Integrative Care for Patients With Multiple Sclerosis

Many neurologists, including specialists in multiple sclerosis (MS), may not practice or completely understand integrative care. Some may readily dismiss integrative care. This is unfortunate both for these neurologists and their patients because integrative care is, by its very nature, more comprehensive than an exclusively conventional medical practice. This article provides a practical, evidence-based approach to integrative care, an important and underutilized care model, for treating patients with MS. More detailed reviews of the approach are in other publications.^1-4

Defining Integrative Care

There are many misunderstandings about integrative care including beliefs that it is not evidence-based, focuses on unusual and unproven alternative therapies, and does not utilize, and may actively discourage use of, conventional medicine. Some of the misconceptions and reluctance to use, or even learn about, integrative care among neurologists may stem from a lack of education and experience in this area or feelings of uncertainty because this approach differs from both their training and the currently predominant model of care.

Integrative care has several components (Box 1).⁵ It utilizes an evidence-based approach to conventional medical care that is identical to that of the current standard of care and also takes an evidence-based approach to lifestyle medicine and unconventional medicine. Lifestyle medicine is defined as daily habits and practices, such as diet and exercise, that are incorporated into conventional medical care in order to treat and also prevent disease. Unconventional medicine, also known as complementary and alternative medicine (CAM), refers to therapies that are generally not taught in medical schools or provided in hospitals, such as acupuncture and herbal medicine. In addition to blending conventional, lifestyle, and unconventional medicine, integrative care has two other essential components—it emphasizes health and wellness of the whole person, and it is practiced through a supportive, not paternalistic, clinician-patient relationship.

Integrative care aims to supportively and collaboratively deliver the best of evidence-based conventional, lifestyle, and unconventional medicine in order to treat and manage disease and also to maintain health of the whole person.

Integrative Care for Persons With Multiple Sclerosis

Although there is wide recognition of advances in MS disease-modifying medications, there is less recognition and clinical use of advances regarding the role of lifestyle and unconventional medicine for patients with MS. Lifestyle practices, including physical activity, diet, emotional health, alcohol use, and tobacco smoking, are associated with potential disease-modification, symptomatic treatment, risk and general health for patients with MS.¹ Neurologists who do not address lifestyle with their patients may be missing important opportunities for beneficial effects in their patients.

Unconventional medicine is used by 50-70% of people with MS and may be beneficial, harmful, or ineffective.^1-4 As a result, the appropriate or inappropriate use of unconventional medicine may also, like lifestyle practices, have significant positive or negative health effects. Neurologists may play an important role by helping their patients differentiate unconventional therapies that are low risk and potentially beneficial from those that are high risk and/or ineffective. Neurologists who take a don't-ask–don't-tell approach and do not address unconventional medicine in clinical practice may actually be silently endorsing unconventional medicine and indirectly perpetuating the inappropriate and unsafe use of unconventional medicine by patients who are under their care.

As indicated in the Figure, there are direct effects of healthy and unhealthy lifestyle practices on MS. Perhaps less apparent, there are lifestyle effects on MS that are exerted indirectly and mediated by lifestyle-associated diseases. An example is physical activity. Lack of physical activity may directly impact MS by worsening MS symptoms and potentially increasing risk for attacks and disability. Physical inactivity may indirectly affect MS by causing various comorbidities (such as obesity, diabetes, and hypertension) with multiple negative effects on MS.

An important consideration for both lifestyle and unconventional therapies is the quality of the research evidence for efficacy. For some of these approaches, especially unconventional therapies, there may be clinical studies but these may not be Class I randomized, controlled trials (RCTs). The tolerance for lower quality efficacy evidence, as with risk tolerance for MS disease-modifying therapies, may be significantly different between neurologists and patients. For unconventional and lifestyle approaches that have little or no significant risk, some patients, including those who understand clinical trial methodology, may be accepting of lower quality studies. A patient of the author's, who is a physician, has stated:

“I have practiced evidence-based medicine for several decades and am very familiar with the rating systems for clinical trial evidence. I also have MS. When considering therapeutic options for my MS, I am interested in Class IV studies with less than 10 patients. I am also interested in trials with MS relevance that are conducted in people with conditions other than MS. I have benefitted significantly from the rational use of low-risk therapies that have limited evidence for efficacy in MS, such as yoga, meditation, and massage.”

