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Integria Healthcare Ltd and Standard Process® sponsor these webinars to provide health care information to practitioners and to provide them the opportunity to hear about the views, recommendations and experiences of other practitioners. Health-related information provided here is not a substitute of medical advice.

Integria, Standard Process and the speaker, Kerry Bone, have not evaluated the legal status of any products (except for MediHerb ® and Standard Process), services or recommendations with respect to state or federal laws, including scope of practice. Integria, Standard Process and Kerry Bone do not and cannot accept responsibility for errors or omissions or for any consequences from applications of the information provided and makes no warranty, expressed or implied, with respect to the information provided.

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Kerry Bone co-founded MediHerb and is the company’s Director of Research and Development. A practicing herbalist of 30 years, he is Principal of the Australian College of Phytotherapy and was appointed as an Adjunct Professor at New York Chiropractic College.

Kerry is a respected author of more than 30 scientific papers on herbal research. He has also written and co-written six popular books on herbal medicine, including his latest, the second edition of Principles and Practice of Phytotherapy, published in 2013 and recipient of the 2013 James A. Duke Botanical Literature Award.

Kerry was appointed to the American Botanical Council (ABC) Advisory Board in 2011 for his long-term support and contribution to the council’s nonprofit educational mission. This appointment is well-earned recognition of Kerry’s long-term commitment and outstanding contribution to herbal therapy. 3

Kerry Bone , BSc (Hons), Dip Phyto, FNHAA, MCPP

Internal Toxins (Endotoxins)

Bowel flora metabolites Liver toxic fats Excessive oxidative

products Advanced glycation end

products (AGEs) Products of inflammation Danger, products of cell

necrosis

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External toxins (Exotoxins)

Heavy metals

Dietary AGEs and other products of cooking

Toxic microbial metabolites

Persistent organic pollutants (POPs)

Other environmental chemicals: BPA, fire retardants etc

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External toxins (Exotoxins)

Ionizing radiation and electromagnetic fields

Drugs, including smoking

Food additives eg nitrosamines, trans fats

Atmospheric pollution

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Air and smoking

Water and drink packaging

Food and food packaging

Skin contact and hand-oral transfer

Personal care products

Dental fillings and body implants

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A study by the Environmental Working Group in 2005 identified 287 environmental contaminants in umbilical cord blood1

The urine of every one of 22 mothers and 26 children testedyielded evidence of exposure to TDCPP, a carcinogenic fire retardant2

1 http://www.ewg.org/research/body-burden-pollution-newborns. Accessed 18 August 2014

2 http://www.ewg.org/research/flame-retardants-2014. Accessed 18 August, 2014

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Vojdani A. A Potential Link between Environmental Triggers andAutoimmunity. Autoimmune Dis 2014;2014, Epub 2014 Feb 12

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Vojdani A. A Potential Link between Environmental Triggers and Autoimmunity. Autoimmune Dis 2014;2014, Epub 2014 Feb 12

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The following toxins have been implicated in human autoimmunity: Heavy metals: mercury, nickel, lead Organic solvents Nail polish chemicals Pesticides Bisphenol A (BPA) Hair dyes

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References1. Hybenova M, Hrda P, Procházková J et al. The role of environmental

factors in autoimmune thyroiditis. Neuro Endocrinol Lett 2010; 31(3): 283-289

2. Napier MD, Poole C, Satten GA et al. Heavy metals, organic solvents and multiple sclerosis: an exploratory look at gene-environment interactions. Arch Environ Occup Health 2014 Aug 19 [Epub ahead of print]

3. Mostafalou S1, Abdollahi M. Pesticides and human chronic diseases: evidences, mechanisms, and perspectives. Toxicol Appl Pharmacol 2013; 268(2): 157-177

4. Kharrazian D. The Potential Roles of Bisphenol A (BPA) Pathogenesis in Autoimmunity. Autoimmune Dis 2014 [Epub 2014 Apr 7]

5. Kouroumalis E. Environmental agents involved in the cause of primary biliary cirrhosis. Dis Markers 2010; 29(6): 329-336

