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![Page 1: Looking Inside the Black Box: Understanding Analytical Approaches, Diagnostic Tools, and Detoxification Strategies for Mercury Intoxication Christopher.](https://reader038.fdocuments.us/reader038/viewer/2022110400/56649dab5503460f94a99d25/html5/thumbnails/1.jpg)
Looking Inside the Black Box: Understanding Analytical Approaches, Diagnostic Tools, and Detoxification Strategies for Mercury Intoxication
Christopher W. Shade, [email protected]
Quicksilver Scientific, LLCLafayette, CO 80026
(303)263-6903Here
tical C
ontent
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Mercury and The Human Detoxification System
1. What the key forms of Hg are
2. How the Natural Detoxification System Works
3. How the Detox System gets subverted leading to biochemical stress
4. Mercury Analysis (Blood is not a dirty word)
5. Intestinal Metals Detox System to repair and amplify the bodies Detoxification System and safely remove mercury
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Forms of mercury• Hg0 – Elemental Mercury
– The metal form; both liquid and gas forms
• HgII – Inorganic Mercury– The salt, formed by oxidation of Hg0
• MeHg - Methylmercury– Organomercurial, formed by bacterial
synthesis
• EtHg - Ethylmercury– Synthetic organomercurial; antimicrobial
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Transport of mercury• Hg0
– 80% uptake in lungs, crossed BBB, diffuses in to tissues; moderate uptake from intestines
• HgII
– Very poor uptakes in intestines; poor mobility; does not cross BBB
• MeHg – 95% uptake from intestines, good mobility, crosses
BBB
• EtHg – 100% absorbtion (inj), good mobility, crosses BBB
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Targets of mercury forms
• Brain/CNS
• Kidney
• Liver
• Heart
• Pituitary/Thyroid– And thus all glandular
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The Heart of the Toxicity
1. Inappropriate Binding – enzymes, redox proteins, membranes
2. Oxidative Damage and related Inflammation, including membrane damage (Parinanada) and apoptosis (cell death)
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The Heart of the Toxicity
• Thiol Binding and Redox Reaction– Reduced sulfur groups, R-SH, – Hg replaces proton and binds to sulfur
• R-SH + Hg2+ = R-SHg+ + H+
– Enzymes use thiols to anchor functional metals (Zn, Ni, Cu, Fe)
– Bind and alter membrane or trigger membrane reorganization and consequent auto-oxidation
– Oxidize Thioredoxin (protein repair molecule)– Deplete Glutathione system
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Inorganic Hg and Poisoning of the Extracellular Matrix
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Mercury and The Human Detoxification System
1. What the key forms of Hg are
2. How the Natural Detoxification System Works
3. How the Detox System gets subverted leading to biochemical stress
4. Mercury Analysis (Blood is not a dirty word)
5. Intestinal Metals Detox System to repair and amplify the bodies Detoxification System and safely remove mercury
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Defense – Glutathione System Antioxidant, Detoxification, Protein Repair
• Glutathione (GSH) - A thiolic tripeptide composed of glutamate, cysteine, and glycine
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Defense – Glutathione System Antioxidant, Detoxification, Protein Repair
• Synthetases (synthesize GSH from precursors) • Transpeptidases (take apart and reassemble)• Transferases (Phase II conjugation)• Peroxidases (radical quenching)• Reductases (repair after quenching)• Redoxins (using GSH as reducing equivalent for
protein repair)• Glutathionylation – protection of Proteins
– What to do? Quench the fire or protect the children?
