Alternative Medicine Review 2001 (Dec); 6 (6): 540–566 ~ FULL TEXT
Parris M. Kidd, PhD
Multiple sclerosis (MS) is aptly named for the
many scars it produces in the brain and spinal cord. A sometimes fatal,
often debilitating disease, MS features autoimmune inflammatory attack
against the myelin insulation of neurons. Thymus derived (T) cells sensitized
against myelin self-antigens secrete tumor necrosis factor, cytokines,
prostaglandins, and other inflammatory mediators that strip away the myelin
and sometimes destroy the axons. Familial and twin inheritance studies
indicate MS is mildly heritable. No single MS locus has been identified,
but an HLA haplotype has been implicated. Unique geographic distribution
of the disease is best attributed to some combination of vitamin D abnormality
and dietary patterns. No pharmaceutical or other therapies exist that confer
prolonged remission on MS, and obvious interrelationships between toxic,
infectious, and dietary factors make a persuasive case for integrative
management. The time-proven MS diet meticulously keeps saturated fats low,
includes three fish meals per week, and eliminates allergenic foods. Dietary
supplementation for MS minimally requires potent vitamin supplementation,
along with the thiol antioxidants, the anti-inflammatory omega-3 fatty
acids, and adaptogenic phytonutrients. Gut malabsorption and dysbiosis
can be corrected using digestive enzymes and probiotics. Long-term hyperbaric
oxygen therapy can slow or remit the disease. Transdermal histamine offers
promise, and adenosine monophosphate may sometimes benefit. Chronic viruses
and other infectious load must be aggressively treated and exercise should
maintain muscle tone and balance. Early intervention with integrative modalities
has the potential to make MS a truly manageable disease.
Multiple sclerosis (MS) is an inflammatory, autoimmune, demyelinating
disease of the central nervous system. It generally strikes at an early
age, most often the early adult years. Its most frequent symptoms include
numbness, impaired vision, loss of balance, weakness, bladder dysfunction,
and psychological changes. Fatigue is an early symptom in MS, often the
earliest. The disease can wax and wane for up to 30 years, but in perhaps
half of all cases it steadily progresses to severe disability and premature
MS owes its name to the presence of multiple sclerotic (hardened) lesions
in the brain and spinal cord multiple scars. The optic tract also
is often involved. This disease has major autoimmune character, with T-cells
and other immune effector populations entering the brain and attacking
the nerve cells, stripping away their myelin insulation and sometimes destroying
their axons and entire remaining structures. Principal patterns of demyelination
and axonal degeneration are schematized in Figure 1.
MS is the most common cause of neurologic disability in young adults.
The lesions of demyelination are histopathologically characteristic of
the disease. Brain examination by MRI (magnetic resonance imaging) can
accurately detect these "white matter plaques." MRI correlates
well with the classic histopathology of the lesions, and is progressively
a more sensitive tool for detecting the characteristic lesions of MS in
situ, as compared to conventional functional evaluation.
Currently approved drug therapies for MS are highly toxic; the immunosuppressants
cortisone, prednisone, methotrexate, and cytoxan are still mainstays of
conventional MS management. In 1993, interferon ß-1b was approved
in the United States as attack prevention therapy,  but this
drug itself is burdened with frequent and severe adverse effects. 
The limitations of the conventional drug therapies for MS make imperative
the development of a less toxic, integrative strategy for its management.
Diagnosis, Prevalence, and Progression of MS
Multiple sclerosis is a complex disease,
perhaps encompassing more than a single
etiopathological entity and very likely subject
to multifactorial etiology.  MS prevalence
worldwide is estimated at one million cases;
in the United States this number is 250,000-
350,000.  Although not generally considered
life threatening, this disease kills about 3,000
people each year in the United States. 
MS overlaps extensively with numerous
other syndromes, including acute disseminated
encephalomyelitis (ADEM), Marburg’s
variant of MS, recurrent optic neuritis, neuromyelitis
optica (Devic’s syndrome), internuclear
ophthalmoplegia, acute transverse
myelitis, and cerebellar, pyramidal, and dorsal
column dysfunctions. Weinshenker proposed
grouping all these into a pathophysiological
matrix of idiopathic inflammatory
demyelinating diseases of the CNS. Optic neuritis
or other single demyelinating syndromes
can develop over time into MS. Such “conversion”
occurs especially in females with relatively
early onset. MRI is currently the technique
of choice to identify those at risk for
conversion to clinical MS.  When a clinician
detects exacerbation of symptoms, MRI will
detect new lesion activity in most cases. However,
patients without clinical activity can still
manifest new lesion activity on MRI examination.
MRI lesion data may strongly predict
probability of subsequent attacks and progression
Onset of MS is usually between the
ages of 10-59 years, but can occur as early as
age two.  Symptoms often begin as sudden but
transient motor and sensory disturbances,
including blurred vision, dizziness, muscle
weakness, and tingling sensations.  In about
two-thirds of the cases onset is between ages
20 and 40 (onset after age 50 is rare), and
women are more frequently affected than men
(60% and 40%, respectively). With the passage
of time, an almost bewildering array of
symptoms can manifest.
MS is difficult to diagnose in its early
stages. Initial symptoms begin alone or in combination,
and are highly variable in duration
and expression. Typically they develop over a
few days, remain for a few weeks, then recede.
Motor symptoms tend to come first, and include
feelings of heaviness, weakness, leg
dragging, stiffness, tendency to drop things,
and clumsiness.  Sensory symptoms include
vague numbness and tingling, and “pins and
needles” and electrical sensations. Often the
sensory organs are also involved. Optic neuritis
and other visual symptoms – blurring, fogginess,
haziness, eyeball pain, blindness,
double vision – can appear early, and afflict
more than one-third of the cases. Problems
with the ear vestibular apparatus can cause
lightheadedness, dizziness, nausea, and vomiting.
Later in the disease process, genitourinary
nerve tract involvement can create loss
of bladder, sexual, and bowel function. Cumulative
increase in the number, size, and distribution
of lesions correlates well with the patterns
of physical and mental disability. 
MS usually damages quality of life to
a marked degree. Progressive motor degeneration
leads to physical disability, while difficulties
with mental functioning are measurable
in some 43 percent of MS patients and can
lead to job loss and social awkwardness. Less
than five percent of cases develop severe dementia.
Death by suicide occurs seven times
more frequently in the MS population than in
the general population. 
The patterns of MS progression vary.
Patients with relapsing-remitting (RR) MS
constitute 70-80 percent of all cases, and primary-
progressive (PP) MS make up the rest.
But 80 percent of the RR MS patients develop
secondarily progressive (SP) MS after some
period, typically within 7-15 years.  For most
patients the transition from RR to SP means
that extended periods of remission will no
longer occur; and on MRI the lesions become
more confluent and extensive.
Impairment scales are used to grade
clinical signs and symptoms based on objective
criteria; disability scales grade limitations
on activities of daily living; and handicap
scales grade limitations of social interactions.
Currently the closest to a “gold standard” for
clinical disability is Kurtzke’s EDSS (extended
disability status scale).  Scoring of disability
extent is most useful to the patient, while for
the clinician lesion scoring is the more reliable
indicator of clinical status and progression.
Some 20-40 percent of all MS cases
become classified “benign” since they have
less than moderate disability after ten years
(meaning the patient can walk more than a half
block without a cane). This is a highly misleading
term for these patients, since by their
fifteenth year with the disease many of them
will require some form of walking aid. 
Arresting the progression of MS means
arresting disability progression. The current
conventional drug therapies do not do so. Half
of all patients reach DSS 6 (moderate disability,
basically unable to walk unaided) within
12-15 years after onset; only about five percent
are better than DSS 6 at 40 years. The
average life expectancy is decreased only
slightly by MS, although for very disabled individuals
the probability of death is more than
four-fold greater than the general population.
