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Durazzo M, Ferro A, Brascugli I, Mattivi S, Fagoonee S, Pellicano R. Extra-Intestinal Manifestations of Celiac Disease: What Should We Know in 2022? J Clin Med 2022; 11:258. [PMID: 35011999 PMCID: PMC8746138 DOI: 10.3390/jcm11010258] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 12/24/2021] [Accepted: 12/30/2021] [Indexed: 01/27/2023] Open
Abstract
Celiac disease (CD) is a chronic, small-intestinal, immune-mediated enteropathy due to gluten exposition in genetically predisposed individuals. It occurs in about 1% of the population and often remains an underdiagnosed condition. This could be due to the fact that the adult population often lacks the classical signs and symptoms of CD, manifesting only atypical symptoms. In this review we analyzed the main extra-intestinal manifestations of CD which include cutaneous and endocrinological disorders, abnormal liver function tests, and neuropsychiatric features. When CD is not diagnosed and therefore is not treated with a gluten-free diet (GFD), it can predispose to severe complications, not only gastrointestinal. Thus, it is important for clinicians to quickly recognize the atypical manifestations of CD, considering that an early diagnosis can significantly impact on a patient's prognosis.
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Affiliation(s)
- Marilena Durazzo
- Department of Medical Sciences, University of Turin, C.so A.M. Dogliotti 14, 10126 Turin, Italy; (A.F.); (I.B.); (S.M.)
| | - Arianna Ferro
- Department of Medical Sciences, University of Turin, C.so A.M. Dogliotti 14, 10126 Turin, Italy; (A.F.); (I.B.); (S.M.)
| | - Isabella Brascugli
- Department of Medical Sciences, University of Turin, C.so A.M. Dogliotti 14, 10126 Turin, Italy; (A.F.); (I.B.); (S.M.)
| | - Simone Mattivi
- Department of Medical Sciences, University of Turin, C.so A.M. Dogliotti 14, 10126 Turin, Italy; (A.F.); (I.B.); (S.M.)
| | - Sharmila Fagoonee
- Institute for Biostructure and Bioimaging, National Research Council, Molecular Biotechnology Centre, 10126 Turin, Italy;
| | - Rinaldo Pellicano
- Unit of Gastroenterology, Città della Salute e della Scienza Hospital, C.so Bramante 88, 10126 Turin, Italy;
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Cheng FW, Handu D. Nutrition Assessment, Interventions, and Monitoring for Patients with Celiac Disease: An Evidence Analysis Center Scoping Review. J Acad Nutr Diet 2020; 120:1381-1406. [PMID: 31953154 DOI: 10.1016/j.jand.2019.09.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2019] [Indexed: 11/21/2022]
Abstract
The objectives of this scoping review were to identify and characterize studies examining nutrition assessment, interventions, and measures to monitor gluten-free diet (GFD) adherence/compliance in patients with celiac disease (CD). An electronic literature search of four databases (Cochrane Database for systematic reviews, CINAHL, Embase, and Ovid MEDLINE) was conducted to identify articles examining nutrition care in CD individuals. Except for narrative review, grey literature, and case study/report, all types of peer-reviewed articles published between January 2007 and August 2018 were eligible. There were a total of 10,823 records; 10,368 were excluded during the first round of screening due to irrelevancy and/or duplication. Of the 455 full-text articles that were assessed, 292 met the criteria and were included. Most of the studies were observational studies (n=212), followed by experimental trials (n=50), evidence-based practice guideline (EBPG)/report/statement (n=16), and systematic review (SR) (n=14). Nine original studies examined assessment, focusing mainly on different tools/ways to assess GFD adherence. The majority of the included original articles (n=235) were in the nutrition intervention category with GFD, oats, and prebiotics/probiotics as the top-three most studied interventions. There were eight SRs on GFD and five on oats. One SR and 21 original studies investigated the effectiveness of different measures to monitor GFD adherence/compliance. Although recent CD EBPGs were identified, different methods with varying levels of rigor, in terms of literature search and assessment of evidence strength, were used. Based on this scoping review, interventions focused on gluten-free diet and oats have been significantly covered by either SRs or EBPGs. Studies related to prebiotics/probiotics and education program/counseling focused interventions, as well as assessment, in CD patients have increased in recent years. Thus, it might be beneficial to conduct SRs/EBPGs focused on these topics to guide practitioners.
