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Evaluating the Risks and the Benefits

Dariush Mozaffarian, MD, DrPH; Eric B. Rimm, ScD

JAMA. 2006;296:1885-1899.

ABSTRACT
Context  Fish (finfish or shellfish) may have health benefits and also contain contaminants, resulting in confusion over the role of fish consumption in a healthy diet.

Evidence Acquisition  We searched MEDLINE, governmental reports, and meta-analyses, supplemented by hand reviews of references and direct investigator contacts, to identify reports published through April 2006 evaluating (1) intake of fish or fish oil and cardiovascular risk, (2) effects of methylmercury and fish oil on early neurodevelopment, (3) risks of methylmercury for cardiovascular and neurologic outcomes in adults, and (4) health risks of dioxins and polychlorinated biphenyls in fish. We concentrated on studies evaluating risk in humans, focusing on evidence, when available, from randomized trials and large prospective studies. When possible, meta-analyses were performed to characterize benefits and risks most precisely.

Evidence Synthesis  Modest consumption of fish (eg, 1-2 servings/wk), especially species higher in the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduces risk of coronary death by 36% (95% confidence interval, 20%-50%; P<.001) and total mortality by 17% (95% confidence interval, 0%-32%; P = .046) and may favorably affect other clinical outcomes. Intake of 250 mg/d of EPA and DHA appears sufficient for primary prevention. DHA appears beneficial for, and low-level methylmercury may adversely affect, early neurodevelopment. Women of childbearing age and nursing mothers should consume 2 seafood servings/wk, limiting intake of selected species. Health effects of low-level methylmercury in adults are not clearly established; methylmercury may modestly decrease the cardiovascular benefits of fish intake. A variety of seafood should be consumed; individuals with very high consumption (5 servings/wk) should limit intake of species highest in mercury levels. Levels of dioxins and polychlorinated biphenyls in fish are low, and potential carcinogenic and other effects are outweighed by potential benefits of fish intake and should have little impact on choices or consumption of seafood (women of childbearing age should consult regional advisories for locally caught freshwater fish).

Conclusions  For major health outcomes among adults, based on both the strength of the evidence and the potential magnitudes of effect, the benefits of fish intake exceed the potential risks. For women of childbearing age, benefits of modest fish intake, excepting a few selected species, also outweigh risks.

INTRODUCTION

Jump to Section  • Top  • Introduction  • Evidence acquisition  • Evidence synthesis  • Conclusions  • Author information  • References

Since the publication of pioneering studies demonstrating low rates of death from coronary heart disease (CHD) among Greenland Eskimos,1 fish (used herein to refer to finfish or shellfish) has been considered a healthy food. During ensuing years, evidence from several research paradigms—including animal-experimental, observational, and clinical studies—further supported this hypothesis and identified 2 long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as the likely active constituents.^2-20 DHA also appears important for neurodevelopment during gestation and infancy.^21-26 Conversely, concern has arisen over potential harm from mercury, dioxins, and polychlorinated biphenyls (PCBs) present in some fish species.^27-34 The public is faced with seemingly conflicting reports on the risks and benefits of fish intake, resulting in controversy and confusion over the role of fish consumption in a healthy diet.^35-36 To elucidate the relative risks and benefits, we reviewed the scientific evidence for adverse and beneficial health effects of fish consumption.

EVIDENCE ACQUISITION

Jump to Section  • Top  • Introduction  • Evidence acquisition  • Evidence synthesis  • Conclusions  • Author information  • References

Identification of Studies

A myriad of exposures and outcomes have been related to fish consumption; we focused on populations and topics for which evidence and concern are greatest. We searched MEDLINE, governmental reports, and systematic reviews and meta-analyses to identify reports published through April 2006 evaluating (1) intake of fish or fish oil and risk of cardiovascular events and mortality, (2) effects of methylmercury and fish oil on early neurodevelopment, (3) risks of methylmercury for cardiovascular and neurologic outcomes in adults, and (4) health risks of dioxins and PCBs in fish.

MEDLINE search terms were (Fish or n-3 PUFA or omega-3) and (coronary or cardiac or cardiovascular or mortality) and (clinical trial or prospective or meta-analysis); (fish or n-3 PUFA or omega-3 or docosahexaenoic or mercury or methylmercury) and (cognitive or neurologic or neurodevelopment) and (clinical trial or prospective or meta-analysis); (mercury or methylmercury) and (coronary or cardiac or cardiovascular or cognition or neurologic) and (clinical trial or prospective or meta-analysis); (dioxin or polychlorinated biphenyl or PCB) and (fish or seafood). MEDLINE searches were restricted to identify only English-language reports, studies in humans, and adult or child populations (as appropriate) and were supplemented by searches of related articles of relevant identified manuscripts as well as by hand reviews of references from identified reports and direct contact with investigators.

Study Selection

One author (D.M.) screened all identified studies, and the final articles included were selected by both authors by consensus. Because fish intake is related to exposure to many different compounds, including n-3 PUFAs, mercury, and PCBs and dioxins, as well as to multiple different health outcomes, including cardiovascular diseases, neurologic outcomes, and cancer, a systematic quantitative review of every possible combination was beyond the constraints of this report. We concentrated on studies evaluating or estimating risk in humans, focusing on the evidence, when available, from randomized clinical trials and large prospective studies. Metabolic studies and animal-experimental evidence were also considered to elucidate potential mechanisms of effect. The evidence for risks and benefits was considered overall and among different at-risk populations. When possible, pooled or meta-analyses were performed to characterize effects most precisely.^37-39 Other potential benefits of fish intake (eg, for cognitive decline or dementia,⁴⁰ depression or neuropsychiatric disorders,^41-42 and asthma or inflammatory disorders^43-44) were not reviewed in this report.