A Practical Approach

For neurologists, using conventional medicine for disease-modifying and symptomatic effects in MS may be extremely complicated. In this context, adding lifestyle and unconventional medicine as well as consideration of health maintenance and whole-body health may seem overwhelming. The author suggests a seven-step approach that is inclusive and flexible and may be adapted to the needs of individual patients and diverse clinical situations (Box 2).¹

An essential consideration is addressing comorbidities, including those that are lifestyle-related (eg, obesity, diabetes, hypertension, cardiovascular disease, and stroke). Comorbidities have negative effects on patients with MS, including lower health-related quality of life, increased risk of relapse and disability, worsened symptoms such as pain and fatigue, and increased hospitalization and mortality.^1,6

Disease-Modifying Medications

There have been major advances in disease-modifying medications for MS, especially relapsing-remitting MS (addressed elsewhere in this issue), and their use is the first step in evidence-based integrative care for patients with MS.

Integrative Symptom Management

Conventional symptomatic treatment, including medications, assistive devices, and physical therapy for managing symptoms of MS are familiar to most treating physicians and are addressed elsewhere in this issue.

In addition, there are more potential treatment options with lifestyle and unconventional strategies for many symptoms of MS (Table 1).^1-4 Specific lifestyle and unconventional approaches, especially those that involve physical activity and/or mind-body strategies, may improve several symptoms of MS, thus providing a single therapy that may improve multiple symptoms (Table 2).^1-3 Clinical trials ranging from Class I to Class IV in MS or other conditions provide support for the approaches listed in Tables 1 and 2. Serious consideration and use of these approaches may require significant shifts in attitude for both neurologists and people with MS. The quality of evidence should be openly discussed with patients. As noted, there may be neurologist-patient differences in tolerance for efficacy evidence, especially for therapies of little or no significant risk.

Cannabis is an unconventional symptomatic therapy that is timely.^1-3 Multiple Class I RCTs demonstrate that cannabis improves MS-associated pain (Table 1) as well as spasticity. Cannabis may also improve bladder dysfunction and sleep. There are no human studies demonstrating a disease-modifying effect on MS. It is important to note that these clinical trials of cannabis in MS have generally been done with standardized, research-grade preparations that are not available in dispensaries in the US. Also, cannabis interactions with drugs have not been well studied, cannabis products may contain toxic contaminants, and cannabis has multiple possible adverse effects, including addiction, cognitive dysfunction, psychosis, myocardial infarction, stroke, and impaired driving.

Physical Activity

Physical activity may improve multiple symptoms of MS, including anxiety, anger, cognitive dysfunction, depression, bowel and bladder dysfunction, fatigue, pain, sleeping difficulties, spasticity, gait dysfunction, and weakness.¹ In addition, there is emerging evidence that physical activity may exert disease-modifying effects by decreasing risk for attacks and disability progression.⁷ Exercise has other important effects that are relevant to general health and prevention and treatment of comorbidities, such as decreasing risk of heart disease and stroke, lowering blood pressure, improving blood lipid levels, reducing weight, preventing and treating diabetes and osteoporosis, and decreasing risk for several cancer types.¹

There are many potential physical activity options for people with MS, including less conventional options such as tai chi, Pilates, and yoga. Conventional exercise programs may be developed as needed with the input of physical therapists. Exercise programs may be modified for those with disabilities.¹ Aquatic exercise (ie, hydrotherapy) may be especially well suited for those with lower extremity weakness or gait difficulties.

