Draft for the book titled " Increase Children's IQ and Adult Cognition with Targeted Detox"
Dennis
N. Crouse 2/24/2020
Research has made it clear
that environmental factors modulate the symptomology of those with a genetic
predisposition to attention deficit hyperactivity disorder (ADHD). Herein is a
review of how this research has cast light on mechanisms that explain why both
environmental aluminum and mercury are modulators and thereby causal factors of
ADHD.
Introduction
Sometimes anecdotal
information forces us to ask: Why? The following anecdotal information was
received shortly after publishing the book “Silica Water the Secret of Healthy
Blue Zone Longevity in the Aluminum Age”18:
1.
“My son has been on Fiji water for about 5 months, and his ADHD
is basically gone. We saw a change in him after one week on Fiji. He had ALL
the symptoms of ADHD to the max. He had little control over his physical
movements or his emotions. But that has really changed since the Fiji.” Nov.
2018
2.
“Personally, I have used Acilis silica water
for my child who has ADHD and monitored any changes. As you may know silica
rich water removes accumulated aluminium from the body. I can now say after
several months of use my son who is 12 has gained better focus to the point
where he is refusing to use ADHD medicating presently (which I am monitoring).
He feels he can now focus without it, and so far, I have had no indication from
school to negate that. He has improved in his self-regulation, his skin is less
dry and minor eczema and dry scalp have gone. After some dietary research it
has been noted he is no longer craving aluminium affected foods which he did
previously. So, I believe he has been affected by aluminium toxicity” Aug. 2019
These two reports from the
U.S. and U.K. indicate that by drinking one of two different silica waters,
Fiji with 124ppm of orthosilicic acid (OSA) or Acilis with 88ppm of OSA, the
symptoms of ADHD are significantly diminished. This review of the scientific
literature answers the question: “Why can
drinking silica water rich in OSA decrease the symptoms associated with ADHD?”
Diagnosis of ADHD
A diagnosis of ADHD depends
on meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition’s
(DSM-V 2013) criteria for symptoms of ADHD1. Criteria for symptoms
of ADHD have remained about the same since 1995 when the fourth edition was
published. In DSM-V ADHD is defined as a neurodevelopmental disorder
characterized by symptoms of inattention, hyperactivity, and impulsivity that “interfere
with or reduce the quality of performance in important life domains”1.
Formerly in DSM-IV an ADHD diagnosis was characterized by the same symptoms but
required “clinically significant impairment”. In 2009 ADHD was the most common
psychiatric disorder among children with 3 – 4 fold increased prevalence in
males2. Although usually diagnosed in childhood, 60% of these ADHD
cases persist into adulthood3. Those diagnosed with ADHD are divided
into three presentations:
·
Predominantly inattentive
presentation
·
Hyperactive-impulsivity
presentation
·
Combined presentation – at
least 6 inattentive and 6 hyperactive-impulsive symptoms
Because of this variety of presentations
among individuals diagnosed with ADHD, more than just one neurotransmitter/hormone
system must be involved4. The primary factors in the development of
ADHD are generally accepted to be the failed ability of several monoamine
systems in the brain to produce sufficient serotonin,
dopamine, norepinephrine, epinephrine and/or acetylcholine2,5.
Pharmacology of ADHD
Based upon the insufficient
monoamine premise underlying ADHD, the pharmaceutical industry has demonstrated
to the satisfaction of the US Food and Drug Administration (FDA) that certain manmade
chemicals (i.e. drugs) that impact these monoamine systems can be used to treat
the symptoms ADHD. These drugs do not increase the total number of monoamine
neurotransmitter molecules in the brain, instead these drugs provide palliative
relief by blocking transporters of monoamine neurotransmitter molecules in the
brain and thereby inhibiting reuptake of monoamine transporters in certain
locations. For example Ritalin, Adderall, and Strattera all potentiate norepinephrine
by blocking its transporter and thereby inhibiting its reuptake. Unfortunately,
most of these drugs have serious side effects and the process of reuptake
inhibition may deplete monoamine neurotransmitters/hormone throughout the body5.
These factors lower the efficacy of these drugs through the course of treatment.
