydroxyphenyl) -3 -hydroxypropionic acid HPHPA human beta oxidation enzymes dopamine analog COOH norepinephrine analog HO glycine 3 -hydroxybenzoylglycine 3 -hydroxybenzoic (3 -hydroxyhippuric) acid

Effect of anti-Clostridia therapy on urine excretion of HPHPA* in woman with depression and chronic fatigue

Effect of anti-Clostridia therapy on urine excretion of HPHPA* in young woman with acute psychosis

Treatments for Clostridia Bacteria • Vancomycin • Flagyl (metronidazole) • Lactobacillus acidophilus GG • (Only probiotic patented for use in • control of Clostridia) Saccharoyces boulardii-occasionally causes hypoglycemia-cannot be used with antifungal agents

Bacteriologist Elie Metchnikoff in his laboratory "Etudes sur la flore intestinale. 1 er mémoire : Putréfaction intestinale " Ann. Inst. Pasteur Paris, 22, pp. 929 -955.

William Shaw Ph. D, in his laboratory Field trip to the Amazon rainforest

Pyrethrins-common insecticide

Pet shampoo: Contain pyrethrins and piperonyl butoxide, inhibitor of cytochrome P-450

I. Hertz-Picciotto, et al Public Health Sciences and the M. I. N. D. Institute, University of California at Davis, International Meeting for Autism Research (IMFAR) Household Pesticide Use in Relation to Autism, May 2008 • Mothers exposed to pet shampoos (almost all pyrethrins) were twice as likely to have a child with autism. • The worst exposure time was the second trimester.

Pesticide Application

E. Guillette et al, "An Anthropological Approach to the Evaluation of Preschool Children Exposed to Pesticides in Mexico, " ENVIRONMENTAL HEALTH PERSPECTIVES 106: 347 -353, 1998. The pesticide-exposed children ● Far less physical endurance in a test to see how long they could keep jumping up and down ● Inferior hand-eye coordination ● Could not draw a simple stick figure of a human being, which the nonexposed children could readily do.

E. Guillette et al, "An Anthropological Approach to the Evaluation of Preschool Children Exposed to Pesticides in Mexico, " ENVIRONMENTAL HEALTH PERSPECTIVES 106: 347 -353, 1998. "Some valley (pesticide-exposed) children were observed hitting their siblings when they passed by, and they became easily upset or angry with a minor corrective comment by a parent. These aggressive behaviors were noted in the [pesticide-free] foothills [children]. "

Eric M. Roberts, et al Maternal Residence Near Agricultural Pesticide Applications and Autism Spectrum Disorders among Children in the California Central Valley Environ Health Perspect. 115(10): 1482– 1489, 2007 • Children exposed to pesticides called organophosphates used to kill insects had more than twice the risk of developing pervasive developmental disorder (PDD). • For organochlorines, there was 7 X autism rate • Mothers exposed to such pesticides were also likely to have shorter pregnancies and their children to have impaired reflexes.

Reduced ability to detoxify pesticides in autism. Life Sciences 78 (2006) 2244 -2248 PON 1 Enzyme activity Autism Controls

Autism rates in Texas 1990 -1993 1998 -2001

Comparison of autism rates and industrial pollution in Texas Autism rate 1998 -2001 Pounds of industrial toxic release

Victim of mercury toxicity

Hair mercury values in Minamata bay victims • Values of hair mercury were all elevated. Most of those who died were extremely elevated(500 -1000 ppm) • 1787 people died • Great Plains has tested some people in this range who used a beauty cream with mercury

Effect of mercury dose on autism incidence in the USA

Environmental mercury release, special education rates, and autism disorder: an ecological study of Texas Raymond F. Palmer, et al • There has been a significant increase in the proportion of children in special education and autism associated with mercury released into the environment. • For every 1000 lb of mercury liberated into the environment, there has been a 43% increase in the rate of special education students and a 61% increase in the percentage of students with autism.

Lead increases death from many diseases

Hair metals in boys with autism n=40 boys per group, age matched Autism 9: 290 -298, 2005

Comprehensive Biochemical Testing • Organic acid test • for genetic disease, • toxics, and yeast and bacterial • byproducts • Yeast culture and • sensitivity • Cholesterol profile • • Heavy metals • Iron stores-ferritin • • Copper/zinc profile Comprehensive Ig. G food allergies Comprehensive inhalant allergies Immune system deficiencies Amino acids and fatty acids Strep antibodies Vitamin D

Nutritional Treatment Autism/ADHD William Shaw Ph. D The Plaza, Kansas City, MO Thank You! The Plaza, Kansas City