Wisconsin presentation Final

Lucine Health Sciences, Inc. |
Hormones Matter I Heal with Friends
Navigating Health
in a Toxic World
Chandler Marrs, PhD
Lucine Health Sciences, Inc.
June 21, 2014
ENDOCRINE DISRUPTORS,
EPIGENETICS AND ENERGETICS

Before we begin
“You did then what you knew how to do,
And when you knew better,
You did better.”
Maya Angelou

Beginning Principles
o Pregnancy is an opportunity to break cycles of bad
health
o Reproduction should be viewed from a much
broader and longer perspective.
o Dad’s health matters
o Perinatal health should include pre-conception – postpartum
year
o Transgenerational – can’t undue sins of our parents and
grandparents, but we can protect our children and
grandchildren
o Everything is connected – a more holistic and
systems approach to health

We are an unhealthy lot
2005
2010
2013
And becoming more unhealthy as
time goes by

Living Sick and Dying Young

Medication Nation
Mayo Clinic Reports
o 70% adults take prescription
medications chronically
o 50% take 2 or more meds
o 20% take 5 or more meds
“Before the SSRIs, drugs were poisons that came with risks. Now they
are fertilizers to be used as widely as possible, being given in ever
larger amounts to children and the elderly - the only risks the
authorities can see it would seem stem from not using enough of
them.” David Healy

During Pregnancy
o 80% of women take at least one medication
during pregnancy
o ~30% take 4 or more medications during
pregnancy
o 60% increase in medication use during
pregnancy in 30 years

We Didn’t Learn
Thalidomide -prescribed for morning
sickness
Diethylstilbestrol (DES) – to prevent miscarriage
At least 3 generations affected, sons, daughters and
grandchildren

Now we Have
80% of pregnant women use one
medication
With little evidence of safety and
efficacy
And yes, Flu vaccines still contain
thimerosal (Johns Hopkins Inst. Vaccine Safety)

And we wonder why
o 1-68 children develop autism
o Neurodevelopmental and behavioral
problems on the rise
o Kids are largest growing market for
psychotropics
o 14% teens
o 4-12% polypharmacy
o 7X increase in antipsychotics ages 0-13
years, from 1998-2009
o 1 in 6 children are obese
o 70% to 80% have NAFLD
o ~30% increase in pediatric type 2 diabetes
2001-2009
JAMA Pediatr. 2013;167(2):141-148; Psychiatry (Edgmont). Aug
2005; 2(8): 14–19; Arch Gen Psychiatry. 2012;69(12):1247-1256;
BMC Pediatrics 2013, 13:40 3; JAMA. 2014;311(17):1778-1786.

Unheralded Environmental
Exposures
o Pervasive
o 2000 environmental
chemicals on the market
(EPA 2004)
o In food, air, every product
on the market
o Up to 99% adults tested
have chemicals in blood,
urine, serum
o Placenta, breast milk, cord
blood
o Infants and children
Certain polychlorinated biphenyls, organochlorine
pesticides, PFCs, phenols, PBDEs, phthalates, polycyclic
aromatic hydrocarbons, and perchlorate were detected
in 99–100% of pregnant women. The median number of
detected chemicals by chemical class ranged from 4 of
12 PFCs to 9 of 13 phthalates. Across chemical classes,
median number ranged from 8 of 17 chemical analytes
to 50 of 71 chemical analytes (NHANES 2003-2004).
BPA and tOP were detected in 92.6% and 57.4% of the
persons, respectively...Females had statistically higher
BPA LSGM concentrations than males (p = 0.043).
Children had higher concentrations than adolescents (p <
0.001), who in turn had higher concentrations than
adults (p = 0.003). LSGM concentrations were lowest for
participants in the high household income category (>
$45,000/year).

Affecting health and hormones
For generations to come
Endocrine disruptors are
synthetic chemicals that when
absorbed into the body either
mimic or block hormones and
disrupt the body's normal
functions.
Most of the endocrine disruptors
on the market are estrogenic or
anti-androgenic.