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6. Vojdani A. A Potential Link between Environmental Triggers and Autoimmunity. Autoimmune Dis 2014, [Epub 2014 Feb 12]

7. Pollard KM1, Hultman P, Kono DH. Toxicology of autoimmune diseases. Chem Res Toxicol 2010; 23(3): 455-466

8. Barragán-Martínez C, Speck-Hernández CA, Montoya-Ortiz G et al. Organic solvents as risk factor for autoimmune diseases: a systematic review and meta-analysis. PLoS One 2012; 7(12): e51506

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The Environmental Working Group published their Dirty Dozen Endocrine Disruptors in 2013

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• BPA• Dioxin• Atrazine• Phthalates• Perchlorate• Fire retardants• Lead

• Arsenic• Mercury• Perfluorinated

chemicals (PFCs)• Organophosphate

pesticides• Glycol ethers

http://www.ewg.org/research/dirty-dozen-list-endocrine-disruptors. Accessed 18 August 2014

Schug TT, Janesick A, Blumberg B et al. Endocrine disrupting chemicals and disease susceptibility. J Steroid Biochem Mol Biol 2011; 127(3-5): 204-215 16

Schug TT, Janesick A, Blumberg B et al. Endocrine disrupting chemicals and disease susceptibility. J Steroid Biochem Mol Biol 2011; 127(3-5): 204-215

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Schecter A, Päpke O, Harris TR et al. Environ Health Perspect 2006; 114(10):1515-1520 18

Mainly the organochlorines: PCBs and DDT and its metabolites

Banned from use in industrialized countries for several decades

Are incredibly stable in the environment and accumulate in fat tissue

Potent endocrine disruptors - especially for thyroid hormone, insulin and sex hormones

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PCBs were positively associated withdiabetes and prediabetes1

Organochlorines are also implicated in type 2 diabetes (T2D); and obesity was not linked to T2D with low serum POPs2

PCBs, DDT metabolites and dioxin were linked to abdominal obesity3

Metabolic syndrome (MetS) was higher in more POP-polluted regions of the US4

1 Gasull M et al. Environ Sci Technol 2012. [Epub ahead of print] 2 Lee DH. Epidemiol Health 2012; 34: e20120023 Lee DH et al. Environ Int 2012; 40: 170-1784 Sergeev AV et al. Int J Environ Res Public Health 2011; 8(3): 762-776 20

Key issues are: Heavy metals Pesticides and other chemicals Reduced defenses: methylation, sulfation,

glutathione Dysbiosis toxicity

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2009 US study: increased urinary porphyrinmetabolites associated with mercury susceptibility/toxicity1

2013 US study: higher levels of lead in red blood cells and higher urinary lead and thallium2

Another 2009 US study: multiple positive correlations between ASD severity and urinary excretion of heavy metals (after challenge)3

1. Geier DA, Kern JK, Garver CR et al. J Neurol Sci 2009; 280(1-2): 101-1082. Adams JB, Audhya T, McDonough-Means S et al. Biol Trace Elem Res 2013; 151(2): 171-

1803. Adams JB, Baral M, Geis E et al. J Toxicol 2009; 2009: 532640

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CHARGE study (Childhood Autism Risks from Genetics and Environment) found proximity to agricultural organophosphates associated with 60% increased risk1

Mothers living closer to agricultural organochlorine use during pregnancy in California: 6 times more likely to have a child with ASD2

1. Shelton JF, Geraghty EM, Tancredi DJ et al. Environ Health Perspect 2014. [Epub ahead of print]

2. Roberts EM, English PB, Grether JK et al. Environ Health Perspect 2007; 115(10): 1482-1489

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24Shelton JF, Hertz-Picciotto I, Pessah IN. Environ Health Perspect 2012; 120(7): 944-951

Agricultural pesticide trends in the United States by percent of sales, 1964–2000 (U.S. Department of Agriculture 2006)

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Decreased plasma levels of reduced glutathione (GSH), sulfate and cysteine1 and S-adenosylmethionine (SAMe)2