Genetic Component of ADHD
Twin, adoption, and molecular
genetic studies all have shown that ADHD is heritable and therefore has genetic
components2,6-8. A genetic variant in the gene (SLC6A2) that encodes the norepinephrine
transporter (NET) has been found. This genetic variant has an abnormal T
allele at nucleotide 3081 that reduces gene expression of NET by 50% in
individuals with this polymorphism. This genetic variation in expression of NET
significantly increases the risk for ADHD6. A genetic variant in the
gene (SLC5A7) that encodes the
presynaptic choline transporter (CHT)
is found in 6% of the human population. This genetic variant encodes a
substitution of valine for isoleucine at position 89 resulting in a CHT polymorph
that exhibits only 50-60% of the maximal rate of normal choline uptake7. This genetic variation in CHT lowers acetylcholine production and significantly
increases the risk for ADHD, particularly in children with the combined presentation2.
Epidemiology of ADHD
Epidemiology studies indicate
that the prevalence of an ADHD diagnosis in young children is increasing in the
U.S. and worldwide. Using The National Survey of Children’s Health (2007-2008,
2011-2012, and 2016) it was found that 1% of U.S. children aged 2 to 5 had an
ADHD diagnosis in 2007-2008, 1.5% had an ADHD diagnosis in 2011-2012, and 2.0%
had an ADHD diagnosis in 20179,10. This data is consistent with a
study of insurance claims for children 2 to 5 receiving clinical care for ADHD
showing a similar increase from 2008 to 201411. All of these
increases in the U.S. were seen during a period of time when there was no
change in the criteria for symptoms of ADHD published in the DSM IV and DSM V. The
worldwide pooled prevalence of ADHD is also rising with 5.29% of children in
2007, 5.9-7.1% in 2012, and 7.2% in 201412-14.
Environmental Causal Factors of ADHD
Assuming this increase in
ADHD as seen in epidemiology studies is real, then the cause of ADHD must have
an environmental component as a genetic change due to one or more mutations
does not move through the population
fast enough to account for the increased prevalence of ADHD. Identifying causal
environmental factors of ADHD requires brain analysis and a mechanism
accounting for how environmental factors cause the pathology seen in those with
ADHD. Clues would include the
identification of one or more environmental factors that lower the biosynthetic
production of the four monoamine neurotransmitters in the brain: serotonin,
dopamine, norepinephrine, and acetylcholine, in addition to the monoamine hormone
epinephrine (a.k.a. adrenaline). All of these monoamines are biosynthesized in
the body from three amino acids: L-tryptophan (TRP), L-phenylalanine (PHE), and
L-serine (SER). These three amino acids are among the 20 amino acids that are
made into proteins by our body. The biosynthesis from TRP, PHE, and SER of
monoamine neurotransmitters/hormone in the body is shown in figures 1-3.
Aluminum Causes THB Deficiency
Without sufficient THB as a
cofactor for either the enzymatic conversion of TRP to 5-HTP (figure 1) or PHE
to L-DOPA (figure 2), the production of serotonin, dopamine, norepinephrine,
and epinephrine will decrease. In addition, without sufficient THB the level of
PHE in the blood will increase (figure 2).
An elevated level of PHE in the blood is in some cases associated with
ADHD symptomology15.and in other cases with phenylketonuria (PKU) symptomology16.
PKU is an inherited genetic condition involving lower levels of the enzyme
phenylalanine hydroxylase. This results in impaired breakdown of PHE to
L-tyrosine (TYR) in the liver that also leads to detrimental PHE accumulation
in the brain16. It was found
that 57% of those diagnosed with PKU responded to THB treatment lowering their
PHE levels by at least 20%. Of those who responded to THB treatment, 32% had
ADHD symptoms prior to treatment and 85% of these were not on medication for
ADHD. After 13 weeks of THB treatment there was a significant improvement in
the attentiveness score of the 32% with ADHD symptoms as compared to the group
given a placebo15.
When THB is used as a
cofactor in the conversions diagrammed in figures 1 and 2 it is oxidized to DHB
(dihydrobiopterin). In order to maintain
levels of THB, the body regenerates THB from DHB with either of two enzymes: dihydrobiopteridine
reductase (DHPR) and dihydrofolate reductase (DHFR)17. An enzyme is
a protein that facilitates the conversion of chemicals and in this case two
enzymes can facilitate the regeneration of THB from DHB. Both of these enzymes
have active sites where DHB can bind and be more easily reduced to THB. This
process of regenerating THB from DHB is diagrammed in figure 4.
