Comment; Glyphosate; N-Methyl Phosphono Glycine, a glycine analog, also known as “Roundup” is used on “GMO” crops engineered to be resistant to the toxin which is used to kill weeds. Glyphosate is toxic to mammals via a variety of pathways. Dr. Jill provides an awesome summary!
- Interference with function of cytochrome (CYP) P450 family of enzymes
- Chelation of important minerals (iron, cobalt, manganese, etc.)
- Interference with synthesis of methionine (which supplies sulfur), leading to shortages of critical neurotransmitters and folate
- Disruption of sulfate synthesis and sulfate transport
- Substitution of glycine for glyphosate during protein synthesis
Jill Carnahan MD
Nothing incites anger and fear in us quite like the thought that we are being slowly poisoned by toxins in our food and water. From endocrine disrupting chemicals in everyday household products to lead in drinking water, it seems that we are increasingly at risk of developing diseases by things that we often have no control over.
And glyphosate is no exception.
The reports of harmful effects of glyphosate are exploding — within the medical and scientific community as well as the general public. At a time when bee populations are already declining, a recent study reported that glyphosate perturbs gut bacteria of bees, making them susceptible to infection.1
But how exactly does this highly controversial chemical affect humans? Glyphosate toxicity is a topic I’ve written about numerous times. This time we’ll talk specifically about the various ways glyphosate exposure could lead to devastating health consequences, one of which includes pretending to be glycine, an amino acid that is crucial for protein synthesis.
Glyphosate’s Pathways to Pathology
Glyphosate acts by disrupting the shikimate pathway (also known as the shikimic acid pathway), a seven-step metabolic pathway used by plants to synthesize the aromatic amino acids tryptophan, phenylalanine, and tyrosine.2
In plants, these amino acids are used as precursors for numerous natural products, such as pigments, alkaloids, hormones, and parts of the cell wall. Glyphosate inhibits the enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), a key component of the shikimate pathway, causing plants to die.
The shikimate pathway is absent in animals, including humans. In fact, humans don’t make tryptophan, phenylalanine, or tyrosine at all, which means we need to get them from our food. This led to the acceptance of a dogma that glyphosate cannot harm humans.
But the shikimate pathway is present in microorganisms, including your gut microbiota.
For this reason, scientists Anthony Samsel and Stephanie Seneff believe that glyphosate can disturb the gut microbiome, preventing them from being able to produce essential nutrients for our bodies. Glyphosate also accumulates in your tissues over time, contributing to the development of diseases and disorders.
Samsel and Seneff published five commentaries on the potential pathways by which glyphosate could lead to pathology. In their research, Samsel and Seneff report that the main toxic effects of glyphosate are as follows:
- Interference with function of cytochrome (CYP) P450 family of enzymes
- Chelation of important minerals (iron, cobalt, manganese, etc.)
- Interference with synthesis of methionine (which supplies sulfur), leading to shortages of critical neurotransmitters and folate
- Disruption of sulfate synthesis and sulfate transport
- Substitution of glycine for glyphosate during protein synthesis
Let’s take a brief look at a few of these hypotheses.
Inhibition of CYP450 Enzymes
In their first commentary on the health impacts of glyphosate, Drs. Samsel and Seneff linked glyphosate ingestion to disruption of gut bacteria, impairment of sulfate transport, and suppression of the activity of cytochrome (CYP) P450 family of enzymes.3
But why is CYP450 so important?
The CYP450 family of enzymes is involved in the synthesis and metabolism of various molecules and chemicals, including those that are potentially toxic.4 Using evidence from multiple studies, Samsel and Seneff hypothesized that glyphosate could disrupt many of the CYP enzymes that are active in the liver, which could affect:
- Cholesterol synthesis and metabolism
- Vitamin D3 synthesis and metabolism
- Detoxification of xenobiotics
- Regulation of retinoic acid
They also expected that glyphosate would travel throughout the bloodstream, disrupting any CYP enzymes it comes into contact with.
Inhibition of Methionine Synthesis
In addition to reduced levels of the aromatic amino acids tryptophan, phenylalanine, and tyrosine, glyphosate can also lower levels of serine, glycine, and methionine in glyphosate-sensitive cells. The reduction of methionine, in particular, can have serious consequences. Methionine is one of four common sulfur-containing amino acids and is the initiating amino acid in virtually all eukaryotic protein synthesis.5
When methionine synthesis is impaired, DNA methylation is also hindered. DNA methylation is the process by which a methyl (CH3) group is added to the DNA. It can alter the activity of the DNA, turning necessary biological switches on for optimal functioning. Optimal methylation can have a significant positive impact on:6
- DNA production
- Detoxification
- Eye health
- Liver health
- Cellular energy
- Fat metabolism
- Estrogen metabolism
Because many neuronal diseases are associated with DNA methylation impairment, Samsel and Seneff believe that the reduction of methionine contribute to this defect.
