CRUCIAL PAPER 37:
New review: The Multiple Health Impacts of Glyphosate
This is a long peer-reviewed article, accompanied by 286 references, which summarises the multiple negative health effects of glyphosate and Roundup, which are widely dispersed through the environment and the food chain, especially in the United States. It makes for sobering reading. It will no doubt be viciously attacked by Monsanto and its friends, but with this much evidence now piling up, NOBODY can claim that Roundup is benign, and that it is perfectly OK for it to be present in the food supply, even in miniscule quantities. When are our political leaders going to wake up to the fact that in pushing the GMO agenda, they are conniving to precipitate a public health disaster?
Review article: Glyphosate's Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases by Anthony Samsel and Stephanie Seneff , Entropy 2013, 15, 1-x manuscripts; doi:10.3390/ e140x000xentropy ISSN 1099-4300 www.mdpi.com/journal/entropy
E-Mail: anthonysamsel@acoustictracks.net E-Mail: Seneff@csail.mit.edu; Tel.: +1-617-253-0451; Fax: +1-617-258-8642.
Received: 15 January 2013; in revised form: 10 April 2013 / Accepted: 10 April 2013
Abstract: Glyphosate, the active ingredient in Roundup®, is the most popular herbicide used worldwide. The industry asserts it is minimally toxic to humans, but here we argue otherwise. Residues are found in the main foods of the Western diet, comprised primarily of sugar, corn, soy and wheat. Glyphosate's inhibition of cytochrome P450 (CYP) enzymes is an overlooked component of its toxicity to mammals. CYP enzymes play crucial roles in biology, one of which is to detoxify xenobiotics. Thus, glyphosate enhances the damaging effects of other food borne chemical residues and environmental toxins. Negative impact on the body is insidious and manifests slowly over time as inflammation damages cellular systems throughout the body. Here, we show how interference with CYP enzymes acts synergistically with disruption of the biosynthesis of aromatic amino acids by gut bacteria, as well as impairment in serum sulfate transport. Consequences are most of the diseases and conditions associated with a Western diet, which include gastrointestinal disorders, obesity, diabetes, heart disease, depression, autism, infertility, cancer and Alzheimer's disease. We explain the documented effects of glyphosate and its ability to induce disease, and we show that glyphosate is the "textbook example" of exogenous semiotic entropy: the disruption of homeostasis by environmental toxins.
Extracts:
13. Discussion
Glyphosate is today the most popular herbicide in use in agricultural practices in the U.S., and, increasingly, throughout the world. Its usage rate has accelerated significantly in the last decade due mainly to two factors: (1) the patent expiration in 2000 led to greatly reduced cost, and (2) the adoption of genetically modified crops that are resistant to its toxic effects allows for higher exposure with little loss in harvest yield. The notion that glyphosate has minimal toxicity in humans, widely popularized by Monsanto, has prevented farmers from using caution in their application of this chemical to their crops. The recent rise in the rates of autism diagnoses in the United States is a cause for alarm. We have recently proposed that autism can be characterized as a chronic low-grade encephalopathy, where the cascade of events taking place in the brain is a process that enables the renewal of severely depleted sulfate supplies to the brain [277]. We identified a dysbiosis in the gut as a source of ammonia that initiates the encephalytic response, and we proposed glyphosate as one of the many environmental toxins that might be responsible for the dysbiosis and for sulfate depletion. A review of the literature on glyphosate has confirmed our suspicions that glyphosate might play a role, and, further, have led us to believe that glyphosate may be the most significant environmental toxin contributing to autism. While it is pervasive in our food supply, the fact that it is deemed by most regulators to be nontoxic makes it especially insidious. The key pathological biological effects of glyphosate -- disruption of the gut bacteria, impairment of sulfate transport, and interference with CYP enzyme activity—can easily explain the features that are characteristic of autism.
The term "developmental immunotoxicity" has been coined to describe permanent modifications to the immune function that take place early in life, leading to later development of allergies, asthma, and autoimmune diseases [278-280]. These authors have argued that prenatal and/or early life exposure to environmental toxins can lead to a phenotype that includes a hyperinflammatory response and disruption of cytokine networks, and they propose that an increased exposure to environmental toxins early in life may contribute to the increased incidence of these conditions observed today. It is significant that these problems often occur in association with autism [281].
