Documented effects of glyphosate and its pathways to modern diseases

Documented effects of glyphosate and its ability to induce disease, show that glyphosate is the “textbook example” of exogenous semiotic entropy: the disruption of homeostasis by environmental toxins.

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.

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.

The foodstuffs of the Western diet, primarily grown by industrial agriculture, are increasingly being produced using a two-part system of engineered plant seeds and toxic chemical application. Novel bacterial genes are incorporated through genetic engineering, and toxic chemical residues are readily taken up by the engineered plants. Research indicates that the new bacterial RNA and DNA present in genetically engineered plants, providing chemical herbicide resistance and other traits, have not yet fully understood biological effects.

A now common practice of crop desiccation through herbicide administration shortly before the harvest assures an increased glyphosate presence in food sources as well. The industry asserts that glyphosate is nearly nontoxic to mammals, and therefore it is not a problem if glyphosate is ingested in food sources. Acutely, it is claimed to be less toxic than aspirin. As a consequence, measurement of its presence in food is practically nonexistent. A vocal minority of experts believes that glyphosate may instead be much more toxic than is claimed, although the effects are only apparent after a considerable time lapse.

Thus, while short-term studies in rodents have shown no apparent toxicity, studies involving life-long exposure in rodents have demonstrated liver and kidney dysfunction and a greatly increased risk of cancer, with shortened lifespan.

Glyphosate’s claimed mechanism of action in plants is the disruption of the shikimate pathway, which is involved with the synthesis of the essential aromatic amino acids, phenylalanine, tyrosine, and tryptophan. The currently accepted dogma is that glyphosate is not harmful to humans or to any mammals because the shikimate pathway is absent in all animals. However, this pathway is present in gut bacteria, which play an important and heretofore largely overlooked role in human physiology through an integrated biosemiotic relationship with the human host. In addition to aiding digestion, the gut microbiota synthesize vitamins, detoxify xenobiotics, and participitate in immune system homeostasis and gastrointestinal tract permeability. Furthermore, dietary factors modulate the microbial composition of the gut. The incidence of inflammatory bowel diseases such as juvenile onset Crohn’s disease has increased substantially in the last decade in Western Europe and the United States. It is reasonable to suspect that glyphosate’s impact on gut bacteria may be contributing to these diseases and conditions.

However, the fact that female rats are highly susceptible to mammary tumors following chronic exposure to glyphosate suggests that there may be something else going on. Our systematic search of the literature has led us to the realization that many of the health problems that appear to be associated with a Western diet could be explained by biological disruptions that have already been attributed to glyphosate. These include digestive issues, obesity, autism, Alzheimer’s disease, depression, Parkinson’s disease, liver diseases, and cancer, among others. While many other environmental toxins obviously also contribute to these diseases and conditions, we believe that glyphosate may be the most significant environmental toxin, mainly because it is pervasive and it is often handled carelessly due to its perceived nontoxicity.

Glyphosate’s Pathological Effects: Controlled Studies

Indeed, corn and soy crops have both been shown to accumulate excess shikimate in response to glyphosate exposure. However, a study comparing glyphosate-tolerant and glyphosate-sensitive carrot cell lines identified several pathologies beyond the inhibition of aromatic amino acids following glyphosate exposure. It was determined that, in addition to abnormally low levels of tryptophan, phenylalanine and tyrosine, the glyphosate-sensitive cells also had 50 to 65% reduced levels of serine, glycine and methionine. The reduction in methionine can have many adverse consequences, as methionine is an essential sulfur-containing amino acid that has to be supplied from the diet.

In addition, there was evidence of excess ammonia in the glyphosate-sensitive but not the glyphosate-adapted cells. Both cell types readily absorbed glyphosate from the medium, with a rapid linear uptake observed during the first eight hours following exposure. This demonstrates that glyphosate would be present in food sources derived from glyphosate-exposed plants.