There are specific exercise guidelines for general population and for those with MS and also for general health.¹ A Canadian expert committee has proposed the following guidelines for those with MS with mild to moderate disability:⁸

• Aerobic activity

• at least 30 minutes of moderate intensity activity

• twice weekly

• Muscle strengthening

• all major muscle groups

• at least twice weekly

For cardiovascular health, the American HeartAssociation (AHA) recommends:

• Aerobic activity

• at least 30 minutes moderate intensity activity

• at least 5 days per week (total of 150 min/week)

OR

• or at least 25 minutes vigorous-intensity activity

OR

• combined moderate and vigorous intensity activity

• at least 3 days per week (total of 75 minutes weekly)

• Muscle strengthening

• moderate-intensity to high-intensity strengthening

• at least 2 days per week

Diet, Dietary Supplements, and Weight Management

Nutrition is of high interest to those with MS and is also an area of great confusion. In this area, it is easy for people with MS and neurologists to “miss the forest for the trees” because of the hundreds of research studies done on dozens of possible diets. For patient care, it is important for clinicians to understand and convey nutrition information at the “forest” level.

It is unlikely that there will ever be one best diet for MS. Rather, we may discover that there is one worst diet for MS, which is the standard American diet. Healthful deviation from this will definitely be helpful in preventing and treating many comorbidities and symptoms of MS and could possibly have symptomatic and disease-modifying effects.^1,9,10

Extensive reviews of diet and MS are available,^1,10 and further review of individual studies leads to four relatively simple, broad-based nutrition guidelines for those with MS.¹

Avoid the many harmful dietary supplements. There is growing evidence that even modest doses of vitamins, minerals, and herbs may have more negative than positive health effects. Limit use of supplements based on reasonable evidence for a favorable benefit-to-risk ratio. There are more than 200 dietary supplements that may have adverse effects in patients with MS. Paradoxically, some are actually marketed as beneficial to people with MS. These potentially harmful products include those that may worsen MS disease activity or antagonize the therapeutic effects of MS disease-modifying therapies, including so-called immune-stimulating supplements such as antioxidant vitamins (vitamins A, C, and E), selenium, zinc, garlic, ginseng, echinacea, ashwagandha, and astragalus (and multiple other Chinese herbs). Other supplements may worsen MS symptoms (eg, fatigue) or decrease therapeutic effects or worsen side effects of other commonly used medications for treating patients with MS.

Consider potentially beneficial dietary supplements: vitamins D and B₁₂. Dozens of studies show association of low vitamin-D levels and increased risk of MS and, in those with MS, increased relapse risk, new MRI lesions, and disability.¹¹ Definitive data from intervention studies is not yet available. It is reasonable to obtain a patient's 25-hydroxyvitamin D level and supplement if needed to obtain a level of approximately 35 ng/mL to 55 ng/mL. Because vitamin B¹² deficiency may produce symptoms similar to MS and a subgroup of people with MS may be prone to vitamin B₁₂ deficiency, it is reasonable also to obtain vitamin B₁₂ levels and supplement if low levels are found.

Aim for a generally healthy diet. There is not one specific diet known to be best for people with MS. Instead, people with MS should be told that there are many different appropriate diets, often referred to as generally healthy diets, that broadly follow the 2015 USDA Dietary Guidelines. These may be primarily plant-based (ie, may include limited meat) and include specific diets such as the Mediterranean, DASH, McDougall, and vegetarian diet. Importantly, some of the most heavily marketed diets, including those specifically for MS, may actually have the least evidence to support their use.

Maintain a healthy weight. Obesity negatively affects patients with MS by increasing risk of many comorbid conditions (eg, diabetes, cardiovascular disease, and arthritis) and worsening symptoms (eg, fatigue, depression, sleep apnea, and bladder dysfunction), and negatively affecting disease course. Critical elements of any weight loss program are a generally healthy diet, physical activity, and changing unhealthy behavior.

