Evaluation of Nutrient Levels in Children with ASD vs. Controls

– Preliminary Results

James B. Adams

Arizona State University

www.eas.asu.edu/~autism

Collaborators• Tapan Audhya• Stephen Coburn• Liz Geis• Julie Ingram• Sanford Newmark• Dena Goldberg• Warren Tripp• Marie Adams

Funded by Autism Research Institute, Greater Phoenix Chapter of the ASA, BHARE, Arizona State University

Special thanks to Vitamin Diagnostics, Doctor’s Data, and Great Plains Labs for discounted/free testing

Outline

• Vitamins and Minerals

• Amino Acids

• Essential Fatty Acids

Basics of NutritionThe essential major components of human nutrition

are:• water• carbohydrates (for fuel)• vitamins and minerals• amino acids (from protein)• essential fatty acidsA deficiency of any of these results in disease, or

even death in extreme cases

Examples of Nutritional Deficiencies

• Lack of vitamin C -> scurvy• Lack of iron -> anemia; mental retardation in

children• Lack of calcium or vitamin D -> rickets

Children with autism are not classically deficient, but most are low in some essential vitamins, minerals, amino acids, and fatty acids .

“Children with Starving Brains” by J. McCandless

Why consider vitamin/mineral supplements for people with autism?

1) vitamin/mineral deficiencies common in general population

2) often restricted diets (“picky eaters”) -> limited vitamin/mineral intake

3) poor digestion (25% have chronic diarrhea, 25% chronic constipation);

Endoscopies by Wakefield, Buie, Krigsman show damage to gut -> limited absorption of nutrients?

4) Rosseneu, Shaw research: overgrowth of harmful bacteria in GI tract:

fewer “good” bacteria which actually produce several vitamins

5) 18 studies demonstrated benefits of vitamin B6/Mg

6) 1 study showed vitamin C was beneficial in autism

7) Prof. Megson: cod liver oil (with high levels of vitamin A, D, and essential fatty acids) helped with gaze aversion, behavior

8) Dr. Rimland’s set of parent-reported case studies on benefits of vitamins/minerals

Goals: 1) Evaluate nutritional status of unsupplemented children with ASD vs. unsupplemented typical children, age and gender matched.2) Check for correlations of symptoms of autism with nutritional levels

Participants:Enrolled: 48 ASD, 35 controlsAge: 3-9 yearsAll children from Arizona.No use of vitamin/mineral supplements in 2 months prior to sample collection.

Tests• Vitamins, minerals, essential fatty acids, amino

acids (blood, urine) – Vitamin Diagnostics• Vitamin B6 variants and enzymes – Stephen Coburn

(Purdue Un.)• Toxic elements and essential minerals in hair –

Doctor’s Data• Urinary Organic Acid Testing – Great Plains Lab• Dietary Assessment of Nutrient Intake (1 week food

diary)All samples sent blinded to labs.

Vitamins

Ref Range (RR) defined as between bottom 15% and top 15%

Only small differences in vitamin levels between autism and controls (not statistically significant)

% diff-avg %diff - med % < RR % > RRVitamin A -3 -3 13 13Carotenes -12 0 5 0Thiamine -7 -10 40 4Pantothene -4 -6 12 12B6 3 -12 20 24Folic acid 0 2 6 25B12 16 -5 25 18Vit C -4 -9 18 18Vit E 2 0 9 7Vit D3 2 -3 11 20

ARI Survey of Parent Ratings of Treatment Efficacy

  % Worse

% No Change

% Better

Number of Reports

Vitamin A 2% 58% 41% 618

Folic Acid 3% 54% 42% 1437

Vitamin B3 4% 55% 41% 659

Vitamin B12 4% 33% 63% 192

Vitamin C 2% 57% 41% 1706

Why do children with autism benefit from vitamins if levels not very different from typical children?

1) Typical children do not eat 5 servings of fresh fruit and vegetables each day, so the level of vitamins in typical children is not optimal.

2) Several studies show children with autism are under increased oxidative stress, suggesting a need for increased levels of antioxidants.

