Anthony Samsel and Stephanie Seneff provided us with another amazing review article this year. I have written up a synopsis of their fantastic article and tried to introduce some of their material in a less scientific manner. (At least I try to. Sorry, some of it is just out-right scientific mumbo jumbo.)
They reviewed a vast quantity of research to support the theory that glyphosate is being substituted for glycine and ending up incorporated into proteins and other places in the body where it should not be. It is a logical idea and explains many of the correlations seen between glyphosate use/ingestion/inhalation and associated diseases.
Please see their actual article for all the details, including the references to support the claims listed below. Their actual paper is lengthy and goes into very specific detail. I have written this short review of their paper for folks to get an inkling of what they have uncovered as this is a VERY IMPORTANT article.
Glyphosate is the number one herbicide sold in the world. It is used everywhere. Both on farms, in apartment complexes, on the side of roads, perhaps in your own yard. Previous articles by Samsel and Seneff have reviewed the myriad health effects that appear to be associated with glyphosate use. I have listed the links for their other articles below as well as a link to another earlier review I did on one of their prior articles.
Their current review, looks at the possible mechanism that appears to be the method behind how glyphosate can be associated with so many disease states. Some of these health conditions they examined were inflammatory bowel disease, obesity, Alzheimer’s disease, parkinson’s disease, kidney disease, various cancers, multiple sclerosis, and diabetes. For a full understanding of the connection between glyphosate and these and other diseases, I suggest you read all of their research reviews on glyphosate.
In prior papers they examined the chelating effect of glyphosate and how it can rob the body of minerals, the negative effect glyphosate has on our intestinal microbiome (gut bugs), how it interferes with production of key nutrients and suppresses one of the major biotransformational (detoxifying) systems of the body called cytochrome P450 enzymes, as well as examining the correlation between glyphosate and many different diseases.
In this article they asked themselves if there was something more insidious and fundamental than these known methods of action taking place with glyphosate. What they realized was that glyphosate, which is a synthetic amino acid analogue, may be substituting for glycine in peptides incorporated into our bodies. Think of what this would mean if glyphosate was pretending to be glycine and incorporating into the peptides and proteins that make up our tissues. If glyphosate incorporates into our cells and tissues it could cause self-destruction of these same cells and tissues when the body recognizes them as abnormal. Our body has a normal process called apoptosis that is used to destroy old or "bad" cells. As tissues are destroyed, it effects the function of those tissues and ultimately the organ those tissues are a part of. This would cause many varied negative effects and would explain how one toxin could cause so many different diseases.
Glyphosate is an N-substituted glycine. Researchers have said that N-substitued glycines can be viewed as amino acids. This would make glyphosate a glycine analogue. The evidence presented by Samsel and Seneff lead you to believe that indeed glyphosate’s deleterious biological effects may largely be due to it being an analogue for glycine.
Basics of how this works in plants:
Glyphosate disrupts chlorophyll synthesis in plants – the main reason is probably due to it’s inhibition of omega aminolevulinic acid synthesis. Aminolevulinic acid synthesis is the rate limiting step in the synthesis of the pyrrole ring. There is also the added disruption of the shikimate pathway. It is thought that Glyphosate competes with glycine and with succinyl coenzyme A for aminolevulinic acid synthesis.
Specifics of what glyphosate does biologically in mammals that supports it being a glycine analogue:
Glyphosate has been shown to activate NMDA receptors in rat hippocampus. (Thought in part to be due to it acting like glycine.)
Over expression of glutamate is induced by glyphosate.
Glyphosate can suppress the growth of some tumor cells. This is probably due to its suppressing glycine synthesis.
It appears glyphosate is interfering with glycine’s activity at cell receptors (as a substance that binds to that receptor and induces biological changes). It also appears to act as a substrate in the place of glycine and suppresses glycine synthesis. It appears it could be taken up in place of glycine in protein synthesis. This has been shown to happen with other analogues of amino acids. Although, not yet proven for glyphosate, the research should be undertaken to study this since other amino acid analogues have shown this behavior. There is some research on plant root microbiomes that points in the direction of possible glyphosate substitution of glycine based on the protein changes in the bacteria found on the roots of the plants.
With these basic ideas in mind, Samsel and Seneff reviewed research literature to see how glyphosate posing as glycine is correlated with and may be a causative factor in many of the diseases that are currently becoming epidemics on our planet since the advent of using RoundUp and other glyphosate containing herbicides.