Personal and Social Wellbeing

MS may have a significant impact on personal and social well-being. In fact, the most common comorbid conditions in patients with MS are disorders of mental, not physical, health.⁶ Rates of 50% for depression and 36% for anxiety have been reported in MS. High levels of stress may increase risk for relapses and worsen symptoms.¹ Similarly, depression may worsen MS symptoms such as fatigue and pain.¹ Psychiatric comorbidities have been associated with disability progression.¹² Both anxiety and depression may increase the risk or severity of various comorbidities, including hypertension, obesity, coronary artery disease, and diabetes, that may then secondarily have negative effects on MS.¹

For anxiety and depression, lifestyle and unconventional medicine greatly expand the treatment options beyond those of conventional medicine (ie, typically medications and psychotherapy). Probably the most effective nonpharmacologic treatment for anxiety and depression is physical activity. Depression or anxiety in some people with MS may even be caused or worsened by lack of physical activity because of the disability caused by MS. In these people, careful escalation of physical activity, often done with physical therapist consultation, may produce significant mental health benefits. There are many other lifestyle and unconventional strategies that in studies of variable quality in MS and other conditions have shown beneficial effects for anxiety and depression (Table 3).^1-3

Tobacco and Alcohol Use

Tobacco smoking and excessive alcohol use in those with MS may have multiple adverse effects on general health and on MS itself, but may not be addressed in clinical practice. It has been reported that alcohol is misused by 15% to 40% of those with MS but that clinician guidance on alcohol use is provided to only about one-quarter of these people.¹³

Smoking may adversely affect MS directly and indirectly and has been associated with increased risk for developing MS.^1,14 In some studies, smoking is associated with increased risk of relapses, lesion development on MRI, conversion from relapsing-remitting to secondary progressive disease, and disability progression. Smoking increases risk for development of neutralizing antibodies to natalizumab and interferons, which may decrease effectiveness of those medications.^15,16 Indirect effects of smoking occur through smoking-induced comorbidities, which are extensive and include multiple forms of cancer, coronary artery disease, stroke, pneumonia, asthma, chronic obstructive pulmonary disease (COPD), and osteoporosis.

Alcohol use, like tobacco smoking, may have direct and indirect effects on MS.¹ There are not any definitive studies that indicate that moderate alcohol use adversely affects the MS disease course. Mild-to-moderate alcohol use that is not done with care may have effects that interfere with function in those with MS, including decreased alertness and cognitive function, incoordination, gait dysfunction, fatigue, and increased reaction times. Excessive alcohol use increases the risk for multiple comorbidities that may indirectly affect MS, including hypertension, multiple cancers, liver disease, and malnutrition.

Neurologists are not typically directly involved in treatment for alcohol and tobacco misuse. However, if these issues are identified in practice, neurologists may play a valuable role by providing input to patients about the adverse health effects of tobacco and alcohol, including those on MS, and referring patients to their primary care providers for treatment.

Prevention and Management of Comorbidities

As noted earlier, comorbidities may have adverse effects on those with MS. Many of these comorbidities may be caused, or worsened by, lifestyle. As a result, steps 3-6 of this paradigm (Box 2) become important both for prevention and treatment of many comorbidities. Ideally, comorbidities are prevented by a healthy lifestyle. There may be great opportunities for comorbidity prevention in those with MS because MS is typically diagnosed between the ages of 20 and 40, an age group that has relatively few comorbid conditions. In those with comorbidities, treatment of the comorbidities should be optimized. Specific attention may be paid to comorbidities that may be improved or even reversed with lifestyle modification, such as diabetes, obesity, hypertension, and hyperlipidemia.

A Diagnosis May Motivate Positive Lifestyle Change

A critical component of effective integrative care for patients with MS is healthy lifestyle change, which neurologists may facilitate. Early in my career, several patients told me that the diagnosis of MS was one of the best things that had ever happened to them. In the moment, I thought these patients, with whom I had never discussed lifestyle, suffered from some variant of la belle indifference. In fact, they were actually wiser and more insightful than I was. On their own, they had worked to leverage the bad news diagnosis of MS into a motivator for living a meaningful, rich, and healthy life that included making lifestyle changes at a young age that they would not have made if they had not been diagnosed with MS.

