Abstract

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease involving several protein mutations in glycine-rich regions with limited treatment options.

90 – 95% of all cases are non-familial with epidemiological studies showing a significant increased risk in glyphosate-exposed workers.

In this paper, we propose that glyphosate, the active ingredient in Roundup®, plays a role in ALS, mainly through mistakenly substituting for glycine during protein synthesis, disruption of mineral homeostasis as well as setting up a state of dysbiosis. Mouse models of ALS reveal a pre-symptomatic profile of gut dysbiosis.

This dysbiotic state initiate a cascade of events initially impairing metabolism in the gut, and, ultimately, through a series of intermediate stages, leading to motor neuron axonal damage seen in ALS. Lipopolysaccharide, a toxic by-product of dysbiosis which contributes to the pathology, is shown to be statistically higher in ALS patients.

In this paper we paint a compelling view of how glyphosate exerts its deleterious effects, including mitochondrial stress and oxidative damage through glycine substitution. Furthermore, its mineral chelation properties disrupt manganese, copper and zinc balance, and it induces glutamate toxicity in the synapse, which results in a die-back phenomenon in axons of motor neurons supplying the damaged skeletal muscles.


Glyphosate Excretion is Associated With Steatohepatitis and Advanced Liver Fibrosis in Patients With Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease in developed countries.1 Patients with nonalcoholic steatohepatitis (NASH) are considered to be at a higher risk of fibrosis progression and development to cirrhosis and hepatocellular carcinoma. Abbreviations used in this paper: AMPA (aminomethylphosphonic acid), NAFLD (nonalcoholic fatty liver disease), NASH (nonalcoholic steatohepatitis), SD (standard deviation)


Glyphosate and Roundup Disrupt the Gut Microbiome by Inhibiting the Shikimate Pathway

Doses of glyphosate and Roundup that regulators have assumed to be safe also cause fatty liver disease and death of liver tissue.
Report by Claire Robinson and Michelle Perro, MD

  • Nearly all genetically modified (GM) crops worldwide are engineered to be grown with glyphosate-based herbicides such as Roundup.
  • A 2019 study in rats provides the first definitive proof that glyphosate and Roundup can inhibit the series of biochemical reactions known as the “shikimate pathway” in the gut microbiome (bacterial population) and can cause alterations in the abundance of certain bacteria at regulatory-permitted (assumed safe) levels of exposure. The shikimate pathway is responsible for the synthesis of aromatic amino acids that are vital for the production of proteins, the building blocks of life. Studies in rats are generally accepted to be relevant to humans.
  • The health implications of these changes in the gut microbiome are unclear.
  • The study found that the inhibition of the shikimate pathway from glyphosate and Roundup exposure caused a dramatic increase in shikimic acid and 3-dehydroshikimic acid in the gut, suggesting that these substances could be used as biomarkers of exposure to these pesticides.
  • The study also showed that Roundup, and to a lesser extent glyphosate, damaged the liver and kidneys of the rats. Some of the test doses of Roundup caused an increase in lesions indicative of fatty liver disease and necrosis (death of tissue), confirming and extending previous research.
  • The new study proposes a specific mechanism through which exposure to glyphosate-based herbicides can cause cancer. Rats fed Roundup and glyphosate showed elevated levels of shikimic acid in their gut. Shikimic acid can either protect the body from oxidative stress, or it can act as a cancer promoter. The mechanism of action of glyphosate on the gut microbiome, newly identified in this study, might be of relevance to glyphosate’s ability to cause cancer.
  • It would be clinically useful to conduct surveys of human populations, such as those in the USA who are generally exposed to higher levels of glyphosate herbicides compared to other regions, to see if there is a correlation between levels of glyphosate in urine and levels of shikimic acid and 3-dehyroshikimic acid in feces, blood, and urine.



als:
http://healthimpactnews.com/2016/study-glyphosate-herbicide-associated-with-greater-risk-to-als/


2019 Mills: Glyphosate Excretion is Associated With Steatohepatitis and Advanced Liver Fibrosis in Patients With Fatty Liver Disease
https://www.cghjournal.org/article/S1542-3565(19)30361-1/fulltext


shikimate: Glyphosate and Roundup Disrupt the Gut Microbiome by Inhibiting the Shikimate Pathway
https://www.gmoscience.org/glyphosate-and-roundup-disrupt-the-gut-microbiome-by-inhibiting-the-shikimate-pathway