Multiple Chemical Sensitivity: Toxicological Mechanisms and Therapeutic Approaches

1
Multiple Chemical Sensitivity Toxicological
Mechanisms and Therapeutic Approaches

• Martin L. Pall
• Professor Emeritus of Biochemistry and Basic
  Medical Sciences, Research Director, 10th
  Paradigm Res. Group

2

• A large number of research groups have proposed
  that
• chronic fatigue syndrome (CFS), fibromyalgia
  (FM),
• multiple chemical sensitivity (MCS) and, in some
  cases,
• posttraumatic stress disorder (PTSD) have
  multiple
• overlaps and may share a common etiology (cause).
  
• They have
• overlapping symptoms
• many people are diagnosed as having more than one
  
• cases of each are commonly initiated by a short
  term
• stressor presumably inducing these chronic
  conditions.
• Gulf War syndrome exhibits elements of all four.

3
The notion that CFS, MCS. PTSD and FM and
several other diseases may share a common
etiology has been proposed by Miller, who asked
"Are we on the threshold of a new theory of
disease?" Toxicol Indust Health 199915284-294
4
For example, Buchwald and Garrity concluded in a
study of CFS, MCS and FM patients that
"despite their different diagnostic labels,
existing data, though limited, suggests that
these illnesses may be similar if not identical
conditions ." Arch Inter Med
19941542049-2053.
5
Donnay and Ziem proposed that CFS, FM and MCS
"may simply reflect different aspects of a common
underlying medical condition." J Chronic
Fatigue Syndr 1999571-80.
6
The scientific literature reports that complete
recoveries from CFS and FM do occur but are
relatively rare. Only about 10 of the CFS and
FM patients have a full recovery, although this
typically take several years. Full recoveries
from MCS rarely if ever occur, although MCS
sufferers do report improved symptoms if they are
able to avoid exposures to the classes of
chemicals that produce sensitivity symptoms.
7
Much but not all of this presentation comes from
information from my book Explaining Unexplained
Illnesses Disease Paradigm for Chronic Fatigue
Syndrome, Multiple Chemical Sensitivity,
Fibromyalgia, Post-Traumatic Stress Disorder,
Gulf War Syndrome and Others.
8
This talk will focus on MCS. However the
comparison with these other multisystem illnesses
is also useful with each shedding light on the
mechanisms of the others. One of the great
puzzles about MCS is how can the diverse
chemicals that are implicated in initiating cases
of MCS and producing sensitivity responses in
those already sensitive, produce a common
response in the body?? Some of the MCS
skeptics, including Ronald Gots, have argued that
there cannot be a common response to such a broad
group of chemicals. I will show here that they
are wrong about that.
9

• Chemicals reported to initiate cases of MCS
  include the following
• Organic solvents and related compounds.
• Organophosphorus/carbamate pesticides.
• Organochlorine pesticides
• Pyrethroid pesticides
• but also
• Hydrogen sulfide
• Carbon monoxide
• Mercury

10
Chemical Action in MCS
11
We also know that members of each of these four
classes of chemicals, the organic solvents and
the three classes of pesticides, when tested in
experimental animals, the following has been
shown One can greatly lower their toxicity in
the body by treating with an NMDA antagonist.
This shows not only that increased NMDA activity
is produced by these chemicals but that this
increased activity has a major role in producing
the toxic responses in the body!
12
What about the other three chemicals that also
initiate cases of MCS?? These are also known to
have similar toxicological properties Hydrogen
sulfide, carbon monoxide and mercury (acting
through its product, methylmercury) can each
produce increased NMDA activity and one can use
NMDA antagonists to lower the toxic responses to
all three of these!
13

