1.
The Association between ADHD and Celiac Disease in Children.
Gaur, S
Children (Basel, Switzerland). 2022;9(6)
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Untreated coeliac disease (CeD) can be accompanied by an array of neurological symptoms. Some of these symptoms are similar to those observed in attention deficit hyperactive disorder (ADHD), like an inability to focus, lack of mental alertness, physical under-activity and clinically measurable under-activity in particular brain regions. The mechanism of such symptoms is not fully understood but is thought to be linked to low-grade inflammation in the brain as a result of permeability in the gut and blood-brain barrier, which could contribute to the presentation of ADHD-like symptoms. CeD can persist for many years in seemingly healthy people (silent CeD) without gut symptoms. In this period, ADHD-like symptoms are particularly common and may be treatment resistant if not accompanied by a gluten-free diet Since 2015, there have been several studies showing an association between CeD and ADHD. This is an updated systematic review including 23 studies of children and young adults, which found an association between ADHD and CeD, in contrast to previous reviews that found no clear association. This review paid particular attention to the diagnostic criteria of ADHD and its subtypes, highlighting the need to examine the subtypes of ADHD in future studies. Specifically, the inattentive subtype may be a behavioural ADHD phenotype that could respond to a gluten-free diet. The authors advocate screening ADHD patients for CeD and encourage the consideration of non-neurological symptoms in the assessment of ADHD to identify potential CeD cases.
Expert Review
Conflicts of interest:
None
Take Home Message:
- There is an association between celiac disease (CeD) and attention deficit hyperactive disorder (ADHD).
- Some children with ADHD may respond well to gluten-free diet.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This systematic review explored the association between coeliac disease (CeD) and attention deficit hyperactive disorder (ADHD).
Methods
The review was conducted following the PRISMA reporting guidelines.
Inclusion criteria for the search:
- Search terms of ADHD and CeD
- Participants < 18 years.
52 papers were retrieved and screened
23 met inclusion/exclusion criteria
Results
- 13 studies (out of the 23) demonstrated an association between ADHD and CeD
- Most studies reporting a positive association were published post 2015
- The largest study reported (112,240 patients with CeD) demonstrates that ADHD showed an association of OR = 1.75 in in CeD.
- The study was limited by several factors including study design of the studies included in the review, which were mostly observational and some without control.
The author declares no conflict of interest.
Clinical practice applications:
- Evidence from across the literature suggests that children with untreated or newly diagnosed CeD may find that following a gluten-free diet can help improve some symptoms associated with ADHD
- The author suggests that there may be a behavioural phenotype of ADHD that responds to a gluten-free diet. If this is the case, it suggests that screening of ADHD patients for celiac disease may be important.
Considerations for future research:
- The number of studies were relatively small and varied in design. Further large-scale studies would help further inform the understanding of the association and potential therapeutic benefits of gluten-free diet.
- It would be interesting to further explore how different subtypes of ADHD, especially the inattentive subtype, may be associated with CeD.
- In particular, it might be useful to consider how the clinical construct of sluggish cognitive tempo (SCT) is associated, since SCT symptoms overlap with the neurological manifestations of CeD.
Abstract
UNLABELLED Controversy around the association between celiac disease (CeD) and attention deficit hyperactive disorder (ADHD) was addressed by a systematic review in 2015, ultimately showing no association. Since 2015, there have been several studies showing an association between celiac disease and attention deficit hyperactive disorder. This is an updated systematic review. BACKGROUND Most experts agree on the recommendation to not screen as part of the standard of care for ADHD in persons with CeD or vice versa. Simultaneously, they propose that untreated patients with CeD and neurological symptoms such as chronic fatigue, inattention, pain, and headache could be predisposed to ADHD-like behavior, namely inattention (which may be alleviated by following a gluten-free diet). The inattentive subtype of ADHD that encompasses the symptoms of inattention is phenotypically heterogeneous, as it includes the clinical construct of sluggish cognitive tempo (SCT). SCT symptoms overlap with the neurological manifestations of CeD. METHODS A systematic search (PRISMA) of PubMed, Google Scholar, EMBASE, Web of Science, Stanford Lane, SCOPUS, and Ovid was conducted for articles up to 21 February 2022. Of these, 23 studies met the criteria. RESULTS Out of the 23 studies, 13 showed a positive association between ADHD and CeD. Most studies that showed a positive association had been published in the last five years. Inconsistencies in the results remain due to the heterogeneous methodology used, specifically for ADHD and the outcome questionnaires, as well as a lack of reporting on ADHD subtypes. CONCLUSION There is an association between ADHD and celiac disease. The current methodological limitations will be lessened if we examine the subtypes of ADHD.
