by Ashton F. Embry
UPDATE: 2/99
Multiple Sclerosis is an autoimmune disease in which the immune system causes damage to tissues in the central nervous system. The disease results from both genetic and environmental factors. Studies of identical twins demonstrate that MS develops only in genetically susceptible individuals due to one or more environmental influences.
The epidemiology of MS provides a number of important constraints for the interpretation of the environmental factor which can be regarded as the main cause of MS. The disease has a very uneven geographic extent and occurs mainly in USA, Canada, western Europe, New Zealand and Australia where prevalences are generally greater than 50 per 100,000 population. In these areas there is a noticeable north/south gradient with MS being more prevalent in higher latitude, temperate regions. Also within individual countries there are significant differences in MS prevalence and incidence.
Other important constraints are the sudden increase in prevalence in the Faroe Islands following World War II occupation by British troops and the fact that residency in Hawaii increases the risk of MS for those of Japanese descent while simultaneously decreasing the risk for Caucasians. Studies have also shown that MS cannot be transmitted by person to person contact or by blood transfusion. Finally MS is a modern disease which appeared about 175 years ago. The prevalence has steadily increased from that time.
The various proposed environmental causes of MS can be tested against the epidemiological data base to see if they are compatible with the various constraints. All but one of the proposed causes, including a specific infectious agent (virus, bacteria) and common infectious agents (e.g. influenza virus), can be eliminated due to various incompatibilities with the established data. The only environmental factor which reasonably fits all the epidemiological constraints is diet.
The main disease processes in MS are breaches in the blood-brain barrier and the passage of activated and inactivated immune cells into the CNS. These cells initiate a variety of immune reactions which eventually destroy the myelin wraps on nerve axons. Myelin loss results in various physical disabilities which increase with progressive destruction of myelin.
The diet factors which can result in such disease processes are the ingestion of hypersensitive food and large amounts of saturated fats. Food hypersensitivities reduce the effectiveness of the blood-brain barrier through Type I (activation of basophils and mast cells) and Type III (deposition of immune complexes) reactions. T-cells are activated against CNS proteins (Type IV reaction) by both molecular mimicry of CNS self proteins by food proteins outside the CNS and by exposure of autoreactive T-cells to previously sequestered CNS proteins following passage of immune elements through a damaged blood-brain barrier. Saturated fats contribute to the disease process by promoting the formation of micro-emboli which also damage the blood-brain barrier.
Abundant anecdotal data indicate that many people have achieved either a permanent remission or a significant slowdown in disease progress through diet revision involving the elimination of hypersensitive food and a great reduction in saturated fat intake.
The most common foods which result in immune reactions and eventual MS are dairy, cereal grains, eggs, yeast and legumes. These are all foods which have been introduced into the human diet relatively recently and are genetically difficult to tolerate for some individuals. The steadily increasing prevalence of MS in the last 50 years is due to the greatly increased consumption of these problematic foods through the popularity of "fast foods".
The most effective treatment for MS is the elimination of all dairy, cereal grains, eggs, yeast and legumes as well as all foods which are shown to be hypersensitive by a blood allergy test for IgE and IgG4. Saturated fat intake should be limited to less than 15 g a day and polyunsaturated fat intake, including both omega 3 and omega 6 essential fatty acids, should be increased. A variety of supplements including vitamins, minerals, antioxidants and oils is also essential for healing and strengthening the blood-brain barrier, CNS tissue, immune cells and the intestinal wall. Strick adherence to this dietary regime will likely greatly reduce or eliminate exacerbations and lead to a partial or complete recovery.
Currently no research is being promoted or done on the relationship between dietary
factors and MS. This is very unfortunate and is definitely not in the best interests of
persons with MS. MS society officials must be informed of the major links between diet and
MS and the great need for strong support of research efforts in this field. A major
clinical trial which tests the efficacy of a hypersensitive food-free, low saturated fat
diet is urgently required.
(top)
In June, 1995 my 18 year old son was diagnosed with multiple sclerosis (MS) with confirmation coming a month later with a Magnetic-resonance imaging (MRI) scan. Since that time I have been reading books, symposium volumes and journal articles on various aspects of this disease as well as visiting many informative websites. From the late 60s I have been a geological research scientist and this has served me well for analyzing the voluminous data and many interpretations and speculations for MS found in the literature. In geology I have dealt mainly with large, multifactorial problems (e.g. origin of the Arctic Ocean, geological history of the Canadian Arctic over a 200 million year time span) for which varied and mainly circumstantial evidence is available. I have spent much of my career synthesizing large, diverse and sometimes conflicting data sets into hypotheses and theories of earth history. In geology we are never absolutely sure we have the "right" answer but we never shy away from making an interpretation. For this we choose the simplest hypothesis which fits the data. This hypothesis becomes the accepted right answer ("truth") until a better (simpler) hypothesis is proposed or new data require a modification or outright rejection of the currently accepted answer. I have provided this background because a geologist's approach to finding an answer to a large, multifactorial problem such as MS differs significantly from that of the medical scientist. In medical research there seems to be only a "100% sure interpretation" or a "don't know" approach.
My approach to the problem of MS has been to try to find the most probable cause of the disease by using published data on MS epidemiology (who gets and who doesn't), MS pathogenesis (how the damage to the body happens) and MS recovery (who has recovered from MS and how they did it). Surprisingly I could not find a single article or book which took this same systematic approach to solving the MS puzzle.
The relevant data on MS epidemiology are presented in the first main section. In the next section all the proposed causes are listed and each is tested against the established epidemiological constraints to see if it is compatible with the data or can be rejected as a probable cause. This has led to the identification of a single factor, diet, which satisfies the epidemiological constraints.
The basic disease process (pathogenesis) is presented in the next section. This is
followed by a discussion which demonstrates that dietary factors can result in the known
disease process. Finally a number of anecdotal accounts of recovery are noted and it is
shown that diet revision played a major role in each of these recovery stories. This
section is concluded with a recent first person account of an impressive recovery which
was based on the diet revision suggestions presented in an earlier version of this essay.
The next part of the paper deals with a suggested treatment which is based on the need for
identifying pathogenic foods and eliminating them from one's diet. The treatment, which
consists of diet revision and supplements, basically counters the effect of a harmful diet
and helps repair the already sustained damage. In this section other environmental factors
which likely contribute to MS and other treatments which may be helpful are discussed.
I conclude the essay with my subjective views of current deficiencies in the MS
research effort and what I believe needs to be done to remedy this unfortunate situation.
I must emphasize this is my best interpretation given all the data I have found and it is
open to revision or rejection when more data are obtained. The reader is encouraged to
critically evaluate my arguments and interpretations and to decide if my conclusions have
merit or not.
(top)
There is solid evidence that MS is an autoimmune disease which means it is the result
of the actions of one's own immune system on specific tissues in the body. For example
when the immune system attacks collagen in the joints the autoimmune disease is called
rheumatoid arthritis. There are almost 100 different autoimmune diseases with each one
being characterized by immune-mediated damage to specific tissues. MS is characterized by
chronic inflammation and damage to tissues in the central nervous system (CNS) due to
immune responses (Van Oosten et al., 1995). More details of the disease process are
presented in a later section.
(top)
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.
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.
(top)
The nine constraints listed above are key to testing if a proposed cause of MS can be taken seriously or not. Clearly if a proposed cause is not compatible with one or more of these constraints then it must be rejected as the probable cause. Only factors which are compatible with all of these constraints can be considered as a probable cause of MS. All of the environmental factors proposed as a cause of MS have been compiled and these include specific virus or bacteria, common virus or bacteria, heavy metal poisoning, industrial pollution, sanitation, diet, sunlight, altitude, climate (temperature), microwave radiation and cosmic radiation. These factors can be placed into three main groups:
indigenous factors: sunlight, altittude, climate, cosmic radiation, microwave radiation
infections: specific virus or bacteria, common virus or bacteria
transportable, non-infectious factors: heavy metals, pollution, sanitation, diet
First of all, the indigenous factors can be readily eliminated on the basis of the Faroe Islands data. These data clearly demonstrated that the environmental factor is not indigenous but can be brought into an area (e.g. the Faroes).
The infectious causes seem to be the most commonly quoted explanation for the environmental factor. The reason for this appears to emanate from an a priori assumption that unexplained diseases are caused by an infectious agent with viruses preferred over bacteria due to their "difficult to detect" nature. The constraints listed above indicate that it is highly unlikely that either a specific virus or bacteria which infects the CNS is responsible for MS. The main reasons for rejecting a specific infectious agent are:
1. The constraints show that MS is not transmitted either person to person or through a blood transfusion.
2. The significant variation in MS prevalence and incidence in ethnically homogenous populations over relatively small areas is hard to reconcile with a specific infectious cause of MS.
3. No physical evidence of a specific MS virus or bacteria has ever been found in the CNS of persons with MS despite a very long and concerted effort to find such material (Poser, 1993).
Before leaving this topic it is important to note that the main evidence which is usually quoted by those advocating a specific viral cause of MS is the greatly increased incidence of MS in the Faroes following British troop occupation. The standard interpretation of these data follows Kurtzke (1977) and is that some of the British troops were infected with the MS virus and that they subsequently infected the Faroe islanders. At first glance such an interpretation seems plausible but a more penetrating analysis of the data, coupled with other constraints, makes the viral hypothesis of the Faroes increased prevalence very unlikely.
First of all, there were less than 2000 British troops in the Faroes and, given the 90/100,000 prevalence of MS in Britain, there were, at best, 2 troops with MS. Furthermore, given that any soldier exhibiting neurological disease would have likely been sent home, it is highly unlikely that there were enough troops to infect the islanders. Kurtzke (1995) has countered this argument by claiming that many people may be carriers of the MS virus but not have the disease themselves. There is certainly no evidence of such a phenomenon and Kurtzke's speculation is unsupportable.
Furthermore, as has been mentioned previously, there is no increased prevalence of MS in children with step brothers and sisters with MS or in individuals whose spouse has MS. These data clearly indicate that a specific viral cause of MS is highly unlikely and that any suggestion that one or two British troops transmitted a MS virus to the Faroe islanders is entirely unsupportable.
With the rejection of the Faroe Islands evidence for a viral cause, the interpretation of a specific virus being the main environmental factor which results in MS does not appear to be tenable. This conclusion was also reached by Poser (1993) who stated "the constant failure to confirm the role of a specific organism in the pathogenesis of MS has raised grave doubts about its existence".
