1. DMPS/DMSA Using DMPS and DMSA in safe and effective ways to assess and treat heavy metal burden
Walter J. Crinnion ND
SpiritMed
Copyright WCrinnion 2013

2. COI and other issues
Thanks to Dr. Dan Carter for some of his slide information.
Dr. Crinnion has no conflict of interest in regards to any compounds covered in the following slides.
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3. Who are they?
DMSA
DMPS
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4. DMSA Chemical name: meso-2,3-dimercaptosuccinic acid Alt: meso-2,3-bis(sulfanyl)succinate
Other drug names
Dimercaptosuccinic acid
Succimer
Chemet™
Captomer™
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5. DMSA Kinetics Second generation from British Anti-Lewisite (BAL)
Absorbed rapidly after oral administration
Approximately 20% absorption
Evidence that enterohepatic circulation occurs
95% binds to albumin via disulfide bond with cysteine
This leaves the other thiol group free to chelate metals
Renal excretion
>90% excreted as mixed disulfides of DMSA
Disulfides only found in urine, not blood
<10% excreted as DMSA
Aposhian HV, Maiorino RM, Rivera M, Bruce DC, Dart RC, Hurlbut KM, Levine DJ, Zheng W, Fernando Q, Carter D, et al. Human studies with the chelating agents, DMPS and DMSA. J Toxicol Clin Toxicol. 1992;30(4): PubMed PMID:
Maiorino RM, Bruce DC, Aposhian HV. Determination and metabolism of dithiol chelating agents. VI. Isolation and identification of the mixed disulfides of meso-2,3-dimercaptosuccinic acid with L-cysteine in human urine. Toxicol Appl Pharmacol Feb;97(2): PubMed PMID:
Copyright WCrinnion 2013

6. DMSA Kinetics Renal excretion (cont’d)
Research evidence indicates that the mixed disulfides of cysteine are the active chelating moiety in humans
This suggests that chelation occurs principally in the kidney
Elimination half-life of total DMSA (parent drug plus oxidized metabolites)
Longer in children with lead poisoning (3hours)
Adults with or without lead poisoning ( hours)
See notes previous slide, also
Aposhian HV, Maiorino RM, Dart RC, Perry DF. Urinary excretion of meso-2,3-dimercaptosuccinic acid in human subjects. Clin Pharmacol Ther May;45(5): PubMed PMID:
Copyright WCrinnion 2013

7. DMSA Indications and Usage
Succimer is a (FDA approved) lead chelator; it forms water soluble chelates and increases the urinary excretion of lead
Succimer is indicated for the treatment of lead poisoning in pediatric patients with blood lead levels above 45 mcg/dL
Succimer is not indicated for prophylaxis of lead poisoning in a lead-containing environment
the use of Succimer should always be accompanied by identification and removal of the source of the lead exposure
DMSA is also clinically useful for chelating
Arsenic
Cadmium
Mercury
It has been suggested that DMSA be utilized following EDTA chelation
Dart RC, Hurlbut KM, Maiorino RM, Mayersohn M, Aposhian HV, Hassen LV. Pharmacokinetics of meso-2,3-dimercaptosuccinic acid in patients with lead poisoning and in healthy adults. J Pediatr Aug;125(2): PubMed PMID:
Fournier L, Thomas G, Garnier R, Buisine A, Houze P, Pradier F, Dally S. 2,3-Dimercaptosuccinic acid treatment of heavy metal poisoning in humans. Med Toxicol Adverse Drug Exp Nov-Dec;3(6): PubMed PMID:
Friedheim E, Corvi C. Meso-dimercaptosuccinic acid, a chelating agent for the treatment of mercury poisoning. J Pharm Pharmacol Aug;27(8): PubMed PMID:
Lenz K, Hruby K, Druml W, Eder A, Gaszner A, Kleinberger G, Pichler M, Weiser M. 2,3-Dimercaptosuccinic acid in human arsenic poisoning. Arch Toxicol. 1981Jun;47(3): PubMed PMID:
Crinnion WJ. EDTA redistribution of lead and cadmium into the soft tissues in a human with a high lead burden - should DMSA always be used to follow EDTA in such cases? Altern Med Rev Jun;16(2): PubMed PMID:
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8. Contraindications
DMSA should not be administered to patients with a history of allergy to the drug
Most typically found in those with a high reactivity to anything containing sulfur
If a patient has experienced unexplained adverse reactions, avoid re-exposure to DMSA
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9. Warnings & Precautions
Mild/moderate neutropenia has been observed
A causal relationship to succimer has not been absolutely established
Neutropenia has been reported drugs in the same chemical class (dithiols)
A complete blood count with white blood cell differential and platelet count should be obtained prior to and weekly during treatment with succimer
Withhold or discontinue therapy if the absolute neutrophil count (ANC) is below 1200/mcL . Follow patient closely to document recovery of the ANC to above 1500/mcL or to baseline neutrophil count
Due to limited experience with re-exposure in patients who have developed neutropenia, such patients should be re-challenged only if the benefit of therapy clearly outweighs the potential risk of another episode of neutropenia and only with careful patient monitoring
Instruct patients treated with succimer to promptly report any signs of infection. If infection is suspected laboratory tests should be performed immediately
(accessed 9/17/2013)
(accessed 9/17/2013)
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10. DMSA Warnings & Precautions
Pregnancy: Category C
Nursing mothers
Many drugs and toxic metals are excreted in human milk, nursing mothers needing DMSA therapy should be discouraged from nursing their infants
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11. Safety of DMSA with children
With mercury overload
A cluster of pediatric metallic mercury exposure cases treated with meso-2,3-dimercaptosuccinic acid (DMSA)
Forman J, et al. Environ Health Perspect 2000;108:
With lead overload
Safety and efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) in children with elevated blood lead concentrations.
