Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure

Entropy 2012, 14, 2227-2253; doi:10.3390/e14112227

Stephanie Seneff 1, *, Robert M. Davidson 2 and Jingjing Liu

1 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology,
Cambridge, MA 02139, USA; E-Mail: jingl@csail.mit.edu (J.L.)

2 Internal Medicine Group Practice, PhyNet, Inc., Longview, TX 75604, USA;
E-Mail: patrons99@yahoo.com (R.M.D.)

* Author to whom correspondence should be addressed; E-Mail: seneff@csail.mit.edu; Tel.: +1-617-253-0451.

Abstract: Autism is a condition characterized by impaired cognitive and social skills, associated with compromised immune function. The incidence is alarmingly on the rise, and environmental factors are increasingly suspected to play a role. This paper investigates word frequency patterns in the U.S. CDC Vaccine Adverse Events Reporting System (VAERS) database. Our results provide strong evidence supporting a link between autism and the aluminum in vaccines. A literature review showing toxicity of aluminum in human physiology offers further support. Mentions of autism in VAERS increased steadily at the end of the last century, during a period when mercury was being phased out, while aluminum adjuvant burden was being increased. Using standard log-likelihood ratio techniques, we identify several signs and symptoms that are significantly more prevalent in vaccine reports after 2000, including cellulitis, seizure, depression, fatigue, pain and death, which are also significantly associated with aluminum-containing vaccines. We propose that children with the autism diagnosis are especially vulnerable to toxic metals such as aluminum and mercury due to insufficient serum sulfate and glutathione. A strong correlation between autism and the MMR (Measles, Mumps, Rubella) vaccine is also observed, which may be partially explained via an increased sensitivity to acetaminophen administered to control fever.

1. Introduction
Autism, and, more broadly, autism spectrum disorder (ASD), is a condition characterized by
impaired cognitive and social skills [1], along with a compromised immune function [2–5]. It can now
no longer be denied that the incidence of ASD is alarmingly on the rise in the U.S. [6]. While it has
been suggested that the observed increase in rates may be due mainly to a change in diagnosis criteria,
the actual criteria have changed very little from 1943 to DSM-IV-TR [7–9]. Despite considerable
research efforts devoted to trying to uncover the cause(s) of autism, thus far no definitive answer
seems available from the research literature. However, the fact that ASD rates have been rapidly
increasing over the last two decades strongly points to an environmental component. Indeed, autism is
recently being reframed from being a strictly genetic disease to representing a complex interaction
between genetics and environmental factors, suggesting that we should focus our attention more on
“environmentally responsive genes” [10].

The ASD community has maintained a long-standing conviction that vaccination plays a causative
role in ASD [11], an idea that has been vehemently denied by the vaccine industry [12], but
nonetheless is still hotly debated [13]. A study published in 2011 has confirmed a positive correlation
between the proportion of children who received vaccinations in each state over the interval from 2001
to 2007 and the incidence of autism or speech and language impairment [14]. For each 1% increase in
vaccination rate, 680 additional children were diagnosed with autism or speech delay.
In [15], we proposed that a causative factor in autism is an inadequate supply of cholesterol sulfate,
both in utero and postnatally. Cholesterol sulfate synthesis in the skin is catalyzed by sun exposure [16].
We hypothesized that autism may be induced by a combination of inadequate dietary sulfur and
insufficient sun exposure to the skin, for both the mother and the child. A meta-study involving
oxidative-stress related biomarkers present in association with autism identified a consistent deficiency
in reduced glutathione [17], an important sulfur-based antioxidant that also plays a role in detoxifying
aluminum. We proposed that cysteine, the rate-limiting amino acid involved in the synthesis of
glutathione [18], is depleted through redirection into an alternative pathway to produce sulfate, due to
the impaired sulfate synthesis from thiosulfate in the skin.

A recent study of biomarkers for 28 individuals with an ASD diagnosis showed reduced
glutathione, cysteine, and sulfate compared to controls, and the authors proposed that a reduced
detoxification capacity might impede mercury excretion [19]. These same authors observed a marked
reduction in serum sulfate in association with ASD in another paper [20]. In particular, the level of free
sulfate in the blood stream was only 33% of the level found in control subjects. We hypothesize that
sulfate deficiency results in insufficient ionic buffering in the vasculature, with grossly inadequate
sulfation of the extracellular matrix proteins that are essential for proper colloidal suspension of
particles and cells [21,22].

Glutathione [23] and sulfate [24] are also essential for the detoxification of xenobiotics and
commonly administered drugs like acetaminophen in the liver. Selenium, a trace metal in the same
column of the periodic table as oxygen and sulfur, has been shown to protect against acetaminophen
toxicity [25], and it has also been shown to be severely depleted in hair and nail samples from
individuals on the autism spectrum [26].

A possible link has been found between acetaminophen and both autism and asthma [27]. The
association of both asthma [28] and eczema [29] with ASD can be explained as an inadequate supply
of filaggrin, due to the fact that cholesterol sulfate in the epidermis stimulates the production of
profilaggrin, its precursor [30]. Filaggrin plays an essential role in maintaining the epithelial barrier [31],
and its impairment leads to increased risk of both asthma [32] and eczema [33,34]. Thus cholesterol
sulfate deficiency provides an explanation for the multiple links among autism, acetaminophen,
asthma, and eczema.

It has been demonstrated that chronic aluminum exposure in rats induces depletion of glutathione in
the liver as well as a significant reduction in the synthesis of bile acids [35], which are conjugated with
taurine, the only sulfonic amino acid [36]. Taurine administration in conjunction with aluminum
greatly ameliorates the adverse effects of aluminum on the liver, and this was explained as possibly
due to the ability of the sulfonate group in taurine to bind with heavy metals such as aluminum [37].
These results suggest that glutathione and taurine are both involved in aluminum detoxification in the liver.
Many children with autism have a low amount of serum glutathione, with a larger fraction of it
oxidized to GSSG [38]. Furthermore, increased use of antibiotics leads to an alteration in gut flora
which impairs the ability to detoxify toxic metals like mercury. Dimercaptosuccinic acid (DMSA), an
organosulfur compound with two thiol groups, has been found to be effective in ameliorating the
symptoms of autism in placebo controlled studies [39], likely through its ability to enable the excretion
of toxic metals such as lead and mercury [40]. It also led to a normalization of glutathione levels in red
blood cells [40].

Vitamin D deficiency has been hypothesized to be a risk factor for autism [41]. The over-zealous
application of sunscreen is strongly implicated in autism, not only because sunscreen interferes with
the production of vitamin D3 and cholesterol sulfate but also because it often contains aluminum,
particularly the high Sun Protection Factor (SPF) sunblock products. Aluminum, due in part to its +3
ionic charge, is highly toxic to biological systems [42,43] as will be described more fully in Section 2.1.
Indeed, there are no known life forms that utilize aluminum in any biological systems. The poorly
developed barrier function of the autistic child’s epidermis would likely lead to an increased
penetration of aluminum through the skin. Furthermore, their serum sulfate deficiency leads to an
impaired ability to dispose of aluminum. Aluminum would therefore be expected to accumulate over
time, and, due to increased permeability of the blood brain barrier associated with autism [44], would
almost certainly interfere with neuron function.

In the next section, we examine the evidence from the literature that aluminum toxicity may play a
role in vaccine adverse reactions, and we describe available theories for the mode of toxicity of
aluminum and other toxic metals.

Read the Full Study Here: http://people.csail.mit.edu/seneff/Entropy/entropy-14-02227.pdf


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