Their Damaging Role in Intestinal Health, Rheumatoid Arthritis and Weight Loss
By Carolyn Pierini, CLS (ASCP), CNC
Located on the surface of cells of all living things lay many thousands of different complex sugar molecules (glycoconjugates) projecting outward from their loose anchors like moving antennae. Genetically unique, these molecules comprise a protective coating for the cell and perform many functions including cell recognition and signaling.
Lectins are a class of protein molecules capable of using these sugar moieties to bind to the surface of cells. Lectins provide the way for one molecule to stick to another molecule without any immunity involved. Lectins play a wide role in health, but their ability to influence the inflammatory process indicates they are involved in inflammatory bowel disease, rheumatoid arthritis and even weight gain. Lectins’ potential involvement in many aspects of our health caused DJ Freed, MD to state, “Lectins are causes in search of diseases.”
This article will introduce you to the world of lectins, the “sticky proteins” we deal with from day to day in our diets and our bodily systems. Furthermore, you will learn how you can build up your defenses against what could be a hidden cause behind many of our health concerns.
Learning About Lectins
Lectins, not to be confused with the endocrine hormone leptin, are types of proteins commonly found in nature in foods such as fruits, vegetables, and seafood, but especially grains, beans and seeds. They are present in about 30 percent of the American diet and are not degraded by stomach acid or proteolytic enzymes, making them virtually resistant to digestion. Microbes carry lectins and use them for attachment to the host cells. The human body contains lectins: 1) On the vascular endothelial linings (selectins) in order for blood cells to escape into the tissues; 2) In the liver to capture microorganisms, and 3) As opsonins, substances that coat foreign antigens, making them more susceptible to phagocytosis (the process where immune cells digest and destroy foreign invaders) by the white blood cells. C-reactive protein (CRP) and mannose-binding protein (MBP) are two examples of opsonins.
The word “lectin” comes from the Latin phrase, “I choose,” a befitting word choice since lectins are very specific as to what they will bind to. Lectins are also called agglutinins because in their binding to many cell surfaces they cause agglutination (cell clumping) reactions. Ricin, for example, from castor beans is such a potent lectin that just a minute amount is capable of causing death due to massive clotting of red blood cells from agglutination. Ricin even has been used as a murder weapon in espionage.
A lectin serves the plant as a type of primitive protection system analogous to an antibody but in a non-immune model. Likewise, human lectins in our bodies also act protectively but as part of an immune system. Known for a century, lectins form a diverse group of molecules of varying molecular weights and shapes and contain multiple binding sites. The only thing lectins have in common with each other is their ability to bind to sugars. Lectins bind to the terminal sugar, the “glyco,” portion of glycoconjugates found on cell membranes. If the sugars are bound to proteins they are called glycoproteins or bound to fats they are called glycolipids. Collectively they are called glycoconjugates of which 11 percent of the human body is composed.
The important point is that some of the lectins consumed in everyday foods act as chemical messengers that can in fact bind to the sugars of cells in the gut and the blood cells, initiating an inflammatory response. In wheat, gliadin, a component of gluten and an iso-lectin of wheat germ agglutinin (WGA), is capable of activating NF kappa beta proteins which, when up-regulated, are involved in almost every acute and chronic inflammatory disorder including neurodegenerative disease, inflammatory bowel disease, infectious and autoimmune diseases.1 WGA needs more recognition as an important dietary problem. Scientific literature shows that dietary 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 polyamine production in the gut. Polyamines are important growth factors that may have negative effects if levels become imbalanced. Excess polyamine production initiated by lectins may be the result of an effort to repair the damage to intestinal microvilli caused by lectins. In addition, a high polyamine level may also decrease NK cell populations2, can contribute to halitosis (bad breath), and is considered an important biological marker for colonic precancer.3-6 A number of animal studies have shown that an increase in polyamines caused by a high lectin diet resulted in increases in the size of the intestines, liver, and pancreas.7
Lectins, Food Allergies and Intestinal Concerns
There is an abundance of literature from the most prestigious journals that lectins such as WGA initiate allergic reactions in the gut causing the release of IL-4, IL-13, and histamine from human basophils producing noticeable allergic symptoms.8-9 WGA has also shown to interfere with protein digestion and increase gut permeability.10-11 Peanut lectin, kidney bean and soybean lectins are other examples of lectins that have influences on bodily tissues. On the bright side, the lectins in broad beans (VFA), jackfruit (JAC), and culinary mushrooms (agraricus bisphorus) have been shown to slow the progression of colon cancer.12-13
