I first met Peter a couple of years ago at an Autism Research Institute Think Tank. At the Think Tank Peter impressed everybody with his knowledge, specially about biochemical pathways. He was my lunch buddy for that couple of days and ever since we have kept in touch. I invited him to write a contribution to my blog and he obliged. You can read about his ideas regarding fever and the clinical manifestations of ASD in a previous blog: http://bit.ly/10NyJFk. Peter now wanted to offer his thoughts regarding some interesting data that was recently published. As you will see, the same is a natural progression from his interest in the effects of fever in ASD individuals. However, before going to the blog a few sentences about Peter.
Many people with an illness or disorder read the medical literature looking for clues or treatments. I didn’t realize I was autistic till I began studying it. After 30 years reading (and writing) about multiple sclerosis – with no degrees or formal education in the medical sciences – I noticed similarities between MS and autism. As I began my study (got to save the Lost Boys!) I was fortunate to encounter three cordial advisers early on. Without their guidance I might easily have lost my way in a forest of evidence and citations: Martha Herbert (Massachusetts General Hospital) told me of fever’s phenomenal benefit; Eugene Kiyatkin (National Institutes of Health) clarified fever’s nature and uniqueness; and Jon Pangborn (Autism Research Institute) told me of high blood ammonia in these children.
Acetaminophen (Tylenol) and the autism epidemic
The incidence of autism has risen 10-fold since the early 1980s, with most of this rise not explainable by changing diagnostic criteria (Previc 2007). Biochemist William Shaw (PhD), founder and director of The Great Plains Laboratory, recently presented fresh evidence implicating acetaminophen (Tylenol) in the epidemic of autism in this country. Shaw (2013) reported that Cuba – with an autism incidence a fraction of ours (1/300th) – requires vaccinations (especially against measles), prohibits over-the-counter acetaminophen, and only rarely gives acetaminophen before vaccinations. Fevers persisting more than two days after vaccination are usually treated with prescription metamizole – a drug banned in the U.S. on questionable grounds.
The implications of this evidence are obvious – and staggering. All children in Cuba are vaccinated, especially against measles. Yet our autism rate is almost 300 times theirs – most of it regressive autism about 18 months of age. We give Tylenol freely; Cuba requires a prescription because Tylenol is limited by embargo. But perhaps Cuba uses a single measles vaccine; some think the triple measles-mumps-rubella vaccine (MMR) is the problem. A measles vaccine was introduced into Cuba in 1971 (Galindo et al. 1998) – the MMR introduced in 1986 (Reed & Galindo 2007). If the MMR hasn’t provoked an epidemic of autism in Cuba since 1986, why would it do so in the U.S.?
The most compelling evidence implicating an environmental cause of autism must be the number of normally developing children who gradually or abruptly regress into autism between 12 and 18 months of age. Parents implicated the diphtheria-pertussis-tetanus vaccine (DPT) in their child’s regression in reports to Bernard Rimland (2000) even before he founded the Autism Research Institute (ARI) in 1967. Rimland (1999) suspected the “autism explosion” in the early 1980s was largely due to accelerated efforts by the Centers for Disease Control beginning 1978 (CDC 2008) to promote wider use of the MMR. Yet the MMR, often implicated by parents in their child’s regression, never used the mercury-based preservative thimerosal the DPT and other vaccines used (though the MMR does contain 10% glutamic acid (glutamate) from gelatin to preserve the viruses (Hoernlein 2012).
Schultz and colleagues (2008) asked whether autistic regression after the MMR might be provoked, not by the vaccine itself, but by acetaminophen (Tylenol) given for its pain and fever. An online survey of parents revealed that children given acetaminophen for adverse reactions to the MMR were significantly more likely to become autistic than children given ibuprofen: “Children who used acetaminophen at age 12 to 18 months were more than eight times as likely to be in the AD [autistic disorder] group when all children were considered . . . and more than 20 times as likely to be in the AD group when limiting cases to children with regression . . . .”
