This document discusses mercury intoxication and detoxification strategies. It describes the various forms and sources of mercury including methylmercury from fish, elemental mercury from dental amalgam, and ethylmercury from vaccines. It outlines the pathways mercury takes to enter and exit the body, including accumulation in tissues. The key aspects of the human detoxification system involving phases I, II, and III are explained. Issues with breakdown or dysfunction of this system leading to mercury retention are covered. The document proposes a therapeutic detoxification system using Intestinal Metals Detox, Clear Way cofactors, and liposomal agents to augment and amplify the natural detoxification pathways and facilitate mercury removal. Clinical trial results and individual case studies

1. Quicksilver Therapeutic Detoxification System:
Understanding Detoxification Strategies for Mercury
Intoxication
Christopher W. Shade, PhD
Andrew Elias, CLSSBB
Quicksilver Scientific, LLC
Lafayette, CO 80026
(303) 531-0861
www.quicksilverscientific.com

2. Forms and Sources of Mercury
• MeHg - Methylmercury
– Organomercurial; found in fish; Also formed
in gut from amalgam mercury
• Hg0 – Elemental Mercury
– The metal form; liquid and gas forms; dental amalgam
• HgII – Inorganic Mercury
– The salt, formed by oxidation of Hg0 in blood and mouth
• EtHg - Ethylmercury
– Synthetic organomercurial; antimicrobial
– Ends up mostly as HgII

3. Pathways In – Dental Amalgam
Hg
0
breaks down to
inorganic mercury (Hg
II
).
Hg
0
distributes throughout
body and nervous
system.
Image from the International
Academy of Oral Medicine
and Toxicology.
Hg
II
accumulates in
the nervous system, liver,
and kidney.
Hg
0
released from
amalgam and inhaled with
80% uptake in the lungs.
Amalgams: Pathway of Exposure
80% Uptake

4. Pathways In – Fish Consumption
MeHg
MeHg
Chemical reactions in the
gut add MeHg to an amino
acid.
Fish contaminated with
methylmercury (MeHg) get
eaten.
MeHg diffuses out of the
gut and circulates
throughout the body,
because it gets mistaken
as an amino acid.
Methylmercury
accumulates in
the body.
Seafood: Pathway of Exposure
95% Uptake

5. Pathways In – Vaccines
EtHg
Hg
II
accumulates in
the body.
EtHg distributes
throughout the body and
nervous system.
EtHg probably does not
leave the body, but enters
tissues and breaksdown
into inorganic mercury
(HgII
).
Ethylmercury (EtHg)
enters the blood through
vaccination
EtHg leaves the blood
after a few days.
Vaccination: Pathway of Exposure
100% Uptake

6. Pathways Out – Methylmercury

7. Pathways Out – Inorganic Mercury
Both Intestinal and Kidneys

8. Heavy Metal Defense – Glutathione
System
Antioxidant, Detoxification, Protein Repair
• Glutathione (GSH) - A thiolic tripeptide
composed of glutamate, cysteine, and glycine
**Binds Inorganic and Methyl Mercury
and escorts out of body**

9. • Detoxification Phases I, II, III
–Phase I is an activation,
–Phase II is conjugation (mobilization)
–Phase III is transport (recently
delineated; control point; elimination)
The Human Detoxification
System

10. • Phase I
– Prepares toxin for conjugation in Phase II
– Not needed for metals, but very important to
have correctly coupled to Phase II
• Creates Essentially Free-Radicals to be used in
Phase II
The Human Detoxification
System

11. • Phase II – conjugation makes toxin more
water soluble and recognizable by
transporters
– Glutathione S-Transferases (GST)
responsible for Glutathione conjugation
• Transfers Mercury (Hg) from protein-bound sites to
Glutathione for transport out
The Human Detoxification
System

12. • Phase III is the transport out!
– Several transport proteins (cMOAT, OAT,
MRP1, MRP2, GS-X)
– Same transporters for many pathways
– In cells, liver, intestines, kidneys – biggest in
liver then intestines then kidneys
The Human Detoxification
System

13. Breakdown of the Defense
System
• GSH deficiency –
– Genetic (GCS polymorphisms, epigenetic dysfunction)
– Environmental (oxidative consumption or inflammation)
• GST problems –
– Genetic (GST polymorphisms, epigenetic dysfunction)
– Environmental (Inflammatory cascade/ARE dysfunction)
• Phase III can get blocked and then
downregulates Phase II enzymes
– Can stop multiple detoxification pathways!

