Multiple Sclerosis, a Review
Dr Todd Born ND, reviews the complexities of MS and explores the potential role of nutrition in prevention and management. Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system (CNS). Multiple sclerosis is a heterogeneous disorder with variable clinical and pathologic features reflecting different pathways to tissue injury. Inflammation, demyelination, and axon degeneration are the major pathologic mechanisms that cause the clinical manifestations. However, the cause of MS remains unknown. The most widely accepted theory is that MS begins as an inflammatory autoimmune disorder mediated by autoreactive lymphocytes. Later, the disease is dominated by microglial activation and chronic neurodegeneration.
Multiple sclerosis affects more women than men. A systematic review of 28 epidemiologic studies found that, from 1955 to 2000, the estimated female to male ratio of MS incidence increased from 1.4 to 2.3. A later systematic review and meta-analysis also found evidence suggesting that the incidence of MS is increasing in females.
The median and mean ages of MS onset are 23.5 and 30 years of age, respectively. The peak age of onset is about five years earlier for women than for men. Relapsing-remitting MS tends to have an earlier onset, averaging 25 to 29 years; this may convert to progressive MS at a mean age of 40 to 44 years. Primary-progressive MS has a mean age of onset of 35 to 39 years. Onset of MS can rarely occur as late as the seventh decade.
In support of a possible autoimmune basis for MS, some, but not all studies have observed that patients with MS are more likely than controls to have other autoimmune disorders, such as autoimmune thyroid disease. In addition, patients with other autoimmune disorders are more likely to have MS.
A possible infectious stimulus of the immune system has received more support than vaccines in the literature. Although many viruses have been associated with MS, no specific evidence linking viruses directly to the development of MS has been reported.
EBV seropositivity among adult MS patients is near 100 percent, significantly higher than healthy controls, and children with MS are significantly more likely than healthy peers to have serological evidence for prior EBV infection, at an age when EBV seropositivity is much less common than in adults.
While these findings do not confirm that EBV is an etiologic agent, they are suggestive and warrant further study.
The incidence and prevalence of MS varies geographically., High frequency areas of the world (prevalence of 60 per 100,000 or more) include all of Europe (including Russia), southern Canada, northern United States, New Zealand, and southeast Australia. In many of these areas the prevalence is more than 100 per 100,000; the highest reported rate of 300 per 100,000 is in the Orkney Islands. In the United States, the prevalence is 100 per 100,000 (0.1 percent), for a total of 250,000 persons with MS. This geographic variance may be explained in part by racial differences; white populations, especially those from Northern Europe, appear to be most susceptible; people of Asian, African, or American Indian origin have the lowest risk, with other groups intermediate.
There is also a widely held belief of an association between latitude and MS, with the risk of MS increasing from south to north. In an analysis from the Nurses’ Health Study, for example, the adjusted rate ratios were 3.5 for the northern United States and 2.7 for the middle tiers relative to the southern tier. Persons migrating from a high to low-risk area after the age of puberty are thought to carry their former high risk with them, while those that migrate during childhood seem to have the risk associated with the new area to which they migrated.
However, the universal association between latitude and risk of MS has been challenged by findings from a 2010 systematic review and meta-analysis of epidemiologic studies of MS. The results showed that, while the prevalence of MS increased with geographic latitude in Western Europe, North America, and Australia/New Zealand, the incidence of MS increased with latitude only in Australia/New Zealand, and not in Western Europe or North America. Thus, there was no latitudinal gradient for MS incidence in the northern hemisphere. In the absence of association with incidence, the observed latitudinal gradient of MS prevalence could be explained by other factors, such as survival time, diagnostic accuracy, and ascertainment probability.
There is a long debate about vitamin D, sunshine exposure and MS risk. One proposed explanation for the possible association of MS with latitude is that exposure to sunlight may be protective, either because of an effect of ultraviolet radiation or of vitamin D. The following observations support of this hypothesis:
- A number of studies have found an inverse relationship between sun exposure, ultraviolet radiation exposure, or vitamin D serum levels, and the risk or prevalence of MS.,
- An analysis of data from the Nurses’ Health Study and Nurses’ Health Study II observed that the risk of developing MS was significantly reduced for women taking ≥400 international units/day of vitamin D (relative risk 0.59, 95% CI 0.38-0.91).
- A longitudinal cohort study of 469 subjects with MS found that vitamin D levels were inversely associated with the risk of new T2-weighted or gadolinium-enhancing T1-weighted lesions on brain MRI.
A 2013 article by Disanto, et al, that appeared in JAMA Neurology, is finding links between being born in the month of May, vitamin D and risk of developing MS. The British researchers theorize that fetal defects in thymic function and inadequate circulating levels of vitamin D may explain the well-recognized influence of birth month on risk for multiple sclerosis. Why May? It is postulated that low circulating levels of 25-hydroxyvitamin D are common as the winter and spring months do not allow the pregnant mother to produce adequate amounts of this prohormone. Those born in November had a mean of 50.9 nmol/L, versus 38.4 nmol/L in those born in May. The researchers also found an inverse correlation between cord blood 25-hydroxyvitamin D and autoreactive CD4+ cells. Correlation doesn’t necessarily equate to causation, but this is further evidence linking vitamin D and multiple sclerosis risk. Torkildsen O, et al, have also found this association in a meta-analysis of 15 published studies and two congress abstracts and the effect of month or season of birth on MS risk.
