Exogenous Toxins: Intervention and Case Histories

Dr. Joseph Pizzorno, NDPresident Emeritus, Bastyr University

Editor, Integrative Medicine: A Clinician’s JournalChair, Scientific Advisory Board, Bioclinic Naturals

President, SaluGenecists, Inc.mail2@DrPizzorno.com

Copyright © 2015

• Avoidance!• Non-specific • Specific• Glutathione Support• Systemic

Interventions

Avoidance• Decrease Exposure!!• Organic, mostly plant-based diet• Choose low mercury fish• Low POP health and beauty aids• Remove amalgams Must be done by ecological dentist

Worst/Best Foods (www.ewg.org 9/14)

Dirty DozenTM1. Apples2. Strawberries3. Grapes4. Celery5. Peaches6. Spinach7. Sweet Bell Peppers8. Nectarines (imported)9. Cucumbers10. Tomatoes11. Snap peas (imported)12. Potatoes• Hot peppers• Kale

Clean 15TM1. Avocado2. Sweet Corn3. Pineapples4. Cabbage5. Sweet Peas6. Onions7. Asparagus8. Mangoes9. Papayas10. Kiwi Fruit11. Eggplant12. Grapefruit13. Cantaloupe (domestic)14. Cauliflower15. Sweet potatoes

Eating Organically Grown Foods Decreases POP Load

• Levels drop measurably within 3 days

• 10-fold increase in POPs doubles ADHD

Curl CL, et al. Organophosphorus pesticide exposure of urban and suburban preschool children with organic and conventional diets. Env Health Perspect. 2003;111:377-82Bouchard MF, et al. Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides. Pediatrics. 2010 Jun;125(6):e1270-7

Mercury In Fish• 10-fold variation from

lowest to highest• All fish contain some

mercury• Pick those with highest

omega-3 and lowest Hg: Sardines Anchovies Small salmon

Source:  http://www.fda.gov/Food/FoodSafety/Product‐SpecificInformation/Seafood/FoodbornePathogensContaminants/Methylmercury/ucm115644.htm 

HABAs Can Be Significant Source of POPs

Duty SM, et al. Personal care product use predicts urinary concentrations of some phthalate monoesters. Environ Health Perspect. 2005 Nov;113(11):1530-5

Duty 2005; Open Access

Non-Specific Detoxification Agents• Fiber• Antioxidants• Alpha lipoic acid• Curcumin

Fiber• Decreases enterohepatic recirculation• Limited research available• Pectin—Russian research• PGX Strong research support for improving insulin sensitivity

and weight loss

2.25 g tid

9

Pectin Increases Excretion and Protects Against Metals • Helps protect neurons from

mercury (rats)• Russian research shows

efficacy against Pb, Hg• 5g g bid for 1 month

decreased 137Cs 62% in children exposed to Chernobyl compared to 21% in controls

da Silva FR, et al. Phytoremediation potential of Maná-Cubiu (Solanum sessiliflorum Dunal) for the deleterious effects of methylmercury on the reproductive system of rats. Biomed Res Int. 2014;2014:309631Nesterenko VB, et al. Reducing the 137Cs‐load in the organism of “Chernobyl” children with apple‐pectin. Swiss Med Wkly2004;134:24–7

Chlorella Decreases HCA Metabolites• Dramatically decreases

HCA (heterocyclic amines from frying meat and fish) metabolites in urine

Binds in gut to prevent absorption of toxins and enter-hepatic recirculation of metabolites

• Chlorella will absorb toxic metals from environment Must ensure clean sourceLee I, et al. Detoxification of chlorella supplement on heterocyclic amines in Korean young adults. Environ Toxicol

Pharmacol. 2015 Jan;39(1):441‐6Kumar RM, et al. Accumulation of heavy metals (Cu, Cr, Pb and Cd) in freshwater micro algae (Chlorella sp.). J Environ Sci Eng. 2013 Jul;55(3):371-6.

