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., 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.
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., 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.,, 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. 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. 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., When there is increased permeability, endotoxin, or lipopolysaccharide (LPS), often associated with gram-negative bacteria, can pass into systemic circulation.,, 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.,,,,
Poor gut health, including constipation and dysbiosis, can further burden our body’s detoxification process., 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.,,, 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. 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.,,,, 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. Activated charcoal also absorbs pesticides and herbicides, volatile organic compounds (such as benzene), and many other toxic compounds., Another very important thing about activated charcoal is that it binds and removes endotoxin, which actually inhibits detoxification pathways,, and is a major contributing factor in Herxheimer reactions.,
Bentonite clay, another well-known binder, is particularly good at absorbing mycotoxins. Mycotoxins are toxic compounds that are naturally produced by certain types of molds. 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.,,,, 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. Bentonite clay also binds bisphenol A (BPA), pesticides and herbicides,, and cyanotoxins, a product of harmful algal blooms that bioaccumulate in fish, shellfish, and other organisms that eat them., Bentonite clay also has an affinity for some heavy metals including lead, cadmium, and nickel.,,
Chitosan, a lesser-known binding agent, is derived from shellfish. It acts in a very similar manner to bile acid sequestrants, preventing the absorption of lipids by binding to bile salts, 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;, ochratoxin, a mold toxin found on many foods;, heavy metals including mercury;, as well as polychlorinated biphenyls (PCBs), phthalates, and BPA. It also has a prebiotic effect, promoting the growth of healthy bifidobacteria and lactobacilli in the gut. 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.
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. It is considered a soluble fiber and exerts multiple potentially beneficial effects including: reducing glucose and cholesterol absorption,, delaying gastric emptying, promoting the growth of beneficial bacteria,, improving GI barrier function, and suppressing endotoxin-induced inflammation. 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., In children hospitalized due to toxic lead levels, MCP was shown to be a safe and effective tool for reducing serum levels of lead.
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.Click here to see References
 Sears M, Genuis S. Environmental determinants of chronic disease and medical approaches: recognition, avoidance, supportive therapy, and detoxification. J Environ Pub Health. 2012:356798.
 Suk W, et al. Environmental hazards to children’s health in the modern world. Mutat Res. 2003 Nov;544(2-3):235-42.
 Sexton K, Hattis D. Assessing cumulative health risks from xxposure to environmental mixtures—three fundamental questions. Environ Health Perspect. 2007 May;115(5):825-32.
 Hodges R, Minich D. Modulation of metabolic detoxification pathways using foods and food-derived components: a scientific review with clinical application. J Nutr Metab. 2015;760689.
 Liska DJ. The detoxification enzyme systems. Alt Med Rev 1998;3(3):187-98.
 Maurel P. The CYP3 Family. In: Ioannides C, ed. Cytochromes P450: Metabolic And Toxicological Aspects. Boca Raton, FL: CRC Press, Inc; 1996:241-70.
Ioannides C, Lewis D. Cytochromes P450 in the bioactivation of chemicals. Curr Top Med Chem. 2004;4(16):1767-88.
 Sampson HA. Food hypersensitivity: manifestations, diagnosis, and natural history. Food Tech. 1992;46(5):141-4.
 Singh MM, Mullin GE. Diet, environmental chemicals, and the gut microbiome. In: Cohen A, vom Saal FS, eds. Integrative Environmental Medicine. New York: Oxford University Press; 2017: 115-140.
 Smyth M. Intestinal permeability and autoimmune diseases. Bioscience Horizons: The International Journal of Student Research. 2017 Jan 1;10.
 O’Dwyer S, et al. A single dose of endotoxin increases intestinal permeability in healthy humans. Arch Surg. 1988;123(12):1459-64.
 Wolff SM. Biological effects of bacterial endotoxins in man. J Infect Dis. 1973 Jul;128:259-64.
 Bahador M, Cross AS. From therapy to experimental model: a hundred years of endotoxin administration to human subjects. J Endotoxin Res. 2007;13(5):251-79.
 Carbonell L, et al. Depletion of liver glutathione potentiates the oxidative stress and decreases nitric oxide synthesis in a rat endotoxin shock model. Crit Care Med. 2000 Jun 1;28(6):2002-6.
 Cai J, Chen J. The mechanism of enterohepatic circulation in the formation of gallstone disease. J Membr Biol. 2014;247:1067-82.
 Floch MH. Bile salts, intestinal microflora and enterohepatic circulation. Dig Liver Dis. 2002 Sep;34 Suppl 2:S54-7.
 Ilan Y. Leaky gut and the liver: a role for bacterial translocation in nonalcoholic steatohepatitis. World J Gastroenterol. 2012 Jun 7;18(21):2609-18.
