scholarly journals Dietary Supplementation with Omega-3 Polyunsaturated Fatty Acids Reduces Opioid-Seeking Behaviors and Alters the Gut Microbiome

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1900 ◽  
Author(s):  
Joshua K. Hakimian ◽  
Tien S. Dong ◽  
Jorge A. Barahona ◽  
Venu Lagishetty ◽  
Suchi Tiwari ◽  
...  

Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses observed in human opioid addiction. The mechanisms associated with opioid dependence, the accompanying withdrawal symptoms, and the relapses that are often observed months or years after opioid dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure whereby the level of administration is self-directed with periods of behavior acquisition, maintenance, and then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that dietary interventions that reduce inflammation, including omega-3 polyunsaturated fatty acids (n-3 PUFAs), may reduce substance misuse liability. Using the self-directed intake model, we characterize the observed profile of opioid use and demonstrate that an n-3-PUFA-enriched diet ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile the microbiome composition and the effects of chronic opioid exposure and n-3 PUFA supplementation. We demonstrate that the withdrawal of opioids led to a significant depletion in specific microbiota genera, whereas n-3 PUFA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we examined the activation state of microglia in the striatum and found that n-3 PUFA supplementation reduced the basal activation state of microglia. These preclinical data suggest that a diet enriched in n-3 PUFAs could be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid addiction.

Author(s):  
Joshua K. Hakimian ◽  
Tien Dong ◽  
Jorge A. Barahona ◽  
Venu Lagishetty ◽  
Suchi Tiwari ◽  
...  

Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses observed in human opioid addiction. The mechanisms associated with opioid dependence, the accompanying withdrawal symptoms and the relapses that are often observed months or years after opioid dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure whereby the level of administration is self-directed with periods of behavior acquisition, maintenance and then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that dietary interventions that reduce inflammation, including omega-3 fatty acids such as docosahexaenoic acid (DHA), may reduce substance misuse liability. Using the self-directed intake model, we characterize the observed profile of opioid use and demonstrate that a diet enriched in polyunsaturated fat acids (PUFAs) ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile the microbiome composition and the effects of chronic opioid exposure and DHA supplementation. We demonstrate that withdrawal of opioids led to a significant depletion in specific microbiota genera whereas DHA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we examined the activation state of microglia in the striatum and found that DHA supplementation reduced the basal activation state of microglia. These preclinical data suggest that a diet enriched in PUFAs could be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid addiction.


2014 ◽  
Vol 4 (6) ◽  
pp. 245 ◽  
Author(s):  
Klaus W. Lange ◽  
Joachim Hauser ◽  
Shigehiko Kanaya ◽  
Ivo Kaunzinger ◽  
Katharina M Lange ◽  
...  

Background: Attention deficit/hyperactivity disorder (ADHD) is one of the most common behavioral disorders in children. Insufficient dietary intake of long-chain polyunsaturated fatty acids (LC-PUFAs) has been suggested to have an impact on the development of symptoms of ADHD in children. Individuals with ADHD have been demonstrated to have significantly reduced blood concentrations of PUFAs and, in particular, reduced levels of omega-3 (n-3) PUFAs. These findings suggest that PUFA supplementation may reduce the attention and behavior problems associated with ADHD.Objective: To provide an overview of the efficacy of dietary LC-PUFA supplementation in the treatment of ADHD. Methods: Literature published up until December 2013 on the effects of n-3 PUFA supplementation on ADHD symptoms was obtained using a PubMed search and critically reviewed.Results: Dietary PUFA supplementation appears to have beneficial effects on ADHD symptoms although these effects are small. The clinical relevance of these observations remains to be determined.Conclusion: There is only limited support for the efficacy of PUFA supplementation for the core symptoms of ADHD. Given the small effect sizes regarding PUFA supplementation, it may not be a sufficient therapy for a majority of patients with ADHD.Keywords: diet, nutrition, polyunsaturated fatty acid, PUFA, attention deficit/hyperactivity disorder, ADHD


Author(s):  
C. Hooper ◽  
P. De Souto Barreto ◽  
M. Pahor ◽  
M. Weiner ◽  
B. Vellas

Significant research attention has focussed on the identification of nutraceutical agents for the prevention of cognitive decline as a natural means of cognitive preservation in the elderly. There is some evidence for a reduction of brain omega 3 polyunsaturated fatty acids (n-3 PUFAs) in normal aging and in Alzheimer’s disease. n-3 PUFAs exhibit anti-inflammatory and anti-amyloidogenic properties as well as being able to reduce tau phosphorylation. Many observational studies have demonstrated a link between n-3 PUFAs and cognitive aging, and some, but not all, randomized controlled trials have demonstrated a benefit of n-3 PUFA supplementation on cognition, particularly in those subjects with mild cognitive impairment. The identification of a biomarker that reflects n-3 PUFA intake over time and consequent tissue levels is required. In this narrative review we discuss the evidence associating red blood cell membrane n-3 PUFAs with cognitive function and structural brain changes associated with Alzheimer’s disease. Key words: Docosahexaenoic acid, omega 3 polyunsaturated fatty aci


