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Effects of Wholegrain Compared to Refined Grain Intake on Cardiometabolic Risk Markers, Gut Microbiota, and Gastrointestinal Symptoms in Children: A Randomized Crossover Trial.
Madsen, MTB, Landberg, R, Nielsen, DS, Zhang, Y, Anneberg, OMR, Lauritzen, L, Damsgaard, CT
The American journal of clinical nutrition. 2024;119(1):18-28
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High consumption of wholegrain foods has been linked to a lower risk of cardiovascular disease (CVD) and type 2 diabetes. Some trials have shown benefits to body weight, blood lipids and glucose homeostasis but most of these studies are with adults. Cardiometabolic disease begins in childhood therefore data is needed for this age group to back up dietary recommendations in order to prevent later development of cardiometabolic disease. The aim of this randomized crossover trial was to look at the effects of wholegrain oats and rye intake on serum low-density lipoprotein (LDL), cholesterol and plasma insulin, other cardiometabolic markers, body composition, the composition of the gut microbiome and gastrointestinal symptoms in children with high body mass index (BMI). 55 healthy Danish children (aged 8 – 13) took part. They ate wholegrain oats and rye (WG) or refined grain products (RG) ad libtum for 8 weeks in random order. Measurements were taken at 0, 8 and 16 weeks. Compared with RG, WG reduced LDL cholesterol as well as total:high-density lipoprotein cholesterol and triacylglycerol. WG also modulated the abundance of specific types of gut bacteria, increased plasma acetate, propionate, and butyrate and fecal butyrate and reduced fatigue with no other effects on gut symptoms. This study supports the recommendation to swap refined grain for wholegrain oats and rye in children. Further studies are needed.
Abstract
BACKGROUND Wholegrain intake is associated with lower risk of cardiometabolic diseases in adults, potentially via changes in the gut microbiota. Although cardiometabolic prevention should start early, we lack evidence on the effects in children. OBJECTIVES This study investigated the effects of wholegrain oats and rye intake on serum low-density lipoprotein (LDL) cholesterol and plasma insulin (coprimary outcomes), other cardiometabolic markers, body composition, gut microbiota composition and metabolites, and gastrointestinal symptoms in children with high body mass index (BMI). METHODS In a randomized crossover trial, 55 healthy Danish 8- to 13-y-olds received wholegrain oats and rye ("WG") or refined grain ("RG") products ad libitum for 8 wk in random order. At 0, 8, and 16 wk, we measured anthropometry, body composition by dual-energy absorptiometry, and blood pressure. Fasting blood and fecal samples were collected for analysis of blood lipids, glucose homeostasis markers, gut microbiota, and short-chain fatty acids. Gut symptoms and stool characteristics were determined by questionnaires. Diet was assessed by 4-d dietary records and compliance by plasma alkylresorcinols (ARs). RESULTS Fifty-two children (95%) with a BMI z-score of 1.5 ± 0.6 (mean ± standard deviation) completed the study. They consumed 108 ± 38 and 3 ± 2 g/d wholegrain in the WG and RG period, which was verified by a profound difference in ARs (P < 0.001). Compared with RG, WG reduced LDL cholesterol by 0.14 (95% confidence interval: -0.24, -0.04) mmol/L (P = 0.009) and reduced total:high-density lipoprotein cholesterol (P < 0.001) and triacylglycerol (P = 0.048) without altering body composition or other cardiometabolic markers. WG also modulated the abundance of specific bacterial taxa, increased plasma acetate, propionate, and butyrate and fecal butyrate and reduced fatigue with no other effects on gut symptoms. CONCLUSION High intake of wholegrain oats and rye reduced LDL cholesterol and triacylglycerol, modulated bacterial taxa, and increased beneficial metabolites in children. This supports recommendations of exchanging refined grain with wholegrain oats and rye among children. This trial was registered at clinicaltrials.gov as NCT04430465.
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Micronutrients for Attention-Deficit/Hyperactivity Disorder in Youths: A Placebo-Controlled Randomized Clinical Trial.
