Transcript Evaluation of Nutrient Levels in Children with ASD vs

Evaluation of Nutrient Levels in
Children with ASD vs. Controls –
Preliminary Results
James B. Adams
Arizona State University
www.eas.asu.edu/~autism
Collaborators
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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 Nutrition
The essential major components of human nutrition
are:
• water
• carbohydrates (for fuel)
• vitamins and minerals
• amino acids (from protein)
• essential fatty acids
A 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 controls
Age: 3-9 years
All 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
% diff-avg
Vitamin A
Carotenes
Thiamine
Pantothene
B6
Folic acid
B12
Vit C
Vit E
Vit D3
-3
-12
-7
-4
3
0
16
-4
2
2
%diff - med
-3
0
-10
-6
-12
2
-5
-9
0
-3
% < RR % > RR
13
13
5
0
40
4
12
12
20
24
6
25
25
18
18
18
9
7
11
20
Ref Range (RR) defined as between bottom 15% and top 15%
Only small differences in vitamin levels between autism and controls
(not statistically significant)
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
RBC
PLP
PMP
Plasma PLP
PA
PL
%Diff - avg % Diff-med p=value units
pmol/g Hb
-12
-1
-12 still measuring controls for PMP
-10
(nmol/L plasma)
10
-12
5
-1
-17
-6
-36
-34 0.0003 umol/g creatinine
Urine
PA
RBC
2
Pyridoxal kinase
-12
Oxidase
5
PLP hydrolase pH 7.4
-4
PLP hydrolase pH 10 (nmol PL/min/g hemoglobin)
4
-31
4
-2
(pmol PLP/min/g Hemoglobin)
(nmol PL/min/g hemoglobin)
• Urinary excretion of pyridoxic acid is low in autism
• Oxidase activity low but not significant
Vitamin B6 levels
First Study
Autism (n=35) 56 +/- 13 ng/ml
Controls (n=11) 36 +/- 9 ng/ml ttest = 0.00002
Second Study
Autism (n=47) 62 +/- 41
Controls (n=33) 53 +/- 27
not significant
Combined First and Second Study
Autism (n=82) 72 +/- 32
Controls (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
Controls (n=16) v. Autistics (n=8-17)
70
60
50
40
KM
30
20
10
0
Pyridoxal kinase
Glutamate
transaminase
Controls
Glutamate
decarboxylase
Autistics
Autistics often have weak B6-dependent enzymes, so may need very high B6
Substrate Requirement for Maximal
Activity of P5P-Dependent Enzymes
1000
900
800
700
600
500
400
300
200
100
0
DOPA decarboxylase
Histidine
decarboxylase
Controls
5-HTP decarboxylase
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
micromoles/100ml
120
100
80
60
40
20
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Months of Treatment
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)
56 (B)
(95:33)
(41:15)
Pyrindoxine HCℓ
5 mg/kg/day
Pyridoxine – HCℓ & Pyridoxal –
PO4
1 mg +4.7 mg/kg/day
Outcome of the study
89 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 highdose 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
Magnesium
Magnesium
Magnesium
Zinc
Zinc
Copper
Copper
Copper
whole blood
serum
RBC
whole blood
RBC
whole blood
serum
RBC
%diff - avg % diff-med
% < RR % > RR
2
1
33
13
1
1
2
15
2
-2
13
22
7
9 p=0.05
9
13
2
2
15
11
1
0
7
2
-3
-8
22
7
15
17
2
24
Zinc slightly high in whole blood, but average in RBC
Copper results mixed – slightly high in RBC, slightly low in serum, not
statistically significant
Disagrees with results by Walsh (possibly due to LabCorp Ref Range
and age of controls?)
Minerals (cont.)
