Presentation is loading. Please wait.

Presentation is loading. Please wait.

Walter J. Crinnion ND SpiritMed www.DrCrinnion.com www.CrinnionOpinion.com Copyright WCrinnion 2013.

Similar presentations


Presentation on theme: "Walter J. Crinnion ND SpiritMed www.DrCrinnion.com www.CrinnionOpinion.com Copyright WCrinnion 2013."— Presentation transcript:

1

2 Walter J. Crinnion ND SpiritMed Copyright WCrinnion 2013

3 Thanks to Dr. Dan Carter for some of his slide information. Dr. Crinnion has no conflict of interest in regards to any compounds covered in the following slides. Copyright WCrinnion 2013

4 DMSA Copyright WCrinnion 2013 DMPS

5 Other drug names Dimercaptosuccinic acid Succimer Chemet™ Captomer™ Copyright WCrinnion 2013

6 Second generation from British Anti-Lewisite (BAL) Absorbed rapidly after oral administration Approximately 20% absorption Evidence that enterohepatic circulation occurs 95% binds to albumin via disulfide bond with cysteine This leaves the other thiol group free to chelate metals Renal excretion >90% excreted as mixed disulfides of DMSA Disulfides only found in urine, not blood <10% excreted as DMSA Copyright WCrinnion 2013

7 Renal excretion (cont’d) Research evidence indicates that the mixed disulfides of cysteine are the active chelating moiety in humans This suggests that chelation occurs principally in the kidney Elimination half-life of total DMSA (parent drug plus oxidized metabolites) Longer in children with lead poisoning (3hours) Adults with or without lead poisoning ( hours) Copyright WCrinnion 2013

8 Succimer is a (FDA approved) lead chelator; it forms water soluble chelates and increases the urinary excretion of lead Succimer is indicated for the treatment of lead poisoning in pediatric patients with blood lead levels above 45 mcg/dL Succimer is not indicated for prophylaxis of lead poisoning in a lead-containing environment the use of Succimer should always be accompanied by identification and removal of the source of the lead exposure DMSA is also clinically useful for chelating Arsenic Cadmium Mercury It has been suggested that DMSA be utilized following EDTA chelation Copyright WCrinnion 2013

9 DMSA should not be administered to patients with a history of allergy to the drug Most typically found in those with a high reactivity to anything containing sulfur If a patient has experienced unexplained adverse reactions, avoid re-exposure to DMSA Copyright WCrinnion 2013

10 Mild/moderate neutropenia has been observed A causal relationship to succimer has not been absolutely established Neutropenia has been reported drugs in the same chemical class (dithiols) A complete blood count with white blood cell differential and platelet count should be obtained prior to and weekly during treatment with succimer Withhold or discontinue therapy if the absolute neutrophil count (ANC) is below 1200/mcL. Follow patient closely to document recovery of the ANC to above 1500/mcL or to baseline neutrophil count Due to limited experience with re-exposure in patients who have developed neutropenia, such patients should be re-challenged only if the benefit of therapy clearly outweighs the potential risk of another episode of neutropenia and only with careful patient monitoring Instruct patients treated with succimer to promptly report any signs of infection. If infection is suspected laboratory tests should be performed immediately (accessed 9/17/2013) Copyright WCrinnion 2013

11 Pregnancy: Category C Nursing mothers Many drugs and toxic metals are excreted in human milk, nursing mothers needing DMSA therapy should be discouraged from nursing their infants Copyright WCrinnion 2013

12  With mercury overload A cluster of pediatric metallic mercury exposure cases treated with meso-2,3-dimercaptosuccinic acid (DMSA) Forman J, et al. Environ Health Perspect 2000;108:  With lead overload Safety and efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) in children with elevated blood lead concentrations. Chisolm JJ. J Toxicol Clinical Toxicology 2000;38(4): Copyright WCrinnion 2013

13 Other drug names Dimaval Unithiol Copyright WCrinnion 2013

14 d.com/doc/ /Dimaval®- Scientific- Product- Monograph Accessed: 9/17/2013 Copyright WCrinnion 2013

15 DMPS is distributed extracellularly and, to a smaller extent, intracellularly. 80% bound by protein, mainly albumin, in the plasma, highly stable prolonging the heavy metal mobilizing activity This results in the half life extending from 1.8 hours of the parent compound to 20 hours of the altered (bound) drug. Copyright WCrinnion 2013

16 Half-life after intravenous dosing - 20 hours Half-life after oral dose hours DMPS undergoes renal excretion with 46 to 59% of the dose detected in the urine after 24 hours of dosing Copyright WCrinnion 2013

