And here we go again, another paper that attempts to link something terrible, in this case, convulsions, to the weedkiller glyphosate, also known as Roundup. Except this is about nematodes or roundworms.
I seem to be writing about roundworms a lot lately, I wonder why. Oh wait, I remember. Quacks were pushing a drug, that treats roundworm infections, to be used against COVID-19. Of course, you all remember ivermectin.
Let’s look at glyphosate and this new paper, which made me laugh. Then I got annoyed.
What is glyphosate?
Glyphosate (Monsanto’s Roundup) is a broad-spectrum systemic herbicide used to kill weeds, especially annual broadleaf weeds and grasses that are known to compete with commercial crops grown around the world. It has several advantages over many herbicides in that it breaks down in the soil into non-toxic organic molecules within a few days to weeks, reducing or eliminating contamination of groundwater and lower soils. This is a large improvement over other types of herbicides.
Roundup, which was produced by Monsanto, is now off-patent and manufactured by a lot of different companies under different brand names. Without a doubt, glyphosate is one of the most popular weed killers in the world.
Glyphosate’s mechanism of action is to attach itself to the enzyme EPSP synthase. When glyphosate binds to this enzyme, it becomes non-functional, and the plant is unable to make the crucial amino acids phenylalanine, tyrosine, and tryptophan. The plant slowly dies without these amino acids.
In case you’re wondering, EPSP synthase is not found in animals, so when humans or pets are exposed to glyphosate, it has nothing to bind to and is excreted almost intact with virtually no effect. I cannot emphasize this enough — glyphosate has no known mechanism of action in humans, livestock, or any other animal because we animals don’t have EPSP synthase. For animals, humans included, glyphosate is innocuous and is just excreted like many other compounds that are inert in humans.
Monsanto developed genetically modified (GMO) grains that are resistant to glyphosate so that farms can apply the herbicide to kill the competitive weeds while not harming the crop. This allows farmers to suppress the weeds while allowing better production out of the grain crop. There is robust evidence that glyphosate does not affect crop yield while reducing pests at a lower cost than other modalities.
Whatever the benefits of glyphosate, it is tied together with GMOs in many minds. And there is a “chemophobia” amongst many people that all chemicals are bad. But as I discussed before, the dose makes the poison – that is, in the real study of toxicology, there are doses of any “chemical” that are safe or unsafe. Water, for example, can be toxic if consumed at certain doses – sure, the dose is high for water toxicity, but it exists. Our culture’s chemophobia makes no sense to people, like me, who understand chemicals – every single thing we consume is made of chemicals, some with complex and indecipherable names.
Of course, as a result of this chemophobia, and misinterpreted scientific research, there has been an ongoing effort by many people to claim that glyphosate causes great harm to people, animals, and the environment. I wrote a whole article debunking the claims that glyphosate causes cancer.
This, of course, has led to Monsanto bashing across the internet along with several lawsuits. My article is agnostic about Monsanto – I just don’t care one way or another about the company. All I care about is the quality of evidence that either supports or refutes the hypothesis that glyphosate causes harm.
We’ll look at the new study that tries to claim that glyphosate causes convulsions I guess if you hate Monsanto and RoundUp, you’ll accept bad science to support your preordained assumptions. But you know what they say – everyone loves science unless it contradicts their beliefs.
The glyphosate convulsions paper
In a paper published on 23 August 2022 in Nature Scientific Reports, Akshay S. Naraine, Ph.D. student at Florida Atlantic University, and colleagues attempted to show that glyphosate caused convulsions in nematodes. It’s hard to write that with a straight face since I rarely accept research that uses mammalian models, like mice and rats, as having any clinical significance. Less than 1% of preclinical studies involving drugs and rodent models ever end up receiving FDA approval. I have no clue what percentage it would be for a nematode model, but it’s laughable that someone would publish a paper attempting to create some correlation between a nematode study and humans.
But I’ll try to overlook my extreme skepticism and attempt to convey what this flawed study was trying to show.
The study tries to tie the fact that the CDC reported that more than 80% of urine samples from children and adults in the USA contained glyphosate to what happens to a simple roundworm. Of course, the CDC report did not make clear what the clinical significance of those levels our, since, as I explained above, glyphosate has no known effect on humans. No one has ever shown that glyphosate binds to or interacts with any mammalian enzyme, protein, cell wall, or anything.
Remember, as I’ve written before, biological plausibility is critical if you are going to establish causality.
This study showed that glyphosate and Roundup increased “convulsions” or seizure-like behavior in soil-dwelling nematodes and provides significant evidence that glyphosate targets GABA-A receptors. These communication points are essential for locomotion and are heavily involved in regulating sleep and mood in humans.