Lucretius said, “One man’s food is another man’s poison” and lectins give us part of the reason why. It is our individual genetic inheritances that determine how and to what degree lectins can affect us. Almost everybody has antibodies to some dietary lectins in their bloodstream. Many food allergies are actually immune system reactions to lectins.14
The trend toward consumption of less processed grain foods, although more nutritious in many respects, results in consumption of more lectins. After ingestion, most dietary lectins bind to the absorptive microvilli of the small intestine (the microvilli are the tiny finger-like projections on the epithelial cells). From there lectins may gain access into the blood and lymph system through a process called endocytosis which carries the intact lectin across the microvilli membranes as a vesicle.15 Then, the lectins may enter the liver, pancreas and systemic circulation. It is estimated that about 5 percent of ingested lectins enter the body systemically, where, depending on the lectin and depending on the person’s unique glycoconjugates, lectin binding occurs on other tissues such as nervous and connective tissue and the bladder, which are very sensitive to the agglutinating effects of lectins. It is a clinical observation that the complete avoidance of wheat lectins will help ameliorate the symptoms of interstitial cystitis. The reactions of lectins in the gut are more potent since the gut is more heavily glycosylated (more sugar receptors). As intestinal cells age they become less glycosylated due to the loss of glycoconjugates. The intestinal lining of people with Crohn’s disease and IBS (irritable bowel syndrome) appear to be more sensitive to the effects of food lectins because the lining is constantly being replaced by new tissue that is made up of immature cells that are more glycosylated and thus more susceptible to lectin attachment. It becomes a vicious cycle. Blood group antigens as glycoconjugates are found on the surface of cells lining the digestive tract in addition to the blood cells and are frequently the target of specific lectins resulting in agglutination reactions. The same reactions in vitro are conducted daily in the clinical lab blood bank as “blood typing.”
Lectins have many other applications in the clinical laboratory from identification of microorganisms to cancer research where lectins serve as probes to investigate the working of the cell through its surface biology. Lectins have been used as carriers for the delivery of chemotherapeutic agents. Mitosis (cell division) can be enhanced with lectins such as pokeweed lectin (PWA).
Lectins and Rheumatoid Arthritis
The fact that lectins appear to aggravate existing inflammatory conditions can be seen in the example of rheumatoid arthritis.16-18 The RA antibody is different structurally from a normal antibody in that the side-chain sugar, galactose, is replaced with N-acetyl glucosamine, the sugar for which the wheat germ lectin (WGA) is highly specific. This may point to why patients with rheumatoid arthritis feel better on a wheat-free diet. The defective RA antibody has also been shown to be reactive with the lectin found in the common lentil bean. According to the eminent immunologist David Freed, “Of the various rheumatogenic foods, wheat and other grains top the list. Avoidance of these is frequently the only dietary maneuver required, especially in early cases.” He proposed that ingested wheat lectin (and other dietary lectins) enter the bloodstream from the intestine and bind strongly to connective tissues (which contain considerable quantities of glycoprotein) and skin proteoglycans making them stiff.19 It is a clinical observation that inflammation of the gut is associated with inflammation of the joints. It has been also observed that the pain and inflammation of fibromyalgia may stem from or be contributed to by intolerance to wheat lectins. In fact, lectins are capable of intensifying the effects of autoimmune disorders in general. Nightshade vegetables like potatoes and tomatoes are very high in lectins and are known to trigger the symptoms of arthritis.
Sticky Proteins in Weight Management
A very important and interesting feature of some lectins is their ability to mimic hormones. As one can imagine, this could contribute a significant impact on metabolism. The hormone insulin stores excess carbohydrates (glucose) as fat. It accomplishes this by attaching itself to the insulin receptor found on the fat cell. Under stimulation from insulin, the fat cell becomes more permeable to glucose, which would otherwise remain in circulation. With mission accomplished, the insulin hormone then disconnects to its receptor. In many people, lectins found in lentils, green peas, corn, potatoes but especially wheat germ agglutinin (WGA), are known to bind to the insulin receptor giving the fat cell the same message that insulin gives, namely to make fat. The lectin, however, due to a lack of feedback inhibition, remains indefinitely attached to the receptor giving the cell a constant message to make fat.20-25 This perhaps explains why many weight loss programs that include a moderate-to-high amount of carbohydrate (especially modern grain) fail.