Why we care about glycine
Samsel and Seneff give a brief statement on how glycine works in the body, but I want to expound on that just a bit here, so people will get an idea as to how important glycine is in our bodies.
• As a neurotransmitter, it is mostly thought to be inhibitory.
• It is a substrate for glutathione. Glutathione is made from three amino acids (glycine, L- cysteine and L-glutamine). Glutathione is very important for our biotransformational system (detox system).
• It is a substrate for heme which is an component of hemoglobin which is the main element of our red blood cells.
• It is a substrate for creatine which combines with phosphate in the body to make phosphocreatine or creatine phosphate which is found in muscle and serves as a storage of energy used for muscle contraction.
• It is a substrate for nucleic acids which as deoxynucleic acid and ribonucleic acid serve as carriers of information and are needed to synthesize proteins.
• Glycine acts as a cell protecting antioxidant
• Glycine plays a part in regulation of the metabolism
• Samsel and Seneff point out that due to glycine's special properties, its most important role is as a residue in many proteins. Especially proteins that require flexibility and mobility such as cellular ion gates that need to open and close.
The destruction of glycine affects every gland, organ and tissue and thus pre-disposes life to mitochondrial dysfunction and disease. Any glycine analogue has the potential to also cause mitochondrial dysfunction and disease.
The Monsanto and Dupont carbon-14 radio-labeled studies show that the glycine analogs incorporate into every gland, organ and tissue at a molecular level.
Considering the fact that glyphosate is an antibiotic and was originally patented as an antibiotic, we know it destroys our gut bacteria. I heard Samsel suggest that the mix of killing of our gut microbiome and its ability to chelate our minerals with the addition of posing as glycine is enough to create a "perfect storm".
I have to warn you that the rest of this article gets a bit more scientific. However, don’t let it stop you from reading it. I try to explain things as much as possible. Sometimes I just need to list scientific data though.
What happens if glyphosate substitutes as glycine in the body
For a starter all the things I just mentioned above that glycine is involved with will be altered and alteration is usually a bad thing. Our bodies are set up to use specific types of amino acids, not amino acid analogues that have slight differences.
Glyphosate research on animals using a single radio-labeled dose of glyphosate orally or intravenously, showed metabolites from glyphosate in the urine (This means the body transformed the glyphosate.), and radioactive CO2 was found in the expired air (shows that it was absorbed into the body and metabolized and part of it expired at CO2). Additionally it was found in all tissues, glands and organs. (Oh my goodness!)
They go on to talk about how glyphosate has been shown to bioaccumulate in other research performed on animals. They look at additional research on chickens, eggs, and goats as proof of this.
They then move on to looking at genetic damage. Yes, we are talking about damage to the blue print of our bodies, DNA. They explain the role of glycine here and how early research by Monsanto showed DNA damage in bone marrow of mice exposed to glyphosate.
They examine the association of glyphosate and obesity. The explain that a substitution of glyphosate for glycine in lipase can be at the root of obesity as well as adrenal insufficiency. They continue on through many disease processes explaining how specific substitutions can increase the risk for Alzheimer’s disease, cancer. They note that insulin receptors can be effected by glyphosate posing as glycine, leading to a defective insulin receptor and ultimately diabetes. They mention the role of glycine in hormonal releasing hormones, that are needed for proper thyroid and adrenal hormone release.
There is a section on how glyphosate may be involved in impaired cholesterol and fat metabolism. Although, the makers of statins would have you believe cholesterol and fat are evil, all your cells need good fats and cholesterol to function. You need cholesterol for hormones. You do not want to impair your natural ability to make healthy cholesterol and fats. They go into detail on hormone sensitive lipases necessary for lipid (fat) hydrolysis (breaking apart with water) and cholesterol ester hydrolysis. Hormone sensitive lipases are also necessary to release fatty acids from tissues for fuel. Hydrolase disruption leads to lipotoxic effects that can induce mitochondrial dysfunction, and inflammation amongst other things. They note that impaired hormone sensitive lipase function is linked to obesity, atherosclerosis and type two diabetes.
Glyphosate has been linked to a new disease of birds called ‘avian keratin disorder’ which is widespread in some parts of the United States and seems to be increased in areas of agricultural runoff. You see crossed beaks and other malformations in the birds. It is especially noted in chickadees who frequent bird feeders with sunflower seeds. (Are you purchasing the GMO sunflower seeds and feeding them to birds. If you are, all I can say is stop! Buy organic sunflower seeds as you can’t trust the rest of it.) Many of the other pesticides have been studied in regard to this disease issue and they do not seem to be the cause, but glyphosate has not been studied in relation to it. The reason Samsel and Sennef think glyphosate is implicated in the bird disease is that it is a disease of hyperkeratosis. It is thought that glyphosate is substituting for KEAP1, causing constitutive expression of Nrf2 leading to hyperkeratosis. If you want details, check out Samsel and Seneffs super duper research review.