Vitamin B6 and Magnesium• Over 20 studies, including 11 double-blind,

placebo-controlled studies, found that high dose vitamin B6 (8 mg/pound bodyweight) with Magnesium (3-4 mg/pound bodyweight) resulted in wide range of behavioral improvements

• Only 2 negative studies: one with very few subjects, and one with half dose

• Overall, very safe, and helps 50% of children and adults.

Vit B6 – Coburn data

• Urinary excretion of pyridoxic acid is low in autism• Oxidase activity low but not significant

%Diff - avg % Diff-med p=value unitsRBC PLP -1 -12 pmol/g Hb

PMP -10 -12 still measuring controls for PMP

Plasma PLP 10 -1 (nmol/L plasma)PA -12 -17PL 5 -6

Urine PA -36 -34 0.0003 umol/g creatinine

RBC Pyridoxal kinase 2 4 (pmol PLP/min/g Hemoglobin)Oxidase -12 -31PLP hydrolase pH 7.4 5 4 (nmol PL/min/g hemoglobin)PLP hydrolase pH 10 (nmol PL/min/g hemoglobin)-4 -2

Vitamin B6 levelsFirst StudyAutism (n=35) 56 +/- 13 ng/mlControls (n=11) 36 +/- 9 ng/ml ttest = 0.00002

Second StudyAutism (n=47) 62 +/- 41Controls (n=33) 53 +/- 27 not significant

Combined First and Second StudyAutism (n=82) 72 +/- 32Controls (n=44) 52 +/- 25 p= 0.05

Conclusion: Some children with autism have unusually high levels of B6, and a few have unusually low levels of B6 -

Explanation: study by Dr. Tapan Audhya found that 4 enzymes for conversion of B6 are defective in autism, such that conversion rate is much lower than normal

Substrate Requirement for Maximal Activity of P5P-Dependent Enzymes

0

10

20

30

40

50

60

70

KM

Pyridoxal kinase Glutamatetransaminase

Glutamatedecarboxylase

Controls (n=16) v. Autistics (n=8-17)

Controls Autistics

Autistics often have weak B6-dependent enzymes, so may need very high B6

Substrate Requirement for Maximal Activity of P5P-Dependent Enzymes

0100200300400500600700800900

1000

DOPA decarboxylase Histidinedecarboxylase

5-HTP decarboxylase

Controls Autistics

Some autistics need high-dose B6 to make important neurotransmitters

Autism Treatment Study: Effect of B6 (10mg/kg/day) + Zn (25mg) +

Mg (400mg) on Kryptopyrrole Levels

0

20

40

60

80

100

120

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Months of Treatment

mic

rom

ole

s/10

0ml

Conclusion: High-dose B6 very helpful for treating pyroluria

High-dose B6 + multivitamin treatment study (Audhya)

184 Volunteers

1. Unsuccessful with Diet Intervention

2. Given Daily one centrum advanced formula Multivitamin Tablet with food, 25 mg Zn++ (as Gluconate and Citrate) and 400 mg Mg ++ (as Gluconate & Oxide)

128 (A)

(95:33)

Pyrindoxine -HCℓ

5 mg/kg/day

56 (B)

(41:15)

Pyridoxine – HCℓ & Pyridoxal – PO4 1 mg +4.7 mg/kg/day

Outcome of the study89 Volunteers Substantial Improvement;

Almost normal

86 Volunteers No perceptible change;

Behaviorally or physically

9 Volunteers No improvement;

and additional adverse reaction

ARI Survey of Parent Ratings of Treatment Efficacy

  % Worse

% No Change

% Better

Number of Reports

Vitamin B6 alone

8% 63% 30% 620

Magnesium 6% 65% 29% 301

Vitamin B6 with

Magnesium 4% 49% 47% 5780

P5P (Vit. B6) 13% 37% 51% 213

Summary re. Vitamin B6

Some children and adults with autism benefit from high-dose B6, to make neurotransmitters, glutathione, and many other important substances

Simple measurement of kryptopyroles in urine determines if high-dose vitamin B6 (or zinc) is needed (caution – destroyed by light, so collect in dark).

