September 25, 2000 Research Update



 

I cannot take credit for this summary. It is an excellent review of the relationship between the gastrointestinal tract and chronic disease.

James Bogash, D.C. Mesa, AZ
info@lifecarechiropractic.com
www.lifecarechiropractic.com

From Nutri-West Marcia White
8-22-00

Dear Doctor, We are becoming more concerned about all of the E-Coli problems we read about in the news. We just heard of a small child in Colorado who is not expected to live because the E-coli was not diagnosed soon enough. This time of year is especially bad, picnics, etc., where food is not handled properly.

A couple of years ago, I read an article that said cinnamon can kill E-coli. Since that time I have made sure that we always have a shaker of cinnamon on the table and use it on fruit, oatmeal, cereals and toast. I also use it when making hamburgers and meat loaf. You can use a few shakes without tasting it in the food

You might want to pass this on to patients, especially those with small children-and tell them wash hands, wash hands, wash hands.

Marcia

NUTRI-NOTES

By Dr. Lynn Toohey

“The immunological mechanisms of rheumatoid arthritis probably begin when antigens cross an excessively permeable intestinal mucosa” Carli P et al. Presse Med 1995;24:606-610.

Inside this issue: Leaky Gut is a major environmental factor in autoimmune disease.

If you combine genetic susceptibility with the right dietary antigens (and possibly viruses which interact in the process), and then you throw in a leaky gut as another factor, the increased intestinal permeability can allow for the translocation of these antigens into the circulation where they can activate autoimmune diseases! Read about how all of this happens, and how to address it inside this issue of Nutri-Notes. Leaky gut connection to RA

The following abstract comes from an article recently accepted for publication in the British Journal of nutrition by the editor of the Nutri-Notes (Lynn Toohey). At the time this newsletter went to press, the article was scheduled for publication around February or March of 2000. The article will be available for a limited time on the following web site: http://nutrition.cabweb.org/BJN/bjnhome.asp

The citation for the article is currently:

Cordain, L. Toohey, L, Smith MJ and Hickey MS. Modulation of Immune Function by Dietary Lectins in Rheumatoid Arthritis. British Journal of nutrition 2000;83:000-000.

ABSTRACT:

Despite the almost universal clinical observation that inflammation of the gut is frequently associated with inflammation of the joints and vice versa, the nature of this relationship remains elusive. In the present review, we provide evidence for how the interaction of dietary lectins with enterocytes and lymphocytes may facilitate the translocation of both dietary and gut-derived pathogenic antigens to peripheral tissues, which in turn causes persistent peripheral antigenic stimulation. In genetically susceptible individuals, this antigenic stimulation may ultimately result in the expression of overt rheumatoid arthritis (RA) via molecular mimicry, a process whereby foreign peptides, similar in structure to endogenous peptides, may cause antibodies or T-lymphocytes to cross-react with both foreign and endogenous peptides and thereby break immunological tolerance. By eliminating dietary elements, particularly lectins, which adversely influence both enterocyte and lymphocyte structure and function, it is proposed that the peripheral antigenic stimulus (both pathogenic and dietary) will be reduced and thereby result in a dimunition of disease symptoms in certain patients with RA.

A note from the editor: This review article presents support for the hypothesis that explains the complex role of genetics, pathogenic organisms, food components, and intestinal permeability (leaky gut) in the development of RA. These factors can all interact and play a role in autoimmune disease. See inside the newsletter for more detail.

Modulation of Immune Function by Dietary Lectins in Rheumatoid Arthritis… by Lynn Toohey, editor of Nutri-Notes This review article (abstract on page 1) reflects the extensive work of a research team at Colorado State University, Fort Collins, CO. I was honored to be a part of this publication, which delves into trying to pinpoint immune activation in rheumatoid arthritis. research in molecular mimicry is in its infancy, however it is gaining credence as a viable theory, as evidenced by the recent appearance in the New England Journal of Medicine of an article entitled, “Mechanisms of Disease: Molecular Mimicry and Autoimmunity” (Albert LJ & Inman RD, 2000;341(27):2068-2074). The New England Journal article ponders how foreign antigens such as viruses can activate immune responses (in genetically susceptible people) against human tissue by exhibiting similarities with human protein (see page 3 for a more detailed description of the molecular mimicry process). In our article, however, we ponder how actual dietary constituents found in common foods can trigger the molecular mimicry process and result in the attack on self-tissue. Genetics of course will play a major role in how an individual manages an immune response, and will determine to some extent how an individual is going to respond to simple common foods. But if you combine the genetic susceptibility with the right dietary antigens (and possibly viruses which interact in the process), and then you throw in a leaky gut, the increased intestinal permeability can allow for the translocation of these antigens into the circulation where they can activate autoimmune diseases.

