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The Clinical Role of Gastrointestinal Binders

Useful agents for detoxification and Herxheimer reactions?

In today’s world of industry, technology, and rapid growth, man is globally exposed to more toxic chemicals, including heavy metals, than ever before.[1],[2] Toxic heavy metals, herbicides, pesticides, plasticizers, and other potentially toxic compounds that we are exposed to that do not naturally occur in the body are known as xenobiotics. All of our cells, but especially those in our liver, kidneys, and intestines, work overtime to detoxify these substances and prevent harm to every system in the body. Chronic exposure to toxic substances can have a cumulative effect, particularly if the detoxification process is impaired.[3]

Detoxification process

The liver, kidneys, and gastrointestinal tract are the key players in the processes by which the body eliminates endogenous (i.e., substances naturally found in the body like hormones and toxic byproducts from cellular metabolism) and exogenous (i.e., pollutants, metals, and medications) substances.[4],[5] Detoxification can most accurately be described as the metabolic process in which a series of enzymatic reactions neutralize both exogenous and endogenous toxins for transport and excretion from the body.[5],[6],[7] There are three primary phases of detoxification:

  • Phase I reactions involve the oxidation, reduction, and hydrolysis of substances via enzymes of the cytochrome P450 (CYP) family. The primary purpose of Phase I is to transform lipid soluble compounds into intermediate metabolites in preparation for Phase II detoxification.
  • Phase II reactions involves several types of nutrient dependent reactions, including glucuronidation, sulfation, glycination, glutathione and amino acid conjugation. Its primary purpose is the conjugation of toxins, creating larger, inactive, water soluble molecules.
  • Phase III is the process of cellular transport and elimination of toxic substances through cellular membranes.

Our gastrointestinal tract and detoxification

Although the liver has long been recognized as the primary organ of detoxification, there is growing evidence that the gut also plays an important role in the detoxification process.[5] The first contact the body makes with the majority of xenobiotics is in the gastrointestinal (GI) tract. Over the course of a lifetime, the gut processes more than 25 tons of food, which represents the largest load of antigens and xenobiotics confronting the human body.[8] Furthermore, since most medications are consumed orally, it also is our first contact with many drugs. As the organs that comprise the GI tract function predominantly to absorb the things we ingest orally, it is likely that its importance in the metabolism of xenobiotics has been significantly underestimated.

The first contact the body makes with the majority of xenobiotics is in the gastrointestinal (GI) tract. Over the course of a lifetime, the gut processes more than 25 tons of food, which represents the largest load of antigens and xenobiotics confronting the human body.

Toxins such as herbicides, pesticides, heavy metals, and alcohol can also trigger intestinal inflammation increasing intestinal permeability.[9],[10] When there is increased permeability, endotoxin, or lipopolysaccharide (LPS), often associated with gram-negative bacteria, can pass into systemic circulation.[11],[12],[13] Systemic exposure to endotoxin induces an immune response, resulting in a cascade of proinflammatory cytokines, leading to increased oxidative stress, which in turn, puts an even greater burden on the body’s detoxification system. Endotoxin can also inhibit parts of the detoxification process by down-regulating critical P450 enzymes, proteins which transport toxins out of the cell, and by reducing the flow of bile, which also contains toxic substances the liver has processed and eliminated from circulation.[10],[11],[12],[13],[14]

Poor gut health, including constipation and dysbiosis, can further burden our body’s detoxification process.[15],[16] When constipation exists, toxic substances that are expelled from the liver via the bile remain in the colon longer and have more time for potential gastrointestinal reabsorption, which can put an even greater strain on the liver and kidneys. Making sure there is a healthy balance of normal flora and addressing pathogens and/or increased permeability are all important factors which must be considered for healthy detoxification.[15],[16],[17],[18] In addition, as we will learn below, certain agents such as activated charcoal, bentonite clay, chitosan, and modified citrus pectin, may prove to be of significant benefit in that they can act as binders and prevent toxic substances from being reabsorbed in the gastrointestinal tract.

The important role of gastrointestinal binding agents

Herxheimer reactions, also known as “die-off” reactions or “Herxing”, can occur any time the body is trying to rid itself of an infection or other toxic substance. In the process, toxins are released or liberated from the microbes that contain them or tissues where they are stored, and stimulate an immune response. Even rapid weight loss can trigger such a response due to the propensity of adipose tissue to store fat-soluble toxic substances.[19] Symptoms ranging from mild to debilitating can occur when the major organs of elimination (liver, kidneys, colon) get overwhelmed and cannot eliminate or neutralize these substances fast enough, due to the inflammatory and oxidative stress cascade that they trigger.[20],[21],[22],[23],[24] Because GI binders dramatically improve elimination of these toxic substances from the body, they can reduce many adverse symptoms of detoxification.

