Alter Med Review 2001 (Dec); 6 (6): 540–566 ~ FULL TEXT
Parris M. Kidd, PhD
Abstract
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. (Alter Med Review 2001 (Dec); 6 (6): 540–566)
Introduction
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
death. [ 1 ]
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, [ 3 ] but this
drug itself is burdened with frequent and severe adverse effects. [ 4 ]
The limitations of the conventional drug therapies for MS make imperative
the development of a less toxic, integrative strategy for its management.
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
show promise.
Anti-Inflammatory Diet
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. [ 54 ]
The delicate endothelial linings of the blood vessels are vulnerable
to pro-inflammatory attack, [ 57 ] and inflammation of blood vessels
in the brain is characteristic of MS. [ 73 ] Plaques frequently arise
around a vein or venule, and active inflammation in these vessels is often
accompanied by thrombosis and increased platelet stickiness. [ 74 ]
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. [ 68 ]
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; [ 55 ]
cod liver oil inhibits autoimmunity in experimental animals; [ 1 ]
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. [ 57 ]
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,
autoimmune-inflammatory process.
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. [ 75 ] 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. [ 55 ]
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. [ 76 ]
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 [ 77 ]
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. [ 78 ]
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. [ 79 ]
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. [ 80 ]
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, [ 82 ] and the CSF [ 80 ] of MS patients. A group
in Denmark [ 82 ] 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. [ 7 ]
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
depleted patients.
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. [ 83 ]
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. [ 84 ]
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). [ 8 ] 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. [ 85 ] 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. [ 86 ]
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.
Minerals: Calcium and magnesium complement and balance each other,
and are essential minerals involved in human metabolism. Goldberg and collaborators [ 87 ]
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.
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