• Six other observations supporting an NMDA role in
  MCS
• 1. MCS patients are sensitive to monosodium
  glutamate and glutamate is the physiological
  agonist of the NMDA receptors.
• An allele of the CCK-B receptor gene that
  produces increased NMDA activity is associated
  with increased prevalence and therefore incidence
  of MCS.
• The NMDA antagonist dextromethorphan is reported
  from clinical observations to produce lowered
  response to chemical exposures in MCS patients.
• Bell and others have proposed that neural
  sensitization has a key role in MCS and the
  probable mechanism for such neural sensitization,
  called long term potentiation, is known to
  involve increased NMDA activity.
• Elevated NMDA activity has been shown to play an
  essential role in several animal models of MCS.
• Elevated NMDA activity appears to play a role in
  such related illnesses as fibromyalgia, chronic
  fatigue syndrome and post-traumatic stress
  disorder, with the most extensive evidence for
  such a role being found in fibromyalgia (Pall,
  2006 and 2007a).
• Compelling evidence for a common toxicological
  response

14
(No Transcript)
15
One thing that you should note from the preceding
discussion is that the receptors for these
various toxic chemicals are NOT the olfactory
receptors. It has been repeatedly stated that
MCS is a response to odors, but this is not the
case! And MCS sufferers with their nasal
passages blocked off still react to chemicals.
Some MCS patients are anosmic, completely lacking
any sense of smell. I am not saying that the
olfactory system is never impacted in MCS, but
rather that the basic mechanism is not olfactory.
16
(No Transcript)
17
The etiologic theory I will be discussing focuses
on nitric oxide and its oxidant product
peroxynitrite, a potent oxidant. .NO .OO-
ONOO- Nitric superoxide peroxynitrite
oxide
18
(No Transcript)
19
The Nitric Oxide - Peroxynitrite Vicious
Cycle(NO/ONOO- Cycle)
20
Two mechanisms intimately involved with the
NO/ONOO- cycle Mitochondrial/energy metabolism
dysfunction Peroxynitrite attacks a number of
components of mitochondria, including several
iron-sulfur proteins. It also depletes NAD/NADH
pools through stimulation of poly
ADP-ribosylation. Nitric oxide inhibits
cytochrome oxidase activity and superoxide also
can lead to mitochondrial dysfunction. Nitric
oxide synthases become uncoupled when deprived of
tetrahydrobiopterin (BH4), synthesizing
superoxide in place of nitric oxide. This can
lead to increased peroxynitrite synthesis, which
oxidizes, in turn, BH4 (a potential vicious
cycle). This may be the core of the NO/ONOO-
cycle!
21
(No Transcript)
22

• Five Principles
• 1. Short-term stressors initiate these
  multisystem illnesses by stimulating nitric oxide
  or other cycle elements.
• The increases in NO and peroxynitrite initiate
  the NO/ONOO- cycle which then causes these
  chronic illnesses.
• The symptoms and signs of these illnesses are
  caused by the elevated elements of the NO/ONOO-
  cycle, nitric oxide, superoxide, peroxynitrite,
  NF-kB, oxidative stress, vanilloid activity, NMDA
  activity, etc.
• The basic biochemistry of the cycle is local,
  because nitric oxide, superoxide and
  peroxynitrite have limited half lives in
  biological tissues and because the positive
  feedback mechanism that maintain the cycle act at
  the cellular level.
• Therapy should focus on down-regulating parts of
  the NO/ONOO- cycle, rather than on symptomatic
  relief.

