Autism, Diet, and Nutrition: Are You What

You Eat?

Susan L. Hyman, M.D.Golisano Children’s Hospital at Strong

June 2009

Dr. Hyman has nothing to disclose related to this presentation.

With Thanks to Patricia A. Stewart, Ph.D. R.D.

Objectives

• Review diagnosis of Autism• Describe food related behaviors in ASD• Examine nutritional effects of food refusal• Review nutrition in children with/without Autism

• Examine a specialized diet used for children with Autism

Autism Spectrum Disorders

•Qualitative abnormality of social give and take

•Qualitative abnormality of language used for communication

•Restricted and repetitive behaviors

•Onset less than 3, not better explained by another diagnosis

Autism Spectrum Disorders

Pervasive Developmental Disorder – Not Otherwise Specified

Rett Disorder

Asperger Disorder

Autism

Associated Symptoms Might Include:

• Seizures• Regression• GI Symptoms• Sensory Symptoms:

-Hyperacusis-Tactile Hypersensitivity-Food Aversion

Are GI Symptoms More Common in Children with ASD?

Chronic

Abdominal Pain

Food Aversions

Chronic Vomiting

Chronic Diarrhea

Reported in 18-72% of children with ASDs

– Increased rate at dx not supported by UK GP Database

– In RUPP cohort, 22%, associated with increased irritability

Why might there be an association of ASDs and GI symptoms ?

• Serotonin metabolism in ASD:- Increased plasma levels- Serotonin: NT in enteric

NS•Vagal nerve is bidirectional•Immunologic factors?•Embryologic or genetic events in common?

GI Questions (continued)

GI Questions (continued)

Lymphonodular hyperplasia in colon - Are the findings due to constipation? Need

to compare to controls with similar GI symptoms – MacDonald, 2007

- Is this autistic enterocolitis? – Wakefield, 2000

- Limited evidence to date for increased gut permeability

Celiac Disease, Allergies and Leaky Gut in ASD:• No increase in celiac disease (gluten enteropathy on an

autoimmune basis)• No increase in general food allergies, may be an increase in

milk allergy (Lucarelli, 1995)• Urine Peptide measurement controversial:

- Shattock (1991), Reichelt (1991), Cade (2000) report increased urinary peptides that suggest gluten and casein peptides

- Hunter et al (2003) or Cass (2008)could not confirm this

finding using more specific technology and did not identify a

difference in DPP IV

Feeding Problems and Autism:Author N Prevalence Discussion

Raiten and Massaro, 1986

40 ASD34 TD

Food idiosyncracies in 53% v. 18%, won’t chew 17.5% v. 6%

No difference in preference for same foods or refusal/dislikes

Schreck et al, 2004

138AD298 TD

Food refusal more common with ASD

Ate fewer foods within each food group

Schreck and Williams, 2006

138AD 72% restricted, 57% refusal (touching, presentation, texture, oral motor)

Preferred fewer foods than their families, family greater influence than ASD!

Valicenti-McDermott, 2006

56 ASD50 DD50 TD

Selectivity 60% ASD, 36% DD, 22% TD

Smelling and not mixing foods more common in ASD

BAMBI (Brief Autism Mealtime Behavior Inventory)- Lukens and Linscheid, 2008

• 18 item parent report scale• Specific for behaviors children with ASD exhibit at mealtime e.g. SIB, food aversions, aggression, rituals•Three factors: Limited variety, food refusal, features of autism•Validity: 24 hour food record, BPFAS

Food refusal in ASD may be secondary to:•Obsessions •Perseverative interests•Sensitivity to taste and/or smell of food •Sensitivity to texture•Food neophobia (fears)•Operant behavior

- Learned aversion- Punishment e.g. pain

Food Neophobia is a fear of new foods (not limited to ASD):

• Rare in infancy (Addessi et al., 2005) • Peaks after 2 yrs, decreases, then is stable 3-12 yrs (Carruth & Skinner, 2000)

•Associated with a limited diet in adolescence (Nicklaus et al., 2005)

• Autonomic arousal in children 7-12 (Pliner & Melo, 1997)