It has also been postulated that common viral and bacterial infections cause MS through a phenomenon called molecular mimicry (Theofilopoulos, 1995b). For this to happen a part of the molecular structure of the infectious agent must closely resemble part of the molecular structure of one or more self-proteins in the CNS. Thus when the immune system is activated against the virus it may also attack the similar self-proteins in the CNS. In support of this it has been demonstrated that some viruses do have molecular sequences similar to those of CNS proteins (Wucherpfennig et al., 1995). Also Sibley et al. (1985) demonstrated a weak correlation between viral infections and MS exacerbations. However it must be mentioned that in Sibley et al's study many exacerbations occurred in the absence of infection and many viral infections did not trigger an exacerbation. Also, as shown by MRI studies (Lai et al., 1996), disease activity is essentially continuous in many cases and viral infections certainly are not.
A constraint which strongly indicates that common viral and/or bacterial infections are not the main cause of MS is the prevalence data for Japanese and Caucasians in Hawaii. The prevalence of common infections in Japan, Hawaii and California is very similar, being perhaps highest in Japan due to high population density. Thus, given that MS is three times more common in Japanese in Hawaii than in Japan, clearly demonstrates that common infectious agents are not the main cause of MS. Another constraint which demonstrates that common infections are not the main cause of MS is the north/south gradient of prevalence in many areas. The occurrence of common infections shows little variation within these areas and thus cannot explain such a pronounced gradient. Other constraints, such as the much higher prevalence of MS on the Canadian Prairies than in Newfoundland, also argue strongly against a common virus for the main cause.
Of the transported, non-infectious factors, heavy metals, industrial pollution and sanitation can also be rejected. The most convincing constraint for this conclusion again is the greatly increased prevalence of MS for Japanese living in Hawaii versus Japan where these factors are much more common than in Hawaii. The Faroe Islands data, as well as the much higher prevalence of MS on the Canadian Prairies than in the highly industrialized area of southern Ontario, also are not compatible with these factors.
This leaves us with one remaining factor which is DIET. Diet is certainly not a new interpretation for the key environmental factor responsible for MS although it tends to be arbitrarily dismissed by numerous authors. However a close reading of the arguments against diet leads to the conclusion that diet has not been rejected on scientific grounds, but rather on rhetorical ones (e.g. Sibley, 1992) . Statements like "diet has not been proven to affect the disease (McIlroy, pers. comm., 1993)" and "no controlled scientific study has proven without doubt that the course of MS can be modified by dietary changes (Girard, pers. comm., 1991)" are commonly quoted but, in effect, add nothing to the question of the role of diet. Such statements really mean "we have no idea if diet plays a role in MS". Notably no sound scientific argument has ever been presented against the possible effects of diet. For this analysis, I have looked at diet in the light of the nine constraints detailed earlier. I have found that diet fits all nine constraints and thus I currently believe the main environmental factor which is the prime cause of MS indeed is diet. In regard to the nine constraints:
1. Diet is obviously found throughout the world and it is specific enough to an individual with given dietary habits to result in MS affecting only half or less of genetically susceptible individuals.
2. Diet also provides a reasonable explanation of the immigrant/twin paradox. Adults who immigrate have a strong tendency to maintain the diet of their homeland whereas their children are far more likely to consume more of the food of the country they live in (especially once they have left home). This results in a change of dietary habits and a consequent change of MS risk in the children but not the adults. Thus the immigration data are best interpreted in the light of immigrant children and immigrant parents experiencing different environmental factors in their new country. This is not surprising because it is well known that immigrant children integrate much more than do immigrant adults.
Identical twins tend to have very similar diets when they live together at home but their dietary habits potentially diverge after they leave home and live apart. Furthermore identical twins can possibly have separate food sensitivities especially when they are older due to long term intestinal damage and increased permeability. Thus dietary and digestive system changes (and MS risk divergence) would occur in twins mainly after age 18. Thus diet and only diet explains this paradox.
3. The overall diets of the high prevalence areas have certain features in common including high dairy, cereal grain and saturated fat consumptions. These are all much higher than in the low prevalence areas. The great differences in diet between the high prevalence areas and the low prevalence areas can readily account for the occurrence of two very different risk areas in the world. It would appear that the foods consumed in high prevalence areas (e.g. dairy, cereal grains, high saturated fat) are more effective in causing MS as has been noted in various statistical studies (Shatin, 1964; Alter et al., 1974; Agranoff and Goldberg, 1974; Malosse et al., 1992; Lauer, 1994). Shatin (1964) found a good correspondence of MS prevalence with wheat consumption. Malosse et al. (1992) state "We have studied the relationship between MS prevalence and dairy product consumption in 27 countries and 29 populations all over the world. A good correlation (p=0.836) was found; this correlation was highly significant (p<0.001)". This echoed Agranoff and Goldberg (1974) who almost 20 years earlier had stated "a geographic predisposing factor in multiple sclerosis ... is directly related to milk consumption". Alter et al. (1974) found a significant correlation (0.7) between consumption of animal fats and MS prevalence. Furthermore on the basis of a recent multivariate analysis, Lauer (1994) concludes "The second MS-related bundle comprised characteristics ... with dietary variables (i.e. a diet low in fish and high in dairy products)".
4. Diet is readily compatible with the north/south gradient because diet varies directly with climate and thus latitude. The diets of cooler, more temperate regions include much more saturated fat, dairy and cereal grains which, as discussed above, are the most problematic foods.
5. Significant differences in diet can occur within a given country and these differences are sufficient to account for different prevalence rates. For example, the maritime Newfoundlanders consume much more fish and less dairy and cereal grains than do Canadians on the prairies and, as noted earlier, they have a far lower prevalence than do the land-locked, prairie dwellers.
6. Most importantly diet explains the paradox of the adversely affected Hawaiians of Japanese ancestry and the beneficially affected Hawaiians of Caucasian descent which Poser (1994) characterized as "puzzling". The diet of Japanese-Hawaiians includes many more elements of the high risk diets of Europe and North America (e.g. saturated fats, dairy products, cereal grains) than does the diet of native Japanese. Thus one would expect a significantly higher prevalence for Japanese in Hawaii. On the other hand the diet of Caucasians in Hawaii includes more elements of the low risk diets (e.g. fish, fresh vegetables and fruits) then does the diet of Caucasians of mainland North America. This of course would result in a lower prevalence for Caucasians in Hawaii. Thus it would appear that diet provides the solution for this puzzling paradox which is inexplicable by other postulated causes.
7. A critical question in this analysis is "Can diet explain the increased prevalence of MS in the Faroes following British troop occupation?" As has been discussed it is highly unlikely that the British brought with them a MS virus but it is clear that they did bring the environmental factor with them. The obvious interpretation is that they brought their own food supplies which would have of course included food high in saturated fat and the foods which most commonly cause hypersensitivity reactions (dairy, eggs, cereal grains, nuts, legumes). The islanders living near the bases (and working on them) would have had easy access to these "non-traditional" foods and added them to their diet. Thus such dietary changes in susceptible islanders can readily explain the sudden increase in MS. These imported foods likely became part of the standard diet of many of the islanders (especially the youth) and this accounts for the ongoing occurrence of MS in the Faroes. Thus diet does indeed provide a solid and reasonable explanation of one of the most specific and well controlled pieces of epidemiological evidence regarding the environmental factor.
8. Diet as the main factor is entirely compatible with the non-transmissible characteristic of MS as noted by Ebers (1996) who, on this basis, clearly stated "In sum these data strongly indicate that the environmental factor is affecting the population risk. Accordingly, factors which influence large populations such as diet... deserve careful reconsideration".
9. The diet of the high risk areas (western societies) has changed significantly over
the last 100 years with substantial increase of saturated fat, a decrease in
polyunsaturated fat and an increase in dairy and cereal grains (Swank and Dugan, 1987).
This trend of a higher consumption of these foods has been significantly accelerated over
the past fifty years with the rise and constant expansion of the "fast food"
(e.g. hamburgers, pizza, donuts) industry. Thus the continued increase of consumption of
these foods readily accounts for the steadily increasing prevalence of MS over the last
100 years.
(top)
In the last section the epidemiological evidence for dietary factors as the main cause of MS was presented. Of course, if diet is the main cause, it must be demonstrable that specific dietary factors are capable of resulting in the various known disease processes of MS. In this and the next sections the basic disease processes (pathogenesis) of MS are reviewed and the theoretical basis for dietary factors resulting in these processes are presented.
The basic pathogenesis of MS involves the entry of immune cells (e.g. T-cells, B-cells, macrophages) into the CNS through the walls of the capillaries and venules (Traugott, 1990; Poser, 1993). Immune reactions occur, a lesion is formed and myelin is eventually destroyed. Myelin consists of fatty tissue which wraps around nerve axons. It essentially acts as nerve insulation and is critical for proper nerve transmissions. Loss of myelin results in degradation of nerve transmissions and a resultant multitude of disabilities which gradually worsen over time as more myelin is destroyed.
It is very important to note that in healthy individuals immune cells cannot pass
through the CNS capillaries and venules into the CNS tissue. This does not happen because
the walls of the capillaries in the CNS are different from those in the rest of the body
in that they have very closely packed cells which do not allow the passage of immune
cells. This special feature of the CNS vascular system is referred to as the blood-brain
barrier (BBB) (Traugott, 1990).
It would seem that an intact blood-brain barrier prevents CNS infiltration of immune components and thus stops the possibility of MS occurring. As noted by Compston (1991), one of Britain's leading MS researchers, "blood-brain barrier penetration can be regarded as the primary disease process". This is especially true because many people carry immune cells which are reactive with brain tissue but only a few develop MS. As explained by Soll (1968) many years ago, "isolation (of the CNS) begins to take place during fetal life, very likely before the so-called immunologic "recognition of self" takes place. Thus, at least parts of our brain may be capable of evoking an immune reaction... provided the immune mechanisms were allowed direct access to the CNS". Thus almost 30 years ago it was recognized that a critical disease process in MS is the breach of the BBB and the exposure of the CNS to autoreactive immune cells. This concept is now widely accepted and Theofilopoulos (1995b) notes in a recent, comprehensive review of autoimmune disease "Induction of autoimmune disease, following contact with antigens of such so-called "immunological privileged" sites, has been well documented".
