connecting the genomic dotsconnecting the genomic dots how to incorporate nutritional genomics in...
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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