INSIDER S GUIDE. Insider s Guide Intestinal Permeability Interpretation and Treatment

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1 Functional Medicine University s Functional Diagnostic Medicine Training Program INSIDER S GUIDE Intestinal Permeability: Interpretation and Treatment By Ron Grisanti, D.C. & Dicken Weatherby, N.D. Limits of Liability & Disclaimer of Warranty We have designed this book to provide information in regard to the subject matter covered. It is made available with the understanding that the authors are not liable for the misconception or misuse of information provided. The purpose of this book is to educate. It is not meant to be a comprehensive source for the topic covered, and is not intended as a substitute for medical diagnosis or treatment, or intended as a substitute for medical counseling. Information contained in this book should not be construed as a claim or representation that any treatment, process or interpretation mentioned constitutes a cure, palliative, or ameliorative. The information covered is intended to supplement the practitioner s knowledge of their patient. It should be considered as adjunctive support to other diagnostic medical procedures. THIS MATERIAL CONTAINS ELEMENTS PROTECTED UNDER INTERNATIONAL AND FEDERAL COPYRIGHT LAWS AND TREATIES. ANY UNAUTHORIZED REPRINT OR USE OF THIS MATERIAL IS PROHIBITED Functional Medicine Training Program Page 1 of 14

2 INTESTINAL EPITHELIAL HYPERPERMEABILITY AKA: LEAKY GUT 3 CONDITIONS THAT MAY CAUSE LEAKY GUT... 4 WHAT DO YOU MEAN BY LEAKY GUT?... 5 THE BIG PICTURE BEHIND LEAKY GUT: THE REAL STORY... 5 THE HEALTHY MUCOSAL LINING... 6 THE DAMAGED MUCOSAL BARRIER... 7 TWO SERIOUS CONSEQUENCES OF CHRONIC LGS... 8 Compromised Liver Function... 8 Autoimmune conditions... 8 Leaky Brain Barrier: Breakthoughs in Clinical Medicine... 9 An Overlooked and Ignored Factor in Health Restoration... 9 FUNCTIONAL DIAGNOSTIC MEDICINE TESTING FOR LEAKING GUT THE INTESTINAL PERMEABILITY TEST 10 WHAT DOES THIS TEST INVOLVE? WHAT DO THE RESULTS MEAN? If elevated Lactulose with an elevated or normal Lactulose/Mannitol ratio OR if normal Lactulose with an elevated ratio: Suspect: If depressed Mannitol with an elevated or normal Lactulose/Mannitol ratio Suspect REPAIRING THE GI TRACT 12 THE 6 R APPROACH TO GI HEALTH: Remove mucosal irritants Reduce Restore Replace Reinoculate Repair Combination Products for Repair of Mucosal Lining Intestinal Repair Complex Pharmax Functional Medicine Training Program Page 2 of 14

3 Intestinal Epithelial Hyperpermeability aka: Leaky Gut Leaky gut is an amazingly common problem. Basically it's a condition that occurs whenever there is inflammation and the "pores" lining of the GI tract remain open too long. Then toxic byproducts in the digestive tract can be absorbed into the bloodstream and transported on to the liver. The molecules of food and toxins "leaked" through the GI lining may eventually affect systems throughout the body by aggravating inflammation in the joints, expressing toxins in skin disorders, triggering food sensitivities, causing "brain fog" or hyperactivity. Managing hyperpermeability is definitely preventive medicine. Reducing this toxic load on the liver and the body can prevent illness or improve its out-come. Like dysbiosis, leaky gut is an example of a general process that can lead to disease, rather than being a specific disorder. This condition is far more typical than many practitioners realize and is often overlooked in designing treatment. Resolving hyperpermeability can produce very real benefits. Leaky gut is associated with a wide range of general symptoms, such as fatigue, fevers of unknown origin, abdominal pain or bloating, diarrhea, feelings of toxicity, memory problems and difficulty with concentration, and poor tolerance of exercise. Hyperpermeability can be an underlying factor in such conditions as: Attention deficit disorders Symptoms resembling autism Chronic and rheumatoid arthritis Chronic fatigue syndrome Eczema Food allergies and intolerances Inflammatory bowel disease Irritable bowel syndrome Joint and collagen problems Compromised liver function Malnutrition Multiple chemical sensitivities Psoriasis Skin disorders ranging from urticaria to acne and dermatitis Symptoms like schizophrenia Functional Medicine Training Program Page 3 of 14

