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Your Gut and Your Health – The Impact of Intestinal Permeability

I think that it is reasonable to state that we are in an epidemic of chronic disease.  The rates of conditions like Type 2 Diabetes, Coronary Artery Disease, Hypertension, Strokes, Alzheimer’s Disease, Cancers, Autoimmunity, Depression, Hormone Imbalances and many more are all on the rise, and have been for several decades, with no end in sight.  Even conditions such as asthma, food allergies, autism, irritable bowel syndrome are all on the rise.

Sobering Statistics:

  • 2012 – 29 million Americans had diabetes, 21 million diagnosed and 8 million undiagnosed.
  • In the same year, 86 million Americans were walking around with Pre-Diabetes.
  • 1.4 million people are diagnosed with Type 2 Diabetes every year.
  • More than 5000 children were diagnosed with “Adult-Onset” Diabetes 2008-2009.
  • That’s almost 1 in every 3 Americans with either Pre-Diabetes or diagnosed Diabetes.
  • The annual cost for the treatment of Type 2 Diabetes is $245 Billion per year – that does not include the care for those that are undiagnosed but still suffer with similar complications.

Data from American Diabetes Association

  • Coronary Heart Disease is the leading cause of death in the US in both men and women.
  • 616,000 deaths in 2008 – that’s responsible for 1 in 4 deaths.
  • 785,000 cases of a first heart attack annually
  • 470,000 suffer an additional heart attack annually.
  • The cost for managing coronary artery disease in the U.S. is $109 Billion annually.

This is just two of the most common diseases that we now see and they contribute to almost $400 Billion in direct costs and the cost in quality of life, years lost and disability are immeasurable in dollar value.  While Type 2 Diabetes is on the rise, the CDC does point out that the prevalence of coronary artery disease has diminished over the past decade, as has the incidence of death from CAD. They attribute this to an improvement in risk factors modification.  While there may be some truth to this statement, I do not believe that there has been as significant of a change in the risk factors as they portray.  Possibly the most significant of all the risk factors that have been modified is that there are less people smoking cigarettes.  I would attribute the decreased rates of deaths from CAD to improved identification, specialized centers that perform interventional techniques to open the artery being more available and aggressive medical management of these individuals.

Coronary Artery Disease, which has traditionally been a disease of the elderly, is now affecting greater numbers of those in their 40’s and 50’s.  In the chart above you can see that 110 out of every 1,000 population between 45 – 54 years of age is having a first heart attack, repeat heart attack or dying from a heart attack.  That’s over 10% of the population in the late 40’s/early 50’s.  That is a startling number.

Approximately 50 million Americans suffer with autoimmune disease.  There are > 100 distinct autoimmune conditions now identified and several more that are considered to have an autoimmune pathology.  The more we come to understand about autoimmunity, and the better our technology to identify it, the more conditions are coming to be recognized as having an autoimmune basis.  These cluster of various conditions are now the 3rd leading cause of morbidity and mortality in the Uniter States.  It is becoming clearer that even conditions like Coronary Artery Disease and Type 2 Diabetes can have an autoimmune basis for their development.

What may all of these conditions have in common?  What is the link that binds them?  Inflammation.

After all, an individual that develops any one of these chronic conditions is at increased risk for any other of these. Someone that is diagnosed with Type 2 Diabetes is at significantly increased risk for also being diagnosed with hypertension, CAD, chronic kidney disease and later Alzheimer’s Disease.  The order for the development of these conditions does not have to follow that pattern, however.  High blood pressure can arise first, then heart disease and finally diabetes.  But one thing seems to be true, one begets the next.

The common link that plays a role in all of these conditions is chronic inflammation. This is something that our ancestors did not have to deal with.  There is a reason that the incidence of heart disease, type 2 diabetes, dementia, asthma, many cancers and all other chronic conditions were all very low prior to the industrial revolution, and did not begin their rapid incline until the mid-20th century.  A lot changed after the 1850’s to the way we live our lives – from the foods we eat to the way we sleep, the air we breathe and the activities we perform.  While we may believe that we have it far better today than our great-great relatives had it, this may not be the case.  Our reliance on technology and conveniences may be the very thing that is killing us slowly – chronically.


