Mercury and The Human Detoxification System

Transcription

1 Mercury and The uman Detoxification System Christopher W. Shade, Ph.D. Quicksilver Scientific, LLC Lafayette, CO (303)

2 Mercury and The uman Detoxification System 1. What are the key forms of g 2. ow the Detoxification System Works 3. Methylmercury Accumulation as a hidden danger in Amalgam toxicity 4. Intestinal Metals Detox System to repair and amplify the bodies detoxification mechanisms and safely remove mercury

3 Transport of mercury g 0 80% uptake in lungs, crossed BBB, diffuses in to tissues; moderate uptake from intestines g II Very poor uptakes in intestines; poor mobility; does not cross BBB Meg 95% uptake from intestines, good mobility, crosses BBB Etg 100% absorbtion (inj), good mobility, crosses BBB

4 The eart of the Toxicity 1. Inappropriate Binding 2. Oxidative Damage and related Inflammation

5 The eart of the Toxicity Thiol Binding and Redox Reaction Reduced sulfur groups, R-S, g replaces proton and binds to sulfur R-S + g 2+ = R-Sg 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

6 Defense Glutathione System Antioxidant, Detoxification, Protein Repair Glutathione (GS) - A thiolic tripeptide composed of glutamate, cysteine, and glycine The system involves Synthetases (synthesize GS from precursors) Transpeptidases (take apart and reassemble) Transferases (conjugation) Peroxidases (radical quenching) Reductases (repair after quenching) Redoxins (using GS as reducing equivalent for protein repair)

7 The uman Detoxification System Detoxification Phases I, II, III Phase I is an activation, Phase II is conjugation Phase III is transport

8 The uman Detoxification System Phase I - an oxidative activation, usually the Cytochrome P450 system Prepares toxin for conjugation in Phase II with GS, 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

9 The uman Detoxification System Phase II conjugation makes toxin more water soluble and recognizable by transporters Glutathione S-Transferases (GST) responsible for GS conjugation Low in people with high Meg and with sensitivity to Thimerosal (Ethylg)

10 The uman Detoxification System Phase III is the transport out! Several transport proteins (cmoat, OAT, MRP1, MRP2, GS-X) Same transporters for many pathways (glucuronide, sulfate, glycinate, GS) In cells, liver, intestines, kidneys biggest in liver then intestines

11 Breakdown of the defense system GS 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!

12 Biggest Reason for Phase III Dysfunction

13 Biggest Reason for Phase III Dysfunction Inflammation in Gut! -allmark of Autism cases -Easily caused by heavy metal induced oxidative damage

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

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

16 Accumulation Retention Toxicity Phase II, III problem? Genetic difficulties: GS, GST deletions Acquired Dysfunctions: Transporter impairment, severe oxidative stress

17 MethylMercury The Unsuspected Factor g

18 Accumulation g Enterohepatic Circulation of Meg

19 Accumulation g Enterohepatic Circulation of Meg

20 Synthesis of Methylmercury from Amalgam-Derived g

21 Synthesis of Methylmercury from Amalgam-Derived g Experimental Results in Monkeys w/ Dr. Anne Summers, University of Georgia

22 Continuous In Vivo Synthesis of C 3 gx from Amalgam g by Intestinal Bacteria in Live Monkeys Time course C 3 gx as a fraction of total g F78 F78 gt*/t (ug/gm) occlusal amalgams placed Day removed Meg (ng/gm) Meg (ng/g) R² = gii (ug/g) QuickSilver gii Calgary gt Meg R87 R gt* (ug/gm) occlusal amalgams placed Meg (ng/gm) Meg (ng/g) R² = Day gii (ug/g) QuickSilver gii Calgary gt Meg

23 In-Gut Meg Synthesis g Meg synthesized from g II derived from amalgam corrosion. Meg absorbed ~95% efficiency versus the 5-10% of g II. Continuous Synthesis plus recirculation can lead to high body burden of Meg

24 In-Gut Meg Synthesis g Meg synthesized from g II derived from amalgam corrosion. Meg absorbed ~95% efficiency versus the 5-10% of g II. Continuous Synthesis plus recirculation can lead to high body burden of Meg

25 Testing for Meg g

26 Testing for Meg g Old Dictum blood is only recent exposure, 3-days

27 Testing for Meg g Old Dictum blood is only recent exposure, 3-days Reality

28 Testing for Meg g Old Dictum blood is only recent exposure, 3-days Reality 3-day residence only the quick decay after a large dose

29 Testing for Meg Old Dictum blood is only recent exposure, 3-days Reality 3-day residence only the quick decay after a large dose For Meg, Steady state develops after initial decay; Then blood reflects body burden! g

30 Testing for Meg g Old Dictum blood is only recent exposure, 3-days Reality 3-day residence only the quick decay after a large dose For Meg, Steady state develops after initial decay; Then blood reflects body burden! Real Problem

31 Testing for Meg g Old Dictum blood is only recent exposure, 3-days Reality 3-day residence only the quick decay after a large dose For Meg, Steady state develops after initial decay; Then blood reflects body burden! Real Problem Most labs detection limits too high to see dynamics

32 Testing for Meg g Old Dictum blood is only recent exposure, 3-days Reality 3-day residence only the quick decay after a large dose For Meg, 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!