Doses up to 10-15 mg/kg may be needed (1000 mg max); takes about 6 months to lower kryptopyroles in urine

Always give at least half as much magnesium (400 mg max).

Vitamin B12• Methyl cobalamin (methyl form of vitamin B12) is

most active form of vitamin B12• Vitamin B12 is very hard for body to absorb orally• Injectable form of methyl-B12 may help up to 70% of

autistics per informal reports by Dr. Jim Neubrander, at doses of 75 mcg/kg bodyweight, 2x/week, for 6+ weeks

• Safe, but needs research to verify effectiveness• Research by Prof. Richard Deth shows it is needed to

produce glutathione, and to help Dopamine 4 receptor function (important for attention)

Low Cysteine and Glutathione

• Studies by Jill James and Tapan Audhya find low cysteine and extremely low glutathione in children with autism; glutathione is important antioxidant and for detoxification

• Treatment study by Jill James finds that 800 mcg of folinic acid and 1000 mcg of TMG over 8 weeks improve cysteine and glutathione levels somewhat

• Addition of 75 mcg/kg of methyl B12 injections helps more

• Informal reports of improvement in behavior

Minerals

Zinc slightly high in whole blood, but average in RBCCopper results mixed – slightly high in RBC, slightly low in serum, not statistically significantDisagrees with results by Walsh (possibly due to LabCorp Ref Range and age of controls?)

%diff - avg % diff-med % < RR % > RRMagnesium whole blood 2 1 33 13Magnesium serum 1 1 2 15Magnesium RBC 2 -2 13 22Zinc whole blood 7 9 p=0.05 9 13Zinc RBC 2 2 15 11Copper whole blood 1 0 7 2Copper serum -3 -8 22 7Copper RBC 15 17 2 24

Minerals (cont.)

Iron: slightly slow in serum, but serum ferritine is more relevant and is “normal”

However, many children with exceptionally low serum ferritine (10 with < 10 mcg/l)

Calcium: low in urine, possibly due to low intake (GFCF diet)

%diff - avg % diff-med % < RR % > RRSelenium whole blood 3 4 4 22Manganese whole blood -6 -6 13 7Iron serum -19 -5 p=0.06 14 0ferritine serum 3 -6 20 9Lithium serum -3 0 0 0Calcium urine -29 -28 p=0.04 30 2

Toxic Elements in Hair

• Most toxic elements are lower in autism, suggesting an overall problem with excretion; aluminum, tin, and possibly nickel are statistically significant

%Diff-avg %Diff - med P-valueAl -38 -37 0.002Sb -7 -23As -3 -11Bi -15 -55Cd -11 -27Pb -25 -34Hg -15 -24U -11 0Ni -26 -13 0.06Ag -9 -23Sn -39 -48 0.003Ti -15 -12

Essential Minerals in Hair

Manganese, molybdenum, and lithium are low in hair.

Manganese slightly low in blood, partially consistent with hair.

Low lithium is consistent with previous study.

%Diff-avg %Diff - medCa 14 67Mg 1 55Na 44 3K -17 -19Cu 22 4Zinc 5 8Mn -47 -32 0.005Cr -4 4V 23 0Mo -17 -15 0.06B -19 -36I 4 3Li -29 -38 0.04

Essential Minerals in Hair (cont.)

Low iron and possibly low cobalt. (iron not reliable in hair)Slightly low selenium. Possibly slightly high sulfur.

%Diff-avg %Diff - med p-valueP 1 -2Se -8 1 0.05Sr -11 67S 2 3 0.07Ba -4 12Co -30 -25 0.07Fe -20 -13 0.02Ge 3 -1Ru -18 -39Zi -17 -7

Lithium – previous ASU study

The only abnormality in mothers of children with ASD was low levels of lithium:all ages: -40%, p=0.05mothers of children ages 3-8: -56%, p=0.005 (highly

significant!)

