o n t e n t - Vitamin C Foundation
Transcript of o n t e n t - Vitamin C Foundation
![Page 1: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/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, L L CL afayette, CO 80026
(303)263-6903Heretical C
ontent
![Page 2: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/2.jpg)
Mercury and The Human Detoxification System
1. What the key forms of Hg are 2. How the Natural Detoxification System
Works3. How the Detox System gets subverted
leading to biochemical stress4. 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 3: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/3.jpg)
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
![Page 4: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/4.jpg)
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
![Page 5: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/5.jpg)
Targets of mercury forms
• Brain/CNS• Kidney• Liver• Heart• Pituitary/Thyroid
– And thus all glandular
![Page 6: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/6.jpg)
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)
![Page 7: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/7.jpg)
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
![Page 8: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/8.jpg)
Inorganic Hg and Poisoning of the Extracellular Matrix
![Page 9: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/9.jpg)
Mercury and The Human Detoxification System
1. What the key forms of Hg are 2. How the Natural Detoxification System
Works3. How the Detox System gets subverted
leading to biochemical stress4. 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 10: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/10.jpg)
Defense – Glutathione System Antioxidant, Detoxification, Protein Repair
• Glutathione (GSH) - A thiolic tripeptide composed of glutamate, cysteine, and glycine
![Page 11: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/11.jpg)
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?
![Page 12: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/12.jpg)
• 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
![Page 13: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/13.jpg)
• 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
![Page 14: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/14.jpg)
• 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
![Page 15: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/15.jpg)
• 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
![Page 16: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/16.jpg)
Mercury and The Human Detoxification System
1. What the key forms of Hg are 2. How the Natural Detoxification System
Works3. How the Detox System gets subverted
leading to biochemical stress4. 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 17: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/17.jpg)
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)
![Page 18: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/18.jpg)
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
![Page 19: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/19.jpg)
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!
![Page 20: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/20.jpg)
Biggest Reason for Phase III Dysfunction
Inflammation!
Especially in Gut!-Hallmark of Autism cases
-Easily caused by heavy metal induced oxidative damage
![Page 21: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/21.jpg)
![Page 22: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/22.jpg)
![Page 23: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/23.jpg)
![Page 24: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/24.jpg)
Coordinated Expression of Phase II and III
MRP2 and GSTπ coregulated
![Page 25: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/25.jpg)
Phase I
Phase III
Phase IIGlutathione Conjugation
Sulfation Glucuronidation
OATPB
lood
LIVER
MRP2
Normal Small Intestine
Cellular MRP1
Oxidative Activation
![Page 26: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/26.jpg)
Phase I
Phase III
Phase IIGlutathione Conjugation
Sulfation Glucuronidation
OATPB
lood
LIVER
MRP2
Inflamed Small Intestine
Cellular MRP1
Oxidative Activation
![Page 27: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/27.jpg)
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
![Page 28: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/28.jpg)
Phase I
Phase III
Phase II
Oxidative Activation
Glutathione Conjugation
Sulfation Glucuronidation
OATPB
lood
LIVERMRP2
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
![Page 29: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/29.jpg)
Amalgam as Cause for Inflammation Cysteine Mouth Rinse
[min.]Time
620 640 660 680 700
[V]
Volta
ge0.0
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]
Volta
ge
-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 – 10ppbAmalgam (2nd Rinse) – 16ppb
[min.]Time
620 640 660 680 700
[V]
Volta
ge0.0
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
![Page 30: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/30.jpg)
MeHg Mitochondrial Inferno – Breakdown of the Thiolic Protection
SystemMitochondrial 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
![Page 31: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/31.jpg)
Mercury and The Human Detoxification System
1. What the key forms of Hg are 2. How the Natural Detoxification System
Works3. How the Detox System gets subverted
leading to biochemical stress4. 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: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/32.jpg)
Testing for Hg1. Ambient Measures
1. Blood2. Hair3. Urine 4. Stool
2. Provoked Measure1. Urine
![Page 33: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/33.jpg)
Testing for Hg
1. Ambient1. Blood – MeHg + HgII (MeHg larger)
2. Hair – MeHg only3. Urine – HgII (little bit of MeHg)4. Stool – MeHg + HgII
2. Provoked1. Urine – MeHg + HgII
H
HH
Hg
![Page 34: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/34.jpg)
Challenge Tests – What do they mean? Are They Necessary?
![Page 35: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/35.jpg)
Mercury Industry Workers
Dentists
Controls (Amalgam)
Amalgam-free Referents
![Page 36: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/36.jpg)
Mercury Industry Workers
Dentists
Controls (Amalgam)
Amalgam-free Referents
![Page 37: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/37.jpg)
![Page 38: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/38.jpg)
![Page 39: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/39.jpg)
Chelation therapy – Dump from blood followed by reloading from cellular
burden
![Page 40: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/40.jpg)
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
![Page 41: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/41.jpg)
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
![Page 42: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/42.jpg)
Inorganic Hg and Poisoning of the Extracellular Matrix
…Uhhh, What Matrix?
