Multiple Sclerosis, An Autoimmune Inflammatory Disease: Prospects for its Integrative Management
 
   

Multiple Sclerosis, An Autoimmune
Inflammatory Disease: Prospects
for its Integrative Management

This section was compiled by Frank M. Painter, D.C.
Send all comments or additions to:
  Frankp@chiro.org
 
   

FROM: Alternative Medicine Review 2001 (Dec);   6 (6):   540566 ~ 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. (Alter Med Review 2001 (Dec);   6 (6):   540566)


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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