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A combined DHA-rich fish oil and cocoa flavanols intervention does not improve cognition or brain structure in older adults with memory complaints: results from the CANN randomized, controlled parallel-design study.
Vauzour, D, Scholey, A, White, DJ, Cohen, NJ, Cassidy, A, Gillings, R, Irvine, MA, Kay, CD, Kim, M, King, R, et al
The American journal of clinical nutrition. 2023;118(2):369-381
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At a population level, interventions that delay the onset of dementia by 2 years are predicted to reduce the number of dementia patients by 20%. Prospective cohort studies have consistently reported cognitive and neurophysiological benefits of the fish-derived omega-3 long-chain polyunsaturated fatty acids (PUFAs), EPA, and DHA and plant-derived flavanols (FLAVs). This study hypothesised that 12-month administration of a combination of 500 mg cocoa FLAVs with 1.5g omega-3 long-chain PUFAs would improve cognitive function in a mixed subjective cognitive impairment and mild cognitive impairment cohort. This study is based on the results of the CANN randomised controlled trial. A total of 258 participants were recruited and randomised to control or test intervention. Following baseline measurements, 125 participants were randomised into the active OM3FLAV intervention group and 121 into the control group. Results showed that the 1-year intervention with EPA and DHA and cocoa FLAVs did not improve cognition or protect the brain against atrophy in older adults with evidence of memory deficits. Authors concluded that given the complexity of neuropathological processes underpinning cognitive decline and dementia risk, multidomain, multinutrient, or whole diet approaches may be needed to positively impact the cognitive trajectory in the medium term (months to 3 years).
Abstract
BACKGROUND There is evidence that both omega-3 long-chain polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and cocoa flavanols can improve cognitive performance in both healthy individuals and in those with memory complaints. However, their combined effect is unknown. OBJECTIVES To investigate the combined effect of EPA/DHA and cocoa flavanols (OM3FLAV) on cognitive performance and brain structures in older adults with memory complaints. METHODS A randomized placebo-controlled trial of DHA-rich fish oil (providing 1.1 g/d DHA and 0.4 g/d EPA) and a flavanol-rich dark chocolate (providing 500 mg/d flavan-3-ols) was conducted in 259 older adults with either subjective cognitive impairment or mild cognitive impairment. Participants underwent assessment at baseline, 3 mo, and 12 mo. The primary outcome was the number of false-positives on a picture recognition task from the Cognitive Drug Research computerized assessment battery. Secondary outcomes included other cognition and mood outcomes, plasma lipids, brain-derived neurotrophic factor (BDNF), and glucose levels. A subset of 110 participants underwent structural neuroimaging at baseline and at 12 mo. RESULTS 197 participants completed the study. The combined intervention had no significant effect on any cognitive outcomes, with the exception of reaction time variability (P = 0.007), alertness (P < 0.001), and executive function (P < 0.001), with a decline in function observed in the OM3FLAV group (118.6 [SD 25.3] at baseline versus 113.3 [SD 25.4] at 12 mo for executive function) relative to the control, and an associated decrease in cortical volume (P = 0.039). Compared with the control group, OM3FLAV increased plasma HDL, total cholesterol ratio (P < 0.001), and glucose (P = 0.008) and reduced TG concentrations (P < 0.001) by 3 mo, which were sustained to 12 mo, with no effect on BDNF. Changes in plasma EPA and DHA and urinary flavonoid metabolite concentrations confirmed compliance to the intervention. CONCLUSIONS These results suggest that cosupplementation with ω-3 PUFAs and cocoa flavanols for 12 mo does not improve cognitive outcomes in those with cognitive impairment. This trial was registered at clinicaltrials.gov as NCT02525198.
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The effects of multi-nutrient formulas containing a combination of n-3 PUFA and B vitamins on cognition in the older adult: a systematic review and meta-analysis.
