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From the Townsend Letter
January 2017

The Importance of Testing for Glyphosate: The World's Most Widely Used Herbicide
by William Shaw, PhD, and Matthew Pratt-Hyatt, PhD
Director and Associate Director of The Great Plains Laboratory, Inc.
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Glyphosate is the world's most widely produced herbicide and is the primary toxic chemical in Roundup™, as well as in many other herbicides. In addition, it is a broad-spectrum herbicide that is used in more than 700 different products from agriculture and forestry to home use. Glyphosate was introduced in the 1970s to kill weeds by targeting the enzymes that produce the amino acids tyrosine, tryptophan, and phenylalanine. This pathway (called the Shikimate Pathway) is also how bacteria, algae, and fungi produce the same amino acids. This pathway is not present in humans, so manufacturers of glyphosate claim this compound is "non-toxic" to humans. However, evidence shows there are indeed human consequences to the widespread use of this product when we consume plants that have been treated with it and animals who've also consumed food treated with it.
     
ProTheraUsage of glyphosate amplified after the introduction of genetically modified (GMO) glyphosate-resistant crops that can grow well in the presence of this chemical in soil. In addition, toxicity of the surfactant commonly mixed with glyphosate, polyoxyethyleneamine (POEA), is greater than the toxicity of glyphosate alone.1 In 2014, Enlist Duo™, a herbicide product which contains a 2,4-dichlorophenoxyacetic acid (2,4-D) salt and glyphosate, was approved in Canada and the US for use on genetically modified soybeans and genetically modified maize, both of which were modified to be resistant to both 2,4-D and glyphosate. 2,4-D, which has many known toxic effects of its own is perhaps better known as a component of Agent Orange, an herbicide used by the United States during the Vietnam War to increase aerial visibility from war planes by destroying plant growth and crops.
 
Glyphosate and Chronic Health Conditions
Recent studies have discovered glyphosate exposure to be a cause of many chronic health problems. One specific scientific paper listed Roundup™ as one of the most toxic herbicides or insecticides tested.2 Exposure to glyphosate has been linked to autism, Alzheimer's, anxiety, cancer, depression, fatigue, gluten sensitivity, inflammation, and Parkinson's.3-4 A 54-year-old man who accidentally sprayed himself with glyphosate developed disseminated skin lesions six hours after the accident.6 One month later, he developed a symmetrical parkinsonian syndrome. Figure 1 shows the correlation between glyphosate usage and rates of autism, tracking services received by autistic children under the Individuals with Disabilities Education Act (IDEA). This data was originally collected by Dr. Nancy Swanson, along with similar data for many other chronic disorders.14 The causes for these disorders have been linked to glyphosate's impact on gut bacteria, metal chelation, and P450 inactivation.5-6 It can enter the body by direct absorption through the skin, by eating foods treated with glyphosate, or by drinking water contaminated with glyphosate. A recent study stated that a coherent body of evidence indicates that glyphosate could be toxic below the regulatory lowest observed adverse effect level for chronic toxic effects, and that it has teratogenic, tumorigenic and hepatorenal effects that can be explained by endocrine disruption and oxidative stress, causing metabolic alterations, depending on dose and exposure time.7

Figure 1

Glyphosate, Cancer, and the Microbiome
The World Health Organization International Agency for Research on Cancer published a summary in March 2015 that classified glyphosate as a probable carcinogen in humans.8 Possible cancers linked to glyphosate exposure include non-Hodgkin lymphoma, renal tubule carcinoma, pancreatic islet-cell adenoma, and skin tumors. Studies have also indicated that glyphosate disrupts the microbiome in the intestine, causing a decrease in the ratio of beneficial to harmful bacteria.9 Thus, highly pathogenic bacteria such as Salmonella entritidis, Salmonella gallinarum, Salmonella typhimurium, Clostridium perfringens, and Clostridium botulinum are highly resistant to glyphosate, but most beneficial bacteria such as Enterococcus faecalis, Enterococcus faecium, Bacillus badius, Bifidobacterium adolescentis, and Lactobacillus spp. were found to be moderately to highly susceptible. The relationship between the microbiome of the intestine and overall human health is still unclear, but current research indicates that disruption of the microbiome could cause diseases such as metabolic disorder, diabetes, depression, autism, cardiovascular disease, and autoimmune disease.