Chisolm JJ. J Toxicol Clinical Toxicology 2000;38(4):
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12. DMPS Chemical name: 2,3-dimercapto-1-propanesulfonic acid Sodium 2,3-dimercaptopropane sulfonate Alt: 2,3-bis(sulfanyl)propane-1-sulfonate
Other drug names
Dimaval
Unithiol
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13. Heyl Dimaval Monograph
d.com/doc/ /Dimaval®- Scientific- Product- Monograph
Accessed: 9/17/2013
Dimaval®: Scientific Product Monograph Ruprecht J. Dimaval®: Scientific Product Monograph. 7th Edition. Berlin: HEYL Chem.-pharm. Fabrik, 2008.
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14. Kinetics
DMPS is distributed extracellularly and, to a smaller extent, intracellularly.
80% bound by protein, mainly albumin, in the plasma, highly stable prolonging the heavy metal mobilizing activity
This results in the half life extending from 1.8 hours of the parent compound to 20 hours of the altered (bound) drug.
Dimaval®: Scientific Product Monograph Ruprecht J. Dimaval®: Scientific Product Monograph. 7th Edition. Berlin: HEYL Chem.-pharm. Fabrik, 2008.
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15. Kinetics Half-life after intravenous dosing - 20 hours
Half-life after oral dose hours
DMPS undergoes renal excretion with 46 to 59% of the dose detected in the urine after 24 hours of dosing
Dimaval®: Scientific Product Monograph Ruprecht J. Dimaval®: Scientific Product Monograph. 7th Edition. Berlin: HEYL Chem.-pharm. Fabrik, 2008.
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16. Toxicology No adverse effects on organ systems at therapeutic doses
Immune system parameters not effected – no neutropenia
Non-Mutagenic, non-teratogenic
Pregnancy category C - It is NOT recommended that pregnant women with chronic toxicity undergo mobilization of heavy metals until completion of lactation
Dimaval®: Scientific Product Monograph Ruprecht J. Dimaval®: Scientific Product Monograph. 7th Edition. Berlin: HEYL Chem.-pharm. Fabrik, 2008.
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17. Indications and Usage
Currently, it is not FDA approved in the United States
Classified by the FDA as a bulk drug substance for pharmacy compounding
Dimaval®: Scientific Product Monograph Ruprecht J. Dimaval®: Scientific Product Monograph. 7th Edition. Berlin: HEYL Chem.-pharm. Fabrik, 2008.
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18. Contraindications
DMPS must not be administered to patients who are hypersensitive to DMPS or its salts
Not recommended for use in patients with serum creatinine greater than 2.5 or stage 4 chronic kidney disease (CKD)
Dimaval®: Scientific Product Monograph Ruprecht J. Dimaval®: Scientific Product Monograph. 7th Edition. Berlin: HEYL Chem.-pharm. Fabrik, 2008.
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19. Precautions Drug Interactions Pregnancy Pediatric Use
None listed
Pregnancy
Category C: The safety of DMPS administration during pregnancy has not been confirmed in humans
Pediatric Use
Pediatric doses have not been specified, do not administer to patients less than 12 months of age
Patients with mercury amalgam fillings
See Aposhian study
Dimaval®: Scientific Product Monograph Ruprecht J. Dimaval®: Scientific Product Monograph. 7th Edition. Berlin: HEYL Chem.-pharm. Fabrik, 2008.
