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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
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“You did then what you knew how to do,
And when you knew better, You did better.” Maya Angelou
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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
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We are an unhealthy lot
2005
2010
2013And becoming more unhealthy as time goes by
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Living Sick and Dying Young
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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
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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
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We Didn’t Learn
Thalidomide -prescribed for morning sickness
Diethylstilbestrol (DES) – to prevent miscarriageAt least 3 generations affected, sons, daughters and
grandchildren
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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)
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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.
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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).
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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.
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What would normally filter the damage
Medicines Toxins Diet
Nutrients Exercise
Has been compromised
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Calorie Rich, Nutrient Poor
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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
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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.
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Paternal Nutrient Deficiency
A Perfect Storm
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Of environmental hazards and reproductive
difficulties.
Drowning in a sea of toxins
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Of our own making
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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?
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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.
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How about Gene Activation/Deactivation?
Can methylation patterns explain chronic illness?
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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?
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“…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?
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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
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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.
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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.
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High Carbohydrate Diet
Damage now, heritable changes
later.
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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
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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.
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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
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Mitochondrial-Nuclear Interdependence
The vast majority of mitochondrial proteins (estimated at >1000 [2] ) are synthesized in the cytosol from nuclear gene transcripts.
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Poor Nutrition plus High Toxic Load
Foundation from which most parents-to-be approach reproduction
With the cascade of ill-health already in
progress.
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Mitochondria Are Targets
Sensors of cell danger
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Mitochondria Integrate Danger Signals
EDCs affect mitochondria.
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Mitochondria Drive Epigenetics
In response to cell danger signals.
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Endocrine Disruption, Epigenetics and Energetics
ExposuresEndocrine Epigenetic Changes
Mitochondrial Damage
Chronic, Multifactorial
Illness
Danger Signals
Chronic Immune
Response
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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
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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
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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
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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
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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
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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.
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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
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Simple Solution
Avoid the toxinsClean up the dietFeed the deficiencies
If only…
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Counterbalance
Nutrients Exercise
ToxinsMedicineJunk food
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Nutrition is Key
Nutrition induces positive and negative epigenetic changes
Nutrients regulate mitochondrial functioning
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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.
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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
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