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Sabtu, 12 Mei 2012

Difficult Diagnostic

By J.E. Block M.D., PhD, FACP
 
An example of a difficult diagnostic dilemma is Lectin Intolerance. Lectin not to be confused with Leptin or Lecithin)occur ubiquitously in nature. They are sugar-binding proteins in both animal and plants. The prototypic lectin is GLUTEN. Lectins aggregates to the cell walls of other plants (bacteria) and our own cells. Medical science is just beginning to understand Lectin physiology and pathology. We naturally consume Lectins in our food. They play a helpful role in the expulsion from our body of harmful bacteria. Lectins and particularly gluten in people who are genetically predisposed who consume them suffer damage to the delicate intestinal lining (the microvilli). This negatively influence gut permeability (leaky gut) and digestion. Lectins are capable of being actively endocytosed (transported) across the intestinal membranes into the general circulation where they may attach to other tissues (connective, nervous, bladder) causing immune dysfunction and systemic inflammation. Lectins play a role in biological recognition involving cells and proteins in animals as well as plants.

They were first discovered by Peter Hermann Stillmark in 1888 initially isolated ricin, an extremely toxic hemaglutinin, from seeds of the castor plant.  The word “Lectin” comes from the Latin phrase, “I choose,” a fitting phrase since Lectins are very specific as to what they chose to bind. Most Lectins are non-enzymatic in action and non-immune in origin. They functions in humans in other ways than the regulation of cell adhesion. These molecules control some of our circulating  proteins and antibodies levels. That can cause problems in those of us that genetically predisposed ! Additionally in the intestine it could help in recognizing carbohydrates that are found exclusively on pathogens and target their destruction, or play havoc  if the target is on friendly bacteria or our intestinal lining.


Our state of health and genetic make-up determine to what Lectins we are sensitive and how we will react to them. Lectin in the gut initiate inflammation that may be expressed in other parts of the body. Also there are other genes that directly and indirectly affect how we deal with Lectins. Many people have no digestive problems but could have Lectins affect them. The damage is cumulative and pathology occurs years later like cancer. As humans we all possess cell surface sugars, such as n-acetylglucosamine, fucose, and mannose. Lectins that bind to those sugars can affect those that are genetically determined.

The toxicity of Lectins has been identified by consumption of food with high content of these proteins, which can lead to organ failure in addition to the GI tract where it destroys its lining and causes bacterial over growth. Lectins elevate NF kappa which, when up-regulated, are involved in almost every acute and chronic inflammatory disorder including neurodegenerative disease, inflammatory bowel disease, infectious and autoimmune diseases.Lectins can dramatically reduce natural killer (NK) cell activity directly and through disruption of intestinal flora. Natural killer cells are one of the body’s most important defenses against viruses and other invaders. Most dietary Lectins will also stimulate gut polyamines which are important growth factors that may have negative effects if levels become imbalanced. High polyamine level may also decrease NK cell populations, can contribute to halitosis (bad breath), and is considered an important biological marker for colonic precancer.  It may also be part of the cause of Ulcerative Colitis and Regional Enteritis. Legume seeds  such as Peanuts, Soybeans and Wheat are  significant for human illness. Wheat has gliadin, a component of gluten which is an iso-lectin of wheat germ. Ancient wheat species had much lower protein contents than the modern varieties.  Genetic altering of grain plants (GMO) increases the protein component and the Lectin load with the resultant potential for inflammation and metabolic disruption much more today than in yesteryear. Heating destroys much of the Leptins in our food, but not so in Soybean and Wheat. In a study published not too long ago in the Journal of Gastoenterology compared the blood that was stored from 10,000 people for gluten antibodies and that of a similar number of persons today and found 400% more in modern humans!

This is part responsible for our new epidemics of heart, thyroid disease, arthritis, cancer and hard to diagnose and treat conditions like acne, rosaccea, fibromyalgia, chronic fatigue, IBS, allergy and obesity.

Lectins also make us fat in two ways! Leptins make us skinny! Lectins decrease leptin activity by binding to the  receptor on our fat cells and amplifying the signal from insulin. This encourages them to take in the circulating fats, rather than let them go to our muscles to be burned. Research has shown that high insulin levels, or in this case, an exaggerated response to normal insulin levels a major causes of obesity. The other mechanism of Lectin obesity is by binding to the cholecystokin receptor in the hypothalamus and turning off the satiety factor while eating.

“Nightshade Arthritis” is the stiff and sometimes painful joints of folks that are genetically predisposed to the toxicity of these vegetable Lectin. Although some experts feel it is just the alkaloid in these, most feel it is the combination. Nightshade is a term used to describe the Solanaceae family of plants to include white potatoes, tomatoes, gogi berries, eggplant,  and all peppers (bell, green, hot, etc) except: black. There are also deadly nightshades to include mandrake, belladomnna, and perhaps tobacco. Most Lectins are destroyed in the sprouting process, which allows for a safer form of grain consumption, not to mention that the sprout is generally higher in overall nutritional value than the seed. Organic, sprouted grain bread products (with no added gluten) appear to be the safest and healthiest way to reap the nutritional benefit of grain without the Lectin burden.