EVIDENCE SYNTHESIS

Jump to Section  • Top  • Introduction  • Evidence acquisition  • Evidence synthesis  • Conclusions  • Author information  • References

Benefits of Fish Intake

Cardiovascular Outcomes. Death from CHD—ie, documented or suspected fatal myocardial infarction—and sudden death—ie, a sudden pulseless condition of presumed cardiac etiology—are clinically defined entities often sharing the final common pathway of ventricular arrhythmia, often ischemia-induced ventricular fibrillation. The evidence from prospective studies and randomized trials^{2-4,6-17,45-51} suggests that consumption of fish or fish oil lowers risk of CHD death and sudden death (Figure 1 and Figure 2). Across different studies (Figure 1), compared with little or no intake, modest consumption ( 250-500 mg/d of EPA and DHA) lowers relative risk by 25% or more. Higher intakes do not substantially further lower CHD mortality, suggesting a threshold of effect.⁵² Pooling all studies, this pattern was clearly evident (Figure 2). At intakes up to 250 mg/d, the relative risk of CHD death was 14.6% lower (95% confidence interval [CI], 8% to 21%) per each 100 mg/d of EPA and DHA, for a total risk reduction of 36% (95% CI, 20% to 50%). At higher intakes, little additional risk reduction was present (0.0% change per each 100 mg/d; 95% CI, –0.9% to +0.8%). This threshold effect explains findings among Japanese populations,^{17, 50} in whom high background fish intake (eg, median 900 mg/d of EPA and DHA⁵⁰) is associated with very low CHD death rates (eg, 87% lower than comparable Western populations^{9, 17}), and additional n-3 PUFA intake predicts little further reduction in CHD death; thus, most of the population is already above the threshold for maximum mortality benefits. Comparing different types of fish, lower risk appears more strongly related to intake of oily fish (eg, salmon, herring, sardines), rather than lean fish (eg, cod, catfish, halibut).^{10, 15} Fish intake may modestly affect other cardiovascular outcomes, but evidence is not as robust as for CHD death (Table 1).^{17, 50, 53-66}

View larger version (74K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 1. Relationship Between Intake of Fish or Fish Oil and Rates of CHD Death in Prospective Cohort Studies and Randomized Clinical Trials Circular data markers indicate prospective studies; square data markers, randomized trials. Absolute coronary heart disease (CHD) mortality rates vary more than 100-fold across different populations (due to differences in age, prior CHD, and other risk factors), but the relative effects of intake of fish or fish oil are consistent, whether for primary or secondary prevention, for cohort studies or randomized trials, or for comparing populations at higher or lower absolute risk. Compared with little or no intake, modest consumption ( 250-500 mg/d eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) is associated with lower risk of CHD death, while at higher levels of intake, rates of CHD death are already low and are not substantially further reduced by greater intake. For instance, populations with very high fish intake (Yokoyama et al17 [secondary prevention; square 16]) already have much lower CHD death rates than otherwise comparable populations (Gruppo Italiano9 [square 19]), and additional intake of fish or fish oil produces little further reduction in CHD mortality. Only 1 study (Burr et al51 [square 20]) found results markedly divergent from this pattern. One study46 was not included due to limited events data and limited multivariable adjustment. *Rates in the control and intervention groups (for randomized trials) or rates in the reference group and multivariable-adjusted relative rates (for cohort studies). Reported data or estimated from similar populations. Populations with prior CHD (secondary prevention). Rates of sudden death, not CHD death.

View larger version (11K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 2. Relationship Between Intake of Fish or Fish Oil and Relative Risks of CHD Death in Prospective Cohort Studies and Randomized Clinical Trials The relationship between intake of fish or fish oil and relative risk of coronary heart disease (CHD) death in a pooled analysis of the prospective studies and randomized trials shown in Figure 1, evaluated nonparametrically using restricted cubic splines38-39 and adjusted for each within-study relationship. Given the much higher reference group intakes in some studies, the reference relative risk was scaled by 0.7 for studies with reference group intakes between 150-500 mg/d of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (n = 5) and by 0.6 for studies with reference group intakes >500 mg/d (n = 1) based on spline relationships prior to including these studies; exclusion of these studies, or of the few groups with intakes >1000 mg/d, had little effect on the pooled spline relationship. A significant threshold effect (P<.001) was evident at intake of 250 mg/d: between 0 and 250 mg/d, mortality risk was lower by 14.6% (95% confidence interval [CI], 8% to 21%) per each 100-mg/d greater intake (total risk reduction, 36%; 95% CI, 20% to 50%; P<.001), while at higher intakes, risk was not further lowered (0.0% change per each 100 mg/d; 95% CI, –0.9% to 0.8%; P = .94). *Relative risks in the control and intervention groups (for randomized trials) or relative risks in the reference group and multivariable-adjusted relative risks in the comparison groups (for cohort studies).

View this table: [in this window] [in a new window] [as a PowerPoint slide]   Table 1. Summary of Evidence for Effects of Consumption of Fish or Fish Oil on Cardiovascular Outcomes

n-3 PUFAs influence several cardiovascular risk factors.^{18-19,43, 49-50,60-75,79-84} Effects occur within weeks of intake and may result from altered membrane fluidity and receptor responses following incorporation of n-3 PUFAs into cell membranes^76-77 and direct binding of n-3 PUFAs to intracellular receptors regulating gene transcription.⁷⁸ The heterogeneity of the effects of fish or fish oil intake on cardiovascular outcomes is likely related to varying dose and time responses of effects on the risk factors (Figure 3). At typical dietary intakes, antiarrhythmic effects predominate, reducing risk of sudden death and CHD death within weeks. At higher doses, maximum antiarrhythmic effects have been achieved, but other physiologic effects may modestly impact other clinical outcomes (possibly requiring years to produce clinical benefits). For instance, nonfatal myocardial infarction may not be significantly affected by lower doses or shorter durations of intake but may be modestly reduced by higher doses or prolonged intake (eg, 1.8 g/d for 5 years¹⁷).

View larger version (58K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 3. Schema of Potential Dose Responses and Time Courses for Altering Clinical Events of Physiologic Effects of Fish or Fish Oil Intake The relative strength of effect is estimated from effects of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) on each risk factor and on the corresponding impact on cardiovascular risk.70-72,79-84 For example, dose response for antiarrhythmic effects is initially steep with a subsequent plateau, and clinical benefits may occur within weeks, while dose response for triglyceride effects is more gradual and monotonic, and clinical benefits may require years of intake. At typical Western levels of intake (eg, <750 mg/d EPA + DHA), the physiologic effects most likely to account for clinical cardiovascular benefits include (1) modulation of myocardial sodium and calcium ion channels, reducing susceptibility to ischemia-induced arrhythmia;18-19 and (2) reduced left ventricular workload and improved myocardial efficiency as a result of reduced heart rate, lower systemic vascular resistance, and improved diastolic filling.67-72,80 At higher levels of intake seen with fish oil supplementation or in Japanese populations49-50 (>750 mg/d EPA + DHA), maximum antiarrythmic effects have been achieved and clinically relevant effects occur on levels of serum triglycerides79 and possibly, at very high doses, thrombosis.75 Potentially important effects on endothelial,73 autonomic,74 and inflammatory43 responses are not shown because dose responses and time courses of such effects on clinical risk are not well established. Effects are not necessarily exclusive: eg, antiarrythmic effects may be partly mediated by effects on blood pressure (BP) or heart rate.

