Glyphosate is a non-selective herbicide. This means that it can kill almost any plant that it contacts. It is now commonly used in herbicides that control weeds that grow among food crops, gardens, lawns, golf courses, public parks, and walkways. Here we will discuss the available literature on the effects of glyphosate on kidney health.

Effects of glyphosate on kidney health

 

By Majd Isreb, MD, FACP, FASN, IFMCP

Glyphosate was patented in 1961 as a chelating agent for mineral deposits that accumulate on pipes and boilers in hot water systems. In 1968, Monsanto (now owned by the pharmaceutical company Bayer) patented glyphosate as an herbicide for agricultural use. It was even patented later as an oral antibiotic.

Because glyphosate is a non-selective herbicide, it was damaging crops. This led to the development of genetically modified organisms (GMO) which are crops resistant to glyphosate. It is estimated that glyphosate is sprayed on U.S. crops at about 150,000 tons yearly.

Humans are exposed to glyphosate by eating crops raised in contaminated soil, drinking contaminated water, and inhaling it. A recent study of the NHANES database found that 80% of American adults and children have glyphosate in their urine.

It has been potentially linked to cancer, mental health issues, endocrine disruption, and other health concerns. But what about its effects on the kidneys?



Glyphosate is present in herbicides as a salt. It is mostly negatively charged, so it binds to positively charged minerals to form various salts. Because of that, it can also bind to other nutrients and heavy metals. This can lead to the depletion of some minerals in crops and increase exposure to heavy metals.

Effects of glyphosate on kidney health

Acute exposure

There have been few case reports of suicide attempts by ingesting glyphosate. These cases were characterized by acute kidney failure due to acute interstitial nephritis, metabolic acidosis, hyperkalemia, and pulmonary edema. Patients may require hemodialysis. Ultimately, they may recover but with persistent chronic kidney disease.

Chronic low-level exposure

The cause of chronic kidney disease of unknown etiology (CKDu) has been debated for years. A recent study showed a possible association between agrochemicals and the development of CKDu.

In 2019, the American Association for the Advancement of Science awarded two Sri Lankan scientists. The scientists reported that glyphosate plays a crucial role in transporting heavy metals to the kidneys of those drinking contaminated water, leading to high rates of chronic kidney disease in farming communities in Sri Lanka.

While the use and exposure to glyphosate are common in the U.S., there is no medical literature connecting it to kidney injury here. Yet, there are various ways that chronic exposure to glyphosate can lead to kidney injury or worsening kidney disease.

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Glyphosate disrupts the mitochondria

The kidneys utilize a significant amount of energy to perform various functions. Many of these functions take place in the tubules. Most of this energy is produced in the mitochondria, which are the powerhouse of the cells.

Glyphosate has been found to cause mitochondrial dysfunction and increase oxidative stress. The mechanism of this complex. However, it is thought to occur by disrupting the mitochondrial membrane potential and oxidative phosphorylation.

Glyphosate also leads to the generation of reactive oxygen species and the depletion of glutathione (the master detoxifier). It also depletes manganese which is necessary for the action of the antioxidant enzyme superoxide dismutase.

 



Glyphosate disrupts the gut microbiome

Glyphosate was patented as an antimicrobial agent in 2010. It was proven to inhibit an enzyme called ESPS synthase in certain bacteria. However, it turns out that most of the good gut bacteria contain that enzyme. In animal studies, exposure to glyphosate decreased these good bacteria in the gut. Other pathogenic (harmful) bacteria have ways to break down glyphosate, making it less effective (more on this later). This can lead to the growth of these harmful bacteria.

This glyphosate-induced dysbiosis has been associated with immune system disruption. This can potentially worsen inflammation in kidney disease and lead to faster progression of CKD.

The makers of the glyphosate herbicide claim that humans cannot break it down and that it is excreted unchanged in the urine. This claim is debated. It is more established that dysbiotic bacteria can break down glyphosate.



There are two major pathways involved in the way bad bacteria break down glyphosate:

  1. One pathway breaks it down into phosphate and sarcosine. The latter is further used to produce the amino acid glycine. Phosphate is used for energy production.
  2. The other process breaks it down into glyoxalate and aminomethylphosphonic acid (AMPA). AMPA is further broken down to formaldehyde. Glyoxalate can further be metabolized to produce glycine and oxalate. Some of that glyoxalate and phosphate may get absorbed.