Copyright WCrinnion 2013

20. Does DMPS pull Hg from fillings?
Urinary mercury after administration of 2,3- dimercaptopropane-1-sulfonic acid: correlation with dental amalgam score
Aposhian HV, et al
FASEB J 1992;6:
10 subjects with amalgams
10 subjects without amalgams
Aposhian HV, Bruce DC, Alter W, Dart RC, Hurlbut KM, Aposhian MM. Urinary mercury after administration of 2,3-dimercaptopropane-1-sulfonic acid: correlation with dental amalgam score. FASEB J Apr;6(7): PubMed PMID:
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21. Aposhian, HV. 1992 300mg DMPS po after 11 hour fast
Urine collected 9 hours post DMPS
10 w/ amalgams to 17.2 ug Hg
10 w/o amalgams 0.27 to 5.1 ug Hg
Aposhian HV, Bruce DC, Alter W, Dart RC, Hurlbut KM, Aposhian MM. Urinary mercury after administration of 2,3-dimercaptopropane-1-sulfonic acid: correlation with dental amalgam score. FASEB J Apr;6(7): PubMed PMID:
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22. Aposhian conclusion
“ A linear relationship exists between the amalgam score and the urinary mercury after DMPS administration” “Two-thirds of the mercury excreted in the urine of those with dental amalgams appears to be derived originally from the mercury vapor released from their amalgams”
Aposhian HV, Bruce DC, Alter W, Dart RC, Hurlbut KM, Aposhian MM. Urinary mercury after administration of 2,3-dimercaptopropane-1-sulfonic acid: correlation with dental amalgam score. FASEB J Apr;6(7): PubMed PMID:
Copyright WCrinnion 2013

23. Where did most of the urinary mercury come from?
The Kidneys!
Aposhian HV, Bruce DC, Alter W, Dart RC, Hurlbut KM, Aposhian MM. Urinary mercury after administration of 2,3-dimercaptopropane-1-sulfonic acid: correlation with dental amalgam score. FASEB J Apr;6(7): PubMed PMID:
Copyright WCrinnion 2013

24. Sulfa allergy & the “Ds”
Sulfa drug allergy? Not a contraindication for either DMSA or DMPS
There has been no demonstrated cross reactivity from a chemical or pharmacological standpoint
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25. W. Crinnion, Unpublished case report
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26. Adverse Reactions Skin General
Pruritus, rashes, allergic skin reactions (rare)
General
Chills, fever, increased transaminases
Dimaval®: Scientific Product Monograph Ruprecht J. Dimaval®: Scientific Product Monograph. 7th Edition. Berlin: HEYL Chem.-pharm. Fabrik, 2008.
Copyright WCrinnion 2013

27. Will Transdermal DMPS work?
Transdermal (TD-DMPS) is an ineffective metal chelator
TD-DMPS is not absorbed, not found in blood samples
There was no increase in urine mercury excretion after TD-DMPS.
Cohen JP, Ruha AM, Curry SC, Biswas K, Westenberger B, Ye W, Caldwell KL,Lovecchio F, Burkhart K, Samia N. Plasma and urine dimercaptopropanesulfonate concentrations after dermal application of transdermal DMPS (TD-DMPS). J MedToxicol Mar;9(1):9-15. doi: /s PubMed PMID:
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28. Transdermal DMPS 48yo M Cd <2 0.2 0.9 0.09 0.3 Pb <5 <dl 13
Metal
DDI
Pre
Post EDTA/
DMPS
Transdermal DMPS Cd
<2
0.2
0.9
0.09
0.3 Pb
<5
<dl 13
0.8 Hg
<4
1.4
7.2
0.5 Ni
<12 3
9.3
2.4
3.4
Crinnion, W. Unpublished research
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29. Pre-testing Provocation and Chelation Periodic testing during therapy
Complete blood count
Comprehensive metabolic panel
GFR – or creatinine WNL
Anti-IgA gliadin antibody – if suspicion of malabsorption is present.
6 hour urine collection for toxic metal assessment
Mineral analysis – when indicated
Serum
RBC
RBC glutathione to show available GSH/GSSG
8-OHdG for oxidative damage assessment
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30. Testing methods
Serum – good for acute exposures, keep in mind the t1/2 in serum.
Urine – also good for acute exposures, when used with chelating agent will indicate relative level of body store.
