Multiple Sclerosis

Multiple Sclerosis

1 Overview

Summary and Quick Facts

  • Multiple sclerosis (MS) is a disease in which the immune system damages structures that help nerve cells communicate. It can cause symptoms that come and go, including numbness or tingling, muscle weakness, vision problems and trouble walking or talking.
  • In this protocol, learn about the causes of MS and what treatments are available. Discover how an imbalanced immune system contributes to the inflammation that drives the disease.
  • Vitamin D supplementation has been shown to modulate the immune response in MS and help improve symptoms, in some clinical trials.

What is Multiple Sclerosis?

Multiple sclerosis (MS) is an autoimmune and inflammatory disease characterized by destruction of the myelin sheath—the coating that insulates and protects neurons. This demyelination causes disruptions in neural communication and potentially neuronal death, leading to disability.

MS may follow several disease courses, the most common of which is relapsing remitting. Relapsing remitting MS is characterized by clearly defined acute attacks followed by periods of remission.

Natural interventions such as vitamin D and essential fatty acids may help relieve inflammation and improve symptoms of MS.

What are the Risk Factors for Multiple Sclerosis?

  • Genetic predisposition
  • Viral infection (eg, Epstein-Barr virus)
  • Vitamin D deficiency
  • Hormonal imbalance
  • Exposure to organic solvents
  • Food sensitivities
  • Smoking

What are the Signs and Symptoms of Multiple Sclerosis?

Note: Symptoms of MS vary widely, depending on the location of affected nerve fibers. Symptoms may include:

  • Fatigue
  • Numbness or tingling in limbs
  • Impaired vision
  • Muscle weakness, clumsiness
  • Loss of balance, dizziness, potential nausea and vomiting
  • Bladder dysfunction
  • Changes in memory, reasoning, and spatial perception

What are Conventional Medical Treatments for Multiple Sclerosis?

Note: There is currently no cure for MS. Treatments include therapies to calm acute attacks, slow or modify the disease course, and alleviate symptoms. Several experimental therapies are currently being evaluated by the Food and Drug Administration.

  • Therapies for acute attacks:
    • Corticosteroids
    • Plasmapheresis (plasma exchange to remove inflammatory factors and antibodies)
  • Disease-modifying therapies:
    • Beta interferons to reduce inflammation and slow disease progression
    • Glatiramer acetate, an immunomodulator
    • Immunosuppressant drugs (eg, mitoxantrone)
    • Monoclonal antibodies (eg, natalizumab)
    • Dalfampridine, a potassium channel blocker, to increase the ability of nerve cells to conduct impulses
  • Symptom management may include:
    • muscle relaxants
    • medications to reduce fatigue
    • antidepressants

What are Additional Therapies for Multiple Sclerosis?

  • Physical therapy
  • Occupational therapy
  • Speech therapy
  • Cognitive rehabilitation
  • Vocational rehabilitation
  • Swank low-fat diet
  • Hormone therapy

What Natural Interventions May Be Beneficial for Multiple Sclerosis?

  • Vitamin D. As vitamin D deficiency is a risk factor for MS, supplementation may be helpful. Several clinical studies have demonstrated that MS patients taking vitamin D had fewer relapses and less inflammation.
  • Essential fatty acids. Omega-3 (ie, DHA and EPA) and certain omega-6 (ie, GLA) fatty acids have been shown to reduce inflammation and improve some symptoms of MS.
  • Antioxidants. Oxidative stress may play a role in the pathogenesis of MS, and MS patients tend to have low levels of the endogenous antioxidant glutathione peroxidase. Supplementing with selenium, vitamin E, vitamin C, and/or N-acetylcysteine may boost glutathione peroxidase levels for potential benefits.
  • Lipoic acid. Lipoic acid has been shown to inhibit the activity of ICAM-1, a protein believed to be involved in the pathogenesis of MS. Supplementation with lipoic acid reduced ICAM-1 levels and T-cell migration into the central nervous system in patients with MS.
  • Vitamin B12. Patients with MS may be deficient in vitamin B12. Supplementation has been shown in several studies to improve symptoms and the clinical course of the disease in patients with MS.
  • Biotin. Biotin (vitamin B7) has demonstrated positive effects in patients with MS. Studies showed high doses of biotin improved measures of MS-related disabilities in some patients.
  • Other natural interventions that may benefit patients with MS include coenzyme Q10, ginkgo biloba, green tea, and curcumin.

2 Introduction

Multiple Sclerosis (MS) is a disease of autoimmunity and inflammation characterized by destruction of the myelin sheath that insulates and protects neurons. When a patient experiences an "attack," or episode of increased disease activity, the resultant impairment of neuronal communication can manifest as a broad spectrum of symptoms, affecting sensory processing, locomotion, and cognition.

Scientific research suggests both genetic and environmental factors contribute to the development of the disease. Current medical treatments for MS include potent immunosuppressive drugs, which reduce immune function, and anti-inflammatory medications as well as invasive procedures such as plasma exchange, which attempts to reduce inflammatory mediators in a patient's blood.