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Bellastella G, Maiorino MI, Cirillo P, Longo M, Pernice V, Costantino A, Annunziata C, Bellastella A, Esposito K, De Bellis A. Remission of Pituitary Autoimmunity Induced by Gluten-Free Diet in Patients With Celiac Disease. J Clin Endocrinol Metab 2020; 105:5841167. [PMID: 32433771 DOI: 10.1210/clinem/dgz228] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Accepted: 05/20/2020] [Indexed: 01/18/2023]
Abstract
CONTEXT An improvement of some autoimmune diseases associated with celiac disease (CD) has been observed after a gluten-free diet (GFD). OBJECTIVE The aim of this longitudinal study was to evaluate the effect of a GFD on autoimmune pituitary impairment in patients with CD and potential/subclinical lymphocytic hypophysitis (LYH). DESIGN Five-year longitudinal observational study. SETTING Tertiary referral center for immunoendocrinology at the University of Campania "Luigi Vanvitelli". PATIENTS Ninety-three newly diagnosed LYH patients (high titer of antipituitary antibodies [APA] and normal or subclinically impaired pituitary function) were enrolled from 2000 to 2013 and grouped as follows: group 1, consisting of 43 patients with LYH + CD, and group 2, consisting of 50 patients with isolated LYH only. INTERVENTION A GFD was started in patients in group 1 after the diagnosis of CD. MAIN OUTCOME MEASURES APA titers and pituitary function were evaluated at the beginning of the study and then yearly for 5 years in both groups. Patients progressing to a clinically overt LYH were excluded from the follow-up. RESULTS Complete remission of LYH (disappearance of APA and recovery of pituitary function in patients with previous subclinical hypopituitarism) occurred in 15 patients in group 1 after a GFD (34%) and spontaneously in only 1 patient in group 2 (2%) (P < .001). Two patients in group 1 and 25 in group 2 progressed to a clinically overt hypopituitarism and dropped out from the study to receive an appropriate replacement therapy. The presence of CD was the only independent predictor of pituitary function recovery (hazard ratio [HR] 0.059, 95% confidence interval [CI] 0.01-0.54, P = .012). CONCLUSION In patients with LYH and CD, a GFD may be able to induce remission of subclinical LYH, or prevent the progression to clinical stage of this disease.
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Affiliation(s)
- Giuseppe Bellastella
- Unit of Endocrinology and Metabolic Diseases, University of Campania "Luigi Vanvitelli", Naples, Italy
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Maria Ida Maiorino
- Unit of Endocrinology and Metabolic Diseases, University of Campania "Luigi Vanvitelli", Naples, Italy
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Paolo Cirillo
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Miriam Longo
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Vlenia Pernice
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Angela Costantino
- Unit of Endocrinology and Metabolic Diseases, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Carmen Annunziata
- Unit of Endocrinology and Metabolic Diseases, University of Campania "Luigi Vanvitelli", Naples, Italy
| | | | - Katherine Esposito
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
- Unit of Diabetes, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Annamaria De Bellis
- Unit of Endocrinology and Metabolic Diseases, University of Campania "Luigi Vanvitelli", Naples, Italy
- Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy
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Borba VV, Zandman-Goddard G, Shoenfeld Y. Prolactin and autoimmunity: The hormone as an inflammatory cytokine. Best Pract Res Clin Endocrinol Metab 2019; 33:101324. [PMID: 31564625 DOI: 10.1016/j.beem.2019.101324] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Nowadays, more than 80 autoimmune disorders are recognized, in which an aberrant immune response against different organs and tissues plays a crucial role. Hormonal homeostasis has great influence in achieving competent and healthy immune system function. Prolactin has a bioactive function acting as a hormone and a cytokine. It influences the immune system modulation, mainly inhibiting the negative selection of autoreactive B lymphocytes. Hyperprolactinemia has been detected in many patients with different autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, multiple sclerosis, autoimmune thyroid disease, systemic sclerosis, among others, and its believed to play a crucial role in disease pathogenesis. A direct correlation between prolactin levels and disease activity was not clear. Genetic factors may have a role in humans as in animal models. Dopamine agonists have proven to offer clinical benefits among autoimmune patients and represent a promising therapy to be explored. In this review, the authors attempt to provide a critical overview on the role of prolactin in the immune system, exploring its contribution to the development of autoimmune diseases.