Molecular Mimicry and Autoimmunity – the mechanism

The recent review article from the New England Journal of Medicine (NEJM) entitled, “Mechanisms of Disease: Molecular Mimicry and Autoimmunity” (Albert LJ & Inman RD, 2000;341(27):2068-2074), explains the concept of 2-way molecular mimicry. That is, substances from outside the body, like bacteria, viruses, can share similar protein sequences with human tissue. When these substances activate the immune system (in genetically susceptible people), antibodies are formed to attack the foreign substances, or antigens. The problem is that the antibodies also recognize the protein sequences in the self or human tissue that are similar to the foreign protein in the bacteria or virus. This is called cross reactivity. As an example of molecular mimicry and cross reactivity, the NEJM cites the case of MS. “In the case of MS, it has been hypothesized that the disease is initiated by an infection early in life by a virus that shares antigenic structures with the host’s central nervous system tissue. The host’s antiviral immune response cross-reacts with central nervous system self-antigens, such as myelin basic protein (MBP), leading to demyelination. Subsequent viral infections are thought to cause exacerbations of the disease by reactivating the immune response against viral antigens and autoantigens.” As a further example of this, the May-June 1997 Nutri-Notes newsletter contained a front page story on “Molecular Mimicry and the MS connection”. It explained how they have discovered that the ubiquitous Epstein Barr virus (EBV), associated with so many diseases, contained a protein sequence that was amazingly similar to one of the protein sequences in MBP. The myelin protein is in the myelin sheath surrounding nerves, and is one of the areas that comes under attack when there is an autoimmune reaction. researchers found that antibodies made to attack MBP in the blood of MS patients cross reacted with EBV. This means that the antibodies, which are supposed to be specific for one thing, were specific for not only a foreign antigen (EBV), but for human tissue (MBP) as well.

Molecular Mimicry, Rheumatoid Arthritis, food antigens, and the role of the leaky gut:

There is ample evidence that the same kind of molecular mimicry suspected in MS could be at play in RA, with the major difference being the self tissue that gets attacked. Whereas in MS it is myelin basic protein, in RA it is suspected to be collagen tissue. Not only can certain undigested food particles cause a problem by mimicking human self-proteins, such as collagen, but the lectins found in some foods, such as lectins, can increase intestinal permeability and allow these mimicking proteins into systemic circulation. Mimicking proteins include bovine serum albumin (BSA) from cow’s milk, which contains a protein sequence similar to human collagen, and glycine-rich protein (found in grains and legumes), which contains a protein sequence similar to cytokeratins (connective tissue). People with hereditary predispositions for autoimmune disease are the ones who are particularly susceptible to food interactions with the immune system. Particular lectins to watch are wheat germ agglutinin (WGA) from wheat and phytohaemagglutinin (PHA) from kidney beans. Other lectin-containing foods include lentils, peas, jack beans, and peanuts. Lectin activity has been demonstrated in rye, barley, oats, and maize (Liener, The Lectins. Orlando, Fla. Academic Press. 1986:527-552) and even rice (Tsuda, M Purification and characterization of a lectin from rice bran. J Biochem. 1979;86:1451-1461). Although soybeans contain some lectins, the good powdered soy formulas have been hydrolyzed and contain the healthful isoflavones but not the soy lectins. For this reason, soy powder can make an excellent base for health drinks for the autoimmune person. Take-home message concerning RA and molecular mimicry: An individual must have the genetic predisposition for autoimmune disease coupled with exposure to antigenic material, whether it be bacteria, virus, or food. However, one of the most important factors is the leaky gut, because it is the intestinal permeability which allows antigens into systemic circulation. Building a strong gut immune barrier can protect against autoimmune attack, and this is why it is one of the first steps to consider in a protocol.

Why the gut barrier is so important:

Implicit in the message to heal the leaky gut is the fact that a healthy intestinal barrier does NOT allow this process of antigen translocation to occur. Excerpts from the arthritis article highlight this. For instance… “From a functional perspective, in healthy subjects the contents of the gut lumen lie outside the body and contain a toxic or antigenic load from which the body needs to be protected”. We sometimes forget that the gut does more than digest our food. It is an immune barrier that protects us from foreign attack.

