Immunoe

Part of the answer is genetic. New genes associated with MS have recently been identified, but this is only part of a complex and unfolding story. Technically, multiple sclerosis is known as a multi-factorial disease. This means that MS is caused by a combination of genetic and environmental factors.

The evidence supporting a genetic risk is convincing. In the United States, only about 1 in 750 ( about 1/10 of one percent of) people will be diagnosed with MS. However, if a close family member has MS, the risk is much higher. For example, an identical twin of someone with MS has about a 25% chance of developing MS but the risk drops to only 3-5% in a non-identical (fraternal) twin. Those with a parent, child, or sibling (non-twin) who has MS have a risk of about 2-4%. The risk for people who have a first cousin who has MS is about 1% and the risk drops quickly for more distant relations.

The twin studies are particularly interesting because identical twins have identical genes. The fact that only 25% of identical twins will develop MS if the other twin has MS teaches two important lessons. First, it demonstrates that there is a genetic link. Those with genes identical to someone with MS have a greatly increased risk of being diagnosed with MS when compared with someone who has no close relatives with MS. Second, these studies teach that there must also be environmental forces at work. If only genetic factors determined MS, the risk for identical twins would be expected to be 100%, which is not the case. Indeed, the lack of a genetic connection is experienced directly by the majority of people with MS. Most people with MS—about 80%—do not have a close relative with the disease.

Support for the theory that environmental factors influence risk in MS also comes from well-known studies that show the risk of MS is greater in the northern United States than in the southern states. However, those living in Minnesota should not move to Florida! In absolute terms, the risk of MS is still low (much less than 1 percent) in Minnesota and other northern states and the relationship between geography and risk of MS is not well-enough understood in any case. Furthermore, the difference in risk may even be diminishing. For example, one study found that for Caucasian women born before 1946 the risk of developing MS was three times greater among those born in the northern states (above the 37th parallel) as compared with those born in Southern states—among those born after 1946, though, there was no difference in risk. Future studies will clarify whether the difference in MS risk between those living in the Northern and Southern states is diminishing. That the environment plays a role in causing MS is, of course, critically important. Identifying such factors would mean that there may be ways for people to reduce their risk of developing MS. And, if environmental factors play a continuing role in the MS disease process, new treatment strategies may be identified for people who already have MS.

High blood levels of vitamin D, dietary vitamin D supplementation, and exposure to ultra violet radiation have all been shown to be associated with a decreased risk of developing MS.

The most fascinating vitamin D study to date is the study, reported about a year ago, that focused on people in the military. Military recruits routinely have blood drawn and stored—and thus blood levels of vitamin D at various points in time are readily available. Selected members of the military who had MS were compared to selected people in the military who did not have MS and their blood levels of vitamin D prior to diagnosis, were compared. The risk of multiple sclerosis decreased with increasing levels of vitamin D, suggesting that higher vitamin D levels protected some people from MS. Indeed, those with the highest levels of vitamin D (the top 20%) were more than 60% less likely to be diagnosed with MS than those with the lowest levels (the lowest 20%).

The most striking protective effect was found among those between the ages 16 and 19 who had high blood levels of vitamin D. A number of other strands of evidence also point to a role for vitamin D in preventing MS. For example, in the animal model of MS (EAE), increased vitamin D seems protective and decreased vitamin D has the opposite effect. Sun exposure in childhood, which is an important source of vitamin D, has also been associated with a reduced risk of MS. One study even raises the possibility that maternal vitamin D may be important. This study involved 40,000 patients from the United Kingdom, Denmark and Sweden and found that fewer people with MS are born in November and significantly more are born in May. The authors cautiously suggested that the birth-month pattern may relate to a protective effect of maternal levels of vitamin D due to sun exposure during the third trimester.

Viruses have frequently been investigated as a possible cause of MS. According to some authors, Epstein-Barr virus (EBV) currently appears to be the most likely candidate. First, almost all patients with MS have evidence of past EBV infection (antibodies to the EBV in their blood), while 5% to 10% of the general population does not have such evidence. In addition, some studies have found increased blood levels of antibodies to EBV during MS exacerbations. Finally, EBV can cause infectious mononucleosis, sometimes known as "the kissing disease" because it is transmitted by saliva. According to one study, people who reported having infectious mononucleosis before age 18 have an eight fold higher risk of MS than those who did not recall having infectious mononucleosis. Of course, such studies depend on human memory (technically, recall bias) and are, therefore, of only limited persuasive value.