In a second paper Schultz (2009) pointed out the synchronicity between the start of the autism epidemic and the CDC’s 1980 warning that aspirin was associated with Reye’s syndrome (Starko et al. 1980) – a rare but often fatal disease in children after a bout of flu or chicken pox. Schultz found the abrupt nationwide shift from aspirin to acetaminophen that began in 1980 was associated with an increased number of children with autistic disorders in California born after 1980.
This synchronicity Schultz detected is intriguing in light of Jon Pangborn’s assessment of the origins of the autism epidemic, based on thousands of cases reported to the ARI since the 1960s. Pangborn, chief ARI biochemist for many years, noted that until about 1980, 50–60% of autistic children were autistic from birth, and 40–50% regressed into autism at about 18 months. “Around 1980,” Pangborn (2002) concluded, “all this began to change. The total frequency of occurrence doubled, doubled again, and by 1995 was approximately 10 times that of 1980. Furthermore, while the onset-at-birth type had increased 3 to 4 times, the onset-at-18-months type had skyrocketed to considerably more than 10 times its 1980 level.” Pangborn concluded that most of the autistic population now appeared to have “an acquired disease caused by something that we were not doing 20 years ago.”
Equally intriguing is a paper by pediatrician James Orlowski and colleagues (2002): Is aspirin a cause of Reye’s syndrome? A case against. They made a variety of arguments: (1) salicylates like aspirin have alleviated fever and pain since the early 1900s, yet Reye’s syndrome was not reported until the early 1950s; (2) other studies worldwide showed no association between aspirin and Reye’s; (3) the incidence of Reye’s was already falling by 1979; (4) Reye’s virtually disappeared from countries that had not given children aspirin since the 1950s, as well as from countries that continued to give children aspirin; (5) U.S. Public Health Service studies between 1980 and 1987 corroborating a link between aspirin and Reye’s were seriously flawed.
My paper “Did acetaminophen provoke the autism epidemic?” in Alternative Medicine Review (2009) emphasized the chronology of the autism epidemic and the toxicity of acetaminophen, a known liver poison. Schultz et al. noted that young children detoxify acetaminophen via sulfation in the liver – a pathway known to be compromised in children with autistic disorders (ASD). I learned that during pregnancy the adrenal androgen and estrogen precursor dehydroepiandrosterone (DHEA) was sulfated to its storage form DHEA sulfate (Leowattana 2001) – most common precursor of placental estrogens (Barker et al. 1994). Did that explain the “extreme male brain” of autism (Baron-Cohen et al. 2005)? Furthermore, sulfation of DHEA required glutathione (GSH) as cofactor (Geier and Geier 2006) – often low in these children.
Shaw presented compelling new evidence confirming acetaminophen depletes glutathione – the body’s primary detoxifying agent and antioxidant, especially in the liver. In a comprehensive indictment of Tylenol and its maker Johnson & Johnson, Shaw implicated acetaminophen in many other disorders, including the epidemic of asthma: “Depletion of GSH as a consequence of acetaminophen toxicity to the liver has attracted the most attention in the medical scientific community, as it can frequently be fatal or require a liver transplant or emergency treatment to prevent liver failure (the liver is the organ with the greatest concentration of GSH). However, acetaminophen toxicity has been implicated in a wide range of other disorders in humans and/or experimental animals including cancer, birth defects, asthma, allergies, and brain toxicity.”
Shaw also noted recent evidence corroborating the association of prenatal and perinatal paracetamol (acetaminophen) with autism. Bauer and Kriebel (2013) pointed out that in the late 1990s the American Academy of Pediatrics recommended paracetamol before and after circumcision: “These guidelines include the suggestion of a first dose of paracetamol two hours prior to the procedure, and doses every 4–6 hours for 24 hours following the procedure. Thus newborn males often receive 5–7 doses of paracetamol during the developmentally vulnerable initial days of life.” Is this another reason boys are 4 times more vulnerable to autism than girls?
Further evidence Shaw reported reveals that in recent years Johnson and Johnson has repeatedly run afoul of the Food and Drug Administration – for mislabeling children’s products (increasing risk of overdose) and poor quality control and contamination at manufacturing plants; millions of bottles of children’s medicines containing acetaminophen have been recalled. Johnson and Johnson also makes Risperdal (risperidone), the antipsychotic drug for ASD with serious side effects.
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