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  • Jefferson Adams
    Jefferson Adams
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    Study Suggests Some Patients with Celiac Disease Might Eat Gluten Without Adverse Effects

    Patients Diagnosed in Childhood Might Evolve toward Latency on a Normal Diet

    Celiac.com 05/23/2007 - The results of a study recently published in the journal Gut indicate that some people who suffer from celiac disease might not need to remain on a gluten free diet for their entire lives, and that some celiac patients might be able to safely introduce gluten containing foods without suffering a relapse.

    Previous Studies Showing Positive Response to Wheat Introduction in Patients with Celiac Disease are Promising, But Incomplete

    Several studies have shown that some patients diagnosed with celiac disease in childhood were able to remain on a gluten-containing diet after gluten challenge without suffering a relapse. However, most of these studies included a small number of patients, or followed the patients for only a short period after gluten was reintroduced into their diets.

    These previous studies also limited their evaluation largely to assessment of celiac disease serology and histology of duodenal biopsies, and did not attempt to identify what factors might predict the development of tolerance to gluten.

    Determining Long-term Response to Gluten Consumption in Celiac Disease Patients

    A research team made up of doctors Tamara Matysiak-Budnik (1), Georgia Malamut (1,2), Natacha Patey-Mariaud de Serre (3), Etienne Grosdidier (2), Sylvie Seguier (3), Nicole Brousse (3), Sophie Caillat-Zucman (4), Nadine Cerf-bensussan (1), Jacques Schmitz (5) and Christophe Cellier (1,2), set out to determine whether children diagnosed with celiac disease must follow a gluten free diet for life.

    To determine the effects of reintroducing gluten into the diets of celiac patients, the research team set out to monitor the clinical and physical progress of adult celiac patients who had been diagnosed as children, who underwent a gluten challenge, and who were asymptomatic.

    The study focused on a specific group of patients, all but two of whom were diagnosed as children and followed until adulthood in the Department of Pediatric Gastroenterology in Necker Hospital and thereafter at the Georges Pompidou European Hospital in Paris; after which, they were entered into a local register of adult celiac patients and were recruited for the study based on two criteria: celiac disease diagnosed in childhood; and adherence to a normal diet.

    The patients in the study were from 18 to 65 years old, and had been diagnosed with celiac disease in childhood. The research team recorded data in the following categories: biological parameters of malabsorption; bone mineral density; clinical celiac status; gluten intake; HLA genotype; serological markers of celiac disease; as well as histological and immuno-histochemical parameters in duodenal biopsies.


    Results Show 20% Long-term Latency in Celiac Patients who Eat Normal Diet

    Of those studied, 61 patients had returned to a normal diet, and were asymptomatic. 48 showed various degrees of villous atrophy (silent celiac disease), and 13 had no detectable atrophy (latent celiac disease) on duodenal biopsies. Compared to those with silent celiac disease, patients with latent celiac disease showed markedly less osteopenia/osteoporosis [1/9 (11%) versus 23/33 (70%), p<0.001)], and lower TcR- + intraepithelial T cell counts (38±20 vs. 55±15, p<0.01).

    Patients with latent celiac disease had a lower mean age at the time of their first gluten free diet compared to patients with silent celiac disease (14.4±5 vs 40.1±47 months, p<0.05).

    Compared to the seven control patients on a long-term gluten free diet, the latent patients did not differ significantly, except for a higher frequency of celiac disease-specific serum antibodies. However, a follow-up found that two of the patients with latent celiac disease had suffered a clinical and histological relapse.

    Results showed that of those patients who remained asymptomatic after the reintroduction of gluten, 20% showed long-term latency.

    The study concludes that some patients with celiac disease may not need to remain on a life-long gluten free diet, and that some may indeed be able to safely reintroduce gluten into their diets with no adverse effects. However, the latency patients may experience may be transient, and therefore a regular follow-up is necessary. Also, patients with silent celiac disease should remain on a gluten free diet.