What would normally filter
the damage
Medicines
Toxins
Diet
Nutrients
Exercise
Has been compromised

Calorie Rich, Nutrient Poor

Nutrient Stripped Food
o Highly processed food-like products
o Sugar, carbs, fats and chemicals
o Genetically culled produce
o 70% reduced nutrient content
o With no genetic variation ( 96%)
o Glyphosate, toxic adjuvants and more
o 8 of the 9 formulations tested were 1000X
more toxic than their active principles
o Chemically laden meats
o Heavy antibiotics, antibiotic resistant bacteria,
growth and other hormones

Maternal Nutrient Deficiency
Oxidative stress caused by free radicals has been implicated in many studies of the etiology
of preeclampsia (38). Because ascorbic acid and vitamin E inhibit free radical formation, a
double-blind randomized trial was conducted in 283 women who had either a previous
history of pregnancy complications or an abnormal ultrasound (39). The supplement
provided 1000 mg ascorbic acid and 400 IU vitamin E daily from week 16–22 of pregnancy,
and resulted in a 76% reduction in preeclampsia, and a 21% reduction in indicators of
endothelial activation and placental dysfunction.
Evidence from experimental animals supports the concept that in addition to primary deficiencies,
secondary embryonic and fetal nutritional deficiencies can be caused by diverse factors including
genetics, maternal disease, toxicant insults and physiological stressors that can trigger a maternal
acute phase response. These secondary responses may be significant contributors to the occurrence
of birth defects. An implication of the above is that the frequency and severity of pregnancy
complications may be reduced through an improvement in the micronutrient status of the mother.
Micronutrient status in fetal and early life may alter metabolism,
vasculature, and organ growth and function, leading to increased risk
of cardiometabolic disorders, adiposity, altered kidney function, and,
ultimately, to type 2 diabetes and cardiovascular diseases.

Paternal Nutrient Deficiency

A Perfect Storm
Of environmental hazards
and reproductive difficulties.

Drowning in a sea of toxins
Of our
own
making

Not your average poisons
o First Generation Damage
o Chronic health issues: Obesity, CVD, ME/CFS
and other autoimmune conditions, T2D, thyroid
disease, Alzheimer’s, cancer
o Impaired fertility – male and female
o Difficult pregnancies
o 2nd Generation
o Males: demasculinization, reduced
anogenital distance (AGD), retained nipples,
cleft phallus with hypospadias, undescended
testes, a vaginal pouch, epididymal
agenesis, and small to absent sex accessory
glands as adults.
o Females: uterine malformations, precocious
puberty, endometriosis, breast and uterine
cancers
o 3rd Generation
o Fertility & health issues

FIND THE SITES AND MECHANISMS OF
DAMAGE
And then correct.

What is the First Domino
in the cascade of ill-health?

Is it the Endocrine Disruptors?
TEDX
Endocrine Disruption Exchange
Critical Windows of Development
http://endocrinedisruption.org/prenatal-origins-
of-endocrine-disruption/critical-windows-of-
development/timeline-test/
At low doses
Yes.

How about Gene
Activation/Deactivation?
Can methylation
patterns explain
chronic illness?

And possibly transgenerational
effects?
“Epigenetic effects can silence genes entirely, or cause
them to overproduce/overexpress (hypomethylate) or
underproduce/underexpress (hypermethylate) the
gene's protein product, influencing the downstream
biochemical milieu that underpins all dimensions of
complex behavior, including human health. Growing
evidence supports the likelihood that the overwhelming
majority of chronic human diseases are driven by
acquired changes in genomic expression over the life
course.”
• Intrauterine period is
highly susceptible to
epigenetic variability.
• Maternal-fetal
exposures linked later
life disease.
But is it enough?

“…epigenetic, and genetic changes are essential, but secondary, and can only be understood
with reference to the prime drivers in metabolism.”
Robert Naviaux, UCSD
Could there be Something
Else?

What is the prime driver of
metabolism?
Energetics.
“…mitochondria are located at the hub of
the wheel of metabolism and play a central
role in non-infectious cellular stress, innate
immunity, inflammasome activation, and
the stereotyped antiviral response, we
searched for a signaling system that was
both traceable to mitochondria and critical
for innate immunity.” Robert Naviaux, UCSD

Mitochondria: Cellular
Powerhouses
o Control dozens of cell processes
o Energetics, steroidogenesis, cell death, CA2+ management
o Bidirectional hormone regulation
o Highly susceptible to endocrine disruptors
o Interact significantly with nDNA
o 90% of factors required for mitochondrial function encoded by nDNA
o Bidirectional cross talk critical for cell homeostasis
o Lack protective histones – susceptible to epigenetic alterations
o Oxidative damage 10X higher than nDNA
o Sit at the center of host immune function
o Sensing and sending danger signals via multiple mechanisms
And so much more.

