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The Influence of n-3PUFA Supplementation on Muscle Strength, Mass, and Function: A Systematic Review and Meta-Analysis.
Santo André, HC, Esteves, GP, Barreto, GHC, Longhini, F, Dolan, E, Benatti, FB
Advances in nutrition (Bethesda, Md.). 2023;14(1):115-127
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Omega 3 polyunsaturated fatty acids (n-3PUFA) are long-chain polyunsaturated fatty acids essential to human health. They play a role in cell membrane integrity, immune and inflammation regulation, cognition and neuromuscular function. As the human body cannot make these fatty acids, they need to be obtained through diet or supplementation. Regarding skeletal muscle, recent research showed that n-3PUFAs may increase the uptake of amino acids by increasing the membrane fluidity in the muscle, and by activating pathways that inhibit protein breakdown. This led to the hypothesis that n-3PUFAs may enhance muscle mass gain and strength. This systematic review sought to gather all available evidence about the impact of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. The review included 14 studies with a total of 1443 participants. The authors found that n-3PUFA supplementation had no significant effect on muscle mass or muscle function in healthy young and older adults, however, a very small but significant positive effect was noted regarding muscle strength. In the discussion section, the authors explain the challenges of their review and how these findings integrate with the current understanding and other research findings. They concluded more research is needed to get a better insight into the effects of n-3PUFA on muscle function and the variants.
Abstract
The effects of omega 3 polyunsaturated fatty acids (n-3PUFA) supplementation on skeletal muscle are currently unclear. The purpose of this systematic review was to synthesize all available evidence regarding the influence of n-3PUFA supplementation on muscle mass, strength, and function in healthy young and older adults. Four databases were searched (Medline, Embase, Cochrane CENTRAL, and SportDiscus). Predefined eligibility criteria were determined according to Population, Intervention, Comparator, Outcomes, and Study Design. Only peer-reviewed studies were included. The Cochrane RoB2 Tool and the NutriGrade approach were used to access risk of bias and certainty in evidence. Effect sizes were calculated using pre-post scores and analyzed using a three-level, random-effects meta-analysis. When sufficient studies were available, subanalyses were performed in the muscle mass, strength, and function outcomes according to participant's age (<60 or ≥60 years), supplementation dosage (<2 or ≥2 g/day), and training intervention ("resistance training" vs. "none or other"). Overall, 14 individual studies were included, total 1443 participants (913 females; 520 males) and 52 outcomes measures. Studies had high overall risk of bias and consideration of all NutriGrade elements resulted in a certainty assessment of moderate meta-evidence for all outcomes. n-3PUFA supplementation had no significant effect on muscle mass (standard mean difference [SMD] = 0.07 [95% CI: -0.02, 0.17], P = 0.11) and muscle function (SMD = 0.03 [95% CI: -0.09, 0.15], P = 0.58), but it showed a very small albeit significant positive effect on muscle strength (SMD = 0.12 [95% CI: 0.006, 0.24], P = 0.04) in participants when compared with placebo. Subgroup analyses showed that age, supplementation dose, or cosupplementation alongside resistance training did not influence these responses. In conclusion, our analyses indicated that n-3PUFA supplementation may lead to very small increases in muscle strength but did not impact muscle mass and function in healthy young and older adults. To our knowledge, this is the first review and meta-analysis investigating whether n-3PUFA supplementation can lead to increases in muscle strength, mass, and function in healthy adults. Registered protocol: doi.org/10.17605/OSF.IO/2FWQT.
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Effect of omega-3 supplementation on lipid profile in children and adolescents: a systematic review and meta-analysis of randomized clinical trials.