Largely ignored and discounted by mainstream medicine, nutrients offer immune-modifying benefits that can help complement pharmacological and clinical interventions and improve quality of life for MS patients.

Furthermore, mounting evidence suggests vitamin D may be a missing link in virtually all autoimmune diseases, including MS. This single vitamin has the ability to modulate the immune system in ways that even pharmaceutical drugs cannot. A multitude of epidemiological studies have revealed that individuals with low levels of vitamin D in their blood are at considerably increased risk for developing MS; in fact, up to 90% of MS patients are deficient in vitamin D.1

3 Understanding Multiple Sclerosis

Within the central nervous system (brain and spinal cord) a vast network of neurons are constantly communicating amongst themselves, and with the peripheral nervous system (outside of the brain and spinal cord), to control every aspect of human function, from sight and hearing, to cognition and mobility. The efficiency and accuracy of communication between individual neurons form the basis for our ability to do things as diverse as complete simple daily tasks and comprehend complex philosophical or mathematical ideas.

Neuronal communication is similar to the transmission of an electrical current through a series of wires. Droves of neurons work together to deliver messages to every corner of the body by transmitting signals along their long, cylindrical mid-sections called axons and passing it on to the next neuron. This is repeated until the message reaches its destination. Like electrical wires, neuronal axons require insulation to ensure that they are able to transmit a signal accurately, and at high speeds. Specialized cells called oligodendrocytes provide this insulation to neurons by wrapping the axons in an insulating material called myelin. Without this myelin sheath, neuronal communication becomes nearly impossible, and neurons become susceptible to damage.

Multiple sclerosis is a disease which ultimately leads to the inability of neurons to communicate amongst themselves. Because multiple sclerosis is not selective for specific neurons, and can progress through the brain and spinal cord randomly, each patient's symptoms may vary considerably.

During the initial stages of the disease, symptoms often emerge for a finite time before regressing for an extended period.

4 Pathology of Disease Progression

Demyelination

MS is an immuno-inflammatory disease in which immune cells enter the central nervous system (CNS) and destroy the myelin sheath. Immune cells, which become activated through complex mechanisms migrate into the CNS, and attack the myelin sheath. The resultant demyelination is thought to be carried out by T lymphocytes, B lymphocytes, and macrophages, three primary classes of immune cells, which are routinely found in MS lesions.2

Loss of myelin followed by subsequent lack of neural communication and neuronal death is accepted as the primary cause of disability in MS patients.3 Axonal transection, or the severing of axons, occurs under conditions of both acute and chronic demyelination.4-6

Remyelination

Remyelination is the process by which demyelinated axons are naturally re-wrapped with myelin, restoring nerve conduction and functionality.7 This phenomenon is the result of oligodendrocytes repairing the damage to the myelin sheath that occurs during an episode of increased disease activity. However, as the disease progresses over years (usually decades) the oligodendrocytes begin to lose their ability to repair the damage, and symptoms become progressively worse and episodes more frequent due to remyelination failure. In addition to developing therapies that slow MS disease progression, many laboratories are developing novel therapeutics that aim to promote remyelination and reverse existing CNS damage.

Inflammation

In addition to immune-mediated loss of myelin, another characteristic feature of MS is inflammation caused by a class of white blood cells called T cells.8,9 Some of the damage in the CNS is directly carried out by two subpopulations of T lymphocytes called T helper 1 and T helper 17 which produce pro-inflammatory factors.10 Recent studies have identified that chemical mediators, interleukin-23 (IL-23) and granulocyte macrophage colony-stimulating factor (GM-CSF), contribute to the autoimmune characteristics of these T cells. Data suggest absence of these pro-inflammatory signals was sufficient to prevent inflammation in the brain.11 This suggests that therapeutic strategies directed at blocking the production of inflammatory mediators could be effective for treating MS.

Vitamin D and Multiple Sclerosis: A Panacea?

Mainstream medicine has failed to recognize the pivotal role of vitamin D in regulating the overactive immune system in MS patients.

Greater than 30 years have passed since vitamin D was originally hypothesized to be an important environmental determinant of the prevalence of MS.12,13 During the three decades following the initial linking of vitamin D and MS, evidence has continued to mount. It is now known that MS occurs more frequently in individuals with lower blood levels of vitamin D. A study published in the prestigious Journal of the American Medical Association found that, compared to those with the highest vitamin D blood levels, those with the lowest blood levels were 62% more likely to develop MS.

MS attacks occur less frequently during seasons corresponding with the highest exposure to sunlight; since vitamin D synthesis depends upon exposure of the skin to sunlight, the summer months also bring the highest blood levels of vitamin D.14 A recent study has quantified the impact of vitamin D blood levels on risk for MS relapse—for each 4 ng/ml increase in 25-hydroxy vitamin D in the blood, the risk for MS relapse is reduced by 12%. The investigators who conducted this study concluded that "Clinically, raising 25-hydroxy vitamin D levels by [20 ng/ml] could halve the hazard of a relapse."15

Vitamin D mediates these disease-modifying effects through complex and powerful interactions with the immune system. Hostile immune cells, which attack the myelin sheath, are calmed upon exposure to vitamin D. In fact, when aggressive immune cells taken directly from MS patients are exposed to the active form of vitamin D, the cells divide and reproduce much more slowly, indicating that vitamin D has the ability to impede the aberrant autoimmunity that is a driving force in MS.