Protection is supplied by a number of mechanisms including: 1. The intestinal mucosa (physical barrier) 2. Intestinal secretions (such as secretory IgA antibodies) 3. Intramural lymphocytes (white blood cells)

Take home message: The gut is an immune barrier, and when it fails to do its job, autoimmune reactions can develop. It is clearly important to build and strengthen that immune barrier. The important immune barrier of the gut deserves a total formula of nutrition:

Nutri-West presents: TOTAL LEAKY GUT (product #2703) Formulated for and researched by Dr. John Brimhall Each tablet contains: vitamin C (sago). 25 mg, vitamin E Succinate 10 i.u., Zinc (as chelate) 500 mcg, L-Glutamine 150 mg, N-Acetyl Glucosamine 75 mg, Lipoic Acid 2 mg, Lactobacillus Acidophilus 1 million units, Lactobacillus Bifidus 1 million units, Cats Claw (bark) 15 mg, Ginkgo Biloba Extract (bark) 2 mg, Ginkgo Biloba (herb) 50 mg, Deglycyrrhizinated Licorice (root) 50 mg, Jerusalem Artichoke (bark) 25 mg, Slippery Elm (bark) 100 mg. Suggested Usage; 1 tablet 3 x day or as directed

Healing the Leaky Gut:

One of the take home messages of this newsletter has been that if the leaky gut is healed to become a barrier to potential antigens and human tissue-mimicking amino acid sequences, it can become a strong asset in the fight against autoimmune disease.

The intestinal lining can provide a barrier to autoimmune triggers, or it can become “leaky” and promote autoimmune disease. The microvilli are the individual cells which make up the lining. Mimicking food particles, dietary lectins, and viral and bacterial antigens can all be triggers for autoimmune disease that “leak” through a lining which is no longer strong, and invade the system.

Glutamine is the main fuel that the intestinal cells need for maintenance and repair. Glutamine reinforces the immune system, and there is considerable evidence that glutamine can enhance the barrier function of the gut against viral, bacterial, and food antigen invaders (Hall JC et al. Br J Surg 1996 Mar;83(3):305-312).

NAG (N-acetyl glucosamine), aside from being able to heal the extracellular tissue surrounding intestinal cells, has the unique ability to decrease the binding of some lectins to the intestinal lining, which can cause inflammation (Int J Parasitol. 1991 Dec; 21(8):941-4). NAG is one of the few nutrients with the ability to bind to the powerful wheat germ agglutinin (WGA) lectin. NAG also increases the quantity and quality of mucus (J Helminthol. 1993;67(3):179-88). It is well known as an arthritis nutrient, and is even listed as an antiarthritic in the Merck index (Merck Index, 11th ed. 1989 Merck and Co. Inc. Rahway, NJ p. 4353).

vitamins C and E, lipoic acid, zinc and ginkgo biloba are all antioxidants which protect the lining from free radical damage. Additionally, vitamin C and lipoic acid bind heavy metals which can cause disease when deposited in the tissues instead of being detoxified in the liver. vitamin E maintains the integrity of all lipid cell membranes. Ginkgo biloba also increases circulation in the smaller vessels and capillaries, which increases nutrient delivery and tissue healing. The New England Journal of Medicine notes that zinc is involved in clearance of infection, increased levels of brush-border enzymes, regeneration of epithelial tissue, and improved absorption of water and electrolytes (NEJMedicine. Sept. 28, 1995. 333(13):839-844).

DGL (deglycyrrhizinated licorice) increases the integrity of the mucosal cells – it increases the life span of the intestinal cells, improves the quality of protective substances, and improves blood supply of nutrients (Glick L. Lancet ii:817, 1982).

Cat’s claw is an interesting herb from Peru that has been researched lately for its, “remarkable ability to cleanse the entire intestinal tract and help those suffering from different stomach and bowel disorders”, including leaky gut and intestinal flora imbalance (Dr. Brent Davis, DC Wellness Advocate Feb 1995;5(1):1-4).

The role of enzymes, detox and probiotics

Enzymes: As we have seen, undigested food particles which cross a leaky gut can become antigens that can stimulate the immune system. Healing a leaky gut is part of the answer but another key is addressing the incomplete digestion of the food particles in question. Amino acids are not antigenic; it is only longer protein sequences which are antigenic, and they can only activate the immune system when they have not been properly broken down. This happens sometimes due to a lack of hydrochloric acid and pancreatic enzymes. This is described in the arthritis article… “Clearly implicit in this model is the ability of intraepithelial pathogens and intact proteins to escape enzymatic digestion and to cross the gastrointestinal barrier and enter peripheral circulation”.

