Matt Pratt-Hyatt
Chief Science Officer, KBMO

Glyphosate is one of the most commonly used herbicide ingredients on the planet, and is used in many broad-spectrum herbicides.

Since its release in 1974, usage of glyphosate has continually increased year on year. This growth skyrocketed in the 90’s, with the introduction of genetically modified crops that were resistant to glyphosate (1), including soybeans, cotton, and corn. Within 10 years, over 90% of these crops were the glyphosate resistant variety (2).

There are over 750 different herbicides that contain glyphosate, which makes it difficult to avoid using products that contain it (3). Fruits, fresh vegetables and processed products have been shown to have up to 85 ppb (4). Human exposure to glyphosate is mainly through food.

Glyphosate has been detected in human blood, urine, umbilical cord blood, and breast milk (5-7). The extensive pervasiveness of glyphosate has resulted in at least 80% of the U.S. population having detectable amounts in their urine by 2014 (8). Although some studies have found glyphosate exposure to be unharmful, many of these studies have looked at acute effects, rather than chronic effects. Many newer studies have found that glyphosate affects human health in at least three distinct areas – the microbiome, hormones, and increased cancer risk.

Glyphosate and the intestinal microbiome

One of the most commonly reported issues with glyphosate exposure is its effects on the intestinal microbiome. Glyphosate crosses the intestinal-epithelial barrier, and is then excreted in feces and urine (9). Common concentrations have been shown to be between 0.16 to 7.6 ppb (10). These concentrations have been shown to disrupt the balance of gut microbiota, which in mice leads to anxiety and depression-like behaviors (11, 12). This is due to glyphosate’s designed ability to inhibit the shikimic acid pathway – a necessary pathway for beneficial bacteria, but unneeded in many pathogenic microorganisms (11). This leads to an increase of harmful bacteria in the gut and a decrease of beneficial bacteria such as Lactobacillus and Bifidobacterium (13).

Glyphosate and the endocrine system

Glyphosate’s interaction with the human endocrine system has been a new avenue of research for many laboratories. There are some conflicting results in this area, but I want to highlight this possibility and hope to update you when new research helps to settle this debate. One avenue of research is whether glyphosate can activate hormonal activity. Some labs have found that glyphosate at relevant concentrations activated estrogen responsive elements (ERE). Research also found that glyphosate had a weak interaction with estrogen receptor-a (14, 15). However, another lab reported no such interactions (16).

These different results may be caused by the use of different cell lines. Where interactions were found, research was done in a human breast cancer cell line, whereas where a lack of interaction was found, Chinese Hamster ovaries (CHO) cells were used.  Other studies have found that glyphosate exposure correlated with reduced progesterone and estrogen production, enhanced uterine sensitivity to estradiol, and shortened pregnancy (17-19).

Glyphosate and cancer

Glyphosate and cancer have been showing up together in the news more and more, with some of the big headlines highlighting multi-million-dollar damage settlements awarded to several California residents. According to Forbes, Monsanto had settled over 100,000 lawsuits and paid out over $11 billion, as of May 2022.

Studies have also identified an increased risk of developing cancer with glyphosate exposure. One meta-analysis found that exposure to glyphosate led to an increased risk of forming Non-Hodgkin Lymphoma (20) because of epigenetic modifications, which are small molecule additions that help the body know which genes to read and which genes should be silenced in certain cells. Several labs are reporting that patients exposed to glyphosate have changes in their DNA modification, which could change which genes are turned on or off (21).  Another recent study showed that when glyphosate was mixed with human blood there was significant genetic damage compared to the negative control (22).

Dealing with high glyphosate load

When dealing with high glyphosate load there are several possible strategies. The most important is avoidance. Second, is to support detoxification pathways. The third strategy is sauna, which has been shown to help push out the toxin. Finally, some practitioners have used different types of binders to help eliminate glyphosate, though more work is needed to determine the efficacy of these.