Similarly, children with ASD had lower levels of lithiumall ages: -15%, not significantages 3-6 yr: -30%, p=0.04

Importance of Lithium• Hair is a reliable measure of lithium• Lithium is probably an essential mineral (not well studied)• Study of goats on lithium-deficient diet found:

– decreased activity of monoamino oxidase, which is of particular importance to manic-depression, chronic schizophrenia, and unipolar depression.

– lowered immunological status, and suffered from more chronic infections (may explain why children with autism had more ear infections)

• Lithium concentrations highest during first trimester, and highest in the brain, so a deficiency of it could affect early fetal development, including early brain development

Lithium - continuedSeveral studies have show low lithium correlates with:• schizophrenia• neurosis• suicide• behavior problems• crime (homicide, rape, burglary, theft, drug use, juvenile runaways)

Finally, a four-week placebo-controlled study of 24 former drug users found that 400 mcg/day of lithium resulted in steady increases in mood scores, especially in subcategories reflecting happiness, friendliness, and energy.

Lithium• Not included in most nutritional supplements, or in prenatal

supplements• An estimated RDA is 1000 mcg/day, and people in the US

consume only about 500 mcg/day• Extremely high doses of lithium (1,000,000 mcg/day) are used as

a psychiatric medication, primarily for “calming/mood stabilization”, especially for bipolar disorder; nearly toxic at that dose

• RECOMMENDATION: a dosage of 200-1000 mcg/day should be safe, and may be beneficial to younger children with autism and their mothers

• More research needed

Essential Minerals - Iodine• Iodine: 45% lower in ASD than controls, p=0.005 (highly

significant!)• in 3-6 yr old group, similar value (-47%)

• Caution: no data showing that iodine in hair correlates with level in body (blood is standard measurement)

• iodine is an essential mineral• major role of iodine in body is in thyroid function• a deficiency of iodine causes goiter (enlarged thyroid) and

mental retardation (Cretinism)• worldwide, the leading cause of mental retardation is iodine

deficiency, affecting roughly 20 million children

Iodine - continued

• In early 1900’s, iodine deficiency was up to 30% in some parts of the US

• iodine in salt is believed to be sufficient to make iodine deficiency very rare in the US/western world

• however, iodine levels in blood have declined 50% from 1970’s to 1990’s per NHANES I and III, possibly due to decreased salt intake

• many fast foods (fries, chips) use non-iodinized salt• CAUTION: too much iodine can also decrease thyroid function• RECOMMENDATION: measure iodine in blood, supplement

at modest level if low

ARI Survey of Parent Ratings of Treatment Efficacy

  % Worse

% No Change

% Better

Number of Reports

CalciumE: 2% 62% 36% 1378

Magnesium 6% 65% 29% 301

Zinc 2% 51% 47% 1244

Summary of MineralsLow iron in some children – supplement only if low.

Low calcium in some children (esp. if dairy-free)

Low lithium in children and mothers, which can affect behavior

Low iodine is a leading cause of mental retardation, and should be supplemented

Low toxic metals in hair suggests problem with excretion of toxic metals.

Research Study of Multivitamin/mineral supplement

• 3 month study of Spectrum Support (by Brainchild Nutritionals)

• Double-blind, placebo-controlled

• Dosage is slowly increased to maximum over first 2 months, then held constant

• parent ratings of changes

• small study - 20 children only

Vitamin C results (at end of study)

range averagePlacebo: 0.9-1.4 1.03Suppl. 1.0-2.0 1.33typical child (age 3-8) 1.45

Placebo children are 2 standard deviations below average value

500 mg raised vitamin C to near-normal levels, but more may be better (1000 mg)

Overall ResultsBased on parent evaluations on final day of study

7 point scale

1=much worse

2=worse

3=slightly better

4=same

5=slightly better

6=better

7=much better

Overall ResultsCategory Placebo Supplement DifferenceSociability 5.1 5.3 +0.1Expr. Language 5.6 5.9 +0.3Rec. Language 4.9 5.8 +0.9Eye Contact 4.9 5.5 +0.6General Behavior4.3 5.1 +0.8Sleep 3.9 5.4 +1.5Gastrointest. 3.9 5.4 +1.5

