Glyphosate Exposure: Genetics and the Impact on Our Health

Key takeaways:
~ Glyphosate is a herbicide used abundantly on crops and in urban areas.
~ Many foods are contaminated with glyphosate, and we are also exposed to it in parks and around houses.
~ Most glyphosate passes through the body and is excreted.
~ One study showed an interaction between the negative effects of glyphosate and the CYP1A1 gene variants. Other studies show that glyphosate affects neuronal and oxidative stress pathways.

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Glyphosate, detoxification, acetylcholine

RoundUp is the most widely used herbicide in the world. It is made by Monsanto, which Bayer now owns. Glyphosate is the active ingredient in RoundUp, and it will kill most broadleaf plants and grasses.[ref]

Glyphosate works by blocking the shikimate pathway, which is an enzyme pathway in plants and some microorganisms. The shikimate pathway is the process by which plants, bacteria, archaea, fungi, and algae make folate (vitamin B9) and certain amino acids (tryptophan, tyrosine, and phenylalanine). Without those amino acids, plants and microorganisms die.

The shikimate pathway isn’t found in animals, and the amino acids it makes are ones that we must get from our diet (essential amino acids for humans).

Thus, glyphosate kills plants and bacteria but doesn’t kill animals.

However, there is recent research that shows that glyphosate may have an impact on human health in certain ways…

Let’s take a look at some of the recent health research and then dive into where glyphosate is used and how it is metabolized by the body.

Glyphosate and inflammation / neuroinflammation:

A cell study found that glyphosate and the glyphosate metabolite aminomethylphosphonic acid (AMPA) altered gene expression, indicating that either the metabolite AMPA or glyphosate was affecting cells. Pathways impacted include tumor necrosis factor-alpha (TNF⍺), TP53, NF-kB, and more in the pathways involving apoptosis, oxidative stress, and cell death.[ref]

In pregnant mice exposed to low doses of glyphosate daily, their offspring had significant behavioral changes. Specifically, the offspring were more anxious and hyperactive.[ref]

Several studies have shown that glyphosate increases TNF-alpha, which is an inflammatory cytokine.[ref][ref]

For example, a study in mice found that exposure to glyphosate infiltrated the brain and elevated TNF levels both in the brain and in the plasma.[ref]

In the intestines, glyphosate has been shown in animal studies (pigs) to increase Nrf2 levels, inducing NF-kB.[ref] Nuclear factor-κB (NF-κB) signals for danger and induces an innate immune response. [ref]

A rat study found that glyphosate exposure at levels that caused no observable signs of dysfunction changed serotonin, dopamine, and norepinephrine levels in the brain.[ref]

Inhaled glyphosate, airway inflammation, and asthma:

Glyphosate can be inhaled when spraying it or when in an agricultural area where it has been recently applied.

Animal studies show that glyphosate in the air at both low and high concentrations can cause airway inflammation. The low concentrations caused just as much airway inflammation as the higher concentrations. In the lungs, there was a significant increase in IL-33 and IL-13, which caused mast cell degranulation and histamine release. These are inflammatory pathways that are activated in asthma.[ref]

Glyphosate and triglycerides:

A mouse study in 2017 showed that glyphosate-based herbicides in very low doses increased triglyceride levels and increased liver fat. [ref] In addition, giving pregnant mice glyphosate caused increased triglyceride and cholesterol levels in the offspring at day 19.[ref]

Glyphosate and metabolic syndrome:

A 2023 study found that kids who had higher levels of glyphosate and glyphosate metabolites (AMPA) in their urine at ages 5 and 14 were much more likely to develop metabolic syndrome and liver problems at adulthood. Kids living in agricultural areas where glyphosate was used on crops were at a more than 50% higher risk of metabolic syndrome.[ref]

Genetics and glyphosate: 

A study was published in 2020 showing that some people are likely more affected by exposure to glyphosate than others.[ref]

The study found that people with CYP1A1 genetic variants were more likely to have problems with cholinesterase inhibition from glyphosate.

Let me explain what cholinesterase inhibition means…

Glyphosate has been shown in animal studies to affect acetylcholinesterase – a little bit. Acetylcholinesterase is the enzyme that breaks down acetylcholine, which is a completely essential neurotransmitter.