23
Table 14-1 Major Disease Paradigms 1.
Infectious diseases. 2. Genetic diseases. 3.
Nutritional deficiency diseases. 4. Hormone
dysfunction diseases. 5. Allergies. 6.
Autoimmune diseases. 7. Somatic
mutation/selection (cancer). 8. Ischemic
cardiovascular diseases. 9. Amyloid (including
prion) diseases. 10. NO/ONOO- cycle diseases
24
Table 14-1 Major Disease Paradigms 1.
Infectious diseases. 2. Genetic diseases. 3.
Nutritional deficiency diseases. 4. Hormone
dysfunction diseases. 5. Allergies. 6.
Autoimmune diseases. 7. Somatic
mutation/selection (cancer). 8. Ischemic
cardiovascular diseases. 9. Amyloid (including
prion) diseases. 10. NO/ONOO- cycle diseases
25
In Chapter 3 of my book, I discuss sixteen
symptoms and signs that occur in some but not all
cases of these four illnesses (MCS, CFS, FM and
PTSD), providing plausible mechanisms for each
based on the action of one or more elements of
the NO/ONOO- cycle. Many of these are summarized
on the next two slides. It should be noted that
these mechanisms for generation of these symptoms
and signs are plausible mechanisms, based on
known and well-described processes but they have
not yet been clearly shown to be demonstrated to
occur in these illnesses.
26
Symptom or Sign Proposed Cause Fatigue Peroxyni
trite attack on energy metabolism Immune
dysfunc- Inflamm. cytokines, oxidative
stress, tion, low NK cell superoxide function
Learning and Elevated brain nitric oxide, low
energy memory dysfunction metabolism in
brain Orthostatic intolerance Nitric
oxide-mediated vasodilation and nitric oxide
influence on autonomic activity. Pain (often
multi- Roles for all of the elements of the
NO/ Organ) ONOO- cycle Depression Inflamm.
cytokines, nitric oxide
27
Symptom or sign Proposed Cause Anxiety Excessiv
e NMDA activity in the amygdala region of
the brain Sleep dysfunction Inflamm. cytokines
nitric oxide NF-kB Oxidative
stress Peroxynitrite Abnormal SPECT Peroxynitrite-
mediated oxidative stress scans (brain) blood
flow effects of nitric oxide and
peroxynitrite Abnormal PET Energy metabolism
effects of peroxy- scans (brain) nitrite blood
flow changes (see above)
28
Each of these four illnesses also have symptoms
that are considered to be specific for that
particular illness. I am not going to discuss
how the specific symptoms of CFS, FM or PTSD may
be generated by the NO/ONOO- cycle rather the
rest of this presentation will focus on the issue
of how the specific symptoms of MCS may be
generated. There have been many difficult
puzzles about the reported properties of MCS.
These include How can people with MCS can be
so extremely sensitive to such a broad range of
chemicals, on the order of 1000 times more
sensitive than normals? And how can previous
chemical exposure generate such high level
sensitivity?
29
One of the big breakthroughs in our understanding
of MCS came from a comparison of the NO/ONOO-
cycle model of these illnesses with the neural
sensitization model of MCS developed by Dr. Iris
Bell (M.D., Ph.D., at the University of Arizona).
Bell argued that the most important mechanism of
MCS was neural sensitization in the hippocampus
region of the brain. This is the same region
that has key functions in learning and memory.
The idea Bell developed was that the synapses in
the brain, the contacts between neurons by which
one stimulates another, may become both
hypersensitive and hyperactive in response to
chemical exposure. The basic idea here is that
this process of neural sensitization which is
involved on a very selective basis in learning
and memory, appears to be activated massively in
MCS.
30
The main mechanism of neural sensitization is
known as long term potentiation (LTP). LTP is
known to involve increased NMDA receptor
activity, increased intracellular calcium nitric
oxide and also superoxide. So one immediately
sees major connections between the NO/ONOO- cycle
mechanism and the neural sensitization mechanism
developed by Bell. So by having chemicals
producing increased NMDA activity, one can see
how they could greatly stimulate the long term
potentiation mechanism. Several of the elements
of the NO/ONOO- cycle have roles in LTP,
including NMDA activity, intracellular calcium,
nitric oxide and superoxide. An oversimplified
diagram of how some of this may play out is shown
on the next slide.
31
Neural Sensitization Cycle
Stimulation of Neurotransmitter Release
(presynaptic cell)
Retrograde Messenger
NMDA stimulation (postsynaptic cell)
ATP (energy) depletion
Increased Nitric Oxide
Increased Peroxynitrite
32