Heterogeneity of clinical effects may also be related to differing pathophysiologies of the clinical outcomes. For instance, disparate pathophysiologies of primary ventricular fibrillation (often ischemia-induced) vs recurrent ventricular tachyarrhythmias (ectopic or reentrant) may explain stronger effects of n-3 PUFAs on the former. Similarly, biological differences in development of atherosclerosis vs acute plaque rupture/thrombosis vs arrhythmia would account for heterogeneous effects of n-3 PUFAs on plaque progression vs nonfatal myocardial infarction vs CHD death. Consumption of fish may displace that of other foods, such as meats or dairy products, in the diet. However, this likely accounts for little of the observed health benefits, because foods replaced would be highly variable among individuals and across cultures, and modest intake of such foods is not associated with CHD risk.⁸⁵

Total Mortality. n-3 PUFAs most strongly affect CHD death^{5, 9, 14-16,18} and are unlikely to affect appreciably other causes of mortality. Effects on total mortality in a population would therefore depend on the proportion of deaths due to CHD, ranging from one quarter of deaths in middle-age populations⁸⁶ to one half of deaths in populations with established CHD.⁹ Thus, given a  36% reduction in CHD death (Figure 2), intake of fish or fish oil would reduce total mortality by between  9% (36% reduction x 25% CHD deaths) to  18% (36% reduction x 50% CHD deaths), or an average of  14% in mixed populations. This is consistent with a meta-analysis of randomized trials through 2003^{3, 9, 51, 56-57,87-93} that found a nonsignificant 14% reduction in total mortality with n-3 PUFAs (pooled relative risk, 0.86; 95% CI, 0.70 to 1.04).⁹⁴ When we added additional placebo-controlled, double-blind, randomized trials^60-62 performed since 2003, marine n-3 PUFAs reduced total mortality by 17% (pooled relative risk, 0.83; 95% CI, 0.68 to 1.00; P = .046) (Figure 4). This can be compared to effects of statins on total mortality—a 15% reduction—in a meta-analysis of randomized trials (pooled relative risk, 0.85; 95% CI, 0.79 to 0.92).⁹⁵

View larger version (26K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 4. Risk of Total Mortality Due to Intake of Fish or Fish Oil in Randomized Clinical Trials The size of the shaded squares indicates each trial's contribution (inverse-variance weight) to the pooled estimate (dotted line) and 95% confidence interval (CI; diamond), determined by random effects meta-analysis.37 Intake of fish or fish oil reduced total mortality by 17% (P = .046), with evidence for heterogeneity between trials (P = .04 for heterogeneity). If 2 trials with methodologic concerns51, 93 were excluded, the pooled relative risk was 0.83 (95% CI, 0.74-0.92; P<.001) with little evidence for heterogeneity (P = .75). A recently reported trial of fish oil among Japanese individuals17 was not included in the primary analysis due to very high fish intake in the reference group (estimated eicosapentaenoic acid + docosahexaenoic acid intake, 900 mg/d) which would obviate mortality benefits of additional fish oil intake. When this trial was added to the secondary analysis, the pooled relative risk was 0.87 (95% CI, 0.76-0.99; P = .048; P = .29 for heterogeneity).

Neurologic Development. DHA is preferentially incorporated into the rapidly developing brain during gestation and the first 2 years of infancy, concentrating in gray matter and retinal membranes.²⁶ Infants can convert shorter-chain n-3 fatty acids to DHA,⁹⁶ but it is unknown whether such conversion is adequate for the developing brain in the absence of maternal intake of DHA.^{22, 25}

Effects of maternal DHA consumption on neurodevelopment have been investigated in observational studies and randomized trials, with heterogeneity in assessed outcomes (visual acuity, global cognition, specific neurologic domains) and timing of DHA intake (gestational vs nursing). In a meta-analysis of 14 trials, DHA supplementation improved visual acuity in a dose-dependent manner.²³ Results for cognitive testing are less consistent, possibly due to differences in neurologic domains evaluated^{21, 25-26}; a quantitative pooled analysis of 8 trials estimated that increasing maternal intake of DHA by 100 mg/d increased child IQ by 0.13 points (95% CI, 0.08 to 0.18).²⁴ Most trials evaluated effects of maternal DHA intake during nursing, rather than pregnancy. In a trial among 341 pregnant women, treatment with cod liver oil from week 18 until 3 months postpartum increased DHA levels in cord blood by 50% and raised mental processing scores, a measure of intelligence, at age 4 years.⁹⁷ This is consistent with observational studies showing positive associations between maternal DHA levels or fish intake during pregnancy and behavioral attention scores, visual recognition memory, and language comprehension in infancy.^98-100 Thus, while dose responses and specific effects require further investigation, these studies together indicate that maternal intake of DHA is beneficial for early neurodevelopment.

Risks of Mercury

Mercury is a reactive heavy metal emitted from natural sources (volcanoes) and human sources (coal-fired electric power plants, gold mining, institutional boilers, chlorine production, and waste incineration).101 From the atmosphere, mercury cycles from rainwater into lakes and oceans, where it is converted by microbial activity into organic methylmercury. Inorganic mercury is poorly absorbed following ingestion, and elemental mercury does not readily cross tissue barriers. In contrast, methylmercury is readily absorbed and actively transported into tissues.²⁷ Thus, methylmercury bioaccumulates in aquatic food chains and has greater potential toxicity than inorganic mercury.^27-28,30 Concentrations of methylmercury in aquatic species depend on levels of environmental contamination and on the predatory nature and lifespan of the species. Larger, longer-living predators (eg, swordfish, shark) have higher tissue concentrations, while smaller or shorter-lived species (eg, shellfish, salmon) have very low concentrations (Table 2).¹²² Preparation methods have little impact on methylmercury content.²⁷

View this table: [in this window] [in a new window] [as a PowerPoint slide]   Table 2. Levels of n-3 Fatty Acids and Contaminants in Commonly Consumed Fish, Shellfish, and Other Foods*

Health effects of very high mercury exposure following occupational or industrial accidents are well documented, including paresthesias, ataxia, and sensory abnormalities in adults, and delayed cognitive and neuromuscular development following in utero exposure.^{27, 131} Toxicity appears related to binding of methylmercury to sulfhydryl groups of enzymes, ion channels, and receptors, resulting in inhibition of antioxidant systems and production of free radicals and reactive oxygen species.^{27, 29} Health effects of chronic low-level mercury exposure—ie, that seen with fish consumption—are less well established. The public is aware of the potential harm from mercury in fish but lacks clear understanding of who is at risk or which seafood species contain mercury.^35-36 We review the evidence for health effects below.

