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Celiac.com 02/14/2024 - Rising celiac disease rates pose a significant health challenge, yet the environmental triggers behind the rise remain elusive. Among the various potential factors, iron deficiency has emerged as a potential contributor to the development of celiac disease. A recent study, employing Mendelian randomization (MR), sought to investigate the intricate relationship between iron status and the prevalence of celiac disease. Understanding Mendelian Randomization Mendelian randomization (MR) is a powerful method that explores potential causal relationships between an exposure and an outcome. In this case, the researchers delved into the connection between genetic variants associated with iron status and the presence of celiac disease. Research Design The study adopted a two-sample MR approach, utilizing single nucleotide polymorphisms (SNPs) linked to iron status. These SNPs were derived from a meta-analysis of three genome-wide association studies (GWAS). The association between these SNPs and celiac disease was then assessed using GWAS summary statistics from the UK Biobank, which included data from 336,638 white British individuals, 1855 of whom had celiac disease. Key Findings - Higher Iron Status Inversely Related to Risk of Celiac Disease The team identified four SNPs strongly associated with systemic iron status. Notably, these were not linked to known risk factors for celiac disease. The harmonized analysis revealed a compelling association: higher iron status was inversely related to the risk of celiac disease. The odds ratio per one standard deviation increase in serum iron was 0.65, with a 95% confidence interval of 0.47 to 0.91. Crucially, leave-one-out analyses consistently supported these findings, and no single SNP disproportionately influenced the association. Importantly, all three assumptions of MR appeared plausible, strengthening the credibility of the study's conclusions. Conclusion and Implications The study's groundbreaking discovery that genetically lower iron levels are associated with an increased risk of celiac disease holds significant implications for prevention strategies. By shedding light on the potential role of iron status in the development of celiac disease, this research opens avenues for targeted interventions and preventive measures. As the scientific community continues to unravel the complex factors contributing to celiac disease, studies like these pave the way for a deeper understanding of the condition and, ultimately, more effective strategies for its prevention and management. This research not only adds valuable insights to the celiac disease puzzle but also underscores the potential impact of addressing iron status in the broader context of preventive healthcare. Read more in BMJ Open Gastroenterology

Celiac.com 10/22/2022 - Close to one quarter of the world’s population, in both industrialized and developing countries, suffer from iron deficiency and/or iron deficiency anemia. Although it is a widespread problem, those who are gluten sensitive should be particularly careful to monitor their iron status regularly. Iron deficiency is not only an important sign of undiagnosed celiac disease, it may also reflect some degree of intestinal damage—and most of our iron is absorbed in the same part of the intestine as calcium. The jejunum is the site of most of the damage caused by gluten, which may explain the significant overlap between gluten sensitivity and iron deficiency anemia. The two primary causes of iron deficiency are either inadequate absorption of iron or excessive blood loss, and intestinal bleeding is common among the gluten sensitive. Iron deficiency can also result from vitamin A deficiency, which can also be a feature of celiac disease. Several years after I began following a gluten-free diet, a blood test that was part of a regular physical exam revealed that I was mildly anemic. By now you may be wondering, just as I did, what the difference is between iron deficiency and iron deficiency anemia. Simply put, iron deficiency anemia is where the hemoglobin content of one’s blood is below normal. This means that there are fewer blood cells that carry oxygen to be distributed throughout the body. My greatest concern with my own inclination to anemia, both before and after diagnosis, is that iron deficiency can impair memory and reduce learning acuity. Most of this impact occurs prior to the development of anemia. Iron deficiency first depletes iron stores in a wide range of tissues and organs before it causes significant losses to hemoglobin. Iron is needed to make several neurotransmitters including dopamine, serotonin, and norepinepherine. These neurotransmitters are involved in a wide range of brain activities related to alertness, attention, remembering, learning, and a variety of other brain functions. Some researchers at the University of Maryland have reported that iron deficient adolescent girls show a significant improvement in IQ test scores after only 8 weeks of taking iron supplements. There are many other symptoms of iron deficiency, including shortness of breath, light-headedness, lethargy, and pale skin. However, it is important not to just rush out and start taking iron supplements. Iron overdose can cause damage to the liver, the heart, or the pancreas. The body must maintain an exquisitely careful balance for optimal health. Further, a significant number of celiacs also suffer from hereditary hemochromatosis which is a condition in which the body is overly thrifty, storing too much iron. Supplementing iron in such a case could have some very serious consequences. Regular testing is an important strategy. Iron deficiency or anemia is more likely to be ignored or to be given less attention simply because of the frequency with which it occurs. However, it is a particularly important issue to those who are gluten sensitive, if only from a quality-of-life perspective. Even if peace of mind is the only result of getting regular check-ups that include a complete blood count, our reward is large. Similarly, early detection and reversal of iron deficiency before it causes memory disturbances and other unwanted symptoms, or before it goes on to develop into anemia, could be a huge dividend to collect from paying careful attention to our iron levels.