This concept has been supported by observations of MS lesions on MRI scans. On the MRI scans it was observed that the CNS lesions could be enhanced by using gadolinium-DTPA (Miller et al., 1988; Kermode et al., 1990). Passage of this substance through the BBB clearly indicated that the MS lesions in the CNS occur where the BBB has been damaged so that various substances, including gadolinium, could readily pass through the damaged walls of the capillaries. Furthermore, Traugott (1990) notes "that MS lesions are preferentially localized around postcapillary venules" which have a "relatively low barrier function". This and other evidence led Poser (1987, 1992, 1993), in a series of watershed papers, to declare in no uncertain terms "In order for MS to become a disease affecting the CNS, it is necessary for the blood-brain barrier's impermeability to be altered" (Poser, 1993, p. 53). Recently, this emphasis on the damage to the BBB as a key disease process in MS has been confirmed by Lai et al. (1996). Based on a study of weekly MRI scans in patients, these researchers state that "this finding suggests that breakdown of the blood-brain barrier is an invariable and perhaps obligatory event in the development of new lesions".
A second part of MS pathogenesis, which is more controversial, is the cause and timing of the activation of the autoreactive T-helper cells (a type of immune cell strongly implicated in MS pathogenesis [Traugott, 1990]) which react to the CNS proteins. Two possibilities have been advanced. One hypothesis is that the T-cells are activated in the blood outside of the CNS and these cells then cross the BBB to attack the myelin or other CNS proteins. The other hypothesis, which has been alluded to earlier, is that the autoreactive T-cells become activated against CNS proteins after they have passed through a breach in the BBB and encounter the previously sequestered CNS proteins.
To me it is most likely that many of the pathogenic, autoreactive T-cells are activated outside of the CNS. My reasoning for this conclusion is that MS is just one of many autoimmune diseases and many of the others have only the presence of a normal capillary wall between the blood and the tissue. These diseases require activation of the T-cells outside the tissue and, thus, I believe such a requirement also is the most reasonable assumption for MS.
The cause of the activation of T-cells against CNS proteins outside the CNS is somewhat problematic. The most widely accepted hypothesis (Theofilopoulos, 1995b) is that peptides (fragments of proteins) from foreign antigens which are presented by macrophages (another type of immune cell) to T-cells may resemble parts of CNS self proteins from a molecular structure point of view. This is referred to as molecular mimicry as was mentioned earlier. Experimental data have clearly shown that such a mechanism by both food and viruses can result in the activation of T-cells against various self proteins (Singh et al., 1989; Wucherpfennig et al., 1995; Ostenstat et al., 1995). Thus molecular mimicry would indeed appear to be a critical factor in the pathogenesis of MS.
In summary, the evidence is strong that a key part of MS pathogenesis is the activation
of autoreactive T-cells both outside and within the CNS and that persons with MS carry
such CNS autoreactive T-cells. These activated T-cells set in motion a series of immune
reactions which results in myelin being destroyed by various immune elements (e.g.
macrophages) (Traugott, 1990). The interested reader is referred to Steinman (1993) for an
excellent review of autoimmune disease in general and multiple sclerosis in specific.
Other articles in the same issue of Scientific American provide a good overview of
immunology.
(top)
One related area regarding MS pathogenesis is that of the outward manifestation of the disease. Most cases of MS start with a relapsing-remitting (RR) character which refers to short periods when new symptoms appear or old ones increase (attack or exacerbation) and long intervals when symptoms improve somewhat or stabilize (remissions). On average it would appear a typical case involves about one attack a year (Sibley, 1992). Notably it has been found through MRI studies that lesion forming activity occurs even during remissions (Lai et al., 1996). Thus in many cases it would appear as if disease activity is essentially continuous with a waxing and waning character.
In many instances RRMS evolves into secondary progressive (or chronic progressive) MS where there are no clear relapses and remissions, only gradual deterioration.
In some cases, MS does not present in a relapsing-remitting manner but rather gradual deterioration begins at onset. This type of MS is known as primary progressive MS.
If untreated, RRMS can have a highly variable course in terms of disabilities although an average rate of decline of one EDDS (a scale for assessing disability state) level every six years has been documented (Swank and Dugan, 1987; Sibley, 1992).
Any proposed cause of MS should be able to explain the various types of MS and the
observed average decline rate.
(top)
As explained in the last section, MS is mainly the result of both the activation of T-cells against CNS protein and damage to the blood-brain barrier which leads to infiltration of immune cells into the CNS tissue and subsequent demyelinization. There are two main components of diet which appear to be responsible for the activation of T-cells and BBB damage.
The first and perhaps most critical component is food antigens. Gell and Coombs (1975) described four classes of hypersensitivity which is defined as "an increased state of reactivity that involves a detrimental immune response" (Elgert, 1996). Each of these types of hypersensitivity causes tissue damage through various types of immune reactions (Elgert, 1996). Type I, III and IV hypersensitivity reactions are relevant to this discussion of reactions involving food (Sampson, 1991).
Type I is the classic immediate, hypersensitivity immune reactions which involve the increased production of IgE antibodies upon introduction of an offending food. This is what is termed a food allergy and the reader is referred to Lichtenstein (1993) for a comprehensive review of the immune response of allergens. Note that only this specific reaction is termed allergy and all other reactions are referred to as hypersensitivities. In brief, an allergen in the blood, through a complex series of immune responses, stimulates mast cells and basophils (specific types of immune cells) to secrete various chemicals and hormones such as histamine, leukotrienes and tumor necrosis factor. It is well established that the chemicals secreted by the activated basophils and mast cells can cause a significant increase in the permeability of capillaries (Lichtenstein, 1993). As stated by Rozniecki et al. (1995), "mast cells ... can participate in the regulation of blood-brain permeability". Thus, food allergens are potentially capable of causing significant, localized, increased permeabilities in the BBB. Activated mast cells may also play a significant role in demyelinization (Johnson et al., 1988; Kruger et al., 1990). Kruger and Nyland (1995) summarize these concepts: "multiple sclerosis arises due to the effect of the various mediators (histamine and protease) released from the perivascular mast cells after stimulation by some diet factor". Also of significant importance is that IgG4 antibodies can also activate mast cells and basophils (Shakib et al., 1986; Elgert, 1996). The role of IgG4 in pathogenic immune reactions has been shown by Gerrard el al. (1976) and Rafei et al. (1989). Rafei et al. (1989) found that only 29% of those with food allergies (as demonstrated by food challenges) had positive IgE skin tests whereas 91% tested positive for IgG4 and IgE. Furthermore one patient who demonstrated a delayed response to peanuts had undetectable IgE but markedly elevated antipeanut IgG4. As recently shown by Bengtsson et al. (1996), non-IgE immune reactions occur in adults due to the ingestion of common foods such as eggs, milk and wheat. IgG4 may well be involved in such reactions.
Type III hypersensitivity involves the production of immune complexes which are formed by the combining of antigens and antibodies. This type of hypersensitivity is likely responsible for many non-IgE reactions. It has been established that these circulating immune complexes can have a pathogenic effect mainly by deposition in blood vessel walls (Cochrane and Koffler, 1973). This causes inflammation of the vessel walls and greatly increased permeability. Immune complexes can also result in the activation of another part of the immune system, complement (plasma proteins), which results in further damage (Elgert, 1996). Thus the increased production of antibodies (mainly IgA, IgG, IgE and IgM), due to the introduction of various food proteins into the circulatory system, can readily result in immune complex formation, deposition in the vascular system of the CNS, activation of complement and a resultant damage to the BBB.
Type IV hypersensitivity refers to cell-mediated reactions and results in the activation of T-cells which then induce an array of damaging immune reactions. These reactions, like Type III reactions, are delayed and often occur days after the offending foods are ingested. The mechanisms by which food antigens induce Type IV reactions are currently poorly understood although such occurrences (e.g. celiac disease in which cereal grain proteins cause cell-mediated reactions) are undoubted. As mentioned earlier, one possible mechanism for foods to induce an activation of T-cells against parts of the CNS is through molecular mimicry. Food proteins which escape into the circulatory system are processed by macrophages which then present peptides (protein fragments) derived from the food protein to T-cells. The molecular sequencing in these peptides may be close enough to the sequencing of self-antigens in the CNS (molecular mimicry) to induce T-cell activation against parts of the CNS. For example it was recently shown that cereal proteins share amino acid homologies with human joint tissue (procollagen) and that T-cells from the joints of arthritic patients were activated by these cereal proteins. Thus molecular mimicry by cereal proteins can result in arthritis (Ostenstad et al., 1995). It is readily conceivable that various proteins found in dairy and grains as well as other foods (e.g. legumes, yeast, eggs) have similar amino acid sequencing as proteins in the CNS.
In summary it is clear that, from a theoretical point of view, hypersensitivity reactions to foods can result in significant damage to and increased permeability of the BBB and can also result in T-cell activation against the CNS. As discussed earlier, such damage to the BBB and activation of T-cells initiates a cascade of immune reactions to happen in the CNS which results in chronic inflammation, demyelination and a diagnosis of MS. The interested reader is referred to the website www.webdirect.net/zeno for a comprehensive discussion of the relationship of food hypersensitivities and disease.
The second component of diet which likely affects MS progression is the types and amounts of fats consumed. The three basic types of fat are saturated, monosaturated and polyunsaturated. The reader is referred to Erasmus (1993) for a comprehensive, yet highly readable, explanation of fats and oils. Swank and Dugan (1987) have presented considerable evidence which demonstrates a relationship between MS and the consumption of saturated fat. This relationship was also noted by Alter et al. (1974). Swank and Dugan (1987) have suggested that a high consumption of saturated fat can result in the formation of micro-emboli. These micro-emboli of fat particles and/or platelets then cause damage to the BBB which aids the subsequent passage of activated immune cells into the CNS. Swank and Dugan (1990) provide convincing evidence from a 35 year longitudinal study of individuals on a low saturated fat diet that such a diet beneficially affects the progression of MS.
Other workers have hypothesized that a deficiency in polyunsaturated fats is also a contributing factor in MS (Thompson 1975; Smith and Thompson, 1977). Clinical trials using supplementation of either omega 6 fatty acids (e.g. sunflower and safflower oil) or omega 3 fatty acids (e.g. fish oil and flax oil) have shown a moderate benefit of these oils on MS (Millar, 1975; Dworkin et al., 1984; Bates et al., 1989). It would appear that these polyunsaturated fats reduce inflammation and are important in CNS cell growth.