Glyphosate and Chelation
Another study found that glyphosate accumulated in bones. Considering the strong chelating ability of glyphosate for calcium, accumulation in bones is not surprising. Other results showed that glyphosate is detectable in intestine, liver, muscle, spleen and kidney tissue.5 The chelating ability of glyphosate also extends to toxic metals.10 The high incidence of kidney disease of unknown etiology (renal tubular nephropathy) has reached epidemic proportions among young male farm workers in sub-regions of the Pacific coasts of the Central American countries of El Salvador, Nicaragua, Costa Rica, India, and Sri Lanka.11 The researchers propose that glyphosate forms stable chelates with a variety of toxic metals that are then ingested in the food and water or, in the case of rice paddy workers, may be absorbed through the skin. These glyphosate-heavy metal chelates reach the kidney where the toxic metals damage the kidney. These authors also propose that these chelates accumulate in hard water and clay soils and persist for years, compared to much shorter periods of persistence for non-chelated glyphosate. Furthermore, these chelates may not be detected by common analytical chemistry methods that only detect free glyphosate, thus dramatically reducing estimates of glyphosate persistence in the environment when metals are high (for example, in clay soil or hard water).

Testing for Glyphosate
Because glyphosate has been linked with many chronic health conditions, testing for glyphosate exposure and particularly the level of exposure is important. The lower limit of quantification (LLOQ) for The Great Plains Laboratory's Glyphosate Test is 0.38 μg/g of creatinine. The Great Plains Laboratory is the only CLIA certified lab currently performing a test for glyphosate in urine. Our Glyphosate Test can be performed on the same urine sample as for some of our other comprehensive tests, including the Organic Acid Test (OAT) or GPL-TOX (Toxic Non-Metal Chemical Profile). See Figure 2 for an example of our Glyphosate Test report.

Figure 2

     
As previously mentioned, glyphosate works by inhibiting the synthesis of tryptophan, phenylalanine, and tyrosine in plants. Humans need to obtain these amino acids from food sources. When food sources have scarce amounts of these amino acids due to glyphosate use, humans are at risk for deficiency too. Humans also require bacteria to maintain a healthy immune system. Research indicates that glyphosate decreases the amount of good bacteria in the gut such as bifidobacteria and lactobacilli and allows for the overgrowth of harmful bacteria such as campylobacter and C. difficile.12 Our lab has observed this in patients. We had a female patient who was suffering from depression who did a Glyphosate Test and an Organic Acids Test. Her glyphosate results were 2.99, which was over the 95th percentile and can be seen in Figure 3.

Figure 3

   
Upon analyzing her OAT we noticed two things. The first was that her 4-cresol was extremely high. This increased 4-cresol can be seen in Figure 4. As stated earlier, glyphosate exposure decreases the good bacteria and allows C. difficile to invade. C. difficile produces a toxin called 4-cresol, which we measure in the OAT. Research has shown that 4-cresol inhibits dopamine beta-hydroxylase.13 Dopamine beta-hydroxylase converts dopamine to norepinephrine. In the OAT we measure both homovanillic acid (dopamine metabolite) and vanillylmandelic acid (norepinephrine metabolite). We have observed patients with a high 4-cresol value have elevated homovanillic acid, which indicates an inability to convert dopamine to norepinephrine. The results from our aforementioned patient were consistent with these other results and can be seen in Figure 5. The recommendations for this patient were to treat her glyphosate exposure and to treat her C. difficile infection.

Figure 4

Figure 5

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