- Fukudome S, et al. Opioid peptides derived from wheat gluten: their isolation and characterization. FEBS Lett. 1992 Jan 13;296(1):107-11.
Four opioid peptides were isolated from the enzymatic digest of wheat gluten. Their structures were Gly-Tyr-Tyr-Pro-Thr, Gly-Tyr-Tyr-Pro,Tyr-Gly-Gly-Trp-Leu and Tyr-Gly-Gly-Trp, which were named gluten exorphins A5, A4, B5 and B4, respectively. The gluten exorphin A5 sequence was found at 15 sites in the primary structure of the high molecular weight glutenin and was highly specific for delta-receptors. The structure-activity relationships of gluten exorphins A were unique in that the presence of Gly at their N-termini increased their activities. Gluten exorphin B5, which corresponds to [Trp4,Leu5]enkephalin, showed the most potent activity among these peptides. Its IC50 values were 0.05 microM and 0.017 microM, respectively, on the GPI and the MVD assays. PMID: 1309704
- Fanciulli G, et al. Gluten exorphin B5 stimulates prolactin secretion through opioid receptors located outside the blood-brain barrier. Life Sci. 2005 Feb 25;76(15):1713-9. PMID: 15698850
- J Hum Nutr. 1980 Apr;34(2):107-12. Diet (gluten) and schizophrenia. Ross-Smith P, Jenner FA. Four aspects of clinical evidence for an association between gluten and schizophrenia are examined. The scientific evidence for the role of gluten is set out. Finally, reference is made to other dietary approaches. PMID: 6989901
- Peptides. 1984 Nov-Dec;5(6):1139-47. Demonstration of high opioid-like activity in isolated peptides from wheat gluten hydrolysates. Huebner FR, Lieberman KW, Rubino RP, Wall JS.
Because of a possible relationship between schizophrenia and celiac disease, a condition in some individuals who are sensitive to wheat gluten proteins in the diet, there has been interest in observations that peptides derived from wheat gluten proteins exhibit opioid-like activity in in vitro tests. To determine the origin of the peptides exhibiting opioid activity, wheat proteins were fractionated by size (gel filtration), by charge differences (ion exchange chromatography) and by differences in hydrophobicity (reversed-phase HPLC). These fractions were hydrolyzed by pepsin or pepsin and trypsin and the resulting peptides separated by gel filtration chromatography. The separated peptides were tested for opioid-like activity by competitive binding to opioid receptor sites in rat brain tissue in the presence of tritium-labeled dihydromorphine. The peptides showed considerable differences in activity; while some peptides exhibited no activity, 0.5 mg of the most active peptides were equivalent to 1 nM of morphine in the binding assay. The most active peptides were derived from the gliadin fraction of the gluten complex. PMID: 6099562
'Trigger' foods we avoid because they make us fall off the proverbial band wagon...
--Pepperidge farm GOLDFISH crackers
--Any breakfast cereal (hardly do we shop the inner aisles anymore)
--Trader Joe's frozen chocolate chip cookies
Why is wheat associated with so many autoimmune conditions?
The opioid peptides from wheat appear to trigger 'civil wars' and 'civil unrest' between the immune system and different organs in our bodies (including the Thyroid -- which HeartHawk is currently discussing)? Not only are wheat opioid peptides implicated in wreaking havoc on the immune system, but also in causing inordinate amounts of inflammation. And . . . inflammation leads to lymphoma (see end), cancer, and heart/vascular disease.
Manifestations of silent celiac disease
Autoimmune disorders (incl Hashimoto's, Grave's,Sjögren’s, Type 1 DM,Biliary cirrhosis, PsoriasisCrohn's, Addison's)
Epilepsy with cerebral calcification
Non-alcoholic fatty liver disease (NAFLD)
Unexplained chronic hypertransaminasemia
The above list originates from the below review article (full text here). If primary focal points of celiac-related inflammation leads to lymphoma (see last citation), then can silent asymptomatic celiac disease also cause heart disease? I believe so and that is why Dr. Davis' assertion for a wheat-cessation program as critical component in the plaque regression process. Are you getting tired of the 'low-fat' mantra? It's interesting how cholesterol and fat has yet to be blamed as the cause for cancer like they have for everything else.... HHhhhmmmm..... Does cholesterol really kill us? What is causing the rise in the conditions listed above? Including autism as well (see next to the last citation)?
Has the culprit always been wheat-c-a-r-b-o-h-y-d-r-a-t-e-s?