17 No adverse effects on organ systems at therapeutic doses Immune system parameters not effected – no neutropenia Non-Mutagenic, non-teratogenic Pregnancy category C - It is NOT recommended that pregnant women with chronic toxicity undergo mobilization of heavy metals until completion of lactation Copyright WCrinnion 2013

18 Currently, it is not FDA approved in the United States Classified by the FDA as a bulk drug substance for pharmacy compounding Copyright WCrinnion 2013

19 DMPS must not be administered to patients who are hypersensitive to DMPS or its salts Not recommended for use in patients with serum creatinine greater than 2.5 or stage 4 chronic kidney disease (CKD) Copyright WCrinnion 2013

20 Drug Interactions None listed Pregnancy Category C: The safety of DMPS administration during pregnancy has not been confirmed in humans Pediatric Use Pediatric doses have not been specified, do not administer to patients less than 12 months of age Patients with mercury amalgam fillings See Aposhian study Copyright WCrinnion 2013

21 Urinary mercury after administration of 2,3- dimercaptopropane-1-sulfonic acid: correlation with dental amalgam score Aposhian HV, et al FASEB J 1992;6: subjects with amalgams 10 subjects without amalgams Copyright WCrinnion 2013

22  300mg DMPS po after 11 hour fast  Urine collected 9 hours post DMPS  10 w/ amalgams 0.70 to 17.2 ug Hg  10 w/o amalgams 0.27 to 5.1 ug Hg Copyright WCrinnion 2013

23 “ A linear relationship exists between the amalgam score and the urinary mercury after DMPS administration” “Two-thirds of the mercury excreted in the urine of those with dental amalgams appears to be derived originally from the mercury vapor released from their amalgams” Copyright WCrinnion 2013

24 The Kidneys! Copyright WCrinnion 2013

25 Sulfa drug allergy? Not a contraindication for either DMSA or DMPS There has been no demonstrated cross reactivity from a chemical or pharmacological standpoint Copyright WCrinnion 2013

26

27 Skin Pruritus, rashes, allergic skin reactions (rare) General Chills, fever, increased transaminases Copyright WCrinnion 2013

28 Transdermal (TD-DMPS) is an ineffective metal chelator TD-DMPS is not absorbed, not found in blood samples There was no increase in urine mercury excretion after TD-DMPS. Copyright WCrinnion 2013

29 MetalDDIPre Post EDTA/ DMPS Transdermal DMPS Cd< Pb<5

30 Complete blood count Comprehensive metabolic panel GFR – or creatinine WNL Anti-IgA gliadin antibody – if suspicion of malabsorption is present. 6 hour urine collection for toxic metal assessment Mineral analysis – when indicated Serum RBC RBC glutathione to show available GSH/GSSG 8-OHdG for oxidative damage assessment Copyright WCrinnion 2013

31 Serum – good for acute exposures, keep in mind the t1/2 in serum. Urine – also good for acute exposures, when used with chelating agent will indicate relative level of body store. Hair – excellent for methylmercury Fecal – good method for children Copyright WCrinnion 2013

32 Choose a standard & consistent basis for testing Serial test interpretation is only possible with the same drug dose and urine collection time Provocation dose for each test remains constant DMSA (30 mg/kg oral) DMPS (3 mg/kg IV) Ca EDTA (50 mg/kg IV) Urine collection time of 6 hours Copyright WCrinnion 2013

33  Rule out potential DMSA sensitivity i.e. reactive to ALL sulfur-containing compounds  No shellfish or seaweed for the week prior to testing  Avoid high arsenic levels  Empty bladder* and stomach Use first morning urine for pre-flush test  Body weight DMSA (30 mg/kg up to 2250mg)  Collect all urine for 6 hours  Food can be consumed after 1 hour. Copyright WCrinnion 2013

34 1. Sensitivity check for DMPS 2. No shellfish or seaweed for 1 week prior 3. Empty bladder* 4. DMPS (3mg/kg up to 250mg) given in a push over minutes hour urine catch – Toxic element analysis. 6. Check serum creatinine. Copyright WCrinnion 2013

35 No shellfish for 1 week prior Empty bladder* and empty stomach 10mg/kg oral DMPS 6 hour urine catch sent in for heavy metal UA. Serum creatinine check Copyright WCrinnion 2013

36 300 mg oral dose given after 11 hour fast Dental technicians – 4.84 pre to post Dentists pre post Non-dental persons pre 27.3 post Positive association between pre coproporphyrin levels and flushed Hg Pos assoc. Hg and cognitive sx and mood J Pharmacol Exper Therapeutics 1995;272: PMID: Copyright WCrinnion 2013

