It is time to start talking about MS prevention and treat your relatives...
We’ve known since the 1980’s that the risk of MS among first-degree relatives (a genetically related child or sibling of a person with MS) is 2-5%. Initially, we did not know if there were factors, preventable or not, conferring either a higher or lower risk of developing MS. Because of this we tended to reassure these families with the knowledge that at least 95% of their offspring or siblings would not develop MS (excluding identical twins). Accumulating evidence of genetic and environment risk factors for MS over the past 20 years strongly suggests that the risk of MS in certain family members may be considerably higher than the quoted 2-5%. For this reason and the mounting evidence that the incidence of MS may be increasing in some population groups, we believe it is time to begin talking about MS prevention.
As a starting point, it is important to remember that the 2-5% risk of MS among first-degree relatives of MS patients is an overall average risk, not a particular individual’s risk. To understand this better let’s consider an example of a theoretical disease that occurs in 1 out of 1000 people or 0.1% of the population. Overtime we may learn that 1 out of 100 first-degree relatives get the disease or 1%. This is useful information (i.e. a 10 fold increased risk over the general population) but perhaps not actionable. If we then learn that 25% of first degree relatives with a particular genotype and exposure to a particular virus develop the disease and only 0.2% of the first degree relatives without this profile develop the disease, you now have information that can be acted upon.
The situation with MS is approaching this level of understanding. To know the individual risk of MS in a first degree relative requires knowledge of the family member affected, when they were affected (younger or older age), environmental risk factors (read below) at different exposure ages, genetic background, the incidence of MS in the area the individual grew up in, and possibly an assessment of particular biomarkers (typically from a test done on a sample of blood, urine or spinal fluid) measured over time. Knowing this information can allow clinicians to develop a risk profile for an individual. In fact, Dr. Philip De Jager and his colleagues at Harvard are working on the development of this type of platform. Based on the profile of an individual family member, it is likely that their risk of developing MS could vary from < 1% to as high as 25%. The actions this individual or their parents would be willing to take to minimize this risk of MS will obviously depend on both the risk of developing MS and, more importantly, the risk that their MS would be particularly severe. Future studies will hopefully allow us to assess both risks.
But what can we do at present without this multidimensional data to guide us? Since we cannot do anything at present about inherited risks, it is important to focus on modifiable risk factors. It is our opinion that there is enough information currently available to help decrease the risk of developing MS among first-degree relatives by simply managing the following known risk factors:
1. There is significant epidemiological evidence that Vitamin D deficiency is associated with a higher risk of developing MS. This risk may begin even before birth based on evidence that MS is more common among children born in winter months when UV light exposure and 25-hydroxy vitamin D levels (25(OH)D) are at their lowest. There is also significant evidence that vitamin D3 supplements in pregnant woman, young children, adolescents and adults are safe in doses much higher than currently recommended by the institute of medicine (IOM) or American College of Gynecology and Obstetrics (ACOG). Although there are no controlled studies demonstrating that vitamin D3 supplements decrease the risk of MS or the level of 25(OH)D (this is what doctors measure in the blood when they check your Vitamin D level ) that must be achieved to decrease this risk, we do have some information to guide us. First, a woman planning pregnancy or pregnant with an unborn child that has a first degree relative with MS (either the mother herself, the father or a sibling of the unborn child has multiple sclerosis) and a 25(OH)D level less than 20 ng/ml (or 50nmol/lt) is Vitamin D deficient by all criteria and requires high dose supplementation with at least 50,000 IU per week of vitamin D3 or equivalent daily dosing (5,000 IU vitamin D3 or greater per day) with a goal of rapidly achieving a 25(OH) D level > 40 ng/ml (100 nmol/lt). We recommend that pregnant woman with levels between 20 and 40 ng/ml (50 to 100 nmoles/lt), supplement with 4,000 to 6,000 IU per day of vitamin D3 to achieve these same 25 (OH) D levels (greater than 40 ng/ml (or greater than 100 nmol/lt) ) although many will require doses over 6,000 IU to achieve these vitamin D levels. Those with levels greater than 40 ng/ml (100 nmols/lt) prior to supplementation should take 2,000 IU of vitamin D3 during pregnancy. Once born the first-degree relative of an MS patient will continue to require vitamin D3 supplementation based on weight. If the average amount required for an adult is 5,000 IU (50 kg) then a 5 kg infant requires one tenth this dose or 500 IU of vitamin D3 per day. Of course, sunlight is also a source of vitamin D3 during the summer months but there is some evidence that sunlight exposure is no longer achieving the desired 25(OH)D levels. Therefore, it is important to maintain vitamin D3 supplementation unless it is demonstrated that you are able to maintain levels greater than 40 ng/ml year round. The important point is to take enough Vitamin D3 supplement to maintain target levels greater than 40 ng/ml. To do this will require periodic blood tests to check 25(OH)D levels.
2. A recent meta analysis of 14 studies shows that being a smoker at any time increases the risk of MS by 50% compared to never smoking. This effect seems to be dose dependent (among and duration of smoking) and particularly strong in adolescence or early adulthood. Although smoking is on the decline there is a disturbing continued tendency for children, adolescents and young adults to experiment with smoking. It is extremely important for children and young adults who have first-degree relatives with MS to learn that any smoking must be avoided. This includes second hand smoke among other individuals in the household. The American Lung Association has an on line program called, “Freedom from Smoking” that is a good starting point for individuals interested in achieving this goal. It is also adapted to both adolescents and adults.
3. More recent evidence suggests that obesity is associated with the risk of developing MS. This risk is particularly strong if you inherit HLA haplotypes (genes) associated with MS. Therefore, diets and exercise programs to improve aerobic fitness and decrease excess weight are important not only for MS patients but essential for first-degree relatives of MS patients.
Let us hope that by instituting these preventative measures we are able to not only decrease the risk of developing MS among your at risk relatives but also decrease the severity of the MS that may still develop in these family members. The next step will be the development of vaccines to control Epstein Barr Virus or mitigate the long-term effects of EBV infection.
-Ben Greenberg, MD, MHS and Rip Kinkel, MD
Benjamin M. Greenberg, MD, MHS
Director, Transverse Myelitis, Neuromyelitis Optica and Pediatric Demyelinating Disease Programs
Director, Neurosciences Clinical Research Center
Department of Neurology and Neurotherapeutics
Department of Pediatrics
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