• Abnl taste and smell discriminated children with ASD from FXS and other delays (Rogers et al., 2003)

• Parent report of atypical smell sensitivity (Nieminen-von Wendt et al., 2005)

• Impaired odor identification in adults with Asperger syndrome (Suzuki et al., 2003)

• Impaired taste and smell identification in adolescents with ASD (Bennetto et al, 2007)

Atypical Sensory Processing in ASD

• Heritability of food preference - Olfaction genes - Taste genes, e.g. bitter taste appreciation associated with aversion to certain textures - Modest heritability of food preference in twins demonstrated (Breen et al., 2006)

• Environmental influences - Exposure influences preference - Schreck and Williams, 2006: in ASD, Food restriction related to family preferences

Why is this Important? It informs treatment for food refusal:

• Consistent meal time expectations• Repetition repetition repetition• Attention to sensory aspects of mealtime

- Quiet environment- Texture, taste and smell of food

• Model mealtime behavior Teachers, parents, peers

Children in the US are OverfedBut Undernourished

0

20

40

60

80

100

120

6-11 Mo. 1 Yr. 1-4 Yrs. 5-8 Yrs. 9-14 Yrs. 15-19 Yrs.

Critical Age

Critical Age

% Children Consuming

Daily Recommende

d Intake

Data compiled by Dr. John Lasekan, Ross Labsfrom NHANES 1999-2000 and the Continuing Food Survey 1994-96, 1998

Nutritional Intake of TD ChildrenFITS (Devaney 2004) N=703

<12 months – mean intake > AI for all nutrients 12 – 24 months – prevalence of inadequacy low for most

nutrients 58% had Vit E intake <EAR

Suitor, 2002 - CSFII 1994 – 96 Vit E – high % of children with intakes < EAR Folate and Mg – many children < age 9 with intakes < EAR Ca – females 9+ < AI Females 14 – 18 highest risk of intakes < RDA Few males met EAR for Vit E and Mg

Healthy Eating Index - USDA

36%

17%

12%

60%

76% 80%

4% 7% 8%

0%

20%

40%

60%

80%

100%

Good Improve Poor

Children 2 -3

Children 4 - 8

Children 7-9

Nutrition in children with Autism:Raiten & Massaro 1986

40 ASD34 TD

7 d diet; no difference between groups

Ho et al. 1997 54 ASD 3 d diet; 33% of un-supplemented low in Ca; 7.4% met Canadian RNI

Cornish 1998 17 ASD 3 d diet & FFQ; low RNI for 53% in one or more of Fe, niacin, riboflavin, B6, Ca, Zn, Vit D, & Vit C

Lindsay et al. 2006 20 ASD FFQ; Mean intake exceed DRI, but individual deficiencies in Ca, B5, Vit D, Vit K

Lockner et al. 2008 20 ASD20 TD

3 d diet; similar nutrient intakes

Herndon et al. 2008 46 ASD31 TD(14 GFCF)

3 d diet; ASD higher vitamin B6 & E, lower calcium, (when exclude GFCF, only B6 diff).

Dosman et al. 2007 43 ASD Fe Insufficiency: 2-5 yr, 69%; 6-10 yr, 35 %

Johnson et al. 2008 19 ASD15 TD

24 hr recall & FFQ; ASD lower percent met vitamin K; greater percent with Mg adequacy

Nutritional Consequences in ASDCase Reports Scurvy (2), Rickets (3), Vitamin A Deficiency (2),

Kwashiorkor (1)

Latif et al. 2002 52 Aut44 AS

11.5% Aut were anemic; 23 Aut had serum ferritin, 50% showed iron deficiency; lower rates of deficiency & anemia in AS vs Aut

