CREATING HEALTH Lecture #3: Inflammation

Lecture by Mark Pettus transcribed by Carolann Patterson

INFLAMMATION: ARE YOU PLAYING WITH FIRE?

Learning Objectives from today's lecture:

1. Explore the root causes of inflammation that fuel chronic-complex disease
2. Examine the connection between inflammation and brain health
3. Examine the mechanisms that link many common environmental triggers with increased inflammation
4. Consider lifestyle changes that can reduce-reverse inflammation to improve longevity and quality of life

The proposition for this lecture: how the outside gets inside

1. Health and disease are byproducts of complex individualized gene-environment interactions that may go back more than a generation before our conception and continue throughout our lives.
2. Your DNA i.e., your “Book of Life” still has a Stone Age imperative, not often adapted for 21st century environmental inputs e.g. the foods in our modern food supply.
3. This incompatibility creates a distorted metabolic trajectory e.g. inflammation that forms the basis of chronic complex disease and diminished quality of life.
4. Through mindful living that aligns conscious choosing with what are are most designed to be in relationship with, our biology can be transformed to promote-restore optimal function and health throughout the life continuum.

Nutrigenomics studies the effects of food and food constituents on gene expression and focuses on the molecular-level interaction between nutrients and genome. It is where we look beyond “food as calories” and see food for what it is: information. Molecules of food have the power to influence life-sustaining pathways. Depending on the quality of a certain food, it will send information that will either trigger inflammation or reduce it.

Does the stress of our present diet create an epigenetic change in our health? Absolutely... 

This is the shape of things to come…and this is the route we are taking to get there…

1. Poor Quality Carbs - information from food leads to...
2. Excess Insulin - It is impossible to burn fat with excess insulin [leads to...]   
3. Fat storage [leads to...]
4. Down-regulation of insulin receptors [leads to...]
5. Insulin Resistance and then on to Leptin Resistance and then on to Eat More + Do Less = NO GOOD

It is not simply a matter of poor food choices that lead to Inflammation and then on to Insulin Resistance. All of the following factors eventually lead to Insulin resistance: Visceral fat, Changes in food consumption, Stress, Sleep disruption,  Altered gut-permeability/microbiome, Social Isolation, Hormonal imbalances, Toxin excess. 

INFLAMMATION IS AT THE CENTER OF IT ALL

Inflammation is connected to every chronic complex disease...and it's got everyone's attention. Scroll through the titles listed below to find articles related to Inflammation and Stroke; Inflammation, Atherosclerosis and Coronary Artery Disease; Inflammation and Cancer; Inflammation and Depression and the Brain; Inflammation and Obesity; Obesity and Periodontitis.

CRP. C-Reative Protein is a marker for inflammation. We can easily test for CRP levels. When tested for CRP, cancer patients' survival rates are higher when there is Low CRP. See graph below: 

Slide courtesy Jeanne Wallace PhD

Inflammation effects cancer prognosis and reaction to chemotherapy: Patients with higher CRP experience poor prognosis; toxicity of chemotherapy; cachexia; and fatigue...

NF-κB is Inflammation’s “Master Switch” - keep it turned off

NF-κB is a nuclear transcription factor that is triggered by diet, stress, environmental toxins, visceral fat, infections, intestinal barrier integrity disruption, oxidized LDL, free radicals, vitamin D deficiency, altered microbiome, LPS, inflammation from other sources. It up-regulates expression of 400+ genes involved with cytokine production, cell proliferation, apoptosis, angiogenesis. Exercise, meditation, Vitamin D, Spices [e.g. turmeric] and many plant flavonoids have shown to inhibit NF-κB in vitro and in vivo. 

Nrf2 is the antidote to NF-κB.

Nrf2 activation is a critical intra-cellular defense: keep it turned on. Exercise, Meditation, EGCG, Resveratrol, Coffee, Sulfurophane, Curcumin all boost Nrf2. 

FOOD AND INFLAMMATION

Changes in our diet trigger inflammation. Watch out for the following inflammation boosters:

• SUGAR and REFINED grain flours, PROCESSED poor quality carbs with high “carbohydrate density”FRUSCTOSE from sugar and High Fructose Corn Syrup
• Not enough vegetables and plant-based fiber to strengthen and balance your microbiome [we need 6-9 servings per day]
• Increased processed seed oils [they are too high in Omega-6 polyunsaturated fatty acids. Excess Omega-6 fatty acids build up in our cell membranes and contribute to inflammation]
• Insufficient healthy saturated fat [e.g. coconut oil and grass-fed-pasture-raised butter, whole milk, cream, eggs, red meat]
• Sensitivity to GLUTEN and DAIRY
• ENVIRONMENTAL TOXINS - contaminated foods such as game fish [mercury], non-organic fruits and vegetables [pesticide residues], food stored in BPA in plastics…and that’s just the short list

SUGAR

Obesity and Diabetes: The Twin Epidemics. Rates of Obesity and Diabetes have risen drastically in the past century. In 1890, one in thirty [adult 60 year old men] was obese. In 2000, 1 in 3 [adult 60 year old men] was obese. In the 1930's, one in 50,000 adults was diabetic. In 2000, one in 9 adults is diabetic [Johnson et al, American Journal Clinical Nutrition, 2007].