• There are 7 mechanisms that may have important
  roles in generating the chemical sensitivity
  reported in MCS
• Chemical action to increase NMDA activity in
  regions of brain where the NO/ONOO- cycle is
  already up-regulated due to previous chemical
  exposure.
• Nitric oxide acting as a retrograde messenger,
  increasing NMDA stimulation.
• Peroxynitrite acting to decrease energy
  metabolism, producing increased NMDA sensitivity
  to stimulation.
• Peroxynitrite acting to decrease energy
  metabolism, producing less transport of
  glutamate, leading to increased NMDA stimulation.
• Nitric oxide, acting to inhibit cytochrome P450
  metabolism of chemicals, leading to increased
  chemical accumulation.
• Peroxynitrite, producing breakdown of the blood
  brain barrier, leading to increased chemical
  access to the brain.
• Oxidants and superoxide, leading to increased
  vanilloid activity, producing increased
  sensitivity to organic solvents.

33
Dr. William Meggs, a physician scientist on the
medical faculty in North Carolina has described
studies that he and others have made showing
chemical sensitivity in other regions of the
body. This peripheral sensitivity occurs in the
lower lungs, in the upper respiratory tract, in
the skin and in the gastrointestinal (GI) tract.
These sensitivity responses are initiated by
previous chemical exposure and the chemicals
involved are similar to those involved in central
(brain) sensitivity. This suggests that similar
mechanisms are involved. Some MCS patients have
each of these peripheral regions involved but
others lack sensitivity in each of these
regions. Meggs and also Heuser have reported two
additional mechanisms involved in these
peripheral sensitivities--called neurogenic
inflammation and mast cell activation. Both of
these are compatible with the NO/ONOO- cycle
mechanism.
34
There are many different types of evidence
supporting the NO/ONOO- cycle mechanism for
MCS There are 13 distinct types of evidence,
outlined above, that excessive NMDA activity has
a role and that it specifically has a role in
transducing chemical actions in MCS. There are 12
distinct types of evidence for a role of nitric
oxide, peroxynitrite and/or oxidative stress in
MCS. Pall and Anderson outlined 12 distinct types
of evidence suggesting that organic solvents and
other compounds can act via the TRPV1 (vanilloid)
receptor in MCS. Ashford and Miller described 10
striking similarities between neural
sensitization and MCS, each of which can be taken
as evidence for a role of neural
sensitization. There are two types of evidence
for a role of inflammatory biochemistry. Thus
there are 49 distinct types of evidence
supporting this model of MCS.
35
Are there any properties that one can measure
that appear to clearly distinguish MCS patients
from others? Bell (in Arizona) has reported on
changes in brain EEG patterns in response to low
level chemical exposure. Kimata (in Japan) has
reported on changes in both NGF levels and
histamine levels that may also be specific in
MCS. Millqvist (in Sweden) has reported on
increased cough sensitivity to the compound
capsaicin in MCS patients. Shinohara (in Japan)
reported chemical hypersensitivity reactions and
Joffres (in Canada) reported changes in skin
conductivity with low level chemical exposure.
There are a number of studies with nasal lavage
measurements, showing that chemically sensitive
individuals respond with increased inflammatory
markers on chemical exposure. Each of these may
be specific changes in MCS patients and each is
compatible with the NO/ONOO- cycle model. These
should be considered as possible specific
biomarkers for MCS.
36
Therapy Almost all of the relevant clinical
trial studies have been on CFS and/or FM
patients, rather than with MCS. Still, these
studies have provided substantial important
evidence supporting the NO/ONOO- cycle
mechanism. For example, the antioxidants
flavonoids, Ecklonia cava extract and ascobate
have all be reported to be helpful, showing that
oxidative stress has a substantial causal role in
these illnesses. Similarly, several NMDA
antagonists have been shown to be helpful so has
magnesium which lowers NMDA activity and
pregabalin, an agent that indirectly lowers
excitotoxicity including NMDA activity. All of
these provide substantial evidence that excessive
NMDA activity has a substantial causal role.
37
Agents lowering mitochondrial/energy metabolism
dysfunction have been shown to be useful,
including acetyl-carnitine/ carnitine and
Coenzyme Q10 hyperbaric oxygen and D-ribose also
probably help with this, as well. It may be
inferred that mitochondrial dysfunction has an