The excess ammonia observed in glyphosate-treated plants could be due to increased activity of phenylalanine ammonia lyase (PAL), an enzyme found in plants, animals, and microbes, that catalyzes the reaction that converts phenylalanine to trans-cinnamate, releasing ammonia. In studies on transgenic tobacco, it was demonstrated that a decrease in the aromatic amino acid pool sizes (a direct consequence of glyphosate exposure) results in an enhancement of metabolic flux through the shikimate pathway, which leads to a rise in PAL activity as well as a doubling of the levels of chlorogenic acid, a polyphenolic compound related to cinnamate. It has been proposed that glyphosate achieves part if not all of its growth-retardation effects on plants through induction of PAL activity. The growth disruption could be due either to toxicity of the derived phenolic compounds or to direct toxicity of the ammonia. A study of olive trees showed that there is a direct relationship between the total phenol concentration and PAL activity, suggesting that PAL is a major producer of phenolic compounds.

Even Roundup Ready® crops typically experience slowed growth following glyphosate applications, and this has been attributed to glyphosate’s role as a chelator of micronutrients.

More recent greenhouse experiments demonstrated that glyphosate application to the root system decreased the levels of calcium, magnesium, iron and manganese in the seeds of the plants.

It was proposed that glyphosate binds to and immobilizes all of these divalent micronutrients, impairing their uptake by the plant. These glyphosate-induced deficiencies would carry over to the food supply, leading to deficiencies in these nutrients in humans who consume foods derived from glyphosate-exposed crops.

Evidence of disruption of gut bacteria by glyphosate is available for both cattle and poultry. It has recently been proposed that glyphosate may be a significant factor in the observed increased risk to Clostridium botulinum infection in cattle in Germany over the past ten to fifteen years. Glyphosate’s demonstrated toxicity to Enterococcus spp. leads to an imbalance in the gut favoring overgrowth of the toxic Clostridium species. Glyphosate has been shown to have remarkable adverse effects on the gut biota in poultry, by reducing the number of beneficial bacteria and increasing the number of pathogenic bacteria in the gut.

A recent genome-wide study of the effect of glyphosate on E. coli revealed metabolic starvation, energy drain, and other effects involving genes that are poorly understood, in addition to suppression of the shikimate pathway.

A switch to anaerobic metabolism is also suggested from a study showing that, in soil treated with glyphosate, the total count of fungi was significantly increased, while oxygen consumption was significantly inhibited.

Research conducted by exposing an outdoor aquatic mesocosm (approximating natural conditions) to two pesticides and two herbicides revealed a unique effect (among the four toxins studied) of the herbicide, glyphosate, to destroy tadpoles.

Other experiments on bullfrog tadpoles showed that prior glyphosate exposure reduced the survival rates of tadpoles exposed to the fungal pathogen, Batrachochytrium dendrobatidis (Bd). It is thus conceivable that glyphosate may be instrumental in the worldwide decimation of frogs currently taking place. This also suggests that glyphosate disrupts embryonic development.

An insidious issue with glyphosate is that its toxic effects on mammals take considerable time to be overtly manifested. Studies on Wistar rats exposed to the highest levels of glyphosate allowed in water for human consumption for 30 or 90 days showed enhanced lipid peroxidation and glutathione peroxidase activity, indicators of oxidative stress.

A long-term study conducted on rats showed remarkable pathologies that became apparent only after the three-month period that is usually allotted for toxicity trials. In this experiment, rats were monitored over their entire lifespan, while being fed either genetically modified (GM) or non-GM maize that had been optionally treated with Roundup®. The rats that were chronically exposed to Roundup® developed several pathologies over the course of their lifespan, including large mammary tumors in the females and gastrointestinal, liver and kidney pathologies, especially in the males. The males developed both skin and liver carcinomas. Premature death in the treated male rats was mostly due to severe hepatorenal insufficiencies. Other researchers have shown that oral exposure to glyphosate in drinking water can induce DNA damage to mouse cells drawn from blood and liver.

