Positive Health Online

Multi-Factorial Trigger

It has been accepted for a long time that several factors play a major role in MS. In fact, the multi-factorial involvement has contributed to the puzzle of determining the etiology of the disease. Among these, suspected triggers include viral, autoimmune, and environmental factors. There is a theory which ties together some of these suspected mechanisms; it is a theory of "mimicry molecules" – molecules similar enough in protein structure to "mimic" the structure of a "self" protein, and may be responsible for activating the autoimmune system. In the case of MS, the "mimicry molecules", which have been found in several viral proteins (including the Epstein-Barr virus, human papillomavirus, and influenza peptides), and which could possibly exist in some gluten-rich cereals, and/or in milk, may explain the connection among the various factors known to be involved in the etiology of MS. Also, the "Leaky Gut syndrome" (permeable intestinal lining) may be an important factor in allowing antigens to pass into the system and activate the immune system.

Immune System Involvement

The autoimmune theory of multiple sclerosis (MS) is not clearly defined; it's believed that somehow T-cells are activated against a "self-peptide", in this case, the myelin basic protein (MBP), which is the protein in the myelin sheath of the nerve. Antibodies to MBP are found in the serum of MS patients, which means that something activates the T-cells to go after the MBP in this subset of people. The immune system is usually activated when a foreign substance, or "antigen", is presented to the T-cells, which then code for antibodies to fight the antigen. The amino acid sequence in the protein is what triggers the immune system to tag it and then present it to the T-cells for destruction. The autoimmune system is activated when T-cells go after "self", or a protein existing in the body. The reactivity to MBP found in subjects with MS is believed to be one of the genetic markers for the disease; this reactivity reflects the affinity of the immune system for the protein, to tag it for destruction. People with MS inherit a tagging system for one of the amino acid regions of MBP.

It is now known that other structures may possess the potential to activate the immune system to attack its "self" cells (MBP). These structures are similar enough in sequence to "mimic" MBP and be recognized by the same T-cells, thus activating the autoimmune system to attack its own nerve cells. Several viral peptides, (most notably from Epstein-Barr virus [EBV] herpes simplex, human papillomavirus, and some influenza viruses) and a bacterial peptide (Pseudomonas aeruginosa) had potent T-cell activation power because of their structural similarity to MBP.

Leaky Gut and Allergies

Now add to this scenario the permeable intestinal lining, or the "leaky gut". Normally, a healthy intestinal lining will prevent the passage of large molecules and antigens into circulation. However, a leaky gut can result in food allergens being absorbed from the gastrointestinal tract and initiating an immunological reaction. Although neither gluten protein nor milk protein have been directly identified as molecular mimics for MBP to date, it is known that both of these substances cause immunological reactions, and both have the potential to cause a leaky gut. Some scientists would argue that the inheritance of the genes for gluten intolerance, which leads to a primary lesion in the gut, is one of the genetic susceptibilities for MS. Milk proteins are also notorious for producing an immunological reaction.

Gluten Intolerance

Let's look first at gluten intolerance. Mechanisms are poorly understood, however it is known that some genetically susceptible individuals lack the ability to tolerate the gliadin fraction of the gluten protein. Theories on the mechanisms involved include a defect in immunity, and possibly a defect in the mucosal cell membrane that allows gluten to act as a cytotoxic agent. This is additional support for the theory that a leaky gut is responsible for some of the nutritional insults which MS patients suffer. At the very least, the damaging effects that the sensitivity has on the mucosal cells includes a setup for malabsorption of proteins (needed for enzymes and the structure of the myelin sheath) and of fatty acids (MS patients are known to exhibit altered fatty acid profiles, and this would partially explain that). Additionally, carbohydrates and valuable vitamins and minerals (especially the fat-soluble ones) are not absorbed correctly.

