It could be Leaky Gut Syndrome

by Laurel Garwin
March 8, 2000

We eat to nourish our bodies and give ourselves energy and vitality. However, if we suffer from Leaky Gut Syndrome, the very food we are eating may be draining our energy away, creating vague symptoms, and may eventually lead to disease. Leaky Gut Syndrome allows food to leak through the intestine and into the body in an undigested state. The body then launches an attack against the wayward food. War ensues, casualties are heavy in terms of tissue damage and organ exhaustion, and the invader is labeled as an allergen. The body is now allergic to this food and instead of giving energy, it has a draining affect on the body as each time it is eaten, a small war breaks out. Thus, because of Leaky Gut Syndrome, we are no longer eating for vitality but rather being drained of it. Leaky Gut Syndrome is much more prevalent than one would think. Dr. Fratkin states in his article "Leaky Gut Syndrome: A Modern Epidemic", that in his practice, Leaky Gut Syndrome accounts for 50% of the chronic complaints, as confirmed by laboratory tests (Fratkin, online, p.1).

Leaky Gut Syndrome may be caused by several mechanisms including inflammation, fungi or pathogenic bacteria overgrowth, parasites, drug or food reactions in the gut, to name just a few. Food and other antigens which have leaked through the intestine cause the body to launch an immune response to rid itself of the foreign matter. It is when and where the body launches its immune responses which leads to the various diseases. Below is a list of clinical conditions associated with altered intestinal permeability, or Leaky Gut Syndrome (Pizzorno, 1998, p. 115):

This paper will discuss Leaky Gut Syndrome, the mechanism by which it acts, and suggest some of its causes. Several tests to diagnose the condition in addition to a protocol to address the syndrome will also be presented. Let us begin by defining and understanding the nature of this condition.

Small Intestine

Function
The small intestine is most known for it's role in assimilating nutrients from food in which to nourish and feed the body. However, the small intestine must protect against harmful substance and therefore is also a part of the immune system. It is responsible for both, absorbing nutrients from food and keeping unwanted substances out. These unwanted substances are called antigens and they cause immune responses as the body tries to rid itself of them. Let us first examine the structure of the small intestine and then the mechanism by which the body responds to antigens. "Food represents the largest antigenic challenge confronting the human immune system"(Murray and Pizzorno, 1997, p. 467). Thus, the very substance we need for life, food, also presents the greatest challenge to our immune's system who's chief role is to preserve life.

Description
Let's begin with a description of the small intestine which is where Leaky Gut Syndrome strikes. The small intestine is, on average, 6 meters long in an adult. The intestine surface has a number of folds called valvulai conniventenes which increase the surface area of the intestine by about three-fold. Located on the entire surface of the small intestine are literally millions of small villi which project about 1 mm from the surface. These villi enhance the surface area another ten-fold.

The villi are covered by epithelial cells. Each epithelial cell has a brush border consisting of about 600 microvilli, 1 micron in length and 0.1 microns in diameter sticking out of the cell. These microvilli increase the intestinal surface another 20-fold. The surface area of the small intestine has been increased 600-fold giving it's original 6 meters in length a total absorptive surface area of 300 square meters. This large area is responsible for absorbing nutrients to feed the body and keeping foreign invaders out. The intestinal tract is the largest organ of immune surveillance and response in the human body (Wallace, 2000, p.18). This entire area is vulnerable to Leaky Gut Syndrome.

MECHANISM OF LEAKY GUT SYNDROME

As stated above, the intestine is composed of many finger like structures called villi, and each villi is covered by many epithelial cells. The epithelial cells are bound together by desmosomes with the space in-between them being called a tight junction (See figure 1). Mixed in with the epithelial are cells which secrete mucous, called goblet cells (See figure 1).

The epithelial cells transport molecules into the body by one of two mechanisms. Intracellular, where the molecule is absorbed into the cell and then passed into the body, or paracellular, where the molecule slips between the epithelial cells through the tight junctions. It is by way of one of these two transport mechanisms that nutrients enter the body. The same mechanisms protect the body from unwanted toxins or antigens.

If the villi or its epithelial cells become damaged or irritated, the goblet cells increase their mucous production. The increased mucous, along with the damaged cells and villi, prevents the body from absorbing nutrients which leads to malnutrition. The gap between the two epithelial cells, the tight junction, is very important in keeping large molecules out of the body. Disruption of tight junction increases the size of the molecules absorbed into the body. A large, macromolecule will cause an immune response in the body. Therefore, if the epithelial cells are damaged or atrophy, the intestinal walls become "leaky", allowing unwanted particles to pass into the body. This is what is termed "leaky gut " and results in leaky gut syndrome.

CAUSES OF LEAKY GUT SYNDROME

Leaky gut may be caused by many factors including, but not limited, to the following: immune system reactions, food allergies, alcohol, antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), celiac disease, coffee, intestinal dysbiosis, malnutrition, pancreatic insufficiency, deficient levels of secretory IgA, and stress. These causes will be briefly discussed. Additional causes of leaky gut , which will not be discussed, include: HIV infection, intestinal infection, aging, and giardiases.

Immune System

Function
When the immune system is functioning properly, it is able to resist almost all types of innate organisms and toxins that damage tissue by one of four methods: phagocytosis of bacteria and other invaders by white blood cells and other cells of the macrophage system; the destruction of organisms by the acid secreted in the stomach; the epithelium or surface layer of cells which acts as a physical barrier; the destruction of foreign organisms or toxins by chemical compounds in the blood stream.

However, the immune system does not always work properly: the stomach may not be producing enough acid to kill the bacteria and other organisms being ingested; the intestinal lining may be damaged letting antigens cross over into the blood stream (leaky gut); the system may be overwhelmed by the sheer number of antigens in the intestine or entering the blood stream and unable to clear or destroy them. Any one of these problems may lead to tissue damage and or disease.

Mechanism
According to Gell and Coombs there are four distinct ways in which the immune system reacts to a food antigen and causes tissue damage (Great Smokies, 1999, p. I-6). Often this tissue damage happens at the first point of contact where the antigen meets with the immune system, specifically the intestinal lining. Keep in mind that an antigen is any substance which causes the formation of antibodies against it. Antigens include undigested proteins, toxins, and other substances that stimulate the immune system. Let us look at the four ways the immune system attacks antigens, the diseases they may cause, and their role in Leaky Gut Syndrome.