The leading causes of death prior to 1900 were infections and trauma.  These were acute and short-lived.  That slowly changed over the early part of the 1900’s and then made a quick jump in the 1950’s and it has never ceased.  There is still plenty of infection, some of them deadly, with many contributing factors for this. Ironically, the immune dysregulation that occurs with the chronic inflammation may be a big contributing factor for why we are as susceptible to infections as we are today.  Despite all the big antibiotics and antivirals that have been discovered and created, there are still tens of thousands that die from infections annually.  Some from seemingly minor infections that result in sepsis.  Today you can literally die from an infection that develops from a minor scratch on your skin.

In conventional medicine (the mainstream) we tend to focus on the “Big Risk Factors” as the causes of heart disease, diabetes, stroke, etc.  They include: obesity, hypertension, sedentary behavior, smoking, family history, high cholesterol and the evils of the “high-fat diet” (thank goodness this is finally coming to its conclusion).  These have been the primary focus of diet and lifestyle modifications that have been focused on since the late 1950’s.  An important point to recognize is that several of these risk factors are identified disease states themselves (diabetes, hypertension, obesity, hypercholesterolemia).  They are all markers of metabolic dysregulation.  We cannot modify family history but it would appear that this risk factor is quite possibly the least significant of them all – even though it is always what something is attributed to when we can’t explain something by any other means – leaving smoking, a high fat diet and sedentary behavior as the only true modifiable risk factors that are recognized to be responsible for all of these different conditions.

The truth is that there are hundreds of risk factors for heart disease with countless potential insults that can result in inflammation and immune dysregulation.  The same holds true for all of the other chronic conditions as well.

  • Consider, just for a moment:
    • All of the thousands of environmental chemicals that we are now exposed to on a regular basis, in our drinking water, the air that we breathe, products that we place on our skin.  There are over 80,000 registered chemicals in the U.S. and very few have ever been tested for safety in humans.
    • The level of pesticide in our foods (glyphosate) – not just in vegetables and fruits.  If the animal proteins (meat/fish) that you eat have been fed grains that have been heavily treated then you are consuming large quantities from them as well.
    • Genetic modification of over a dozen different common foods that are a huge part of the food supply, not only in whole foods but also in condiments, sauces, body care products.  Corn, soy, potatoes, papaya.  The list keeps growing.
    • The recommended amount of sleep is 7 to 9 hours per night of “quality” sleep.  How many can say that they achieve this?  The average American is probably lucky to get 5 t 6 hours of sleep, only some of that being of any quality (deep sleep + REM) and those that sleep more are usually only through the use of chemical interventions like Ambien and Lunesta that disrupt the sleep cycles. Lack of quality sleep leads to inflammation and immune dysregulation.
    • Exercise – we seem to be either hot or cold in the United States – we either exercise too much or don’t exercise at all.  Both of which contribute to inflammation. There is a happy medium that we should be at.  Unfortunately, for many us, the reason we may not get enough exercise is because of poor sleep, busy work lives or chronic illness that keeps us from doing it.  All additional contributors to chronic inflammation.
    • Stress – does anyone really have any of this?  Our ancestors used to be stressed because of inclement weather, lack of food, risk of danger from predators or other tribes.  For the most part, they were probably not very stressed most of the time.  They lived with clean air, clean water, slept well in a cave or under the stars, and had a large family or tribe that they relied upon.  Today, we are awakened by buzzing alarms, halted by stand-still traffic, screaming children with multiple demands on an already overwhelmed schedule, numerous deadlines, endless bills, a challenging job, dings and whistles from our electronic devices incessantly notifying us of something that is going on or has to be done.  Do you still feel like you are not stressed?
    • Medications – for all the benefits that they may seemingly have in impacting on our function, they also have numerous adverse effects.  They impact on metabolic pathways.  They work, for example, by stopping B from going to C, resulting in improved symptoms (e.g. headache gone) but they also then prevent the progress to D, E, F and so on.  All necessary steps in the functions of life.  Those steps were not randomly created with no particular purpose in mind.  Preventing them can lead to the development of disease.  Maybe you have heard recently that Statins can cause Diabetes. They have also been attributed to muscle breakdown, memory loss and several other conditions.  Ever consider why that may be?  Many medications are like a poison to our metabolic machinery, to our mitochondria and our cellular network of communication.
    • Chronic Infections – Epstein Barr Virus, Lyme Disease, Mycoplasa Pneumoniae, Herpes Simplex Virus – to name a few.  These organisms like to linger and wreak havoc in our bodies.  They require a highly functioning, robust immune system to deal with them whenever they flare up.  An immune system that is in disarray will not respond appropriately, which can lead to symptomatic flare-ups (e.g. Shingles) and can result in an internal environment that continuities to the chronic conditions we are discussing.  Other forms of chronic infections (e.g. gum disease, candida overgrowth, mold exposure) also continue to chronic inflammation.