2.
Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review.
Martín-Masot, R, Nestares, MT, Diaz-Castro, J, López-Aliaga, I, Alférez, MJM, Moreno-Fernandez, J, Maldonado, J
Nutrients. 2019;11(11)
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Anaemia is a common clinical expression of Celiac Disease (CD) alongside vitamin B12, iron and folate deficiencies. This review looks at the latest evidence and effects of a gluten free diet, the mainstay of treatment for CD. Typically, symptoms subside whilst adhering to a GF diet however in 20% of people anaemia and nutrient deficiencies can persist. Some of this is attributed to lack of adherence to the diet, oftentimes accidental given the wide range of foods containing gluten. This in turn leads to further damage of the intestine and can be difficult to detect and monitor effectively. Inflammation of the gastrointestinal tract, and malabsorption, are the main reasons for nutrient deficiencies leading to anaemia in CD. Iron is a critical nutrient which can easily be affected by damage to the intestinal villi, common in CD, and over time lead to iron deficiency anaemia as the body is unable to absorb dietary iron and the body’s iron stores are depleted. Likewise, absorption of vitamins B12 and B9 (folate) are also impaired by damaged villi and vitamin B12 is further affected by small intestine injuries including decreased gastric acid production, bacterial overgrowth and reduced intrinsic factor efficiency. Deficiencies of these two nutrients can lead to macrocytic anaemia with low blood cell volumes. Overall a gluten free diet is shown to reduce symptoms of CD in a matter of weeks. The more patients adhere to the diet, the more the risk of nutrient deficiencies and anaemia reduces.
Abstract
Celiac disease (CD) is a multisystemic disorder with different clinical expressions, from malabsorption with diarrhea, anemia, and nutritional compromise to extraintestinal manifestations. Anemia might be the only clinical expression of the disease, and iron deficiency anemia is considered one of the most frequent extraintestinal clinical manifestations of CD. Therefore, CD should be suspected in the presence of anemia without a known etiology. Assessment of tissue anti-transglutaminase and anti-endomysial antibodies are indicated in these cases and, if positive, digestive endoscopy and intestinal biopsy should be performed. Anemia in CD has a multifactorial pathogenesis and, although it is frequently a consequence of iron deficiency, it can be caused by deficiencies of folate or vitamin B12, or by blood loss or by its association with inflammatory bowel disease (IBD) or other associated diseases. The association between CD and IBD should be considered during anemia treatment in patients with IBD, because the similarity of symptoms could delay the diagnosis. Vitamin B12 deficiency is common in CD and may be responsible for anemia and peripheral myeloneuropathy. Folate deficiency is a well-known cause of anemia in adults, but there is little information in children with CD; it is still unknown if anemia is a symptom of the most typical CD in adult patients either by predisposition due to the fact of age or because biochemical and clinical manifestations take longer to appear.
3.
Movement Disorders Related to Gluten Sensitivity: A Systematic Review.
