Randomised controlled trial of the effects of kefir on behaviour, sleep and the microbiome in children with ADHD: a study protocol.

INTRODUCTION: Current interventions for children with attention-deficit/hyperactivity disorder (ADHD) are primarily medication, behavioural therapy and parent training. However, research suggests dietary manipulations may provide therapeutic benefit for some. There is accumulating evidence that the gut microbiome may be atypical in ADHD, and therefore, manipulating gut bacteria in such individuals may help alleviate some of the symptoms of this condition. The aim of this study is to explore the effects of supplementation with kefir (a fermented dairy drink) on ADHD symptomatology, sleep, attention and the gut microbiome in children diagnosed with ADHD. METHODS AND ANALYSIS: A 6-week randomised, double-blind, placebo-controlled trial in 70 children aged 8-13 years diagnosed with ADHD. Participants will be recruited throughout the UK, through support groups, community groups, schools, social media and word of mouth. Children will be randomised to consume daily either dairy kefir or a placebo dairy drink for 6 weeks. The primary outcome, ADHD symptomatology, will be measured by The Strengths and Weakness of ADHD-symptoms and Normal-behaviour scale. Secondary outcomes will include gut microbiota composition (using shotgun metagenomic microbiome sequencing), gut symptomatology (The Gastrointestinal Severity Index questionnaire), sleep (using 7-day actigraphy recordings, The Child's Sleep Habits Questionnaire and Sleep Self Report questionnaire), inattention and impulsivity (with a computerised Go/NoGo test). Assessments will be conducted prior to the intervention and at the end of the intervention. Interaction between time (preintervention/postintervention) and group (probiotic/placebo) is to be analysed using a Mixed Model Analysis of Variances. ETHICS AND DISSEMINATION: Ethical approval for the study was granted by St Mary's University Ethics Committee. Results will be disseminated through peer-reviewed publications, presentations to the scientific community and support groups. TRIAL REGISTRATION NUMBER: NCT05155696.

A combination of green tea, rhodiola, magnesium and B vitamins modulates brain activity and protects against the effects of induced social stress in healthy volunteers.

BACKGROUND: Magnesium (Mg), green tea and rhodiola extracts have, in isolation, been shown to possess stress and anxiety relieving effects. Green tea and rhodiola have been shown to modulate EEG oscillatory brain activity associated with relaxation and stress perception. The combined capacity of these ingredients to confer protective effects under conditions of acute stress has yet to be examined. We tested the hypothesis that a combination of Mg (with B vitamins) + green tea + rhodiola would acutely moderate the effects of stress exposure. METHODS: A double blind, randomised, placebo controlled, parallel group design was employed (Clinicaltrials.gov:NCT03262376; 25/0817). One hundred moderately stressed adults received oral supplementation of either (i) Mg + B vitamins + green tea + rhodiola; (ii) Mg + B vitamins + rhodiola; (iii) Mg + B vitamins + green tea; or (iv) placebo. After supplementation participants were exposed to the Trier Social Stress Test. The effects of the study treatments on electroencephalogram (EEG) resting state alpha and theta, subjective state/mood, blood pressure, heart rate variability and salivary cortisol responses after acute stress exposure were assessed. RESULTS: The combined treatment significantly increased EEG resting state theta (p < .02) - considered indicative of a relaxed, alert state, attenuated subjective stress, anxiety and mood disturbance, and heightened subjective and autonomic arousal (p < .05). CONCLUSIONS: Mg, B vitamins, rhodiola and green tea extracts are a promising combination of ingredients that may enhance coping capacity and offer protection from the negative effects of stress exposure.Trial registration: ClinicalTrials.gov identifier: NCT03262376.

Ready-to-eat cereal and milk for breakfast compared with no breakfast has a positive acute effect on cognitive function and subjective state in 11-13-year-olds: a school-based, randomised, controlled, parallel groups trial.