Methylmercury and Neurodevelopment

Methylmercury crosses the placenta, and fetal exposure correlates with maternal exposure.¹³² Marked neurodevelopmental abnormalities occur in children following very high gestational exposure,^{27, 131} such as from maternal consumption of highly contaminated fish (10-30 ppm mercury) from industrially polluted Minimata Bay, Japan, in the 1950s, or of contaminated grain in Iraq in 1971 (maternal intake, 710-5700 ug/kg per day; 18-598 ppm mercury in maternal hair). More typical methyl mercury exposures are substantially lower: among US women of childbearing age, median (10th-95th percentiles) levels of mercury in hair were 0.19 (0.04-1.73) ppm overall and 0.34 (0.09-2.75) ppm among women consuming 3 or more servings of fish per month.¹³³ These exposure levels do not produce symptomatic neurodevelopmental deficits, but several prospective studies have evaluated whether subclinical effects, detectable with specialized testing, might occur.^{98, 100, 134-140} Among children from the Faroe Islands,^134-135 New Zealand,^136-137 and Poland,¹³⁸ higher gestational exposure to mercury was associated with lower scores on some neurologic tests (eg, finger tapping, naming tests) but not others. In contrast, higher gestational exposure to mercury was associated with higher scores on some neurologic tests among Seychellois children.^139-140 In a US cohort, gestational maternal fish intake was positively associated with, but mercury levels in hair were negatively associated with, visual recognition memory scores in infancy,⁹⁸ indicating possible opposing effects of overall fish consumption (ie, providing DHA) and methylmercury exposure. In a British cohort, gestational mercury exposure was not associated with, but maternal and infant fish intake was associated with, improved neurodevelopmental scores.¹⁰⁰ Other studies did not detect consistent associations between gestational exposure to mercury and neurologic test scores during childhood.¹⁴¹

Comparisons across studies are limited by heterogeneity of study designs (prospective vs cross-sectional), mercury assessment methods, neurologic tests used, timing of assessment (infancy vs childhood), and statistical methods. Some analyses are also limited by multiple statistical testing (eg, 30 neurologic variables) or incomplete adjustment for other potential risk factors. Randomized trials to test effects of reducing low-level methylmercury exposure during gestation have not been performed. Nevertheless, given associations with some lower neurologic test scores in some studies, and clinical neurotoxicity of methylmercury following high-level accidental exposures, it is prudent to conclude that subclinical neurodevelopmental deficits may occur at lower exposure levels.

Based on this, the Environmental Protection Agency determined a reference dose, ie, the allowable upper limit of daily intake, for methylmercury of 0.1 ug/kg per day ( 50 µg/wk for a 70-kg woman, calculated from the lower 95% confidence limit at which gestational exposure to mercury may produce abnormal neurologic test scores, multiplied by a 10-fold uncertainty factor)¹³² and published a focused advisory for women of childbearing age, nursing mothers, and young children.¹⁴² The advisory specifically advises such individuals to avoid shark, swordfish, golden bass, and king mackerel (each containing >50 µg methylmercury per serving) (Table 2); to eat up to 12 oz/wk (2 average meals) of a variety of fish and shellfish lower in mercury, including up to 6 oz/wk of albacore tuna (30 µg methylmercury per serving); and to consult local advisories for locally caught freshwater fish. This advisory was not intended for the general population, because the importance of this reference dose to health effects in adults was unclear.¹⁴³ We review the evidence for such effects below.

Health Effects of Methylmercury in Adults

Cardiovascular Disease. Several studies^144-148 have evaluated the relationship between mercury exposure and incidence of cardiovascular disease (Figure 5). The conflicting results provide inconclusive evidence for cardiovascular toxicity of mercury. Notably, in the 2 studies observing higher risk with higher mercury levels, the net effect of fish consumption was still beneficial: greater mercury exposure lessened the benefit associated with consumption of fish or n-3 PUFAs but did not increase overall risk.^{146, 148, 150} Thus, the principal question may not be whether consumption of mercury-containing fish increases cardiovascular risk but whether consumption of such fish would decrease risk even further if mercury were not present. This would be most true for oily fish species containing higher amounts of n-3 PUFAs (ie, most mercury-containing ocean fish), compared with lean freshwater fish. This is an important public health issue, which requires balancing potentially attenuated benefits of fish intake due to presence of mercury with the costs and practicality of reducing mercury contamination in fish species. Nevertheless, this should not obscure evidence for net cardiovascular benefits of fish consumption, particularly fish richer in n-3 PUFAs.

View larger version (14K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 5. Multivariate Risk of Incident Coronary Heart Disease (CHD) With Higher Levels of Mercury Exposure Relative risk and 95% confidence intervals (CIs) are shown comparing the highest to the lowest quantile of mercury exposure after adjustment for other risk factors. In 2 studies in Sweden, higher mercury levels were associated with trends toward lower risk,144-145 but findings may have been limited by relatively few numbers of events. In 2 larger European studies, positive associations between mercury levels and CHD risk were reported.146, 148 A large US study observed no association,147 but most participants were dentists, in whom mercury levels in part represented occupational exposure to inorganic mercury,149 which may be less toxic than methylmercury in fish.27-28,30 The overall pooled relative risk (dotted line) and 95% CI (diamond), estimated using inverse-variance random-effects meta-analysis,37 was 1.12 (95% CI, 0.71-1.75; P = .62), with significant heterogeneity between studies (P = .008).