Hair – excellent for methylmercury
Fecal – good method for children
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31. Provocation Testing Choose a standard & consistent basis for testing
Serial test interpretation is only possible with the same drug dose and urine collection time
Provocation dose for each test remains constant
DMSA (30 mg/kg oral)
DMPS (3 mg/kg IV)
Ca EDTA (50 mg/kg IV)
Urine collection time of 6 hours
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32. DMSA protocol Rule out potential DMSA sensitivity
i.e. reactive to ALL sulfur-containing compounds
No shellfish or seaweed for the week prior to testing
Avoid high arsenic levels
Empty bladder* and stomach
Use first morning urine for pre-flush test
Body weight DMSA (30 mg/kg up to 2250mg)
Collect all urine for 6 hours
Food can be consumed after 1 hour.
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33. Protocol for DMPS challenge test
Sensitivity check for DMPS
No shellfish or seaweed for 1 week prior
Empty bladder*
DMPS (3mg/kg up to 250mg) given in a push over minutes.
6 hour urine catch – Toxic element analysis.
Check serum creatinine.
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34. Oral DMPS challenge No shellfish for 1 week prior
Empty bladder* and empty stomach
10mg/kg oral DMPS
6 hour urine catch sent in for heavy metal UA.
Serum creatinine check
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35. Oral DMPS testing 300 mg oral dose given after 11 hour fast
Dental technicians – 4.84 pre to post
Dentists pre post
Non-dental persons pre post
Positive association between pre coproporphyrin levels and flushed Hg
Pos assoc. Hg and cognitive sx and mood
J Pharmacol Exper Therapeutics 1995;272: PMID:
Gonzalez-Ramirez D, Maiorino RM, Zuniga-Charles M, Xu Z, Hurlbut KM, Junco-Munoz P, Aposhian MM, Dart RC, Diaz Gama JH, Echeverria D, et al. Sodium 2,3-dimercaptopropane-1-sulfonate challenge test for mercury in humans: II. Urinary mercury, porphyrins and neurobehavioral changes of dental workers in Monterrey, Mexico. J Pharmacol Exp Ther Jan;272(1): PubMed PMID:
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36. EDTA/DMPS Flush protocol
Serum creatinine WNL
Empty bladder prior to injection*
2,000mg glycine given 2 hours pre if possible
CaNa2EDTA 2,000 mg (10cc) with sterile H2O in one syringe. Slow push. 20 min
Flush with 3 cc saline
DMPS (3 mg/kg) slow push 15 min
Collect all urine for the next six hours
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37. Assessing Kidney Function
Creatinine clearance
Compliance for 24 hour UA often poor
Serum creatinine being WNL
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38. NO TEST CAN SHOW TOTAL BODY BURDEN OF HEAVY METALS!!!!
These tests are measuring the amount LEAVING the body,
NOT the total IN the body
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39. What to expect DMSA flush gives a good representation of Hg and Pb.
DMPS gives a much higher dump of Hg and much lower dump of Pb
EDTA will give the highest dumps of Cd, Pb and will mobilize Al. It will give VERY POOR dumping of Hg.
If GSH is low you may get a deceptively low reading of Hg
Pre-treatment with NAC & MSM
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40. The differences in Pb and Hg between DMPS and DMSA flushing
in one adult female
Metal
Reference
Range
Pre
Post DMSA
Post DMPS AS
<57 12 17 54 CD
<.9
0.3
0.4
0.5 PB
<6 13
4.3 HG
<7.2 1
6.4 11
Case Study – unpublished research
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41. Doing initial pre and post testing
Helps identify current exposures
Helps identify how effective the proposed chelating agent is
Can give information about absorptive ability of the person
Pre-testing is the ONLY means available to identify toxic levels of Cd
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42. Recognizing current exposures
CDC National reports provide us with ‘normal’ ranges for US residents for the first time.
Levels above 75th percentile would typically indicate current exposure.
