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    Untangling the Relationship Between Celiac Disease and Infertility


    Diana Gitig Ph.D.

    Celiac.com 07/11/2011 - Is celiac disease associated with infertility? Although some reports suggest that as much of 8% of women with unexplained infertility have celiac disease, others found no correlation between the two conditions. And there is little hard evidence that celiac disease is an actual cause of infertility. To begin to bring some clarity to this issue, Khoshbaten et al. tried to determine the prevalence of celiac disease among couples with unexplained infertility in Iran. Their results are reported in the Journal of Obstetrics and Gynaecology Research.


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    Infertile couples were recruited in Tabriz, Iran, between October 2006 and September 2007. After a complete evaluation of their endocrine status, one hundred couples with unexplained infertility were chosen for this study. Two hundred couples with at least one child and no reproductive problems served as controls. Thirteen infertile subjects - 5 men and 8 women - had elevated levels of tissue transglutaminase antibodies, compared to eleven controls - 4 men and 7 women. Fourteen infertile subjects and eleven controls were found to be IgA deficient; of these, three of each had elevated tissue transglutaminase IgG. Based on this serology, the researchers note that the likelihood of celiac disease in infertile patients is 2.39 times higher than in controls; the frequency of celiac disease is 8% in infertile patients, compared to 3.5% in controls.

    Only five infertile subjects and four controls with elevated tissue transglutaminase antibodies agreed to have duodenal mucosal biopsies; the remainder had no gastrointestinal complaints or other symptoms, so they opted out of the endoscopy. According to the biopsy, celiac disease was indicated in three cases of unexplained infertility compared to one case in the control group.

    Previous studies have demonstrated that men with celiac disease have an increased incidence of hypogonadism, sexual dysfunction, and poor semen quality. Women with celiac disease can have major menstrual problems. Systemic diseases like celiac can exert subtle effects on the reproductive system in both genders. A gluten free diet can alleviate infertility if it is caused by nutritional imbalances due to celiac disease, such as malabsorption of zinc, selenium, iron, and folate.

    This Iranian study, like previous studies in Finland, Italy, Israel, and the US, thus seems to come down on the side of celiac disease, as measured by serological markers, being more significantly frequent among couples with unexplained infertility than in controls.

    Source:

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  • Related Articles

    Scott Adams
    Hyperprolactinaemia is seen in 25% of celiac patients, which causes impotence and loss of libido. This quote was taken from an abstract at the following cite: Dig Dis, 12(3):186-190 1994, May-Jun. The title of the article is Infertility, Obstetric and Gynaecological Problems in Celiac Sprue. Here are some more references:
    Molteni N, Bardella MT, Bianchi PA. Obstetric and gynecological problems in women with untreated celiac sprue. J Clin Gastroenterol 1990; 12: 37-9. Sher KS, Mayberry JF. Female fertility, obstetric and gynaecological history in celiac disease. A case control study. Digestion 1994; 55: 243-6. Sher KS, Jayanthi V, Probert CS, Stewart CR, Mayberry JF. Infertility, obstetric and gynaecological problems in celiac sprue. Dig Dis 1994; 12:186-90. McCann JP, Nicholls DP, Verzin JA. Adult celiac disease presenting with infertility. Ulster Med J 1988; 57: 88-9. Ferguson R, Holmes GKT, Cooke WT. Celiac disease, fertility and pregnancy. Scand J Gastroenterol 1982; 17: 65-8. The good news is that the overwhelming opinion was that adherence to a strict gluten free diet should and would restore fertility if the infertility was a result of celiac disease.