Neurologic Outcomes. Very high methylmercury exposure from accidents (eg, Minimata)^{27, 151} or prolonged high intakes of mercury-containing fish (eg, 1-2 fish servings/d, including species high in mercury, for >10 years¹⁵²) can produce sensorimotor symptoms in adults, most commonly paresthesias, which are often reversible when mercury exposure is reduced. Whether lower exposures produce neurologic abnormalities in adults is not clear.Cross-sectional studies have evaluated associations between mercury levels in hair or blood and subclinical neurologic function in adults. Among Amazon basin and Quebec Cree individuals, both positive and inverse associations were seen between mercury levels and some neurologic measures,^153-155 but findings were limited by minimal adjustment for other risk factors and multiple testing (typically 20-30 neurologic tests or participant subgroups). Among US adults, mercury levels were associated with lower visual memory scores (P = .01) but better motor and manual dexterity scores (P = .02) among 20 different outcomes evaluated.¹⁵⁶ Among elderly Swedish adults, no associations were found between mercury levels and cognitive function.¹⁵⁷ Thus, it is unclear whether low-level methylmercury affects subclinical neurologic outcomes in adults and, if so, what quantities or durations of exposure are necessary. Conversely, a growing body of evidence suggests that fish consumption may favorably affect clinical neurologic outcomes in adults, including ischemic stroke,⁵³ cognitive decline and dementia,⁴⁰ and depression and other neuropsychiatric disorders.^41-42

Possible Mercury-Selenium Interaction. Health effects of mercury may partly result from selenoprotein inactivation, which might be mitigated by adequate intake of selenium, an essential dietary trace element.^158-161 Selenium also may reduce tissue accumulation of mercury in fish¹⁶² and humans.¹⁶³ Seafood species are rich dietary sources of selenium.¹²¹ A protective effect of selenium may partly account for conflicting results of studies of mercury exposure and neurodevelopmental indices in children¹⁶⁰ and of mercury exposure and risk of CHD.¹⁶⁴ A potential selenium-mercury interaction would have important public health implications, and additional investigation is warranted.

Risks of PCBs and Dioxins

PCBs are synthetic organochlorine compounds previously used in industrial and commercial processes.³⁴ Dioxins—commonly referring to dibenzodioxins and dibenzofurans—are organochlorine by-products of waste incineration, paper bleaching, pesticide production, and production of polyvinyl chloride plastics.³³ Manufacture and processing of PCBs was prohibited in 1977,³⁴ and regulatory and industry efforts have reduced dioxin emissions by more than 90% since 1987.³³ Nevertheless, these contaminants persist for long periods in the environment, and thus while levels are steadily declining,^{33, 110, 112, 127-128} PCBs and dioxins continue to be present in low concentrations in many foods (Table 2).

Cancer Risks. Animal experiments and some evidence in humans indicate that PCBs and dioxins are carcinogenic, possibly related to effects on the aryl hydrocarbon receptor, a transcription factor affecting gene expression.^{32, 165} Multiple congeners (structural variants) of PCBs and dioxins exist. Potential toxicities of foods are calculated using toxic equivalence (TEQ): the sum of each congener's level in the food multiplied by that congener's toxic equivalency factor (standardized against 2,3,7,8-tetrachlorodibenzo-p-dioxin). In the United States, PCBs comprise 28% and dioxins 72% of total TEQ exposure.¹²⁰ Among adults, major dietary sources of PCBs and dioxins are beef, chicken, and pork (34% of total TEQ); dairy products (30%); vegetables (22%); fish and shellfish (9%); and eggs (5%).¹²⁰ Dietary sources are similar for children.¹²⁰

Although major sources of exposure to PCBs and dioxins are meats, dairy products, and vegetables, considerable attention has been given to fish sources (Table 2). When PCBs and dioxins were measured in farmed and wild salmon,^{115, 166} levels were similar to those in several other foods (Table 2). Farmed and wild salmon also contained substantial levels of n-3 PUFAs: 4504 and 1774 mg of EPA and DHA per 6 oz, respectively.166 Cancer risks and CHD benefits were evaluated in a quantitative risk-benefit analysis, assuming regular farmed or wild salmon intake to provide 1000 mg/d of EPA and DHA over a 70-year lifetime.^167-168 Per 100 000 individuals, consumption of farmed vs wild salmon would result in 24 vs 8 excess cancer deaths, respectively, while consumption of either farmed or wild salmon would result in 7125 fewer CHD deaths.¹⁶⁷ We further evaluated age-specific estimates, based on allocation of lifetime cancer risks¹⁶⁷ (adjusted for competing risks) by age-specific cancer mortality¹⁶⁹ and 25% reduction in age-specific CHD mortality.¹⁶⁹ For all ages evaluated (25-34 to 85 years), CHD benefits outweighed cancer risks by 100- to 370-fold for farmed salmon and by 300- to more than 1000-fold for wild salmon.

Notably, estimated CHD benefits are based on prospective studies and randomized trials in humans (Figures 1 and 2); estimated cancer risks include a 10-fold safety factor and are based on animal-experimental data and limited studies in humans at high doses.¹⁶⁸ Cancer estimates also assumed lifetime salmon consumption to provide 1000 mg/d of EPA and DHA (eg, four 6-oz servings of wild salmon every week for 70 years). However, CHD mortality reduction may be achieved with lower intake:  250 mg/d (Figures 1 and 2), or one 6-oz wild salmon serving per week. At this intake, CHD benefits would be largely unchanged ( 7125 fewer CHD deaths), while lifetime cancer risk would decrease by  75% (6 and 2 estimated deaths per 100 000 lifetimes for farmed and wild salmon, respectively). Consistent with these very low cancer risks, prospective studies in humans have seen little evidence for effects of fish intake on cancer risk.¹⁷⁰

Other Risks. PCBs and dioxins may have noncancer risks in adults, such as immune system or neurologic effects.^32-34 Conversely, fish consumption may also have other benefits, possibly lowering risk of other cardiovascular outcomes (Table 1), dementia,⁴⁰ neuropsychiatric disorders,^41-42 and inflammatory disorders.^43-44 If present, such additional possible risks would have to exceed additional possible benefits by more than 100-fold to meaningfully alter the present estimates of risks vs benefits. PCB content in fish can be reduced 12% to 40% by trimming belly and back fat during filleting and by not consuming the skin.¹³⁰ Also, contaminant levels are typically measured in unprepared foods, and cooking may reduce PCB and dioxin content.¹⁰⁶

Prenatal (but not postnatal) exposure to PCBs and dioxins has been associated with childhood neurodevelopmental deficits in several,^171-177 though not all,^178-179 studies. Because most exposure (>90%) generally comes from meat, dairy, and vegetable sources,^{120, 180} this concern is not specific to fish consumption, particularly since fish also contains potentially beneficial DHA. However, women consuming 1 or more servings/d of commercial freshwater fish or consuming locally caught freshwater fish from highly contaminated inland sources may be more greatly exposed to PCBs and dioxins¹⁸⁰ and should consult regional advisories.

Related Considerations

Costs. We evaluated potential costs of consuming 250 mg/d of EPA and DHA from fish (Figure 6). The daily cost was as low as 9 cents, or 63 cents/wk. For combinations of different types of salmon; salmon and tuna; or salmon, tuna, anchovies, and sardines, the average cost was 37 cents/d ($2.59/wk) or less. Actual (net) costs would be lower because intake of fish would replace intake of other foods.

