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 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."
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
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.
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?"
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