14. Biggest Reason for Phase III
Dysfunction
Inflammation!
Especially in Gut!
-Hallmark of Autism cases
-Easily caused by heavy metal induced
oxidative damage

17. Phase I
Phase III
Phase II
Glutathione
Conjugation
Sulfation Glucuronidation
OATP
Blood
LIVER
MRP2
Normal Small Intestine
Cellular MRP1
Oxidative Activation

18. Phase I
Phase III
Phase II
Glutathione
Conjugation
Sulfation Glucuronidation
OATP
Blood
LIVER
MRP2
Inflamed Small Intestine
Cellular MRP1
Oxidative Activation

19. Phase I
Phase III
Phase II
Glutathione
Conjugation
Sulfation Glucuronidation
OATP
Blood
LIVER
Inflamed Small Intestine
Cellular MRP1
Oxidative Activation
Inflammation
causes
Downregulation
of MRP2
Negative
Feedback –
Inhibition of
Phase II
MRP2

20. Phase I
Phase III
Phase II
Oxidative Activation
Glutathione
Conjugation
Sulfation Glucuronidation
OATP
Blood
LIVER
MRP2
Inflamed Small Intestine
Cellular MRP1
Negative
Feedback –
Inhibition of
Phase II
Inflammation
causes
Downregulation
of MRP2
Oxidative Stress From
Phase I/Phase II mismatch
Build-up of both
cellular and
blood-borne
toxins
Oxidative Activation

21. Pathways Out – Amalgam Poisons
Intestinal Function
Corrosion Products of Amalgam
(Inorganic Hg) are swallowed with saliva
and create inflammation
Phase I
Phase III
Phase II
Oxidative Activation
Glutathione
Conjugation
Sulfation Glucuronidation
OATP
Blood
LIVER
MRP2
Inflamed Small Intestine
Cellular MRP1
Negative
Feedback –
Inhibition of
Phase II
Inflammation
causes
Downregulation
of MRP2
Build-up of both
cellular and
blood-borne
toxins
Oxidative Activation

23. Pathways Out – Gut Blocked
Toxin Retention and
High Stress on
Kidneys
Then Kidneys Weaken
from Constant Load
and Can’t Filter Hg
= Even More
Retention
Intestinal Load
Goes to Kidneys
Excretion Rates
Decrease
Kidney Load
Increases
Gut Inflames,
Blocking Exit

24. Pathways Out – Amalgam Poisons
Intestinal Function
Corrosion Products of Amalgam
(Inorganic Hg) are swallowed with saliva
and create inflammation
Phase I
Phase III
Phase II
Oxidative Activation
Glutathione
Conjugation
Sulfation Glucuronidation
OATP
Blood
LIVER
MRP2
Inflamed Small Intestine
Cellular MRP1
Negative
Feedback –
Inhibition of
Phase II
Inflammation
causes
Downregulation
of MRP2
Build-up of both
cellular and
blood-borne
toxins
Oxidative Activation

25. Removal of Hg
Amplifying and Augmenting Natural
Detoxification Systems with IMD,
Clear Way Cofactors and
Nanosphere Liposomal Agents

26. Biochemical Hg Removal
Requirements
1. Intracellular Glutathione Sufficiency
2. Effective GST Activity (Phase II-
Mobilization)
3. Effective Phase III Clearance including
intestinal binding and Elimination

27. System for Intestine-Based
Metals Detoxification
1. IMD Intestinal Cleanse
- Opens Phase III and Stops Reabsorption
2. Clear Way Cofactors Phytonutrients
- Upregulate Synthesis of Phase II enzymes and
Intra-Cellular Antioxidants
3. Nanosphere Glutathione Support
- Liposomal EDTA with R-Lipoic Acid
- Liposomal Vitamin C with R-Lipoic Acid
- Liposomal Glutathione

28. System for Therapeutic
Metals Detoxification
• Intestinal Metals Detox (IMD)
– Use Intestines NOT Kidneys for Metal Removal
– NON-ABSORBED silica particles saturated with
strong (thiol) binding groups
– Binds Mercury in the intestines and moves out of
body
• Opens Phase III transporters
• Stops Enterohepatic Circulation (Reabsorption)
• Restores and Amplifies on the Natural
Detoxification System