Arnold et al. 2003

36 ASD(10 GFCF)24 DD

Decreased essential amino acids, GFCF lower in TRP

Dosman et al. 2006

96 ASD Fe Deficiency: 1-2 yr, 8.3%; 3-5 yr, 14.3%; 6-10 yr,20% (CDC: 7%, 5%, 4% respectively)

Hediger et al. 2008

75 ASD males

Decreased bone cortical thickness; effect greater on casein free diet

1963-67 1971-74 1976-80 1988-1994 2003-06 1966-70 1999-2002

Percent

2010 Target: 5%

Decrease desired

*Data for 1966-70 are for adolescents 12-17 years of age.Note: Overweight is defined as BMI ≥ gender- and age-specific 95th percentile from the 2000 CDC Growth Charts for the United States. Source: National Health Examination Surveys II (ages 6-11) and III (ages 12-17), National Health and Nutrition Examination Surveys I, II, III and National Health and Nutrition Examination Survey, NCHS, CDC.

Obj. 19-3a, b

1963-65 1971-74 1976-80 1988-1994 2003-06 1966-70* 1999-2002

Child and Adolescent Overweight

Male 12-19Male 6-11Female 12-19Female 6-11

40

30

20

10

0

Body Mass Index (BMI)Mouridsen et al. 2002 117 ASD Lower BMI distribution of male, but not female;

32% males below 10th percentile

Whiteley 2004 50 ASD 58% above >75th Percentile, 42% overweight, 10% exceeded cutoff for obesity

Curtin et al. 2005 42 ASD ASD: 35.7% at risk overweight, 19% overweight Similar prevalence of overweight

Hediger et al. 2007 75 ASD males

ASD males taller, heavier, higher BMI than average; 18.7% in 85th-95th percentile; 26.7% in >95th percentile

Mouridsen et al. 2008 198 ASD Lower BMI distribution of male, but not female; ~15% of males had BMI below 5th percentile

National Children’s Health Study

483 ASD No difference in BMI for ASD

STAART, Rochester Mean BMI 62nd percentile; not overweight

Dietary Treatments for Symptoms of Autism:

• Complementary therapies popular

- Levy et al (2003) – 30% of children with ASD on dietary interventions by time of diagnosis

• Interactive Autism Network (IAN) survey

- 54% respondents using supplements

- 30% using dietary intervention

Why a Gluten free and Casein free diet as an intervention for Autism?

• Clinical observations of behavioral improvement in single cases using elimination diets (1970s)

• Hypothesis (Shattock; Reichelt) that opiate-like peptides (proteins) in foods containing casein or gluten act like false neuropeptides and cause or increase symptoms of autism.

• Cass et al (2008) did not confirm presence of urinary peptides

Opioid Related

Gastro-

Intestinal

Peptide Related

Immune Dysregulation/ Autoimmune related

From Christison & Ivany, 2006

Absorption of opioid peptides across a leaky gut

Decreased peptidase activity leading to peptide leakage

Gluten or casein leads to mucosal inflammation

Antibodies to dietary peptides react with CNS antigens

CaseinFoods to Avoid

• Dairy (Milk, yogurt, butter, cheese, cream, cream cheese)– casein, caseinate, lactose, whey

Foods to Check (may contain casein)• Baked goods (bread, pastries, pies)• Non-dairy creamer (will say “milk” in ingredients)• Whipped Topping• Soy Cheese• Candy• Sauce (tomato, pesto)• Salad dressing• Cereals

Sounds like Dairy/Milk, but does not contain milk• Calcium lactate, calcium/sodium stearoyl lactylate, cocoa butter,

cream of tartar, lactic acid, sodium lactate

Casein = Lactose

GlutenFoods to Avoid

• Wheat – wheat starch, wheat bran, wheat germ, cracked

wheat, hydrolyzed wheat protein – einkorn, emmer, spelt, kamut, faro– durum, graham, semolina

• Barley• Rye• Triticale (cross between wheat & rye)• Malt, malt flavoring, malt vinegar (generally made from

barley, verify the source)

Gluten

• Bouillon cubes

• Brown rice syrup

• Candy

• Chips/flavored potato chips/seasoned tortilla chips

• Cold cuts, hot dogs, salami, sausage

• Communion wafers

• French fries

• Gravy

• Vegetables in sauce

• Breading & coating mixes

• Imitation seafood/ fish• Matzo• Rice mixes• Sauces• Self-basting turkey• Soups• Soy sauce• Energy bars• Imitation bacon• Marinades• Herbal & nutritional supplements• Drugs & OTC medication• Play-Doh ©