Metal Chelation
In their third commentary, Samsel and Seneff introduce the link between glyphosate and manganese dysbiosis.7Manganese is one of the 14 essential trace elements and place a role in various important processes, including:
- Antioxidant protection
- Glutamine synthesis
- Bone development
- Sperm motility
Manganese is also a transition metal and an EPSPS catalyst, a substance that helps speed up chemical reactions. It is reasonable then, Seneff and Samsel argue, to expect that glyphosate, a metal chelator, could deplete the body of manganese. In fact, this is exactly how glyphosate kills plants.
But what about in the human body? Samsel and Seneff propose that certain species of gut bacteria utilize manganese in various ways for protection from oxidative damage. The chelation of manganese by glyphosate would result in reduced numbers of essential gut bacteria.
Samsel and Seneff also link chelation of manganese by glyphosate to the development of several neurological disorders and diseases. In particular, they point out that manganese chelation could cause the misfolding of prion proteins. Although the normal functions of prions are not fully understood, their misfolding has been shown to be involved in several prion diseases and other protein misfolding diseases, including:8
- Creutzfeldt-Jakob disease
- Gerstmann-Straussler-Scheinker syndrome
- Fatal familial insomnia
- Kuru
- Alzheimer’s disease
- Parkinson’s disease
- Huntington’s disease
- Type 2 diabetes
- Spinocerebellar ataxias
- Amyotrophic lateral sclerosis
Prion proteins bind to the element copper in the body. However, Seneff and Samsel propose that they can also bind to manganese instead of copper, which causes the prion proteins to misfold.910 Manganese binding also prevents the degradation of proteins, a characteristic feature of prion diseases, and promotes prion protein aggregation.11
Substitution of Glycine for Glyphosate During Protein Synthesis
In their fifth commentary, Samsel and Seneff present a hypothesis linking glyphosate toxicity to mistakes made in protein synthesis.12 At the core of this proposal is the fact that glyphosate is very similar in structure to another amino acid that plays crucial roles in protein synthesis and human physiology, glycine.
In fact, the chemical name of glyphosate is N-phosphomethyl-glycine, which indicates that it is a derivative of glycine.
Still, how does glyphosate fool our cells’ proofreading mechanisms? Samsel and Seneff present a direct quote from another study to suggest that these mechanisms aren’t foolproof: “Certain structural analogues of the protein amino acids can escape detection by the cellular machinery for protein synthesis and become misincorporated into the growing polypeptide chain of proteins to generate non-native proteins.”13
Samsel and Seneff cite another study to bolster their hypothesis that the substitution of glyphosate for glycine is possible. In a 2010 report, Godballe et al. used N-substituted glycines to construct mimics of antibacterial peptides called peptoids.14 The modification of the reactive side chain in glycine was moved to the backbone nitrogen, resulting in greater metabolic stability.
The higher stability of peptoid chains can be beneficial in many ways because it allows antimicrobial agents to stay in the body for longer before being broken down. However, the resistance to proteolysis can have adverse effects when it comes to glyphosate, which can also be considered a peptoid unit. If glyphosate is mistaken for glycine and misincorporated into a peptide, Seneff and Samsel believe that it could interfere with the disassembly of the defective peptide. This could result in protein misfolding and the slow accumulation of undegraded and damaged peptide chains, possibly leading to disease.
