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Lucine Health Sciences, Inc. | Hormones Matter I Heal with Friends

Navigating Health in a Toxic

WorldChandler Marrs, PhDLucine 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 Principleso 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 matterso Perinatal health should include pre-conception –

postpartum yearo 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

2013And becoming more unhealthy as time goes by


Living Sick and Dying Young


Medication NationMayo Clinic Reportso 70% adults take

prescription medications chronically

o 50% take 2 or more medso 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 Pregnancyo 80% of women take at least one

medication during pregnancy o ~30% take 4 or more medications

during pregnancyo 60% increase in medication use during

pregnancy in 30 years


We Didn’t Learn

Thalidomide -prescribed for morning sickness

Diethylstilbestrol (DES) – to prevent miscarriageAt least 3 generations affected, sons, daughters and

grandchildren


Now we Have80% 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 psychotropicso 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 2001-2009JAMA 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 Exposureso 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, serumo Placenta, breast milk,

cord bloodo 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 chemicalso Genetically culled produce

o 70% reduced nutrient contento With no genetic variation ( 96%)

o Glyphosate, toxic adjuvants and moreo 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.

http://ajcn.nutrition.org/content/81/5/1206S.full#ref-38

http://ajcn.nutrition.org/content/81/5/1206S.full#ref-39


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 poisonso First Generation Damage

o Chronic health issues: Obesity, CVD, ME/CFS and other autoimmune conditions, T2D, thyroid disease, Alzheimer’s, cancero 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?

TEDXEndocrine Disruption ExchangeCritical 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 processeso Energetics, steroidogenesis, cell death, CA2+ management

o Bidirectional hormone regulationo Highly susceptible to endocrine disruptors

o Interact significantly with nDNAo 90% of factors required for mitochondrial function

encoded by nDNAo 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 functiono Sensing and sending danger signals via multiple mechanisms

And so much more.


At the most basic levelo 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 Channelo Cholesterol into

mitochondriao Pregnenolone o ROS & ATP production

o High fat diet downregulates TSPO o Up to 90%o Increased fat storage in

white adipocyteso Increased immune

responseo Decreased ATPo Hormone dysregulationo Cell death


First Warnings of Mitochondrial Dangero Orexin/Hypocretin system

o Brain energy sensorso Maintain wakefulness,

initiate eating o Exquisitely sensitive to

changes in ATP, glucose and temperatureo Low ATP = diminished firingo High glucose = diminished

firingo 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.

http://www.stress.org/about/hans-selye-birth-of-stress/

http://www.stress.org/about/hans-selye-birth-of-stress/


Mitochondria: Not all about Mom

o Inherited maternallyo 37 genes that code for 13

proteins, 22 RNAs, 2 rRNAso Interact significantly with

nDNAo 90% of factors required for

mitochondrial function encoded by nDNAo Silenced or activated genes in mom

and dad can evoke mitochondrial damage and mutations

o Interact significantly with extracellular (host) environmento 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

ExposuresEndocrine Epigenetic Changes

Mitochondrial Damage

Chronic, Multifactorial

Illness

Danger Signals

Chronic Immune

Response


Environmentally Induced Mitochondrial Dysfunction

mtDNA damage

Functional deficits

mtDNA mutations

Altered ETCDecreased

ATPMito damage

Increased ROS

Oxidative stress

Toxic ExposuresMedications, 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 variablyo Fatigue, hypersomnia

o Orexin/hypocretin systemo Migraines, seizures

o Muscle weakness, neuropathieso Hair losso Cognitive & psychiatric

symptomso Gait, balance and tremorso GI disturbances

o Food intoleranceso Gastroparesis, dysmotility, cyclic

vomiting, anorexiao Autonomic dysregulation

o Temperatureo 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

http://www.ncbi.nlm.nih.gov/pubmed/22360484

http://www.ncbi.nlm.nih.gov/pubmed/22360484


Here’s the Kickero 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.

NAVIGATING HEALTH


Simple Solution

Avoid the toxinsClean up the dietFeed the deficiencies

If only…


Counterbalance

Nutrients Exercise

ToxinsMedicineJunk 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 Principleso 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 matterso Perinatal health should include pre-conception –

postpartum yearo 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 Meo Websites

o LucineHealthSciences.com I Businesso HormonesMatter.com I online journal, medication adverse

events surveyso HealwithFriends.com I Social health – in beta testing

o Social Media o Facebook pages: Hormones Matter, Lucine Women

Communityo Twitter: @chanatlucine, @lucinewoman, @hormonesmattero Email: [email protected] or

[email protected]


mailto:[email protected]

mailto:[email protected]

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