WHOLE DETOX: How to Thrive in a Toxic World through ... · •N=20 patients with self-claimed sx of “mercury poisoning” •N=20 patients who had amalgams removed because of symptoms

WHOLE DETOX: How to Thrive in a Toxic World

through Nutrition & Lifestyle

Deanna Minich, PhD Fellow and Board Member, American College of Nutrition Certified Nutrition Specialist Certified Functional Medicine Practitioner University of Western States, Professor Institute for Functional Medicine, Faculty www.drdeannaminich.com [email protected]

Objectives • To understand the role of toxins in disease,

sources of toxins, and assessment of exposure • To identify biochemical and genetic pathways

involved in detoxification processes: ARE gene upregulation biotransformative enzyme induction or inhibition, alkalinization, and heavy metal metabolism

• To understand the role of nutrition, nutrient actives, and botanicals in modulating detoxification processes

• To learn the importance of addressing nutrition and lifestyle protocols as part of detox

PART 1: Toxic Burden, Toxin Sources,

and Assessment

30 min.

5

Is toxicity for real? “The emerging problem of ubiquitous adverse toxicant exposures in modern society has resulted in escalating numbers of individuals developing a chemical sensitivity (CS) disorder. As usual in medical history, iconoclastic ideas and emerging evidence regarding novel disease mechanisms, such as the pathogenesis of CS, have been met with controversy, resistance, and sluggish knowledge translation.”

6 Clin Ther. 2013 May;35(5):572-7. doi: 10.1016/j.clinthera.2013.04.003. Epub 2013 May 1.

Public Health Reports, 2002, Vol 117: 315-323

“All humans are now exposed to synthetic pollutants in drinking water, air, and the food supply, as well as in consumer products and home pesticides. The quantity of an exogenous substance or its metabolites that accumulates in an individual or a population is defined as a ‘body burden.’”

The “Chemical

Body Burden”

7

Scientists estimate that everyone alive today

carries within her or his body at least 700

contaminants, most of which have not been

well studied.

http://www.chemicalbodyburden.org/whatisbb.htm 8

What is a toxin?

Any external or internal agent that interferes with good health

Toxicity & Key Definitions • Toxic: An physical, emotional, or mental effect or

substance capable of causing injury or death, especially by chemical means; poisonous to life

• Toxicant: A type of poison that is typically made by humans or introduced into the environment by human activity

• Toxin: An organic or inorganic harmful substance • Endotoxin: An internally-generated toxin • Exotoxin: An externally-generated toxin

• Xenobiotic: A chemical or organic compound that is foreign to the human body

• Xenohormesis: Stress compounds from a plant having benefit in human health

Types of Toxic Exposure • Heavy metals • Persistent organic pollutants • Food-related toxins

o Genetically-modified organisms o Hormones and antibiotics in animal foods o Lipophilic toxins in dietary fats o Gluten? o Aflatoxins o Sugar o Food allergens o AGEs

• Xenoestrogens • EMFs • Other

Public Health Reports, 2002, Vol 117: 315-323

“The general population’s body burden indicates

that even very small releases of persistent,

bioaccumulative substances can

build to significant levels over time.”

Patient’s Potential Disease Risk Due to Toxins =

Toxin Potency x

Duration x

Dose x

Genetic Susceptibility x

Environmental Factors

How Toxicity “Stacks Up”

Toxicity Effects Every Organ System • Typically starts with an immune dysfunction

• Refractory asthma • Extends into neurological (cholinesterase

inhibitors), endocrine, and gastrointestinal systems

• Pleiotropic effects of a single toxin and the toxin’s metabolites

14

How do you recognize toxicity in patients? Topline indications:

• Patients who are not responsive to therapies that are known to be effective

• Allergies, infections, autoimmunity • Occupational, hobby-related or residential

exposures prior to illness • “Florida is making me sick. I always feel

better when I leave.”

Clinical Pearls: Toxic Load • Evaluate your patient’s exposures • Look at the broad spectrum of inner and outer

toxins • Assess your patient’s vulnerabilities • Look to toxins when other therapies are not

resulting in significant change • Examine neurological and reproductive issues

within the toxin context

16

TOXIC METALS • Lead • Mercury • Cadmium • Arsenic • Aluminum

17

Toxic Elements: Where are they found?

• Drinking water, foods, dust, fish, dental amalgams, consumer products, and old pesticides

• Probable or established carcinogens • Accumulate in brain, kidney, liver, and bone • Endocrine disruption by Pb and immune

system impairment by Hg

18

Mechanisms of Heavy Metal Pathology

“…heavy metals bind to oxygen, nitrogen, and sulfhydryl groups in proteins, resulting in alterations of enzymatic activity.”

Soghoian S, et al. “Toxicity, Heavy Metals” 2009; http://www.emedicine.com/EMERG/topic237.htm

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Heavy Metals Signs of Chronic Exposure • Skin lesions as the first clinical expression: hyperkeratosis,

hyperpigmentation, transverse white lines on nails • Cardiovascular: atherosclerosis, ischemic heart disease,

hypertension, arrhythmias, PVD • Neurological: peripheral neuropathy, sensory and motor

disorders, cerebrovascular disease, headaches, disturbances of sleep, memory, and concentration;

• Hematological: anemia, leukopenia, thrombocytopenia • Gastrointestinal: Diffuse abdominal pain, dyspepsia,

hepatomegaly with hepatic fibrosis and portal hypertension • Increased cancer (lung, bladder, kidney, skin, liver, colon and

prostate)

“…the odds ratios for type 2 diabetes comparing participants at the 80th vs the 20th percentiles were 3.58 for the level of total arsenic (95% CI, 1.18-10.83), 1.57 for dimethylarsinate (95% CI, 0.89-2.76), and 0.69 for arsenobetaine (95% CI, 0.33-1.48)…This finding supports the hypothesis that low levels of exposure to inorganic arsenic in drinking water, a widespread exposure worldwide, may play a role in diabetes prevalence.”

Navas-Acien A, et al. JAMA. 2008 Aug 20;300(7):814-22.

Changes in serum levels of cytokines after removal of amalgam restorations “…removal of all dental amalgam restorations and replacement with other dental restorative materials was associated with decreased concentrations of Th1-type proinflammatory markers in serum.”

22

Toxicol Lett. 2012 Jun 1;211(2):120-5. doi: 10.1016/j.toxlet.2012.03.769. Epub 2012 Mar 28.

Urinary Hg higher in those with amalgams

• N=19 healthy controls without amalgams • N=21 healthy controls with amalgams • N=20 patients with self-claimed sx of “mercury

poisoning” • N=20 patients who had amalgams removed because

of symptoms • DMPS (2 mg/kg BW) IV; followed by urine collection

30 and 120 min after injection and throughout next 22 hours

• Persons with amalgam fillings excreted about three times more mercury than those without. 23 J Dent Res. 2000 Mar;79(3):868-74.

MERCURY AND AUTISTIC SPECTRUM DISORDERS

Maedica (Buchar).2012 Jan;7(1):38-48.

