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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 llipski@muih.edu www.muih.edu www.innovativehealing.com

Liz Lipski 2015