Researchers have discovered that Roundup® is sometimes much more toxic than glyphosate by itself, and this discrepancy can be explained by the fact that Roundup® includes a surfactant which greatly enhances cytotoxic effects of glyphosate.

A study on three microorganisms commonly used as starters in dairy technologies demonstrated that Roundup®, but not glyphosate, inhibited microbial growth at lower concentrations than those recommended in agriculture. This result illustrates an amplified effect of glyphosate’s toxicity through the adjuvants found in Roundup®.

In humans, a prolonged accidental skin exposure to a glyphosate-surfactant herbicide has been shown to produce local swelling, bullae, and exuding wounds, followed by osteopenia, neurological impairment, and reduced nerve conduction. Similarly oral exposure to glyphosate produces chemical burns and ulceration of the oral cavity.

It is now well established that autism spectrum disorder (ASD) is associated with dysbiosis in the gut, and, indeed, this is viewed by many as an important contributor to ASD. An increase in short chain fatty acids and ammonia in the gut has been found in association with autism. Since these are by-products of anaerobic fermentation, this suggests an overgrowth of anaerobic bacteria such as Clostridia, Bacteriodetes, and Desulfovibrio. Clostridia have indeed been found in excess in the feces of autistic children. By-products of fermentation by anaerobes, such as phenols, amines, ammonia, and hydrogen sulfide, can be toxic to the large bowel. A strong link between autism and hepatic encephalitis has been identified, where the key underlying pathology may be excess ammonia in the blood stream. Ammonia plays an important role in the etiology of hepatic encephalopathy associated with both acute and chronic liver dysfunction. The source of the ammonia is believed to be intestinal bacteria, including those in both the small and large intestine. Impaired liver function prevents detoxification of ammonia via the urea pathway. Thus, the increased activity of Entropy 2013, 15 1422 PAL induced by glyphosate could play a role in creating a hyperammonemic environment in the gut and initiating subsequent pathology.

C. difficile is a well-established causal factor in colitis. The incidence of C. difficile-associated disease has increased significantly in North America in recent years, and research into the association of this increase with inflammatory bowel disease has borne fruit. In an observational study involving patients in a hospital in Wisconsin between 2000 and 2005, it was shown that C. difficile infection was almost nonexistent in patients with inflammatory bowel disease prior to 2003, but the rate grew from 4% to 7% to 16% in 2003, 2004, and 2005. One hypothesis presented was antibiotic use disrupting the beneficial gut bacteria, but it is conceivable that increased exposure to glyphosate is contributing to this increase.

A recent paper found that formula-fed infants had an overrepresentation of C. difficile in the gut bacteria. In a case-control study, children with autism were found to be significantly more likely to have been formula-fed rather than breast-fed. The study did not distinguish between organic and non-organic formula, but one can surmise that non-organic soy formula might be contaminated with glyphosate, and this could be a contributing factor to both the autism and the C. difficile.

Beginning in around 2006, an alarming die-off of honeybees became apparent in the United States, and researchers are still struggling to understand what is causing this die-off. Since the application of glyphosate also reached record levels that year, and has continued to increase since then, with no abatement in the bee colony collapse disorder, glyphosate could be playing a role in the bees’ plight. While correlation does not necessary imply causation, there are strong reasons why glyphosate might interfere with bees’ resistance to other environmental toxins.

The obesity epidemic began in the United States in 1975, simultaneous with the introduction of glyphosate into the food chain, and it has steadily escalated in step with increased usage of glyphosate in agriculture. While it is common knowledge that Americans are continuing to grow more and more obese with each passing year, there may be less awareness that obesity aligns with glyphosate usage elsewhere in the world. For example, South Africa arguably has the highest obesity rates in all of Africa, and it is also the African country that has most heavily embraced glyphosate usage since the 1970’s and has freely adopted genetically modified crops with little regulation. According to World Health Organization statistics, only 2.7% of adults in the United Kingdom were obese in 1972, a number that rose to 25.8% in 1999. Today, two thirds of U.K. citizens are either overweight or obese.