These are just a few examples of contributors to chronic inflammation.  A key factor that has been completely neglected by mainstream medicine and is only now beginning to be recognized – though it has been on the radar of alternative medicine practitioners for a couple of decades – is a condition known as Intestinal Permeability – aka “Leaky Gut”.  More specifically, when we are discussing risks for disease, we can refer to it as Impaired Intestinal Permeability.


Leaky gut is a completely natural process that plays a crucial role during certain times of life.  We have built-in mechanisms that actually causes our guts to become permeable, allowing more nutrients and other contents within the intestine, including bacteria, to penetrate this barrier.  A protein, called Zonulin, is released from intestinal cells and opens the gates between the cells.  Infancy and pregnancy are 2 periods of life where intestinal permeability is naturally increased with a suspected beneficial effect (allowing for immune system training in the infant and for colonization of the gut biome (probiotics) of the child prior to birth.  There can also be increased intestinal permeability in pathologic conditions – these include severe stressors like sepsis, severe burns, major trauma.  Other than these very specific times, intestinal permeability should be absent or at a minimum.

A little background about the gut:  It is a hollow tube that extends from your mouth through to the anus.  It is, for all intents and purposes, outside of your inner body.  Nutrients and other substances need to penetrate through the gut lining in order to enter into your inner body, traveling through your blood stream and then reaching cells all throughout the body.  The gut cells pick and choose what can come through and what cannot.  Intestinal Permeability, however, can allow for all types of larger molecules to get in, including large proteins, bacterial by-products, toxins, etc.  Seventy to Eighty Percent of our immune system resides at the border just beneath that single layer of intestinal cells.  There must be some significance to this gut barrier and the risk for disease that we would mount almost our entire immune defenses along that border.

The gut is the primary entry point for the majority of foreign proteins (foods, allergens, toxins, hormones, bacterial by-products) to enter our body, resulting in a full-on assault by the immune system. This is a process we would recognize as inflammation.  These invaders (particularly a molecule called Lipopolysaccharide, from gram negative bacteria on our gut) can travel up to the liver through the Portal Vein and lead to further immune system activation. The liver then produces alarm signals, called cytokines (e.g. CRP, TNF-alpha and many more) that travel though the circulation, notifying the rest of the body that you are under attack. This, in turn, activate other immune cells, that then travel to the sites of inflammation to join the battle.  These immune cells release a barrage of chemical weapons like hydrogen peroxide, superoxide, etc that destroy invading organisms (bacteria, viruses, fungi) but can also cause damage to neighboring cells – your cells.  This results in a process called oxidation that leads to an increased burden (oxidative stress) that perpetuates inflammation.  Eventually, as the battle wanes and our immune system senses victory, antioxidants help to clean up the mess and neutralize the free radicals.

What I just described in the paragraph above is a normal physiologic process that we are designed to carry out as often as needed to protect us from foreign invasion.  This is how we fight infections, heal wounds, stop bleeding from a cut.  What happens when the immune system doesn’t respond as its supposed to – when its signals are crossed or one branch of our immune system is dominant or the other branch is in a haze.  What about when we are constantly under assault, perpetual leaky gut, and our immune system is constantly on the attack and in defense mode?  A unique characteristic of the standard American diet (now the diet of western civilizations) is the paucity of quality nutrients and antioxidants.  If our immune cells are producing all of these pro-oxidants, free radicals, and we cannot provide anti-oxidants to diffuse them then what happens?  Cellular damage.  This leads to further inflammation.

This is a cycle that needs to be stopped if we are to truly focus on preventative strategies for chronic diseases of modern civilization.  Intestinal Permeability is, by far, the greatest contributing factor to the conditions that most individuals now suffer from and to the cost of trillions of dollars in annual costs when these are all considered together.

What are some of the things that contribute to Impaired Intestinal Permeability?

