Multiple SclerosisLife Extension Suggestions
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 (see figure at left) 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
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 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.
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. Results of a large scale, randomized, controlled clinical trial to assess the effects of vitamin D in MS are currently pending (ClinicalTrials.gov [NCT01285401]).
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 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 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).
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.”
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).
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).
Those individuals interested in protecting themselves from organic solvents and other environmental toxins should read Life Extension’s Metabolic Detoxification protocol.
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. 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?”
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).
MS is a tremendously variable and unpredictable disease. Different patients will experience different symptoms, rates of disease progression, and responses to treatment.