Toxins Have Become the

Primary Drivers of Disease

Dr. Joseph Pizzorno, ND
President Emeritus, Bastyr University
Editor, Integrative Medicine: A Clinicians Journal
Chair, Scientific Advisory Board, Bioclinic Naturals
President, SaluGenecists, Inc.
mail2@DrPizzorno.com

Copyright 2016
Overview

1. Worldwide Epidemic of Chronic Disease

2. Causes?
3. Methodology: Disease Risk to Disease Cause
4. Most Chronic Disease is Now Caused by Toxins
5. The Worst Toxins
6. Sources of Toxins
7. Toxicity has Become the New Normal
Normal Laboratory Ranges Are Toxic Ranges
8. Summary
 There is Some Good News
Banning lead in gasoline
and paint workedblood
levels down dramatically.
No threshold for safety
Children who had whole blood
lead concentrations of <5 g/dL
(supposedly safe) associated
with decreased IQ
2.4 million children at levels
between 5 and 9.9 ug/dL
July 2012: CDC changed
recommended level to intervene
in children from 10 to 5.0 ug/dL.
Also eliminated term level of
concern, to avoid giving false
sense of safety.
Iqbal S, et al. Estimated burden of blood lead levels 5 microg/dl in 1999-2002 and declines from 1988 to 1994.
Environ Res. 2008
http://www.cdc.gov/nceh/lead/acclpp/cdc_response_lead_exposure_recs.pdf
http://www.environment.ucla.edu/reportcard/article3772.html
A Note About the Data
Human data
Primarily US as a lot more research available
Spot checking toxins in other countries shows
the same toxin overload, but variations in which
are most prevalent:
Australia (higher PDBEs)
Canada (higher lead)
New Zealand (higher cadmium)
Sweden (higher most toxic metals)
UK (highest PDBEs in world, 3x OCP of US)
ADHD Epidemic

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6433a11.htm
 Obesity Epidemic

http://www.theobesityepidemic.org/introduction (Accessed 6/16)

 Kidney Disease Epidemic

Stevens L. http://www.slideshare.net/ringer21/liaison-meeting-esrd-presentation (accessed 6/16)

Diabetes Epidemic
 Diabetes Increasing World-Wide
Australian Adults

Childhood diabetes in Hong Kong

Sources:AIHW analysis of ABS NHS 198990, 1995, 2001, 200405 and 200708 NHS (reissue) and ABS 201112 Australian
Health Survey data (Release 7 June 2013).
Co-ordinaring Committee, Epidemiology Study of Childhood & Adolescent Diabetes, Hong Kong: KF Huen, et al
WHY THE CHRONIC DISEASE
EPIDEMICS?
 Increase in Diabetes Due to Sugar?

Diabetes 1%

http://wholehealthsource.blogspot.com/2012/02/by-2606-us-diet-will-be-100-percent.html
 How About Persistent Organic Pollutants?

Neel BA, Robert M. Sargis RM. The paradox of progress: Environmental disruption of metabolism and the
diabetes epidemic. DIABETES, 2011; 60:1838-48
 Global Production and Consumption of
Selected Toxic Metals, 18501990

The British Council 2003; all rights reserved Lars Jrup Br Med Bull 2003;68:167-182
Cadmium World Production
 Mercury in the Air

EPA-452/R-97-003 December 1997

 Mercury in Water

http://water.epa.gov/scitech/datait/models/maps/poster.cfm
 Ground Water Sources of Arsenic
10% of US public
water supplies have
levels of arsenic
known to induce
disease
No data on private
water supplies

http://www.atsdr.cdc.gov/csem/arsenic/docs/arsenic.pdf (accessed 2015-08-18)

 Example POPs
Chemical Abbr. Uses Exposure
Bisphenol A BPA Plastics Canned food
Organochlorine OCPs Pesticide Food, fumigation
pesticides
Organophosphate OPPs Pesticide Food
pesticides
Polybrominated PBDEs Flame retardant Clothing
diphenyl ethers
Polychlorinated PCBs Industrial Everywhere
biphenyls
Perflourinated PFOAs Non-stick, stain prevention, Teflon, Gortex,
water repellant Scotchguard
Phthalates Plastics, fragrances Shower curtains,
cosmetics
 POPs - Prediabetes
Over 1200 participants, fasting
glucose and OGTT performed,
with serum levels of 5 POPs
All individual POPs tested were
associated with progressive
increase in prevalence of
prediabetes
More than triple prevalence of
prediabetes seen in those in the
5th quartile, with a synergistic
effect from 5 POPs

Ukropec J, et al. High prevalence of prediabetes and diabetes in a population exposed to high levels of an organochlorine cocktail.
Diabetologia. 2010 May;53(5):899-906.
 POPs and Diabetes Risk

Graph: http://www.ourstolenfuture.org/NewScience/obesity/2006/2006-0715leeetal.html
Data: Lee DH, Lee IK, Song K, et al. A strong dose-response relation between serum
concentrations of persistent organic pollutants and diabetes: results from the National Health and
Examination Survey 1999-2002. Diabetes Care. 2006 Jul;29(7):1638-44
Toxic Load and Disease Risk
References for Toxins and Disease Risk
 Converting Disease Risk to % Caused:
Attributable Fraction Calculation

p = underlying prevalence of risk factor in the population

rr = relative risk (risk of contracting a disease in an exposed population divided

by the risk of contracting the disease in an unexposed population)

AF = % of disease due to the toxin

Levin, M. The occurrence of lung cancer in man. Acta Unio Int. Contra Cancrum. 1953, 9, 531-541
Example: Smoking and Lung Cancer
Number of smokers and nonsmokers who contract
lung cancer.
A=5
Number of smokers
16
who contract Lung
Number of people who contract Lung Cancer per year

Cancer due to
14
smoking
12
C = 15
10 Number of
nonsmokers
8 who contract
Lung Cancer
6
B=5
Number of smokers 4
who contract
Lung Cancer not 2
due to smoking
0
Smokers (N=100) Nonsmokers (N=300)

Baseline Additional due to smoking

Our Process In Summary
1. Determine threshold for increased disease risk
2. Determine % of population above threshold
3. Determine incidence of disease (OR) in those
above threshold
4. Determine incidence of disease in unexposed
population
5. Calculate AF, i.e., % of disease

As whole population is exposed, probably

UNDERESTIMATES % of disease!
 Toxin Type Use Threshold for % of US Disease Associations
disease above
association threshold
Chlordane OC pesticide Termites, corn, citrus, lawns, 14.5ng/g lipid 63% Diabetes (2.0)
Toxicity Has Become the New Normal

gardens (diabetes)
BPA Plasticizer Water bottles, canned food, 4.8 men; 5.1 ~18% Diabetes, hypertension
water pipes, thermal sales women (urine, (diabetes)
receipts ng/mL)

Octachloro Polychlorinated Incineration or burning of 1010 pg/g 10-25% Hypertension (7.9 for
dibenzo-p- dibenzo-p- waste; bleaching processes lipid (highest (hypertensio women, highest
dioxin dioxin used in pulp and paper mills quartile) n) quartile), diabetes (2.1),
(OCDD) obesity, learning
disability (2.72)
MEP Phthalate Toothbrushes, automobile >17.5 ng/mL ~60% Diabetes (1.48), lower
(mono- (plasticizer, parts, tools, toys, and food (urine) (diabetes) BMD, obesity
ethyl fragrance) packaging; aspirin,
phthalate) cosmetics, food packaging

p,p'-DDE DDT Agricultural crops 1,560ng/g 25% Diabetes (2.3-4.3),

metabolite (OC lipid (diabetes) early menopause,
pesticide) impaired cognitive
function (2-3x; 6.5x in
highest 5th percentile),
peripheral arterial
disease
Arsenic Toxic metal Mining/smelting, wood 7.4ug/L total 20% Cancers, diabetes (2.6-
preservative, pesticides arsenic (urine) (diabetes) 4.6), dyslipidemia, gout
 AF, OR, Prevalence

Arsenic Gout in women

Smoking Lung cancer

BPA Diabetes

Rosen L. An intuitive approach to understanding the attributable fraction of disease due to a risk factor: the
case of smoking. Int J Environ Res Public Health. 2013 Jul 16;10(7):2932-43
 Status of Our Research
26 toxins and toxin classes, e.g. lead, mercury,
BPA, OCPs
100s of chemicals and POPs in some classes
18 cancers
24 chronic diseases

1,092 cells in spreadsheet

Large Personal Ongoing Research Investment

Huge Amount of Research Work!
Toxins Studied
Aluminum Acrylamide
Arsenic Acrylonitrile
Cadmium Benzene
Fluoride Bisphenol A (BPA)
Lead Chloroform
Manganese DDT
Mercury Dioxins
Glyphosate
Organochlorine pesticides (OCPs)
Organophosphate pesticides
Parabens
Phthalates
Polybrominated diphenyl ethers (PBDEs)
Polycyclic aromatic hydrocarbons (PAHs)
Polychlorinated biphenols (PCBs)
Vinyl chloride
Diseases Studied Cancer, Bladder
ADHD Cancer, Bone
Juvenile Obesity
Alzheimer's Disease Cancer, Brain
Metabolic Syndrome
ALS Cancer, Breast
Mitochondrial dysfunction
Angiosarcoma Cancer, Cervix
Myocardial Infarction
Anxiety Cancer, Colorectal
Obstructive Lung Disease
Atopic Conditions Cancer, Endometrial
Osteoporosis
Diabetes Cancer, Head & Neck
Peripheral Artery Disease
Dyslipidemia Cancer, Liver
Peripheral Neuropathy
Gout Cancer, Lung
Prediabetes
Fetal Abnormalities Cancer, Lymph & Blood
Renal Disease
Hyperuricemia Cancer, Ovarian
Rheumatoid Arthritis
Infertility Cancer, Pancreatic
Thyroid Dysfunction
Juvenile IQ Cancer, Prostate
Cancer, Renal
Cancer, Skin
Cancer, Testicular
Cancer, Thyroid
OCPs Throughout the World

Rathore HS, Nollet LML. Pesticides: Evaluation of Environmental Pollution. CRC Press
2012, page 562
How to Interpret the Following Slides

Threshold Threshold exposure at which there is

an increased risk of disease outcome

% Above Threshold Percentage of the population

with higher exposure than the threshold

Odds Ratio Increased disease risk in those above

threshold

% of Dz Percent contribution of the toxin to that

disease outcome
 Attention Deficit Hyperactivity Disorder
Toxin Threshold % Above Odds Ratio % of Dz Reference
Threshold PMID
DDT 1.26 ng/g 25.0% 1.8 16.6% 20106937
serum (p,p'-
DDE)

Lead 2.3 ug/dL 1.3% 2.54 2.0% 27659349

Mercury 1.6 24952233

Organophosphate 2.0
pesticides
Polycyclic 2.27 ng/m3 94.0% 1.25 19.0% 22440811
Aromatic
Hydrocarbons
PCBs 1.04 ng/g 25.0% 1.76 16.0% 20106937
serum (sum
of 50 PCBs)
Diabetes
Toxin Threshold % Above Odds % of Dz Reference
Threshold Ratio PMID
Arsenic 16.5 ug/L 20.0% 2.1 18.0% 18714061

BPA 2.8 ug/L 28.0% 1.45 11.2% 26119400

DDE 545 ng/g serum 20.0% 2.30 3.1% 26119400

(p,p'-DDE)
Dioxins 26119400
2 pg/g lipid 5.0% 1.91 4.3%
PCBs 26119400
104 ng/g (PCB 153) 25.0% 2.39 25.8%
Phthalates 26119400
17.5 ug/L 69.0% 1.48 24.9%
1-naphthalene 1.67 ug/dL 15.2% 1.82 11.1% 26340343

2-napthalene 4.14 ug/dL 55.0% 2.24 21.4% 26340343

1-phenanthrene 167 ng/L 57.0% 1.78 15.1% 26340343

1-pyrene 85 ng/L 66.0% 1.80 17.4% 26340343

 Lung Cancer
Toxin Threshold % Above Odds Ratio % of Dz Reference
Threshold PMID
Acrylonitrile Uncertain* Uncertain 1.25 25% 17114112
occupational
exposure

Arsenic 121.3 ug/L 4.36% of Asian 3.4 9.5% in AA; PMC2682945

Americans 0.1-1%
~0.1% of total
US population
Cadmium Uncertain+ Uncertain 4.67 10% in 17184399
smokers
DDT Any exposure All US pop 1.7 76% increased 8923607
below LOD risk
Breast Cancer
Toxin Threshold % Above Odds Ratio % of Dz Reference
Threshold PMID
Cadmium 0.580 ug/g 12.6% 2.05 47.9% 16788160
creatinine
PCB 138 39.6 ng/g 20.2% 3.16 63.0% 27717745
creatinine
PCB 187 1.08 ng/g lipid 60.0% 1.94 36.0% 21480306
 Miscellaneous Diseases
Toxin Disease Threshold % Above Odds % of Dz Reference PMID
Threshold Ratio
Aluminum Alzheimer 0.1 mg/L 40.0% 2.03 0.5-44% 26592479
Dz drinking
H20
Benzene AML 100ppm/yrs 1-3% 3.20 6.0% PMC2903550

DDT NHL 0.512 ug/L 1-2% 2.40 0.1% 17722095

Lead ALS 2.38 ug/dL 33.0% 1.81 21.0% 25479292

blood
Lead Brain CA 0.005 ug/dL 14% 1.9 ~50.0% 17164378

Dioxin-like RA 32.6 ng/g 25.0% 2.19 22.0% 17589595

PCBs lipid
PAHs Asthma 1.24 ng/m3 93.5% 2.00 48.3% 19221603
The Potency of Arsenic
Disease Threshold % Above Odds Ratio % of Dz Reference
Threshold PMID
Bladder CA 10ug/L H20 10.0% 2.7 14.5% 24889821
Pancreatic CA 13.32 ug/g 20.0% 2.46 23.0% 23800676
Prostate CA 13.32 ug/g 20.0% 3.3 31.5% 23800676
Gout 12.5 ug/L 24.5% 5.46 52.2% 25499256
Diabetes 16.5 ug/L 20.0% 2.1 18.0% 18714061
 Arsenic (18.0% of Diabetes)
How it causes diabetes Where it comes from
Blocks sugar stimulating Water (>10% of US
insulin secretion water supplies have
Epigenetic inhibition of high levels)
sugar regulation Rice (naturally
absorbs if in the
water)
Chicken (added to
make meat whiter)

Pan W-C, Seow WJ, Kile ML, et al. Association of low to moderate levels of arsenic exposure with risk of Type
2 diabetes in Bangladesh. American Journal of Epidemiology. 2013;178(10):1563-70
 Portion of Population with Toxin Load Which
Doubles Disease Risk
Toxin Disease % with Doubled Risk
Polycyclic aromatic hydrocarbons Asthma 94%
PCB187 Breast Cancer 60%
Phthalates Diabetes 55%
Lead ALS 33%
Aluminum Alzheimer's Disease 25%
DDT ADHD 25%
PCBs Diabetes 25%
Dioxin-like PCBs Rheumatoid Arthritis 25%
Arsenic Gout 23%
Bisphenol A Diabetes 22%
Cigarette smoking Lung Cancer 21%
Arsenic Diabetes 20%
Polycyclic aromatic hydrocarbons Diabetes 20%
Huge Detoxification Variability
CYP2C19
Proton pump inhibitors and some antidepressants.
5-fold difference in activity between poor metabolizers and
extensive metabolizers, more so if CYP3A4 is also inhibited
Ultrarapid allele in 18% of both Swedes and Ethiopians
CYP2D6
Metabolizes a large number of drugs (~25%)
7 % of Caucasians poor metabolizers
~30% ultra rapid metabolizers in Arabian and Eastern
African populations
More adverse effects in poor metabolizers, and ineffective
dosing in ultrarapid metabolizers
Inhibited by ginger

Desta Z, et al. Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmaco 2002
Sim SC, et al. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug
response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther. 2006
Wilkinson GR. Drug metabolism and variability among patients in drug response. N Engl J Med. 2005
Kirchheiner J, et al. Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to
CYP2D6 duplication. Pharmacogenomics J. 2007
 Toxin Half Lives in Blood
Toxin Normal (mg/L) Acute Toxic (mg/L) Half-Life
Arsenic 0.002-0.07 0.05-0.25 2-4 days (CDC)
Benzene 0.0002 0.5-1.0 days
Cadmium 0.0003-0.0065 0.015-0.05 16 years
Chlordane 0.001 0.0025 3-4 days
DDT/DDE 2-10 years
Dieldrin 0.0015 0.15-0.30 2-12 months
Ethanol 1000-2000 15%/hour
Lead 0.09 0.4-0.6 1-1.5 mo (2+ yrs bone)

Mercury 0.0015-0.002 0.05-0.2 2 months (CDC)

PCBs 3-25 years!
Toluene 0.5-3 days
Schulz M, et al. Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics. Crit Care. 2012 Jul 26;16(4):R136
 Bioaccumulation (POPs)!

DDT banned in 1972 PCBs banned in 1977

Serdar B, et al. Potential effects of polychlorinated biphenyls (PCBs) and selected organochlorine pesticides
(OCPs) on immune cells and blood biochemistry measures: a cross-sectional assessment of the NHANES 2003-
2004 data. Environ Health. 2014;13:114.
Bioaccumulation (Cd)!
Think Broadly
Exogenous Endogenous
Metals Gut-derived toxins
Chemicals Non-end product metabolites
Inorganic
Poorly detoxified hormones
Fluoride
Organic Catecholamines (if SNP)
POPs
Toxins of Choice
Drugs
Alcohol
Particulate matter
Molds Marijuana
Microbial Food constituents
Radiation High fructose corn syrup
Light Salt (acid-forming diet)
Medical
Wheat if zonulin (70%)
Cell phone
 Obesity Epidemic POPs AND HFCS

Bray GA. Fructose: should we worry? Int J Obes (Lond). 2008 Dec;32 Suppl 7:S127-31 47
How Toxins Cause Damage 1/3

Increase free radical production

Cd induces production of ROS
Malathion inhibits catalase and glutathione peroxidase
Homocysteine oxidizes LDL cholesterol
Poison enzyme systems (compete with
nutritional cofactors for binding sites)
Pb poisons delta aminolevulinic acid dehydratase
Cd inhibits catalase, glutathione reductase, and lowers
glutathione levels
Replace structural minerals
Pb displaces Ca in bone
How Toxins Cause Damage 2/3

Damage DNA
Benzene - causes chromosomal damage
Pesticides fruit growers have more DNA damage
Phthalates and insecticides damage sperm DNA
4-hydroxy catechol estrogen (4-OHE) damages breast DNA
Epigenetic dysmodulation
Higher cord blood levels of hexachlorobenzene associated
with 2x greater risk for obesity in children
Damage cell membranes
Common mechanism for heavy metals, inactivates
membrane enzymes, ion channels and pumps
How Toxins Cause Damage 3/3

Block insulin receptor sites

PCBs and phthalates
Highest levels associated with a 4 to 20-fold greater diabetes risk
Imbalance hormones, many toxin examples
Arsenic
Disrupts thyroid hormone and retinoic acid receptors
Phthalates
Act as anti-androgens
More than 75% of the U.S. population has measurable levels of
several phthalate metabolites in the urine
PCBs
Lower testosterone levels in men
Which are the Worst Toxins?
According to the CDC
Toxicity
Population toxic load
Prevalence in toxic waste sites
According to clinical importance
Exposure
% of disease
Ability of the body to detoxify/excrete
Agency for Toxic
Substances and
Disease Registry
Priority List
 The Worst Toxins Clinically
My Rank Toxin Diseases Primary Sources
1 Arsenic Cancers, diabetes, gout Water, chicken, rice
2 DDT ADHD, dementia, diabetes Everywhere
3 Phthalates ADHD, diabetes Soft plastics, HABAs
4 PBDEs ADHD, diabetes Flame retardant fabrics
5 PAHs ADHD, cancers, dyslipidemia Smoking, charbroiling
6 PCBs Cancers, diabetes, MI, RA Everywhere
7 Mercury Dementia Silver fillings, fish
8 Lead Cardiovascular disease, IQ Paint, water
? Glyphosate Research invalid
Conventional Laboratory Tests Reflect
Toxic Load in Normal Range
Surprising number show toxin exposure
CBC: RBC, WBC, platelet count, hemoglobin, basophilic
stippling
Liver enzymes: ALT, GGTP
Inflammatory markers: CRP
Lipids: LDL, oxLDL, triglycerides
Blood sugar: insulin, FBS, 2-hour PP
Metabolites: bilirubin, uric acid, homocysteine, 8-OHdG
Thyroid: T3, T4, TSH
The historic normal range has been changing
as the population has become more toxic
 WBC Lowered by PCB and OCP Exposure

Strong inverse WBC

8
correlation with
7
PCBs and OCPs
and CBC 6

5
Linear with almost 4
all PCBs 3
High variability with 2
OCPs 1

Within normal 0
1st Quartrile 2nd Quartile 3rd Quartile 4th Quartile
range!
Serdar B, et al. Potential effects of polychlorinated biphenyls (PCBs) and selected organochlorine pesticides
(OCPs) on immune cells and blood biochemistry measures: a cross-sectional assessment of the NHANES 2003-
2004 data. Environ Health. 2014;13:114.
 Effects on WBC Worsen with Years
of Exposure to Benzene and CO
Petrol filling workers
Healthy non-smokers

Uzma N, Salar BM, Kumar BS, et al. Impact of organic solvents and environmental pollutants on the
physiological function in petrol filling workers. Int J Environ Res Public Health. 2008 Sep;5(3):139-46
 Platelet Count Decreases with Years
of Exposure tp Benzene and CO
Petrol filling workers
Healthy non-smokers

Uzma N, Salar BM, Kumar BS, et al. Impact of organic solvents and environmental pollutants on the
physiological function in petrol filling workers. Int J Environ Res Public Health. 2008 Sep;5(3):139-46
 Solvents Decrease Platelet Count
Compared workers exposed 2.3 hr/day to those
exposed most of day to toluene
All wore face masks and protective gear
Platelet count 14% lower: 252 versus 216/ml
Impairment of sympathetic nerves (OR = 4.13)
Impairment of peripheral nerves (OR = 6.94)
Positive relationship between neurological
abnormalities and a self-reported
neuropsychiatric measurement (r = 0.35-0.66)

Shih HT, et al. Subclinical abnormalities in workers with continuous low-level toluene exposure. Toxicol Ind Health. 2011
Sep;27(8):691-9
 Basophilic Stippling of Red Cells
Toxins Diseases
Arsenic Alpha-thalassemia, HbH Disease
Lead Beta thalassemia
Hereditary pyrimidine 5'-
nucleotidase deficiency
Myelodysplastic syndrome
Sideroblastic anemia
Thrombotic thrombocytopenic
purpura
 GGT: Indirect Measure of POPs
Glutathione is key intracellular defense against oxidative stress
Cellular GGT metabolizes extracellular GSH, allowing precursor
amino acids to be reutilized for intracellular GSH.
Exposure to POPs induces GGT as a defensive mechanism.
Within normal range predicts type 2 diabetes, coronary heart disease,
hypertension, stroke, dyslipidemia, chronic kidney disease and
cancer.
Men with GGT >50 U/I had ~26 fold risk for diabetes compared to
those with <10. Those with 40-49 had a ~20 fold risk.
Levels within normal range occur with obesity, xs alcohol, cigarette
smoking, physical inactivity, high meat /low fruit and vegetable intake
Cumulative biomarker for environmental pollutants.
Lee DH, et al (2003) Gamma-glutamyltransferase and diabetesa 4 year follow-up study. Diabetologia 46:359364
Pamela A, et al. Serum gamma-glutamyltransferase: linking together environmental pollution, redox equilibria and progression of atherosclerosis? Clin Chem
Lab Med. 2009;47(12):1583-4.
Lee DH, et al. Serum gamma-glutamyltransferase: new insights about an old enzyme. J Epidemiol Community Health. 2009 Nov;63(11):884-6.
Lee DH, et al.Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and
women. Eur Heart J 2006;27:21706
Lee DH, et al. Gamma-glutamyltransferase and diabetes--a 4 year follow-up study. Diabetologia. 2003 Mar;46(3):359-64.
Lee DH, et al. Can persistent organic pollutants explain the association between serum gamma-glutamyltransferase and type 2 diabetes? Diabetologia. 2008
Mar;51(3):402-7.
 GGT and Alcohol Consumption
GGT directly correlates 80
Grams of Ethanol per Week
with alcohol consumption
In a non-uniform 70

population, 40 g/d will 60

elevate GGT ~15% 50

Watch for false negatives 40

Genomic variation 30

Are these the ones most 20

sensitive to/damaged by 10

chemical toxins? 0
Could up-regulation of GGT 0 200 400 600 800

in light alcohol consumption

be reason for benefit?
Adapted from: Nagaya T, et al. Dose-response relationships between drinking and serum tests in Japanese men
aged 4059 years. Alcohol 1999 Feb. 17(2): 1338.
 GGT Correlates With Toxic Metal Levels

Lee DH, et al. Graded associations of blood lead and urinary cadmium concentrations with oxidative-stress-related markers in the
U.S. population: results from the third National Health and Nutrition Examination Survey. Environ Health
perspect. 2006 Mar;114(3):350-4
GGT and Diabetes Risk
30

25

20
Diabetes Risk

15

10

0
<10 10-19 20-29 30-39 40-49 >50
GGT
GGT Levels
Correlate with
Risk of Death
GGT over 50
associated with
tripling of death rate!
30-40 associated
with doubling

Brenner H, et al. Distribution, determinants, and prognostic value of gamma-glutamyltransferase for all-cause
mortality in a cohort of construction workers from southern Germany. Prev Med 1997; 26: 30510.
GGT From Small US Company
with Young Workers
60%

50%

40%

30%

20%

10%

0%
0 20 40 60 80 100
GGT Data from Canadian Oil Field
Workers
GGTP
450

400

350

300

250

200

150

100

50

0
<10 10-20 20-30 30-40 40-50 50-60 60-07 70-80 80-90 90-100 100-110 110-120 >120

20-fold increased risk of diabetes

 Uric Acid: Indirect Measure of POPs
Poly-fluorinated hydrocarbons (PFOA and PFOS) associated
with increased serum uric acid

Steenland 2010: Open Access

Lin CY, et al. Association among serum perfluoroalkyl chemicals, glucose homeostasis, and metabolic syndrome
in adolescents and adults. Diabetes Care. 2009 Apr;32(4):702-7.
Steenland K et al. Association of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) with uric
acid among adults with elevated community exposure to PFOA. Environ Health Perspect. 2010 Feb;118:229-33.
 ALT: Indirect Measure of POPs
ALT (proxy marker) elevation in 10.4% (not including viral
hepatitis, hemochromatosis, or alcoholic liver disease) of
NHANES 03-04 subset
Risk of elevated ALT increased dose-dependently with
cadmium, lead, mercury, and PCB exposure
100% of individuals had detectable PCBs, 92.5% mercury,
and 99.6% had detectable lead
In 2005-08, prevalence of NAFLD in US was 11%, a
growing cause of chronic liver disease.

Cave M, et al. Polychlorinated biphenyls, lead, and mercury are associated with liver disease in American adults:
NHANES 2003-2004. Environ Health Perspect. 2010 Dec;118(12):1735-42.
Younossi ZM et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United
States from 1988 to 2008. Clin Gastroenterol Hepatol. 2011 Jun;9(6):524-530.e1;
 Bilirubin as a Marker of POPs
Degree of serum bilirubin increase is
prognostically significant in chronic liver
dysfunction
Mono-ortho PCB TEQ values were found to be
significantly positively associated with bilirubin
(=0.71, P=0.008) following adjustment for
multiple potential confounders.
Bilirubin levels significantly correlated with PCBs
-105,-118,-126, and -194
Smoking appears to be the biggest confounder
Dufour, D.R., et al., 2000. Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory
tests in screening, diagnosis, and monitoring. Clin. Chem. 46, 205068.
Kumar J, et al. Persistent organic pollutants and liver dysfunction biomarkers in a population-based human sample
of men and women. Environ Res. 2014;134:251-256
 Perfluorinated POPs and
Common Blood Tests

Gleason JA, et al. Associations of perfluorinated chemical serum concentrations and biomarkers of liver function and uric acid in the
US population (NHANES), 2007-2010. Environ Res. 2015;136:8-14
 Liver Enzymes Reflect Toxic Load
AST, ALT and
GGT increase
with body load
of PCBs and
OCPs
Some non-linear
Oxychlordane
top quartile:
ALT 10%
GGT 25%

Serdar B, et al. Potential effects of polychlorinated biphenyls (PCBs) and selected organochlorine pesticides
(OCPs) on immune cells and blood biochemistry measures: a cross-sectional assessment of the NHANES 2003-
2004 data. Environ Health. 2014;13:114.
 LDL-Cholesterol as Measure of POPs?

