Glyphosate: Chronic Disease Degeneration

Glyphosate is assumed to be safe for humans. As a result, it’s become the world’s best-selling herbicide. However, a groundbreaking study documents that it may actually be fueling the plague of chronic & immune diseases, including cancer and autism. This study documents the underlying systemic damage produced by glyphosate, then discusses how that damage leads to specific diseases.

by Heidi Stevenson
Gaia-Health.com

This article is split into three parts. This is Part 1, Glyphosate: Chronic Disease Degeneration. It gives an overview and then goes on to discuss the primary findings of a new study about the human effects of Monsanto’s herbicide, glyphosate. Part 2, titled Glyphosate: Disease Creator, discusses specific diseases, applying the basic harms produced by glyphosate and showing how they lead to each disease. Part 3, titled Glyphosate: A Trajectory of Human Misery, discusses glyphosate’s use throughout the world and then draws conclusions.

Monsanto’s herbicide, glyphosate, has become virtually ubiquitous based on a presumption of harmlessness in humans.  In spite of noxious and aggressive superweeds that have developed in response and a host of reports citing harm and potential harm to the environment and farm animals, this premise of innocence has resulted in its use nearly everywhere. Because of that same image of innocence, its use has multiplied astronomically.

However, a new report from the journal Entropy turns the proposition of glyphosate’s innocence in human health upside down. An exhaustive review of existing research in which 287 studies were reviewed, coupled with irrefutable logic, produces a frightening picture of the reality: Glyphosate may be the single most devastating substance ever introduced into agribusiness. As the authors, Anthony Samsel and Stephanie Seneff, concluded:

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.

The range of diseases that can be associated with glyphosate is frightening. Its biological effects are so primary that virtually every bodily system—if not every one—is adversely affected. The authors state:

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 …

Glyphosate’s Metabolic Disruptions

The study documents that glyphosate disrupts several significant basic biological processes in humans with devastating results. Certain primary functions at the most basic levels are disrupted or diverted. These include:

• Disruption of the shikimate pathway in gut biota.
• Disruption of sulphate transport
• Increase in Flavonoid Synthesis
• Disruption of cytochrome P-450 enzymes

This section will explain and discuss each of these.

Shikimate Pathway Disruption

Glyphosate is believed to operate by disrupting the shikimate (pronounced shə kih mut) pathway in plants, a process for manufacturing a group of amino acids called aromatic (though the term has nothing to do with odor). These include phenylalanine, tyrosine, and tryptophan. Aromatic amino acids are required for a plant’s survival.

It’s been assumed that glyphosate is harmless in humans because the shikimate pathway does not exist in any animal. However, the shikimate pathway does exist in bacteria, including those in the mammalian gut. Until fairly recently, the importance of gut biota in health has largely been ignored. However, it’s now understood to be key in many aspects of the body’s function.

Gut bacteria are in a symbiotic relationship with the body. They digest food, synthesize vitamins, detoxify foreign substances, and are key in immune system function and gut permeability. Thus, anything that interferes with the shikimate pathway has the potential of causing severe harm.

Disruption of Sulphate Transport

Sulphate transport, the method by which sulphate is moved into and out of cells, is a delicate balance. When glyphosate is present, this balance becomes a tightrope walk. The problem is that both sulphate and glyphosate are kosmotropes, which can have a devastating impact on the blood.

A kosmotrope is a substance that can cause water to become gelled. Too much sulphate in blood can turn it into sludge, so it cannot circulate and bring nutrients and oxygen to cells or remove waste. Therefore, transport of sulphate is always a balancing act between cellular requirements and blood viscosity.

However, when glyphosate is added to the picture, the risk is even greater. Glyphosate is also a kosmotrope, which makes it significantly more difficult for sulphate to be transported where it’s needed. As a result, sulphate transport is disrupted in the presence of glyphosate.

Increase in Flavonoid Synthesis

Glyphosate interferes with synthesis of the aromatic amino acid, tryptophan, instead favoring the production of flavonoids by as much as 20 times normal. While flavonoids are generally believed to be health-inducing,  Samsel & Seneff’s paper presents the likelihood that the picture is far more complex, and they propose a role for them in sulphate transport in the presence of glyphosate.

It’s known that, in both plants and microbes, glyphosate induces synthesis of two kinds of phenols: monophenolic compounds and polyphenolic flavonoids. Although monophenols are known to be toxic, flavonoids are generally thought to be beneficial for heath. However, their metabolic mechanisms are unknown.

Carbon rings are part of the molecular structure of phenols. Molecules with carbon rings have a special capability. They can diffuse the effects of kosmotropes. Therefore, phenols, including monophenols and flavonoids, are able to diffuse the effects of sulphate by binding to it and escorting it through the bloodstream.

