• Sudden transient motor and sensory disturbances, including blurred vision, dizziness, muscle weakness, and tingling sensations
• Evidence of demyelination visible on MRI
Multiple sclerosis (MS) is a syndrome of progressive nerve disturbances that usually occurs early in adult life. It is caused by gradual loss of the myelin sheath that surrounds the nerve cell. This process is called demyelination. One of the key functions of this myelin sheath is to facilitate the transmission of the nerve impulse. Without the myelin sheath, nerve function is lost. Symptoms correspond to the nerves that have lost their myelin sheath.
In about two-thirds of the cases, onset is between ages 20 and 40 (rarely is the onset after age 50), and women are affected more often than men (60% female to 40% male). MS affects about 1 of 1,000 people in the United States, Canada, and northern Europe.1
Clinically, MS can cause various neurological problems depending on the location and severity of MS plaques (see the table opposite). In about 85% of cases, MS starts with a relapsing-remitting course.2Patients experience relapses or attacks of MS during which they confront a new neurological problem, the return of an old problem that had resolved, or worsening of preexisting symptoms. Relapses develop over a few days or weeks, and then a period of improvement and stability ensues. In between relapses, patients are clinically stable, although they may have residual permanent neurological symptoms from previous relapses of MS; and they can continue to have demyelination without additional symptoms.3
Causes
The cause of MS remains to be identified conclusively. One of the more interesting features of MS is the geographic and racial distribution of the disease. First, MS is most common among Caucasians, particularly those of northern European descent.4,5 Typical MS is rare among Asians and black Africans but is relatively common among African-Americans, suggesting a dietary link. The racial predilection of MS is one piece of evidence indicating the strong influence of genetics on the risk of developing MS.
In regard to the geographic distribution of the disease, areas with the highest prevalence are located in higher latitudes in both the northern and southern hemispheres.6,7 These high-risk areas include the northern United States, Canada, Great Britain, Scandinavia, northern Europe, New Zealand, and Tasmania. It appears that the initial event in the development of MS may occur in early life. This statement is based on the observation that people who move from a low-risk area to a high-risk area before age 15 have a higher risk of developing MS, whereas those who make the same move after age 15 retain their low risk. There are many possible reasons for the geographic distribution of MS, such as genetics, vitamin D, diet, and other environmental factors. These factors are discussed more fully below.
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Symptoms of Multiple Sclerosis and Their Neurological Causes |
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SYMPTOMS |
CAUSES |
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Weakness, numbness, and tingling in legs and arms; stiffness in legs |
Spinal cord lesions |
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Urinary urgency, retention, incontinence, and recurrent bladder infections |
Spinal cord lesions |
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Constipation |
Spinal cord lesions; diet |
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Sexual dysfunction |
Spinal cord lesions |
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Blurred vision and blindness |
Optic nerve lesions |
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Double vision |
Brain stem lesions |
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Imbalance |
Spinal cord and cerebellar lesions |
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Tremor of arms |
Brain lesions |
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Impaired memory and concentration |
Brain lesions; effects of inflammatory cytokines |
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Fatigue |
Effects of inflammatory cytokines; nerve fiber fatigability resulting from demyelination |
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Heat sensitivity and elevations in body temperature |
Sensitivity of demyelinations to elevations in body temperature |
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Depression and other mood disorders |
Associated with elevations in inflammatory cytokines |
Genetics
Substantial evidence indicates that genetic background influences the risk of developing MS.8,9 Having a parent or sibling with MS increases your risk of developing MS by fivefold to tenfold. Perhaps the most compelling evidence of the genetic influence on the risk of developing MS comes from studies of twins in which at least one twin has the disease.10 Among fraternal twins, the chance of the second twin’s having MS is 1 to 2%, which is similar to that of non-twin sibling pairs. Among identical twins, the chance of the second twin’s having MS is 25%, indicating a strong genetic influence. An estimated 10 to 15 different genes may affect the risk of developing MS, and major research efforts are under way to identify these genes. However, the fact that only 25% of identical twins develop MS if their twin develops it clearly shows that dietary, environmental, and lifestyle factors are required for the disease to manifest itself in most cases. In other words, genetics alone does not inevitably lead to MS.11
Viruses
Viruses and other microbes have been suggested as possible factors in developing MS. Viruses can cause several demyelinating diseases in humans and animals that are quite similar to MS. A number of viruses have been isolated from cultures of material in patients with multiple sclerosis, including herpes simplex virus, scrapie virus, parainfluenza virus, subacute myelo-opticoneuropathy virus, measles virus, Epstein-Barr virus, and coronavirus. The most suspicious viruses now are the measles and Epstein-Barr viruses. However, all of these viruses may simply be bystanders, rather than the cause of MS.12,13
The cerebrospinal fluid (the fluid that surrounds the brain and spinal cord) of most MS patients contains an elevated level of antibodies (protein molecules made by white blood cells that bind to foreign molecules such as bacteria, viruses, and cancer cells) in a pattern that is characteristic of an infectious process. According to one theory, this pattern is, in fact, due to an unrecognized infectious agent that causes MS. This theory has been termed the “sense antibody” theory. An alternative theory states that MS is not an infectious disease and that the antibodies in the cerebrospinal fluid are nonspecific or “nonsense” antibodies. At present, the available data do not appear to support a common virus as the cause for the increased antibody levels, which are more likely the result of an autoimmune reaction. However, it is possible that the trigger is a virus or another organism.