Fairbairn, P, Dyall, SC, Tsofliou, F
The British journal of nutrition. 2023;129(3):428-441
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Due to the insidious onset, cognitive impairment often goes unnoticed for several years, with clinical diagnosis being made late into the disease progression. Cognition is critical for functional independence as people age, and intact cognition is vital for humans to communicate effectively. The aims of this study were to (i) investigate whether supplementation with a combination of omega-3 polyunsaturated fatty acids (n-3 PUFA) and B vitamins alone or as part of a multi-nutrient formula can prevent cognitive decline in older adults, and (ii) determine whether the effects of a single nutrient intervention with either n-3 PUFA or B vitamins could be modified by the status of the other nutrient. This study is a systematic review and meta-analysis of fourteen studies of which eleven were randomised controlled trials and the rest were post hoc analysis of randomised controlled trials. Results show a benefit of supplementing with nutrient formulas that contain both n-3 PUFA and B vitamins on global cognition and episodic memory with small to moderate effect sizes. In fact, they can help preserve cognition in the older adults. Authors conclude that more experimental work providing a combination of nutrients including both n-3 PUFA and B vitamins, in healthy older adults or those showing early signs of cognitive decline, is clearly warranted to better explore how nutrition can impact the trajectory of cognition in older adults.
Abstract
There is now evidence to suggest that there may be an interaction between B vitamins and n-3 PUFA, with suggestions that increasing intake of both nutrients simultaneously may benefit cognition in older adults. The aim of this systematic review was to investigate whether supplementation with a combination of n-3 PUFA and B vitamins can prevent cognitive decline in older adults. Randomised controlled trials conducted in older adults that measured cognitive function were retrieved. The included trials provided a combination of n-3 PUFA and B vitamins alone, or in combination with other nutrients. Trials that provided n-3 PUFA alone and also measured B vitamin status or provided B vitamin supplementation alone and measured n-3 PUFA status were also included. The databases searched were The Cochrane Library, EMBASE, CINAHL, Scopus and MEDLINE. A total of 14 papers were included in the analysis (n 4913; age: 60-70 years; follow-up 24 weeks to 4 years). The meta-analysis results found a significant benefit of nutrient formulas, which included both n-3 PUFA and B vitamins alongside other nutrients, v. placebo on global cognition assessed using composite scores from a neuropsychological test battery (G = 0·23, P = 0·002), global cognition using single measures of cognition (G = 0·28, P = 0·004) and episodic memory (G = 0·32, P = 0·001). The results indicate that providing a combination of n-3 PUFA and B vitamins as part of a multi-nutrient formula benefits cognition in older adults v. a placebo, and the potential for an interaction between these key nutrients should be considered in future experimental work.
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Precision Medicine Approach to Alzheimer's Disease: Successful Pilot Project.
Toups, K, Hathaway, A, Gordon, D, Chung, H, Raji, C, Boyd, A, Hill, BD, Hausman-Cohen, S, Attarha, M, Chwa, WJ, et al
Journal of Alzheimer's disease : JAD. 2022;88(4):1411-1421
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Neurodegenerative diseases such as Alzheimer’s disease are without effective therapeutics. The aim of this study was to compare the effects of a precision medicine approach to historical controls in patients with mild cognitive impairment or early dementia. This study is a proof-of-concept study which recruited twenty-five patients with Alzheimer’s disease or mild cognitive impairment, aged between 50–76 years. Patients were treated for nine months with a personalised, precision medicine protocol that addressed each patient’s identified potentially contributory factors. Results show that a precision medicine approach to the cognitive decline of Alzheimer’s disease and mild cognitive impairment may be an effective strategy, especially with continued optimization over time. Authors conclude that their findings indicate that it is possible to reverse cognitive decline in mild cognitive impairment and early dementia with a personalised, precision medicine (/systems medicine) protocol. This is a small study that requires larger scale initiatives, including examining the practicalities of integrating this approach into healthcare systems.
