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    How Solid is the Evidence for Non-celiac Gluten Sensitivity?


    Jefferson Adams
    Image Caption: Photo: CC--Owwe

    Celiac.com 05/15/2017 - For all the talk of studies touting evidence for non-celiac gluten sensitivity, the actual data don't stack up very well, according to an recent assessment by two researchers, whose results appear in Clinical Gastroenterology and Hepatology.


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    In an effort to determine the accuracy of using a double-blind, placebo-controlled study to confirm diagnosis of non-celiac gluten sensitivity in patients who respond to a gluten-free diet, researchers Javier Molina-Infante, and Antonio Carroccio recently set out to assess data on a series of such studies. Both researchers are affiliated with the Department of Gastroenterology, Hospital Universitario San Pedro de Alcantara in Caceres, Spain.

    For their study, the pair analyzed data from 10 separate double-blind, placebo-controlled, gluten-challenge trials on a total of 1312 adults. The available studies varied significantly in many ways. The duration of the gluten challenge, for example, varied from 1 day to 6 weeks. The daily doses for those gluten challenges varied from 2 grams to 52 grams, with 3 studies administering 8 grams or less each day. The composition of the gluten-free placebo also varied considerably between tests; including variation by gluten-free product type, and levels of xylose, whey protein, rice, or corn starch containing fermentable carbohydrates.

    Most of the studies did find gluten challenge to significantly increase symptom scores compared with placebo. However, out of 231 NCGS patients, only 38 patients (16%) showed gluten-specific symptoms. Moreover, nearly half (40%) of these patients showed similar or increased symptoms in response to placebo; something researchers term a 'nocebo' effect. That leaves just 6 or 7 patients out of 231 showing gluten-specific symptoms.

    The researchers also point to heterogeneity and to potential methodology flaws in gluten challenge studies. They also present powerful questions about gluten as the trigger for symptoms in most patients with presumptive NCGS. Lastly, they highlight the importance of the nocebo effect in these types of studies.

    These results certainly invite more careful, rigorous studies on the matter, and challenge researchers to provide solid data from well-crafted double-blind placebo controlled studies.

    Basically, what little evidence we thought we had to support the existence of non-celiac gluten sensitivity has been shown to be thin at best. Until solid evidence arrives, the status of non-celiac gluten sensitivity will remain open to question and doubt by both researchers and potential sufferers.

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    Guest F. Sawyer

    Posted

    First off to test positive for Gluten you must be on a full regiment of gluten foods when tested. And yes, there is such a thing as having the same symptoms when you do not test positive. In fact, these individuals are more sensitive that the ones who test positive. Because most of these people cannot even eat gluten free food.

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    Guest Jeff Adams

    Posted

    This study does not take a position on whether or not there might be a condition called non-celiac gluten sensitivity. Nor does the study negate the possibility that some people with celiac-like symptoms fail to test positive for anti-gliadin antibodies. The study merely describes the lack of evidence to support NCGS in double-blind studies. Could it still be a thing? Sure. Does the clinical evidence support it? Not in this study. Another serious problem, as pointed out by the study is the fact that 40% of patients routinely report celiac-like symptoms after receiving a placebo. This indicates either a psycho-somatic aspect to these symptoms, or possibly an unknown sensitivity. Either way, many questions need to be answered before we will have a solid scientific answer.

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    Guest aileen

    Posted

    First off to test positive for Gluten you must be on a full regiment of gluten foods when tested. And yes, there is such a thing as having the same symptoms when you do not test positive. In fact, these individuals are more sensitive that the ones who test positive. Because most of these people cannot even eat gluten free food.

    So true...I got tested many times for gluten sensibility and already got most of the tests available on the market (endoscopy,colonoscopy, barium, igA,igG) all with negative results. (except for early stage of Hashimoto (not confirmed by doctor yet) and probably IBS , but the doctor told me that she is not sure of right diagnosis, polycystic ovary, zero vitamin D, candida and pylori) anyway the gluten free product hurt my stomach more than the gluten. I can consume gluten for a week or two before my stomach gets upset, headaches and I start to get rash or eczema on my skin but it takes me a few gluten free cookies (2-3) to get upset stomach. At some point the doctor tell me is all stress and psychological problems.

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    Guest aileen

    Posted

    This study does not take a position on whether or not there might be a condition called non-celiac gluten sensitivity. Nor does the study negate the possibility that some people with celiac-like symptoms fail to test positive for anti-gliadin antibodies. The study merely describes the lack of evidence to support NCGS in double-blind studies. Could it still be a thing? Sure. Does the clinical evidence support it? Not in this study. Another serious problem, as pointed out by the study is the fact that 40% of patients routinely report celiac-like symptoms after receiving a placebo. This indicates either a psycho-somatic aspect to these symptoms, or possibly an unknown sensitivity. Either way, many questions need to be answered before we will have a solid scientific answer.