Best estimates suggest more than three-quarters
of MS patients live longer than 25 years
after diagnosis. 
Potential Etiological and Triggering Factors
Numerous factors undoubtedly
contribute to the causation, exacerbation, or
progression of multiple sclerosis. There is a
familial component, although no single gene
has been identified and the genetic contribution
seems relatively minor.  The gender
component of women having greater
susceptibility has been confirmed.  Most
likely the disease is a product of innate
susceptibility spread over several different
genes that interact with multiple environmental
factors. People who move from a low-risk to a
high-risk area before age 15 have a higher risk
of developing the disease.
The disease evolves over decades, going
through periods of relative stability and
increased activity in relation to exogenous triggers. 
Agents that can trigger exacerbations include
allergic reactions to foods, and
irritation or provocation by environmental agents.
Among the short-term triggering factors, the best documented are
minor respiratory infections (which in one study preceded
27 percent of relapses), 
sinusitis,  and
Although now obsolete, a hot
bath test was formerly used in the diagnosis
of MS. 
The major etiological factors best supported
by the available evidence are inherited
susceptibility, microbial infection, and environmental
toxin exposure. Diet has been less
studied but undoubtedly makes important contributions.
The Genetics of MS
Almost one-quarter of multiple sclerosis
patients have an affected relative, and a
genetic influence on susceptibility is strongly
suggested from population, twin, and family
studies.  One group of Class II MHC genes of
the D class, located on chromosome 6p21, has
been consistently implicated.  Studies of several
ethnic groups confirmed that the human
leukocyte antigen (HLA) haplotypeDR2Dw2
is a modest contributor to disease susceptibility.  In patients with this haplotype, certain T-cell
polymorphisms are also MS risk factors. 
Several genome scans conducted on
MS populations around the world have failed
to indict any individual genes.  This probably
means that many genes contribute to MS, each
with a small effect on disease susceptibility;
but separate, “modifier” genes may control the
clinical symptoms. A large Canadian study of
15,504 patients did not find support for any
transmissible MS factor between spouses, but
did suggest that offspring of MS pairings have
a substantially greater risk for developing the
Studies with siblings and fraternal
twins indicate the genetic component of the
disease has relatively low penetrance. The concordance
rate in identical twins is around 25-35 percent, suggesting that some 65-75 percent
of MS must be attributable to non-genetic
One promising area for further genetic
exploration is mitochondrial DNA. Wherever
oxidative stress and/or inflammation are involved,
cumulative failure of the mitochondria,
the cells’ “energy power plants,” has to be examined
as a potential factor.  Optic neuritis,
which is common in RR MS, has similarities
with Leber’s hereditary optic neuropathy
(LHON), a known mitochondrial failure syndrome
which also can feature demyelination.
MRI studies of the MS brain suggest energetic
abnormalities, even in the normal appearing
white matter.  Findings from at least a dozen
studies seem to prove that MS can occur in
individuals lacking pathogenic mitochondrial
mutations of any kind.  However, a consistent
association was found between the mitochondrial
ancestral K* and J* haplotypes and
MS in caucasians. 
Candidates for Infectious Involvement
Epidemiological studies suggest multiple
sclerosis is initiated by a primary encounter
with an environmental (i.e., non-genetic)
agent during childhood or early adulthood.
Evidence that this might be an infectious agent
is suggested by increased levels of IgG and
the presence of alkaline oligoclonal bands in
the CSF. These bands occur in greater than 95
percent of MS patients and in 10 percent of
other CNS diseases that are infectious. This
pattern of elevated IgG and oligoclonal bands
is thought to be characteristic of antibody production
within the CNS in response to infectious
Viruses are obvious candidates for the
infectious villains in MS because several cause
demyelination in humans and animals,  conditions
that can present clinically as relapsing-remitting
symptoms.  The demyelination of
MS may result from direct viral damage to
brain cells, or from viral infection leading to
formation of antibodies, which then attack the
myelin. Over the years many virus candidates
for MS have been considered and discarded.
Currently, human herpesvirus-6 (HHV-6) is the
front-runner candidate for MS causation or
Human Herpesvirus Type 6 (HHV-6)
HHV-6 is perhaps the most
neuroinvasive member of the herpesvirus family.
It has been detected both in normal brain
and in the brains of patients with MS.  CNS
infection with HHV-6 is a major cause of seizures
in children, as well as more severe pediatric
neurological disorders, including disseminated
demyelination and infarction of the basal
ganglia.  In both children and adults, the virus
can produce encephalitis that can be fatal
unless successfully treated with antiviral
therapy.  As with HIV, its genome becomes
integrated into the human genome (at chromosome
17); its intervention in AIDS may
result in dementia. The recurrent infection
pattern of HHV-6 recalls the clinical relapse
patterns of MS. 
HHV-6 can be lethal even to immunologically
intact adults. In this population, focal
encephalitis, chronic, demyelinating myelopathy,
and other CNS dysfunction can
sometimes result in death.  Particularly relevant
to MS is that demyelination is the most
consistent finding in HHV-6 attack on the
CNS. The pattern and extent of HHV-6 associated
demyelination range from diffuse and
extensive loss of myelin to sharply circumscribed
foci of demyelination, combined with
axon destruction within those zones most severely
involved. [20, 22] These parallel the distinctive
histopathological features of MS. [23, 24]
Challoner and colleagues showed in
MS patients that the nucleic acid of strain
HHV-6B was preferentially distributed in and
around the zones of demyelination.  Sanders
and colleagues found HHV-6 (and other herpesviruses)
generally more associated with active
MS plaques than inactive ones,  and Knox
and colleagues used immunohistochemical
staining to identify cells in the CNS actively
infected with HHV-6. They detected such cells
in 8 of 11 patients diagnosed with MS (73%),
versus 2 of 28 controls (7%), comprising normal
persons and patients with non-MS inflammatory
demyelinative diseases. In the MS patient
group, 17 of 19 tissue slices showing active
demyelination (90%) had HHV-infected
cells, compared with 3 of 23 tissue sections
free of active disease (13%; p<0.0001).
Knox et al found lymphoid tissue
samples from MS patients revealed active
HHV-6 infection (in six of nine patients examined,
or 67%; all controls negative).  Blood
samples from 22 of 41 MS patients (54%) had
active HHV-6 infections, compared to 0 of 61
control patients. Repeated blood analyses indicated
the MS patients were more consistently
burdened with active HHV-6 infection than
were immunosuppressed patients, namely
those who had received liver transplants.
The Knox study made a pivotal contribution
to the circumstantial case for HHV-6
causal involvement in MS. Four arguments
support this position:
(1) HHV-6 can cause demyelinative CNS degeneration and active HHV-6 infections are associated with other demyelinating diseases of the CNS;
(2) a strong relationship was found between the presence of cells actively infected with HHV-6 and active demyelination;
(3) the cumulative outcomes of previous studies pointed to an HHV-6 association with MS; and
(4) the high degree of neuroinvasiveness of HHV-6 combined with its capacity to establish latent infections that periodically reactivate is consistent with the periodic exacerbations of clinical MS.
Previous to the Knox study, efforts to
unequivocally define HHV-6 involvement in
MS produced mixed results. DNA of HHV-6
had been detected in the brain tissues and occasionally
in the cerebrospinal fluid (CSF) of
patients with MS. Abnormally high titers of
antibodies to HHV-6 were found in the serum.
The Polymerase Chain Reaction (PCR) is a
means to tremendously amplify DNA and facilitate
detailed matching of gene identities.