It is quite possible that the actions of the chemicals secreted by the mast cells and basophils (Type I hypersensitivity), the actions of the immune complexes (Type III hypersensitivity), and the constrictions caused by saturated fat-related micro-emboli all work in concert to increase the permeability of the BBB and to allow the passage of various activated (Type IV hypersensitivity) and inactivated immune components. The introduction of these immune cells into the CNS would then lead to various immune reactions against previously sequestered CNS proteins and the eventual destruction of myelin. Thus we now have theoretical evidence to go along with the solid epidemiological evidence that a diet which contains substantial hypersensitive food, a large amount of saturated fat, and a deficiency of polyunsaturated fat can lead to the development of MS in a genetically susceptible person.
Dietary factors as the main cause of MS also provides a reasonable explanation for the different types of MS. For any individual the ingestion of specific kinds and amounts of sensitive and fatty foods, which potentially affect the BBB and activate T-cells, will vary significantly with time but can have a daily effect. This fact, in concert with random infections by common viruses and bacteria which also affect the BBB and activate T-cells, results in an ongoing disease process but a randomness in the severity of disease activity and a consequent relapsing-remitting character for MS.
As the BBB continues to degrade through time, by the daily irritation by dietary factors and by gradual aging processes, a point is often reached when ongoing disease activity maintains a relatively high level and RRMS transforms into secondary progressive MS.
Primary progressive MS is likely a reflection of an individual's extreme hypersensitivity to various substances combined with high exposure and a relatively easy path for the antigens to reach the circulatory system. In such a case almost continuous BBB failure and T-cell activation might be expected with no periods of relief.
Thus it would appear as if dietary factors do provide a reasonable explanation for the
great variation in presentation and progression of MS.
(top)
If indeed food hypersensitivities are a main factor in the cause of MS it would be
expected that persons with MS as a group, would have many more hypersensitivities than the
general public. Soll and Grenoble (1984) noted that "individuals with multiple
sclerosis frequently display a profile of numerous allergies" (i.e.
hypersensitivities). My own experience, through both personal and internet contacts with
persons with MS, has confirmed Dr. Soll's statement. Food hypersensitivities seem to be
very common and this is currently being demonstrated by ELISA blood tests which test for
IgE and IgG4 immune reactions to 190 foods. Currently 15 of 18 persons with MS who have
had such a test have had numerous, significant food hypersensitivities with dairy, cereal
grains, eggs, yeast and legumes being the most common reactive foods. Given that it is
estimated that between 1 in 50 to 1 in 100 people have significant food hypersensitivities
(Sampson, 1991), if MS and food hypersensitivities were not related, the chance of a
person with MS also having food hypersensitivities would also be between 1 in 50 and 1 in
100. Current data suggest at least 50%, if not 75%, of persons with MS have notable food
hypersensitivities indicating that MS and food hypersensitivities are definitely
related.
(top)
A final area of potential useful data is anecdotal evidence regarding recoveries from MS or significant positive changes in the course of MS. Such data are quite rightly regarded as "soft" and by themselves provide little, if any, good evidence for interpreting the cause of MS. However, taken from another point of view, these independent accounts of positive changes in MS progression can provide another test of any proposed cause. For example, if dietary factors are the main cause of MS, then it might be expected that diet revision, involving the avoidance of hypersensitive and high saturated fat food, was a critical factor in many of the documented anecdotal accounts.
To test this I searched for all the accounts of "MS recovery" that I could find in the literature, on the Internet, and through conversations with persons with MS. On the basis of the results of this investigation it would indeed appear that diet revision is a very critical treatment for achieving positive results in the halting or significantly altering the progression of MS. Perhaps the most impressive account of recovery is that of Roger MacDougall (1980) which is described in "My Fight Against Multiple Sclerosis". Mr. MacDougall went from being near blind and confined to a wheelchair to normal health and activity level (for over 35 years) by faithfully adhering to a low fat, food sensitivity-free diet. Other published "success" stories which used diet revision as the main therapy include those of Rachelle Breslow, Alan Greer, Judy Graham, Bob Lawrence, John Pageler and Bryan Forbes. Recently a number of accounts of recovery have been gathered on a website (www.2cowherd.net/q) by an individual who himself has recovered from chronic progressive MS (wheelchair confined) to a normal, healthy lifestyle through diet revision.
Of special interest is a scientific paper (Meyer et al., 1954) published over forty years ago when "allergy" was seriously considered as a possible cause of MS. The authors describe 17 case histories of persons with MS whose symptoms were greatly alleviated by avoidance of identified food and inhalant "allergies" (non IgE-mediated). Importantly the authors note that in cases where offending substances were reintroduced that MS symptoms returned.
In another well known study of diet revision, Swank and Dugan (1987) reported that 66 patients who reduced their daily saturated fat intake to less than 20 grams experienced, on average, only very minor deterioration over 35 years. This result contrasted with 31 patients who did not follow such a low fat diet and suffered major deterioration during the same 35 year study. It should be noted that such a low fat dietary regime also resulted in a greatly reduced consumption of the foods which most commonly cause hypersensitivity reactions (dairy, grains, eggs). These impressive results are perhaps the best documented evidence of the beneficial effects of diet revision on the course of MS.
And what of my son? I had my son tested for food sensitivities on the basis of the concepts presented herein. He came back with numerous significant hypersensitivities with dairy products, legumes and eggs being very problematic. After he began avoiding his offending foods and went on a very low fat diet, a number of "minor" ailments which had plagued him for years completely disappeared. These included night sweats, headaches, petechia (bruising), rhinitis, slight hand tremor and light sensitivity. These ailments are related to inflammatory reactions and are very common in persons with MS (Swank and Dugan, 1987). All of his MS symptoms also disappeared and a subsequent neurological examination revealed no neurological deficits. There is no doubt that such drastic diet revision has been difficult but my son takes the philosophical approach of DIET or WHEELCHAIR. This certainly provides the necessary incentive to faithfully stick to his strict, but absolutely essential, dietary regime. He has remained in excellent health for the past 15 months.
Notably a number of persons with MS who read the first "edition" of this
essay, which was put on the Internet in early 1996, have reported significant improvement
through diet revision therapy. One example is Deidre's story which was written by her
mother and is transcribed below.
(top)
by Barbara MacLellan
"Deidre contracted MS at age 11 and the hospital put her on steroids which had a limited benefit. At age 25 she began to deteriorate quite rapidly: first her vision became distorted and she developed nystagmus. Her whole body would go into spasm and rigidity; her head and neck then went into spasm and shook all the time. Her left hand and arm began to shake just as if she had palsy. Then her right hand began to shake so that she was unable to feed herself, write or brush her teeth. Deidre was also a wall walker and needed a wheelchair if she went any distance. Cognitively Deidre was very confused and unable to continue with her university studies. She was terribly fatigued. The diagnosis was chronic progressive MS.
In February a plea for help was made on the Internet Newsgroup alt.support mult-sclerosis. Ashton Embry sent us his essay on MS and suggested that Deidre immediately stop all dairy, gluten and egg products. We decided to follow his advice and went a step farther by eliminating gluten, dairy, chicken, potatoes, sugar, caffeine and aspartame. She mainly ate lots of vegetables, rice products, lamb, fish and fruit. We had both RAST and ELISA tests done which confirmed the presence of many significant allergies. Deidre also began taking various supplements including bilberry, kelp, vitamin B and C, cod liver oil, efamol and selenium.
Her head shakes stopped first and soon she no longer felt "stupid and confused". Over the past nine months Deidre has improved to the point where her arms and hands shake minimally and she is able to cut her own food. Her body no longer goes into spasm, she is able to write again and she can walk longer distances without help. Deidre shows gradual improvement every week and we feel confident that in another year, Deidre will be nearly symptom-free".
Although the above anecdotal data cannot be regarded as strong evidence that dietary
factors are the main cause of MS, I believe such data are important for strongly
supporting the case for dietary factors which has been built on referenced epidemiological
and theoretical scientific data.
(top)
It appears that specific types of food are most commonly responsible for causing
various hypersensitivity reactions which lead to MS. Such foods are dairy, cereal grains,
eggs, yeast and legumes. The evidence supporting this comes from the previously-quoted
statistical studies of food consumption and MS prevalence (e.g. Malosse et al., 1992) and
the abundant anecdotal data (e.g. MacDougall, 1980). As noted by Eaton and Konner (1985)
these food types, as well as substantial saturated fats have been added relatively
recently to the human diet in terms of our two million year evolutionary history. Our
distant ancestors did not consume such foods and did not suffer from most of the current
lifestyle diseases, including MS, which are now common in Western societies. It would seem
that humans are genetically less tolerant of these "recently" introduced foods
which cause a great variety of health problems (e.g. heart, stroke, cancer, autoimmune)
for genetically susceptible individuals in societies which consume large quantities of
them (Eaton and Konner, 1985).
To me the best explanation for the appearance and steady increase of MS in Western
societies is the continued increase over the last 150 years in the consumption of the
"late, genetically-hard-to-handle" foods such as dairy, cereal grains, yeast,
eggs, legumes and saturated fats. Thus, although these "late", potentially
problematic foods have been consumed for thousands of years, it is only recently that
large quantities have been ingested so as to exceed tolerance levels for many genetically
susceptible individuals. Later a suggested treatment for MS is put forward and it is based
on the final conclusion of Eaton and Konner (1985) - The diet of our ancestors is
perhaps the best defense against the diseases of civilization.
(top)
The interpretation that diet is the main environmental factor for the cause of MS is well supported by our current data base. For those who would counter this interpretation I would ask them to provide either a better interpretation for the environmental factor using the current epidemiological data base or to provide solid, well reasoned evidence of why diet cannot possibly be the main environmental factor in most cases. I am not saying that one specific food type (e.g. dairy) is responsible for MS. Rather it is mainly the activation of T-cells by one or more food proteins (specific to an individual) and the constant weakening of the blood-brain barrier by the immune reactions caused by a variety of individual food hypersensitivities and the micro-emboli which result from a high ratio of saturated to unsaturated fat intake. Other environmental factors such as viruses and heavy metals also likely add to the environmental burden and thus contribute to the disease process.
When considering this entire debate it is essential to realize that diet is basically
outside the world of conventional medicine and is rarely even considered. Thus the subject
is commonly either ignored or quickly brushed off. Furthermore there is not one dime of
research money being spent to test the hypothesis of diet control for MS despite the
obvious links between the two. I would urge anyone with MS to maintain an open mind on
this subject and to consider the foregoing information objectively as possible. From my
geological background I never forget that the theory of continental drift, which is now a
fundamental concept of our science, was suppressed for 50 years (1912-1962) by the
geological establishment. It was simply too threatening to too many careers of those in
power. A diet cause for MS appears to represent a similar threat to conventional medicine.
