Dr. Steve Hinder Consultant Psychiatrist April 23rd 2008

Sulphate and Autism 10 years ago, very few biological markers ↑ platelet serotonin in 30% Proxy for reduced serotonin brain function Borne out by success of SSRI’s and Risperidone Rosemary Waring found low sulphate as a marker in autistic children Pursued links with Allergy Induced Autism group, finding migraine in mothers

n Foods that worsen behaviour contain PHENOLS n Phenols are metabolized by Sulphation, catalyzed by Sulphotransferase enzyme (PST) n PST is low in migraine

RESULTS IN AUTISTIC CHILDREN n Very low Sulphate levels (10% of normal) n High Cysteine levels n PST very low in individuals with food reactions n PST normal in other children

CYSTEINE AND SULPHATE VALUES IN AUTISTIC ADULTS AND CONTROLS Mean Cysteine Mean Free Sulphate Ratio Autism (n=20) Severe LD (n=10) Mild LD (n=7) Controls (n=60)

(TMG)

Gaining New Knowledge Autism Research Unit Durham conferences Allergy Induced Autism Hyperactive Childrens Support Group Informal networking Andrew Wakefield Developmental histories Taking parents more seriously Dietary history Immunity Vaccines Eventually brave enough to give advice ! PeoplePractice

OPIATE EXCESS THEORY OF AUTISM n Reduced crying when isolated n Decreased pain sensitivity n Insistence on sameness n Increased stereotypical behaviour n Fearlessness n Abnormal social play n Unusual body postures n Changes in eating patterns n Increase in seizures n Social withdrawal n Hyperactivity n Lack of response to sensory stimuli All signs of opiate addiction or withdrawal

EXOGENOUS OPIOIDS è Intact peptides can cross mucosa (Gardner, 1983) è Gluten and Casomorphin fragments have opioid activity è Peptide peaks in urine of autistic patients have opioid activity (Shattock, Reichelt) è Abnormal intestinal permeability in autism (D'Eufemia et al, 1996) è Effect of gluten and casein- free diets?

CAUSES OF LEAKY GUTS l Trauma Cytokines l Immunodeficiency/Allergy l Gut flora imbalance or Candida l Ankylosing Spondylitis or Arthritis l Low Glycosaminoglycans l Measles/MMR ? l ? Learning disability?

GLYCOSAMINOGLYCANS (GAG's) + CANDIDA n GAG's required for gut wall integrity n Normally sulphated - produces negative charge n Lack of sulphate interrupts normal production n Candida no longer repelled n Candida very common in autism n Known to deplete sulphate n Positive feedback ?

Recent Trends - Increased incidence, was 1 in 2000 now 1 in majority feel due to better diagnosis and wider definitions, but significant minority feel genuinely increasing - “Active but odd” group now more prominent ? - Less LD than you would expect (20% rather than 80%) - Children with autism seem to be making extraordinary progress

If autism is increasing, what might the cause be ? - “Leaky Gut syndrome” - MMR/other vaccines - Overuse of antibiotics  Candida or clostridium - Pesticides or organophosphates - Food additives (Eg. MSG, Aspartame) - Lowered immunity/increased autoimmune disease - Mercury toxicity - Unusual viruses or other infections - Opiate use during delivery - Chemicals in environment

A Model for Causation in Autism LEAKY GUT ALTERED OPIATE RECEPTOR FUNCTION EARLY INSULT IN DEVELOPMENT GENETIC CONDITION CLOSELY INTERACTS WITH SEROTONIN GENETICALLY DETERMINED LOW DPP IV ? CANDIDA MMR SULPHATE + OTHERS ALTERED IMMUNITY CO-INHERITED WITH OTHER BIOCHEMICAL DIFFERENCES BRAIN MORE SUSCEPTIBLE TO INSULTS DRUG TREATMENTS ALTERED BIOCHEMISTRY

Possible causes of autism Leaky Gut Biochemical Causes Gluten/Casein free Anti-Candida Sulphate replacement Digestive enzymes Secretin Glutamine Cod liver oil/vitamin A Evening Primrose oil Zinc/minerals Megadose B6 + Mg DMG or TMG Allergies MSG/Aspartame free

Gluten/Casein-free Combination of both works best May be easiest to start with casein, but often not enough Persevere with casein for at least 2 months ? Persevere with gluten for at least 6 months ? May get “cold turkey”, esp. with casein Constipation/MMR history suggests gluten May previously have craved these substances, or avoided Sunderland urine test can be non-specific May work better in younger children May be less effective if clear genetic cause Improvement in 40% on combined diet ? NEED TOTAL ELIMINATION (in most, but not all) Re-exposure can cause severe behaviours

Sulphate No blood test available May be low in 90% of children Causes diarrhoea if taken orally Can try slowly increasing epsom salt baths Glucosamine sulphate Cranberry juice Cut out citrus fruit, apples, vinegar, tomatoes Avoid paracetamol Overlap with Feingold diet for hyperactivity Epsom Salts

Treating Candida Suggested by early antibiotic use Difficult to test (we all have it) NYSTATIN oral drops Low sugar Capryllic acid + other natural products Probiotics (acidophilus, Lactobacillus, Bifidus) Possibly low yeast diet Can get massive die-off reaction

Essential fatty acids Cod liver oil, may be vitamin A, omega 3 Evening Primrose oil, omega 6 (GLA) Flaxseed (Linseed) oil Zinc may aid absorption Good for hyperactivity/concentration May improve eye contact Caution with EPO in epilepsy

Other supplements Good evidence for high dose B6, Magnesium May tie in with sulphate pathways DMG/TMG may have additive effect

(TMG)

Other supplements Good evidence for high dose B6, Magnesium May tie in with sulphate pathways DMG/TMG may have additive effect Can all improve core social symptoms Digestive enzymes promising (CCK connection, DPP IV) Secretin not yet safe Other vitamins/minerals may help Glutamine can heal leaky gut? Monosodium glutamate/Aspartame important MANY OTHER THINGS BEING TRIED (Methyl B12, Glutathione)

Things to consider Early treatment probably best Interventions can also help ADHD/LD Is mercury important? Are UK and USA children different? – cysteine levels seem paradoxical DAN protocol – Is it humanly possible? Dilemma re single versus many treatments, as may be synergistic Do not take lightly (do have biological action), but give dietary interventions a try Therapeutic alliance with parents