Watanabe Y, Tatsuno I. Omega-3 polyunsaturated fatty acids for cardiovascular diseases: present, past and future. Expert Rev Clin Pharmacol. 2017 Aug;10(8):865-873. doi: 10.1080/17512433.2017.1333902. 

Abstract. Large-scale epidemiological studies on Greenlandic, Canadian and Alaskan Eskimos have examined the health benefits of omega-3 fatty acids consumed as part of the diet, and found statistically significant relative reduction in cardiovascular risk in people consuming omega-3 fatty acids. Areas covered: This article reviews studies on omega-3 fatty acids during the last 50 years, and identifies issues relevant to future studies on cardiovascular (CV) risk. Expert commentary: Although a meta-analysis of large-scale prospective cohort studies and randomized studies reported that fish and fish oil consumption reduced coronary heart disease-related mortality and sudden cardiac death, omega-3 fatty acids have not yet been shown to be effective in secondary prevention trials on patients with multiple cardiovascular disease (CVD) risk factors. The ongoing long-term CV interventional outcome studies investigate high-dose, prescription-strength omega-3 fatty acids. The results are expected to clarify the potential role of omega-3 fatty acids in reducing CV risk. The anti-inflammatory properties of omega-3 fatty acids are also important. Future clinical trials should also focus on the role of these anti-inflammatory mediators in human arteriosclerotic diseases as well as inflammatory diseases.

Hamazaki K. Role of Omega-3 Polyunsaturated Fatty Acids in Mental Health－Studies from Japan. J Oleo Sci. 2019 Jun 6;68(6):511-515. doi: 10.5650/jos.ess19008. 

Abstract. Omega-3 polyunsaturated fatty acids is a generic term that encompasses eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are abundant in fish, and α-linolenic acid, which is abundant in perilla oil. These fatty acids became well known following an epidemiological study conducted in Greenland about 50 years ago. EPA formulations, with their putative prophylactic effect against cardiovascular disease, first became clinically available in the 1990s in Japan. There were reports of their association with mental health, especially depression, and from around the year 2000 several epidemiological studies and clinical trials were conducted. This article introduces the epidemiological studies and clinical trials conducted in Japan and the knowledge gained.

Campos-Staffico AM, Costa APR, Carvalho LSF, Moura FA, Santos SN, Coelho-Filho OR, Nadruz W Jr, Quinaglia E Silva JC, Sposito AC; Brasilia Heart Study. Omega-3 intake is associated with attenuated inflammatory response and cardiac remodeling after myocardial infarction. Nutr J. 2019 May 6;18(1):29. doi: 10.1186/s12937-019-0455-1. 

Abstract. Background: Myocardial infarction (MI) elicits an intense acute inflammatory response that is essential for cardiac repair. However, an excessive inflammatory response also favors myocardial apoptosis, cardiac remodeling, and cardiovascular mortality. Omega-3 polyunsaturated fatty acids (ω-3) bear anti-inflammatory effects, which may mitigate the inflammatory response during MI. This study investigated whether ω-3 intake is associated with attenuation of the MI-related inflammatory response and cardiac remodeling....Conclusion: These findings suggest that a reduced daily intake of ω-3 may intensify outcome-determining mechanisms after STEMI, such as acute inflammatory response and late left ventricular remodeling.

Wang JF, Zhang HM, Li YY, Xia S, Wei Y, Yang L, Wang D, Ye JJ, Li HX, Yuan J, Pan RR.  A combination of omega-3 and plant sterols regulate glucose and lipid metabolism in individuals with impaired glucose regulation: a randomized and controlled clinical trial. Lipids Health Dis. 2019 May 1;18(1):106. doi: 10.1186/s12944-019-1048-x.

Abstract. Background: Lipid metabolism imbalance has been recognized as one of the major drivers of impaired glucose metabolism in the context of type 2 diabetes mellitus (T2DM), the rates of which are steadily increasing worldwide. Impaired glucose regulation (IGR) plays a vital role in the prevention and treatment of T2DM. The goal of this study was to further clarify whether the combination of plant sterols (PS) and omega-3 fatty acids yields any synergistic effect that enhances the prevention and treatment of IGR.....Conclusions: In summary, this study has demonstrated for the first time that PS, omega-3 fatty acids or the combination thereof significantly improved inflammation, insulin resistance, as well as glucose and lipid metabolism in IGR individuals. These findings may provide a scientific basis for the development of nutritional products incorporating PS and omega-3 fatty acids, and also for the development of nutritional supplement strategies aimed at preventing the development of disease in the IGR population.

Freitas RDS, Campos MM. Protective Effects of Omega-3 Fatty Acids in Cancer-Related Complications. Nutrients. 2019 Apr 26;11(5):945. doi: 10.3390/nu11050945. 

Abstract. Omega-3 polyunsaturated fatty acids (PUFAs) are considered immunonutrients and are commonly used in the nutritional therapy of cancer patients due to their ample biological effects. Omega-3 PUFAs play essential roles in cell signaling and in the cell structure and fluidity of membranes. They participate in the resolution of inflammation and have anti-inflammatory and antinociceptive effects. Additionally, they can act as agonists of G protein-coupled receptors, namely, GPR40/FFA1 and GPR120/FFA4. Cancer patients undergo complications, such as anorexia-cachexia syndrome, pain, depression, and paraneoplastic syndromes. Interestingly, the 2017 European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines for cancer patients only discuss the use of omega-3 PUFAs for cancer-cachexia treatment, leaving aside other cancer-related complications that could potentially be managed by omega-3 PUFA supplementation. This critical review aimed to discuss the effects and the possible underlying mechanisms of omega-3 PUFA supplementation in cancer-related complications. Data compilation in this critical review indicates that further investigation is still required to assess the factual benefits of omega-3 PUFA supplementation in cancer-associated illnesses. Nevertheless, preclinical evidence reveals that omega-3 PUFAs and their metabolites might modulate pivotal pathways underlying complications secondary to cancer, indicating that this is a promising field of knowledge to be explored.