A negative finding for HHV-6 DNA in the CSF
was probably due to interference with the PCR
assay by CSF constituents, and perhaps also
by the low absolute level of HHV-infected cells
ambient in the CNS. When technologies were
used that could detect active HHV-6 infections,
differences between MS patients and controls
were found. Techniques that did not distinguish
between active and latent HHV-6 infections
failed to show differences. Recent studies
demonstrated that at least 50-70 percent of
MS patients carry HHV-6 specific IgM antibodies,
and at least 30 percent have HHV-6 in
their sera. 
The mechanisms by which HHV-6 affects
demyelination and other degenerative
CNS changes in MS remain to be elucidated.
Case reports establish beyond doubt that HHV-6 can trigger fulminant demyelinating disease
and encephalitis in MS patients. Fulminant
demyelinating activity in the MS brain can
feature virtually total segregation of HHV-6
from the areas free of demyelinative changes. 
This virus can infect and destroy oligodendrocytes,
the cells which produce myelin. However,
the relatively low number of HHV-6 infected
cells in brains of MS patients, as compared
with encephalitis patients, suggests
mechanisms other than direct cell destruction
may be involved.
The cytokine tumor necrosis factor-alpha
(TNF-±) may be an indirect mediator
of HHV-6 damage to the CNS cell populations
of MS patients. Cells that produce this cytokine
have been identified in MS lesions,  and the
expression of TNF-± in blood monocytes of
MS patients correlates with disease activity.
As illustrated graphically in Figure 2,
significant differences in cellular expression
of TNF-± were observed between clinically
active patients and
patients with active
lesions from MRI,
compared to stable
patients or healthy
control subjects. 
HHV-6 is unique,
even within its own
virus family, for its
ability to up-regulate
TNF-± production in
blood monocytes. 
A second indirect
to the CNS of
MS patients by
HHV-6 may be the
induction of autoimmunity
tissues. A large body
of evidence indicates
MS is an autoimmune
(as well as inflammatory)
Antigen mimicry is
whereby one or more
on an HHV-6
protein may cross-react
with a myelin
determinant, such as
myelin basic protein
or myelin oligodendrocyte glycoprotein.  Of
the majority of MS patients with RR MS, most
change to a progressive disease course and at
the time of their death many have antibodies
specific for myelin proteins bound within their
CNS tissues. [30, 31]
The antiviral drug acyclovir, which
provides effective prophylaxis against HHV-6 infections in bone marrow transplant patients,
has been shown to markedly reduce the
frequency of disease exacerbations in patients
with MS. 
The latest organism implicated as an MS pathogen is Chlamydia pneumoniae, an intracellular bacterium known to infect humans.  A great deal of circumstantial evidence links Chlamydia to MS:
(1) several chlamydial species produce a relapsing-remitting pattern of disease;
(2) one species – C. trachomata – is more common in women than in men, and may prefer the HLA-DR16 gene allele that is also linked to MS; and
(3) some chlamydial species are linked to immune-mediated, inflammatory neurodegeneration. Still, direct proof of C. pneumoniae involvement in MS has been lacking.
In 1999 Sriram, and collaborators 
reported isolating C. pneumoniae from the
CSF of 64 percent of a group of 37 MS patients,
compared with 11 percent of non-MS
controls (n = 27). Using sophisticated assay
technology, they claimed the C. pneumoniae
gene was present in the CSF of 97 percent of
their MS patients, and that in 86 percent the
CSF carried oligoclonal antibodies to the organism. 
Unfortunately, other labs have so far
been unable to replicate these remarkable findings.  The organism has been identified from
CSF in only a minority of MS cases; sensitive
techniques of immunohistochemistry and in
situ DNA hybridization failed to detect it in
the CNS tissue; and, in contrast to CSF, it did
not culture out of brain tissue.  Little is known
about how the MS host responds immunologically
to this infectious agent. It could be directly
causal for MS, or could nonspecifically
potentiate the disease. The degree of actual participation,
if any, of C. pneumoniae in MS remains to be elucidated.
One under-appreciated microbe
present in MS is Mycoplasma pneumoniae.
This virus-like, primitive bacterium has been
proven capable of invading the human CNS 
where it can cause acute meningoencephalitis,
perivascular demyelination, autoimmune
sequelae, and a CNS vasculitis. In many cases
the organism cannot be detected by sensitive
DNA identification techniques, does not culture
out from CSF, and leaves no antibody trail.
Nicolson and Nicolson reported 50 percent of
MS patients they examined had mycoplasmal
infections, often as coinfections with HHV-6
(found in 60 percent of their patients), Chlamydia
(20%), or other bacteria (25%). [36, 37] They
also reported finding mycoplasmas contaminating
commercial vaccines. 
Under active investigation for MS are
Varicella zoster, [38, 39] retroviruses, and nidoviruses. The retroviruses can generate
human CNS symptoms that closely resemble
MS. Of the nidoviruses, Coronavirus produces
an MS-type demyelinating syndrome in
experimental animals.  A virus called IM and
closely resembling the Japanese SMON (subacute-
myelo-optic-neuropathy) virus reportedly
was isolated from several MS patients. 
All MS patients are seropositive for Epstein-Barr Virus (EBV), although supposedly it does
not reach the brain. 
Surveying the considerable bulk of information
about the wide variety of viruses or
other microbes proven capable of entering the
brain, attacking cells therein, and creating
neurodegenerative damage, the thoughtful
reader might be tempted to suspect that any
single one could be pathogenic in MS. The
microbe that succeeds may be specified by the
genotypic and/or phenotypic characteristics of
that individual; or conversely, the MS patient,
while in a weakened state, may be subject to
colonization by any combination of these infectious
agents. Some clinicians favor empirical
treatment against putative infectious agents
in MS; for example, doxycycline for Chlamydia
pneumoniae and acyclovir or valacyclovir
for HHV-6 and/or other herpesviruses. 
A real-life approach to consideration of MS might suggest that virtually any acute or chronic stressor that weakens the immune system – toxic attack, intensified oxidative stress, illness from a “garden variety” virus or bacterium, malnutrition, even sustained emotional stress – could conceivably create a time window for one of these organisms to enter the brain and establish itself. After that, interaction of the organism with responsive host immunity might set the stage for recovery or for eventual progression to full-blown MS.
Toxins and Other Environmental Factors Linked to MS
Environmental factors that are prime
candidates for MS causation include toxins
(solvents, pesticides), exposure to X-rays (diagnostic
or occupational), and exposure to
domesticated animals (dogs, cats, caged
Multiple sclerosis can occur in high
concentrations within limited geographic areas.
These clusters are reminiscent of other
disease clusters stemming from community
infectious or toxic exposure. In 1973 Eastman
and colleagues reported on a cluster in
Mansfield, Massachusetts.  There the frequency
of MS in 1970 was 141 per 100,000 –
two to three times the prevalence rate reported
in other portions of the northeastern United
States. A historical analysis revealed that eight
patients had lived within several blocks of each
other in the center of the town in the 1930s.
During that period the water supply was
heavily contaminated with bacteria and perhaps
also with toxins. The time window between
this exposure and subsequent development
of MS – 23 years – was in line with the
estimated incubation period for MS. The authors
failed to mention the center of town also
housed a large iron foundry.
The Mercury Connection
Ingalls reviewed and analyzed several MS clusters  and suggested Mansfield’s iron
foundry probably also produced compounds
of lead and/or mercury. He further demonstrated
by mapping that the tiny town of
Mossyrock, Washington (population 500) had
a cluster of six very tightly localized cases.