Inflamed About Obesity, Michael Lehrke & Mitchell A Lazar: Two studies find that adipocytes and macrophages have more in common than previously thought. The work bolsters the notion that the inflammatory response might link obesity to afflictions such as diabetes. The epidemic of obesity stems from a clash between genes that allowed our ancestors to survive extended periods of famine and the caloric excess and sedentary lifestyle of our modern environment. Obesity is a major risk factor for diabetes and atherosclerosis, afflictions associated with a constellation of insulin resistance, hypertension and lipid abnormalities that is now defined as Metabolic Syndrome [Nature Medicine, Vol 10, No. 2, February 2004]

What is metabolic syndrome? Metabolic syndrome is not a disease in itself. Instead, it's a group of risk factors- high blood pressure, high blood sugar, unhealthy cholesterol levels, and abdominal fat at the following levels [Source AHA]:

• Waist Circumference > 35” in women and > 40” in men
• BMI > 30 (= obese)
• Elevated blood pressure: > 130/85
• High triglycerides: > 150 mg/dL
• low HDL: < 40 mg/dL men, < 50 wome
• Elevated fasting glucose: >100 mg/dL

Visceral Adipose stores [mid-section weight gain, belly fat] is linked to Insulin Resistance; Dyslipidemia [high TGA and low HDL]; Elevations of Blood Pressure; and increased risk of chronic complex disease. It is the outward signal that internal fat surrounds organs and can penetrate the liver, causing the liver to respond as though it is Hepatitis. 

The Quality of carbohydrates you eat matters. 

Different carbohydrates produce unique genomic responses. NF-κB is the Inflammation Master Switch: keep it turned off...

High Glycemic Carbs [NF-κB turned on = bad]. 

Low Glycemic Carbs [NF-κB turned off = good]. 

... and stay away from those seemingly innocent rice cakes and pretzels!

GLUTEN

Gluten attacks the intestinal tract. Boston Mass General's Alessio Fasano is a gastroenterologist and pioneering researcher whose team discovered Zonulin, the molecule which regulates intestinal permeability, a.k.a. Leaky Gut.

Gluten triggers Zonulin. Over-production of Zonulin has been linked to a series of autoimmune diseases, including Type 1 Diabetes, Celiac Disease and Multiple Sclerosis.

Gluten is the primary cause of Celiac Disease. Fasano's research in 2003 demonstrated the prevalence of Celiac Disease in the U.S. to be far higher than previously thought, at a rate of 1 in 133 persons. Currently, 1.4% of Americans have Celiac Disease.

Primary source of Gluten is Wheat, and Wheat is NOT what it used to be...

GLUTEN MIND and GLUTEN MOOD 

Inflammation is a systemic process. Inflammatory triggers such as Gluten cause inflammatory manifestations in all parts of the body, not just at the "point of entry" e.g. the stomach and can disrupt coordination/balance, cause joint pain and brain fog and... 

• Celiac Disease is caused by Gluten and associated with many neuro-psychiatric diagnoses e.g. ADHD seen in approx. 60%!
• Celiac Disease is associated with white matter changes on MRI…similar to that seen with MS
• Gluten increases insulin resistance in individuals who are sensitive
• Brain wave patterns in ADHD improve consistently with gluten restriction
• Gluten sensitivity enhances zonulin that increases intestinal permeability
• Gluten sensitivity can alter blood flow to frontal lobes

From Gut to Brain: Gluten sensitivity is linked to:

• Dementia
• Depression
• Headaches
• Movement disorders
• ADHD
• Pain 

The intestines are only one cell layer thick. What causes Intestinal Permeability?