(top)
An effective treatment for MS clearly depends on knowing the cause of the disease. The treatment which is suggested below assumes that diet is the main cause of MS onset and progression because it best fits the extensive epidemiological data base and is theoretically plausible. The treatment has two components: (1) halting the activation of T-cells against the CNS and reducing the ongoing damage to the BBB and (2) strengthening the BBB.
1. The first step in halting T-cell activation and reducing the continuous irritation of the BBB is the scientific identification of all food hypersensitivities. There are various methods used to test for food hypersensitivities (Bateson-Koch, 1994) and each has advantages and disadvantages The three most reliable methods, which are scientifically based, are described and evaluated below.
For IgE-mediated, immediate hypersensitivity, the cheapest and most easily accessible method is skin testing. The main drawback to this method is that it only looks at one component of hypersensitivity (IgE) and thus, at best, it provides only very limited data for identifying one's offending foods. If only such a test is used many major food hypersensitivities may well be overlooked.
A second method for identifying immune-reactive foods is a blood test using either a RAST (Radioallergosorbent) or ELISA (enzyme-linked immunosorbent assay) methodology. Both of these methodologies measure the amounts of various antibodies produced when a blood sample is challenged with a given food protein. The ELISA methodology is somewhat more sensitive than the RAST (Elgert, 1996) and is cheaper to do. Usually both IgE and IgG4 (a subclass of IgG, the most common antibody type) are measured. In some tests all four subclasses of IgG are measured. The advantages of this type of test is that it is non-invasive ("in vitro"), easy to administer, relatively cheap and can cover most common foods. Also, by measuring IgG4, foods which cause delayed hypersensitivity (e.g. Type III reactions), are also uncovered. The disadvantage of such blood tests is that they tend to be only about 80% accurate and false negatives can occur. Also, because these tests only measure antibody production, they do not provide direct data on foods causing the activation of T-cells against the CNS (Type IV reactions). Thus the data should be regarded as a guide to your food sensitivities with the realization that others may remain to be identified.
A third method is the use of an elemental diet followed by individual food challenges. Foods which cause a reaction and result in a symptom (e.g. headache, stomach ache, numbness, etc.) are readily identified as being hypersensitive. This methodology, because it involves the body's reactions ("in vivo") to foods, is perhaps the most reliable method for identifying foods which cause hypersensitivity reactions. Also foods which result in all three types of hypersensitivity reactions can be identified. The drawbacks are that it is very time consuming and potentially expensive. Also there is some question if MS symptoms consistently become apparent on food challenges.
Other blood tests which may help uncover foods which cause damaging immune reactions are the cytotoxic test and a test which measures the level of immune complexes in the blood. The relationship of the results of these tests to food hypersensitivities is somewhat debatable but such data are undoubtedly of some value.
There are a number of unconventional tests available such as muscle tests and pulse tests. It is difficult to evaluate the reliability of these tests because there is no theoretical basis for the relationship between food hypersensitivities and the measured effects and they have never been scientifically validated. I would suggest such tests not be used in place of the above scientific tests until more data on their reliability and scientific basis are obtained.
From my experience I strongly recommend that all dairy, cereal grains, yeast, eggs and legumes be completely avoided. These are the foods with the highest potential to cause the activation of T-cells against the CNS. I would also suggest the use of an ELISA blood-allergy test (see Appendix). It will detect most food hypersensitivities (Type I, III) and it provides a quantitative result. As discussed, use of this test in my son's therapy was very valuable and successful and many others have also found it to be very informative. The food challenge method can be used subsequently if problems remain after all ELISA-identified, offending foods are removed from one's diet. Also one should always be aware of how a given food affects them and eliminate foods which consistently result in discomfort and minor symptoms (fatigue, tingling, etc.).
2. As has been discussed, MS is in part due to a leaky BBB caused by food-induced immune reactions and high intake of saturated fats. One of the reasons that food-induced immune reactions occur in the circulatory system is the occurrence of another "leaky" area in the body, a "leaky gut". A leaky gut refers to increased permeability of the intestinal tract and results in food proteins being able to pass between intestinal cells into the circulatory system. This of course sets off the destructive immune reactions which eventually result in various diseases including MS (Butkus and Mahan, 1986). Laboratories offer intestinal permeability tests (see appendix) although I would suggest you save time and money and assume that you have a leaky gut and take steps to heal it. Increased permeability has various causes including NSAID (non-steroidal anti-inflammatory drugs) useage, infection, candida overgrowth, parasites, ingestion of allergic foods, alcoholism, and trauma. It is important to eliminate the source of the problem (e.g. candida overgrowth) and to take various supplements to heal and protect the gut. These include acidophilus, enzymes, fish oil, borage oil and glutamine.
3. Finally, to protect against the formation of damaging micro-emboli, it is essential to decrease your intake of saturated fats to 15 grams or less a day. In this regard stop eating any margarine and any red meat. Swank and Dugan (1987) provide much information on saturated fats in foods and foods to avoid. As noted earlier these authors also present impressive data from a thirty-five year, longitudinal study which demonstrates the effectiveness of an ultra-low fat diet (Swank and Dugan, 1990). This study, which is unique in MS research, was misrepresented and wrongly interpreted by Sibley (1992).
I would also suggest that you have routine cholesterol level tests to make sure your low fat diet is effective. If cholesterol levels remain high you might consider drug therapy to lower the level.
There is very little literature on possible ways to strengthen the BBB. Recently an essay on this subject was posted on a web site (http://spider.lloyd.com/~tstout/articles) by T. Stout. Much of the information in this section is taken from this excellent contribution.
Experiments with animals have shown that there are three related chemicals, anthocyanosides, proanthocyanidins and procyanidolic oligomers, which strengthen the BBB (Robert et al., 1977; Detre et al., 1986). These chemicals are found in blueberries, cherries, black berries, grapes and the bark and needles of certain pine trees. They are currently available as encapsulated supplements called bilberry, grape seed extract and pycnogenol. These supplements and/or substantial quantities of the above fruits should be ingested daily to help strengthen the BBB.
The anthocyanosides and proanthocyanidins act as very powerful anti-oxidants, block enzyme actions and bind with the BBB and it is these properties which likely result in their beneficial effect on the BBB (see Stout essay for details). Other supplements which are anti-oxidants (much less powerful) include vitamin A (cod liver oil), vitamin C (with bioflavonoids) and vitamin E. These, along with vitamin B complex and vitamin D, should be taken daily. Calcium and magnesium supplements are also essential and have been shown to beneficially affect MS progression (Goldberg et al., 1986).
As described earlier, micro-emboli, formed due to high saturated fat intake, also
damage the BBB. As a complementary treatment to the reduced intake of saturated fats,
consumption of polyunsaturated fats should be increased. Such fats aid in the
desegregation of platelets and are important for cell growth and reducing inflammation.
These fats include unrefined safflower, sunflower and flax oil as well as
encapsulated evening primrose oil and borage oil. It was recently scientifically shown
that gamma-linolenic acid, the key ingredient of evening primrose oil and borage oil,
greatly reduced arthritis attacks (Zurier et al., 1996). Fish also contain valuable
polyunsaturated fats (omega 3 EFA) and should be eaten at least two or three times a week.
Fish oil (e.g. salmon oil) is also available in capsules. Notably fish oil has been found
to be very beneficial in controlling another autoimmune disorder, Crohn's disease
(Belluzzi et al., 1996). The interested reader is referred to the comprehensive book by
Erasmus (1993) which provides detailed information on the harmful effects of some fats and
the beneficial effects of others.
(top)
The following list of supplements is suggested for daily ingestion. The indicated amounts are well below any toxicity levels but should not be exceeded except on a physician's advice. Graham (1989) provides detailed rationales for their therapeutic value for MS:
1. up to 300 mg grape seed extract (use pycnogenol or bilberry if you are sensitive to grapes)
2. 2 grams cod liver oil (includes 5,000 IU vitamin A and 400 IU vitamin D)
3. 4 grams salmon oil
4. 100 mg of B-50 complex
5. 100 mcg of B-12 (have your B-12 level routinely checked)
6. up to 3 g of vitamin C
7. up to 800 IU of vitamin E
8. up to 1500 mg of calcium depending on dairy consumption (I strongly suggest no dairy consumption ever)
9. up to 500 mg of magnesium (a good Ca/Mg ratio is 2:1)
10. 25 mg of zinc
11. 50 mcg of selenium
12. up to 5 g of evening primrose oil or borage oil
13. up to 10 g of flax oil (make sure you are not hypersensitive to flax!)
14. 4 capsules of acidophilus
15. 6 capsules of enzymes (see Bateson-Koch, 1994 for use of enzymes for relieving food hypersensitivities)
Other supplements which have been recommended as helpful for MS are co-enzyme Q10,
amino acids, lecithin and octacosanol. The acidophilus, enzymes and various oils are
especially important for healing the gut. Graham (1989) provides details on the use and
value of most of these products.
(top)
I believe it would be naive to think that every single case of MS had the same cause and that most cases have only a single cause. MS is basically "an effect", a chronic inflammation and demyelination of the CNS, and it seems to me a number of environmental factors can in combination, result in such a condition. For example, it is known that a bacterial infection can cause chronic inflammation and demyelination but, because the cause is known, it is called Lyme Disease rather than MS. Furthermore, in rare cases, measles vaccination has also resulted in chronic demyelination and once again, because the cause is known, it is not referred to as MS but rather as chronic rubella encephalitis. Thus MS is basically a catch all term for chronic demyelination of unknown cause.
As I have discussed in the first part of this essay, dietary factors are most probably the main (but not the only) cause of most (but not all) cases of MS. Given this, it is essential to find out through testing if indeed your MS is caused mainly by food hypersensitivities and high saturated fat intake. If you avoid dairy, cereal grains, eggs, yeast, legumes and other hypersensitive food and follow a low fat diet with supplements and the progression of MS is not abated, then it is likely your MS is mainly caused by another environmental factor. The factors discussed below are other likely contributors to MS and, although in most cases they are subsidiary to hypersensitive foods, they may be major factors in some cases.