Geographic and Seasonal Influences
As we have noted, MS is more common in populations that live farther from the equator. People who move from a low-risk area to a high-risk area before age 15 acquire a higher risk of developing MS, whereas those who make the same move after adolescence retain a lower risk. These observations suggest that environmental exposure,14 and in particular early sunlight exposure (which is correlated to serum vitamin D levels), in the first two decades of life influences the risk of developing MS.
Although not consistently seen in all geographic areas, an association between season of birth and risk of developing MS has been shown in several European population studies.15 These studies observe that there is a lower risk of MS for births occurring after October and a higher risk for MS for births occurring after May. The authors reporting these findings suggest that maternal levels of vitamin D levels during the third trimester of pregnancy may influence risk of MS: there is a lower risk when maternal vitamin D levels are high (summer months) and a higher risk when maternal vitamin D levels are low (winter months).
The research is now very clear: low levels of vitamin D, as measured by serum 25-hydroxyvitamin D, are strongly correlated with an increased risk of MS. Early trials of supplementation with vitamin D in MS are showing encouraging results.
Of particular interest is a recent study showing that the MS protection afforded by being closer to the equator may not be due simply to increased vitamin D production.16 Apparently sun exposure itself is protective against MS, independent of increasing vitamin D levels.
Diet
Diet may play a role as an additional risk factor in acquiring MS. The first investigations into diet and MS led by Roy Swank, M.D., centered on trying to explain why inland farming communities in Norway had a higher incidence than areas near the coastline. It was discovered that the diets of the farmers were much higher in animal and dairy products than the diets of the coastal dwellers, whose diet featured more cold-water fish.17 Additional studies have since correlated MS with consumption of meat and animal fat.18
However, a large prospective cohort study using data from the Nurses Health Study and Nurses Health Study II found no evidence linking risk of MS with intake of saturated fats. The authors did note, however, that intake of alpha-linolenic acid, an omega-3 fatty acid, but not fish oils, was associated with a trend toward a lower risk for MS.19 Data from this study also showed no relationship between intake of fruits and vegetables and risk of MS.20 A study in Canada found a positive association between animal fat intake and risk of MS.21 Taken together, these studies suggest that diet has a modest influence on the risk of developing MS.
Therapeutic Considerations
From a natural medicine standpoint, the primary approach is to utilize dietary therapy and nutritional supplements shown to be helpful in arresting the disease process, along with exercise and effective stress management.
The conventional medical approach to treating MS includes the use of medications to control disease activity and additional medications plus rehabilitation interventions designed to alleviate symptoms resulting from damage to the central nervous system. Medications that help decrease disease activity (also called disease-modifying agents) in relapsing-remitting MS include human recombinant interferon beta (Avonex, Betaseron, and Rebif), glatiramer acetate (Copaxone), a monoclonal antibody against alpha-4 integrin (Tysabri), and the immunosuppressant mitoxantrone (Novantrone). Compared with a placebo, these medications decrease the relapse rate by about one-third, decrease new lesion formation in the brain as detected by MRI, and decrease the risk of developing permanent neurological disability.22–27 The immunosuppressant mitoxantrone has also been shown to decrease disease activity in patients with rapidly progressive forms of MS.28 Tysabri, which prevents inflammatory cells from entering the central nervous system, has been shown to decrease the rate of MS exacerbations and reduce the disease activity (new lesions) when compared with a placebo.22 Corticosteroids, such as methylprednisolone, given in high doses can decrease the duration of relapses of MS but do not affect the degree of eventual recovery from those relapses. A number of different medications are useful for treating various symptoms of MS such as fatigue, bladder dysfunction, and spasticity, but these medications do not reverse damage that has already occurred or decrease disease activity.