Chlorella Decreases Toxic Metals• Oral administration (rats): • Increases stool and urinary

excretion of mercury • Decreases mercury in kidneys

and brain, but not liver• No apparent benefit with

removing cadmium• Benefit preventing cadmium

absorptionUchikawa T, et al. Enhanced elimination of tissue methylmercury in Parachlorella beijerinckii-fed mice. J Toxicol Sci. 2011 Jan;36(1):121-6Kumar RM, et al. Accumulation of heavy metals (Cu, Cr, Pb and Cd) in freshwater micro algae (Chlorella sp.). J Environ Sci Eng. 2013 Jul;55(3):371-6Kim YJ, et al. Effect of Chlorella vulgaris intake on cadmium detoxification in rats fed cadmium. Nutr Res Pract. 2009 Summer;3(2):89-94Jee Ae Shim JA, et al. Effect of Chlorella intake on Cadmium metabolism in rats. Nutrition Research and Practice (2009), 3(1), 15-22

• Binds metals so well, being used to clean up toxic waste sites

Must ensure clean source

Alpha Lipoic Acid

• Protects brain neurons from oxidative damage from mercury (rats)

• Pre-treatment (injected) at 35 μmol/kg (5.5 mg/kg)

• Increases glutathione (decreases depletion)

Yang TY, et al. Alpha‐lipoic acid protects against methylmercury‐induced neurotoxic effects via inhibition of oxidative stress in rat cerebral cortex. Environ Toxicol Pharmacol. 2015 Jan;39(1):157‐66

Curcumin to the Rescue

• Many of the mechanisms of damage from toxins are mitigated by curcumin

• Emerging research showing direct protection from specific toxins• Protects DNA from

perfluorooctane sulfonate

Çelik A, et al. The protective role of curcumin on perfluorooctanesulfonate‐induced genotoxicity: single cell gel electrophoresis and micronucleus test. Food Chem Toxicol. 2013 Mar;53:249‐55

POP Elimination• Little research for elimination/removal• Fiber• Bile sequestrants (eg., colestimide, cholestyramine)• Glutathione support• Antioxidant support, increased sweating, and

reducing intake all likely to benefit Vegan diet associated with lower PCB serum content, but

vegetarian diet associated with higher pesticide intake Organic diet eliminated OP pesticide metabolites in children

• Detoxification support – cruciferous vegetables• Systemic (sauna, fasting, hydrotherapy)

Arguin H, et al. Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies. Br J Nutr. 2010 May;103(10):1433-41.Van Audenhaege M, et al. Impact of food consumption habits on the pesticide dietary intake: comparison between a French vegetarian and the general population. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2009 Oct;26(10):1372-88.

DMSA • 2,3-Dimercaptosuccinic acid • SH-containing, water-soluble, low-toxicity, oral (IV toxic)• Developed in 1950s as alternative to more toxic

chelating agents• 10-20% of oral dose absorbed• Chelates all forms of mercury (more effective for Pb)• ½ through urine, ½ through bile• Amount of Hg bound: ~7.5 ug/g of oral DMSA• Increases glutathione production• ½ life in blood 2-3 hours

16

Ruha AM, Curry SC, Gerkin RD, et al. Urine mercury excretion following meso-dimercaptosuccinic acid challenge in fish eaters. Arch Pathol Lab Med. 2009 Jan;133(1):87-92Roels HA, Boeckx M, Ceulemans E, Lauwerys RR. Urinary excretion of mercury after occupational exposure to mercury vapour and influence of the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA). Br J Ind Med. 1991 Apr;48(4):247-53

DMSA• Nutrients to improve efficacy

Alpha lipoic acid NAC Probiotics

Fiber• Research studies use 30 mg/kg/day

7 days on, 7 off Not recommended

• Protocol we used: 50 mg trial dose; if no reaction within 2

hours: • 250 mg qd for 3 days then off for 11 days, or• 250 mg every 3rd day before bed

17Graziano JH, et al. 2,3-Dimercaptosuccinic acid as an antidote for lead intoxication. Clin Pharmacol Ther. 1985;37(4):431-8

NAC

• Most research animal and human cell lines

• Multiple benefits: Increases production of glutathione Protects human neurological cells

from Hg toxicity Reverses damage to human

pancreatic cells from Hg Directly binds to Hg, esp. MeHg, and

excrete through kidneys

18

Aremu DA, et al. N-acetylcysteine as a potential antidote and biomonitoring agent of methylmercury exposure. Environ Health Perspect. 2008 Jan;116:26-31Ballatori N, et al. N-acetylcysteine as an antidote in methylmercury poisoning. Environ Health Perspect. 1998 May;106:267-71

NAC• IV Treatment of acute acetaminophen

poisoning 150 mg/kg body weight given over 15-60

minutes Effective but high incidence of adverse

events—ER only!!• Oral Safe: No serious adverse events in

review of 4,000 patients 500 mg: 1-2 times a day

19Atkuri KR, et al. N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 2007 Aug;7(4):355-9

Watch for Sulfur Sensitive Patients• Clinical indications:

• Allergies Onion and/or garlic intolerance• GURD Sulfite sensitivity• IBS

• Laboratory:• Increased sulfite/sulfate ratio in urine• Decreased Phase II sulfation

