Possible Connection of Heavy Metal Toxicity and Autism

Autism 2002
Mercury, Heavy Metals... Toxicity

For reasons beyong our control, the sheduled presentation by Dr. James Laidler has was replace by a prenentation fromo Dr. James B. Adams.

James B. Adams, Ph.D.' is a Professor in the Dept. Of Chemical and materials Engineering, and the Co-Director of the Interdisciplinary Science and engineering Materials Program at Arizona State University. He teaches a course on heavy metals and chemical toxicit, and des research on autism focused on heavy metals and nutritional interventions. Dr Adams is the President of the Greater Phoenix Chapter of the Autisme Society of America, and the father of a child with autism.

Possible Connection of Heavy Metal Toxicity and Autism

Collaborators

Charles E. Holloway - ASU
Brittany Done, ASU
Mary Kerr
Michael Margolis, D.D.S.
Frank George, D.O.
Karen Medville, D.Sc.
Woody McGinnis, M.D.
Xianchen Liu, M.D., Ph.D.

Hypothesis

Do mercury and other heavy metals contribute to the causes and/or symptoms of autism in some cases?

Background - Lead Toxicity

Lead- most widespread case of heavy metal poisoning
1991-1994: 4.4% of US children ages 1-5 "affected" (blood levels >10 ug/dL)
loss of 4-7 IQ points per 10 ug
even levels below 10 ug may affect children
can affect every organ
correlates with lower class rank, absenteeism, slower reaction times, worse coordination
effects often life-long
exposure of parents can affect their child 30 years later (greater risk of learning disabilities)

Children more susceptible than Adults

more exposure (crawling, playing in dirt, licking hands)
less excretion (adults retain only 1%, children retain 33%)
brain still developing
lead crosses placenta, no blood/brain barrier in fetuses
low calcium in mothers results in lead stored in bone being released

Major Sources of Lead

Leaded Gasoline:
major source of lead, permanently contaminating soil near roads
introduction of unleaded gasoline in 1980’s has greatly reduced emissions (95 million kg in 1979 to only 2 million kg in 1989); average blood lead levels now much lower than 20 years ago
Old paint:
up to 1955, most household paint 50% lead
1955-1971: voluntary limit of 1% lead
1971: 1% lead required
1977: "lead-free" paint limited to 0.06% lead
note that remodeling an old home (especially sanding) is very hazardous
Lead Pipes:
still used in many homes
replaced with copper, but used lead solder until 1991
brass faucets contain up to 8% lead
most filters useless; only reverse osmosis removes lead

Prevention and Treatment for Lead Poisoning

Most states require check of blood lead level in school-age children (but often too late)
Reduce children’s exposure lead (remediation of environment by removing paint chips, dust, dirt)
increasing calcium intake (to reduce lead intake)
chelation if high blood lead level (> 40 ug/dL);
for blood lead level of 20-40 ug/dL, large study of 780 children found that chelation with DMSA for 1 month did temporarily lower blood lead levels, but rapidly returned and no long-term benefit (however, could longer-term treatment help?)
The only truly effective current treatment is prevention

Mercury Exposure: Sources

Coal-burning Power Plants: emit 52 tons of Hg/year into air (unregulated); most ends up in water, and then in fish
Seafood: larger fish have most mercury, due to eating smaller fish
Water: limited to 2 ppb (regulated)
Fungicides/Pesticides: some contain mercury (decreasing)
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

Thimerosal Toxicity

Previous studies of thimerosal had two major limitations:
only tested thimerosal in adult animals
only followed animals for 14-45 days, even though lethal doses in humans may not produce any symptoms for 3 months
Thus, actual lethal dose may be much lower than believed.

Comparison of thimerosal toxicity

Humans: immediately lethal at 10,000-30,000 mcg/kg

Lower doses lethal after several months 3000 mcg/kg?
Infants more vulnerable 1000 mcg/kg?
Vulnerable population (1 in 250) 100 mcg/kg?
Neurological damage instead of death 10 mcg/kg?
Oral antibiotics prevent excretion 1 mcg/kg?
exposure to other heavy metals 0.1 mcg/kg?
Note: the EPA safe limit for mercury exposure is 0.1 mcg/kg
Thimerosal in vaccines: up to 237 mcg total; in 2-month children, about 60 mcg/5 kg, or 12 mcg/kg in one day

Conclusion: amount of thimerosal in vaccines could have harmed children, especially those on oral antibiotics or genetically vulnerable

Thimerosal Settling

Thimerosal molecule is far denser than other molecules in vaccine, due to heavy mercury atom
So, thimerosal may settle to bottom of 10-dose vial, so that some unlucky children could have received up to 10x the dose of thimerosal
Rather than replacing thimerosal with other preservatives, single-dose vials would be safer at modest cost