Khorshidi, M, Hazaveh, ZS, Alimohammadi-Kamalabadi, M, Jamshidi, S, Moghaddam, OM, Olang, B, Hatefi, S, Hosseini, A, Jamilian, P, Zarezadeh, M, et al
Nutrition journal. 2023;22(1):9
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Dyslipidaemia is considered as a substantial risk factor for cardiovascular disease (CVD). It is characterised by increased levels of triglyceride and low-density lipoprotein (LDL) and decreased levels of high-density lipoprotein (HDL). Consumption of omega-3 supplements play an important role in reduction of CVD events and its associated mortality by ameliorating lipid profile via lowering triglyceride levels. The aim of this study was to evaluate the effect of omega 3 supplementation on lipid profile in children and adolescents. This study is a systematic review and meta-analysis of fourteen studies. Three trials out of 14 had cross-over design, while others were parallel randomised trials. Results show that omega-3 supplementation may exert therapeutic effects on triglyceride (TG) levels, however, there weren’t any remarkable effects on HDL, LDL, and total cholesterol status. The subgroup analysis showed an improvement in TG levels in studies conducted on participants ≤13 years old and those with hypertriglyceridemia. Furthermore, due to meta-regression results, the omega-3 supplementation improved HDL levels when administered with longer duration. Authors conclude that omega-3 supplementation may have favourable hypolipidemic effects through reduction of TG levels. Additionally, clinical trials with longer duration of intervention and appropriate designs are recommended for younger children and those with hypertriglyceridemia.
Abstract
PURPOSE Dyslipidemia is considered as a known risk factor for cardiovascular disease. Yet various trials with wide ranges of doses and durations have reported contradictory results. We undertook this meta-analysis of randomized controlled trials (RCTs) to determine whether omega-3 supplementation can affect lipid profile in children and adolescents. METHODS Cochrane Library, Embase, PubMed, and Scopus databases were searched up to March 2021. Meta-analysis was performed using random-effect method. Effect size was expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Heterogeneity was assessed using the I2 index. In order to identification of potential sources of heterogeneity, predefined subgroup and meta-regression analysis was conducted. RESULTS A total of 14 RCTs with 15 data sets were included. Based on the combination of effect sizes, there was a significant reduction in TG levels (WMD: -15.71 mg/dl, 95% CI: -25.76 to -5.65, P=0.002), with remarkable heterogeneity (I2=88.3%, P<0.001). However, subgroup analysis revealed that omega-3 supplementation significantly decreased TG only in studies conducted on participants ≤13 years old (WMD=-25.09, 95% CI: -43.29 to -6.90, P=0.007), (I2=84.6%, P<0.001) and those with hypertriglyceridemia (WMD=-28.26, 95% CI: -39.12 to -17.41, P<0.001), (I2=0.0%, P=0.934). Omega-3 supplementation had no significant effect on total cholesterol, HDL, and LDL levels. Also, results of nonlinear analysis showed significant effect of treatment duration on HDL status (Pnon-linearity=0.047). CONCLUSION Omega-3 supplementation may significantly reduce TG levels in younger children and those with hypertriglyceridemia. Also, based on the HDL-related results, clinical trials with longer duration of intervention are recommended in this population.
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Docosahexaenoic acid (DHA) intake estimated from a 7-question survey identifies pregnancies most likely to benefit from high-dose DHA supplementation.
Christifano, DN, Crawford, SA, Lee, G, Brown, AR, Camargo, JT, Kerling, EH, Gajewski, BJ, Valentine, CJ, Gustafson, KM, DeFranco, EA, et al
Clinical nutrition ESPEN. 2023;53:93-99
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Preterm birth (PTB) is the primary cause of infant mortality worldwide; and infants who survive have a higher risk of child disability. A recent Cochrane Review concluded that there is strong evidence that omega-3 fatty acids, especially docosahexaenoic acid (DHA), reduce early PTB (EPTB, <34 weeks gestation) and PTB (<37 weeks gestation) by 42% and 11%, respectively. The aim of this study was to investigate whether DHA intake at baseline alone could identify pregnancies for which high dose DHA supplementation lowered risk of EPTB and PTB. This study used the results from two randomised clinical trials of DHA supplementation during pregnancy in which participants completed the DHA-Food Frequency Questionnaire (FFQ) before randomisation to 200mg/day or high dose DHA, i.e., 800mg/day or 1000mg/day. A total of 1400 participants were enrolled in the two trials. Results show that the DHA-FFQ predicted participants whose risk of EPTB and PTB was reduced by consuming a DHA supplement of 800mg/day or 1000mg/day compared to 200mg/day. In fact, participants who started the study with an average daily DHA intake of <150mg had a 64% lower rate of EPTB and a 24% lower rate of PTB if they were assigned to 800mg/day or 1000mg/day compared to 200mg/day DHA. Authors conclude that the DHA-FFQ identifies women who could benefit from high dose DHA supplementation at least as effectively as a blood measure of DHA but with far fewer barriers for clinical implementation.
