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