Possible Connection of Heavy Metal Toxicity and Autism

Prof. James B. Adams, Ph.D.

Chemical and Materials Engineering

Arizona State UniversityCharles 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: 2.5xp=0.00006

Symptom or cause?1) could be an indication of weakened immune system2) 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 ReactionsModerate 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

GROUPS

0

2

4

6

8

10

12

14

16

18

20Hair Hg level(ppm) Female

Male

AutisticMean=0.47

n=94

Non-autisticMean=3.79

n=34

HAIR MERCURY BY SEVERITY OF AUTISM

0

0.2

0.4

0.6

0.8

1

1.2

1.4Hair Hg level(ppm)

MildMean=0.71

n=27

Female

Male

ModerateMean=0.46

n=43

SevereMean=0.21

n=24

DMSA resultsBradstreet 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, DMPSRecent 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 ResidentsBorn 1988-1999full 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/~autismCharles 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

MethodologyHair 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 neckSent 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 lithiumall 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 ToneChildren 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.com623 376-0758 (email preferred)

Funded by Autism Research Institute and NIEHS