Abstract
BACKGROUND Two randomized trials found women with low blood docosahexaenoic acid (DHA; an omega 3 fatty acid) had fewer early preterm births (<34 weeks gestation) if they were assigned to high dose DHA supplementation, however, there is currently no capacity for clinicians who care for pregnancies to obtain a blood assessment of DHA. Determining a way to identify women with low DHA intake whose risk could be lowered by high dose DHA supplementation is desired. OBJECTIVE To determine if assessing DHA intake can identify pregnancies that benefit from high dose DHA supplementation. STUDY DESIGN This secondary analysis used birth data from 1310 pregnant women who completed a 7-question food frequency questionnaire (DHA-FFQ) at 16.8 ± 2.5 weeks gestation that is validated to assess DHA status. They were then randomly assigned to a standard (200 mg/day) or high dose (800 or 1000 mg/day) DHA supplement for the remainder of pregnancy. Bayesian logistic regressions were fitted for early preterm birth and preterm birth as a function of DHA intake and assigned DHA dose. RESULTS Participants who consumed less than 150 mg/day DHA prior to 20 weeks' gestation (n = 810/1310, 58.1%) had a lower Bayesian posterior probability (pp) of early preterm birth if they were assigned to high dose DHA supplementation (1.4% vs 3.9%, pp = 0.99). The effect on preterm birth (<37 weeks) was also significant (11.3% vs 14.8%, pp = 0.97). CONCLUSION The DHA-FFQ can identify pregnancies that will benefit most from high dose DHA supplementation and reduce the risk of preterm birth. The DHA-FFQ is low burden to providers and patients and could be easily implemented in obstetrical practice.
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Effects of camelina oil supplementation on lipid profile and glycemic control: a systematic review and dose‒response meta-analysis of randomized clinical trials.
Jalili, C, Talebi, S, Mehrabani, S, Bagheri, R, Wong, A, Amirian, P, Zarpoosh, M, Ghoreishy, SM, Kermani, MAH, Moradi, S
Lipids in health and disease. 2022;21(1):132
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Research indicates that alpha-linolenic acid (ALA) can reduce the risk of cardiovascular disease by improving blood lipids, blood pressure, and haemostatic factors, among others. Camelina oil, considered a good source of ALA compared to other edible oils, is one of the richest dietary sources of omega-3 fatty acids, with a polyunsaturated fatty acid content over 50%. The aim of this study was to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycaemic control in human studies. This study is a systematic review and meta-analysis of seven randomised controlled trials with a total of 428 individuals (202 participants in the COS group and 226 in the control group). Results did not show any affects of COS on lipid profile and glycaemic indices compared with placebo intake. However, subgroup analysis showed that COS for more than 8 weeks and at a dose lower than 30g/d could decrease total cholesterol. Authors conclude that COS may be a beneficial nonpharmacological strategy for the improvement of this lipid marker. However, further studies are required to confirm the findings of this study.
Abstract
BACKGROUND This systematic review and dose-response meta-analysis of published randomized controlled trials (RCTs) was conducted to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycemic indices. METHODS Relevant RCTs were selected by searching the ISI Web of Science, PubMed, and Scopus databases up to July 1, 2022. RTCs with an intervention duration of less than 2 weeks, without a placebo group, and those that used COS in combination with another supplement were excluded. Weighted mean differences and 95% confidence intervals were pooled by applying a random-effects model, while validated methods examined sensitivity analyses, heterogeneity, and publication bias. RESULTS Seven eligible RCTs, including 428 individuals, were selected. The pooled analysis revealed that COS significantly improved total cholesterol in studies lasting more than 8 weeks and utilizing dosages lower than 30 g/d compared to the placebo group. The results of fractional polynomial modeling indicated that there were nonlinear dose-response relations between the dose of COS and absolute mean differences in low-density cholesterol, high-density cholesterol, and total cholesterol, but not triglycerides. It appears that the greatest effect of COS oil occurs at the dosage of 20 g/day. CONCLUSION The present meta-analysis indicates that COS may reduce cardiovascular disease risk by improving lipid profile markers. Based on the results of this study, COS at dosages lower than 30 g/d may be a beneficial nonpharmacological strategy for lipid control. Further RCTs with longer COS durations are warranted to expand on these results.