There are other autoimmune diseases that are associated with birth month. These include celiac disease, type 1 diabetes, Grave, Hashimoto’s, Crohn’s and even narcolepsy.,,,,, Whether these tie in with vitamin D status, has not been elucidated, but rather these studies point more to viral triggers and month of birth.
Given the common prevalence of vitamin D insufficiency and frank deficiency, it would behoove the clinician to test status, particularly in pregnancy. Doctor’s Data utilizes a Blood Spot test is which is fast, simple and requires only a finger prick of blood for the tip of the patients finger.
The “optimal” 25(OH) vitamin D status has yet to be determined and new data is showing that it is different for different ethnicities, liver status, genetics and weight.,, These factors make dosing more difficult to determine and should change, based upon sun exposure for given latitudes and seasons.
To simplify matters, one may state that sure to have vitamin D levels checked after 3 or 4 months, ensuring it doesn’t go much beyond 125 nmol/ml, until you know how that individual responds to vitamin D dosing.,
Present data reveal that healthy dietary molecules have a pleiotropic role and are able to change cell metabolism from anabolism to catabolism and down-regulate inflammation by interacting with enzymes, nuclear receptors and transcriptional factors. The control of gut dysbiosis and the combination of hypo-caloric, low-fat diets with specific vitamins, oligoelements and dietary integrators, including fish oil and polyphenols, may slow-down the progression of the disease and ameliorate the wellness of MS patients.
One of the more novel areas of interest is in the health of the gastrointestinal tract and its inhabitants. Changes in gut barrier function have been recorded in patients with MS and preliminary studies using a mouse model has shown positive effects from the use of special bacteria in the gut to prevent demyelination.
Vitamin D has also been considered as a promoter risk factor, as geographically MS appears more prevalent in northern hemispheres. Ensuring adequate vitamin D status from in utero and throughout life appears to confer benefit in risk reduction and may provide some symptom management. Correct dosing must be based on periodic blood tests. A vitamin D test will tell you how much of the storage form of vitamin D, known as 25(OH)D or calcidiol, is present in your blood serum.
In summary, exclusion of neurological triggers as described as well as saturated animal fats, cows milk combined with caloric restriction represent the ‘remove’ section of treatment – what to ‘give’ needs to include relevant essential fatty acids, probiotics, nutrients and food groups that favour inflammation, and immunological benefit such as flavonoids, polyphenols, resveratrol, curcumin, olive oil, lycopene, green tea, ALA, acetyl glutathione’s, B12 and selenium .,
 Lewy H, et al. Seasonality of birth month of children with celiac disease differs from that in the general population and between sexes and is linked to family history and environmental factors. J Pediatr Gastroenterol Nutr. 2009 Feb;48(2):181-5. (View Abstract).
 Lewy H, et al. Seasonality of month of birth differs between type 1 diabetes patients with pronounced beta-cell autoimmunity and individuals with lesser or no beta-cell autoimmunity. Pediatr Diabetes. 2008 Feb;9(1):46-52. Epub 2007 Nov 23. (View Abstract).
 Krassas GE, et al. Seasonality of month of birth of patients with Graves’ and Hashimoto’s diseases differ from that in the general population. Eur J Endocrinol. 2007 Jun;156(6):631-6. (View Abstract).
 Laron Z, et al. Seasonality of month of birth of children and adolescents with type 1 diabetes mellitus in homogenous and heterogeneous populations. Isr Med Assoc J. 2005 Jun;7(6):381-4. (View Abstract).
 Gallagher JC, et al. Effects of vitamin d supplementation in older african american women. J Clin Endocrinol Metab. 2013 Mar;98(3):1137-46. doi: 10.1210/jc.2012-3106. Epub 2013 Feb 5. (View Abstract).
 Ochoa-Repáraz J, Mielcarz DW, Wang Y, Begum-Haque S, Dasgupta S, Kasper DL, Kasper LH. A polysaccharide from the human commensal Bacteroides fragilis protects against CNS demyelinating disease. Mucosal Immunol. 2010 Sep;3(5):487-95. Epub 2010 Jun 9. (View Abstract)
 McDowell TY, Amr S, Culpepper WJ, Langenberg P, Royal W, Bever C, Bradham DD. Sun Exposure, Vitamin D Intake and Progression to Disability among Veterans with Progressive Multiple Sclerosis. Neuroepidemiology. 2011 Aug 5;37(1):52-57. [Epub ahead of print] (View Abstract)
 Riccio P, Rossano R, Liuzzi GM. May diet and dietary supplements improve the wellness of multiple sclerosis patients? A molecular approach. Autoimmune Dis. 2011 Feb 24;2010:249842. (View Abstract)
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