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By comparing hair concentration of autistic vs nonautistic children, elevated hair concentrations were noted for aluminum, arsenic, cadmium, mercury, antimony, nickel, lead, and vanadium. Hair levels of calcium, iron, iodine, magnesium, manganese, molybdenum, zinc, and selenium were considered deficient. There was a significant positive correlation between lead & verbal communication (p = 0.020) and general impression (p = 0.008). In addition, there was a significant negative correlation between zinc & fear and nervousness (p = 0.022).

25

Clinical Takeaways: • Hg comes from whole

foods • Alcohol may potentiate

toxic effects

Effect of vitamin E and C supplementation on oxidative damage and total antioxidant capacity in lead-exposed workers

• Antioxidants (vitamin E 400 IU + vitamin C 1 g/day) supplemented for 1 year to 15 workers exposed to Pb compared with non-Pb exposed workers.

• Pb intoxication = high oxidative damage • Antioxidant supplementation decreased the

oxidative damage. 26

Environ Toxicol Pharmacol. 2014 Jan;37(1):45-54. doi: 10.1016/j.etap.2013.10.016. Epub 2013 Nov 13.

The influence of beta-carotene on homocysteine level and oxidative stress in lead-exposed workers • N=33 healthy male workers exposed to Pb were

supplemented with beta-carotene at 10 mg per day for 12 weeks. N=49 control group

• After supplementation, the level of MDA significantly decreased, compared to baseline, by 16%, and to the reference group.

• When compared to the reference group, Hcy level was also significantly decreased.

• The level of thiol groups was significantly higher after supplementation with beta-carotene compared to the reference group.

27 Environ Toxicol Pharmacol. 2014 Jan;37(1):45-54. doi: 10.1016/j.etap.2013.10.016. Epub 2013 Nov 13.

How the body naturally detoxifies heavy metals

Blood

Kidneys

Liver

Stool

Urine

Metallothionein protein sequesters Hg inside cell

Metallothionein-Hg complex circulates

through blood to organs of elimination

Hg is excreted from body in form of urine and stool

• Proteins composed of about 30% cysteine • In absence of heavy metals, primary role is

to transport Zn and Cu • Known to efficiently bind several toxic

metals (particularly Cd and Hg) and act as transporter of toxic metals to the liver or kidneys for conjugation and excretion

• Prevents reaction of toxic metals with other biomolecules, thus attenuating their toxicity

• Inducible Andrews GK. Regulation of metallothionein gene expression by oxidative stress and metal ions. Biochem Pharmacol. 2000 Jan 1;59(1):95-104. Lichtlen and Schaffner. Bioessays. 2001 Nov;23(11):1010-7

More on metallothioneins

30 Andrews GK. Regulation of metallothionein gene expression by oxidative stress and metal ions. Biochem Pharmacol. 2000 Jan 1;59(1):95-104. Lichtlen and Schaffner. Bioessays. 2001 Nov;23(11):1010-7

Sweat helps to excrete metals • Blood, urine, and sweat were collected from 20

individuals (10 healthy participants and 10 participants with various health problems) and analyzed for approximately 120 various compounds, including toxic elements.

• Many toxic elements appeared to be preferentially excreted through sweat.

• Induced sweating appears to be a potential method for elimination of many toxic elements from the human body.

Arch Environ Contam Toxicol. 2011 Aug;61(2):344-57. doi: 10.1007/s00244-010-9611-5. Epub 2010 Nov 6.

Clinical Pearls: Heavy Metals • Provide a complex antioxidant supplement • Ensure adequate methylation support • Examine heavy metal toxicity at the same time

you look at mineral depletion/insufficiency • Give multi-mineral support • Induce sweating as a therapeutic modality

32

Environmental Toxins

Heavy Metals Persistent Organic Pollutants (POPs) Food-Based Toxins Xenoestrogens EMFs Other

Persistent Organic Pollutants (POPs) • Diverse group of chemicals • Dioxins and furans (herbicide contaminants,

incineration products, environmental product of antimicrobial “triclosan”)

• Polychlorinated biphenyls and polybrominated diphenyl ethers (old and newer flame retardants)

• Polyfluorinated stain replellents • Anti-wrinkle and nonstick compounds (e.g., Teflon) • Organochlorine chemicals (e.g., hexachlorbenzene,

DDT, DDT metabolite, DDE)

34

Persistent Organic Pollutants (POPs) • Biomagnify up the food chain • Accumulate in adipose tissue • Carcinogenic • Those with conjugated ring structures act as

endocrine disruptors • May bind with the aryl hydrocarbon receptor to elicit

toxic responses • Linked to diabetes, obesity, metabolic syndrome, and

endometriosis

35

Persistent Organic Pollutants are associated with increased markers of inflammation.

J Prev Med Public Health. 2012 Mar;45(2):62-9. 36

Organochlorine (OC) pesticides showed positive associations with CRP concentrations.

Organochlorines and Hormone Disruption

37

Kristin M. Bircsak, et al. J Biochem Mol Toxicol. 2013 February;27(2):157-164.

Organochlorine Levels High in Breast Adipose Tissue

Muñoz-de-Toro et al. Breast Cancer Research 2006, 8:R47 (doi:10.1186/bcr1534) 38

Organochlorines are associated with increased breast carcinoma proliferation

Muñoz-de-Toro et al. Breast Cancer Research 2006, 8:R47 (doi:10.1186/bcr1534) 39

Organochlorine pesticides and prostate cancer

“…serum levels of six OC pesticides and self-reported breast cancer (n = 63) or prostate cancer (n = 65) among 4,237 adult participants…revealed that participants with increasing serum concentrations of beta-hexachlorocyclohexane (HCH), trans-nonachlor, and dieldrin were more likely to report a history of prostate cancer than participants with OC concentrations below the limits of detection, based on covariate-adjusted odds ratios.”

Xu et al. Environ Health Perspect. 2010 Jan;118(1):60-6. Associations of serum concentrations of organochlorine pesticides with breast cancer and prostate cancer in u.s. Adults.

Autoimmune Disease and Insecticides

“Compared to never use, personal use of insecticides was

associated with increased RA/SLE risk, with significant trends for greater frequency and duration.” Parks CG, et al. Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the women's health initiative observational study. Arthritis Care Res (Hoboken). 2010 Aug 25. [Epub ahead of print]

41

“These findings suggest that persistent organic pollutants (POP’s) may be associated with type 2 diabetes risk by increasing insulin resistance, and POP’s may interact with obesity to increase the risk to type 2 diabetes”.

Diabetes Care 2007; 30: 622-28.

42

Why GGT?

• GGT gene expression increases in oxidative stress

• Related to resynthesis of intracellular glutathione

• Glutathione conjugates are formed during metabolism of xenobiotics

43 Lee DH, Jacobs DR, Porta M, J Epidemiol Community Health, 2006 ;60(12):1006-8.

Lee DH, Jacobs DR, Porta M, J Epidemiol Community Health, 2006 ;60(12):1006-8.

HIGH NORMAL SERUM GGT ASSOCIATED WITH TYPE 2 DIABETES IRRESPECTIVE OF BODY WEIGHT

20

40

60

80

100

<25 25-29.9 30-34.9 35+

GGT Q1

GGT Q2 GGT Q3

GGT Q4

HO

MA

BMI

44

Weight Loss and POPs

Serum concentrations of most POPs were higher in those with long-term weight loss, whereas they were lower in those with long-term weight gain.