PURPOSE: We tested the acute effect of breakfast (ready-to-eat-cereal [RTEC] and milk) versus (vs.) no breakfast on cognitive function and subjective state in adolescents. METHODS: Healthy adolescents (n = 234) aged 11-13 years were recruited to take part in this school-based, acute, randomised, controlled, parallel groups trial with two interventions; Breakfast or No Breakfast. The breakfast intervention consisted of ad libitum intake of RTEC (up to 70 g) with milk (up to 300 ml) administered in a naturalistic school breakfast programme environment. Cognitive function was assessed at baseline and + 70 and + 215 min post-intervention in a group-testing situation, similar to a school classroom context. The CANTAB test battery included: Simple Reaction Time (SRT), 5-Choice Reaction Time (5-CRT), Rapid Visual Information Processing (RVIP), and Paired Associates Learning (PAL; primary outcome). Data collection commenced January 2011 and ended May 2011. This trial was retrospectively registered at www.clinicaltrials.gov as NCT03979027 on 07/06/2019. RESULTS: A significant effect of the intervention (CMH[1] = 7.29, p < 0.01) was found for the number of levels achieved on the PAL task. A significant difference between interventions was found when baseline performance reached level 2 (JT, z = 2.58, p < 0.01), such that 100% of participants in the breakfast intervention reached the maximum level 4 but only 41.7% of those in the no breakfast intervention reached level 4. A significant baseline*intervention interaction (F[1,202] = 6.95, p < 0.01) was found for total errors made on the PAL task, indicating that participants who made above-average errors at baseline reduced the total number of errors made at subsequent test sessions following breakfast consumption whilst those in the no breakfast intervention did not. There was a positive effect of breakfast on reaction time and visual-sustained attention. The results also demonstrated interactions of intervention with baseline cognitive performance, such that breakfast conferred a greater advantage for performance when baseline performance was poorer. CONCLUSION: Consuming breakfast has a positive acute effect on cognition in adolescents.

Modeling the dose effects of soybean oil in salad dressing on carotenoid and fat-soluble vitamin bioavailability in salad vegetables.

Background: Previously, we showed that vegetable oil is necessary for carotenoid absorption from salad vegetables. Research is needed to better define the dose effect and its interindividual variation for carotenoids and fat-soluble vitamins.Objective: The objective was to model the dose-response relation between the amount of soybean oil in salad dressing and the absorption of 1) carotenoids, phylloquinone, and tocopherols in salad vegetables and 2) retinyl palmitate formed from the provitamin A carotenoids.Design: Women (n = 12) each consumed 5 vegetable salads with salad dressings containing 0, 2, 4, 8, or 32 g soybean oil. Blood was collected at selected time points. The outcome variables were the chylomicron carotenoid and fat-soluble vitamin area under the curve (AUC) and maximum content in the plasma chylomicron fraction (Cmax). The individual-specific and group-average dose-response relations were investigated by fitting linear mixed-effects random coefficient models.Results: Across the entire 0-32-g range, soybean oil was linearly related to the chylomicron AUC and Cmax values for α-carotene, lycopene, phylloquinone, and retinyl palmitate. Across 0-8 g of soybean oil, there was a linear increase in the chylomicron AUC and Cmax values for ß-carotene. Across a more limited 0-4-g range of soybean oil, there were minor linear increases in the chylomicron AUC for lutein and α- and total tocopherol. Absorption of all carotenoids and fat-soluble vitamins was highest with 32 g oil (P < 0.002). For 32 g oil, the interindividual rank order of the chylomicron AUCs was consistent across the carotenoids and fat-soluble vitamins (P < 0.0001).Conclusions: Within the linear range, the average absorption of carotenoids and fat-soluble vitamins could be largely predicted by the soybean oil effect. However, the effect varied widely, and some individuals showed a negligible response. There was a global soybean oil effect such that those who absorbed more of one carotenoid and fat-soluble vitamin also tended to absorb more of the others. This trial was registered at clinicaltrials.gov as NCT02867488.

Concord grape juice, cognitive function, and driving performance: a 12-wk, placebo-controlled, randomized crossover trial in mothers of preteen children.

BACKGROUND: Daily consumption of Concord grape juice (CGJ) over 3-4 mo has been shown to improve memory function in adults with mild cognitive impairment and reduce blood pressure in hypertensive adults. These benefits likely result from the high concentration of polyphenols in CGJ. Increased stress can impair cognitive function and elevate blood pressure. Thus, we examined the potential beneficial effect of CGJ in individuals with somewhat stressful and demanding lifestyles. OBJECTIVE: We sought to examine the effects of the daily consumption of CGJ for 12 wk on cognitive function, driving performance, and blood pressure in healthy, middle-aged working mothers. DESIGN: Twenty-five healthy mothers (aged 40-50 y) of preteen children who were employed for ≥30 h/wk consumed 12 ounces (355 mL) of either CGJ (containing 777 mg total polyphenols) or an energy-, taste-, and appearance-matched placebo daily for 12 wk according to a randomized crossover design with a 4-wk washout. Verbal and spatial memory, executive function, attention, blood pressure, and mood were assessed at baseline and at 6 and 12 wk. Immediately after the cognitive battery, a subsample of 17 women completed a driving performance assessment at the University of Leeds Driving Simulator. The 25-min driving task required participants to match the speed and direction of a lead vehicle. RESULTS: Significant improvements in immediate spatial memory and driving performance were observed after CGJ relative to placebo. There was evidence of an enduring effect of CGJ such that participants who received CGJ in arm 1 maintained better performance in the placebo arm. CONCLUSIONS: Cognitive benefits associated with the long-term consumption of flavonoid-rich grape juice are not exclusive to adults with mild cognitive impairment. Moreover, these cognitive benefits are apparent in complex everyday tasks such as driving. Effects may persist beyond the cessation of flavonoid consumption, and future studies should carefully consider the length of washout within crossover designs. This trial was registered at clinicaltrials.gov as NCT01411631.

