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Short-term effects of an elimination diet and healthy diet in children with attention-deficit/hyperactivity disorder: a randomized-controlled trial.
Huberts-Bosch, A, Bierens, M, Ly, V, van der Velde, J, de Boer, H, van Beek, G, Appelman, D, Visser, S, Bos, LHP, Reijmers, L, et al
European child & adolescent psychiatry. 2023
Abstract
An Elimination Diet (ED) may be effective in reducing symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD), but has never been compared to an active control condition [i.e., Healthy Diet (HD)]. In a two-armed RCT, a total of N = 165 children (5-12 years) with ADHD were randomized by means of minimization (1:1) to either an ED (N = 84) or HD (N = 81) within two Dutch child and adolescent psychiatry centers. The design included a non-randomized comparator arm including N = 58 children being treated with Care as Usual (CAU). Treatment allocation was unblinded. The primary outcome was a 5-point ordinal measure of respondership based on a combination of parent and teacher ratings on ADHD and emotion regulation, determined after 5 weeks of treatment. Ordinal regression analyses were done on an intention-to-treat basis. Fewer ED (35%) than HD (51%) participants showed a partial to full response, despite overall good-to-excellent treatment adherence (> 88%) and comparable high parental prior believes. A younger age and higher problem severity predicted a better respondership. CAU-preferring participants responded more often favorably (56%) compared to ED-but not HD-participants. Small-to-medium improvements in physical health (blood pressure, heart rate, and somatic complaints) were found in response to ED/HD versus decrements in response to CAU (74% received psychostimulants). The lack of superiority of the ED versus HD suggests that for the majority of children, dietary treatment response is not rooted in food-allergies/-sensitivities. The comparable results for treatment with HD and CAU are remarkable given that CAU participants were probably 'easier to treat' than HD (and ED) participants with proportionally fewer with a (suboptimal/non-response to) prior treatment with medication (4% versus 20%). Further assessment of long-term effects is needed to evaluate the potential place of dietary treatment within clinical guidelines. The trial is closed and registered in the Dutch trial registry, number NL5324 ( https://www.onderzoekmetmensen.nl/en/trial/25997 ).
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Diet, Physical Activity, and Disinhibition in Middle-Aged and Older Adults: A UK Biobank Study.
Schweren, LJS, van Rooij, D, Shi, H, Larsson, H, Arias-Vasquez, A, Li, L, Grimstvedt Kvalvik, L, Haavik, J, Buitelaar, J, Hartman, C
Nutrients. 2021;(5)
Abstract
Disinhibition is a prominent feature of multiple psychiatric disorders, and has been associated with poor long-term somatic outcomes. Modifiable lifestyle factors including diet and moderate-to-vigorous physical activity (MVPA) may be associated with disinhibition, but their contributions have not previously been quantified among middle-aged/older adults. Here, among N = 157,354 UK Biobank participants aged 40-69, we extracted a single disinhibition principal component and four dietary components (prudent diet, elimination of wheat/dairy/eggs, meat consumption, full-cream dairy consumption). In addition, latent profile analysis assigned participants to one of five empirical dietary groups: prudent-moderate, unhealthy, restricted, meat-avoiding, low-fat dairy. Disinhibition was regressed on the four dietary components, the dietary grouping variable, and self-reported MVPA. In men and women, disinhibition was negatively associated with prudent diet, and positively associated with wheat/dairy/eggs elimination. In men, disinhibition was also associated with consumption of meat and full-cream dairy products. Comparing groups, disinhibition was lower in the prudent-moderate diet (reference) group compared to all other groups. Absolute βs ranged from 0.02-0.13, indicating very weak effects. Disinhibition was not associated with MVPA. In conclusion, disinhibition is associated with multiple features of diet among middle-aged/older adults. Our findings foster specific hypotheses (e.g., early malnutrition, elevated immune-response) to be tested in alternative study designs.
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Effects of the Mediterranean Diet or Nut Consumption on Gut Microbiota Composition and Fecal Metabolites and their Relationship with Cardiometabolic Risk Factors.
Galié, S, García-Gavilán, J, Camacho-Barcía, L, Atzeni, A, Muralidharan, J, Papandreou, C, Arcelin, P, Palau-Galindo, A, Garcia, D, Basora, J, et al
Molecular nutrition & food research. 2021;(19):e2000982
Abstract
SCOPE To examine whether a Mediterranean Diet (MedDiet) compared to the consumption of nuts in the context of a habitual non-MedDiet exerts a greater beneficial effect on gut microbiota and fecal metabolites; thus, contributing to explain major benefits on cardiometabolic risk factors. METHODS AND RESULTS Fifty adults with Metabolic Syndrome are randomized to a controlled, crossover 2-months dietary-intervention trial with a 1-month wash-out period, following a MedDiet or consuming nuts (50 g day-1 ). Microbiota composition is assessed by 16S rRNA gene sequencing and metabolites are measured using Nuclear Magnetic Resonance (NMR) and liquid chromatography coupled to triple quadrupole mass spectrometry (LC-qTOF) platforms in a targeted metabolomics approach. Decreased glucose, insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) is observed after the MedDiet compared to the nuts intervention. Relative abundances of Lachnospiraceae NK4A136 and an uncultured genera of Ruminococcaceae are significantly increased after the MedDiet compared to nuts supplementation. Changes in Lachnospiraceae NK4A136 are inversely associated with insulin levels and HOMA-IR, while positively and negatively with changes in cholate and cadaverine, respectively. CONCLUSIONS Following a MedDiet, rather than nuts, induces a significant increase in Lachnospiraceae NK4A136 and improves the metabolic risk. This genera seems to affect the bile acid metabolism and cadaverine which may account for the improvement in insulin levels.
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A two arm randomized controlled trial comparing the short and long term effects of an elimination diet and a healthy diet in children with ADHD (TRACE study). Rationale, study design and methods.
Bosch, A, Bierens, M, de Wit, AG, Ly, V, van der Velde, J, de Boer, H, van Beek, G, Appelman, D, Visser, S, Bos, L, et al
BMC psychiatry. 2020;(1):262
Abstract
BACKGROUND Food may trigger Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms. Therefore, an elimination diet (ED) might be an effective treatment for children with ADHD. However, earlier studies were criticized for the nature of the control group, potential confounders explaining the observed effects, unsatisfactory blinding, potential risks of nutritional deficiencies and unknown long term and cost-effectiveness. To address these issues, this paper describes the rationale, study design and methods of an ongoing two arm randomized controlled trial (RCT) comparing the short (5 week) and long term (1 year) effects of an elimination diet and a healthy diet compared with care as usual (CAU) in children with ADHD. METHODS A total of N = 162 children (5-12 years) with ADHD will be randomized to either an ED or a healthy diet. A comparator arm including N = 60 children being solely treated with CAU (e.g. medication) is used to compare the effects found in both dietary groups. The two armed RCT is performed in two youth psychiatry centers in the Netherlands, with randomization within each participating center. The primary outcome measure is response to treatment defined as a ≥ 30% reduction on an ADHD DSM-5 rating scale (SWAN) and/or on an emotion dysregulation rating scale (SDQ: dysregulation profile). This is assessed after 5 weeks of dietary treatment, after which participants continue the diet or not. Secondary outcome measures include the Disruptive Behavior Diagnostic Observational Schedule (DB-DOS), parent and teacher ratings of comorbid symptoms, cognitive assessment (e.g. executive functions), school functioning, physical measurements (e.g. weight), motor activity, sleep pattern, food consumption, nutritional quality of the diet, adherence, parental wellbeing, use of health care resources and cost-effectiveness. Assessments take place at the start of the study (T0), after five weeks (T1), four months (T2), eight months (T3) and 12 months of treatment (T4). T0, T1 and T4 assessments take place at one of the psychiatric centers. T2 and T3 assessments consist of filling out online questionnaires by the parents only. DISCUSSION This RCT will likely contribute significantly to clinical practice for ADHD by offering insight into the feasibility, nutritional quality, (cost-)effectiveness and long term effects of dietary treatments for ADHD. TRIAL REGISTRATION www.trialregister.nl, NTR5434. Registered at October 11th, 2015.
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The Role of the Gut-Brain Axis in Attention-Deficit/Hyperactivity Disorder.
Dam, SA, Mostert, JC, Szopinska-Tokov, JW, Bloemendaal, M, Amato, M, Arias-Vasquez, A
Gastroenterology clinics of North America. 2019;(3):407-431
Abstract
Genetic and environmental factors play a role in the cause and development of attention-deficit/hyperactivity disorder (ADHD). Recent studies have suggested an important role of the gut-brain axis (GBA) and intestinal microbiota in modulating the risk of ADHD. Here, the authors provide a brief overview of the clinical and biological picture of ADHD and how the GBA could be involved in its cause. They discuss key biological mechanisms involved in the GBA and how these may increase the risk of developing ADHD. Understanding these mechanisms may help to characterize novel treatment options via identification of disease biomarkers.
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Stress matters: Randomized controlled trial on the effect of probiotics on neurocognition.
Papalini, S, Michels, F, Kohn, N, Wegman, J, van Hemert, S, Roelofs, K, Arias-Vasquez, A, Aarts, E
Neurobiology of stress. 2019;10:100141
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Increasing animal studies indicate the role of probiotics in regulating mood and cognition through the gut-brain axis, however in human studies evidence of this causal association is lacking. The aim of this double-blind, randomised, placebo-controlled intervention was to investigate the effects of probiotics on neurocognitive measures in 58 healthy participants. Participants were randomly assigned to either probiotic or placebo group and were tested once before and after the 28-day intervention. The neurocognitive outcomes measured included emotion reactivity, emotion regulation, cognitive control and the effects of acute stress on working memory. These were assessed through functional MRI (fMRI) and questionnaires. This study found when stress was induced, probiotic supplementation led to a significant improvement in working memory performance. Without stress, there was no causal association between neurocognitive outcomes and probiotic intake. Based on these results, the authors conclude that during challenging situations, probiotics can aid in buffering the detrimental effects of stress on cognition.
Abstract
Probiotics are microorganisms that provide health benefits when consumed. In animals, probiotics reverse gut microbiome-related alterations in depression-like symptoms, in cognition, and in hormonal stress response. However, in humans, a causal understanding of the gut-brain link in emotion and cognition is lacking. Additionally, whether the effects of probiotics on neurocognition are visible only in presence of stress, remains unclear. We investigated the effects of a multispecies probiotic (Ecologic®Barrier) on specific neurocognitive measures of emotion reactivity, emotion regulation, and cognitive control using fMRI. Critically, we also tested whether probiotics can buffer against the detrimental effects of acute stress on working memory. In a double blind, randomized, placebo-controlled, between-subjects intervention study, 58 healthy participants were tested once before and once after a 28-day intervention. Without stress induction, probiotics did not affect brain, behavioral, or related self-report measures. However, relative to placebo, the probiotics group did show a significant stress-related increase in working memory performance after supplementation. This change was associated with intervention-related neural changes in frontal cortex during cognitive control exclusively in the probiotics group. Overall, our results show neurocognitive effects of a multispecies probiotic in healthy women only under challenging situations, buffering against the detrimental effects of stress on cognition.