During the Great Depression one enterprising
young man sought to improve his lot by salvaging
“quicksilver” (mercury) from cinnabar
(HgS, mercuric sulfide) leftover from an old
mining venture in the area. He melted the cinnabar
on the family stove in the presence of
six siblings and cousins aged 14 to 18, all of
whom subsequently developed MS.
The largest-ever MS cluster observed
was the 1983-1985 “outbreak” of 30-40 cases
that occurred in Key West, Florida.  Of 19
cases confirmed as MS, three-fourths were
women and seven were nurses who worked at
the same hospital. Across the street from the
hospital was a landfill from which red matter
oozed continuously, and which would regularly
catch fire and fill the air with burning
matter. The red matter was strongly suspected,
although never officially confirmed, to be anti-fouling
ship paint containing mercury. Soon
after publishing his analysis of the Key West
cluster, Ingalls published a reasoned claim that
his own symptoms of MS were triggered by
his mercury dental fillings.  Mercury is well
known to combine with and alter the structure
of numerous proteins. Huggins and Levy published
a study  which involved the
photo-labeling of proteins in CSF drawn from
MS patients before and after removal of their
mercury amalgams. Previous to amalgam removal,
the CSF had an abnormal content of
multiple extraneous proteins. After amalgam
removal (24-48 hours) there was marked absence
of protein except for a single band of
albumin. These researchers hypothesized that
mercury from amalgam in the body could generate
multiple abnormal proteins that might
help trigger MS.
Siblerud and Kienholz  examined two
groups each of 24 MS patients, one group who
had their mercury amalgams removed 2.75
years previously and the other still with amalgams.
Subjects with amalgams had significantly
lowered red blood cell counts, hemoglobin,
and hematocrit, compared to those
without amalgams. The mercury-contaminated
group had significantly lowered thyroxine,
serum IgG, total T-cells, and CD8 (suppressor)
cells. This group also reported significantly
more (33.7%) amalgams than during the
previous 12 months. Interestingly, the MS subjects
combined had significantly higher hair
mercury than did the non-MS control subjects.
In a previous study, Siblerud similarly compared MS patients and determined their mental and emotional status.  Those still carrying amalgams scored significantly higher for depression, anger, hostility, psychosis, and obsessive-compulsive disorder.
A number of epidemiological studies
have targeted occupational exposures, including
exposures to organic solvents. Landtblom
and colleagues did a sophisticated meta-analysis
that covered all studies from the period
1966-1994 and found 13 published studies. 
They then did three separate analyses, each of
which generated two slightly differing calculations
of relative risk (RR). Their results are
illustrated in Figure 3. All six of their derived
RR estimates were in the range of 1.7-2.6,
uniformly consistent with organic solvent exposures
increasing the risk of MS. These findings,
derived using solid methodology, point
to organic solvents as major toxic contenders
for MS causation.
While the field of immunity seeks microbial
antigens as possible explanations for
MS causation, solvents and heavy metals or
other toxins can also present novel antigens to
the immune system. By chemically reacting
with a biomolecule, they can change its topography
or other antigenic aspects; this is known
as a haptenic reaction. As one example,
Thrasher and colleagues demonstrated evidence
of formaldehyde antibodies and altered
cellular immunity in persons exposed to formaldehyde
from contaminated homes. 
Dietary/Digestive Contributions to MS Etiology
Much of the epidemiological data in
multiple sclerosis is consistent with a role for
diet in its initiation, exacerbations, or progression.
This type of research is also unable to
clearly differentiate between “risk factors” and
“triggers.” Some of the dietary factors contributing
to the worsening of MS include a high
animal-fat diet; food allergies and intolerances;
and digestive malfunctions, including malabsorption
High Animal Fat Diet
Swank and his colleagues reported in
1952 on a comprehensive geographical assessment
of diet and MS in Norway.  The inland
farming communities in Norway had a higher
MS incidence than the coastal areas, and included
much more animal and dairy products
than did the coastal diets, which consisted
largely of cold-water fish. They reported a
strong positive association between butterfat
consumption and MS incidence, and a strong
negative association with fish consumption.
Subsequent studies have supported a
strong association between dietary animal and
dairy intake and MS. Agranoff and Goldberg 
found an extremely high correlation between
milk consumption and MS in 1949-1967 mortality
rates in the United States. Fish and vegetable
intake were negatively correlated. Their
protective correlation data for fish and vegetables
held across 20 countries, while the dietary
categories total fat, animal protein, butter
fat, and meat fat all were positively associated
with the disease. This pattern has basically
maintained through a number of subsequent
studies. As reviewed in Lauer,  MS rates
have repeatedly correlated with consumption
of animal fat, animal protein, and meat from
non-marine mammals. The negative correlation
with vegetable and/or fish intake has also
Controlled clinical trials support a beneficial
role for certain long-chain fatty acids
in MS.  A meta-analysis of three trials revealed
that intakes of large amounts of linoleic
acid, an omega-6 polyunsaturated fatty acid
(17.2 or 23 grams per day) lowered severity
of relapses and slowed progression in some
cases.  In another trial, when omega-3 fatty
acids were added to this high omega-6 intake
the added benefits were few, if any.  This was
a faulty trial design, as enzymes in the omega-6 fatty acid pathway are known to compete
with those in the omega-3 pathway.  Nonetheless,
the cumulative epidemiological, experimental,
and clinical data dictate that MS
patients reduce animal fat intake and increase
intakes of vegetables and cold-water marine
A modified-fat diet has been empirically
proven for MS. Beginning in 1948, Dr.
Roy Swank began treating MS patients with
his modified diet consisting of 50-90 grams
of protein (with one egg per day and several
glasses of skim milk for animal protein); a
maximum of 15 grams of animal fat, 10-15
grams of fluid vegetable oils, and 5 grams of
cod liver oil; and carbohydrates as required
for calories. Margarine, shortening, and hydrogenated
oils were not allowed; three fish
meals per week were encouraged; and most
patients increased their fruit and vegetable intakes.
This diet is not very different from what
would currently be considered a healthy diet.
In 1988 Dr. Swank reported on 150
patients followed long-term, from 1949 to
1984. [58, 59] Those who complied, with daily fat
consumption of less than 20 grams of fat (<15
grams of saturated fat), fared much better on
morbidity and length of life than did those who
consumed larger amounts of fat. The death rate
was lower in the former group compared with
the latter (31 percent versus approximately 80
percent). Swank also concluded that 95 percent
of the patients placed on his diet before
the development of disability suffered no significant
increased disability from MS during
the 35-year period. [60, 61]
Diets high in gluten and milk are generally
much more common in areas with high
MS prevalence, [62, 63] and a connection between
MS and food allergies has been suspected since
the 1930s. In addition, patients with generalized
allergy may be more readily susceptible
to symptom exacerbation. In one study of 15
patients, the avoidance of allergenic foods,
tobacco, or house dust led to almost complete
control of symptoms. 
MS patients can manifest anatomic
proof of food allergy. Small-intestinal biopsy
indicated 50 percent of a small group (6 of
12) had inflammatory abnormalities of the lining
reminiscent of celiac disease and other
food allergies.  Celiac disease is closely linked
to gluten allergy, but negative findings from
controlled studies seemed to rule out any central
role for gluten allergies in MS.  But other
foods, or the cumulative effects of food allergy,
may be MS triggers. Thus, a 1952 study found
31 percent of 49 MS patients improved when
they avoided foods to which they were found
allergic.  Reintroduction of such foods caused
their symptoms to recur. According to Gaby,
cow’s milk and sulfite food additives can trigger
exacerbations, and in occasional MS cases
the degree of improvement from an allergy
elimination diet can be highly impressive. 
Compelling rationale for an intestinal-immune
system axis in MS has been articulated
by Embry.  Constituents of common
foods are known to cause autoimmune diseases.