However, vitamin D does more than just arrest damaging immune cells; it also supercharges protective immune cells.

T-reg cells are specialized components of the immune system that help keep immunity balanced. If too few T-reg cells are present, the immune system becomes overactive, as in autoimmune diseases like MS. Vitamin D increases the number of protective T-reg cells, restoring equilibrium to an overactive immune system.16

In a randomized controlled trial, supplementation with doses of vitamin D ranging from 10,000 IU to 40,000 IU daily over the course of 52 weeks resulted in a reduction in relapses and a reduction in the number of aggressive immune cells in patients with MS.17

Despite robust findings across a range of studies on the link between vitamin D and MS, mainstream medicine and the federal government have only just recently begun to realize the need to initiate federally funded trials. Results of a large scale, randomized, controlled clinical trial to assess the effects of vitamin D in MS are currently pending.1

Life Extension customers should not be surprised if vitamin D emerges as a frontline treatment for MS in the coming years. However, instead of waiting for mainstream physicians to begin recommending vitamin D to MS patients, Life Extension suggests all individuals monitor their blood levels of 25-hydroxyvitamin D and maintain a blood level of 50–80 ng/mL. This is because low vitamin D levels are also an emerging risk factor for numerous other diseases, such as type 1 diabetes, heart disease, and rheumatoid arthritis.18-22 The amount of supplementation required to achieve this blood level varies from person to person, but it appears many individuals require supplementation of 5,000‒8,000 IU vitamin D daily to reach these levels.

More information about the role of vitamin D in health is available in the compelling Life Extension Magazine article entitled "Startling Findings About Vitamin D Levels in Life Extension Members."

5 Risk Factors for MS

Genetics and Family History

Studies have established a definitive role for genetics as contributing factor for developing MS. The most compelling data reveal that while unrelated adopted siblings have a 0‒2% disease risk, identical twins demonstrate a 25% disease risk.23 Several studies have identified susceptibility genes related to many aspects of immune function.24-28 While these genetic links are helpful in understanding MS population clusters, findings such as the 25% disease risk among identical twins and the geographic distribution of MS suggest that up to 75% of MS must be attributable to non-genetic or environmental factors.

Infection

Infection is one of the more widely suspected non-genetic risk factors for MS. Data suggest that, in genetically predisposed individuals, exposure to an infectious agent may lead to MS.29 One common theory, molecular mimicry, proposes that presentation of foreign antigens that are molecularly similar to self-antigens leads to an autoimmune response.30,31 In other words, viruses involved in the development of autoimmune diseases could possibly display very similar proteins to the proteins found on nerves making these nerves also a target for antibodies. Investigators have probed the involvement of several viruses including: herpes simplex virus (HSV), rubella, measles, mumps, and Epstein Barr virus (EBV).32 Currently, the strongest evidence for the involvement of an infectious agent implicates EBV. Virtually all patients who have MS are infected with the EBV.32 Further, levels of antibodies to EBV are strongly correlated with the risk of developing the disease.33

Low Vitamin D Levels

Considering the regulatory role that vitamin D plays in immune system reactivity, it is not surprising that population-based studies have consistently found lower levels of vitamin D in the blood of patients with MS compared to healthy control subjects.

Data from the Nurses' Health Study (more than 92,000 women followed from 1980 to 2000) and the Nurses' Health Study II (more than 95,000 women followed from 1991 to 2001), support the notion of a protective effect for vitamin D against the risk of developing MS. The incidence of MS was 33% lower in women that consumed the most vitamin D as compared to those that consumed the least. In addition, those that consumed at least 400 IU daily of vitamin D from supplements had an astounding 41% lower incidence of MS.18

In a recent study, researchers at the University of California, San Francisco discovered low 25-hydroxyvitamin D blood levels in African Americans with MS as compared to controls.34 The senior author, who is also the associate director of UCSF Multiple Sclerosis Center concluded, "It seems relatively clear low vitamin D levels are a risk factor for developing multiple sclerosis."

Hormones

Studies have shown that MS is more common in women than men, and that the disease course is affected by the fluctuation of steroid hormones during the female menstrual cycle.35 It is also widely reported that MS patients who become pregnant experience a significant decrease in relapses, enabling women who have MS to bear children safely.36 Animal models of multiple sclerosis have shown that the pregnancy hormone, estriol, can ameliorate disease and can cause an immune shift.36,37 Other studies note that pregnant women who have MS tend to experience a rebound of their disease within three months post-delivery.38

These findings suggest hormones can regulate the course of MS, and this theory is further supported by research demonstrating that steroid hormones (eg, estrogens, testosterone, progesterone, and, dehydroepiandrosterone [DHEA]) can modulate the immune system.39-41

The specific relationship of hormones to the disease process of MS is complex, with ratios between the individual hormones also playing a role. For example, during a human study that examined the presence of MS lesions by magnetic resonance imaging (MRI), patients with high estradiol and low progesterone levels had more lesions that those who had low levels of both hormones. Further, patients with a high estrogen to progesterone ratio had a significantly greater number of "active," inflamed lesions than patients who had a low ratio.42 These studies suggest that maintaining youthful hormone balance may ease the symptoms of MS.

