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Possible Connection of Heavy Metal Toxicity and Autism

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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 – PowerPoint PPT presentation

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Title: Possible Connection of Heavy Metal Toxicity and Autism


1
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, Doctors Data
  • Funded by Arizona State University, Greater
    Phoenix Chapter of ASA, and Pima County Chapter
    of ASA
  • www.eas.asu.edu/autism

2
Mercury Exposure Major Sources
  • Seafood larger fish have most mercury, due to
    eating smaller fish
  • Vaccines many childhood vaccines used to
    contain 12.5-25 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

3
Mercury Toxicity
  • According to the ATSDR Toxicity Profile on
    mercury
  • 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.

4
Bernard et. al. Autism A Novel Type of Mercury
PoisoningMedical 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

5
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

6
Results of Heavy Metal Questionnaire
  • Caveat mostly based on mothers 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 (plt0.02)
  • presumably mercury in the seafood is the major
    problem

7
Results of Heavy Metal Questionnaire (cont.)
  • Ear Infections during first three years of
    life
  • ASD 11x controls 4x
  • median ASD 10x controls 2.5x
  • p0.00006
  • 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
    gt100 days if also on milk diet, gt300 days
  • (possibly due to yeast/bacterial overgrowth,
    which can last for years in children with autism)

8
Preliminary Results of Heavy Metal Questionnaire
(cont.)
  • Chronic GI Severity
  • 62 of ASD had moderate or severe GI problems, vs
    2 of the controls.
  • plt0.0000000000001
  • consistent with a major gut dysbiosis
  • Sleep
  • 60 of ASD had moderate or severe sleep problems,
    vs 2 of the controls
  • plt0.00000000001
  • GI and Sleep partially correlated correlation
    coefficient 0.31 (0no correlation, 1perfect
    correlation)

9
  • Low Muscle Tone
  • 30 had moderate to severe loss of muscle tone,
    vs. 2 of the controls p0.000000002
  • Excessive Drooling/Salivation
  • 6 severe, 10 moderate, 18 mild vs 4 of the
  • controls with mild problems p0.0003
  • Low Muscle Tone and Drooling/Salivation
    correlated correlation coefficient0.47

10
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
  • p0.001 - highly significant
  • Since mercury has a latency period of several
    months, this is probably due to other components
    of the vaccine.

11
ASD Reports of Adverse Vaccine Reactions - Severe
  • 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 didnt 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

12
ASD Reports of Adverse Reactions to Vaccinations
- Moderate
  • 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

13
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 p0.09 (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

14
HAIR MERCURY OF AUTISTIC VS. CONTROL GROUPS
Hair Hg level (ppm)
Autistic Mean0.47 n94
Non-autistic Mean3.79 n34
15
HAIR MERCURY BY SEVERITY OF AUTISM
Hair Hg level (ppm)
Mild Mean0.71 n27
Moderate Mean0.46 n43
Severe Mean0.21 n24
16
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.

17
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

18
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

19
Conclusions
  • Seafood consumption gt 2 servings/month yields
    2.7x risk
  • Ear infections gt 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

20
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
  • removal of thimerosal from vaccines
  • limiting maternal seafood consumption
  • reduced use of oral antibiotics
  • no mercury fillings placed during pregnancy

21
Autism- Baby Tooth Study
  • James B. Adams, Arizona State Un.
  • Marvin Legator, Un. Texas- Galveston
  • Jane Romdalvik
  • Funded by Autism Research Institute

22
  • 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

23
Initial Results (10 autism, 8 controls)
  • Lead almost identical between two groups
  • Autism 0.36 /- 0.13 mcg/g
  • Controls 0.29 /- 0.14
  • Zinc almost identical between two groups
  • Autism 94 /- 10
  • Controls 91 /- 9
  • Mercury much higher in autism
  • Autism 0.18 /- 0.11
  • Controls 0.05 /- 0.05
  • p0.01 very statistically significant, but more
    samples needed

24
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?)

25
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., Doctors Data
  • Funding from Arizona State University, Greater
    Phoenix Chapter of ASA, Pima County Chapter of ASA

26
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

27
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 Doctors Data (blinded) for testing with
    ICP-Mass Spectrometry
  • analyzed 39 elements

28
Results - Toxic Metals
  • Aluminum slightly lower in ASD (-16, p0.05),
    especially in 3-6 yr old group (-24, p0.04)
  • Arsenic pica subgroup had 25 lower level
  • Uranium non-pica group had lower uranium (-27,
    p0.05)
  • Barium pica group had higher barium (99,
    p0.04)
  • Overall, only small differences in toxic metals,
    and not very statistically significant

29
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
    (p0.22)
  • no abnormal levels of other heavy metals in ASD
    mothers

30
Essential Minerals - Iodine
  • Iodine 45 lower in ASD than controls, p0.005
    (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

31
Iodine - continued
  • In early 1900s, 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 1970s to 1990s per NHANES I and III,
    possibly due to decreased salt intake
  • RECOMMENDATION supplement at modest level
    measure iodine in blood test thyroid function

32
Lithium
  • The only abnormality in mothers of children with
    ASD was low levels of lithium
  • all ages -40, p0.05
  • mothers of children ages 3-8 -56, p0.005
    (highly significant!)
  • Similarly, children with ASD had lower levels of
    lithium
  • all ages -15, not significant
  • ages 3-6 yr -30, p0.04

33
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

34
Lithium - continued
  • Low lithium in urine correlated with increase in
    schizophrenia diagnosis, neurosis, and homicide.
  • Another study found highly significant (p0.005
    to 0.01) inverse associations between water
    lithium levels and rates of homicide, suicide,
    and rape, and significant (p0.01-0.05) 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.

35
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

36
Phosphorus
  • Slightly low levels in children with ASD (-11,
    p0.001). Minor difference, but highly
    statistically significant.

37
Pica Sub-Group
  • Pica subgroup had
  • low levels of chromium (-38, p0.002)
  • highly significant
  • low levels of sodium (-58, p0.05)
  • elevated levels of copper (67, p0.03) and
    strontium (112, p0.03)
  • Could chromium supplements help decrease pica?

38
Low Muscle Tone
  • Children with low muscle tone had
  • very low potassium (-66, p0.01)
  • potassium is needed for muscle contractions
  • high zinc (30, p0.01)
  • high barium (109, p0.03)
  • 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

39
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

40
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

41
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
    Aspergers) vaccination records with
    manufacturers lot number (just call your
    pediatrician).
  • Controls needed - please help!
  • Contact Jane Romdalvik jromdalvik_at_aol.com
  • 623 376-0758 (email preferred)
  • Funded by Autism Research Institute and NIEHS
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