  1. Gluten (a large protein found primarily in wheat, barley and rye) – causes the release of zonulin
  2. Grains – (corn, brown rice, quinoa, millet, etc) many, if not all grains, may cause leaky gut through proteins called saponins that break down cell membranes.  This is likely also the case with legumes (e.g. beans, peanuts).
  3. Dysbiosis – an imbalance in growth of the healthy (probiotic) bacteria and viruses in our gut [gut biome] with the unhealthy organisms.  There can either be an overgrowth of “bad” bacteria, yeasts and viruses or a decreased amount of the good bacteria, or a decrease in the diversity of these good bacteria.  All of these result in an imbalance that can lead to increased intestinal permeability.  Our gut biome is heavily impacted by antibiotics (used to treat infection but also in our foods), food choices, environmental toxins, our sleep and our stress.
  4. Small Intestinal Bacterial Overgrowth (SIBO) – this is a form of dysbiosis where there is excessive growth of bacteria higher up in the intestines where their numbers are supposed to be very low.
  5. Extreme Stress – this can be emotional, psychological or physical stressors.  This is one mechanism by which excess exercise contributes to inflammation that can lead to chronic diseases (e.g. marathon runners and heart disease).  Other stressors include severe infections, trauma and burns.
  6. Excessive alcohol consumption – the amount will vary from individual to individual.  It will not take much.
  7. Food Sensitivities and Allergies – these may initially develop as a result of leaky gut but will then perpetuate it due to the inflammation that occurs every time they are consumed.
  8. Several conditions that result in prolonged intestinal permeability that may have its roots in leaky gut include Celiac Disease, Crohn’s Disease and Ulcerative Colitis.

There are many conditions that may be the result of Intestinal Permeability or, at least in part, contributed to by it because of the altered pathways that are created by it:

  1. Coronary Artery Disease
  2. Type 2 Diabetes
  3. Obesity
  4. Non-Alcoholic Fatty Liver Disease
  5. Hormone Imbalances (Estrogen, Progesterone, Testosterone, Cortisol, DHEA) – PMS, Infertility, Decreased Lbido, PCOS, etc
  6. Insulin Resistance
  7. Hypertension
  8. Cerebrovascular Disease (Stroke)
  9. Cancers (Breast, Prostate, Ovarian)
  10. Autoimmunity (all types)
  11. Autism Spectrum
  12. Parkinson’s Disease
  13. Alzheimer’s Disease
  14. Depression, Anxiety, Mood Disorder
  15. Inflammatory Bowel Disease (Crohn’s, Ulcerative Colitis)
  16. Nutritional Deficiencies
  17. Osteoporosis
  18. Clotting Disorders

The list can go on and on…

Our tendency in western medicine is to focus on manifestations (symptoms) or laboratory abnormalities to provide us a diagnosis that we can treat with either pharmaceutical medications or surgery.  It makes us feel like we are “fixing” something.  The truth is that we are never addressing the root causes in this way and the dysfunction will continue, our bodies constantly trying to adapt to this worsening environment that it is provided with, struggling to keep us alive, which is how we end up with abnormal labs in the first place.  It may seem strange to think but “Leaky Gut” may be the very reason that our healthcare system is going broke and why there is no end in sight.  We need to change our focus to where the real pathology begins and the best ways to address it.  There will not be a lot of interest in this from big pharma because there really is little money to be made, since the measures to address this can largely be done for little to no cost at all for the individual affected.

This is not a comprehensive review.  An entire book could probably be written on this topic alone.  I am just attempting to provide an introductory discussion about an entity that can change people’s lives forever.  It’s the difference between wellness vs disease, vibrant & vital vs debilitated.  We cannot prevent all disease, clearly, and death is the one true certainty that we will all face one day.  How do we want to live our lives until the time that it arrives?

I fully recognize that the majority of the world’s population will never effect the changes that would be needed to change the course that we are on as a population.  I come from a Portuguese background, where bread is always in one hand while a meal is being eaten.  People feel deprived and lost when it is suggested to them that they need to give something up.  I have fielded this in my office on several occasions:  “what will I eat if I can’t have these?”.  There is testing available for confirmation of Intestinal Permeability – Zonulin can now be tested for in the blood and stool.  There are additional tests that can be performed to assess for dysbiosis, bowel inflammation and pancreatic insufficiency that may contribute (e.g. GI Effects Comprehensive Stool Profile by Genova Diagnostics), as well as testing for SIBO, food sensitivities, gluten sensitivity and more.  The answers are available if you know where to seek.

This is an area that needs more attention and if we can have an impact on the food industry and the federal government that would be quite a start.  Ultimately, both care about money.  The food industry wants to sell us things that we want to consume (demand drives production), the federal government cares about cost containment (decreasing healthcare expenditure).  Other impacting factors would follow from there.  This is a lofty dream but it is surmountable.  For now, I go on impacting on one individual at a time.  I hope that you have found this to be informative and that you will seek out further information that may help you in your path to wellness.

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