Celiac disease is caused solely by gluten
from grains. Clinical trials in rheumatoid
arthritis and in Crohn’s disease have shown
that avoidance of milk, grains, and legumes
results in major symptom improvements. T-lymphocytes
reactive with milk proteins are
very common in persons with MS; experimentally,
such cells cross react with self-antigens
in myelin. Peptides (small proteins) from milk
have been found to be molecular mimics of
self-antigens in myelin. Patterns of CNS degeneration
closely resembling MS can be precipitated
in mice by injecting milk peptides or
including them in the diet.
Digestive Malfunctions and Dysbiosis
Aside from food allergy per se, poor
GI function seems endemic in MS. According
to Wright, a majority of the patients he sees
with MS have poor digestion and assimilation
of nutrients.  Most have poor stomach
function, with inadequate acid and pepsin
production. Some have inadequate intestinal
digestive enzyme secretion. This problem is
commonly seen in otherwise healthy
individuals as they age.
Gupta and colleagues examined 52 MS patients and found
42 percent had fat malabsorption,
41 percent demonstrated undigested meat fibers,
27 percent had abnormal absorption, and
12 percent experienced malabsorption of vitamin B12. 
Pancreatic enzyme preparations may
help correct malabsorption as well as to help
disperse circulating immune complexes.
Gut dysbiosis has been implicated in
MS.  Perlmutter reported finding anti-Candida
antibodies or Candida immune complexes in
seven of ten MS patients evaluated.  Eight of
these patients also demonstrated depressed
levels of colonic symbiotic bacteria
(Lactobacillus species). Aggressive anti-Candida treatment together with the
requisite re-colonization of probiotic
organisms has been claimed to
occasionally resolve MS symptoms. 
Gut dysbiosis is also commonly
recognized in patients with inflammatory
bowel disease (IBD). One study used
MRI to look at MS-type lesions (“white
matter plaques”) in IBD patients compared
to normal individuals (Figure 4). 
Hyper-intense, focal lesions 2-8
mm in diameter were found in 42 percent
of patients with Crohn’s disease and
in 46 percent of those with ulcerative
colitis. Only 16 percent of the healthy
volunteers showed lesions. The authors
stated, “The frequency of focal white-matter
lesions in the patients with inflammatory
bowel disease was almost as high
as that in patients with multiple sclerosis.…” 
Current Medical Management of MS
Conventional drug development
has yielded several new drugs to treat
multiple sclerosis, all classed as “partially
effective.” Interferon β-1b
(Betaseron®), interferon β-1a (Avonex®), and
glatiramer acetate (Copaxone®) have all been
approved by the U.S. Food and Drug Administration
for use in relapsing forms of MS. 
Each of these reduces clinical evidence of
acute, relapse-associated worsening of the disease.
In addition, evidence from European trials
indicates a role for intravenous immunoglobulin
in reducing relapses.
The use of these drugs is not without
side effects, however. Investigators from Europe
and Canada report that doses of interferon
β-1a, exceeding those previously evaluated in
the United States, reduced clinical and MRI
evidence of disease progression.  But this drug
(Avonex) produced flu-like symptoms in up
to 61 percent of patients who took it at the
currently recommended lower dose, as well
as nausea in 33 percent and anemia in eight
percent.  In another study, interferon β-1b was
shown to delay clinical and MRI worsening
in patients with secondary progressive MS.
This drug (Betaseron) produced flu-like symptoms
in 76 percent of the patients receiving it
and significant injection site reactions in 85
percent. It caused asthenia in 49 percent, myalgia
in 44 percent, menstrual disorders in 28
percent of the female patients, sweating in 23
percent, was liver toxic in 19 percent, and
caused depressed white cell counts in 16 percent
of patients. 
These drugs are regarded by some parties
as significant therapeutic advances against
MS, although they are expensive (at approximately
$11,000 per year in U.S. currency),
inconvenient since they are not effective by
mouth, and have marked adverse effects. Although
they reduce relapse rate by 35 percent,
to date no effort has been made to collect data
that might help assess long-term benefits for
quality and length of life.
Copaxone is a synthetic peptide drug
designed to interfere with receptors on myelin-sensitized
T-cells. It does appear to have a degree
of effectiveness against the autoimmune
aspect of the disease. Although it may be
slightly less toxic than the interferons,
Copaxone has a fierce adverse effects profile.
Some of the more frequent toxic effects reported
from clinical trials include bacterial
infection, lymphadenopathy, vaginal moniliasis,
edema, weight gain, eye disorders, palpitations,
vasodilatation, dyspnea, nausea, and
A number of other possible drug
therapies are in the pipeline for MS, but the
development scenario has become more
challenging. To demonstrate benefits that
would exceed the existing “partially effective”
therapies would require longer and larger trials.
The most promising among these are:
Valacyclovir, an anti-herpesvirus medication;
TNF inhibitors and other inhibitors of pro-inflammatory
transforming growth factor-β, and other agents
to enhance the TH2 arm of immunity; dpenicillamine
and other matrix
metalloproteinase inhibitors; antibodies of
many kinds to manipulate MHC and other Tcell
antigenic sites; inhibitors of cathepsin B,
a proteinase linked to the inflammatory
demyelination of MS; oxygen radical
scavengers; autologous bone marrow
transplantation; gene therapy; implantation of
oligodendroglial precursor cells; and the use
of mathematical modelling to conduct virtual
clinical trials that screen new agents. 
Rational Bases for Integrative Management of MS
Multiple sclerosis is a frustrating disease to have, to treat, and to
study, particularly since its etiology and triggers are so poorly understood.
The seemingly arbitrary waxing and waning of MS symptoms and the omnipresent
likelihood of disease exacerbation necessarily dictate strict adherence
to a basic plan, with willingness to augment or otherwise modify the plan
as circumstances change. As with many other diseases, diet and lifestyle
changes, dietary supplementation, and moderate physical exercise all contribute
to better quality of life in MS, but additional medical modalities also
Steadily accumulating data indicate the "mainstream" Western
diet is pro-inflammatory, imposing oxidative challenge on the body while
failing to adequately support antioxidant defenses. One class of pro-inflammatory
dietary constituents is the animal-source fats. These have a significant
content of saturated fats; a low content of the anti-inflammatory omega-3
fatty acids docosahexanoic acid (DHA) and eicosapentanoic acid (EPA); and
a high proportion of their omega-6 fatty acids in the form of long-chain
omega-6 arachidonic acid (AA). Unlike the omega-6 linoleic acid, AA is
a precursor to pro-inflammatory prostaglandins; and as reviewed by Lauer,
coastal populations that consume more fish, therefore less AA and more
DHA and EPA, have lower MS rates. 
The delicate endothelial linings of the blood vessels are vulnerable
to pro-inflammatory attack,  and inflammation of blood vessels
in the brain is characteristic of MS.  Plaques frequently arise
around a vein or venule, and active inflammation in these vessels is often
accompanied by thrombosis and increased platelet stickiness. 
Omega-3 fatty acids help maintain anti-inflammatory balance in the circulation,
while supporting myelination and nerve cell membrane renewal. Wright monitors
systemic fatty acid (FA) balance by testing red cell membrane FA profiles,
then prescribes omega-3 FAs as necessary. 
Swank's healthy-fat MS diet probably benefits MS in several ways. From
its overall composition it would be expected to lower cholesterol and reduce
platelet stickiness. Polyunsaturated oils appear to help prevent MS deterioration; 
cod liver oil inhibits autoimmunity in experimental animals; 
and keeping the "bad" fatty acids low (saturates, trans-fats)
reduces their competition with the "good" fatty acids, including
the omega-6 gamma-linolenic acid and the omega-3 alpha-linolenic acid,
EPA, and DHA. 