Abstract
BACKGROUND Effective therapeutics for Alzheimer's disease are needed. However, previous clinical trials have pre-determined a single treatment modality, such as a drug candidate or therapeutic procedure, which may be unrelated to the primary drivers of the neurodegenerative process. Therefore, increasing data set size to include the potential contributors to cognitive decline for each patient, and addressing the identified potential contributors, may represent a more effective strategy. OBJECTIVE To determine whether a precision medicine approach to Alzheimer's disease and mild cognitive impairment is effective enough in a proof-of-concept trial to warrant a larger, randomized, controlled clinical trial. METHODS Twenty-five patients with dementia or mild cognitive impairment, with Montreal Cognitive Assessment (MoCA) scores of 19 or higher, were evaluated for markers of inflammation, chronic infection, dysbiosis, insulin resistance, protein glycation, vascular disease, nocturnal hypoxemia, hormone insufficiency or dysregulation, nutrient deficiency, toxin or toxicant exposure, and other biochemical parameters associated with cognitive decline. Brain magnetic resonance imaging with volumetrics was performed at baseline and study conclusion. Patients were treated for nine months with a personalized, precision medicine protocol, and cognition was assessed at t = 0, 3, 6, and 9 months. RESULTS All outcome measures revealed improvement: statistically significant improvement in MoCA scores, CNS Vital Signs Neurocognitive Index, and Alzheimer's Questionnaire Change score were documented. No serious adverse events were recorded. MRI volumetrics also improved. CONCLUSION Based on the cognitive improvements observed in this study, a larger, randomized, controlled trial of the precision medicine therapeutic approach described herein is warranted.
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Effect of Docosahexaenoic Acid and Eicosapentaenoic Acid Supplementation on Sleep Quality in Healthy Subjects: A Randomized, Double-Blinded, Placebo-Controlled Trial.
Yokoi-Shimizu, K, Yanagimoto, K, Hayamizu, K
Nutrients. 2022;14(19)
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Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are unsaturated Omega-3 fatty acids, primarily found in fish and seafood. The fatty acids fulfil many vital roles in the body, such as creating cell membranes, supporting brain functions and being associated with many disease-protective benefits. These fatty acids also influence sleep in children and young adults, but less is known about their effect in older people. Hence, this Japanese study investigated the impact of EPA and DHA on sleep quality in people above the age of ≥ 45. 66 males and females with poor sleep participated in this randomized, placebo-controlled, double-blinded, parallel-grouped study. They either received 860 mg of combined DHA/EPA per day (576 mg DHA/284 mg EPA) or a placebo of corn oil for 12 weeks. The outcome was assessed subjectively via sleep quality and mood questionnaires, as well as objectively with a sleep scanner and blood samples. Blood samples and blood pressure where also monitored as a safety measure. Upon completion of the study there was a subjective improvement, which was backed-up by the results of the sleep scanner. This study confirmed that DHA/EPA improves sleep quality in the middle aged and older population and does so at doses lower than those administered in previous studies. The authors had set the daily minimum intake of DHA/EPA at 860 mg/day for this trial, as previous research showed no effects at lower doses. They also noted that poor responders tended to be people with pre-existing conditions or those who were pregnant. This population may require higher dosages of DHA/EPA than healthy patients. Overall, the intervention was well tolerated. Ensuring adequate DHA and EPA levels and intake could be part of nutritional strategies for sleep support.
Abstract
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)-omega-3 fatty acids with various functions-influence sleep in children and young adults. However, only limited studies on their effects on sleep in middle- and old-aged adults have been reported. Therefore, we investigated the effects of DHA and EPA on sleep quality in subjects aged ≥ 45 years. We performed a randomized, placebo-controlled, double-blinded, parallel-grouped study, in which we randomly assigned 66 healthy Japanese males and females. Each individual received six 480 mg capsules containing 576 mg DHA and 284 mg EPA per day (DHA/EPA group, n = 33), or corn oil (placebo group, n = 33), for 12 weeks. Before and after the intervention, the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA) and the sleep state test were conducted. In the DHA/EPA group, factor III (frequent dreaming) scores among the OSA-MA scores were significantly improved compared to the placebo group. Additionally, sleep state tests revealed that sleep efficiency improved in the DHA/EPA group. To our knowledge, this study is the first to report that DHA/EPA improves sleep quality in middle- and old-aged individuals, even at doses lower than those administered in previous studies.
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Impact of α-Linolenic Acid, the Vegetable ω-3 Fatty Acid, on Cardiovascular Disease and Cognition.