Diagnosing a Leptin problem is difficult. First it must be suspected and most doctors do not even know the word let alone identify it!  Lectins contribute to food sensitivities (or food intolerances) and provokes the immune system to make antibodies against them. Allergy skin test, a myriad of blood tests such as IgG, IgE, Sage, and Promethius are used. Elimination diets are also helpful for determining the demon food.

Another test we have found very helpful is the HYDROGEN BREATH TEST. This is an inexpensive, paid by insurance study that gives a presumptive diagnoses for Lectin intolerance. It detects bacterial overgrowth in the small intestine. This is most common in intestinal diseases in which the mucosa of the intestine is compromised like in Lectin problems, but also small intestinal diverticulosis, abnormal flora, parasites and previous surgery where the usual anatomy of the intestine has been change. An example of this is By Pass surgery for weight loss. Also if the intestine cannot make the enzymes to break down food stuff there is Hydrogen produced. In cases of abnormal gases due to the fermentation from normal bacteria such as in Lactose intolerance it is positive. Normally there should be NO hydrogen in the breath if the bacteria, the enzymes and the anatomy is doing its job and there is no Lectin intolerance. But if something is awry then hydrogen which is normally produced in minute amounts goes up. Gastroenterologist picked the cut point of 10 parts per million or more to be abnormal. However other experts feel that anything above 0 is an indication of something wrong in the intestine. The test is done by holding ones breath for 30 seconds then exhaling through a cardboard tube into a special handheld device. In 20 seconds, the results are apparent. There are several challenge test that can be done such as by loading the subject up with lactose or sucrose and in particular a Lectin in question like gluten and repeating the test to see how much increase of hydrogen is produced thus nailing down the exact culprit.

Treatment is to completely remove the offending agent from the diet. It also adjunctively can not hurt in improving bowel health by food enzymes and pre/probiotics. Presriptive drugs like Diclocyamine also improve the problem but is only a bandaid. In severe cases in which the offending food can not be found antibiotics may improve the situation. Flagyl, Doxycycline, Cipro, are good and the best and most expensive is Xifixam.  When all else fails, the off- lable use of the asthma drug Xolair will solve the allergy problem. Acupuncture, NAET, Vibrational Therapy and Psychotherapy, should be considered when nothing seems to help.

There are however more specific supplements that are individually listed below such as NAG (N-Acetyl Glucosamine), DPP IV, Bladderwack (Fucus vesiculosus), D-Mannose, Pepsin, and Aloe vera, Xylitol and Okra. They can be used alone or in combination. The doses are not fixed and it may be trial and error until fine tunning of the bowel and body are achieved.

Aloe Vera provides the main ingredient the intestinal cells need to reproduce, which they do every four days. This is the amino acid L-glutamine of which we do not get enough in our diet. Aloe Vera contains this compound thereby enhancing the ability of cell regeneration. If "leaking gut syndrome" develops, long chain polysaccarides (Acemannan is a D-isomer mucopolysaccharide) in aloe vera leaves. This has been known to have immunostimulant, antiviral, antineoplastic and heals the intestinal lining. Aloe has amazing anti-inflamatory attributes which are very effective in calming the intestinal spasms that cause abdominal pain, as well as soothing other Irritable Bowel Syndrome Symptoms. Aloe Vera works gently within the intestinal tract to help break down food residues that have become impacted and help clean out the bowel. When the bowel is cleaned out, it greatly reduces bloating, discomfort, and helps ease stress. Aloe Vera contains 75 micro- nutrients  (vitamins, minerals, amino acids and enzymes) essential for keeping our body in good working order. Aloe can be consumed as a food or in a supplement. As a food, break off the bottom succulent leaf from the plant that should be in everybody’s kitchen. Peal off the diarrhea causing bitter “skin” and eat two to four square inches of this wonder vegetable. It can be eaten plain or as part of a salad. Another way to get glutamine is buying the glutamine powder and take one or two teaspoons a day on an empty stomach.

Bladderwack (Fucus vesiculosus), Primary chemical constituents of this plant include , iodine, alginic acid, fucoidan, beta-carotene, zeaxanthinbromine, potassium, volatile oils, and other minerals. One of the emerging fields of research with regards to microorganisms (and lectins) centers about an idea of adherence and anti-adherence. Basically, an unwanted organism can do little harm if it cannot attach to or anchor itself to intestinal lining. Lectin damages the cells and the pathogenic organisms add insult to injury.

