MS: Probable Cause and Best Bet Treatment

BEST BET DIET BOOK
Scientific Papers

"MS: Probable Cause and Best Bet Treatment" Dr. Ashton Embry © 1996
Section 8: Dietary Factors, MS Pathogenesis and MS Types
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.
End section 8.