A Potential Therapy for Accidental Wheat Gluten Ingestion

Wheat Gluten Allergy:  Treatment with Anti-Histamines and Aspirin Case Study:

A female in her late forties on a gluten free diet for the past decade, enjoyed wheat pizza, and ingested one piece every 1-2 weeks.  To prevent inflammation of her tonsils, she followed each ingestion with  25mg Benadryl (diphenyhydramine hydrochloride) antihistamine immediately and every 4-6 hours for the next 48 hours.  During the past year,  the subject ingested wheat on Day One with antihistamine therapy immediately following and every 4-6 hours for the next 48 hours.  On Day Three she again ingested wheat and continued with antihistamines.  On Day Five, she presented with an infection in her ears, sinuses, throat, and chest.  One week later, the infection had not resolved.   The subject was placed on amoxicillin antibiotic for 10 days.  The infection cleared, however, a bronchial cough with fatigue continued for the next few weeks.  She was then placed on a 10 day azithromycin prescription.  The cough and fatigue persisted.

It was suspected that gliadin peptide-antibody-collagen complexes formed in her bronchi.  The subject was taking no other medications including no anti-coagulant medication that would thin her blood. The subject was placed on aspirin (salicylic acid) therapy.  Aspirin (975mg) was given the first evening, followed by  aspirin (650mg) every 6 hours on the first full day, and aspirin(650mg) every 8 hours on subsequent days.   By the second day, most of the cough symptoms had resolved.  Therapy continued for a total of seven days during which time the cough resolved completely.  The subject now avoids all wheat, oats, and rye.  Should accidental ingestion occur, she uses antihistamines and aspirin as needed to block inflammation and gliadin peptide-antibody-collagen complex formation.

Antihistamines Discussion

On a wheat gluten free diet, subjects will unexpectedly or intentionally encounter the ubiquitous wheat.  The immune response to the gliadin peptide,after abstention,can be significantly more pronounced. “Y” shaped IgE antibodies that have been secreted in response to previous exposures are now attached by their Fc base to the Fc receptor of mast cells and basophils.

In the oral cavity, wheat may irritate the tonsils or sinuses.  As wheat enters the gastrointestinal tract, it is digested into gliadin peptide fragments which enter the blood stream.  As the finger like tips of the antibodies (attached to the Fc receptors of mast cells and basophils) recognize and attach the gliadin peptide, the mast cells and basophils release histamine.  Histamine binds H1 receptors on blood vessel walls causing migration of immune cells into tissue (Reiner PB, et.al. 1994). This immune response consisting of B cells, T cells, macrophages, basophils initiates inflammation. Inflammation is generally cleared by the lymph system. While it may be difficult to visualize internal inflammation, external signs/symptoms such as coughing, sneezing, runny nose, swollen tonsils, watery eyes, and clogged sinuses may be noticeable.

An immune response happens rapidly.  The more time the body is given to generate inflammation, typically the greater the response.  An antihistamine such as Benadryl (diphenhydramine hydrochloride) blocks the histamine H1 receptor and the migration of immune cells into tissue, diminishing the response (Yamashiro K, et.al. 2001).

Aspirin Discussion:

While an antihistamine may suppress inflammation,  a second problem with wheat ingestion is the gliadin peptide circulating in blood vessels available for  attachment to collagen fibers.

The gliadin peptide is a component of the wheat plant’s defense system.  The wheat plant has two coded regions called wheat germ agglutinin lectins. These lectins, which are more prevalent in the stem and spike of wheat, enable the plant to fend off disease (Xiang Y, et.al. 2011). Once inside the body, wheat defense lectins can attack human tissues.  Wheat germ agglutinin is commonly used in research to identify penetrance because it attaches to many human cell types. Potatoes have two defense lectins (Allen AK, et.al. 1996) while rice and sweet potatoes each have one (Xiang Y, et.al. 2011).  Thus, a diet of rice or sweet potatoes is more compatible to the human immune system.

