This is one of the main reasons that the Chemical Farmers must be Boycotted! 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, increasingly, worldwide. Celiac sprue is a more specific disorder, characterized by gluten intolerance along with autoantibodies to the protein, transglutaminase, which builds crosslinks in undigested fragments of gliadin, a major constituent of gluten (Green & Cellier, 2007). The autoantibodies are produced as an immune response to undegraded fragments of proteins in gluten. A remarkable set of symptoms develop over time in association with celiac disease, including weight loss, diarrhea, chronic Correspondence address: Stephanie Seneff, PhD. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Rm G-438 MIT Stata Center, 32 Vassar Street, Cambridge, MA 02139, USA tel.: +1-617-253-0451 • fax: +1-617-258-8642 e-mail: [email protected] fatigue, neurological disorders, anemia, nausea, skin rashes, depression, and nutrient deficiencies. Usually, but not always, a strict gluten-free diet can alleviate many of the symptoms. A key associated pathology is an inflam- matory response in the upper small intestine, leading to villous atrophy, a flattening of the microvilli which impairs their ability to function in their important role in absorbing nutrients. Some have suggested that the recent surge in celiac 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 results with sera obtained from a matched sample from people living today (Rubio-Topia et al., 2009). They identi- fied a four-fold increase in the incidence of celiac disease in the newer cohort compared to the older one. They also determined that undiagnosed celiac disease is associ- 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 of undiagnosed celiac disease has increased dramatically in the United States during the past 50 years. Transglutaminases play many important roles in the body, as they form covalent crosslinks in complex proteins in connection with blood coagulation, skin- barrier formation, extracellular matrix assembly, and fertilization, endowing the substrate with protection from degradation by proteases (Lorand & Graham, 2003). They also form crosslinks in undigested fragments of gliadin derived from wheat, and sensitivity to certain of these fragments leads to the development of autoantibodies to tissue transglutaminase (Esposito et al., 2002) that inhibit its activity. Glyphosate is the active ingredient in the herbicide Roundup. It is a broad-spectrum herbicide, considered to be nearly nontoxic to humans (Williams et al., 2000). However, a recent paper (Samsel & Seneff, 2013), argued that glyphosate may be a key contributor to the obesity epidemic and the autism epidemic in the United States, as well as to several other diseases and conditions, such as Alzheimer’s disease, Parkinson’s disease, infertility, depression, and cancer. Glyphosate suppresses 5-enolpyr- uvylshikimic acid-3-phosphate synthase (EPSP synthase), the rate-limiting step in the synthesis of the aromatic amino acids, tryptophan, tyrosine, and phenylalanine, in the shikimate pathway of bacteria, archaea and plants (de María et al., 1996). In plants, aromatic amino acids col- lectively represent up to 35% of the plant dry mass (Franz, 1997). This mode of action is unique to glyphosate among all emergent herbicides. Humans do not possess this pathway, and therefore we depend upon our ingested food and our gut microbes to provide these essential nutrients. Glyphosate, patented as an antimicrobial (Monsanto Technology LLC, 2010), has been shown to disrupt gut bacteria in animals, preferentially killing beneficial forms and causing an overgrowth of pathogens. Two other properties of glyphosate also negatively impact human health – chelation of minerals such as iron and cobalt, and interference with cytochrome P450 (CYP) enzymes, which play many important roles in the body. We will have much more to say about these aspects in later sec- tions of this paper. A recent study on glyphosate exposure in carnivorous fish revealed remarkable adverse effects throughout the digestive system (Senapati et al., 2009). The activity of protease, lipase, and amylase were all decreased in the esophagus, stomach, and intestine of these fish follow- ing exposure to glyphosate. The authors also observed “disruption of mucosal folds and disarray of microvilli structure” in the intestinal wall, along with an exag- gerated secretion of mucin throughout the alimentary tract. These features are highly reminiscent of celiac disease. Gluten peptides in wheat are hydrophobic and therefore resistant to degradation by gastric, pancreatic and intestinal proteases (Hershko & Patz, 2008). Thus, the evidence from this effect on fish suggests that glyphosate may interfere with the breakdown of complex proteins in the human stomach, leaving larger fragments of wheat in the human gut that will then trigger an autoimmune 77 67 57 47 37 27 Celiac incidence Glyphosate on wheat 199019911992199319941995199619971998199920002001200220032004200520062007200820092010 Year 20000 18000 16000 14000 12000 10000 8000 6000 4000 2000 0 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).
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