One other point with regard to lectin contribution to weight gain is the fact that lectins have been shown to block digestive hormones. WGA can bind to the receptor for cholecystokinin (CCK), a hormone involved in appetite control, suppressing its function.26-27 This essentially leads to an increase in appetite and impairment in the release of digestive enzymes.
Detrimental Dietary Component
Consider the fact that there are many varieties of wheat grown worldwide. Ancient wheat species had much lower protein contents than the modern varieties. Lectins are proteins. Increasing the protein component has also increased the lectin load with the resultant potential for inflammation and metabolic disruption. Genetic altering of grain plants (GMO) has also changed the lectin content.
Interestingly, 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 burdens.
Some lectins are resistant to heating by cooking. As a side note, soaking beans before cooking them reduces the lectin content dramatically. Most people do not know why beans prepared this way makes them easier to digest but it is simply because the water-soluble lectins have been nearly completely removed through the changing of the water during soaking.
Protecting Against Lectins
Because lectins are so prevalent in a typical diet, undertaking a supplement regimen to help combat the damaging effects of lectins can help contribute to optimal health, improve the health of the intestinal tract and contribute to weight loss. Certain seaweeds, especially those high in the sugar fucose (Bladderwrack) and mucilaginous vegetables like okra have the ability to bind to lectins in a way that makes them unavailable to the vulnerable cells of the gut. These foods act as sacrificial decoys and attach to the problematic lectins that would ordinarily attach and bind to gut epithelial cells. A specific glycoprotein, N-acetylglucosamine (NAG), is also a favorite target for dietary lectins and is concentrated in connective tissue. Supplementation with NAG is an excellent strategy for lectin protection. Another sugar with similar activity is D-mannose, which is capable of binding to lectins located on the cells of microorganisms. Some bacteria responsible for urinary tract infections contain lectins specific for the sugar mannose and use these lectins to bind tightly to mannose-rich tissue in the bladder walls, initiating urinary tract infections (UTIs).28 As with Bladderwrack and NAG, supplementation with D-mannose provides a decoy for these lectins and protects the bladder. Supplementing prior to a meal with these decoy sugars allows for the binding of potentially harmful lectins and protection from attack. This concept of lectin-shielding devices has exciting clinical application now and in the future.29
The subject of lectins is very broad and deserves more discussion. There are even some lectins that are beneficial to the body, such as those found in some species of edible snails, which may be capable of preventing the metastasis of cancer cells.30 The involvement of lectins in our health and their relationship to degenerative disease is still an emerging science. Studies performed on animals will continue to be the model in the future for the study of lectins. The glycosylation of the human gut is basically similar to that of higher animals and it may be confidently predicted that the effects of dietary lectins will have similarities in both humans and animals. In short, dietary lectins, by their chemical reactivity with cell surface receptors on the intestinal epithelium, are metabolic signals for the gut and are capable of modulating immune and hormone functions.14
- Jones, David S., ed.. Textbook of Functional Medicine. Gig Harbor:The Institute for Functional Medicine, 2005, 303.
- Imir T, Bankhurst AD. Inhibition of Natural Killer and interleukin 2-activated NF cell cytotoxicity by monosaccharides and lectins. Mikrobiyol Bul. 1987 Oct;21(4): 245-50.
- Chamaillard L, Quemener V, Havouis R, Moulinoux JP. Polyamine deprivation stimulates natural killer cell activity in cancerous mice. Anticancer Res. 1993 Jul-Aug; 13(4):1027-33, Jun; 115(6):600-2.
- Zagrebin VM. (Biological markers of precancer of the large intestine). (Article in Russian) Arkh Patol. 1995 Jul-Aug;57(4) :89-92.
- Luk GD, Desai TK, Conteas CN, Moshier JA, Silverman AL. Biochemical markers in colorectal cancer: diagnostic and therapeutic implications. Gastroenterol Clin North AM. 1988 Dec;17(4):931-40.