For Hg, this is NOT from dental amalgams
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43. Trimethylarsine oxide Total Arsenic 8.24 7.04 14.1 30.4 50.4
Compound
Geometric mean
50th percentile
75th percentil e
90th percentil e
95th percentile
Arsenous (III) acid NA
<LOD
Arsenic (V) acid
3.04
MMA
1.33
2.22
2.86
DMA
3.69
3.37
5.71
9.09
13.0
Arsenobetaine
1.55
1.00
5.20
16.8
35.0
Arsenocholine
Trimethylarsine oxide
Total Arsenic
8.24
7.04
14.1
30.4
50.4
(accessed 9/17/2013)
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44. Compound 50th percentile 75th percentile 90th percentile
Geometric Mean
50th percentile
75th percentile
90th percentile
95th percentile
Antimony NA
.080
.135
.208
.277
Arsenic (total)
8.24
7.04
14.1
30.4
50.4
Barium
1.48
1.41
2.68
4.92
7.10
Cadmium
.210
.412
.678
.940
Cesium
4.64
4.42
6.11
8.51
10.6
Cobalt
.314
.290
.455
.737
1.02
Lead
.632
.622
.979
1.49
1.97
Mercury
.443
.447
.909
1.65
2.35
Thallium
.154
.153
.214
.286
.350
Uranium
.008
.007
.012
.021
.029
(accessed 9/17/2013)
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45. Hg mostly organic – not elemental
Ug/L of Hg in blood
Geometric Mean
50th percentile
75th percentile
90th percentile
95th percentile
Total Blood Hg
.797
.800
1.70
3.30
4.90
Inorganic blood Hg NA
<LOD
.600
.700
(accessed 9/17/2013)
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46. Pre and Post Giving Information on Current Exposures
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47. Levels of Hg ABOVE CDC 75% = CURRENT EXPOSURE
AND an expectation of a large dump post DMSA
Metal
MMX Reference
Range
CDC 90/95%
Pre AS
<57 49 CD
<.9
.68 / .94
0.4 PB
<4.4
1.5 / 2 HG
<7.4
1.65 / 2.35
4.2
Crinnion W. Case Study – unpublished research
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48. Right on both counts Ate tuna 3-4 times weekly Metal CDC 90/95% Pre
MMX
Reference
Range
CDC 90/95%
Pre
Post DMSA AS
<57 49 50 CD
<.9
.68 /.94
0.4
0.9 PB
<4.4
1.5 / 2 14 HG
<7.4
1.65 /
2.35
4.2
Right on both counts
Ate tuna 3-4 times weekly
Crinnion W. Case Study – unpublished research
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49. Eats Halibut or King Salmon five times weekly
Metal
MMX Ref
CDC 90/95%
Pre DMSA
Post DMSA Hg
<7.4
1.65 /
2.35
2.9
9.4
Case Study – unpublished research
Meager Hg levels on post flush would NOT have been reflective on a current exposure WITHOUT the pre!
Also look for poor absorption or GSH deficiency!
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50. No amalgams, no fish intake??
Metal
MMX Ref
CDC 90/95%
Pre DMSA
Post DMSA PB
<4.4
1.5 / 2
2.2 23 Hg
<7.4
1.65 /
2.35
4.7 38
Case Study – unpublished research
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51. The culprit (s)
Possible exposure in some supplements (as yet untested) But, found a broken Hg thermometer in her car, and vacuumed it up with vacuum used regularly inside of home. pills.htm#cleanup
Case Study – unpublished research
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52. Pre and post testing gives information on absorption of DMSA or DMPS oral
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53. Multiple amalgams in mouth, but no regular fish intake
Metal
MMX Ref
CDC 90/95%
Pre DMSA
Post DMSA PB
<4.4
1.5 / 2
0.3 11 Hg
<7.4
1.65 /
2.35
0.7 (CDC mean .4) 1
Case Study – unpublished research
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54. Why such a small increase in Hg?
Positive anti-gliadin IgG
Non-positive transglutaminase IgA
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55. 29 yo f with amalgams and history of gluten sensitivity
Metal
MMX
Ref
CDC 90/95
Pre DMSA
Post DMSA Pb
<4.4
1.5 / 2
<dl
6.6 Hg
<7.4
1.65 /
2.35
0.8
4.5
Case Study – unpublished research
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56. 29yo f with amalgams and history of gluten sensitivity
No gluten in diet.
Anti-gliadin IgA of 26!!