D-Mannose is a five-carbon sugar that has specific Lectin and Gram negative (stains red rather than blue) anti-bacterial properties. It prevents bacterial adhesion and binds to Lectins.  This changes the configuration of the Lectin and decreases its “inflammatory” and adhesive qualities. Interestingly, the so called ‘friendly’ bacteria are left “unharmed” by mannose because they lack the pili (bridging protein) that pathogenic bacteria develop for adhesion.  This allows the body to shed pathogenic bacteria through the stool. One half a teaspoon of the powdered form is advised.

DPP IV (DiPeptidyl Peptidase IV) enzyme is a serine exopeptidase that cleaves X-proline dipeptides from the end of polypeptides from Lectins such as gluten and casein.  Research determined that the rate-limiting bond in the digestion of these Lectins requires an enzyme known as DPP IV (dipeptidyl dipeptidase IV).  Biocore® DPP IV is a proprietary formulation of proteases providing a standardized DPP IV activity. The DPP IV activity in Biocore® DPP IV is standardized at 5000 units/g. Biocore® DPP IV also provides 300,000 HUT/g and 85 aminopeptidase units per gram of the product. The recommended dose for Biocore® DPP IV is 100 mg. The proteases in Biocore® DPP IV are stable in the acidic environment of the stomach.

Lycopene has the ability to prevent macrophage (a Pac-Man type white blood cell) activation induced by gluten and IFN-gamma (an inflammatory immune signaling chemical). Gut microflora ,bacteria in the gut, reponses trigger tumor necrosis factor-induced intercellular adhesion molecule-1 (ICAM-1) upregulation, and are inhibited by the flavinoid apigenin.  When ICAM-1 is increased or upregulated – we are more prone to infection with viruses and it also promotes Leaky Gut Syndrome.  Apigenin helps reduce this. Prepared tomatoes (spaghetti sauce etc.) are a good source of lycopene. But beware, tomatoes, a night shade, for some predisposed people may be a source of a Lectin problem.

NAG binds to Lectins in the gut so they will not damage the intestinal wall.  Also many pathogenic bacteria are made up of Lectins and the NAG will glue these organisms together rendering them harmless.  Doses of 3000 to 5000 mg a day have no toxicity and decrease gut Lectin load and the bad bacteria within.

Okra is source of Lectin-binding protective mucilage. It protects the digestive tract from Lectins and maybe the pathogenic bacteria. It also removes existing Lectins that are already attached to cells. Okra is also beneficial for ulcers, colitis, and other causes of malabsorption.

Pepsin is an proteolytic enzyme, that breaks down certain amino acid molecules to include Leptins. It comes in capsules with HCl containing 648 mg or in half doses. It also is available with Okra which as noted below improves Leptin intolerance.  Pepsin clears away excess mucous formed as a result of food intolerance  allowing for better absorption of micronutrients. One full dose with or without HCl or Okra with ameal breaks down the Leptin.

Quercetin has also been shown to have a specific activity against antigen-induced histamine secretion in intestinal mast cells.  Histamine promotes an allergic response, and quercetin reduces this problem. Frequently, the flavinoid, luteolin, is given along with quercetin. The  Luteolin is a PDE4 inhibitor and a general phosphodiesterase inhibitor, and an Interleukin 6 inhibitor. Both Quercetin and Leteolin have demonstrated the ability to prevent lipopolysaccharide-induced NF-kappaB kinase activity in intestinal epithelial (wall) cells and dendritic (brain and nerve) cells as well as TNF-alpha and IL-8 on colon epithelial cells.

The Quarcetin Luteolin combination cover up the Lipopolysaccharides  (also known as lipoglycans), the large molecules consisting of a fat joined loosely with a chain of sugar molecules (polysaccharides). They are found in the outer membrane of Gram-negative bacteria, act as endotoxins (toxins within our body) and elicit strong immune responses in animals and humans.  NF-kappaB plays a key role in regulating the immune response to infection. On the converse, incorrect regulation of NF-kappaB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-kappaB has also been implicated in processes of synaptic plasticity and memory.

Xylitol is an intestine-friendly," nonfermentable sugar alcohol. It is a prebiotic that feeds the nonpathogenic gut bacteria, discourages the harmful organisms and acts as a bowel friendly laxative! Two to three teaspoons a day used as a sweetener is recommended.

Final thoughts for this hard to diagnose and easy to treat disease is to consider that there can be more than one offending agent. To remove it (them) is key.  Beyond that since there is always a chance that a small amount of the offending Lectin such as gluten is consumed in some prepared food, I suggest doing the DDP IV first then adding the Pepsin/Okra. If there are still problems try the others depending upon availability and your pocketbook. Some folks may need to do three or four of the supplements together. Lots of luck in your journey to health.

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