- Erickson RH, Kim J, Sleisenger MH, Kim YS. Effect of lectins on the activity of brush border membrane-bound enzymes of rat small intestine. J Pediatr Gastroenterol Nutr. December 1985; 4(6):984-91.
- Grant G. Anti-nutritive effects of soybean:a review. J Anim Sci. 1982;55:1087-1098.
- Watzl B, Neudecker C, Hansch GM, Rechkemmer G, Pool-Zobel BL. Dietary wheat germ agglutinin modulates ovalbumin-induced immune responses in Brown Norway rats. Br J Nutr. 2001 Apr;85(4):483-90.
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- Falth-Magnusson K., et al. Elevated levels of serum antibodies to the lectin wheat germ agglutinin in celiac children lend support to the gluten-lectin theory of celiac disease. Pediatr Allergy Immunol. May 1995; 6(2): 98-102.
- Hollander D, Vadheim CM, Brettholz E, Pertersen GM, Delahunty T, Rotter JI. Increased intestinal permeability in patients with Crohn’s disease and their relatives. A possible etiologic factor. Ann Intern Med, December 1986; 105(6):883-85.
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- Pusztai A. Dietary lectins are metabolic signals for the gut and modulate immune and hormonal functions. Eur J Clin Nutr. 1993 Oct; 47(10):691-699 ( Pusztai A Rowett Research Institute, Bucksburn, Aberdeen, UK.)
- Pusztai A, Ewen SW, Grant G, Brown DS, Stewart JC, Peumans WJ, Van Damme EJ, Bardocz S. Antinutritive effects of wheat germ agglutinin and other N-acetylglucosamine-specific lectins. Br J Nutr. 1993 Jul;70(1):313-321.
- Hoss VK, Raabe G, Muller P. [Lectin arthritis: a new arthritis model]. Allerg Immunol (Leipz). 1976;22:311-316
- Braun J, Sieper J. Rheumatologic manifestations of gastrointestinal disorders. Curr Opin Rheumatol. 1999;11: 68-74.
- Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Br J Nutr. 2000;83:207-217.
- Freed. Dietary Lectins and the Anti-Nutritive Effects of Gut Allergy. In: Protein Transmission Through Living Membranes. Elsevier / North Holland Biomedical Press., 1979, pg. 411-422. Livingston JN, Purvis BJ. Effects of wheat germ agglutinin on insulin binding and insulin sensitivity of fat cells. Am J Physiol. 1980 Mar; 238(3) : E267-75. Freed DJ. Dietary Lectins in Food Allergy and Intolerance. Brostoff and Callacombe Editors Bailliere Tindale Publishers, London.
- Shemer J, LeRoith D. The interaction of brain insulin receptors with wheat germ agglutinin. Neuropeptides. 1987 Jan; 9(1) : 1-8.
- Ponzio G, Debant A, Contreras JO, Rossi B. Wheat germ agglutinin mimics metabolic effects of insulin without increasing receptor autophosphorylation. Cell Signal. 1990;2(4):377-86. Shechter Y. Bound lectins that mimic insulin produce persistent insulin-like activities. Endocriology. December 1983; 113(6): pp. 1921-26.
- Kitano N, Taminato T, Ida T, Seno M, Seino Y, Matsukura S, Kuno S, Imura H. Detection of antibodies against wheat germ agglutinin bound glycoproteins on the islet-cell membrane. Diabet Med. 1988 Mar; 5(2):139-44.
- Messina JL, Hamlin J, Larner J. Insulin-mimetic actions of wheat germ agglutinin and concanavalin A on specific mRNA levels. Arch Biochem Biophys. 1987 Apr; 254(1):110-5.
- Leiner, Sharon, Goldstein,. The Lectins…., Orlando, Academic Press, 1986, p 529-552
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- Jordinson, M, et al. Soybean lectin stimulates pancreatic exocrine secretion via CCK-A receptors in rats. Am J Physiol, April 1996; 270(4 Pt I): pp. G653-59.
- Lenard, Lane, and Jonathan V Wright. D-Mannose: Natural Treatment for Urinary Tract Infections. Vitamin Research News. 2003;17: 5-7.
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