Scott Clack, BSc, ND Touchstone Naturopathic Centre Oakville, ON copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Tonight’s Subjects Mitochondrial Dysfunction vs Disorder Cerebral Folate Deficiency How do we know Biomedical is working? Supplementation trials (suspending use) Increasing focus & attention Heavy metal toxicity & treatments New Research Food reactions: Histamine (DAO) Caring for Care-Givers copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre The Triggers: Metabolism, Environment & Lifestyle: Oxidative Stress & Inflammation Methylation, Transulfuration deficits, GSH Metabolic Dysfunction/Mitochondrial Dysfunction Infections/Immune Deficiency/Autoimmunity Nutritional deficiencies Food Allergies & Intolerances Excitotoxicity Heavy Metal Toxicity Genetic anomolies phenotypic expression (“autisms”) copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Emerging Model of Autism source: Elizabeth Mumper, MD Exposures: Infections Heavy metals Pollutants Pesticides Food sensitivities Food preservatives & additives Biologic Effects Neurologic impairment Gut dysfunction Metabolic disorders Immune dysregulation Regulatory problems Cellular damage Prevention efforts Treatment efforts copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Who can help us? Drugs and bad nutrition Oxidative Norman The Neuron stress Compromised Metabolism Excitotoxicity copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre 10 Americans : EWG 2003 study: detecting toxins in umbilical blood Medical theory: umbilical circulation/placenta protects fetus from toxins Findings: on average, over 212 known chemicals, including carcinogens, banned for 30+ years, were present in the blood samples Conclusion: children are exposed to harmful toxins throughout their prenatal lives, during various stages of organ development, contributing to the onset of neurodevelopment problems copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Government concedes vaccines cause autism in Poling case. March 6, 2008 copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre •19 month old girl, normal development, 20 word vocabulary •chronic ear infections delayed many vaccinations •After 9 immunizations (diphtheria, tetanus, and pertussis; Haemophilus influenzae B; measles, mumps, and rubella; polio; and varicella (Varivax)), the following developed with 48 hours: fever to 38.9°C, inconsolable crying, irritability, and lethargy and refused to walk. •Four days later, the patient was waking up multiple times in the night, having episodes of opisthotonus (arching), and could no longer normally climb stairs. Instead, she crawled up and down the stairs. Low-grade intermittent fever was noted for the next 12 days. •Ten days following immunization, the patient developed a generalized erythematous macular rash beginning on the abdomen. The patient’s pediatrician diagnosed this as due to varicella copyright: Scott Clack, BSc, ND/Touchstone vaccination. Naturopathic Centre For 3 months •the patient was irritable and increasingly less responsive verbally •clear autistic behaviors, such as spinning, gaze avoidance •disrupted sleep/wake cycle •perseveration on specific television programs •all expressive language was lost by 22 months Four months later, an evaluation with the Infant and Toddlers Early Intervention program for possible autism was initiated. her appetite remained poor for 6 months, body weight did not increase. This resulted in a weight decline from the 97th to the 75th percentile. •Muscle biopsy revealed deficiencies of the mitochondrial respiratory chain (3 of 4 complexes, and technically the 4th) Poling JS, et al. J Child Neurol 2006;21(2):170-172 copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Respiratory complexes I-V copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Defective respiratory complexes (I,II,III,IV) in Hannah Poling’s biopsy E n z y m e A c t i v i t y IVb 1600 III 1400 IVa 1200 1000 800 Poling Control mean II+III 600 400 200 0 Ia Ib I+III I + I I I copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre E n z y m e A c t i v i t y Signs of Mitochondrial dysfunction Cleve Clin J Med. 2001 Jul;68(7):625-6, 629-42. Muscles-low muscle tone, weakness, low exercise tolerance, muscle pain, cramps Brain-developmental delay, mental retardation, autism, dementia, seizures, migraines, stroke Nerves-nerve pain, absent deep tendon reflexes, lack of or excessive sweating, abnormal temperature regulation Gastrointestinal problems-reflux, constipation copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Mitochondrial Disorder (MD) Primary (genetic) and Secondary (impaired function) Primary MD estimated at 1 in 200 (Elliot, 2008) Synaptic neurotransmitter release decreases 50% when MD exists Decreases GABA that contributes to seizures, regression Increases with age –mtDNA mutations, w/ maternal inheritance Most common cause of MD is defects in nDNA copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Secondary MD Medications: Valproic acid, salicylates, antiretroviral HIV meds Estrogen increases mitochondrial efficiency, testosterone decreases (thus predominance in males) Oxidative stress, lowered Glutathione Hypoxia Heavy metals: Hg, Pb, Arsenic, Cd, Al Pesticides Diesel exhaust Proprionic acid from Clostridia copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Evidence of mt Dysfunction Am J Biochem