Type I
Type I or immediate hypersensitivity reactions cause responses such as asthma, hives, and anaphylaxis (accounts for only 10-15% of all food-allergies) (Murray, 1993, p.251). The reaction occurs less than 2 hours after eating the allergen and is IgE mediated. IgE is a class of immunoglobulins that is distributed throughout the body. The cells synthesizing IgE are predominantly found in association with mucosal tissues such as those found in the nose, mouth, and gastrointestinal tract (nutramed.com, online, p.1). During the first exposure to an antigen, the body produces immunoglobulin IgE antibodies, which bind to the surfaces of basophil and mast cells. With further exposures, when the antigen binds with the attached antibody, the basophil or mast cell releases histamine, leukotrienes, and other chemicals that induce the inflammatory response. The release of these chemicals initiates a variety of responses: vasodilatation, increased capillary permeability, increased mucous secretion, and constriction of smooth muscle tissue.

The location of the mast cell during a reaction determines the symptoms experienced. For instance, if the reaction takes place in the nasal passage, you get sinus congestion; in the bronchioles, it's constriction (asthma); in the skin, hives and eczema; in the synovial cells that line the joints, arthritis; in the intestinal mucosa, inflammation resulting in malabsorption; in the brain, headaches, loss of memory, and inability to concentrate (Great Smokies, 1999, p. I-7). If the mast cells release chemicals in the ears, nose, and throat, then there may be itching in the mouth and there may be trouble breathing or swallowing (pharminfo.com, online, p.3). A severe Type I reaction results in Anaphylaxis which may result in death if not treated immediately.

Type II
Type II or cytotoxic reactions result in the destruction of cells. "It has been estimated that at least 75% of all food allergy reactions are accompanied by cell destruction" (Murray, 1993, p.251). Cytotoxic reactions involve either IgG or IgM antibodies. These antibodies bind to cell-bound antigens (antigens which have attached themselves to a cell), and by doing so, activate the factors which cause the destruction of the complex. In other words, the antigen-antibody complex binds to a cell and the immune system destroys the cell along with the antigen-antibody complex to which it is bound. An example of this would be immune hemolytic anemia where antigen-antibody complexes bind to red blood cells. The red blood cells are then destroyed along with the antigen-antibody complex. This results in a lack of red blood cells, or anemia. More to the point, intestinal cells are normally the cells which are destroyed because the intestine is where the antigen and the immune system first meet.

Type III
Type III or immune complex-mediated reactions involve IgE and IgG immune complexes and usually occur at least 2 hours and sometimes days after exposure to the antigen (Murray, Pizzorno, 1998, p.468). The immune complexes are formed when the antigens bind to the antibodies. These complexes are usually cleared from circulation by the phagocytic system. However, if the complexes are deposited in the tissues, the tissues may become damaged. Tissue may be damaged further by the presence of histamines and other amines that increase the vascular permeability and increase the number of immune complexes being deposited in the tissues. Arthritis is caused by this mechanism. The complexes are deposited between the joints and inflammation ensues.

Type IV
Type IV or T-cell-dependent reactions occur usually within 36 to 72 hours after contact with the allergen. These delayed reactions are mediated primarily by T-lymphocytes and result when an allergen makes contact with a mucosal surface such as the intestinal tract. This type of reaction does not involve antibodies. Examples include poison oak, allergic colitis (inflammation of the colon), and regional ileitis (inflammation of the ileum). Inflammation of the colon leads to Leaky Gut Syndrome.

In summary, when the immune system is working properly, it fends off antigens and protects the body from harm. However, when it is baraged with antigens from the foods we eat or other sources, it can actually cause damage. Since the intestinal lining is where most antigens first come in contact with the immune system, this is most often where the damage occurs. An overwhelmed or over active immune system may contribute greatly to leaky gut syndrome.

Food Allergies
Food allergies and Leaky Gut Syndrome go hand in hand; the relationship is circular. It is difficult to determine which causes which. This is similar to the proverbial question, "Which came first, the chicken or the egg". It has been shown that following exposure to allergenic foods, permeability sharply increases, thus food allergies cause "leaky gut" (Galland, 1995, p.62). It is also well known that a permeable or "leaky gut" is one of the chief causes of food allergy.

It is believed that at least 60% of all Americans, both healthy and sick, suffer from symptoms associated with food reactions (Pizzorno, 1998, p.212). Infact, nutritionally oriented physicians believe that food allergies are the leading cause of most undiagnosed symptoms and contribute to most chronic diseases (Pizzorno, 1998, p.212). Diseases associated with food allergies are similar to those of Leaky Gut Syndrome, and once again it is hard to separate the two.

Food allergies and food intolerances may be caused by several factors including heredity, gut permeability, an overly sensitive immune system, poor digestion, or an excessive exposure to a limited number of foods. For example, in terms of hereditary, if both parents have allergies, then the child has a 67% chance of having allergies, while if only one parent has allergies, child's chances of having allergies drops to 33% (Murray, 1993, p. 250). Blood type also plays a role. According to Gittleman, people with type O blood have a greater predisposition to celiac disease, a type of food intolerance (Gittleman, 1997, p. 33). Celiac disease is characterized by an inability to digest foods that contain gluten. Finally, as the famous Greek physician Hippocrates noted in relationship to milk and gastric upset, "to many this has been the commencement of a serious disease when they have merely taken twice in a day the same food which they have been in the custom of taking once..."(Murray, 1993, p.248). The average American gets about 80% of their calories from only eleven foods (Braly, 1992, p. 48). Eating the same foods too often, especially if a leaky gut condition already exists, is a sure way to develop allergies (Braly, 1992, p. 48).