References:

1. S. O. Duke, Perspectives on transgenic, herbicide-resistant crops in the United States almost 20 years after introduction. Pest Manag Sci 71, 652-657 (2015).
2. S. O. Duke, Taking stock of herbicide-resistant crops ten years after introduction. Pest Manag Sci 61, 211-218 (2005).
3. K. Nagy, R. A. Tessema, L. T. Budnik, B. Adam, Comparative cyto- and genotoxicity assessment of glyphosate and glyphosate-based herbicides in human peripheral white blood cells. Environ Res 179, 108851 (2019).
4. B. M. Kolakowski et al., Analysis of Glyphosate Residues in Foods from the Canadian Retail Markets between 2015 and 2017. J Agric Food Chem 68, 5201-5211 (2020).
5. A. Steinborn et al., Determination of Glyphosate Levels in Breast Milk Samples from Germany by LC-MS/MS and GC-MS/MS. J Agric Food Chem 64, 1414-1421 (2016).
6. C. Ferreira et al., Urine biomonitoring of glyphosate in children: Exposure and risk assessment. Environ Res 198, 111294 (2021).
7. M. Cellier, N. Anthony, C. Bruneau, A. Descatha, Determination of Glyphosate and AMPA in Blood Can Predict the Severity of Acute Glyphosate Herbicide Poisoning. Lab Med 53, 394-398 (2022).
8. M. Ospina et al., Exposure to glyphosate in the United States: Data from the 2013-2014 National Health and Nutrition Examination Survey. Environ Int 170, 107620 (2022).
9. D. W. Brewster, J. Warren, W. E. Hopkins, 2nd, Metabolism of glyphosate in Sprague-Dawley rats: tissue distribution, identification, and quantitation of glyphosate-derived materials following a single oral dose. Fundam Appl Toxicol 17, 43-51 (1991).
10. C. Gillezeau et al., The evidence of human exposure to glyphosate: a review. Environ Health 18, 2 (2019).
11. L. Rueda-Ruzafa, F. Cruz, P. Roman, D. Cardona, Gut microbiota and neurological effects of glyphosate. Neurotoxicology 75, 1-8 (2019).
12. Y. Aitbali et al., Glyphosate based- herbicide exposure affects gut microbiota, anxiety and depression-like behaviors in mice. Neurotoxicol Teratol 67, 44-49 (2018).
13. Q. Tang, J. Tang, X. Ren, C. Li, Glyphosate exposure induces inflammatory responses in the small intestine and alters gut microbial composition in rats. Environ Pollut 261, 114129 (2020).
14. R. Mesnage et al., Evaluation of estrogen receptor alpha activation by glyphosate-based herbicide constituents. Food Chem Toxicol 108, 30-42 (2017).
15. S. Thongprakaisang, A. Thiantanawat, N. Rangkadilok, T. Suriyo, J. Satayavivad, Glyphosate induces human breast cancer cells growth via estrogen receptors. Food Chem Toxicol 59, 129-136 (2013).
16. H. Kojima, E. Katsura, S. Takeuchi, K. Niiyama, K. Kobayashi, Screening for estrogen and androgen receptor activities in 200 pesticides by in vitro reporter gene assays using Chinese hamster ovary cells. Environ Health Perspect 112, 524-531 (2004).
17. P. I. Ingaramo et al., Effects of neonatal exposure to a glyphosate-based herbicide on female rat reproduction. Reproduction 152, 403-415 (2016).
18. M. Guerrero Schimpf, M. M. Milesi, E. H. Luque, J. Varayoud, Glyphosate-based herbicide enhances the uterine sensitivity to estradiol in rats. J Endocrinol 10.1530/JOE-18-0207 (2018).
19. L. P. Walsh, C. McCormick, C. Martin, D. M. Stocco, Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression. Environ Health Perspect 108, 769-776 (2000).
20. L. Zhang, I. Rana, R. M. Shaffer, E. Taioli, L. Sheppard, Exposure to glyphosate-based herbicides and risk for non-Hodgkin lymphoma: A meta-analysis and supporting evidence. Mutat Res Rev Mutat Res 781, 186-206 (2019).
21. M. F. Rossetti et al., Epigenetic Changes Associated With Exposure to Glyphosate-Based Herbicides in Mammals. Front Endocrinol (Lausanne) 12, 671991 (2021).
22. C. Alvarez-Moya, M. Reynoso-Silva, Assessment of Genetic Damage Induced via Glyphosate and Three Commercial Formulations with Adjuvants in Human Blood Cells. Int J Mol Sci 24 (2023).