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Impulsiveness in children with attention-deficit/hyperactivity disorder after an 8-week intervention with the Mediterranean diet and/or omega-3 fatty acids: a randomised clinical trial.
San Mauro Martin, I, Sanz Rojo, S, González Cosano, L, Conty de la Campa, R, Garicano Vilar, E, Blumenfeld Olivares, JA
Neurologia. 2022;37(7):513-523
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From a clinical perspective, impulsiveness is an important diagnostic characteristic of several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). ADHD is a neurodevelopmental disorder characterised by a persistent pattern of lack of attention and/or hyperactivity and impulsiveness. Dietary approaches to the treatment of ADHD include fatty acid supplementation, particularly with omega-3 polyunsaturated fatty acids (n-3 PUFA) The aim of this study was to analyse changes in the Barratt Impulsiveness Scale (BIS-11c) scores in children with ADHD after an 8-week intervention with the Mediterranean diet, omega-3 fatty acid supplementation, or Mediterranean diet plus omega-3 fatty acid supplementation, as compared to a control group. This study is a cross-sectional, observational cohort study of an 8-week dietary intervention in children with ADHD. Participants (n= 60) were divided into 4 groups, with a control group and 3 intervention groups. Results show that participants with ADHD taking n-3 PUFA supplements (550 mg EPA and 225 mg DHA daily) showed significantly lower levels of impulsiveness than those adopting a Mediterranean diet and controls. These participants also scored lower on all subscales of the BIS (cognitive, motor, and lack of planning). However, there weren’t any differences in impulsive behaviour between patients taking n-3 PUFA supplements and those taking supplements and adhering to the Mediterranean diet. Authors conclude that omega-3 rich (EPA/DHA) supplements should be considered for paediatric patients with ADHD, particularly those with the predominantly hyperactive-impulsive subtype.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The results from this study show no statistically significant differences between groups, except for the group of children receiving omega-3 supplementation.
- Patients with ADHD receiving omega 3 fatty acids (550 mg eicosatetraenoic acid [EPA] and 225 mg docosahexaenoic acid [DHA]) daily presented with less impulsive behaviour than controls with ADHD and patients who adopted a Mediterranean diet.
- EPA/DHA supplements may be considered for paediatric patients with ADHD, particularly those with the predominantly hyperactive-impulsive subtype.
Evidence Category:
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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
A randomized, cross-sectional study was conducted to investigate the effects of a Mediterranean diet and Omega-3 supplementation on the impulsiveness in children with attention-deficit/hyperactivity disorder (ADHD).
Methods
76 Children ages 6-16 years of either sex, with a diagnosis of ADHD, were divided into 4 groups, with a control group and 3 intervention groups. Group 1 (controls) followed their usual diet. Group 2 (Mediterranean diet) adopted a Mediterranean diet according to a series of recommendations. Group 3 (omega-3) received omega-3 fatty acid supplements. Group 4 (Mediterranean diet + omega-3) adopted the same diet as group 2 and also received omega 3 fatty acid supplements.
Dieticians provided a tailored Mediterranean diet for each participant. The Omega-3 supplement comprised of 550mg EPA and 225mg of DHA sourced from deep-sea sardines and anchovies.
The Barratt Impulsiveness Scale (BIS-11c) was administered to every child individually to evaluate impulsiveness. The KIDMED questionnaire was administered to evaluate the participant’s adherence to the Mediterranean diet. The study was conducted over 8 weeks. At the endpoint, 60/76 subjects completed the study.
Results
Primary clinical outcomes were:
- Children in the omega-3 supplement group showed a significant drop in the Barratt Impulsiveness Scale score after the intervention (from 49 to 45.10; p =.049).
- Children in the Mediterranean diet and supplement group showed higher cognitive scores (from 2.758 to 2.631).
Limitation
There was a statistically significant difference between groups for the KIDMED score (a measure of adherence to a Mediterranean diet), reflecting a higher adherence to the Mediterranean diet by the control group.
Clinical practice applications:
- Approximately 20%-40% of patients with ADHD do not respond to pharmacological treatment therefore there is a need for alternative options.
