Glyphosate, a chemical compound found in Roundup and other herbicides, can cross the blood-brain barrier, the layers of cells under the skull that protect the brain, new research from a group of Arizona scientists suggests.
The research, which was conducted in mice, showed that glyphosate entered the brain and elevated levels of certain molecules that are associated with disorders such as Alzheimer's disease in humans.
Further research will be necessary to prove a causal link between glyphosate and neurodegenerative diseases, according to scientists associated with the study from Arizona State University and the Arizona-based Translational Genomics Research Institute.
But the research serves as a starting point in understanding the chemical's effects on the brain, the scientists say.
Some existing research has already suggested links between glyphosate and cancer, though those links are controversial.
The International Agency for Research on Cancer, the specialized cancer agency of the World Health Organization, classified the substance as “probably carcinogenic to humans" in 2015. However, the U.S. Environmental Protection Agency has concluded that "glyphosate is not likely to be carcinogenic to humans," according to the agency's website, which asserts that the EPA evaluated a "more extensive and relevant" dataset than the International Agency for Research on Cancer.
Bayer AG, maker of the popular weedkiller Roundup, provided a statement to The Arizona Republic that says the ASU research conflicts with "data from high quality studies" that show glyphosate doesn't harm the nervous system. The company, which is headquartered in Germany, says it stands "fully behind" the safety of glyphosate and says it's one of the most extensively studied products of its time.
"There is overwhelming consensus among the leading health authorities around the world that glyphosate can be used safely, and no regulatory authority has found that glyphosate is neurotoxic," the statement says.
"Most recently, in May 2022, the European Chemicals Agency (ECHA) completed a hazard assessment of glyphosate and yet again reaffirmed that glyphosate is not neurotoxic."
But the ASU and TGEN researchers say there's been very little scientific study of the neurological effects of glyphosate, which is why their work is so necessary.
"This is an area that really hasn't been thoroughly investigated," said Ramon Velazquez, an assistant professor at ASU, researcher at the Biodesign Neurodegenerative Disease Research Center and the senior author of the study, which was recently published in the Journal of Neuroinflammation.
"We're interested in this because there's a lot of data suggesting correlation. So we know that correlations do not mean causation. We're trying to fill that gap and see if there's in fact some sort of causal impact (of glyphosate on neurodegenerative diseases)," Velazquez added.
A network of blood vessels brings blood to the tissues of your brain. But at the junctions where they meet, special cells serve an important function.
This is the blood-brain barrier, and it's a crucial protective layer inside your head. Its job is to prevent unwanted toxins or foreign chemicals from entering and potentially damaging the brain and spinal cord.
The blood-brain barrier is picky. Sometimes it keeps out drugs that scientists want to cross over into the brain, Velazquez said. But because previous studies in mice had shown behavioral changes related to glyphosate exposure, Velazquez said he thought it was possible that the molecule was finding a way to sneak through.
So Velazquez and his team gave mice three different doses of glyphosate for 14 days to see whether it would show up in their brains.
The dosages were based on a metric called the No Observable Adverse Effect Level, or NOAEL for short. That means the highest dose given doesn't produce any observable negative outcomes — in other words, the mice don’t look sick — and from there, the doses are given at lower and lower levels.
Then Velazquez sent samples of mouse urine, blood and brain tissue to Patrick Pirrotte, an associate professor in the cancer and cell biology division at TGEN, a nonprofit genomics research institute.
Pirrotte and his team unpacked the mouse urine, which is stored at minus 80 degrees Celsius, as well as the mouse plasma isolated from the samples and the small pieces of excised brain tissue. They wanted to look at the urine and plasma to see how much of the glyphosate was being excreted and compare it with the amounts found in the brain. They used special machines to measure the minute concentrations of chemical compounds in each sample.
When they looked at the mouse brains, in every dosage, they found glyphosate. And the amount of glyphosate they found depended on the dose: The more glyphosate they gave the mice, the more ended up in their brains.
What's more, the scientists found a correlation between amount of glyphosate exposure and amounts of a particular pro-inflammatory protein called TNF-α. That's important because in humans, elevated levels of TNF-α in the brain have been associated with neuroinflammation, a hallmark of Alzheimer's disease.
The ASU and TGEN research has not established that glyphosate causes diseases of the brain like Alzheimer's, the researchers emphasize. Velazquez noted that there are likely multiple factors that appear to contribute to Alzheimer's, not a single cause.
"I think this might be one component that makes up a whole host of components of the environment that accelerates the disease or might induce the disease," Velazquez said.
Nevertheless, they haven't ruled out the possibility that there might be a causal link. "We're just trying to get at the forefront of whether there is maybe some potential causality or acceleration of a disorder," he added.