At the most basic level
o Consume O2 to
produce energy from
nutrients
o Mitochondria take
electrons from food to
produce ATP
o ATP = cellular
energy/cell survival
o ROS is a by-product
of energy production
o Too much or too little
ROS impaired
function
o Food supplies
mitochondria vitamins,
minerals necessary to
produce cellular
energy
o Without nutrients
functional
mitochondrial deficits
and cell death
Mitochondria produce ATP.
ATP is the universal
energy currency of
life.

High Carbohydrate Diet
Damage now, heritable
changes later.

High Fat Diet
Obesity is a safety mechanism.
o TSPO Channel
o Cholesterol into
mitochondria
o Pregnenolone
o ROS & ATP production
o High fat diet downregulates
TSPO
o Up to 90%
o Increased fat storage in
white adipocytes
o Increased immune response
o Decreased ATP
o Hormone dysregulation
o Cell death

First Warnings of Mitochondrial
Danger
o Orexin/Hypocretin system
o Brain energy sensors
o Maintain wakefulness, initiate
eating
o Exquisitely sensitive to changes
in ATP, glucose and temperature
o Low ATP = diminished firing
o High glucose = diminished firing
o High temp = diminished firing
o Conservation of resources
As Hans Selye observed many decades ago, one
of the first, and indeed, most consistent of the
sickness behaviors, no matter the disease, is
lethargy, fatigue and sleepiness. Orexin is at the
center of this behavior.
Excessive sleeping, fatigue,
anorexia.

Mitochondria: Not all
about Mom
o Inherited maternally
o 37 genes that code for 13 proteins, 22
RNAs, 2 rRNAs
o Interact significantly with nDNA
o 90% of factors required for mitochondrial
function encoded by nDNA
o Silenced or activated genes in mom and
dad can evoke mitochondrial damage and
mutations
o Interact significantly with extracellular
(host) environment
o Sense and send danger signals
o Medical and environmental exposures
matter
Dad’s health matters

Mitochondrial-Nuclear
Interdependence
The vast majority of mitochondrial
proteins (estimated at >1000 [2] )
are synthesized in the cytosol from
nuclear gene transcripts.

Poor Nutrition plus High Toxic
Load
Foundation from
which most parents-
to-be approach
reproduction
With the cascade of ill-
health already in progress.

Mitochondria Are Targets
Sensors of cell danger

Mitochondria Integrate Danger
Signals
EDCs affect mitochondria.

Mitochondria Drive Epigenetics
In response to cell
danger signals.

Endocrine Disruption, Epigenetics
and Energetics
Chronic,
Multifactorial
Illness
Danger
Signals
Chronic
Immune
Response

Environmentally Induced
Mitochondrial Dysfunction
mtDNA
damage
Functional
deficits
mtDNA
mutations
Altered ETC
Decreased
ATP
Mito damage
Increased
ROS
Oxidative
stress
Toxic Exposures
Medications, Vaccines, Environmental
Direct
 Induce mitochondrial
membrane permeability
changes
 Alter channel open times
 Activate death pathways
Indirect
 Block critical nutrient co-
factors for ATP
 Alters hormone activity
(endocrine disruptors)
 Activate/deactivate critical
transcription and repair
proteins (epigenetics)
Cell Death
Disease

How prevalent is Mito
Damage?
“Disorders of the mitochondrial respiratory chain affect at least 1 in 8000 of the population,
making them among the most common genetically determined diseases.”
Patrick Chinnery, Medical School, Newcastle upon Tyne.
Prevalence is likely underestimated because
functional mitochondrial damage is often
overlooked and most mitochondrial
deficits, especially those emerging later in
life, remain undiagnosed.
Not widely recognized.
1 in 500

What Happens with Mito
Damage?
“These are partial defects. Mitochondrial dysfunction doesn’t really cause anything, what it does
is predisposes towards seemingly everything. It’s one of many risk factors in multifactorial
disease. It can predispose towards epilepsy, chronic fatigue, and even autism, but it doesn’t do it
alone. It does it in combination with other factors, which is why in a family with a single
mutation going through the family, everyone in the family is affected in a different way. Because
it predisposes for disease throughout the entire system.”
Dr. Richard Boles, Director of the Metabolic and Mitochondrial Disorders Clinic at Children’s
Hospital Los Angeles