• Food sensitivities
• Dysbiosis – Too much bad and not enough good bacteria. Gut microbiome needs diversity to balance
• Acid suppression [Causes overgrowth of bad bacteria. Prolonged acid suppression is not good for you Short-term use only e.g Prilosec]
• Stress response
• Environmental toxins
• Medications e.g. regular steroids and NSAID use [irony: anti-inflammatory drugs such as Tylenol and Ibuprofen promote inflammation]

A-cellular carbohydrates [not from vegetables or legumes] cause increased inflammation which leads to:

• Insulin-fueling lipogenesis
• Insulin resistance in muscle and liver
• Inhibits capacity to burn fat
• NF-κB goes up [bad]
• Increased LPS - Lipopolysaccharides elicit a variety of inflammatory responses and may be a part of the pathology of Gram-negative bacterial infections [bad]
• Cytokine up-regulation [bad]
• Leptin resistance [hungry and less energy to move]
• Poor health and many symptoms [including Periodontal disease]

The Host Genotype Affects the Bacterial Community in the Human Gastrointestinal Tract

Host genes shape the gut microbiota. 90% of our bodies is not human: it's microbial. Microbes are essential to our health and most of them live in the gut sending out messages to support digestion, immunity, metabolism. When the microbiome is disrupted and out of balance [dysbiosis] messaging in our body gets mixed up. Big time.

The F-Word: FIBER [and F. prausnitzii]

When the mucous layer in the intestines is reduced, opportunists can move close to the gut lining, inciting inflammation. Fermentation of plant-based fiber seems to keep the mucous layer intact. So does the presence of peace-keeping microbes such F. prausnitzii.

Speculative interpretation of current research is that gut colonization is most beneficial before the age of 3 and is strengthened by these three key factors at birth to age 3:

1. Vaginal delivery
2. Breast-feeding
3. Minimal or no use of antibiotics and anti-bacterial products [both contribute to a less diverse ecosystem and microbiome]

Diversity of gut colonization relies on:

1. One organism preventing overgrowth of another 
2. Cross-talk influencing the immune system

Late colonization/infection + poor microbial diversity + genetics = sickness

Scientific America explains why our progeny may not be inheriting their fair share... "Because the critical issue is the inter-generational transfer of microbes and its timed assembly, three periods are relevant: before pregnancy, during pregnancy and in the child's early life.

For all three periods, antibiotic use is relevant because it may directly change maternal microbes prior to transfer or the child’s microbes afterward. Elective cesarean sections mean that the child misses the birth canal transit, and anti-bacterials in soaps and foods directly affect microbiota composition. Infant formulas have not been constructed with the benefit of millions of years of mammalian evolution, because breast milk contains nutrients that specifically select for the growth of preferred co-evolved organisms and inhibit opportunists and pathogens.

The aggregate of modern assaults on the early-life microbiome suggests that our progeny may not be inheriting their fair share. Exceeding the developing microbiome’s plasticity predictably leads to consequences, as growing evidence evinces.

Studies have linked C-sections and exposures to prenatal and postnatal antibiotics to increased risk of obesity, diabetes, celiac disease, asthma and allergies, among other ailments that have their roots in development."

PSYCHOBIOTICS

The brain responds to the gut. Researchers have learned which strains of gut bacteria affect the nervous system and have mapped out the pathways they use to influence the brain.  Gut flora can improve mood; some can produce neurotransmitters such as norepinephrine, serotonin, and dopamine; while other microbes such as L. helveticus and B. longum operate through the neuro-endocrine system and can lower cortisol.

A specific strain of Lactobacillus reuteri can increase the level of oxytocin, the hormone that kicks in when you cuddle, hug, or have sex. Lactobacillis acidophilus [found in yougurt, sauerkraut, and kimchi] is critical to regulating pain. B infantis and L reuteri and other strains attack inflammation by suppressing pro-inflammatory cytokines. They also send signals to increase Leptin [The “I am Full” hormone].

Watch this space – Psychobiotics might just be the next happy pill because of their links to:  

• Protection of intestinal barrier function
• Influence on local and systemic antioxidant status
• Direct neurochemical production e.g. Gamma Amino Butyric Acid
• Indirect influence on neurotransmitter function
• Experimental evidence of links to depression, anxiety, and autism
• Stress-induced alterations in microbiota
• Direct activation of neural pathways between gut and brain
• Regulation of immune response - inflammatory cytokines
• Can influence production of Brain Derived Neurotrophic Factor [BDNF]*
• Loss of microbiome “heritage” a contributor to many modern diseases

[Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013 Nov 15;74(10):720-6. doi: 10.1016/j.biopsych.2013.05.001. Epub 2013 Jun10. Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry Eva M Selhub1*†, Alan C Logan2† and Alison C Bested3 Journal of Physiological Anthropology 2014, 33:2]

*BDNF - Brain Derived Neurotrophic Factor

Up your Game and Up your Brain. Your Brain Derived Neurotrophic Factor [BDNF] is Known as "Miracle Grow." BDNF is decreased in Depression, Alzheimer's, Epilepsy, Schizophrenia and OCD.