Gluten in supplements from discount store
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57. 29yo f with amalgams and gluten sensitivity after 6 months clean diet
Metal
MMX Ref
CDC 90/95
Pre DMSA
Post DMSA Pb
<4.4
1.5 / 2
<dl
6.6 14 Hg
<7.4
1.65 /
2.35
0.8
4.5 86
Case Study – unpublished research
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58. Pre and Post Testing Giving information on the effectiveness (or lack thereof) of your chosen ‘chelating’ agents
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59. Pre and Post Tests Metal Free and DMSA
MMX ref
Pre Metal Free
Post Metal Free
Post DMSA Cd
<.9
0.3 Pb
<4.4
<dl Hg
<7.4
1.9
0.7
Crinnion W. Case Study – unpublished research
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60. Pre and Post Tests Metal Free and DMSA
MMX ref
Pre Metal Free
Post Metal Free
Post DMSA Cd
<.9
0.3
0.7 Pb
<4.4
<dl 28 Hg
<7.4
1.9 33
Crinnion W. Case Study – unpublished research
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61. Oral EDTA, pt 1(50yo F) Metal MMX ref Pre DMSA Post DMSA Pre EDTA
Post EDTA Cd
<.9
0.4 Pb
<4.4
<dl Hg
<7.4 Ni NA
Crinnion W. Case Study. Unpublished research
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62. Oral EDTA, pt 1(50yo F) Metal DDI ref Pre DMSA Post DMSA Pre EDTA
Post EDTA Cd
<2
0.4
0.6 Pb
<5
<dl
6.5 Hg
<4
3.1 Ni
<12
Copyright WCrinnion 2013
Crinnion, W. Unpublished research

63. Oral EDTA, pt 1(50yo F) Metal DDI ref Pre DMSA Post DMSA Pre EDTA
Post EDTA Cd
<2
0.4
0.6
0.2 Pb
<5
<dl
6.5 1 Hg
<4
3.1 Ni
<12
Crinnion, W. Unpublished research
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64. Oral EDTA, pt 1(50yo F) Metal DDI ref Pre DMSA Post DMSA Pre EDTA
Post EDTA Cd
<2
0.4
0.6
0.2
0.5 Pb
<5
<dl
6.5 1
2.3 Hg
<4
3.1 Ni
<12
1.3
Crinnion, W. Unpublished research
Copyright WCrinnion 2013

65. Oral EDTA, 28 yo F Metal MMX Ref Pre DMSA Post DMSA Pre oral EDTA
Post o –EDTA
Pre IV EDTA
Post IV EDTA AL
<61 Sb
<1.72 35 Cd
<.9
0.8 Pb
<4.4
0.4 Hg
<7.4
1.3
Crinnion W. Case Study. Unpublished research
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66. Oral EDTA, 28 yo F Metal MMX Ref Pre DMSA Post DMSA Pre oral EDTA
Post o –EDTA
Pre IV EDTA
Post IV EDTA AL
<61 Sb
<1.72 35 38 Cd
<.9
0.8
0.6 Pb
<4.4
0.4 14 Hg
<7.4
1.3
9.8
Crinnion W. Case Study. Unpublished research
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67. Oral EDTA, 28 yo F Metal MMX Ref Pre DMSA Post DMSA Pre oral EDTA
Post o –EDTA
Pre IV EDTA
Post IV EDTA AL
<61
4.6 Sb
<1.72 35 38
0.04 Cd
<.9
0.8
0.6
0.5 Pb
<4.4
0.4 14
0.3 Hg
<7.4
1.3
9.8 1
Crinnion W. Case Study. Unpublished research
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68. Oral EDTA, 28 yo F Metal MMX Ref Pre DMSA Post DMSA Pre oral EDTA
Post o –EDTA
Pre IV EDTA
Post IV EDTA AL
<61
4.6 Sb
<1.72 35 38
0.04 Cd
<.9
0.8
0.6
0.5
0.3 Pb
<4.4
0.4 14
0.9 Hg
<7.4
1.3
9.8 1
1.1
Crinnion W. Case Study. Unpublished research
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69. Oral EDTA, 28 yo F Metal MMX Ref Pre DMSA Post DMSA Pre oral EDTA
Post o –EDTA
Pre IV EDTA
Post IV EDTA AL
<61
4.6 Sb
<1.72 35 38
0.04 12 Cd
<.9
0.8
0.6
0.5
0.3 Pb
<4.4
0.4 14
0.9 Hg
<7.4
1.3
9.8 1
1.1
Crinnion W. Case Study. Unpublished research
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70. Oral EDTA, 28 yo F Metal MMX Ref Pre DMSA Post DMSA Pre oral EDTA
Post o –EDTA
Pre IV EDTA
Post IV EDTA AL
<61
4.6
230 Sb
<1.72 35 38
0.04 12
0.06 Cd
<.9
0.8
0.6
0.5
0.3
4.1 Pb
<4.4
0.4 14
(x35)
0.9 11 Hg
<7.4
1.3
9.8
(x7.5) 1
1.1
Crinnion W. Case Study. Unpublished research
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71. Zeolite 31 yo M– 40 gtt qid Followed protocol from www. ncdtest
Zeolite 31 yo M– 40 gtt qid Followed protocol from Dr. Lyn Hanshew
Metal
MMX Ref
Pre Zeolite
Post Zeolite
EDTA/
DMPS Cd
<.9
0.2 Pb
<4.4
1.1 Hg
<7.4
0.5
Crinnion W. Case Study. Unpublished research
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72. Zeolite 31 yo M – 40 gtt qid Metal MMX Ref Pre Zeolite Post Zeolite
EDTA/
DMPS Cd
<.9
0.2
0.3 Pb
<4.4
1.1
0.1 Hg
<7.4
0.5
0.6
Crinnion W. Case Study. Unpublished research
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73. Zeolite 31 yo M – 40 gtt qid Metal MMX Ref Pre Zeolite Post Zeolite
EDTA/
DMPS Cd
<.9
0.2
0.3
1.3 Pb
<4.4
1.1
0.1 18 Hg
<7.4
0.5
0.6
5.7
Crinnion W. Case Study. Unpublished research
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74. Pre and post testing The ONLY means of assessing Cadmium toxicity
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75. Cd in the CDC 4th Report
Mean
50th
75th
90th
95th
Blood Cd (ug/L)
.304
.300
.500
1.10
1.60
Urinary (ug/g creatinine)
.210
.208
.412
.678
.940
Urinary cadmium reflects both cumulative exposure AND the concentration of cadmium in the kidneys
(accessed 9/17/2013)
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76. Cadmium
2-fold increase in urinary cadmium in non- exposed persons correlated with
73% increased risk of fractures in women
60% increased risk of height loss in men
(By CDC that would be 0.4 ug/g)
Increased urinary cadmium excretion and renal tubular dysfunction were associated with signs of osteoporosis, as measured by bone mineral density, in men and older women.