    Participating hospitals:
    (1) INSERM, U793, Faculté de Médecine René Descartes, IFR94, Paris, France.
    (2) AP-HP, H&OCIRC;pital Européen Georges Pompidou, Department of Hepato-Gastroenterology,
    Paris, France.
    (3) AP-HP, H&OCIRC;pital Necker-Enfants Malades, Department of Pathology, Paris, France.
    (4) INSERM, Equipe Avenir, Faculté de Médecine René Descartes, Paris, France.
    (5) AP-HP, H&OCIRC;pital Necker-Enfants Malades, Department of Pediatric Gastroenterology, Paris, France.

    Gut 2006;13(10).

    Comments on this Study by Ron Hoggan

    • This is dressed up like a new finding, but it isn't. There are a number of studies that show similar findings. Part of that problem lies in the interpretation of the biopsies, and part of the problem arises out of failing to recognize the variable nature of the disease. It has long been known to wax and wane for reasons beyond our ken. Samuel Gee (1888) and Gibbons (1889) both reported the cyclic nature of their patients symptoms.
    • They cited a study to support the idea of a two year rule saying that relapse would usually occur within two years, yet Kuitunen P, Savilahti E, Verkasalo M., in Late mucosal relapse in a boy with coeliac disease and cows milk allergy. Acta Paediatr Scand. 1986 Mar;75(2):340-2. reported one patient who at 4.3 years on a normal diet showed normal villous architecture. It was not until a follow-up biopsy at more than 8 years of eating a gluten-containing diet that he showed villous atrophy.
    • These findings, along with all the other studies that have shown long delays in some patients before relapsing, argue strongly for Michael N. Marsh's position that we should concentrate on treating any immune system that is sensitized to gluten with a gluten-free diet. His rectal challenge is an excellent tool for identifying such sensitized immune systems. Dr. Fines fecal antibody test probably fits into the same category.
    • The underlying assumption is that the biopsy will identify all cases of intestinal lesion regardless of the possibility of patchy lesions that are well documented in the literature.
    • They deal with increased IEL counts as if they were a feature of latent celiac disease when that is not the case.
    • There are several other points on which this study falters. They admit that the latency can be transient. Unfortunately, they have not exchanged emails with people where they have returned to eating gluten and have developed an abdominal cancer. I exchanged emails with such a young man who blamed himself for having killed himself with his carelessness about his diet. How awful that was for him! Yet these authors seem to think it is quite acceptable for patients to indulge during their latency periods and only consider a diet if there is a relapse of intestinal lesion.

     


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    Ron Hoggan is very resistant to the idea that celiac disease may be 'curable' in a functional sense. I agree with him that we should be careful and strict about our diets until we have better understanding. However, I believe that the development of celiac disease is neither genetically preordained, nor is it a one-way ratchet. Studies strongly suggest that some family members of celiacs having the genetic predisposition never develop celiac disease. We need to pay attention to, and think openly and critically about, all ideas. Studying the relatively rare 'celiacs' who appear able to eat gluten seems like a good idea to me.

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  • About Me

    Jefferson Adams earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, and science. He previously served as Health News Examiner for Examiner.com, and provided health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

