| Increased levels of endocannabinoids, 2-arachidonoylglycerol (2-AG) and arachidonoyl ethanolamide (AEA)
have a pathophysiological role in the setting of cardiometabolic diseases. This systematic review was carried out
to appraise the effect of omega-3 on cardiometabolic risk factors by highlighting the mediating effect of endocannabinoids.
SCOPUS, PubMed, Embase, Google Scholar and ProQuest databases were searched until
January 2020. All published English-language animal studies and clinical trials that evaluated the effects of
omega-3 on cardiometabolic diseases with a focus on endocannabinoids were included. Of 1407 studies, 16
animal studies and three clinical trials were included for analysis. Eleven animal studies and two human studies
showed a marked reduction in 2-AG and AEA levels following intake of omega-3 which correlated with decreased
adiposity, weight gain and improved glucose homeostasis. Moreover, endocannabinoids were elevated
in three studies that replaced omega-3 with omega-6. Omega-3 showed anti-inflammatory properties due to
reduced levels of inflammatory cytokines, regulation of T-cells function and increased levels of eicosapentaenoyl
ethanolamide, docosahexaenoyl ethanolamide and oxylipins; however, a limited number of studies examined a
correlation between inflammatory cytokines and endocannabinoids following omega-3 administration. In conclusion,
omega-3 modulates endocannabinoid tone, which subsequently attenuates inflammation and cardiometabolic
risk factors. However, further randomized clinical trials are needed before any recommendations are
made to target the ECS using omega-3 as an alternative therapy to drugs for cardiometabolic disease improvement. |