A study from Italy provided further evidence that abnormal hormone levels may play a role in the development of MS. The investigators measured hormone levels in 35 women and 25 men with MS, and in 36 people without the disease. Women with low testosterone levels were found to have more brain tissue damage, as determined using magnetic resonance imaging (MRI). The women with MS had lower levels of testosterone throughout their monthly cycle compared to women who did not have the condition. Testosterone levels did not vary between men with MS and unaffected men. However, men with MS who had the highest levels of the female hormone estradiol were found to have the greatest degree of brain tissue damage.43

More information about optimizing and balancing hormone levels can be found in Life Extension's "Male Hormone Restoration" and "Female Hormone Restoration" protocols.

Organic Solvents

In the mid-1990s, researchers in Sweden evaluated 13 studies investigating the connection between solvent exposure and autoimmune disease. Organic solvents include chemicals such as toluene, paint thinner, and acetone, the latter of which is commonly found in nail polish remover. Ten of those studies indicated a significant relationship between organic solvent exposure and MS. All of the analyses suggested exposure to solvents increases a person's relative risk of developing MS.44 In another study scientists analyzed the occupational health records of more than 57,000 workers in Norway, covering a 16-year period. They concluded that workers, such as painters, who are routinely exposed to organic solvents, had twice the risk of developing MS than those who were not occupationally exposed. These results were compatible with the hypothesis that organic solvents are a possible risk factor for MS.45

Individuals interested in protecting themselves from organic solvents and other environmental toxins should read Life Extension's "Metabolic Detoxification" protocol.

Food Sensitivities

Sensitivities to certain foods may also play a role in the development or exacerbation of MS. Antibodies to gluten, which is a protein found in wheat, is more common in patients with MS.46,47 MS is also most prevalent in areas where consumption of wheat gluten and milk are also high.48 This relationship led scientists to explore a possible link between antibodies produced to bovine milk proteins and the ability of those antibodies to cross-react to the protective sheathes around nerves triggering an MS episode. Indeed, this immunologic cross-reactivity has been demonstrated in the laboratory in rodents that have MS.49,50 Further investigations have revealed that in MS patients, higher levels of these antibodies are produced within the central nervous system.51 Additional studies are still needed to understand how this cross-reactivity plays into the development and progression of MS.

To help rule out food sensitivities, Life Extension suggests blood testing such as the Food Safe Allergy test and the Celiac Disease Antibody Screen. Call 800-226-2370 for more information on how to obtain this type of testing. Additional information about food allergies is available in the Life Extension Magazine article entitled "What's Really Making You Sick?"

Smoking

A recently published literature review, evaluating more than 3,000 MS cases and 450,000 controls, supports the emerging consensus that smoking increases the risk of developing MS by approximately 50%.52 It is unlikely that smoking alone accounts for the worldwide variation in MS prevalence, and thus, the interplay between genetic markers and smoking has also been investigated. One such study reported that smokers that have two known genetic markers for MS had two times the risk for developing MS than their non-smoking counterparts.53 Another study has also verified that smokers diagnosed with MS but in remission have 3.5 times the risk of reactivating and progression of their disease than their non-smoking counterparts.54,55

6 Symptoms and Diagnosis

MS can affect people of all ages; however, the average age of disease onset is between 20 and 40 years.48 Fatigue, numbness in the limbs, impaired vision, muscle weakness, loss of balance, and bladder dysfunction are frequent symptoms.

Symptoms of multiple sclerosis vary widely, depending on the location of affected nerve fibers.48

  • Symptoms affecting mobility tend to appear early in the course of MS and they may include weakness, clumsiness, leg dragging, stiffness, and a tendency to drop objects.
  • Common sensory symptoms include numbness, sensations of heaviness, tingling, and electrical sensations.
  • Visual symptoms are also common, affecting more than one-third of all people who have MS. The classic visual disturbances, such as blurred or foggy vision and eyeball pain, usually appear early in the course of the disease.
  • MS can also interfere with the nerves that supply the vestibular apparatus in the inner ear, which is where balance is perceived. This can result in dizziness, nausea, and vomiting.
  • In the later stages of the disease, involvement of the genitourinary tract may result in loss of bladder, sexual, and bowel function.56
  • Over 40% of MS patients suffer from changes in memory, reasoning, spatial perception, and verbal fluency.57
  • Symptoms of MS are often triggered or worsened by an increase in body temperature.

MS is a tremendously variable and unpredictable disease. Different patients will experience different symptoms, rates of disease progression, and responses to treatment.