BDNF increases with Exercise, Coffee [and other phytonutrients], DHA-omega 3, Curcumin-turmeric, EGCG [green tea], Meditation, Reduction in gut permeability. 

Evidence for increased inflammation in:

• MCI/Alzheimer’s disease
• Depression
• Pain
• PD
• MS
• ADD and ADDHD
• Brain fog i.e., trouble with concentration, focus, memory
• Anxiety and Panic
• Autism spectrum

What is happening in the brain doesn't necessarily originate there.

The contemporary convergence:

Gene-Epigenome + Environment + Microbiome = 

OUTCOME [how the outside gets inside]

Sugar triggers inflammation. Diabetes and pre-diabetes prevention and glucose control in midlife may protect against late-life cognitive decline. Higher glucose levels are associated with an increased risk of dementia. Studies show higher levels of fasting plasma glucose correspond to a higher rate of shrinkage of memory center [Neurology 2012;79:1019-1026].

High glucose is reversible and highly preventable.

High intake of energy from carbohydrates and low intake from fat may have inverse implications for development of Mild Cognitive Impairment [MCI]. In a study of 1,230 individuals age 70 and older, individuals with higher carbohydrate intake had nearly four times the risk of developing Mild Cognitive Impairment. Those individuals with the highest fat intake compared to the lowest fat intake were 42% less likely to have MCI.

MOTION is the LOTION:

Exercise training increases the size of the hippocampus and improves memory. "A physical activity program of an additional 142 minutes of exercise per week on average modestly improved congnition relative to controls in older adults with subjective and objective memory impairment" JAMA, September 3, 2008, Vol 300, No 9.

A six-month exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. Studied followed 24 healthy men with low level baseline activity levels before and after 6-month exercise program. There were 30 controls as genome-wide methylation patterns were examined in adipose tissue. Several patterns changed in exercise group demonstrating reduced lipogenesis and a “silencing” of genes associated with obesity, inflammation and impaired insulin signaling.

SLEEP WELL

Disrupted sleep and loss of entrainment is a major inflammatory risk

• 15% of Americans experience insomnia
• 1 out of 3 has sleep disruption on one or more nights each week
• Major risk factor for many chronic complex diseases
• Neuro-endocrine-immune disruption
• Sleep hygiene
• Obstructive Sleep Apnea
• Avoid pitfalls of sleeping medications
• Follow the Circadian Rhythm strategy [below] and work up to a healthy sleeping pattern:

ALLOSTASIS

The process of achieving stability or balance through physiological or behavioral change in response to changes in one’s environment. Simply put: Ability to achieve stability through change. Here are some helpful tips that are at the heart of an an Anti-Inflammatory Lifestyle:

• Sleep well. Get your ZZZ's and your Zeitgebers [Time Givers] - Light, Ambient temperature, Social Interactions, Exercise, Meal Timing
• Get your Vitamin D through supplements or sensible sun exposure each day. Vitamin D influences many things - Cardiovascular Disease, Cancer, Autoimmunity, Depression, CHF, Osteoporosis, Fall Risk, Pain Syndromes
• Whole foods always trump processed foods
• Reduce-eliminate sugar, fructose and refined-processed, grain-based flour [carbohydrate-dense foods] e.g. breads, pasta, bagels, chips, pretzels, muffins, donuts, and many cereal grains
• Consider an elimination trial e.g. gluten, dairy, sugar
• Eat lots of vegetables, plant-fiber, sweet potatoes, plantains, beans
• Reduce processed seed-vegetable oils e.g. corn, safflower, sunflower, canola, peanut and introduce more healthy fats e.g. grass-fed butter, EVOO, coconut oil, lard, ghee, and an increase in O-3s fatty fish, nuts, seeds, avocados
• Lean, red meat  (grass fed-finished ideal), eggs
• Eat organic for “the dirty dozen” produce

Round off an anti-inflammatory lifestyle with these healthy practices...

• Movement: Motion is the Lotion: walking, aerobic, resistance, yoga, tai chi
• Mind-Body awareness
• Prayer, Breathing techniques, Relaxation Response, Meditation
• Mindfulness-based stress reduction; HRV-Heartmath
• Sleep hygiene-entrainment
• Laughter
• Volunteer Work
• Social connection
• Cultivate meaning in work, love, and play
• More time outdoors during sun season

Recommended Reading: 

The Wahls Protocol, by Terry Wahl, M.D.