Ideally, food should be broken down to assure that macromolecules do not enter the system. Plant enzymes work in a wide pH range, increasing their effectiveness along the GI tract.

Nutri-West Presents: TOTAL ENZYMES (product #2404) Plant based enzymes Formulated for and Rese arched by Dr.

John Brimhall Each 360 mg capsule contains: Amylase 4,500 DU, Protease 15,000 HUT, Lipase 65 LU, Invertase 0.25 IAU, Malt Diastase 150 DP°, Lactase 200 LacU, Cellulase 60 CU, in base of pure Beet Root fiber. Suggested Usage: 1 capsule with meals

Detox: Removing toxic assaults on the system can improve the immune system’s ability to handle antigenic material. Additionally, all foreign antigens must be cleared from the body, and detoxing helps facilitate this process. The liver removes antibody-antigen complexes that have been formed from immune activation. This is also described in the arthritis article… “The primary intestinal barrier is supported by the liver, through which all enterically (from the intestines) derived substances must pass before entering the peripheral circulation”.

Nutri-West Presents: TOTAL SYSTEMIC D-TOX (Product #2705) Each tablet contains: vitamin A (palmitate) 333 i.u., vitamin B-1 3.33 mg, vitamin B-2 3.33 mg, Niacin 4.17 mg, vitamin B-12 8.33 mcg, vitamin C (sago palm) 125 mg, vitamin E (succinate) 33.33 i.u., D-Calcium Pantothenate (Pantothenic Acid) 7.66 mg, Folic Acid 50mcg , Biotin 33.33 mcg, Calcium (as aspartate, gluconate) 3.6 mg, Magnesium (as glycinate, citrate, aspartate) 10.6 mg, Selenium (as methionine) 20 mcg, Chromium (as chelate) 8.3 mcg, Manganese (as aspartate)83.33 mcg, Zinc (as chelate) 666mcg, Molybdenum (Citrate) 8.33 mcg, also contains: Beta Carotene 1250 units, Pyridoxal-5-Phosphate 3.33 mg, Choline Bitartrate 8.16 mg, Inositol 8.33mg, N-Acetyl Cysteine 5mg, L-Glutathione 3.33 mg, Propolis 8.33 mg, Co Enzyme Q-10 1.06 mg, Quercetin 4.17 mg, L-Glutamine 33.33 mg, Glucaronic Acid 830 mcg, L-Taurine 8.33 mg, L-Glycine 8.33 mg, L-Ornithine 3.33 mg, L-Methionine 8.33 mg, L-Glutamic Acid 3.33 mg, L-Arginine 3.33 mg, L-Lysine 3.33 mg, L-Tyrosine 3.33 mg, Milk Thistle (leaf, seed) 8.33 mg, Silymarin (leaf) 830 mcg, Beet (root) 8.33 mg, Turmeric Powder (herb) (Curcumin) 830 mcg, Yellow Dock (root) 4.17 mg, Chlorophyll 1.67 mg, Asparagus (shoots) 2.5 mg, Broccoli (tops, stem) 2.5 mg, Dandelion (root) 4.17 mg, Mullein (leaf) 4.17 mg, Siberian Ginseng (root) 5 mg. Suggested Usage: 1 capsule 3 x day or as directed

Probiotics: “Patients with RA have also been shown to maintain a high frequency of small-intestinal bacterial overgrowth” (Henriksson et al. Annals of the Rheumatic Diseases 1993;52:503-510, as noted in the arthritis article, page 2). It is pointed out in the arthritis article that there are three circumstances that can cause a translocation of bacteria from the intestines to sites such as the lymph nodes, liver, spleen, kidney and blood – these include 1. disruption of the intestinal equilibrium (bacterial overgrowth), 2. deficiencies in host defenses, and 3. increased permeability of the intestinal barrier. Probiotics guard against all three of these situations that promote transference of arthritis-causing bacteria from the intestines to other parts of the body. Additionally, friendly bacteria especially counteract candida, which can spread long mycelial arms right through the intestinal lining and perforate it, permitting wide-open entry to microorganisms and toxins.

All but one of the remaining children experienced only minor reactions, including fever, local reactions, and/or lethargy, during the 7 days following immunization.

 

James Bogash

For more than a decade, Dr. Bogash has stayed current with the medical literature as it relates to physiology, disease prevention and disease management. He uses his knowledge to educate patients, the community and cyberspace on the best way to avoid and / or manage chronic diseases using lifestyle and targeted supplementation.







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