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• Detoxification Phases I, II, III– Phase I is an activation,
– Phase II is conjugation
– Phase III is transport (recently delineated; control point)
The Human Detoxification System
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• Phase I - an oxidative activation, usually the Cytochrome P450 system– Prepares toxin for conjugation in Phase II with
GSH, Glucuronic acid, Sulfate, Gycine or other amino acid, Taurine, Methyl group
– Not needed for metals, but very important to have coupled to Phase II
• Creates Essentially Free-Radicals
The Human Detoxification System
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• Phase II – conjugation makes toxin more water soluble and recognizable by transporters– Glutathione S-Transferases (GST)
responsible for GSH conjugation– Low expression in people with high MeHg and
with sensitivity (allergy) to Thimerosal (EthylHg)
The Human Detoxification System
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• Phase III is the transport out!– Several transport proteins (cMOAT, OAT,
MRP1, MRP2, GS-X)• Organic Anion Transporters
– Same transporters for many pathways (glucuronide, sulfate, glycinate, GSH)
– In cells, liver, intestines, kidneys – biggest in liver then intestines
The Human Detoxification System
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Mercury and The Human Detoxification System
1. What the key forms of Hg are
2. How the Natural Detoxification System Works
3. How the Detox System gets subverted leading to biochemical stress
4. Mercury Analysis (Blood is not a dirty word)
5. Intestinal Metals Detox System to repair and amplify the bodies Detoxification System and safely remove mercury
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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)
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Disease and Gen Polymorphisms of GSH genes
• Hemolytic Anemia – GST (Beutler et al 1988)• Sensitivity to DDT – GCS and GST (Hung et al.
2004)• Bladder Cancer (Hung et al. 2004)
– O.R. GSTM1 = 1.69– O.R. GSTT1 = 1.74– O.R. GSTM1 + Env Exposure = 2.77
• Acute leukemia – GST
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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!
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Biggest Reason for Phase III Dysfunction
Inflammation!
Especially in Gut!-Hallmark of Autism cases
-Easily caused by heavy metal induced oxidative damage
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Coordinated Expression of Phase II and III
MRP2 and GSTπ coregulated
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Phase I
Phase III
Phase IIGlutathione Conjugation
Sulfation Glucuronidation
OATPB
lood
LIVER
MRP2
Normal Small Intestine
Cellular MRP1
Oxidative Activation
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Phase I
Phase III
Phase IIGlutathione Conjugation
Sulfation Glucuronidation
OATPB
lood
LIVER
MRP2
Inflamed Small Intestine
Cellular MRP1
Oxidative Activation
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Phase I
Phase III
Phase IIGlutathione Conjugation
Sulfation Glucuronidation
OATPB
lood
LIVER
Inflamed Small Intestine
Cellular MRP1
Oxidative Activation
Inflammation causes
Downregulation of MRP2
Negative Feedback – Inhibition of Phase II
MRP2
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Phase I
Phase III
Phase II
Oxidative Activation
Glutathione Conjugation
Sulfation Glucuronidation
OATPB
lood
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
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Amalgam as Cause for Inflammation Cysteine Mouth Rinse
[min.]Time
620 640 660 680 700
[V]
Vol
tage
0.0
0.5
1.0
C:\Clarity\WORK1\20090224_Chrom_200908_0023 ARDL Waters
614.
810
48
627.
340
49
630.
537
50
644.
467
51
648.
993
52
663.
460
53
667.
730
54
680.
447
55
685.
300
56
699.
743
57
702.
963
58
[min.]Time
1540 1560 1580 1600 1620
[V]
Vol
tage
-0.5
0.0
0.5
1.0
C:\Clarity\WORK1\20090224_Chrom_200908_0023 ARDL Waters
1539
.837
1
05
1553
.067
1
06
1557
.593
1
07
1570
.753
1
08
1575
.140
1
09
1589
.303
1
10
No Amalgam 25ppt MeHg, 5ppt HgII
Amalgam – 10ppb
Amalgam (2nd Rinse) – 16ppb
[min.]Time
620 640 660 680 700
[V]
Vol
tage
0.0
0.5
1.0
C:\Clarity\WORK1\20090224_Chrom_200908_0023 ARDL Waters
614.
810
48
627.
340
49
630.
537
50
644.
467
51
648.
993
52
663.
460
53
667.
730
54
680.
447
55
685.
300
56
699.
743
57
702.