The foods which people are most commonly allergic to are the foods most commonly eaten, the staples of the American diet. They are as follows (Braly, 1992, p. 230, Pizzorno, 1998, p. 212):

However, determining which food one is reacting to is not always easy. Reactions to foods are not always immediate, they may be delayed. The immediate reactions, IgE mediated reactions, are thought to account for only 10% to 15% of all food allergies (Murray, 1993, p. 251). Some researchers claim that delayed food reactions may account for up to 90% of all allergy symptoms (Barrie, 1987, section 2, p.1). This makes identifying the allergenic food difficult.

Technically there are food allergies and food intolerances. A food allergy occurs when the immune system generates an antibody in response to the ingested food. A food intolerance is when the body is unable to digest and process a food correctly usually due to a lack of a certain enzyme or enzymes. Food intolerance can lead to food allergies however, if particles of the undigested food manage to enter the blood stream and cause an immune reaction (Balch and Balch, 1997, p.110). However, both food intolerances and food allergies cause intestinal damage and result in increased intestinal permeability. Celiac disease is an example of a food intolerance to the gluten protein in grain, while anaphylactic shock triggered by eating a peanut is an example of a food allergy.

"When proteins are not digested to amino acids, dipeptides, or short chain polypeptides, they retain their antigenic properties" (Great Smokies, 1999, p. I-5). With this in mind, let us explore the mechanism by which food causes Leaky Gut Syndrome. A person eats a food to which they have become intolerant. The food is inadequately digested in the stomach and small intestine so that intact proteins come into contact with the cells lining the intestine. Antibodies in and on the intestinal lining combine with the food protein, initiating an inflammatory reaction. The inflammatory reaction causes damage to the nearby intestinal cells, continued exposure results in progressive damage to the intestinal cell lining. The damaged lining decreases the surface area of the intestine, resulting in fewer nutrients being absorbed, and allows antigens to "leak" into the body. Thus, this is an explanation of how food causes Leaky Gut Syndrome. Conversely, here is the mechanism by which Leaky Gut Syndrome causes food allergies. An undigested protein "leaks" accross the intestinal lining and is tagged as an antigen, antibodies are made, and a food allergy is born. The person is now sensitized to this food and whenever it is eaten, the body will launch an immune response damaging nearby cells which again leads to Leaky Gut Syndrome if the "nearby" cells are in the intestinal lining.

Common signs and symptoms of food allergy consist of the following (Pizzorno, 1998, p.213):

• Dark circles under the eyes (allergic shiners)
• Eczema
• Puffiness under the eyes
• Hives
• Horizontal creases in the eye lower lids
• Canker sores
• Chronic non cyclic fluid retention and bloating
• Asthma
• Chronic swollen glands
• Excessive mood swings
• Chronic diarrhea
• Bed wetting
• Chronic infections
• Irritable bowel syndrome
• Chronic Fatigue

Food reactions are one of the must common causes of Leaky Gut Syndrome and ironically enough, Leaky Gut Syndrome causes food allergies. The two go hand in hand, each excasberating the other. Therefore it is extremely important to eliminate any foods from the diet which may be causing reactions and irritating the gut. It is only in this manner that the gut may begin to heal and Leaky Gut Syndrome may be addressed.

Alcohol

According to Dr. Braly, alcohol, even in moderation, appears to cause an increase in permeability of the gastrointestinal tract (Braly, 1992, p.318). When alcohol passes through the stomach and intestinal tract it causes subtle cellular damage in the lining of these digestive organs. In time, alcohol damages these organs to the point where they become increasingly porous, allowing large, incompletely digested food particles to pass directly into the blood stream (Occhipinti, online, p.1). A study conducted by Bjarnason of 36 non-intoxicated alcoholics indicated that not only did they have higher intestinal permeability than controls, but that this condition could last for up to two weeks after they had stopped drinking (Bjarnason, 1984, abstract). Additionally, alcohol inhibits the breakdown of nutrients into usable molecules by decreasing secretion of digestive enzymes from the pancreas (Occhipinti, online, p.1). This results in undigested foods which ferment in the intestinal tract resulting in increased gut permeability.

Antibiotics

The small and large intestines are host to over 400 different kinds of bacteria (Fratkin, online, p.2). The beneficial bacteria breaks down complex foods, synthesizes vitamins like B12 and Biotin, and performs various other functions which are required for healthy metabolism and immune responses. For example, beneficial bacteria breaks down hormone secretions, including estrogen, which are discharged into the small intestine by the liver (Fratkin, online, p.3). If there is not enough beneficial bacteria to break down the estrogen, and if the intestinal permeability has been altered, the estrogen may be reabsorbed into the body. The estrogen may then be deposited in estrogen sensitive areas such as the breast, uterus, or ovaries, which may lead to fibroids and tumors (Fratkin, online, p.3). Dr. Fratkin believes that this reabsorption of estrogen is also responsible for premenstrual syndrome (Fratkin, online, p.3).

Antibiotics cause damage in two ways, they destroy beneficial bacteria and foster the growth of pathogenic fungi, including candida, and yeast. When healthy, beneficial bacteria plays a crucial role in protecting the body against fungi (Candida albicans) and amoebic (parasitic) infections. Antibiotics kill the beneficial bacteria, and by doing so, they allow harmful bacteria to multiply. Harmful bacteria results in intestinal damage and Leaky Gut Synrome.

Aspirin/NSAIDs

Aspirin and ibuprofen-type drugs, also called NSAIDs (nonsteroidal anti-inflammatory drugs) are commonly used for pain relief and for inflammation. Studies have shown that NSAIDs disrupt the intestinal barrier function and cause increased permeability (Pizzorno, 1998, p.120). The most common side affect of these over the counter seemingly safe drugs is gastrointestinal bleeding. When a NSAID is combined with alcohol, the chances of developing gastrointestinal bleeding go up by a factor of four (Mindell and Hopkins, 1999, p. 287). It is estimated that 41,000 people a year are hospitalized from the side effects of taking too many NSAIDs and some 6,000 people a year die from complications directly related to NSAIDs (Mindell and Hopkins, 1999, p. 286).