There are some researchers who feel that the search for causes of neurological dysfunction in celiac disease has largely ignored the immunological aspect and has concentrated on vitamin deficiencies (B12, E, D, folic acid, pyridoxine) as a result of malabsorption. However, vitamin replacement alone rarely improves the neurological deficit, and it appears that the initial cause of malabsorption has to be addressed. There is evidence which suggests the possibility of autoimmune reactivity from these proteins found in gluten. It has been suggested that gluten sensitivity should be considered as "a state of heightened immunological responsiveness (T- and B-lymphocyte based) to ingested gluten proteins in genetically predisposed individuals".[1]

Because neurological dysfunction is a known complication of celiac disease, authors investigated the frequency of antigliadin antibodies, as a measure of cryptic gluten sensitivity and celiac disease in neurological patients (the antibodies are a marker for untreated celiac disease, but also can be found in individuals with normal bowel mucosa). Thirty out of 53 patients with neurological disease of unknown origin tested positive for the antibodies.[2]

Recent studies have demonstrated that asymptomatic celiac disease is common. Some individuals with serum antigliadin antibodies and non-specifically abnormal or even normal small-bowel mucosa may go on to develop celiac disease. "It is possible (though unproven) that strict adherence to a gluten-free diet, with elimination of antigliadin antibodies may result in stabilization or even improvement of neurological dysfunction."[3] If these antibodies are directly or indirectly neurotoxic, why do patients with neurological dysfunction and on a gluten-free diet not always improve? Some proposed reasons are: a) damaged neural tissue (ie cerebellar Purkinje cells) does not regenerate; b) compliance and c) diet may be insufficient to suppress the immunological process completely, especially since patients without gastrointestinal symptoms are unlikely to adhere to a gluten-free diet. The current author believes that another important reason is the multifactorial etiology involved. Mayer et al., in their study of antigliadin antibodies, found high concentrations only when the neurological disorder was of unknown origin. This begs the speculation that these particular antibodies are associated with some neurological dysfunctions of unknown origin, but obviously there were other causes (the antibodies were not found in all subjects). And, in the case of MS, the multifactorial etiology suggests that gluten may be playing a role, but that it is not the only factor that can activate the immune system or cause leaky gut.

Diet and Cereal Cultivation

The environmental factor has also been implicated in MS. After studying relatives of twins with MS, some researchers theorized that frequency of gene expression for MS could be influenced by another environmental factor, and that the environmental factor was climate and latitude.[4] Then, the possible existence of some environmental factor which correlated with climate and latitude "clearly emerged from the criteria for any theory of the pathogenesis of MS suggested by Alter M and associates, as a result of their extremely evocative study in Israel."[5] They found that the incidence of MS could be more significantly correlated with the geography of cereal cultivation, being high in wheat- and rye-growing areas, less high in corn-growing regions, and absent in the three widely separate continents where cassava (S America), millet (tropical Africa), and rice (East and Southeast Asia) are predominantly grown. "Thus, the dietary habits of man which follow the geography of wheat and rye, which in turn is related to climate and hence to latitude, and the geography of their protein content may be the unknown environmental factor". . . [6] (p. 338)

The same suggestion has been made by other scientists, and it is believed that "these dietary habits which follow Europeans wherever they settle are significant perhaps as etiological factors in the pathogenesis of MS", and that the prevalence of this disease may be diminished in those communities where wheat and rye cereals are not the most important source of protein.[7] Some people speculate that the favourable response to a low-carbohydrate diet reported by Eckel & Lutz may have been due to the exclusion of wheat and rye proteins rather than all carbohydrates. "In this analysis of the causes of MS the suggested ecological environmental factor, the dietary habits of man, seems to correlate with the geography of the disease. . . the susceptibility to MS is the intolerance to gluten".[6] (p. 344)

Again, attributing MS to one factor, or even to one environmental factor, is probably an oversimplification. However, there is a lot of evidence associating gluten with MS. Additionally, milk protein is associated with similar strong evidence implicating it as an environmental factor. Malosse D et al. found that milk consumption was more correlated with MS prevalence than latitude was, and milk consumption was better correlated with latitude than MS prevalence was.[8]

This association is made even more clear when different MS prevalence rates are found for two different populations living throughout the same country. Therefore, an association with latitude cannot explain their results. (It was more correlated to differing consumptions of dairy products within the same latitude.) The researchers believe that it is more likely that food toxins in combination with genetic background may interact with a factor acquired from the environment in regions at risk. Such a multifactorial etiology that associates a food toxin and genetic background with a latent virus has already been reported in the case of nasopharyngeal carcinoma.[9] It is reasonable to assume that a similar pattern of multifactorial interaction is conceivable in MS. These studies suggest that dairy is at least a major cofactor, and that it may be a major environmental factor influencing reactivation of a latent virus, or modifying the host-virus relationship, precipitating the appearance of a clinical manifest disease.