33 Testing for Meg g

34 Testing for Meg g Meg g II Meg g II

35 The Great Tuna Experiment Wade Wimer 2 cans of Albacore Tuna in one sitting hours later hours later Blood Meg (ng/ml) hours later Pre-Tuna 2 hours later 0 10/26/08 10/27/08 10/28/08 10/31/08

36 The Great Tuna Experiment Wade Wimer 2 cans of Albacore Tuna in one sitting hours later hours later Blood Meg (ng/ml) hours later Pre-Tuna 2 hours later 0 10/26/08 10/27/08 10/28/08 10/31/08 Decay Excretion? Redistribution to Tissues? Or some of Both?

37 Testing for Meg g Dr. uggins Observation Patients with high Meg take much longer to recover! -testing can give indication of rate of recovery

38 Removal of g Amplifying and Augmenting Natural Systems

39 Product/System for Intestinal Detoxification

40 Product/System for Intestinal Detoxification MicroSilica (IMD)

41 Product/System for Intestinal Detoxification MicroSilica (IMD) Use Intestines NOT Kidneys for Metal Removal

42 Product/System for Intestinal Detoxification MicroSilica (IMD) Use Intestines NOT Kidneys for Metal Removal Insoluble Spheres saturated with strong binding groups

43 Product/System for Intestinal Detoxification 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

44 Product/System for Intestinal Detoxification 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

45 Product/System for Intestinal Detoxification 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 Opens Phase III transporters

46 Product/System for Intestinal Detoxification 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 Opens Phase III transporters Bilirubin levels fall dramatically too!

47 Product/System for Intestinal Detoxification 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 Opens Phase III transporters Bilirubin levels fall dramatically too! System adds Phytonutrients that enhance Phase II enzymes and strengthen the vascular system and Liposomal GS to raise GS levels (Phospholipid Exchange)

48 A Look at Natural Attenuation Post- Revision albach et al., 2008, Environ Research 107:69-78

49 Changes in RBC g after Dental Revision Revision- Meg No Revision - Meg No Revision - g II Revision- g II albach et al., 2008, Environ Research 107:69-78

50 Meg Moving from tissues to Bloodstream But NOT Out! Modeled Trend - Revision Modeled Trend - No Revision albach et al., 2008, Environ Research 107:69-78

51 Blood Stream Decrease with MicroSilica (IMD) gii Meg Blood Meg (ng/ml) /01/08 02/03/08 02/05/08 02/07/08 01/09/08

52 Blood Stream Decrease with MicroSilica (IMD) gii Meg Blood Meg (ng/ml) /01/08 02/03/08 02/05/08 02/07/08 01/09/08

53 Blood Stream Decrease with MicroSilica (IMD) gii Meg Blood Meg (ng/ml) /01/08 02/03/08 02/05/08 02/07/08 01/09/08

54 Blood Stream Decrease with MicroSilica (IMD) gii Meg Blood Meg (ng/ml) /01/08 02/03/08 02/05/08 02/07/08 01/09/08

55 Blood Stream Decrease with MicroSilica (IMD) gii Meg Blood Meg (ng/ml) /01/08 02/03/08 02/05/08 02/07/08 01/09/08 Depressed Phase II Transferases keep Meg in cells; Once they kick in again, enterohepatic circulation retards excretion from body

56 Small Clinical Trial Results

57 Effect of Liposomal GS enhancing cocktail (Phospholipid Exchange) Enhancing Both Organ Drainage and Blood Drainage

58 Effect of Liposomal GS enhancing cocktail (Phospholipid Exchange) Liposomal Glutathione Added to regimen Enhancing Both Organ Drainage and Blood Drainage

59 Excretion Rates Liposomal GS Supplementation A truly effective chelation based on the natural detox system!

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

61 Summary Retention Toxicity Related to Dysfunction of Natural Glutathione Detox System, BUT Affects other detox systems Inflamation as major trigger

62 Summary Retention Toxicity Related to Dysfunction of Natural Glutathione Detox System, BUT Affects other detox systems Inflamation as major trigger Meg big hidden danger with amalgam

63 Summary Retention Toxicity Related to Dysfunction of Natural Glutathione Detox System, BUT Affects other detox systems Inflamation as major trigger Meg big hidden danger with amalgam Blood Meg testing way to monitor detox

64 Summary Retention Toxicity Related to Dysfunction of Natural Glutathione Detox System, BUT Affects other detox systems Inflamation as major trigger Meg big hidden danger with amalgam Blood Meg testing way to monitor detox IMD safe effective supplement to open up the detox channels and drain retained toxicity

65 Thank You Dr. Klinghardt