• Intervention:• Molybdenum 300 ug/d• Manganese 20 mg/d

• DMSA and possibly NAC contraindicated until S metabolism improved 20

Lead Detoxification• Chelators: DMPS, DMSA, EDTA, d-penicillamine

(DPA)• Long history of EDTA use, most often used IV• EDTA also depletes Zn, Cu, Fe, Co, and Mn• Oral DMSA as effective as IV EDTA

• Pt example decreased from 3.7 to 2.4• Not clear if DMSA removes lead from bone, but does

reduce hippocampal lead• Combination of EDTA and DMSA increase amount

excretedBradberry, S et al. A comparison of sodium calcium edetate (edetate calcium disodium) and succimer (DMSA) in the treatment of inorganic lead poisoning. Clinical Toxicology 2009Bradberry Use of oral DMSA in adult patients with inorganic lead poisoning. QJM. 2009 Lee BK, Provocative chelation with DMSA and EDTA: evidence for differential access to lead storage sites. OccupEnviron Med. 1995

Cadmium Detoxification• Little data for chelation, but EDTA primarily used• Chelators may redistribute cadmium and increase

its toxicity• Extreme care as easily concentrates in kidneys• In workers with high exposure, a 14 year study found

if urinary levels were initially > 10 microg/g Cr, renal damage was irreversible with EDTA

• DMSA will chelate small amount• In a case study, glutathione was used with EDTA,

and appeared to increase both blood cadmium and renal excretion of cadmium

Gil HW, et al. Effect of glutathione on the cadmium chelation of EDTA in a patient with cadmium intoxication. Hum Exp Toxicol. 2011 Jan;30(1):79-83.Wu X, et al. Lack of reversal effect of EDTA treatment on cadmium induced renal dysfunction: a fourteen-year

follow-up. Biometals. 2004 Aug;17(4):435-41.

Cadmium – Sweat it Out!• Cadmium eliminated efficiently

through sweat • 20 individuals sweat via exercise,

steam or infrared sauna• Cadmium found in sweat in those

with undetectable serum levels, suggesting it could be used for assessment of burden

• Elimination of other minerals (Cu, Mn) suggests need replenishment during induced sweat

Genuis SJ, et al. Blood, Urine, and Sweat (BUS) Study: Monitoring and Elimination of Bioaccumulated Toxic Elements. Arch Environ Contam Toxicol. 2011 Aug;61(2):344-57

Arsenic Detoxification• Supporting methylation pathways seems logical• Increased urinary MMAV in arsenic-exposed subjects

suggests an inefficient methylation and probably an increased cellular concentration of the highly toxic MMAIII

• Dietary intake and serum concentration of cysteine, methionine, choline, selenium, zinc, folate, niacin, vitamin B12, ferritin, may all modify the metabolism, retention, and toxicity of arsenic

• Arsenic related skin conditions are more common in those with low folate status

• 400ug folate per day in those with low plasma folateincreased urinary DMA, and lowered blood MMA, which would seem likely to reduce disease risk

Gamble MV, et al. Folic acid supplementation lowers blood arsenic. Am J Clin Nutr. 2007 Oct;86(4):1202-9.

Glutathione: Critical• Difficult to overstate its importance• Most important intracellular and intra-mitochondrial

antioxidant• Binds and transports mercury out of cells and brain• Irreversibly(?) binds to mercury in the brain• Neutralizes oxidative damage from mercury and POPs• Facilitates detoxification of POPs• Depleted by oxidative stress, metals, alcohol• Even predictor of healthy aging!

Baker, SM. The Metaphor of Oceanic Disease. IMCJ February, 2008;7:1.Mosharov, E., Cranford, M.R., Baneriee, R. The Quantitatively Important Relationship between Homocysteine Metabolism and Glutathione Synthesis by the Transsulfuration Pathway and Its Regulation by Redox Changes. Biochemistry. 2000 Sept;39:13005-13011.

Glutathione• Tripeptide (cysteine, glycine and

glutamic acid)• Relatively high (5 millimolar)

concentrations in most cells• Exists in reduced state (GSH)

and oxidized state (GSSG)• Ratio determines cell redox

status Healthy cells at rest have a

GSH/GSSG ratio >100 Ratio drops to 1-10 in cells

exposed to oxidant stress• Produced exclusively in the

cytosol and actively pumped into mitochondria

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Wikipedia Commons

Synthesis, Regeneration & Recycling• GSH is made available in 3 ways:

Synthesis via a 2 step process catalyzed by the enzymes GCL and glutathione synthetase—requires ATP

Regeneration of oxidized GSSG to reduced GSH by glutathione reductase—requires NADPH

Recycling of cysteine from conjugated glutathione—requires NADPH

• Regulation of synthesis, regeneration & recycling Glutathione synthesis is primarily controlled by GCL because the rate-limiting step

is the cellular level of the amino acid cysteine GCL is in part regulated by GSH feedback inhibition

• If GSH is depleted due to oxidative stress, inflammation, or exposure to xenobiotics, de novo synthesis of GSH is up regulated, as is cysteine synthesis.