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Affiliation(s)
- Vânia Vieira Borba
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
| | - Gisele Zandman-Goddard
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Department of Medicine C, Wolfson Medical Center, Tel Aviv, Israel
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Russia.
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Walker MD, Zylberberg HM, Green PHR, Katz MS. Endocrine complications of celiac disease: a case report and review of the literature. Endocr Res 2019; 44:27-45. [PMID: 30198791 DOI: 10.1080/07435800.2018.1509868] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE The purpose of this article is to review recent literature regarding endocrine disorders related to celiac disease (CD). METHODS We describe a case report and review existing literature on the endocrine manifestations of CD. RESULTS CD is an autoimmune disorder characterized by intestinal inflammation in response to gluten. CD can cause a wide range of extra-intestinal complications, including endocrine manifestations. Metabolic bone disease including osteoporosis and osteopenia, vitamin D deficiency, secondary hyperparathyroidism and less frequently osteomalacia can be seen. In CD, fracture risk is increased by 30-40%, while risk for hip fracture is approximately doubled. The risk for other endocrine disorders, particularly autoimmune endocrinopathies, is also increased in those with CD compared to the general population. Epidemiologic data indicate the risk for hypothyroidism is 3-4 times higher among those with CD, while risk of type 1 diabetes is greater than double. Risk for primary adrenal insufficiency is a striking 11-fold higher in those with versus without CD, though the absolute risk is low. Fertility is reduced in women with CD before diagnosis by 37% while male fertility in the absence of hypogonadism does not appear to be affected. Other endocrine conditions including hyperthyroidism, ovarian failure, androgen insensitivity, impaired growth and growth hormone deficiency and autoimmune polyendocrine syndromes have also been associated with CD. CONCLUSIONS CD is associated with a wide range of endocrine manifestations.
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Affiliation(s)
- Marcella D Walker
- a Department of Medicine , Columbia University , New York , NY , USA
| | | | - Peter H R Green
- a Department of Medicine , Columbia University , New York , NY , USA
| | - Michael S Katz
- c Department of Medicine , University of Texas Health Science Center at San Antonio , San Antonio , TX , USA
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Khater D. Endocrinopathies in celiac disease: When the endocrinologist sees what is invisible to the gastroenterologist. ACTA BIO-MEDICA : ATENEI PARMENSIS 2018; 89:117-121. [PMID: 29633735 PMCID: PMC6357610 DOI: 10.23750/abm.v89i1.7119] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Accepted: 02/21/2018] [Indexed: 12/30/2022]
Abstract
Celiac disease (CD) is a systemic, immune mediated and genetically determined small intestinal disorder characterized by intolerance to dietary gluten that generally presents with gastrointestinal symptoms in young children and extra-intestinal manifestations. Furthermore, there is close association between CD and endocrine diseases, including diabetes, autoimmune thyroid diseases, growth and pubertal disorders, etc. probably due to the presence of a common genetic predisposition. The present review aims to highlight and give more insight to the endocrine changes in CD, especially when there are few or no gastrointestinal symptoms and to emphasize on screening opportunities in some endocrine diseases. (www.actabiomedica.it)
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7
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Borba VV, Zandman-Goddard G, Shoenfeld Y. Prolactin and Autoimmunity. Front Immunol 2018; 9:73. [PMID: 29483903 PMCID: PMC5816039 DOI: 10.3389/fimmu.2018.00073] [Citation(s) in RCA: 127] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2017] [Accepted: 01/11/2018] [Indexed: 12/17/2022] Open
Abstract
The great asymmetry of autoimmune diseases between genders represents one of the most enigmatic observations among the mosaic of autoimmunity. Sex hormones are believed to play a crucial role on this dimorphism. The higher prevalence of autoimmunity among women at childbearing ages, disease onset/relapses during pregnancy, and post-partum are some of the arguments that support this hypothesis. Certainly, motherhood represents one of the most remarkable challenges for the immune system, which not only has to allow for the conceptus, but also has to deal with complex endocrine alterations. Hormonal homeostasis is known to exert a crucial influence in achieving a competent and healthy immune system. Prolactin (PRL) has a bioactive function acting as a hormone and a cytokine. It interferes with immune system modulation, mainly inhibiting the negative selection of autoreactive B lymphocytes. Likewise, hyperprolactinemia has been described in relation to the pathogenesis and activity of several autoimmune disorders. Dopamine is an effective inhibitor of PRL secretion due to either a direct influence on the hypophysis or stimulation of postsynaptic dopamine receptors in the hypothalamus, arousing the release of the PRL inhibitory factor. Hence, dopamine agonists have proven to offer clinical benefits among autoimmune patients and represent a promising therapy to be explored. In this review, we attempt to provide a critical overview of the link between PRL, autoimmune diseases, and motherhood.