Mercury in Seafood - highest level

SPECIES MEAN (PPM) RANGE (PPM) NO. OF SAMPLES

Tilefish 1.45 0.65-3.73 60
*Swordfish 1.00 0.10-3.22 598
*Shark 0.96 0.05-4.54 324
King Mackerel 0.73 0.30-1.67 213
Grouper (Mycteroperca) 0.43 0.05-1.35 64
* commonly consumed

data from US-Food and Drug Administration, 2001

Mercury in Seafood - Lower Levels

SPECIES MEAN (PPM) RANGE (PPM) NO. OF SAMPLES

Tuna (fresh or frozen) 0.32 ND-1.30 191
*Lobster Northern (American) 0.31 0.05-1.31 88
*Halibut 0.23 0.02-0.63 29
*Sablefish 0.22 ND-0.70 102
*Pollock 0.20 ND-0.78 107
*Tuna (canned) 0.17 ND-0.75 248
*Crab Blue 0.17 0.02-0.50 94
*Crab Dungeness 0.18 0.02-0.48 50
*Scallop 0.05 ND-0.22 66
*Catfish 0.07 ND-0.31 22
*Salmon ND ND-0.18 52
*Oysters ND ND-0.25 33
*Shrimp ND ND 22

FDA Recommendations - 2001

Avoid fish from the highest category
limit consumption to 12 ounces/week (2-3 servings) of other fish
Example: 12 ounces (340 g) of canned tuna would contain 58 ug of mercury, roughly the amount excreted by a mouthful of old amalgams over a week, or the amount in 2-4 vaccines
Note: nearly 100% of mercury from seafood is absorbed into body

Prevalence of Mercury Toxicity

National Academy of Sciences estimates 60,000 children/yr in US suffer neurological damage due to mercury poisoning.
Who are they? Mostly not diagnosed, since mercury only briefly stays in blood, and limited physician knowledge/experience for diagnosing
Are some children with mercury/heavy metal toxicity diagnosed with a behavioral label of autism, Asperger’s, ADD/ADHD, or learning disabilities?

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

Combined Toxicity of Lead and Mercury

Since lead, mercury, and other heavy metals are excreted by the same mechanism, then a combined dose is more dangerous
A study of rats found that the LD1 of lead and the LD1 of mercury resulted in LD100 (all the rats died). Schubert et al, J. Toxicology and Env. Health V4, 763-776, 1978.
Note that humans are usually exposed to many toxic metals simultaneously, but most toxicology tests done on individual metals

Present Study

Participants

55 children with ASD ages 3-24 years (mostly 3-10), chosen from Phoenix ASA mailing list
50 typical children chosen from their friends/neighbors (unrelated), same age and sex

Methodology

heavy metal exposure questionnaire
hair analysis
dental exam
psychological testing (Gilliam Autism Rating Scale)
urine test of sulfate (results pending)

Preliminary Results of Heavy Metal Questionnaire

Caveat: mostly based on mother’s memory

Seafood: 60% of ASD mothers consumed more than 2 servings/month during pregnancy/breastfeeding, compared to 30% of controls;

yields a 3.4x relative risk of ASD (p<0.02);

presumably mercury in the seafood is the major problem

Preliminary Results of Heavy Metal Questionnaire (cont.)

Ear Infections: during first three years of life:

ASD: 10x controls: 2x

yields an 8x relative risk of ASD if > 8 infections; p<0.001

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: ASD: 1.8 controls: 0.1 (scale of 0-3) p<0.0000001
consistent with a major gut dysbiosis
Pica: 30% of ASD vs 0% of the controls
a major source of heavy metals
symptom and/or cause?
Pesticides: 2x higher use of pesticides in autism homes (p<0.02)
note that Edelson found elevated levels of a wide variety of toxic chemicals in blood of children with autism
could indicate a general problem with detoxification

Preliminary Results of Heavy Metal Questionnaire (cont.)

Negative immediate reaction to vaccines:

None. Mild Moderate Severe

ASD 53% 27% 12% 18%

Controls 72% 21% 7% 0%
p=0.01 - highly significant;
Since mercury has a latency period of several months, this is probably due to other components of the vaccine.

Still analyzing vaccination records for long-term effects of vaccines.

Preliminary Hair Data

Children: ASD cntrl p value
lead 0.40 0.54 0.10
mercury 0.14 0.17 0.67

Mothers:
mercury 0.39 0.17 0.34
There is a trend that children with autism excrete slightly less lead and mercury than typical children. Surprising, since 30% exhibit pica (those children excrete more than controls).

Mothers of autistic children seem to excrete roughly 2x mercury than typical mothers, presumably due to higher seafood consumption.