963
58
Amalgam – 10ppb
MeHg
HgII
MeHg
HgII
MeHg
HgII
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MeHg Mitochondrial Inferno – Breakdown of the Thiolic Protection System
Mitochondrial Stress – The MeHg-induced Blaze
Leaking ROS and cyt c
ROS and Hg Oxidize TrX
1) Covering Exposed Thiols
2) Mopping up ROS
3) Binding Hg
TrX releases ASK1
Decay in GSH
Insufficient Protection
from GSH
Apoptosis – Cell Death
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Mercury and The Human Detoxification System
1. What the key forms of Hg are
2. How the Natural Detoxification System Works
3. How the Detox System gets subverted leading to biochemical stress
4. Mercury Analysis (Blood is not a dirty word)
5. Intestinal Metals Detox System to repair and amplify the bodies Detoxification System and safely remove mercury
![Page 32: Looking Inside the Black Box: Understanding Analytical Approaches, Diagnostic Tools, and Detoxification Strategies for Mercury Intoxication Christopher.](https://reader038.fdocuments.us/reader038/viewer/2022110400/56649dab5503460f94a99d25/html5/thumbnails/32.jpg)
Testing for Hg
1. Ambient Measures
1. Blood
2. Hair
3. Urine
4. Stool
2. Provoked Measure
1. Urine
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Testing for Hg
1. Ambient
1. Blood – MeHg + HgII (MeHg larger)
2. Hair – MeHg only
3. Urine – HgII (little bit of MeHg)
4. Stool – MeHg + HgII
2. Provoked
1. Urine – MeHg + HgII
H
HH
Hg
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Challenge Tests – What do they mean? Are They Necessary?
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Mercury Industry Workers
Dentists
Controls (Amalgam)
Amalgam-free Referents
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Mercury Industry Workers
Dentists
Controls (Amalgam)
Amalgam-free Referents
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Chelation therapy – Dump from blood followed by reloading from cellular
burden
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Mercury Speciation Testing
• Separates the two main forms of mercury in the human body– Once separately measured, ambient
measurements reveal A LOT without challenge tests
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Whole Blood vs. RBC
• Partitioning between RBC and plasma different for MeHg and HgII
– MeHg 90% RBC/10% Plasma• Access to brain, intracellular, metabolic-heme
– HgII 50%/50% • Lymph an extension of plasma: ~5X the volume of blood• Extracellular Matrix, also concept of terrain
– Look at both forms with whole blood
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Inorganic Hg and Poisoning of the Extracellular Matrix
…Uhhh, What Matrix?
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MethylMercuryThe Unsuspected Factor H
HH
Hg
1. Direct toxicity not as high as Hg(II)
1. One binding site vs. 2 major and 2 minor
2. BUT…has many insidious properties
3. Is slow to excrete bank of mercury
1. Constant source of inorganic mercury from breakdown
1. Can continue symptoms of hypersensitivity from amalgam after amalgams removed
4. Has “all-access pass”
1. Intracellular, BBB, placental barrier
5. Can form allergy that will persist till all gone
6. If phase II enzymes weak, can stay for long, long time
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Accumulation
Enterohepatic Circulation of MeHg
H
HH
Hg
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Blood Testing
• Old Dictum – blood is only recent exposure, 3-days
• Reality– 3-day residence only the quick decay after a large
dose– For MeHg, Steady state develops after initial decay;
Then blood reflects body burden!
• Real Problem– Most labs detection limits too high to see dynamics– Need sensitive equipment!
H
HH
Hg
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Blood Testing: The Great Tuna Experiment
• 2 cans of Albacore Tuna in one sitting
2 hours later
24 hours later
2 hours later
24 hours later
0.00
0.50
1.00
1.50
2.00
2.50
10/26/2008 10/27/2008 10/28/2008 10/29/2008 10/30/2008 10/31/2008
Blo
od
MeH
g (
ng
/mL
)
2 hours later
24 hours later
Initial Decay – Redistribution to Tissues
Pre-Tuna
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The Great(er) Walleye Experiment*Nothing is new under the sun*
Clarkson et al., Arch. Env. Health, 1980
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Walleye Experiment – Decay and Body Burden
After initial peak and decay, Blood reflects Body Burden!
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Mercury Speciation Testing
H
HH
Hg
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[min.]Time
4020 4030 4040 4050 4060
[mV]V
olta
ge
-600
-400
-200
0
200 My GC - 6 (05.August 2008)
4019
.867
3
41
4024
.440
3
42
4037
.647
3
43
4042
.010
3
44
4055
.427
3
45
4059
.930
3
46
MeHg
HgII
MeHg
HgII
H
HH
Hg
Testing for MeHg
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Mercury Speciation Testing and Compartment Ratio Testing
Ambient Measurement Suite
1. Blood – MeHg + HgII
2. Hair – MeHg only
-Compare to blood MeHg for excretion measurement
3. Urine – HgII
-Compare to blood inorganic mercury for excretion measurement
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Dentist Levels - Healthy
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Dentist Levels – Chronic Inflammation
I n dicat ion of M er cur y E xcr et ion A bilit y
0
4 00
-1 2 0 -1 00 -8 0 -6 0 -4 0 -2 0 0 2 0
B lo o d Me Hg (n g /mL )
Below Average Excretion of blood mercury through the hair.