Foods to Check (may contain gluten)

OatsNeed to be certified gluten-free

• Oats do not contain gluten, but may be contaminated with wheat during processing

• Celiac.org no longer strictly limits oats

The Challenge of Introducing New Foods:

•Complexities of gluten free baking

•Taste, texture and acceptability issues

Nutritional Characteristics of the GFCF diet

• Elimination of milk protein (casein)• Elimination of Wheat, Barley, and Rye products

(contain gluten)

• Oats inherently do not contain gluten, but they may be contaminated during processing

• Diet inherently deficient in calcium and vitamin D

GFCF StudiesThere have been 8 clinical trials, but only 2 were controlled studies

Author Design N Measure Outcome

Knivsberg

2002

Single blind,

Peptide pattern

20 ITPA, DIPAB

Over 1 yr

Significant effect in: overall autistic traits, social interaction, and ability to communicate & interact

Elder

2006

Double blind,

placebo controlled, crossover

15 CARS, EOC No change

Baseline

Establishment of the GFCF diet (two weeks)

4 weeks on GFCF diet

12 weeks of double blind placebo controlled challenge snacks (gluten, casein, gluten and casein, placebo)

Follow up at 30 weeks

STAART Diet Study Protocol

Cochrane Library 2008

• Millward et al, Gluten and casein-free diets for autistic spectrum disorder.

– “Current evidence for efficacy of these diets is poor”.

GFCF Nutritional Consequences

Hediger et al. 2007 75 ASD males

Effect of decreased bone cortical thickness in ASD males greater on casein-free diet

Herndon et al. 2008 46 ASD31 TD(14 GFCF)

More Vit E & less Ca than control

Cornish 2002 37 ASD(8 GFCF)

No differences in nutrient intake on/off diet

What’s Listed on a Food LabelLabels must clearly identify the source of all ingredients that are (or

are derived) from the 8 most common food allergens.• Milk• Eggs• Fish (bass, flounder, cod)• Crustacean Shellfish (crab, lobster, shrimp)• Tree nuts (almonds, walnuts, pecans)• Peanuts• Wheat• Soy

Ingredient labels must use the common name “MILK” to identify dairy-containing foods

Wheat-Free does not mean Gluten-Free

Food Allergen Labeling & Consumer Protection Act (FALCPA)

OPTION 1Ingredients: Enriched flour (wheat flour, malted barley, niacin, reduced iron, thiamin mononitrate, riboflavin, folic acid), sugar, partially hydrogenated soybean oil, and/or cottonseed oil, high fructose corn syrup, whey (milk), eggs, vanilla, natural and artificial flavoring, salt, leavening (sodium acid pyrophosphate, monocalcium phosphate), lecithin (soy), mono- and diglycerides (emulsifier)

OPTION 2Contains Wheat, Milk, Eggs and Soy

"These statements are not required if the major food allergen's common name already identifies its food source," For example, the ingredients whole wheat flour, buttermilk, and peanut butter already state that they contain wheat, milk, and peanuts, respectively, so no further explanatory terms are required.

How Daily Values (DV) compare in ChildrenNutrient  DV 2 - 3

years4 - 8 years 9 - 13

years14 - 18 yr

girls14 - 18 yr

boys

Iron (mg) 18 7 10 8 15 11

Calcium (mg)

1,000 500 800 1300 1300 1300

Vitamin A (IU)

5000 1000 1333 2000 2333 3000

Vitamin C (mg)

60 15 25 45 65 75

%DV is based on adults.

