Possible Connection of Heavy
Metal Toxicity and Autism
Prof. James B. Adams, Ph.D.
Chemical and Materials Engineering
Arizona State University
Charles E. Holloway - ASU
Michael Margolis, D.D.S.
Frank George, D.O.
David Quig, Doctor’s Data
Funded by Arizona State University, Greater Phoenix Chapter
of ASA, and Pima County Chapter of ASA
www.eas.asu.edu/~autism
Mercury Exposure: Major Sources
• Seafood: larger fish have most mercury, due to eating
smaller fish
• Vaccines: many childhood vaccines used to contain 12.525 ug of thimerosal, so that a fully-vaccinated child could
receive up to 237.5 ug of thimerosal injected into them
• Dental amalgams: usually emit 1-10 ug/day; amount of
mercury in brain strongly correlated with number of dental
fillings; could release much more when first placed or
removed
Mercury Toxicity
According to the ATSDR Toxicity Profile on mercury:
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“Mercury is considered to be a developmental toxicant. … The symptoms
observed in offspring of exposed mothers are primarily neurological in origin
and have ranged from delays in motor and verbal development to severe brain
damage.”
“The infant may be born apparently normal, but later show effects that may
range from the infant being slower to reach developmental milestones, such as
the age of first walking and talking, to more severe effects including brain
damage with mental retardation, incoordination, and inability to move.”
“Other severe effects observed in children whose mothers were exposed to
very toxic levels of mercury during pregnancy include eventual blindness,
involuntary muscle contractions and seizures, muscle weakness, and inability
to speak.”
“It is important to remember, however, that the severity of these effects
depends upon the level of mercury exposure and the time of dose.”
Bernard et. al. “Autism: A Novel Type of Mercury Poisoning”
Medical Hypothesis 56(4) 462-471 (2001)
They discuss the many similarities between autism and mercury toxicity, including:
Psychiatric Disturbances: social withdrawal; repetitive behaviors; anxiety; irritability; poor
eye contact
Speech/Language Deficits: loss of speech or delayed speech; speech comprehension deficits
Sensory Abnormalities: oral, touch, light and sound sensitivities
Motor Disorders: flapping motions; poor coordination; abnormal gait
Cognitive Impairments: low intelligence; poor memory; difficulty with abstract ideas
Unusual Behaviors: self-injurious; sleep difficulties; ADHD
Physical Disturbances: gastrointestinal disorders
Biochemistry: reduced glutathione; decreased detoxification ability of liver; disrupted purine
metabolism;
Immune System: increased likelihood of auto-immune response, allergies, and asthma
CNS Structure: mercury accumulates in amygdala, hippocampus, basal ganglia, and cerebral
cortex, which are damaged in autism; mercury also damages Purkinje and granule cells (seen
in autism); disruption of neuronal organization
Neurochemistry: decreased serotonin synthesis; elevated norepinephrine and epinephrine;
demyelination
Neurophysiology: abnormal EEGs; abnormal vestibular nystagmus response
Gender bias: higher sensitivity/occurrence in males vs. females
Present Study
Participants
• 53 children with ASD ages 3-15 years, chosen from
Phoenix ASA mailing list
• 48 typical children chosen from their friends/neighbors
(unrelated), same age and sex
Methodology
• heavy metal exposure questionnaire
• hair analysis
• dental exam
Results of Heavy Metal Questionnaire
Caveat: mostly based on mother’s memory
Seafood: 58% of ASD mothers consumed more than 2
servings/month during pregnancy/breastfeeding, compared
to 33% of controls;
yields a 2.7x relative risk of ASD (p<0.02);
presumably mercury in the seafood is the major problem
Results of Heavy Metal Questionnaire (cont.)
Ear Infections: during first three years of life:
ASD: 11x
controls: 4x
median: ASD 10x
controls: 2.5x
p=0.00006
Symptom or cause?
1) could be an indication of weakened immune system
2) In a study of rats given high doses of oral antibiotics
(Rowland, Archives of Environmental Health 1984: 39(6); 401-408),
half-life for excretion of mercury increased from 10
days to >100 days; if also on milk diet, >300 days
(possibly due to yeast/bacterial overgrowth, which can last
for years in children with autism)
Preliminary Results of Heavy Metal Questionnaire (cont.)