    Jefferson Adams
    Celiac.com 12/08/2011 - Researchers have shown that celiac disease and Toxoplasma gondii infection can both cause a strong neutrophil-mediated immune reaction that can have an adverse impact pregnancy outcomes.
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    This suggests that celiac disease may increase the risk of Toxoplasma gondii infection.
    From these observations, the research team proposes that celiac disease predisposes individuals to Toxoplasma gondii infection and may promote distribution of the ingested Toxoplasma gondii oocysts beyond small bowel lesions and might increase sensitivity to gluten in some way.
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    Source:

    American Journal of Gastroenterology doi: 10.1038 / ajg.2010.425

    Diana Gitig Ph.D.
    Celiac.com 12/20/2011 - There has been some controversy surrounding the idea that there is a higher prevalence of undiagnosed celiac disease in people with infertility, with some studies finding it but others not. Most of these studies have been performed in Europe; only two to date have taken place in the United States. Peter Green’s group at Columbia recently tried to establish the actual prevalence of undiagnosed celiac disease in the infertile population in the United States, to determine if it would make sense to routinely screen a subgroup of infertile patients for celiac disease. Their results are published in The Journal of Reproductive Medicine.
    Study participants were recruited from the population who came to Columbia’s Center for Women’s Reproductive Care to deal with their infertility issues, which they had been coping with for at least a year. One hundred eight-eight women, ages 25-39, volunteered to participate in the study. They underwent serological screening for tissue transglutaminase (tTG IgA) and endomysial antibodies (EMA IgA), and measurement of total IgA and both IgA and IgG antigliadin antibodies was done to control for the potential IgA deficiency in some individuals. Four of the 188 patients enrolled in the study were diagnosed with celiac disease, making the prevalence of celiac disease in this population 2.1%. Yet a subgroup analysis of the prevalence of celiac disease in women with unexplained fertility revealed a prevalence of 5.9%, which achieves statistical significance.
    All four women reported suffering from gastrointestinal symptoms before their diagnosis, and they had a significantly increased prevalence of Irritable Bowel Syndrome as well. The authors admit that this is quite a small sample, and because screening was voluntary, it is also a selected population.
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    All four women conceived within ten months after starting on a gluten free diet, two naturally and two with help. And all of them went on to deliver healthy babies.
    Source:

    Choi JM, Lebwohl B, Wang J, Lee SK, Murray JA, Sauer MV, Green PH. Increased prevalence of celiac disease in patients with unexplained infertility in the United States. J Reprod Med. 2011 May-Jun; 56(5-6):199-203.

    Jefferson Adams
    Celiac.com 11/05/2012 - Over the last 40 years, studies have shown higher rates of menstrual abnormalities and pregnancy complications among women with celiac disease.
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    Because it is an abstract, the study data and conclusions should be regarded as preliminary until they appear in a peer-reviewed journal, where they can be given a fuller context and be more widely scrutinized.
    For their study, Dr. Moleski and her colleagues recruited patients treated for celiac disease at Thomas Jefferson University Hospitals, as well as members of the National Foundation for Celiac Awareness and the Gluten Intolerance Group, to respond in an anonymous Internet-based survey about fertility and pregnancy. Women without celiac disease also completed the survey and served as a control group.
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    The data also revealed important differences between women with and without celiac disease. In all, 22.4% of women with celiac disease had consulted with fertility specialists, compared with 19% of those without (P=0.04). Also, 43.3% of celiacs had a history of spontaneous abortion, compared with 36.6% of non-celiacs (P=0.02).
    Compared with the control group of non-celiacs, women with celiac disease also had higher rates of cesarean delivery, 26.4% versus 23.8% of non-celiac women.
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    Among women reporting a history of spontaneous abortion, more than 80% of miscarriages occurred prior to diagnosis of celiac disease, said Dr. Moleski.
    She concluded that the retrospective analysis done by her team shows a clear relationship between celiac disease, fertility, and pregnancy outcomes, and suggests that the results demonstrate "a need for increased awareness of this association among patients and physicians."
    Sources:
    Medpagetoday.com American College of Gastroenterology, 2012; Moleski SM, et al "Infertility and pregnancy outcomes in celiac disease" ACG 2012; Abstract 15.