It is ironic that many people take NSAIDs for relief of arthritic pain when intestinal permeability is thought to be a key factor in the disease process. The British Medical Journal reported that taking aspirin before consuming an allergenic food results in more of the allergy-provoking food being absorbed (Balch & Balch, 1997, p.112). Food allergies are believed to be an initiator of the rheumatoid arthritis process, while the removal of allergenic foods from the diet has been shown "to offer significant benefit to some individuals with rheumatoid arthritis" (Pizzorno, 1998, p.184). However, NSAIDs promote the allergenic condition by contributing to Leaky Gut Syndrome. Since the very thing people are taking to relieve the symptoms of arthritis are causing the disease, it is a vicious cycle.

Celiac Disease

Celiac disease is also known as non tropical sprue, gluten-sensitive enteropathy, or celiac sprue (Murray and Pizzorno, 1998, p.325). Celiac disease, characterized by gluten intolerance, appears to be largely genetic. This disease, once considered rare, may be more prevalent than previously thought. A study published in the Scandanavian Journal of Gastroenterology found that increased anti-endomysium antibodies (AEA), a strong indicator of celiac disease, was present in as many as one in every 250 healthy American blood donors (Not, et. all, 1998). In Europe, subsequent small intestinal biopsies have confirmed celia disease in all those with AEA positivity (Not, et. al., 1998, abstract). This leads one to believe that there may be many undiagnosed cases of celiac disease in the Untied States.

Celiac disease is an inflammatory condition of the small intestine precipitated by the ingestion of wheat and other gluten containing grains such as barley, rye, and oats. It is believed to be the gladian portion of the gluten which is the allergen or irritant (Murray, Pizzorno, 1998, p.325). The biopsy of a celiac patient reveals a blunted or flattened intestinal surface (Gottschall, 1997, p35). The cause of this damage is believed to be the immune system trying to neutralize the gladian portion of the gluten protein and damaging the intestinal tissue in the process (Murray, Pizzorno, 1998, p.326). This damage results in increased intestinal permeability leading to food allergies.

Ann Louise Gittleman states in her book, "Your Body Knows Best", that people with type O blood have a greater predisposition to celiac disease and that they often suffer from milk intolerance (Gittleman, 1997, p.33). These are not unrelated. Celiac disease damages the intestinal lining which can lead to milk intolerance. The enzyme lactase which is needed to digest lactose, present in milk, is located in the brush border cells of the villi. Damaged villi results in a deficiency of the lactase enzyme. Without the lactase enzyme to digest the lactose, the lactose ferments and aids in the growth of harmful intestinal microbes (Gottschall, 1997, p.26). A gluten free diet appears to be the only solution at this point in time to treat celiac disease. A long-term gluten free diet appears to normalize permeability tests (Vogelsang, et.al., 1998, abstract).

Coffee

Foods consumed while drinking a cup of coffee are appear more likely to pass into the blood stream in a partially digested state (Braly, 1992, p.47). Thus coffee may increase gut permeability and add to the allergen load in the body.

Dysbiosis (Flora imbalance)

Intestinal dysbiosis occurs when unwanted microorganisms such as bacteria, yeast, and protozoa, colonize the gut, bind to the mucosal wall, and in some cases penetrate the gut barrier. An example of one such pathogenic fungi is Candida albicans. Candida, in its fungal form, may cause intestinal permeability by putting down 'roots' into the intestinal wall allowing comparatively large molecules to pass through into the bloodstream (Martin, 1995, p.1). The harmful bacteria competes with the host for the food in the gut causing malnutrition, and damages the intestinal lining. Bacterial overgrowth may be caused by hypochlorhydria (insufficient HCl), maldigestion, or stasis (stagnation, sluggish bowel movement, constipation) (Galland, 1995, p.64).

Damage from bacterial overgrowth is caused by bacterial enzyme activity. Bacterial mucinase destroys the protective mucus coat of the intestinal lining, while proteinases (protein enzymes) degrade pancreatic and brush border enzymes and attack structural proteins (Galland, 1995, p.64). Unhealthful bacteria in the gut can ferment carbohydrates and produce excess gas, bloating, and abdominal distention. The bacteria can break down protein via putrefaction to produce vasoactive amines (Murray and Pizzorno, 1998, p.139). Vasoactive amines cause constriction and relaxation of blood vessels by action on the smooth muscle which surrounds the vessels. This leads to increased gut permeability ("leaky gut"), abdominal pain, and altered gut motility.

A study published in the journal of Annals of the Theumatic Diseases in 1993 demonstrated that many people with rheumatoid arthritis exhibit small intestine bacterial overgrowth and that the severity of symptoms is related to the level of disease activity (Murray and Pizzorno, 1998, p.139). Dysbiosis causes damage to the intestinal lining resulting in leaky gut syndrome and may exacerbate such diseases as arthritis.

Malnutrition

Under normal conditions, the intestinal epithelium cells have the fastest rate of reproduction of any tissue in the body (Galland, 1995, p.62). The old cells slough off and a new epithelium is generated every three to six days (Galland, 1995, p.62). The energy demands for this rapid cell turnover must be met if the healing and replacement of the damaged cells in the epithelium is to occur. The small intestine must obtain 50% of the energy it needs from the food actually present in it (Emsley and Fell, 1999, p.36). If the intestinal lining is damaged and the energy needs are not met, hyperpermeability ensues (Galland, 1995, p.62). Therefore, proper nutrition and an epithelium healthy enough to absorb the nutrients provided by the food are essential for combating Leaky Gut Syndrome.