Average Excretionof blood mercury though the hair (290:1).
Indication of Mercury Excretion Ability
0
400
800
1200
1600
2000
2400
2800
0 2 4 6 8 10
Blood MeHg (ng/mL)
Hai
r M
eHg
(n
g/g
)
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Dentist Levels – Kidney Problem
0 0.5 1 1.5 2 2.5
Concentration of Mercury (ng/mL or ug/L)
HgT
Hg(II)
MeHg
Blood Mercury
Patient BloodQS Average
I n dicat ion of M er cur y E xcr et ion A bilit y
0
4 00
-1 2 0 -1 00 -8 0 -6 0 -4 0 -2 0 0 2 0
B lo o d Me Hg (n g /mL )
Average Excretionof blood mercury though the hair (290:1).
Below Average Excretion of blood mercury through the hair.
Indication of Mercury Excretion Ability
0
400
800
1200
0 1 2 3 4 5
Blood MeHg (ng/mL)
Hai
r M
eHg
(n
g/g
)
Indication of Kidney Mercury Excretion Ability
0.000.50
1.001.50
2.002.50
3.003.50
4.004.50
5.00
0 0.5 1 1.5
Blood Hg(II) (ng/mL)
Uri
ne
Hg
(II)
(n
g/m
L)
Good Hg(II) Excretion Line (7:1)
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Patient – MeHg: Detox Enzyme Defficiency
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Hg Retention – Hair:Blood
0
200
400
600
800
1000
1200
0.000 1.000 2.000 3.000 4.000 5.000
Blood MeHg (ng/mL)
Hai
r M
eHg
(n
g/g
)
0
100
200
300
400
500
600
700
0.000 1.000 2.000 3.000 4.000 5.000
Blood MeHg (ng/mL)
Hai
r:B
lood
MeH
g ra
tio
Normal Excretion
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Problem of Toxicity Diagnosis
• Levels can not show toxic response
• Toxic response from – Abilities of your defense systems– Hyper-sensitivities/Allergies developed during
exposure
• Must be Diagnosed from combination of: – Clinical Symptomology, and– Auxiliary Testing
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Auxiliary Testing
• Allergy Testing – MELISA, ELISA• Porphyrins – stress to ATP cycle and to kidneys• GSH Levels – antioxidant/detoxifier defense• GST Activity• Trx and TrxR• Genetic Susceptibilities
– GCL, GSTm, GSTp, ApoE, CPox
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Mercury and The Human Detoxification System
1. What the key forms of Hg are
2. How the Natural Detoxification System Works
3. How the Detox System gets subverted leading to biochemical stress
4. Mercury Analysis (Blood is not a dirty word)
5. Intestinal Metals Detox System to repair and amplify the bodies Detoxification System and safely remove mercury
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Removal of HgAmplifying and Augmenting Natural
Systems
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Biochemical Hg Removal Requirements
1. Intracellular Glutathione Sufficiency-Liposomal gets in some cells-Transpeptidases dissemble/reassemble
2.Effective GST Activity (Phase II - mobilization)
3.Effective Phase III Clearance including intestinal binding
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Product/System for Intestinal Detoxification
1. Intestinal Metals Detox (IMD)
-Phase III opener (dietary supplement)
2. Phytonutrients – Antioxidant Response Element
- Upregulate Transcription of Phase II, GSH, SOD via ARE
3. Source of GSH
-ReadiSorb Liposomal GSH; Livon Labs
-Nutritional Therapy; OSR
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Product/System for Intestinal Detoxification
• Intestinal Metals Detox (IMD)– Use Intestines NOT Kidneys for Metal Removal
– Insoluble (NON-ABSORBED) silica particles saturated with strong (thiol) binding groups
– Binds Mercury in Intestines and moves out of Body
• Interrupts Enterohepatic Circulation
• Opens Phase III transporters– Bilirubin levels fall dramatically too!