Sulphate transport comes under pressure in the face of glysophate’s kosmotropic gelling effect on the blood. Therefore, aromatic amino acids may be oxidized into phenolic compounds to compensate, that is, to provide more phenols for sulphate transport.

However, once a phenol has delivered its sulphate, it becomes highly toxic. Sulphate-free phenols are destructive to phospholipids and DNA.

Therefore, to fulfill the more pressing need of sulphate transport, authors Samsel & Seneff propose that flavonoids are synthesized instead of tryptophan. That is, because of flavonoids’ ability to counter the kosmotropic effects of glyphosate, they are produced at the expense of tryptophan.

They propose that, in the presence of glyphosate, flavonoids and phenols can transport sulphur from the gut to the liver, and then return to the gut by way of the hepatic portal vein to repeat the process. However, once a phenol has given up the sulphate anion in the liver, it becomes toxic, over time causing damage to the liver and the digestive system.

While the immediate problem of sulphate transport is resolved by overproducing flavonoids, there’s a distinct downside in the long term. First, of course, is underproduction of tryptophan, with resultant harmful effects on tryptophan-associated processes. It also results in loss of sulphates from the gut, resulting in development of chronic disorders.

Disruption of Cytochrome P450 Enzymes

Glyphosate causes an excess build-up of shikimate by inhibiting EPSP synthase, a critical enzyme in the process that leads to the aromatic amino acids.  As a consequence, the precursors are sent down other pathways that produce toxic compounds. For example, activity of the enzyme PAL is substantially increased, leading to the release of ammonia.

This appears to be a significant factor in glyphosate’s damaging effects.

At the same time that PAL activity is increased, a side branch of the tryptophan synthesis pathway is opened to synthesize flavonoids. As noted before, flavonoids’ metabolic function is not yet understood, so their benefits may not be the whole story.

Cytochrome P450 (CYP) is a large family of enzymes that catalyze the oxidation of organic substances and is critical for detoxing xenobiotics. It’s been established since 1998 that glyphosate inhibits CYP in plants. Therefore, it follows that their detoxing function is disrupted.

Retinoic acid is catabolized (destroyed) by a CYP enzyme called CYP26A1. Though retinoic acid is required for the process of developing neural differentiation, the neuron cannot mature until retinoic acid is removed by CYP26A1. Therefore, glyphosate’s inhibition of the CYP enzyme prevents the neuron from maturing.

CYP enzymes function throughout the body, both inside cells and through the bloodstream. Glyphosate is also carried in the blood. Thus, by inhibiting their function, glyphosate can disrupt any activity in which CYP enzymes are active. This is of particular concern in blood clotting, where two CYP enzymes are involved. Thromboxane A2 synthase (CYP5A1) regulates clotting and prostacyclin synthase (CYP8A1) regulates hemorraging. Glyphosate in the blood can inhibit these enzymes, thus disturbing the delicate balance of blood clotting and dissolution.

Endothelial nitric oxide synthase (eNOS) is a member of the CYP family. It’s important for production of nitric oxide (NO), which is needed to relax blood vessels to ease blood flow.

Though not yet documented, it’s predicted that glyphosate disrupts the production of sulphate by eNOS in the endothelium, further exacerbating the sulphate transport concern.

Evidence of CYP Enzyme Inhibition

Multiple evidence from several areas demonstrates that glyphosate inhibits CYP enzyme activity. It inhibits aromatase, which is a CYP enzyme that’s key in converting testosterone to estrogen. Retinoic acid activity is enhanced, which can be explained by suppression of the CYP enzyme that breaks it down. Studies document that glyphosate suppresses certain detoxifyng CYP enzymes.

Two studies demonstrate that activity of CYP19, aromatase, is inhibited by glyphosate. It takes only 10 parts per thousand to disrupt aromatase’s activity in a human liver cell line. At concentrations just one-hundredth the recommended agricultural use, aromatase is inhibited in human placental cells. Worse, when glyphosate is combined with chemicals in RoundUp, these effects happen with just 1/20 as much glyphosate.

In another study, a 15 micromoles concentration of glyphosate resulted in cutting the activity of benzene-detoxing CYP enzymes to one-fourth of normal. When the concentration was increased to 35 micromoles of glyphosate, the CYP activity was completely stopped.

A compelling study documented that rats given glyphosate intragastrically for two weeks suffer a reduction of CYP activity in the liver. This result is not surprising, since glyphosate is an organophosphate, and it’s well established that this class of pesticides inhibits CYP enzyme function in human liver cells. Therefore, it would be unsurprising to find that glyphosate’s inhibition of CYP liver enzymes that detox benzene could lead to severe adverse effects, since it’s known to cause cancer.

Glyphosate may also be an indirect factor in the ongoing die-off of bees. The class of insecticides called neonicotinoids is known to kill bees. One study has found reduced pollination in genetically modified Roundup-Ready canola compared to organic canola. The authors suspect that a synergistic effect between glyphosate and neonicotinoids is worsening bee die-off.