Int J Obes (Lond).2011 May;35(5):744-7. 45

Gastric Bypass-Increased Plasma Concentrations of EDCs • Plasma organochlorine concentration

increased with weight loss and was related to magnitude of weight loss

• After surgery, 388.2% increase after 1 year

Hue et al. Obesity Surgery 2006;16:1145-1154 46

Modulating POPs through Nutrition • Nutrition modulates vulnerability to disease risks

associated with exposure to environmental pollutants.

• Healthful nutrient polyphenols are protective by upregulating antioxidant and anti-inflammatory pathways.

• Polyphenols can be used in sensing, capture, and remediation technologies.

• Healthy nutrition may provide a cost-effective and environmentally friendly means of modulating environmental toxicity.

Vitamin C lowers POPs in healthy women

• N=15 women • 2 mo supplementation with 1000 mg

vitamin C • Statistically significant decreases in 6

PCBs and 2 OCPs after supplementation

48 Food Chem Toxicol. 2016 Apr 15.

Clinical Pearls: POPs • Assess POP exposure through subjective and

lab assessment in patients with repeat weight loss/weight gain and metabolic issues

• Measure GGT as an indicator of oxidative stress and upregulated xenobiotic exposure

• Ensure a phytonutrient-rich diet

49

The “not-easily-degraded” toxins: Poly-Fluorinated Compounds

• Fluorine-containing chemicals to make materials resistant to stains and adhesion

• Source: Grease-resistant packaging (FAST FOOD), Scotchgard, Teflon, leather treatments, shampoos, dental floss, denture cleaners

• Exposure associated with developmental toxicity, neurotoxicity, reproductive toxicity, cardiovascular toxicity, metabolic dysregulation, development of arthritis, carcinogenesis, and immunotoxicity

• Not easily biodegraded • Several years half life

Environ Health Perspect 119:119-124 (2011). ISRN Toxicol. 2013 Sep 3;2013:483832.

Limiting PFC Exposure 1. Don’t eat fast food. 2. Avoid microwave popcorn bags, French fry

boxes and treated pizza boxes 3. Avoid products with Scotchgard, Stainmaster or

other stain-resistant coatings 4. Avoid Teflon and other non-stick cookware.

Discard products with ANY signs of deterioration

5. Check personal-care products. Avoid products with “fluoro” or “perfluoro” ingredients. PFCs may be found in dental floss and cosmetics, including nail polish, facial moisturizers & eye make-up.



We eat toxic foods.

53

AGEs are aging: “Gerontoxins” “In this review, we put forward the hypothesis that advanced glycation end products (AGEs) and their precursors, including methylglyoxal, are both biomarkers and causative agents (‘‘gerontotoxins”) characteristic for this disorder [Alzheimer’s disease].” Krautwald and Münch, Experimental Gerontology (2010)

• Slow, low cooking • Steaming, poaching rather than grilling, frying

• Adding in fresh leafy greens • Spices

How to Reduce AGEs

EPA List of Mercury in Fish www.cfsan.fda.gov/%7Efrf/sea-mehg.html

Most Toxic Least Toxic

1. Tilefish (Gulf of Mexico) 1.45 ppm 2. Shark 0.988 3. Swordfish 0.976 4. King Mackerel 0.730 5. Tuna (bigeye) 0.639 6. Orange Roughy 0.554 7. Marlin 0.485 8. Grouper 0.465 9. Mackerel Spanish 0.454 10. Tuna (fresh/frozen) 0.414 11. Chilean Bass 0.386 12. Bluefish 0.337 13. Lobster 0.310 14. Croaker, white (Pacific) 0.287 15. Scorpion fish 0.286 16. Weakfish (Sea trout) 0.256 17. Halibut 0.252 18. Sablefish 0.222 19. Bass (saltwater, black) 0.219 20. Snapper 0.189

1. Clam ND 2. Ocean Perch ND 3. Salmon (canned) ND 4. Shrimp ND 5. Whiting ND 6. Tilapia 0.010 7. Oyster 0.013 8. Salmon (fresh/frozen) 0.014 9. Hake 0.014 10. Sardine 0.016 11. Haddock 0.031 12. Crawfish 0.033 13. Pollock 0.041 14. Anchovies 0.043 15. Herring 0.044 16. Flounder/Sole 0.045 17. Mullet 0.046 18. Catfish 0.049 19. Scallop 0.050 20. Atlantic Mackerel 0.050

Is Butter Better? • Highest PCB levels in butter from Europe

and North America; Lowest from Australia and New Zealand

• Levels of p,p-DDT, p,p-DDE and HCH were highest in butter from areas where those compounds are in regular use (DDT = India and South/Central America; HCH = India, China, Spain).

Kalantzi OI, Environ Sci Technol 2001;35(6):1013-1018.

59

Glyphosate as Toxicant

60

61

Clinical Pearls: Food-Based Toxins • Limit animal-based products • Reduce high-heat cooking to reduce AGEs • Limit sugar and avoid artificial sweeteners • Avoid farmed fish (due to PCB contamination) • Avoid gluten and any GMOs

62



What are xenoestrogens?

The connection of

toxins to HORMONES

64

Plastics

• Vinyl an issue for additives and challenges with disposal

• Degraded plastic is most toxic • Can include bisphenols, phthalates, and

stabilizers and dyes

65

Why are some toxins called “endocrine disruptors”?

“Historically, the term was invented in 1991 and was defined by the US Environmental Protection Agency as ‘an exogenous agent that interferes with the production, release, transport. metabolism, binding, action or elimination of natural hormones in the body responsible for the maintenance of homeostasis, reproduction, development, and/or behavior’.”

Diamanti-Kandarakis Eet al. Endocrine Disruptors on Endocrinopathies ... Horm Metab Res 2010; 42: 543-552 66

Why Should We Care About Endocrine Disruptors? • Environmental xenobiotics as “endocrine

disruptors” that modify intercellular communication and function

• Produce a higher ratio of the 4 and 16 hydroxylated estrogen derivatives that are potentially more genotoxic by modifying members of the CYP450 enzyme family

• Changes in DNA methylation (epigenetic modification) which can ultimately change ER activity

• May play role in cancer, obesity (“obesogens”) Gore, Hormones 2010; 9(1):16-27

Endocrine Disruptors

“disrupt” metabolic pathways

Chen et al. Biochim Biophys Acta. 2009 July ; 1793(7): 1128–1143. doi:10.1016/j.bbamcr.2009.03.009.

“OBESOGENS” 68

Where to find EDs

Includes:

• Industrial compounds • Plastics and

plasticizers • Fungicides • Pesticides • Pharmaceuticals

Gore, Hormones 2010; 9(1):16-27; Latini et al., Mini-Reviews in Medicinal Chemistry, 2010, 10, 846-855

“Endocrine disruptors may be found in many everyday products– including plastic bottles, metal food cans, detergents, flame retardants, food, toys, cosmetics, and pesticides.” NIEHS-NIH: http://www.niehs.nih.gov/health/topics/agents/endocrine/index.cfm, Accessed 8/28/10

69

Phthalate Exposure and Allergy in the U.S. Population: Results from NHANES 2005-2006 In this cross-sectional analysis of a nationally representative sample, HMW phthalate metabolites, particularly mono-benzyl phthalate, were positively associated with allergic symptoms and sensitization in adults, but there was no strong evidence for associations between phthalates and allergy in children aged 6-17 years.