Another possible cause of immune reactions which damage the BBB and possibly activate T-cells are hypersensitivities (type I, III, IV) to inhalants. IgE, immediate sensitivity reactions to inhalants seem relatively rare in persons with MS (Oro et al., 1996) but IgG reactions may be more common and problematic. Once again a blood-allergy ELISA or RAST test which measures IgE and IgG4 production on antigen challenge for a variety of inhalants is a reasonable way of determining if this is a major contributing factor to your MS. If the test is positive for a number of inhalants then once again it is essential to avoid or greatly lower the exposure to these substances. This maybe more difficult than for foods but allergists should be able to advise on various methods of avoidance and reduction. Extreme measures such as moving to another part of the country may be necessary in rare cases.
As discussed earlier common viral and bacterial infections undoubtedly can affect the BBB and activate T-cells against the CNS. It is very doubtful if common viral and bacterial infections are the main cause of MS onset and progression as revealed by the epidemiological data but, in a few cases, such occurrences may play a major role in progression. In regard to a bacterial cause of MS the reader is referred to the website, "ourworld.compuserve.com/homepages/GShannon". Strong antibiotics are useful in cases where bacteria play a significant role in MS. In general, strategies to avoid infections should be adopted and any common bacterial infection should be treated with standard antibiotics as soon as possible.
Minerals such as zinc and selenium, which strengthen the immune system, may well have value in warding off viral infections (Macknin et al., 1996). It has also been suggested that herbs such as goldenseal and echinacea have value in strengthening the immune system (Balch and Balch, 1996). One problem with these herbs is that they may cause hypersensitivities (goldenseal is closely related to ragweed) and questions still remain concerning the wisdom in taking these herbs over a long time period. I would suggest caution in their use for MS treatment with echinacea perhaps being the safest herb to use to ward off viruses.
Heavy metals can be very toxic to the CNS and thus, in some cases, may play a significant role in MS onset and progression. One of the most obvious sources of heavy metal toxicity is mercury in dental fillings. Currently there is considerable debate on this point and it is difficult to separate the data from the hype. Replacement of mercury amalgams is very expensive and may itself cause problems. However there is enough theoretical and anecdotal data available to indicate that mercury fillings may contribute to MS progression. If diet revision does not result in an effective halt of MS progression then it may well be worth the trouble and expense to have the fillings replaced.
An interesting and insightful study of the effect of toxins on the CNS concerns the response of 26 women with failed, silicone breast implants (Shoab and Patten, 1996). "All patients had evidence of disseminated CNS lesions" and 80% had oligoclonal bands (IgG antibodies) in their spinal fluid. All the women had "systemic, inflammatory, autoimmune disease with CNS involvement" which was "triggered by the foreign material (silicone) in their body". This example clearly indicates that foreign, "antigenic" material can cause BBB failure and demyelinating immune reactions.
It is worth having a blood test and perhaps even a hair analysis for levels of heavy metals (see appendix). Chelation therapy can be valuable for detoxifying when anomalously high levels of heavy metals are detected.
Poser (1986, 1993) has stated that vaccinations may be an important factor in MS onset and progression. Given the fact that vaccinations cause immune reactions it is clear that they may well affect the BBB and cause CNS inflammation (not necessarily an exacerbation). Poser (1986) provides references for a number of incidences where vaccinations resulted in MS. The most reasonable explanation of such occurrences is that the vaccination provided the final stress on an already embattled CNS. Overall I would suggest that vaccinations (including the flu shot) be avoided unless they are absolutely necessary.
Currently three different, but very closely related, drugs which consist of beta-interferon, a protein (cytokine) secreted by immune cells, are available for MS therapy (Betaseron, Avonex, Rebif). Clinical trials have demonstrated that these drugs reduce the number of exacerbations and lesion forming activity and thus are beneficial for treating MS. A number of immediate side effects (flu-like symptoms, site reactions) are often associated with these drugs but in most cases are not intolerable or dangerous. Depression can be a troublesome side effect and notably 3% of the study group on betaseron attempted or committed suicide whereas no one in the placebo group attempted or committed suicide. One major concern in the use of these drugs is that up to 40% of those taking them for up to 3 years develop neutralizing antibodies to the injected beta-interferon (Thompson and Noseworthy, 1996). The immediate result of this is that the drug no longer will have any beneficial effect. Of more concern is the possibility that the produced antibodies will cross-react with and neutralize the individual's natural beta-interferon. If this happens the individual's immune system will be severely compromised with likely catastrophic results. There have been no confirmed reports of such disastrous cross reactions having occurred. Thus the decision to take these drugs is a bit of a gamble and I suggest that the pros and cons be thoroughly considered before deciding to accept such drug therapy.
The latest drug available for treating relapsing-remitting MS is copaxone which is a synthetic chemical (amino acid copolymer) that resembles myelin basic protein. It was in development for about 30 years. It is not certain how the drug works to reduce the number of exacerbations and lesion activity but the most likely explanation is that it acts as a "decoy" for the T-cells and antibodies which are activated against myelin. Thus, instead of attacking the myelin, many immune cells react against the copaxone (Wolinsky, 1995). The drug seems to be most effective in individuals in the early stages of MS (minimum disability). A clear understanding of the short and long term side effects of copaxone has not been achieved. Initial data indicate the side effects and risks are less than those for the beta interferon drugs.
Recently the concept of oral tolerance has been suggested as the basis for MS treatment (Weiner et al., 1993). The main concept is, that by eating CNS proteins of bovine derivation, an individual desensitizes the immune system to CNS proteins and causes the development of suppressor immune cells which inhibit immune action against CNS proteins.
Presently, a Phase III trial, which is testing this treatment, is going on and the results are expected by mid-1997. The "drug" which is currently being tested is refined bovine CNS proteins (including myelin basic protein) and is called Myloral. In reality Myloral is nothing more than a food supplement which has been patented. To me this therapy, like other suggested supplements such as grape seed extract, holds promise because it likely has few side effects and helps to offset the immune reactions associated with the ingestion of offending foods. The most serious potential side effect is a hypersensitivity reaction (i.e. oral tolerance is not achieved) to the Myloral. Obviously immune reactions against ingested myelin proteins which pass into the circulatory system will likely result in substantial damage to the CNS. Clearly it will not solve the problem on its own but is a useful addition to the suggested dietary revisions and other supplements.
It is worth noting that two non-patented, bovine brain products are currently available, Sphingolin and Ora-brain. Given the above theoretical basis it might be worth taking one of these products although optimum dosage is not known. As a caution I suggest you make sure you are not hypersensitive to this substance. Also there might be a remote possibility of disease transmission (Creutzfeld-Jakob?) by them.
Overall the oral myelin therapy may turn out to be a very beneficial therapy in
fighting MS for many people and would be complimentary to diet revision.
(top)
The one therapy method, for which MS societies, MS clinics and many neurologists
provide reasonably up to date information, is drug therapy (Carter, 1995; Bansil et al.,
1995; Van Oosten et al., 1995). A variety of immunosuppressive drugs is being used to
fight MS although results are mixed. Cladribine and possibly Methotrexate appear to hold
some promise for CPMS. For those who prefer drugs to diet revision and supplements I
suggest you discuss the options and the various side effects with a neurologist.
(top)
Numerous "alternative" therapies have been suggested to relieve MS symptoms
and to alter the progression. These are all listed and discussed in Graham (1989) and
Thomas (1995). Much anecdotal data are available to indicate that various alternative
therapies have value and are worth investigating. Of course common sense approaches to
health such as adequate rest, exercise and a reduction of stress are undoubtedly very
beneficial.
(top)
Perhaps after you have read all the preceding information you are wondering if any definitive research has been done on MS and diet. Unfortunately no such research is currently being done and very, very little has been done over the past 25 years. The complete lack of research in this field is not in the best interests of persons with MS given the obvious and plentiful theoretical, empirical and anecdotal evidence which has been available for many years linking MS and diet. Furthermore, this dearth of research is inexcusable given the great interest the MS community has in the possible benefits of diet in MS treatment. When this topic is voiced, as it frequently is, the same line is quoted by medical personnel "There is no proof diet affects the course of MS". It comes as no surprise that there is no proof one way or the other because the necessary research has not been done or even promoted. Due to this neglect the MS community has been left in limbo with the agonizing dilemma of "to diet or not to diet - that is the question". Thus the concerns and questions of the persons with MS regarding diet are going unheeded and this must be rectified.
I would suggest if you really want to know beyond a reasonable doubt if diet is a significant cause of MS and significantly affects its progression, then you must lobby the elected officials and directors of your national MS society. It is essential to realize that the research which is currently being supported by your MS Society, with money raised on your behalf, will have very little, if any, impact on your health. This research is almost exclusively long term, fundamental research (molecular immunology, genetics, etc.) which will result in no practical applications for decades, if ever. Such academic research is fine up to a point but the almost complete lack of research of practical value (e.g. diet research) is not a reasonable balance (50-50 would be reasonable). For example, here in Canada 90% of research funds are for molecular and genetic research.
In conclusion, it would seem that the MS community is not being well served from a
research point of view. The main reason for this appears to be that the officials of the
societies are not aware of the large and varied data base supporting the relationship
between diet and MS. It seems only reasonable that the societies should be promoting and
supporting research which could quite possibly benefit the members in the next five to ten
years. Diet research is of course one area which desperately needs a serious research
effort and I am sure there are others. I urge you to become proactive and write your
Society soon. Let them know you want hard data as to whether or not diet influences MS and
whether or not other alternative therapies are of value.
(top)
The diverse data sets for MS are all compatible with the hypothesis that diet is the
main environmental factor in the cause of the disease. Only diet is compatible with the
extensive and varied epidemiological data base. It appears that the activation of T-cells
against the CNS by molecular mimicry initiated by food proteins and the constant
irritation and weakening of the blood-brain barrier by immune reactions caused by food
hypersensitivities and by micro-emboli related to saturated fats eventually result in the
onset and progression of MS. On this basis the best treatment for MS is to remove the
foods which activate the T-cells and which damage the BBB and to add supplements which
strengthen the CNS, the immune system, the BBB and the gut. One should avoid all dairy,
cereal grains, eggs, yeast and legumes, identify all food hypersensitivities by an ELISA
test and remove these offending foods from one's diet, reduce saturated fat intake to less
than 15 g a day, increase polyunsaturated fat (unrefined oils) intake and take a variety
of supplements including vitamins, minerals and anthocyanosides. Substantial evidence
indicates that a faithful adherence to this dietary regime will greatly reduce, and may
well eliminate, MS exacerbations. Unfortunately, no research is being done on the
relationship between MS and diet despite the very obvious links between the two. The MS
community must become proactive and lobby National MS Societies to promote and support
research which will decide beyond a reasonable doubt if diet affects the progression of
MS. The community must adopt a comrade-in-arms approach in fighting against MS and insist
on substantial research initiatives which will possibly benefit them in the near term.