37  Serum creatinine WNL  Empty bladder prior to injection*  2,000mg glycine given 2 hours pre if possible  CaNa 2 EDTA 2,000 mg (10cc) with sterile H2O in one syringe. Slow push. 20 min  Flush with 3 cc saline  DMPS (3 mg/kg) slow push 15 min  Collect all urine for the next six hours Copyright WCrinnion 2013

38 Creatinine clearance Compliance for 24 hour UA often poor Serum creatinine being WNL Copyright WCrinnion 2013

39 CAN SHOW TOTAL BODY BURDEN OF HEAVY METALS!!!! These tests are measuring the amount LEAVING the body, NOT the total IN the body Copyright WCrinnion 2013

40 DMSA flush gives a good representation of Hg and Pb. DMPS gives a much higher dump of Hg and much lower dump of Pb EDTA will give the highest dumps of Cd, Pb and will mobilize Al. It will give VERY POOR dumping of Hg. If GSH is low you may get a deceptively low reading of Hg Pre-treatment with NAC & MSM Copyright WCrinnion 2013

41 Metal Reference Range PrePost DMSA Post DMPS AS< CD< PB< HG< The differences in Pb and Hg between DMPS and DMSA flushing in one adult female Case Study – unpublished research

42 Helps identify current exposures Helps identify how effective the proposed chelating agent is Can give information about absorptive ability of the person Pre-testing is the ONLY means available to identify toxic levels of Cd Copyright WCrinnion 2013

43 CDC National reports provide us with ‘normal’ ranges for US residents for the first time. Levels above 75 th percentile would typically indicate current exposure. For Hg, this is NOT from dental amalgams Copyright WCrinnion 2013

44 Compound Geometric mean 50 th percentile 75 th percentil e 90 th percentil e 95 th percentile Arsenous (III) acid NA

45 Compound Geometric Mean 50 th percentile 75 th percentile 90 th percentile 95 th percentile AntimonyNA Arsenic (total) Barium Cadmium Cesium Cobalt Lead Mercury Thallium Uranium Copyright WCrinnion 2013

46 Ug/L of Hg in blood Geometric Mean 50 th percentile 75 th percentile 90 th percentile 95 th percentile Total Blood Hg Inorganic blood Hg NA

47

48 Metal MMX Reference Range CDC 90/95% Pre AS<5749 CD<.9.68 / PB< / 2 HG< / Levels of Hg ABOVE CDC 75% = CURRENT EXPOSURE AND an expectation of a large dump post DMSA Crinnion W. Case Study – unpublished research

49 Copyright WCrinnion 2013 Metal MMX Reference Range CDC 90/95% PrePost DMSA AS< CD<.9.68 / PB< / 214 HG< / Right on both counts Ate tuna 3-4 times weekly Crinnion W. Case Study – unpublished research

50 MetalMMX Ref CDC 90/95% Pre DMSA Post DMSA Hg< / Copyright WCrinnion 2013 Meager Hg levels on post flush would NOT have been reflective on a current exposure WITHOUT the pre! Also look for poor absorption or GSH deficiency! Case Study – unpublished research

51 MetalMMX Ref CDC 90/95% Pre DMSA Post DMSA PB< / Hg< / Copyright WCrinnion 2013 Case Study – unpublished research

52 Possible exposure in some supplements (as yet untested) But, found a broken Hg thermometer in her car, and vacuumed it up with vacuum used regularly inside of home. pills.htm#cleanup Copyright WCrinnion 2013 Case Study – unpublished research

53 Copyright WCrinnion 2013

54 MetalMMX Ref CDC 90/95% Pre DMSA Post DMSA PB< / Hg< / (CDC mean.4) 1 Copyright WCrinnion 2013 Case Study – unpublished research

55 Positive anti-gliadin IgG Non-positive transglutaminase IgA Copyright WCrinnion 2013

56 MetalMMX Ref CDC 90/95 Pre DMSA Post DMSA Pb< / 2

57  No gluten in diet.  Anti-gliadin IgA of 26!!  Gluten in supplements from discount store Copyright WCrinnion 2013

58 MetalMMX Ref CDC 90/95 Pre DMSA Post DMSA Pb< / 2

59 Copyright WCrinnion 2013

60 MetalMMX refPre Metal Free Post Metal Free Post DMSA Cd<.90.3 Pb<4.4


61 MetalMMX refPre Metal Free Post Metal Free Post DMSA Cd< Pb<4.4


62 MetalMMX ref Pre DMSA Post DMSA Pre EDTA Post EDTA Cd<.90.4 Pb<4.4


63 Metal DDI ref Pre DMSA Post DMSA Pre EDTA Post EDTA Cd< Pb<5

64 Metal DDI ref Pre DMSA Post DMSA Pre EDTA Post EDTA Cd< Pb<5

65 Metal DDI ref Pre DMSA Post DMSA Pre EDTA Post EDTA Cd< Pb<5


66 MetalMMX Ref Pre DMSA Post DMSA Pre oral EDTA Post o – EDTA Pre IV EDTA Post IV EDTA AL<61 Sb< Cd<.90.8 Pb< Hg< Copyright WCrinnion 2013 Crinnion W. Case Study. Unpublished research

