Science has not been able to blame the protein gluten for all of the detrimental symptoms experienced by those with gluten sensitivity. It is common scientific knowledge that grain research is in its infancy. On that note, we discuss the lectin compound – wheat germ agglutinin (WGA)…
The following was written by nutrition educator – Sayer Ji www.greenmedinfo.com Sayer does a fantastic job describing the effects of WGA on human health…You can watch this interview with Sayer Here.
Below the radar of conventional serological testing for antibodies against the various gluten proteins and genetic testing for disease susceptibility, the WGA “lectin problem” remains almost entirely obscured. Lectins, though found in all grains, seeds, legumes, dairy and our beloved nightshades: the tomato and potato, are rarely discussed in connection with health or illness, even when their presence in our diet may greatly reduce both the quality and length of our lives.
Nature engineers, within all species, a set of defenses against predation, though not all are as obvious as the thorns on a rose or the horns on a rhinoceros. Plants do not have the cell-mediated immunity of higher life forms, like ants, nor do they have the antibody driven, secondary immune systems of vertebrates with jaws. They must rely on a much simpler, innate immunity. It is for this reason that seeds of the grass family, e.g. rice, wheat, spelt, rye, have exceptionally high levels of defensive glycoproteins known as lectins. Cooking, sprouting, fermentation and digestion are the traditional ways in which man, for instance, deals with the various anti-nutrients found within this family of plants, but lectins are, by design, particularly resistant to degradation through a wide range of pH and temperatures.
Lectins are glycoproteins, and through thousands of years of selectively breeding wheat for increasingly larger quantities of protein, the concentration of WGA lectin has increased proportionately. This, no doubt, has contributed to wheat’s global dominance as one of the world’s favored monocultures, offering additional “built-in” pest resistance. The word lectin comes from the same etymological root as the word select, and literally means “to choose.” Lectins are designed “to choose” specific carbohydrates that project off the surface of cells and upon which they attach. In the case of WGA the two glycoproteins it selects for, in order of greatest affinity, are N-Acetyl Glucosamine and N-Acetylneuraminic acid (sialic acid).
WGA is Nature’s ingenious solution for protecting the wheat plant from the entire gamut of its natural enemies. Fungi have cell walls composed of a polymer of N-Acetylglucosamine. The cellular walls of bacteria are made from a layered structure called the peptidoglycan, a biopolymer of N-Acetylglucosamine. N-acetylglucosamine is the basic unit of the biopolymer chitin, which forms the outer coverings of insects and crustaceans (shrimp, crab, etc.). All animals, including worms, fish, birds and humans, use N-Acetyglucosamine as a foundational substance for building the various tissues in their bodies, including the bones. The production of cartilage, tendons, and joints depend on the structural integrity of N-Acetylglucosamine. The mucous known as the glycocalyx, or literally, “sugar coat” is secreted in humans by the epithelial cells which line all the mucous membranes, from nasal cavities to the top to the bottom of the alimentary tube, as well as the protective and slippery lining of our blood vessels. The glycocalyx is composed largely of N-Acetylglucosamine and N-Acetylneuraminic acid (also known as sialic acid), with carbohydrate end of N-Acetylneuraminic acid of this protective glycoprotein forming the terminal sugar that is exposed to the contents of both the gut and the arterial lumen (opening). WGA’s unique binding specificity to these exact two glycoproteins is not accidental. Nature has designed WGA perfectly to attach to, disrupt, and gain entry through these mucosal surfaces.