Overall 5.1 5.5 +0.4

Sleep and GI results are statistically significant (p<0.005);other results positive, and worth further investigation

My recommended daily dose per 20 pounds of bodyweight, up to 100 pounds (i.e., for a 60 pound child, multiply by 3)

Take with food, split into 3 doses

Vitamin A 1000 IUVitamin B1 7.5 mgVitamin B2 7.5 mgVitamin B3 25 mg(10 mg niacin, 15 mg

niacinamide)Vitamin B5 20 mgVitamin B6 80 mgVitamin B12 200 mcgFolic Acid 50 mcgFolinic Acid 100 mcgBiotin 100 mcgCholine 70 mg Inositol 30 mgPABA 5 mgVitamin C 300 mgVitamin E 60 mgMixed Carotenes 3000 IU

Chromium 20 mcg

Copper 0 mg (most autistics don’t need)

Iodine 30 mg

Lithium 0.2 mg

Magnesium 120 mg

Manganese 1 mg

Molybdenum 40 mcg

Selenium 25 mcg

Vanadium 13 mcg

Zinc 5-15 mg

Calcium: Dosing independent of bodyweight: 400 mg for ages 2-5, 500-600 mg for older children

Potassium from fruits and vegetables (esp. potatoes, avocados), esp. for low muscle tone

Recommended Vitamin/Mineral Supplements

• Kirkman’s Super Nu Thera – the original high-B6/Mg supplement for autism; contains many vitamins/minerals, but not a complete formulation; www.kirkmanlabs.com

• Kirkman’s Spectrum Complete: broad-spectrum formulation, with moderate B6

• Brainchild’s Spectrum Support: broad-spectrum liquid vitamin/mineral supplement with moderate B6; www.brainchildnutrionals.com

• D-Plex: broad-spectrum vitamin/mineral supplement with some amino acids; www.danplex.com

• Awaken Nutrition: broad-spectrum liquid multivitamin/mineral with high B6; www.awakennutrition.com

Need extra Calcium with most of above products.

Amino Acids

• Protein is composed of long strands of many amino acids

• The body needs to digest protein to small peptides or individual amino acids

• Amino acids can be measured in plasma (fasting) or urine (24-hr best)

• Caution – high level in urine sometimes indicates wasting, resulting in low levels in body

Essential Amino Acids in Urine

• Lysine high and possibly significant;• Methionine slightly low but not significant;• Histidine slightly high but not significantNote: high level in urine may mean low level in body

% Diff-avg % Diff-med p-valueThreonine 12 3Valine -2 3Methionine 3 -21Isoleucine 3 -4Leucine 2 13Phenylalanine 0 2Lysine 37 28 p=0.07Tryptophan 7 8Histidine 17 15

Conditionally Essential Amino Acids in Urine

High glycine and high cystine in urine suggests low level in body;

Worrisome that cystine excretion is high

% Diff - avg % Diff - med P-valueArginine -3 -9Asparic acid -1 -2Serine 11 10Glutamic acid 1 21Glutamine -7 -9Glycine 31 17 p=0.04Alanine 3 20Asparagine 3 1Cystine 21 19 p=0.03Tyrosine 5 9Proline 16 -18

Metabolic Amino Acids in Urine

Taurine and beta aminoisobutyric high but not statistically significant; high taurine probably suggests wasting, and hence a need for taurine

%diff - avg %diff - med P-valuePhosphoserine 2 -2Taurine 26 40Phosphoethanolamine -11 -14Hydroxyproline -17 -8Alpha aminoadipic acid -4 11Beta aminoisobutyric acid 46 76 p=0.1Hydroxylysine -3 5Ethanolamine 2 1Ornithine 10 63-Methylhistidine 8 2Homocysteine 1 -3Creatinine -1 -8

Summary of Amino Acids

• Some children with autism have low levels of amino acids in body

• Recommendation: measure levels, and supplement if low

• Also, consider measuring neurotransmitter levels in platelets, and then supplement with precursors if low (neurotransmitters made from amino acids) – more research needed

Essential Fatty AcidsEssential Fatty Acids are termed “essential” because they are

necessary for human life.The major types of essential fatty acids are Omega-3 and

Omega-6.Ancient human diets contained a roughly 1:1 ratio of Omega-3

to Omega-6 fatty acids.However, since Omega-3 fatty acids spoil much faster than

Omega-6, commercial food processors usually remove them or “hydrogenate” them to increase shelf life.