Another implication from its anti-inflammatory orientation is that the
Swank Diet should down regulate autoimmunity in the MS patient. The potent
immune-suppressing steroids have short term symptomatic efficacy, but dietary
rebalancing of the omega-6 to omega-3 ratio could favorably reset the body's
autoimmune-inflammatory set point.
Rational Dietary Supplementation
As with the other neurodegenerative diseases, supplementation of the
diet with vitamins and other nutrients is indicated, both to support well
being and to ameliorate deficiencies engendered by the ongoing demyelinating,
Linoleic Acid: Linoleic acid is an essential omega-6 fatty acid,
meaning a deficiency state is known and it must be obtained from the diet.
Homa and collaborators found abnormally low levels in the red cells of
14 percent of their MS patients.  Plant oil sources of linoleic
acid were administered to MS patients in three double-blind, placebo-controlled
trials. The results were mixed: two of the trials found benefit while one
did not. A meta-analysis of the 181 patients concluded that linoleic acid
at 20 grams per day reduced disability and the severity and duration of
relapses, especially in patients with early disease and minimal disability. 
Gamma-Linolenic Acid (GLA): Gamma-linolenic acid contributes
to anti-inflammatory balance by competing with the pro-inflammatory arachidonic
acid. The use of GLA bypasses the enzymatic conversion of LA to GLA, which
is subject to inactivation by a number of factors including viral activity.
Initial studies used encapsulated evening primrose oil as a source of GLA
and failed to find effectiveness in MS. Horrobin theorized that the capsule
dyes (tartrazine, Ponceau R) interfere with GLA utilization. 
Working with two collaborators, he conducted a preliminary non-controlled
trial on 14 patients using primrose oil in dye-free capsules, either by
itself or in conjunction with colchicine. They reported that five of eight
patients benefited from primrose oil supplementation (2.4 mL/day) and four
out of the remaining six benefited from primrose oil plus colchicine (2.4
mL/day plus 1.0 mg/day, respectively. New Zealand researchers noted that
MS patients often have cold hands and feet, usually an indication of impaired
peripheral blood flow. Their non-controlled study on 16 patients 
concluded that GLA from primrose oil improved peripheral blood flow characteristics
and consequently, hand-grip strength.
Omega-3 Fatty Acids: Omega-3 fatty acids include alpha-linolenic
acid from flax, and the longer-chain EPA and DHA from cold-water fish and
algae. Immunological experiments showed omega-3 fatty acids suppressed
inflammatory reactivity in the mouse EAE model of MS, and increased omega-3
FA intake in humans has been shown beneficial for the autoimmune diseases
rheumatoid arthritis and Crohn's disease. From red cell analysis, it was
suggested MS patients might have low systemic DHA and EPA content. 
A small clinical trial (12 patients) with no control patient group suggested
that omega-3 fatty acid supplements from fish oil might reduce MS exacerbations. 
Antioxidants: Due to their high propensity for oxidation, long-chain
fatty acid preparations should always be administered in conjunction with
high intakes of antioxidants. These nutrients offer benefit in virtually
any clinical scenario that involves inflammation and oxidative stress.
There is little doubt that oxidative stress is increased in MS. 
Vitamin E was reported low in MS patients' serum, and lipid peroxidation
markers were increased in the CSF, especially during periods of disease
exacerbation. The enzyme glutathione peroxidase (GP), which detoxifies
peroxides, is markedly decreased in the red cells, [81,82] the
white cells,  and the CSF  of MS patients. A group
in Denmark  gave a high-dose mixed antioxidant supplement (sodium
selenite 6 mg per day, providing 2,740 micrograms of elemental selenium;
vitamin C 2000 mg; vitamin E 480 mg) to 18 MS patients daily for five weeks.
GP activity, which was abnormally low at baseline, increased five-fold
to the normal range without significant side effects.
The GP enzyme has an absolute requirement for selenium, a dietarily
essential trace mineral, at its active sites. It also has an absolute requirement
for the thiol (SH) tri-peptide glutathione (reduced glutathione; GSH)
as its substrate cofactor. Perlmutter has reported cases of successful
oral application of GSH precursors in Parkinson's, Alzheimer's, stroke,
and multiple sclerosis. 
GSH replacement, whether by mouth or combined with intravenous supplementation,
is safe and well tolerated. But when taken orally, GSH may have poor systemic
bioavailability. One orally effective GSH precursor is N-acetylcysteine
(NAC), a potent antioxidant. Following its intestinal absorption, NAC is
first metabolized to cysteine, then cysteine is incorporated into GSH in
The antioxidant alpha-lipoic acid (ALA) is another orally effective
GSH repleter. ALA is a broad-spectrum, fat- and water-phase antioxidant
with potent electron-donating capacity (more so even than GSH), and has
added biochemical versatility as a Krebs cycle cofactor. ALA has shown
consistently impressive efficacy for the treatment of neuropathies in a
number of controlled trials. 
Flavonoids: Derived from plant sources, these potent free-radical
scavengers support overall antioxidant defense and particularly protect
capillary integrity. In an effort to decrease intestinal epithelial and
blood-brain barrier permeability, both of which are reported abnormal in
MS, standardized preparations of flavonoids may offer benefit.
The popular Ginkgo biloba leaf contains, in addition to flavonoids,
terpene substances which are also anti-inflammatories. One such terpene,
ginkgolide B, is a potent inhibitor of platelet-activating factor, a well-characterized
inflammatory mediator. In a double-blind, placebo-controlled trial, ginkgolide
B failed to acutely reduce MS exacerbations. The extremely short period
of study only seven days limits the meaning of this trial. 
Vitamin D, Possible Key to MS Geographical Distribution: One
factor that correlates with MS is latitude. The higher latitudes, in both
the northern and southern hemispheres, have up to 10 times higher rates
of MS (50 to 100 cases per 100,000 population, versus 5 to 10 cases per
100,000 in the tropics).  One hypothesis most likely to explain
this phenomenon is the influence of latitude over production of vitamin
D in the skin.
Availability of vitamin D, the "sunshine vitamin," decreases
with increasing latitude in patterns closely correlated with increasing
MS rates.  Individuals with a high exposure to sunlight have
a significantly lower risk of MS, independent of country of origin, age,
sex, race, and socioeconomic status. Conversely, most MS patients have
vitamin D deficiency, which leads to low bone mass and high risk of fracture,
compounded by the osteopenic effects of the glucocorticoids widely used
in MS therapy. 
Fish oil is an excellent vitamin D source. Within specific nations,
fishing communities located on the coast consistently have lower MS incidence
compared with farming communities living inland.52,54 In addition to lower
rates of MS in coastal communities, rates are generally lower in countries
in which a lot of fish is eaten. Perhaps the vitamin D component of fish
oil complements the benefits afforded by the omega-3 fatty acids. The case
for this vitamin being the determinant of MS geography is circumstantial,
but in any case it is an important dietary supplement for MS patients.
Calcium and magnesium complement and balance each other,
and are essential minerals involved in human metabolism. Goldberg and collaborators 
administered dietary supplements with calcium (about 1,100 mg daily), magnesium
(about 680 mg), and 20 grams of cod liver oil to 16 young MS patients for
periods of one to two years. They found the number of exacerbations observed
during the program was less than one-half the predicted number.
