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Glyphosate, Pathways to Modern Diseases II: Celiac Sprue and Gluten Intolerance

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Glyphosate, Pathways to Modern Diseases II: Celiac Sprue and Gluten Intolerance Interdiscip Toxicol. 2013; Vol. 6(4): 159–184. interdisciplinary doi: 10.2478/intox-2013-0026 Published online in: www.intertox.sav.sk & www.versita.com/it Copyright © 2013 SETOX & IEPT, SASc. This is an Open Access article distributed under the terms of the Creative Commons Attribu- tion License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. REVIEW ARTICLE Glyphosate, pathways to modern diseases II: Celiac sprue and gluten intolerance Anthony SAMSEL 1 and Stephanie SENEFF 2 1 Independent Scientist and Consultant, Deerfield, NH 03037, USA 2 Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA, USA ITX060413R01 • Received: 24 September 2013 • Revised: 10 November 2013 • Accepted: 12 November 2013 ABSTRACT Celiac disease, and, more generally, gluten intolerance, is a growing problem worldwide, but especially in North America and Europe, where an estimated 5% of the population now suffers from it. Symptoms include nausea, diarrhea, skin rashes, macrocytic anemia and depression. It is a multifactorial disease associated with numerous nutritional deficiencies as well as reproductive issues and increased risk to thyroid disease, kidney failure and cancer. Here, we propose that glyphosate, the active ingredient in the herbicide, Roundup®, is the most important causal factor in this epidemic. Fish exposed to glyphosate develop digestive problems that are reminiscent of celiac disease. Celiac disease is associated with imbalances in gut bacteria that can be fully explained by the known effects of glypho- sate on gut bacteria. Characteristics of celiac disease point to impairment in many cytochrome P450 enzymes, which are involved with detoxifying environmental toxins, activating vitamin D3, catabolizing vitamin A, and maintaining bile acid production and sulfate supplies to the gut. Glyphosate is known to inhibit cytochrome P450 enzymes. Deficiencies in iron, cobalt, molybdenum, copper and other rare metals associated with celiac disease can be attributed to glyphosate’s strong ability to chelate these elements. Deficiencies in tryptophan, tyrosine, methionine and selenomethionine associated with celiac disease match glyphosate’s known depletion of these amino acids. Celiac disease patients have an increased risk to non-Hodgkin’s lymphoma, which has also been implicated in glyphosate exposure. Reproductive issues associated with celiac disease, such as infertility, miscarriages, and birth defects, can also be explained by glyphosate. Glyphosate residues in wheat and other crops are likely increasing recently due to the growing practice of crop desiccation just prior to the harvest. We argue that the practice of “ripening” sugar cane with glyphosate may explain the recent surge in kidney failure among agricultural workers in Central America. We conclude with a plea to governments to reconsider policies regarding the safety of glyphosate residues in foods. KEY WORDS: celiac disease; gluten; glyphosate; food; cytochrome P450; deficiency 1 Introduction Gluten intolerance is a growing epidemic in the U.S. and, fatigue, neurological disorders, anemia, nausea, skin increasingly, worldwide. Celiac sprue is a more specific rashes, depression, and nutrient deficiencies. Usually, but disorder, characterized by gluten intolerance along with not always, a strict gluten-free diet can alleviate many of autoantibodies to the protein, transglutaminase, which the symptoms. A key associated pathology is an inflam- builds crosslinks in undigested fragments of gliadin, a matory response in the upper small intestine, leading major constituent of gluten (Green & Cellier, 2007). The to villous atrophy, a flattening of the microvilli which autoantibodies are produced as an immune response to impairs their ability to function in their important role in undegraded fragments of proteins in gluten. A remarkable absorbing nutrients. set of symptoms develop over time in association with Some have suggested that the recent surge in celiac celiac disease, including weight loss, diarrhea, chronic disease is simply due to better diagnostic tools. However, a recent study tested frozen sera obtained between 1948 and 1954 for antibodies to gluten, and compared the Correspondence address: results with sera obtained from a matched sample from Stephanie Seneff, PhD. people living today (Rubio-Topia et al., 2009). They identi- Computer Science and Artificial Intelligence Laboratory, fied a four-fold increase in the incidence of celiac disease Massachusetts Institute of Technology, Rm G-438 MIT Stata Center, 32 Vassar Street, Cambridge, MA 02139, USA in the newer cohort compared