4 Hyperpermeability can also be caused by any number of different conditions. Any substance or condition that causes inflammation (such as GI infection), severe trauma (such as burns or surgery), or mechanical overstimulation (such as certain medications or NSAIDs) anything that overstimulates the pores in the lining and keeps them open too long is said to cause leaky gut, known as hyperpermeability. Conditions that May Cause Leaky Gut The following conditions sometimes cause hyperpermeability: The aging process HIV AIDS with diarrhea Alcoholism Malnutrition Burns NSAIDs Cancer Pancreatitis Celiac disease Psoriasis Certain drugs Radiation therapy Chemotherapy Rheumatoid arthritis Chronic hepatitis Shock or anaphylaxis Crohn's disease Toxic shock syndrome Functional Medicine Training Program Page 4 of 14

5 Cystic fibrosis Trauma Giardia and other parasites Ulcerative colitis What Do You Mean By Leaky Gut? The intestinal lining has two opposite functions: 1. The absorption of nutrients from food in the digestive tract 2. A barrier function, to control microbes or large food particles (potential allergens) from going beyond the gut environment (translocate) and get into our bloodstream The digestive tract has tiny permeable openings between the cells (called tight junctions) so that nutrients can be absorbed from our food. If these pore-like structures open too wide, toxins from the gut can spill over into the bloodstream, overwhelming the liver and causing allergies or any of dozens of other ailments. This is known as hyperpermeability because the lining has become too permeable (porous). It's also called leaky gut syndrome because the gut begins leaking larger food particles and toxins from the gut. It's not an disease per se but rather a natural process gone bad. Under normal optimal conditions these pores open and close whenever nutrients are absorbed from our food. It's only when the pores open too wide that leaky gut is said to occur. The Big Picture Behind Leaky Gut: The Real Story Here's a detailed account of how leaky gut occurs. Let's use the example of someone who has a food allergy. Suppose Mary has a wheat allergy and innocently eats a bagel; this can elicit a reaction in her body. If she has an immediate food allergy, her immune system may begin reacting right away. If she has delayed allergies, the reaction may not occur for as long as three hours, but it could take as long as forty-eight hours to occur. What is surprising is that no matter when it occurs, Mary may not even be aware that it's happening. She may have a vague feeling of discomfort that could include a mild indigestion, a headache, even joint or muscle aches. Although she may not notice anything more than vague discomfort at the time, later down the road she may develop some chronic problem such as auto-immune disorders, allergies, asthma, or arthritis. And she probably won't link it to this microscopic process going on in her digestive tract as the lining becomes too permeable and begins leaking tiny particles. Functional Medicine Training Program Page 5 of 14

6 On the other hand, she may have noticed that if she cheats on her allergy diet and has milk for breakfast, sometime that day or the next her joints may be achy and exercise will become a major effort. The response of Mary s body to the offending food also activates her immune system. To alert the system that an invader is present (the wheat food she just ate), her immune system sounds the alarm through chemical messengers, the cytokines. They act like horn-blowers calling out the cavalry, and their job is to bring in the infection fighters (the antibodies). This sets the immune system in motion. While we always have cytokines as an essential part of our system, when there are too many cytokines and other immune chemicals circulating in the bloodstream, the gut will start leaking. The Healthy Mucosal Lining (Healthy Mucosa) When Mary's system is working properly, absorption is occurring through tiny structures in the lining of the small intestine. All this is happening on a microscopic level. Nutrients are being absorbed through three structures: Directly through the cells of the gut lining, called transcellular absorption Between the cells, in paracellular absorption In the crypts, tiny crevices in the lining of the gut Each structure is programmed to absorb nutrient molecules of a particular size and electromagnetic charge. Between the fingerlike villi that line the gut are the crypts, crevices at the base of each villi, like the webbing between your fingers. Because of their larger size the crypts absorb bigger molecules, such as the disaccharides, which are complex sugars. Between every cell in the gut lining is a tiny porelike structure called a tight junction. These tiny pores are also active during digestion. They expand and contract just as other muscles do, opening and closing to release nutrients from the gut into the bloodstream or contain the food mix as it passes through the gut. Functional Medicine Training Program Page 6 of 14