WGA is most concentrated in the seed of the wheat plant, likely due to the fact that the seeds are the “babies” of these plants and are invested with the entire hope for continuance of their species. Protecting the seed against predation is necessarily a first priority. WGA is an exceedingly small glycoprotein (36 kilodaltons) and is concentrated deep within the embryo of the wheat berry (approximately 1 microgram per grain). WGA migrates during germination to the roots and tips of leaves, as the developing plant begins to project itself into the world and outside the safety of its seed. In its quest for nourishment from the soil, its roots are challenged with fungi and bacteria that seek to invade the plant. In its quest for sunlight and other nourishment from the heavens the plant’s leaves become prey to insects, birds, mammals, etc. Even after the plant has developed beyond the germination and sprouting stages it contains almost 50% of the levels of lectin found in the dry seeds. Approximately one third of this WGA is in the roots and two thirds is in the shoot, for at least 34 days 
One way to gauge just how pervasive the adverse effects of WGA are among wheat-consuming populations is the popularity of the dietary supplement glucosamine. In the USA, a quarter billion dollars’ worth of the glucosamine is sold annually. The main source of glucosamine on the market is from the N-Acetylglucosamine rich chitin exoskelotons of crustaceans, like shrimp and crab. Glucosamine is used for reducing pain and inflammation. We do not have a dietary deficiency of the pulverized shells of dead sea critters, just as our use of NSAIDs is not caused by a deficiency of these synthetic chemicals in our diet. When we consume glucosamine supplements, the WGA, instead of binding to our tissues, binds to the pulverized chitin in the glucosamine supplements, sparing us from the full impact of WGA. Many millions of Americans who have greatly reduced their pain and suffering by ingesting glucosamine and NSAIDs may be better served by removing wheat, the underlying cause of their malaise, from their diets. This would result in even greater relief from pain and inflammation along with far less dependency on palliative supplements and medicines alike.
- WGA may be Pro-inflammatory
- At exceedingly small concentrations (nanomolar) WGA stimulates the synthesis of pro-inflammatory chemical messengers (cytokines) including Interleukin 1, Interleukin 6 and Interleukin 8 in intestinal and immune cells.
- WGA has been shown to induce NADPH-Oxidase in human neutrophils associated with the “respiratory burst” that results in the release of inflammatory free radicals called reactive oxygen species WGA has been shown to play a causative role in patients with chronic thin gut inflammation.
- WGA may be Immunotoxic
- WGA induces thymus atrophy in rats and may directly bind to, and activate, leukocytes .
- Anti-WGA antibodies in human sera have been shown to cross-react with other proteins, indicating that they may contribute to autoimmunity .
Indeed, WGA appears to play a role in the pathogenesis of celiac disease (CD) that is entirely distinct from that of gluten, due to significantly higher levels of IgG and IgA antibodies against WGA found in patients with CD, when compared with patients with other intestinal disorders. These antibodies have also shown not to cross-react with gluten antigens 
- WGA may be Neurotoxic
- WGA can pass through the blood brain barrier (BBB) through a process called “adsorptive endocytosis” and is able to travel freely among the tissues of the brain which is why it is used as a marker for tracing neural circuits. WGA’s ability to pass through the BBB, pulling bound substances with it, has piqued the interest of pharmaceutical developers who are looking to find ways of delivering drugs to the brain. WGA has a unique binding affinity for N-Acetylneuraminic acid, a crucial component of neuronal membranes found in the brain, such as gangliosides which have diverse roles such as cell-to-cell contact, ion conductance, as receptors, and whose dysfunction has been implicated in neurodegenerative disorders. WGA may attach to the protective coating on the nerves known as the myelin sheath and is capable of inhibiting nerve growth factor  which is important for the growth, maintenance, and survival of certain target neurons. WGA binds to N-Acetylglucosamine which is believed to function as an atypical neurotransmitter functioning in nocioceptive (pain) pathways.
- WGA may be Cytotoxic – WGA has been demonstrated to be cytotoxic to both normal and cancerous cell lines, capable of inducing either cell cycle arrest or programmed cell death (apoptosis). 
- WGA may interfere with Gene Expression – WGA demonstrates both mitogenic and anti-mitogenic activities. WGA may prevent DNA replication WGA binds to polysialic acid (involved in posttranslational modifications) and blocks chick tail bud development in embryogenesis, indicating that it may influence both genetic and epigenetic factors.