Vitamin B12 is a key nutrient factor
supporting myelin formation. Acquired B12
deficiency and inborn errors in its metabolism
are recognized causes of CNS demyelination,
so its deficiency in MS would be expected to
contribute to progression. Early studies of B12
status in MS produced conflicting results, but
improved testing techniques confirmed B12
levels were lower in the CSF of MS patients,
if not always lower in the serum.  For more
than 30 years, clinicians have been reporting
consistent clinical improvement of MS from
B12 injections. Many integrative physicians
routinely prescribe intramuscular injections of
B complex with B12 and folic acid to their
MS patients, reportedly with improvement.
Reynolds and colleagues at Kings College,
London, reported on a significant association
between MS and disturbed B12 metabolism.
They discovered some of their MS
patients were significantly macrocytic, a condition
reminiscent of classic B12 deficiency.
Their patient group also had significantly lower
serum B12.  Kira and collaborators confirmed
this observation in Japan, administering
methylcobalamin by mouth at a large dose of
60 mg per day to patients for six months. 
They observed improvement in sensory nerve
potentials, but no motor nerve improvement.
Immune-suppressive steroids or cyclophosphamide
can produce comparable results, but
with severely adverse side effects. 
Adenosine Monophosphate (AMP)
Fatigue can be a significant factor in
MS. Wright reported success from patients
self-administering intramuscular injections of
AMP, which is a precursor of the “energy currency”
substance ATP (adenosine triphosphate).
AMP has been used to treat viral infections
and other conditions. In one uncontrolled
study, 16 patients with severe disability
from established MS received a series of
AMP injections over 6-10 months. Marked
improvements were noted in endurance and
in bladder function.  Intravenous AMP administration
is not advised. 
Some of the herbs used in traditional
folk medicine may make a difference in MS.
In a double-blind study, 100 MS patients received
a traditional Tibetan herbal formula
known as Adaptrin (formerly Padma 28). 
Half of the patients who received this formula
experienced overall improvement in addition
to increased muscle strength and improved
Natural Interferon Treatment
Whereas the beta-interferons currently
approved for MS drug therapy are synthetic, a
natural alpha-interferon derived from leukocytes
could prove just as advantageous and
perhaps with a better benefit-risk profile. In
three preliminary studies conducted between
1987 and 1991, 45 patients were treated with
5-30 million units per week for 3-12 months,
and were observed for two years.  Side effects
included flu-like symptoms, myalgias,
and fatigue which caused some patient dropout.
In the first year of treatment, 58 percent
of the patients improved and 22 percent stabilized,
and after the second year 53 percent remained
improved and 22 percent stable. Additional
controlled studies are needed.
Histamine Replacement Rediscovered
Histamine is a small orthomolecule
which exists naturally in the body. In humans,
histamine is synthesized from histidine, a conditionally-
essential amino acid. Histamine is
a proven mediator of allergy, and one of the
most persistent dogmas in medicine is that
anti-histamines are the best way to block allergy.
Yet in MS patients, raising histamine
may help block autoimmunity.
According to Drs. Gillson and Wright
and their collaborators,  in the 1940s while
anti-histamines were being discovered, Horton
and others at the Mayo Clinic were achieving
remarkable results for allergies and other illnesses
by raising the body’s histamine
(through injection). Later, Horton’s disciple
Dr. Hinton Jonez set up a clinic in Tacoma,
Washington, exclusively for MS management.
Treatments included elimination of food- and
other allergies, injections of histamine, B12
and AMP, and physical therapy. The clinic was
closed after Dr. Jonez died in 1952.
Physicians at the Tahoma Clinic, in
Kent, Washington, recently collaborated in a
revival of histamine application for MS. A proprietary
transdermal cream (Procarin) was
developed by Elaine Delack, RN, herself afflicted
with MS, and was administered through
the clinic to 55 MS patients. It was judged effective
in 67 percent of the cases.  Patients
improved in one or more areas, including extremity
strength, balance, bladder control, fatigue,
activities of daily living, and cognitive
functioning, sustained for periods of up to three
months. This promising work continues.
Oral Antigen Therapy
Oral tolerance is the phenomenon
whereby oral dosing of an antigen can neutralize
the body’s immune sensitization against
the molecule. Oral tolerance was first observed
when guinea pigs given hen’s egg protein
orally were found to become resistant to the
anaphylactic reactions normally induced by the
ingested protein. In 1986 the oral administration
of human collagen was employed to suppress
collagen-induced arthritis. Subsequently,
attention turned to MS.
In experimental allergic encephalomyelitis
(EAE), rats develop an MS-like disease
that features autoimmune reactivity against
myelin basic protein (MBP). When such rats
were orally fed MBP, their EAE was suppressed,
demyelination was reduced, clinical
neurological signs improved, and antibodies
against MBP decreased.  A preliminary study
with human subjects indicated they did produce
the class of T-cells required (in theory, at
least) to suppress autoimmunity in the brain,
but with appreciable subject-to-subject variation.  However, a later controlled human trial
failed to find significant clinical improvement.  Recent reports from animal research
have sparked debate about possible adverse
Hyperbaric Oxygen Therapy (HBOT)
Hyperbaric oxygen therapy involves
exposure to oxygen at pressures higher than
normal air, in multiple sessions repeated almost
on a daily basis. Most HBOT protocols
involve 20 sessions of 90 minutes each for four
weeks, in a chamber with oxygen supplied at
1.75-2.0 times normal atmospheric pressure.
Side effects are generally minor. Earlier, uncontrolled
trials and anecdotal reports indicated
benefit from HBOT for MS. The first
double-blind trial reported initial marked improvement
in 12 of 17 patients, with more favorable
and lasting response in those with less
severe disease.  Seven controlled trials
showed virtually no improvement. A 1995
meta-analysis of these eight available studies
concluded HBOT therapy had little to offer for
MS;  however, all these trials were short term,
lasting less than two months.
The Federation of Multiple Sclerosis
Therapy Centres in the United Kingdom has
very different data on HBOT outcomes in MS.
Their HBOT protocol involves indefinite long-term
treatment, preferably on a weekly basis,
following the initial intense treatment period
of four weeks. Their network of 56 treatment
centers has treated more than 10,000 patients
over a period of 14 years. In 1996, the
Federation’s Perrins and James reported on the
progress of 703 patients followed for up to 13
years;  the results suggested HBOT significantly
The degree of benefit obtained from
HBOT was clearly related to the number and
frequency of treatments the patients obtained
over the years. Patients with all the MS subtypes
were interviewed immediately following
the initial course and assigned a Kurtzke
Disability Scale (KDS) score. They were later
assessed at three years (2-4), seven years (6-
8), and 10-13 years after beginning treatment.
After the initial course there was little average
change in the KDS, although 25 percent
of the RR patients had improved scores. Of
all the patients, 59-77 percent reported symptomatic
improvement. Visual defects were reported
by 51 percent of the patients, but many
resolved during the initial course. Other initial
adverse effects occurred in a minority of
the patients, and featured mostly fatigue, leg
weakness, and limb numbness, none of which
persisted. Minor problems with eardrum pressure
did not necessitate stopping treatment.
Following the initial treatment course,
66 percent of the patient cohort continued for
three years, 34 percent for seven years, and 24
percent for a minimum of 10 years. At three
years there was overall average deterioration
on the KDS, but those patients with more treatments
had deteriorated less. At seven years,
none of the 10 RR patients who had received
at least eight treatments in every quarter of
each year had deteriorated and four of them
had actually improved.
At 10-13 years, 447 patients of the
Federation’s initial cohort of 703 remained
eligible for assessment. Of these, 23 percent
were no worse after regular treatments for 10-13 years; seven percent had actually improved;
and the eight percent who had received less
than one follow-up treatment per year had
seriously deteriorated. Further analysis
revealed that a minimum of one treatment
every two weeks was correlated with
appreciable arrest of progression, and that one
per week was probably most effective.