Sala-Vila, A, Fleming, J, Kris-Etherton, P, Ros, E
Advances in nutrition (Bethesda, Md.). 2022;13(5):1584-1602
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α-Linolenic acid (ALA) is an omega-3 fatty acid found in seeds and nuts such as flaxseeds, chia seeds, and walnuts and in oils such as canola oil, soybean oil, flaxseed oil and walnut oil. It has been shown to reduce the risk of coronary heart disease and cardiovascular disease. This meta-analysis examined the results of various studies, including epidemiologic studies, randomized controlled trials, and systematic reviews, to evaluate the beneficial effects of ALA in improving cognitive function and reducing the risk of cardiovascular disease and coronary heart disease. The included studies showed a correlation between ALA intake and a decreased risk of cardiovascular disease and coronary heart disease, possibly due to ALA's anti-inflammatory properties, as well as its ability to reduce total cholesterol, LDL cholesterol, triglycerides, and blood pressure. The analysis also found that ALA intake may reduce the risk of type 2 diabetes and cognitive impairment. Healthcare professionals can leverage the findings of this analysis to educate individuals about the benefits of dietary ALA in improving cardiovascular and cognitive outcomes. However, further studies are necessary to establish definitive conclusions and determine therapeutic dosage.
Abstract
Given the evidence of the health benefits of plant-based diets and long-chain n-3 (ω-3) fatty acids, there is keen interest in better understanding the role of α-linolenic acid (ALA), a plant-derived n-3 fatty acid, on cardiometabolic diseases and cognition. There is increasing evidence for ALA largely based on its major food sources (i.e., walnuts and flaxseed); however, this lags behind our understanding of long-chain n-3 fatty acids. Meta-analyses of observational studies have shown that increasing dietary ALA is associated with a 10% lower risk of total cardiovascular disease and a 20% reduced risk of fatal coronary heart disease. Three randomized controlled trials (RCTs) [AlphaOmega trial, Prevención con Dieta Mediterránea (PREDIMED) trial, and Lyon Diet Heart Study] all showed benefits of diets high in ALA on cardiovascular-related outcomes, but the AlphaOmega trial, designed to specifically evaluate ALA effects, only showed a trend for benefit. RCTs have shown that dietary ALA reduced total cholesterol, LDL cholesterol, triglycerides, and blood pressure, and epidemiologic studies and some trials also have shown an anti-inflammatory effect of ALA, which collectively account for, in part, the cardiovascular benefits of ALA. A meta-analysis reported a trend toward diabetes risk reduction with both dietary and biomarker ALA. For metabolic syndrome and obesity, the evidence for ALA benefits is inconclusive. The role of ALA in cognition is in the early stages but shows promising evidence of counteracting cognitive impairment. Much has been learned about the health benefits of ALA and with additional research we will be better positioned to make strong evidence-based dietary recommendations for the reduction of many chronic diseases.
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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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Plant-based dietary quality and depressive symptoms in Australian vegans and vegetarians: a cross-sectional study.
Lee, MF, Eather, R, Best, T
BMJ nutrition, prevention & health. 2021;4(2):479-486
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Poor diet and mood disorders are known leading causes of morbidity and mortality. Some studies suggest that plant-based diets are associated with improved mood and mental health. The aim of this study was to explore the association between vegan and vegetarian dietary patterns and depressive symptoms in adults by exploring the overall dietary quality of these patterns. This study is an online cross-sectional study which invited vegan and vegetarian adults aged between 18 and 44 years who live in Australia to complete an online survey through social media platforms. Results show that high plant-based diets quality was associated with decreased risk of depressive symptoms. However, this study also shows that following a plant-based diet does not necessarily mean the individual consumes a ‘healthy’ dietary pattern. Authors conclude that further studies are needed which should focus on the specific quality of vegan and vegetarian diets in relation to depression and mental well-being.
Abstract
Plant-based dietary patterns (vegan and vegetarian) are often considered 'healthy' and have been associated with broad health benefits, including decreased risk of obesity and ill health (cardiovascular disease, blood glucose and type II diabetes). However, the association between plant-based diets and mood disorders such as depression remains largely equivocal. This cross-sectional study of 219 adults aged 18-44 (M=31.22, SD=7.40) explored the associations between an estimate of overall plant-based diet quality and depression in vegans (n=165) and vegetarians (n=54). Overall plant-based diet quality was associated with depressive symptoms in vegans and vegetarians F(1, 215)=13.71, p<0.001 accounting for 6% of the variation in depressive symptoms. For those without depression, higher diet quality was protective against depressive symptoms F(1, 125)=6.49, p=0.012. Conversely, for those with depression no association with diet quality was found F(1, 89)=0.01, p=0.963. These findings suggest that a high-quality plant-based diet may be protective against depressive symptoms in vegans and vegetarians. In line with emerging research between food and mental health, higher-quality dietary patterns are associated with a reduced risk of depressive symptoms. Given the rapidly increasing rate of vegan and vegetarian food products within Australia, understanding the potential mechanisms of effects through which a plant-based diet may influence depressive symptoms is required.