important causal nrole in these illnesses as
well. The potent nitric oxide scavenger
hydroxocobalamin has been shown in a clinical
trial to be helpful to CFS-like patients there
is evidence that it is not acting to allay a B12
deficiency, suggesting that it may act to lower
nitric oxide levels. Fish oil has been shown to
be useful in clinical trials and it is known to
be an effective antiinflammatory, lowering iNOS
induction and inflammatory eicosanoid synthesis
this suggests that excessive inflammation has an
important causal role.
38
High dose, intravenous ascorbate has been shown
to be useful in four clinical trials with CFS and
one with MCS. It and also high dose folate which
has also been tested in a clinical trial are
known to help restore BH4 levels, suggesting that
BH4 depletion also has a substantial causal role.
In conclusion, clinical trials mostly with the
CFS and FM with one for MCS, provide evidence for
causal roles for each of the following
Oxidative stress, excessive NMDA activity,
mitochondrial dysfunction with lesser but still
suggestive evidence for a causal role from these
studies along for nitric oxide, inflammatory
responses and BH4 depletion. It is difficult to
see how this could be true unless the NO/ONOO-
cycle or something very similar to it is the
causal mechanism of this group of illnesses.
39
In my book, I discuss five different protocols
developed by different physicians and scientists,
using from 14 to 18 agents/classes of agents
predicted to down-regulate the N/ONOO- cycle
biochemistry. These seem to be considerably more
effective than the individual agents discussed
previously. But from the published descriptions,
they still seem to fall short of curing these
diseases. I wish to discuss an additional
protocol, one that I developed with the Allergy
Research Group, a nutritional support protocol
that is entirely made up of over-the-counter
nutritional supplements. It contains 22
different agents predicted to down-regulate the
NO/ONOO- cycle biochemistry. The following is
a description of unpublished observations, ones
that are derived from physicians clinical
observations and anecdotal reports as with all
such information, you should view these with
substantial skepticism.
40
About 80 to 85 of sufferers appear to respond
positively to the protocol. This percentage
seems to be similar for CFS, FM or MCS patients
or for those who suffer from multiple
illnesses. Generally, improvements are
maintained by those staying on the protocol, that
is relapses are rare. The extent of improvement
varies among sufferers with some having amazing
improvements within three weeks or less, but
others requiring longer time to see more modest
improvement and some showing no distinct
improvement. Surprisingly, many who have been
ill for two decades or more and many who have
been severely ill respond well to the protocol.
Some of these respond quite rapidly. People who
have high levels of mercury in their bodies do
not tolerate the protocol, presumably because 4
out of 7 of the pills contain alpha-lipoic acid,
an agent known to mobilize stored mercury.
41
I suggest that individuals start with one of the
seven supplement combinations, for three days to
determine whether there is any difficulty in
tolerating it, before adding a second for three
days and so forth. That way if there is a
problem with tolerating a supplement combination,
it can be dropped out before continuing. Not
surprisingly, lack of tolerance seems to be most
common in the MCS group, but even when two or
three or even four are not tolerated, there seem
to be improvements produced by those parts of the
protocol that are well tolerated. I believe that
to get a good clinical response, it is very
important to avoid stressors that will otherwise
up-regulate the NO/ONOO- cycle. In the MCS
group, clearly chemical exposure is the most
important of these, but allergens including food
allergens and psychological stress may play
roles. Other illnesses bring other stressors
into play, as well.
42
In general, even though positive and sustained
improvement seems to be the rule, we are not
seeing any substantial number of cures over
periods of six months to a year. And yet if we
understand the NO/ONOO- cycle adequately, we
should be able to obtain substantial numbers of
cures with a properly designed protocol. Why are
we not seeing it here?? My working hypothesis
is that the central couplet, the reciprocal
interactions of peroxynitrite and BH4 depletion
is not being adequately treated. peroxynitrite
BH4 depletion There are agents that
are predicted to help lower this couplet, but it
is not clear that they work very well!
43