• Then relies on the Natural Detox System (GSH)
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Phase I
Phase III
Phase II
Oxidative Activation
Glutathione Conjugation
Sulfation Glucuronidation
OATPB
lood
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
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Phase I
Phase III
Phase IIGlutathione Conjugation
Sulfation Glucuronidation
OATPB
lood
LIVER
MRP2
Normal Small Intestine
Cellular MRP1
Oxidative Activation
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Phase III EnhancementBilirubin (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 IIGlutathione Conjugation
Sulfation Glucuronidation
OATP
Blo
od
LIVER
MRP2
Normal Small Intestine
Cellular MRP1
Oxidative Activation
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Halbach et al., 2008, Environ Research 107:69-78
A Look at Natural Attenuation Post-Revision
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Halbach et al., 2008, Environ Research 107:69-78
Changes in RBC Hg after Dental Revision
No Revision - MeHg
Revision
Revision-MeHg
RevisionRevisionRevision-HgII
No Revision - HgII
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Modeled Trend -Revision
Modeled Trend - No Revision
Halbach et al., 2008, Environ Research 107:69-78
MeHg Moving from tissues to Bloodstream… But NOT Out!
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Blood Stream Decrease with Quicksilver IMD
0
0.2
0.4
0.6
0.8
1
1.2
1.4
11/24/2007 1/13/2008 3/3/2008 4/22/2008 6/11/2008 7/31/2008 9/19/2008 11/8/2008
Blo
od
Me
Hg
(n
g/m
L)
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0.5
Blo
od
Hg
II (n
g/m
L)
MeHg HgII
Depressed Phase II Transferases keep MeHg in cells; Once they kick in again, enterohepatic circulation retards excretion from body
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IMD Decreases Half-Life in Blood
With IMD
½-Life ~ 17 days
To Baseline = 40 days
No Treatment (Walleye)
½-Life = 46-66 days
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
Blo
od
Me
Hg
(n
g/m
L)
0.000
0.050
0.100
0.150
0.200
0.250
0.300
0.350
Fe
ca
l Me
Hg
(n
g/g
-ww
)
blood MeHg
Fecal MeHg Excretion
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Small Clinical Trial Results
Table 3.1 Changes in blood mercury levels during 7-10 day intervention with amalgam revision and nutritional support.
Clinic 1 Clinic 2 IMD (n=8) No Treatment (n=4) IMD only (n=5) IMD+OSR (n=7) %Decr HgT 23.9 0.4 16.3 17.5 %Decr MeHg 22.9 5.1 15.9 32.3 %Decr HgII 12.4 -4.1 7.1 -15.0
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Individual Trial Results
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
3/14/200912/10/2008QS Average
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
8/8/20081/23/2009QS Average
7 months while continuing to eat fish
3 months, stopped fish consumption
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Patient – MeHg: Detox Enzyme Deficiency
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Patient – MeHg: Detox Enzyme Deficiency
Amalgam Removal and 5 months IMD w/ phytonutrients and nutritional therapy
0 2 4 6 8 10 12 14 16 18 20
1
22/12/209
4/16/2009
5/7/2009
7/8/2009
8/25/2009
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Huggins Protocol
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6
C o n ce n tr atio n o f M e r cu r y (n g /m L o r u g /L )
HgT
Hg(II)
MeHg
Blo o d M e rcu ry Co mp ar iso n
2/23/20097/6/2009QS A v erage
Includes Ancestral Diet, Matrix Supplements, IMD, and OSR
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Product/System for Intestinal Detoxification
1. Intestinal Metals Detox (IMD)
-Phase III opener
2. Phytonutrients – Antioxidant Response Element
- Upregulate Transcription of Phase II, GSH, SOD
3. Source of GSH
-ReadiSorb Liposomal GSH
-Nutritional Therapy
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“Phytogenomics”• Certain Phytochemicals upregulate Phase
II enzymes as well as GSH, SOD
• The Anti-Inflammatory Cascade
• Polyphenols
• Sulfur compounds – Crucifers– Garlic oil– NOT CHELATORS!!!
Also Progesterone and Pregnenolone very strong in this regard.