Although conventional medications are able to reduce disease activity in relapsing-remitting MS, they have limitations: they have only a modest effect on prolonging time to disability; they are available in an injectable form only; the average cost is $20,000 to $30,000 per year; and they have a high incidence of side effects (e.g., injection site reactions, neutralizing antibodies). Given these consideration, identifying natural therapies that have benefit for people with MS is warranted.
The Swank Diet
Roy Swank, M.D., former professor of neurology at the University of Oregon Medical School, provided strong evidence over a lifetime of research that a diet low in saturated fats, maintained over a long period of time, tends to retard the disease process, reduce the number of attacks, and decrease mortality.29–31 Swank began treating patients with his low-fat diet in 1948. The idea of using a low-fat diet supplemented with cod liver oil was based on population studies that found a decreased incidence of MS in populations with a low consumption of animal fats and a high consumption of cold-water fish (such as mackerel, salmon, and herring).
On the basis of our current knowledge of the disease process of MS, the rationale for using the Swank Diet or other diets low in saturated fats in patients with MS relates to the general health benefits of such a diet and the anti-inflammatory and perhaps nerve-cell-membrane-stabilizing effects of a diet rich in the long-chain omega-3 fatty acids EPA and DHA. Although red meat consumption is significantly restricted on the Swank Diet, fish is highly recommended because of its excellent protein content and, perhaps more important, its high omega-3 fatty acid content. In addition, because optimal neuronal functioning depends on cell membrane fluidity, which in turn depends on lipid composition, optimal essential fatty acid levels may have an important neuroprotective effect.32
Since Dr. Swank’s observational studies suggesting that this diet is beneficial for patients with MS, two pilot studies evaluating diet in MS have been conducted. An open-label study looked at the effects of a diet low in saturated fats combined with fish oil supplementation, vitamin B complex, and vitamin C in newly diagnosed relapsing-remitting MS.33 Besides dietary modifications, subjects were advised to reduce their sugar, coffee, tea, and alcohol consumption and to stop smoking. Diet was monitored over two years by dietary record, and plasma fatty acid levels were noted at baseline, year one, and year two. Patients on the diet showed a significant increase in plasma levels of omega-3 fatty acids and a significant decrease in plasma omega-6 fatty acids. They also had a significant reduction in both relapse rates and disability.
One study evaluated the effect of low-fat dietary intervention with omega-3 fatty acid supplementation in 31 MS patients.34 Subjects were randomized into one of two groups: those on a low-fat diet (no more than 15% of calories from fat) plus fish oil (EPA 1.98 g and DHA 1.32 g per day), and those on a moderate-fat diet (no more than 30% of calories from fat) plus olive oil capsules (1 g per day). The group on the low-fat diet plus fish oil had better quality-of-life scores (as measured on a questionnaire) for physical well-being than the group taking olive oil supplementation, although the result was not statistically significant. The mental health scores were similar in the two intervention groups. The olive oil group reported an improvement in fatigue as compared with the fish oil group. For both intervention groups, relapse rates were reduced as compared with the year prior to their entering the study. This study thus suggested that a diet low in fat (especially saturated fat) with fish oil supplementation might promote better physical and mental health for people with MS.
Nutritional Supplements
Fish Oil Supplements and Other Beneficial Fats
As we have seen, there is a good rationale for supplementation with fish oil in the treatment of MS. For example, one published study documented the effects of fish oil supplementation on the production of inflammatory compounds known as cytokines in MS patients.35 Twenty subjects with MS and 15 age-matched healthy controls were given 6 g per day of fish oil containing 3 g EPA and 1.8 g DHA for six months. All MS subjects had had a stable course of MS for at least three months before enrollment, had not modified their diet as a consequence of developing MS, and were not on any disease-modifying therapies. After three and six months of fish oil supplementation, a significant decrease in the levels of inflammatory cytokines was noted. Cytokine levels returned to baseline values when fish oil supplementation was discontinued for three months.
Another large double-blind study in which 312 MS patients were given 3.1 g EPA + DHA daily for two years reported a trend in improvement in the omega-3 group compared with controls. Although the results did not achieve statistical significance, both groups in the study were advised to follow a diet low in animal fat, and this may have affected the results.36
While linoleic acid—an essential omega-6 fatty acid—has shown some benefit in some (but not all) clinical trials in MS,37 nonetheless we recommend restricting omega-6 fatty acid intake by eliminating common vegetable oils such as corn, safflower, sunflower, and soy from the diet and instead focusing on using monounsaturated oils such as olive oil and macadamia nut oil for cooking and flaxseed oil (which is high in alpha-linolenic acid, a shorter-chain omega-3 fatty acid) in salad dressing. Though evening primrose oil, which is rich in the omega-6 fatty acid gamma-linoleic acid, is commonly used by MS patients, we do not recommend it, because it is an omega-6 oil and clinical research has shown it to be of little if any benefit in MS.38
Vitamin D
As we have noted, population-based and clinical studies have found that low vitamin D intake and low serum vitamin D levels may increase the risk of MS.39–41 A recent study looked at the serum vitamin D levels in 199 people with MS and found 84% of them to be deficient.42 In addition to this circumstantial evidence, studies involving the animal model of MS have shown that vitamin D has the ability to decrease immune-cell-mediated inflammation and prevent MS-like lesions.43,44 The vitamin D may affect the ability of inflammatory white blood cells from entering the central nervous system.45
In human studies, higher levels of vitamin D are associated not only with a lower incidence of MS (in women) but also with lower levels of the inflammatory cytokines linked to MS.46,47 Given the extremely high frequency of vitamin D deficiency in MS patients, it makes sense to evaluate serum vitamin D levels.
Alpha-Lipoic Acid
Alpha-lipoic acid (ALA) is a unique antioxidant with multiple modes of action. ALA can regenerate other antioxidants such as glutathione, vitamin C, and vitamin E; serve as a reactive oxygen species scavenger; repair oxidative damage; and chelate metallic ions involved in oxidative injury.48–50 ALA is present in both lipid (fat) and aqueous (water) compartments of cells and exerts antioxidant effects in both locations.51
In studies using an animal model of MS, ALA has been shown to suppress the development of disease by preventing inflammatory immune cells from entering the central nervous system (this is similar to the way vitamin D acts).52,53 ALA has also been shown to modulate the immune system in a manner very beneficial in MS.54
One double-blind study evaluated ALA in 37 MS patients. The patients were randomly assigned to one of four groups: placebo; ALA, 600 mg twice a day; ALA, 1,200 mg once a day; or ALA, 1,200 mg twice a day. The study found that ALA given at 600 mg twice a day was barely measurable in serum, while ALA given at dose of 1,200 mg showed significantly higher serum levels. The study also found an association between higher ALA serum levels and lower inflammatory mediator levels.55
Proteolytic Enzymes
Proteolytic enzymes (proteases) digest protein by breaking it down into smaller units. These enzymes include chymotrypsin and trypsin from pancreatin (from hog pancreas), bromelain (pineapple enzyme), papain (papaya enzyme), and fungal and bacterial proteases. Like other autoimmune diseases, MS is associated with an increased level of circulating immune complexes. Experimental and clinical studies have shown that proteolytic enzyme preparations are effective in reducing levels of circulating immune complexes in several autoimmune diseases, including MS. In the treatment of multiple sclerosis, pancreatic enzyme preparations have been shown to reduce the severity and frequency of symptom flare-ups. Especially good results were noted in cases of visual disturbance, bladder and intestinal malfunction, and sensory disturbances. However, little effect on spasticity, dizziness, or tremor was reported.56
QUICK REVIEW
• Multiple sclerosis appears to be an autoimmune disease, but what triggers the autoimmune process has not been determined conclusively.
• Although genetics plays a role, it is clear that dietary, environmental, and lifestyle factors are required for the disease to manifest itself in most cases.
• Areas with the highest prevalence of MS are located in higher latitudes, in both the northern and the southern hemispheres.
• There is a lower risk of MS for births occurring after the summer and a higher risk of MS for births occurring after the winter, suggesting that maternal vitamin D levels during the third trimester of pregnancy may influence the risk of MS.
• Population-based and clinical studies have found that low vitamin D intake and low serum vitamin D levels increase the risk of MS.
• A high intake of saturated fats and animal fats is linked to MS.
• The conventional medical approach to treating MS includes the use of medications to control disease activity plus other medications and rehabilitation interventions designed to alleviate symptoms resulting from damage to the central nervous system.
• There is evidence that the Swank Diet (low in saturated fats), maintained over a long period of time, tends to retard the disease process, reduce the number of attacks, and decrease mortality.
• Alpha-lipoic acid is a unique antioxidant that may be of benefit in MS.
• Ginkgo biloba extract has shown a number of beneficial effects that might be helpful in MS, including an ability to improve mental function.
• Regular exercise is beneficial for people with MS.
• Hyperbaric oxygen does not seem to be warranted for treatment of MS.