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Do B Vitamins Enhance the Effect of Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Diseases? A Systematic Review of Clinical Trials.
Zhu, J, Xun, PC, Kolencik, M, Yang, KF, Fly, AD, Kahe, K
Nutrients. 2022;14(8)
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Dietary intake of B-vitamins or omega-3 polyunsaturated fatty acids (PUFAs) has been found to be inversely related to cardiovascular disease (CVD). The aim of this study was to examine whether the combined supplementation of B-vitamins and omega-3 PUFAs could provide additional beneficial effects on improving risk factors to prevent CVD beyond the effects of either of them alone. This study is a systematic review of fifteen studies. The sample sizes ranged from 12 to 2501 participants with study duration ranging from 4 weeks to 4.7 years. Results show that the combined supplementation with B-vitamins and omega-3 PUFAs may be promising and more effective at reducing plasma homocysteine, triglycerides and low-density lipoprotein cholesterol than each supplementation alone. Authors conclude that: - there is no solid evidence that the joint supplementation of B-vitamins and omega-3 PUFAs can offer a synergistic effect on preventing CVD and decreasing the relevant morbidity and/or mortality in susceptible populations. - dietetic strategies for preventing CVD need to focus more on the importance of considering effects at the whole food and dietary patterns level. - further well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are required.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Combined vitamin B and n3 PUFA supplementation might have favourable health effects
- Combined vitamin B and n3 PUFA supplementation could help in the primary and secondary prevention of cardiovascular disease
- The suggested favourable dose ranges are vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day, and n3 PUFA 0.2–2) g/day.
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:
- The paper reviews whether combined supplementation of vitamin B (B2, B6, B9, and B12) and omega-3 polyunsaturated fatty acids (n3 PUFA) outweighs the individual cardiovascular benefits of each supplement. Registered in PROSPERO under CRD42018085993
- A total of 15 clinical studies including 8,263 individuals published from December 2021, that investigated the combined effects of the supplements met inclusion criteria and were included in the review
- Although the results indicate the beneficial effects of combined supplementation in primary and secondary cardiovascular prevention, firm conclusions cannot be drawn from the existing data, and more studies are needed in this area.
Clinical practice applications:
In comparison with a single supplement alone, the combined administration of vitamin B and n3 PUFA might have:
- Hypolipidemic effects, by reducing triglycerides and LDL-cholesterol. Some of the studies indicate a lowering of LDL-c up to 13% and triglycerides up to 24%
- Anti-inflammatory effects, by reducing homocysteine. Based on some of the studies, the lowering effects might go up to 39%.
Dietary practice might benefit from the following:
- The authors highlighted food-based and healthy dietary pattern-based strategies should include food sources rich in these nutrients such as fish, vegetables, fruit, legumes, nuts, and eggs
- The authors conclude that intake of whole foods and whole diets rich in desirable foods (such as MedDiet) should be encouraged
- The supplementation dose ranges in the studies covered by the review were the following: vitamin B6: 2.5–80 mg/day, vitamin B12: 20–1000 μg/day, folic acid: 150–10000 μg/day and n3 PUFA 0.2–2) g/day
- Limitations of the systematic review include different supplementation regimens, variability of study designs in terms of duration of the intervention, existence of placebo group, dosages and the inability to monitor study subjects’ habitual diet.
Considerations for future research:
- Future studies should be designed regarding the need for a uniform methodological approach in testing the combined effects of vitamin B complex and n3 PUFA supplements
- The studies should investigate supplementation strategies and dietary patterns rich in both nutrients.
Abstract
Studies have suggested that B vitamins or omega-3 polyunsaturated fatty acids (PUFAs) may deter the development of cardiovascular disease (CVD). This systematic review aims to examine whether the combined supplementation of both B vitamins and omega-3 PUFAs could provide additional beneficial effects to prevent CVD beyond the effect of each supplement based on clinical trials published up to December 2021. The overall findings are inconsistent and inconclusive, yet the combined supplementation of these two nutrients may be more effective at reducing plasma homocysteine, triglyceride, and low-density lipoprotein-cholesterol than the individual components. The underlying mechanisms mainly include alleviating endothelial dysfunction, inhibiting atherosclerosis and lesion initiation, reducing oxidative stress, suppressing activation of pro-inflammatory cytokines, regulating endothelial nitric oxide synthase, and interfering with methylation of genes that promote atherogenesis. Although biologically plausible, the existing literature is insufficient to draw any firm conclusion regarding whether B vitamins can further enhance the potential beneficial effects of omega-3 PUFA intake on either primary or secondary prevention of CVD. The inconsistent findings may be largely explained by the methodological challenges. Therefore, well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are warranted.