Pancreatic Insufficiency

Pancreatic insufficiency may result in increased intestinal permeability via several mechanisms. The pancreas secretes lipases, proteases, and amylases which are enzymes responsible for the breakdown of food in normal digestion. Insufficient secretion of these enzymes results in poorly or partially digested foods. These undigested foods are fermented by the bacteria in the gut and toxic by-products such as indole, phenol, skatole, methane, putrescine, cadaverine, and hydrogen gas are produced (Tyler, 1999, p.1). These toxins act on the mucosal epithelial cells and compromise the integrity of the gut causing intestinal permeability, adding to food sensitivity problems, and allowing the toxic by-products to cross the intestinal wall into the body. The toxic by-products may also damage the beneficial bacteria in the gut causing chronic imbalances in the intestinal microflora, or dysbiosis. A deficiency in pancreatic enzyme proteases also adds to dysbiosis in that proteases are largely responsible for keeping the small intestine free from parasites, including bacteria, yeast, protozoa, and helminths, or parasitic worms (Murray & Pizzorno, 1998, p.127). This imbalance contributes to intestinal infection and inflammation as the harmful bacteria takes hold. Intestinal infection and inflammation may also lead to increased intestinal permeability (Tyler, 1999, p.1).

sIgA Deficiency - Secretory IgA

Secretory IgA (sIgA) is a key immunological component of gut barrier function. It is found in large amounts in saliva, gastrointestinal fluid, and breast milk. It coats the entire course of the intestinal tract and combines with lumen antigens (antigens passing through the gastrointestinal tract) including undigested food, toxins, etc. Once combined with an antigen it prevents it from adhering to the gut lining and thus prevents its absorption into the body.

Decreased sIgA may be caused by a genetic predisposition, by chronic attack on the mucosa (intestinal lining), by pathogenic bacteria, parasites, yeast, stress, or by exposure to toxic compounds. Decreased sIgA is associated with dramatic increases in the absorption of food allergens and microbial antigens (Murray, Pizzorno, 1998, p.467). Unbound antigens attach to the intestinal lining, cause irritation, immune responses, and result in intestinal permeability, or leaky gut syndrome.

Stress

Stress compromises digestion. When a person is experiencing stress, the sympathetic nervous system (the flight or fight response) is activated. When in the sympathetic mode, the body shunts blood to the brain, heart, and long muscles so that the person may fight or flee in response to the stress. Blood however, is shunted away from the digestive tract where it is needed for proper digestion. This results in decreased enzyme secretion and peristalsis, allowing food to sit in an undigested state. The undigested food may then ferment, causing damage to the mucosal lining. Additionally, stress reduces the secretion of secretory IgA. This may result in unbound antigens that attach, irritate, and are absorbed into the intestinal lining (Murray and Pizzorno, 1998, p.140). The results of eating when stressed may be malnutrition, toxicity, and Leaky Gut Syndrome.

In contrast, when eating in a relaxed state, the parasympathetic nervous system is activated. The parasympathetic nervous system is responsible for digestion, repair, restoration, and rejuvenation. When the body is in the parasympathetic mode, blood is shunted to the digestive tract, the pancreas secretes digestive enzymes, the intestines contract, food is digested and absorbed, and toxins and waste products are cleared from the intestinal tract. The parasympathetic mode is reached when one is in a relaxed, non-stressed state. Therefore, it is critical to be in a relaxed state while eating so that proper digestion can take place.

Toxins/Food Additives

Over 3,000 chemicals (substances produced by a chemical process) are added to the American diet in addition to over 10,000 chemical contaminants from the environment (Braly, 1992, p.47). All told, there are about 8 to 15 pounds of potentially harmful chemicals consumed per person annually (Braly, 1992, p.47). These chemicals have far reaching affects. For example, in the early 1970s Feingold found that about 50% of children with hyperactivity were improved on a diet that excluded artificial color, preservatives, and naturally occurring salicylates (Middleton, et.al., 1998, p.1173). Some of the chemicals added to our foods have the ability to change the digestive process and distort the permeability of the intestinal lining (Braly, 1992, p.47). In addition to the physical damage toxins may cause, the sheer number of them may overwhelm our intestinal immune system. There may not be enough secretory IgA to bind all the toxins. This results in toxins adhering to the mucosal lining, irritating the lining, causing damage and gaining access into the body. It is important to limit exposure to toxins whenever possible. In terms of food, this means eating an organic, whole foods, unprocessed diet. Commercially grown foods may have residues of pesticides, herbicides and other chemicals. Processed foods are full of artificial, man-made ingredients, many of which the body does not recognize and cannot digest. Anything the body cannot recognize as food is considered an enemy to the body and the body will try to rid itself of it. Subjected to a large amount of toxins, the body's clearing mechanisms such as the digestive tract, liver, immune and lymph systems may become overwhelmed resulting in general body toxicity and disease.

TESTS

In summary, there are many factors and mechanisms which may cause the gut to become permeable leading to Leaky Gut Syndrome. These factors include, but are not limited to, immune responses, food allergies, alcohol, antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), celiac disease, coffee, intestinal dysbiosis, malnutrition, pancreatic insufficiency, deficient levels of secretory IgA, and stress. The challenge is to determine which factor or factors are causing the increased permeability and elliminate it or them. There are several tests which are useful in for diagnosing leaky gut syndrome and its causes. In this section, the following tests will be briefly discussed:

Lactolose/Mannitol Absorption Test
The lactolose/mannitol absorption test may be used as a diagnostic tool for leaky gut syndrome, to determine suspect food allergens or sensitivities (Galland, 1995, p. 62), and is the only non-invasive functional test for celiac disease (Vogelsang, Schwarzenhofer, Oberhuber, 1998, abstract).

The lactolose/mannitol absorption test uses two non metabolized sugar molecules (mannitol and lactulose) to test for intestinal permeability. The first sugar molecule, mannitol, is used to test for diffusion through the cells (transcellular uptake). The molecule is a small enough to passively diffuse into and through the intestinal mucosa cells. The second sugar molecule, lactulose, is a larger molecule and is used to assess the integrity of the mucosal lining. This larger molecule may gain access across the intestinal lining only by passing between the cells (paracellular uptake) through the tight junctions. To perform the test, the patient mixes pre-measured amounts of lactulose and mannitol and drinks the solution. A urine sample is then taken 6 hours later and the results assessed (Great Smokies, 1999, p.G-32).

The results are interpreted as follows:

• High levels of mannitol and low levels of lactulose indicate a healthy intestinal lining.
• Low levels of both mannitol and lactulose are indicative of malabsorption.
• High levels of both sugars are indicative of increased permeability, or "leaky gut".
• A high level of lactolose with a low level of mannitol may be indicative of "leaky gut" and malabsorption.
  

The lactulose/mannitol ratio also supplies useful information. An elevated ratio indicates that the pore size of the gut mucosa has increased, allowing larger, possibly antigenic, molecules access into the body.