Acetylcholine transfers the signal between the nerves that control your muscles (and also neurons in the brain). Think of it as the on switch for a muscle nerve that causes a contraction. For every ‘on’ impulse, you need to stop the signal with an ‘off switch’ — that would be acetylcholinesterase.

Prior animal studies showed that glyphosate inhibits acetylcholinesterase (a little).[ref][ref] If you inhibit acetylcholinesterase too much, it leads to paralysis, convulsions, and death due to asphyxiation (not being able to move the muscles around the lungs to breathe). This is how nerve gas, such as Sarin gas, works in chemical warfare. Not pretty… but also nothing like the very low levels that we are talking about here.

Serum cholinesterase is used as a marker of herbicide poisoning because levels decrease when liver function is damaged.[ref]

Getting back to glyphosate and how it affects people…

A recent study was done on workers who make glyphosate in China. The workers were exposed only to glyphosate and not to other pesticides, thus reducing the confounders seen in studies on agricultural workers. The glyphosate manufacturing workers had blood tests done to determine what their serum acetylcholinesterase levels were.[ref]

The study showed that people with a specific CYP1A1 variant (listed below in the genotype report) had significantly lower acetylcholinesterase levels due to glyphosate exposure. This variant alters CYP1A1 expression. Lower acetylcholinesterase was assumed to be a marker of liver damage.

CYP1A1 is a member of the cytochrome P450 group of enzymes. It metabolizes or breaks down many different compounds, such as polycyclic aromatic hydrocarbons (PAHs), paracetamol, caffeine, and nicotine. Once compounds are metabolized using the CYP enzymes, they can be more easily eliminated from the body.

Important in the study:
First, there is an effect of glyphosate on acetylcholinesterase levels, especially at higher exposure levels. Most of the EPA information says that glyphosate passes through people without being metabolized — which apparently isn’t accurate for everyone, depending on their genotype.

Second, the urinary glyphosate metabolite levels of these Chinese glyphosate manufacturer workers were not all that high. A recent study of children in Mexico showed similar average concentrations to that of the Chinese glyphosate manufacturing workers.[ref] This means that everyday glyphosate exposure in agricultural areas could be a problem for some individuals.

Let’s dig into glyphosate a bit more to understand its prevalence.

Glyphosate as a Herbicide: Where is it used?

The creation of RoundUp Ready genetically modified crops has increased the use of RoundUp by 100-fold since the 1970s.

These RoundUp Ready crops can be sprayed with glyphosate and not die. Thus, farmers can spray their RoundUp Ready crops, killing all the weeds and leaving their crops standing tall.

Roundup Ready crops include soy, corn, canola, alfalfa, cotton, and sugar beets.

The EPA says: “there are no risks to public health when glyphosate is used in accordance with its current label and that glyphosate is not a carcinogen”.[ref]

On the other hand, the International Agency for Research on Cancer (IARC) lists glyphosate as a “probable carcinogen”, and several recent lawsuits have successfully shown the link between glyphosate exposure and non-Hodgkin’s lymphoma.[ref]

How are we exposed to glyphosate?

Glyphosate is used on many agricultural crops as well as for killing weeds in residential and commercial areas. It is ubiquitous in our environment.

Here is a USGS map showing agricultural use in the US:

Crops that are regularly sprayed with glyphosate include:[ref]

• Corn
• Soybeans
• Cotton
• Pasture Grass and Hay (often used for animal feed)
• Wheat

The half-life of glyphosate and its metabolite, AMPA, in soils, ranges from 2 to 197 days and 76 to 240 days.

It was also detected in 31% of harvest samples, but all were below the EPA’s limit.[ref]

A 2023 study in Europe found that when glyphosate is used as a pre-emergent to kill weeds before planting, glyphosate residue is not found in the crop that is later planted in the field. However, the same study showed that when glyphosate is sprayed on plants as a desiccant (drying agent) before harvest, it does come through in the grains. Additionally, glyphosate was stable in the harvested grains and remained for a year or more.[ref]

A study of groundwater in WA, WY, MD, and IA found glyphosate in 100% of sampled water sources.[ref]

Here is how glyphosate usage has grown over the past couple of decades:

Dust in the Wind:
While it is understandable glyphosate is detected in foods that have been sprayed with it, the results of a recent study surprised me…

Researchers sampled vacuum cleaner bags from 60 households, both rural and urban, in France. The results showed that 100% of the household dust contained glyphosate. Higher concentrations were found in rural homes close to agricultural fields and in homes that used weed killers around their driveways and yards.[ref]

Exposure limits and classification:
The European Food Safety Authority sets the Acceptable Daily Intake at 0.5 mg/kg of body weight per day.[ref]

Again, the U.S. EPA classifies glyphosate as “not likely to be carcinogenic to humans”. However, the WHO (World Health Organization) classifies glyphosate as “probably carcinogenic to humans.”[ref]

Which foods are more likely to contain glyphosate?

Glyphosate usage is not allowed on foods that are grown as certified organic.

Studies show that foods sprayed with glyphosate before harvest are likely to have glyphosate residue in them.[ref][ref]

• Cereals and cereal grain products (wheat products, corn, snacks, bread, barley) very often contain glyphosate, with detection frequency varying from country to country.
• Wheat bran or whole wheat was more likely to contain glyphosate than white flour.
• Honeybees visit agriculture fields and bring glyphosate back to the hive with them. Thus, the amount of glyphosate in honey is going to reflect how much is being used in the surrounding agricultural fields. One study showed 28% of US honey samples contained glyphosate, while another found that 98% of Canadian honey samples contained glyphosate.
• Canola oil (rapeseed oil) contains glyphosate if used during the growing season. Specifically, it was found in cold-pressed oil.
• A European study found that glyphosate was not detected in any of the olive oil samples.
• Fruits tend not to have much glyphosate contamination on them.

How often are we exposed to glyphosate?

Researchers can test urine to see how much of the population has glyphosate (or a metabolite of glyphosate) in them at any given time.

• A recent study in the UK found glyphosate in the urine of 53% of study participants.[ref]
• Studies in the US find glyphosate in the urine of 60-80% of the population.[ref]
• A 2023 study of pregnant women in Canada found that 75% had glyphosate or a metabolite of glyphosate in their urine. Whole grain bread intake was positively associated with glyphosate in the urine.[ref]

Glyphosate Metabolism:

Animal studies show the absorption of glyphosate is ~30-36% when ingested. Absorption through the skin, though, is really low (~2% over 8 hours).[ref]

Most of the glyphosate you eat will be excreted in feces or urine. A small percentage of it is metabolized or broken down into aminomethylphosphonic acid (AMPA).[ref]

So if glyphosate mostly just passes on through, why worry about it? 

Impact on the gut microbiome:

As I mentioned above, glyphosate’s mechanism of action blocks the shikimate pathway, which bacteria, archaea, fungi, and plants use to create folates and certain amino acids.

The real question here is one of gut health: what is glyphosate doing to the bacteria, archaea, and fungi that make up our gut microbiome? 

A recently published study found that about one-half of the human microbiota is sensitive to glyphosate. Firmicutes were more resistant, while Proteobacteria and Actinobacteria were more sensitive to glyphosate.[ref]

Researchers have found that certain strains of Clostridium and Salmonella are resistant to glyphosate. This may cause an increase or overgrowth of these bacterial species in the gut microbiome.[ref]

Keep in mind that we rely on the gut microbiome to produce part of our essential vitamins. For example, riboflavin and niacin are produced by Proteobacteria. Several different families of bacteria also make folate in the gut.[ref]

Part of the difficulty in determining whether glyphosate is causing changes to the gut microbiome is that we all have various different pesticides in our guts, along with different genetic interactions that influence our microbiome. So teasing out the differences in how glyphosate really impacts the microbiome is confounded by many different variables.[ref] The real-life human impact on a daily basis is not as simple as the animal studies indicate.

Lifehacks: Ways to avoid glyphosate and genetic connections

First, I will cover a few ways to mitigate glyphosate exposure to some extent. Realistically, I don’t know that most people can avoid it altogether.

Next, I will go into some more speculative ways that glyphosate could interact with your genes and gut microbiome.

Avoiding Glyphosate:

Related Articles and Topics:

Should you eat organic? Detoxifying Organophosphates

BPA: How Your Genes Influence BPA Detoxification