Glyphosate Metabolite AMPA is a Neurotoxin
Two years ago, the first experimental evidence that glyphosate and its most prevalent metabolite AMPA can cross the blood brain barrier and induce increased production of a pro-inflammatory cytokine called tumor necrosis factor alpha and soluble amyloid beta plaque, was published in the Journal of Neuroinflammation. I summarized the results here on Quora:
A recently published transgenic rodent experiment found that 13 weeks of chronic exposure to technical glyphosate at the EPA’s no observable adverse effect limit (500 mg/kg body weight) and a 10x lower dose followed by a 6 month recovery period of no exposure induced long lasting increases in inflammatory cytokines and chemokines in peripheral blood plasma of mice with Alzheimer's disease pathologies as well as long lasting inflammatory dose dependent changes in cortical tissue for both transgenic and non-transgenic control mice for inflammatory cytokines that are markers of accelerated aging, neurodegeneration, macrophage activation, cell proliferation and prevention of programmed cell death. Earlier glyphosate exposure also created a dose-dependent increase in an anti-inflammatory cytokine type associated with homeostasis maintenance that is higher in people with Alzheimer’s Disease in both transgenic and non-transgenic mice. Chronic exposure led to a dose-dependent increase of amyloid beta plaque fractions in the hippocampus and cortex of transgenic mice with Alzheimer’s disease pathologies 6 months after exposure had ceased. This is the first experiment to demonstrate that the glyphosate metabolite AMPA can accumulate in brain tissue increasing Alzheimer disease pathology in humanized mice and increasing risk of neurodegenerative disease development in non-transgenic mice without Alzheimer’s disease through the hallmarks of neuroinflammation and amyloid beta plaque build up by altering amyloid precursor protein processing. In the Morris Water Maze test part of this experiment transgenic mice exposed to glyphosate showed a higher tendency to remain near walls than non-exposed transgenic mice indicating increased anxiety suggesting the neuroinflammation may affect the amygdala as well.
While no IRB would approve of any remotely similar experiment on humans we still have evidence from human cell culture studies and epidemiological research that chronic glyphosate exposure is neurotoxic and associated with cognitive impairment in older adults.
A urianalysis of samples submitted by senior participants in the 2013-14 National Health and Nutrition Examination Study who are at least 60 years of age and provided prior data on glyphosate urine concentrations and cognitive performance tests (n = 465) found that 84% of participants had urinary concentrations of glyphosate and its metabolites above the lower limit of detection (0.2 ng/mL) with an average concentration of 0.628 ng/mL. Urinary glyphosate concentrations were positively associated with impairment scores of animal familiarity and delayed response on the cognitive performance test in the highest quartile of glyphosate concentration compared to the lowest quartile.
A cross sectional study conducted among 10-12 year old school children in Cyprus recruited from 6 randomly selected schools (n = 177) found that AMPA concentrations above the limit of quantification (0.1 micrograms/L) was positively associated with DNA oxidative damage markers.
A peripheral blood mononuclear cell experiment demonstrated that a 0.1 and 1 microgram/mL concentration of glyphosate significantly reduced interferon gamma release, a 0.01 and 0.1 microgram/mL concentration significantly increased interleukin-4 release, a 1 microgram/mL concentration of glyphosate significantly reduced interferon gamma positive cells and a 10 microgram/mL concentration of glyphosate significantly reduced the ratio between interferon gamma positive cells and interleukin-4 positive cells. The authors note that the results of this experiment indicate that small doses of glyphosate can affect T helper cell differentiation between type 1 and type 2 leading to disproportionate increase in type 2 that release pro-inflammatory cytokines. The results show that glyphosate, like most environmental toxins, has a non-monotonic effect on t helper cell differentiation with smaller concentrations sometimes larger effects than larger concentrations.
As I mentioned in The EPA is Lying About Forever Chemicals in Pesticides, a cell culture study using human embryonic kidney cell lines found that RoundUp’s supposedly inert co-formulants are 3-358x more cytotoxic than glyphosate in isolation. This would include not only the heavy metals found in the formula but also the polyoxyethylene amines.