Pathology Induction by Glyphosate

Gyphosate causes disruption of the shikimate pathway in gut bacteria, which results in a domino effect of pathology. It causes formation of excess shikimate, along with deficiencies of aromatic amino acids in plants.

Aromatic amino acids include phenylalanine, tryptophan, and tyrosine, among others. All three can be in short supply as a result of glyphosate’s enzymatic suppression. Phenylalanine cannot be synthesized in the body and is required for synthesis of tyrosine. Its suppression results in a cascade of adverse effects, including of course, reduction in tyrosine.

Excess ammonia is observed in the cells of plants treated with glyphosate. This is true for both natural and Roundup Ready plants. A likely cause of the excess ammonia is glyphosate-induced increase in the activity of phenylalanine ammonia lyase (PAL), an enzyme found in both plants and microbes that catalyzes release of ammonia. Most of glyphosate’s ability to retard plant growth is probably a result of PAL activity, which produces both toxic ammonia and phenolic compounds.

Glyphosate Effects on Gut Bacteria

Evidence of glyphosate’s disruption of gut bacteria is found in cattle and poultry. Over the last ten to fifteen years, Clostridium botulinum infection has increased in German cattle. Glyphosate is toxic to Enterococcus, a friendly bacterium. This leads to a gut imbalance that favors overgrowth of Clostridium.

Research documents that glyphosate reduces beneficial bacteria and increases pathological bacteria in the gut. Particularly pathogenic strains of drug-resistant Salmonella and Clostridium were found, while beneficial Enterococcus, Bacillus, and Lactobacillus are susceptible to glyphosate. The result is overgrowth of pathogenic bacteria at the expense of beneficial bacteria.

In one instance, pathogenic bacteria do a good turn—but in the end, negate it with a particularly nasty by-product. Antibiotic-resistant Pseudomonas are opportunistic pathogens that can break glyphosate down into metabolically-safe and usable phosphate and carbon. Unfortunately, a by-product of the process is neurotoxic formaldehyde, which can cause amyloid-like misfolding of tau protein in neurons, much like those found in Alzheimer’s brains, among other mischief.

Escherichia coli (E. coli) suffers starvation, energy drain, and shut-down of the shikimate pathway in the presence of glyphosate. A switch to anaerobic fermentation occurs instead of oxidizing glucose (sugar), which is a less efficient method of producing energy. It is reminiscent of changes in soil microbes with glyphosate application.

Frogs and Embryonic Development

In research comparing the effects of pesticides on frogs, glyphosate was unique in being able to destroy tadpoles. Out of four species, two had no survivors, one had almost none, and the overall survival of the four species was 70 percent.

Glyphosate had a synergistic effect with a fungal pathogen, Batrachochotrium dendrobatidis, which reduced survival of tadpoles.

It is probable that glyphosate is a factor in the worldwide disappearance of frogs, and also that embryonic development is disrupted.

Slow Effects in Mammals

Samsel & Seneff state:

An insidious issue with glyphosate is that its toxic effects on mammals take considerable time to be overtly manifested.

Nonetheless, evidence is building in mammalian studies. Research on rats given glyphosate in quantities equivalent to the highest legally-allowed doses demonstrated that they suffered oxidative stress in only 30-90 days.

A long term study examined rats fed genetically modified (GM) maize, nonGM maize without glyphosate, or GM maize with glyphosate. The experiment ran for the rats’ lifetimes, about two years. Unlike previous short-term research that had ended at 3 months. The results were dramatic. Rats fed the genetically-modified glyphosate-treated maize suffered multiple pathologies, including enormous mammary tumors in females, and gastrointestinal, liver, and kidney pathologies in males, which also developed skin and liver carcinomas. Male rats tended to die prematurely of liver and kidney deficiencies.

Roundup is a compound that includes both glyphosate and a surfactant called TN-20. Studies have found that the combination greatly increases glyphosate’s toxicity, resulting in mitochondrial damage, and both apoptic and necrotic cell death. It’s suspected that TN-10 disrupts the integrity of the cell barrier, which allows entry by glyphosate.

The synergistic effects of TN-20 with glyphosate were demonstrated in a study showing that dairy product starter microorganisms were inhibited by Roundup, but not by glyphosate alone. That study’s authors wondered if a recent loss in the biodiversity of raw milk might be caused by Roundup.

Read the Full Article Here: http://gaia-health.com/gaia-blog/2013-04-26/xxx-3/

Visit Gaia-Health.com to read Part 2 and Part 3:

Part 2, Glyphosate: Disease Creator
Part 3, Glyphosate: A Trajectory of Human Misery

Source:

Samsel, Anthony; Seneff, Stephanie. 2013. “Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases.” Entropy 15, no. 4: 1416-1463; doi:10.3390/e15041416