ORIGINAL ABSTRACT

Epidemiological studies have found 2 significant factors associated with the increased incidence of autism spectrum disorder (ASD): the increased use of acetaminophen in the 1970s when this drug largely replaced the use of aspirin for many patients because of a fear of Reye syndrome, and the agricultural use in the 1990s of the herbicide glyphosate on crops that were genetically modified (GM) to tolerate glyphosate. The incidence of autism in the United States, where acetaminophen is widely available, is more than 1000 times greater than in Cuba, where acetaminophen is available only by prescription. Metabolites of both glyphosate and acetaminophen likely alter the function of the developmental protein sonic hedgehog (SHH). Glyphosate likely affects SHH indirectly by decreasing the beneficial flora of the gastrointestinal tract and increasing pathogenic Clostridia bacteria, which are resistant to glyphosate. The marked increase of certain Clostridia species caused by glyphosate results in Clostridia production of large amounts of 3-(3-hydroxyphenyl)-3-hydroxypropionate (HPHPA) and 4-cresol (p-cresol). The 4-cresol metabolite 4-methyl-o-hydroquinone and the acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) likely react with the sulfhydryl group of the N-terminal cysteine of SHH, blocking the function of this critical amino acid required for the activation of SHH. HPHPA and 4-cresol also inhibit dopamine β-hydroxylase, resulting in overproduction of dopamine and its toxic metabolites, such as aminochrome, that cause biochemical damage to mitochondria and structural proteins in brain cells. Elevated amounts of these Clostridia products in body fluids in people with autism and in animals with autistic signs have been documented in laboratories throughout the world. The synthesis of the HPHPA molecule in extremely large quantities depletes the body of free coenzyme A, which is needed for the palmitoylation of SHH. SHH covalently coupled to palmitic acid is 30 times more active than SHH without palmitic acid. These possible modifications of SHH help to explain the significantly altered quantities of SHH in the blood serum of patients with autism. The severity of autism is related to the degree of SHH abnormality. The spread of pathogenic Clostridia worldwide from soil to food animals to humans, which may be promoted by glyphosate use, is a great public health concern, not only for autism but perhaps for all the neuropsychiatric diseases that appear to be related to gastrointestinal Clostridia overgrowth These diseases include seizures, tremors, tic disorders, Parkinson disease, chronic fatigue syndrome, obsessive compulsive disorder, schizophrenia, bipolar and unipolar depression, ADHD, and anorexia nervosa.