preventing autism and more through preconception … deth, r. neurotoxicology. jan2008, vol. 29...
TRANSCRIPT
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Getting to the Root Causes
of Autism
Liz Lipski, PhD, CCN, CNS, CFM, LDN
Maryland University of Integrative Health
& InnovativeHealing.com Liz Lipski 2015
Boys: 1/42 Girls: 1/189
CDC: March 28, 2014 / 63(SS02);1-21 Liz Lipski 2015
Who is at risk?
• Increasingly everyone
• Males more than females
• SNPS: detox, methylation
• Family history
Liz Lipski 2015
Genes
Triggers
Environment
Liz Lipski 2015
2011
2003 2007
http://www.cdc.gov/ncbddd/adhd/prevalence.html
Incidence of ADD/ADHD by State
Liz Lipski 2015
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Type 2 Diabetes US and Puerto Rico by State
2010
1995-2010
CDC: November 16, 2012 / 61(45);918-921 Liz Lipski 2015
Brady, D. Townsend Newsletter, June 2012
Liz Lipski 2015
Auto-Immune Conditions
Preconception Planning: Changing the Odds
Liz Lipski 2015
Leslie & Michael Stone, MD’s, et al. • Affect of Personalized Nutrition Programs during pregnancy
• Study group, private practice, and community clinic
• 1st trimester: serum zinc, 25-OHD, MTHFR, COMT;
• 2nd trimester and postpartum: zinc, carnitine, 25-OHD
• Nutrition & Lifestyle education, supplementation of folate, Mg, EFA, probiotics and targeted supplementation of zinc, carnitine and vitamin D
• Outcomes: < total complications, < gestational DM, < PI-HTN
• Limitatoins: Small study, healthy population
Liz Lipski 2015 Stone L, Stone M. (2014) GAIMJ. 3(6) Nov.
Genetics and Autism
• Family with an autistic child: nearly 20% risk of each subsequent child having autism • Identical Twins: when one has autism, other does 70% of
the time • Symptoms differ • What about the other 30%?
Dr. J. Mill: “Sometimes risky environmental conditions can be avoided or even changed.” Wong, CCY, Mill, J. et al. (2014) Molecular Psychiatry 19, 495–503.
Liz Lipski 2015
David Berger, MD, FAAP
• 10 years in practice
• 500 patients who joined practice at birth
• Not one has developed autism, diabetes, or asthma
• Only in one family (3 children) developed recurring
• otitis media
Berger, D. Autism Science Digest, J or Autism One. Issue 04.
Liz Lipski 2015
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Liz Mumper MD/ Rimland Clinic
• No new cases of autism in her practice since established 2000
• From 2005 294 consecutive patients well care at or prior to age 2 months, followed until at least age 2
• Typical first visit between 3-5 days of age.
• 11 well baby check ups
• Researched their developmental milestones
• 0% cases of autism
• Expected: 6 new cases of autism
Mumper. N. Amer J of Med and Sci. 2013, 6(3).
Liz Lipski 2015
Autism
Liz Lipski 2015
Liz Lipski 2015 Liz Lipski 2015
Liz Lipski 2015
Autism
Oxidative stress
Impaired methylation
Toxic exposure
Liz Lipski 2015
< B12 activity
< folate dependent Methionine
Impairs sulfur
metabolism
< Dopamine
Adapted: Deth, R. NeuroToxicology. Jan2008, Vol. 29 Issue 1, p190-201
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Liz Mumper MD David Berger MD, FAAP
Preconception planning Preconception Planning: SNPS, maternal nutrition, screen for celiac, gluten sensitivity, maternal allergies, dysbiosis, metals, thyroid, nutrients: D, Folate, iron. Supplementation: calcium, iron
Minimize toxin exposure Minimize toxin exposure
Maximize breastfeeding Maximize breastfeeding
Probiotics: colic, eczema, wheezing, rhinitis Probiotics: colic, eczema, wheezing, rhinitis
Nutritional Counseling
Prudent use of antibiotics Prudent use of antibiotics
Minimize use of acetaminophen
Modified vaccination schedule Modified vaccination schedule
Treat Candida Liz Lipski 2015
Pre-conception planning • Moms of autistic children less likely to have taken iron supplements or
multivitamins during pregnancy.
• Pregnant women with low serum folate > risk
• Women who had a daily intake of > 600 mcg folate during early pregnancy < risk (P.02), most apparent in in women with methylation SNPs.