Today, American diets contain a roughly 1:15 ratio of Omega 3 to Omega-6; in other words, most people in the US are very low in Omega 3 fatty acids.

EFA’s in Autism

A recent study in France found that children with autism had normal levels of Omega-6, but their levels of Omega-3 were 25% below “normal”, and even “normal” is probably far from “optimal”.

A small preliminary study by Gordon Bell (Un. Stirling) of 7 children with ASD also found less EPA and DHA, and sometimes more arachidonic acid, than control subjects.

Sources of Omega-3 Fatty Acids

In human diets, the major source of omega-3 fatty acids is fish. Fish contain two important types of Omega-3 fatty acids, EPA and DHA.

Some fish contain much more omega-3’s than others.

Importance of EPA and DHA

EPA is important in reducing inflammation (such as in the GI tracts of children with autism).

DHA is critical to brain development, and 20% of an infant’s brain is made of DHA.

Both are critical to all cell membranes in the body; they regulate nutrients going into the cell, and waste leaving the cell.

They also affect the release and reuptake of neurotransmitters.

ω3 ω6

Dry Skin Excessive Thirst & Sweating

Impairment of Vision Frequent Urination

Sticky Platelet Dandruff

Tingling in Arm & Leg Kidney Degeneration

Learning Disability Drying up Glands

Motor In-coordination Dry, Dull and Loss of Hair

High Blood Pressure Rough & Dry Skin

Mental Deterioration Susceptibility to Infection

Immune Dysfunction Male Sterility/Miscarriage

Heart/Circulatory Problem

Growth Retardation

Poor Wound Healing

Behavioral Disturbance

Common Symptoms of Essential Fatty Acid Deficiency

Treatment with EFA’s

Supplements of fish oil have recently been shown to be effective in treating a range of psychiatric illnesses, including:

• schizophrenia• depression• bipolar• ADD/ADHD

Several physicians are using them to treat autism, with some good anecdotal results, but there has not yet been a formal study of EFA supplements in people with autism.

Essential Fatty Acid Study – 2 month

Double-Blind, Placebo ControlledPhased in gradually over 2 weeks, continued for 6 weeksAges 3-6: 2 gel caps per dayAges 7-12: 3 gel caps per dayAges 13 and over: 4 gel caps/day

ProOmega: 175 mg EPA, 125 mg DHA, 50 mg other omega 3 per capsule

ProDHA: 250 mg DHA, 100 mg EPA, 50 mg other omega 3 per capsule

Results - Total ATEC Score

Start End Difference

ProDHA 66.7 58.1 -8.6

ProOmega 55.9 52.8 -3.2

Placebo 64.8 57.7 -7.1

ProDHA group improved slightly more than Placebo, primarily due to slightly improved Sociability

ProOmega was slightly worse than placebo

Who improved?

Changes of more than 10 points occurred in:

ProDHA: 8 of 24 improved, 0 worse ProOmega: 3 of 31 improved, 4 worsePlacebo: 3 of 26 improved, 0 worse

In the ProDHA group, the responders consumed only 1.5 servings of seafood/month, vs. 5 servings/month in non-responders. So, people with low seafood consumption are more likely to be low in Omega 3’s, and hence more likely to benefit from supplement

Sociability Subscale of ATEC

0

2

4

6

8

10

12

14

16

18

ProDHA ProOmega Placebo

Pre

Post

EFA Study – 9 months

• Pre/post measurements of EFA levels in children with autism vs. typical children

• Open design (no placebo group)

