Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how?

Low rates of coronary heart disease was found in Greenland Eskimos and Japa nese who are exposed to a diet rich in fish oil. Suggested mechanisms for t his cardio-protective effect focused on the effects of n-3 fatty acids on e icosanoid metabolism, inflammation, beta oxidation, endothelial dysfunction , cytokine growth factors, and gene expression of adhesion molecules; But, none of these mechanisms could adequately explain the beneficial actions of n-3 fatty acids. One attractive suggestion is a direct cardiac effect of n -3 fatty acids on arrhythmogenesis. N-3 fatty acids can modify Na+ channels by directly binding to the channel proteins and thus, prevent ischemia-ind uced ventricular fibrillation and sudden cardiac death. Though this is an a ttractive explanation, there could be other actions as well. N-3 fatty acid s can inhibit the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) and IL- 2 that are released during the early course of ischemic heart disease. Thes e cytokines decrease myocardial contractility and induce myocardial damage, enhance the production of free radicals, which can also suppress myocardia l function. Further, n-3 fatty acids can increase parasympathetic tone lead ing to an increase in heart rate variability and thus, protect the myocardi um against ventricular arrhythmias. Increased parasympathetic tone and acet ylcholine, the principle vagal neurotransmitter, significantly attenuate th e release of TNF, IL-1 beta, IL-6 and IL-18. Exercise enhances parasympathe tic tone, and the production of anti-inflammatory cytokine IL-10 which may explain the beneficial action of exercise in the prevention of cardiovascul ar diseases and diabetes mellitus. TNF alpha has neurotoxic actions, where as n-3 fatty acids are potent neuroprotectors and brain is rich in these fa tty acids. Based on this, it is suggested that the principle mechanism of c ardioprotective and neuroprotective action(s) of n-3 fatty acids can be due to the suppression of TNF alpha and IL synthesis and release, modulation o f hypothalamic-pituitary-adrenal anti-inflammatory responses, and an increa se in acetylcholine release, the vagal neurotransmitter. Thus, there appear s to be a close interaction between the central nervous system, endocrine o rgans, cytokines, exercise, and dietary n-3 fatty acids. This may explain w hy these fatty acids could be of benefit in the management of conditions su ch as septicemia and septic shock, Alzheimer's disease, Parkinson's disease , inflammatory bowel diseases, diabetes mellitus, essential hypertension an d atherosclerosis. (C) 2000 Harcourt Publishers Ltd.