7 The Damaged Mucosal Barrier (Abnormal Mucosa) Too many immune chemicals can cause the pores to open too wide, causing too much permeability. When there's inflammation or any kind of crisis in the body, if too many of the immune-signaling chemicals are circulating in the bloodstream, they can overstimulate the tight junctions, causing the pores to open too wide. This process can be compared to a house with doors wired to a fire alarm system. If the alarm system malfunctions, it may keep all the doors in the house open and won't let them close. Clearly other problems can result. Intruders could easily enter the house. Leaky gut can raise the body's exposure to intruders, such as bacteria, yeast, or large food particles that would normally remain in the gut. Again, when the pores open too wide, material is inappropriately released into the bloodstream. In Mary s case, if her immune system detects large food particles in the bloodstream (perhaps other innocent foods, released through the leaky gut), it will assume they're allergens and launch a second attack, flooding her system with more cytokines. Then the whole dynamic just gets worse. Functional Medicine Training Program Page 7 of 14

8 Two Serious Consequences of Chronic LGS If leaky gut occurs frequently, it can cause chronic conditions. The importance of this increase in the permeability of the small intestine is not to be taken lightly, because two additional serious problems usually develop: liver overload and autoimmune conditions. Compromised Liver Function Leaky gut places an increased toxic load on the liver, producing harmful chemical by-products as the liver attempts to clean up the overload. Unfortunately, this worsens leaky gut, creating a vicious cycle. Over time these toxic by-products can cause gallstones or eventually even cancer. In order to break the cycle, it's important to control the underlying problem that has caused the leaky gut syndrome in the first place. The liver is the chief detoxifying organ of the human body. All products absorbed across the intestinal barrier must pass through the liver before entering the general circulation. There must be a balance between the size of the toxic load presented to the liver and the liver's capacity to metabolize this load. Unless the liver's detoxification system has enough reserve capacity to adjust to an increased toxic load, serious consequences can and often do result. Autoimmune conditions Hyperpermeability sets the stage for possible autoimmune complications. When the total load of foreign material (antigens) is increased for a prolonged period, the immune system can become hyperactive, and a hyperimmune state can follow. As the immune system becomes overstimulated, "immune soldiers" the antibodies actually begin to attack the cells of the body as if they were the invaders. If one of the invading molecules resembles tissue within the body, the antibody produced to attack the foreign molecule will be unable to distinguish friend from foe, attacking both the original invader and the body's own tissue. This is known as the innocent-bystander phenomenon. In the gut, these conditions include Crohn's disease, food allergies, and celiac disease. Elsewhere in the body conditions such as asthma or rheumatoid arthritis can result. Functional Medicine Training Program Page 8 of 14

9 Leaky Brain Barrier: Breakthoughs in Clinical Medicine Mental disorders. A number of mental conditions have been linked to increased permeability. The elevated toxins that leak into the system from hyperpermeability can produce symptoms that range from spaciness and brain fog to attention deficit disorder. We now know that many children with ADHD have increased gut permeability. In the most extreme form hyperpermeability can cause disorientation resembling autism or schizophrenia. In some cases these disorders are also linked to specific food sensitivities such as gluten intolerance. And a number of stresses can be affecting the body at once: Toxic load on the system appears to affect neurotransmitter production, and specific allergies may directly affect the nervous system as well. Recent research links some allergic responses with brain chemistry and reactions in the receptor sites An Overlooked and Ignored Factor in Health Restoration The widespread frequency and critical importance of leaky gut syndrome has been largely underrated. In one study that tested for leaky gut syndrome in an intensive care unit, all patients studied had leaky gut syndrome, regardless of the condition that originally brought them to intensive care. Because of the incredibly high incidence of chronic diseases today and the high frequency of leaky gut syndrome in patients with chronic diseases, testing for intestinal permeability is worthwhile whenever associated conditions are present. Skillful management of this syndrome will help alleviate the primary illness, regardless of its nature. Functional Medicine Training Program Page 9 of 14

10 Functional Diagnostic Medicine Testing for Leaking Gut The Intestinal Permeability Test What does this test involve? Following an overnight fast, the patient collects a urine sample and then drinks a premeasured challenge drink containing lactulose and mannitol (two nonmetabolized sugar molecules). A second urine sample is later drawn from a six-hour collection. Functional Medicine Training Program Page 10 of 14