For more "news to use" and the science to go with it, visit The Health Edge: Translating the Science of Self-Care. Not all research slides are shown in this article. To download complete lecture, follow this link to BHS Creating Health Wellness Series.

CREATING HEALTH Lecture #1: Exploring the Causes of the Causes

Lecture by Mark Pettus transcribed by Carolann Patterson

CREATING HEALTH - Exploring the Causes of the Causes is the first of eight lectures created to form "a wellness road map." The Creating Health lecture series is about how you function. How you function determines how you feel. In eight weeks we will explore the key metabolic underpinnings of how we function. We will learn how our biology becomes our biography.

The #1 cause of death and diminished quality of life are the choices we make.  Healthy living does not happen at the doctor’s office.  Good Health requires that we transform perceptions of self-care and what we as humans are capable of. It’s not the hand you’re dealt. It's how you play your cards. 

Every choice we make has the power to transform our DNA. Lifestyle choices, our thoughts, the food we eat can all alter the microbiome [that is what lives inside us]. For better or worse, our choices lead to Wellness or Disease that takes shape as fatigue, depression, pre-diabetes, diabetes, obesity, and more...

How did the outside get inside?

Yogi Berra, my favorite yogi, once said “The future ain't what it used to be.” In a medical sense, this translates to the need to deconstruct our ways of thinking about self-care so that we may learn and acknowledge the impact of our choices. What we bring into our lives and what we put into our bodies matters.

In his short story Dubliners James Joyce said “Mr. Duffy lived a short distance from his body.” It's a perfect quote to illustrate how in this modern age we have so little time to examine who we really are. This dynamic leads to a total disconnect between the Mind, Body and Spirit. Now, more than ever, we need to be more mindful about all that is around us and learn more about the choices we make in order to understand our good health, and bad.

Albert Einstein said it best with “Reality is an illusion, albeit a persistent one” to explain that reality constantly shifts and changes so that truths become...less true with time [and research]. When we apply this message to self-care, one of the most significant changes to surface through research is that Your DNA in NOT Your Destiny, a key theme that will resonate throughout the Creating Health lectures.

A proposition for Creating Health 

'Creating Health' is different from 'Preventing Disease,' 'Early Detection,' and 'Managing Disease.' It works from the starting point that the choices we make have the power to optimize our biology. Good choices yield kick-ass performance in our lives. Creating Health assumes that Good Health is more than a healthy blood pressure, cholesterol reading, and heart rate. It's about looking at our health in new ways and from many angles in order to create a new definition of self-care that reduces or eliminates the bad and fills up on the good. 

Here are some key "take-away" points from the Creating Health lectures: 

• All health and disease are byproducts of complex individualized gene-environment interactions that may go back more than a generation before conception and continue throughout our lives and into the next generation. [yep, if Grandpa smoked then it has a bearing on you] 
• Your genes i.e., your “Book of Life” have a Stone Age imperative, not often compatible with 21st century environmental inputs.
• This incompatibility creates a disrupted biology e.g. inflammation that forms the basis of chronic complex disease and diminished quality of life. Our environment is no longer suited for "the Book of Life" to adapt to environmental toxins, stress, and modern day:night rhythms. 
• Epigenetics is the relationship between our choices and how our genes function.
• You can reduce-eliminate inflammation by aligning your lifestyle choices with your genes. Simply put: You can Create Health through the choices you make by getting to know what choices are best suited to your genes. 

There's been an explosion of knowledge.

Epigenetics research has doubled; microbiome research has doubled in the past year; and we're shifting away from Nature vs Nature to Nature via Nurture. To provide some context, here is a list of the different "moving pieces" on the playing field:

• Ancestral 'Book of Life" - Evolutionary Biologic Lens
• Functional – Systems Biology Model
• Personalized Lifestyle Medicine
• N = 1  (the quantified-self), measuring as much as you can about yourself, lots of Data Analysis
• Food as Medicine, what you eat is a 'promoter' or 'disrupter'

If you change something in your environment, evidence will determine what is best for you.  Each of us has a unique "Book of Life." Changing variables - such as your intake of gluten, sugar or alcohol; your exposure to environmental toxins; or the positive addition of exercise, yoga and meditation - will alter your ability to thrive. 

Mark Twain had another way of defining Reality: “It’s not what we don’t know that gets us into trouble, it’s what we know that ain't so.”  What did we once know that turned out not to be so? …Smoking is not bad for your health; If you live long enough you will get hypertension; My doctor told me I am feeling poorly because I am just getting old…

Daniel Boorstin refers to the illusion of knowledge - “The greatest obstacle to discovering the shape of the earth, the continents, and the oceans was not ignorance but the illusion of knowledge.”  So what does that say about the current state of our health? It signals that we need to re-examine what we think we know and discover new "truths" to treat mounting health issues as outlined below.