29. Phase I
Phase III
Phase II
Glutathione
Conjugation
Sulfation Glucuronidation
OATP
Blood
LIVER
MRP2
Normal Small Intestine
Cellular MRP1
Oxidative Activation
Phase I
Phase III
Phase II
Oxidative Activation
Glutathione
Conjugation
Sulfation Glucuronidation
OATP
Blood
LIVER
MRP2
Inflamed Small Intestine
Cellular MRP1
Negative
Feedback –
Inhibition of
Phase II
Inflammation
causes
Downregulation
of MRP2
Oxidative Stress From
Phase I/Phase II mismatch
Build-up of both
cellular and
blood-borne
toxins
Oxidative Activation
Correct Phase III Elimination

30. Phase III Enhancement
Bilirubin (unrelated to GSH) falls too
Table 2. Bilirubin Levels on Select Patients with
Elevated Blood Bilirubin (From Clinics 1 & 2, 7-
10 interventions)
Before After % Change
2 1.1 -45
1.7 0.9 -47.1
1.4 1.3 -7.1
1.2 0.9 -25.0
3.4 2.6 -23.5
1.7 1.2 -29.4
Phase I
Phase III
Phase II
Glutathione
Conjugation
Sulfation Glucuronidation
OATP
Blood
LIVER
MRP2
Normal Small Intestine
Cellular MRP1
Oxidative Activation

31. Accumulation
Enterohepatic Circulation
of Hg
Drainage
IMD Blocking Enterohepatic
Circulation of Hg
LOW EXCRETION HIGH EXCRETION!
Stop Reabsorption

32. Half-life times – Iraq Poisoning
Genetically Sensitive Population ~12%

33. Pathways Out – Clear Way
= Greatly Facilitated
Elimination!!!
Transporters Open
& Recirculation
Interrupted

34. IMD Decreases Half-Life in Blood
With IMD
½-Life ~ 17 days
To Baseline = 40 days
No Treatment (Walleye)
½-Life = 46-66 days
Up to 120 days - Iraq
To Baseline = 160+ days
0
0.2
0.4
0.6
0.8
1
1.2
1.4
08/10/08 08/20/08 08/30/08 09/09/08 09/19/08 09/29/08 10/09/08 10/19/08 10/29/08
BloodMeHg(ng/mL)
0.000
0.050
0.100
0.150
0.200
0.250
0.300
0.350
FecalMeHg(ng/g-ww)
blood MeHg
Fecal MeHg Excretion

35. Small Clinical Trial Results
Clinic 1
IMD (n=8) No Treatment (n=4)
%Decr HgT 23.9 0.4
%Decr MeHg 22.9 5.1
%Decr HgII 12.4 ‐4.1
Changes in Blood Mercury Levels during 7-10 day
intervention with amalgam removal and nutritional
treatment
~20% change typical in first 1-2 weeks followed by gradual lowering as
mercury is displaced from cells into blood following initial rapid lowering

36. Individual Cases
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 10 10.5
Concentration of Mercury (ng/mL or ug/L)
HgT
Hg(II)
MeHg
Before Blood Mercury Comparison
3/14/2009
12/10/2008
QS Average
Methylmercury
Inorganic Hg
Total Hg
Patient #1: Fish Consumption Ceased
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7
Concentration of Mercury (ng/mL or ug/L)
HgT
Hg(II)
MeHg
Before Blood Mercury Comparison
8/8/2008
1/23/2009
QS Average
Methylmercury
Inorganic Hg
Total Hg
Patient #2: Fish Consumption Continued
Even with Continuous
Exposure, Levels Fall!

37. Patient – Methylmercury Suspected
Detox Enzyme Deficiency
30% Removal of MeHg in 2 months
80% Removal of MeHg in 6 months
90% Removal of HgII in 6 months
0 2 4 6 8 10 12 14 16 18 20
1
2 2/12/209
4/16/2009
5/7/2009
7/8/2009
8/25/2009
Hg(II)
MeHg

38. Hg Detox Product Comparison
Material
Area of
Action
Hg-specific
Binding
Safety Efficacy Risks
IMD Intestinal Yes High High Low
DMSA
Blood/
Kidney
Yes Low High
Kidney, Liver,
Demineralization
DMPS
Blood/
Kidney
Yes Low High
Kidney, Liver,
Demineralization
EDTA
Blood/
Kid/Intest
No Moderate Moderate Demineralization
Zeolite Intestinal No High Low Demineralization
Chlorella Intestinal No High Low Low
Combines Strength of Pharmaceuticals (DMSA and
DMPS) with the Safety of Zeolite and Chlorella!

