Randomized trial of omega-3 for autism spectrum disorders: Effect on cell membrane composition and behavior

Parellada, Mara; Llorente, Cloe; Calvo, Rosa; Gutiérrez, Sílvia; Lázaro, Luisa; Graell, Montserrat; Guisasola, M.C.; Dorado, María Luisa; Boada, Leticia; Romo, J.; Dulín, Elena; Sanz, Inmaculada; Arango, Celso; Moreno, Carmen

doi:10.1016/j.euroneuro.2017.08.426

Cited by 55 publications

(64 citation statements)

References 56 publications

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“…PUFA content, brain development and the prevalence of neurodevelopmental disorders 17 . The n-3 PUFA index, which reports the level of n-3 PUFAs (EPA+DHA) in erythrocytes and that is used as a biomarker for cardiovascular diseases 67 , is now considered as a new biomarker for several neurodevelopment diseases such as ASD 68 , attention deficit hyperactivity disorder (ADHD) 69 and schizophrenia 70,71 . Since these essential fatty acids are necessary for healthy brain development, low dietary supply or impairment of their metabolism is suggested to be involved in the etiology of several psychiatric diseases, including neurodevelopmental 1 5 controllers of synaptic architecture due to their phagocytic activity 24,25,27,91 , we show for the first time that specific lipid mediators drive microglia phagocytic activity towards synapses.…”

Section: Discussionmentioning

confidence: 99%

Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain

Madore

Leyrolle²,

Morel

et al. 2019

Preprint

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Omega-3 fatty acids (n-3 polyunsaturated fatty acids; n-3 PUFAs) are essential for the functional maturation of the brain. Westernization of dietary habits in both developed and developing countries is accompanied by a progressive reduction in dietary intake of n-3PUFAs. Low maternal intake of n-3 PUFAs has been linked to neurodevelopmental diseases in epidemiological studies, but the mechanisms by which a n-3 PUFA dietary imbalance affects CNS development are poorly understood. Active microglial engulfment of synaptic elements is an important process for normal brain development and altered synapse refinement is a hallmark of several neurodevelopmental disorders. Here, we identify a molecular mechanism for detrimental effects of low maternal n-3 PUFA intake on hippocampal development. Our results show that maternal dietary n-3 PUFA deficiency increases microglial phagocytosis of synaptic elements in the developing hippocampus, through the activation of 12/15-lipoxygenase (LOX)/12-HETE signaling, which alters neuronal morphology and affects cognition in the postnatal offspring. While women of child bearing age are at higher risk of dietary n-3 PUFA deficiency, these findings provide new insights into the mechanisms linking maternal nutrition to neurodevelopmental disorders.One Sentence Summary: Low maternal omega-3 fatty acids intake impairs microgliamediated synaptic refinement via 12-HETE pathway in the developing brain.

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Section: Discussionmentioning

confidence: 99%

Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain

Madore

Leyrolle²,

Morel

et al. 2019

Preprint

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“…Finally, we identified 23 full text articles corresponding to 10 RCTs [40][41][42][43][44][45][46][47][48][49] through the search strategy for experimental studies (see also Additional file 2 and Fig. 1).…”

Section: Studies Retrieved Through the Search Strategy For Rctsmentioning

confidence: 99%

“…We retrieved 809 citations from database searching and 3 studies from unstructured web searching. We excluded 788 documents from title and abstract, and after excluding 15 full text articles for various reasons (see Additional file 2) we finally included 10 non-randomized studies reporting data on equity, acceptability or feasibility [9,[41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] (see Fig. 1).…”

Section: Non-randomized Studies Retrieved Through the Search Strategymentioning

confidence: 99%

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Equity, acceptability and feasibility of using polyunsaturated fatty acids in children and adolescents with autism spectrum disorder: a rapid systematic review