11 The report includes lactulose percent recovery, mannitol percent recovery and a lactulose/mannitol ratio. Lactulose and mannitol recoveries are elevated, suggesting an overall increase in permeability both between and through the intestinal epithelial cells. The elevated lactulose reflects increased paracellular permeability (between the cells), which can result in macromolecules, toxins and antigens crossing the intestinal barrier into the lymph and circulatory systems, a condition termed "leaky gut". These particles increase the load on the body's detoxification system and may stimulate immune reactivity. Increased lactulose recovery has been associated with food allergy, inflammatory bowel disease, arthritis and other inflammatory conditions. The elevated mannitol reflects increased transcellular permeability (through the cells) which may result in the passage of small antigens across the mucosal barrier, thereby triggering an immune response. What Do the Results Mean? If elevated Lactulose with an elevated or normal Lactulose/Mannitol ratio OR if normal Lactulose with an elevated ratio: Suspect: Increased intestinal permeability/ leaky gut Possible causes: Exposure to toxic substances (drugs such as NSAIDS and alcohol, chemical exposure) Food allergy/intolerance Intestinal dysbiosis Parasite, yeast, viral, or bacterial infection Maldigestion (includes hypochlorhydria, pancreatic insufficiency, and disaccharidase insufficiencies) Bacterial overgrowth of the small bowel Prolonged fasting/nutrient insufficiencies Inflammatory bowel disease, e.g. Crohn s disease Insufficient mucosal glycocalyx and/or siga If depressed Mannitol with an elevated or normal Lactulose/Mannitol ratio Suspect Intestinal malabsorption Increased intestinal permeability/ leaky gut Functional Medicine Training Program Page 11 of 14

12 Repairing the GI Tract The 6 R approach to GI health: Remove mucosal irritants These would be things such as allergenic foods, alcohol, gluten (if sensitive), NSAIDS, possible pathogens (bacteria, yeast, parasites) Reduce Sugar, refined carbohydrates, saturated fat, red meat (meat can induce bacterial enzyme activity) Restore Proper bowel transit time Increase dietary fiber (esp. insoluble) and water Fiber Permavite is a supplement that contains an insoluble fiber, cellulose, which seems to decrease and clear toxins. Based on observations made by Dr. Leo Galland different kinds of fiber affect intestinal permeability. He found that insoluble fibers reduce intestinal permeability and that soluble fibers tend to increase it. So this formula is based on insoluble cellulose and has other components in it to soothe and heal the GI tract. Cellulose products available in drugstores include Citracel and Fiber-Con, however, Permavite contains specific added nutrients, and is available from Allergy Research Group. In powder form it mixes well with water and has a mild flavor. The general recommendation is to use this prior to two meals a day. Replace Agents for digestive support: Proteolytic Enzyme Therapy Enzymes and enzyme stimulants provide digestive support using either digestive enzymes to promote thorough digestion or glandular products to stimulate the body's own enzyme production. Related but stronger products are Wobenzyme and Marcozyme, excellent quality digestive enzymes from Germany (available through Lifespan). There are vegetarian equivalents to these products; Interplexus has such a Functional Medicine Training Program Page 12 of 14

13 product, which is called Polyzyme. We also recommend Inflazyme-Forte from American Biologics. Reinoculate With friendly bacteria, if low: Consider probiotic supplementation, including Lactobacilli and Bifidobacteria Consider fructooligosaccharides and inulin to enhance growth of friendly flora Repair The mucosal lining: Consider L-glutamine, EFAs, zinc, pantothenic acid, vitamins C, E, and A, beta carotene, N-acetyl glucosamine, gamma oryzanol, glycerrhiza, aloe vera Bioflavonoids aid in strengthening the gastric mucosa and also help settle or reduce liver reactivity due to allergies. N-acetyl cysteine (NAG) is also important in reestablishing normal flora because it helps decrease the toxicity of abnormal bacteria while the per-son is rebuilding normal flora. Consider Saccharomyces boulardii, whey globulin concentrate, or bovine colostrum to improve local immunity Consider ginkgo biloba to enhance circulation to intestinal epithelium Functional Medicine Training Program Page 13 of 14

14 Combination Products for Repair of Mucosal Lining Intestinal Repair Complex Pharmax Permeability Complex 1 Permeability Complex 2 Call Jennifer: Functional Medicine Training Program Page 14 of 14