MS: Probable Cause and Best Bet Treatment

BEST BET DIET BOOK
Scientific Papers

"MS: Probable Cause and Best Bet Treatment" Dr. Ashton Embry © 1996
Section 4: Constraints on Interpretations of the Cause of Multiple Sclerosis
Click to jump to Summary.
CONSTRAINTS ON INTERPRETATIONS OF THE CAUSE OF MULTIPLE SCLEROSIS There are two different aspects to a possible cause of multiple sclerosis. One is a genetic cause and the other is an environmental cause. The importance of both of these factors can be understood when one considers the research which has been done on identical twins. Current data from Europe and North America, which are both high risk areas for MS, indicate that, for identical twins with MS, about 20- 30% of such twins both have MS (Ebers et al., 1986; Mumford et al., 1994). This compares with only 2% of affected fraternal twins both having MS (Ebers et al., 1986). The fact that MS is more prevalent in women than men (~1.5/1) also demonstrates the role of genes in MS. Thus there is little doubt that there is a genetic factor in MS and it is likely that only genetically susceptible individuals have the possibility of getting the disease. This interpretation was recently confirmed by Ebers et al. (1995). However, it appears that there is no one dominant gene which determines genetic susceptibility and that many genes, each with a small influence, are involved (Ebers, 1996). Not much more can be said about the genetic factor and the best we can do is accept the fact that it exists. Importantly the twin data also convincingly show that, in high prevalence areas, only about 50-60% of individuals (5 of 8 identical twins) who are genetically capable of getting MS, actually contract the disease. Thus almost half the people in high prevalence areas who are "genetically programmed" for MS don't get it. In low prevalence areas it would seem that less than 10% of susceptible individuals have MS. This demonstrates that there is at least one dominant environmental factor which results in a genetically susceptible individual being afflicted with MS. These are very important constraints on interpreting the environmental factor which can be regarded as the "ultimate cause of MS". It must be so common that it occurs over much of the world but it has to be very specific such that only half or less of susceptible people are affected by it. Furthermore this environmental factor must be much more prevalent or effective in certain areas of the world. Another important facet of MS research has been the investigation into the timing of the action of the environmental factor on the individual. Immigration data have been used to elucidate this question (Alter et al., 1966; Dean and Kurtzke, 1971). It has been determined that adult immigrants retain the risk factor of their country of origin whereas their children tend towards the risk factor of the country they have immigrated to. This has been interpreted to indicate that the environmental factor only affects an individual before puberty (approx. age 15). The more obvious interpretation, that the adults do not experience the same environmental influences as their children do in the new country, was seemingly ignored. The data on identical twins also provide insight into the question of timing. Twins share essentially the same environment until they leave home (16-21). Thus, the fact that only 25% of identical twins both have MS, is good evidence for the interpretation that the environmental factor comes into play mainly after age 18. Thus we have an apparent paradox. Immigration data apparently indicate the environmental factor acts before age 15 whereas identical twin data indicate that it acts mainly after age 18. Any interpreted cause of MS must explain this paradox. Another area of research which yields important constraints for interpretation is the global variance in MS prevalence (the number of people having MS which is usually recorded as the number for each 100,000 population) and incidence (the number of people who get MS per year, again recorded as the number for each 100,000 population). As alluded to earlier, the world can be divided into a high prevalence (risk) area which encompasses Europe, Canada, United States, Australia and New Zealand and a low prevalence (risk) area which encompasses the rest of the world (Kurtzke, 1980). In the high risk area prevalences between 50 and 100 per hundred thousand people are common. In the low risk areas MS prevalences are an order of magnitude less (Kurtzke, 1980). This distribution is in part due to the genetic factor because all the high risk areas are dominantly populated by individuals of European origin (Poser, 1994). However, the environmental factor is also responsible for the occurrence of these two very different risk regions. One line of evidence for this is the fact that immigrants to London, U.K. from areas of low risk (e.g. West Indies) have a low prevalence but their British-born children have the same high prevalence as British Caucasians (Elian et al., 1990). An interpretation of the environmental factor must take into account these two different risk areas with the factor being much more common or active in the high risk area. There are also lower order geographic trends in MS prevalence. One of the most oft quoted trends is the occurrence of a north/south gradient within the areas of high prevalence. For Canada and USA, prevalences are lowest in the southern USA, become higher in the northern states and are highest in Canada (Kurtzke, 1980). In western Europe the gradient is not as well expressed but prevalences are higher in the nordic countries and Britain than in the more southerly Mediterranean countries (Rosati, 1994). The north/south gradient is well expressed in Australia and New Zealand with the highest prevalences in the temperate, southern portions of these countries (Sadovnick and Ebers, 1993). In all these cases genetics cannot explain