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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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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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Enriched Marine Oil Supplement Increases Specific Plasma Specialized Pro-Resolving Mediators in Adults with Obesity.
Al-Shaer, AE, Regan, J, Buddenbaum, N, Tharwani, S, Drawdy, C, Behee, M, Sergin, S, Fenton, JI, Maddipati, KR, Kane, S, et al
The Journal of nutrition. 2022;152(7):1783-1791
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Specialised pro-resolving mediators (SPMs) are highly potent oxylipins [metabolites] synthesized from omega-3 and omega-6 polyunsaturated fatty acids. SPMs have a critical role in resolving inflammation and returning damaged tissues to homeostasis. The main aim of this study was to determine if a marine oil supplement increased specific metabolites of the SPM biosynthetic pathway in adults with obesity. This study is a non-randomised uncontrolled clinical trial in adults with obesity. Twenty-three participants (n = 13 females, 10 males) aged between 50–65 years were enrolled. Only postmenopausal females were included in order to reduce confounding effects of oestrogen on lipid metabolism during supplementation. Results show that: - the marine oil supplement significantly increased some oxylipins of the SPM biosynthetic pathway. - there wasn’t an increase in the concentration of D-series resolvins upon intervention, although several docosahexaenoic acid-derived metabolites were increased. - the supplement decreased some HETEs [metabolites], which are synthesized from arachidonic acid. Authors conclude that their findings provide a framework for futures studies on the use of a marine oil supplement to examine the effects of how SPMs and their metabolic intermediates control varying aspects of inflammation and immunity, including antibody concentrations, in subjects with obesity.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Marine oil enriched with specialised pro-resolving mediators raise levels of EPA, DPA and DHA-metabolites in adult subjects with obesity
- Larger randomised, blinded and placebo-controlled trials are required to inform healthcare practitioner clinical practice decisions relating to SPM enriched marine oil supplementation
- Future research is required to determine if increased concentrations of SPMs control the resolution of inflammation in humans with obesity.
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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X
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:
- Specialised pro-resolving mediators (SPMs) are oxylipins synthesised from omega-3 and -6 PUFAs which play a role in resolving inflammation.
- The authors highlight mouse studies have found that increasing the levels of SPMs and their metabolic intermediates can improve a range of obesity related complications. Thus, there is scientific interest in increasing the levels of SPMs in humans with diseases associated with chronic inflammation, such as obesity.
- This small non-randomised uncontrolled clinical trial of 23 individuals (13 female; 10 male) aged 50-65 years with obesity (BMI 30-40), aimed to determine the impacts of 1 month supplementation with marine oil particularly enriched with 14-hydroxydocosahexanenoic acid (14-HDHA), 17-HDHA and 18-hydroxydocosahenaenoic acid (HEPE) on:
- The change in levels of PUFA-derived oxylipins from baseline
- The change in abundance of circulating peripheral blood mononuclear cells (PBMCs)
- The change in antibody production
Intervention
- 2g enriched marine oil (4 capsules of SPM Active provided by Metagenics, study sponsor) once daily for 28-30 consecutive days.
Inclusion/Exclusion Criteria
- Only post-menopausal women were included to reduce confounding effects of oestrogen on lipid metabolism
- Individuals were excluded if diagnosed with Type 1 or 2 diabetes, autoimmunity, liver disease, coagulopathy, uncontrolled hypothyroid or active malignancy
- Individuals were excluded if they consumed omega-3 PUFA supplements within 3 months of intervention, regularly consumed >2 servings per week of fatty fish, had a fish/shellfish allergy or were taking a predetermined list of medications.