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3455
Author(s):  
María Isabel Martínez-Martínez ◽  
Antoni Alegre-Martínez ◽  
Omar Cauli

Omega-3 long-chain polyunsaturated fatty acids play a central role in neuronal growth and in the development of the human brain, since they are essential elements which depend on intake through diet to ensure an adequate amount. Fish and seafood are the main dietary sources of these fatty acids in Spain and in other countries. In order to assess the effect of the intake of common foods containing high amounts of omega-3 polyunsaturated fatty acids, a food frequency questionnaire was administered to parents of children and adolescents attending a primary school in Valencia (Spain), and the intake of dietary omega-3 such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was estimated based on their fish/seafood consumption. Low frequencies of intake were significantly (p < 0.05) lower for many types of fish/seafood in children compared to adolescents. 27.5% of children/adolescents did not eat lean fish or other types (19.8% of the sample did not eat fatty fish, and 71.8% did not eat smoked fish) and 20–60% of the sample consumed seafood only once–three times a month, leading to a reduced estimated intake of EPA+DHA below that recommended for both groups by public health agencies. Social aspects, such as the type of work done by mothers and their educational levels are significant factors (p < 0.05 in both cases) affecting children’s/adolescents’ intake of DHA+EPA. Dietary interventions to increase the consumption of fish and seafood are strongly advised, and health promotion strategies should be aimed at the family level and fight against gender disparities.


Author(s):  
Xueliang Zhu ◽  
Zhichao Bi ◽  
Chen Yang ◽  
Yanhui Guo ◽  
Jieli Yuan ◽  
...  

Background: Omega-3 polyunsaturated fatty acids (PUFAs) play beneficial roles in metabolism and health. Little is known about the effects of different doses of omega-3 PUFAs on gut microbiota. Objective: In this study, we focus on the effects of different doses of omega-3 PUFAs on gut microbiota and immunity. Design: BALB/c mice was first treated with ceftriaxone sodium for 7 days, and then they received saline or different doses of omega-3 PUFAs (30, 60 and 90 mg omega-3 PUFAs) via daily gavage for 21 days. Alterations of cecum microbiota; the tight junction proteins, zonula occludens 3 (ZO3) and occludin, in the ileal wall; serum lipopolysaccharide (LPS); Interleukin-10 (IL-10), interleukin-1β (IL-1β), and Tumour Necrosis Factor α (TNF-α) ; mucus SIgA levels were measured. Results: Compared with the ceftriaxone sodium administration group, significant increases in bacterial richness and diversity were observed in the 60- and 90-mg omega-3 PUFA groups, while only a slight increase was observed in the 30-mg omega-3 PUFA group. A higher percentage of several genera, including Lactobacillus, Helicobacter, and Ruminococcus, and a lower percentage of Bacteroides, Clostridium, and Prevotella were observed in the 60- and 90-mg omega-3 PUFA groups when compared with those in the 30-mg group. The expression of ZO3 and occludin proteins increased in 60- and 90-mg omega-3 PUFA groups compared with the natural recovery group. The mucus SIgA and serum IL-10 levels were increased, and serum levels of LPS, IL-1β, and TNF-α were decreased in the 60- and 90-mg omega-3 PUFA groups when compared with those in the ceftriaxone sodium-treated group. Conclusion: Different doses of omega-3 PUFAs have different therapeutic effects on the intestinal microbiota. The 60- and 90-mg omega-3 PUFA supplementation had better recovery effects on the gut microbiota and immunity than those of the 30 mg omega-3 PUFAs supplementation.


Author(s):  
Timothy D. Mickleborough

Increased muscle oxidative stress and inflammatory responses among athletes have been reported consistently. In addition, it is well known that exhaustive or unaccustomed exercise can lead to muscle fatigue, delayed-onset muscle soreness, and a decrement in performance. Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to decrease the production of inflammatory eicosanoids, cytokines, and reactive oxygen species; have immunomodulatory effects; and attenuate inflammatory diseases. While a number of studies have assessed the efficacy of omega-3 PUFA supplementation on red blood cell deformability, muscle damage, inflammation, and metabolism during exercise, only a few have evaluated the impact of omega-3 PUFA supplementation on exercise performance. It has been suggested that the ingestion of EPA and DHA of approximately 1–2 g/d, at a ratio of EPA to DHA of 2:1, may be beneficial in counteracting exercise-induced inflammation and for the overall athlete health. However, the human data are inconclusive as to whether omega-3 PUFA supplementation at this dosage is effective in attenuating the inflammatory and immunomodulatory response to exercise and improving exercise performance. Thus, attempts should be made to establish an optimal omega-3 fatty-acid dosage to maximize the risk-to-reward ratio of supplementation. It should be noted that high omega-3 PUFA consumption may lead to immunosuppression and prolong bleeding time. Future studies investigating the efficacy of omega-3 PUFA supplementation in exercise-trained individuals should consider using an exercise protocol of sufficient duration and intensity to produce a more robust oxidative and inflammatory response.


Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 893
Author(s):  
Aleksandra Veselinović ◽  
Snježana Petrović ◽  
Vladica Žikić ◽  
Miško Subotić ◽  
Vladimir Jakovljević ◽  
...  

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction across multiple contexts and restricted, repetitive patterns of behavior, interests and activities. The maternal status of polyunsaturated fatty acids (PUFA) regulates microglial activity and neuroinflammatory pathways during a child’s brain development. In children with ASD, the metabolism of PUFA is thought to be deficient or abnormal, leading to increased production of proinflammatory cytokines, increased oxidative stress and an imbalance in the formation and action of neurotransmitters. In addition, nutritional deficits in omega-3 PUFA may affect gut microbiota and contribute to ASD by the gut–brain axis. The aim of this study was to review the possible role of neuroinflammation in ASD development and the effect of omega-3 PUFA supplementation in children with ASD. Due to a wide heterogeneity across RCTs, no definitive conclusion about omega-3 PUFA effects in ASD can be drawn. Supplementation with PUFA could be considered as one of the aspects in regulating the biological status of the organism and could provide added value to standard medical and psychological interventions for reducing behavioral deficits.


Genes ◽  
2013 ◽  
Vol 4 (3) ◽  
pp. 485-498 ◽  
Author(s):  
Hubert Cormier ◽  
Iwona Rudkowska ◽  
Elisabeth Thifault ◽  
Simone Lemieux ◽  
Patrick Couture ◽  
...  

2013 ◽  
Vol 59 (7) ◽  
pp. 503-510 ◽  
Author(s):  
Sonica Sharma ◽  
Sanjay Chhibber ◽  
Harsh Mohan ◽  
Saroj Sharma

The immune benefits associated with the optimal intake of dietary fatty acids are widely known. The objective of the present investigation was to elucidate the role of omega-3 polyunsaturated fatty acids (n-3 PUFA) food source on acute pneumonia induced by Klebsiella pneumoniae. Three different n-3 PUFA preparations (cod liver oil, Maxigard, and flaxseed oil) were orally supplemented and infection was induced in different groups of experimental mice. Mice fed olive oil and normal saline served as oil and saline controls, respectively. After 2 weeks of fatty acid feeding, no effect on the establishment of infection was observed when acute pneumonia was induced in animals. On the other hand, 6 weeks of n-3 PUFA administration was found to improve resistance in mice, as reduced lung bacterial load coupled with significant improvement in pathology was seen in infected mice. Alveolar macrophages collected from all 3 groups of mice fed n-3 PUFA exhibited a significant decrease in the level of apoptosis following infection with K. pneumoniae and an enhanced in vitro phagocytic potential for the pathogen. Lower lung levels of nitric oxide, malondialdehyde, and lactate dehydrogenase were associated with a decrease in the severity of tissue damage. There was a significant increase in the lung levels of pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)). No significant change was observed in the levels of interleukin-10 (IL-10). This study highlights that dietary n-3 PUFA supplementation exerts an overall beneficial effect against acute experimental pneumonia. This mechanism is operative through upregulation of nonspecific and specific immune defenses of the host.


2021 ◽  
Vol 11 ◽  
Author(s):  
Hildur Arnardottir ◽  
Sven-Christian Pawelzik ◽  
Ulf Öhlund Wistbacka ◽  
Gonzalo Artiach ◽  
Robin Hofmann ◽  
...  

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 triggers an immune response with local inflammation in the lung, which may extend to a systemic hyperinflammatory reaction. Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications. In addition to the release of cytokines, referred to as cytokine release syndrome or “cytokine storm,” increased pro-inflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an “eicosanoid storm,” which contributes to the uncontrolled systemic inflammation. Specialized pro-resolving mediators, which are derived from omega-3 PUFA, limit inflammatory reactions by an active process called resolution of inflammation. Here, the rationale for omega-3 PUFA supplementation in COVID-19 patients is presented along with a brief overview of the study protocol for the trial “Resolving Inflammatory Storm in COVID-19 Patients by Omega-3 Polyunsaturated Fatty Acids - A single-blind, randomized, placebo-controlled feasibility study” (COVID-Omega-F). EudraCT: 2020-002293-28; clinicaltrials.gov: NCT04647604.


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