While glyphosate is not generally believed to be a carcinogen, a study on a population of professional pesticide applicators who were occupationally exposed to glyphosate revealed a substantial increased risk to multiple myeloma. Myeloma has been associated with agents that cause DNA damage, and DNA damage is a known consequence of chronic exposure to inflammatory agents, which, we have argued, are induced by glyphosate acting on the gut bacteria and suppressing CYP activity.

Another type of cancer that may be implicated with glyphosate exposure is breast cancer. The strongest evidence for such a link comes from the studies on rats exposed to glyphosate in their food supply throughout their lifespan, described previously, where some of the female rats succumbed to massive mammary tumors. The incidence of breast cancer has skyrocketed recently in the United States, to the point where now one in three women is expected to develop breast cancer in their lifetime.

Today, Americans spray more than 100 million pounds of Roundup®, the most popular among Monsanto’s chemicals, on their yards and farms every year. According to the most recent statistics from the U.S. Environmental Protection Agency (EPA), the U.S. currently represents 25% of the total world market on herbicide usage. Glyphosate, first registered for use in 1974, has been the most common herbicide used in the United States since 2001, and the amount of glyphosate usage has increased steadily since then. In 2007, the most recent year for which such numbers are available, the U.S. used an estimated 180 to 185 million pounds of glyphosate, more than doubling the amount used just six years before.

The Western diet is a delivery system for toxic chemicals used in industrial agriculture. The diet consists primarily of processed foods based on corn, wheat, soy and sugar, consumed in high quantities. Chemical residues of insecticides, fungicides and herbicides like glyphosate contaminate the entire diet.

Over the last decade, there has been widespread adoption in the U.S. of Roundup Ready® (RR) crops, particularly for the major productions of soy, beet sugar, and corn that supply the processed food industry. The recent alarming rise in type-2 diabetes has been attributed to excess intake of high fructose corn syrup, which has increased to unprecedented levels in the last decade. This refined sugar is now usually derived from glyphosate-exposed GM corn. GM cotton is also increasingly being used as a source for cottonseed oil, widely present in processed foods such as potato chips, due to its low cost.

A recent comparison between glyphosate-sensitive and glyphosate-resistant soybean crops revealed that the resistant plants took up much higher levels of glyphosate into their leaves. A corollary is that these plants would be expected to yield much higher glyphosate concentrations in derived food sources, compared to their non-GMO counterparts.

Confined animal feeding operations (CAFOs) are used to produce dietary animal protein for a mostly non-agrarian population. Cows, pigs, sheep, goats, chickens and even farm-raised fish and shrimp are fed a diet primarily of genetically engineered grains and forage materials laced with herbicide. As a consequence, animal products like, eggs, butter, cheese and milk are also contaminated with these residues. The highest levels of glyphosate are found in grain and sugar crops. The herbicide Entropy 2013, 15 1442 is not only used with RR crops, but also, as previously mentioned, it is used as a preharvest desiccant on sugar cane, wheat and also RR sugar beets, canola, and cottonseed for oils, among others.

It is difficult to get information on actual amounts of glyphosate present in foods, due to the perception that it is nontoxic to humans. The USDA Pesticide Data Program (PDP) is a voluntary program which randomly monitors agricultural chemical residues in the food supply. A search of the most recent data for 2010, published in May 2012, found statistics for the most popular agricultural chemicals except for glyphosate and glufosinate, another organophosphate. Residue data for the most popular herbicide on the planet were not available, but, interestingly, information on atrazine and other herbicides were readily available. Communication with USDA revealed that no data were available due to lack of monitoring. However, in 2013, for the first time, the USDA will be releasing a small amount of data for glyphosate residues only in soy. Lack of program funding was cited as the reason for this lack of data.

More refined and economical methods for detecting glyphosate in the food supply, and in the water supply, 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.

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.

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.