the north/south gradient and it is clear that the environmental factor is primarily responsible for this general increase in MS in areas of higher latitude. Any interpretation of the environmental factor must be compatible with the north/south gradient of MS prevalences. MS also shows large differences in prevalence within some individual countries in the high risk area. For example in Norway MS is up to five times more common in the inland farming areas than in the relatively nearby coastal fishing areas (Alter, 1977). Similarly in Canada, MS is at least twice as prevalent in the Prairie provinces (100-225) as it is on the island of Newfoundland (50) (Sadovnick and Ebers, 1993). In these cases genetics has no bearing on this distribution (Newfoundland has a higher percentage of Caucasians) and the environmental factor must be primarily responsible for such drastic differences. This conclusion has been recently confirmed by Rosati (1994) who states in his review of MS in Europe "variations in both prevalence and incidence rates in ethnically homogeneous populations confirm the importance of environmental factors". These macro and micro differences of MS prevalence in the world must be explained by any interpretation of the environmental factor. Crucial data for constraining the nature of the environmental factor come from prevalences for both those of Japanese and Caucasian descent in Hawaii. Those of Japanese descent have a prevalence of 6.5 (i.e. 6.5 Japanese with MS per 100,000 Japanese in Hawaii) which is over three times that of Japan (2.1) (Kuroiwa et al., 1983; Alter et al., 1971). Conversely the Caucasians who were born and raised in Hawaii have a prevalence of 10.5 which is only one third that of the Caucasians of California (29.9) (Poser, 1994). Thus we have another paradox concerning the environmental factor. In Hawaii it acts such that it adversely affects those of Japanese descent whereas at the very same time it has a very beneficial effect on Caucasians. This puzzling paradox must be regarded as a critical constraint for an objective interpretation of the environmental factor. One of the most interesting and widely quoted epidemiological studies of MS is that of the greatly increased prevalence of MS in the Faroe Islands (North Atlantic, west of Norway) following the occupation by 1500-2000 British troops between 1941 and 1944 (Kurtzke, 1977, 1980, 1995). Kurtzke has classified this increase as an epidemic although other authors have challenged this view (Benedikz et al., 1994, Poser et al. 1988). Regardless, there can be no doubt that MS prevalence substantially increased in the Faroes following the British occupation. Furthermore, the relationship between MS in the Faroe islanders and the presence of British soldiers is strongly supported by the fact the cases of MS all occurred in islanders who lived close to British bases (Kurtzke, 1980, fig. 15). This is an extremely important constraint because it demonstrates that the environmental factor is not solely indigenous and can transported from one area to another. Any interpretation of the cause of MS must satisfactorily explain the sudden increased prevalence in the Faroes and the mobility of the environmental factor. Recently another very important epidemiological study was published by Ebers et al. (1995). These authors were able to demonstrate that children, who were raised in families in which non-blood relatives (step parents, step brothers and sisters, adoptees, etc.) had MS, had no increased risk of MS. This provided good evidence of the genetic factor in MS but more importantly demonstrated that MS is not transmitted by person to person contact. An earlier study which involved spouses of persons with MS also demonstrated this. Another important piece of evidence for determining MS cause is the fact that there is no recorded case of MS having been transmitted to another person through a blood transfusion (Theofilopoulos, 1995a). Finally it is important to note that MS is a relatively new disease with the first recorded case being from the beginning of the nineteenth century (Swank and Dugan, 1987). As argued by Swank and Dugan (1987), MS is basically a "disease of modern times" although it is possible a few cases occurred earlier than 1800. There is no doubt that incidence and prevalence of the disease has been increasing over the last century. Thus the cause of the disease must be due to an environmental factor(s) which is progressively having more effect over the last 100 years. In summary an acceptable interpretation of the environmental factor, which plays a critical role in the onset and progression of MS, must explain the following constraining data.
Summary
1. It must be found throughout the world but be specific enough to affect only half or less of the susceptible individuals. 2. It must affect immigrant children more than it does immigrant adults. On the other hand it must affect susceptible identical twins mainly when they are adults rather than when they are children. 3. It must be much more common or effective in northwestern Europe, Canada, United States, Australia and New Zealand than in the rest of the world. 4. It must be more common or effective in higher latitude areas so as to create a pronounced north/south gradient of MS prevalence. 5. It must have enough variation so as to create significant MS prevalence and incidence differences within ethnically homogeneous populations over relatively short distances. 6. In Hawaii it must adversely affect those of Japanese origin whereas at the same time have a positive effect on Caucasians. 7. It must be transportable so as to explain the sudden increase in MS prevalence in the Faroes following British troop occupation during World War II. 8. It cannot be transmitted by either person to person contact or by a blood transfusion. 9. It must be increasingly more widespread and effective over the last 100 years.
End section 4