~MS - Multiple Sclerosis

~MS - Multiple Sclerosis
Reprinted with permission of Life Extension®.



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 that 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 (SOLAR trial).

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 forms 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.

Pathology of Disease Progression

Demyelination

Multiple sclerosis (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 (Noseworthy 2000).

Loss of myelin followed by subsequent lack of neural communication and neuronal death is accepted as the primary cause of disability in MS patients (Dutta 2007). Axonal transection, or the severing of axons, occurs under conditions of both acute and chronic demyelination (Trapp 1998; Bjartmar 2000; Lovas 2000).

Remyelination

Remyelination is the process by which demyelinated axons are naturally re-wrapped with myelin, restoring nerve conduction and functionality (Smith 1979). 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 (Compston 2002, Friese 2006). 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 (Goverman 2009). 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 suggests that absence of these pro-inflammatory signals was sufficient to prevent inflammation in the brain (El-Behi 2011). 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 (Goldberg 1974; Craelius 1978). 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 (Tremlett 2008). 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” (Simpson 2010).

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 (Correale 2009).

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 (Burton 2010).

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.

A large scale, randomized, controlled clinical trial to assess the effects of vitamin D in MS is now recruiting; the study is expected to be complete in 2014 (ClinicalTrials.gov [NCT01285401]).

Life Extension® followers 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 that 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 (Munger 2004; Holick 2005; Merlino 2004; Ponsonby 2002; Ponsonby 2005). The amount of supplementation required to achieve this blood level varies from one person to another, but it appears that many individuals require supplementation of 5,000 – 8,000 IU of vitamin D each day 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.”

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 (Dyment 2004). Several studies have identified susceptibility genes related to many aspects of immune function (Ebers 1996; Sawcer 1996; Zhang 2005; Gregory 2007; Ramagopalan 2007). 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 suggests that, in genetically predisposed individuals, exposure to an infectious agent may lead to MS (Orbach 2010). One common theory, molecular mimicry, proposes that presentation of foreign antigens that are molecularly similar to self-antigens leads to an autoimmune response (Fujinami 1983; Zabriskie 1986). 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) (Ascherio 2007). Currently, the strongest evidence for the involvement of an infectious agent implicates EBV. Virtually all patients who have MS are infected with the EBV. (Ascherio 2007). Further, levels of antibodies to EBV are strongly correlated with the risk of developing the disease (Lünemann, 2006).

Vitamin D

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 international units (IU) daily of vitamin D from supplements had an astounding 41% lower incidence of MS(Munger 2004).

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 (Gelfand, 2011). 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 (Pozzilli 1999). 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 (Hughes 2004). Animal models of multiple sclerosis have shown that the pregnancy hormone, estriol, can ameliorate disease and can cause an immune shift (Sicotte 2002, Hughes 2004). Other studies note that pregnant women who have MS tend to experience a rebound of their disease within 3 months post-delivery (El-Etr 2005).

These findings suggest that hormones can regulate the course of MS and this theory is further supported by research demonstrating that steroid hormones, such as estrogens, testosterone, progesterone, and, dehydroepiandrosterone (DHEA), can modulate the immune system (Soldan 2003, Bebo 1998; Dalal 1997).

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 (Bansil 1999). 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 (Tomassini 2005).

More information about optimizing and balancing hormone levels can be found in Life Extension’s Male Hormone Restoration protocol and the Female Hormone Restoration protocol.

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 that exposure to solvents increases a person's relative risk of developing MS (Landtblom 1996). 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 (Riise 2002).

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 (Rodrigo 2011; Shor 2009). MS is also most prevalent in areas where consumption of wheat gluten and milk are also high (Kidd 2001). This relationship lead 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 (Guggenmos 2004; Stefferl 2000). Further investigations have revealed that in MS patients, higher levels of these antibodies are produced within the central nervous system (Klawiter, 2010). 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.

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% (Handel 2011). 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 (Hedstrom 2011). 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 (Hernan 2005; Riise 2003).

Symptoms & Diagnosis

MS can affect people of all ages; however the average age of disease onset is between 20 and 40 years (Kidd, 2001). 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 (Kidd, 2001).

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 (Hartung 2004).

Over 40% of MS patients suffer from changes in memory, reasoning, spatial perception, and verbal fluency (Rao 1991).

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

  1. 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.

  2. 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.

  3. 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. 10% of diagnosed MS are PPMS.

  4. Relapsing Remitting (RR) MS represents 85 percent 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 demylination slows nerve conduction) and evaluation of how the symptoms progress through time (D. Miller 2005).