Here are some of the many issues I have with this research:
- Using nematodes as the model for glyphosate effects is simply laughable. Nematodes are simple organisms, about as distantly related to humans as anything else in the animal kingdom.
- Nematodes have a very simple nervous system. They don’t have the same receptors, second messengers, or even neurotransmitters as vertebrate animals do (mammals in particular).
- Naraine et al. statistical analysis was confusing at best and unconvincing at worst. If you examine Figure 1 from their paper, the data appears to be random. They appeared to use statistical methods that ignore the significant randomness of the data. I am not a statistician, but I’ve spoken to individuals who have reviewed this data, and they are troubled by the validity of their statistical methods.
- An important issue with this research is that they used Roundup, which contains more than just glyphosate. There are so many confounding ingredients in Roundup that we cannot ascertain what, if anything, caused the results claimed by the authors.
- A systematic review (at the top of the hierarchy of biomedical research) of glyphosate and neurological outcomes concluded that “Taken together, these studies do not demonstrate a consistent impact of glyphosate on the structure or function of the mammalian nervous system.”
- Research from Adriana Martinez and Abraham Jacob Al-Ahmad, Department of Pharmaceutical Sciences, Texas Tech University Health Sciences Center, showed that glyphosate in extremely high doses could pass through the blood-brain barrier and cause neurological issues. However, as I have stated, there is little evidence that glyphosate could bind to anything in the brain, and the levels used by Martinez and Al-Ahmad in their experiments were over 1000 times higher than is seen in farm workers exposed to glyphosate.
- Sometimes the absence of evidence is evidence of absence. If glyphosate had a serious neurological effect, robust epidemiological studies would have shown that there was an increased risk of convulsions in farm workers or people who lived close to farms. There just isn’t any.
- I was wrong, there is evidence that there’s no link between glyphosate and neurological outcomes. It’s in another systematic review published in May 2022.
As someone with a clinical trial background, I tend to dismiss anything that’s not a clinical trial or a well-designed cohort or case-control study. But nematodes? Doused with large doses of Roundup? I’m just not buying the results and the applicability to humans (or any other animals).
There are a lot of studies out there with glyphosate and animals. Some show nothing. Some show something (at very very high doses). But systematic reviews of animal studies appear to conclude that there is no link between glyphosate and neurological issues.
And epidemiological studies also show no link between glyphosate and neurological issues, like convulsions, in humans.
The authors of the study seem to want to show that there’s something in a really bad animal model. But they seem to have failed to notice that there are a lot of human epidemiological studies that show no link. If you can’t even show a correlation in humans (and other mammalian models), then trying to show something reminds me of the pseudoscience pushed by anti-vaccine “scientists.”
One more thing. Naraine et al. seemed to have a conclusion in mind, that glyphosate is bad, and tried to use nematodes as a model to support that conclusion. That’s not science, that’s what we see in pseudoscience time and time again.
I don’t think that glyphosate is a perfect chemical and it does no harm. That would be a very naïve opinion. But, I am a scientist, and the only thing that matters to me when you’re making a claim is the quality of evidence that supports it. This study does not provide any convincing evidence of a link between glyphosate and neurological conditions in humans. Moreover, I’m not sure it provides a convincing link between glyphosate and convulsions in nematodes.
- Chang ET, Odo NU, Acquavella JF. Systematic literature review of the epidemiology of glyphosate and neurological outcomes. Int Arch Occup Environ Health. 2022 May 23. doi: 10.1007/s00420-022-01878-0. Epub ahead of print. PMID: 35604441.
- Martinez A, Al-Ahmad AJ. Effects of glyphosate and aminomethylphosphonic acid on an isogeneic model of the human blood-brain barrier. Toxicol Lett. 2019 Apr;304:39-49. doi: 10.1016/j.toxlet.2018.12.013. Epub 2018 Dec 31. PMID: 30605748.
- Moser VC, Morris-Schaffer K, Richardson JR, Li AA. Glyphosate and neurological outcomes: A systematic literature review of animal studies. J Toxicol Environ Health B Crit Rev. 2022 May 19;25(4):162-209. doi: 10.1080/10937404.2022.2083739. Epub 2022 Jun 8. PMID: 35676826.
- Naraine AS, Aker R, Sweeney I, Kalvey M, Surtel A, Shanbhag V, Dawson-Scully K. Roundup and glyphosate’s impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegans. Sci Rep. 2022 Aug 23;12(1):13655. doi: 10.1038/s41598-022-17537-w. PMID: 35999230.