67 MetalMMX Ref Pre DMSA Post DMSA Pre oral EDTA Post o – EDTA Pre IV EDTA Post IV EDTA AL<61 Sb< Cd< Pb< Hg< Copyright WCrinnion 2013 Crinnion W. Case Study. Unpublished research

68 MetalMMX Ref Pre DMSA Post DMSA Pre oral EDTA Post o – EDTA Pre IV EDTA Post IV EDTA AL<614.6 Sb< Cd< Pb< Hg< Copyright WCrinnion 2013 Crinnion W. Case Study. Unpublished research

69 MetalMMX Ref Pre DMSA Post DMSA Pre oral EDTA Post o – EDTA Pre IV EDTA Post IV EDTA AL<614.6 Sb< Cd< Pb< Hg< Copyright WCrinnion 2013 Crinnion W. Case Study. Unpublished research

70 MetalMMX Ref Pre DMSA Post DMSA Pre oral EDTA Post o – EDTA Pre IV EDTA Post IV EDTA AL<614.6 Sb< Cd< Pb< Hg< Copyright WCrinnion 2013 Crinnion W. Case Study. Unpublished research

71 MetalMMX Ref Pre DMSA Post DMSA Pre oral EDTA Post o – EDTA Pre IV EDTA Post IV EDTA AL< Sb< Cd< Pb< ( x35) Hg< (x7.5) Copyright WCrinnion 2013 Crinnion W. Case Study. Unpublished research

72 MetalMMX Ref Pre Zeolite Post Zeolite EDTA/ DMPS Cd<.90.2 Pb< Hg< Copyright WCrinnion 2013 Crinnion W. Case Study. Unpublished research

73 MetalMMX Ref Pre Zeolite Post Zeolite EDTA/ DMPS Cd< Pb< Hg< Copyright WCrinnion 2013 Crinnion W. Case Study. Unpublished research

74 MetalMMX Ref Pre Zeolite Post Zeolite EDTA/ DMPS Cd< Pb< Hg< Copyright WCrinnion 2013 Crinnion W. Case Study. Unpublished research

75 Copyright WCrinnion 2013

76 Mean50 th 75 th 90 th 95th Blood Cd (ug/L) Urinary (ug/g creatinine) Copyright WCrinnion 2013 Urinary cadmium reflects both cumulative exposure AND the concentration of cadmium in the kidneys

77 2-fold increase in urinary cadmium in non- exposed persons correlated with 73% increased risk of fractures in women 60% increased risk of height loss in men (By CDC that would be 0.4 ug/g) Increased urinary cadmium excretion and renal tubular dysfunction were associated with signs of osteoporosis, as measured by bone mineral density, in men and older women. Staessen JA, et al. Lancet 1999; 353:1140–1144. PMID: Alfven T, et al. J Bone Miner Res 2000;15(8):1579–1586. PMID: Copyright WCrinnion 2013

78 Kidneys hold the highest burden of Cd Avg. 20 ug/g nonsmokers, 40 ug/g smokers Urinary Cd µ g/g creatinine associated with renal damage (Sweden)* Corresponded to mg/kg ug/g (Japan)** Urinary Cd of 2.5 µ g/g creatinine: 4-fold higher risk of tubular damage “ Significant effects were already seen at a mean level of 0.6 ug/g ” *** *Jarup, et al. Scan J Work Environ Health 1998;24:1-51 PMID: ** Uno, et al. Scan J Work Environ Health 2005;31: PMID: ***Akesson, et al. EHP 2005;113: PMID: Copyright WCrinnion 2013

79 Increased risk of developing diabetes Increased risk of high blood pressure and cardiovascular disease. Increased risk of obstructive pulmonary disorders Increased risk of breast, bladder and lung cancer. Copyright WCrinnion 2013

