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Possible Connection of Heavy Metal Toxicity and Autism - PowerPoint

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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
                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 12.5-
  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
                        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.”
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
•   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


  •   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
Hair Hg level
(ppm)       18      GROUPS                      Female

                                                Male
                16
                14
                12
                10
                8
                6
                4
                2
                0
                     Non-autistic    Autistic
                     Mean=3.79      Mean=0.47
                        n=34          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      Moderate     Severe
                    Mean=0.71   Mean=0.46   Mean=0.21
                      n=27        n=43        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:
  –   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:         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
   – 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 ICP-
  Mass 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.
•   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=0.01-
  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.
                       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