![Page 43: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/43.jpg)
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
![Page 44: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/44.jpg)
Accumulation
Enterohepatic Circulation of MeHg
H
HH
Hg
![Page 45: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/45.jpg)
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
![Page 46: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/46.jpg)
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
Bloo
d M
eHg
(ng/
mL)
2 hours later
24 hours later
Initial Decay – Redistribution to Tissues
Pre-Tuna
![Page 47: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/47.jpg)
The Great(er) Walleye Experiment
*Nothing is new under the sun*Clarkson et al., Arch. Env. Health, 1980
![Page 48: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/48.jpg)
Walleye Experiment – Decay and Body Burden
After initial peak and decay, Blood reflects Body Burden!
![Page 49: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/49.jpg)
Mercury Speciation Testing
H
HH
Hg
![Page 50: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/50.jpg)
[min.]Time
4020 4030 4040 4050 4060
[mV]Vo
ltage
-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
![Page 51: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/51.jpg)
Mercury Speciation Testing and Compartment Ratio Testing
Ambient Measurement Suite1. Blood – MeHg + HgII
2. Hair – MeHg only-Compare to blood MeHg for excretion
measurement
1. Urine – HgII
-Compare to blood inorganic mercury for excretion measurement
![Page 52: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/52.jpg)
Dentist Levels - Healthy
![Page 53: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/53.jpg)
Dentist Levels – Chronic Inflammation
Indication of Mercury Excretion Ability
0
4 00
-1 2 0 -1 00 -8 0 -6 0 -4 0 -2 0 0 2 0
Blood Me Hg (ng /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/m L)
Hai
r MeH
g (n
g/g)
![Page 54: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/54.jpg)
Dentist Levels – Kidney Problem
0 0.5 1 1.5 2 2.5
Concentration of Mercury (ng/m L or ug/L)
HgT
Hg(II)
MeHg
Blood Mercury
Patient BloodQS Average
Indication of Mercury Excretion Ability
0
4 00
-1 2 0 -1 00 -8 0 -6 0 -4 0 -2 0 0 2 0
Blood Me Hg (ng /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/m L)
Hai
r MeH
g (n
g/g)
Indication of Kidney Mercury Excretion Ability
0.000.501.001.50
2.002.503.003.504.004.505.00
0 0.5 1 1.5
Blood Hg(II) (ng/m L)
Urin
e H
g(II)
(n
g/m
L)
Good Hg(II) Excretion Line (7:1)
![Page 55: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/55.jpg)
Patient – MeHg: Detox Enzyme Defficiency
![Page 56: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/56.jpg)
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/m L)
Hai
r MeH
g (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:Blo
od M
eHg
ratio
Normal Excretion
![Page 57: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/57.jpg)
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
![Page 58: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/58.jpg)
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
![Page 59: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/59.jpg)
Mercury and The Human Detoxification System
1. What the key forms of Hg are 2. How the Natural Detoxification System
Works3. How the Detox System gets subverted
leading to biochemical stress4. 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 60: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/60.jpg)
Removal of HgAmplifying and Augmenting
Natural Systems
![Page 61: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/61.jpg)
Biochemical Hg Removal Requirements
1. Intracellular Glutathione Sufficiency-Liposomal gets in some cells-Transpeptidases dissemble/reassemble
1.Effective GST Activity (Phase II - mobilization)
2.Effective Phase III Clearance including intestinal binding
![Page 62: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/62.jpg)
Product/System for Intestinal Detoxification
1. Intestinal Metals Detox (IMD)-Phase III opener (dietary supplement)
1. Phytonutrients – Antioxidant Response Element
- Upregulate Transcription of Phase II, GSH, SOD via ARE
1. Source of GSH-ReadiSorb Liposomal GSH; Livon Labs-Nutritional Therapy; OSR
![Page 63: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/63.jpg)
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)
![Page 64: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/64.jpg)
Phase I
Phase III
Phase II
Oxidative Activation
Glutathione Conjugation
Sulfation Glucuronidation
OATPB
lood
LIVERMRP2
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
![Page 65: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/65.jpg)
Phase I
Phase III
Phase IIGlutathione Conjugation
Sulfation Glucuronidation
OATPB
lood
LIVER
MRP2
Normal Small Intestine
Cellular MRP1
Oxidative Activation
![Page 66: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/66.jpg)
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
Bloo
d
LIVER
MRP2
Normal Small Intestine
Cellular MRP1
Oxidative Activation
![Page 67: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/67.jpg)
Halbach et al., 2008, Environ Research 107:69-78
A Look at Natural Attenuation Post-Revision
![Page 68: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/68.jpg)
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
![Page 69: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/69.jpg)
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!
