Fish oil and the prevention and regression of atherosclerosis

Epidemiological studies in the seventies have put forward that dietary rather than genetic factors are responsible for the lower incidence of ischemic heart disease in Greenland Inuit and have generated a large body of both in vitro and in vivo experimental studies, exploring the putative favorable effects of fish (oil) on atherogenesis and its risk factors. The first part of this report reviews the in vivo animal studies, concentrating on the hypercholesterolemic models and the arterialized vein graft model. In the hypercholesterolemic animal studies, the results are inconclusive as the studies reporting a protective effect are matched by the number of studies showing no effect or an adverse effect. The diversity in species, dose of fish oil, duration of study, type of vessel studied and type of fish oil preparation (content of n-3 fatty acids, unesterified n-3 fatty acids, ethylesters or triglycerides) could all contribute. Furthermore, the definitions and criteria used in the literature to evaluate atherogenesis are diverse and it appears that while one parameter is affected, another is not necessarily modified in the same direction, stressing the importance of extending the analysis of the effects on atherogenesis to more than one parameter. We also believe that it is time to reach a consensus as to which animal model mimics most closely a particular human situation. Only in appropriate models, investigating more than one atherosclerosis variable, can the effects of a putative anti-atherogenic drug or diet be verified. In the veno-arterial autograft model, mimicking the patient after coronary bypass grafting, dietary fish oil has been consistently effective in preventing accelerated graft intima proliferation. It could therefore be of interest to evaluate the effects of fish oil on graft patency in patients after coronary bypass surgery after a period of years. The results from studies on restenosis after percutaneous transluminal angioplasty are also reviewed and it is concluded that the two large scale trials, that are currently underway, might reliably answer the question whether fish oil is effective as a non-pharmacological adjuvants in the prevention of restenosis. Lastly, the studies on the effects of fish oil on the regression of experimental atherosclerosis are reviewed. In view of the small number of studies (i.e., four) investigating the effects of fish oil on the regression of atherosclerosis, it is premature to draw any conclusion, and therefore further experimental work is required.