- Based on these findings, a practitioner could therefore consider recommending 550mg of eicosatetraenoic acid (EPA) and 225mg of docosahexaenoic acid (DHA) sourced from deep-sea sardines and anchovies for at least 8 weeks to help reduce impulsiveness and improve cognitive function in patients with a hyperactive-impulsive subtype of ADHD.
Considerations for future research:
- This study included combined types of ADHD therefore further investigations are needed on each type of ADHD using different interventions to establish which intervention works best.
- Assessment of diet and omega status before intervention was not conducted, which may have affected outcomes in this study. Further research could consider gathering this data at baseline.
- Larger studies are also needed to determine the relationship between BIS scores and treatments to deepen our understanding of this topic.
- Conflict of interest statement: This study was fully funded by the manufacturer of the provided Omega 3 supplement.
Abstract
INTRODUCTION The Barratt Impulsiveness Scale (BIS) is a self-administered instrument designed to assess the personality/behavioural construct of impulsiveness. Impulsiveness has been associated with several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). This study assesses the progression of impulsive behaviour in children with ADHD after an 8-week dietary intervention with the Mediterranean diet and/or omega-3 fatty acid supplementation, by using a version of the 11-item BIS adapted for children (BIS-11c). METHODS This cross-sectional study includes 60 children with ADHD from the region of Madrid, Spain. Participants were divided into 4 groups, with one control group and 3 intervention groups (Mediterranean diet; omega-3 supplementation; and Mediterranean diet plus omega-3 supplementation). A personalised Mediterranean diet was designed for members of groups 2 and 4. The BIS-11c was administered to determine the level of impulsiveness, and the KIDMED test was used to assess adherence to the Mediterranean diet. RESULTS The supplementation group showed a fairly significant decrease in the total BIS-11c (P = .049). Total cognitive score slightly decreased in the diet and supplementation groups. Only the control group showed a considerable decrease in the total motor score. Total nonplanning scores were lower in all groups after the intervention. Baseline and final BIS-11c scores were positively correlated with treatments (r > 0.9). CONCLUSION An intake of 550 mg EPA fatty acid and 225 mg DHA fatty acid per day for 8 weeks is associated with less marked impulsive behaviour in children with ADHD. A Mediterranean diet may improve BIS scores, although our results are not conclusive in this population.
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The Influence of Prenatal DHA Supplementation on Individual Domains of Behavioral Functioning in School-Aged Children: Follow-Up of a Randomized Controlled Trial.
Gould, JF, Anderson, PJ, Yelland, LN, Gibson, RA, Makrides, M
Nutrients. 2021;13(9)
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Omega-3 fatty acids such as docosahexaenoic acid (DHA) are thought to be beneficial for the development of the fetal brain. Women with a singleton pregnancy at <21 weeks’ gestation enrolled in this multicentre, double-blind, randomised controlled trial to assess the fetal neurodevelopment effects of 800 mg/day, which they took until the birth of their children. A follow-up assessment was arranged when the children reached age seven to evaluate their neurodevelopment. Children of women who took DHA supplements showed increased risk scores on hyperactivity, behavioural problems that may impact daily activities, ADHD, peer relationships, Metacognition Indexes, Shift, Inhibit, Monitor, Working Memory, and Organization of Materials scales. Supplementing with high doses of DHA during pregnancy might not have any protective effects on neurodevelopment in women with high baseline DHA levels. However, further robust studies are required to confirm the results to determine the clinical applicability of DHA supplementation in pregnant women. Healthcare professionals can use the results of this study to understand the dose-dependent therapeutic application of DHA and its impact on fetal neurodevelopment.