  • Related Articles

    Jefferson Adams
    Study Shows Gluten Intolerance Without Celiac Disease
    Celiac.com 02/14/2011 - In what may seem for some like an obvious finding, a team of Australian researchers has shown that people can suffer gluten intolerance without having celiac disease. Their study is published in The American Journal of Gastroenterology.
    I say obvious, because many in the celiac and surrounding community have long understood and accepted the concept of gluten-intolerance as distinct from celiac disease. Surprisingly, there has been very little scientific research to establish the existence of gluten-intolerance as distinct from celiac disease. That is changing, and the recent Australian study offers some support for gluten-intolerance as distinct from celiac disease.
    For their study, a team of researchers led by Peter Gibson, professor of medicine at Eastern Health Clinical School at Monash University in Australia, recruited 34 people with irritable bowel syndrome, but who were clinically proven to be free of celiac disease. All participants had previously benefited from a gluten-free diet.
    The 34 volunteers were all fed bread and muffins, half of which contained gluten, half of which were gluten-free. Nearly 70 per cent of the volunteers who ate the gluten reported pain, bloating, toilet problems and extreme tiredness.
    ''Gluten is indeed a trigger of gut symptoms and tiredness,'' the researchers concluded. Professor Gibson said: ''These symptoms have a big impact on quality of life. But conservative medicine has not been so good at dealing with this because we haven't had any evidence.''
    A number of the volunteers had sought help from alternative health practitioners, a fact that impaired recruitment of volunteers, as many of these folks had adopted a gluten-free diet without proving or disproving celiac disease via colonoscopy and biopsy.
    It was important for the team to exclude celiac disease for several reasons, including the fact that although it was safe to use gluten to test people who may have an intolerance, it could harm people with celiac disease.
    "If you go back on gluten while you have celiac disease - even if you only eat a few pieces of bread - you will damage your body and undo many months of healing," Professor Gibson said.
    For that reason, and also to prove gluten intolerance alone was the symptom cause, the team recruited people  clinically proven to be free of celiac disease, and who were already on gluten-free diets.
    For those patients with irritable bowel syndrome, excluding celiac disease, who were symptomatically controlled on a gluten-free diet, the team crafted a double-blind, randomized, placebo-controlled re-challenge trial.
    Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. The team evaluated symptoms using a visual analog scale and markers of intestinal inflammation, injury, and immune activation monitoring.
    A total of 4 men and 30 women between the ages of 29–59-years old completed the study as per protocol. Overall, 56% showed human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high.
    Of 19 patients (68%) in the gluten-consuming group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation).
    On a visual analog scale, patients were significantly worse within one week of consuming gluten for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001).
    In no cases did gluten-consumption trigger anti-gliadin antibodies. Moreover, there where were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with the DQ2/DQ8 and those without.
    Gibson calls the general lack of research into gluten intolerance "almost unbelievable." He plans to now investigate the prevalence of non-celiac gluten intolerance, why it occurs and whether low levels of gluten can be eaten safely.

    Source:

    American Journal of Gastroenterology: 11 January 2011. doi: 10.1038/ajg.2010.487

    Jefferson Adams
    Celiac.com 04/18/2012 - Biopharmaceutical development company, BioLineRx, has announced results from pre-clinical trials which show that their compound, BL-7010, an orally available treatment for celiac disease, reduces the toxic effects of gluten in patients with celiac disease.
    The findings, which appear in the February issue of Gastroenterology, show that BL-7010, which was previously labeled P(HEMA-co-SS, lowers gluten toxicity by  reducing the body's digestion of wheat gluten.
    The findings also show that BL-7010 also improves the immune response to gluten in rodents, as well as preventing gluten-induced pathological damage to the small intestine.
    Furthermore, they note that BL-7010 is not absorbed systemically, indicating that its gluten-neutralizing effects are likely safe. These data demonstrate BL-7010's therapeutic potential for reducing or blocking gluten-induced disorders in humans with celiac disease.
    Because it can be difficult to maintain a life-long, strict, gluten-free diet, the fact that BL-7010 may attenuate the immune response to gluten and reduce subsequent damage to the small intestine, suggests that this drug, or others like it may be useful in improving quality of life for millions of celiac disease patients.
    Source:

    http://www.news-medical.net/news/20120222/BioLineRx-BL-7010-may-reduce-gluten-toxicity-in-patients-with-celiac-disease.aspx