• Likely to be low in vitamin D
• Parental age affects risk in girls
• Women who have diabetes, HTN, or obesity during pregnancy > risk
• Parent immigration with high fish consumption > risk Rebecca J. Schmidt American Journal of Epidemiology, September 2014 Mumper. N. Amer J of Med and Sci. 2013, 6(3). Am J Clin Nutr. 96(1):80-89. Epidemiology. 2011;22(4):476-485. Fernell, E. et al. Molecular Autism 2015, 6:3
Liz Lipski 2015
Environmental & Lifestyle Risks for ASD
• Multivitamins and folate probably protective:
• Schmidt et al. reported a 40% reduced risk of ASD with prenatal vitamins
• Increased fatty acid intake probably protective
• Air pollution and heavy metal exposure > risk
• > risk of ASD in babies conceived in summer/born in spring
• Pregnancies spaced < one year apart (possibly due to nutrient insufficiencies)
Liz Lipski 2015
Int J Epidemiol. 2014 Apr; 43(2): 443–464. Schmidt. Epidemiology. 2011 Jul; 22(4): 476–485. Autism Res. 2010 Aug;3(4):185-90. doi: 10.1002/aur.136. Pediatrics. 2011 Feb;127(2):246-53
Liz Lipski 2015
Berger, D. Autism Science Digest, J or Autism One. Issue 04.
Phase 2 Response from Fruits/Vegetables
Spinach Beets Lettuce Chicory Mizuna Corn Peas Carrots Potato Tomato
Apples Oranges Lemons Grapefruit Pears Rhubarb Mango Avocado Peach Nectarine Grapes Dates Figs Apricot
Collards Turnips Leeks Garlic Chives Onion
Blueberries Raspberries Plum Pumpkin Squash Green Beans Watermelon Canteloupe Honeydew Strawberries Oregano Basil Cardamon Cinnamon Cloves Pepper Noni Juice
Broccoli
Watercress
Cauliflower
Cabbage
Brussels Sprouts
Arugula
Kale
Kohlrabi
Daikon
Red Radish
Horseradish
Chinese Cabbage
Bok Choy
Malterre, T. ARI / & BrocColinate
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Preconception Planning: Detox/Cleansing • Plan 1-6 months preconception
• Clean up diet / Therapeutic diet?
• Get regular exercise • Hydrate
• Develop good sleep habits
• Stop or limit alcohol
• Stop recreational drugs
• Limit chemical exposure • Find out about possible issues with Rx drugs
• Cleansing program of some sort
• Limit caffeine
• Lab testing: chemistry, HmgA1C, vitamin D, iron status, carnitine, Folate, zinc, Magnesium, nutrient status
• Men: bicycle seats, avoid saunas, hot tubs Liz Lipski 2015
2015 Shopper’s Guide: EWG.org
Liz Lipski 2015
Preconception Supplements
• Good Prenatal
• With folate = >600 mcg
• Fish oil in supplements or diet
• Liver support: dandelion root, burdock root, milk thistle, greens
• Base other supplements on specific need
Liz Lipski 2015
Anti-Brain Antibodies
• 23% of mothers who have children with autism produce
auto- antibodies
• 1% of control mothers
• These antibodies cross the blood brain barrier of the mother and also pass into the BBB of the fetus
• Biomarkers: 99% specificity for autism risk:
• 7 specific maternal antibodies affecting: cell migration, neural tube formation, cell division, neuritogenesis, dendritic branching, axon outgrowth, transcription regulation, & metabolism
Liz Lipski 2015
Van de Water, J. (2014) ARI Think Tank, Braunshweig et al. Translational Psychiatry, July 9, 2013
Pregnancy
Liz Lipski 2015
Prenatal Nutrition & Long-Term Health Issues • Energy/Protein Restriction: > risk insulin resistance, diabetes, HTN,
dyslipidemia, atherosclerosis, and cardiovascular death
• Omega 3 FA Deficiency: > risk HTN, insulin resistance
• Micronutrients Deficiencies: (folate, B12, A, iron, Mg, Zn, CA)
>CVD risk
• Maternal overnutrition: > risk high birth weight, > cardio-metabolic risk as adults
• Pregnant women who are obese or diabetic: > risk of cardiometabolic diseases, and permanently increased appetities
Liz Lipski 2015
Szostak-Wegierek, D (2014) Inter J Women’s Health. 11 July. Arnoldussen IAC, & Kiliaan AJ. (2014) Mar. Drugs, 12(6190-6212)
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Research on prenatal care & Autism
• Prenatal exposure to stress such as infections is associated with > risk for neurodevelopmental disorders.