• My candidate for an approach that may adequately
  down-regulate this couplet is high dose, IV
  ascorbate (vitamin C), an agent that can work in
  three ways to help lower this couplet (and note
  the previously described clinical trials on IV
  ascorbate)
• Ascorbate is a peroxynitrite scavenger although
  it is unclear that it is effective at the normal
  levels obtained in the blood from oral ascorbate.
  However IV ascorbate can give levels 30 times or
  more these levels may be vastly more effective!
• The oxidation product produced by peroxynitrite
  from BH4 is BH3 and BH3 can be reduced back to
  BH4 by ascorbate again high doses may be
  particularly effective!
• High dose ascorbate generates hydrogen peroxide
  in the body which induces the enzyme GTP
  cyclohydrolase I which is the first and rate
  limiting enzyme in the de novo synthesis of BH4.
  So may help increase BH4 availability in that way.

44
Because of the unlikely possibility that a
patient may have elevated levels of iron, and
therefore may be sensitive to high dose
ascorbate, such patients should be tested for
transferrin saturation before being put on this
treatment. It is quite likely that other
additions to the high dose IV ascorbate will be
very useful including hydroxocobalamin to
scavenge nitric oxide and reduced glutathione to
provide antioxidant support. I would like to
emphasize that I think that the high dose IV
ascorbate should be used along with a wide
ranging nutritional support protocol that will
act to lower other parts of the NO/ONOO- cycle.
45
Evidence How much evidence provides support for
the NO/ONOO- cycle mechanism of MCS? In my key
FASEB Journal paper, I described 10 discrete
types of evidence for a role of increased nitric
oxide and peroxynitrite in MCS. These ranged
from evidence that organic solvents can produce
increases in nitric oxide, evidence for oxidative
stress (presumably from peroxynitrite), evidence
from an animal model for an important causal role
of nitric oxide and evidence for an important
NMDA role (it is known that NMDA stimulation
produces increases in nitric oxide and
peroxynitrite). More recent evidence, as you
have seen, links each of the chemical classes of
initiating chemicals to increases in NMDA
activity and therefore nitric oxide and
peroxynitrite. The reported blood brain barrier
breakdown in MCS, presumably caused by
peroxynitrite, is a 12th type of evidence.
46
Ashford and Miller in their important 1998 book
on MCS listed 10 striking similarities between
MCS and neural sensitization, each providing
evidence that neural sensitization has a role in
MCS. Dr. Julius Anderson and I have provided 12
types of evidence implicating the TRPV1
(vanilloid) receptor to MCS in our paper on that
receptor. 13 types of evidence implicating
increased NMDA activity. There are now at least
47 distinct types of evidence, each providing
support for important properties of the NO/ONOO-
cycle mechanism of MCS.
47
A mechanism, like that of the NO/ONOO- cycle must
be judged not just by the evidence that may
support it, but also as an explanatory model.
Can it provide explanations for the puzzling
features of whatever it claims to describe? In
this case, we need to ask, how well does the
NO/ONOO- cycle mechanism explains each of the
most puzzling features of MCS? The NO/ONOO-
cycle mechanism is stunningly successful as an
explanatory model of MCS. It provides
explanations, for each of the most puzzling
features of MCS. Lets go through them one at a
time.
48
How do the four classes of chemicals implicated
in MCS initiate these illnesses and trigger
sensitivity symptoms? They each act via known
pathways to produce increases in NMDA activity
which produces, in turn, increased nitric oxide
and peroxynitrite. Why are MCS patients so
exquisitely sensitive to chemicals, on the order
of 1000 times more sensitive than normals?
Because of the action of six distinct mechanisms,
five involving nitric oxide or peroxynitrite and
the sixth involving superoxide. It is the
combination of these mechanisms acting together
that produce this extreme level of sensitivity.
49
There are also five specific puzzles that need
to be explained. Most of these we have not
discussed. The possible specific responses of
MCS patients to chemicals that I discussed as
possible biomarkers. Already discussed--each can
be explained as a being linked to the NO/ONOO-
cycle mechanism. The role of such aspects as
neurogenic inflammation and mast cell activation
in peripheral sensitivity. Also consistent with
mechanism--this was documented in my
Environmental Health Perspectives article on
MCS. Changes in porphyrin metabolism in MCS
patients can also be explained. Also consistent
with mechanism - discussed in article.
50
The role of mold toxins in the initiation of
cases of MCS has never been explained. Anderson
and I proposed that because some mold toxins are
known to stimulate the TRPV1 receptor, that molds
may act by that pathway in this process. The
vanilloid receptor also explains the phenomenon
of desensitization/masking in MCS (also discussed
in the Pall and Anderson article).
51
Why are the four types of illnesses, MCS, CFS, FM
and PTSD so often diagnosed together in the same
patients? (Why are they comorbid?) Because they
share a common cause--the NO/ONOO- cycle. Why
are these four illnesses all chronic? Because
the NO/ONOO- cycle is a vicious cycle,
propagating itself over time. How are the
symptoms and signs of these illnesses generated?
They are produced through the action of the
elements of the NO/ONOO- cycle. Why is there so
much variation in symptoms from one patient to
another? Because of the variation in tissue
distribution of the underlying biochemistry.
Different patients have different regions of
their bodies impacted, and differ from each other
in symptoms, for this reason.
52
(No Transcript)
53