    Jefferson Adams
    Celiac.com 06/13/2012 - In general, doctors and researchers know a good deal about how celiac disease works, and they are finding out more all the time. However, they know very little about non-celiac gluten sensitivity (NCGS).
    In an effort to learn more about non-celiac gluten sensitivity, a team of researchers recently carried out a study to measure the presence of somatization, personality traits, anxiety, depression, and health-related quality of life in NCGS individuals, and to compare the results with celiac disease patients and healthy control subjects. They also compared the response to gluten challenge between patients with non-celiac gluten sensitivity and those with celiac disease.
    The research team included M. Brottveit, P.O. Vandvik, S. Wojniusz, A. Løvik, K.E. Lundin, and B. Boye, of the Department of Gastroenterology at Oslo University Hospital, Ullevål in Oslo, Norway.
    In all, the team looked at 22 patients with celiac disease and 31 HLA-DQ2+ NCGS patients without celiac disease. All patients were following a gluten-free diet.
    Over a three day period, the team challenged 17 of the celiac disease patients with orally ingested gluten. They then recorded the symptoms reported by those patients. They did the same with a group of 40 healthy control subjects.
    The team then had both patients and healthy control subjects complete questionnaires regarding anxiety, depression, neuroticism and lie, hostility and aggression, alexithymia and health locus of control, physical complaints, and health-related quality of life.
    Interestingly, patients with non-celiac gluten sensitivity reported more abdominal (p = 0.01) and non-abdominal (p < 0.01) symptoms after the gluten challenge than patients with celiac disease. The increase in symptoms in non-celiac gluten sensitivity patients was not related to personality.
    However, the two groups both reported similar responses regarding personality traits, level of somatization, quality of life, anxiety, and depressive symptoms. Responses for both groups were about the same as for healthy controls.
    The results showed that patients with non-celiac gluten sensitivity did not show any tendencies toward general somatization, as both celiac disease patients and those with non-celiac gluten sensitivity showed low somatization levels.
    Source:
    Scand J Gastroenterol. 2012 Apr 23.

    Jefferson Adams
    Celiac.com 02/04/2013 - Ever wonder what happens to all those celiac disease patients who volunteer to do a gluten-challenge in the name of science? Well, the short answer is that they likely suffer, and may incur gut damage, at least in the short term.
    A team of researchers looking for ways to reduce or eliminate that problem recently conducted a study using larazotide acetate, a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated problems.
    The research team included C. P. Kelly, P. H. R. Green, J. A. Murray, A. DiMarino, A. Colatrella, D. A. Leffler, T. Alexander, R. Arsenescu, F. Leon, J. G. Jiang, L. A. Arterburner, B. M. Paterson, R. N. and Fedorak. They are affiliated with the Celiac Center of Beth Israel Deaconess Medical Center at Harvard Medical School in Boston, the Celiac Disease Center at Columbia University in New York, NY, the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, MN, Thomas Jefferson University Hospital in Philadelphia, PA, the Pittsburgh Gastroenterology Associates in Pittsburgh, PA, with Gastrointestinal Specialists of Troy, MI, the Department of Internal Medicine at the University of Kentucky, in Lexington, KY, with Alba Therapeutics Corporation in Baltimore, MD, and with the Division of Gastroenterology at the University of Alberta in Edmonton, AB.
    The team wanted to find out how well larazotide acetate worked and how well it was tolerated by celiac disease patients undergoing a gluten challenge.
    To do this, the team conducted an exploratory, double-blind, randomized, placebo-controlled study that included 184 patients who maintained a gluten-free diet before and during the study.
    After a gluten-free diet run-in, the team randomly divided patients into groups and gave them either larazotide acetate in doses of 1, 4, or 8 mg three times daily, or a placebo. Both groups also received 2.7 grams of gluten daily for six weeks.
    The team then assessed ratios of lactulose-to-mannitol (LAMA), an experimental biomarker of intestinal permeability, and measured clinical symptoms by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels.
    They found no significant differences in LAMA ratios between larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (P = 0.002 vs. placebo).
    They did find that the average ratio of anti-tissue transglutaminase IgA levels was 19.0 over baseline in the placebo group compared with 5.78 (P = 0.010) in the 1mg larazotide acetate group, 3.88 (P = 0.005) in the 4mg larazotide acetate group, and 7.72 (P = 0.025) in the 8mg larazotide acetate group.
    Both the larazotide acetate and placebo groups showed similar rates of "adverse events."
    Overall, the team found that larazotide acetate reduced gluten-induced immune reactivity and symptoms in celiac disease patients undergoing gluten challenge and was generally well tolerated.
    However, the team found no significant difference in LAMA ratios between the larazotide acetate and placebo groups.
    Even though they did not find anything revolutionary, the results and design of their study will likely be helpful in shaping future gluten-challenge studies in patients with celiac disease.
    Source: 
    Aliment Pharmacol Ther. 2013;37(2):252-262.

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