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Affiliation(s)
- Vânia Vieira Borba
- Department "A" of Internal Medicine, Coimbra University Hospital Centre, Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, Coimbra, Portugal.,Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel
| | | | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel.,Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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8
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Freeman HJ. Endocrine manifestations in celiac disease. World J Gastroenterol 2016; 22:8472-8479. [PMID: 27784959 PMCID: PMC5064028 DOI: 10.3748/wjg.v22.i38.8472] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 08/05/2016] [Accepted: 08/23/2016] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison’s disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet.
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9
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Stefanucci A, Mollica A, Macedonio G, Zengin G, Ahmed AA, Novellino E. Exogenous opioid peptides derived from food proteins and their possible uses as dietary supplements: A critical review. FOOD REVIEWS INTERNATIONAL 2016. [DOI: 10.1080/87559129.2016.1225220] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Azzurra Stefanucci
- Dipartimento di Farmacia, Università di Chieti-Pescara “G. d’Annunzio”, Chieti, Italy
| | - Adriano Mollica
- Dipartimento di Farmacia, Università di Chieti-Pescara “G. d’Annunzio”, Chieti, Italy
| | - Giorgia Macedonio
- Dipartimento di Farmacia, Università di Chieti-Pescara “G. d’Annunzio”, Chieti, Italy
| | - Gokhan Zengin
- Department of Biology, Science Faculty, Selcuk University, Konya, Turkey
| | - Abdelkareem A. Ahmed
- Department of Physiology and Biochemistry, Faculty of Veterinary Science, University of Nyala, Nyala, Sudan
| | - Ettore Novellino
- Dipartimento di Farmacia, Università di Napoli “Federico II”, Naples, Italy
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10
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Merkin SS, Phy JL, Sites CK, Yang D. Environmental determinants of polycystic ovary syndrome. Fertil Steril 2016; 106:16-24. [DOI: 10.1016/j.fertnstert.2016.05.011] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 05/03/2016] [Accepted: 05/16/2016] [Indexed: 12/17/2022]
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Larouche V, Correa JA, Cassidy P, Beauregard C, Garfield N, Rivera J. Prevalence of autoimmune disease in patients with prolactinomas and non-functioning pituitary adenomas. Pituitary 2016; 19:202-9. [PMID: 26700946 DOI: 10.1007/s11102-015-0699-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
PURPOSE Prolactin can affect autoimmune response and evidence suggests that hyperprolactinemia can primarily precipitate autoimmunity. We postulate that patients with prolactinomas are more prone to autoimmune disease (AID). METHODS We conducted a retrospective case-control study comparing prevalence of AID in 100 prolactinoma patients (PRL-P, cases) and 100 age- and gender-matched non-functioning pituitary adenoma patients (NFPA-P, controls) assessed at the Neuroendocrine Clinics of the McGill University Health Centre between January 2005 and December 2014. Comparisons were done using a conditional logistic regression (CLR) analysis. Multiple imputation was used to account for missing data values. RESULTS Sixty-eight women and 32 men were in each group. Median age was 37 years for PRL-P and 46 years for NFPA-P. AID was diagnosed in 28/100 cases and 16/100 controls. Autoimmune thyroid disease was the most common AID reported in both groups, representing 70 and 61% of the AID diagnoses respectively. CLR analysis revealed a multiplicative interaction effect between AID prevalence and age (p 0.004). Odds ratios for AID in PRL-P compared to NFPA-P increase with age and become significant at age 43, reaching 4.17 (95% CI 1.26, 13.82) at age 45 and 8.09 (95% CI 1.96, 33.43) at age 50 (p 0.05). CONCLUSION Our data showed a higher prevalence of AID in both PRL-P and NFPA-P than in a reference population. In both groups, prevalence of AID increased with age, given a multiplicative interaction effect. A significant higher prevalence of autoimmunity in PRL-P compared with NFPA-P occurs after age 43. These associations may have significant implications for the management of prolactinoma patients.
