Could one of the most widely prescribed antibiotics amoxicillin/clavulanate “augmentin™” be a risk factor for autism?
Section snippets
History of autism
Autism is an ever increasing problem in the United States. Characterized by multiple deficits in the areas of communication, development, and behavior; autistic children are found in every community in this country and abroad. Estimates now hover around the 4–20 per 100,000 children [1], [2], [3], [4]. Recent findings from the MIND Institute at the University of California Davis states that: “the unprecedented increase in autism in California is real and cannot be explained away by artificial
Etiologies
Many causes of autism have been postulated. They range from environmental to toxicological causes. The most current thinking including that of some in Congress is that vaccination and more specifically the mercury based preservative in the vaccination is causing brain damage in children resulting in autism [6]. Other theories such as that of Andrew Wakefield a pediatric gastroenterologist who found the measles virus in the biopsied small intestines of autistic children on whom he performed
Examining the time-line
In looking at temporal factors which may be connected to the onset of the increase in autism, one needs to examine what types of medication, and/or drug introductions have been made to coincide with the onset of autism. One such potential causative factor which fits the time-line test is amoxicillin/clavulanate. Introduced in the early 1980s use of this preparation for otitis media began to appear in the literature in the mid to late 1980s [11], [12], [13], [14]. It appears that no other new
Clinical findings
206 children with autism not related to a known genetic condition, birth trauma, or known neurological disease was seen in the office and a detailed case history was obtained. The 206 children had a mean number 9.96 bouts of otitis media (standard error of the mean of ±1.83). This represented a sum total for the 206 children under the age of three years of 2052 bouts of otitis media. These children received a mean number of 12.04 courses of antibiotics. (The standard error of the mean of
Mechanism of clavanic acid/amoxicillin
Clavulanic acid (CA) is a β-lactamase inhibitor is used commercially as a component of a pharmaceutical formulation, generally in the form of a salt, especially potassium clavulanate. CA is produced commercially by culturing the microorganism streptomyces clavuligerus. CA and its alkali metal salts and esters are active inhibitors of β-lactamase produced by some gram positive as well as gram negative micro-organisms. Additionally, CA and its alkali metal salts also have a synergistic action
Manufacturing clavulanate/amoxicillin
Clavulanic acid and its derivatives such as potassium clavulanate are extremely moisture sensitive, and its formation must be carried out under conditions of relatively low humidity. When CA is prepared, it is done so by the process of adding urea or an available ammonia source to a fermentation broth. The fermentation process for producing CA are particularly sensitive to concentrations of ammonia in the system. While ammonia is needed to catalyze the fermentation system, it needs to be kept
Urea nitrogen poisoning
Urea and nitrogen poisoning is well known in the agriculture literature. While much has been written about nitrate and nitrite poisoning in livestock, little is written about it in humans. There is generally a two-fold effect of urea poisoning: (1) the neurotoxic effect on brain tissue, and (2) the highly alkaline corrosive effects of NH3 levels in the digestive tract. Moderate to acute signs of urea poisoning include abdominal colic, bloating, diarrhea, muscle tremor, incoordination, weakness,
Conclusion
In light of these findings, It is important that further studies be undertaken. Such studies could include endoscopic studies pre and post administration of Augmentin™ as well other neurotoxicological studies which would measure the potential residue of CA in the GI systems of children, especially in infants and toddlers. Since Augmentin™ is one of the most widely prescribed drugs for children and that its introduction into the marketplace for use in the treatment of childhood illnesses
References (24)
- et al.
On the twin risk in autism
Am J Hum Genet
(2002) Modern management of otitis media
Pediatr Clin North Am
(1989)- et al.
A randomized controlled trial of amoxicillin plus clavulanate compared with cefaclor for treatment of acute otitis media
J Pediatr
(1986) Cot-death: the ammonia factor
Med Hypoth.
(1985)- et al.
Ammonia intoxication: a hazard during rehabilitation of protein-deprived rats
J Nutr
(1975) - et al.
Childhood disintegrative disorder. Re-examination of the current concept
J Am Acad Child Adolesc Psych
(2002) Autism – what is it and where does it come from?
QJM
(2002)- et al.
The epidemiology of autistic spectrum disorders: is the prevalence rising
Ment Retard Dev Disabil Res Rev
(2002) - et al.
Descriptive epidemiology of autism in a California population: Who is at risk?
Autism Dev Disord
(2002) - University of California, Davis, MIND Institute (October 2002). Report to the Legislature on the Principal Findings...
NIEHS investigates links between children, the environment, and neurotoxicity
Environ Health Perspect
Enterocolitis, autism and measles virus
Mod Psych
Cited by (34)
Evidence the U.S. autism epidemic initiated by acetaminophen (Tylenol) is aggravated by oral antibiotic amoxicillin/clavulanate (Augmentin) and now exponentially by herbicide glyphosate (Roundup)
2018, Clinical Nutrition ESPENCitation Excerpt :Autistic regression between 12 and 18 months was commonly associated with gastrointestinal symptoms [20]. Fallon found many autistic children under three with otitis media treated with oral antibiotic amoxicillin/clavulanate (Augmentin), made with ammonia [21]. ASD children had more ear infections than typical children and were treated with more antibiotics [22].
Gut-to-Brain Axis in Autism Spectrum Disorders: Central Role for the Microbiome
2016, International Review of NeurobiologyCitation Excerpt :Two human studies report on the effects of antibiotic use on the (development) of ASD. Children with ASD have significantly more ear infections and use significantly more antibiotics (Fallon, 2005; Niehus & Lord, 2006). Moreover, the use of antibiotics during pregnancy was regarded as potential risk factors for ASD (Atladóttir, Henriksen, Schendel, & Parner, 2012).
Complementary and Alternative Medicine Treatments for Children with Autism Spectrum Disorders
2015, Child and Adolescent Psychiatric Clinics of North AmericaDoes infectious fever relieve autistic behavior by releasing glutamine from skeletal muscles as provisional fuel?
2013, Medical HypothesesCitation Excerpt :Horvath and Perman found autistic regression between 12 and 18 months was associated with the onset of gastrointestinal symptoms [126]. Fallon found many autistic children under the age of three with otitis media treated with the antibiotic amoxicillin/clavulanate (Augmentin), which she thought might elevate blood ammonia [127]. Analyzing medical records, Niehus and Lord concluded that ASD children had more ear infections than typical children, and were treated with more antibiotics [128].
Do salt cravings in children with autistic disorders reveal low blood sodium depleting brain taurine and glutamine?
2011, Medical HypothesesCitation Excerpt :Acetaminophen for vaccine reactions may impair the liver’s clearance of vasopressin – and underlie the autism epidemic [46,81]. Intestinal colonization by harmful bacteria initiated by amoxicillin/clavulanate (Augmentin) [82–84], an oral antibiotic introduced in 1981, may also explain why the epidemic began in the early 1980s [59]. One might first simply ask: Does your child crave salt?