Velazquez mentioned several future directions for research. So did Joanna Winstone, a neuroscience Ph.D. candidate at ASU, who was the first author on the study. She also did a lot of reading to help design the first of what she believes will be several more experiments necessary to understand glyphosate's long-term effects on the brain.
"When we have these chemicals that are going into production for agricultural use, a lot of times we look at short-term effects," Winstone said. "Maybe (we need to) delve deeper into looking at long-term chronic exposure to chemicals when we start putting (products) on the market."
To do that, Velazquez, Winstone and Pirrotte hope that they will be able to study glyphosate in human brains. To do so, Velazquez says they will use brains donated by individuals who developed Alzheimer's before their deaths. They can then examine those tissues for the presence of glyphosate.
That work, which the researchers hope will happen within the next few years, will build on the results of this study.
"This is the very first time an assay like that was developed," said Pirrotte of their mouse study. "So no other assay was published that was accurate enough to detect this in the brain."
Pirrotte also mentioned that they will need to fine-tune their dosing regimen to more closely resemble human patterns of glyphosate exposure, so they can do more precise work on human samples in the future.
"Humans usually ingest small amounts of glyphosate daily. So we want to fine-tune the dosing of glyphosate so that we can get closer to how much a human usually ingests on a daily basis," Pirrotte said.
For now, Pirrotte underscored the uncertainty of their findings in terms of implications for humans, but also noted the possibilities for future discovery.
"It is an imperfect answer, I know, but that's the truth about where we are. I think we're running down the odds on something really important, and the results are very, very interesting," he said. "But we can't deal in absolutes at this point in time."
Echoing Pirrotte, Velazquez said that "to tell people to stay away from these products that have been sprayed for glyphosate ... at least for the research we've published, that's too premature at the moment."
Still, the finding that glyphosate crossed the blood-brain barrier in mice has potential implications for humans when it comes to knowing what might contribute to neurodegenerative diseases like Alzheimer's, Parkinson's and multiple sclerosis.
"I think that this is a first step. What we've shown is that glyphosate has the ability to infiltrate the brain and has the ability to change these specific molecular/cellular/biological pathways," Velazquez said.
Research into the health effects of glyphosate has predominantly focused on cancer, which is why the ASU work on glyphosate and its possible effect on neurodegenerative diseases is helpful, said Danielle Melgar, food and agriculture advocate at U.S. Public Interest Research Group.
"This is the first that we've seen any concerns about Alzheimer's. It's definitely very interesting, this new research coming out," Melgar said.
"We definitely encourage a precautionary approach when it comes to chemical regulation and want to see more research like this that can establish what those health linkages might be so that humans are informed about what the health risks potentially are."
PIRG has long sounded the alarm on pesticide use, arguing that there are safer alternatives.
"At one time, the benefits of using pesticides to increase crop yields to feed a growing nation may have made sense," the group's website says. "But modern agriculture has no problem growing enough food to feed us all, and we now know so much more about the devastating impacts of these pesticides on our health and our ecosystems."
Avoiding glyphosate is difficult, but there are ways to reduce one's individual exposure.
PIRG encourages using alternatives in landscaping and lawn management, such as pulling weeds by hand instead of spraying, planting pollinator gardens and using xeriscaping where appropriate in Arizona, promoting the natural landscape, Melgar said. Other ways include watering deeply and infrequently, and using organic fertilizers.
If public parks are using herbicides and one's neighbors are using it, there's a risk of exposure. Also, glyphosate has been found in food, including corn, soybeans, beer and wine.
"People are ingesting glyphosate when they eat all different kinds of food," Melgar said. "The bottom line is it is really hard to avoid, which is why we should be using significantly less of it and looking for other ways to manage land more sustainably."
Melgar said she's particularly encouraged by the ASU researchers' interest in studying low-level exposure to glyphosate over a longer periods of time and what those impacts would be.
"A lot of what the industry is really talking about is short-term exposure," she said. "Is one exposure one time going to cause cancer? Probably not. But if you are consistently exposed to it as a worker or a kid rolling around in the grass, is that going to be something that is enough?"
Pirrotte, the TGEN researcher, said there's a lot more work to be done, including studying the brains of deceased people, both with and without Alzheimer's. He expects to find traces of glyphosate in all brains, but the question is whether there will be an increased amount of glyphosate in patients with Alzheimer's.
"All the data in mice points towards that," he said. "We have to know when it's a product that it makes sense to use, and when not to. Understanding what exposure of glyphosate does to the human body is something that we should be spending more time on."
Melina Walling is a bioscience reporter who covers COVID-19, health, technology, agriculture and the environment. You can contact her via email at mwalling@gannett.com or on Twitter @MelinaWalling.
Reach the reporter at Stephanie.Innes@gannett.com or at 602-444-8369. Follow her on Twitter @stephanieinnes.