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.

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 (Virley 2005).

Plasma exchange (plasmapheresis)

Plasmapheresis is a process 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 (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 understood (Yu, 1996; Heine, 2006) This specific treatment may be accompanied by adverse effects such as suicidal depression, liver damage, flu-like symptoms, and injection site reactions (Paty 2001)

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 (Ziemssen, 2007). Side effects may include flushing, rapid heartbeat, nausea, shortness of breath after injection, and injection site reactions (Sela, 2001).

Mitoxantrone (Novantrone®) and Fingolimod (Gilenya®) are immunosuppressants. Clinical data show that 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 (Fox, 2006).

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 (Ransohoff 2005), this is a controversial drug that is only available for patients enrolled in the Tysabri Outreach Unified Commitment to Health (TOUCH) program (Warnke , 2010). This medication is reserved for people who do not see results from other types of treatments.

Dalfampridine (Ampyra®) is a medication approved in 2010 that increases the ability of nerve cells to conduct impulses (Center Watch, 2011). 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 has 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 (Nicholas 2011).

Alemtuzumab (Campath®) is anantibody 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 (Holmoy 2011).

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 (Schilling, 2006).

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.

Multiple Sclerosis Nutritional Protocol

Overview

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 (Shinto 2005). 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 (Smolders 2008; Burton 2010; Wingerchuk 2005). In a one year-long Vitamin D study, recurrence rate of MS “attacks” was 27% lower compared to baseline (Wingerchuk 2005). 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 (Kimball, 2007). 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 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 EPA and 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 3 months of treatment with 6 grams of fish oil per day (Gallai 1995). 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 2 years. The results of this trial exhibited a trend toward decreased disease severity in the omega-3 FA group when compared with control (Bates 1989). More recent studies have shown that MS patients given 10g of fish oil per day for 3 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 (Shinto 2009). 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 (Weinstock-Guttman 2005). 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 & 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 (Kidd 2001; Horrobin 1997). 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 (Harbige 2007).

Some studies have shown significantly reduced relapse rates and disease progression scores, while others have found no differences between treatment and control groups (Harbige 2007;Bates 1977; Paty 1978). A closer look at the 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 (Dworkin 1984).

Selenium and Vitamin E

Patients who have MS tend to have abnormally low levels of glutathione peroxidase, a powerful endogenous antioxidant (Mai 1990; van Meeteren 2005).

Researchers in Denmark conducted a small study in which patients with MS were given an antioxidant mixture containing ~2,000 mcg of selenium, 2 grams of vitamin C, and 480 mg of vitamin E, once a day 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 (Mai 1990). “… oxidative 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.” (Hadzovic-Dzuvo 2011)

N-acetylcysteine (NAC)

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 (Kidd 2001; Arfsten 2004). NAC’s potential benefit in the context of MS has been noted by some researchers (Kidd 2001; Singh 1998).

In a rodent MS model, NAC was able to to diminish clinical symptoms and pathological evidence of CNS injury, and attenuate inflammation (Gilgun-Sherki 2005).

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 (Ortiz, 2009; Miller, 2009). 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 (Biernacki 2004; Cournu-Rebeix 2003; Dedrick 2003).

In an animal MS model, LA produced a significant reduction of demyelination and infiltration of the CNS by T lymphocytes (Marracci 2002; Morini 2004; Schreibelt 2006). Other researchers have followed up on these studies. In a pilot clinical trial, thirty-seven patients with MS were randomly assigned to receive various doses of LA (up to 2400 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 (Yadav 2005).

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 (Bonakdar 2005; Siemieniuk 2005). CoQ10 was low in patients with MS (Syburra 1999). 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 (Spindler 2009). 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 suggests that patients with MS have abnormally low levels of vitamin B12 in their cerebrospinal fluid, blood serum, or both (Reynolds 1992). In fact, clinical vitamin B12 deficiency and MS share remarkably similar characteristics, occasionally rendering correct diagnosis difficult (Miller 2005). 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 suggests that patients given vitamin B12 supplements have experienced clinical improvements in their symptoms (Kidd 2001). For example, in the United Kingdom, researchers investigated the effects of 6 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 (Wade 2002).

Gingko biloba

Gingko 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 Gingko biloba on cognitive function have generated inconsistent findings, more recent studies found encouraging results for patients with MS (Birks 2007; Birks 2009; Lovera 2007). In one study, patients received 120mg of Gingko biloba extract or placebo twice per day for 12 weeks. Those patients taking Gingko biloba exhibited improved measures of attention and reported fewer difficulties with memory.