Consistent with the known natural history of
MS, the relapsing-remitting patients and those
who began HBOT at earlier stages experienced
greater benefit. The Federation’s study
concluded that the degree of KDS maintenance
attainable after 10
years could make the
and needing canes or
HBOT in the
UK has proven beneficial,
minimal adverse effects.
also advises its patients
to take advantage
and to adopt healthy
dietary habits consistent
with the Swank
diet and other natural
principles . 
Perlmutter  and other
HBOT available to
MS patients in an integrative
Emerging Options for Modulating MS Autoimmunity
The immune system is normally able
to distinguish between foreign invaders and
“self” body tissues in healthy individuals. 
Autoimmunity results when the immune
system inappropriately attacks self tissues. In
MS the targets of autoimmunity are mainly the
myelin-producing cells in the CNS.  T-cells
reactive to the major constituents of myelin
such as myelin basic protein and proteolipid
protein (PLP), migrate from the peripheral
circulation, across the blood-brain barrier, and
into the brain. There they proceed to attack
myelin-ensheathed axons and myelin-producing
cells, initiating an inflammatory
cascade that eventuates in the white matter
lesion or plaque of multiple sclerosis.
Myelin-reactive T-cells in the peripheral
circulation may become activated by microbes.
Structural similarities between the foreign
antigens on the microbe, and the self-antigens
of myelin may lead to inadvertent auto-sensitization
of the T-cell against self. This is
the concept of molecular mimicry (Figure 5). 
MBP, for example, shares extensive homologies
in amino acid sequences with measles,
influenza virus, adenovirus, herpesviruses,
papilloma virus, and bacteria, including
Cytokines are small peptide substances
that act as cell-to-cell messengers to regulate
immune cell activity. Patterns of cytokine production
can set the immune system into one
of two dominant modes: T-helper types 1 (Th1)
or 2 (Th2).  Th1 activation features predominantly
cell-mediated cytotoxicity, and inflammatory
and hypersensitivity reactions. Th2
activation features predominantly antibody-mediated,
allergic responses. Various chronic
diseases show differing cytokine patterns; in
MS the Th1 pattern clearly dominates. Of the
known Th1 cytokines, interferon-gamma
worsens disease when given systemically to
MS patients, and IL-12 has been implicated
in a number of experimental autoimmune diseases;
both these cytokines were found to be
up-regulated in MS patients.  IL-12 was even
found abnormally elevated in the serum of secondary
progressive MS patients. Therapeutics
are being pursued that down-regulate Th1
cytokines, with the goal of systemically turning
off the autoimmunity of MS.
Vitamin D3 is a potent immune-modulating
substance;  it acts via specific receptors
carried on antigen-presenting cells and
activated T-cells. Exogenous 1,alpha,25-dihydroxyvitamin D3 (DHD3), the biologically
active metabolite of vitamin D3, can inhibit
different experimental models of autoimmune
disease and can significantly ameliorate
EAE, the “mouse multiple sclerosis.” [105, 106]
Experiments conducted in vitro and in vivo
with both DHD3 and its synthetic analogue
Ro 63-2023 showed specific inhibition of the
Th1 cytokines IL-12 and IFN-gamma. As a
consequence of this down-regulation of Th1,
inflammation, demyelination, and axonal loss
were markedly lowered in the EAE mice. 
Interestingly, this effect did not up-regulate
Th2 pathways; but appeared to calm an
overactivated Th1 immune mode. Th1 may not
be typically pro-inflammatory, but in the case
of EAE/MS, this pathway has seemingly become
locked into an exaggerated sensitivity
to myelin-related antigens.
An Integrative Management Strategy for MS
A few physicians have been practicing
for decades what is effectively integrative
medical management of MS. They concur that
the implementation of a personalized regimen
early in the course of MS can facilitate symptom-free, long-term stabilization of the disease
with good quality of life, all without the use
of pharmaceuticals. [17, 58, 91] Dietary supplementation
combined with dietary reform can halt
the deterioration and bring about improvement,
as achieved by 94 percent of the patients with
newly diagnosed RR-MS over a period of two
years.  Conscious adherence to an anti-inflammatory
diet that incorporates the Swank
principles, and aggressive dietary and injectable
supplementation with nutrients, are the
foundation of the patients’ responsibility for
managing their disease.
In addition to the obvious aspects of
dietary and lifestyle modification required of
the integrative, personalized approach to health
maintenance, other measures of personal attention
to good health are important, including
moderate exercise that reinforces balance
and muscle tone,  and the conscious avoidance
of toxic situations, excessive fatigue,
emotional stress, or marked hot and cold temperature
An integrative protocol for MS management
is submitted (Table 1). For the most
effective management of MS, it is suggested
the practitioner work closely with the patient
to eliminate toxic metals (e.g., lead, mercury)
and chemicals from the daily environment and
to deplete the total body load. All solvents, insecticides
and other pesticides, and for some
patients every synthetic in their environment,
must be considered
smoke can be an
exacerbating factor.  Allergies,
food or inhalant,
should be tested
for and eliminated.
an early stage of
likely to benefit
food allergy testing.
of nutrient deficiencies,
should be identified
patients who sincerely
still progress to significant disability, a desire
may arise to try a pharmaceutical intervention.
At this point it becomes crucial to retain the
integrated program, as a means to protect
against the toxicity attendant with any of the
approved MS pharmaceuticals. Hyperbaric
oxygen might first be tried, if it is available.
Although a fully controlled study on HBOT is
still lacking, the use of this modality seems to
offer an additional dimension for healing with
little risk. And the histamine strategy may provide
breakthrough benefit for some patients.
Making a commitment to explore
“natural” treatment modalities does not have
to mean abandoning opportunities for benefit
from pharmaceutical medications, and vice
versa. Nutrients and other modalities support
homeostasis and help protect the system from
the shock of synthetic monotherapies such as
Avonex, Betaseron, and Copaxone.
Prospects for Eventual Effective Management of MS
Its unpredictable behavior and apparent
complex etiopathogenesis render multiple
sclerosis a particularly challenging disease.
Whatever the perspectives brought to bear on
further studies of MS, it is clear these will require
large sample sizes and longer periods of
study in order to adequately define benefit.
Experts in the MS field have much to disagree
about, but there is consensus that MS has significant
genetic and environmental components.
The genetic contributions are progressively
being defined, but discrete environmental
factors (viruses, chemical toxins) are still
Most workers in the field agree that
infectious agents play a key role in MS, but
no one of the several current candidate agents
has been conclusively proven. Exogenous toxins
are linked with MS clusters but do not account
for the north-south gradient of disease
prevalence. A role exists for diet, but (with
notable exceptions) hardly any organized effort
has been made to investigate dietary factors.
The overlapping areas of nutrition,
lifestyle, and the overall potential for an authentic
integrative strategy to stabilize or reverse
the disease have generally been neglected
in favor of the pharmacological intervention
model. Authentic research into the integrative
management of MS is sorely needed.
Multiple sclerosis, once established, is
likely to lead to serious disability, and in this
scenario the best prognosis is partial improvement.
But if management is begun early, an
authentic integrative strategy will in many
cases achieve near-complete relief of symptoms.
Strict adherence to diet and lifestyle
changes; elimination of toxic and microbial
body load; aggressive use of nutrients; and
exceptional commitment to minimizing stress,
are all mandatory requisites for a quality coexistence
with this disease.
A number of ambitious new strategies,
mainly high-tech, are being brought to bear
on MS. These include the predictable trio of
gene therapy, stem cell transplantation, and
pharmacological neuroprotection. But the unraveling
of its autoimmune component may
well be the final frontier for conquering MS.
Once this challenging task can be achieved,
multiple sclerosis should yield to integrative
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