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Chemoprevention by Keap1-Nrf2 Signaling pathway by Phase II Inducers
Kwak et al., 2004, Mutation Research, 555:133-148
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Putting it All Together
Mitochondrial Stress – The Hg-induced Blaze
Leaking ROS and cyt c
ROS and Hg Oxidize TrX
1) Covering Exposed Thiols
2) Mopping up ROS
3) Binding Hg
TrX releases ASK1
Decay in GSH
Insufficient Protection
from GSH
Apoptosis – Cell Death
Decrease Exposure/ Increase Export
Increase GSH Enzyme Activity
Increase Trx and TrxR
Increase GSH synthesis and Recycling
Put out the Fires – Save the cells
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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-cancer• Cross BBB
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Flavanols (Polyphenolics)
Epicatechin – in tea, cocoa; monomer for OPC’s from Pine Bark, Grape seeds,
Ellagic Acid
Quercetin
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Haritaki –
Terminalia Chebula
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1. Aged rates had higher markers of mitochondrial free-radical damage
2. Also Uptick of CAT and GPx, downturn of MnSOD, GR, GST, GSH. Vit C, Vit E
- normal defenses and export system can’t keep up wit the load, resulting in more accumulation of free-radical generating molecules and more reliance on downstream protections
-further depleting GSH
3. ALL MARKERS REVERSED TO YOUNG LEVELS WITH HARITAKI
Haritaki –
Terminalia Chebula
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The Clearing, The Clearing. The Great Clearing
This is the path to fulfillment.
So be it!
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Sulfur Compounds
• Anti-inflammatory cascade• Upregulate Phase II (and Phase III)
enzymes through binding to membrane and nuclear receptors (transcription factors)
• Vascular protective effects• Anti-carcinogenic
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Sulfur CompoundsSulforaphane – the famous crucifer
compound
Allicin – from garlic
Allyl-isothiocyanate – “Oil of mustard”, horseradish
Erucin – from crucifers; not as strong as SF
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Product/System for Intestinal Detoxification
1. Intestinal Metals Detox (IMD)
-Phase III opener
2. Phytonutrients – Antioxidant Response Element
- Upregulate Transcription of Phase II, GSH, SOD
3. Source of GSH
-ReadiSorb Liposomal GSH or Livon Labs
-Nutritional Therapy
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Liposomal Glutathione
Unilamellar liposomes
Liposomal Encapsulation•Phospholipid bilayer
•Bypasses peptidases that break down glutahione
•Direct absorption in upper intestine
•Some evidence that they enter cells
•Macrophage oxidative damage protection
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Nutritional GSH Augmentation
• Vitamin C
• Antioxidant Phytonutrients
• Glutathione Precursors
• NAC, glutamate, glycine
• NAC and Vit C
• Whey powder
• GGC – gamma glutamyl cysteine (product in development from Australia)
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Summary• Retention Toxicity Related to Dysfunction of
Natural Glutathione Detox System, BUT Affects other detox systems
• Inflammation as major impediment to detox
• MeHg a hidden danger with amalgam
• Hg speciation testing and Compartment Ratio Analysis to monitor detox
• Opening channels and upregulating natural system a safe and effective detox strategy
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Thank You Huggins Alliance!
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Organic Anion Transporters: GSH Ionization in Aqueous Solutions
_
H2O
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Mercuric DiGlutathione DiAnionHg(GSH)2
-2 - Soluble, mobile, recognizable
Hg
-2
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MethylMercuric Glutathione MonoAnion
CH3Hg(GSH)-1 - Soluble, mobile, recognizable
-1
Hg
CH3
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Cruciferous Compounds
Sulforaphane – the famous crucifer compound
Glucosinolate
Glucobrassicin
Indole-3-Carbinol
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Transformations of mercury
• Hg0 HgII (saliva, blood and tissues)
• HgII Hg0 (intestines)
• HgII MeHg (intestines)
• MeHg HgII (intestines, tissues)
• EtHg HgII (tissues, blood)
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Small Clinical Trial Results
Table 3.1 Changes in blood mercury levels during 7-10 day intervention with amalgam revision and nutritional support.
Clinic 1 Clinic 2 IMD (n=8) No Treatment (n=4) IMD only (n=5) IMD+OSR (n=7) %Decr HgT 23.9 0.4 16.3 17.5 %Decr MeHg 22.9 5.1 15.9 32.3 %Decr HgII 12.4 -4.1 7.1 -15.0
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Individual Trial Results
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
3/14/200912/10/2008QS Average
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
8/8/20081/23/2009QS Average