By this mechanism, Seneff and Samsel propose a link between glyphosate exposure and a large spectrum of diseases and disorders, some of which include:
- Diabetes
- Obesity
- Asthma
- Chronic obstructive pulmonary disease
- Pulmonary edema
- Adrenal insufficiency
- Hypothyroidism
- Alzheimer’s disease
- Amyotrophic lateral sclerosis
- Non-Hodgkin’s lymphoma
- Hypertension
- Glaucoma
- Infertility
The Debate on Glyphosate Toxicity
The commentaries by Samsel and Seneff aren’t without controversy. In a review titled “Facts and Fallacies in the Debate on Glyphosate Toxicity” published in 2017, Robin Mesnage and Michael N. Antoniou wrote that the commentaries are a “misrepresentation of glyphosate’s toxicity [that] misleads the public, the scientific community, and regulators. Although evidence exists that glyphosate-based herbicides are toxic below a regulatory set safety limits, the arguments of Samsel and Seneff largely serve to distract rather than to give a rational direction…”
Regarding the first commentary, Mesnage and Antoniou argued that although CYP450 is inhibited by high levels (agricultural use concentrations) of glyphosate, typical environmental exposure levels do not show the same results.15Additionally, they mention that Seneff and Samsel do not acknowledge animal studies in which environmentally-relevant levels of glyphosate show an increase in CYP450 activity, not suppression.16
Furthermore, the reduction in CYP450 cannot be solely attributed to glyphosate toxicity. Samsel and Seneff point to a study in which rats exposed to Roundup at levels allowed for human consumption showed a reduction in CYP450 levels. However, glyphosate is not the only ingredient in Roundup. It also contains co-formulant adjuvants, which are highly toxic in their own right. Studies have established that co-formulants often make commercial pesticides more toxic than the active ingredient alone.1718 This means that the exact cause for CYP450 suppression is unclear.
It’s also unclear whether glyphosate has any affect on the gut microbiome, especially at environmental exposure levels. While some studies demonstrate an adverse effect,19 others have reported no effects.20
Mesnage and Antoniou also point out multiple logical fallacies in the commentaries. Samsel and Seneff propose that the chelation of manganese could cause it to out-compete copper in binding to prion protein. The misfolding that results is thought to contribute to prion diseases. However, the evidence of such effects is lacking.
The authors also indicate that if glyphosate acts by sequestering manganese, that means it would make the micronutrient unavailable for participation in interactions with proteins. It would actually be unable to out-compete copper for binding to prion proteins. If this is true, then the chelation of manganese by glyphosate would have a protective effect against prion disease, not a causative one.
The hypothesis regarding the substitution of glyphosate for glycine has also received criticism. Samsel and Seneff argue that glyphosate can replace glycine in peptoids, and therefore, it can also replace glycine in regular polypeptides. However, Mesnage and Antonious write, peptoids do not exist naturally in living organisms. Therefore, it is not valid to extrapolate the observations from the laboratory-manufactured peptoids to naturally-occurring polypeptides as they are structurally distinct.
Perhaps the most striking argument against Samsel and Seneff’s fifth commentary is that direct experimentation has shown that glyphosate does not get incorporated into proteins.21 Studies involving E. coli cultured in the presence of high concentrations (1 g/L) of glyphosate showed that there were no shifts in molecular weight of proteins or incorporation of glyphosate in polypeptides. Had glyphosate been incorporated into the proteins of E. coli, protein molecular weight would have changed and glyphosate would have been detectable by the analytical methods used in the studies.
7 Ways to Protect Yourself Against Glyphosate
Despite the controversy, we know glyphosate use is widespread, and it’s getting more difficult to avoid. But there are ways to reduce your risk and possibly reverse some of its toxic effects. Here are a few ways you can safeguard yourself and your family against glyphosate.
1) Extracts from Dandelions, Barberry, and Burdock
Glyphosate is toxic to liver and embryonic cells at doses far below those used in agriculture. A few studies have suggested that a specific combination of plant medicinal herbs may have protective effects against glyphosate. In one study using rats, extracts from dandelion, barberry, and burdock reversed many of the adverse effects provoked by glyphosate when taken prior to and during the 8 days of exposure. Most of the biochemical disturbances caused by glyphosate were also reversed by the combination of plant extracts.22
2) Charcoal and Humic Acids
Animals like cows are frequently exposed to glyphosate through their feeds. A 2014 study reported that a treatment regimen with activated charcoal, sauerkraut juice, humic acids, and their combinations significantly reduced glyphosate in the cows’ urine. This enhanced the animals’ immune systems, which induced appropriate immune responses to Clostridium botulinum, the bacteria responsible for producing the neurotoxin botulinum.23
Dr. Seneff believes that these treatments could also be effective in humans when trying to detox glyphosate.
3) Important Nutrients
Raising your sulfate levels isn’t easy because it can be hard to transport. Dr. Seneff recognizes several important nutrients that act as sulfur suppliers:
- Curcumin
- Garlic
- Vitamin C
- Probiotics
- Methyl tetrahydrofolate
- Cobalamin
- Glutathione
- Taurine
- Epsom salt baths
4) Get Grounded
Grounding is the direct physical contact between the body and the surface of the earth. Emerging research has shown that grounding (also called earthing) generates “a kind of electric nutrition.”24
How does this occur?