View larger version (34K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 6. Estimated Costs of Consuming the equivalent of 250 mg/d EPA + DHA From Fish Costs were calculated for commonly consumed seafood species, based on retail prices (averaging the most commonly sold items in each of 6 US cities in the east, midwest, and south from a national online grocery store181 or, for wild king and silver salmon, from online retailers182-184) and on species-specific eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) content.121 Least expensive was canned pink salmon (9 cents/250 mg of EPA + DHA); the average cost per 250 mg of EPA + DHA for these 12 types of seafood was 92 cents. The corresponding ounces per week needed to achieve 250 mg/d of EPA + DHA is also shown.

Supplements. Fish oil capsules contain 20% to 80% of EPA and DHA by weight (200-800 mg/g^185-186), little to no mercury,¹⁸⁷ and variable levels of PCBs (0-450 ng/g,^{116, 188}) and dioxins (0.2-11 TEQ pg/g^{114, 189}). Given small amounts of fish oil consumed (1-3 g/d), exposure to PCBs and dioxins from fish oil intake is low. "Functional foods" supplemented with EPA and DHA (eg, dairy products, salad dressings, cereals) can also provide reasonable intake to individuals not consuming seafood.¹⁹⁰ Compared with supplements, fish intake also provides potentially beneficial protein, vitamin D, and selenium.¹²¹

Commercial Preparation. Commercially-prepared fried fish meals from fast food restaurants or supermarket frozen sections123-124 are often made using white-meat fish (lower in n-3 PUFAs)^{27, 123} and prepared with partially hydrogenated oils (containing trans fats) or oils reused for multiple frying cycles (introducing oxidative/deteriorative products¹⁹¹). Higher cardiovascular risk seen with fried fish intake^{15, 54, 63, 66} may relate to this unfavorable balance of benefit vs harm (lower levels of EPA and DHA; higher levels of trans fats/deteriorative products) or to residual confounding from other lifestyle factors. While further research is needed, it appears unlikely that most commercially prepared fried fish meals lower cardiovascular risk.

n6:n3 Ratio. Ecologic studies and limited animal-experimental data suggest that linoleic acid (18:2n-6) may counteract potential benefits of n-3 fatty acids,^192-193 but this hypothesis has not been supported by clinical trials or prospective studies in humans.^{16, 194} A much greater change in the dietary ratio of n-6 fatty acids to n-3 fatty acids can be practically achieved by increasing intake of n-3s (eg, going from no intake of oily fish to 1 serving/wk) compared with lowering intake of n-6s (which are widely consumed in cooking oils, salad dressings, and prepared foods). Thus, for most populations, attention to relative intakes of n-6 vs n-3 fatty acids may be less important than simply increasing n-3 intake.

Aquaculture. Concerns exist about sustainability of some aquaculture and commercial fishing practices.^195-197 Conversely, aquaculture contributes to global fish production,¹⁹⁸ and sustainability concerns are not unique to aquaculture or fishing but also exist for agricultural, forestry, freshwater, atmospheric, and energy resources.^{195, 199-200} Some progress has been made, such as changes in fish feeds to reduce dependence on fish meal or oil.¹⁹⁵ Given the importance of n-3 PUFAs for health, balance must be achieved between environmental and economic concerns to allow sustainable, financially viable aquaculture and commercial fishing.^195-196,199

Plant Sources. Alpha-linolenic acid (ALA) (18:3n-3) is an n-3 fatty acid present in flaxseed, canola, soybeans, and walnuts.¹²¹ In humans, ALA is converted to EPA in small quantities (in women more than men); further conversion to DHA is very limited.²⁰¹ Consumption of ALA (eg, 2-3 g/d) may reduce cardiovascular risk²⁰² or affect neurodevelopment, but benefits are less established compared with those for EPA and DHA.

Optimal Intakes

Optimal intake of n-3 PUFAs may vary depending on population and outcome of interest. In the general population, 250 mg/d of EPA and DHA is a reasonable target intake to reduce CHD mortality. Because dietary n-3 PUFAs persist for weeks in tissue membranes,²⁰³ this can be converted to a weekly intake of  1500-2000 mg. This corresponds to one 6-oz serving/wk of wild salmon or similar oily fish, or more frequent intake of smaller or less n-3 PUFA–rich servings (Table 2). For individuals with CHD, 1000 mg/d of EPA and DHA is currently recommended to reduce CHD mortality.^204-205 Our analysis suggests that lower doses may be sufficient, but given this population's higher risk and that most data are from primary prevention studies, a target intake of 500 to 1000 mg/d—consistent with the largest secondary prevention trial to date⁹—appears reasonable. This could be approximated by one 6-oz serving/wk of fish richest in n-3 PUFAs (eg, farmed salmon, anchovies, herring), more frequent consumption of other fish (Table 2), or supplements. Optimal intake levels for other clinical outcomes are not well established.

The effects, if any, of low-level methylmercury exposure in adults are not established; mercury may modestly reduce the cardiovascular benefits of fish intake. One can minimize concerns by choosing fish higher in n-3 PUFAs and lower in mercury or by simply consuming a variety of different seafood. Individuals with high consumption (5 servings/wk) should limit intake of selected species highest in mercury (Table 2).

DHA appears important for early neurodevelopment. Women who are or may become pregnant and nursing mothers should avoid selected species (shark, swordfish, golden bass, and king mackerel; locally caught fish per local advisories) and limit intake of albacore tuna (6 oz/wk) to minimize methylmercury exposure.31, 142 However, emphasis must also be placed on adequate consumption—12 oz/wk—of other fish and shellfish to provide reasonable amounts of DHA^{31, 142} and avoid further decreases in already low seafood intake among women (74% of women of childbearing age and 85% of pregnant women consume <6 oz/wk).^206-207

Continued efforts to limit environmental contamination from organochlorine compounds are appropriate. However, levels of PCBs and dioxins in fish are low, similar to those in several other foods, and the magnitudes of possible risks in adults are greatly exceeded by benefits of fish intake and should have little impact on individual decisions regarding fish consumption (for locally caught freshwater fish, women of childbearing age should consult regional advisories).

CONCLUSIONS

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Potential risks of fish intake must be considered in the context of potential benefits. Based on strength of evidence and potential magnitudes of effect, the benefits of modest fish consumption (1-2 servings/wk) outweigh the risks among adults and, excepting a few selected fish species, among women of childbearing age. Avoidance of modest fish consumption due to confusion regarding risks and benefits could result in thousands of excess CHD deaths annually and suboptimal neurodevelopment in children.