Staessen JA, et al. Lancet 1999; 353:1140–1144. PMID:
Alfven T, et al. J Bone Miner Res 2000;15(8):1579–1586. PMID:
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77. Cadmium and the kidneys
Kidneys hold the highest burden of Cd
Avg. 20 ug/g nonsmokers, 40 ug/g smokers
Urinary Cd µg/g creatinine associated with renal damage (Sweden)*
Corresponded to mg/kg
ug/g (Japan)**
Urinary Cd of 2.5 µg/g creatinine:
4-fold higher risk of tubular damage
“Significant effects were already seen at a mean level of 0.6 ug/g” ***
*Jarup, et al. Scan J Work Environ Health 1998;24:1-51 PMID:
** Uno, et al. Scan J Work Environ Health 2005;31: PMID:
***Akesson, et al. EHP 2005;113: PMID:
Järup L, Berglund M, Elinder CG, Nordberg G, Vahter M. Health effects of cadmium exposure--a review of the literature and a risk estimate. Scand J Work Environ Health. 1998;24 Suppl 1:1-51. PubMed PMID:
Uno T, Kobayashi E, Suwazono Y, Okubo Y, Miura K, Sakata K, Okayama A, Ueshima H, Nakagawa H, Nogawa K. Health effects of cadmium exposure in the general environment in Japan with special reference to the lower limit of the benchmark dose as the threshold level of urinary cadmium. Scand J Work Environ Health Aug;31(4): PubMed PMID:
Akesson A, Lundh T, Vahter M, Bjellerup P, Lidfeldt J, Nerbrand C, Samsioe G, Strömberg U, Skerfving S. Tubular and glomerular kidney effects in Swedish women with low environmental cadmium exposure. Environ Health Perspect Nov;113(11): PubMed PMID:
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78. Cadmium and ….. Increased risk of developing diabetes
Increased risk of high blood pressure and cardiovascular disease.
Increased risk of obstructive pulmonary disorders
Increased risk of breast, bladder and lung cancer.
Schwartz GG, Yasova DI, Ivanova A. Urinary cadmium, impaired fasting glucose, and diabetes in the NHANES III. Diabetes Care 2003;26:
Menke A, Muntner P, Silbergeld E, Platz E, Guallar E. Cadmium levels in urine and mortality among U.S. adults. Environ Health Perspect 2009:117:
Gallagher CM, Meliker JR. Blood and urine cadmium, blood pressure, and hypertension: A systematic review and meta-analysis. Environ Health Perspect 2012;118:
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79. Treatment Options
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80. Treatment Options The Proven and the UnProven
DMSA (great for lead and mercury)
CaNa2EDTA (great for lead, cadmium, aluminum, nickel)
DMPS (oral or IV – great for mercury)
Commonly used but not substantiated
Chlorella & Cilantro
Metal Free & NDF
Oral CaEDTA
Zeolite
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81. My Treatment Protocols for the D’s
DMPS
3mg/kg IV (up to 250mg)
10mg/kg po
Once every 2-4 weeks
Bowel Cleansing
Mag Sulf. 2 cc after each shot
Supportive nutrients
DMSA
10 mg/kg tid (up to 2250mg daily)
5 days on, 9 days off****
Bowel Cleansing
Mag sulf 2 cc after each week on
Supportive nutrients
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82. DMSA options if cleansing reactions are too intense.