Environ Health Perspect. 2013 Jun 25. [Epub ahead of print]

Circulating serum xenoestrogens and mammographic breast density Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density.

Breast Cancer Res. 2013 May 27;15(3):R45. [Epub ahead of print]

Consider a detox program for women and men who are considering conception

Timing of Exposure to Endocrine Disruptors “Early life exposures to EDCs may alter gene expression via non-genomic, epigenetic mechanisms, including DNA methylation and histone acetylation, thus interfering with the germ-line.” Latini et al., Mini-Reviews in Medicinal Chemistry, 2010, 10, 846-855 Grun and Blumberg, Molecular Endocrinology 23: 1127-1134,2009

72

Endocrine Disruptors Can Accumulate in Adipose Tissue

Latini et al., Mini-Reviews in Medicinal Chemistry, 2010, 10, 846-855

“…Greater exposure to persistent ED is associated with the high consumption of fatty foods of animal origin.”

73

PCBs and Estrogen Metabolites “These data suggest that PCBs may significantly alter the metabolism of catechol estrogens in vivo and that this effect may be mediated by catechol metabolites of PCBs. It is further speculated that methyltransferase inhibition by PCB catechols may contribute to PCB-mediated endocrine effects and liver carcinogenesis.”

Catechol Metabolites of Polychlorinated Biphenyls Inhibit the Catechol-O-methyltransferase-Mediated Metabolism of Catechol Estrogens. Garner, C. E., Burka, L. T., Etheridge, A. E., and Matthews, H. B. (2000). Toxicol. Appl. Pharmacol. 162, 115–123.

Aromatase Activity and Endocrine Disruptors “Our results showed that TCDD increased the aromatase activity in a time- and dose-dependent manner.Further investigation indicated that TCDD slowed down the CYP19 mRNA degradation…”

Chan et al. Mol Cell Endocrinol. 2010 Apr 12;317(1-2):8-13. Epub 2009 Dec 3.

“…the neuroendocrine systems do not exist in a vacuum: they communicate with one another and this cross-talk could exacerbate effects of exposures across multiple homeostatic systems.” Gore, Hormones 2010; 9(1):16-27

Our data suggest three practices that may contribute to these lower levels (of phthalates): (1) Consuming mostly homegrown produce; (2) No cosmetics and limited use of PCPs (3) Transportation primarily by sources other than

automobiles 76

Sources of Bisphenol A • Hard, clear, near shatterproof plastic – polycarbonate. • Epoxy resin coating in metal food cans • Plastic bottles and cups for babies. Heating these bottles releases up to

55-times more BPA • Precursor of flame-retardant – tetrabromobisphenol A • Bicycle helmets • Car safety seats • Water coolers • Medical devices • CD’s, credit cards, cell phones, computers, cars • Sports equipment • Household electronics • Some drinking water • Cash receipts printed with the heat process such as those dispensed by

ATM’s. In some cases receipts contained 250 to 1000 times more BPA than is found in baby bottles

Source: “Fact Sheet on Bisphenol A” by the Cancer Association of South Africa, Aug 2010; Dr. C. Albrecht 77

Exposure to bisphenol A from drinking canned beverages immediately increases blood pressure • N= 60 • A total of 60 participants visited the study site 3 times, and they were

provided the same beverage in 2 glass bottles, 2 cans, or 1 can and 1 glass bottle at a time. The sequence of the beverage was randomized.

• Urinary BPA concentration, blood pressure, and heart rate variability was measured 2 hours after the consumption of each beverage.

• The urinary BPA concentration increased after consuming canned beverages by >1600% compared with that after consuming glass bottled beverages. SBP increased by ≈4.5 mm Hg after consuming 2 canned beverages compared with that after consuming 2 glass bottled beverages, and the difference was statistically significant.

78 Hypertension. 2015 Feb;65(2):313-9.

Childhood “Obesogens”

Urinary BPA concentration was

significantly associated with obesity in this

cross-sectional study of children and adolescents.

JAMA. 2012 Sep 19;308(11):1113-21. 79

No significant differences in food intake or physical activity. The difference was low dose neonatal exposure to an environmental estrogen.

Mol Cell Endocrinol. 2009 May 25;304(1-2):84-9. 80

Greater rates of metabolic syndrome with higher concentrations of bisphenol A

Int J Endocrinol. 2012;2012:598180. doi: 10.1155/2012/598180. Epub 2012 Nov 28. 81

“Based upon analysis of data from the NHANES report a strong relationship between urine concentrations of Bisphenol A and the incidence of CVD, type 2 diabetes, and liver-enzyme abnormalities in a representative sample of the adult US population”. JAMA 2008; 300: 1353-54.

“After adjusting for potential confounders, we found that higher BPA concentrations were associated with diagnoses of cardiovascular disease and diabetes. We also found associations between higher BPA concentrations and clinically abnormal concentrations of the 3 liver enzymes examined, namely GGT, alkaline phosphatase, and lactate dehydrogenase.” Lang et al. JAMA. 2008;300(11):1303-1310 (doi:10.1001/jama.300.11.1303)

BPA and PCOS • “BPA levels were significantly higher in the total

PCOS group compared with the controls.” • “PCOS women, lean and overweight, had higher

BPA levels compared to the corresponding control group lean and overweight.”

• “A significant association of testosterone and androstenedione with BPA was observed.”

• “Multiple regression analysis for BPA showed significant correlation with the existence of PCOS. BPA was also positively correlated with insulin resistance in the PCOS group.” Kandaraki et al., J Clin Endocrinol Metab. 2010 Dec 30. [Epub ahead of print]

PCOS and perfluorinated compounds

84

Vagi et al., Biomedical Central, 2014

Urinary bisphenol A concentration and thyroid function in Chinese adults High urinary BPA level was associated with increased thyroid function (adjusted odds ratio= 1.71 [1.26 to 2.32]).

Epidemiology. 2013 Mar;24(2):295-302. doi: 10.1097/EDE.0b013e318280e02f.

It’s not just BPA… 86

BPA BPF BPS

87

BPS Relatively high levels of BPS have been measured in thermal paper receipts, tickets, boarding passes, and luggage tags.

88

Environ Health Perspect. Mar 2013; 121(3): a76.

BPS, once considered a safe substitute for BPA, disrupts membrane-initiated E2-induced cell signaling, leading to altered cell proliferation, cell death, and prolactin release. Environ Health Perspect. Mar 2013; 121(3): 352–358.

Bisphenol AF In the present study, we found bisphenol AF to be a strong ligand for both ERα and ERβ receptors, although it shows a 3 times greater preference for ERβ over ERα. Bisphenol AF is a full agonist for ERα but an antagonist for ERβ.

89

Environ Health Perspect. Sep 2010; 118(9): 1267–1272.

Clinical Pearl: Reduce BPA in your body by reducing the intake of packaged foods. An organic, fresh (no cans or plastic) food diet dropped BPA levels by 66% within 3 days. Rudel RA, et al. Environ Health Perspect. 2011.