The hypothesis about grounding/earthing is based on the fact that the earth is satiated with free electrons. When two objects make contact, either directly or indirectly, there is an instantaneous migration of “mobile” electrons so that the electrical potentials of the two objects equalize. Some studies have suggested that these free electrons can have potent antioxidant and anti-inflammatory effects by neutralizing reactive oxygen species.25
Simply put, the earth is a giant negatively-charged battery. By making direct contact with the ground, the electrons flow right into your body, helping you to regenerate the negative charge.
5) Go Organic
Although it may be difficult to completely avoid being exposed to glyphosate, eating an organic diet will reduce your exposure to the herbicide. Furthermore, it’ll increase the demand for foods that don’t use glyphosate. It’s also important to be careful with meat and dairy products, which can be sources of glyphosate exposure. Check with your local farms to find the healthiest meat and dairy products for you and your family.
6) Eat Foods Containing Manganese
Since glyphosate can chelate manganese, Dr. Seneff recommends eating foods high in manganese to replenish your body of the mineral. Examples of such foods include26:
- Organic bread
- Organic tofu
- Almonds
- Pecans
- Peanuts
- Spinach
- Tea (green/black)
- Pineapple
- Brown rice
- Beans (lima, pinto, navy)
- Sweet potato
7) Eat Foods Containing Sulfur
In addition to eating foods high in manganese, eating an organic diet rich in sulfur can help protect from glyphosate poisoning. Examples of foods with high sulfur content include the following:
- Seafood
- Eggs
- Onion and garlic
- Cruciferous vegetables (ex: broccoli, cauliflower, etc.)
- Organ meat such as liver
- Cheddar and parmesan cheese
- Veal, beef, chicken, and pork
- Nuts
- Cow’s milk
- Peaches and apricots
Does Glyphosate Cause DNA Damage?
So what does all of this mean? It means that the science isn’t settled yet. The effects of glyphosate on DNA and need to be investigated under controlled laboratory conditions.
Still, there is enough evidence to be concerned about the potential devastating effects of glyphosate on your health. What’s even more concerning is that the current safety standards for glyphosate-based herbicides are simply not good enough. Many animal studies have reported that prolonged exposure to the “safe” level of glyphosate can still have adverse effects. While we wait for further research, I would highly recommend that everyone take the steps I outlined above to reduce your exposure to glyphosate.
Now it’s time to hear from you. What steps have you taken to reduce your exposure to glyphosate? What are your thoughts on the widespread use of glyphosate in the environment? Share your thoughts in the comments below!
Interested in a glyphosate test kit from HRI Labs? Get 10% off when you use code ‘DrJill’ at checkout. This makes the price $89.
References:
- https://www.pnas.org/content/115/41/10305
- https://www.ncbi.nlm.nih.gov/pubmed/15012217
- https://www.mdpi.com/1099-4300/15/4/1416/htm
- https://ghr.nlm.nih.gov/primer/genefamily/cytochromep450
- https://www.ncbi.nlm.nih.gov/pubmed/16702333
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521964/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4392553/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3330701/
- https://www.ncbi.nlm.nih.gov/pubmed/15488650
- https://www.ncbi.nlm.nih.gov/pubmed/15908137
- https://www.ncbi.nlm.nih.gov/pubmed/15766554
- http://renewablefarming.com/images/2016Images/2016PDF/Samsel-glyphosate-5.pdf
- https://www.ncbi.nlm.nih.gov/pubmed/18329946
- https://onlinelibrary.wiley.com/doi/full/10.1111/j.1747-0285.2010.01067.x
- https://www.sciencedirect.com/science/article/pii/S027869151530034X
- https://www.ncbi.nlm.nih.gov/pubmed/20979644
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955666/
- https://www.ncbi.nlm.nih.gov/pubmed/23000283
- https://mbio.asm.org/content/6/2/e00009-15
- https://www.ncbi.nlm.nih.gov/pubmed/27230806
- https://www.ncbi.nlm.nih.gov/pubmed/2146161
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4957837/#CR1
- https://www.omicsonline.org/open-access-pdfs/oral-application-of-charcoal-and-humic-acids-influence-selected-gastrointestinal-microbiota-2161-0525.1000256.pdf
- https://www.ncbi.nlm.nih.gov/pubmed/28987038
- https://www.ncbi.nlm.nih.gov/pubmed/18047442/
- https://lpi.oregonstate.edu/mic/minerals/manganese
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