• Chronic GI Severity:
– 62% of ASD had moderate or severe GI problems, vs 2% of the controls.
– p<0.0000000000001
consistent with a major gut dysbiosis
• Sleep:
– 60% of ASD had moderate or severe sleep problems, vs 2% of the controls
– p<0.00000000001
• GI and Sleep partially correlated: correlation coefficient =0.31
(0=no correlation, 1=perfect correlation)
Low Muscle Tone:
30% had moderate to severe loss of muscle tone, vs. 2%
of the controls; p=0.000000002
Excessive Drooling/Salivation:
6% severe, 10% moderate, 18% mild vs 4% of the
controls with mild problems; p=0.0003
Low Muscle Tone and Drooling/Salivation correlated:
correlation coefficient=0.47
Preliminary Results of Heavy Metal Questionnaire (cont.)
Negative immediate reaction to vaccines:
None. Mild Moderate
Severe
ASD
48% 23% 11%
18%
Controls
68% 26% 4%
2%
p=0.001 - highly significant;
Since mercury has a latency period of several months, this
is probably due to other components of the vaccine.
ASD Reports of Adverse Vaccine Reactions - Severe
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MMR, DTaP, varicella (12 mo)
respiratory arrest led to hospitalization for 5
days, and then autistic symptoms began
DTaP (18 mo) high fever the next day, which lasted for 10 days; hospitalized on
day 6 for 3 days; very lethargic; major regression started 4 months later
MMR (15 mo) high fever, very listless/passive for 5 days with no eating or
drinking, then began regression into autistic behavior
DTaP, IPV, MMR, HIB, Varicella (14 mo) began wheezing within a few days,
developed asthma within 2 weeks
Petusssis (8 mo) severe diarrhea for 3 months, continued to some extent for 27
months
DTaP (2 mo): 105 fever for 1 week
– MMR (12 mo): high fever; didn’t eat for 3 months
DTaP (6 mo): screamed loudly for six hours, and then began long-term regression
resulting in autism
MMR (13 mo) high fever, very sick for 1 week, then ear infection and little sleep;
slow development before, and slower afterwards – possible regression
MMR - within 1 week started seizures (none prior)
HepB (21 mo) fever; cough; after several weeks developed ITP (severe blood
disorder) and bruised head to toe for 9 months
ASD Reports of Adverse Reactions to Vaccinations - Moderate
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HepB: high fever for 2 days
DTaP: greatly swollen thigh for 1 day
DTP/MMT: very high fever, screaming, hives for 2 days
Most vaccinations caused high fever for 1-2 days
Controls: Reports of Adverse Vaccine Reactions
Moderate and Severe
•Varicella (12 mo): lethargic for 2 weeks, rested in bed
•MMR: 104 fever for 2 days; several seizures lasting 1-2 minutes for
2 days; then okay
•MMR/DTP/Polio: 103 fever for 3 days; rash; lethargic
Dental Amalgams
• Number of dental amalgams in mothers:
– ASD: 10.0
controls: 8.3
not statistically significant
• Fillings placed during pregnancy:
– ASD: 6
controls: 1
p=0.09 (trend)
• Our recent study found that a new dental amalgam releases
approximately 450 mcg/day (about 500x what an old
amalgam emits), so new amalgams should be avoided in
women who are planning to conceive, pregnant, or
nursing
• Future epidemiological studies should focus on placement
of amalgams during pregnancy/nursing, not the total
number of amalgams
HAIR MERCURY OF
AUTISTIC VS. CONTROL
20
GROUPS
18
Hair Hg level
(ppm)
Female
Male
16
14
12
10
8
6
4
2
0
Non-autistic
Mean=3.79
n=34
Autistic
Mean=0.47
n=94
HAIR MERCURY BY
SEVERITY OF AUTISM
1.4
Hair Hg level
(ppm)
Female
1.2
Male
1
0.8
0.6
0.4
0.2
0
Mild
Mean=0.71
n=27
Moderate
Mean=0.46
n=43
Severe
Mean=0.21
n=24
DMSA results
Bradstreet et al. used a 3-day, 9 dose, 10 mg/kg-dose DMSA
treatment in roughly 200 children with autism and 19
controls. He found that children with ASD excreted 5x as
much mercury as the controls.