Biswas SK, Rahman I. Environmental toxicity, redox signaling and lung inflammation: the role of glutathione. Mol Aspects Med. 2009 Feb-Apr;30(1-2):60-76Townsend DM, Tew KD, Tapiero H. The importance of glutathione in human disease. Biomed Pharmacother. 2003 May-Jun;57(3-4):145-55

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Hall MN, Niedzwiecki M, Liu X, et al. Chronic arsenic exposure and blood glutathione and glutathione disulfide concentrations in bangladeshi adults. Environ Health Perspect. 2013 Sep;121(9):1068-74 Creative Commons Attribution License

Depleted GSH Has Been Implicated In:• Neurodegenerative disorders (Alzheimer's, Parkinson's

and Huntington's diseases, amyotrophic lateral sclerosis, Friedreich's ataxia)

• Pulmonary disease (COPD, asthma, and acute respiratory distress syndrome)

• Immune diseases (HIV, autoimmune disease)• Cardiovascular diseases (hypertension, myocardial

infarction, cholesterol oxidation)• Liver disease• Cystic fibrosis• Chronic age-related diseases (cataracts, macular

degeneration, hearing impairment, and glaucoma)• Aging process itself

Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem. 2009 Mar;390(3):191-214

Factors that Affect GGTIncrease• Excessive alcohol

• Acetaminophen worsens• Meat intake• Fried food intake• Smoking• Elevated blood sugar• Obesity• Anticonvulsants, OCAs

Decrease• Dietary vitamins C & E,

carotenoids and fiber• Fruit and vegetable intake• Bean and lentil intake• Whole grain intake• Nut intake• Physical activity• Coffee!

Lee DH, Gross MD, Jacobs DR Jr. Association of serum carotenoids and tocopherols with gamma-glutamyltransferase: the Cardiovascular Risk Development in Young Adults (CARDIA) Study. Cardiovascular Risk Development in Young Adults Study. Clin Chem. 2004;50(3):582-8Dixon JB, et al. Weight loss and non-alcoholic fatty liver disease: falls in gamma-glutamyl transferase concentrations are associated with histologic improvement. Obes Surg. 2006;16(10):1278-86Seifert CF, Anderson DC. Acetaminophen usage patterns and concentrations of glutathione and gamma-glutamyltransferase in alcoholic subjects. Pharmacotherapy. 2007;27(11):1473-82Lee DH, et al. Is serum gamma glutamyltransferase a marker of oxidative stress? Free Radic Res. 2004;38(6):535-9

Glutathione Strategies• Decrease depletion• Directly administer• Promote production• Lifestyle

Glutathione: Decrease Depletion• Decrease utilization

Decrease toxic exposure, esp alcohol• Decrease oxidative stress

Decrease oxidative markers, increase GSH Alpha-lipoic acid for mitochondria

• Increases GSH in skeletal muscle cells with CoQ10

Vitamin D for brain Melatonin for brain

Addolorato G, et al. Effects of short-term moderate alcohol administration on oxidative stress and nutritional status in healthy males. Appetite. 2008 Jan;50(1):50-6Liu J. The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: overview. Neurochem Res 2008;33:194-203Garcion E, et al. New clues about vitamin D functions in the nervous system. Trends Endocrinol Metab. 2002 Apr;13(3):100-5Herrera J,. Melatonin prevents oxidative stress resulting from iron and erythropoietin administration. Am J Kidney Dis. 2001 Apr;37(4):750-7Wagner AE, et al. A combination of lipoic acid plus coenzyme Q10 induces PGC1α, a master switch of energy metabolism, improves stress response, and increases cellular glutathione levels in cultured C2C12 skeletal muscle cells. Oxid Med Cell Longev. 2012;2012:835970

Wagner 2012; Creative commons

Glutathione: Direct Administration• IV glutathione• Nebulized glutathione• Oral glutathione• Oral liposomal glutathione• Topical glutathione• Intranasal glutathione

Witschi A, et al. The systemic availability of oral glutathione. Eur. J. Clin. Pharmacol 1992;43(6): 667–9Cooke RW, Drury JA. Reduction of oxidative stress marker in lung fluid of preterm infants after administration of intra-tracheal liposomal glutathione. Biol Neonate. 2005;87(3):178-80Buhl R, et al. Augmentation of glutathione in the fluid lining the epithelium of the lower respiratory tract by directly administering glutathione aerosol. Proc Natl Acad Sci USA 1990;87:4063–7Kern JK, et al. A clinical trial of glutathione supplementation in autism spectrum disorders. Med Sci Monit. 2011 Dec;17(12):CR677-82.