Four Disease Courses Have Been Identified in MS

  • Progressive relapsing (PR) MS, which is the least common disease course, shows progression of disability from onset but with clear acute relapses, with or without full recovery. Approximately 5% of people with MS appear to have PRMS at diagnosis.
  • Secondary progressive (SP) MS begins with an initial relapsing-remitting disease course, followed by progression of disability. Typically, secondary-progressive disease is characterized by: less recovery following attacks, persistently worsening functioning during and between attacks, and accompanied by progressive disability. Many patients with RRMS do develop SPMS ultimately.
  • Primary progressive (PP) MS is characterized by progression of disability from onset, without plateaus or remissions or with occasional plateaus and temporary minor improvements. A person with PPMS, by definition, does not experience acute attacks. Ten percent of diagnosed MS are PPMS.
  • Relapsing remitting (RR) MS represents 85% of clinical diagnoses of the disease. It is characterized by clearly defined acute attacks with full recovery or with residual deficit upon recovery. Periods between disease relapses are characterized by a lack of disease progression.

Diagnosis

No single test gives a definitive diagnosis for MS, and variable symptoms and disease course make early diagnosis a challenge. Most presumptive diagnoses of MS are based on the clinical symptoms seen in an acute attack. These presumptions are then supported by a combination of diagnostic imaging with magnetic resonance imaging (MRI), antibody testing of the fluid found in the CNS, measurements to evaluate how efficiently nerves conduct impulses (since demyelination slows nerve conduction) and evaluation of how the symptoms progress through time.58

7 Conventional Therapies

A cure for MS has yet to be discovered, and although recent efforts have brought advances in available treatments, substantial room for improvement remains. Presently, conventional medical treatment typically focuses on strategies to treat acute attacks, to slow the progression of the disease, and to treat symptoms.

Conventional Medical Treatments to Treat Acute Disease Flares

Corticosteroids. For acute MS flares, corticosteroids, such as methylprednisolone, are commonly administered in high doses to suppress the immune system and decrease the production of proinflammatory factors. These drugs are often prescribed for short periods and can be effective at alleviating the symptoms of MS. Corticosteroids should not be used for long-term therapy, however, because of their many side effects, including increased risk of infection, osteoporosis, high blood pressure, cataracts, elevated blood sugar, mood swings and weight gain. Also, while corticosteroids may reduce the symptoms of the disease, they have no effect on its progression.59

Plasma exchange (plasmapheresis). Plasmapheresis is a process in which whole blood is separated into blood cells and plasma, the liquid part of blood. In MS patients the plasma contains unusually high levels of antibodies and proinflammatory factors that exacerbate symptoms. Plasma exchange helps remove these factors quickly and is sometimes used to help combat severe symptoms of multiple sclerosis relapses in people who are not responding to intravenous steroids.

Conventional Medical Treatment to Modify the Course of the Disease

Beta interferons. Beta interferons (Avonex, Betaseron) reduce inflammation and slow progression of the disease, but like many medications used in conventional medical treatment of MS, the mechanism of action is poorly understood60,61 This specific treatment may be accompanied by adverse effects such as suicidal depression, liver damage, flu-like symptoms, and injection site reactions.62

Glatiramer acetate. Glatiramer acetate (Copaxone) is an MS treatment that yields fewer adverse side effects than beta interferon while still remaining clinically effective. Glatiramer has a chemical structure similar to the protective myelin sheath around nerves and serves as a decoy for antibodies that would otherwise attack this sheath.63 Side effects may include flushing, rapid heartbeat, nausea, shortness of breath after injection, and injection site reactions.64

Mitoxantrone and fingolimod. Mitoxantrone (Novantrone) and fingolimod (Gilenya) are immunosuppressants. Clinical data show these drugs can slow the rates at which disability progresses and the rate at which new lesions form in the brain and spinal cord. These therapies, however, are not used as a first-line treatment as they can cause severe side effects including heart disease, leukemia, decreased white blood cell counts, and increased rates of infection.65

Natalizumab. Natalizumab (Tysabri) is thought to block a protein that allows white blood cells to enter the brain and spinal cord and cause disease progression in MS. Due to an association with three cases of a potentially fatal infection of the CNS,66 this is a controversial drug that is only available for patients enrolled in the Tysabri Outreach Unified Commitment to Health (TOUCH) program.67 This medication is reserved for people who do not see results from other types of treatments.

Dalfampridine. Dalfampridine (Ampyra) is a medication approved in 2010 that increases the ability of nerve cells to conduct impulses.68 This drug represents a new class of therapies that is aimed at addressing neurologic deficits directly.

Medications to Treat Symptoms

Muscle relaxants. Multiple sclerosis patients may experience painful or uncontrollable muscle stiffness or spasms, particularly in the legs. Muscle relaxants such as baclofen (Lioresal) and tizanidine (Zanaflex) may improve muscle spasticity. However, baclofen may increase weakness in the legs, and tizanidine may cause drowsiness or a dry mouth.

Medications to reduce fatigue. Drugs such as amantadine (Symmetrel) may help reduce fatigue.

Other medications. Medications may also be prescribed for depression, pain and bladder or bowel control problems that may be associated with multiple sclerosis.

Medications on the Horizon

There are approximately 20 experimental therapies that are on the pathway to approval by the Food and Drug Administration's (FDA). Investigators are making progress toward developing treatments that may be capable of protecting the CNS as well as encouraging repair of brain and spinal cord lesions. Many of these drugs are potentially valuable as treatments for MS, but are months or years from traversing all phases of the FDA process.