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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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Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial.
Ramsden, CE, Zamora, D, Faurot, KR, MacIntosh, B, Horowitz, M, Keyes, GS, Yuan, ZX, Miller, V, Lynch, C, Honvoh, G, et al
BMJ (Clinical research ed.). 2021;374:n1448
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This study could be of interest to practitioners who are interested in dietary interventions that may decrease the incidence or severity of headaches in women. Omega 3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are believed to be precursors for molecules that may have pain reducing properties. Whereas omega 6 fatty acids such as linoleic acid are believed to be precursors for molecules that may have pain promoting effects. The objective of this 3 armed randomised, double blinded controlled trial was to determine whether increasing dietary intake of omega 3 EPA and DHA, whilst either maintaining or decreasing omega 6 linoleic acid, may lead to a decrease in headache frequency and severity. 182 participants were assigned into one of 3 treatment groups, the first, H3 diet, increasing EPA and DHA to 1.5g/day and maintaining linoleic acid, the second, H3-L6 diet, increasing EPA and DHA to 1.5g/day whilst decreasing linoleic acid and the control group maintaining EPA, DHA and linoleic acid. Both the H3 and H3-L6 diets increased the levels of the molecule believed to be involved in reducing pain to a statistically significant level. This was found to be consistent with the results reported by the patients both in headache hours per day and days with headache in the month. The authors conclude that increasing levels of omega 3 fatty acids in the diet whilst decreasing levels of omega 6 fatty acids in the diet may decrease the frequency and severity of headaches. This study was for 16 weeks and predominantly women with a mean age of 38, further studies for longer and on other populations such as men, children and older populations, would be required to see if the same results could be obtained.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Important from a public health perspective
- Increasing n-3 levels and decreasing n-6 levels could be modified by dietary change and appear to reduce the frequency and duration of headaches in migraine sufferers
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:
Background
Circulating lipid mediators have been implicated in headache pathogenesis.
Objective
To determine whether dietary interventions that increase n-3 fatty acids with and without reduction in n-6 linoleic acid can alter circulating lipid mediators implicated in headache pathogenesis, and decrease headache in adults with migraine.
Study Design
Three arm, parallel group, randomized, modified double blind, controlled trial.
Participants
182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine).
Interventions
Three diets designed with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid altered as controlled variables:
- H3 diet (n=61)—increase EPA+DHA to 1.5 g/day and maintain linoleic acid at around 7% of total energy intake
- H3-L6 diet (n=61)—increase n-3 EPA+DHA to 1.5 g/day and decrease linoleic acid to ≤1.8% of total energy intake
- Control diet (n=60)—maintain EPA+DHA at <150 mg/day and linoleic acid at around 7% of total energy intake
All participants received foods accounting for two thirds of daily food energy and 1/3rd from foods not provided by the Research Kitchen. For these foods participants rely on their training by the dietitian and website diet guides for shopping and choosing foods in restaurants. Participants were encouraged to continue seeing their headache physician and continue usual care.
Results
In intention-to-treat analyses (n=182) at 16 weeks
- The H3-L6 and H3 diets increased circulating 17-HDHA compared with the control diet (baseline-adjusted mean difference 0.6, 95% confidence interval 0.2 to 0.9; 0.7, 0.4 to 1.1, respectively).
- The observed improvement in HIT-6 scores (quality of life) in the H3-L6 and H3 groups was not statistically significant (−1.6, −4.2 to 1.0, and −1.5, −4.2 to 1.2, respectively).
- Compared with the control diet, the H3-L6 and H3 diets decreased total headache hours per day (−1.7, −2.5 to −0.9, and −1.3, −2.1 to −0.5, respectively), moderate to severe headache hours per day, (−0.8, −1.2 to −0.4, and −0.7, −1.1 to −0.3, respectively) and headache days per month (−4.0, −5.2 to −2.7, and −2.0, −3.3 to −0.7, respectively).