Contrary to the current widely-held misconception that glyphosate is relatively harmless to humans, the available evidence shows that glyphosate may rather be the most important factor in the development of multiple chronic diseases and conditions that have become prevalent in Westernized societies. In addition to autism, these include gastrointestinal issues such as inflammatory bowel disease, chronic diarrhea, colitis and Crohn's disease, obesity, cardiovascular disease, depression, cancer, cachexia, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ALS, among others. While glyphosate is obviously not the only environmental toxin to contribute to these diseases and conditions, glyphosate's ability to disrupt the gut bacteria, to impair serum transport of sulfate and phosphate, and to interfere with CYP enzymes, logically progresses to this multitude of diseased states, through well-established biological processes. And glyphosate's disruption of the body's ability to detoxify other environmental toxins leads to synergistic enhancement of toxicity. While genetics surely play a role in susceptibility, genetics may rather influence which of these conditions develops in the context of glyphosate exposure, rather than whether any of these conditions develops. We have explained the logical sequence of events leading to serotonin deficiency and subsequent pathologies, following glyphosate's disruption of tryptophan synthesis by gut bacteria [10,29], and its further sequestration into macrophages that infiltrate the intestinal tissues in order to detoxify lipopolysaccharides released from pathogenic bacteria, whose overgrowth is induced by glyphosate [35]. Sulfate depletion arises in the gut, both because of impaired transport of free sulfate in the bloodstream and impaired sulfate synthesis by eNOS [63,64]. Disruption of gut bacteria, exposure to toxic phenolic compounds necessary to enable sulfate transport, and deficient sulfate supply to the mucopolysaccharides in the gut all contribute to the leaky gut syndrome that is a common feature in autism [51]. The evidence shows that glyphosate can interfere with development through its suppression of aromatase synthesis [110] and through its interference with the breakdown of retinoic acid [113] and its interference with CDKs and sulfate supplies. Glyphosate could also be a factor in the current epidemic in vitamin D3 deficiency [166] through its disruption of the CYP enzymes that activate this hormone in the liver [164,165]. The kosmotropic property of the glyphosate molecule combined with its disruption of CYP enzymes in the blood stream can lead to excess thrombosis and hemorrhaging, common problems today among the elderly.
We propose that glyphosate's disruption of the synthesis of sulfate by the CYP orphan enzyme, eNOS, leads to widespread deficiencies in cholesterol and sulfate in the blood stream and all the tissues. We have previously described how disruption of eNOS' synthesis of sulfate would lead to diabetes and cardiovascular disease [177]. Glyphosate's induction of excess synthesis of ammonia in the gut, combined with depletion of zinc through impaired absorption, depletion of serotonin through dysbiosis of its substrate, tryptophan, depletion of dopamine through impaired synthesis of its substrate, tyrosine, depletion of vitamin D3, due to impairments in the CYP enzyme responsible for its activation, and depletion of sulfate through interference with its synthesis, can all lead to a multitude of pathologies in the brain, including autism, Alzheimer's disease, ADHD, Parkinson's disease, multiple sclerosis and ALS.
There is a substantial alignment among countries, worldwide, with low or decreasing birth rates, emerging obesity problems, and an increasing glyphosate burden. Given the arguments presented here, it is plausible that glyphosate is causal in these trends. It may also be possible to demonstrate strong correlations between glyphosate usage and both autism and breast cancer. Formal epidemiological studies should be conducted to look at these issues more closely.
In our opinion, it is imperative that governments around the globe unite in investing significant research funds to support independent studies evaluating the long-term effects of glyphosate. Other researchers should try to reproduce the results obtained in [9] showing tumorigenesis and premature death in rats with life-long exposure to glyphosate. The study on the gut microbiome of chickens [35] needs to be reproduced in other species, and the gene array study on E. coli [39] needs to be reproduced for other common gut bacteria. The novel idea that glyphosate disrupts sulfate transport through its kosmotropic effects, as predicted given biophysical laws, needs to be verified in specific studies among a variety of species. This could be done by comparing the levels of free sulfate in the blood under conditions of glyphosate exposure against controls. The study on glyphosate's effects on bees [126] should be reproduced by other researchers, along with further studies examining the impact of prior exposure to glyphosate on bees' resistance to pesticides. More refined and economical methods for detecting glyphosate in the food supply, such as in [282,283], and in the water supply [284], need to be developed, and then applied to a variety of different food items. Most critical in our view are the vegetable oils derived from GM crops ‒ canola oil, soybean oil, corn oil, and cottonseed oil, as well as soy-derived protein, beet sugar, and high fructose corn syrup – ingredients that are pervasive in processed foods. Glyphosate is likely also present in meat, eggs, cheese, and other dairy products derived from animals fed glyphosate-contaminated grass, alfalfa, corn, and soy [285,286].
14. Conclusion
This paper presents an exhaustive review of the toxic effects of the herbicide, glyphosate, the active ingredient in Roundup®, in humans, and demonstrates how glyphosate's adverse effects on the gut microbiota, in conjunction with its established ability to inhibit the activity of cytochrome P450 enzymes, and its likely impairment of sulfate transport, can remarkably explain a great number of the diseases and conditions that are prevalent in the modern industrialized world. Its effects are insidious, because the long-term effects are often not immediately apparent. The pathologies to which glyphosate could plausibly contribute, through its known biosemiotic effects, include inflammatory bowel disease, obesity, depression, ADHD, autism, Alzheimer's disease, Parkinson's disease, ALS, multiple sclerosis, cancer, cachexia, infertility, and developmental malformations. Glyphosate works synergistically with other factors, such as insufficient sun exposure, dietary deficiencies in critical nutrients such as sulfur and zinc, and synergistic exposure to other xenobiotics whose detoxification is impaired by glyphosate. Given the known toxic effects of glyphosate reviewed here and the plausibility that they are negatively impacting health worldwide, it is imperative for more independent research to take place to validate the ideas presented here, and to take immediate action, if they are verified, to drastically curtail the use of glyphosate in agriculture. Glyphosate is likely to be pervasive in our food supply, and, contrary to being essentially nontoxic, it may in fact be the most biologically disruptive chemical in our environment.