%0 Journal Article %T Endocannabinoid system and cardiometabolic risk factors: A comprehensive systematic review insight into the mechanistic effects of omega-3 fatty acids. %A Saleh-Ghadimi S %A Kheirouri S %A Maleki V %A Jafari-Vayghan H %A Alizadeh M %J Life Sci %V 250 %N 0 %D Jun 2020 1 %M 32184122 %F 6.78 %R 10.1016/j.lfs.2020.117556 %X 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.