(top)
I would like to acknowledge the great help and support I received from my wife Joan and my sons, Matt, Dean and Duncan, during the compilation of this research. Irwin, Cathy, Joel and Michael kindly critically read the manuscript and offered many valuable suggestions for improvement. Billie Chiang expertly processed the manuscript. Many persons with MS have shared their stories and their test results and this has provided me with much more insight into a very frightening and sometimes devastating disease. I would especially like to thank Barbara McLellan in this regard. Dave Q, Aapo Halko and Jean Sumption have kindly placed this essay on their terrific websites and I am grateful for their generosity.
This essay is dedicated to the memory of Roger MacDougall who defeated MS through
logic, intuition and dedication to his dietary program.
(top)
This material is provided as general
medical information and is not intended as advice for individual patients; please contact
your physician for specific recommendations. The International MS Support Foundation does
not advocate, promote or verify the contents of this information.
1. An absolute must-read is Multiple Sclerosis - a self-help guide to its management by Judy Graham 2nd edition 1989. Published by Healing Arts Press. One Park Street, Rochester, Vermont 05767. A 3rd edition (1993) is available only in England, Contact MSRC 4a Chapel Hill, Stansted Essex, UK CM24 8AG. This book contains excellent discussions of various therapies used to combat MS.
2. The Multiple Sclerosis Diet Book by R.L. Swank and B.B. Dugan, 1987. Published by Doubleday & Co. Garden City, New York. This book promotes the ultra-low fat diet and has much useful general information. The data demonstrate the lack of decline of numerous patients who were on the ultra-low fat diet for 35 years.
3. MS Something Can Be Done and You Can Do It by R.W. Soll and P.B. Grenoble, 1984. Contemporary Books, Chicago. A good book for the role of food allergens and MS.
4. My Fight Against Multiple Sclerosis by R. MacDougall, 1980. A pamphlet available from Regenics Inc., Rt. 10, 2660 Touby Road, Mansfield Ohio 44903, Telephone (419) 756-2994 (Cost $2). An excellent account of the permanent remission (40 years) achieved by using an allergy-free, ultra low fat diet.
5. New Hope Real Help for those who have Multiple Sclerosis by John Pageler, 1987. A booklet available from the author 6200, 102 Terrace N., Pinellas Park, FL 33782 (cost $9). Another inspiring personal account of avoiding MS progression through diet revision.
6. Fats that Heal, Fats that Kill by Udo Erasmus, 1993. Alive Books, 7436 Fraser Park Drive, Burnaby, British Columbia, Canada V5J 5B9. A comprehensive account of the relationship between saturated fats and lifestyle diseases such as multiple sclerosis.
7. Allergies-Disease in Disguise by C. Bateson-Koch, 1994, Alive Books, Burnaby, B.C.,
Canada. An excellent review of allergy with suggestions for reversing the condition.
1. Blood Allergy Test by ELISA
Absolutely essential for establishing your food sensitivities. Available from
Meridan Valley Clinical Laboratory
515 W. Harrison St.
Kent, Washington 98032
Tel: (206) 859-1135
Fax: (206) 859-8700
2 food panels covering 190 foods available (approximate cost $125US). If you have trouble finding a doctor who will do the test for you, phone or fax the laboratory and they will likely be able to give you the name of a physician in your area who will arrange the test.
2. Intestinal Permeability
Increased permeability can result in macromolecules, toxins and antigens crossing the intestinal barrier into lymph and circulatory systems. These particles trigger an immune response. It is very useful for MS patients to determine if they have a "leaky gut" and if so, take the proper steps to reverse the condition. Available from
Great Smokies Diagnostic Laboratory
18A Regent Park Blvd.
Asheville, North Carolina 28806
3. Candida Analysis
Candida overgrowth can result in greatly increased intestinal permeability and food hypersensitivities and is very common in MS patients. This condition should be reversed if present. Available from
Antibody Assay Laboratories
1715E Wilshire #715
Santa Ana, California 92705
Tel: (714) 972-9979
4. Whole Blood Elements
Heavy metals can, although rarely, play a role in MS. Mercury from dental fillings may cause severe problems. Iron deficiency has also been implicated in MS. Available from
Doctor's Data Laboratories
170 W. Roosevelt Rd.
West Chicago, Illinois
Toll free: (800-323-2784)
Fax: (708) 231-9190
Hair Multielement Analysis also available.
Ashton F. Embry
3303-33rd St. NW
Calgary, Alberta
Canada T2L 2A7
Voice: 403-292-7125 (office), 403-282-0028 (home)
Fax: 403-292-4961
Email: embry@gsc.nrcan.gc.ca (office)
embrya@cadvision.com (home)
Please feel free to copy and distribute all or parts of this essay. An electronic
version is available upon email request.
(top)
Agranoff, B.W. 1974, Diet and the geographical distribution of multiple sclerosis. Lancet, p. 1061-1066.
Alter, M., Leibowitz, U. and Spector, J., 1966, Risk of multiple sclerosis related to age at immigration. Arch. Neurol., v. 15, p. 234-237.
Alter, M., Okihiro, M., Rowley, W. and Morris, T., 1971, Multiple sclerosis among Orientals and Caucasians in Hawaii. Neurology, v. 21, p. 122-130.
Alter, M., Yamoor, M. and Harashe, M., 1974, Multiple Sclerosis and nutrition. Arch. Neur., v. 31, p. 267-272.
Alter, M., 1977, Clues to the cause based upon the epidemiology of multiple sclerosis. in, Field, E.J. (ed.). Multiple Sclerosis: A critical conspectus. Lancaster, MTP Press Ltd., p. 35-81.
Balch, J.F. and Balch, P.A., 1996, Prescription for nutritional healing, 2nd edition. Avery Publishing Group, New York, 600 p.
Bansil, S., Cook, S.D. and Rohowsky-Kochan, C., 1995, Multiple Sclerosis: immune mechanism and update on current therapies. Annals of Neurology, v. 37, p. S87-S101.
Bates, D., 1989, A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry, v. 52, p. 18-22.
Bateson-Koch, C., 1994, Allergies-Disease in disguise. Alive Books, Burnaby.
Belluzzi, A. et al., 1996, Effect of an enteric-coated fish oil preparation on relapses in Crohn's Disease. N. Engl. J. Med., v. 334, p. 1557-1560.
Benedikz, J., Magnusson, H. and Guomundsson, G., 1994, Multiple Sclerosis in Iceland with observations on the alleged epidemic in the Faroe Islands. Annals of Neurology, v. 36, supplement 2, p. S175-S179.
Bengtsson, U. et al., 1996, Non IgE-mediated food allergy. Gut., v. 39, p. 130-135.
Butkus, S.N. and Mahan, L.K., 1986, Food allergies: immunological reactions to food. N. Am. Dietetic Assoc. Cont. Ed., p. 601-608.
Carter, J.L., 1995, Disease modifying therapies in multiple sclerosis. CNS Drugs, v. 3, p. 99-114.
Cochrane, C.G. and Koffler, D., 1973, Immune complex disease in experimental animals and man. Adv. Immunology, v. 16, p. 185.
Compston, A., 1991, Limiting and repairing the damage in multiple sclerosis. Jour. of Neurology, Neurosurgery and Psychiatry, v. 54, p. 945-948.
Dean, G. and Kurtzke, J., 1971, On the risk of multiple sclerosis according to age at immigration to South Africa. BMJ, v. 3, p. 725-729.
Detre, Z. et al., 1986, Studies on vascular permeability in hypertension: action of anthocyanosides. Clin. Physiol. Biochem. n. 4, p. 143-149.
Dworkin, R.H., Bates, D., Millar, J.H.D. and Paty, D.W., 1984, Linoleic acid and multiple sclerosis: a reanalysis of three double blind trials. Neurology, v. 34, p. 1441-1445.
Eaton, S.B. and Konner, M., 1985, Paleolithic Nutrition: A consideration of its nature and current implications. New England Journal of Medicine, v. 312, p. 283-289.
Ebers, G.C., 1996, Genetic epidemiology of multiple sclerosis. Current Opinion in Neurology and Neurosurgery.
Ebers, G., Bulman, D., Sadovnick, A. et al., 1986, A population-based study of MS twins. N. Engl. J. Med., v. 315, p. 1638-1642.
Ebers, G., Sadovnick, A.D. and Risch, N.J., 1995, A genetic basis for familial aggregation in multiple sclerosis. Nature v. 377, p. 150-151.
Elgert, K.D., 1996, Immunology. John Wiley and Sons, New York, 468 p.
Elian, M., Nightingale, S. and Dean, G., 1990, Multiple sclerosis among the United Kingdom-born children of immigrants from the Indian subcontinent, Africa, and the West Indies. J. Neurol Neurosurg Psychiatry, v. 53, p. 906-911.
Erasmus, U., 1993, Fats that heal, fats that kill. Alive Books, Burnaby, B.C., Canada.
Gell, P.G.H. and Coombs, R.R.A., 1975, Classification of allergic reactions responsible for hypersensitivity and disease. In Clinical Aspects of Immunology, P. Gell, R. Coombs and P. Lachmann (eds.). New York, Blackwell, p. 761-781.
Gerrard, J.A. and Zaleski, A., 1976, Functional bladder capacities in children with enuresis and recurrent urinary infections. In Clinical Ecology, L. Dickey (ed.). Springfield, Illinois, Charles C. Thomas, p. 224-233.
Goldberg, P., Fleming, M.C. and Picard, E.H., 1986, Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. Medical Hypotheses, v. 21, p. 193-200.
Graham, J., 1989, Multiple sclerosis - a self-help guide to its management. Healing Arts Press, Rochester, Vermont.
James, P.B., 1982, Evidence for subacute fat embolism as the cause of multiple sclerosis. Lancet, p. 380-385.
Johnson, D., Seeldrayers, P.A. and Weiner, H.L., 1988, The role of mast cells in demyelination 1 myelin protein are degraded by mast cell proteases and myelin basic protein and P2 can stimulate mast cell degranulation. Brain research, v. 444, p. 195-198.
