Review of Research Article:
Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases
Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases
Anthony Samsel, Stephanie Seneff, Entropy, 2013. 15, 1416-1463;doi:10.3390/e15041416 www.mdpi.com/journal/entropy
Dr. Seneff and Anthony Samsel reviewed 286 research articles relating to Glyphosate (the active ingredient in Roundup® ) and/or disease processes that appear to be related to Glyphosate usage on agricultural products.
This paper provides adequate evidence to make everyone concerned about the use of glyphosate on the world food supply. Everyone in the health field should read this paper as I think practitioners would start prescribing organic food to all their patients after reading this well written review of 286 research papers regarding glyphosate.
The herbicide industry has given the impression that Glyphosate is perfectly safe. These researchers beg to differ with that idea and have went to extensive lengths to gather all the known data together to prove glyphosate is actually quite toxic. The main reason for its toxicity stems from the fact that it inhibits cytochrome P450 (CP450) enzymes. These enzymes have many important roles in our bodies. One of those important roles is to take toxic chemicals that are either made in the body or come from outside of our body and transform them into substances that can be safely excreted. This protective function stops hazardous chemicals in our environment from harming us. Without the CP450 system functioning properly, environmental toxins can build up in our body and cause many of the insidious diseases we face in our modern world. These reviewers show how the interference of the CP450 system disrupts gut bacteria activity and impairs serum sulfate transport. They claim the consequences of this leads to the major diseases known to people eating the Western diet. This includes gastrointestinal disorders, obestity, diabetes, heart disease, depression, autism, infertility, cancer and Alzheimer’s disease.
Their introduction examines the fact that industrial agriculture is now largely a system using engineered plants with toxic chemical applications. The plants are engineered with novel bacterial genes that protect the plant from being damaged by chemicals and in the case of some plants these plants actually make chemicals themselves. Even though a plant may be resistant to glyphosate, it still takes the chemical up into its tissues. They point out that these new bacterial RNA and DNA that are present in theses genetically engineered plants (GE/GMO) have biological effects (on us, the animals and plants) that are not yet fully understood. The authors decided to examine the toxic chemical that currently gets used in the largest amounts on most of these genetically engineered plants as well as other forms of industrial agriculture. They chose glyphosate as 80% of the GMO crops are created to resist glyphosate (The ingredient in Roundup® as well as other generic brands of this chemical.)
With the advent of GMO food more and more glyphosate was used on industrial farm land. Originally it used to kill weeds before or after crop plantings, or on areas that were fallow. However, once they made crops that could resist the weed killer, the industrial agriculturalists (I hesitate to call them farmers.) began using it during the crops growth. As weeds have become resistant to glyphosate, more and more of it has been used trying to kill the “super weeds.” It also became a common practice to spray the crops with the glyphosate shortly before harvest to cause desiccation which enhances the shelf life of the crop. Unfortunately this practice also ensures enhanced levels of glyphosate remaining on the crops when it gets to the table.
The authors of this review point out that glyphosate has been claimed to be practically nontoxic to mammals. Due to this prevelent view, levels of glyphosate in food products is almost never measured. There are however, a small group of experts who have been warning the public that this chemical is more toxic than claimed and that it has went un-noticed due to the effects being long term consequences. Whereas short term research in rodents have shown a lack of toxicity, studies involving life-long exposure in rodents have shown a great increase in cancer as well as damage to the liver and kidneys as well as a shortened lifespan. Since people and animals who eat industrially grown (the conventional food in most markets) eat it all their life and not just short term, this should be of great concern for for human health as well as our companion pets who eat this food.
About 2% of ingested glyphosate is metabolized to aminomethylphosphonic acid in the human body and the rest enters the blood stream and eventually is eliminated in the urine. It is claimed that glyphosates mechanism of action in plants is the shikimate pathway. This pathway is absent in animals but it is present in gut bacteria. Research has shown we are VERY dependant on these intestinal microbes. Gut bacteria aid in our digestion, they create vitamins we depend upon, they detoxify toxins we consume, they are intricately involved in our immune system and permeability of our gut. Research has shown gut bacteria to be involved in many different types of disease processes.