Laquinimod. Laquinimodhas been shown to decrease proinflammatory factors and increase factors that promote nerve protection without increasing risk of infection. Laquinimod was well tolerated by most patients, with only a few reports of adverse effects.69

Alemtuzumab. Alemtuzumab (Campath) is an antibody specific for mature white blood cells that targets them for destruction by the immune system. This drug is approved for the treatment of certain types of lymphoma and leukemia. In one study, it was shown to be more effective than beta interferon in reducing disability progression and relapse rate, however, the trial was discontinued early due to serious side effects.70

Fumaric acid. Fumaric acid is a substance that has been used in the treatment of psoriasis and shows promise in MS to decrease white blood cell infiltration into the spinal cord.71

Therapy and Rehabilitation to Improve Quality of Life

In addition to one or more drug-based therapies, MS patients will often participate in rehabilitation programs intended to maintain or improve their ability to perform at home and at work. More specifically these programs focus on general fitness and aim to address problems related to mobility, speech and swallowing, and cognitive deficits.

Common rehabilitation strategies include:

  • Physical therapy. Practices that aide mobility and functionality through structured physical activity on a scheduled basis.
  • Occupational therapy. Skills aimed at using work, self-care, and leisure activities to foster development and limit disability.
  • Speech therapy. Work with speech therapists can help MS patients overcome speech and language difficulties and help with troublesome swallowing.
  • Cognitive rehabilitation. Assistance in managing difficulties with memory, high order thinking, and perception. A variety cognitive rehabilitation options are available. For example, playing chess regularly is a great way to promote neuronal function and communication; computer-based "brain training" programs are also helpful.
  • Vocational rehabilitation. Support in making career plans, gaining job skills, and approaches to remaining gainfully employed.

8 Multiple Sclerosis Nutritional Protocol

Most patients that employ complementary treatments for MS do so as an accompaniment with conventional drug treatments and find both classes of therapy to provide clinical benefits.72 The following section outlines key details and evidence-based findings concerning the latest complementary approaches to treating MS.

Vitamin D

As previously mentioned, mainstream medicine has overlooked a critical missing link in MS management—vitamin D. This hormone-like vitamin is capable of safely interacting directly with the genome to modulate a variety of physiological functions, including aspects of immune function involved in autoimmune diseases like MS.

Two human clinical trials demonstrated that individuals with MS using vitamin D tended to have fewer relapses and less inflammation.17,73,74 In a year-long Vitamin D study, recurrence rate of MS "attacks" was 27% lower compared to baseline.74 In another large-dose Vitamin D trial, MS patients given 28,000‒280,000 IU weekly were found to have fewer active lesions during the 28-week long study.75 In light of the accumulating epidemiological and clinical evidence of the importance of vitamin D in this disease, supplementing the diet with vitamin D appears to be a low cost means to address this risk.

Omega-3 Fatty Acids

Omega-3 fatty acids (FAs) are polyunsaturated FAs which cannot be synthesized in humans and therefore must be provided via dietary sources. Both plant and animal foods are potential sources of omega-3 FAs. For example, linolenic acid, found in flaxseed, flaxseed oil, and preferably, fish and fish oils have very high levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

A small study looking at the effects of omega-3 FAs on MS found that immune cells from treated patients and healthy controls produced significantly fewer pro-inflammatory cytokines after three months of treatment with 6 grams of fish oil per day.76 One double-blind placebo-controlled study exists to date looking at the effect of omega-3 FAs on MS disease progression. In this study 312 patients were given either fish oil or olive oil placebo for two years. The results of this trial exhibited a trend toward decreased disease severity in the omega-3 FA group when compared with control.77 More recent studies have shown that MS patients given 10 grams of fish oil per day for three months exhibited significantly reduced levels of matrix metalloproteinase-9 (MMP-9), a factor correlated with disease progression, and also had greater concentrations of omega-3 FAs in their red blood cell membranes.78 Other work has shown that MS patients, while on a low-fat diet with omega-3 FA supplementation, experienced significantly reduced fatigue and lower relapse rates.79 Based upon clinical data and patient accounts, omega-3 FAs appear to be well tolerated and safe with no reports of adverse events.

Linoleic Acid and Omega-6 Fatty Acids

Linoleic acid is converted to gamma-linolenic acid (GLA), a beneficial omega-6 FA, after it is taken orally. However, this conversion is occasionally impaired, especially during inflammatory disease states.48,80 GLA has been shown to quell inflammation and research involving an animal model of MS has demonstrated that GLA administration significantly improved clinical outcomes when compared with control treatment.81

Some studies have shown significantly reduced relapse rates and disease progression scores, while others have found no differences between treatment and control groups.81-83 A closer look at data from these trials revealed that patients with lower levels of disability at the beginning of the trial exhibited a smaller increase in disability over the study period than did controls. In addition, linoleic acid was found to reduce the severity and duration of MS episodes in patients at all levels of disease severity.84

Selenium and Vitamin E

Patients who have MS tend to have abnormally low levels of glutathione peroxidase, a powerful endogenous antioxidant.85,86