Sezai A, Unosawa S, Taoka M, Osaka S, Obata K, Kanno S, Sekino H, Tanaka M. Long-Term Comparison of Ethyl Icosapentate vs. Omega-3-Acid Ethyl in Patients With Cardiovascular Disease and Hypertriglyceridemia (DEFAT Trial). Circ J. 2019 May 24;83(6):1368-1376. doi: 10.1253/circj.CJ-18-0764.

Abstract. Background: Numerous studies have demonstrated a reduction in cardiovascular events when the low-density lipoprotein cholesterol (LDL) level is decreased by statin therapy. However, despite good control of LDL, cardiovascular events may increase if the triglyceride (TG) level is high. We conducted a long-term comparison of treatment of hypertriglyceridemia with ethyl icosapentate (EPA) vs. omega-3-acid ethyl (EPA+docosahexaenoic acid [DHA]).Methods and Results:Cardiac surgery patients with hypertriglyceridemia were randomized to an EPA group (1.8 g t.i.d.) or an EPA+DHA group (2 g s.i.d.) and observed for 3 years. The primary endpoints were the serum TG level and its percent change. Secondary endpoints included lipid markers, fatty acid parameters, serum creatinine, cystatin-C, oxidized LDL, high-sensitivity C-reactive protein, and MACCE. An interview to assess study drug adherence was conducted 6 months after completing the study. TG levels were significantly lower in the EPA+DHA group than in the EPA group. Levels of remnant-like particles-cholesterol, oxidized LDL, and cystatin-C were also significantly lower in the EPA+DHA group than in the EPA group. Compliance with treatment was significantly worse in the EPA group. Conclusions: Better results were obtained in the EPA+DHA group, but more patients showed poor compliance with treatment in the EPA group, making detailed comparison of the 2 groups difficult. Even so, TG were reduced while EPA and DHA levels were increased in the EPA+DHA group, together with a reduction in oxidative stress and remnant-like particles-cholesterol. Decreased compliance with medication in the EPA group significantly affected the results of this study, clearly indicating the importance of good compliance.

Yang J, Fernández-Galilea M, Martínez-Fernández L, González-Muniesa P, Pérez-Chávez A, Martínez JA, Moreno-Aliaga MJ. Oxidative Stress and Non-Alcoholic Fatty Liver Disease: Effects of Omega-3 Fatty Acid Supplementation. Nutrients. 2019 Apr 18;11(4):872. doi: 10.3390/nu11040872.

Abstract. Aging is a complex phenomenon characterized by the progressive loss of tissue and organ function. The oxidative-stress theory of aging postulates that age-associated functional losses are due to the accumulation of ROS-induced damage. Liver function impairment and non-alcoholic fatty liver disease (NAFLD) are common among the elderly. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and evolve to hepatic cirrhosis or hepatic carcinoma. Oxidative stress, lipotoxicity, and inflammation play a key role in the progression of NAFLD. A growing body of evidence supports the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFA), mainly docosahaexenoic (DHA) and eicosapentaenoic acid (EPA), on metabolic diseases based on their antioxidant and anti-inflammatory properties. Here, we performed a systematic review of clinical trials analyzing the efficacy of n-3 PUFA on both systemic oxidative stress and on NAFLD/NASH features in adults. As a matter of fact, it remains controversial whether n-3 PUFA are effective to counteract oxidative stress. On the other hand, data suggest that n-3 PUFA supplementation may be effective in the early stages of NAFLD, but not in patients with more severe NAFLD or NASH. Future perspectives and relevant aspects that should be considered when planning new randomized controlled trials are also discussed.

 Upala S, Yong WC, Theparee T, Sanguankeo A. Effect of omega-3 fatty acids on disease severity in patients with psoriasis: A systematic review. Int J Rheum Dis. 2017 Apr;20(4):442-450. doi: 10.1111/1756-185X.13051. Epub 2017 Mar 5. PMID: 28261950.

Macpherson H, Brownell S, Duckham RL, Meyer B, Mirzaee S, Daly RM. Multifaceted intervention to enhance cognition in older people at risk of cognitive decline: study protocol for the Protein Omega-3 and Vitamin D Exercise Research (PONDER) study. BMJ Open. 2019 May 9;9(5):e024145. doi: 10.1136/bmjopen-2018-024145. PMID: 31072850; PMCID: PMC6527972.

Jang H, Park K. Omega-3 and omega-6 polyunsaturated fatty acids and metabolic syndrome: A systematic review and meta-analysis. Clin Nutr. 2020 Mar;39(3):765-773. doi: 10.1016/j.clnu.2019.03.032. Epub 2019 Apr 5. PMID: 31010701.

Parikh R, Bates JHT, Poynter ME, Suratt BT, Parsons PE, Kien CL, Heyland DK, Crain KI, Martin J, Garudathri J, Stapleton RD. Pharmacokinetics of omega-3 fatty acids in patients with severe sepsis compared with healthy volunteers: A prospective cohort study. Clin Nutr. 2020 Mar;39(3):958-965. doi: 10.1016/j.clnu.2019.03.040.