Multiple Sclerosis

What Is Multiple Sclerosis?

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS). It is an inflammatory and immune-mediated disease, but the exact etiology is unknown.[1] Current theories support environmental triggers activating the process in genetically susceptible individuals.[2] The underlying pathology of MS is characterized by loss of myelin sheaths, axonal degeneration, and chronic inflammation.[1] Myelin sheaths are replaced by scar tissue, which explains the “sclerosis” part of the name. T-lymphocytes and macrophages are involved in the inflammatory response, as are free radicals.[1]

The clinical syndrome of MS varies widely in severity and symptoms, depending on the area of the CNS involved. Typical symptoms include numbness, weakness, dizziness, visual disturbance, and fatigue. Associated symptoms may include depression and urinary dysfunction. Common presentations of MS involve optic neuritis (unilateral pain on eye movement) or numbness representing a sensory myelopathy of the spinal cord.[3][4] MS affects women in a 3:1 ratio relative to men and has a median age at diagnosis of 29.[5] The unpredictability of the disease adds to the challenge of making the diagnosis and also makes this a challenging condition for patients to cope with.

How Is Multiple Sclerosis Diagnosed?

Making the diagnosis of MS remains a challenge, due to the variability in symptoms and the unpredictable disease course. The basic requirement for diagnosis is the involvement of “multiple” areas of the CNS at “multiple” points in time. The patient’s symptoms, exam findings, and MRI scans are used to make the diagnosis. MRI has made it possible to make an earlier diagnosis, and now some patients can be diagnosed after one clinical attack (known as a clinically isolated syndrome). The advantage of an earlier diagnosis is that patients may qualify for disease-modifying treatments at earlier stages. The most recent guidelines for the diagnosis of MS are known as the McDonald criteria.[4] Despite these guidelines, making a definitive diagnosis based on the symptoms and MRI findings remains difficult. A physician experienced in treating MS should be involved in making the diagnosis.

What Are the Types of MS and the Prognosis?

At the time of diagnosis, 85% of patients have a relapsing-remitting course and 15% have a progressive course.[1] Various subtypes of these major categories do exist.[4] The disease can change types over time, and some patients with a relapsing-remitting course develop a progressive course, known as secondary progressive MS.

The major prognostic concern in MS is the degree of disability over time. For most individuals, life expectancy does not change.[6] Good prognostic factors include infrequent exacerbations in the first year, predominant sensory symptoms, and good recovery from individual exacerbations. The number of attacks early in the disease course seems to affect long-term disability.[1] This provides the theoretical basis for treatment with disease-modifying agents early in course of the disease. The treatments focus on decreasing attacks and slowing the accumulation of sclerotic lesions, with the hope of reducing long-term disability.

What Treatments Are Typically Used for MS?

MS treatments involve treatment of acute symptoms and ongoing treatments attempting to prevent long-term disability. The mainstay treatment of acute exacerbations is corticosteroids.[6] These are traditionally given intravenously at high doses, but they may be given orally as well.

Disease-modifying treatments have been a major advance in the treatment of MS and have only been available since the 1990s.[2] The array of treatment options has continued to expand in recent years, and now several disease-modifying options are available. As choices have expanded, so has the complexity of making treatment decisions. In addition, treatments are now being offered earlier in the course of the disease, mostly due to diagnostic criteria that allow for earlier diagnosis.

The current primary treatment options are referred to as the “ABC” treatments: Avonex (interferon beta 1a), Betaseron (interferon beta 1b), and Copaxone (glatiramer). All of these are injectable therapies, ranging in frequency from daily to once weekly. These medications have comparable effectiveness, on average reducing relapse rates by approximately one-third. They also reduce new MRI brain lesions.[5] Starting in 2010, three new medications have gained FDA approval. These are the first oral treatments for the prevention of relapse. They have varying side effect profiles and are considered second-line therapies to date. Unfortunately, none of these mentioned therapies has evidence of effectiveness in progressive MS.[5]

Is There a Role for a Whole Health Approach?

Despite the advances in treatments for relapsing MS, the available therapies are far from perfect, and their ability to reduce disability long-term remains uncertain (most trials involve time frames of just 1-3 years).[5] MS has an unpredictable course and significantly impacts quality of life. Dealing with MS means not only dealing with a physical disease, but also coping with the mental and emotional burden. It can change how a person can interact with family, friends, co-workers, and their community.

The beauty of a Whole Health approach to treating MS is that it offers a framework for treating patients that takes into account the many diverse challenges the disease can present. Incorporating self-care strategies such as nutrition, exercise, and meditation allows patients to regain a sense of control in a disease that is difficult to control. In addition, it allows for an open conversation regarding the combination of evidence-based conventional treatments with beneficial complementary approaches.