Glutathione – IV• Extremely short half-life in the plasma• High blood levels may carry mercury from blood into

brain (animal research)• Parkinson’s disease (symptomatic improvement )• Peripheral artery disease (improved pain-free walking

distance and several markers of circulation )• Study comparing IV glutathione to IV N-acetylcysteine

found the former to be more effective in preventing contrast-induced nephropathy

Sechi G, et al. Reduced intravenous glutathione in the treatment of early Parkinson's disease. ProgNeuropsychopharmacol Biol Psychiatry. 1996 Oct;20(7):1159-70.Hauser RA, et al. Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease. Mov Disord. 2009 May 15;24(7):979-83.Arosio E, et al. Effect of glutathione infusion on leg arterial circulation, cutaneous microcirculation, and pain-free walking distance in patients with peripheral obstructive arterial disease: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc. 2002 Aug;77(8):754-9.Saitoh T, et al. Intravenous glutathione prevents renal oxidative stress after coronary angiography more effectively than oral N-acetylcysteine. Heart Vessels. 2011 Sep;26(5):465-72

Glutathione - Nebulized• Elevates local and systemic levels• In cystic fibrosis found to improve several clinical

indicators, such as peak flow. • Case reports of success in emphysema

Bishop C, Hudson VM, Hilton SC, Wilde C. A pilot study of the effect of inhaled buffered reduced glutathione on the clinical status of patients with cystic fibrosis. Chest. 2005 Jan;127(1):308-17.Lamson DW, Brignall MS. The use of nebulized glutathione in the treatment of emphysema: a case report. AlternMed Rev. 2000 Oct;5(5):429-31

Glutathione – Oral• 3g oral showed no change in plasma glutathione• Recent trial @ Bastyr:

500mg bid to 40 healthy volunteers, randomized & double-blinded, placebo-controlled – 4 weeks long

Measured RBC GSH & GSSG (and ratio), as well as urinary markers of oxidative stress (F2-isoprostanes and 8-hydroxy-2′-deoxyguanosine)

Analyzed and contained >98% reduced glutathione, <1.4% oxidized glutathione, and was free of microbial contamination and heavy metals.

No significant changes in any parameter measured• Recent trial @ Penn State:

• 6 months long, using 250-1000mg GSH GSH levels were increased 30–35% in RBC, plasma, and lymphocytes, and

260% in buccal cells at higher dosage NK cytotoxicity up 2x Was benefit due to much longer time of dosage? i.e., expensive cysteine.

Witschi A, et al. The systemic availability of oral glutathione. Eur. J. Clin. Pharmacol 1992;43(6): 667–9Allen J, Bradley RD. Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. J Altern Complement Med. 2011 Sep;17(9):827-33. Richie, et al. Enhanced Glutathione Levels in Blood and Buccal Cells by Oral Glutathione Supplementation. (The FASEB Journal. 2013;27:862.32)

Lipoceutical & Transdermal -Glutathione • A small study of children with autism spectrum

disorders found that both oral lipoceutical and transdermal glutathione had some efficacy in improving plasma reduced glutathione levels.

Kern JK, et al. A clinical trial of glutathione supplementation in autism spectrum disorders. Med Sci Monit. 2011 Dec;17(12):CR677-82

Glutathione - Intranasal • Intriguing as does not transport Hg from blood• Lung absorption documented (very effective)• Children with chronic otitis media with effusion given

glutathione as a nasal aerosol had improvement in 67% versus 8% of controls

• Uncontrolled survey found 78.8% success for multiple chemical sensitivity, allergies/sinusitis, Parkinson disease, Lyme disease, fatigue and “other.” 12.1% reported ADRs.