Certain agents such as activated charcoal, bentonite clay, chitosan, and modified citrus pectin, may prove to be of significant benefit in that they can act as binders and prevent toxic substances from being reabsorbed in the gastrointestinal tract.

Activated charcoal is well-known for its ability to bind and absorb toxic substances. It is even used in emergency settings when a poisonous substance has been consumed or there is an overdose of a medication.[25] Activated charcoal also absorbs pesticides and herbicides,[26] volatile organic compounds (such as benzene),[27] and many other toxic compounds.[28],[29] Another very important thing about activated charcoal is that it binds and removes endotoxin, which actually inhibits detoxification pathways[22],[23],[30] and is a major contributing factor in Herxheimer reactions.[31],[32]

Bentonite clay, another well-known binder,[33] is particularly good at absorbing mycotoxins. Mycotoxins are toxic compounds that are naturally produced by certain types of molds.[34] Molds that produce mycotoxins include black mold, which commonly occurs in water-damaged or damp homes, and other molds that grow on common consumables such as grains, dried fruits, coffee, nuts, and spices.[35],[36],[37],[38],[39] Mycotoxins appear in the food chain as a result of mold infection of crops both before and after harvest. Exposure to mycotoxins can happen either directly (from eating contaminated food) or indirectly from animals (that are fed contaminated feed). When animals eat contaminated feed, these substances then appear in their milk.[40] Bentonite clay also binds bisphenol A (BPA),[41] pesticides and herbicides,[42],[43] and cyanotoxins, a product of harmful algal blooms that bioaccumulate in fish, shellfish, and other organisms that eat them.[44],[45] Bentonite clay also has an affinity for some heavy metals including lead, cadmium, and nickel.[46],[47],[48]

Chitosan, a lesser-known binding agent, is derived from shellfish. It acts in a very similar manner to bile acid sequestrants,[49] preventing the absorption of lipids by binding to bile salts,[50] but more importantly with regards to detoxification, removing many toxins secreted in the bile. It has been shown to be an effective binder of endotoxin;[51],[52] ochratoxin, a mold toxin found on many foods;[53],[54] heavy metals including mercury;[55],[56] as well as polychlorinated biphenyls (PCBs), phthalates,[57] and BPA.[58] It also has a prebiotic effect, promoting the growth of healthy bifidobacteria and lactobacilli in the gut.[59] Nanoparticle chitosan was even shown, in a small clinical trial of patients with a with a Borrelia burgdorferi infection (the spirochete bacteria that causes Lyme disease), to help reduce symptoms commonly associated with a Herxheimer reaction including pain, sleep disturbances, and mood changes.[60]

In children hospitalized due to toxic lead levels, modified citrus pectin was shown to be a safe and effective tool for reducing serum levels of lead.

And last, but certainly not least, modified citrus pectin (MCP) is worthy of mention. Also known as fractionized pectin, MCP is a complex polysaccharide obtained primarily from the peel and pulp of citrus fruits.[61] It is considered a soluble fiber and exerts multiple potentially beneficial effects including: reducing glucose and cholesterol absorption,[62],[63] delaying gastric emptying,[64] promoting the growth of beneficial bacteria,[65],[66] improving GI barrier function, and suppressing endotoxin-induced inflammation.[67] Research has also shown MCP may inhibit the metastasis of certain cancers and functions as a toxin binder, binding and reducing levels of heavy metals such as arsenic, cadmium, and lead.[68],[69] In children hospitalized due to toxic lead levels, MCP was shown to be a safe and effective tool for reducing serum levels of lead.[70]

Given the tremendous exposure in today’s world to environmental toxicity and the sheer volume of people who suffer from poor gastrointestinal health (leaky gut, irritable bowel syndrome, inflammatory bowel disease, small intestinal bacterial overgrowth [SIBO] and other dysbiosis), the primary detoxification organs can often be overwhelmed. Whether supporting detoxification processes, healing the gut, or minimizing die-off reactions, gastrointestinal binders are an invaluable tool that help us deal with these common challenges.

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