Celiac.com 07/16/2020 - Iron deficiency is sometimes considered the most common sign of untreated celiac disease (1) so it may be surprising to learn that iron overload can also signal the presence of untreated celiac disease. I recently spoke at a support group in Comox, B.C. A member of the audience approached me afterward asking whether there is a link between celiac disease and hemochromatosis (iron overload). He has hemochromatosis, which is a genetic condition in which so much iron is stored in the body that it becomes toxic to organs such as the liver and kidneys. He also has celiac disease. In his case, a gluten-free diet seems to reduce his iron absorption which has led him to suspect that intestinal inflammation played a role in his excessive absorption of iron. He recently stated: “I was diagnosed with hemochromatosis in 1980 and had phlebotomies regularly until 2005 when I began a gluten free diet. It was the sudden drop in my ferritin level after going gluten free that made me begin to relate the two conditions because of the co-incident timing.” In my own experience where celiac disease and hemochromatosis have struck the same person, the opposite seems to happen. These patients only develop iron overload after their celiac disease has been diagnosed and they have adopted a gluten-free diet. However, when I began to search through the literature, I discovered that the gentleman in Comox is not alone. Geier et. al. reported in World Journal of Gastroenterology, that their 65 year old female patient, who was previously treated for almost ten years with regular phlebotomies (blood lettings) to dispose of excess iron (2) had developed celiac disease. The lady in question did eventually become anemic due to celiac disease. However, if one accepts the notion that celiac disease is a life-long illness, her celiac disease and hemochromatosis coexisted for many years, and her iron overload occurred in the context of untreated celiac disease. The authors of this paper argue that the intestinal damage caused by untreated celiac disease works against iron overload to establish something of a balance in iron metabolism that masks celiac disease. While this may or may not be true in some cases, it does not appear to apply to the case these authors offer as support for their argument. After all, for almost ten years, this patient underwent regular blood lettings to divest herself of excess iron. Since her celiac disease was undiagnosed and untreated during this same period this patient’s history may well suggest support for the notion that gluten ingestion may, in the context of hemochromatosis, somehow induce increased iron absorption. As this patent’s intestinal damage worsened, she eventually reached a point where she lost the capacity to absorb excessive, even adequate quantities of iron. However, during the years leading up to this stage, she was clearly absorbing and retaining too much iron. Since most intestinal damage, in the context of celiac disease, is to the region where most iron is absorbed, the issue may not be as simple as it appears. Geier and colleagues reported large shifts in the transport mechanisms that move iron across the intestinal barrier. The protein for absorbing ferrous iron (divalent metal transporter 1) was significantly reduced before beginning a gluten free diet but it rebounded quickly after treatment with the diet. It was not long before these proteins were more plentiful than is considered normal. Thus, the patient may soon have to undergo regular phlebotomies again. Understandably, the authors did not supply us with that information but it may provide data for a future publication. On the other hand, perhaps this patient will be like the gentleman I met in Comox. She, too, may be able to avoid phlebotomies if she carefully follows her gluten-free diet. Only time will tell. And it might prove very valuable to other celiacs if the authors publish this information in a follow-up article. Sources: Freeman, Hugh James. “Hepatobiliary and pancreatic disorders in celiac disease” World J Gastroenterol 2006 March 14;12(10):1503-1508 Geier A, Gartung C, Theurl I, Weiss G, Lammert F, Dietrich C, Weiskirchen R, Zoller H, Hermanns B, Matem S. “Occult celiac disease prevents penetrance of hemochromatosis” World J Gastroenterology 2005;11(21): 3323-3326

Celiac.com 10/17/2017 - Are primary care physicians under-testing for celiac disease in patients with iron deficiency anemia? A new survey of primary care doctors indicates that they are. It's fairly common for people with celiac disease to develop iron deficiency anemia (IDA), but researchers don't know much about the frequency with which primary care physicians test for celiac disease in patients with IDA. A team of researchers recently set out to describe how primary care doctors approach testing for celiac disease in asymptomatic patients with IDA. The research team included Marisa Spencer, Adrienne Lenhart, Jason Baker, Joseph Dickens, Arlene Weissman, Andrew J. Read, Seema Saini, and Sameer D. Saini. They are variously affiliated with the Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America; the Department of Internal Medicine, Henry Ford Health System, in Detroit, Michigan, United States of America; the Department of Statistics, University of Michigan, Ann Arbor, Michigan, United States of America; the Research Center at the American College of Physicians, in Philadelphia, Pennsylvania, United States of America; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America, Ambulatory Care, Veterans Affairs Medical Center, Ann Arbor, Michigan, United States of America. For their study, the team began by electronically distributing a survey to primary care doctors who are members of the American College of Physicians. The survey asked whether doctors would test for celiac disease, either by serologic testing, referral for esophagogastroduodenoscopy [EGD], or referral to GI) in hypothetical patients with new IDA, including: (1) a young Caucasian man, (2) a premenopausal Caucasian woman, (3) an elderly Caucasian man, and (4) a young African American man. The team chose the scenarios to assess differences in testing for celiac disease based on age, gender, and race. They used multivariable logistic regression to identify independent predictors of testing. Testing for celiac disease varied significantly according to patient characteristics, with young Caucasian men being the most frequently tested (61% of respondents reporting they would perform serologic testing in this subgroup (p Interestingly 80% of doctors surveyed said they would definitely or probably start a patient with positive serologies for celiac disease on a gluten-free diet prior to confirmatory upper endoscopy, which is contrary to guideline recommendations. This survey indicates that primary care doctors are under-testing for celiac disease in patients with IDA, regardless of age, gender, race, or post-menopausal status. The majority of primary care doctors surveyed do not strictly adhere to established guidelines regarding a confirmatory duodenal biopsy in a patient with positive serology for celiac disease. Clearly, even with all of the advances in celiac disease awareness and with more refined protocols, primary care doctors have some work to do when it comes to testing IDA patients for celiac disease, and even more work to do in following proper referral guidelines before putting patients on a gluten-free diet. Source: PLOSONE