Complementary therapies in MS are aimed at either modifying the disease course or managing MS-related symptoms. There are currently no complementary or alternative therapies with evidence of effectiveness in the treatment of acute attacks.

When considering integrative MS therapy, it is important to consider research results carefully. Many MS studies exist that have very small patient numbers or are based on animal models. Many studies of complementary approaches fall into these categories; they often undergo very small “pilot” studies to test the feasibility of the treatment, making it difficult to generalize these results to the broad range of MS patients.

What Is the Role of Nutrition in MS?

In the search for causes and triggers for MS, numerous dietary factors have been implicated over time. Among these include dietary fat, sugar, alcohol, dairy, and gluten.[7] Most of these associations have since been refuted, although controversy remains regarding the overall influence of diet on the development and progression of MS. Several different dietary interventions have emerged, largely based on these associations.

Swank diet

The dietary link was initially investigated in observational studies conducted by Dr. Roy Swank in the 1930s to1940s. He concluded that MS prevalence in Norway was associated with the amount and type of fat consumed in different geographical regions. People from the inland areas who consumed more dairy fat had higher incidences of MS, and those from coastal areas who consumed more fish had lower rates.[8] Epidemiological studies on MS in other parts of the world, including the United States, have come to similar conclusions, associating high rates of MS with high intake of dairy and animal fat.[7] However, case-control trials have not confirmed these findings, making the epidemiologic data difficult to interpret.[7]

Based on his findings, Dr. Swank constructed and studied a diet low in saturated fats and high in omega-3 fats. This was accomplished through significantly limiting red meat and dairy intake while supplementing with cod liver oil. He conducted uncontrolled, longitudinal studies on this diet in MS patients and found positive long-term effects. Patients with the best adherence to a low saturated fat intake showed less neurologic deterioration and had better survival compared to those in the study with higher saturated fat intake.[9] The results of his studies were impressive; however, the study was limited by a lack of a control group and blinding.

Other diets

Several other diets have been constructed with the intent of improving MS. The McDougall low-fat diet is another diet that has followed the lead of the Swank philosophy and is currently being studied. It is a low-fat, vegan diet that limits fat intake to 10% of calories, as opposed to 15% in the Swank diet. Low-fat vegan diets have been found beneficial in other autoimmune diseases such as rheumatoid arthritis.[8]

Gluten-free diets have become popular for many diseases, including MS. A few studies have examined the relationship between MS and celiac disease. One small study showed a higher incidence of celiac disease in the MS group, and symptoms of both diseases improved on gluten-free diet.[8] However, most research has not supported the link between gluten sensitivity and MS.[10] Currently, the main support for a gluten-free diet in MS would be if a patient also had a diagnosis of celiac disease.

Another diet that has gained traction in recent years is the “Brain Nutrient Diet” designed by Terry Wahls, MD, a physician with MS. She promotes a paleo-style diet that is high in vegetable intake and specific meats, with little to no grains or legumes.[8] This has not yet been studied in MS patients.

Summary

The most likely dietary association in MS is the intake of saturated fats from red meats and dairy products, but this relationship has not been definitively proven. A diet that is low in red meats and dairy and high in fruits, vegetables, and omega-3 fats from fish seems like a reasonable approach, especially given the likely benefit this style of eating has in preventing other chronic diseases. Known diets that would fit well with these recommendations include Mediterranean, anti-inflammatory, or plant-based vegetarian diets.

Are There Supplements that May Be Useful in the Prevention of Attacks?

Note: Please refer to the Passport to Whole Health, Chapter 15 on Dietary Supplements for more information about how to determine whether or not a specific supplement is appropriate for a given individual.  Supplements are not regulated with the same degree of oversight as medications, and it is important that clinicians keep this in mind.  Products vary greatly in terms of accuracy of labeling, presence of adulterants, and the legitimacy of claims made by the manufacturer.

The use of dietary supplements in MS can be an overwhelming topic. Supplement options may include those that are intended to modify the disease process, as well as those intended to treat specific MS-related symptoms. This section focuses on supplements with potential disease-modifying properties.

There are several challenges in determining appropriate supplements to use in MS. First, the potential options are numerous. Second, the majority of trials on supplements are small or based on experimental models of MS in animals. It is usually premature to draw definitive conclusions from these types of studies. Lastly, many supplements have theoretical effects on the immune system. Some experts in the field recommend avoiding anything that is potentially “stimulating” to the immune system.[9] This issue is addressed in more detail below.