90

Clinical Pearls: Xenoestrogens • Avoid all plastics • Assess GGT, alkaline phosphatase, and lactate

dehydrogenase as lab markers for exposure to xenoestrogens

• Avoid eating/drinking out of plastics and cans and reduce xenoestrogens significantly within days.

91



Exposure to EMF sources • Household and Office Wiring • High Tension Electrical Cables

and Towers • Electrical Powerlines • Substations, Transformers • Radio & Television Transmission

Towers • Cell Phone Masts/Towers • Cell Phones • Bluetooth & Headphone Devices • Cordless Phones, Baby

Monitors

• WiFi Routers & Wireless Devices • WiFi Hotspots • Computers, Laptops • Microwave Ovens • Electric Clocks, Razors, Blankets,

Hairdryers • Fluorescent and Compact

Fluorescent Lighting • Airport Radars &

Telecommunication Equipment • Airport Body Scanners • Military Radars, RF and ELF • Smart Meters

Summary of the effects of electromagnetic fields at the cellular level

Clin Exp Reprod Med. 2012 March; 39(1): 1–9

“The current study found that there is possible evidence linking mobile phone use to an increased risk of tumors from a meta-analysis of low-biased case-control studies.” “Results from present studies on use of mobile phones for > or =10 years give a consistent pattern of increased risk for acoustic neuroma and glioma.”

Cell phones and electromagnetic radiation

Myung et al. J Clin Oncol. 2009 Nov 20;27(33):5565-72. Epub 2009 Oct 13.

Hardell et al. Occup Environ Med. 2007 Sep;64(9):626-32. Epub 2007 Apr 4.



The Effects of Long-term Air Pollution Exposure and Mortality

“We conclude that our analysis showed an increased risk of mortality for all and specific causes associated with PM2.5, and the risks are higher than what was previously observed for PM10. In addition, coarse particles are also associated with more deaths.” Environ Health Perspect 117:898–903 (2009). doi:10.1289/ehp.0800108 available via http://dx.doi.org/ [Online 13 February 2009]

Volatile Organic Compounds (VOCs) • Large group of chemicals • Lower molecular weight and volatility • Solvents such as gasoline and fragrance

ingredients. • May interfere with cellular membranes and

cause diverse neurological effects • Some such as formaldehyde, benzene, and

synthetic musks are carcinogens

98

Metabolic Toxins • Metabolic endotoxemia • Hormones • Free radicals • Bacteria/fungi/viruses • Psychological toxins

We generate our own psychological toxins. Emotional expression is a means of ‘detox’.

100

Our Psychology Becomes Our Biology.

J Immunotoxicol. 2008 Apr;5(2):221-5. doi: 10.1080/15476910802131444.

Risk of developing certain diseases correlates with human personality.

TYPE B

TYPE A

TYPE C

TYPE D

KUBZANSKY L D Cleveland Clinic Journal of Medicine 2011;78:S65-S68 ©2011 by Cleveland Clinic

Ask your patients…

• What level of stress do they have in their lives? • How long have they experienced chronic stress? • What are their coping mechanisms? • How much does stress get in the way of a healthy

lifestyle? • Is detox a form of stress? How can it be made less

stressful?

Solutions for Stress During a Detox

• Track stress levels before, during and after the detox

• Replacing yang activity with nourishing yin activity (e.g., yoga instead of running)

• Try to increase exposure to nature • Ensuring adequate sleep/rest • Avoid stressful stimuli from movies, video games,

etc. during detox

“…Patients who were moved to tears had a more easily controlled RA compared with those who were emotionally affected but not moved to tears.” Clin Exp Rheumatol. 2003 Sep-Oct;21(5):611-6.

Tears as Toxin Removal

Separate studies showed that the risk of developing heart disease is significantly increased for people who impulsively vent their anger as well as for those who tend to repress angry feelings. A. Siegman et al. J Behav Med. 1998; 21(4) D. Carroll et al. J Epidemiol Comm Health. 1998; Sept. In a groundbreaking study of 1,200 people at high risk of poor health, those who learned to alter unhealthy mental and emotional attitudes through self-regulation training were more than four times more likely to be alive 13 years later than an equal-sized control group. R. Grossarth-Maticek & H. Eysenck. Behav Res Ther. 1991; 29(1)

Toxic Emotional Expression & Disease

Emotional suppression leads to overeating, especially in overweight/obese individuals

• N=314 participants • Questionnaires

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Eur Eat Disord Rev. 2016 Apr 21.

Pessimism & Inflammation • People who have negative expectations

for the future also have greater risk for the diseases associated with aging and early death as supported by elevated levels of inflammatory compounds in their bodies compared with people who are optimistic.

• Stress and pessimism have been shown to shorten telomeres and decrease telomerase.

Matthews KA, Räikkönen K, Sutton-Tyrrell K, Kuller LH Optimistic attitudes protect against progression of carotid atherosclerosis in healthy middle-aged women. Psychosom Med. 2004 Sep-Oct;66(5):640-4; O'Donovan A, Lin J, Dhabhar FS, et al. Pessimism correlates with leukocyte telomere shortness and elevated interleukin-6 in post-menopausal women. Brain Behav Immun. 2009 May;23(4):446-9.

Stress Turns on Inflammatory Markers

Pro-inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) are secreted by immune and neural cells in response to both physical (i.e., pathogens) and psychological stressors.

Explore (NY). 2010 Jan-Feb;6(1):29-41. Top-down and bottom-up mechanisms in mind-body medicine: development of an integrative framework for psychophysiological research. Taylor AG, et al.

Assessments

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Toxin Measurements

• Direct assessments of exogenous or endogenous toxic agents in a biological medium (blood, urine, hair, nails, stool, sweat, adipose tissue)

• Indirect assessments of metabolites from endogenous or exogenous agents

112

A single toxicity panel – can use as a baseline intervention to assess body burden

113

• Whole blood test • 10 volatile solvents • Neurological complaints • Carcinogens (kidney, liver damage) • Quick half-life, but some bioaccumulation • GST and glycine – biotransformation

Think Styrofoam

cups, gasoline,

home remodeling, new carpets,

labs, etc.