![Page 70: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/70.jpg)
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 M
eHg
(ng/
mL)
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0.5
Blo
od H
gII (
ng/m
L)
MeHg HgII
Depressed Phase II Transferases keep MeHg in cells; Once they kick in again, enterohepatic circulation retards excretion from body
![Page 71: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/71.jpg)
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 M
eHg
(ng/
mL)
0.000
0.050
0.100
0.150
0.200
0.250
0.300
0.350
Feca
l MeH
g (n
g/g-
ww
)
blood MeHgFecal MeHg Excretion
![Page 72: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/72.jpg)
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
![Page 73: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/73.jpg)
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/m L 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/m L 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
![Page 74: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/74.jpg)
Patient – MeHg: Detox Enzyme Deficiency
![Page 75: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/75.jpg)
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
2 2/12/209
4/16/2009
5/7/2009
7/8/2009
8/25/2009
![Page 76: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/76.jpg)
Huggins Protocol
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6
Concentration of M ercury (ng/m L or ug/L)
HgT
Hg(II)
MeHg
Blood Mercury Comparison
2/23/20097/6/2009QS Average
Includes Ancestral Diet, Matrix Supplements, IMD, and OSR
![Page 77: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/77.jpg)
Product/System for Intestinal Detoxification
1. Intestinal Metals Detox (IMD)-Phase III opener
1. Phytonutrients – Antioxidant Response Element
- Upregulate Transcription of Phase II, GSH, SOD
1. Source of GSH-ReadiSorb Liposomal GSH-Nutritional Therapy
![Page 78: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/78.jpg)
“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.
![Page 79: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/79.jpg)
Chemoprevention by Keap1-Nrf2 Signaling pathway by Phase II Inducers
Kwak et al., 2004, Mutation Research, 555:133-148
![Page 80: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/80.jpg)
Putting it All TogetherMitochondrial 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
![Page 81: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/81.jpg)
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
![Page 82: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/82.jpg)
Flavanols (Polyphenolics)
Epicatechin – in tea, cocoa; monomer for OPC’s from Pine Bark, Grape seeds,
Ellagic Acid
Quercetin
![Page 83: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/83.jpg)
Haritaki –
Terminalia Chebula
![Page 84: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/84.jpg)
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
![Page 85: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/85.jpg)
![Page 86: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/86.jpg)
The Clear ing, The Clear ing. The Great Clear ing
This is the path to fulfillment.
So be it!
![Page 87: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/87.jpg)
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
![Page 88: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/88.jpg)
Sulfur CompoundsSulforaphane – the famous
crucifer compound
Allicin – from garlic
Allyl-isothiocyanate – “Oil of mustard”, horseradish
Erucin – from crucifers; not as strong as SF
![Page 89: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/89.jpg)
Product/System for Intestinal Detoxification
1. Intestinal Metals Detox (IMD)-Phase III opener
1. Phytonutrients – Antioxidant Response Element
- Upregulate Transcription of Phase II, GSH, SOD
1. Source of GSH-ReadiSorb Liposomal GSH or Livon Labs-Nutritional Therapy
![Page 90: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/90.jpg)
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
![Page 91: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/91.jpg)
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)
![Page 92: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/92.jpg)
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
![Page 93: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/93.jpg)
Thank You Huggins Alliance!
![Page 94: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/94.jpg)
![Page 95: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/95.jpg)
Organic Anion Transporters: GSH Ionization in Aqueous Solutions
_
H2O
![Page 96: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/96.jpg)
Mercuric DiGlutathione DiAnionHg(GSH)2
-2 - Soluble, mobile, recognizable
Hg
-2
![Page 97: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/97.jpg)
MethylMercuric Glutathione MonoAnion
CH3Hg(GSH)-1 - Soluble, mobile, recognizable
-1
HgCH3
![Page 98: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/98.jpg)
Cruciferous Compounds
Sulforaphane – the famous crucifer compound
Glucosinolate
GlucobrassicinIndole-3-Carbinol
![Page 99: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/99.jpg)
Transformations of mercury
• Hg0 HgII (saliva, blood and tissues)• HgII Hg0 (intestines)• HgII MeHg (intestines)• MeHg HgII (intestines, tissues)• EtHg HgII (tissues, blood)
![Page 100: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/100.jpg)
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
![Page 101: o n t e n t - Vitamin C Foundation](https://reader030.fdocuments.in/reader030/viewer/2022012704/61a60371458c3f2fd3656b0f/html5/thumbnails/101.jpg)
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/m L 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/m L or ug/L)
HgT
Hg(II)
MeHg
Before Blood Mercury Comparison
8/8/20081/23/2009QS Average