Vitamin D

Vitamin D has long been associated with MS. Geographic areas that get more sunlight have lower rates of MS. Vitamin D deficiency is associated with MS, as are other autoimmune processes such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease.[11] In addition, vitamin D receptors are found on many cells, but notably, they are found in the central nervous system.[11] A recent study published in 2014 established vitamin D level as a predictor of disease progression.[12] Vitamin D levels above 50 nmol/L were associated with lower disease activity and slower progression.[12] Small trials have established safety with supplementation at high doses, up to blood levels of 150 nmol/L.[13] These trials have suggested therapeutic benefit, but the small sample sizes limit the ability to generalize results.[9] The optimal dose and blood level of vitamin D is currently unknown in MS.[13] Based on the 2014 study results, supplementing to ensure a blood level of greater than 50 nmol/L seems reasonable and safe.

Omega-3 supplementation

Omega-3 fatty acids are known to be anti-inflammatory and thus have a theoretical basis for benefit in MS. Studies to date have been mixed in regards to disease benefit in MS. The largest trial of over 300 patients showed a trend toward a beneficial effect in MS disease progression with high-dose omega-3 supplementation.[14] Another trial showed no improvement in multiple clinical and MRI parameters.[9] Omega-3 supplementation has been found beneficial in rheumatoid arthritis, also an autoimmune process.[15] Doses should be standardized based on the amount of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) present in the supplement, and should exceed 2 grams per day of EPA plus DHA to get the desired benefit. Omega-3 supplements are quite safe and may improve other aspects of health, such as lipid profiles.

Linoleic acid

Linoleic acid is an omega-6 fatty acid, also with known anti-inflammatory properties. It is found in seeds and nuts such as flaxseed, sesame seed oil, or sunflower oil. It can also be taken as a supplement. Linoleic acid was studied as a therapy in MS patients in 1970s, with two studies showing a slower progression of disability and reduced severity of attacks.[9] A third study did not find benefit with linoleic acid, although the patients involved in this study had more severe disease.[9] The optimal dose is not known. The dosage used in the studies was 17 grams/day of linoleic acid. A dose of 4 tsp/day of linoleic acid–containing oils is sometimes recommended.[9] There are theoretical reasons why gamma-linoleic acid could be superior to linoleic acid, but studies have not shown this to be effective.[9]

Turmeric

Turmeric is an intriguing supplement due to its anti-inflammatory and neuroprotective properties. Animal models show that this could improve the state of the blood brain barrier, which is damaged in MS.[8] There are not yet trials of turmeric in MS patients.

Alpha-lipoic acid

This is a naturally occurring antioxidant that is important for normal mitochondrial function. It has shown promise in treating peripheral neuropathy and also has shown benefit in studies focusing on animal models of MS.[16] A pilot study of alpha-lipoic acid use in MS patients showed improvement in biomarkers related to T-cell function, the prominent immune culprit in MS.[17] Further studies are needed to clarify if this leads to true clinical benefit.

Are There Supplements that Should Be Avoided?

MS is thought to be an autoimmune-mediated process, specifically associated with overactivity of T-cells. One concern of some supplements would be “immune-enhancing” effects, as this could theoretically stimulate an already over-stimulated immune system.[9] Unfortunately, the concept of “stimulating or suppressing” the immune system in MS is overly simplistic. Stimulating the immune system isn’t necessarily counterproductive in MS, as demonstrated by other therapeutic modalities. Exercise, for example, is known to have positive effects on the immune system, but is also beneficial for MS as described above. Perhaps a better characterization for the immune system effects of beneficial therapies would be one of “normalizing” as opposed to stimulating or suppressing. Unfortunately, there is still much to be learned on both ends—the underlying biology of the disease process and the mechanism of action of many supplements and therapies.

In the meantime, it makes sense to use caution with supplements that could be stimulating to the immune system, unless there is good reason to believe a supplement could be a beneficial addition to an individual’s treatment plan. Supplements listed below do not have evidence of benefit in MS-related symptoms and may stimulate T-cell activity:

  • Alfalfa
  • Arnica
  • Astragalus
  • Cat’s claw
  • Echinacea
  • Garlic
  • Ginseng (Asian and Siberian)
  • Licorice
  • Saw palmetto

Are Mind-Body Therapies Useful in MS?

Mind-body interventions represent multiple psychological, social, and spiritual approaches to medicine, including psychotherapy, meditation, relaxation, imagery, hypnosis, and biofeedback. Mind-body approaches can have multiple positive effects in MS patients and have been shown to improve overall quality of life.