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Affiliation(s)
- V Larouche
- Internal Medicine Residency Training Program, Department of Medicine, McGill University, Montreal, QC, Canada.
| | - J A Correa
- Department of Mathematics and Statistics, McGill University, Montreal, QC, Canada
| | - P Cassidy
- Department of Pharmacology, Université de Montréal, Montreal, QC, Canada
| | - C Beauregard
- Division of Endocrinology, McGill University Health Centre, Montreal, QC, Canada
| | - N Garfield
- Division of Endocrinology, McGill University Health Centre, Montreal, QC, Canada
| | - J Rivera
- Division of Endocrinology, McGill University Health Centre, Montreal, QC, Canada
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Pruimboom L, de Punder K. The opioid effects of gluten exorphins: asymptomatic celiac disease. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2015; 33:24. [PMID: 26825414 PMCID: PMC5025969 DOI: 10.1186/s41043-015-0032-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/07/2015] [Accepted: 11/08/2015] [Indexed: 06/05/2023]
Abstract
Gluten-containing cereals are a main food staple present in the daily human diet, including wheat, barley, and rye. Gluten intake is associated with the development of celiac disease (CD) and related disorders such as diabetes mellitus type I, depression, and schizophrenia. However, until now, there is no consent about the possible deleterious effects of gluten intake because of often failing symptoms even in persons with proven CD. Asymptomatic CD (ACD) is present in the majority of affected patients and is characterized by the absence of classical gluten-intolerance signs, such as diarrhea, bloating, and abdominal pain. Nevertheless, these individuals very often develop diseases that can be related with gluten intake. Gluten can be degraded into several morphine-like substances, named gluten exorphins. These compounds have proven opioid effects and could mask the deleterious effects of gluten protein on gastrointestinal lining and function. Here we describe a putative mechanism, explaining how gluten could "mask" its own toxicity by exorphins that are produced through gluten protein digestion.
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Affiliation(s)
- Leo Pruimboom
- Natura Foundation, Edisonstraat 66, 3281 NC, Numansdorp, Netherlands.
- Department of Laboratory Medicine, University Medical Center Groningen (UMCG), University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, Netherlands.
| | - Karin de Punder
- Natura Foundation, Edisonstraat 66, 3281 NC, Numansdorp, Netherlands.
- Institute of Medical Psychology, Charité University Medicine Berlin, Hufelandweg 14, 10117, Berlin, Germany.
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Behavioral effects of food-derived opioid-like peptides in rodents: Implications for schizophrenia? Pharmacol Biochem Behav 2015; 134:70-8. [PMID: 25661529 DOI: 10.1016/j.pbb.2015.01.020] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2014] [Revised: 01/09/2015] [Accepted: 01/28/2015] [Indexed: 01/08/2023]
Abstract
Dohan proposed that an overload of dietary peptides, such as those derived from wheat gluten and milk casein, could be a factor relevant to the development or maintenance of schizophrenia (SZ) symptoms in at least a subset of vulnerable individuals. Rodent behavioral models may offer insight into the plausibility of Dohan's exorphin hypothesis by providing a means to directly study the effects of such peptides. Accordingly, a review of the literature on the behavioral effects of food-derived opioid-like peptides in rodents was undertaken. Studies using a variety of behavioral tests to examine the effects of several classes of food-derived opioid-like peptides were identified and reviewed. Peptides derived from casein (β-casomorphins; BCMs, n=19), spinach (rubiscolins; RCs, n=4), and soy (soymorphins; SMs, n=1) were behaviorally active in various paradigms assessing nociception, spontaneous behavior, and memory. Surprisingly, only a single study evaluating a gluten-derived peptide (gliadorphin-7; GD-7, n=1) was identified and included in this review. In conclusion, food-derived peptides can affect rodent behavior, but more studies of GDs using diverse behavioral batteries are warranted. Assuming they occur in sufficient quantities during protein digestion and can access central opioid receptors (which entails crossing both the gastrointestinal and blood-brain barriers intact), these peptides may affect human behavior. Although BCMs and GDs may not be directly pathogenic in SZ, documented associations of casein and gluten sensitivity with SZ justify increased patient screening and dietary intervention where necessary.
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