Selenium
Manganese
Iron
ferritine
Lithium
Calcium
whole blood
whole blood
serum
serum
serum
urine
%diff - avg % diff-med
% < RR % > RR
3
4
4
22
-6
-6
13
7
-19
-5 p=0.06
14
0
3
-6
20
9
-3
0
0
0
-29
-28 p=0.04
30
2
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)
Toxic Elements in Hair
Al
Sb
As
Bi
Cd
Pb
Hg
U
Ni
Ag
Sn
Ti
%Diff-avg %Diff - med
P-value
-38
-37
0.002
-7
-23
-3
-11
-15
-55
-11
-27
-25
-34
-15
-24
-11
0
-26
-13
0.06
-9
-23
-39
-48
0.003
-15
-12
• Most toxic elements are lower in autism, suggesting an
overall problem with excretion; aluminum, tin, and
possibly nickel are statistically significant
Essential Minerals in Hair
Ca
Mg
Na
K
Cu
Zinc
Mn
Cr
V
Mo
B
I
Li
%Diff-avg %Diff - med
14
67
1
55
44
3
-17
-19
22
4
5
8
-47
-32
-4
4
23
0
-17
-15
-19
-36
4
3
-29
-38
0.005
0.06
0.04
Manganese, molybdenum, and lithium are low in hair.
Manganese slightly low in blood, partially consistent with hair.
Low lithium is consistent with previous study.
Essential Minerals in Hair (cont.)
P
Se
Sr
S
Ba
Co
Fe
Ge
Ru
Zi
%Diff-avg %Diff - med
p-value
1
-2
-8
1
0.05
-11
67
2
3
0.07
-4
12
-30
-25
0.07
-20
-13
0.02
3
-1
-18
-39
-17
-7
Low iron and possibly low cobalt. (iron not reliable in hair)
Slightly low selenium.
Possibly slightly high sulfur.
Lithium – previous ASU study
The only abnormality in mothers of children with
ASD was low levels of lithium:
all ages: -40%, p=0.05
mothers of children ages 3-8: -56%, p=0.005 (highly
significant!)
Similarly, children with ASD had lower levels of
lithium
all ages: -15%, not significant
ages 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 - continued
Several 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 Minerals
Low 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
Placebo:
0.9-1.4
Suppl.
1.0-2.0
typical child (age 3-8)
average
1.03
1.33
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 Results
Based 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 Results
Category
Sociability
Expr. Language
Rec. Language
Eye Contact
General Behavior
Sleep
Gastrointest.
Placebo
5.1
5.6
4.9
4.9
4.3
3.9
3.9
Supplement
5.3
5.9
5.8
5.5
5.1
5.4
5.4
Difference
+0.1
+0.3
+0.9
+0.6
+0.8
+1.5
+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 IU
Vitamin B1
7.5 mg
Vitamin B2
7.5 mg
Vitamin B3
25 mg
(10 mg niacin, 15 mg
niacinamide)
Vitamin B5
20 mg
Vitamin B6
80 mg
Vitamin B12
200 mcg
Folic Acid
50 mcg
Folinic Acid
100 mcg
Biotin
100 mcg
Choline
70 mg
Inositol
30 mg
PABA
5 mg
Vitamin C
300 mg
Vitamin E
60 mg
Mixed 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
% Diff-avg
Threonine
Valine
Methionine
Isoleucine
Leucine
Phenylalanine
Lysine
Tryptophan
Histidine
% Diff-med
12
-2
3
3
2
0
37
7
17
p-value
3
3
-21
-4
13
2
28 p=0.07
8
15
• Lysine high and possibly significant;
• Methionine slightly low but not significant;
• Histidine slightly high but not significant
Note: high level in urine may mean low level in body
Conditionally Essential Amino Acids in Urine
% Diff - avg
Arginine
Asparic acid
Serine
Glutamic acid
Glutamine
Glycine
Alanine
Asparagine
Cystine
Tyrosine
Proline
% Diff - med
-3
-1
11
1
-7
31
3
3
21
5
16
P-value
-9
-2
10
21
-9
17 p=0.04
20
1
19 p=0.03
9
-18
High glycine and high cystine in urine suggests low level in body;
Worrisome that cystine excretion is high
Metabolic Amino Acids in Urine
%diff - avg %diff - med
P-value
Phosphoserine
2
-2
Taurine
26
40
Phosphoethanolamine
-11
-14
Hydroxyproline
-17
-8
Alpha aminoadipic acid
-4
11
Beta aminoisobutyric acid
46
76 p=0.1
Hydroxylysine
-3
5
Ethanolamine
2
1
Ornithine
10
6
3-Methylhistidine
8
2
Homocysteine
1
-3
Creatinine
-1
-8
Taurine and beta aminoisobutyric high but not statistically significant;
high taurine probably suggests wasting, and hence a need for taurine
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 Acids
Essential 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.