Inflammation is a part of many if not most chronic disease processes. They go into a lengthy explanation of how glyphosate has been shown to cause acute inflammation. They give the example of acute poisonings with glyphosate by Indian farmers who commit suicide by drinking glyphosate. They also go into a fascinating explanation of how it may be related to the fourth largest cause of death in the United States, which is Chronic Obstructive Pulmonary Disease or COPD. They support their reasoning with Monsanto research that until recently, the EPA had kept sealed and away from the public. (Thanks to Anthony Samsel for his requests for these documents under the Freedom of Information Act we now know about this research.) Pseudomonas aeruginosa infections are seen in people with more severe forms of COPD. Samsel and Seneff mention Pseudomonas aeruginosa is one of the very few microbes known to metabolize glyphosate and use it as a source of phosphorus. Glyphosate is also known to disrupt normal bacterial activity leading to overgrowth of unhealthy bacteria. This could lead to a lack of healthy bacteria and increased Pseudomonas aeruginosa. This would make me concerned about people with COPD eating or inhaling glyphosate. (OK, I am concerned about all of us really, not just the folks with COPD.) In fact it leads me to wonder if the rise in COPD has something to do with the vast amount of glyphosate being sprayed on our planet.
Samsel and Seneff mention the fact that the USGS has found glyphosate to be present in our atmosphere and therefore people could be inhaling glyphosate directly into their lungs. (I have written a prior article on inhalation of glyphosate.) Glyphosate is sprayed heavily in cities as well as on conventional and GMO farms. Driving down the freeway or country road with your car window open in the spring can be a health hazard due to the heavy spraying and volatilization that goes on. Please read this article I wrote and check out the link to research showing glyphosate may be directly absorbed into the brain from the olfactory mucosa.)
And now back to their rocking article. We can’t leave out hypothyroidism. They explain how the substitution of glyphosate for glycine in the conserved CAGYC region of the beta-subunit of thyroid stimulating hormone could be taking place. They further note this could take place in adrenocorticotropic hormone also.
Next they talk about endothelia nitric oxide synthase (eNOS) which plays a variety of roles in our bodies. The family of NOS enzymes are important for vascular tone, insulin secretion, airway tone, and peristalsis as well as angiogenesis and neural development. They go into some lesser known theories expounded by researchers of how eNOS is acting in the body which are very interesting and I suggest you take a look at the original article for the details. They explain the necessity of glycine for eNOS activity. They note that eNOS is not the only enzyme that contains a conserved N-terminal glycine that supports myristoylation. They mention a number of other important enzymes. If glyphosate is substituted for glycine on eNOS, depending on where it is replaced, it will either have an issue with producing sulfate or nitric oxide. They note that this could cause many effects such as anemia, a decreased supply of cholesterol sulfate to tissues, vascular constriction leading to hypertension. They also mention a substitution on iNOS could lead to impaired immunity.
They next examine neurodegenerative diseases and the relationship of glyphosate to Prion disease, Alzheimer’s, and Parkinson’s disease. (Remember that prion diseases are those new and scary diseases that we call Spongiform Encephalophathies and are due to misfolded proteins. In cows we call it “Mad Cow” or “Bovine spongiform encephalopathy. In people it is called “Creutzfeld Jacob Disease”. In deer it is called “Wasting Disease”. They point out that Bovine spongiform encephalopathy first appeared in the United Kingdom in 1986 after glyphosate had been used to control weeds in the process of growing animal feed, for about ten years. This was the original appearance of this disease which is not usually discussed. We hear how it is spread from eating tissues from these diseased animals, but never is the original cause of this disease examined. Guess what Samsel and Seneff point out. That prion proteins contain lots of glycine. I bet you already guessed this.