• MRI showed 53% increase in brain after 20 mg intranasal 200 mg/ml

Testa B, et al. Management of chronic otitis media with effusion: the role of glutathione. Laryngoscope. 2001 Aug;111(8):1486-9Mischley LK, et al. Safety survey of intranasal glutathione. J Altern Complement Med. 2013 May;19(5):459-63

Glutathione: Increase Production• Silymarin Standardized extract, 100 mg tid

• NAC (also directly binds methyl-Hg) 300-1000 mg bid

• Whey powder 15 g bid

• SAMe Not methionine as it also increases homocysteine

Soltan-Sharifi MS, et al. Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione. Hum Exp Toxicol. 2007;26(9):697-703Micke P, et al. Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients. Eur J Clin Invest. 2001;31(2):171-8Jariwalla RJ, et al. Restoration of blood total glutathione status and lymphocyte function following alpha-lipoic acid supplementation in patients with HIV infection. J Alt Comp Med. 2008;14(2):139-46Liber CS, Packer L (November 2002). "S-Adenosylmethionine: molecular, biological, and clinical aspects—an introduction". Am J Clin Nutr. 76 (5): 1148S–50S

NAC Elevates Glutathione

• N-acetylcysteine• Amino acid cysteine is a rate-limiting factor for

GSH synthesis• Variety of both clinical trials and in-vitro/in-vivo

data suggest that supplying cysteine as NAC is an effective strategy for enhancing GSH production and intracellular cysteine.

• Increases intracellular glutathione• Dosage dependent increase

Dodd S, Dean O, Copolov DL, Malhi GS, Berk M. N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther. 2008 Dec;8(12):1955-62Soltan-Sharifi MS, et al. Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione, and extracellular thiol molecules and anti-oxidant power: evidence for underlying toxicological mechanisms. Hum Exp Toxicol. 2007 Sep;26(9):697-703.

NAC Decreases GGT• 600mg/day for 4 weeks reduced GGT from 62.7

to 46.3 U/L.• Expected result as decreases need for recycling

glutathione

Pamuk GE, Sonsuz A. N-acetylcysteine in the treatment of non-alcoholic steatohepatitis. J Gastroenterol Hepatol. 2003;18(10):1220-1

How About Beer (Alcohol-Free)?• 29 nuns, 58 to 73 y old, live in a convent with a

disciplined, regular, and homogeneous lifestyle• 500 mL/d of alcohol-free beer (0.0%) divided

into two doses over 45-days• 29% increase in RBC glutathione!

Martínez Alvarez JR, et al. Effects of alcohol-free beer on lipid profile and parameters of oxidative stress and inflammation in elderly women. Nutrition. 2009 Feb;25(2):182-7

Glutathione: Stimulate Production• Resveratrol

• 1 g/d (human study)

• Milk thistle/Silymarin• 166 mg bid in hepatitis C patients treated

with antiviral drugs

Kode A, et al. Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2008 Mar;294(3):L478-88Chow HH, et al. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer Prev Res (Phila). 2010 Sep;3(9):1168-75Nencini C, et al. Protective effect of silymarin on oxidative stress in rat brain. Phytomedicine. 2007 Feb;14(2-3):129-35

Cruciferous Vegetables• Cruciferous vegetables with intact glucosinolates

boost glutathione levels and detoxifying enzyme activity

• Cooking the cabbage before enzyme activation from damaged cells eliminates most of benefit

Tarozzi A, et al. Sulforaphane as an inducer of glutathione prevents oxidative stress-induced cell death in a dopaminergic-like neuroblastoma cell line. Neurochem. 2009 Dec;111(5):1161-71

Glutathione & Meditation

• Forty-two Sudarshan Kriya practitioners (practiced at least 1 year) and 42 normal healthy controls – cross sectional study

• Controls and practitioners had the same socioeconomic status, comparable BMI, were vegetarians, and were nonsmokers

• Practitioners had higher glutathione levels – 76.7±4.06 nmol/ml in controls, and 96.5±4.41 in practitioners

• Also had higher antioxidant enzyme activities, and transcriptional level for glutathione peroxidase, catalase, and higher GST-P1 levels

Sharma H, et al. Gene expression profiling in practitioners of Sudarshan Kriya. J Psychosom Res. 2008 Feb;64(2):213-8

Glutathione & Exercise• Hours/week of moderate exercise positively

associated with blood glutathione levels (not excessive exercise!)

• Aerobic and weight training combined more effective than either alone

Rundle AG, et al. Preliminary studies on the effect of moderate physical activity on blood levels of glutathione. Biomarkers. 2005 Sep-Oct;10(5):390-400.Elokda et al. Effects of exercise training on the glutathione antioxidant system. Eur J Cardiovasc Prev Rehabil. 2007 Oct;14(5):630-7.Abdull Razis AF, et al. Intact glucosinolates modulate hepatic cytochrome P450 and phase II conjugation activities and may contribute directly to the chemopreventive activity of cruciferous vegetables. Toxicology. 2010 Nov 9;277(1-3):74-85.