AUTHOR INFORMATION

Jump to Section  • Top  • Introduction  • Evidence acquisition  • Evidence synthesis  • Conclusions  • Author information  • References

Corresponding Author: Dariush Mozaffarian, MD, DrPH, Harvard School of Public Health, 665 Huntington Ave, Bldg 2, Room 315, Boston, MA 02115 (dmozaffa{at}hsph.harvard.edu).

Author Contributions: Dr Mozaffarian had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design; acquisition of data; drafting of the manuscript; critical revision of the manuscript for important intellectual content: Mozaffarian, Rimm.

Analysis and interpretation of data; statistical analysis; obtained funding: Mozaffarian.

Administrative, technical, or material support; study supervision: Rimm.

Financial Disclosures: Dr Rimm reports that he has received research funding from Merck, Pfizer, and GlaxoSmithKline, and that he has received payment or honoraria for presentations about food and diets from the US Environmental Protection Agency, the US Food and Drug Administration, the Institute of Medicine, the Culinary Institute of America, the International Chefs Association, and academic conferences funded by Bunge and Unilever. Dr Mozaffarian reported no financial disclosures.

Funding/Support: This study was supported by National Heart, Lung, and Blood Institute, National Institutes of Health grant K08-HL-075628.

Role of the Sponsor: The National Heart, Lung, and Blood Institute had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript.

Acknowledgment: We thank Ingeborg Brouwer, PhD, Wageningen Centre for Food Sciences, Wageningen, the Netherlands, for providing mortality results from the Study on Omega-3 Fatty Acids and Ventricular Arrythmia trial; Calle Bengtsson, MD, PhD, Cecilia Björkelund, MD, PhD, Lauren Lissner, PhD, and Valter Sundh, BSc, The Sahlgrenska Academy at Göteborg University, Gothenburg, Sweden, for providing results from their analysis of mercury and coronary heart disease in Sweden; and Walter Willett, MD, DrPH, Meir Stampfer, MD, DrPH, and Russ Hauser, MD, ScD, Harvard School of Public Health, Boston, Mass, for insightful comments. None of those acknowledged received compensation for their contributions.

We encourage authors to submit papers for consideration as a Clinical Review. Please contact Michael S. Lauer, MD, at lauerm{at}ccf.org.

Author Affiliations: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School; and Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, Mass.

