Beruflich Dokumente
Kultur Dokumente
Copyright 2016
Overview
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6433a11.htm
Obesity Epidemic
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
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
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
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)
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
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
Rathore HS, Nollet LML. Pesticides: Evaluation of Environmental Pollution. CRC Press
2012, page 562
How to Interpret the Following Slides
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
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)
Bray GA. Fructose: should we worry? Int J Obes (Lond). 2008 Dec;32 Suppl 7:S127-31 47
How Toxins Cause Damage 1/3
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
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
Genomic variation 30
sensitive to/damaged by 10
chemical toxins? 0
Could up-regulation of GGT 0 200 400 600 800
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
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
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
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
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
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
(Progresso)
20
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
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
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