 Claus S, et al. The gut microbiota: a major player in the toxicity of environmental pollutants? NPJ Biofilms Microbiomes. 2017;3:17001.
 Jackson E, et al. Adipose Tissue as a Site of Toxin Accumulation. Compr Physiol. 2017 Sep 12;7(4):1085-1135.
 Nolan J, et al. Endotoxin binding by charged and uncharged resins. Proc Soc Exp Biol Med. 1975 Jul;149(3):766-70.
 Du X, et al. Effect of activated charcoal on endotoxin adsorption. Part I. An in vitro study. Biomater Artif Cells Artif Organs. 1987;15(1):229-35.
 Butler T. The Jarisch-Herxheimer reaction after antibiotic treatment of spirochetal infections: a review of recent cases and our understanding of pathogenesis. Am J Trop Med Hyg. 2017 Jan 11;96(1):46-52.
 Webster G, et al. Jarisch-Herxheimer reaction associated with ciprofloxacin administration for tick-borne relapsing fever. Pediatr Infect Dis J. 2002 Jun;21(6):571-3.
 Maloy AL, et al. Lyme disease complicated by the Jarisch-Herxheimer reaction. J Emerg Med. 1998 May-Jun;16(3):437-8.
 American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical Toxicologists. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol. 1999;37(6):731-51.
 Zhelezova A, et al. Effect of biochar amendment and ageing on absorption and degradation of two herbicides. Water Air Soil Pollut. 2017;228(6):216.
 Chiang Y, et al. Effects of pore structure and temperature on VOC adsorption on activated carbon. Carbon. 2001 Apr 30;39(4):523-34.
 Monge M, et al. Activated carbons as potentially useful non-nutritive additives to prevent the effect of fumonisin B1 on sodium bentonite activity against chronic aflatoxicosis. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2016 Jun;33(6):1043-5.
 Schulman G. A nexus of progression of chronic kidney disease: tryptophan, profibrotic cytokines, and charcoal. J Ren Nutr. 2012 Jan;22(1):107-13.
 Pegues A, et al. The removal of 14C labeled endotoxin by activated charcoal. Int J Artif Organs. 1979 May;2(3):153-8.
 Gelfand J, et al. Endotoxemia associated with the Jarisch-Herxheimer reaction. N Engl J Med 1976; 295:211-3.
 Bryceson AD. Clinical pathology of the Jarisch-Herxheimer reaction. J Infect Dis. 1976 Jun;133(6):696-704.
 Moosavi M. Bentonite clay as a natural remedy: a brief review. Iran J Public Health. 2017 Sep; 46(9): 1176-83.
 World Health Organization. Mycotoxins [Internet]. Geneva (Switzerland):WHO;2018 [cited 19 Sep 2019]. Available from: https://www.who.int/news-room/fact-sheets/detail/mycotoxins
 Tuomi T, et al. Mycotoxins in crude building materials from water-damaged buildings. Appl Enviro Microbiology. 2000 May 1;66(5):1899-904.
 Abdel-Wahhab M, et al. Absorption of sterigmatocystin by montmorillonite and inhibition of its genotoxicity in the nile tilapia fish (Oreachromis nilaticus). Mutat Res. 2005 Apr 4;582(1-2):20-7.
 Prelle A, et al. Comparison of clean-up methods for ochratoxin A on wine, beer, roasted coffee and chili commercialized in Italy. Toxins (Basel). 2013 Oct 22;5(10):1827-44.
 Abbès S, et al. Preventive role of phyllosilicate clay on the immunological and biochemical toxicity of zearalenone in Balb/c mice. Int Immunopharmacol. 2006 Aug;6(8):1251-8.
 Bhatti S, et al. Comparative efficacy of bentonite clay, activated charcoal and Trichosporon mycotoxinivorans in regulating the feed-to-tissue transfer of mycotoxins. J Sci Food Agric. 2018 Feb;98(3):884-90.
 Prandini A, et al. On the occurrence of aflatoxin M1 in milk and dairy products. Food Chem Toxicol. 2009 May;47(5):984-91.
 Park Y, et al. Bisphenol A sorption by organo-montmorillonite: implications for the removal of organic contaminants from water. Chemosphere. 2014 Jul;107:249-56.
 Lagaly G. Pesticide-clay interactions and formulations. App Clay Sci. 2001 May 31;18(5):205-9.
 Park Y, et al. Removal of herbicides from aqueous solutions by modified forms of montmorillonite. J Colloid Interface Sci. 2014 Feb 1;415:127-32.
 Sukenik A, et al. Removal of cyanobacteria and cyanotoxins from lake water by composites of bentonite with micelles of the cation octadecyltrimethyl ammonium (ODTMA). Water Res. 2017 Sep 1;120:165-73.