Abstract
Docosahexaenoic acid (DHA) accumulates in the fetal brain during pregnancy and is thought to have a role in supporting neurodevelopment. We conducted a multicenter, double-blind, randomized controlled trial in women with a singleton pregnancy who were <21 weeks' gestation at trial entry. Women were provided with 800 mg DHA/day or a placebo supplement from trial entry until birth. When children reached seven years of age, we invited parents to complete the Strengths and Difficulties Questionnaire (SDQ), the Behavior Rating Inventory of Executive Function (BRIEF), and the Conners 3rd Edition Attention-Deficit Hyperactivity Disorder (ADHD) Index to assess child behavior and behavioral manifestations of executive dysfunction. There were 543 parent-child pairs (85% of those eligible) that participated in the follow-up. Scores were worse in the DHA group than the placebo group for the BRIEF Global Executive, Behavioral Regulation and Metacognition Indexes, and the Shift, Inhibit, Monitor, Working Memory, and Organization of Materials scales, as well as for the Conners 3 ADHD index, and the SDQ Total Difficulties score, Hyperactivity/Inattention score, and Peer Relationship Problems score. In this healthy, largely term-born sample of children, prenatal DHA supplementation conferred no advantage to childhood behavior, and instead appeared to have an adverse effect on behavioral functioning, as assessed by standardized parental report scales.
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Augmenting Clinical Interventions in Psychiatric Disorders: Systematic Review and Update on Nutrition.
Offor, SJ, Orish, CN, Frazzoli, C, Orisakwe, OE
Frontiers in psychiatry. 2021;12:565583
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Mental disorders are widespread and impact significantly on health. “Nutritional psychiatry” pivots on the impact of nutrition (food) on the state of mind and mood. The aim of this study was to justify the inclusion and recognition of nutrition in the management of psychiatric illnesses. This study is a systemic review which included 97 studies. The literature shows that several foods and food compounds modulate biomarkers and molecular mechanisms involved in the aetiogenesis [the origin and development of a pathological condition] of several mental disorders. Furthermore, the evidence-based approach warrants the inclusion and co-recognition of nutrition in the management of psychiatric illnesses. Authors conclude that there is a need to advocate for policies aimed at bridging the knowledge gap and encourage the utilization and integration of nutrition in addition to contemporary therapies in clinical settings.
Abstract
There is a strong relationship between a healthy diet and mental well-being. Several foods and food compounds are known to modulate biomarkers and molecular mechanisms involved in the aetiogenesis of several mental disorders, and this can be useful in containing the disease progression, including its prophylaxis. This is an updated systematic review of the literature to justify the inclusion and recognition of nutrition in the management of psychiatric illnesses. Such foods and their compounds include dietary flavanols from fruits and vegetables, notable antioxidant and anti-inflammatory agents, probiotics (fermented foods) known to protect good gut bacteria, foods rich in polyunsaturated fatty acids (e.g., Omega-3), and avoiding diets high in saturated fats and refined sugars among others. While the exact mechanism(s) of mitigation of many nutritional interventions are yet to be fully understood, the evidence-based approach warrants the inclusion and co-recognition of nutrition in the management of psychiatric illnesses. For the greater public health benefit, there is a need for policy advocacy aimed at bridging the knowledge gap and encouraging the integration of nutritional intervention with contemporary therapies in clinical settings, as deficiencies of certain nutrients make therapy difficult even with appropriate medication.
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Early evidence of efficacy for orally administered SPM-enriched marine lipid fraction on quality of life and pain in a sample of adults with chronic pain.
Callan, N, Hanes, D, Bradley, R
Journal of translational medicine. 2020;18(1):401
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Alternatives for the management of chronic pain are needed due to the high side effect profiles, high incidence of developing tolerance, and high potential for addiction in the most common treatments which are currently used. Marine lipids (i.e. fish oil) are a well-known source of the long chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). EPA and DHA can be metabolised in the body into potent anti-inflammatory and pro-resolving mediators, which are integral parts of a fatty acid metabolite class known as specialized pro-resolving mediators (SPMs). The aim of this study was to collect preliminary data on the effects of SPM-enriched marine lipid supplementation on quality of life, pain, mood, and inflammation in adults with a history of chronic pain. This study is a single-arm, open-label clinical trial. Forty-four adults with moderate pain intensity for at least 3 months were recruited. Results show improved quality of life in an adult population with chronic pain after supplementation. Furthermore, there were also reductions in measures of pain intensity, pain interference, depression, and anxiety, as well as an increase in physical function. Authors conclude that orally administered supplements containing resolving precursors may improve the quality of life, reduce pain intensity and interference, and improve mood within 4 weeks of supplementation.