  • Recent Articles

    Jefferson Adams
    Celiac.com 06/19/2018 - Could baking soda help reduce the inflammation and damage caused by autoimmune diseases like rheumatoid arthritis, and celiac disease? Scientists at the Medical College of Georgia at Augusta University say that a daily dose of baking soda may in fact help reduce inflammation and damage caused by autoimmune diseases like rheumatoid arthritis, and celiac disease.
    Those scientists recently gathered some of the first evidence to show that cheap, over-the-counter antacids can prompt the spleen to promote an anti-inflammatory environment that could be helpful in combating inflammatory disease.
    A type of cell called mesothelial cells line our body cavities, like the digestive tract. They have little fingers, called microvilli, that sense the environment, and warn the organs they cover that there is an invader and an immune response is needed.
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    That message, which is transmitted with help from a chemical messenger called acetylcholine, seems to encourage the gut to shift against inflammation, say the scientists.
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    The research was funded by the National Institutes of Health.
    Read more at: Sciencedaily.com

    Jefferson Adams
    Celiac.com 06/18/2018 - Celiac disease has been mainly associated with Caucasian populations in Northern Europe, and their descendants in other countries, but new scientific evidence is beginning to challenge that view. Still, the exact global prevalence of celiac disease remains unknown.  To get better data on that issue, a team of researchers recently conducted a comprehensive review and meta-analysis to get a reasonably accurate estimate the global prevalence of celiac disease. 
    The research team included P Singh, A Arora, TA Strand, DA Leffler, C Catassi, PH Green, CP Kelly, V Ahuja, and GK Makharia. They are variously affiliated with the Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Lady Hardinge Medical College, New Delhi, India; Innlandet Hospital Trust, Lillehammer, Norway; Centre for International Health, University of Bergen, Bergen, Norway; Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Gastroenterology Research and Development, Takeda Pharmaceuticals Inc, Cambridge, MA; Department of Pediatrics, Università Politecnica delle Marche, Ancona, Italy; Department of Medicine, Columbia University Medical Center, New York, New York; USA Celiac Disease Center, Columbia University Medical Center, New York, New York; and the Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India.
    For their review, the team searched Medline, PubMed, and EMBASE for the keywords ‘celiac disease,’ ‘celiac,’ ‘tissue transglutaminase antibody,’ ‘anti-endomysium antibody,’ ‘endomysial antibody,’ and ‘prevalence’ for studies published from January 1991 through March 2016. 
    The team cross-referenced each article with the words ‘Asia,’ ‘Europe,’ ‘Africa,’ ‘South America,’ ‘North America,’ and ‘Australia.’ They defined celiac diagnosis based on European Society of Pediatric Gastroenterology, Hepatology, and Nutrition guidelines. The team used 96 articles of 3,843 articles in their final analysis.
    Overall global prevalence of celiac disease was 1.4% in 275,818 individuals, based on positive blood tests for anti-tissue transglutaminase and/or anti-endomysial antibodies. The pooled global prevalence of biopsy-confirmed celiac disease was 0.7% in 138,792 individuals. That means that numerous people with celiac disease potentially remain undiagnosed.
    Rates of celiac disease were 0.4% in South America, 0.5% in Africa and North America, 0.6% in Asia, and 0.8% in Europe and Oceania; the prevalence was 0.6% in female vs 0.4% males. Celiac disease was significantly more common in children than adults.
    This systematic review and meta-analysis showed celiac disease to be reported worldwide. Blood test data shows celiac disease rate of 1.4%, while biopsy data shows 0.7%. The prevalence of celiac disease varies with sex, age, and location. 
    This review demonstrates a need for more comprehensive population-based studies of celiac disease in numerous countries.  The 1.4% rate indicates that there are 91.2 million people worldwide with celiac disease, and 3.9 million are in the U.S.A.
    Source:
    Clin Gastroenterol Hepatol. 2018 Jun;16(6):823-836.e2. doi: 10.1016/j.cgh.2017.06.037.