What Does Mito Damage
Look Like?
o Manifests broadly and variably
o Fatigue, hypersomnia
o Orexin/hypocretin system
o Migraines, seizures
o Muscle weakness, neuropathies
o Hair loss
o Cognitive & psychiatric symptoms
o Gait, balance and tremors
o GI disturbances
o Food intolerances
o Gastroparesis, dysmotility, cyclic vomiting,
anorexia
o Autonomic dysregulation
o Temperature
o Cardiovascular – Cardiometabolic
o Salt/potassium balance
o Thyroid damage
o Likely other endocrine disruptions

Microbiota > Mitochondria
Evolution
o Common evolution
o From O2-scavenging bacterial
symbionts into primary control
centers for energy production
and cell life-and-death
processes
o Shared function – ensure
survival of host
o Shared defense mechanisms
o ROS signaling – membrane
permeability (Curr Med Chem.
2012;19(10):1519-29.)
“The fascinating thing is that these organelles, the
mitochondria, come from some bacterial origin—they
were free-living bacteria and then invaded cells and
somehow made a deal to become the cells’ primary
energy producer. They also delegated functions to the
rest of the cell: only 13 out of 1,100 mitochondrial
proteins are encoded in the mitochondria; the rest are
encoded by the nucleus and produced in the
cytoplasm. So there is an effective symbiosis between
mitochondria and the rest of the cell, which involves a
great deal of communication and signaling.” Gyorgy
Hajnoczky, MD, PhD

Here’s the Kicker
o Interaction between diet, environmental toxins and
epigenetics, endocrine and mitochondrial dysfunction sits
squarely in ‘hands’ of the gut microbiota
Lack of proper nutrition for microbiota is a major
factor under-pinning dysfunctional microbiota,
dysbiosis, chronically elevated inflammation, and the
production and leakage of endotoxins through the
various tissue barriers. Furthermore, the over-
consumption of insulinogenic foods and proteotoxins,
such as advanced glycation and lipoxidation molecules,
gluten and zein, and a reduced intake of fruit and
vegetables, are key factors behind the commonly
observed elevated inflammation and the endemic of
obesity and chronic diseases, factors which are also
likely to be detrimental to microbiota. As a
consequence of this lifestyle and the associated eating
habits, most barriers, including the gut, the airways,
the skin, the oral cavity, the vagina, the placenta, the
blood-brain barrier, etc., are increasingly permeable.

Three Sisters Controlling Health
…if the gut microbiome is a major, if not dominant, component of the
DNA of a host animal, then changes in the gut microbiome can quite
naturally lead to new adaptations and speciation just like changes in
nuclear genes. We adhere to this view and suggest that the gut
microbiome must be considered a major portion of the genetics of an
animal, in combination with the nuclear genome and organelles –
what is now called a hologenome.
“…collaborative, cooperative and competitive cellular ecologies composed of our innate cells and almost incalculably
numerous microbial inhabitants.” William B Miller, Jr. M.D. The Microcosm Within: Evolution and Extinction in the
Hologenome.

Simple Solution
Avoid the toxins
Clean up the diet
Feed the deficiencies
If only…

Counterbalance
Nutrients
Exercise
Toxins
Medicine
Junk food

Nutrition is Key
Nutrition induces positive
and negative epigenetic
changes
Nutrients regulate
mitochondrial functioning

And Exercise Helps Too
Use it or lose it.
Exercise Induces
Mitogenesis
Exercise Increases
Microbial Diversity
…athletes had a higher diversity of gut micro-
organisms, representing 22 distinct phyla, which
in turn positively correlated with protein
consumption and creatine kinase… compared to
controls.
Endurance exercise-training
results in an increase in the size
and number of mitochondria in
the skeletal muscles that are
involved in the exercise. In early
studies of this phenomenon,
long-term training programs of
progressively increasing intensity
and duration were used.

Ending Principles
o Pregnancy is an opportunity to break cycles of bad
health
o Reproduction should be viewed from a much
broader and longer perspective.
o Dad’s health matters
o Perinatal health should include pre-conception – postpartum
year
o Transgenerational – can’t undue sins of our parents and
grandparents, but we can protect our children and
grandchildren
o Everything is connected – a more holistic and
systems approach to health
Same as in the beginning.

How to Find Me
o Websites
o LucineHealthSciences.com I Business
o HormonesMatter.com I online journal, medication adverse events
surveys
o HealwithFriends.com I Social health – in beta testing
o Social Media
o Facebook pages: Hormones Matter, Lucine Women Community
o Twitter: @chanatlucine, @lucinewoman, @hormonesmatter
o Email: chandler@lucinehealthsciences.com or
chandler@hormonesmatter.com

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