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Mercury and The Human Detoxification System

Christopher W. Shade, Ph.D.Quicksilver Scientific, LLC

Lafayette, CO 80026(303)263-6903

[email protected]

Saturday, 11 September 2010

Mercury and The Human Detoxification System

1. What are the key forms of Hg2. How the Detoxification System Works3. Methylmercury Accumulation as a hidden

danger in Amalgam toxicity4. Intestinal Metals Detox System to repair

and amplify the bodies detoxification mechanisms and safely remove mercury


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


The Heart of the Toxicity

1. Inappropriate Binding 2. Oxidative Damage and related

Inflammation


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


Defense – Glutathione System Antioxidant, Detoxification, Protein Repair

• Glutathione (GSH) - A thiolic tripeptide composed of glutamate, cysteine, and glycine

• The system involves – Synthetases (synthesize GSH from precursors) – Transpeptidases (take apart and reassemble)– Transferases (conjugation)– Peroxidases (radical quenching)– Reductases (repair after quenching)– Redoxins (using GSH as reducing equivalent for

protein repair)


• Detoxification Phases I, II, III–Phase I is an activation, –Phase II is conjugation–Phase III is transport

The Human Detoxification System


• 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



• Phase II – conjugation makes toxin more water soluble and recognizable by transporters– Glutathione S-Transferases (GST)

responsible for GSH conjugation– Low in people with high MeHg and with

sensitivity to Thimerosal (EthylHg)



• Phase III is the transport out!– Several transport proteins (cMOAT, OAT,

MRP1, MRP2, GS-X)– Same transporters for many pathways

(glucuronide, sulfate, glycinate, GSH)– In cells, liver, intestines, kidneys – biggest in

liver then intestines



Breakdown of the defense system

• GSH deficiency – genetic and/or environmental

• GST problems – genetic and/or environmental

• Phase III can get blocked and then downregulates Phase II enzymes – Can stop multiple detoxification

pathways!


Biggest Reason for Phase III Dysfunction


Biggest Reason for Phase III Dysfunction

Inflammation in Gut!-Hallmark of Autism cases

-Easily caused by heavy metal induced oxidative damage


Phase I

Phase III

Phase IIGlutathione Conjugation

Sulfation Glucuronidation

OATPB

lood

LIVER

MRP2

Normal Small Intestine

Cellular MRP1

Oxidative Activation


Phase I

Phase III

Phase II


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



Accumulation

• Retention Toxicity – Phase II, III problem?– Genetic difficulties: GS, GST deletions– Acquired Dysfunctions: Transporter

impairment, severe oxidative stress


MethylMercuryThe Unsuspected Factor

H

HH

Hg


Accumulation

Enterohepatic Circulation of MeHg

H

HH

Hg


Synthesis of Methylmercury from Amalgam-Derived Hg


Synthesis of Methylmercury from Amalgam-Derived Hg

Experimental Results in Monkeys

w/ Dr. Anne Summers, University of Georgia


0.001

0.010

0.100

1.000

10.000

100.000

-23 -1 10 17 60 66 80 940.01

0.10

F78

HgT

*/T (u

g/gm

)

Day

MeH

g (n

g/gm

)QuickSilver HgII Calgary HgT MeHg

0.001

0.010

0.100

1.000

10.000

100.000

-79-74-60-46-235 1219284054738489981191331590.00

0.01

0.10

1.00

10.00

R87

HgT

* (ug

/gm

)

Day

MeH

g (n

g/gm

)

QuickSilver HgII Calgary HgT MeHg

Continuous In Vivo Synthesis of CH3HgX from Amalgam Hg by Intestinal Bacteria in Live Monkeys

0.010

0.100

0.001 0.010 0.100 1.000 10.000 100.000

R² = 0.5255

F78

MeH

g (n

g/g

)

HgII (ug/g)

0.001

0.010

0.100

1.000

10.000

0.001 0.010 0.100 1.000 10.000 100.000

R² = 0.7097

R87

MeH

g (n

g/g

)

HgII (ug/g)

Time course CH3HgX as a fraction of total Hg

16 occlusal amalgams placed

12 occlusal amalgams placed

removed


In-Gut MeHg Synthesis H

HHHg

MeHg synthesized from HgII derived from amalgam corrosion.

MeHg absorbed ~95% efficiency versus the 5-10% of HgII.

Continuous Synthesis plus recirculation can lead to high body burden of MeHg


Testing for MeHg

H

HH

Hg


Testing for MeHg

• Old Dictum – blood is only recent exposure, 3-daysH

HH

Hg


Testing for MeHg

• Old Dictum – blood is only recent exposure, 3-days• Reality

H

HH

Hg


Testing for MeHg


– 3-day residence only the quick decay after a large dose

H

HH

Hg


Testing for MeHg



– For MeHg, Steady state develops after initial decay; Then blood reflects body burden!