Together, all data suggests ASD children have higher
exposure to mercury, and inhibited ability to excrete
mercury
Our study of a single dose of DMSA, 10 mg/kg, in 17
children with ASD vs. 15 controls, found no significant
difference between the groups. This suggests that DMSA
challenges should involve multiple doses.
Limitation of DMSA, DMPS
Recent study by Dr. Aposhian of chelation of rats found:
• DMSA and DMPS both effective in totally removing
mercury from kidney
• DMSA, DMPS have ZERO effect on removing mercury
from brain (cannot cross blood-brain barrier)
• Vitamin C, glutathione, and alpha lipoic acid have NO
EFFECT on mercury levels in kidney or brain
• Vitamin C, glutathione, and alpha lipoic acid have NO
EFFECT on mercury in brain when used with DMSA or
DMPS
• Currently, we do NOT know how to chelate mercury from
the brain
Sulfate
• Waring has reported that children with autism:
– Excrete 2x normal amount of sulfate in urine
– Have 1/5 normal amount of sulfate in blood
• Lack of sulfate would decrease ability to excrete heavy
metals
• Treatment Note: in one child with ASD, we measured very
low levels of plasma sulfate (1/10 normal), and high
urinary sulfate; epsom salt baths had no effect, but 1300
mg of MSM raised sulfate to 1/2 normal
Conclusions
Seafood consumption > 2 servings/month yields 2.7x risk
Ear infections > 8x (first 3 years) yields 8x risk ; antibiotics
greatly reduce mercury excretion
Pica is common in ASD (major source of heavy metals)
Vaccine reactions are more common in ASD
Hair data suggests an impairment in mercury excretion,
especially in infants
DMSA results strongly suggest children with autism cannot
excrete heavy metals;
Overall, mercury and other metals appear to be a major risk
factor for ASD
Recommendations for Prevention
• Larger, more controlled study is needed to
confirm results
• However, if the results are correct, then many
cases of autism might be prevented by:
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removal of thimerosal from vaccines
limiting maternal seafood consumption
reduced use of oral antibiotics
no mercury fillings placed during pregnancy
Autism- Baby Tooth Study
James B. Adams, Arizona State Un.
Marvin Legator, Un. Texas- Galveston
Jane Romdalvik
Funded by Autism Research Institute
Goal: Measure amount of mercury, lead, and zinc in
baby teeth in children with autism vs. controls
Rationale: crown of tooth forms during pregnancy,
but continues to grow until age 4 years; thus,
provides a measure of cumulative exposure during
early childhood
Criteria:
Arizona Residents
Born 1988-1999
full vaccination records
Initial Results
(10 autism, 8 controls)
• Lead: almost identical between two groups
– Autism:
– Controls:
0.36 +/- 0.13 mcg/g
0.29 +/- 0.14
• Zinc: almost identical between two groups
– Autism:
– Controls:
94 +/- 10
91 +/- 9
• Mercury: much higher in autism
– Autism:
0.18 +/- 0.11
– Controls:
0.05 +/- 0.05
– p=0.01 very statistically significant, but more samples
needed
Conclusion
Preliminary results consistent with:
• Holmes baby hair study - limited excretion
• Bradstreet DMSA study - more Hg in body
• our heavy metal questionnaire study: more
exposure to Hg (seafood, dental fillings, pica) and
less excretion due to antibiotics
These results justify detoxification studies (TTFD,
DMSA, other?)
Toxic Metals and Essential
Minerals in the Hair of Children
with Autism and their Mothers
James B. Adams, Ph.D.
Arizona State University
www.eas.asu.edu/~autism
Charles Holloway - ASU
Frank George, D.O.