Other infectious agents that have been associated with MS include Chlamydia pneumonia, human herpesvirus 6, and the viruses that cause measles, mumps, and rubella. However, none of these findings has been consistent and the search for other viral associations with MS continues.

Given that some viruses have been considered to be involved in causing MS, it may be surprising to learn of another theory that suggests that exposure to infectious agents in childhood may protect against MS. According to this theory, a child's immune system needs to be challenged to develop correctly and failure to be challenged by exposure to agents such as viruses and parasites can cause alterations in the immune system that may predispose people to MS. In fact, infection with some parasites, such as tape worms, causes changes in the immune system that would theoretically be beneficial in MS. And there is even some evidence among people with MS supporting the idea that a parasite may be protective in MS. Of course, this does not mean that someone with MS should deliberately expose themselves to parasites! It does, however, provide a clue to researchers in their search for ways to mimic the protective effect that seems to be induced by parasites.

Smoking Cigarettes
Cigarette smoke has also emerged as a potential environmental risk factor for MS. Five different studies have identified an increased risk of MS among smokers. In these studies the increase in risk ranged from 40-80%. The risk of MS also seems to go up with the number of cigarettes smoked and smoking seems to intensify the risk of progressive MS. In one study, smoking tripled the risk of developing secondary progressive MS among those with relapsing-remitting MS at onset.

The reason for the possible connection between smoking and MS is not clear, but smoking certainly exposes the body to many substances known to be toxic. The authors of one study speculate that the culprit may be the free radical named nitric oxide or the toxin cyanide. Obviously, a possible connection to MS is only one of many reasons not to smoke and to begin a smoking cessation program if you do smoke.

Exercise and Other Methods for Increasing Cognitive Reserve
There is increasing evidence to support the concept that exercise can modify the disease course among people who already have MS. This may happen through a variety of mechanisms, including by developing cognitive reserve. Improved cognitive reserve, as such, is not likely to reduce the risk of MS, but rather, may reduce the clinical consequences if someone does have MS. Other factors that improve cognitive reserve include social connectedness, education, and intellectual stimulation.

Exercise, however, plays an important role in immune regulation. And, based on animal studies, may itself reduce the risk of developing MS by helping to regulate the immune system.

Dietary fat
A connection between dietary fat and multiple sclerosis was first proposed in the 1950s. Since then, some studies have found that diets high in animal fats (saturated fat) and low in fish and vegetable oils (polyunsaturated fats) may increase the risk of MS while other studies have not found this to be the case. There is a clear scientific rationale that would support a connection between dietary fat and multiple sclerosis. In particular, fats rich in omega-3 fatty acids cause changes in the blood of people with MS that, in theory, would be beneficial. And there is even some evidence suggesting that polyunsaturated dietary fats can favorably modify the course of MS. These studies are complicated to interpret and a detailed review of them is beyond the scope of this article.

Psychological stress
Psychological stress has long been associated with MS exacerbations and the even the onset of MS. This connection raises the possibility that an individual may reduce the risk of MS (or an exacerbation of MS) by learning to better manage stress through activities like meditation, spirituality or prayer. Exercise may also be a particularly effective way to manage stress.

A large number of other possible risk factors have also been proposed to increase risk of MS, such as organic solvents. For each of these, the data is generally more tenuous than for the other possible associations described above.

For years, information has circulated on the internet suggesting that aspartame (e.g., Nutrasweet brand artificial sweetener) causes MS—no published scientific report supports this. However, an informal survey has found that almost 25% of people with MS perceive new or worsened MS symptoms in relation to consuming Nutrasweet. Of course, for someone who perceives symptoms in relation to Nutrasweet, it makes sense to discontinue it and use sugar or stevia (a low calorie herbal sweetener) instead as there are certainly no health benefits to consuming Nutrasweet given the alternatives. To read more about the informal survey please click here.

Mercury amalgam from dental fillings is an example of an environmental factor for which there is persistent attention but little scientific support. It is not a good idea to have fillings removed as a strategy to improve MS related symptoms or for disease control.