Common Symptoms of Essential Fatty Acid Deficiency
ω3
ω6
Dry Skin
Excessive Thirst & Sweating
Impairment of Vision
Frequent Urination
Sticky Platelet
Dandruff
Tingling in Arm & Leg
Learning Disability
Motor In-coordination
Kidney Degeneration
Drying up Glands
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
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 Controlled
Phased in gradually over 2 weeks, continued for 6 weeks
Ages 3-6: 2 gel caps per day
Ages 7-12: 3 gel caps per day
Ages 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
ProDHA
66.7
ProOmega 55.9
Placebo
64.8
End
58.1
52.8
57.7
Difference
-8.6
-3.2
-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 worse
Placebo: 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
18
16
14
12
10
Pre
8
Post
6
4
2
0
ProDHA
ProOmega
Placebo
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
Fatty Acid Level in Autistic Populations (nmole/ml)
7 – 17 years; mean 14 years
Control (n=42) Autistic (n = 67)
ά-Linolenic (18:3n3)
Eicosapentaenoic (20:5n3)
Docosapentaenoic (22:5n3)
Docosahexaenoic (22:6n3)
1.0 – 5.2
1.4 - 4.1
1.8 - 20.2
26 - 69
34 - 106
1.3 - 15.9
21.5 - 47.6
25.2 - 78.7
Linoleic (18:2n6)
Gamma Linolenic (18:3n6)
Dihomo Gamma Linolenic (20:3n6)
Arachidonic (20:4n6)
Docosadienoic (22:2n6)
Docosatetraenoic (22:4n6)
70 – 150
0.9 – 2.8
20 – 39
120 - 235
0.5 – 2.0
8.5 – 106
93 - 220
2.3 – 5.6
31 - 67
167 - 260
0.9 - 3.8
7.2 – 95.4
Erucic (22:1 n12)
Nervonic (24:1 n15)
2.2 – 9.6
32 - 68
1.4 – 10.8
5.5 – 32.0
Arachidic (20:0)
Behenic (22:0)
Hexacosanoic (26:0)
1.7 – 11.9
27.6 – 75.7
1.0 - 8.9
1.0 – 8.3
4.3 – 40.6
3.9 – 21.3
Biochemical Effect of Fatty Acid in Autistic Children
N= 67
(47 boys, 20 girls)
7 – 17 years age
Dose Given 2g ω3(EPA:DHA= 1:1.63) + 0.5 g ω6 + 400 mg Ca++ with VitD
Polyunsaturated/Saturated fat Ratio = 4.8
Duration 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)
Thromboxane A2 (Pro-Coaglulation)
Leukotrienes (Pro-Inflammatory)
HDL
LDL
14 – 21%
8 – 15%
19 – 30%
11 – 20%
No Change
Fatty Acid Level in Autistic Populations (nmole/ml)
7 – 17 years; mean 14 years
Control
Autistic
( n=42)
(n=67)
Autistic + EFA
(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
(20:3n6)
Arachidonic (20:4n6)
31 - 67
120 - 235 167 – 260
26 – 49
132 - 206
Parental Assessment after Treatment with Fatty Acids
Symptoms
Improvement
Abnormal Bowel movement
80% Improvement (63/63)
Cognitive and Motor Skill
Hyper Irritability
25% Improvement (20/63)
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
Sleep Patterns
Significant improvement
(48/63)
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 6week 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
Fatty Acids
%
Worse
% No
Change
%
Better
2%
42%
55%
Number
of Reports
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)
0.46
Chart Title
120
Caution:
ATEC
Correlation is
not necessarily
causation!
100
80
60
40
20
0
0
50
100
Carotenes
150
200
Correlations with ATEC – Speech subscale
Carotenes
-0.40
Serum Ferritine -0.25
Hematocrit
-0.28
Amino Acids (urine)
Valine
Leucine
Phenylalanine
Glutamine
Alanine
Phosphoserine
0.28
0.28
0.30
0.28
0.28
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
Niacin
Serum Ferritin
Hematocrit
GABA
RBC Copper
Phosphoserine
Arsenic (hair)
-0.47
-0.25
-0.31
-0.33
-0.26
0.32
0.25
0.29
Correlations with ATEC Health
Subscale
Carotenes
Serum Molybdenum
Sulfur (hair)
Manganese (hair)
-0.33
-0.26
-0.30
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