A quantitative method for estimating and comparing the duration of human satiety responses: statistical modeling and application to liquid meal replacers.

Current methods of analyzing appetite-related self-report data do not allow for representation or statistical comparison of results in terms of common units or response durations. Using data from 13 previous studies, we assessed the suitability of several alternative approaches (interpolation, linear regression, non-linear models) for quantitatively estimating and comparing time to return to baseline pre-prandial levels (TTRTB, min). Curve modeling using the Weibull distribution gave the best fit and ability to determine mean TTRTB values with 95% confidence intervals. We then applied this in a study comparing liquid meal replacers (MR, 190 kcal) to 3 'meals' of similar weight and equal or greater energy content (yogurt, 190 kcal; bagel with cream cheese and juice, 400 kcal; hamburger with bun and soft drink, 400 kcal). While area under the curve data did not significantly differ amongst these, TTRTB was significantly longer for MR than yogurt. When corrected for energy content, TTRTB (min/kcal) was greater for MR than all other treatments. While further method development and validation are needed, the Weibull modeling procedure appears most suitable for estimating and quantitatively comparing durations of appetite-related responses to foods, providing an absolute response measure that can be expressed in commonly understood units.

Effect of hydrolysed egg protein on brain tryptophan availability.

Serotonin synthesis critically depends on plasma levels of tryptophan (TRP). Earlier studies have shown that for mood and cognitive benefits to occur, the ratio between TRP and other large neutral amino acids (LNAA) has to be increased by approximately 40 %. The present study investigated the dose-dependent effects of a TRP-rich hydrolysed protein (egg-protein hydrolysate, EPH) on the plasma TRP:LNAA. Moreover, it was investigated whether EPH could increase TRP:LNAA in the presence of 2 g of milk protein (MP). In a randomised double-blind crossover design, plasma amino acids were measured every 30 min for 3·5 h after ingestion of a drink containing either three different doses of 4, 8 and 12 g EPH containing 270, 560 or 800 mg of TRP, respectively, the combination of 4 g EPH and 2 g MP (74 mg TRP), or 4 g MP (148 mg TRP) in twenty healthy subjects with a mean age of 52 years. All three EPH doses caused significant increases of TRP:LNAA above 40 % at 30, 60 and 90 min after consumption in a dose-dependent manner. Compared with the 4 g EPH, the increase in TRP:LNAA in the 4 g EPH with 2 g MP condition was significantly lower at 60 min (63 v. 44 %, P < 0·001) and did not differ significantly at 90 min (58 v. 53 %, P>0·05). The present study showed that a low dose of 4 g EPH with even the addition of 2 g MP was sufficient to increase the ratio of TRP:LNAA above 40 %. Thus, EPH offers a viable ingredient to increase TRP availability.

Manipulation of glycemic response with isomaltulose in a milk-based drink does not affect cognitive performance in healthy adults.

Previous research suggests that glucoregulation and nutrient interventions, which alter circulating glucose, impact cognitive function. To examine the effect of modulating glycemic response using isomaltulose on cognitive function 24 healthy male adult participants consumed energy and macronutrient-matched milk-based drinks containing 50 g isomaltulose, 50 g sucrose or a water control in a counterbalanced within-subject design. Interstitial glucose was measured continuously in 12 subjects and all provided 9 capillary measures on each test day. A 30-min cognitive test battery was administered before and twice (+35 and +115 min) after drink ingestion. Immediate, delayed, recognition, verbal and working memory, and psychomotor performance were assessed. Glycemic profiles induced by the drinks differed significantly during the first but not the second post-drink test battery. Neither administration of the sucrose nor isomaltulose drinks produced consistent effects on verbal or working memory, or psychomotor performance. This study used isomaltulose as an investigative tool to lower glycemic response. Importantly, it demonstrates a lack of effect of modulating glucose on cognitive performance based on reliable, continuously measured glycemia. It refutes the hypothesis that glycemia is associated with cognitive performance and questions the suggestion that isomaltulose has an effect on cognitive performance.