Omega-3 Fatty Acids and Vulnerability to Addiction: Reviewing Preclinical and Clinical Evidence

Abstract

Omega-3 (N3) fatty acids are dietary nutrients that are essential for human health. Arguably, one of their most critical contributions to health is their involvement in the structure and function of the nervous system. N3 fatty acids accumulate in neuronal membranes through young adulthood, becoming particularly enriched in a brain region known to be the locus of cognitive control of behavior-the prefrontal cortex (PFC). The PFC undergoes a surge in development during adolescence, coinciding with a life stage when dietary quality and intake of N3 fatty acids tend to be suboptimal. Such low intake may impact neurodevelopment and normative development of cognitive functions suggested to be protective for the risk of subsequent substance and alcohol use disorders (UD). While multiple genetic and environmental factors contribute to risk for and resilience to substance and alcohol use disorders, mounting evidence suggests that dietary patterns early in life may also modulate cognitive and behavioral factors thought to elevate UD risk (e.g., impulsivity and reward sensitivity). This review aims to summarize the literature on dietary N3 fatty acids during childhood and adolescence and risk of executive/ cognitive or behavioral dysfunction, which may contribute to the risk of subsequent UD. We begin with a review of the effects of N3 fatty acids in the brain at the molecular to cellular levels–providing the biochemical mechanisms ostensibly supporting observed beneficial effects. We continue with a review of cognitive, behavioral and neurodevelopmental features thought to predict early substance and alcohol use in humans. This is followed by a review of the preclinical literature, largely demonstrating that dietary manipulation of N3 fatty acids contributes to behavioral changes that impact drug sensitivity. Finally, a review of the available evidence in human literature, suggesting an association between dietary N3 fatty and neurodevelopmental profiles associated with risk of adverse outcomes including UD. We conclude with a brief summary and call to action for additional research to extend the current understanding of the impact of dietary N3 fatty acids and the risk of drug and alcohol UD.

The Metabolic Matrix: Re-engineering ultraprocessed foods to feed the gut, protect the liver, and support the brain

“…The third pillar is to “ support the brain .” The Western diet is characterized as the habitual consumption of ultraprocessed food products, characterized by an elevated intake of omega-6 fatty acids (which in excess can promote inflammation) ( 48 ), with simultaneous insufficiency in brain-essential omega-3 fats, excessive sugar and sodium, reduced micronutrient intake, and a high intake of refined carbohydrates ( 49 ). The omega-6 to omega-3 ratio consistent with Western-type dietary patterns appears to be a primary contributing factor to the premature development of all NCDs, including metabolic dysfunction such as heart disease and stroke ( 50 , 51 ), neurodegenerative diseases ( 52 ); addiction ( 53 , 54 ), and depression ( 55–57 ).…”

Omega-3 for the Prevention of Alcohol Use Disorder Relapse: A Placebo-Controlled, Randomized Clinical Trial

“…A systematic review analyzed 2,231 studies involving omega-3 and alcohol dependence and, despite the inconclusive results obtained in clinical trials, improvements at the behavioral, cellular and molecular levels were found in preclinical studies (6). In turn, a narrative review suggested that the intake of the omega-3 metabolite docosahexaenoic acid (DHA) in childhood and adolescence plays an important role in the neurodevelopment of the prefrontal cortex, an area involved in impulse control, contributing to a decrease in vulnerability to alcohol dependence (28). In addition, a clinical trial evaluated the effect of omega-3 supplementation (1 g of fish oil daily) for 3 weeks in a group of patients hospitalized due to alcohol use disorder.…”

Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury

“…It is no surprise that omega-3 fatty acids (FAs) are regarded as important dietary nutrients, due to their critical value in the structure and functioning of the nervous system (Darcey and Serafine 2020). Intriguingly, administration of omega-3 FAs was previously highlighted as a safe and efficacious therapy to alleviate organ failure evoked by sepsis (Wolbrink et al 2020).…”