Volatile solvents

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CHLORINATED PESTICIDES • Serum specimen • Source: high-fat animal foods • Most of these chlorinated pesticides have been banned, but still in

environment. Carcinogenic and detrimental during fetal development • Results = current exposure; Lipid-adjusted: body-burden • Ratio between amount of lipids to toxins (correlates with adipose levels, so

no biopsy needed) • CDC (lipid adjusted results)

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PCBs • Serum specimen • Fast weight loss = potential toxic reaction due to lipolysis and liberation of

toxins into blood stream • Note bariatric surgery patients – support with detox intervention • Coolants, lubricants, fluorescent lights, fatty foods (farmed salmon, butter,

sushi) • Carcinogenic, immune/neuro/endocrine effects, low IQ, thyrotoxins, children

vulnerable to attentional issues

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Organophosphates • Urine specimen • Found in pesticides/insecticides • Inhibit cholinesterase – buildup of Ach – neurological dysfunction • Obesogens • Look at atrazine mercapturate (sulfur residue from glutathione) to get an

indication of biotransformation (follow up with IV glutathione, nutrition support for glutathione regeneration, remove toxic trigger)

117

BPA • Urine specimen • Cans, plastics, spermicide • EU – banned BPA • Epigenetic toxicant • Increased urinary triclosan associated with increased sensitization

118

Phthalates and Parabens • Urine specimen • Personal care products and dietary supplements (enteric coating), water

bottles • Endocrine disruptors • Mitochondrial toxins (methyl and propyl)

Other Labs

• Adrenal Stress Profile • Anti-Candida Antibody • Complete Sex Hormones • Thyroid Hormones • IgE Mold • SNPs – Detoxigenomic • Nutrient status • Oxidative stress • Blood glucose and insulin • Blood lipids • Blood pressure • Homocysteine • Oxidative stress/TBARS/8-OH-dG • SNPs for detox enzymes: COMT and MTHFR • Gut flora panel • Pesticide levels • RBC Micronutrients (e.g., selenium, copper, zinc) • LFTs, particularly GGT

119

Putative Serological Biomarkers for Toxicity

• Gamma-glutamyltransferase (GGT)

• >40 units/L • Uric acid

• >8mg/dl • Homocysteine

• >11 micromol/L • hsC-reactive protein

• >0.5 mg/L

• Hemoglobin A1c • >5.5%

• 25-Hydroxyvitamin D3 • <30 ng/ml

• Body Mass Index • >25

• Body Composition • >30% body fat

Review of Basic Paper Assessments – Tier 1 • Intake Form • Adult Toxin Exposure Questionnaire • Toxic Exposure Timeline • Medical Detoxification Questionnaire • Food & Lifestyle Journal

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122

Adult Toxin

Exposure Questionnaire

Source: IFM Toolkit

123

Adult Toxin


Source: IFM Toolkit

124

Adult Toxin


Source: IFM Toolkit

125

Detoxification Questionnaire

A subjective review of organ systems to be used in conjunction with your physical exam and health history to help you determine severity of patient symptoms and duration of detoxification. Tracking tool that allows practitioner and patient to establish a baseline and evaluate symptom improvement.

Clinical Protocol: MDQ Assessment Individualize your treatment not only based upon the diagnosis but the severity of symptoms and the fragility of the patient.

Start low, go slow. Strong medicine, serious side effects for serious diseases.

MDQ ≥ 100 – Severe symptomatology (suspect fragility) MDQ ≥ 70 – Significant symptomatology MDQ ≥ 50 – Indicates need for detoxification MDQ ≥ 30 – Indicates need for continued intervention

Aim for 3 consecutive days

Review of Basic Paper Assessments – Tier 2 • Feeling Wheel (find online) • Emotion Log (Whole Detox book) • Whole Detox Questionnaire (Whole

Detox book and online at www.whole-detox.com)

• Life Stress Questionnaire (IFM Tool Kit) • Surroundings Inventory (IFM Tool Kit) • Social Network Inventory (IFM Tool Kit)

129

130 Source: IFM Toolkit

131

Major detox organs and their emotional symbolism

• Gut – Letting go

• Liver - Anger

• Kidney - Fear

• Skin – Self-esteem

• Lung – Grief/Acceptance

133

Evaluate social networks

• Social integration, social support, and social conflict have been related to inflammatory processes.

• Social relationships impact gene expression, intracellular signaling mechanisms, and inflammatory biomarkers.

Neurosci Biobehav Rev. 2010 September ; 35(1): 33–38. doi:10.1016/j.neubiorev.2009.09.003.

Social conflict, stress, & inflammation • Social conflict and interpersonal stress have been

associated with inflammation. • In a six-month longitudinal study of adolescent females,

greater interpersonal stress was associated with larger lipopolysaccharide (LPS)-stimulated IL-6 production and bigger NFκB increases over time (Miller et al., 2009).

• Among adults diagnosed with rheumatoid arthritis, greater daily interpersonal stress was also related to higher LPS-stimulated IL-6 production (Davis et al., 2008).

• Similarly, adolescents who reported more daily interpersonal stressors had higher CRP plasma levels than those with less interpersonal stress (Fuligni et al., 2009).

Neurosci Biobehav Rev. 2010 September ; 35(1): 33–38. doi:10.1016/j.neubiorev.2009.09.003.

Giving & Receiving: Exploring Social Network Support

Questions to ask your patients: • Do you have a tribe you trust? • Do you feel supported by friends/family? • Do you feel like there are people who

“drain your energy”? • Are there people in your life who are toxic?

Review of Environment

• Water analysis • Home mold • Air quality

137

Water Analysis

138

139

140

141

142

Some facts about home mold inspection • Houses “breathe” – the #1 way to destroy a

home through mold is to leave it unheated or damp

• 20-30% of homes have mold in the Pacific NW

• Older homes that use plaster instead of dry wall have less mold; Mold requires moisture + cellulose

• Wallboard moisture can be tested. Needs to be under 40%.

143

Assessing moisture in walls

144

145

Air Analysis for Spores

146

Mycotoxins: Look for the random symptoms • Blurry vision • Imbalance • Shooting pain • Strange sx in certain places • Difficult to classically profile • Without patterns

147

Good websites • www.survivingmold.com – VCS Test • Contrastsensitivity.net - Free

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Where is mold? • Everywhere – food, bathrooms, clothing,

books • Certain molds are toxic • Only a certain % of people seem to be

susceptible. • Mold spore count – allergy (headache,

stuffy nose, chronic sinus infection) – Candida, food sensitivities cross reacting to mold

• Neurologic, ADD, autoimmune disease, hand numbness 149

Mold testing • Home testing – mold spore count • Doesn’t deal with the toxic molds and gases

they give off • Your body knows more than any test! • If more chronic, look at urine; RealTime Labs –

Dallas, TX ERMI test • Go to hotel or relative’s house and stay in the

same city • Work buildings or children in schools • Do sx improve?

150

Moving into a house: Steps to take • Can sense that it is there • ERMI test – buy house conditional on whether

this comes up negative • Traditional mold test • Spend some time in the place

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PART 2: Detoxification Pathways &

the Role of Nutrients

60 min.

Detox from the 50,000 ft. view

Metabolic Detoxification

Toxic Exposure

Toxins enter the body. Some are eliminated via the stool or sweat,

while others are transported to the

liver. The liver processes the toxins

and then they are eliminated via urine or

stool.

Metabolic Detoxification

Phase I Biotransformation

Enzymes in the liver breakdown xenobiotics, a process that produces

harmful free radicals

Phase II Conjugation

Molecules are joined with the modified xenobiotics to

produce harmless, water- soluble substances. These

water-soluble substances are then released to the kidney or back to the GI tract.

Personalized Nutrition Approaches: Tailoring Foods to Pathways

156

1. Fortify the ARE production of antioxidant enzymes

2. Maximize (hepatic) biotransformation pathways, such as methylation

3. Induce heavy metal metabolism and removal

4. Promote alkalinization

Personalizing Foods to Exposomic Pathways

J Nutr Metab. 2015;2015:760689. doi: 10.1155/2015/760689. Epub 2015 Jun 16. Review.