 Antoniou MG, et al. Cyanotoxins: New generation of water contaminants. J Enviro Eng. 2005 Sept;131(9):1239-43.
 Naseem R, Tahir SS. Removal of Pb (II) from aqueous/acidic solutions by using bentonite as an adsorbent. Water Res. 2001 Nov 30;35(16):3982-6.
 Pradas E, et al. Adsorption of cadmium and zinc from aqueous solution on natural and activated bentonite. J Chemical Tech Biotech. 1994 Mar 1;59(3):289-95.
 Vieira M, et al. Sorption kinetics and equilibrium for the removal of nickel ions from aqueous phase on calcined Bofe bentonite clay. J Haz Mat. 2010 May 15;177(1):362-71.
 Vahouny GV, et al. Comparative effects of chitosan and cholestyramine on lymphatic absorption of lipids in the rat. Am J Clin Nutr. 1983 Aug;38(2):278-84.
 Gallaher CM, et al. Cholesterol reduction by glucomannan and chitosan is mediated by changes in cholesterol absorption and bile acid and fat excretion in rats. J Nutr. 2000 Nov;130(11):2753-9.
 Davydova V, et al. Interaction of bacterial endotoxins with chitosan. Effect of endotoxin structure, chitosan molecular mass, and ionic strength of the solution on the formation of the complex. Biochemistry (Mosc). 2000 Sep;65(9):1082-90.
 Solov’eva T, et al. Marine compounds with therapeutic potential in gram-negative sepsis. Mar Drugs. 2013 Jun 19;11(6):2216-29.
 Al-Anati L, Petzinger E. Immunotoxic activity of ochratoxin A. J Vet Pharmacol Ther. 2006 Apr;29(2):79-90.
 Polizzi V, et al. JEM Spotlight: Fungi, mycotoxins and microbial volatile organic compounds in moldy interiors from water-damaged buildings. J Enviro Monitor. 2009;11(10):1849-58.
 Gerente C, et al. Application of chitosan for the removal of metals from wastewaters by adsorption—mechanisms and models review. Crit Rev Enviro Sci Tech. 2007 Jan 1;37(1):41-127.
 Shafaei A, et al. Equilibrium studies of the sorption of Hg (II) ions onto chitosan. Chem Eng J. 2007 Sep 15;133(1):311-6.
 Salim CJ, et al. Comparative study of the adsorption on chitosan beads of phthalate esters and their degradation products. Carbo Polymers. 2010 Jul 7;81(3):640-4.
 Dehghani M, et al. Adsorptive removal of endocrine disrupting bisphenol A from aqueous solution using chitosan. J Enviro Chem Eng. 2016 Sep 30;4(3):2647-55.
 Lee HW, et al. Chitosan oligosaccharides, dp 2-8, have prebiotic effect on the Bifidobacterium bifidium and Lactobacillus sp. Anaerobe. 2002 Dec;8(6):319-24.
 Allergy Research Group. Detoxification with Nanomolecular Chitosan Found Helpful for Lyme Patients in Small Clinical Trial. FOCUS Newsletter. July 2007;9-10.
 Ho Y, et al. Evaluation of the prebiotic effects of citrus pectin hydrolysate. J Food Drug Anal. 2017 Jul;25(3):550-8.
 Silalahi J. Anticancer and health protective properties of citrus fruit components. Asia Pac J Clin Nutr. 2002;11(1):79-84.
 Jenkins D, et al. Effect of dietary fiber on complication of gastric surgery. Gastroenterology. 1977;72:215-7.
 Schwartz S, et al. Sustained pectin ingestion delays gastric emptying. Gastroenterology. 1982;83:812-7.
 Chung W, et al. Prebiotic potential of pectin and pectic oligosaccharides to promote anti-inflammatory commensal bacteria in the human colon. FEMS Microbiol Ecol. 2017 Nov 1;93(11):fix127.
 Jiang T, et al. Apple-derived pectin modulates gut microbiota, improves gut barrier function, and attenuates metabolic endotoxemia in rats with diet-induced obesity. Nutrients. 2016 Feb 29;8(3):126.
 Chen C, et al. Suppression of endotoxin-induced proinflammatory responses by citrus pectin through blocking LPS signaling pathways. Biochem Pharmacol. 2006 Oct 16;72(8):1001-9.
 Glinsky VV, Raz A. Modified citrus pectin anti-metastatic properties: one bullet, multiple targets. Carbohydr Res. 2009 Sep 28;344(14):1788-91.
 Eliaz I, et al. The effect of modified citrus pectin on urinary excretion of toxic elements. Phytother Res. 2006 Oct;20(10):859-64.
 Zhao Z, et al. The role of modified citrus pectin as an effective chelator of lead in children hospitalized with toxic lead levels. Altern Ther Health Med. 2008 Jul-Aug;14(4):34-8.