It is thought by some researchers and physicians that glyphosates action on the gut bacteria is contributing to some of the health care problems of today. Additionally, it is felt that glyphosate is contributing to disease in other ways than its effect on the gut bacteria. The current researchers point out that all environmental toxins are a problem. However, they believe glyphosate is one of the main environmental problems causing our modern day diseases. Their premise of this paper is that the extreme increase we have seen in modern diseases is associated with a combination of gut bacteria disorders, impaired sulfate transport and suppression of various cytochrome P450 enzymes. (P450 enzymes are necessary to detoxify the body of harmful substances.) They provide evidence in this review that shows how glyphosate negatively affects mammals, plants, microbes and amphibians. They explain the role of gut bacteria disorders and show how these disorders are due to glyphosate exposure. They also connect glyphosate exposure to inflammatory bowel disease and its relationship to autism. They show the relationship of glyphosate to impaired transport of free sulfate and evidence that it impairs CYP450 enzymes. They show how obesity arises from low serum tryptophan (The amino acid in turkey that makes you sleepy at Thanksgiving.) due to its being held by macrophages (type of white blood cell) responding to inflammation.
The authors start by exploring the pathological effects of glyphosate in controlled studies:
They looked at carrot studies with carrot cell lines which are sensitive to glyphosate and glyphosate adapted cell lines. In carrot cell lines glyphosate sensitive cells when applied with glyphosate were shown to have decreased levels of tryptophan, phenylalanine, tyrosine, serine, glycine and methionine. (Methionine is an essential sulfur-containing amino acid that has to be supplied from the diet. It was shown to be 50-65% less in these cells.) The glyphosate sensitive cells also had excess ammonia while the glyphosate adapted cells did not. Both cells quickly absorbed glyphosate which tells us that glyphosate would be present in food sources from exposed plants. This is important to note since the public has been assured in the past that it was not in their food.
Roundup Ready® crops usually slow their growth after glyphosate applications. It is believed this is due to glyphosates chelating of micronutrients. Older research has shown it interferes with the soybean plants uptake of divalent cations such as calcium and magnesium via the plants roots. Newer research has shown a decrease of calcium, magnesium, iron and manganese in the seeds of non-glyphosate resistant soybeans. This means glyphosate resistant plants may have less nutrients than their organic counter-parts.
They found research showing gut bacterial disruption by glyphosate in cattle and poultry. Some researchers, such as the soil scientist Don Huber think the increase of Clostridium botulinum infections in cattle is due to this effect by glyphosate. Any time you decrease the activity or the quantity of an animals/humans gut bacteria you set them up for an overgrowth of harmful organisms.
Research using two pesticides and two herbicides on an outdoor site that was set up to approximate a natural water habitat found glyphosate destroyed the tadpoles. After two weeks two species of tadpoles were completely dead and a third one almost eliminated. Scientists have questioned if the loss of frogs happening all over the world is related to glyphosate use.
Research on rats given the highest levels of glyphosate that is allowed in water for human consumption showed oxidative stress at 30-90 days. A longer term similar study showed that it took more than 3 months for real pathologies to show. These were breast tumors in females, and stomach, intestinal, kidney, and liver problems especially in the males. The males also had skin and liver cancer. Premature deaths were due to liver and kidney problems. Other researchers have shown glyphosate exposure in drinking water can cause DNA damage to mouse cells in the blood and liver.
Some research shows Roundup® is more toxic than glyphosate as Roundup® has a surfactant added that enhances the cytotoxic effects of glyphosate.
Autism Spectrum disorder is associated with gut microbe imbalance. Clostridia bacteria have been found in excess in the feces of autistic children. The researchers link Clostridia induced ammonia as a possible cause of autism. Clostridia difficile was not usually found in patients with colitis (gut inflammation) prior to 2003. However by 2005 it was found in 16% of patients with colitis. This could be due to antibiotic use disrupting the good gut bacteria or increased glyphosate exposure could be a contributing factor.
Further-more, children with autism have been found to be significantly more likely to have been formula-fed rather than breast fed. Most formula is made from Roundup Ready Soy® unless it is organic. This means it is likely to contain glyphosate. And may be contributing to the Clostridium difficile growth and autism. The authors also show how glyphosates effect on gut bacteria could lead to depleted sulfate supplies in the gut and cause inflammatory bowel disease that could be associated with autism. They give a long explanation as to how they believe this connection exists.