IV Glutathione Protects Neurons• 50% less glutathione (GSH) in the

substantia nigra of Parkinson's patients

• But not in other parts of brain => used up in neutralization of local toxins

• GSH 600 mg IV bid x 30 days 42 % decline in disability Lasted 2-4 months after stopped

• Protects both telomeres and mtDNA

Perry TL, et al. Idiopathic Parkinson's disease: A disorder due to nigral glutathione deficiency. Neuroscience Letter 1986;67:269-74Sechi G, et al. Reduced intravenous glutathione in the treatment of early Parkinson's disease. ProgNeuropsychopharmacol Biol Psychiatry 1996;20:1159-70Johnson WM, et al. Dysregulation of glutathione homeostasis in neurodegenerative diseases. Nutrients. 2012 Oct 9;4(10):1399-440. doi: 10.3390/nu4101399.

Adapted from Johnson 2012; Creative Commons Attribution license

Systemic Detoxification• Sauna• Fasting• Hydrotherapy• Spa Program

Sauna (Heat Chamber Depuration)• Extended time: 1-2 hours• Modest temperature: 150-170oF• Increases excretion of:

Heavy metals: arsenic, cadmium, lead, mercury Chemicals: phthalates, PCBs, PBBs, and HCBs Essential trace minerals

Sears ME, et al. Arsenic, cadmium, lead, and mercury in sweat: a systematic review. J Environ Public Health. 2012;2012:184745 Schnare DW, et al: Body burden reductions of PCBs, PBBs, and chlorinated pesticides in human subjects. Ambio, 1984Tretjak Z, et al: PCB reduction & clinical improvement by detoxification: and unexploited approach? Hum Exp Toxicol, 1990Cohn JR, et al: The excretion of trace metals in human sweat. Ann Clin Lab Sci 1978Lammintausta T, et al: Change in hormones reflecting sympathetic activity in Finnish sauna. Ann Clin Res, 1976

Hydrotherapy• Bath General Hospital Lead poisoning (colica pictonum) 120 years of records analyzed 3,377 patients with lead poisoning 45.4% cured; 93% improved

• Treatment 1+ hour full body (standing) immersion at 35oC 3 times per week; average stay 150 days

• Physiological research Standing full immersion:

• Increases cardiac output 50%• Increases excretion of lead 250%• Peak lead excretion at 2.5 hours

Heywood A: A trial of Bath waters: The treatment of Pb poisoning. Med Hist Supl 10:82-101, 1990

Spa Program• Juice fast, caloric restriction (800), meditation• Colonics (4)• 1 week residential

Wintering, N, et al. A pilot study to evaluate the physiological effects of a spa retreat that uses caloric restriction and colonic hydrotherapy. IMCJ 2011, 11:26-32

Silybum Marianum for Diabetes? • Increases antioxidant activity• Increases reduced glutathione• Decreases inflammation

• Decreases fasting blood sugar and HbA1c!

• Decreases LDL, triglyceride, SGOT and SGPT – all indicative of improved blood sugar control and decreased toxicity

• Curative use of a botanical medicine as addresses cause

Koujan SE, et al. Effects of Silybummarianum (L.) Gaertn. (silymarin) extract supplementation on antioxidant status and hs‐CRP in patients with type 2 diabetes mellitus: a randomized, triple‐blind, placebo‐controlled clinical trial. Phytomedicine. 2015 Feb 15;22(2):290‐6Huseini HF, et al. The efficacy of Silybummarianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double‐blind, placebo‐controlled, clinical trial. Phytother Res. 2006 Dec;20(12):1036‐9

Summary Intervention• Find and eliminate source of toxins• Eat organically grown foods, esp. dirty dozen• Use low POP HABAs (Health and Beauty Aids)• Facilitate detoxification: High fibre diet Multivitamin and mineral Long saunas

• Protect from damage by promoting glutathione NAC: 500 mg/d

• DMSA if high mercury or lead

Interventions We Used In Canada• Removal of amalgams—must use ecological dentist!!• IV DMPS

Stopped because of excessive adverse events “Brain fog”

• DMSA 250 mg x 3 days, 11 days off

• NAC 600 mg bid

• Fibre PGX: 2.25 g tid

• Supportive nutrients Multivitamin designed to promote glutathione production Ca/Mg/Zn until custom multivitamin available

Results of Oral Chelation Intervention• DMPS challenge test, ~ 1 year apart

40% reduction!

0.0

2.0

4.0

6.0

8.0

10.0

12.0

Post Hg Amalgams

Urinary Challenge Hg After 1 Year

StartRepeat

It All Started After Amalgams (MB)Intervention

All amalgams removed B-complex Vitamin C Infrared sauna IV DMPS

Results “Feel better now both

physically and mentally than I have in 15 years.”