to the older one. They also TEL.: +1-617-253-0451 • FAX: +1-617-258-8642 determined that undiagnosed celiac disease is associ- E-MAIL: [email protected] ated with a 4-fold increased risk of death, mostly due to 160 Glyphosate – celiac disease Anthony Samsel and Stephanie Seneff increased cancer risk. They concluded that the prevalence all emergent herbicides. Humans do not possess this of undiagnosed celiac disease has increased dramatically pathway, and therefore we depend upon our ingested food in the United States during the past 50 years. and our gut microbes to provide these essential nutrients. Transglutaminases play many important roles in Glyphosate, patented as an antimicrobial (Monsanto the body, as they form covalent crosslinks in complex Technology LLC, 2010), has been shown to disrupt gut proteins in connection with blood coagulation, skin- bacteria in animals, preferentially killing beneficial forms barrier formation, extracellular matrix assembly, and and causing an overgrowth of pathogens. Two other fertilization, endowing the substrate with protection from properties of glyphosate also negatively impact human degradation by proteases (Lorand & Graham, 2003). They health – chelation of minerals such as iron and cobalt, also form crosslinks in undigested fragments of gliadin and interference with cytochrome P450 (CYP) enzymes, derived from wheat, and sensitivity to certain of these which play many important roles in the body. We will fragments leads to the development of autoantibodies to have much more to say about these aspects in later sec- tissue transglutaminase (Esposito et al., 2002) that inhibit tions of this paper. its activity. A recent study on glyphosate exposure in carnivorous Glyphosate is the active ingredient in the herbicide fish revealed remarkable adverse effects throughout the Roundup. It is a broad-spectrum herbicide, considered digestive system (Senapati et al., 2009). The activity of to be nearly nontoxic to humans (Williams et al., 2000). protease, lipase, and amylase were all decreased in the However, a recent paper (Samsel & Seneff, 2013), argued esophagus, stomach, and intestine of these fish follow- that glyphosate may be a key contributor to the obesity ing exposure to glyphosate. The authors also observed epidemic and the autism epidemic in the United States, “disruption of mucosal folds and disarray of microvilli as well as to several other diseases and conditions, such structure” in the intestinal wall, along with an exag- as Alzheimer’s disease, Parkinson’s disease, infertility, gerated secretion of mucin throughout the alimentary depression, and cancer. Glyphosate suppresses 5-enolpyr- tract. These features are highly reminiscent of celiac uvylshikimic acid-3-phosphate synthase (EPSP synthase), disease. Gluten peptides in wheat are hydrophobic and the rate-limiting step in the synthesis of the aromatic therefore resistant to degradation by gastric, pancreatic amino acids, tryptophan, tyrosine, and phenylalanine, in and intestinal proteases (Hershko & Patz, 2008). Thus, the the shikimate pathway of bacteria, archaea and plants (de evidence from this effect on fish suggests that glyphosate María et al., 1996). In plants, aromatic amino acids col- may interfere with the breakdown of complex proteins in lectively represent up to 35% of the plant dry mass (Franz, the human stomach, leaving larger fragments of wheat 1997). This mode of action is unique to glyphosate among in the human gut that will then trigger an autoimmune 20000 Celiac incidence 18000 Glyphosate on wheat 77 16000 1,000 lbs) 14000 × 67 12000 57 10000 8000 47 6000 Incidence (thousands) Incidence 4000 37 2000 ( wheat applied to Glyphosate 27 0 1991 1993 1995 1997 1999 2001 2003 2005 2007 2009 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 Year Figure 1. Hospital discharge diagnosis (any) of celiac disease ICD-9 579 and glyphosate applications to wheat (R=0.9759, p≤1.862e-06). Sources: USDA:NASS; CDC. (Figure courtesy of Nancy Swanson). ISSN: 1337-6853 (print version) | 1337-9569 (electronic version) Interdisciplinary Toxicology. 2013; Vol. 6(4): 159–184 161 Also available online on PubMed Central response, leading to the defects in the lining of the small the beneficial bacteria that are negatively impacted by intestine that are characteristic of these fish exposed to glyphosate can protect from celiac disease through their glyphosate and of celiac patients. As illustrated in Figure 1, enzymatic activities on gluten, and point to several articles the usage of glyphosate on wheat in the U.S. has risen recommending treatment plans based on probiotics. sharply in the last decade, in step with the sharp rise in Pathogens, through their activation of a potent signal- the incidence of Celiac disease. We explain the reasons for ing molecule
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