The biochemical basis of autism: Strong evidence that increased acetaminophen use in genetically vulnerable children appears to be the major cause of the autism epidemic.
By William Shaw, Ph.D.
It appears that the marked increase in the rate of autism throughout much of the world may be largely mediated by the marked increase in the use of acetaminophen in genetically and/or metabolically susceptible children and perhaps the use of acetaminophen by pregnant women.
The evidence for this hypothesis is already in the peer-reviewed medical literature. Toxicity of acetaminophen appears to cause autism by multiple means including defective sulfation pathways to eliminate acetaminophen that leads to marked increases in the metabolites of a number of species of intestinal Clostridia bacteria prevalent in autism. The increase in Clostridia metabolites significantly decrease brain dopamine beta hydroxylase activity causing an overproduction of brain dopamine and reduced concentrations of brain nor epinephrine. This leads to obsessive, compulsive, stereotypical behaviors associated with brain dopamine excess, reduced exploratory behavior, and learning in novel environments that are associated with norepinephrine deficiency. Such increases in dopamine have been verified by finding marked increases in the major dopamine metabolite homovanillic acid (HVA) in urine. The increased concentrations of dopamine are directly related to the degree of abnormal behavior.
With sulfation of acetaminophen diminished in autism, a larger than usual amount of acetaminophen is detoxified by the cytochrome p450 2E1 system that leads to excessive production of N-acetyl-p-benzoquinone imine (NAPQI) a very toxic metabolite that depletes glutathione, reducing the ability to detoxify a host of toxic chemicals in the environment. The increase of NAPQI creates oxidative stress leading to protein, lipid, and nucleic acid damage from free radicals, causing an increased rate of mitochondrial damage and damage to mitochondrial and nuclear DNA. Impairment of mitochondrial is prevalent in autism. NAPQI production has been found to be increased in humans at recommended dosages of acetaminophen and would be expected to be even higher in people with diminished sulfation capacity.