39. System for Therapeutic
Metals Detoxification
1. Intestinal Metals Detox (IMD)
-Opens Phase III and Stops Reabsorption
2. Clear Way Cofactors Phytonutrients
- Upregulate Synthesis of Phase II enzymes and
Intracellular Antioxidants
1. Glutathione Support
-N-Acetyl Cysteine, Vitamin C, Alpha Lipoic Aced,
Phytonutrients
-Liposomal GSH

40. Chemoprevention by Keap1-Nrf2 Signaling
Pathway by Phase II Inducers
Kwak et al., 2004, Mutation Research, 555:133-148

41. “Phytogenomics”
• Certain Phytochemicals upregulate Phase II
enzymes as well as GSH, SOD (cellular
antioxidants)
• The Anti-Inflammatory Cascade
• Polyphenolic Antioxidants
• Sulfur compounds
– Alpha Lipoic Acid
– Crucifers
– Garlic oil

42. Polyphenolics
• Anti-inflammatory cascade
• Upregulate Phase II enzymes through
binding to membrane and nuclear receptors
(transcription factors)
• Vascular protective effects (strengthen
capillaries and improve oxygen delivery)
• Anti-carcinogenic
• Cross Blood-Brain Barrier

43. Flavanols (Polyphenolics)
Epicatechin – in green tea,
cocoa; monomer for OPC’s from
Pine Bark, Grape seeds
Ellagic Acid -
Pomegranates
Quercetin – Fruit and
Vegetable Skins

44. Clear Way
Polyphenolic:
Haritaki

45. Coordinated Expression of Phase II
and III
MRP2 and GSTπ co
regulated

46. Clear Way Cofactors
Ingredient per 3 caps % DV
Vitamin B1 100 mg 6667
Vitamin B6 125 mg 6250
Vitamin B5 100 mg 1003
Iodine 450 mcg 300
as Kelp Extract
Selenium 200 mcg 286
as Selenomethionine
Na-form R-Lipoic Acid 150 mg -
Lumbrokinase 20 mg -
20,000 units/mg
Kelp Extract 100 mg -
Proprietary Blend: 1205 mg
Haritaki Extract ** -
45% Tannins
Pomegranate Extract ** -
40% Ellagic Acid
Quercetin ** -
Pine Bark Extract ** -
95% OPC
Gotu Kola Extract ** -
10:1
Dandelion Extract ** -
12:1
Other Ingredients: Gelatin (capsule), rice bran

47. System for Therapeutic Metals
Detoxification
1. Intestinal Metals Detox (IMD)
-Opens Phase III and Stops Reabsorption
2. Phytonutrients – Clear Way Cleanse Cofactors
- Upregulate Synthesis of Phase II enzymes and
Intracellular Antioxidants
3. Nanosphere Glutathione Support
Liposomal Vitamin C with R-Lipoic Acid
Liposomal Glutathione
Liposomal EDTA with R-Lipoic Acid

48. Liposomes
Liposomal Encapsulation
•Nanosphere Essential Phospholipid
(EPL) bilayer (100-150 nanometers)
•Bypasses peptidases that break down
glutathione and barrier to EDTA and high-
dose Vitamin C
•Direct absorption in upper intestine
•Evidence of cellular absorption
•Macrophage oxidative damage protection

49. Therasomal Detox
Liposomal Encapsulation
•Same Essential Phospholipid (EPL)
source as Lipostabil – injectable grade
•1.8g/tsp.
•Near complete absorption
•R-Lipoic Acid (much stronger and more
anti-inflammatory than RS-ALA)
•Mix of Na, Ca, Mg, and K-EDTA
Strengthen effect on Pb, Cd, As, and Ni
Extend Detox out to the Hard metals – Al

50. Can L-GSH Improve GSH
Concentration across Membranes?
• Neuron cell culture depleted of GSH by DEM (diethyl
maleate)
• L-GSH was > 100-fold more potent than plain GSH in
solution (non-L-GSH) in replenishing intracellular
GSH
EC50 GSH
Plain GSH
575 µM
Mol Wt. GSH -
304
Liposomal GSH
4.75 µM
Zeevalk G, Guilford F, Bernard L. Liposomal glutathione for replenishment and
maintenance of intracellular glutathione in mesencephalic cultures. Abstract
Neuroscience 2009: Soc. for Neuroscience 2009 Chicago, Oct 17, 2009