A study sought to understand what factors led more than 100 people to make successful or failed lifestyle change.¹⁷ In general, success factors did not involve common approaches (eg, New Year's resolutions, motivational books, or buying exercise equipment). Rather, they were associated with crystallizations of discontent, often characterized by unexpected focal life events from external threats (eg, health problems) that produced intense negative emotional experiences. A diagnosis of MS and events in the disease course (eg, relapses, new MRI lesions, or the onset of secondary progressive disease) are such focal events and may be potent motivators for lifestyle change. Neurologists who help patients identify and leverage these in a positive way may produce lifelong health benefits for their patients. Likewise, neurologists who do not address this may be missing opportunities to improve their patients' health.

Conclusion

Integrative care of patients with MS is underappreciated and underutilized by neurologists. This is unfortunate because this paradigm is ideally suited to MS and provides treatment approaches and health opportunities that are not provided by exclusive conventional medical practice. The concepts and approaches in this article should allow neurologists to begin using this treatment model in day-to-day clinical practice.

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2. Bowling AC. Complementary and alternative medicine in multiple sclerosis. In: Giesser B. Primer on Mutliple Sclerosis. 2nd ed. New York: Oxford University Press; 2016.

3. Bowling AC. Complementary and alternative medicine and multiple sclerosis. Neurol Clin North Amer. 2011;29:465-480.

4. Yadav V, Bever C, Bowen J, et al. Summary of evidence-based guideline: complementary and alternative medicine in multiple sclerosis: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2014;82:1083-1092.

5. Rakel D, and Weil A. Philosophy of integrative medicine. In: Rakel, D. Integrative Medicine. 3rd ed. Philadelphia: Elsevier; 2012.

6. Marrie RA. Comorbidity in multiple sclerosis: implications for patient care. Nat Rev Neurol. 2017;13:375-382.7.

7. Motl RW, Pilutti LA. Is physical exercise a multiple sclerosis disease modifying treatment? Exper Rev Neurother. 2016;16:951-960.

8.. Latimer-Cheung AE, Pilutti LA, Hicks AL, et al. Effects of exercise training on fitness, mobility, fatigue, and health-related quality of life among adults with multiple sclerosis: a systematic review to inform guideline development. Arch Phys Med Rehabil. 2013;94:1800-1828.

9. Fitzgerald KC, Tyry T, Salter A, et al. Diet quality is associated with disability and symptom severity in multiple sclerosis. Neurology. 2018;90:e1-e11.

10. Altowaijri G, Fryman A, Yadav V. Dietary interventions and multiple sclerosis. Can Neurol Neurosci Rep. 2017;17:28.

11. Pierrot-Deseilligny C, Souberbielle JC. Vitamin D and multiple sclerosis: an update. Mult Scler Rel Disord. 2017;14:35-45.

12. McKay KA, Tremlett H, Fisk JD, et al. Psychiatric comorbidity is associated with disability progression in multple sclerosis. Neurology. 2018;90:e1316-e1323.

13. Turner AP, Hawkins EG, Hazelkorn JK, et al. Alcohol misuse and multiple sclerosis. Arch Phys Med Rehabil. 2009;90:842-848.

14. Weston M, Constantinescu CS. What role does tobacco smoking play in multiple sclerosis disability and mortality: a review of the evidence. Neurodegener Dis Manag. 2015;5:19-25.

15. Hedstrom AK, Alfredsson L, Lundkvist Ryner M, et al. Smokers run increased risk of developing anti-natalizumab antibodies. Mult Scler. 2014;20:1081-1085.

16. Hedstrom AK, Ryner M, Fink K, et al. Smoking and risk of treatment-induced neutralizing antibodies to interferon β-1a. Mult Scler. 2014;20:445-450.

17. Heatherton TF, Nichols PA. Personal accounts of successful versus failed attempts at life change. Personal Social Psychol Bull. 1994;20:664-675.

Allen C. Bowling, MD, PhD

Physician Associate
Colorado Neurological Institute
Englewood, CO
Clinical Professor of Neurology
University of Colorado
Aurora, CO

Disclosure

The author receives royalties from Springer Publishing and fees for research, consulting, advising, or speaking from Acorda, Bayer, EMD-Serono, Genentech, Genzyme, Mallinckrodt, Sanofi-Aventis, Teva Neuroscience, the Consortium of MS Centers (CMSC), and the Mandell Center for Multiple Sclerosis.