• Only treating those children with low EFA levels

Control (n=42) Autistic (n = 67) ά-Linolenic (18:3n3) 1.4 - 4.1 1.0 – 5.2

Eicosapentaenoic (20:5n3) 1.8 - 20.2 1.3 - 15.9

Docosapentaenoic (22:5n3) 26 - 69 21.5 - 47.6

Docosahexaenoic (22:6n3) 34 - 106 25.2 - 78.7

Linoleic (18:2n6) 70 – 150 93 - 220

Gamma Linolenic (18:3n6) 0.9 – 2.8 2.3 – 5.6

Dihomo Gamma Linolenic (20:3n6)20 – 39 31 - 67

Arachidonic (20:4n6) 120 - 235 167 - 260

Docosadienoic (22:2n6) 0.5 – 2.0 0.9 - 3.8

Docosatetraenoic (22:4n6) 8.5 – 106 7.2 – 95.4

Erucic (22:1 n12) 2.2 – 9.6 1.7 – 11.9

Nervonic (24:1 n15) 32 - 68 27.6 – 75.7

Arachidic (20:0) 1.4 – 10.8 1.0 – 8.3

Behenic (22:0) 5.5 – 32.0 4.3 – 40.6

Hexacosanoic (26:0) 1.0 - 8.9 3.9 – 21.3

Fatty Acid Level in Autistic Populations (nmole/ml)

7 – 17 years; mean 14 years

Biochemical Effect of Fatty Acid in Autistic Children

N= 67 (47 boys, 20 girls) 7 – 17 years ageDose Given 2g ω3(EPA:DHA= 1:1.63) + 0.5 g ω6 + 400 mg Ca++ with Vit-DPolyunsaturated/Saturated fat Ratio = 4.8Duration of study 9 – 11 months.

Blood Pressure 4.8/2.2 – 6.1/3.0 mm Hg

Heart Rate 6 – 14 Beats/Min

Norepinephrine 18 – 26%

Prostacyclin-I-(PGI2) ( Vasodilation) 14 – 21%

Thromboxane A2 (Pro-Coaglulation) 8 – 15%

Leukotrienes (Pro-Inflammatory) 19 – 30%

HDL 11 – 20% LDL No Change

Control Autistic Autistic + EFA ( n=42) (n=67) (n =26)

Eicosapentaenoic (20:5n3) 1.8 - 20.2 1.3 - 15.9 2.2 – 28.7

Docosapentaenoic (22:5n3) 26 - 69 21.5 - 47.6 28.9 – 86.7

Docosahexaenoic (22:6n3) 34 - 106 25.2 - 78.7 49 - 132

Dihomo Gamma Linolenic 20 – 39 31 - 67 26 – 49

(20:3n6)

Arachidonic (20:4n6) 120 - 235 167 – 260 132 - 206

Fatty Acid Level in Autistic Populations (nmole/ml)

7 – 17 years; mean 14 years

Parental Assessment after Treatment with Fatty Acids

Symptoms Improvement

Abnormal Bowel movement 80% Improvement (63/63)

Cognitive and Motor Skill 25% Improvement (20/63) Hyper Irritability 35% Improvement (22/63)

Limited Eye Contact 40% Improvement (22/63)

Social Withdrawal 33% Improvement (30/63)

Short Attention Span 20% Improvement (10/63)

Repetitive Movements, such as, Rocking 35% Improvement (63/63)

Speech Regression Significant improvement (48/63)

Sleep Patterns 50% Improvement (32/63)

• Biol Psychiatry. 2006 Aug 22; [Epub ahead of print] Omega-3 Fatty Acids Supplementation in Children with Autism: A Double-blind Randomized, Placebo-controlled Pilot Study.Amminger G. Berger GE, Schafer MR, Klier C, Friedrich MH, Feucht M.Department of Child and Adolescent Neuropsychiatry (GPA, MRS, CK, MHF, MF), Medical University of Vienna; Vienna, Austria; and ORYGEN Research Centre (GPA, GEB), University of Melbourne, Melbourne, Australia.