REFERENCES

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1. Bang HO, Dyerberg J. Lipid metabolism and ischemic heart disease in Greenland Eskimos. In: Draper H, ed. Advances in Nutrition Research. New York, NY: Plenum Press; 1980:1-22. 2. Kromhout D, Bosschieter EB, de Lezenne Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med. 1985;312:1205-1209. ABSTRACT 3. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet. 1989;2:757-761. WEB OF SCIENCE | PUBMED 4. Dolecek TA, Granditis G. Dietary polyunsaturated fatty acids and mortality in the Multiple Risk Factor Intervention Trial (MRFIT). World Rev Nutr Diet. 1991;66:205-216. PUBMED 5. Siscovick DS, Raghunathan TE, King I, et al. Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA. 1995;274:1363-1367. FREE FULL TEXT 6. Kromhout D, Feskens EJ, Bowles CH. The protective effect of a small amount of fish on coronary heart disease mortality in an elderly population. Int J Epidemiol. 1995;24:340-345. FREE FULL TEXT 7. Daviglus ML, Stamler J, Orencia AJ, et al. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med. 1997;336:1046-1053. FREE FULL TEXT 8. Albert CM, Hennekens CH, O’Donnell CJ, et al. Fish consumption and risk of sudden cardiac death. JAMA. 1998;279:23-28. FREE FULL TEXT 9. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999;354:447-455. FULL TEXT | WEB OF SCIENCE | PUBMED 10. Oomen CM, Feskens EJ, Rasanen L, et al. Fish consumption and coronary heart disease mortality in Finland, Italy, and The Netherlands. Am J Epidemiol. 2000;151:999-1006. FREE FULL TEXT 11. Yuan JM, Ross RK, Gao YT, Yu MC. Fish and shellfish consumption in relation to death from myocardial infarction among men in Shanghai, China. Am J Epidemiol. 2001;154:809-816. FREE FULL TEXT 12. Hu FB, Bronner L, Willett WC, et al. Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. JAMA. 2002;287:1815-1821. FREE FULL TEXT 13. Albert CM, Campos H, Stampfer MJ, et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med. 2002;346:1113-1118. FREE FULL TEXT 14. Lemaitre RN, King IB, Mozaffarian D, Kuller LH, Tracy RP, Siscovick DS. n-3 Polyunsaturated fatty acids, fatal ischemic heart disease, and nonfatal myocardial infarction in older adults: the Cardiovascular Health Study. Am J Clin Nutr. 2003;77:319-325. FREE FULL TEXT 15. Mozaffarian D, Lemaitre RN, Kuller LH, Burke GL, Tracy RP, Siscovick DS. Cardiac benefits of fish consumption may depend on the type of fish meal consumed: the Cardiovascular Health Study. Circulation. 2003;107:1372-1377. FREE FULL TEXT 16. Mozaffarian D, Ascherio A, Hu FB, et al. Interplay between different polyunsaturated fatty acids and risk of coronary heart disease in men. Circulation. 2005;111:157-164. FREE FULL TEXT 17. Yokoyama M, Origasu H, Matsuzaki M, et al. Effects of eicosapentaenoic acid (EPA) on major cardiovascular events in hypercholesterolemic patients: the Japan EPA Lipid Intervention Study (JELIS). Presented at: American Heart Association Scientific Sessions; November 17, 2005; Dallas, Tex.18. McLennan PL. Myocardial membrane fatty acids and the antiarrhythmic actions of dietary fish oil in animal models. Lipids. 2001;36(suppl):S111-S114.19. Leaf A, Kang JX, Xiao YF, Billman GE. Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Circulation. 2003;107:2646-2652. FREE FULL TEXT 20. Wang C, Harris WS, Chung M, et al. n-3 Fatty acids from fish or fish-oil supplements, but not {alpha}-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review. Am J Clin Nutr. 2006;84:5-17. FREE FULL TEXT 21. Simmer K. Longchain polyunsaturated fatty acid supplementation in infants born at term. Cochrane Database Syst Rev. 2001;(4):CD000376. PUBMED 22. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). Washington, DC: The National Academies Press; 2002/2005.23. Uauy R, Hoffman DR, Mena P, Llanos A, Birch EE. Term infant studies of DHA and ARA supplementation on neurodevelopment: results of randomized controlled trials. J Pediatr. 2003;143:S17-S25. WEB OF SCIENCE | PUBMED 24. Cohen JT, Bellinger DC, Connor WE, Shaywitz BA. A quantitative analysis of prenatal intake of n-3 polyunsaturated fatty acids and cognitive development. Am J Prev Med. 2005;29:366-374. FULL TEXT | WEB OF SCIENCE | PUBMED 25. McCann JC, Ames BN. Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? an overview of evidence from cognitive and behavioral tests in humans and animals. Am J Clin Nutr. 2005;82:281-295. FREE FULL TEXT 26. Lewin GA, Schachter HM, Yuen D, Merchant P, Mamaladze V, Tsertsvadze A, Agency for Healthcare Research and Quality (AHRQ). Effects of omega-3 fatty acids on child and maternal health. Evid Rep Technol Assess (Summ). August 2005;(118):1-11. PUBMED 27. US Environmental Protection Agency. Mercury Study report to Congress. http://www.epa.gov/mercury/report.htm. Accessed January 24, 2006.28. US Geological Survey. Mercury in the environment. http://www.usgs.gov/themes/factsheet/146-00/. Accessed October 25, 2005.29. Committee on the Toxicological Effects of Methylmercury, Board on Environmental Studies and Toxicology; Commission on Life Sciences, National Research Council. Toxicological Effects of Methylmercury. Washington, DC: National Academies Press; 2000.30. Risk Assessment Information System. Toxicity summary for mercury. http://risk.lsd.ornl.gov/tox/profiles/mercury_f_V1.shtml. Accessed January 24, 2006.31. Center for Food Safety and Applied Nutrition, US Food and Drug Administration. Seafood information and resources. http://www.cfsan.fda.gov/seafood1.html. Accessed January 30, 2006.32. World Health Organization (WHO). Assessment of the health risk of dioxins: re-evaluation of the Tolerable Daily Intake (TDI). WHO Consultation; May 25-29, 1998; Geneva, Switzerland.33. National Center for Environmental Assessment, US Environmental Protection Agency. Dioxin and related compounds. http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=55264. Accessed March 14, 2006.34. US Environmental Protection Agency. Polychlorinated biphenyls (PCBs). http://www.epa.gov/opptintr/pcb/. Accessed March 14, 2006.35. Verbeke W, Sioen I, Pieniak Z, Van Camp J, De Henauw S. Consumer perception versus scientific evidence about health benefits and safety risks from fish consumption. Public Health Nutr. 2005;8:422-429. FULL TEXT | WEB OF SCIENCE | PUBMED 36. Center for Food Nutrition and Agriculture Policy, University of Maryland. Real mercury facts. http://www.realmercuryfacts.org/index.htm. Accessed March 23, 2006.37. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177-188. FULL TEXT | WEB OF SCIENCE | PUBMED 38. Smith PL. Splines as a useful and convenient statistical tool. Am Stat. 1979;33:57-62.39. Durrleman S, Simon R. Flexible regression models with cubic splines. Stat Med. 1989;8:551-561. WEB OF SCIENCE | PUBMED 40. Morris MC, Evans DA, Tangney CC, Bienias JL, Wilson RS. Fish consumption and cognitive decline with age in a large community study. Arch Neurol. 2005;62:1849-1853. FREE FULL TEXT 41. Peet M, Stokes C. Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs. 2005;65:1051-1059. FULL TEXT | WEB OF SCIENCE | PUBMED 42. Young G, Conquer J. Omega-3 fatty acids and neuropsychiatric disorders. Reprod Nutr Dev. 2005;45:1-28. FULL TEXT | WEB OF SCIENCE | PUBMED 43. Mori TA, Beilin LJ. Omega-3 fatty acids and inflammation. Curr Atheroscler Rep. 2004;6:461-467. PUBMED 44. Mickleborough TD, Lindley MR, Ionescu AA, Fly AD. Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma. Chest. 2006;129:39-49. FREE FULL TEXT 45. Fraser GE, Sabate J, Beeson WL, Strahan TM. A possible protective effect of nut consumption on risk of coronary heart disease: the Adventist Health Study. Arch Intern Med. 1992;152:1416-1424. FREE FULL TEXT 46. Mann JI, Appleby PN, Key TJ, Thorogood M. Dietary determinants of ischaemic heart disease in health conscious individuals. Heart. 1997;78:450-455. FREE FULL TEXT 47. Osler M, Andreasen AH, Hoidrup S. No inverse association between fish consumption and risk of death from all-causes, and incidence of coronary heart disease in middle-aged, Danish adults. J Clin Epidemiol. 2003;56:274-279. FULL TEXT | WEB OF SCIENCE | PUBMED 48. Folsom AR, Demissie Z. Fish intake, marine omega-3 fatty acids, and mortality in a cohort of postmenopausal women. Am J Epidemiol. 2004;160:1005-1010. FREE FULL TEXT 49. Nakamura Y, Ueshima H, Okamura T, et al. Association between fish consumption and all-cause and cause-specific mortality in Japan: NIPPON DATA80, 1980-99. Am J Med. 2005;118:239-245. FULL TEXT | WEB OF SCIENCE | PUBMED 50. Iso H, Kobayashi M, Ishihara J, et al. Intake of fish and n3 fatty acids and risk of coronary heart disease among Japanese: the Japan Public Health Center-Based (JPHC) Study Cohort I. Circulation. 2006;113:195-202. FREE FULL TEXT 51. Burr ML, Ashfield-Watt PA, Dunstan FD, et al. Lack of benefit of dietary advice to men with angina: results of a controlled trial. Eur J Clin Nutr. 2003;57:193-200. FULL TEXT | WEB OF SCIENCE | PUBMED 52. Siscovick DS, Lemaitre RN, Mozaffarian D. The fish story: a diet-heart hypothesis with clinical implications: n-3 polyunsaturated fatty acids, myocardial vulnerability, and sudden death. Circulation. 2003;107:2632-2634. FREE FULL TEXT 53. He K, Song Y, Daviglus ML, et al. Fish consumption and incidence of stroke: a meta-analysis of cohort studies. Stroke. 2004;35:1538-1542. FREE FULL TEXT 54. Mozaffarian D, Longstreth WT Jr, Lemaitre RN, et al. Fish consumption and stroke risk in elderly individuals: the cardiovascular health study. