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Effects of a Synbiotic on Plasma Immune Activity Markers and Short-Chain Fatty Acids in Children and Adults with ADHD-A Randomized Controlled Trial.
Yang, LL, Stiernborg, M, Skott, E, Xu, J, Wu, Y, Landberg, R, Arefin, S, Kublickiene, K, Millischer, V, Nilsson, IAK, et al
Nutrients. 2023;15(5)
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Attention deficit hyperactivity disorder (ADHD) is a common childhood-onset neurodevelopmental psychiatric disorder. The core symptoms of the disorder are inattention and hyperactivity/impulsivity. The aim of this study was to explore the effects of Synbiotic 2000 on concentrations of plasma immune activity markers and short-chain fatty acids (SCFAs) in ADHD. This study is a double-blind randomised controlled trial over a period of 9-weeks. Patients (n= 248) were randomly allocated to one of the two treatments: Synbiotic 2000 or placebo. Results show that there was no statistically significant overall effect of Synbiotic 2000 compared to placebo on any analyte analysing all the paediatric and all adult participants as one group. However, age-group stratified analyses showed that plasma levels of several of the analytes were at baseline different in the children compared to in the adults. Authors conclude that Synbiotic 2000, in children with ADHD, reduces markers of intestinal and vascular inflammation, the latter in part through increasing SCFAs levels. Furthermore, they suggest that the findings warrant further studies to determine if persons with ADHD would benefit inflammation-wise from dietary intake of Synbiotic 2000 or a similar synbiotic.
Abstract
Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota-gut-brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1β-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels.
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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.
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The effect of vitamin D and magnesium supplementation on the mental health status of attention-deficit hyperactive children: a randomized controlled trial.
Hemamy, M, Pahlavani, N, Amanollahi, A, Islam, SMS, McVicar, J, Askari, G, Malekahmadi, M
BMC pediatrics. 2021;21(1):178
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Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder and studies have found it to be associated with nutrient deficiencies, namely magnesium and vitamin D. The aim of this randomized, controlled study is to assess the effect of vitamin D and magnesium supplementation on mental health and behavioral outcomes in children with ADHD. Sixty-six children with ADHD were randomly allocated to receive both vitamin D plus magnesium or placebo for eight weeks, and a validated children’s mental health questionnaire was assessed. After eight weeks, serum vitamin D and magnesium, as well as various behavioural outcomes (emotional problem, peer problem, total difficulties and internalising), were all significantly improved among the treatment group compared to placebo. Based on these results, the authors conclude co-supplementing vitamin D and magnesium can improve the behavioral function and mental health of children with ADHD. They suggest larger, well-designed studies are needed to both validate these findings and further explore whether micronutrient deficiencies in ADHD are a cause or effect of the disorder.
Abstract
BACKGROUND Attention-Deficit / Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder, characterized by varying severity in attention deficit and hyperactivity. Studies have shown deficiencies in the serum level of magnesium and vitamin D in people with ADHD. The aim of this study is to determine the effect of vitamin D and magnesium supplementation on mental health in children with ADHD. METHODS We conducted a randomized, double blind, placebo-controlled clinical trial of 66 children with ADHD. Participants were randomly allocated to receive both vitamin D (50,000 IU/week) plus magnesium (6 mg/kg/day) supplements (n = 33) or placebos (n = 33) for 8-weeks. Strengths and difficulties questionnaire was used to evaluate children's mental health at baseline and the end of the study. RESULTS After eight weeks of intervention, the serum levels of 25-hydroxy-vitamin D3 and magnesium increased significantly in the intervention group compared with the control group. Also, children receiving vitamin D plus magnesium showed a significant reduction in emotional problems (p = 0.001), conduct problems (p = 0.002), peer problems (p = 0.001), prosocial score (p = 0.007), total difficulties (p = 0.001), externalizing score (p = 0.001), and internalizing score (p = 0.001) compared with children treated with the placebo. CONCLUSION Vitamin D (50,000 IU/week) and magnesium (6 mg/kg/day) co-supplementation for a duration of 8-weeks could improve the behavioral function and mental health of children with ADHD. However, further well-designed studies with a larger sample size are needed. TRIAL REGISTRATION IRCT2016030326886N1 .