To determine suspect allergens with the lactolose/mannitol absorption test, the test is first taken while fasting, the suspect food is then eaten, and the test is retaken . If the test produces an increase in lactulose excretion (signifying hyperpermeability) or a decrease in mannitol excretion (signifying malabsorption), food intolerance is likely and warrants further investigation (Galland, 1995, p.64). However, if the initial fasting mannitol absorption is low, suspect malabsorption. Look for evidence of celiac disease, intestinal parasites, ileitis, small bowel bacterial overgrowth and other disorders associated with malabsorption (Galland, 1995, p.64). If the initial fasting lactulose is elevated, or if the initial fasting lactulose/mannitol ratio is elevated, consider the possibility of mild inflammatory bowel disease or gluten enteropathy (Galland, 1995, p.64).

Comprehensive Digestive Stool Analysis (CDSA)
The Comprehensive Digestive Stool Analysis (CDSA) is a battery of laboratory tests which evaluate digestion, intestinal function, intestinal environment, and absorption by examining the stool (Murray, Pizzorno, 1998, p.129). The test will show if proteins, carbohydrates and fats are being properly digested, the amount and type of bacteria in the intestine, levels of secretory IgA, pH levels, and a myriad of other pertinent parameters. The results of this test are very useful in determining which part of the digestive system needs treatment or support. Due to the complexity of the test and interpretation, it will not be discussed further in this paper, although this test is strongly recommended as a diagnostic tool.

Food Allergies
Food allergies and intolerance may be tested for either by a food challenge or laboratory testing. The food challenge test is considered to be the definitive method or "gold standard" for diagnosing food allergies and food intolerance (Pizzorno, 1998, p.117), however it is very time consuming and requires discipline and motivation. The laboratory methods can supply immediate identification of suspected allergens, but they are generally expensive and are considered less reliable and somewhat controversial.

There are many different types of laboratory tests specifically for allergens, and food sensitivities, however, for the purposes of this paper, only the two most popular tests will be discussed: the skin prick test and the blood test, specifically the ELISA (enzyme-linked immunosorbent assay) blood test. Both types of tests diagnose food allergies by attempting to measure the levels of antibodies relative to food antigens. The ELISA test diagnosis allergies and sensitivities, where the skin-prick test only tests for allergies.

Food challenge
The food challenge test is an experimental test which challenges the patient with suspected allergens while carefully monitoring for reactions. There are two basic food challenge tests, the elimination or oligoantigenic diet and the pure water fast, each is followed by a food challenge. There is also an adjunct test, the coca pulse test, which may be used in combination with the other two food challenge tests.

The pure water fast followed by a food challenge requires fasting on water only for 5 days, symptoms should disappear by 4th day. Then foods are slowly reintroduced one at a time while keeping careful notes. The immune system should be in a hyperreactive state as a result of giving it a rest and therefore, the symptoms should be more acute and pronounced (Murray & Pizzorno, 1998, p.470). This fast is only to be done by people who are physically and mentally capable of a 5 day fast and doctor supervision is highly recommended.

The coca pulse test may be used by itself but is best used in conjunction with a food challenge during the reintroductory period. The test is conducted by first taking the resting pulse. This pulse is taken before eating a suspect food. Take the pulse in the morning for a full minute. A suspect food is then eaten and the pulse rate is immediately retaken for a full minute. The pulse rate is then taken again at 30 minute, 60 minute, and 90 minute intervals. If your pulse rate has gone up by more than 10 beats a minute, the suspect food is thought to be an allergen (Page, 1998, p.433).

Skin-Prick
The skin-prick or skin-scratch test is very popular among allergists. A patient's skin is scratched or pricked with a needle that contains the suspected allergen. After a period of time, the skin is examined for reactions. If there is a reaction, it is thought that an allergy exists. This test is limited, and not definitive. It only tests for IgE-mediated allergies, which accounts for only 10-15% of all food allergies. Furthermore, although a negative skin-prick test is strong evidence against a food allergy, a positive food skin-prick test is only slightly to moderately predictive of a food allergy. Only 50% of all positive skin-prick challenges were able to be confirmed by DBPCFC(double blind positive confirmed food challenge)(Burks, Sampson, 1999, abstract). This test appears to be both limited in that it only tests for IgE related immune responses, and is not definitive in that it results in false positives.

Enzyme-Linked Immunosorbent Assay (ELISA)
The enzyme-linked immunosorbent assay (ELISA) test appears to be the best and most popular laboratory blood test currently available because it is both reasonably priced and convenient (Murray, Pizzorno, 1998, p.471). The test uses an enzyme bonding process to detect antibody levels (Great Smokies, 1999, p. I-9). This test is able to measure IgE, IgG, and IgG4, antibodies. This enables the test to identify both immediate (IgE) and delayed (IgG) onset allergic reactions. Measuring IgG antibodies is very important since they are estimated to be involved in 80% of food allergy reactions (Murray, 1993, p.251).

PROTOCOL

Leaky Gut Syndrome is complex and is best addressed by a combination of diet, supplements, herbs, and lifestyle changes. All of these factors will be discussed in the framework of the "4R Program". The "4R Program" is an efficient way to promote gastrointestinal healing and optimal food absorption. The four "R"s stand for remove, replace, re-inoculate, and rebuild/repair. This program will be discussed in detail starting with the first phase, remove. It is crucial to implement and accomplish the remove phase before implementing the rest of the program. The replace, re-inoculate, and rebuild/repair stages may be implemented simultaneously, or in the order presented. The remove phase must be followed during the entire program.

Remove
Remove any thing from diet and system which is perpetuating the cycle of inflammation and leading to increased permeability. Follow this stage for at least two weeks before starting the other stages and continue through maintenance. Remove the following:

• Parasites and pathogenic bacteria or yeast and non-pathogenic yeast and bacteria overgrowths.
• NSAIDs and other medications (except as required).
• Food allergens and food to which the body is sensitized.
• Foods, herbs, and spices which cause inflammation or irritate the mucosal lining such as alcohol, caffeine, chilies, curries, vinegar, pepper, mustard, and cayenne.
• Refined carbohydrates such as sweets, chocolate, soft drinks, and white bread.
• Stress
• Toxins including herbicides, pesticides, house-hold products, etc.