    Can it be possible that other genes cause this problem which are not yes discovered? It looks to me that there are not that many serious studies of non celiac gluten sensibility or possibly this can be connected to other autoimmune problems. There must be some connection that have been missing in the studies? Maybe there is something more than gluten that affects the autoimmune system and triggers all the problems?

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    Sources:
    1. Toft M, Dietrichs E. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson’s disease--two cases. BMC Neurol. 2011 Apr 8;11:44.
    2. Tani T, Sakai Y. Stuttering after right cerebellar infarction: a case study. J Fluency Disord. 2010 Jun;35(2):141-5. Epub 2010 Mar 15.
    3. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    4. Jäncke L, Hänggi J, Steinmetz H. Morphological brain differences between adult stutterers and non-stutterers. BMC Neurol. 2004 Dec 10;4(1):23.
    5. Kell CA, Neumann K, von Kriegstein K, Posenenske C, von Gudenberg AW, Euler H, Giraud AL. How the brain repairs stuttering. Brain. 2009 Oct;132(Pt 10):2747-60. Epub 2009 Aug 26.
    6. Galantucci S, Tartaglia MC, Wilson SM, Henry ML, Filippi M, Agosta F, Dronkers NF, Henry RG, Ogar JM, Miller BL, Gorno-Tempini ML. White matter damage in primary progressive aphasias: a diffusion tensor tractography study. Brain. 2011 Jun 11.
    7. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    8. [No authors listed] Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 43-1988. A 52-year-old man with persistent watery diarrhea and aphasia. N Engl J Med. 1988 Oct 27;319(17):1139-48
    9. Molteni N, Bardella MT, Baldassarri AR, Bianchi PA. Celiac disease associated with epilepsy and intracranial calcifications: report of two patients. Am J Gastroenterol. 1988 Sep;83(9):992-4.
    10. http://ezinearticles.com/?Food-Allergy-and-Stuttering-Link&id=1235725 
    11. http://www.craig.copperleife.com/health/stuttering_allergies.htm 
    12. https://www.celiac.com/forums/topic/73362-any-help-is-appreciated/
    13. Ford RP. The gluten syndrome: a neurological disease. Med Hypotheses. 2009 Sep;73(3):438-40. Epub 2009 Apr 29.
    14. Hadjivassiliou M, Gibson A, Davies-Jones GA, Lobo AJ, Stephenson TJ, Milford-Ward A. Does cryptic gluten sensitivity play a part in neurological illness? Lancet. 1996 Feb 10;347(8998):369-71.

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    Jefferson Adams
    Celiac.com 06/12/2018 - A life-long gluten-free diet is the only proven treatment for celiac disease. However, current methods for assessing gluten-free diet compliance are lack the sensitivity to detect occasional dietary transgressions that may cause gut mucosal damage. So, basically, there’s currently no good way to tell if celiac patients are suffering gut damage from low-level gluten contamination.
    A team of researchers recently set out to develop a method to determine gluten intake and monitor gluten-free dietary compliance in patients with celiac disease, and to determine its correlation with mucosal damage. The research team included ML Moreno, Á Cebolla, A Muñoz-Suano, C Carrillo-Carrion, I Comino, Á Pizarro, F León, A Rodríguez-Herrera, and C Sousa. They are variously affiliated with Facultad de Farmacia, Departamento de Microbiología y Parasitología, Universidad de Sevilla, Sevilla, Spain; Biomedal S.L., Sevilla, Spain; Unidad Clínica de Aparato Digestivo, Hospital Universitario Virgen del Rocío, Sevilla, Spain; Celimmune, Bethesda, Maryland, USA; and the Unidad de Gastroenterología y Nutrición, Instituto Hispalense de Pediatría, Sevilla, Spain.
    For their study, the team collected urine samples from 76 healthy subjects and 58 patients with celiac disease subjected to different gluten dietary conditions. To quantify gluten immunogenic peptides in solid-phase extracted urines, the team used a lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant GIPs and an LFT reader. 
    They detected GIPs in concentrated urines from healthy individuals previously subjected to gluten-free diet as early as 4-6 h after single gluten intake, and for 1-2 days afterward. The urine test showed gluten ingestion in about 50% of patients. Biopsy analysis showed that nearly 9 out of 10 celiac patients with no villous atrophy had no detectable GIP in urine, while all patients with quantifiable GIP in urine showed signs of gut damage.
    The ability to use GIP in urine to reveal gluten consumption will likely help lead to new and non-invasive methods for monitoring gluten-free diet compliance. The test is sensitive, specific and simple enough for clinical monitoring of celiac patients, as well as for basic and clinical research applications including drug development.
    Source:
    Gut. 2017 Feb;66(2):250-257. &nbsp;doi: 10.1136/gutjnl-2015-310148.