Johnstone, JM, Hatsu, I, Tost, G, Srikanth, P, Eiterman, LP, Bruton, AM, Ast, HK, Robinette, LM, Stern, MM, Millington, EG, et al
Journal of the American Academy of Child and Adolescent Psychiatry. 2022;61(5):647-661
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Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition that affects about 5-7% of children. Characteristics of ADHD are age-inappropriate hyperactivity, impulsivity, and difficulties in focusing attention which arise from an impaired ability to regulate executive and emotional functions. The condition often persists into adulthood, where it presents an increased risk for poor educational achievements, substance abuse, incarceration, and mental health problems. In many cases, drug treatment can improve ADHD symptoms, yet concern remains about the side effects of these treatments. Some research has investigated the impact of nutrient supplementation on ADHD management, as many nutrients are essential for healthy brain function and are also involved in the production of neurotransmitters. In previous studies, supplementation with nutrients has shown some benefits but likewise also inconsistent results. This eight-week randomised placebo-controlled clinical trial evaluated the effects of a multi-nutrient supplement in 135 children with ADHD, aged 6-12 years. The study specifically focused on irritable mood symptoms. The multi-nutrient formula contained vitamins, minerals, amino acids, and antioxidants. Outcomes were measured by scores rated by clinicians (Clinical Global Impression-Improvement aka CGI-I) and scores rated by parents (Child and Adolescent Symptom Inventory-5 aka CASI-5). The multi-nutrient formula showed overall benefit in the blinded clinician rating but not by parental reports. According to the parents, overall improvement was reported, both in the placebo and intervention groups. The authors discussed how this absence of difference can be explained. Yet, on a subscale, the multi-nutrient group parents were more likely to report improvements. In addition, children with the additional micronutrients demonstrated greater height growth during the intervention. The supplement was well tolerated with good adherence and the monitored blood markers demonstrated safety of use.
Expert Review
Conflicts of interest:
None
Take Home Message:
This fully-blinded RCT of micronutrients addresses several concerns related to existing ADHD treatment, including the possibility of counteracting height suppression and treating associated irritable mood, emotional dysregulation, and aggression.
Although further research is needed, multinutrient supplementation should be considered for children with ADHD.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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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:
Introduction
Attention-deficit hyperactivity disorder (ADHD) is a common psychiatric condition that can result in low educational performance and achievement. Around 5-7% of children are believed to be affected. Alongside inattention and hyperactivity, emotional dysregulation is a common feature of ADHD. Psychiatric problems can continue into adulthood and an increased risk of incarceration and substance abuse have been reported.
Treatment with prescription medications may improve symptoms of ADHD, however, potential side effects include mild growth suppression, and mood and emotional dysregulation. Non-pharmacological treatments are therefore being investigated.
Previous research on single nutrients have shown mixed results for emotional dysregulation and mood issues in ADHD. The aim of this study was to test whether supplementation with a multi-nutrient could be beneficial to children aged 6-12 years with ADHD and irritability.
Methods
126 unmedicated children from North America with ADHD (mean age 9.8 years) completed this 8-week study. All participants had at least 1 symptom of anger, irritability, peer conflict or Disruptive Mood Dysregulation Disorder (DMDD).
Randomisation was into an intervention (n=71) or placebo (N=55) group with a 3:2 ratio to promote enrolment. Participants were required to take 6-12 capsules daily, depending on age and tolerance, of micronutrients or a placebo. Micronutrient dosages were above the recommended dietary allowance (RDA). Outcomes were measured using clinician and parent rated assessments and by a further adult who knew the child well.
The trial was blinded to all participants, parents and study staff.
Results
The clinician-rated results found 54% of the micronutrient group and 18% of the placebo group had improvements in irritability symptoms (Risk ratio =2.97, 97.5% CI: 1.5, 5.90, p<0.001). This was not replicated in the parent/adult rated results. Children in the micronutrient group grew on average 6mm more than the placebo group (p=0.002). No serious adverse treatment effects were reported. Adherence to protocol was met by >74% of participants (n=93).
Conclusions
In this study, clinicians reported that micronutrients showed greater benefits than placebo for treating irritability and supporting growth in children with ADHD.
The study and authors received funding from several research and association bodies. However, no funder was involved in the study design or reporting. No conflicts of interest were declared.