Biotech 2008; 4:208-217 (Rossignol & Bradstreet) “Environmental toxins ... directly damage the mitochondria and reduce their efficiency, or impair functional activity by increasing body burden of free radicals and resultant oxidative stress (e.g. Thalidomide; Valproic Acid). mercury, arsenic, cadmium, lead, pesticides, and industrial chemicals inhibit mitochondrial function Propionic acid produced by Clostridia in the ‘GI’ tract ...impairs mitochondrial function by directly inhibiting oxidative phosphorylation By increasing oxidative stress and lowering glutathione levels, MtD may actually lead to problems in detoxifying environmental contaminants and consequently increase susceptibility to metal toxicity. copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Mitochondrial disease in autistic spectrum disorder: a cohort analysis. J. Weissman et al; PLOS One: 3:e3815 Most common abnormal symptoms in children with Autism and mitochondrial disorders: Prenatal complications-52% Gastrointestinal dysfunction-64% Exercise intolerance-68% Multiple regressions-36% Delayed walking-32% copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Treatment of Mitochondria disorder Coenzyme Q-10 (5-15 mg/Kg)-slow acting, months for improvement-divided dosages Idebenone: 45-360 mg/day (or ubiquinol) Carnitine or acetyl carnitine 50-100 mg/Kg/day (adult 1-3 g per day)-divided dosages Carnitine: helps transport long chain fatty acids into mitochondria for beta-oxidation. Neutralizes free radicals, incl. those from ETC. High doses can cause diarrhea. Thiamine, Riboflavin & Vit. B5:15mg/Kg/day Antioxidants: Vitamin E, Vitamin C, Selenium, Lipoic acid copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Treatment of Mitochondrial Disorder Methylation Support: Folate -1000-10,000 mcg/day Vitamin B12 (methylcobalamin) Vitamin K3: 5-80 mg/day Creatine monohydrate: 5-10 gram/day Succinate, Ginkgo biloba D-Ribose: 0.5-1 gram bid Chelation/Heavy metal detox – include Lipoic Acid HBOT Outcomes: Varies by person; usually good but can be gradual. copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Cerebral Folate Deficiency Frye RE et al, Molecular Psychiatry (2012): 1-13 A syndrome described as a neurometabolic disorder characterized by low concentrations of 5MTHF in the cerebrospinal fluid despite normal levels elsewhere in the body Impaired transport of folates across the BBB 1st case: spastic paraplegia, cerebellar ataxia, dyskinesia, seizures, developmental regression, acquired microcephaly; vision disturbances and hearing loss developed later copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Cerebral Folate Deficiency Involves a subset of ASD children, typically low functioning w/ significant neurological problems Folate deficiencies promote methylation deficits (frontal cortex) and oxidative stress (several cortical regions including speech, emotion and social areas) Folate is essential for production of purines & pyrimidines for RNA, DNA reduced cellular proliferation, reduced transcription & translation, DNA instability and chromosome breakage Folate receptor protein (FRA) is important for repair and regeneration of CNS after injury copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Cerebral Folate Deficiency Diagnosis: Cerebral spinal fluid from lumbar puncture Blood test for FRA concentrations (SUNY, Brooklyn NY, Dr. Edward Quadros PhD) Outcomes Leucovorin or Folinic acid (0.5-2.0 mg/kg) improvements ranging from partial improvement in communication, social interaction, attention, stereotypical behaviours, to complete recovery of both neurological and ASD symptoms copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre How to know if Biomedical is working? Repeat labwork where possible – confirm the metabolism is changing Labwork cannot tell how great certain deficiencies have been Consider genomic testing: identify blockages that prevent treatments from achieving results Lack of obvious improvements does not mean biomedical isn’t working – treatment may not have progressed far enough, or key treatment(s) might not have been implemented copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Knowing if Biomedical is working A.M. 3.5 y.o. at first visit Complaints: ASD, Diarrhea, Food Allergies also sinus congestion, dermatitis, speech d/o, lethargic (with bouts of hyperactivity) Extensive testing pursued by parents: Clostridia, Enterococcus, Yeast & 2 parasites (contracted from daycare provider) Organophosphorus pesticide exposure & toluene Poor detox: abnl sulfate, free radicals & lipid peroxide, SOD/GSH/cysteine Was on comprehensive treatment list: Multivitamin, enzyme, probiotic, 5-HTP, AminoPlex, SacB, chelation, BioCidin/Rx antifungals GF/CF diet; later SCD IV treatments – chelation, GSH Weekly allergy desensitization treatments (NAET method) All treatments were implemented over a 6-8 month period, continued for 2-3 years Today this child is a ‘recovered’ 15 y.o. teenager in school, playing sports Therefore: lots of treatments are needed to achieve recovery, and sooner than later copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Improving Attention Finding the cause will require trials Potential causes include: Reactions to foods or food additives (excitotoxins; see Dr. Russel Blaylock for more information) Nutrient deficiencies: Iron, Zinc, Acetyl-L-Carnitine, Tyrosine, Vitamin B6 & C – all support Dopamine Infections – yeast, virus Heavy metals – if not treated, this is probably the root cause copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Improving Attention Herbal medicines as short term solutions Ginseng (Korean, panax ginseng) Rhodiola Bacopa moniera Lemon Balm, Passionflower, Skullcap Pycnogenol (Pinus maritima) Other options Omega-3 fatty acids Vinpocetine (Periwinkle) L-Theanine (green tea extract, lowers anxiety, improves sleep, increased alpha waves) Altern Med Rev. 2011 Dec;16(4):348-54. Asia Pac J Clin Nutr 2008;17 Suppl 1:167-8 copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre L-Theanine & Attention Brain Topogr. 