1. Phase I Cytochrome Systems 2. Phase II Conjugation Enzymes 3. Antioxidant Response

Element/Nrf2 4. Metallothionein Response

Element

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158





Genetic Upregulation of Detoxification ARE Enzymes through Targeted Nutrients

J Physiol. Sep 1, 2011; 589(Pt 17): 4125–4136.

Mitigating effects of toxins through ARE gene expression • PCBs can initiate

inflammation • This process can be

exacerbated or ameliorated by nutrition

• Omega-6 fats can worsen PCB-induced vascular toxicity

• Omega-3 fats and flavonoids can reduce.

Clinical and in vivo examples of phytonutrient INDUCERS of ARE enzymes

Hodges and Minich, J Nutr Metab. 2015;2015:760689.

Food, Beverage or Bioactive Food Sources in Italics

Type of Study Clinical Notes and References

Fish oil Clinical 3 x 1 g/day fish oil containing 1098 mg EPA and 549 mg DHA (Magbanua et al., 2011)

Lycopene Tomatoes, rose hips, guava, watermelon, papaya (USDA)

Clinical 2 x 15 mg/day lycopene (Magbanua et al., 2011)

Resveratrol Grapes, wine, peanuts, soy, and Itadori tea (Burns et al., 2002)

In vivo 10 mg/kg/day (Tamaki et al., 2014) 20 mg/kg/day (Sadi et al., 2014)

Ginger In vivo 100 mg/kg/day [6]-shogaol (Chen et al., 2014) 10 and 100 mg/kg dried ginger extract (Bak et al., 2012)

Purple sweet potato In vivo 100 and 200 mg/kg anthocyanin extract (Hwang et al., 2011) Isoflavones Soy, kudzu root, red clover (Delmonte & Rader, 2006)

In vivo 80 mg/kg/day soy isoflavones (Xi et al., 2014) 60 and 120 mg/kg−1 puerarin form kudzu root (Li et al., 2013)

Coffee In vivo 2.0 mL/day coffee to an average animal weight of 200 g +/- 10g (Vicente et al., 2014)

Xanthohumol

1. Liu M, Hansen PE, Wang G, et al. Pharmacological profile of xanthohumol, a prenylated flavonoid from hops (Humulus lupulus). Molecules. 2015;20:754-79. 2. Plazar J, Zegura B, Lah TT, Filipic M. Protective effects of xanthohumol against the genotoxicity of benzo(a)pyrene (BaP), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and tert-butyl hydroperoxide

(t-BOOH) in HepG2 human hepatoma cells. Mutat Res. 2007;632:1-8. 3. Plazar J, Filipic M, Groothuis GM. Antigenotoxic effect of Xanthohumol in rat liver slices. Toxicol In Vitro. 2008;22:318-27. 4. Dorn C, Heilmann J, Hellerbrand C. Protective effect of xanthohumol on toxin-induced liver inflammation and fibrosis. Int J Clin Exp Pathol. 2012;5:29-36. 5. Pinto C, Duque AL, Rodriguez-Galdon B, Cestero JJ, Macias P. Xanthohumol prevents carbon tetrachloride-induced acute liver injury in rats. Food Chem Toxicol. 2012;50:3405-12. 6. Rodriguez RJ, Miranda CL, Stevens JF, Deinzer ML, Buhler DR. Influence of prenylated and non-prenylated flavonoids on liver microsomal lipid peroxidation and oxidative injury in rat hepatocytes.

Food Chem Toxicol. 2001;39:437-45 7. Lee YM, Hsieh KH, Lu WJ, et al. Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), Prevents Platelet Activation in Human Platelets. Evid Based Complement Alternat Med.

2012;2012:852362. 8. Harikumar KB, Kunnumakkara AB, Ahn KS, et al. Modification of the cysteine residues in IkappaBalpha kinase and NF-kappaB (p65) by xanthohumol leads to

suppression of NF-kappaB-regulated gene products and potentiation of apoptosis in leukemia cells. Blood. 2009;113:2003-13 9. Albini A, Dell'Eva R, Vene R, et al. Mechanisms of the antiangiogenic activity by the hop flavonoid xanthohumol: NF-kappaB and Akt as targets.

Faseb J. 2006;20:527-9.

• The phytochemical xanthohumol is the most abundant prenylated flavonoid found in the female flowers of hops. – Beer is the major dietary source of

xanthohumol, but the amount is very low; at less than 0.2 mg/L.1

• Xanthohumol exhibits a broad spectrum of anti-inflammatory activity in vitro 2-6

• Xanthohumol has been shown to inhibit signaling pathways (including PI3K/MAPK/NF-κB) in in vitro and in vivo models of inflammation4, 7-9

Xanthohumol

IκB/NF-κB pathway

TNFα, COX-2, iNOS, MCP-1, ILs, etc

Inflammation

Keap1/Nrf2 pathway

HO-1, NQO1, GST, etc

Antioxidant protection

Cardiovascular disease, metabolic disorders, digestive disorders, neurological disorders, etc.

THIAA

RIAA

Bioavailable xanthohumol induces expression of Nrf-2 dependent enzymes responsible for anti-oxidant protection while RIAA and THIAA do not

Bioavailable xanthohumol induces expression of Nrf-2 dependent enzymes responsible for anti-oxidant protection while RIAA and THIAA do not

00.5

11.5

22.5

33.5

4

Fold

Indu

ctio

n

Quinone Reductase activity

0

0.5

1

1.5

2

Fold

Indu

ctio

n

GST activity

Keap1/Nrf2 pathway

HO-1, NQO1, GST, etc

Antioxidant protection

Xanthohumol

V.Konda, unpublished results


166





Cytochrome P450 (CYP)

Cytochrome P450 is a family of more than 60 different enzymes found in all human tissues, responsible for Phase I reactions involved in biotransformation of a vast majority of drugs, dietary substances, and endogenous chemicals.

Cytochrome P450 (CYP) Cytochrome P450 contains three cofactors and two enzymes

Cofactors

NADPH

FAD

Fe++ (Heme)

Nicotinamide adenine dinucleotide phosphate

Flavin adenine dinucleotide

Riboflavin (vitamin B2)

Niacin/Nicotinamide (vitamin B3)

Iron (Fe)

CYP Bioactivity and Variability Among Individuals The bioactivity of CYPs is affected by: • Transcriptional factors • Genetic variability (e.g. SNPs) • CYP inducers

Tang X. (2015), Current Drug Metabolism

CYP Inducers include: Toxins (alcohol, caffeine, drugs) Nutrition

Metabolic Detoxification Antioxidants support the neutralization of reactive intermediary compounds and other free radicals produced by phase I enzymes

Antioxidants Comprehensive vitamin profile

including vitamins A, C, E, a broad spectrum of B vitamins help

neutralize reactive intermediary compounds

ATP (energy)

Pantothenic acid supports the production of ATP to power the

reactions

Supporting Phase I Detox through Food-Based Nutrition

Nutrient Food Sources Riboflavin (vitamin B2)

Soybeans, spinach, tempeh, crimini mushrooms, eggs, asparagus, almonds, turkey

Niacin (vitamin B3) Tuna, chicken, turkey, salmon, lamb, beef, sardines, brown rice Pyridoxine (vitamin B6)