Vinagre-Aragón, A, Zis, P, Grunewald, RA, Hadjivassiliou, M
Nutrients. 2018;10(8)
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Gluten related disorders (GRDs) is an umbrella term for diseases triggered by gluten, including coeliac disease and gluten sensitivity. People with GRDs may experience a wide range of symptoms including digestive and nervous system issues. Movement Disorders (MDs) refers to a group of nervous system conditions that cause abnormal movements, which may be voluntary or involuntary. This literature review looked at the current research on GRDs and MDs such as epilepsy, Parkinson’s disease, restless leg syndrome and tremors. 48 papers were used for the review. Most papers looked at MDs in those diagnosed with coeliac disease, rather than other GRDs. The authors found many examples where the symptoms of MDs, including chorea, restless leg syndrome, stiff person syndrome and tics, improved on a gluten free diet. The authors concluded that gluten-related MDs may be more common than previously thought, and that following a gluten free diet can be beneficial in many cases. They recommended that gluten sensitivity and coeliac disease should be considered in patients with MDs of unknown cause.
Abstract
Gluten related disorders (GRD) represent a wide spectrum of clinical manifestations that are triggered by the ingestion of gluten. Coeliac disease (CD) or gluten sensitive enteropathy is the most widely recognised, but extra-intestinal manifestations have also been increasingly identified and reported. Such manifestations may exist in the absence of enteropathy. Gluten sensitivity (GS) is another term that has been used to include all GRD, including those where there is serological positivity for GS related antibodies in the absence of an enteropathy. Gluten ataxia (GA) is the commonest extraintestinal neurological manifestation and it has been the subject of many publications. Other movement disorders (MDs) have also been reported in the context of GS. The aim of this review was to assess the current available medical literature concerning MDs and GS with and without enteropathy. A systematic search was performed while using PubMed database. A total of 48 articles met the inclusion criteria and were included in the present review. This review highlights that the phenomenology of gluten related MDs is broader than GA and demonstrates that gluten-free diet (GFD) is beneficial in a great percentage of such cases.
4.
Fast food fever: reviewing the impacts of the Western diet on immunity.
Myles, IA
Nutrition journal. 2014;13:61
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This 2014 review delves into the impact that an over-indulgence in foods high in sugar, salt, saturated fats, genetically modified foods, gluten and artificial sweeteners may have on our immune system. The modern western diet is generally characterised as being abundant in these nutrient-poor foods, which exert an unhealthful impact on the body. They report that sugars increase inflammatory markers and reduce white blood cell production. Artificial sweeteners appear to be less inflammatory however data is limited. There is some suggestion that saccharin and sucralose interfere with digestive enzymes and are implicated in Inflammatory Bowel Disease. High salt may increase inflammatory cytokines. Saturated fats and high omega 6 fatty acids from vegetable oils increase inflammatory immune markers such as C-Reactive protein. Omega 3 polyunsaturated fats are generally associated with anti-inflammatory effects and regulating immune mediators. Gluten inappropriately activates an immune T-cell response. GM foods may have protective effects against malnutrition but have been shown to induce an allergic response in some cases. There is also concern that genetic modifications can be internalised by our gut bacteria and passed on to offspring. The review concludes that poor dietary choices are encoded into our gut and increase inflammation, and thus reduce our immune resilience to control infection.
Abstract
While numerous changes in human lifestyle constitute modern life, our diet has been gaining attention as a potential contributor to the increase in immune-mediated diseases. The Western diet is characterized by an over consumption and reduced variety of refined sugars, salt, and saturated fat. Herein our objective is to detail the mechanisms for the Western diet's impact on immune function. The manuscript reviews the impacts and mechanisms of harm for our over-indulgence in sugar, salt, and fat, as well as the data outlining the impacts of artificial sweeteners, gluten, and genetically modified foods; attention is given to revealing where the literature on the immune impacts of macronutrients is limited to either animal or in vitro models versus where human trials exist. Detailed attention is given to the dietary impact on the gut microbiome and the mechanisms by which our poor dietary choices are encoded into our gut, our genes, and are passed to our offspring. While today's modern diet may provide beneficial protection from micro- and macronutrient deficiencies, our over abundance of calories and the macronutrients that compose our diet may all lead to increased inflammation, reduced control of infection, increased rates of cancer, and increased risk for allergic and auto-inflammatory disease.