Findings
- Statistically significant increases were found in certain EPA, DPA and DHA-derived metabolites in response to supplementation relative to baseline. However, only 17-HDHA concentrations increased relative to baseline, with no effect on 14-HDHA or 18-HEPE, despite the supplement being enriched with all 3 metabolites
- Statistically significant decreases were found in arachidonic acid (AA)-derived oxylipins post supplementation relative to baseline
- Increases in immune cell populations in circulation did not reach significance post supplementation when measured by PBMCs.
Conclusions
An enriched marine oil supplement increased select SPMs in adults with obesity.
Clinical practice applications:
- Healthcare practitioners working with adults with obesity can use the results from this trial to understand that 1 month supplementation with 4g of enriched marine oil supplementation raises levels of certain EPA, DPA and DHA metabolites
- Practitioners may want to follow the research in this area as larger, controlled trials are conducted and comparisons made with non-enriched fatty acid supplements.
Considerations for future research:
- Future clinical studies of SPM supplementation are required that are double-blind, randomised and placebo-controlled to inform scientific findings in this area
- This study was inadequately powered to assess differences between female and male participants and therefore larger trials are needed to inform the sex differences in oxylipins within the population with obesity
- Further research is required in younger subjects with obesity to assess SPMs as a possible chronic inflammation preventative strategy, due to inflammation complications over time
- Future research should take account of the heterogeneity in the population with obesity, such as microbiome profiles, food intake and baseline metabolic status
- Further studies comparing impacts of standard marine oil with enriched marine oil on chronic inflammation would inform healthcare practitioners in their clinical practice.
Abstract
BACKGROUND Specialized pro-resolving mediators (SPMs), synthesized from PUFAs, resolve inflammation and return damaged tissue to homeostasis. Thus, increasing metabolites of the SPM biosynthetic pathway may have potential health benefits for select clinical populations, such as subjects with obesity who display dysregulation of SPM metabolism. However, the concentrations of SPMs and their metabolic intermediates in humans with obesity remains unclear. OBJECTIVES The primary objective of this study was to determine if a marine oil supplement increased specific metabolites of the SPM biosynthetic pathway in adults with obesity. The second objective was to determine if the supplement changed the relative abundance of key immune cell populations. Finally, given the critical role of antibodies in inflammation, we determined if ex vivo CD19 + B-cell antibody production was modified by marine oil intervention. METHODS Twenty-three subjects [median age: 56 y; BMI (in kg/m2): 33.1] consumed 2 g/d of a marine oil supplement for 28-30 d. The supplement was particularly enriched with 18-hydroxyeicosapentaenoic (HEPE), 14-hydroxydocosahexaenoic acid (14-HDHA), and 17-HDHA. Blood was collected pre- and postsupplementation for plasma mass spectrometry oxylipin and fatty acid analyses, flow cytometry, and B-cell isolation. Paired t-tests and Wilcoxon tests were used for statistical analyses. RESULTS Relative to preintervention, the supplement increased 6 different HEPEs and HDHAs accompanied by changes in plasma PUFAs. Resolvin E1 and docosapentaenoic acid-derived maresin 1 concentrations were increased 3.5- and 4.7-fold upon intervention, respectively. The supplement did not increase the concentration of D-series resolvins and had no effect on the abundance of immune cells. Ex vivo B-cell IgG but not IgM concentrations were lowered postsupplementation. CONCLUSIONS A marine oil supplement increased select SPMs and their metabolic intermediates in adults with obesity. Additional studies are needed to determine if increased concentrations of specific SPMs control the resolution of inflammation in humans with obesity. This trial was registered at clinicaltrials.gov as NCT04701138.
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Low omega-3 polyunsaturated fatty acids predict reduced response to standard antidepressants in patients with major depressive disorder.
Cussotto, S, Delgado, I, Oriolo, G, Kemper, J, Begarie, D, Dexpert, S, Sauvant, J, Leboyer, M, Aouizerate, B, Martin-Santos, R, et al
Depression and anxiety. 2022
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Plain language summary
Major depressive disorder (MDD) is a leading cause of disability, and antidepressant drug treatment is only effective in over half of patients with a high prevalence of treatment resistance. The importance of nutrition in mental health is gaining recognition. Omega-3 is an essential polyunsaturated fatty acid (PUFA) vital for anti-inflammatory processes and brain integrity. In the absence of the body's ability to make Omega-3, it or its precursors must be acquired from the diet. Yet altered metabolic pathways can hamper the process and the adequate balance with PUFA Omega‐6 is also crucial, as elevated levels of Omega-6 are linked to several diseases. An extensive amount of research suggests that higher Omega-3 levels reduce the occurrence of depression. Yet results using just Omega-3s for depression have been varied. This European-wide study sought to investigate how the PUFA status could affect the clinical response to treatment with antidepressants. 60-adults with an average age of 41 with major depressive disorders received antidepressive treatment. Their red blood cell fatty acids content was determined, and at the end of the 8-week trial treatment responders and non-responders were identified. Findings affirmed the existing knowledge that depressive symptoms are strongly associated with PUFA status. Patients who did not respond to treatment showed low levels of Omega-3 and an unfavourable ratio of Omega-3 to Omega-6 at the start of treatment. Higher levels of Omega-3 fatty acid of DHA seemed to produce a better clinical response to treatments than the Omega-3 of EPA. The authors discussed some potential mechanisms and suggested that PUFA intake and metabolism could be a potential tool for the management of treatment-unresponsive patients with depression. This review highlights the clinical importance of considering PUFA status and metabolism in the support of major depressive disorders.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Healthy eating such as that with low omega-6 diets has more than a physiological result on the human body and carries significant biochemical consequences when the omega-6 to omega-3 ratio is deemed to be ‘high’.
- The result of this research has pharmaceutical implications - if the findings could be imparted to the general public in layman’s terms, practitioners could empower individuals to take greater control of their mental health through more naturalistic means, i.e., optimised nutrition.
- There are wider cognitive considerations of healthy eating beyond that of treating Major Depressive Disorder due to implicated blood-brain-barrier effects, as concluded in this study.
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:
Sixty adults suffering from major depressive disorder (MDD) were recruited into a multicenter study assessing the impact of baseline polyunsaturated (PUFA) levels on responsiveness to antidepressants. Neuropsychiatric evaluations producing MADRS (Montgomery Åsberg Depression Rating Scale) scores at baseline, four weeks and again at eight weeks, were performed. The pre-recorded baseline PUFA levels were then used as an associative and predictive indicator when viewing the end point scoring of participants, thus categorising into responsive and nonresponsive strata.
Of those with low omega-3 and high omega-6 to omega-3 ratio at baseline, there was increased association with ‘non-responsive’ classification at end point (week 8). Participants were deemed ‘non-responsive’ to anti-depressant treatment when scores at week 8 failed to demonstrate ≥50% reduction in MADRS scoring.
Clinical practice applications:
- Clinicians could monitor MDD within at-risk-groups, such as those who are overweight (mean BMI of ALL study participants was 24.20 kg/m2 with a standard deviation of 4.21) or those experiencing an inflammatory state with blood-brain-barrier involvement, as part of a mental ill-health prevention programme.
- When presenting with symptoms of major depressive disorder and prescribing antidepressants, clinicians could recommend increasing consumption of foods high in omega-3 and/or querying the patient about their dietary habits.
- Article supports recommendations for an increase in the consumption of omega-3 rich foods amongst the general population to prevent or intervene in cases of major depressive disorder.
- Wider cognitive implications beyond major depressive disorder in the presence of low omega-3, such as cognitive decline as seen with dementia, theorised due to altered blood-brain-barrier (Cussotto et al., 2022; Gustafson et al., 2020).
Considerations for future research:
- Repeated studies, with normalised distribution of antidepressant and sample size by country, with greater geographic inclusion, along with age categorisation. The broader geographic inclusion is necessary to rule out cultural diets as a confounding variable. An example of how different cultural diets could influence the results, which has potentially been highlighted in this study, is the more predominant consumption of a Mediterranean diet which may have been the case for the participants from Spain or, as could also be the case, an underlying vitamin D deficiency of the participants from Germany.
- Novel studies for assessing diet against mood could be beneficial to fully apply the findings of this study to clinical practice applications and that of the practice of nutritional therapists. The thinking here is the potential for anti-inflammatory foods inducing better mood results through gut-brain axis links and resultant influence on microbiome.