• 1. Tinnitus
• 2. Post-Radiation Syndrome
• 3. Multiple Sclerosis (MS)
• 4. Autism
• 5. Overtraining Syndrome
• 6. Silicone Implant Associated Syndrome
• 7. Sudecks Atrophy
• 8. Post-Herpetic Neuralgia (Pain)
• 9. Chronic Whiplash Associated Disorder
• 10. Amyotrophic Lateral Sclerosis (ALS)
• Parkinsons Disease
• 12. Alzheimers Disease
• 13. Asthma
• 14. Irritable Bowel Syndrome
• Other proposed NO/ONOO- cycle diseases from my
  book

54

• 1. Tinnitus
• 2. Post-Radiation Syndrome
• 3. Multiple Sclerosis (MS)
• 4. Autism
• 5. Overtraining Syndrome
• 6. Silicone Implant Associated Syndrome
• 7. Sudecks Atrophy
• 8. Post-Herpetic Neuralgia (Pain)
• 9. Chronic Whiplash Associated Disorder
• 10. Amyotrophic Lateral Sclerosis (ALS)
• Parkinsons Disease
• 12. Alzheimers Disease
• 13. Asthma
• 14. Irritable Bowel Syndrome
• The colored diseases also are initiated by
  solvents and pesticides.

55
(No Transcript)
56
Table 14-1 Major Disease Paradigms 1.
Infectious diseases. 2. Genetic diseases. 3.
Nutritional deficiency diseases. 4. Hormone
dysfunction diseases. 5. Allergies. 6.
Autoimmune diseases. 7. Somatic
mutation/selection (cancer). 8. Ischemic
cardiovascular diseases. 9. Amyloid (including
prion) diseases. 10. NO/ONOO- cycle diseases
57
(No Transcript)
58
(No Transcript)