You can see that this creates a positive feedback loop, in which long-term exposure to glyphosate continuously kills the good bacteria and feeds the harmful bacteria.



Glyphosate and toxic metals

The negatively charged glyphosate can bind to heavy metals. These glyphosate-metal complexes have been proposed as the cause of the epidemic of kidney disease in Sri Lanka.  These complexes tend to concentrate in the kidneys and lead to kidney disease.

On the other hand, glyphosate structure is similar to the amino acid glycine. Glycine, like other amino acids, is used to produce protein in the body. Glyphosate substitution for glycine during protein synthesis is thought to be a contributory cause of diabetes, obesity, Alzheimer’s disease, and other modern chronic diseases.

Glycine substitution in the proteins of the aquaporin, chloride channels, cytochrome C oxidase, and collagen has been proposed to contribute to dehydration, increased urinary acidification, kidney scarring, muscle breakdown, and mitochondrial dysfunction.

Glyphosate and acid load

Potential Renal Acid Load (PRAL) measures the amount of acid or alkali the kidneys are exposed to. It is usually used to assess the potential acid load contained in various food. A higher dietary acid load has been linked to the faster progression of CKD.

Chronic exposure to glyphosate may increase the acid load by various mechanisms. As seen above, the dysbiotic bacteria in the gut can continuously break it down with chronic exposure. Formaldehyde is one of the products of this metabolism. It can be further broken down into formic acid.

In addition, glyphosate uncouples oxidative phosphorylation in the mitochondria. This shifts the mitochondrial energy production to perform anaerobic respiration, which generates more lactic acid.

Glyphosate salts ingestion by itself leads to the release of protons (H+) under typical blood acidity. This further increases the acid load on the kidneys.

Finally, some authorities claim that glyphosate can inhibit an enzyme called glutamine synthetase. This is evidenced by the accumulation of glutamate in the nervous system. It is, therefore, plausible that glyphosate can also inhibit the glutamine-glutamate loop between the liver and the kidneys. This can decrease the kidney’s ability to handle acid excretion.



Glyphosate is a source of oxalate and phosphate

As seen above, glyphosate gets metabolized by harmful bacteria in the gut with further production of oxalate and phosphate. While most of the phosphate is used by these bacteria, some of it could get absorbed. This could partly explain the high phosphate burden in the standard American diet (in addition to food additives).

Most importantly, though, oxalate is produced by the glyphosate metabolism. In the setting of the standard American diet, oxalate formed by the dysbiotic gut bacteria can get absorbed. This further increase the oxalate burden on the body. Oxalate is well known to accelerate kidney disease and bind with calcium in the urine to form kidney stones.

What can you do?

So, you can see that glyphosate is all around us, and most of the U.S. population is exposed to it. Bayer said in 2021 that it would stop selling glyphosate-based weedkillers in the U.S. residential market for non-professional gardeners. Yet, it will continue to sell glyphosate-based weedkillers to farmers, who rely on it heavily. Therefore, your crop will likely continue to be contaminated by it.

Whether Bayer eventually stops selling glyphosate completely or not, you need to take steps to protect yourself. Here are a few recommendations:

  1. Avoid GMO food. Non-GMO certification programs test products to ensure they contain an insignificant amount of GMO material.
  2. Consume organic produce as much as possible. I understand that sometimes buying all organic can be expensive. So, you can use the EWG Dirty DozenTM list to avoid buying highly contaminated produce. These products must be purchased organic.
  3. Filter your water using a reliable water filtration system that removes glyphosate. One product that we recommend is ClearlyFiltered®.
  4. Avoid processed food as much as possible. Processed food is laden with toxins and full of unhealthy preservatives. Soy and corn products in the U.S. are highly processed, and most crops are GMO.
  5. Enhance your diet with antioxidants and supplements containing glutathione and other nutrients chelated by glyphosate, such as manganese.

The bottom line

Glyphosate is all around us. While no clear epidemiological data link it to kidney disease in the U.S., several mechanisms can lead to potential kidney damage. Taking the steps outlined above can help you decrease exposure.