Green Tea – Epigallocatechin-3-gallate (EGCG)

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 (Aktas 2004). 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 (Wong, 2011).

Curcumin

Curcumin is an active component of turmeric, a popular Indian spice. Laboratory studies have demonstrated that curcumin has potent anti-inflammatory effects (Abe 1999). 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 (Natarajan 2002). In a follow-up study, laboratory researchers found curcumin not only suppressed disease severity, but also was associated with reduction of levels of interleukin-17 (IL-17) a cytokine that has been directly implicated in the progression of MS (Xie 2009).

Swank Diet

Dr. Roy Swank first proposed a connection between increased consumption of saturated animal fat and the incidence of MS in 1950 (Swank 1950). He conducted a study which enrolled 208 patients with MS in the early 1950’s, all of whom had experienced at least two acute relapses, and followed their progress over 34 years (Swank 1990). In this study, patients maintained the now termed Swank Diet, which consists of: less than 15g/day of saturated animal fat, 10-15g/day of vegetable oil, 5g/day of cod liver oil, and one multivitamin (full details below). 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 multi-vitamin, 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.


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 (8mg/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 (Sicotte 2002). 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 (Soldan 2003).

Other studies have shown that male MS patients treated with 10mg of testosterone exhibited improved cognitive performance and reduced brain atrophy, although MRI data showed no change in lesion formation (Sicotte 2007). In another similar study, testosterone treatment in males was associated with reduced production of inflammatory cytokines and increased production of neuroprotective factors (Gold 2008).

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 (El-Etr, 2011).

Life Extension Suggestions

Neuronal support and immune regulation:

  • Vitamin D3: 5000 – 8000 IU daily, depending upon blood levels of 25-OH-vitamin D
  • EPA/DHA: 700 – 1400 mg of EPA and 500 – 1000 mg of DHA daily
  • GLA: 1300 – 2600 mg daily of borage oil
  • Turmeric extract (Curcumin): 400 – 1200 mg daily
  • Vitamin B12: 1000 – 5000 mcg daily in the form of sublingual methylcobalamin


Antioxidants:

  • NAC: 600 – 1200 mg daily with 1800 mg of vitamin C
  • Vitamin E: 400 IU daily
  • Selenium: 400 mcg daily
  • Lipoic acid (preferably R-lipoic acid): 240 – 600 mg daily
  • CoQ10 (as Ubiquinol): 100 – 200 mg daily


Additional support:

  • Green tea; (standardized to EGCG): 700 – 2100 mg daily
  • Ginkgo biloba extract: 120 – 240 mg per day
  • Hormonal therapy with bioidentical hormones may also be considered.
  • Before bioidentical hormonal therapy is initiated, hormone blood testing is important.


In addition, the following blood testing resources may be helpful:

  • Vitamin D, 25-Hydroxy
  • Omega Score™
  • Food Safe™ Allergy
  • Female Panel / Male Panel
  • Female Comprehensive Hormone Panel / Male Comprehensive Hormone Panel


Multiple Sclerosis Safety Caveats

DHEA: Do not use DHEA if you are at risk for or have been diagnosed as having any type of hormonal cancer, such as prostate or breast cancer.

EPA/DHA: If you are taking anti-coagulant or anti-platelet medications, or have a bleeding disorder, consult your healthcare provider before taking this product.

GLA: If you are taking anti-coagulant or anti-platelet medications, or have a bleeding disorder, consult your healthcare provider before taking this product.

Lipoic Acid: If you are sensitive to changes in blood sugar and/or being treated for diabetes with blood sugar–lowering drugs, please consult with your physician before supplementing with R-lipoic acid. In this context, start with a low dose and assess for effect. Inform your physician should you notice any changes while taking this product.

NAC: Those who supplement with NAC should drink six to eight glasses of water daily to prevent cysteine renal stones. Cysteine renal stones are rare but do occur.

Vitamin D: Individuals consuming more than 2,000 IU/day of vitamin D (from diet and supplements) should periodically obtain a serum 25-hydroxy vitamin D measurement. Do not exceed 10,000 IU per day unless recommended by your doctor. Vitamin D supplementation is not recommended for individuals with hypercalcemia (high blood calcium levels). People with kidney disease, certain medical conditions (such as hyperparathyroidism or sarcoidosis), and those who use cardiac glycosides (digoxin) or thiazide diurectics should consult a physician before using supplemental vitamin D.

Vitamin E: If you are taking anti-coagulant or anti-platelet medications, or have a bleeding disorder, consult your healthcare provider before taking this product.
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