    Jefferson Adams
    Celiac.com 06/16/2018 - Summer is the time for chips and salsa. This fresh salsa recipe relies on cabbage, yes, cabbage, as a secret ingredient. The cabbage brings a delicious flavor and helps the salsa hold together nicely for scooping with your favorite chips. The result is a fresh, tasty salsa that goes great with guacamole.
    Ingredients:
    3 cups ripe fresh tomatoes, diced 1 cup shredded green cabbage ½ cup diced yellow onion ¼ cup chopped fresh cilantro 1 jalapeno, seeded 1 Serrano pepper, seeded 2 tablespoons lemon juice 2 tablespoons red wine vinegar 2 garlic cloves, minced salt to taste black pepper, to taste Directions:
    Purée all ingredients together in a blender.
    Cover and refrigerate for at least 1 hour. 
    Adjust seasoning with salt and pepper, as desired. 
    Serve is a bowl with tortilla chips and guacamole.

    Dr. Ron Hoggan, Ed.D.
    Celiac.com 06/15/2018 - There seems to be widespread agreement in the published medical research reports that stuttering is driven by abnormalities in the brain. Sometimes these are the result of brain injuries resulting from a stroke. Other types of brain injuries can also result in stuttering. Patients with Parkinson’s disease who were treated with stimulation of the subthalamic nucleus, an area of the brain that regulates some motor functions, experienced a return or worsening of stuttering that improved when the stimulation was turned off (1). Similarly, stroke has also been reported in association with acquired stuttering (2). While there are some reports of psychological mechanisms underlying stuttering, a majority of reports seem to favor altered brain morphology and/or function as the root of stuttering (3). Reports of structural differences between the brain hemispheres that are absent in those who do not stutter are also common (4). About 5% of children stutter, beginning sometime around age 3, during the phase of speech acquisition. However, about 75% of these cases resolve without intervention, before reaching their teens (5). Some cases of aphasia, a loss of speech production or understanding, have been reported in association with damage or changes to one or more of the language centers of the brain (6). Stuttering may sometimes arise from changes or damage to these same language centers (7). Thus, many stutterers have abnormalities in the same regions of the brain similar to those seen in aphasia.
    So how, you may ask, is all this related to gluten? As a starting point, one report from the medical literature identifies a patient who developed aphasia after admission for severe diarrhea. By the time celiac disease was diagnosed, he had completely lost his faculty of speech. However, his speech and normal bowel function gradually returned after beginning a gluten free diet (8). This finding was so controversial at the time of publication (1988) that the authors chose to remain anonymous. Nonetheless, it is a valuable clue that suggests gluten as a factor in compromised speech production. At about the same time (late 1980’s) reports of connections between untreated celiac disease and seizures/epilepsy were emerging in the medical literature (9).
    With the advent of the Internet a whole new field of anecdotal information was emerging, connecting a variety of neurological symptoms to celiac disease. While many medical practitioners and researchers were casting aspersions on these assertions, a select few chose to explore such claims using scientific research designs and methods. While connections between stuttering and gluten consumption seem to have been overlooked by the medical research community, there is a rich literature on the Internet that cries out for more structured investigation of this connection. Conversely, perhaps a publication bias of the peer review process excludes work that explores this connection.
    Whatever the reason that stuttering has not been reported in the medical literature in association with gluten ingestion, a number of personal disclosures and comments suggesting a connection between gluten and stuttering can be found on the Internet. Abid Hussain, in an article about food allergy and stuttering said: “The most common food allergy prevalent in stutterers is that of gluten which has been found to aggravate the stutter” (10). Similarly, Craig Forsythe posted an article that includes five cases of self-reporting individuals who believe that their stuttering is or was connected to gluten, one of whom also experiences stuttering from foods containing yeast (11). The same site contains one report of a stutterer who has had no relief despite following a gluten free diet for 20 years (11). Another stutterer, Jay88, reports the complete disappearance of her/his stammer on a gluten free diet (12). Doubtless there are many more such anecdotes to be found on the Internet* but we have to question them, exercising more skepticism than we might when reading similar claims in a peer reviewed scientific or medical journal.
    There are many reports in such journals connecting brain and neurological ailments with gluten, so it is not much of a stretch, on that basis alone, to suspect that stuttering may be a symptom of the gluten syndrome. Rodney Ford has even characterized celiac disease as an ailment that may begin through gluten-induced neurological damage (13) and Marios Hadjivassiliou and his group of neurologists and neurological investigators have devoted considerable time and effort to research that reveals gluten as an important factor in a majority of neurological diseases of unknown origin (14) which, as I have pointed out previously, includes most neurological ailments.
    My own experience with stuttering is limited. I stuttered as a child when I became nervous, upset, or self-conscious. Although I have been gluten free for many years, I haven’t noticed any impact on my inclination to stutter when upset. I don’t know if they are related, but I have also had challenges with speaking when distressed and I have noticed a substantial improvement in this area since removing gluten from my diet. Nonetheless, I have long wondered if there is a connection between gluten consumption and stuttering. Having done the research for this article, I would now encourage stutterers to try a gluten free diet for six months to see if it will reduce or eliminate their stutter. Meanwhile, I hope that some investigator out there will research this matter, publish her findings, and start the ball rolling toward getting some definitive answers to this question.
    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.

