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The potential benefit of fish oil (omega-3 fatty acids) consumption to reduce cardiovascular disease (CVD) risk remains controversial. Some investigations report reduced CVD risk associated with fish or fish oil consumption while others report no benefit. This controversy is in part resolved when consideration is given to omega-3 blood levels in relation to CVD risk as well as blood levels achieved in clinical trials of omega-3 supplementation and CVD benefit. There is a wide variation in omega-3 blood levels achieved between individuals in response to a given dose of an omega-3 supplement. Many studies tested a daily dose of 1 gram omega-3 supplementation. The individual variation in blood omega-3 levels achieved in response to a fixed daily dose helps to explain why some individuals may obtain CVD protection benefit while others do not due to failure to achieve a therapeutic threshold. Recent development of a population range in a United States population helps to provide clinical guidance since population omega-3 blood level ranges may vary due to environmental and genetic reasons. Omega-3 supplementation may also be of benefit in reducing the adverse impact of air pollution on CVD risk.