Kermode, A.G., Tofts, P.S., Thompson, A.J. et al., 1990, Heterogeneity of blood-brain barrier changes in multiple sclerosis: an MRI study with gadolinium-DTPA enhancement. Neurology, v. 40, p. 229-235.
Kruger, P.G., Bø, L., Myhr, K.M. et al., 1990. Mast cells and multiple sclerosis: a
light and electron microscope study of mast cells in multiple sclerosis emphasizing
staining procedures. Acta. Neurol. Scand., v. 81, p. 31-36.
Kruger, P.G. and Nyland, H.I., 1995, The role of mast cells and diet in the onset and
maintenance of multiple sclerosis: a hypothesis. Medical Hypotheses, v. 44, p. 66-69.
Kuroiwa, Y., Shibasaki, H. and Ikeda, M., 1983, Prevalence of MS and north-south gradient in Japan. Neuroepidemiology, v. 2, p. 62-69.
Kurtzke, J.F., 1977, Multiple sclerosis from an epidemiological point of view in. Field, E.J. (Ed.), Multiple Sclerosis: A critical conspectus. MTP Press Inc., Lancaster, p. 83-142.
Kurtzke, J.F., 1980, Epidemiologic contributions to multiple sclerosis: an overview. Neurology, v. 30, p. 61-79.
Kurtzke, J.F., 1995, MS epidemiology worldwide. One view of current status. Acta. Neurol. Scandin., Supplement 161, p. 23-33.
Lai, M. et al., 1996, A preliminary study into the sensitivity of disease activity detection by serial weekly magnetic resonance imaging in multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry, v. 60, p. 339-341.
Lauer, K., 1994, The risk of multiple sclerosis in the USA in relation to sociogeographic features: a factor analytic study. J. Clin. Epidemiology, v. 47, p. 43-48.
Lichtenstein, L.M., 1993, Allergy and the immune system. Scientific American, v. 269, p. 117-124.
MacDougall, R., 1980, My fight against multiple sclerosis. Regenics Inc., Mansfield, Ohio.
Macknin, M.L. et al., 1996, Zinc lozenges shorten duration of common cold. Ann. Intern. Med., v. 125, p. 81-88.
Malosse, D., Perron, H. and Seigneurin, J.M., 1992, Correlation between milk and dairy product consumption and multiple sclerosis prevalence, a worldwide study. Neuroepidemiology, v. 11, p. 304-312.
Meyer, M.G., Johnston, A. and Coca, A.F., 1954, Is Multiple Sclerosis a manifestation of idioblaptic allergy? The Psychiatric Quarterly, Jan. p. 1-15.
Millar, J.H.D., 1975, Clinical management: Linoleic acid diet. In Multiple Sclerosis Research, New York, Elsevier, p. 217-225.
Miller, D.H., Rudge, P.Johnson, G. et al., 1988, Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis. Brain, v. 111, p. 927-939.
Mumford, C., Wood, N., Kellar-Wood, H. et al., 1994, The British Isles Survey of multiple sclerosis in twins. Neurology, v. 44, p. 11-15.
Oro, A.S. et al., 1996, Regulation of disease susceptibility: decreased prevalence of IgE-mediated allergic disease in patients with multiple sclerosis. J. Allergy Clin. Immunology, v. 97, p. 1402-1408.
Ostenstad, B., Dybwad, A., Lea, T., Forre, O., Vinje, O. and Sioud, M., 1995, Evidence for monoclonal expansion of synovial T cells bearing VÓ2.1/Vß5.5 gene segments and recognizing a synthetic peptide that shares homology with a number of putative autoantigens. Immunology, v. 86, p. 168-175.
Poser, C.M., 1986, Pathogenesis of multiple sclerosis. Acta Neuropathol., v. 71, p. 1-10.
Poser, C., 1987, Trauma and multiple sclerosis. J. Neurol. v. 254, p. 155-159.
Poser, C., 1992, Multiple sclerosis. Observations and reflections - a personal memoir, J. Neuro. Sci., v. 107, p. 127-140.
Poser, C., 1993, The pathogenesis of multiple sclerosis. Additional considerations. J. Neuro. Sci., v. 115 (suppl.) p. S3-S15.
Poser, C.M., 1994, The epidemiology of multiple sclerosis: a general overview. Ann. Neurology, v. 36, p. S181-S193.
Poser, C. et al., 1988, An analysis of the "epidemic" of MS in the Faroe Islands. I. Clinical and epidemiological aspects. Neuroepidemiology, v. 7 , p. 168-180.
Rafei, A.E., Peters, S.M., Harris, N. et al., 1989, Diagnostic value of IgG4 measurements in patients with food allergy. Ann. Allergy, v. 62, p. 94-99.
Robert, A.M. et al., 1977, Action of anthocyanosides of vaccinium myrtillis on the permeability of the blood-brain barrier. Journal of Medicine, v. 8, p. 321-332.
Rosati, G., 1994, Descriptive epidemiology of multiple sclerosis in Europe in the 1980s: a critical overview. Annals of Neurology, v. 36, p. S164-S174.
Rozniecki, J.J., Hanser, S.L., Stein, M. et al., 1995, Elevated mast cell tryptase in cerebrospinal fluid of multiple sclerosis patients. Ann. of Neurology, v. 37, p. 63-66.
Sadovnick, A.D. and Ebers, G., 1993, Epidemiology of multiple sclerosis: a critical overview. Can. Jour. Neur. Sci., v. 20, p. 17-29.
Sampson, H.A., 1991, Immunologic mechanisms in adverse reactions to foods. Immunology and Allergy Clinics of North America, v. 11, p. 701-716.
Shakib, F., Brown, H.M., Phelps, A. and Redhead, R., 1986, Study of IgG sub-class antibodies in patients with milk intolerance. Clin. Allergy, v. 16, p. 451-458.
Shatin, R., 1964, Multiple Sclerosis and geography. Neurology, v. 14, p. 338-344.
Shoab, B.O. and Patten, B.M., 1996, Human adjuvant disease: presentation as a multiple sclerosis - like syndrome. South. Med. J., v. 89, p. 179-188.
Sibley, W.A., Bamfield, C.R. and Clark, K., 1985, Clinical viral infections and multiple sclerosis. Lancet, p. 1313-1315.
Sibley, W.A., 1992. Therapeutic claims in multiple sclerosis. Demos Publications, New York, New York, 202 p.
Singh, V.K., Yamaki, K., Donoso, L. and Shinohara, T., 1989, Yeast histone H3-induced experimental autoimmune uveitis. Journal of Immunology, v. 142, p. 1512-1517.
Smith, A.D. and Thompson, R.H.S., 1977, Lipids and multiple sclerosis. In Multiple Sclerosis: A critical Conspectus. Lancaster, MTP Press Ltd., p. 225-244.
Soll, R.W., 1968, Delayed hypersensitivity: a possible mechanism in the etiology of multiple sclerosis in Alter, M. and Kurtzke, J. (eds.). The epidemiology of multiple sclerosis. C.C. Thomas, Springfield, Illinois, p. 110-128.
Soll, R.W. and Grenoble, P.B., 1984, MS - Something can be done and you can do it. Contempory Books, Chicago, Illinois.
Steinman, L., 1993, Autoimmune Disease. Scientific American, v. 269, p. 107-114.
Swank, R.L. and Dugan, B.B., 1987, The Multiple Sclerosis diet book, Doubleday, Garden City, New York.
Swank, R.L. and Dugan, B.B., 1990, Effect of low saturated fat diet in early and late cases of multiple sclerosis. Lancet, v. 336, p. 37-39.
Theofilopoulos, A.N., 1995a, The basis of autoimmunity: Part II Genetic predisposition.
Immunology Today, v. 16, p. 150-158.
Theofilopoulos, A.N., 1995b, The basis of autoimmunity: Part I Mechanisms of aberrant
self-recognition. Immunology Today, v. 16, p. 90-98.
Thomas, R., 1995, The Natural Way-Multiple Sclerosis. Element Books Ltd., Rockport, MA, 133 p.
Thompson, R.H.S., 1975, Unsaturated fatty acids in multiple sclerosis. In Multiple Sclerosis Research. New York, Elsevier, p. 184-197.
Traugott, U., 1990, Evidence for Immunopathogenesis. in, Handbook of Multiple Sclerosis, S.D. Cook (ed.). Marcel Dekker Inc., New York, p. 101-127.
van Oosten, B.W., Truyen, L., Barkhof, F. and Polman, C.H., 1995, Multiple sclerosis therapy, a practical guide. Drugs, v. 49, p. 200-212.
Weiner, H., Mackin, G., Matsui, M. et al., 1993, Double-blind pilot trial of oral tolerance with myelin antigens in multiple sclerosis. Science, v. 293, p. 1321-1324.
Wolinsky, J.S., 1995, Copolymer 1: an editorial. Neurology, v. 45, p. 1245-1247.
Wucherpfennig, K.W., 1995, Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell, v. 80, p. 695-705.
Zurier, R.B. et al., 1996, Rheumatoid arthritis symptoms improve with gamma-linolenic acid. Arthritis Rheum., v. 39, p. 1808-1817.
(top) 33
This
material is provided as general medical information and is not intended as advice for
individual patients; please contact your physician for specific recommendations.
© 1996-1999 International MS Support
Foundation
International MS Support Foundation
9430 E. Golf Links Rd. #291
Tucson, Arizona 85730
HOME || WHAT IS MS? || IMSSF || THANKS
(Acknowledgments) ||
ANA 1998 || Audio || Awards
|| Books || Britell, MD || BB-C-Giver
||BB-PwMS||
BB-YPwMS || Cam-Live || Chat || Clinics-MS || Dedicated Docs || Desert Adventure
|| Diary || Disaster || Doctor's Corner || Doctor Chat || Employment
|| Equipment || Escape
|| Events || FAQ's-Weinreb, MD
|| FAQ's
Shabas, MD || Forums || Founder
|| Freed Psy.D || Glossary || HelpingHands
|| Humor || Ideas
|| Images (Jean's
watercolors) || Ind. Living || Japan
Chapter || Kids || Listserv-subscribe || Maggie || Mchenry, MD || Medications || Memorials
|| NewsLetter ||
Nutrition || Organizations
|| Prayer Corner || Photos || Recipes
|| Research || Schapiro, MD || Shabas, MD || Teen Connect || Teens With MS || Thoughts || Vollmer, MD || Warnings || Weinreb, MD || What's New || Yanofsky,
MD ||
Your Help