Flintstone’s Vitamins

Flintstone’s Vitamin Analysis

1%2%190015002%3%1200100025Sodium (mg)

75%100%400300150%200%200150300Folate (mcg)

5%8%300200214%250%7615Vitamin E (mg alpha

tocopherol)

20%20%20002000200%200%200200400Vitamin D (IU)

38%63%6504001000%1667%2515250Vitamin C (mg)

NANANDND375%500%1.20.94.5Vitamin-B12 (mcg)

3%4%4030175%210%0.60.51.05Vitamin-B6 (mg)

90%135%1510169%225%8613.5Niacin-B3 (mg)

NANANDND200%240%0.60.51.2Riboflavin-B2 (mg)

NANANDND175%210%0.60.51.05Thiamin-B1(mg)

83%125%30002000188%250%133310002500Vitamin A (IU)

%UL(4-8)

%UL(1-3)

UL (4-8)

UL (1-3)

%RDA(age 4-8)

%RDA(age 1-3)

RDA(age 4-8)

RDA (age 1-3)VitaminNutrient

1%2%190015002%3%1200100025Sodium (mg)

75%100%400300150%200%200150300Folate (mcg)

5%8%300200214%250%7615Vitamin E (mg alpha

tocopherol)

20%20%20002000200%200%200200400Vitamin D (IU)

38%63%6504001000%1667%2515250Vitamin C (mg)

NANANDND375%500%1.20.94.5Vitamin-B12 (mcg)

3%4%4030175%210%0.60.51.05Vitamin-B6 (mg)

90%135%1510169%225%8613.5Niacin-B3 (mg)

NANANDND200%240%0.60.51.2Riboflavin-B2 (mg)

NANANDND175%210%0.60.51.05Thiamin-B1(mg)

83%125%30002000188%250%133310002500Vitamin A (IU)

%UL(4-8)

%UL(1-3)

UL (4-8)

UL (1-3)

%RDA(age 4-8)

%RDA(age 1-3)

RDA(age 4-8)

RDA (age 1-3)VitaminNutrient

Autism Treatment Network:

Goal to Set Best Practices for Medical Management of children with ASD15 sites across the US and CanadaTargeted areas of interest:

GI symptomsSleepNeurologic/metabolic/genetic evaluations

AIRP - Diet and Nutrition Provide prospective and accurate data to allow for guideline development regarding diet and nutrition for children with ASD

Obtain accurate data regarding What Children with Autism Eat in America, a topic of great interest to parents and clinicians

– Are diets with limited variety providing adequate nutrition?– Do commonly used supplements have side effects?– Are low iron stores associated with sleep problems?– Could diet be related to GI symptoms?

Child

ren

with A

utism

Summary:•You are what you eat: Parents of children with ASD should be counseled by their health care provider regarding nutrition and health in children

• Families whose children take restricted diets or therapeutic supplements may benefit from consultation with a Nutritionist

• Clinical trials will assist in evidence based decision making

•Do ask, do tell: Familes should tell their Health Care Provider about supplements and dietary interventions and Health Providers should ask

•Review the data supporting – and refuting – nutritional interventions: Nutrition does affect behavior and overall health in children with and without ASD

Science is facts; just as houses are made of stone, so is science made of facts; but a pile of stones is not a house, and a collection of facts is not necessarily science. Jules Henri Poincaré (1854-1912) French mathematician.

Shall I refuse my dinner because I do not fully understand the process of digestion?

Oliver Heaviside (1850-1925) English physicist.

Acknowledgements:• Patricia Rodier• Loisa Bennetto• Carol Stamm• Tristram Smith• Danielle Morris• Jennifer Foley• Joy Valvano• Robin Peck• Usa Cain• Kay Valerioti• Jennifer Handzel• Jonathan Mink•Joshua Diehl•Philip Ng

• Jennifer Kwon• Eileen Blakely• Laura Silverman• Emily Kuschner• Betsy Smith• Mariellen Cupini• John McEachen• Doreen Greenspesheh• Denise Rhine• Jack Bennetto• Emily Healy• Meaghan Miller• General Clinical Research Center 5MO1RR00044• STAART (NIMH)U54MH066397•ATN/Autism Speaks

And the children and families of children with autism in upstate NY who helped identify the problems and are

helping to find the answers.

AIRP Acknowledgements:

Autism Speaks/Autism Treatment Network, NCC and Jim Perrin,

Leann Birch, Usa Cain, NDSR, and Traci Clemons