Mindfulness meditation has been studied in a number of chronic diseases, including MS. A 2010 randomized trial of 150 MS patients compared an 8-week mindfulness meditation class to usual care. The meditation participants had improvements in fatigue, depression, anxiety, and quality of life.[18] These improvements persisted at follow-up 6 months later.[18] Another study showed a decrease in new brain lesions on MRI in MS patients during a 24-week stress management program that included meditation.[19] When studied in other chronic conditions, meditation has proven beneficial in improving pain intensity, sleep, and stress management and is worth suggesting to people with MS.[20][21][22]

There are many options when considering mind-body interventions, and specifically which one to choose will depend a lot on which treatment resonates most with each patient. With the current research base, mindfulness meditation is an excellent recommendation for MS patients. There is evidence of improvements in multiple MS-related symptoms, stress management, and coping skills. This form of meditation can be self-taught, is free, and can continue indefinitely as a self-care modality. There are also many resources that can be offered to patients to assist in learning about the practice and in performing the meditation itself. Refer to the “Mindful Awareness” and “Power of the Mind” modules for more information and guidance regarding the use of specific mind-body approaches.

What Is the Role of Exercise and Movement in the Treatment of MS?

Exercise is a well-established pillar of a healthy lifestyle. It has the ability to prevent and treat a wide range of illnesses from cardiovascular disease to depression and from dementia to osteoarthritis. However, until recently, physicians often recommended that MS patients avoid exercise. The main concerns included exercise causing a rise in the body temperature that might trigger symptoms in heat-sensitive patients and exacerbate MS-related fatigue.[23] The “Uhthoff phenomenon” describes a transient amblyopia that can occur with exercise or overheating.[24] Fortunately, these symptoms are reversible and are not thought to be triggers of exacerbations. Also reassuring is that normal exercise does not significantly raise the core temperature.[24]

Overall, exercise should now be recommended routinely for MS patients. Research has demonstrated improvements in disease-related fatigue, mobility, and quality of life.[25] A 2005 Cochrane review supports the use of exercise in MS.[26] A 2009 meta-analysis found an improvement in walking mobility in MS patients after a training program.[27] A randomized trial in 2004 showed improvement in fatigue in MS patients with either yoga or general exercise classes.[28]

Implementing an exercise program requires an initial assessment of a person’s current functional status and limitations. Patients with significant mobility needs, weakness, or spasticity should create an exercise plan with the help of a physical therapist or other person with experience in this area. For those with significant impairments, exercise programs can start with passive range-of-motion exercises, then advance to flexibility and active range-of-motions exercises.[23] If that is well tolerated, more integrated exercises such as walking, swimming, or yoga can be initiated. If the goal is improved mobility, weight-bearing exercises should be included.[24] Water-based exercises can be a good substitute for some patients. For those with few or no mobility issues, recommendations mirror those without MS: Find an activity you like to do, start slowly, and stick with it! Refer to “Moving the Body” for additional information.

What Complementary Modalities May Be Effective in Treating MS-Related Fatigue?

Fatigue is the most common symptom in MS, with over 70% of patients reporting the symptom.[24] Fatigue is a leading cause for unemployment due to MS.[24] Fatigue is both a lack of energy and muscular fatigue, likely from both central and peripheral causes.[24] Interestingly, the duration and severity of MS do not correlate to degree of fatigue.[24] It is important to consider causes of fatigue other than MS, such as medications, depression, alcohol use, life stressors, and other medical problems (e.g., hypothyroidism, anemia, sleep apnea, etc.).

Fatigue is best managed by first addressing lifestyle components such as sleep, exercise, and nutrition. Exercise alone has been shown to improve fatigue in MS, as well as in other chronic conditions.[28] Exercise is also known to improve sleep and depressive symptoms, both of which contribute to energy levels.[29][30] Stress management is another important topic to discuss. Stress can negatively impact energy directly or contribute to sleep problems. Meditation is an excellent intervention, as it has been shown to improve sleep, stress management, and fatigue.

There are some supplements to consider in managing MS-related fatigue. A small study of acetyl L-carnitine showed some effectiveness in MS-related fatigue. The dose is 1,000 mg twice a day.[9] Ginkgo biloba has been studied in MS with mixed results. Small studies have shown improvements in MS-related fatigue and cognitive deficits.[9] A 2012 trial did not replicate the benefit in cognitive function; it showed no benefit in MS patients.[31] Ashwagandha is an herbal remedy often categorized as an adaptogen, and it is sometimes recommended for MS-related fatigue. This compound does stimulate some cells in the immune system, so it poses a theoretical risk in MS. (Refer to the list of supplements to avoid, above.)[9] However, it also has anti-inflammatory and antioxidant properties that could theoretically benefit MS.[32] There are no specific studies that involve MS patients. The dose of ashwagandha is 1-2 grams of the whole herb 2-3 times per day.[13] If falling asleep itself is contributing to fatigue, melatonin and valerian are both reasonable supplement options. Valerian also may be used for mild anxiety symptoms.