Wheat plant lectins have a complex three dimensional structure which is stabilized by disulfide bonds (Nizheradze KA, 2000).  These bonds attach carbohydrate surface structures on collagen fibers which are found in joints, cartilage, organs, tissues, and ducts. The strength and flexibility of collagen, for example, provides for fluid movement in a joint, the lattice support structure in pulmonary tissue, and the passage of nutrients in a liver duct.  The binding of lectins on collagen changes the alignment, density, and uniformity of the fiber network (Nizheradze KA, 2000).

Imagine thin collagen fibers, like a cotton ball, stretched out as a wispy cloud. Collagen function is altered when small amounts of lectin are glued throughout. Collagen plus lectin “glue” causes rheumatoid arthritis in a joint, asthma in lung tissue, and primary biliary cirrhosis in the liver.  Perhaps, instead of these conditions being “disease”, they are analogous to grease in the plumbing.

To eliminate this wheat lectin from the body, we look to the manufacturing industry, where wheat gluten is used to produce biodegradable plastics.  To lengthen the temperature window for the hardening of these plastic products, aspirin (salicyclic acid) can be utilized. Salicylic acid reduces the viscosity of wheat gluten by delaying the formation of the disulfide bonds such that the aggregation and cross-linking rate of the hardening plastic is slower (Ullstein H, et.al. 2011).  It has also been found that on collagen fibers in human cell culture, the binding of wheat germ agglutinin is significantly decreased by chemicals such as salicylic acid (Nizheraze KA, 2000).

The scientific investigate community is cognizant of aspirin’s anti-platelet aggregation properties, however, these scientists may not have realized that it also weakens wheat gluten-antigen-collagen bonds.  Given aspirin’s widespread use, this recent finding has been inadvertently discovered. Dr. James Watson (Watson and Crick, Nobel Prize 1964, DNA double helix) on Reach MD,  tells us to return to biochemistry to thwart disease.  Indeed, the discovery of this interconnection provides a practical basis to confirm the accuracy of man’s research.

References:

Allen AK, Bolwell GP, Brown DS, Sidebottom C, Slabas AR, “Potato lectin: a three-domain glycoprotein with novel hydroxyproline-containing sequences and sequence similarities to wheat-germ agglutinin”.  Int J Biochem Cell Biol. 1996 Nov;28(11):1285-91

Di Domenico F, Owen JB, Sultana R, Sowell RA, Perluigi M, Cini C, Cai J, Pierce WM, Butterfield DA,  “The wheat germ agglutinin-fractionated proteome of subjects with Alzheimer’s disease and mild cognitive impairment hippocampus and inferior parietal lobule: Implications for disease pathogenesis and progression”.  J Neurosci Res. 2010 Dec;88(16):3566-77. doi: 10.1002/jnr.22528. Epub 2010 Oct 8.

Nizheradze KA, “Binding of wheat germ agglutinin to extracellular network produced by cultured human fibroblasts”. Folia Histochem Cytobiol. 2000;38(4):167-73  PMID 11185721

Reiner PB, Kamondi A, “Mechanisms of antihistamine-induced sedation in the human brain: H1 receptor activation reduces a background leakage potassium current”. Neuroscience 59 (3): 579–88. DOI:10.1016/0306-4522(94)90178-3. PMID 8008209, April 2004

Ullsten HN, Sung-Woo C, Spencer G, Gallstedt M, Johansson E, Hedenqvist M, “Properties of Extruded Vital Wheat Gluten Sheets with Sodium Hydroxide and Salicyclic Acid”.  Biomacromolecules 2009, 10, 479-488

Xiang Y, Song M, Wei Z, Tong J, Zhang L, Xiao L, Ma Z, Wang Y, “A jacalin-related lectin-like gene in wheat is a component of the plant defense system”. J Exp Bot. 2011 Nov;62(15):5471-83. Epub 2011 Aug 23

Yamashiro, K; Kiryu, J; Tsujikawa, A; Nonaka, A; Honjo, M; Tanihara, H; Nishiwaki, H; Honda, Y et al. (2001). “Suppressive effects of histamine H1 receptor antagonist diphenhydramine on the leukocyte infiltration during endotoxin-induced uveitis”. Experimental eye research 73 (1): 69–80. DOI:10.1006/exer.2001.1008. PMID 11428864.

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July 10, 2012

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