H

HH

Hg


Testing for MeHg




• Real Problem

H

HH

Hg


Testing for MeHg




• Real Problem– Most labs detection limits too high to see dynamics

H

HH

Hg


Testing for MeHg




• Real Problem– Most labs detection limits too high to see dynamics– Need sensitive equipment!

H

HH

Hg


Testing for MeHg

H

HH

Hg


MeHg

HgII

MeHg

HgII

H

HH

Hg

Testing for MeHg


The Great Tuna Experiment• Wade Wimer – 2 cans of Albacore Tuna in one sitting

2 hours later

24 hours later

2 hours later

24 hours later

0

0.75

1.50

2.25

3.00

10/26/08 10/27/08 10/28/08 10/31/08

Blo

od M

eHg

(ng/

mL)

2 hours later

24 hours later

Pre-Tuna


The Great Tuna Experiment• Wade Wimer – 2 cans of Albacore Tuna in one sitting

2 hours later

24 hours later

2 hours later

24 hours later

0

0.75

1.50

2.25

3.00

10/26/08 10/27/08 10/28/08 10/31/08

Blo

od M

eHg

(ng/

mL)

2 hours later

24 hours later

Decay – Excretion? Redistribution to Tissues? Or some of Both?

Pre-Tuna


Testing for MeHg

H

HH

Hg

Patients with high MeHg take much longer to recover!

-testing can give indication of rate of recovery

Dr. Huggins Observation


Removal of HgAmplifying and Augmenting Natural

Systems


Product/System for Intestinal Detoxification



• MicroSilica (IMD)



• MicroSilica (IMD)– Use Intestines NOT Kidneys for Metal Removal



• MicroSilica (IMD)– Use Intestines NOT Kidneys for Metal Removal– Insoluble Spheres saturated with strong binding groups



• MicroSilica (IMD)– Use Intestines NOT Kidneys for Metal Removal– Insoluble Spheres saturated with strong binding groups– Binds Mercury in Intestines and moves out of Body




• Stops Enterohepatic Circulation




• Stops Enterohepatic Circulation• Opens Phase III transporters





– Bilirubin levels fall dramatically too!





– Bilirubin levels fall dramatically too!• System adds Phytonutrients that enhance Phase II

enzymes and strengthen the vascular system and Liposomal GSH to raise GSH levels (Phospholipid Exchange)


Halbach et al., 2008, Environ Research 107:69-78

A Look at Natural Attenuation Post-Revision



Changes in RBC Hg after Dental Revision

No Revision - MeHg

Revision

Revision-MeHg

RevisionRevisionRevision-HgII

No Revision - HgII


MeHg Moving from tissues to Bloodstream… But NOT Out!


Modeled Trend -Revision

Modeled Trend - No Revision


Blood Stream Decrease with MicroSilica (IMD)

0

0.3750

0.7500

1.1250

1.5000

01/01/08 02/03/08 02/05/08 02/07/08 01/09/08

Blo

od M

eHg

(ng/

mL)

HgII MeHg


Blood Stream Decrease with MicroSilica (IMD)

0

0.3750

0.7500

1.1250

1.5000

01/01/08 02/03/08 02/05/08 02/07/08 01/09/08

Blo

od M

eHg

(ng/

mL)

HgII MeHg

Depressed Phase II Transferases keep MeHg in cells; Once they kick in again, enterohepatic circulation retards excretion from body


Small Clinical Trial Results


Effect of Liposomal GSH enhancing cocktail (Phospholipid Exchange)

Enhancing Both Organ Drainage and Blood Drainage


Effect of Liposomal GSH enhancing cocktail (Phospholipid Exchange)

Liposomal Glutathione Added to regimen

Enhancing Both Organ Drainage and Blood Drainage


Excretion Rates Liposomal GSH Supplementation

A truly effective chelation based on the natural detox system!


Summary

• Retention Toxicity Related to Dysfunction of Natural Glutathione Detox System, BUT Affects other detox systems


Summary


• Inflamation as major trigger


Summary


• Inflamation as major trigger• MeHg big hidden danger with amalgam


Summary


• Inflamation as major trigger• MeHg big hidden danger with amalgam• Blood MeHg testing way to monitor detox


Summary


• Inflamation as major trigger• MeHg big hidden danger with amalgam• Blood MeHg testing way to monitor detox• IMD safe effective supplement to open up

the detox channels and drain retained toxicity


Thank You Dr. Klinghardt


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