    Jefferson Adams
    Celiac.com 06/14/2018 - Refractory celiac disease type II (RCDII) is a rare complication of celiac disease that has high death rates. To diagnose RCDII, doctors identify a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs). 
    However, researchers really don’t have much data regarding the frequency and significance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. Such data could provide useful comparison information for patients with RCDII, among other things.
    To that end, a research team recently set out to try to get some information about the frequency and importance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. The research team included Shafinaz Hussein, Tatyana Gindin, Stephen M Lagana, Carolina Arguelles-Grande, Suneeta Krishnareddy, Bachir Alobeid, Suzanne K Lewis, Mahesh M Mansukhani, Peter H R Green, and Govind Bhagat.
    They are variously affiliated with the Department of Pathology and Cell Biology, and the Department of Medicine at the Celiac Disease Center, New York Presbyterian Hospital/Columbia University Medical Center, New York, USA. Their team analyzed results of TCR-GR analyses performed on SB biopsies at our institution over a 3-year period, which were obtained from eight active celiac disease, 172 celiac disease on gluten-free diet, 33 RCDI, and three RCDII patients and 14 patients without celiac disease. 
    Clonal TCR-GRs are not infrequent in cases lacking features of RCDII, while PCPs are frequent in all disease phases. TCR-GR results should be assessed in conjunction with immunophenotypic, histological and clinical findings for appropriate diagnosis and classification of RCD.
    The team divided the TCR-GR patterns into clonal, polyclonal and prominent clonal peaks (PCPs), and correlated these patterns with clinical and pathological features. In all, they detected clonal TCR-GR products in biopsies from 67% of patients with RCDII, 17% of patients with RCDI and 6% of patients with gluten-free diet. They found PCPs in all disease phases, but saw no significant difference in the TCR-GR patterns between the non-RCDII disease categories (p=0.39). 
    They also noted a higher frequency of surface CD3(−) IELs in cases with clonal TCR-GR, but the PCP pattern showed no associations with any clinical or pathological feature. 
    Repeat biopsy showed that the clonal or PCP pattern persisted for up to 2 years with no evidence of RCDII. The study indicates that better understanding of clonal T cell receptor gene rearrangements may help researchers improve refractory celiac diagnosis. 
    Source:
    Journal of Clinical Pathologyhttp://dx.doi.org/10.1136/jclinpath-2018-205023