Tuna, turkey, beef, chicken, salmon, sweet potato, potato, sunflower seeds, spinach, banana

Folic acid Lentils, pinto beans, garbanzo beans, black beans, navy beans, turnip greens, broccoli

Vitamin B12 Choose methylcobalamin for supplemental source, sardines, salmon, tuna, cod, lamb beef

Glutathione Undenatured whey protein, asparagus, curcumin, broccoli, avocado, spinach, garlic, foods high in vitamin C (e.g., citrus fruits) and selenium (e.g., Brazil nuts)

Branched-chain amino acids

Whey protein, chicken, fish, eggs

Flavonoids Virtually all plant foods, including apples, apricots, blueberries, pears, raspberries, strawberries, black beans, cabbage, onions, parsley, pinto beans, and tomatoes

Phospholipids Soy, sunflower seeds, eggs

Detoxigenomics

• Substrates • Inducers • Inhibitors

Food, Beverage or Bioactive Food Sources in Italics

Type of Study Clinical Notes and References

Cruciferous vegetables

Clinical 500 mg/d indole-3-carbinol (Michnovicz & Bradlow, 1990)

Diet containing cruciferous vegetables (Ioannides, 1999 )

Resveratrol

Grapes, wine, peanuts, soy, and Itadori tea (Burns et al., 2002)

Clinical 1 g/d resveratrol (Chow et al., 2010)

Green tea In vivo 45 mL/d/rat (avg. 150 g animal weight) green tea (Yao et al., 2014)

Black tea In vivo 54 mL/d/rat (avg. 150 g animal weight) black tea (Yao et al., 2014)

Curcumin

Turmeric, curry powder (Tayyem et al., 2006)

In vivo 1,000 ppm/d/rat curcumin (Bansal et al., 2014 )

Soybean In vivo 100 mg/kg (Bogacz et al., 2014) Garlic In vivo 30 to 200 mg/kg garlic oil (Chen et al., 2003)

Fish oil In vivo 20.5 g/kg fish oil (Chen et al., 2003) Astaxanthin

Algae, yeast, salmon, trout, krill, shrimp and crayfish (Ambati et al., 2014)

In vivo 10 – 300 ppm astaxanthin (Gradelet et al., 1996)

174

Clinical and in vivo examples of phytonutrient INDUCERS of CYP1A1

Hodges and Minich, Submitted, 2015

CRUCIFEROUS VEGETABLES

• Arugula • Cabbage • Watercress • Bok Choy • Turnip Greens • Mustard Greens • Collard Greens • Broccoli • Cauliflower • Brussels sprouts • Napa or Chinese cabbage • Kale

175

Handling broccoli for optimum detox activity • Glucosinolate (glucoraphanin) converts to

isothiocyanates (I3C) • Frozen broccoli products do not retain

sulforaphane (myrosinase destroyed during blanching)

• Adding powdered mustard seeds (hardier myrosinase) to boiling water to cook broccoli can result in increased sulforaphane formation

• Glucosinolates decrease with cooking and lutein, beta-carotene, and tocopherols increase with cooking of broccoli. Copyright 2013 by Food & Spirit,

Deanna Minich

J Food Sci. 2013 Sep;78(9):H1459-63. doi: 10.1111/1750-3841.12221. Epub 2013 Aug 5. Food Chem. 2013 Jun 1;138(2-3):1734-41. doi: 10.1016/j.foodchem.2012.10.119. Epub 2012 Nov 12. Int J Food Sci Nutr. 2013 Feb;64(1):103-11. doi: 10.3109/09637486.2012.704904. Epub 2012 Jul 10.

Glucosinolates • From Brassicaceae vegetables • Glucosinolate metabolite: I3C • Further active metabolites: ICZ

& DIM formed in stomach • Anti-estrogenic effects • Inhibit breast cancer cell growth

in vitro • Favorably affect balance of

good (2-hydroxyestrone) to bad (16 alpha-hydroxyestrone, 4-hydroxyestrone & 4-hydroxyestradiol) estrogen metabolites

Why a standardized sulforaphane supplement?

• Important and novel to have a specialized broccoli standardized to glucoraphanin and active myrosinase – in combination with glucoraphanin from broccoli seed extract for more reliable sulforaphane conversion.

• Sulforaphane is a potent activator of body’s own antioxidant and detoxifying enzymes via the Keap1/Nrf2 pathway and is responsible for many positive health benefits associated with broccoli consumption.

Sulforophane glucosinolate. Monograph. Altern Med Rev. 2010;15:352-360.

1. Fahey JW, Wehage SL, Holtzclaw WD, Kensler TW, Egner PA, Shapiro TA, Talalay P. Protection of humans by plant glucosinolates: efficiency of conversion of glucosinolates to isothiocyanates by the gastrointestinal microflora. Cancer prevention research. 2012;5:603-611.

2. Cramer JM, Teran-Garcia M, Jeffery EH. Enhancing sulforaphane absorption and excretion in healthy men through the combined consumption of fresh broccoli sprouts and a glucoraphanin-rich powder. Br J Nutr. 2012;107:1333-1338.

Solution for a reliable delivery of sulforaphane Ingredient Glucoraphanin Myrosinase Sulforaphane potential

Fresh broccoli Yes, but limited Active 50% conversion of glucoraphanin

Brassinase Yes, 1% Active 50% conversion of glucoraphanin

Glucoraphanin supplements

(broccoli extracts)

Yes, high concentrations

possible Inactive Highly variable, between 1% -

40%

Fresh broccoli + glucoraphanin supplements

(broccoli extracts)

Yes, high concentrations Active

50% of glucoraphanin from fresh broccoli and 40% from

the supplements

Sulforaphane supplement*

Yes, high concentrations Active

50% of glucoraphanin from Brassinase and 40% from

broccoli extract

Case Study CC: • 37 yo Caucasian female • Health professional, works FT in a clinic • Single, no children • Primary complaint: PMS sx, concern regarding

estrogen-sensitive cancers • Other conditions: Hx endometriosis as a

teenager, hx estrogen excess according to labs from past 2 yrs; Osteopenia dx 3 yrs.

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Case Study Known Toxic Exposures: • Diet

– Eats “pure” – has eliminated gluten, dairy, and for most part, sugar

– Eats significant quantities of vegetables, especially cruciferous vegetables and leafy greens

– Eats organic – Makes most meals at home

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Case Study

Coffee: Is it good or bad for you? That depends!

Coffee, CYP1A2 Genotype, & Risk of Myocardial Infarction

JAMA, 2006, Vol 295(10): 1135-1141

• CYP1A2 inactivates caffeine • N=4028 Costa Ricans, 50% with history of one heart

attack & 50% controls • 55% of both groups carried the gene for slow caffeine

clearance (CYP1A2*1F) • 2 copies of slow gene + drinking >4 cups coffee/d

increased risk of MI by 64% overall; those younger than 50 had quadrupled risk of MI

• 3-4 cups coffee/d + 2 copies of fast gene = slightly decreased risk of MI

Documents

WHOLE DETOX: How to Thrive in a Toxic World through ... · •N=20 patients with self-claimed sx of “mercury poisoning” •N=20 patients who had amalgams removed because of symptoms