Botanical Medicines
Cognitive impairment affects up to 40 to 50% of people with MS, and ginkgo biloba extract has shown a number of beneficial effects that might be helpful in MS, including an ability to improve mental function.57 It has also been evaluated for its effect on cognitive impairment in Alzheimer’s disease, with mixed findings (see the chapter “Alzheimer’s Disease”). In the only study to look at the effects of ginkgo biloba on cognitive performance in MS, 43 patients were randomly assigned to receive either 120 mg ginkgo biloba extract twice a day or a placebo for 12 weeks. Ginkgo biloba was shown to significantly improve performance on several tests that measured attention and executive function.58
Other Considerations
Exercise
In the past MS patients were often advised not to exercise because increased body temperature and nerve fiber fatigue resulting from exercise were thought to induce transient symptomatic worsening and provide no long-term benefit. However, research has since shown that regular exercise is beneficial for people with MS, as it leads to an improvement in feelings of fatigue, quality of life, well-being, and walking ability.59–62 The exercise need not be strenuous: yoga, tai chi, swimming, and light exercise have shown significant benefit.63–66
Stress
MS patients often report that stress worsens their MS symptoms. A review of the scientific literature concluded that perceived stress is definitely associated with flare-ups of MS.67,68 For natural ways to manage stress, see the chapter “Stress Management.”
Hyperbaric Oxygen
Early reports described promising results from the use of hyperbaric (higher-pressure) oxygen in the treatment of MS. However, these reports were largely anecdotal or from uncontrolled clinical trials. The first double-blind, placebo-controlled trial of hyperbaric oxygen indicated an apparently beneficial effect in the treatment of MS.69 Objective improvement was noted in 12 of 17 patients in the study group, compared with only 1 of 20 in the placebo group. Although the improvements were mild and transient in most of the patients, it appeared that patients with milder forms of MS and a shorter duration of disease derived a more pronounced and longer-lasting benefit. This encouraging preliminary study led to further trials on a larger number of subjects, with longer periods of follow-up. The results showed no significant improvement, apart from a subjective improvement in bowel and bladder function in one of the studies. The results from these larger, well-designed studies cast substantial doubt on the efficacy of hyperbaric oxygen in MS. Detailed reviews and analysis of the 14 controlled trials of hyperbaric oxygen treatment showed that only one of the trials produced a significant positive effect. At this time, we do not feel the evidence warrants use of hyperbaric oxygen therapy in MS.70,71
TREATMENT SUMMARY
Treatment of MS with diet, nutritional supplementation, exercise, and stress reduction should be the basis for the natural medicine approach to MS. Although this approach (combined therapies) has not so far been proven to be beneficial for MS in randomized, controlled trials, its individual components have shown considerable benefit, indicating that a combination of these benefits could be quite profound. (One of our major frustrations with medical research is that it studies individual therapies rather than comprehensive approaches, which are much more likely to be effective.) The natural medicine approach can be used in conjunction with conventional therapies that have been proven in controlled trials to be beneficial for MS.
Diet
Follow the general recommendations given in the chapter “A Health-Promoting Diet,” while also incorporating the following features of the Swank Diet:
• Saturated fat intake: 15 g per day or less
• Unsaturated fat intake: minimum 20 g per day, maximum 50 g per day
• No red meat consumption for the first year (this includes dark meat of turkey and chicken); following the first year, only 3 oz red meat weekly
• White-meat poultry, fish, and shellfish are permissible in any amounts as long as they are low in saturated fat
• Elimination of dairy products containing 1% fat or more
Nutritional Supplements
• A high-potency multiple vitamin and mineral formula as described in the chapter “Supplementary Measures”
• Fish oils: 3,000 mg EPA + DHA per day
• Vitamin C: 500 to 1,000 mg per day
• Vitamin D3: 2,000 to 4,000 IU per day (we strongly recommend relying on blood levels in the treatment of MS, with an ideal range of 50 to 80 ng/ml 25-hydroxyvitamin D)
• One of the following:
Grape seed extract (>95% procyanidolic oligomers): 150 to 300 mg per day
Pine bark extract (>95% procyanidolic oligomers): 150 to 300 mg per day
• Specialty supplements:
Alpha-lipoic acid: 600 to 1,200 mg once per day with meals
Proteolytic enzymes: pancreatin (10X USP) 350 to 750 mg between meals three times per day, or bromelain 250 to 750 mg (1,800 to 2,000 MCU) between meals three times per day
Botanical Medicines
• Ginkgo biloba extract (24% ginkgo flavonglycosides): 120 to 160 mg twice a day is recommended for patients with cognitive impairment
Exercise
Mild to moderate exercise for at least 30 minutes three times per week is recommended. Types of exercises recommended for MS include walking, stretching, bicycling, low-impact aerobics, stationary bicycling, swimming or water aerobics, yoga, and tai chi.
Stress Reduction
Stress reduction therapies recommended for MS include meditation, deep breathing or breathing exercises, and prayer.