Researchers in Denmark conducted a small study in which patients with MS were given an antioxidant mixture containing about 2,000 mcg selenium, 2 grams vitamin C, and 480 mg vitamin E once daily for five weeks. Although glutathione peroxidase levels were initially lower in patients with MS than in normal control subjects, after five weeks of antioxidant therapy, levels of this antioxidant enzyme increased five-fold and reported side effects were minimal.85 "[O]xidative stress plays an important role in pathogenesis of multiple sclerosis. This finding also suggests the importance of antioxidants in diet and therapy of MS patients."87

N-Acetylcysteine

An effective strategy for increasing the body's supply of the powerful antioxidant glutathione is taking the oral supplement N-acetylcysteine (NAC), a potent antioxidant that serves as a precursor to glutathione.48,88 NAC's potential benefit in the context of MS has been noted by some researchers.48,89

In a rodent MS model, NAC was able to diminish clinical symptoms and pathological evidence of CNS injury, and attenuate inflammation.90

Lipoic Acid

Lipoic acid (LA) is a dietary supplement with antioxidant properties and has been studied specifically in MS. Reactive oxygen species (ROS), generated primarily by immune cells, are implicated as mediators of demyelination and nerve damage.91,92 Known to cross the blood-brain barrier, LA decreases the activity of intercellular adhesion molecule-1 (ICAM-1), which is thought to play a role in the pathogenesis of MS. It is believed that ICAM-1 and other adhesion molecules are responsible for allowing certain pro-inflammatory immune cells, like T-lymphocytes, to enter the CNS, paving the way for induction or exacerbation of inflammation and tissue damage.93-95

In an animal MS model, LA produced a significant reduction of demyelination and infiltration of the CNS by T lymphocytes.96-98 Other researchers have followed up on these studies. In a pilot clinical trial, 37 patients with MS were randomly assigned to receive various doses of LA (up to 2,400 mg/day) or placebo. After two weeks, patients were assessed for levels of ICAM-1 and tolerability of high-dose LA. In addition to being well tolerated by patients, LA treatment was associated with reduced ICAM-1 levels and reduced T-cell migration into the CNS.99

Coenzyme Q10

Coenzyme Q10 (CoQ10) is an antioxidant that is an essential part of healthy mitochondrial function and energy production with potential usefulness in treating MS. Decreased levels of CoQ10 are associated with many disease states, including heart disease, cancer, and neurodegenerative diseases.100,101 CoQ10 was low in patients with MS.102 Several clinical trials of CoQ10 have been performed in neurodegenerative disease, such as Parkinson's disease, Huntington's disease, Alzheimer disease, Friedreich's ataxia, and amyotrophic lateral sclerosis.103 CoQ10 is a powerful lipid-soluble antioxidant that is also capable of regenerating the antioxidant capacity of vitamin E in the body. Based upon clinical evidence, CoQ10 appears to be well tolerated and safe with potential usefulness in the management of MS.

Vitamin B12

Some data suggest patients with MS have abnormally low levels of vitamin B12 in their cerebrospinal fluid, blood serum, or both.104 In fact, clinical vitamin B12 deficiency and MS share remarkably similar characteristics, occasionally rendering correct diagnosis difficult.105 Notably, vitamin B12 plays a key role in the generation of myelin and thus, for decades, integrative physicians have prescribed B12 injections for patients who have MS.

Data suggest patients given vitamin B12 supplements have experienced clinical improvements in their symptoms.48 For example, in the United Kingdom, researchers investigated the effects of six months of vitamin B12 (1 mg/week injection) on 138 patients with MS. The researchers concluded that the clinical course of patients with MS improved after beginning vitamin B12 treatment.106

Ginkgo Biloba

Ginkgo biloba extracts are primarily composed of flavonoids and terpenoids and have been reported to have properties that can influence neural activity and improve cognitive performance. While controlled trials of the effects of ginkgo biloba on cognitive function have generated inconsistent findings, more recent studies found encouraging results for patients with MS.107-109 In one study, patients received 120 mg of ginkgo biloba extract or placebo twice per day for 12 weeks. Those patients taking ginkgo biloba exhibited improved measures of attention and reported fewer difficulties with memory.

Green Tea (Epigallocatechin-3-Gallate)

Epigallocatechin-3-gallate (EGCG) is one of many active ingredients of green tea that have been reported to have beneficial effects on the nervous and immune systems. In an animal study of MS, ECGC was found to prevent severity of clinical signs by decreasing inflammation and protecting nerve cells.110 According to animal research, green tea has the ability to significantly increase regulatory T cells which are critical to providing balance to the immune system and suppressing autoimmunity.111

Curcumin

Curcumin is an active component of turmeric, a popular Indian spice. Laboratory studies have demonstrated that curcumin has potent anti-inflammatory effects.112 A research group carrying out animal studies has demonstrated exciting findings that curcumin treatment results in a significant reduction in disease severity and a reduction in duration of acute attacks.113 In a follow-up study, laboratory researchers found curcumin not only suppressed disease severity, but also was associated with reduction of levels of IL-17 a cytokine that has been directly implicated in the progression of MS.114