The Current State and the Stats:

Doctors, health care providers, and care-givers are constantly "mopping up," putting out fires and helping patients gain traction. It's increasingly difficult to get to the source of many health problems. In the end, what gets treated is more often the symptoms, not the cause. This section references statistics to demonstrate the state we're in:

The Growing Burden of Chronic Complex Disease

• 7 out of 10 deaths among Americans each year are from chronic diseases. Heart disease, cancer and stroke account for more than 50% of all deaths each year
• In 2005, 133 million Americans – almost 1 out of every 2 adults – had at least one chronic illness
• Obesity has become a major health concern. 1 in every 3 adults is obese and almost 1 in 5 youth between the ages of 6 and 19 is obese
• About one-fourth of people with chronic conditions have one or more daily activity limitations
• Diabetes continues to be the leading cause of kidney failure, non-traumatic lower-extremity amputations, and blindness among adults, aged 20-74
• You can reduce-eliminate inflammation by aligning your lifestyle choices with that which your genes are best suited for.

Health Patterns of Our Children and Young Adult

•  Infants come into the world with over 200 measurable environmental toxins
• Asthma: in 1980, 1 out of 30 kids were diagnosed. In 2010, 1 out of 10 kids
• Obesity- rates have tripled in the age 12-19 adolescent group over the last 25 years
• Allergies: according to JACI, the rate of serious peanut allergies has tripled over the last 10 years
• Behavioral: Rates of attention deficit-hyper activity disorder [ADHD] diagnosis increased an average of 3% per year from 1997-2006, ever increasing to an average of 5.5% per year from 2003-2007. In 2007, almost 10% of America's children aged 4-17 years of age are or have been diagnosed with ADHAD.
• Children aged 2 to 19 consume seven trillion calories of sugar-sweetened beverages a year. It’s a $24 billion industry just for kids alone. 
• Obesity prevalence among men would rise from 32% in 2008 to approximately 50% and from 35% to between 45% and 52% among women
• 7.8 million extra cases of diabetes
• 6.8 million more cases of coronary heart disease and stroke
• 539,000 additional cases of cancer
• Annual spending on obesity-related diseases would rise by 13-16%, leading to 2.6% increase in national health spending

Environments are changing across the globe with the rise of Diabetes, now a pan-species epidemic. 

Growth beyond maturity-macroeconomics. Global Deaths from Infectious Disease by 2020 will be Less than 20 MILLION. More than 50 MILLION deaths will be caused by chronic disease.

Diabetes

Today one in four Americans over 60 years old has type 2 diabetes. By 2020, one in two Americans will have pre-diabetes or diabetes. From 1983 to 2008, world-wide diabetes incidence has increased 7 fold from 35 to 240 million. Remarkably, in just the last 3 years from 2008 to 2011, we have added another 110 million to the diabetes roll call. Increasingly, small children as young as eight are being diagnosed with type 2 diabetes (formerly called adult onset diabetes). They are having strokes at 15 years old and needing cardiac bypasses at 25 year old. The economic burden of caring for these people with pre-diabetes and diabetes will be $3.5 trillion over 10 years.

We're a Drugged Culture. There is a tremendous role for pharmaceuticals and behavioral health drugs, especially when patients are in free-fall, but we can deconstruct the ways we think about them and how we use them...

We're More Medicated than ever before...

We're More Stimulated than ever before...

“The one thing that distinguishes man from other creatures is man's desire to take medications,” William Osler - 1910

How does a Functional-Systems Biology Model differ from the way we are currently looking at our health? Instead of looking at "the leaves" of disease to determine treatment, Functional Biology turns the model on its head and shifts analysis to begin at the roots, to find the root causes. Once we discover the root causes we can change our biology by changing our behavior. Our DNA is more malleable than we think. We are NOT locked in to our genetic legacy.

Disease [how things appear] - Pre-Diabetes, Diabetes, Obesity, Metabolic Syndrome, Heart Disease, Stroke, Depression, Autoimmunity, Alzheimer’s, Cancer, Autism, ADD, Hypertension

Core Metabolic Imbalances [what drives them] - Inflammation-Immunomodulation, Fight-Flight (HPA axis), Microbiome (Gut-Immune), Detoxification, Hormonal, Insulin resistance 

Root Causes [what are their origins] - Gene-Epigenome Environment, Nutrition, Movement   Stress Response, Environmental -toxins, Sleep   Social Connection, Traumatic events, Conflict Management   Mindfulness, Meaning in Work, Love & Play

What are the conditions of your ‘soil’?