Several recent studies: children with ASD have abnormal sulfation chemistry, limited thiol availability and decreased GSH reserve capacity2,3

1. Geier DA, Kern JK, Garver CR et al. J Neurol Sci 2009; 280(1-2): 101-1082. Adams JB, Audhya T, McDonough-Means S et al. Nutr Metab (Lond) 2011; 8(1): 343. Kern JK, Haley BE, Geier DA et al. Int J Environ Res Public Health 2013; 10(8):3 771-3800

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Often associated with higher heavy metal levels1,2

Consequences: increased oxidative stress, decreased detoxification, decreased methylation and mitochondrial dysfunction3

1. Hodgson NW, Waly MI, Al-Farsi YM et al. Exp Biol Med (Maywood) 2014; 239(6): 697-7062. Mutter J, Naumann J, Schneider R et al. Neuro Endocrinol Lett 2005; 26(5): 439-4463. Rossignol DA, Frye RE. Front Physiol 2014; 5: 150

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Adams JB, Audhya T, McDonough-Means S et al Nutr Metab (Lond) 2011; 8(1): 34

28Adams JB, Audhya T, McDonough-Means S et al Nutr Metab (Lond) 2011; 8(1): 34

Several independent studies have shown dysbiosis compared to age-matched controls1

One theory promoted by MacFabe is that antibiotic-induced dysbiosis leads to abnormally high levels of propionic acid production that acts as a neurotoxin2

1. Petrof EO, Claud EC, Gloor GB et al. BenefMicrobes 2013; 4(1): 53-65

2. Macfabe DF. Microb Ecol Health Dis 2012; 23 29

Exposure Detoxification and

excretion pathways Compensation for genetic

weaknesses Protective dietary factors

and cofactors Repair of damage

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31Maher J, Yamamoto M. Toxicol Appl Pharmacol 2010; 244(1): 4-15

Nrf2 expressed in all tissues: higher levels in key detoxifying organs: the liver and kidneys

Nrf2 activation enhances DNA repair, heme metabolism,efflux transport of toxins andglutathione synthesis

Activates detoxification, stabilizes proteins, increases metallothioneins and reduces inflammatory response

Maher J, Yamamoto M. Toxicol Appl Pharmacol 2010; 244(1): 4-15Lewis KN, Mele J, Hayes JD et al. Integr Comp Biol 2010; 50(5): 829-843

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Glutathione is a major non-protein cellular thiol It provides the fundamental antioxidant

protection for cells Also a signaling molecule in cell regulation and

apoptosis A key modulator of xenobiotic toxicity

Pizzorno JE,Katzinger JJ.

J Restor Med 2012; 1(1):24-37

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Glutathione Glutathione is a key detoxifier of HMs in the

body: HM binds to sulfur atoms in the tripeptide and excreted via the bile

Results in cellular depletion ofglutathione andsubsequent risk ofoxidative damage

Patrick L. Altern Med Rev 2006; 11(2): 114-127Patrick L. Altern Med Rev 2003; 8(2): 106-128Quig D. Altern Med Rev 1998; 3(4): 262-270

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Metallothioneins (MTs) Metal responsive transcription factor-1 (MTF-1)

is involved in cellular adaptation to stress, mainly HM exposure, but also hypoxia and oxidative stress

It is the main activator of the MT genes MTs are small cysteine-rich proteins that can

scavenge toxic HMs and free radicals They are induced by zinc, which upregulates

MTF-1Günther V, Lindert U, Schaffner W. Biochim Biophys Acta 2012; 1823(9) 1416-1425

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Transport proteins/channels used by essential metals in the gut (iron, zinc, calcium, magnesium) are thought to be involved in HM uptake

When dietary essential metals are in short supply and deficiencies develop, Cd absorption and toxicity are enhanced

This will apply for other HMs

Vesey DA. Transport pathways for cadmium in the intestine and kidney proximal tubule: focus on the interaction with essential metals. Toxicol Lett 2010; 198(1): 13-19

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