- WGA may disrupt Endocrine Function – WGA has also been shown to have an insulin-mimetic action, potentially contributing to weight gain and insulin resistance . WGA has been implicated in obesity and “leptin resistance” by blocking the receptor in the hypothalamus for the appetite satiating hormone leptin. WGA stimulates epidermal growth factor which when upregulated is associated with increased risk of cancer. WGA has a particular affinity for thyroid tissue and has been shown to bind to both benign and malignant thyroid nodules WGA interferes with the production of secretin from the pancreas, which can interfere with digestion and can cause pancreatic hypertrophy. WGA attaches to sperm and ovary cells, indicating it may adversely influence fertility.
- WGA may be Cardiotoxic
- WGA induces platelet activation and aggregration . WGA has a potent, disruptive effect on platelet endothelial cell adhesion molecule-1, which plays a key role in tissue regeneration and safely removing neutrophils from our blood vessels.
- WGA may adversely effect Gastrointestinal Function – WGA causes increased shedding of the intestinal brush border membrane, reduction in surface area, acceleration of cell losses and shortening of villi, via binding to the surface of the villi. WGA can mimic the effects of epidermal growth factor (EGF) at the cellular level, indicating that the crypt hyperplasia seen in celiac disease may be due to the growth-promoting effects of WGA. WGA causes cytoskeleton degradation in intestinal cells, contributing to cell death and increased turnover. WGA decreases levels of heat shock proteins in gut epithelial cells leaving these cells less well protected against the potentially harmful content of the gut lumen.
- WGA may share pathogenic similarities with certain Viruses – There are a number of interesting similarities between WGA lectin and viruses. Both viral particles and WGA lectin are several orders of magnitude smaller than the cells they enter, and subsequent to their attachment to the cell membrane, are taken into the cell through a process of endocytosis. Both influenza and WGA gain entry through the sialic acid coatings of our mucous membranes (glycocalyx) each with a sialic acid specific substance, the neuriminidase enzyme for viruses and the sialic acid binding sites on the WGA lectin. Once the influenza virus and WGA lectin have made their way into wider circulation in the host body they are both capable of blurring the line in the host between self-and non-self. Influenza accomplishes this by incorporating itself into the genetic material of our cells and taking over the protein production machinery to make copies of itself, with the result that our immune system must attack its own virally transformed cell, in order to clear the infection. Studies done with herpes simplex virus have shown that WGA has the capacity to block viral infectivity through competitively binding to the same cell surface receptors, indicating that they may effect cells through very similar pathways. WGA has the capability of influencing the gene expression of certain cells, e.g. mitogenic/anti-mitogenic action, and like other lectins associated with autoimmunity, e.g. soy lectin, and viruses like Epstein-Barr Virus, WGA may be capable of causing certain cells to exhibit class 2 human leukocyte antigens (HLA-II), which mark them for autoimmune destruction by white blood cells. Since human antibodies to WGA have been shown to cross react with other proteins, even if WGA does not directly transform the phenotype of our cells into “other,” the resulting cross-reactivity of antibodies to WGA with our own cells would result in autoimmunity nonetheless.
It is my belief that a careful study of the wheat plant will reveal that, despite claims to the contrary, man does not have dominion over nature. All that he deems fit for his consumption may not be his inborn right. Though the wheat plant’s apparently defenseless disposition would seem to make it suitable for mass human consumption, it has been imbued with a multitude of invisible “thorns,” with WGA being its smallest and perhaps most potent defense against predation. While WGA may be an uninvited guest at our table, wheat is equally inhospitable to us. Perhaps the courteous thing to do, having realized our mistaken intrusion, is to lick our wounds and simply go our separate ways. Perhaps as the distance between man and his infatuation with wheat grows, he will grow closer to himself and will discover far more suitable forms of nourishment that Nature has not impregnated with such high levels of addictive and potentially debilitating proteins.