Need more data to be conclusive (still collecting)

Dental Amalgams

Mothers of children with autism had an average of 9.9 dental amalgam surfaces, vs 8.2 for mothers of typical children: not statistically significant
However, 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

Preliminary DMSA results

DMSA results (continued)

Child 16: excess Sn (60x normal)
Child 50: excess Al (700x), Sb(13x), Bi(5x), Cd(6x), Pb(5x), Ni(5x), W (5x), U(200x) - most severe case
Child 53: excess Sb (8x)
Child 2: excess Sb (7x), As(10x), Hg(150x)
Child 51: nothing unusual
Child 35: excess Hg (6x)
Child 36: excess Al(35x), U(60x)

DMSA results

Bradstreet used a 3-day, 30 mg/kg-day 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, our data suggests ASD children have inhibited ability to excrete heavy metals

Conclusions

Seafood consumption > 2 servings/month yields 3.4x 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)

Home pesticide use is important

Vaccine reactions are more common in ASD

Hair data intriguing but not yet conclusive

DMSA results strongly suggest children with autism cannot excrete heavy metals; need more data and pre-test data

Overall, mercury and other metals appear to be a major risk factor for ASD

Edelson/Cantor Studies

S. Edelson and D. Cantor, Toxicology and Industrial Health (2000) 16 1-9.
Evaluated 39 children with autism
blood test of 20 toxic chemical solvents by Accu-Chem; compared against labs reference range for "maximum acceptable for adult"
- 3-methylpentane (n=24, 3.7x adult max)
- N-Hexene (n=17, 9.5x adult max)
- 2-methylpentane (n=13, 9.2x adult max)
- toluene (n=13, 6.1x adult max)
- tetracholorethylene (n=10, 8.5x adult max)
- 13 other chemicals: n=1-6, levels = 1.8-21.5x adult max)
  89% of children had 1 or more excess levels of toxic chemicals
  Consistent with their earlier study of 20 children with autism.
  (Toxicology and Indus. Health, 1998, V.14, 799-811)

Edelson/Cantor Studies - continued

Liver Detoxification Test: challenge with caffeine, Tylenol, aspirin (Great Smokies)

Measure % of abnormal results (n=36) - compared to adults?
phase 1 value 81
plasma cysteine 8
plasma sulfate 25
glutathione conjugation 22
glycine conjugation 31
sulfation 19
glucoronidation 19
phase 1/sulfation 42
phase 1/gluconation 81
phase 1/glucuronidation 81
plasma cysteine/sulfate 14

Phase I overactive compared to phase II: 86%
Functional Phase I, but impaired phase II: 14%
100% of children with autism had abnormal liver detoxification (compared to adults?)

Revised Hypothesis

Liver detoxification problems in autism could lead to impaired ability to excrete heavy metals and chemical toxins, as well as waste products from body’s metabolism

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:
limiting maternal seafood consumption (warning labels on fish)
reduced use of oral antibiotics (especially many repeated uses)
removal of thimerosal from vaccines

Testing and Treatment Recommendations

DMSA challenge test of heavy metals
check levels of toxic chemicals (Accu-Chem labs)
check mercury in baby hair (if available)
Limit exposure to heavy metals (check drinking water and paint; avoid seafood, especially those with high mercury; limit pica; wash hands)
support liver detoxification
consider DMSA chelation
consider sauna
other? still a lot to learn
Caveat: unclear if damage caused by heavy metals can be reversed, especially in older children/adults

Case Study: Adult recovery from mercury toxicity

April 1999: Airline pilot (Gulf War Veteran) suffered from abnormal weight loss (40 pounds), elevated liver enzymes, elevated blood pressure, esophagitis, gastritis, duodenitis, anxiety, depression, insomnia, muscle joint pain, and short term memory loss. Voluntarily removed himself from active flight status

8/1999: Carl Hayden VA Hospital evaluates patient at 66% intellectual ability. Diagnosis of Severe Depression, Adjustment Disorder and Post Traumatic Stress Disorder, with variable to poor short-term memory, and Acalculus Cholecystitis.

11/1999 - Gulf War veteran found to have high level of mercury in hair (14.2 ppm, >5 ppm indicative of mercury toxicity)

2/2000 - Chelation challenge with 250 mg DMPS found 74 ug/g-creatinine in urine, compared with pre-challenge level of 3.3 ug/g-creatinine

11/2000 - after removing dental amalgams and 9 months of chelation therapy, complete symptom relief; urine level after DMPS reduced from 74 -> 10; hair level reduced from 14.2 -> 1.2; VA Hospital evaluates intellectual function at 93%, no diagnosis; returned to active flying status

Current and Future Studies

More DMSA testing
Expanded epidemiological study
baby hair collection (duplicate Holmes’ results)
protein/gene abnormalities
chelation treatment study?

Acknowledgements

Funded by Arizona State University, Greater Phoenix Chapter of ASA, and Pima County Chapter of ASA
www.eas.asu.edu/~autism
for copy of talk and other information

More info on Dr Adams's research is available at is site