2009 Jun;22(1):44-51. Conclusions This pattern of results implies that L- theanine plays a more general role in attentional processing, facilitating longer-lasting processes responsible for sustaining attention across the timeframe of a difficult task, rather than affecting specific moment-to-moment phasic deployment processes. copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Heavy Metal Toxicity Lead, Mercury, Cadmium, Aluminum, Arsenic are all toxic to the nervous system Lead intoxication is known to develop in fetuses and infants during pregnancy, lactation Mercury – fish, meat, fructose (HFCS), corn Lead – comes from remodelling of bones during pregnancy Food, water and air are the main routes or sources for metals copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Heavy Metal Toxicity The severity of autism is associated with toxic metal body burden and red blood cell glutathione levels. J Toxicol 2009; Epub 2009 Aug 26 PMID 20107587 Adams JB et al Assessing urine levels of metal before and after oral DMSA (dimercaptosuccinic acid) Conclusion: severity of autism increased with the level/burden of heavy metals. copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Heavy Metal Toxicity Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: part B – behavioral results. BMC Clin Pharmacol 2009 Oct 23; 9:17 Adams JB et al. PMID 19852790 65 children received one round (3 days) or 7 rounds (if they excreted high levels on first round) DMSA was tolerated and possibly helpful in reducing some of the symptoms of autism copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Heavy Metal Toxicity Cutler Protocol Andrew Cutler has a PhD in biochemistry Developed his approach from personal experience and research Websites for more information www.livingnetwork.co.za www.curezone.com Groups.yahoo.com/group/frequent-dose-chelation copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Cutler protocol DMSA & ALA dose – 1/8 to ½ mg per pound per capsule 1 capsule every 3-4 hours for up to 3 hours Night-time doses are necessary Mineral replacement recommended – especially zinc, chromium, manganese and molybdenum Cilantro, Chlorella or Laminaria recommended to increase elimination of metals, preventing them reimplanting in other parts of the body copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Cutler protocol Minimal side-effects: spacey, disoriented Can be done every weekend Doesn’t seem to affect school/therapies Mondays might be a little shaky Other treatments to integrate: Infrared sauna Epsom baths and Clay baths Liver and kidney support on a quarterly basis copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Natural Chelators In cases of mild/low level intoxication: Glutathione – preferred products are MAX-GXL or HMS 90/Immunocal Curcumin Metagenics Metalloclear Laminaria or Chlorella Be sure to check source – could be contaminated Optimize B6, magnesium, N-Acetylcysteine, as well as MeB12/Folinic Acid/TMG or DMG copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre New Treatments to Watch Oxytocin – social enhancement Curcumin – inhibiting seizures; stimulating nerve growth or regeneration Histamine & DAO (diamine oxidase) food reactions Laminaria, Garlic – heavy metal detox/ chelators Restoring Cellular Communication Pathways protocol (from Physica Energetics) – homeopathic & herbal program to support/kickstart the healing processes copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Caring for the Care-Givers Take care of yourself so you can take better care of your children! Eat according to the GF/CF diet, like your child – you will feel better too Multivitamin, fish oil and antioxidants – core supplements B12 injections – boost your energy, feel better Green tea – 2 or 3 cups/day Regular liver/kidney cleanses (spring & fall) Epsom baths – 2X/week – and take a fun book! Massage therapy copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Care for the Care-givers Sleep!! In your own bed, without children (get help for this if your children are having problems) Avoid or minimize internet searching late at night (or the early morning): if you’re doing this, you’re not using your Biomedical practitioners properly Adrenal support – reduces your risk for burn out Take a break (aka Respite care): 24/7 care, 365 days a year will burn you out – ask for help from family or the community. Respite care is available. copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre Thank you! Scott Clack, B.Sc., N.D. Touchstone Naturopathic Centre 2390 Bristol Circle, Suite 4A Oakville, ON L6H 6M5 Tel: 905-822-2046 www.touchstonecentre.com Email: info@touchstonecentre.com copyright: Scott Clack, BSc, ND/Touchstone Naturopathic Centre