Aluminum is an environmental
pollutant whose production is increasing exponentially worldwide18. Because
of this, worldwide aluminum exposure is also increasing exponentially18
and could be a causal factor of ADHD accounting for the increasing rate of ADHD
in the U.S. and worldwide. Aluminum inhibits
regeneration of THB by reducing the activity of DHPR by 40%19,20.
What inhibits DHPR also likely inhibits DHFR as both of these enzymes have
similar amino acid sequences at their active sites. Both of these amino acid
sequences involve the amino acids tyrosine (TYR) and lysine (LYS) separated by
three amino acids21. Aluminum is known to bind tightly with both TYR
and LYS22. Therefore aluminum likely inhibits DHFR as well as DHPR.
When aluminum inhibits the
regeneration of THB from DHB there is a less THB. Less THB results in less
production of both 5-hydroxytrypthophan (5-HTP) and L-DOPA (see figures 1 and 2).
Since 5-HTP and L-DOPA are the precursors of serotonin, dopamine,
norepinephrine, and epinephrine, the question is: does administration of 5-HTP
and L-DOPA reverse the symptoms of ADHD? Just such a protocol was tested with
85 patients, aged 4-18 years, diagnosed with ADHD. The results published in
2011 demonstrated that the efficacy of this protocol appears superior to some
ADHD prescription drugs5.
This work supports the contention that environmental pollutants, such as
aluminum, that reduce the activity of DHPR and DHFR and thereby lower DHB to THB regeneration, may be a casual factor of ADHD.
Lower than normal THB levels
in the cerebrospinal fluid is a characteristic of several neurodevelopmental disorders,
including autism (ASD)23-25. Children diagnosed with ASD compared
with normal children have 42% lower than normal THB levels in the cerebrospinal
fluid25. ASD is symptomatically a clinically heterogeneous neurodevelopmental
disorder. Some children with ASD have a high rate of executive function
problems, inattention, and hyperactivity and these ADHD-like symptoms suggest
dopamine and norepinephrine deficits26-28. The DSM-V diagnostic
criteria permit ADHD to be diagnosed in conjunction with ASD1. In
the past it was felt that ADHD symptoms were always better explained by the
child’s autism.
By administering drugs that
are designed to increase dopamine and norepinephrine levels, these ADHD like
behaviors are mitigated in some children diagnosed with ADHD and ASD29,30. Therefore it is not surprising that oral
administration of THB as Kuvan has been shown to improve these behaviors of
some children with ADHD and ASD15,31. Also administration of a
chelator of aluminum (desferoxamine) reverses DHPR inhibition by aluminum in
humans20. Since drinking silica rich water has been shown to lower
aluminum in all major organs of the body, including the brain, it is not
surprising that drinking silica rich water also improves these behaviors in
some children with ASD18 and ADHD (see anecdotal information in the
introduction). Recently much higher than normal levels of aluminum has been
found in the brains of those diagnosed with ASD32. Currently levels
of aluminum have not been tested in the brains of those diagnosed with ADHD.
Aluminum Causes SAM Deficiency
There is experimental
evidence that acetylcholine increases the response to major stimuli of cortical
circuits in the brain while suppressing minor background stimuli and enhancing
encoding of memory for specific stimuli resulting in improved attention33.
Therefore acetylcholine improves attention and an attention deficit will be
observed when its biosynthesis is inhibited. The biosynthesis of acetylcholine requires three
molecules of SAM (S-adenosyl-methionine, SAMe) to trimethylate each molecule of
2-aminoethanol to choline (figure 3). Also the biosynthesis of epinephrine from
norepinephrine requires SAM (figure 2) and the enzyme phenylethanolamine
N-methyltransferase (PNMT).
Aluminum inhibits the activation of methionine synthase, an enzyme
involved in SAM biosynthesis,
thereby lowering availability of SAM and decreasing production of acetylcholine
and epinephrine34,35. SAM also increases the half-life of PNMT by
protecting it from degradation36. Aluminum inhibition of SAM biosynthesis results in less PNMT and less
epinephrine. This inhibition by aluminum may be reversed by drinking silica
rich water18.
