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CHELATION: PUBLIC HEALTH CONCERNS Carl Herbrandson, PhD Minnesota Department of Health

Minnesota Department of Health St. Paul, MN

Our Mission: Protecting, Maintaining, and Improving the Health of all

Minnesotans

Environmental Health at MDH - Touching Everyone’s Life Every Day -

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This presentation has not been reviewed or approved by the Minnesota Department of Health.

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Mercury Maze

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Loncraine Broxton & Partners, Ltd. Made In England (1978) escoinfo.com

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Pre-Chelation Checklist Diagnosis

•  Extraordinary Exposure •  Biomarkers •  Symptoms

Benefit – (Removing metal ≠ Improving outcome!) •  Availability of effective chelator, treatment delay, seriousness of symptoms,...

•  Relief from symptoms •  Longterm prognosis

Risk •  Reactivation of stores (target and non-target metals/minerals) •  Remove essential metals and minerals

•  Shortterm Risk •  Subtle and/or latent effects

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Chelation: Public Health Concerns •  1 large incident

•  2 unpublished case reports

• Chelation following 1971-72 Iraqi MeHg incident

• Summary – improper use of biomarkers

• Recommendations to ACMT

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3.3% Hg

1.3%, 1.7% Hg

0.6% Hg

0.5% Hg

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3 forms of Mercury • Elemental

•  Inorganic •  calomel (mercurous Cl) • mercuric Cl (I,S, acetate)

• Organic • methylmercury •  thimerosal (ethylmercury

thiosalicylate, or merthiolate)

• merbromine •  phenylmercuric acetate

 Historic exposures

 Historic medicinal uses  teething powder, cream  syphilis, cream

 Primarily historic  seedcoat, fish  merthiolate , vaccines

 mercurochrome  paint, flooring

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•  Include questions about skin-lightening cream use in patient history.

•  Discuss skin-lightening product use with patient. Mercury or other regulated chemicals (including retinoic acid or steroids) may be the active ingredient in these products.

•  Conduct standard disease workup. Include inorganic mercury exposure in differential diagnoses...

•  For symptomatic patients, please contact the Regional Poison Center at 1-800-222-1222 for consultation with a poison specialist and/or toxicologist.

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•  Include questions about skin-lightening cream use in patient history.

•  Discuss skin-lightening product use with patient. Mercury or other regulated chemicals (including retinoic acid or steroids) may be the active ingredient in these products.

•  Conduct standard disease workup. Include inorganic mercury exposure in differential diagnoses...

•  For symptomatic patients, please contact the Regional Poison Center at 1-800-222-1222 for consultation with a poison specialist and/or toxicologist.

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•  Be suspicious. The safest course of action is to discontinue use of all skin-lightening products not used at the direction of a dermatologist.

•  Most patients will require no testing; the most effective treatment is discontinuation of use.

•  Severe mercury poisoning can be treated with chelation after careful assessment of risk/benefit. Chelation treatment of asymptomatic or mildly symptomatic patients is unlikely to benefit patients, and may actually be harmful.

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Chelation Conundrums • Patients want a single, clear explanation for symptoms

o In all but a few extraordinary instances exposures are too small to result in any symptoms – incorrect diagnosis.

• Patients want treatment o  There is a difference between successfully removing a toxin and

having a positive health outcome – questionable efficacy.

• Subtle and latent effects of chelation are not understood o  There are health risks from the treatment (the drug, mineral

replacement) and from potential reactivation of stores (targeted metal or other metals).

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Would you chelate? •  7 year old child with acrodynia • Mercury exposure (chronic) found and removed • BP 130/100 (controlled w/medication to 100/65) • Other symptoms resolving

•  2 DMSA treatments in 2 months •  5 months following exposure removal (3 mos post-DMSA)

– BP 98/57

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Caller information •  55 year old male – memory loss, depression

•  “toxic” for mercury, selenium, lead and thallium

• Selenium supplement, otherwise exposures unknown

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- µg/g

Mahaffey et al. 2004

~ 2 µg Hg/L Blood

~ 2.8 µg Hg/L Blood EPA RfD – 5.8 µg Hg/L Blood

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Serious errors in interpretation of biomarkers of exposure

• Use of provocation or challenge test data

• Use of non-standard biomarkers

• Comparing results with population statistics, not health data •  acceptable ranges based on commercial

laboratory’s judgment – not referenced

•  high % of population will be “toxic”

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Serious errors in interpretation of biomarkers of exposure

• Evaluation often subjective Appeal to emotions

Treatment not result of risk/benefit analysis

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Use of a non-systemic chelator (thiol resin) – modeling MeHg in blood

•  1971-72 Iraqi MeHg poisoning •  one to several weeks between end of exposure and

beginning of treatment •  non-treatment, placebo, 4 treatments:

•  DMPS, thiol resin, NAP, PEN

• Blood MeHg t1/2 (60-65 days) •  10, 20, 24, 26 days, respectively

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(Clarkson et al., 1981)

Use of a non-systemic chelator (thiol resin) – modeling MeHg in blood

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Implications of Mouse Data/Model – Human Hg-Bile Re-absorption

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Public Health Needs • Guidance for physicians

• When is chelation appropriate? • When is chelation not appropriate? • What are the important components of a chelation

risk/benefit analysis

• Research • metal sequestration and effects of chelation

• subtle and latent health effects of metal exposure / chelation

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(Korbas et al. 2010)

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National Geographic, 1972