These scientists Ch'ng et al note a phenomenal explosion in the presentation of celiac conditions (silent and non-silent) in the last 30yrs. Is it coincidental this mirrors changes in the pathetic SAD (standard American diet) and low-fat 'paradigm shift' to an over-reliance on wheat and whole-grains? (Is whole-grains just whole-cr**p?) The celiac researchers report that most individuals with celiac disease have subtle or NO SYMPTOMS at all. In fact many test false negatively secondary to the changes in immunity (reduced IgA). Can treatment change the natural course or prevent autoimmune conditions (like Hashimoto's and Grave's disease)? Here at TYP, we strongly believe complete wheat withdrawal reverses many things. Including heart disease! These scientists summarize how research supports the improvement of many non-silent celiac disorders and the significant correction and resolution in auto-antibodies associated with Thyroid conditions.
- Ventura et al 39 found that diabetes- and thyroid-related antibodies tended to disappear following a gluten-free diet (11.1% at diagnosis, 5.6% at 6 months and none at 12 or 24 months follow-up for diabetes related antibodies and 14.4%, 11.1%, 6.6% and 2.2% for thyroid related antibodies, respectively)
- Identifying and treating CD in high-risk patients should confer benefit in reducing complications such as malabsorption, infertility, osteoporosis and lymphoma.95,96
Celiac disease (CD) or gluten sensitive enteropathy is relatively common in western populations with prevalence around 1%. With the recent availability of sensitive and specific serological testing, many patients who are either asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD have modest increases in risks of malignancy and mortality compared to controls. The mortality among CD patients who comply poorly with a gluten-free diet is greater than in compliant patients.The pattern of presentation of CD has altered over the past three decades. Many cases are now detected in adulthood during investigation of problems as diverse as anemia, osteoporosis, autoimmune disorders, unexplained neurological syndromes, infertility and chronic hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased prevalence of CD has been found in patients with autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease. Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary biliary cirrhosis in prospective studies. Conversely, there is also an increased prevalence of immune based disorders among patients with CD.The pathogenesis of co-existent autoimmune thyroid disease and CD is not known, but these conditions share similar HLA haplotypes and are associated with the gene encoding cytotoxic T-lymphocyte-associated antigen-4. Screening high risk patients for CD, such as those with autoimmune diseases, is a reasonable strategy given the increased prevalence.Treatment of CD with a gluten-free diet should reduce the recognized complications of this disease and provide benefits in both general health and perhaps life expectancy. It also improves glycemic control in patients with type 1 diabetes mellitus and enhances the absorption of medications for associated hypothyroidism and osteoporosis. It probably does not change the natural history of associated autoimmune disorders. PMID: 18056028
Autism is a pervasive developmental disorder that affect children early in their life. Immunological disorders is one of several contributing factors that have been suggested to cause autism. Thirty autistic children aged 3-6 years and thirty non-autistic psychologically-free siblings were studied. Circulating IgA and IgG autoantibodies to casein and gluten dietary proteins were detected by enzyme-immunoassays (EIA). Circulating IgG antibodies to measles, mumps and rubella vaccine (M.M.R) and cytomeglovirus were investigated by EIA. Results revealed high seropositivity for autoantibodies to casein and gluten: 83.3% and 50% respectively in autistic children as compared to 10% and 6.7% positivity in the control group. Surprisingly, circulating anti-measles, anti-mumps and anti-rubella IgG were positive in only 50%, 73.3% and 53.3% respectively as compared to 100% positivity in the control group. Anti-CMV IgG was positive in 43.3% of the autistic children as compared to 7% in the control group. It is concluded that, autoimmune response to dietary proteins and deficient immune response to measles, mumps and rubella vaccine antigens might be associated with autism, as a leading cause or a resulting event. Further research is needed to confirm these findings. PMID: 17974154
Hoggan R. Considering wheat, rye, and barley proteins as aids to carcinogens. Med Hypotheses. 1997 Sep;49(3):285-8. The increased incidence of lymphoma in celiac sprue (CS) is well documented, and the risk of developing this malignancy is 40-100-fold greater than in the general population. The author believes that gluten may also be at the root of lymphomas in asymptomatic and latent celiac sprue, as well. Among the 20-30% of the population which has the HLA factors most common in celiac, increased intestinal permeability leads to absorption of macromolecular peptides with opioid activity, which derive from pepsin digests of wheat. The presence, in the bloodstream, of these peptides may increase the risk of lymphomas for the entire hereditary group, which includes CS. Several processes contribute to the effect that is herein hypothesized, including opioid attachment at the hypothalamic-pituitary-adrenal axis (HPA), and subsequent downregulation of production of natural killer cells. This may offer an explanation for our longstanding awareness that there is an 'impaired lymphocyte reactivity against tumor cells in patients with coeliac disease' which may also apply to first-degree relatives with the same HLA markers. PMID: 9293475