5-year prospective
study to determine if
POP levels predict
future elevation in
LDL-cholesterol
598 subjects initially
at age 70
Looked at 23 POPs
Best correlation with
PCB 194

Penell J, Lind L, Salihovic S, et al. Persistent organic pollutants are related to change in circulating
lipid levels during a 5 year follow-up. Environ Res 134(2014)190197
 oxLDL as Measure of POPs?
992 70-year old individuals (50% women)
Sum of PCBs showed strong, significant positive
associations with ox-LDL, and significant
negative associations with glutathione-related
markers (GSSG and GSSG/GSH)
A number of POPs (PCB-99, 138, 153, 156, 170,
180, 194, 206 and 209) showed strong
significant positive association with ox-LDL

Kumar J, et al. Influence of persistent organic pollutants on oxidative stress in population-based samples.
Chemosphere. 2014;114:303-309.
 Homocysteine is Increased by Pb & Cd

Guallar E, et al. Confounding of the relation between homocysteine and peripheral arterial disease by lead, cadmium, and
renal function. Am J Epidemiol. 2006 Apr 15;163(8):700-8
 Nutrient Deficiencies Accentuate
Effects of Lead on Homocysteine
Deficiencies in folate, B6 or B12 make lead more toxic!

Lee YM. Et al. Association of homocysteine levels with blood lead levels and micronutrients in the US general population. J
Prev Med Public Health. 2012 Nov;45(6):387-93
T4 & T3 and PCBs
PCBs decrease T4
production
PCBs inhibit iodotyrosine
deiodinase activity
Study done in pregnant
women which implies
effect on fetus IQ

Kim S, Park J, Kim HJ, et al. Association between several persistent

organic pollutants and thyroid hormone levels in serum among the
pregnant women of Korea. Environ Int. 2013 Sep;59:442-8
Shimizu R, Yamaguchi M, Uramaru N, et al. Structure-activity
relationships of 44 halogenated compounds for iodotyrosine
deiodinase-inhibitory activity. Toxicology. 2013 Dec 6;314(1):22-9
T4 & T3 and PCBs
Not just humans
being affected
Large study of
dolphins shows
exactly the same
effects

Schwacke LH, Zolman ES, Balmer BC, et al. Anaemia,

hypothyroidism and immune suppression associated with
polychlorinated biphenyl exposure in bottlenose dolphins
(Tursiops truncatus). Proceed Royal Society B,
doi:10.1098/rspb.2011.0665
 8-OHdG
Oxidized nucleoside
Direct measure of
DNA damage
Indirect measure of
oxidative stress and
toxin load
Correlates with:
Multiple cancers
Mitochondrial damage
Rate of aging
Smoking
Walter Crinnion Total Toxic Load, AANP 2015
Several toxins
 8-OHdG Correlates with Pack-Years
of Smoking

Yano T, et al. Significance of the urinary 8-OHdG level as an oxidative stress marker in lung cancer patients. Lung Cancer.
2009 Jan;63(1):111-4
 8-OHdG Correlates
with Mercury

Chen C, et al. Increased oxidative DNA damage, as assessed by urinary 8-hydroxy-2'-deoxyguanosine

concentrations, and serum redox status in persons exposed to mercury. Clin Chem. 2005 Apr;51(4):759-67
 Toxin Effects Worse with Aging?
Thyroid function
decreases with
PFOA levels
But only after
age 63!

Shrestha S, Bloom MS, Yucel R, et al. Perfluoroalkyl substances and thyroid function in older adults. Environ
Int. 2015 Feb;75:206-14
 Insightful 23-Year Prospective Study
1. < 50, there is no difference
between those with the
lowest and highest PCBs
2. In youngest group, insulin
production increases in
response to toxin level
As expected since blocking of
insulin receptor sites by PCBs
requires more insulin
3. That adaptive ability
decreases with aging
4. At age 50, all the measures
show very strong toxin-
dose response.

Cumulative damage
impairs ability to adapt

Suarez-Lopez JR, et al. Persistent organic pollutants in young adults and changes in glucose related
metabolism over a 23-year follow-up. Environ Res. 2015 Feb;137:485-94
 Recommendations
High body toxic load:
GGT: > 25
Uric acid: > 5.0 mg/dl
ALT: >30 U/L
Bilirubin: >0.8 mg/dl
CBC: < 6,000
Platelet: < 250,000
Low T3 and/or T4

Monitor Total Toxic Load

8-OHdG: >4
Unconventional Laboratory Tests
Challenge testing
Hair analysis
Direct measures of solvents and POPs in blood,
urine, adipose tissue
 Evaluation of Metal Exposure Provocation
Provocation the use of a chelating agent before urine
collection often done clinically, but several limitations
No official reference range for provoked urine
Most chelating agents do not extract metals from all tissues, thus
does not necessarily represent total body burden
Example: Brain is one of the main target organs for both elemental and organic
mercury, yet agents do not chelate brain mercury
Despite limitations, widely used and advocated by
clinicians, in part, to see efficacy of chelating agent as a
guide to treatment, and based on empirical evidence

Rooney JP. The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury.
Toxicology. 2007
Is Challenge Testing Valid?
Poor correlations of standard tests for mercury
Unpublished research from corporate wellness
project
Published amalgam number correlation
Published fish consumption correlation
What We Found In Canada