• Alter gene expression without altering DNA coding
• > Schizophrenia
• > Autism
• Sex specific
• Prenatal timing is critical
Liz Lipski 2015
Hormones & Behavior. Aug2012, Vol. 62 Issue 3, p237-242. BioEssays. Apr2014, Vol. 36 Issue 4, p353-358. Stress: The International Journal on the Biology of Stress. Jul2011, Vol. 14 Issue 4, p348-356 Hays, B. Integrative Medicine. (2009) V. 8. #6. Liz Lipski 2015
Dutch Famine and Consequences for Adult Health 1944-1946
1st Trimester • Glucose intolerance • Atherogenic lipid
profiles • Blood coagulation
disorders • > Stress
responsiveness • > obesity • > breast cancer
2nd Trimester • Glucose intolerance • Microalbuminuria • Obstructive airway disease
3rd Trimester • Glucose intolerance • Hypertension
Roseboom 2006 Early human development 82 485-91
Micronutrient Insufficiencies
Liz Lipski 2015
The main point is that genome damage caused by moderate micronutrient deficiency is of the same order of magnitude as the genome-damage levels caused by exposure to sizeable doses of environmental genotoxins such as chemical carcinogens, UV radiation and ionising radiation…..a dose of radiation that is approximately ten times greater than the annual allowed safety limit of exposure for radiation workers
Liz Lipski 2015
Stone, L. & Stone, M. (2014) GAHMI. 3(6) Nov. Liz Lipski 2015
Stone L, & Stone M (2014) GAHMJ. 3(6) Nov.
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Birth: C-section vs. Vaginal delivery
• Babies born by C-section when mom has general anesthesia have a 1.52 increased risk compared to babies born vaginally.
• Other studies are beginning to confirm this > risk. • Mothers who breastfed for 3-5.9 months were less “concerned”
about developmental milestones than non-nursing mothers.
Neurosciences (Riyadh). 2014 Oct;19(4):291-6.
J Autism Dev Disord. 2015 Apr;45(4):932-42.
Med Hypotheses. 2014 Jun;82(6):713-8.
Ann Epidemiol. 2014 Apr;24(4):260-6.
East Mediterr Health J. 2013 Sep;19(9):769-74.
Liz Lipski 2015
Infants and Toddlers
Liz Lipski 2015
Genes
Triggers
Environment
Liz Lipski 2015
Prevention of autism after baby is born
• SNP testing
• Deal with colic and GI issues
• Give probiotics
• Limit or exclude use of acetaminophen
• Immunizations
• Food
• Signs
Liz Lipski 2015
Normal Flora and Immune System: In Early Life • Sets up develop of innate and adaptive immune system during infancy
• Is mandatory for normal development
• Insures tolerance and intolerance correctly
• Primes the immune system to react appropriately to potentially harmful challenges
Plummer, N. (2013) Integrative Health Symposium
Liz Lipski 2015
Brain Development
wk 3 / embryo wk 8 until age 2
organogenesis proliferation/maturation
Liz Lipski 2015
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Microbiome and Health • Cardiovascular Disease
• Digestive Health
• Depression
• Schizophrenia
• Anxiety
• Autism/ADHD
• Atopy
• Autoimmune Disease
• Skin
• Pain
• Obesity
• Diabetes Liz Lipski 2015 Liz Lipski 2015
Factors that influence the infant gut mucosal immune system
Pediatric Allergy & Immunology, Aug2013, Vol. 24 Issue 5, p414-421.
Microbiome
Nutrition Maternal Immunity
Microbiome and Neurological Development in Infants
Liz Lipski 2015 Trends in Molecular Medicine September 2014, Vol. 20, No. 9
Breast Feeding
• Breast feeding lowers risk of autism
• Late initiation of breast feeding, and no colostrum > risk
• Exclusive breastfeeding reduced risk
• Mothers who breastfed for 3-5.9 months were less “concerned” about developmental milestones than non-nursing mothers.
Liz Lipski 2015
Nutrition. 2012 Jul;28(7-8):e27-32. Neurosciences (Riyadh). 2014 Oct;19(4):291-6. Pediatrics. 2007;119(Suppl 1):S92-S98.
Liz Lipski 2015
Nutrient Brain Requirement for Nutrient Brain Process affected by deficiency
Protein/Calories Cell proliferation & differentiation Synaptogenesis, Growth factor synthesis
Global Cortex HIppocampus
Iron Myelin, monoamine synth, neural and glial energy metabolism
White matter Striatal-frontal Hippocampal-frontal
Zinc DNA synthesis Neurotransmitter release
Autonomic nervous sys. Hippocampus, cerebellum
Copper Neurotransmitter synthesis, neuronal and glial energy, antiox.
Cerebellum
LC-PUFAs Synaptogenesis Myelin
Eyes Cortex
Choline Neurotransmitter synth. DNA methylation Myelin synth.