2 days on (weekends) followed by 5 days off.
Lower levels of DMSA given every 4 hours (patients does NOT need to wake themselves up at night for this)
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83. Hg clearing with DMSA 30mg/kg/day in 9 children
Forman J, Moline J, Cernichiari E, Sayegh S, Torres JC, Landrigan MM, Hudson J, Adel HN, Landrigan PJ. A cluster of pediatric metallic mercury exposure cases treated with meso-2,3-dimercaptosuccinic acid (DMSA). Environ Health Perspect Jun;108(6): PubMed PMID:
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84. EDTA, DMPS and DMSA
Day 1 – EDTA (2,000 – 3,000mg CaNa2EDTA and saline or sterile water) [50mg/kg] - Flush line with 3cc saline - DMPS (body weight) with saline or sterile water Day 2 – 6 - DMSA oral per body weight in 3 divided doses Day 7 – 14 - Heavy metal support - Colonics - Mag sulf
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85. Relative Affinities of chelators
DMPS
Mercury
Lead
Silver
Cadmium
Nickel
Arsenic
Antimony
Copper
Molybdenum
Zinc
Manganese
DMSA
Lead
Cadmium
Mercury
Silver
Nickel
Arsenic
Molybdenum
Copper
Zinc
Manganese
Iron
Tin
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86. Suppositories DMSA suppositories at 20 mg/kg
EDTA (Detoxamin) 750mg nightly
Supplement with Zn in daytime
50% decrease in Pb in 3 months
Neither seem to work as a flush-test agent
D. Quig, personal communication
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87. The unproven
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88. Rachel 35 y.o. female wanting to conceive
April 5- H/O Hg fillings recently removed
7 months of detox with Metal Free + more from local D.C.
Eats fish
Blood Hg levels
3/10/04 Hg 10
4/5/04 Hg 11
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89. Pre and Post Tests Metal Free and DMSA
DDI ref
Pre Metal Free
Post Metal Free
Post DMSA Cd
<2
0.3 Pb
<5
<dl Hg
<4
1.9
0.7 Ni
<10
1.5
1.1
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90. Pre and Post Tests Metal Free and DMSA
DDI ref
Pre Metal Free
Post Metal Free
Post DMSA Cd
<2
0.3
0.7 Pb
<5
<dl 28 Hg
<4
1.9 33 Ni
<10
1.5
1.1
2.1
Copyright WCrinnion 2013
Crinnion, W. Unpublished research

91. Clinical Study : Chlorella and Mercury Excretion
Test popular, unsubstantiated belief that “chlorella enhances biliary/fecal excretion of mercury”
No published human studies available to date regarding metal detoxification
Japanese research pertaining to growth stimulating effects in animals and humans
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92. Chlorella (pyrensoida)
Single celled marine algae (green)
Triple cell wall (cellulose microfibrils)
High protein and chlorophyll content
Metal binding capacity (ponds)
Absorption from human gut?
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93. CONCLUSIONS
No effect of 8-10 gm chlorella/day on fecal excretion of Hg in subjects with average intestinal Hg exposure
Undesirable GI side effects in all subjects
2/7 subjects exhibited trend for increased urinary Hg excretion (AA deficiencies?)
D. Quig, unpublished research
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94. Contraindications ?
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95. Length of treatment Standard Protocol at my old clinic
Retest urine every ten weeks
20% are cleared by twenty weeks
60% are cleared by 30 – 50 weeks
20% take more than 50 weeks
If lead is present repeat as needed.
Combination EDTA, DMPS and DMSA are giving very rapid cleansing results
And causing some increased LFTs!
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96. Pros and Cons
DMPS Pro Ease of use Great for Hg Con Legality Cannot reduce dose once it is given
DMSA Pro Easy manipulation of dose to adverse responses Great for lead Con Amount of capsules Sulfur reaction
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97. Adverse cleansing effect
Generally begin to show up on the third or fourth “round”.
Usually begin on day three of taking DMSA.
Can be relieved by:
Activated charcoal
Colonic irrigations
Reduction of DMSA intake (no help with DMPS)
Mentharil for GI problems with DMSA
Copyright WCrinnion 2013

98. Adverse Effects of Cleansing
Sulfur
Nausea
Diarrhea
Belching
Arsenic
Fatigue
Irritability
Blistering on
mucus mem
Bruising on
face
Hive-like rash
Mercury
Insomnia
Anxiety
Depression
Anger
Copyright WCrinnion 2013
Crinnion, W. Unpublished research

99. Don’t forget the colonic
70% of methylmercury is recirculated via enterohepatic recirculation!
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