And so, there are many factors which are implicated in the etiology of MS. Food toxins, autoimmune reactions and leaky gut are some of the main factors which may help to explain the enigma of MS. It is important not to lose sight of the big picture: not all MS patients are gluten-intolerant or dairy intolerant – these are just some of the proposed mechanisms with the potential to activate the immune system. Again, the multifactorial contributions make the understanding of MS pathophysiology an elusive topic.

It does appear, however, that food toxins are involved somehow. It also appears that leaky gut is involved. This connection, too, has been puzzling – Badenoch reported four cases of malabsorption all associated with lesions of the small gut, complicated by demyelination, but admitted that he couldn't interpret it.[10]

Approaches to Treating Leaky Gut

Susie Cornell, who heads an MS clinic called "Under Pressure" in the UK, was one of the first people to tie together the MS-leaky gut connection in her book, The Complete MS Body Manual.[11] She has found considerable success in utilizing nutritional supplements to address leaky gut and malabsorption problems. It is known that many MS patients have multiple nutritional deficiencies, but that merely supplementing vitamins and nutrients does not seem to have much effect. Mrs. Cornell finds that when she tries to get at the root of the deficiency problem – the leaky gut causing the malabsorption – that she sees beneficial clinical results (see case studies).

Leaky gut is "strongly implicated in MS not only because many of the symptoms of MS – such as muscle spasms, inability to exercise for long, poor memory and concentration, shallow breathing, fatigue, depression, diarrhoea and constipation, food allergies, and pain in the joints and muscles are those associated with leaky gut syndrome but also because many of the factors that I consider can cause MS are those behind leaky gut syndrome too."[11] (p.175) These factors include stress, trauma, nutritional deficiencies, viral infections, and candidiasis. (It should be noted that many factors, including bacterial toxins, food allergens and non-steroidal anti-inflammatory drugs [i.e. aspirin and ibuprofen] can all injure the mucosal cells of the intestines and cause "leaky gut".)

Digestive Support

The researchers at the Under Pressure clinic have found stress and emotional trauma to be highly correlated to the onset of MS. Additionally, they point out the impact of stress on the digestive system. When our sympathetic nervous system is activated by stress, digestion becomes low priority, and hydrochloric acid (HCL) secretion can dramatically decrease. HCL is secreted from the same parietal cells in the stomach as intrinsic factor, which is essential for attaching to vitamin B12 and facilitating its absorption. Vitamin B12 is notoriously deficient in MS patients.

For intestinal support: It should be noted here that in addition to factors already mentioned which can cause leaky gut (food allergens/toxins, stress, trauma, nutritional deficiencies, viral infections, and candidiasis), other factors, including bacterial toxins and non-steroidal anti-inflammatory drugs [i.e. aspirin and ibuprofen] can injure the mucosal cells of the intestines and cause "leaky gut"). To help support a leaky intestinal lining, glutamine is a major nutrient. Glutamine is the major fuel of the small intestine, and it has been proven that oral glutamine administration improves mucosal structure and healing.[12] N-acetyl glucosamine and gamma linolenic acid are also helpful in rebuilding damaged mucosal cells.

Probiotics

Probiotics, such as Lactobacillus acidophilus, bulgaricus, and bifidus are the "friendly" bacteria in the gut, and they help keep the populations of bad bacteria at bay. The probiotics prevent bacterial toxins from causing a leaky gut. By policing the harmful bacteria and candida, probiotics have a favourable effect by supporting the whole immune system. Recently, the prebiotics have come into the picture. Fructooligosaccharides, for instance, are known as a prebiotic because they attract bifidobacteria to flourish in the gut.

