Introduction
Glyphosate is the most common herbicide in the world. The United States has been using glyphosate in agriculture since 1974, and it is also popular as the formulation Roundup to control weeds in residential maintenance of lawns. Starting in the late 1990s, a breakthrough technology involving genetically modified crops allowed glyphosate to be sprayed indiscriminately on the crop without killing it. Glyphosate is considered to be a great boon to agriculture because it kills all plants except those that have been engineered to resist it, yet is “practically harmless” to humans or to animals in general.

However, in recent years this rosy picture is beginning to unravel. We had been assured that glyphosate affects a biological pathway in plants (the shikimate pathway) that does not exist in human cells, and therefore the chemical is very safe. However, our gut microbes do have this pathway, and they use it to make essential nutrients for the host that our cells can’t make. For many decades, toxicologists had not thought to study glyphosate at low exposure levels, assuming that the results would be negative. However, a seminal study by Prof. Séralini et al., published in 2012, revealed that exposure to low-dose glyphosate over the entire lifespan led to many toxic effects in rats, including massive mammary tumors in the females, liver and kidney damage in the males, and reproductive issues in both genders [1]. This study was retracted without justification under pressure from the industry but was soon republished in another journal [2].

Since 2012, and, increasingly, in the past few years, many studies are coming out showing that glyphosate is toxic to many animal species at very low doses (often below regulatory limits). A recent review study with over 200 references showed that glyphosate has many characteristics of a classic endocrine disruptor, causing multiple imbalances in hormones that lead to disrupted development and disease [3]. Glyphosate disrupted the hypothalamic-pituitary-thyroid axis in rats, and induced hypothyroidism in offspring from exposed rat dams. Glyphosate suppresses aromatase, a crucial enzyme for converting testosterone to estrogen, and this disrupts development in utero. Glyphosate induced teratogenic effects in tadpoles through disruption of retinoic acid signaling.

Correlations with Diseases
Glyphosate usage in the United States has been rising steadily over time for the past two decades. A paper published by Swanson et al. in 2014 contained 19 figures showing stunning correlations between glyphosate usage on core crops over time and the rising prevalence in a long list of debilitating chronic diseases [5]. The diseases included diabetes, obesity, Alzheimer’s, dementia, autism, Parkinson’s disease, pancreatic cancer, thyroid cancer, hepatitis C, liver cancer, kidney cancer, intestinal infection, and inflammatory bowel disease, among others. Skeptics are quick to point out that correlation doesn’t always mean causation, but something is causing the alarming rise in all these diseases, and such perfect correlations cannot be found with any other environmental chemicals.

Autism
My main interest originally in studying toxic environmental chemicals was to try to determine what is causing the autism epidemic in the United States. The Centers for Disease Control claim that one in 54 12-year-old children in the United States suffer from autism today, an astounding number. Autism begins in the gut, and glyphosate clearly disrupts the gut microbiome, causing inflammation and a leaky gut barrier [6]. An overgrowth of pathogens such as certain species of Clostrida leads to toxic metabolites that disrupt dopamine metabolism in the brain, causing neuroexcitotoxicity [7]. Rats exposed to glyphosate early in life exhibit impaired cognition that is associated with defective development of synapses in the hippocampus [8]. Glyphosate suppresses cytochrome P450 enzymes, and this leads to many pathologies, one of which is impairment in vitamin D activation. Vitamin D deficiency is another causal factor in autism and is an epidemic in the United States today.

Cancer
In April 2015, the World Health Organization’s International Agency for Research on Cancer (IARC) identified glyphosate as a probable human carcinogen, and this led the way to lawsuits linking glyphosate to non-Hodgkin’s lymphoma (NHL). Following three spectacularly successful lawsuits with large awards in jury trials, huge numbers of plaintiffs claimed glyphosate caused their NHL. Bayer, who acquired Monsanto in 2018, is now trying to negotiate a settlement for 125,000 cases to the tune of $11 billion dollars, which in my view is not nearly enough.

A recent study looked at correlations between glyphosate usage and rates of testicular cancer across the United States, based on online US government sources, and they found a correlation coefficient of 0.915 with a p-value (representing the likelihood that the correlation could have occurred by chance) that was less than 0.0000000004. The same study also found a strong inverse correlation between sperm counts and glyphosate usage (p-value less than 0.000015). Glyphosate exposure to breast-cancer cells grown in vitro at levels of parts per trillion caused the cells to proliferate [4].