The authors provide evidence for how glyphosate inhibits the cytochrome P450 system enzymes. They examine studies that inhibit Cytochrome P450 enzymes in both plants and animals when small amounts of glyphosate are used. For those of you who do not know what the cytochrome P450 system enzymes do, I will briefly explain. This is a system that is very important to our bodies as it detoxifies our body. It protects us from building up too many hormones made in our body as well as alters toxins coming from our environment. Although all cells use these enzymes to protect us, they are the busiest in our gut and liver. If this enzyme system is not working up to par, we get sick. Toxins in our environment easily makes us ill without this system functioning normally.
The authors theorize that glyphosate is disrupting the P450 system in honeybees which then leaves them open to damage from pesticides which they would usually use their P450 system to detoxify.
Obesity is another issue these authors tackle. The obesity epidemic began in 1975 in the United States. This was the same time glyphosate was introduced into the food supply. Obesity has increased as glyphosate use has increased. They give a well thought out explanation of how they believe glyphosate is a causative factor in the U.S. populations obesity problem.
It has been shown in research that if we put gut bacteria from a skinny mouse into a fat mouse the skinny mouse will get fat and vice versa. Recently researchers also transferred a strain of endotoxin-producing bacteria from the gut of an obese person to the sterile guts of germ-free mice. These mice and control mice were fed the exact same diet. Only the mice with the introduced bacteria became obese over a 16 week period. They also had a chronic low-grade inflammatory state that the control mice did not have. We know glyphosate can disrupt our normal gut bacteria. It seems like common sense to wonder if it is causing obesity through this gut bacteria disruption.
The authors remind us that glyphosate can deplete tryptophan and they show how this can lead to obesity due to suppressed serotonin signaling. Studies support this by showing tryptophan levels are low in obesity.
They also explain how really severe tryptophan deficiency without sufficient fat stores to harbor toxins and supply sterol sulfates can lead to an inability to control microbial invasion, a severely inflamed digestive system, leaky gut leading to pathogen penetration, uncontrollable diarrhea and paradoxically, anorexia.
The authors question if glyphosate is involved with autism, depression and Alzheimer’s disease through the same impaired serotonin activity they explained in the section on obesity. They go through an in-depth explanation of links of Alzheimer’s and touch on depression as well as Parkinsons and their link to glyphosate.
They end their 286 research article review by briefly looking at the connection between glyphosate and liver disease, cancer, cachexia and developmental and fertility problems. They make a good case for all of these being connected to glyphosate in the food and water supply.
It is important to read their data on “glyphosate in food sources” at the very end of the paper. They point out that glyphosate is the most common herbicide used on the planet. They state that 90% of GMO crops are glyphosate resistant. This has lead to an increase in the use of glyphosate and glyphosate-resistant super weeds have been a result. I was shocked to read that 185 million pounds of glyphosate was used in 2007 in the U.S. (Last year there is data.) They point out that the average Western diet consists of high quantities of glyphosate laden foods. They point out that the industrial animal farms (confined animal feeding operations) use cows, pigs, sheep, goats, chickens and farm fish and shrimp that are raised on GMOs and forage materials laced with herbicide. Consequently animal products such as eggs, butter, milk, cheese as well as the meat is contaminated with these residues. They mention that the highest levels of glyphosate are found in grain and sugar crops. It is used both on the crops as they are growing but additionally it is being sprayed on the crop prior to harvest as a desiccant on sugar cane, wheat, sugar beets, canola, and cottonseed for oils. They said it is hard to get current information on how much glyphosate is in foods due to the erroneous perception that it is nontoxic to humans. Other popular agricultural chemical residue data, including other herbicides is available but not for glyphosate. Due to the higher rates and frequency of glyphosate application, the chemical and biotech industry have demanded approval for higher residue rates to be allowed in the European Union and the UK. In the U.S. residue rates were changed in 2011. For instance the rates for corn was 6ppm and it was raised to more than double at 13 ppm.
This paper has provided adequate evidence to make everyone concerned about the use of glyphosate on the world food supply. If you don't already eat organic food, I hope reading this has steered you in that direction.