Global Hippocampus White matter
Am J Clin Nutr 2007;85(suppl):614S–20S. Liz Lipski 2015
Epigenetic Roles of Nutrition
Embryonic
Development
Folate
Choline
Protein
restriction
Alcohol
DNA methylation, imprinting
DNA methylation
DNA methylation
Histone modification
DNA methylation
Histone acetylation
Stem Cell Butyrate DNA methylation
Immune
function
Folate DNA methylation
Neurocognitive Choline DNA methylation
Histone methylation
Adapted from: SangWoon Choi (2010) Adv. Nutr. Nov 1:8-16.
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Nutrigenomics
• The interplay between food and our genes
• Explains why certain foods/diets work best for each of us
• Genes encode proteins that perform specialized functions
• Food "talks" to a gene
• Gene reacts talk to our cells/cell
signaling and regulation
MTHFR
• Bipolar disorder
• Miscarriage/Infertility
• Neural tube defects
• Strokes
• Macular degeneration
• Mood swings
• Depression
• Anxiety
• Fatigue
• Autism
• Heart disease
• Lyme disease
• Chronic fatibue
• Pandas
• High homocysteine
• Low SAMe
• Cancers
• <B12
Methylation Defects in Autism
• Abnormal plasma metabolite levels in many autistic children
• < methionine
• Reduced SAM/SAH ratio associated with: (hypomethylation of DNA, RNA, proteins phospholipids, and neurotransmitters (dopamine synthesis specifically)
• < cysteine + < glutathione
• Altered reduced to glutathione ratios
James J. Et al. J Autism Dev Disord (2012) 42:367–377
Liz Lipski 2015 http://www.easytolovebut.com/?p=2782
Prenatal methylation nutrients And continue until through first month of conception to address methylation issues Stone. M. (2014) IFM Symposium
8-Hydroxy-2’ deoxyguanosine (8-OHdG)
• Normal product of DNA oxidative damage and repair
• Organic Acid testing
GI Healing Diets
Whole Foods
Diet
Gluten Free/Dairy Free Diet
Specific Carbohydrate
Diet
GAPS Diet
Anti Candida
Diet
Elemental Diet/Poly-meric Diet
Rotation Diet
Low Histamine or
Oxylate
Restorative Diet
FODMAP Diet
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TYPICAL IMPROVEMENTS
• Language
• Eye contact
• Ability to focus
• Toilet training
• Eating patterns
• Social interactions
• Mood and behavior
• Sleep quality and pattern
• Digestive and bowel function
• Aggression reduction/resolution
• Skin rashes and eczema reduction/resolution
Dana Laake RDH, MS, LDN Liz Lipski 2015
Autism Research Institute 2013 Parent Ratings Got Worse Improved Greatly
Improved
Ratio:
Impr/Worse
# of
children
Candida Diet 3% 39% 58% 21:1 1141
Feingold Diet 2% 40% 58% 26:1 1041
Gluten-Casein
Free
3% 28% 69% 24:1 3593
Low Oxylate Diet 7% 43% 50% 6.8:1 164
Removed
Chocolate
2% 46% 52% 28:1 2264
Removed Eggs 2% 53% 45% 20:1 1658
Removed
Milk/Dairy
2% 44% 55% 32:1 6950
Removed Sugar 2% 46% 52% 27:1 4589
Removed Wheat 2% 43% 55% 30:1 4340
Rotation Diet 2% 43% 55% 23:1 1097
Specific Carb. D. 7% 22% 71% 10:1 537
Vojdani, et al Nutr Neuroscience June 2004, pp 151-161
• Vojdani, et al Nutr Neuroscience June 2004, pp 151-161
Vojdani, et al Nutr Neuroscience June 2004, pp 151-161
Vojdani, et al Nutr Neuroscience June 2004, pp 151-161
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Liz Lipski 2015
Preconception Planning:
Look at parent’s lifestyle SNP testing Nutrient status Toxic exposure Detoxification program Prenatal supplement with folate Fish oil Test for antibodies
Pregnancy & Birth Whole Foods Diet Prenatal supplements Probiotics Limit toxic exposures Limit medications Vaginal delivery C-Section = innoculate
Infants and Toddlers Breast feeding Probiotics Possible SNP testing Deal with small problems: colic, fussiness, gas < use of acetaminophen < use of antibiotics Modified vaccination schedule Elimination Diets Nutrient Status
Getting to the Root Causes
of Autism
Liz Lipski, PhD, CCN, CNS, CFM, LDN [email protected] www.muih.edu www.innovativehealing.com
Liz Lipski 2015