Candida

Candida toxins especially can open the tight junctions between the intestinal epithelial cells, allowing food allergens to enter. Several case studies on MS patients improving after anticandida therapy have been reported by the pioneers in yeast-connected illnesses, such as Dr. Orion Truss, and Dr. William Crook.[13] In a book entitled Can a Gluten-free Diet Help?, Lloyd Rosenvold, MD reports that after he became aware of Dr. Truss's work, he initiated anticandida treatment for a patient, whose MS symptoms subsequently improved. When her episodes returned two years later, celiac disease was suspected, and she was placed on a gluten-free diet. Within 36 hours, her most violent symptoms had almost totally cleared.[14] Anticandidal nutrients include caprylic acid, garlic, citrus seed extract, coenzyme Q 10, goldenseal, pau d'arco, and of course probiotics and probiotic flora.

Digestive enzymes can be helpful in reducing the amount of large macromolecules of food which can pass through a leaky gut and activate the immune system. They are recognized as foreign objects that the body tags for destruction and can be associated with various food allergy-related conditions. Papain, for example, has been shown "to be effective in celiac disease patients by digesting the wheat gluten and rendering it harmless".[15] Enzymes can also help increase absorption of necessary amino acids and fatty acids.

Malabsorption, especially of fatty acids, is a problem in MS. Generally speaking, the intake of omega 3 fatty acids is lower than ideal. Omega 3s are found in oily fishes, and "there is now evidence that eating lots of oily fish such as tuna, sardines, herring and mackerel can help. Oily fish contain high amounts of a particular sort of essential fatty acid that appears to reinforce the gut lining".[11] (p.176) Although many studies have focused on the favourable effects of omega 3 fatty acids on the immune system, recent research is showing specific benefits for the intestinal immune barrier. If taken as a food supplement in capsule form, the authors recommend trying to find a source that is guaranteed to be free of metal toxicity and the noticeable "fish odour", and which also provides for antioxidant protection of the oil (fish oil is highly unsaturated and therefore susceptible to oxidation).

Note that this recommendation for increased omega 3 intake does not contradict the Swank diet, which advises a total low fat regimen, or the recommendation to avoid animal fats high in saturated fatty acids. It means that of the daily fat intake, care should be taken to increase the ratio of omega 3 fatty acids. Saturated fats will interfere with the prostaglandin pathways of the fatty acids, and will diminish the beneficial results of the other essential fatty acids. It is possible that the lean, unadulterated meats such as buffalo and venison, which were eaten by our paleolithic ancestors, and which are very low in saturated fats, may provide a good protein source. Paleolithic man, despite the fact that he did not eat much fish, had a much better omega 3 fatty acid profile. This is due as much to what he didn't eat as to what he did – in other words, paleolithic man ate fresh fruits and vegetables, and didn't have processed, refined, nutrient-stripped food filled with saturated, oxidized and trans fatty acids to interfere with essential fatty acid pathways!

Gamma linolenic acid, which can be found in black currant seed oil and evening primrose oil, is an omega 6 fatty acid which provides anti-inflammatory and immune supporting benefits. Flax seed oil, which is an omega 3 fatty acid, is converted in the body to the omega 3s we find in fish oils, however, this conversion is not believed to be optimal, and ingestion of the fish oil source is recommended for the most direct effect.

Conclusion

In conclusion, there is much about MS we don't know. We do know about some factors which seem to be related, however. These include nutritional influences such as food toxins/allergens and leaky gut, which seem highly correlated to autoimmune reactions. It's possible that these factors are related in ways we have yet to discover. What we do know now, though, is that there is a connection there, and that it is probably prudent to pay attention to that connection, and also to future developments which will further elucidate the MS puzzle.

With Thanks

The authors would like to extend special thanks to Mrs. Susie Cornell, founder of the MS Under Pressure Program. For further information on the clinical treatment of MS, we would highly recommend her book, The complete MS body manual. The book, and an exercise video for MS, are available from the following address: Under Pressure, PO Box 1270, Chelmsford, Essex, CM2 6BQ, UK

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