1. What am I getting too much of that is undermining my health and how can I reduce it?
2. What do I need more of that I am not getting enough of to improve my health and how can I bring more of it in?
3. What would my great grandparents have done when confronting ____?

Health as a byproduct of gene-environment compatibility

An Ancient Design in Modern Times The social and cultural context in which we live has moved forward at lightning speed into the 21st century.  Our genetic endowment and the survival edge it brings with it, is still primitive.  Our design has maintained many of the Stone Age imperatives, but life in the fast lane has not. We are not well adapted for this and we we will eventually break down. Here's a THEN and NOW to show how things have shifted: 

• THEN: Targeted fight-flight [quick turn off and on]
• NOW: Anxiety, fear, PTSD, depression, all chronic, complex diseases [always on]
• THEN: Energy Conservation [quick turn off and on]
• NOW: Obesity and Metabolic Syndrome [does not turn off, we are always saving for a rainy day that will never come]
• THEN: Immunity [quick turn off and on]
• NOW: Autoimmunity and allergy [constant hyper-vigilant state]
• THEN: Promotion of clotting
• NOW: Heart attack and stroke [hyper-vigilant clotting]

!Kung People in the Kalahari Desert, Botswana have been around for 2.5 Million years living as foragers [Hunter gatherers] and eating everything - leaves, roots, berries, meat, fish - everything but processed food. Their diets exceed RDAs 2-10 fold [O’Keefe Mayo Clinic Poc 2004 Jan; 79(1):101-8]

Robert Sapolsky has studied the lives of baboons for decades. He is well known to the baboon tribe and is able to study them closely. Baboons are highly social. They groom one another and communicate threats. With the growth of African safari retreats and hotels came...DUMPSTERS. The primates had access to those dumpsters, and the food in those dumpsters. Naturally, they ate as much of it as they could. Sapolsky's primates became Junk Food Monkeys with:

• Increased weight with increased BMI
• Metabolic Syndrome
• Insulin resistance with elevated fasting and post-prandial insulin leves
• Increased TGAs
• Decreased Movement
• Less Socialization and less play
• Less fertility
• Earlier Death

Westernized Lifestyle

A recent study [noted below] provides compelling evidence that changes in lifestyle associated with Westernization play a major role in the global epidemic of type 2 diabetes. Prevalence of type 2 diabetes is 5 times higher in Arizona Pima Indians compared to Mexican Pima's. The researchers concluded that "the much lower prevalence of type 2 diabetes and Obesity in the Pima Indians in Mexico than in the US indicates that even in populations genetically prone to these conditions, their development is determined mostly by environmental circumstances, thereby suggesting that type 2 diabetes is largely preventable."

Pictured above: Mean body mass indices in hunter gatherers and non-westernized Populations show the BMI not exceeding normal limits in Australian Aborigines, Pygmies, !Kung, Innnuit, Yanomamo, Kren-Akore, Massai, Evenki and New Guineans. Recommended Reading: Jared Diamond, The World Until Yesterday - What Can We Learn from Traditional Societies? Diamond explores the introduction of grains and mono-commodities [corn, wheat] and its impact on growth and health [ie. lower height and greater number of cavities].

In 1890, Barnum & Bailey's Fat Man Freak Show – Chauncey “Human Freight Car” Morlan was RARE. Now, one in three adults is obese. Obesity may be the shape of things to come and "the new norm," but bigger is definitely not better. Research shows that the stress of our present diet and life choices create epigenetic change in our health. 

Epigenetics

What else do we know that “ain’t so”? We now know that You are not a prisoner of your DNA. Case in point: TWINS. While genes of identical twins may be the same, their epigenome changes throughout life. Your epigenome is your “Book of Life’s” memory of prior environmental events and conditions.

Recommended reading: A Life Decoded, by J. Craig Venter explores what we have learned from the human genome project. The genome has far fewer genes than expected [23k]; the variation of the genes is far greater than expected with 3 million SNPs; there are no specific "disease genes"; our phenotype results from genes + environment that work through our epigenome.

Who's Randy Jirtle and what's an Agouti mouse? The Agouti mouse has a genetic mutation that interferes with the ability to feel full. They can't exercise and are depressed and overweight. Dr Jirtle administered maternal supplements [methylating agents] to pregnant Agouti mice and guess what? Their offspring [and their offspring in turn] were smaller and a different color and experienced lower risk of cancer, diabetes and obesity and they had a prolonged lifespan. The offspring were 'social superstars,' highly active and able to navigate the maze with ease and speed.  Dr. Jirtle's research is a game-changer. See charts below for more details

MTHFR Polymorphism and Depression. DNA Methylation is essential for normal functioning of an organism. Patients who have the MTHFR C-T genotypes have a greater likelihood of having depression compared to those without the SNP. 