Biotin

Biotin, a water-soluble B-complex vitamin, is sometimes referred to as vitamin B7. Biotin participates in biochemical reactions catalyzed by decarboxylase enzymes, supporting energy production and fatty acid and myelin synthesis.115,116 The Adequate Intake for biotin is 30 micrograms, and low-to-moderate amounts are common in multivitamin supplements.117,118 Biotin's role in neuron functioning is evidenced by its therapeutic effect in a rare genetic disease known as biotin-thiamine responsive basal ganglia disease.118 Children affected by this disease experience progressive neurological dysfunction, including speech and motor dysfunction, mental retardation, seizures, and possibly death. Early treatment with biotin and thiamine (vitamin B1) appears to prevent progression in most cases.119,120 More recently, researchers have been exploring biotin's potential benefits in patients with MS.

In the first clinical trial to demonstrate the potential of high-dose biotin in MS therapy, 23 patients with progressive MS were treated with 100–300 mg biotin daily for an average of 9.2 months. While improvements were not seen for two to eight months after initiating biotin therapy—suggesting biotin may instigate a slow and progressive repair of MS-related nerve damage—vision improved in all four participants with MS-related optic nerve injury, and motor function and overall disability improved in 16 of 18 participants (89%) with prominent spinal cord involvement.116,118

In a randomized controlled trial, 154 patients with progressive MS received either 100 mg biotin three times daily or placebo for 12 months. Thirteen (12.6%) of the biotin-treated subjects versus none of the placebo subjects exhibited improvements in measures of MS-related disability after nine months that persisted through the end of the trial. In addition, only 4.2% of biotin-treated subjects compared with 13.6% of placebo subjects had progressively worsening disability scores at nine months. At the end of the 12 months, placebo subjects were switched to high-dose biotin, and overall stabilization of disability was seen in all subjects at a 24-month follow-up.121

Biotin levels in the cerebrospinal fluid of MS patients have been observed to be lower than those of healthy people, leading to speculation that low biotin availability may contribute to the pathology of MS.122 Although the mechanism of biotin's ability to prevent or repair nerve damage is unknown, biotin may prevent progressive demyelination by improving mitochondrial function, increasing brain energy production, supporting myelin production by increasing lipid synthesis, and affecting gene expression.118,123

Biotin is excreted through the urinary system, and high doses appear to be well tolerated in trials to date.118,124 However, high doses of biotin may interfere with certain lab tests, including thyroid function tests, leading to misdiagnosis of thyrotoxicosis.117,125,126 In addition, the possibility of teratogenicity has been suggested by animal research124; therefore, the safety of high-dose biotin in pregnancy is not established.

Swank Diet

Dr. Roy Swank first proposed a connection between increased consumption of saturated animal fat and the incidence of MS in 1950.127 He conducted a study which enrolled 208 patients with MS in the early 1950s, all of whom had experienced at least two acute relapses, and followed their progress over 34 years.128 In this study, patients maintained the now termed Swank diet, which consists of: less than 15 grams/day of saturated animal fat, 10‒15 grams/day of vegetable oil, 5 grams/day of cod liver oil, and one multivitamin. Long-term follow-up results from this study indicate that the patients adhering to the Swank diet experienced reduced MS disease activity and progression of disability when compared to patients that did not follow the regimen. While these results are encouraging, this trial is criticized for its lack of a proper control group and un-blinded design. Nevertheless, the Swank diet remains one of the most popular complementary approaches to treating MS.

Swank Low-Fat Diet: Detailed Guidelines

  • Saturated fat should remain less than 15 grams per day
  • Unsaturated fat should be approximately 20‒50 grams per day
  • No red meat should be consumed during the first year
  • After the first year, a maximum of 3 oz. of red meat per week
  • Dairy products must have 1% butterfat or less
  • Processed foods containing saturated fat should not be eaten
  • A source of omega-3, a multivitamin, and a mineral supplement are recommended daily
  • Wheat, gluten or dairy product quantities are not restricted, unless they are foods which cause allergies or reactions.

9 Hormone Therapy

Because women often experience improvement of MS symptoms while pregnant, hormone therapy using estrogen has been studied as a treatment for the disease. In human studies, estriol treatment (8 mg/day) in nonpregnant women with MS was associated with reduced lesion numbers and lesion volumes and when treatment ceased, these values returned to levels observed before treatment.37 Patients given estriol also had enhanced cognitive function. With respect to immune studies, estriol was associated with reduced pro-inflammatory and increased anti-inflammatory cytokine production and these changes correlated well with the reduced formation of lesions.39

Other studies have shown that male MS patients treated with 10 mg of testosterone exhibited improved cognitive performance and reduced brain atrophy, although MRI data showed no change in lesion formation.129 In another similar study, testosterone treatment in males was associated with reduced production of inflammatory cytokines and increased production of neuroprotective factors.130

There is currently debate among researchers about the role of hormones with MS and how that relationship may be exploited as a means of therapy. Some studies argue for hormone replacement as a new therapeutic approach.131 More information can be found in Life Extension's "Male Hormone Restoration" and "Female Hormone Restoration" protocols.

Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.

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