Abstract
BACKGROUND Marine lipids contain omega-3 fatty acids that can be metabolized into anti-inflammatory and pro-resolving mediators-namely 17-HDHA and 18-HEPE-which can serve as modulators of the pain experience. The purpose of this study was to determine the impact of 4 weeks of oral supplementation with a fractionated marine lipid concentration, standardized to 17-HDHA and 18-HEPE, on health-related quality of life and inflammation in adults with chronic pain. METHODS This study was a prospective, non-randomized, open-label clinical trial. Forty-four adults with ≥ moderate pain intensity for at least 3 months were recruited. The primary outcome was change in health-related quality of life (QOL) using the Patient Reported Outcomes Measurement Information System-43 Profile (PROMIS-43) and the American Chronic Pain Association (ACPA) QOL scale. Exploratory outcomes assessed safety and tolerability, changes in anxiety and depression, levels of pain intensity and interference, patient satisfaction, and impression of change. Changes in blood biomarkers of inflammation (hs-CRP and ESR) were also explored. RESULTS Outcome measures were collected at Baseline, Week 2, and Week 4 (primary endpoint). At Week 4, PROMIS-43 QOL subdomains changed with significance from baseline (p < 0.05), with borderline changes in the ACPA Quality of Life scale (p < 0.052). Exploratory analyses revealed significant changes (p < 0.05) in all measures of pain intensity, pain interference, depression, and anxiety. There were no statistically significant changes in either hs-CRP or ESR, which stayed within normal limits. CONCLUSION We conclude that oral supplementation with a fractionated marine lipid concentration standardized to 17-HDHA and 18-HEPE may improve quality of life, reduce pain intensity and interference, and improve mood within 4 weeks in adults with chronic pain. The consistency and magnitude of these results support the need for placebo-controlled clinical trials of marine lipid concentrations standardized to 17-HDHA and 18-HEPE. Trial registration ClinicalTrials.gov: Influence of an Omega-3 SPM Supplement on Quality of Life, NCT02683850. Registered 17 February 2016-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02683850 .
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A Mediterranean Diet with Fresh, Lean Pork Improves Processing Speed and Mood: Cognitive Findings from the MedPork Randomised Controlled Trial.
Wade, AT, Davis, CR, Dyer, KA, Hodgson, JM, Woodman, RJ, Keage, HAD, Murphy, KJ
Nutrients. 2019;11(7)
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Dementia is characterised by severe cognitive impairment and reduced quality of life. Observational studies have demonstrated that populations following a traditional Mediterranean diet experience less cognitive decline and a lowered risk of dementia. The aim of this study was to examine a Mediterranean diet modified to include 2–3 fresh servings of pork each week across measures of cognitive function and well-being. The study is a 24-week parallel randomised controlled crossover design to compare a Mediterranean diet with 2-3 weekly servings of fresh, lean pork (MedPork) and a low-fat control diet (LF). It recruited adults aged 45–80 years due to their increased risk of developing cardiovascular disease. Results indicate that compared with the LF control diet, the MedPork intervention led to higher performance in the cognitive domain of processing speed and higher scores for the SF-36 subscale emotional role functioning. No significant differences were observed for other domains of cognitive function, nor for additional measures of psychological well-being. Authors conclude that the MedPork intervention can improve processing speed and mood in a population at risk of cardiovascular disease and therefore dementia.
