Controversy has arisen among the public and in the media regarding the health effects of fish intake in adults. Substantial evidence indicates that fish consumption reduces coronary heart disease mortality, the leading cause of death in developed and most developing nations. Conversely, concerns have grown regarding potential effects of exposure to mercury found in some fish. Seafood species are also rich in selenium, an essential trace element that may protect against both cardiovascular disease and toxic effects of mercury. Such protective effects would have direct implications for recommendations regarding optimal selenium intake and for assessing the potential impact of mercury exposure from fish intake in different populations. Because fish consumption appears to have important health benefits in adults, elucidating the relationships between fish intake, mercury and selenium exposure, and health risk is of considerable scientific and public health relevance. The evidence for health effects of fish consumption in adults is reviewed, focusing on the strength and consistency of evidence and relative magnitudes of effects of omega-3 fatty acids, mercury, and selenium. Given the preponderance of evidence, the focus is on cardiovascular effects, but other potential health effects, as well as potential effects of polychlorinated biphenyls and dioxins in fish, are also briefly reviewed. The relevant current unanswered questions and directions of further research are summarized.

Introduction

Controversy is present among the public and in the media regarding the health effects of fish consumption. Considerable evidence indicates that consumption of fatty fish reduces coronary heart disease (CHD) mortality [1] the leading cause of death in developed and most developing nations. On the other hand, concerns regarding potential harm from exposure to mercury [2–6], a heavy metal present in some fish species, have tempered the perception of fish as a healthy food. Very high levels of mercury exposure are known to cause sensorimotor symptoms in adults, which are often reversible when mercury exposure is reduced [7–9]. However, for the great majority of individuals, the main concern is the potential health effects of chronic low-level mercury exposure from modest fish consumption. Seafood species are also rich in selenium, an essential dietary trace element that plays an important role in antioxidant defense systems and may protect against both cardiovascular disease (CVD) and the toxic effects of mercury. A protective effect of selenium could directly inform recommendations relating to both optimal selenium intake and the potential impact of mercury exposure from fish consumption in selenium-replete vs. selenium-deficient populations. Because fish consumption appears to have significant health benefits, elucidating the relationship between fish intake, mercury exposure, and health risk is of considerable scientific and public health importance. The evidence for health effects of fish consumption in adults is reviewed, particularly the strength and consistency of evidence and relative magnitudes of cardiovascular effects of marine omega-3 polyunsaturated fatty acids (n-3 PUFA), mercury, and selenium in fish. Other potential health effects, including potential effects of polychlorinated biphenyls (PCBs) and dioxins in fish, are also briefly reviewed. This article does not consider possible cardiovascular benefits of plant-based omega-3 fatty acids, which have been reviewed elsewhere [10]. This review also focuses on health effects in adults – the potential effects on infant neurodevelopment, and corresponding recommendations for women who are or may become pregnant, have been reviewed elsewhere [1,11,12].

Fish and Cardiovascular Risk

Consumption of fish or fish oil favorably affects several cardiovascular risk factors (Figure 1) [13–24]. Changes in most risk factors are generally evident within weeks of changes in consumption and may result from altered cell membrane fluidity and receptor responses following incorporation of n-3 PUFA into cell membrane phospholipids [25,26] as well as direct binding of n-3 PUFA to cytosolic receptors that regulate gene transcription [27]. These physiologic effects of n-3 PUFA have varying dose-responses and time-responses of effect [1]. For example, at typical dietary intakes (< 1 g/d of n-3 PUFA), anti-arrhythmic effects appear to predominate, with such effects reducing the risk of cardiac death within weeks to months. At higher levels of consumption, maximum antiarrhythmic benefits appear to have been achieved, but now other physiologic effects of n-3 PUFA consumption (Figure 1) may begin to influence other clinical outcomes, such as stroke or nonfatal CVD events. Time courses of benefit also vary; for instance, some of these effects (such as triglyceride-lowering) might require months or years of consumption before an impact on incidence of clinical outcomes are evident. These benefits on intermediate risk factors are compelling, but inference for health effects of an exposure on chronic disease outcomes requires confirmation in studies of actual disease endpoints in humans.

This evidence exists. Results of case-control studies, prospective cohort studies, and randomized controlled trials each indicate that modest consumption of fish or fish oil lowers the risk of cardiac mortality, specifically CHD death and sudden cardiac death [1]. This effect appears to be nonlinear: compared with little or no intake, modest consumption (~250 mg/d) of the marine n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) significantly lowers risk of cardiac mortality, whereas higher intakes do not substantially further lower risk, suggesting a threshold of effect [1]. The similarity of findings between observational studies of fish consumption and randomized controlled trials of n-3 PUFA supplementation suggests that, at least for cardiac mortality, much of the benefit of fish intake is related to the n-3 PUFA content. Consistent with this, when different types of fish meals are considered, lower risk is more strongly related to intake of fatty (oily or dark meat) fish, compared with lean (white meat) fish [28,29]. The quantity of fish servings needed to consume an average of 250 mg/d EPA+DHA varies depending on the particular fish species, but for fatty fish (e.g., anchovies, herring, salmon, sardines, trout, white tuna) is ~1–2 servings/week. (figure2)

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