To eliminate toxic bacteria and yeast, try goldenseal and garlic. Goldenseal kills abnormal bacteria, and inhibits the activity of the bacterial enzymes that damage the intestinal cells. Garlic, on the other hand, is very good for eliminating toxic microorganisms, especially yeast, from the intestine. Garlic also directly inhibits several toxic intestinal microorganisms, such as Staphylococcus, Streptococcus, Bacillus, Brucella, Salmonella enteritidis, Candida albicans, Mycobacteria, Cyryptococcus neoformans, and Vibrio species, even at low concentrations (Pizzorno, 1998, p.137).

To eliminate intestinal toxins, try a high fiber diet. Fiber binds toxins and speeds transit time resulting in fewer toxins being absorbed and less time for the toxins to irritate the mucosal lining. Dietary fiber also acts as food for the healthful bacteria. The best sources of fiber include a diet of whole, unprocessed grains, fruits, and vegetables. Fiber may also be obtained through supplement form. Soluble forms of fiber, such as pectin, bind toxins and are easy on the digestive tract. Good sources of soluble fiber include apples, bananas, beets, cabbage, carrots, citrus fruits, dried peas, and okra. A note of caution, if suffering from inflammatory bowel disease (ulcerative colitis and Crohn's disease), it is wise to avoid harsh insoluble fibers such as wheat bran which may further irritate the intestinal lining.

To help eliminate toxins, continually flush the body with water. Drink at least 8, eight ounce, glasses of pure water a day.

To help eliminate the attack of antigens against the mucus membrane, chew food thoroughly. This promotes saliva which is high in IgA and binds to antigens or toxins. The bound toxins are escorted out of the body, unable to irritate or be absorbed into the intestinal mucosa.

To eliminate inflammation, cut down on land-based animal proteins such as red meat and pork which are high in inflammatory fats. Switch to a more vegetarian based diet with the inclusion of fish. Fish is high in anti-inflammatory fatty acids.

Foods in which an IgE or Type I immune response is elicited are considered a true allergy and are best eliminated for life (Great Smokies, 2000, p.8). Whenever this food is eaten, the body will always react with an immune response. This immune response may become stronger or more severe with subsequent exposures to the allergenic food. In extreme cases, anaphylactic shock may occur. It is best just to avoid food which result in an IgE immune mediated response. However, foods to which the body is merely sensitized are best avoided in the short run but may eventually be re-introduced into the diet and tolerated if eaten infrequently.

The simplest method of treating a food sensitivity is simply to avoid eating the offending food. This may prove to be difficult or impractical as common food allergens such as corn, wheat, milk, and soy are staples in the American diet and hidden in many foods. For instance, processed foods may be sweetened with high fructose corn syrup, contain soy or corn oil, or use milk solids or textured soy protein as fillers. Avoiding processed foods would be optimal, but may prove to be too difficult.

Many experts believe the key to controlling food allergies is the "Rotary Diversified Diet" first developed by Dr. Herbert J Rinkel in 1934 (Murray and Pizzorno, 1998, p.471). The diet consists of a large variety of foods which are eaten in a definite rotation. The idea is to prevent new allergies from forming and to manage existing ones. Tolerated foods are eaten every four to seven days while allergenic foods must be completely avoided. For example, if someone eats corn on Monday, they should not eat corn or anything with corn in it until at least Friday. Additionally, foods from the same food family may cross-react and therefore should not be eaten two days in a row (Murray and Pizzorno, 1998, p.472). For instance, beans and peas are both part of the legume family. If one eats beans one day, peas or any other food from that family should be avoided on the following day. This is thought to prevent food intolerance from getting worse, and to prevent new allergies from forming. Since the body loses its sensitivity to some foods with time, it is possible to slowly add these foods back into the diet, also on a rotational basis, being careful to check for reactions. If a food causes a reaction, it should be discontinued immediately but may be reintroduced at a later date. In this manner, food allergies may be controlled and foods which the body was not able to tolerate may be slowly reintroduced.

Supplements:

Replace
Replace necessary digestive factors which may be deficient due to the gut's weakened state. These include gastric acid, pancreatic enzymes, and bile secretions. Supplement as needed based on CDSA results. Basically, in this section of the protocol, we are looking to support proper digestion and absorption of nutrients. This phase may be followed for 3 to 4 weeks, or as needed.

The first and most important way to help support the digestive function is to chew food thoroughly. Chewing food aids in proper digestion. Saliva contains amalyse which starts the digestion of starches. The basic mechanical function of breaking up food by chewing is crucial for protein digestion. When food is chewed properly, 98% of the proteins eaten are absorbed as amino acids and small peptides (Murray, 1993, p.252). As your mother may have told you, chew your food!

Eating in a relaxed state is also essential for proper digestion. When eating in a relaxed state, the parasympathetic nervous system is activated, digestive enzymes flow and the body may digest, absorb, and eliminate food from the body.

Do not drink liquids while eating, this dilutes the stomach juices and prevents proper digestion. Overeating will also hamper digestion by overwhelming the digestive process.

To support a deficient production of gastric acid, increase hydrochloric acid (HCl) intake. One way to do this is to drink the juice of half a lemon in water, or 1 tsp. of apple cider vinegar in warm water, 20 to 30 minutes before eating. Another way is to take HCl capsules, as described below.

To support pancreatic enzymes, eat foods high in natural enzymes. Natural enzymes may be found in raw foods such as fruits and vegetables. Enzymes are extremely sensitive to heat, so foods must be eaten raw. Foods which contain natural enzymes include avocados, papayas, pineapples, bananas, mangos, and sprouts (Balch & Balch, 1997, p.48).

To support bile secretion, bitter foods and herbs such as dandelion, artichoke, and turmeric may be eaten.

Supplements:

Reinoculate
Reinoculate or rebuild the gut with beneficial flora and nutrients that support their colonization. Healthy bacteria (probiotics) inhibits the growth of toxic bacteria, viruses, fungi, yeast and parasites (Pizzorno, 1998, p.138). Healthy bacteria also aids in digestion, vitamin synthesis (folic acid and other B vitamins), and stimulates the immune system. The primary strains of probiotics used to reseed the intestines are Lactobacilli and Bifidobacteria. For the healthy bacteria to reseed and grow, it needs food. This food is called prebiotics and consists of fructooligosaccharides (FOS) and inulin. This phase is best followed for 2 to 4 weeks.

Probiotics (healthy bacteria) may be obtained through the diet from fermented foods such as yogurt, miso, and some cheeses. However, if buying commercial products, beware. Many commercial strains of probiotics are chosen for their ability to be massed produced rather for than their usefulness in the body. Consequently, commercial products frequently contain so few live bacteria that they have little effect (Pizzorno, 1998, p.138). Therefore, culture your own foods, or pick your manufactured food products carefully.

Prebiotics, or healthy bacteria food, may be found in onions, asparagus, bananas, and maple syrup. In fact, bananas are not only high in fuctooligosaccharides, but they also help heal the damaged intestinal mucosa because they contain water-soluble polysaccharides, pectin, and valuable phospholipids (Pizzorno, 1998, p.139). So eat your bananas.

Supplements:

Rebuild/Repair
Rebuild and repair the mucosal lining of the small intestine. Rebuilding and repairing the mucosal lining will result in fewer antigens or toxins entering the body, increased nutrient absorption, and decreased inflammation. To rebuild and repair the intestinal lining, it is important to support the mucosa, the epithelial cells, and decrease inflammation. The rebuild/repair phase is best followed for 3 to 4 weeks.

To reduce inflammation, consume a wide variety of anti-oxidants including carotonoids and flavonoids. Anti-oxidants neutralize free radicals which damage the cells and cause inflammation and tissue damage. Anti-oxidants such as vitamins A, E, and C, zinc, selenium along with carotoniods and flavonoids may be found in a wide variety of fruits and vegetables. In general, the more pigment the fruit or vegetable has, the more anti-oxidant properties and nutrients it contains. Therefore, foods such as blueberries and dark leafy greens are excellent sources. Good sources of vitamin E, which is fat soluble, include nuts and seeds.

Essential fatty acids found in flax, evening primrose oil, borage seed oil, and fatty fish are also an essential component in reducing inflammation. Essential fatty acids make the anti-inflammatory prostaglandins which reduce inflammation. Pro-inflammatory and anti-inflammatory prostaglandins are made from different fatty acids, but both use many of the same steps and enzymes. Therefore, by increasing the fatty acids which are made into non-inflammatory prostaglandins, the amount of pro-inflammatory prostaglandins are decreased (Pizzorno, 1998, p.170). Fatty acids that produce pro-inflammatory prostaglandins include arachidonic acid which is found in land-animal fats. Therefore, reducing land animal fats and increasing fats from fish and flax will result in a decrease in inflammation.

To rebuild the mucosa and epithelial cells, a wide variety of nutrients must be taken. Glutamine is particularly important in that it is one of the principle fuels used by the epithelial cells, accounting for 35% of their energy production (Pizzorno, 1998, p. 141). Additionally, glutamine prevents intestinal mucosal damage and has been shown to decrease the amount of bacteria leaking across the intestines after they are damaged (Pizzorno, 1998, p.141). Glutathione is also very important in that it stimulates cell regeneration and acts as an anti-oxidant protecting the cells against further damage.

Foods and herbs which are especially soothing and beneficial to intestinal healing include cabbage, okra, onion, and dyglycyrrhizinated licorice.

Supplements:

Pre-packaged Program
Listed above are a lot of supplements to mix and match. Listed below is a pre-packaged alternative which may be taken instead of the individual supplements listed above. Note that the remove phase of the "4R" program must still be followed.

Tyler Protocol (Take as directed on label)
Re-inoculation (2 to 4 weeks)
Para-Gard - Suppresses intestinal pathogens (do not use if pregnant or nursing).
Protease Concentrate - Plant enzymes for protein digestion.
Fiber Formula - Soothing fiber formula, absorbs intestinal toxins (do not use if pregnant or nursing).
Replace and Repair/Rebuild (4 to 6 weeks)
Similase - Plant enzymes.
Permeability factors - Nutrients which repair and rebuild the intestinal lining.
Oxyperm - Antioxidants.
Fiber Formula - Soothing fiber formula, absorbs intestinal toxins (do not use if pregnant or nursing).
Enterogenic Concentrate - Probiotics and prebiotics.

Maintenance
When the intestinal permeability has returned to normal, as per diagnostic tests or after symptoms have improved by 50% or more, continue to support and maintain proper gut functioning with the following maintenance program:

Avoid allergenic foods.
Eat "tolerated" foods infrequently and never two days in a row.
Avoid processed foods and unnecessary toxins.
Eat a diet of whole, unprocessed foods high in fruits and vegetables.
Drink at least 8 glasses of pure water a day.
Take a good quality multivitamin and mineral supplement.
Chew food thoroughly.
Eat in a relaxed state.

CONCLUSION

It is time to start eating for vitality! It is time that foods start nourishing the body instead of slowly draining away health in the form of diseases, vague symptoms, and allergic reactions. The underlying cause of food's adverse affect is, more often than not, leaky gut syndrome. To gain the most from our foods and suffer the least amount of ill effects, the gut must be supported in its task of assimilating food into the body and acting as a barrier against harmful substances. This means supporting the integrity of the gut and protecting it from damage. This paper has discussed leaky gut syndrome, the diseases associated with it, where it occurs, its mechanism, its causes, tests to diagnose it and food reactions, and has put forth a protocol to address the problem. It is my hope that through proper diet and lifestyle, people will heal their intestines, and gain the energy and vitality needed to live happy and fulfilling lives.

About the Authour:
Laurel Garwin, NC, is a practicing nutrition consultant in the San Francisco Bay Area. She specializes in gastrointestinal disorders, food allergies, weight loss, diabetes, fibromyalgia, alcoholism, and depression. She may be reached for individual consultations at: This e-mail address is being protected from spam bots, you need JavaScript enabled to view it

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