Clinical practice applications:
- Multinutrient supplementation including vitamins, minerals, amino acids, and antioxidants may support height growth in children who take pharmacologic treatment
- Multi nutrient supplementation may also help with irritable mood, emotional dysregulation, and aggression in ADHD children
- Micronutrients given at doses between the Recommended Dietary Allowance and Upper Tolerable Intake Level appear safe and may be developed into an alternative or complementary treatment for ADHD.
Considerations for future research:
- Further large scale research is needed into the potential benefits of micronutrients for children with ADHD and irritability
Abstract
OBJECTIVE To evaluate whether micronutrients (vitamins/minerals) benefit attention-deficit/hyperactivity disorder (ADHD) and irritability in a North American pediatric sample. METHOD A 3-site, 8-week, placebo-controlled, randomized clinical trial of micronutrients was conducted in nonmedicated children aged 6 to 12 years with ADHD and at least 1 impairing irritability symptom by parent report on the Child and Adolescent Symptom Inventory-5 (CASI-5). A priori-defined primary outcomes were Clinical Global Impression-Improvement (CGI-I) (CGI-I of 1 or 2 = treatment responder) and parent-rated CASI-5 composite score of ADHD, oppositional defiant, disruptive mood dysregulation, and peer conflict symptoms, including impairment scores. RESULTS Of 135 randomized (mean age 9.8 years), 126 youths (93%) comprised the modified intention-to-treat population. Blinding was maintained. For the CGI-I, 54% of the micronutrient and 18% of the placebo group were responders (risk ratio = 2.97, 97.5% CI = 1.50, 5.90, p < .001). CASI-5 composite scores improved significantly for both groups (p < .01), with a mean change of -0.31 (95% CI = -0.39, -0.23) in the micronutrient group and a mean change of -0.28 (95% CI = -0.38, -0.19) in the placebo group. However, the between-group difference was not significant (mean change = -0.02; 97.5% CI = -0.16, 0.12, effect size = 0.07, p = .70). The micronutrient group grew 6 mm more than the placebo group (p = .002). No serious adverse events or clinically significant changes from baseline in blood and urine tests occurred. CONCLUSION Micronutrients showed global benefit over placebo by blinded clinician rating, but not by parent-report CASI-5 composite rating in a population with ADHD and irritability. Micronutrients showed greater height growth. Micronutrients were well tolerated, and the majority of participants adhered to the number of capsules prescribed. This randomized controlled trial replicates safety and efficacy reported for ADHD in 2 smaller trials of a similar formula containing all vitamins and known essential minerals in amounts between the Recommended Dietary Allowance and Upper Tolerable Intake Level. CLINICAL TRIAL REGISTRATION INFORMATION Micronutrients for ADHD in Youth (MADDY) Study; https://clinicaltrials.gov; NCT03252522.
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Effect of Alpha-Lipoic Acid Supplementation on Endothelial Function and Cardiovascular Risk Factors in Overweight/Obese Youths: A Double-Blind, Placebo-Controlled Randomized Trial.
Tromba, L, Perla, FM, Carbotta, G, Chiesa, C, Pacifico, L
Nutrients. 2019;11(2)
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Children who are obese or overweight are at a higher risk of developing heart disease. Damage to the lining of the blood vessels may be an early indicator of potential heart disease. Alpha-lipoic acid (ALA) is a supplement that has anti-oxidant and anti-inflammatory effects, and has been shown to improve blood vessel function in adults with metabolic diseases, and children with type 1 diabetes. It is not yet known whether ALA supplementation can benefit cardiovascular health in overweight/obese youths. The aim of this double-blind placebo-controlled randomised trial was to investigate whether supplementation with ALA improved endothelial function and risk factors for cardiovascular disease in overweight and obese youths. 64 overweight/obese youths aged 8-16 years old were given either 800mg ALA or a placebo for 12 weeks. All participants were instructed to follow a balanced low-calorie diet and advised to engage in a moderate daily exercise program (60 min/day at least five days a week). At the end of the study, blood vessel function, as assessed by flow-mediated dilation (FMD) of the brachial artery, did not change significantly in either of the groups. However, the basal and peak diameter of the brachial artery significantly increased after ALA treatment, compared to placebo. There were no significant changes between groups or over time for blood pressure, weight or body mass index (BMI), nor were there any significant changes in glucose, insulin or fat levels within the blood. The authors concluded that ALA supplementation improves the tone of blood vessels and may have a beneficial effect on heart health in overweight/obese youths.