Reproductive Issues
Many recent studies, both on humans and in animal models, are showing that glyphosate exposure is linked to infertility and health issues during pregnancy and development. A 2021 study conducted in Puerto Rico showed that women who had high (> 0.65 micrograms/liter) levels of AMPA (a breakdown product of glyphosate) in their urine at 26 weeks of gestation had a 4.5-fold increased risk of premature birth (p < 0.006) [9]. High urinary glyphosate was associated with a 3.77-fold increased risk. According to the American Psychological Association, preterm birth is a national epidemic, costing the United States $26.2 billion each year.

Another pregnancy study on American women published in 2021 found that high maternal urinary glyphosate levels mid-pregnancy were associated with an abnormally long anogenital distance in female babies [10]. This metric is known to be linked to excessive testosterone exposure in utero. Ominously, this anatomical feature is also a very strong risk factor for polycystic ovary syndrome (PCOS), the biggest factor in female infertility.

Conclusion
The United States, with 4% of the world’s population, consumes 19% of the world’s glyphosate. I suspect this may be the primary reason why we have a healthcare crisis in this country. Glyphosate is not the only chemical used in agriculture that is harmful to our health. There is an urgent need to dramatically change the way we grow food, by reverting back to organic renewable agricultural methods mainly on small family farms. Technology should be able to assist in our efforts to control weeds economically without the need for toxic chemicals on our food crops.

My new book on glyphosate, “Toxic Legacy: How the Weedkiller Glyphosate is Destroying Our Health and the Environment,” will be available for purchase by major booksellers on July 1, 2021. In the book, I explain the unique mechanism by which I believe glyphosate is able to be causal in so many diverse diseases. It involves its demonic ability to act as an imposter for the amino acid glycine. Glyphosate insidiously erodes our health as it accumulates slowly over time in all of our tissues. Glyphosate needs to be banned worldwide, and we desperately need to figure out how to grow food economically without using toxic chemicals.

References
[1] G-E Séralini, E Clair, R Mesnage, et al. RETRACTED: Long Term Toxicity of a Roundup Herbicide and a Roundup-Tolerant Genetically Modified Maize. Food and Chemical Toxicology 2012; 50(11): 4221-4231.

[2] G-E Séralini, E Clair, R Mesnage, et al. Republished Study: Long-Term Toxicity of a Roundup Herbicide and a Roundup-Tolerant Genetically Modified Maize. Environ Sci Eur 2014; 26: 14.

[3] JP Muñoz, TC. Bleak, GM. Calaf. Glyphosate and the Key Characteristics of an Endocrine Disruptor: A Review. Chemosphere 2021; 270: 128619.

[4] S Thongprakaisang, A Thiantanawa, N Rangkadilok, et al. Glyphosate Induces Human Breast Cancer Cells Growth via Estrogen Receptors. Food and Chemical Toxicology 2013; 59: 129-136.

[5] NL Swanson, A. Leu, J. Abrahamson, et al.Genetically Engineered Crops, Glyphosate and the Deterioration of Health in the United States of America. J Org Syst 2014; 9: 6-37.

[6] AA Shehata, W Schrödl, AA Aldin, et al. The Effect of Glyphosate on Potential Pathogens and Beneficial Members of Poultry Microbiota in Vitro. Curr Microbiol 2013; 66(4): 350-8.

[7] W Shaw. Elevated Urinary Glyphosate and Clostridia Metabolites with Altered Dopamine Metabolism in Triplets With Autistic Spectrum Disorder or Suspected Seizure Disorder: A Case Study. Integrative Medicine 2017; 16(1): 50-57.

[8] S Luna, LP Neila, R Vena, et al. Glyphosate Exposure Induces Synaptic Impairment in Hippocampal Neurons and Cognitive Deficits in Developing Rats. Arch Toxicol 2021; 95: 2137-2150.

[9] MK Silver, J Fernandez, J Tang, et al. Prenatal Exposure to Glyphosate and Its Environmental Degradate, Aminomethylphosphonic Acid (AMPA), and Preterm Birth: A Nested Case-Control Study in the PROTECT Cohort (Puerto Rico). Environmental Health Perspectives 2021; 129(5): 057011.

[10] C Lesseur, P Pirrotte, KV Pathak, et al. Maternal Urinary Levels of Glyphosate during Pregnancy and Anogenital Distance in Newborns in a US Multicenter Pregnancy Cohort. Environmental Pollution 2021; 280: 117002.