D’Alò

Crescenzo

Morgano

et al. 2020

Health Qual Life Outcomes

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Introduction: Some recent randomized controlled trials (RCTs) assessed the efficacy and safety of polyunsaturated fatty acids (PUFAs) for the treatment of autism spectrum disorder (ASD). To optimally inform the Italian guideline for the management of ASD in children and adolescents, we reviewed the impact on equity, acceptability and feasibility for developing a pilot recommendation for PUFAs. Methods: We performed a rapid systematic review of observational and experimental studies on PUFAs for children and adolescents with ASD, extracting data on resources required, equity, acceptability, and feasibility of PUFAs. We followed the framework provided by the grading of recommendations assessment, development and evaluation (GRADE) methodology, and we assessed risk of bias and methodological quality of included studies. Results were synthesized both narratively and quantitatively to address clinically relevant questions on equity, acceptability, and feasibility. Results: We found 14 papers related to equity. PUFAs did not seem to impact equity importantly. We did not find variation in effectiveness across subgroups and in a base case scenario, the cost of a 12 weeks cycle of therapy with 1.155 g/day of PUFAs was €65.51 euro. The acceptability of PUFAs was evaluated in 17 studies, 9 of which were RCTs. PUFAs were widely used among children and adolescents with ASD (18 to 51%), and 50% of parents considered nutritional supplementation as useful. Difficulty in swallowing capsules and bad taste were identified as possible causes of poor compliance, but treatment adherence, when measured in included RCTs, was judged to be good to excellent. Discontinuation due to any cause for PUFAs could not differ from placebo (low certainty of evidence). The feasibility of using PUFAs was assessed in 12 studies. PUFAs were probably sustainable, and no particular critical issue emerged from the feasibility assessment. However, the evidence appeared scarce and indirect.

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“…The studies on pregnant women showed that DHA deficiency might lead to poor language skill among children (Mulder et al, 2014). Even autistic spectrum disorder or ADHD among teenagers is related to DHA deficiency (Bos et al, 2015;Parellada et al, 2017). Due to DHA deficiency, neurocognitive functional insufficiency in young adults or loneliness related memory problems in middle age has been observed (Bauer et al, 2014;Jaremka et al, 2014).…”

Section: Dha Deficiency and Human Brain Functionmentioning

confidence: 99%

Docosahexaenoic acid, 22:6n‐3: Its roles in the structure and function of the brain

Mallick

Basak

Duttaroy

2019

Intl J of Devlp Neuroscience

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Docosahexaenoic acid,22:6n-3 (DHA) and its metabolites are vital for the structure and functional brain development of the fetus and infants, and also for maintenance of healthy brain function of adults. DHA is thought to be an essential nutrient required throughout the life cycle for the maintenance of overall brain health. The mode of actions of DHA and its derivatives at both cellular and molecular levels in the brain are emerging. DHA is the major prevalent fatty acid in the brain membrane. The brain maintains its fatty acid levels mainly via the uptake of plasma free fatty acids. Therefore, circulating plasma DHA is significantly related to cognitive abilities during ageing and is inversely associated with cognitive decline. The signaling pathways of DHA and its metabolites are involved in neurogenesis, antinociceptive effects, anti-apoptotic effect, synaptic plasticity, Ca 2+ homeostasis in brain diseases, and the functioning of nigrostriatal activities. Mechanisms of action of DHA metabolites on various processes in the brain are not yet well known. Epidemiological studies support a link between low habitual intake of DHA and a higher risk of brain disorders. A diet characterized by higher intakes of foods containing high in n-3 fatty acids, and/or lower intake of n-6 fatty acids was strongly associated with a lower Alzheimer's Disease and other brain disorders. Supplementation of DHA improves some behaviors associated with attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior, as well as cognition. Nevertheless, the outcomes of trials with DHA supplementation have been controversial. Many intervention studies with DHA have shown an apparent benefit in brain function. However, clinical trials are needed for definitive conclusions. Dietary deficiency of n-3 fatty acids during fetal development in utero and the postnatal state has detrimental effects on cognitive abilities. Further research in humans is required to assess a variety of clinical outcomes, including quality of life and mental status, by supplementation of DHA.

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Randomized trial of omega-3 for autism spectrum disorders: Effect on cell membrane composition and behavior

Cited by 55 publications

References 56 publications

Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain

Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain

Equity, acceptability and feasibility of using polyunsaturated fatty acids in children and adolescents with autism spectrum disorder: a rapid systematic review

Docosahexaenoic acid, 22:6n‐3: Its roles in the structure and function of the brain

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