Comment to FDA on acetaminophen

toxicity and regressive autism 2009

   Kerry Scott Lane MD

PUBLIC SUBMISSION As of: July 28, 2009
Tracking No. 809c7480
Comments Due: June 08, 2009
Late comments are accepted

Docket: FDA-2009-N-0138
Joint Meeting of the Drug Safety and Risk Management Advisory Committee, Nonprescription Drugs Advisory Committee, and the Anesthetic and Life Support Drugs Advisory Committee; Notice of Meeting.

Comment On: FDA-2009-N-0138-0001
Joint Meeting of the Drug Safety and Risk Management Advisory Committee, Nonprescription Drugs Advisory Committee, and the Anesthetic and Life Support Drugs Advisory Committee; Notice of Meeting – Notice of Meeting

Document: FDA-2009-N-0138-0005
Kerry Scott Lane MD – Comment


Submitter Information
Organization: St. Mary’s Medical Center, W. Palm Beach, FL


General Comment

Acetaminophen, Glutathione Depletion, and Regressive Autism

Acetaminophen toxicity in the liver is well established. One of the known toxic effects of this commonly used drug is depletion of the most important antioxidant, glutathione. Disease states linked to depletion of glutathione and excessive amounts of oxidized glutathione, versus reduced glutathione, include Diabetes, Atherosclerosis, AIDS, Alzheimer’s, Pregnancy Induced Hypertension (PIH), and others.

Regressive Autism is a condition that has defied a definitive pathobiology to
date. The attachments enclosed reveal that acetaminophen, by exacerbating an
already depleted glutathione antioxidant system due to a preexisting condi-tion, triggers autism in the peri-vaccination period by reducing glutathione levels to below a critical level. Adequate glutathione levels are crucial to the effective functioning of the Metallothionein (MT) System. The MT system is involved in metabolism of metals, as is glutathione. However, the MT system is especially critical to the metabolism of Zinc in the brain. In states of depleted glutathione and excess oxidized glutathione, free Zinc is released in brain cells. This free zinc is toxic to the mitochondria, causing cellular hypoxia and a generalized neurological malfunctioning that we now recognize as Autism.

It appears acetaminophen alone is not enough to cause Autism. The co-morbid
pathobiology is due to the creation of a state of abnormal gastrointestinal biology due to antibiotic administration to the infant. This allows the replacement of the normal GI flora with yeast overgrowth by Candida species and others. Many yeasts and fungi produce mycotoxins which have been shown to be pathological to man and animal alike.

Recently interest has focused on a mycotoxin known as Gliotoxin which has
been shown to be immunosuppressive, by killing CD4 cells, along with a multitude of other deleterious effects. Gliotoxin has been shown to form adducts with glutathione, essentially removing it from the pool of bioavailable antioxidants. Over fifty per cent of Candida species have been shown to produce Gliotoxin. If we envision a sequence of events that results in an undesirable yeast in the GI tract, causing a depletion of glutathione and generalized oxidative stress, followed by a vaccination that includes a metal adjuvant (mercury or aluminum), followed by the administration of aceta-minophen (antipyretic) to an infant – at a critical period of neurodevelopment – we can envision the pathobiology of Autism.

The enclosed attachments from peer-reviewed articles are a roadmap to the
above described pathobiology. I suggest the FDA act with all due haste to make this material public so the autism epidemic can be properly managed. Additional focus should be directed to the AIDS syndrome, which also involves depletion of glutathione. It would seem acetaminophen is inappropriate in this setting, and possibly in most settings.

Kerry Scott Lane MD
St. Mary’s Medical Center
June 6, 2009


Aschner M, Syversen T, Souza DO, Rocha JB. Metallothioneins: mercury species-specific induction and their potential role in attenuating neurotoxicity. Exp Biol Med (Maywood). 2006;231(9):1468-1473.

Bernardo PH, Brasch N, Chai CL, Waring P. A novel redox mechanism for the glutathione-dependent reversible uptake of a fungal toxin in cells. J Biol Chem 2003;278(47):46549-46555.

Bernardo PH, Chai CL, Deeble GJ, Liu XM, Waring P. Evidence for gliotoxin-glutathione conjugate adducts. Bioorg Med Chem Lett 2001;11(4):483-485.

Kaur P, Aschner M, Syversen T. Glutathione modulation influences methyl mercury induced neurotoxicity in primary cell cultures of neurons and astrocytes. Neurotoxicology 2006;27(4):492-500.

Kromidas L, Trombetta LD, Jamall IS. The protective effects of glutathione against methylmercury cytotoxicity. Toxicol Lett 1990;51(1):67-80.

Liu J, Liu Y, Hartley D, Klaassen CD, Shehin-Johnson SE, Lucas A, Cohen SD. Metallothionein-I/II knockout mice are sensitive to acetaminophen-induced hepatotoxicity. J Pharmacol Exp Ther 1999;289(1):580-586.

Micheli L, Cerretani D, Fiaschi AI, Giorgi G, Romeo MR, Runci FM. Effect of acetaminophen on glutathione levels in rat testis and lung. Environ Health Perspect 1994;102(Suppl 9):63-64.

Shah DT, Larsen B. Clinical isolates of yeast produce a gliotoxin-like substance. <>

Terneus MV1, Kiningham KK, Carpenter AB, Sullivan SB, Valentovic M. Comparison of S-Adenosyl-L-methionine and N-acetylcysteine protective effects on acetaminophen hepatic toxicity. J Pharmacol Exp Ther 2007;320(1):99-107.