Now they move onto Alzheimers. Samsel and Seneff point out that amyloid beta contains conserved glycines at two positions. They think that glyphosate takes the place of glycine here, increasing the solubility and preventing proteolysis. So ultimately they say that this substitution interferes with removal of residues 41 and 42 by gamma-seretase which damages the beta42 peptide. They also explain how the chelation of magnesium, copper, zinc and ferrous iron by glyphosate may be involved with amyloid formation. (Glyphosate chelates these minerals.) Now, don’t think they stop here. They go on to explore the binding of aluminum by glyphosate and the formation of fibrils that may be related to the neurofibrillary tangles of phosphorylated tau protein seen along with the amyloid beta plaques. Lastly they link Alheimers plaques and cataracts. It seems the same amyloid plaques seen in Alzheimer's brains are seen in cataracts. Hmmmm. Monsanto found a link between rat exposure to glyphosate and cataracts. They go over this research.
If this was not enough, they next wade into the link between Parkinson’s disease, ALS and glyphosate. This is followed by information on glyphosate and microbes regarding glycine activity. They also mention glyphosates inherent toxicity to microbes. Many people don’t seem to know it was first patented as an antimicrobial agent. So, of course it damages the gut microbiome. However, Samsel and Seneff explore the fact that it disturbs the shikimate pathway in the microbes and the other possible disruptions it may be involved with surrounding glycines relationship with the microbiome.
They additionally discuss the disruption of human tyrosine phosphatase vaccinia H1- related (VHR) which is found in high amounts in immune cells called T lymphocytes. VHR may play an important role in protection from HIV due to its expression in T-cells. VHR is disrupted by glyphosate. For full explanation of VHR and how it relates to HIV and glyphosate disruption of VHR, read their wonderful review.
They make a good case for glyphosate substitution in protoporphyrinogen oxidase leading to a non-genetic porphyria and the substitution in KEAP1 would enterfere with KEAPS’s ability to suppress the overexpression of Nrf2. This would lead to protoporphyrin-induced fatty liver disease, cholelithiasis and end stage liver disease and liver failure.
There has been an epidemic of kidney disease and kidney failure in agricultural workers around the world. This has been associated with glyphosate use and some countries have restricted its use due to the kidney failure associated with it. Samsel and Seneff explain how the tubular necrosis seen in the kidney is linked to simultaneous iron deficiency and iron toxicity due to defective uptake from siderophores in the proximal tubes. They examine the details of glyphosate causing this, as well as how it may be involved in additional kidney damage as a glycine imposter.
We then come to the big cytochrome P450 effect. Research on rats has shown glyphosate suppresses Cytochrome P450 enzymes in the liver. They explain how glyphosate substitution of glycine in CYPs can cause mutations that enterfere with the proper folding and binding of the CYPs.
Glycine is the most common amino acid in collagen. They point out that osteogenesis imperfecta is a disease wshere there is genetic mutations in collagen. These mutations are often due to substitutions for glycine. They go into a case of a child born with tryptophan substituted for glycine and how it caused the child to be born with numerous fractures at birth and many more after birth. He suffered from generalized osteoporosis. They think that random replacements of any of the glycines molecules in collagen with glyphosate would also disrupt the collagen structure leading to osteoporosis and increased bone fractures. The mention the “shaken Baby Syndrome” that may be relted to this as well as the fact that Osteoporosis has become a modern epidemic.
They go on to link non-hodgkin’s lymphoma and neural tube defects as well as autism to a glyphosate substitution for glycine. I will leave you in suspence and let you read about the lymphoma connection when you read their article.
Glyphosates ability to pass through the placental membrane to the fetus enables it to cause birth defects. Samsel and Seneff mention microcephaly, anencephaly, cleft palates and facial defects as an issue in areas where there is extensive use of glyphosate on crops in S. America. In Yakima Washington in an area where there has been extensive use of glyphosate to control waterway weeds, the number of anencephaly births are 4 times the national average. Samsel and Seneff mention research on zebrafish embryos where they used glyphosate to induce microcephaly in the zebrafish.
They provide extensive data on various studies regarding neural tube defects and how glyphosate disrupts folate production in plants and gut microbes. They also link glyphosate substitutions of glycine at multiple key points to neural tube defects, large ratios of grey matter to white matter in the brain (features of autism), and vanishing white matter disease. Their data is riveting.
This research article is a labor of love as is all the glyphosate reviews that Samsel and Seneff have offered up to the public. I am very thankful to them for the immense amount of time they have spent on this project and highly recommend you read all their research reviews on glyphosate and its relationship to various diseases.
I reviewed the Samsel and Seneff first article on Glyphosate and CYP450 and you can find that synopsis here. Their full article is linked below also.
Samsel and Seneffs Review Articles
Glyphosate, pathways to modern diseases III: Manganese, neurological diseases, and associated pathologies