80

81 DMSA (great for lead and mercury) CaNa2EDTA (great for lead, cadmium, aluminum, nickel) DMPS (oral or IV – great for mercury) Commonly used but not substantiated Chlorella & Cilantro Metal Free & NDF Oral CaEDTA Zeolite Copyright WCrinnion 2013

82 DMPS  3mg/kg IV (up to 250mg)  10mg/kg po  Once every 2-4 weeks  Bowel Cleansing  Mag Sulf. 2 cc after each shot  Supportive nutrients DMSA  10 mg/kg tid (up to 2250mg daily)  5 days on, 9 days off****  Bowel Cleansing  Mag sulf 2 cc after each week on  Supportive nutrients Copyright WCrinnion 2013

83 2 days on (weekends) followed by 5 days off. Lower levels of DMSA given every 4 hours (patients does NOT need to wake themselves up at night for this) Copyright WCrinnion 2013

84

85 Day 1 – EDTA (2,000 – 3,000mg CaNa2EDTA and saline or sterile water) [50mg/kg] - Flush line with 3cc saline - DMPS (body weight) with saline or sterile water Day 2 – 6 - DMSA oral per body weight in 3 divided doses Day 7 – 14 - Heavy metal support - Colonics - Mag sulf Copyright WCrinnion 2013

86 DMPS Mercury Lead Silver Cadmium Nickel Arsenic Antimony Copper Molybdenum Zinc Manganese DMSA Lead Cadmium Mercury Silver Nickel Arsenic Molybdenum Copper Zinc Manganese Iron Tin Copyright WCrinnion 2013

87 DMSA suppositories at 20 mg/kg EDTA (Detoxamin) 750mg nightly Supplement with Zn in daytime 50% decrease in Pb in 3 months Neither seem to work as a flush-test agent D. Quig, personal communication Copyright WCrinnion 2013

88

89  35 y.o. female wanting to conceive  April 5- H/O Hg fillings recently removed  7 months of detox with Metal Free + more from local D.C.  Eats fish  Blood Hg levels 3/10/04 Hg 10 4/5/04 Hg 11 Copyright WCrinnion 2013

90 Metal DDI ref Pre Metal Free Post Metal Free Post DMSA Cd< Pb<5

91 Metal DDI ref Pre Metal Free Post Metal Free Post DMSA Cd< Pb<5

92 Test popular, unsubstantiated belief that “chlorella enhances biliary/fecal excretion of mercury” No published human studies available to date regarding metal detoxification Japanese research pertaining to growth stimulating effects in animals and humans Copyright WCrinnion 2013

93 Single celled marine algae (green) Triple cell wall (cellulose microfibrils) High protein and chlorophyll content Metal binding capacity (ponds) Absorption from human gut? Copyright WCrinnion 2013

94  No effect of 8-10 gm chlorella/day on fecal excretion of Hg in subjects with average intestinal Hg exposure  Undesirable GI side effects in all subjects  2/7 subjects exhibited trend for increased urinary Hg excretion (AA deficiencies?) D. Quig, unpublished research Copyright WCrinnion 2013

95

96 Standard Protocol at my old clinic Retest urine every ten weeks  20% are cleared by twenty weeks  60% are cleared by 30 – 50 weeks  20% take more than 50 weeks If lead is present repeat as needed. Combination EDTA, DMPS and DMSA are giving very rapid cleansing results And causing some increased LFTs! Copyright WCrinnion 2013

97 DMPS Pro Ease of use Great for Hg Con Legality Cannot reduce dose once it is given DMSA Pro Easy manipulation of dose to adverse responses Great for lead Con Amount of capsules Sulfur reaction Copyright WCrinnion 2013

98 Generally begin to show up on the third or fourth “round”. Usually begin on day three of taking DMSA. Can be relieved by:  Activated charcoal  Colonic irrigations  Reduction of DMSA intake (no help with DMPS)  Mentharil for GI problems with DMSA Copyright WCrinnion 2013

99 Sulfur Sulfur Nausea Nausea Diarrhea Diarrhea Belching Belching Arsenic Arsenic Fatigue Fatigue Irritability Irritability Blistering on Blistering on mucus mem mucus mem Bruising on Bruising on face face Hive-like rash Hive-like rash Mercury Mercury Fatigue Fatigue Irritability Irritability Insomnia Insomnia Anxiety Anxiety Depression Depression Anger Anger Crinnion, W. Unpublished research Copyright WCrinnion 2013

100 70% of methylmercury is recirculated via enterohepatic recirculation! Copyright WCrinnion 2013


Download ppt "Walter J. Crinnion ND SpiritMed www.DrCrinnion.com www.CrinnionOpinion.com Copyright WCrinnion 2013."

Similar presentations


Ads by Google