Virtually all symptoms alleviated

All prescription drugs discontinued

Improvement within 2 weeks of removal of amalgams but full relief took ~ 2 years

57Bertsch M. A patient’s report of mercury poisoning. IMCJ 2010;9:14-15

48 yo male, employee, CalgaryRelevant medical history

Symptoms began 2 mo after amalgams and gold crowns

• Chest pain followed by weakness, dizziness and shortness of breath.

• Multiple trips to emergency room with no answers.

• Neck pain, gastrointestinal problems and insomnia. Extreme fatigue, chronic sinusitis.

8 amalgams, 2 gold crowns

Challenge urinary Hg : 5.8 ug/gcreat

MB Symptoms That Went Away• Chest pains• Completely exhausted all the time• Amalgam tattooing on the gums• Muscle twitching and muscle

tremors• Burning in the mouth and tongue• Numbness in the feet and hands-

feeling of something crawling under the skin

• Insomnia• Night Sweats• Tingling on the face• Tingling and prickly feeling on the

scalp and legs• Severe lower back pain• Sore muscles and joint pain• Double vision• Blurred vision

• Jabbing pain in the eyes• Dizziness • Depression• Anxiety – panic attacks• Memory loss• Brain fog – impaired cognitive

thinking• Sour and metallic taste• Increased saliva production• Intestinal problems• Elevated liver enzymes• Itchy hands• High pitch whining in the ears• Persistent cough and sore throat• Cold hands and feet• No appetite to eat

58

Am I Losing my Mind? April 2012• 67 yo white woman• I had the odd feeling that I

was living in a fog, that things were very fuzzy and that my memory was very sporadic. I was having trouble sleeping and had a lot of muscle aches during the night. I always had a metal taste in my mouth and felt that my breath lacked freshness other than the first few minutes after brushing my teeth. My skin and scalp were always sore and especially dry.

Hg = 50!

2 years IV chelation discontinued due to side effects & no benefit

November 2012

• I do know that things really improved once I started your protocol and I was happy to see the light at the end of the Mercury tunnel.

Hg = 12

June 2013

• With each successive test the symptoms were lessening and I was feeling more normal.

Hg = 7.3

December 2013• It was a day of

celebration when I received the last test results.

• I would caution people to remember that clearing mercury out of one’s system is a long process but it is worth the effort even if it takes many years. Being healthy is a good reward for all the patience required to do the heavy mercury lifting.

• Good luck with your seminars. I will always be in your debt for your help.

Hg = 3.5!

The Wealthy Business Man• 60 yo relatively healthy, but noticing progressive

loss of energy and brain function• Involved in aggressive healthy aging program• Seeing integrative medicine MD, who sought my

advice due to high mercury levels• Also seeing an acupuncturist

Blood Tests Show Current Exposure• 6/2013• Blood test results Bilirubin:high at 1.6 (0.2-1.2 mg/dl) ALT: high at 51 (9-46 U/L)

Hg: high at 19 (10 mcg/L)

FBS: High at 117 (65-99 mg/dL)

Current exposure to chemicals and Hg (possibly other metals, but not tested)

Elevated Body Load Hg and Pb

• 8/2013• Challenge test: Oral DMSA: 500 mg Oral DMPS: 300 mg

• High Hg and Pb• No fillings• Only eats low Hg fish• Put on my standard

metal elimination protocol

Blood Tests Still Not Normal• 7/2014• Blood test results Bilirubin still elevated at 1.7 (0.2-1.2 mg/dl) ALT “normal, but marginal 30 (9-46 U/L) Mercury still high at 18 (10 mcg/L) FBS still high at 111 (66-99 mg/dL)

Continuing current exposure to chemicals and Hg (possibly other metals)

• Told to stop taking Chinese herbal formulas and stop eating any fish

Blood Tests Still Not Good, But Hg Down• 12/2014• Blood test results Bilirubin still elevated at 1.5 (0.2-1.2 mg/dl) ALT “normal, but high 33 (9-46 U/L) Mercury normal at 6 (10 mcg/L) FBS still high at 109 (66-99 mg/dL)

Problem was fish and possibly Chinese herbal medicines

Still unidentified chemical exposure

Summary1. Body load of exogenous toxins substantial2. Most of the population has body loads at levels

associated with increased incidence of a wide range of diseases

3. Avoidance works, but exposure not avoidable4. Many effective natural medicine treatments: Fiber Specific nutrients Specific botanicals Systemic detoxification Drugs when needed