Abstract
BACKGROUND Major depressive disorder (MDD) is characterized by a high rate of treatment resistance. Omega (ω)-3 polyunsaturated fatty acids (PUFAs) were shown to correlate with depressive phenotype both in rodents and in humans. However, few studies to date have investigated the role of PUFAs in antidepressant response. The primary aim of this study was to assess the link between baseline PUFA composition and changes in depressive symptoms as well as antidepressant response in a multicenter study of depressed patients. METHODS Sixty depressed adults who met criteria for MDD according to DSM-IV-TR were recruited. Neuropsychiatric evaluations occurred at baseline and after 4 and 8 weeks of treatment with standard antidepressants, including escitalopram (N = 45), sertraline (N = 13) and venlafaxine (N = 2). At study endpoint, patients were stratified into responders (R) or non-responders (NR) based on their MADRS (Montgomery-Åsberg Depression Rating Scale) score. Baseline PUFA levels were assessed and their association with clinical response was determined. RESULTS Lower ω-3 PUFA levels were associated to worse baseline symptomatology. Baseline levels of PUFAs were significantly different between R and NR, with R exhibiting lower docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and ω-3 index; and higher ω-6/ω-3 ratio than NR before the start of antidepressant treatment. DHA levels as well as the ω-3 index and ω-6/ω-3 ratio significantly predicted response to antidepressants at study endpoint. CONCLUSIONS These results show that baseline levels of PUFAs predict later response to standard antidepressants in depressed subjects. They suggest that PUFA intake and/or metabolism represent a novel modifiable tool for the management of unresponsive depressed patients.
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10.
Vegan diet in young children remodels metabolism and challenges the statuses of essential nutrients.
Hovinen, T, Korkalo, L, Freese, R, Skaffari, E, Isohanni, P, Niemi, M, Nevalainen, J, Gylling, H, Zamboni, N, Erkkola, M, et al
EMBO molecular medicine. 2021;13(2):e13492
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Plain language summary
As vegan diets gain popularity amongst families, there is little known about the impact of strict plant-based diets on metabolism and micronutrient status in children, apart from reduced average growth within the norm. This small study looked at 40 Finnish children from one day centre, and compared children following an omnivore or vegetarian diet to those raised on a vegan diet. The diets were analysed, and biomarkers and metabolites were measured. The metabolic profile and nutrient status of children who followed a vegan diet from birth were distinctively different to other diet patterns, including vegetarians. The authors suggest that little animal source foods are enough to shift the metabolism of children. Dietary analysis showed that vegan children had higher folate consumption and lower protein and saturated fats intake. Despite intake appearing adequate, serum markers for fat-soluble vitamins A and D were low. While the fatty acid ALA was higher compared to omnivores, DHA and overall cholesterol were decreased. The authors concluded that the bodies own cholesterol production does not seem to compensate for a lack of dietary cholesterol in this case and it remains to be established whether lower cholesterol in vegan children are negative to health. Furthermore, the circulating amino acids pool was decreased in vegan children, particularly branch chained amino acids. The most distinct difference, however, was seen in the variance of bile acid patterns. The physiological functions of bile acids go beyond digestion, yet the consequences of diverging bile acid profiles in children’s health are unknown. In conclusion, the data shows that a strict vegan diet affects the metabolism of healthy children, but much of the long-term impact on health is currently still unclear. This article highlights some of the differences, risks and uncertainties that come with raising young children on a strictly vegan diet.
Abstract
Vegan diets are gaining popularity, also in families with young children. However, the effects of strict plant-based diets on metabolism and micronutrient status of children are unknown. We recruited 40 Finnish children with a median age 3.5 years-vegans, vegetarians, or omnivores from same daycare centers-for a cross-sectional study. They enjoyed nutritionist-planned vegan or omnivore meals in daycare, and the full diets were analyzed with questionnaires and food records. Detailed analysis of serum metabolomics and biomarkers indicated vitamin A insufficiency and border-line sufficient vitamin D in all vegan participants. Their serum total, HDL and LDL cholesterol, essential amino acid, and docosahexaenoic n-3 fatty acid (DHA) levels were markedly low and primary bile acid biosynthesis, and phospholipid balance was distinct from omnivores. Possible combination of low vitamin A and DHA status raise concern for their visual health. Our evidence indicates that (i) vitamin A and D status of vegan children requires special attention; (ii) dietary recommendations for children cannot be extrapolated from adult vegan studies; and (iii) longitudinal studies on infant-onset vegan diets are warranted.