- The H3-L6 diet decreased headache days per month more than the H3 diet, suggesting additional benefit from lowering dietary linoleic acid (−2.0, −3.2 to −0.8).
- The H3-L6 and H3 diets altered n-3 and n-6 fatty acids and several of their nociceptive oxylipin derivatives in plasma, serum, erythrocytes or immune cells, but did not alter classic headache mediators calcitonin gene related peptide and prostaglandin E2.
Conclusions
The H3-L6 and H3 interventions altered bioactive mediators implicated in headache pathogenesis and decreased frequency and severity of headaches, but did not significantly improve quality of life.
Clinical practice applications:
These findings might be useful for Nutritional Therapists and Clinical Practitioners:
- To inform practitioners of the benefits of assessing n-3 and n-6 fatty acids in migraine patients.
- Inform practitioners of the potential benefits to reducing n-6 as well as increasing n-3 levels in migraine patients
- Inform practitioners of the potential lack of correlation between headache duration and frequency and quality of life measures
Considerations for future research:
- Trialing larger doses of n-3
- Longer term follow up whilst maintaining these diets
- Attempting to validate an optimal serum level of 17-HDHA for these patients that could be used in clinical practice
Abstract
OBJECTIVE To determine whether dietary interventions that increase n-3 fatty acids with and without reduction in n-6 linoleic acid can alter circulating lipid mediators implicated in headache pathogenesis, and decrease headache in adults with migraine. DESIGN Three arm, parallel group, randomized, modified double blind, controlled trial. SETTING Ambulatory, academic medical center in the United States over 16 weeks. PARTICIPANTS 182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine). INTERVENTIONS Three diets designed with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid altered as controlled variables: H3 diet (n=61)-increase EPA+DHA to 1.5 g/day and maintain linoleic acid at around 7% of energy; H3-L6 diet (n=61)-increase n-3 EPA+DHA to 1.5 g/day and decrease linoleic acid to ≤1.8% of energy; control diet (n=60)-maintain EPA+DHA at <150 mg/day and linoleic acid at around 7% of energy. All participants received foods accounting for two thirds of daily food energy and continued usual care. MAIN OUTCOME MEASURES The primary endpoints (week 16) were the antinociceptive mediator 17-hydroxydocosahexaenoic acid (17-HDHA) in blood and the headache impact test (HIT-6), a six item questionnaire assessing headache impact on quality of life. Headache frequency was assessed daily with an electronic diary. RESULTS In intention-to-treat analyses (n=182), the H3-L6 and H3 diets increased circulating 17-HDHA (log ng/mL) compared with the control diet (baseline-adjusted mean difference 0.6, 95% confidence interval 0.2 to 0.9; 0.7, 0.4 to 1.1, respectively). The observed improvement in HIT-6 scores in the H3-L6 and H3 groups was not statistically significant (-1.6, -4.2 to 1.0, and -1.5, -4.2 to 1.2, respectively). Compared with the control diet, the H3-L6 and H3 diets decreased total headache hours per day (-1.7, -2.5 to -0.9, and -1.3, -2.1 to -0.5, respectively), moderate to severe headache hours per day (-0.8, -1.2 to -0.4, and -0.7, -1.1 to -0.3, respectively), and headache days per month (-4.0, -5.2 to -2.7, and -2.0, -3.3 to -0.7, respectively). The H3-L6 diet decreased headache days per month more than the H3 diet (-2.0, -3.2 to -0.8), suggesting additional benefit from lowering dietary linoleic acid. The H3-L6 and H3 diets altered n-3 and n-6 fatty acids and several of their nociceptive oxylipin derivatives in plasma, serum, erythrocytes or immune cells, but did not alter classic headache mediators calcitonin gene related peptide and prostaglandin E2. CONCLUSIONS The H3-L6 and H3 interventions altered bioactive mediators implicated in headache pathogenesis and decreased frequency and severity of headaches, but did not significantly improve quality of life. TRIAL REGISTRATION ClinicalTrials.gov NCT02012790.
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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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Plain language summary
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.