BACKGROUND: There is increasing evidence that fatty acid deficiencies or imbalances may contribute to childhood neurodevelopmental disorders. METHODS: We conducted a randomized, double-blind, placebo-controlled 6-week pilot trial investigating the effects of 1.5 g/d of omega-3 fatty acids (.84 g/d eicosapentaenoic acid, .7 g/d docosahexaenoic acid) supplementation in 13 children (aged 5 to 17 years) with autistic disorders accompanied by severe tantrums, aggression, or self-injurious behavior. The outcome measure was the Aberrant Behavior Checklist (ABC) at 6 weeks. RESULTS: We observed an advantage of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy, each with a large effect size. Repeated-measures ANOVA indicated a trend toward superiority of omega-3 fatty acids over placebo for hyperactivity. No clinically relevant adverse effects were elicited in either group. CONCLUSIONS: The results of this study provide preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism.

Conclusion• Most autistic children have low level of ω3 fatty

acids.• Some autistic children have high level of ω6 fatty

acid.• The ratio of ω3/ω6 can be altered by administration of

ω3 & ω6 fatty acid (4:1 ratio) for 9 -10 months.• Younger children need a ratio higher in DHA (for

growth of neurons), and older children/adults need more EPA

Recommendation

• Measure EFA levels in RBC membranes, especially if GI or sleep problems

• Supplement with 1-2 g/day of omega’s from fish oil and 250-500 mg/day of omega 6’s in borage oil (younger children at lower dose, teens/adults at higher dose)

• Also give calcium to improve absorption (500 mg/day)

ARI Survey of Parent Ratings of Treatment Efficacy

  % Worse

% No Change

% Better

Number of Reports

Fatty Acids 2% 42% 55%626

Summary

• Vitamins – little difference (but probably needed)

• Vit B6 – many studies show that high-dose B6 helps some children and adults

• Minerals – many children need calcium supplement esp. if GFCF

– iron levels similar to “typicals”, but many need iron

– Lithium supplement may help many children

• Amino Acids – measure levels of amino acids and possibly neurotransmitters, and give customized supplement if needed

• Hair: low toxics in hair, suggesting poor detoxification

• Fatty Acids – most children with autism need fish oil (omega 3) with some omega 6 (evening primrose oil or borage oil)

Correlations with ATEC - total

Correlations are marginally significant at .25 or greater (p=0.1)

• Carotenes -0.52

• Calcium -0.26

• GABA (urine) -0.24

• Phosphoserine (urine) 0.30

• Arsenic (hair) 0.29

• Manganese (hair) 0.46Chart Title

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Carotenes

AT

EC

Caution:

Correlation is not necessarily causation!

Correlations with ATEC – Speech subscale

Carotenes -0.40Serum Ferritine -0.25Hematocrit -0.28Amino Acids (urine)

Valine 0.28Leucine 0.28Phenylalanine 0.30Glutamine 0.28Alanine 0.28Phosphoserine 0.28

Manganese (hair) 0.25

Correlations with ATEC – Sociability Subscale

Carotenes -0.43

Niacin -0.28

Hematocrit -0.26

Serum Iron -0.32

GABA -0.26

Phosphoserine 0.25

Manganese (hair) 0.39

Correlations with ATEC – Sensory/Cognition Subscale

Carotenes -0.47Niacin -0.25Serum Ferritin -0.31Hematocrit -0.33GABA -0.26RBC Copper 0.32Phosphoserine 0.25Arsenic (hair) 0.29

Correlations with ATEC Health Subscale

Carotenes -0.33

Serum Molybdenum -0.26

Sulfur (hair) -0.30

Manganese (hair) 0.44

Conclusion of Statistical Analysis

Many measurements correlate with severity of autism, and with subscales of severity – Caution: need to replicate with larger study

Conclusion

Children with autism are “Children with Starving Brains and Starving Bodies”

• Many need essential vitamins and minerals• Some need some amino acids• Many need essential fatty acids

Balanced diets rich in vegetables, fruits, and protein are needed

Supplements also needed in most cases, and have proven benefit