Connecting the Genomic Dots How to incorporate nutritional genomics in treatment modalities in

ASD

Objectives

• Clarify and define the concepts of Nutritional Genomics.

• Identify various genetic SNP’s and their subsequent impact on

health.

• How to create nutritionally supportive meal plans with the use of the

nutritional genomic data.

Nutritional Genomics

• Explores how genetic variations affect the interaction between diet and health.

• Identifies genetic susceptibility to a disease

• How people respond to nutrients depending on genetic variation.

• Not every persons responds the same way (i.e. obesity, diabetes, cancer)

Nutri-Genomics

Focuses on how food constituents impact gene expression

• How a particular food affects gene expression.

• How compounds in food can influence molecular pathways

• impact disease risk.

• What you eat turns genes on/off

Food is information for our genes

• Food sends signals to the genes

• Everything we take in food, emotions,

• toxins: Affects cells and DNA

Epigenetics is Everywhere

• What you EAT

• Where you live

• Who you interact with

• When you SLEEP

• How you MOVE

• Even Aging

Can eventually cause chemical modifications that will turn genes on or off over time.

Epigenetics

Genetic

Predisposition

Environmental

Triggers

Altered Biochemical

Pathways

Etiology of Autism Spectrum Disorders

Epigenetics: It’s role in ASD

What environment is doing to our genes

• Onset of the disorder is periods of fetal maturation & development

• Stress of mother

• Endocrine disruption

• Pesticide exposure

• Exposure to drugs

• Premature birth

Possible Environmental Factors Associated with ASD (Post Natal)

• Childhood vaccines

• MMR

• Mercury-containing vaccines

• 54% of parents believe child’s ASD caused by immunization

• Allergies (good and/or environmental)

• Inflammation

• Oxidative stress

Epigenetics

• Days 20-24 of gestation

• Establishment of epigenetic bookmarks

• Permanent- persisting through life

• Determine expression across multiple genes

• Exposure to toxic chemicals

• Permanent physical and mental abnormalities

• Dominant biochemical factors

• Methylation and acetylation

• 95% of ASD children are undermethylated

Methyl- THFR- WHAT???

Polymorphisms associated with ASD

• Glutamate Decarboxylase 1 (GAD1)

• Methylene Tetrahydrofolate Reductase (MTHFR C677T)

• Catechol-o-methyltransferase (COMT)

• Monoamine Oxidase (MAO-A)

Polymorphisms associated with ASD

• Methionine Synthase (MTR)

• Methionine Synthase Reductase (MTRR)

• Cystathione Beta Synthase (CBS)

• Transcobalamin receptor II (TCN2)

• Folate receptor 1 (FOLR1)

• Betaine Homocysteine S- Methyltransferase (BHMT)

MET Gene Variant & Maternal Autoantibodies in Fetal Brain

• MET gene codes for MET receptor tyrosine kinase

• MET variant (C allele) present in 9% of mothers of children with ASD compared to controls

• MET C allele in ASD women:

• Strongly linked to maternal autoantibodies to fetal brain proteins

• Decreased MET protein leading to more intense and prolonged immune response to bacteria or viral exposure

• Deficiency in IL-10, important cytokine that suppresses pro-inflammatory responses leading to more prolonged inflammatory response.

• Van de Water et al. (2011) Transl Psychiatry (online Oct 18)

Neurotransmitters Oxidative Stress

Inflammation

Mitochondrial

Dysfunction

Gastrointestinal

DisturbancesNeurological

Abnormalities

Altered Metabolic Systems in ASD Children

Inflammation in ASD Children

• Brain

• Abnormalities of the microglia

• Elevated pro-inflammatory cytokines in frontal cortex

• Peripheral immune system

• Increased levels of cytokines in brain, CSF, blood and GI tract (upper and lower small intestine)

• Increased antibody levels

• Allergies in 62% of ASD children

• Strange skin rashes

• Ear infections and coughs

Reduced Antioxidant Activity in ASD Children

• GSHPx activity in plasma and RBC decreased in ASD children compared to controls

• Decreased catalase and SOD activity in RBCs

• Reduced levels of total glutathione in plasma

• Lower redox ratio of GSH and GSSG in plasma

Oxidative Stress

Mitochondrial Dysfunction in ASD Children

• Mitochondrial dysfunction in CNS (30 to 40 %)

• Developmental regression

• Learning disabilities

• Behavioral issues

• Metabolic lactic acidosis seen with ASD

• maybe associated with pyruvate dehydrogenase deficiency or mitochondrial respiratory chain defects (CoQ10)

• Carnitine deficiency commonly found with ASD

• Essential for fatty acid utilization by mitochondria

• Impairment of ATP production, which can explain fatigue

Gastrointestinal Tract Disturbances in ASD

• Signs and symptoms in 68% of ASD children

• Reflux Constipation

• Sensitivity to food Abnormal flora

• Frequent abdominal pain

• Inflammatory reaction to gliadin (gluten peptide)

• Microscopic changes

• Swollen lymph nodes within submucosa of intestinal wall

• Mucosal abnormalities • Absorptive epithelium disrupted

• Connective tissue weak

• Muscularis mucosae

Repairing the GUT

• Prevent undigested proteins from reaching the brain

• Allows desired nutrients to feed the brain

• Allows food to be digested

• Prevents further inflammation of the gut

GI

Oxidative Stress Biomarkers

• 99% > excessive oxidative stress

• Pervasive Zinc deficiency

• Low Copper/Zinc/SOD

• Copper overload/low Ceruloplasmin

• Low Glutathione, selenium, or MT proteins

• Seizures

Biochemical Features of Autism

• Low Glutathione

• Under methylation

• Elevated Mercury/Lead/Toxins

• Copper overload and Ceruloplasmin insufficiency

• Zinc deficiency

• Vitamin A deficiency

• Low magnesium levels

• Low selenium and cysteine

• Elevated urine Pyrroles (Autism 38%)

• Elevated carboxyethylpyrroles1

• Depressed metallothianine levels• (MT protects cells from free radical exposure)

Gu, X., Meer, S.G., Miyagi, M., Rayborn, M.E., Hollyfield, J.G., Crabb, J.W., & Salomaon, R.G. (2003).Carboxyethylpyrrole protein adducts and autoantibodies, biomarkers for age0-related macular degeneration. The Journal of Biochemistry, 278(43), 42027-35. http://doi.org/10.1074/jbcM305460200

Genomic Nutrition Roadmaps

Recommendations for ASD

• Maternal lifestyle choices

• Very conservative use of pharmaceutical medicines

• Avoid toxic cleaning products, solvents and pesticides

• Flexible vaccination schedules

• Identify ASD subset using appropriate biomarkers

• Genomic tests help determine predisposition to clinical imbalances

Recommendations:

• Address altered metabolic systems:

• GI/Inflammation/Oxidative Stress/Neurologic/Mitochondria Dysfunction

• Nutritional support

• Antioxidants

• Anti-inflammatories

• Reliance on organic and whole foods

Include nutritional bioactives to support gene cross talk

Thank you!

Meryl Brandwein, RD/LDN

954-727-9006

MerylBrandweinNutrition

Merylbrand

Merylbrandwein.com