Abstract
BACKGROUND The Mediterranean diet may be capable of improving cognitive function. However, the red meat restrictions of the diet could impact long-term adherence in Western populations. The current study therefore examined the cognitive effects of a Mediterranean diet with additional red meat. METHODS A 24-week parallel crossover design compared a Mediterranean diet with 2-3 weekly servings of fresh, lean pork (MedPork) and a low-fat (LF) control diet. Thirty-five participants aged between 45 and 80 years and at risk of cardiovascular disease followed each intervention for 8 weeks, separated by an 8-week washout period. Cognitive function was assessed using the Cambridge Neuropsychological Test Automated Battery. Psychological well-being was measured through the SF-36 Health Survey and mood was measured using the Profile of Mood States (POMS). RESULTS During the MedPork intervention, participants consumed an average of 3 weekly servings of fresh pork. Compared to LF, the MedPork intervention led to higher processing speed performance (p = 0.01) and emotional role functioning (p = 0.03). No other significant differences were observed between diets. CONCLUSION Our findings indicate that a Mediterranean diet inclusive of fresh, lean pork can be adhered to by an older non-Mediterranean population while leading to positive cognitive outcomes.
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Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment.
Oulhaj, A, Jernerén, F, Refsum, H, Smith, AD, de Jager, CA
Journal of Alzheimer's disease : JAD. 2016;50(2):547-57
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Many studies are exploring preventative measures to delay or prevent mild cognitive impairment (MCI) and Alzheimer’s disease. A recent trial (VITACOG) demonstrated that omega-3 fatty acid status enhances the protective effects of B-vitamins on brain atrophy. The present study uses the VITACOG data to investigate whether there is an association on cognitive function. This study revealed that a higher baseline omega-3 fatty acid status enhances the beneficial effects of B vitamins on both brain atrophy and cognitive decline. The authors conclude that this interaction may slow down the disease process in MCI and warrants further clinical trials investigating this relationship.
Abstract
A randomized trial (VITACOG) in people with mild cognitive impairment (MCI) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline. We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment. 266 participants with MCI aged ≥70 years were randomized to B vitamins (folic acid, vitamins B6 and B12) or placebo for 2 years. Baseline cognitive test performance, clinical dementia rating (CDR) scale, and plasma concentrations of total homocysteine, total docosahexaenoic and eicosapentaenoic acids (omega-3 fatty acids) were measured. Final scores for verbal delayed recall, global cognition, and CDR sum-of-boxes were better in the B vitamin-treated group according to increasing baseline concentrations of omega-3 fatty acids, whereas scores in the placebo group were similar across these concentrations. Among those with good omega-3 status, 33% of those on B vitamin treatment had global CDR scores >0 compared with 59% among those on placebo. For all three outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins, while eicosapentaenoic acid appeared less effective. When omega-3 fatty acid concentrations are low, B vitamin treatment has no effect on cognitive decline in MCI, but when omega-3 levels are in the upper normal range, B vitamins interact to slow cognitive decline. A clinical trial of B vitamins combined with omega-3 fatty acids is needed to see whether it is possible to slow the conversion from MCI to AD.
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Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial.
Jernerén, F, Elshorbagy, AK, Oulhaj, A, Smith, SM, Refsum, H, Smith, AD
The American journal of clinical nutrition. 2015;102(1):215-21
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Mild cognitive impairment (MCI) is a characterised by a decline in cognitive function between normal aging and the development of dementia. While brain atrophy occurs in normal aging, patients with MCI or dementia exhibit much higher rates of atrophy. Results from a recent trial demonstrated that homocysteine-lowering B vitamins resulted in a significant reduction in brain atrophy rates, and links between omega-3 fatty acids and homocysteine have been suggested. The purpose of this study was to investigate whether plasma omega-3 fatty acid concentrations modify the treatment effect of B vitamins on brain atrophy rates among 168 elderly adults with MCI. Participants were randomly assigned to receive placebo or high-dose vitamin B supplementation and both brain scans and plasma concentrations were done at baseline and 2 years. The findings of this study demonstrated that, in patients with high omega-3 plasma concentrations, B vitamin supplementation slowed brain atrophy by 40% compared with those in the placebo group. This indicates that the effect of B vitamin supplementation on brain atrophy rates depend on plasma omega-3 fatty acid concentrations.
Abstract
BACKGROUND Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia. OBJECTIVE We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG). DESIGN This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations. RESULTS There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 μmol/L). High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group. CONCLUSIONS The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials. This trial was registered at www.controlled-trials.com as ISRCTN94410159.