What Complementary Modalities May Be Effective in Treating MS-Related Pain?

Pain in MS is also common. Estimates in prevalence vary, but the majority of patients will experience pain at some point in their illness.[33] Types of pain that may be directly related to MS are muscle spasticity and neuropathic pain. There are three common types of neuropathic pain in MS: “dysesthetic” limb pain (burning pain of legs and feet, often worse at night), trigeminal neuralgia, and “Lhermitte’s sign” (brief, electric shock-like sensation triggered by neck flexion).[33] Other pain syndromes, such as headache and low back pain, may be more common in patients with MS.[33]

There are several integrative therapies with evidence of effectiveness for pain syndromes in general. A review of these therapies is available in the “Supplements for Pain” tool. Exercise and mind-body therapies are both effective for chronic pain and also effective for other MS symptoms, as discussed above. In addition, omega-3 supplementation and vitamin D supplementation also have some research support in certain pain syndromes.[15][34]

There are few complementary treatments that have been studied extensively in neuropathic pain or spasticity in MS. Here are a few potential options to consider:

Acupuncture has the potential of being an excellent therapeutic option for MS-related pain, but this has received very little study in MS patients. Acupuncture has been found to treat many types of pain, including common syndromes such as headache and low back pain.[35] There is some evidence of benefit in some neuropathic pain syndromes, although research regarding this is mixed.[36] There is also some evidence of benefit in stroke rehabilitation.[37] Acupuncture also has the added benefit of treating some coexisting symptoms, such as insomnia and fatigue.[38] Despite the lack of studies in MS patients, acupuncture is a reasonable therapeutic option for MS-related pain given its evidence of benefit in related pain conditions and excellent safety profile.

Cannabis is one of the few alternative treatments that has been studied for treatment of spasticity. A recent randomized controlled trial demonstrated benefit for cannabis over placebo for MS-related spasticity.[39] Not all trials have demonstrated a large treatment effect, and there are well-known intoxication side effects. Laws remain the major barrier to more widespread use, as marijuana remains illegal federally in the United States despite now being legal in several states.

Alpha-lipoic acid, which is discussed above, has evidence supporting its use for treating pain related to diabetic peripheral neuropathy.[40] It is a reasonable option for treating the peripheral dysesthetic pain, especially given other potential benefits in MS.

Summary

Multiple sclerosis is a chronic, immune-mediated disease that causes variable degrees of neurologic disability, fatigue, and pain. It can lead to significant impacts on quality of life. Conventional medical therapies offer the hope of reducing long-term disability, although this is not yet proven. Integrative therapies should not be used in place of conventional treatments, but do offer other options to potentially modify the disease course and improve disease-related symptoms.

Several integrative therapies are being supported by the evidence as having benefit. The most promising therapies include regular exercise and meditation, which are shown to improve multiple MS-related symptoms and quality of life. A plant-based diet low in red meats and dairy and high in sources of omega-3 fatty acids may improve the disease course as well as offer other preventative health benefits. It is reasonable to supplement or monitor vitamin D levels in MS patients. Integrative options are also reasonable to consider for MS-related symptoms such as fatigue and pain.

Resources

Organization

Meditation Sources

  • Stahl B, Goldstein E. A Mindfulness-Based Stress Reduction Workbook. Oakland, CA: New Harbinger Publications; 2010.
  • Kabat-Zinn J, Hanh TN. Full Catastrophe Living: Using the Wisdom of Your Body and Mind to Face Stress, Pain, and Illness. New York, NY: Random House LLC; 2009.
  • Kabat-Zinn J. Wherever You Go, There You Are: Mindfulness Meditation in Everyday Life. New York, NY: Hyperion; 1994
  • Breathing Exercises: Handout: http://www.fammed.wisc.edu/sites/default/files//webfm-uploads/documents/outreach/im/handout_breathing.pdf
  • Guided Mindfulness Meditation Series, CDs, by Jon Kabat-Zinn

Author(s)

This tool was written by Russell Lemmon, DO, Assistant Professor and integrative medicine family physician in the Department of Family Medicine, University of Wisconsin-Madison School of Medicine and Public Health.

References

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