Deviations from the mean of 14%,

29% and 91% respectively
DMPS is spreading distribution,
suggesting that it is better at
differentiating mercury body load
Some VERY high
Hg Assessment Correlations
Extensive measurements in 65
Whole blood Hg 60.0

Oral DMPS challenge

50.0
Amalgam surfaces
Correlations 40.0

Post Urine Hg ug/g

Whole blood w pre urine: r = 0.40
Whole blood w post urine: r = 0.57 30.0

Pre urine w post urine: r = 0.68

Amalgams w pre urine: r = 0.26 20.0

Amalgams w whole blood: r = 0.36

10.0
Amalgams with post urine: 0.44 Number of amalgams
Clear documentation that 0.0
0 10 20 30 40 50
challenge testing is better
 Modest Correlation with # of Fillings

Very large study

Surprisingly only
reported none versus
1 or more fillings
Huge overlap!
Not controlled for fish
consumption

Dutton DJ, et al. The association between amalgam dental surfaces and urinary mercury levels in a sample of
Albertans, a prevalence study. J Occup Med Toxicol. 2013;8(1):22
 Strong Correlation with Fish
Consumption
Compared 0 to 1-2 to 3
or more servings per
week
First urine showed
essentially no
differentiation
Challenge testing
showed clear correlation
Still a lot of variation
Ruha AM, et al. Urine mercury excretion following meso-dimercaptosuccinic acid challenge in fish eaters. Arch
Pathol Lab Med. 2009;133(1):87-92.
Measuring POP
Levels Directly
Urine sample
150+
environmental
chemicals
$287
Sources of Toxins
70% Food
10% Water
10% House and yard chemicals
5% Air
5% Health and beauty aids
 Eating Conventionally Grown Foods
Dramatically Increases POP Load
Study done in Seattle
children
10-fold increase in
POPs doubles ADHD
Levels drop
measurably within
3 days of eating
only organically
grown foods
Curl CL, et al. Organophosphorus pesticide exposure of urban and suburban preschool children with organic and
conventional diets. Env Health Perspect. 2003;111:377-82
Bouchard MF, et al. Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides.
Pediatrics. 2010 Jun;125(6):e1270-7
 Hg From Fish
Total Hg urinary
excretion proportional to
amount of fish eaten
Impaired psychomotor
performance
R = 0.38 blood
R = 0.77 urine
Huge variation in amount
of Hg in fish

Apostoli P, ICortesi I, Mangili A, et al. Assessment of reference values for mercury in urine: the results of an Italian
polycentric study. The Science of the Total Environment 289 (2002)13-24
Carta P, et al. Sub-clinical neurobehavioral abnormalities associated with low level of mercury exposure through
fish consumption. NeuroToxicology 24 (2003) 617623 94
 POPs, Fish
Consumption and
Breast Feeding
Eating fish increases POPs
Breast feeding decreases POPs

Bjermo H, et al. Fish intake and breastfeeding time are

associated with serum concentrations of organochlorines in
a Swedish population. Environ Int. 2013 Jan;51:88-96
 BPA: Canned Versus Home-Made Soup
Soymilk in Cans Versus Glass
One 12oz serving daily for 1 week of BPA (ug/L urine)
either fresh soup or canned soup 25

(Progresso)
20

12-fold increase in BPA

2 servings of 6 ounces Soy milk in 15

can compared to glass

10
16-fold increase in BPA
Systolic BP elevated 4.5 mm Hg 5

Diabetes risk threshold?

0
Soy in Glass Soy in Can Made Soup Canned Soup

Carwile JL1, Ye X, Zhou X, et al. Canned soup consumption and urinary bisphenol A: a randomized
crossover trial. JAMA. 2011 Nov 23;306(20):2218-20.
Bae S1, Hong YC2. Exposure to bisphenol A from drinking canned beverages increases blood
pressure: randomized crossover trial. Hypertension. 2015 Feb;65(2):313-9.
 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
Case Histories
>35 at www.thetoxinsolution.com
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 Hg = 50!
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.
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
ones system is a long Hg = 3.5!
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.
No More Kidney Stones
40 yo male (emergency room physician)
Wants to enter space medicine, BUT
Kidney stone attack every 4-6 months
Otherwise healthy
Intervention:
50% decrease in salt intake
Increased attention to Mediterranean diet with emphasis
on whole citrus fruit
Calcium carbonate: 0.5 g bid
Magnesium citrate: 250 mg bid
Potassium citrate: 50 mg bid
No attacks for 3 years!
Normal is Degeneration with Aging

But the Degeneration is Actually

Accumulated Avoidable Damage

4 Generations
Motorcycling Australia on the
Wrong Side of the Road
Summary
1. Toxins are now ubiquitous in the industrialized
world
2. Toxins are now the primary drivers of chronic
disease
3. Standard laboratory tests now include in
normal range the bodys adaptations to and
damage from toxins

Thank you
Chrissie Cirovic, ND & Geoff Bender, ND
For Your Excellent Research Work
 2 New Books!
The Toxin Solution

Clinical Environmental
Medicine
With Walter Crinnion, ND