David Quig, Ph.D., Doctor’s Data
Funding from Arizona State University, Greater Phoenix
Chapter of ASA, Pima County Chapter of ASA
Participants
Participants included:
– ASD: 51 children, 29 mothers
– controls: 40 children, 25 mothers
Children aged 3-15 years (average= 7 yr),
age and gender matched
Recruited from Arizona, primarily greater
Phoenix
Methodology
Hair washed for 2 weeks with Johnson and Johnson
baby shampoo; no other hair care products during
that time
No dyes, bleaches, perms, etc. of hair in 2 months
prior
Used 1 inch of hair closest to nape of neck
Sent to Doctor’s Data (blinded) for testing with ICPMass Spectrometry;
analyzed 39 elements
Results - Toxic Metals
• Aluminum: slightly lower in ASD (-16%, p=0.05),
especially in 3-6 yr old group (-24%, p=0.04)
• Arsenic: pica subgroup had 25% lower level
• Uranium: non-pica group had lower uranium (-27%,
p=0.05)
• Barium: pica group had higher barium (99%, p=0.04)
• Overall, only small differences in toxic metals, and not
very statistically significant
Mercury
• Children with ASD had same level as controls
(0.29 vs. 0.29)
- suggests that Holmes’ finding of inhibited excretion of mercury in
infants does not occur in older children with ASD
• Mothers: 57% more mercury in ASD mothers
than control mothers (consistent with higher
seafood consumption), but not statistically
significant (p=0.22)
• no abnormal levels of other heavy metals in ASD
mothers
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
• RECOMMENDATION: supplement at modest level;
measure iodine in blood; test thyroid function
Lithium
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:
– decrease of the activity of many enzymes, including enzymes of
the citrate cycle (ICDH, MCH), glycoloysis (ALD) and N
metabolism
– 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
• 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
• Low lithium in urine correlated with increase in
schizophrenia diagnosis, neurosis, and homicide.
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Another study found highly significant (p=0.005 to 0.01)
inverse associations between water lithium levels and rates
of homicide, suicide, and rape, and significant (p=0.010.05) inverse associations with rates of arrest for burglary
and theft, possession of narcotic drugs, and rates of
juvenile runaways (ie, low lithium associated with
behavior problems).
• 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
Phosphorus
Slightly low levels in children with ASD (11%, p=0.001). Minor difference, but
highly statistically significant.
Pica Sub-Group
Pica subgroup had:
• low levels of chromium (-38%, p=0.002)
– highly significant
• low levels of sodium (-58%, p=0.05)
• elevated levels of copper (+67%, p=0.03) and
strontium (+112%, p=0.03)
• Could chromium supplements help decrease pica?
Low Muscle Tone
Children with low muscle tone had:
• very low potassium (-66%, p=0.01)
– potassium is needed for muscle contractions
• high zinc (+30%, p=0.01)
• high barium (+109%, p=0.03)
Could an increase in potassium intake help with low muscle
tone?
CAUTION:
• Best source of potassium is fruits and vegetables,
especially potatoes and avocado.
• Prescription needed for significant potassium supplement,
due to concerns re. heart function
Conclusions
• Low iodine in children could cause mental
retardation
• Low lithium in mothers and young children
could cause behavior problems, and could
cause increased ear infections in children
• Pica associated with low chromium
• Low muscle tone likely due to low
potassium
Preliminary Recommendation
• Measure iodine in blood or urine; supplement if
low
• Give lithium supplement of 200-1000 mcg/day to
children and mothers (safe)
• For pica, test chromium levels in blood, consider
nutritional supplement
• For low muscle tone, increase consumption of
potassium (fruits, vegetables, esp. potatoes); might
need prescription for potassium if diet change
ineffective
Recruiting for Autism-Baby Hair Study
Goal: Measure level of mercury and other toxic and essential
minerals in baby hair of autism vs. controls
Criteria: born 1988-1999; autism (not PDD/NOS or
Asperger’s); vaccination records with manufacturers lot
number (just call your pediatrician).
Controls needed - please help!
Contact Jane Romdalvik: jromdalvik@aol.com
623 376-0758 (email preferred)
Funded by Autism Research Institute and NIEHS