Abstract
Endothelial dysfunction is recognized as an early sign of systemic atherosclerosis, and it represents a therapeutic target to prevent long-term cardiovascular (CV) consequences. Alpha-lipoic acid (ALA) is a commonly used dietary supplement exerting anti-oxidant and anti-inflammatory effects. We investigated whether a three-month treatment with ALA improves endothelial function, as assessed by flow-mediated dilation (FMD) of the brachial artery, and clinical and metabolic risk factors in overweight/obese youths. We enrolled 67 overweight/obese children, and 22 normal-weight metabolically healthy controls. Overweight/obese youths were randomly allocated in a double-blinded manner to receive ALA (n = 34) or placebo (n = 33). Of these, 64 (32 ALA, 32 placebo) completed the follow-up. At baseline, in ALA and placebo groups, FMD was similar, but lower as compared with that in controls (p = 0.045). At three months, within the ALA and placebo groups, FMD did not change significantly. However, the basal and peak diameter of brachial artery significantly increased after ALA treatment as compared to placebo (p = 0.036 and p = 0.01, respectively). There were no significant within- and between-group changes for anthropometric and metabolic variables. The results show that ALA supplementation improves vascular tone and may have a beneficial effect on CV health in overweight/obese youths.
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Effects of fasting and preoperative feeding in children.
Yurtcu, M, Gunel, E, Sahin, TK, Sivrikaya, A
World journal of gastroenterology. 2009;15(39):4919-22
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Preoperative fasting is usually carried out to prevent the risk of vomiting during anaesthesia. The study investigated whether children should have a long period of fasting before surgery. Eight groups of 10 children (aged 1-10 years) with disorders of groin and scrotum were orally fed normal liquid food (NLF) or a high calorie diet (HCD) in 2 divided doses at 6 hour intervals, then fasted for 2, 3, 4 or 5 hours prior to surgery. Four groups had NLF and 4 groups had HCD. All children had their glucose, prealbumin and cortisol levels measured twice, just after the oral feeding and just before surgery. Once anaesthesia was sufficient and stable, gastric liquid was collected and measured. Patients with disease that could delay gastric emptying, had high acid production or were on medication were excluded from the trial. The researchers found that there was no significant difference in blood prealbumin levels in all groups. There was significant increase in blood cortisol in 4 groups when fasted (NLF-2h fasted, HCD-2h fasted, NLF-3h fasted and HCD-5h fasted). Stomach aid residue liquids were at tolerable levels of 1-2ml in all children. Anaesthesia was uneventful, with no coughing, laryngospasm or vomiting reported, and outcomes of surgery and wound healing were not affected. The authors noted that drinking clear liquids up to 2 hours before surgery was unlikely to substantially affect the volume of gastric fluids, and did not appear to increase the risk of vomiting in normal, healthy children. Glucose and insulin infusions appeared to minimise endocrine stress response and normalised post-op insulin sensitivity. Additionally, there may be a psychological benefit for children as irritability appeared to decrease prior to surgery. The study concluded that there was no need for fasting longer than 2 hours prior to inguinoscrotal region surgery.
Abstract
AIM: To investigate whether children should undergo surgery without a long period of fasting after feeding. METHODS Eighty children with inguinoscrotal disorders (aged 1-10 years) were studied prospectively. They were divided into eight groups that each contained 10 children who were fed normal liquid food (NLF) and a high-calorie diet (HCD) 2, 3, 4 and 5 h before surgery, in two doses at 6-h intervals. NLF was given to four groups and HCD to the other four. In all groups, glucose, prealbumin and cortisol levels in the blood were measured twice: just after oral feeding and just before the operation. After the establishment of adequate anesthesia, gastric residue liquid was measured with a syringe. RESULTS Blood glucose levels in all patients fed NLF and HCD were high, except in patients in the HCD-4 group. There was no significant difference in the blood prealbumin levels. There was a significant increase in the blood cortisol levels in the NLF-2 (14.4 +/- 5.7), HCD-2 (13.2 +/- 6.0), NLF-3 (10.9 +/- 6.4), and HCD-5 (6.8 +/- 5.7) groups (P < 0.05). CONCLUSION The stress of surgery may be tolerated by children when they are fed up to 2 h before elective surgery.