Aluminum Inhalation Increases the Prevalence of ADHD
A study of 65 aluminum
welders revealed above normal levels of aluminum in their urine and serum when
compared with 25 mild steel welders. Concentration and memory difficulties were
the two most prevalent symptoms among the aluminum welders. The severity of
these symptoms correlated with urine and serum aluminum levels (P-values 0.005
and <0.001 respectively) 37. These attentional deficits seen in
adult welders due to the inhalation of aluminum vapor is also seen in children
of mothers who smoked during pregnancy. Tobacco and cannabis contain aluminum, as
much as 3.7mg per gram, and it is vaporized, inhaled, and absorbed by the lungs
during smoking38. A study of 209 preschool children in New York
found that maternal smoking during pregnancy was associated with an increased
risk of ADHD39. In a second case-control
study of 222 children it was found that maternal smoking during pregnancy
increased the odds of ADHD40.
Mercury Inhibits Acetylcholine Biosynthesis
Inorganic mercury ions (Hg2+)
inhibit the biosynthesis of acetylcholine at concentrations of 1 micromolar by
inhibiting the enzyme, choline acetyltransferase (ChAT)41. Organic methylmercury chloride (MMC) at
concentrations of 20 micromolar has also been shown to inhibit ChAT and lower both
choline uptake and the production of acetylcholine in vitro42. Both
organic and inorganic mercury had no effect on cholinesterase activity. This result
proves that lower levels of acetylcholine are due to ChAT inhibition by mercury
and not increased acetylcholine metabolism. Chronic in vivo treatment of rats with MMC lowers acetylcholine levels in
their brains43. In vivo mercury
inhibition of ChAT is reversed with mercury chelators, such as
2,3-dimercapto-propanol (BAL)39. This inhibition by organic and
inorganic mercury can also be reversed by taking a daily selenomethionine
supplement44.
Mercury Inhibits AADC and Serotonin Biosynthesis
Inorganic mercury ions (Hg2+)
from mercuric acetate and organic methylmercury chloride (MMC) at a level of
100 micromolar have both been shown to inhibit AADC (aromatic amino acid
decarboxylase) an enzyme required for biosynthesis of three monoamine
neurotransmitters and serotonin45. Because of this it is not
surprising that chronic treatment of rats with MMC lowers serotonin levels in
their brains43.
Mercury Exposure Increased the Prevalence of ADHD
A meta-analysis of
epidemiology studies looking at the association between ADHD and environmental
mercury exposure during embryo and early infancy found the odds of ADHD being 1.6 fold greater among those exposed to
organic (methylmercury chloride) and inorganic (Hg2+) environmental
mercury46.
This meta-analysis also found
exposure to Thiomersal (a.k.a. mercury((o-carboxyphenyl)thio)ethyl sodium salt)
used clinically to protect vaccines from biological contamination had no associated risk of ASD or ADHD65.
This finding is supported by fact that the rate of ASD in the U.S. continues to
climb exponentially despite elimination of Thiomersal from routine childhood
vaccines in the summer of 200118.
Aluminum, used as an adjuvant
in vaccines, is a much more likely candidate for being a causal factor of the recent
dramatic rise in the rates of ASD18 and possibly ADHD. Aluminum (inhaled, ingested, and injected),
environmental organic (e.g. methylmercury chloride), and environmental inorganic
(e.g. Hg2+) mercury exposures are casual factors of ADHD as
described herein.
Conclusion
Although a casual factor of
ADHD is genetics, this does not explain a two fold increase in ADHD prevalence seen
in the decade between 2007 and 2017 using diagnostic criteria published in 2013
with no change in ADHD symptoms from diagnostic criteria published in 1995. This
increased prevalence of ADHD suggests that environmental factors are modulating
the severity of ADHD symptoms, resulting in the doubling of diagnosed cases of
ADHD. The two environmental factors that have been implicated by scientific
research as causal factors of ADHD are aluminum and mercury. The data linking
these environmental factors to ADHD and a mechanism showing how these factors
modulate monoamine systems in the brain is presented in this review of the
recent scientific literature. There are two recommended ways to reverse the
effects of these two environmental factors:
1.·
Silicic (e.g. OSA) rich drinking
water for aluminum detox and facilitated aluminum elimination in the urine and
sweat36
2·
Selenomethionine supplementation
for mercury detox and facilitated mercury elimination in the urine44
These treatments are proven safe
by multiyear daily use and involve only supplementing substances normally found
in our bodies18,47. These treatments remove the environmental causes
of ADHD and offer hope that ADHD can be treated in some cases without drugs. Palliative
relief of ADHD symptoms with THB as Kuvan, 5-HTP, L-DOPA, and SAM
supplementation is possible, but taking these supplements does not remove
causal factors and these supplements have numerous undesirable side effects48-52.
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