Representative clinical conditions suggested to have epigenetic origins

• Type 2 DM and Metabolic Syndrome
• Coronary artery disease
• Autoimmune Diseases
• Cancer
• Allergic Disorders
• Depression
• Neurologic: Alzheimer’s, PD, ALS, Autism

Epigenetics and Nutrigenomics: Getting beyond 'food as calories' and thinking of food as medicine. Food has an impact on the methylation and a body's on/off switches. For example, Green Tea and EGCG produce epigenetic effects that repair genes.

NRf2 Activation is a critical intracellular defense, as it protects us from inflammation and is linked to Caloric Reduction; EGCG [in green tea];Resveratrol; Coffee; Sulfurophane; Curcumin/Turmeric [and brocolli, kale and cauliflower, too]

Brain Derived – Neurotrophic Factor (BDNF)

BDNF is decreased in depression, Alzheimer’s, epilepsy, schizophrenia and OCD. BDNF expression increases with Exercise; Caloric restriction; DHA - Omega 3; Curcumin/turmeric; EGCG and Meditation.*

*Results of the MIDAS trial: Effects of docosahexaenoic acid on physiological and safety parameters in age-related cognitive decline. Karin Yurko-Mauro, Deanna McCarthyMIDAS Investigators. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, July 2009 (Vol. 5, Issue 4, Supplement, Page P84).

 Xenohormesis

Plant based foods are nutrient dense.Things that the plant produces to protect itself are good for us, too.

Plants transfer the protective benefits to those eating them.

The converse principal holds true for foods raised in stressful, unethical environments.

Michael Skinner wrote in Scientific American [2013] “the ability of environmental factors to promote a disease state not only for the individual but also subsequent progeny for successive generations is termed transgenerational inheritance...Epigenetic changes in methylation of the genome of germ cells after specific environmental toxin exposure that become permanently programmed allow transmission of epigenetic transgenerational phenotypes."

Trauma in pregnant mothers can carry over into the offspring of survivors...

Project Ice Storm - data provide first evidence in humans supporting the conclusion that PNMS results in a lasting, broad, and functionally organized DNA methylation signature in several tissues in offspring. We can infer that the epigenetic effects found in Project Ice Storm are due to objective levels of hardship experienced by the pregnant women.

• FTO genotype did not predict obesity in people born before 1942
• Higher risk when born after 1972
• Greatest risk when born after 2000
• As it turns out, it’s not just about who you are but in addition, when you are!

Get Moving! Acute exercise remodels promoter methylation in human skeletal muscle

Examined methylation patterns in skeletal muscle of sedentary men and women before and after 45 minutes of moderate-intense exercise revealed Methylation patterns changed significantly in genes coding for PPAR gamma and IL-6 suggesting more favorable gene expression patterns as they relate to inflammation and insulin signaling. Barres R et al. Cell Metab Mar 2012

SCIENTIFIC AMERICAN – November 2014 The Neuroscience of Meditation [How it changes the brain, boosting focus and easing stress]

Meditate more. Stress Less. Mindfulness Based Stress Reduction [MBSR] and Reduction in Inflammatory Biomarkers

• Randomized controlled trial of 40 individuals
• Half received training in MBSR technique
• Treatment group scored better on emotional wellness
• Down regulation of inflammatory gene expression patterns
• Diminished NF-kappa B expression
• C-reactive protein reduced

Change of Scenery [Change of 'genery'] - where you live and how you live change your gene expression:

Environmental Programming of Gene Activity - Bonding and the Glucocorticoid Receptor Gene

Social Connection is critical to the methylation patterns. Child abuse disrupts methylation patterns and cortisol signalling function. Whereas bonding with children creates a different epigenetic pattern [of love].

Stamatis Moraitis left America after being told he had six months to live. He moved with his wife back to his ancestor's home on the isle of Ikaria. Almost four decades after the lung cancer diagnosis, he outlived the doctors who predicted his imminent death back in the 1970's. Ikaria is located in The Blue Zone, a geographical area known for the longevity of its inhabitants. The BBC made this heart-warming video of Stamatis in his olive orchard. Living there in the sunshine with healthy food and social connections kept Stamatis Moraitis busy, and very much alive.

"The doctor of the future will give no medicine, but will interest her or his patients in the care of the human frame, in a proper diet, and in the cause and prevention of disease.”  Thomas A. Edison

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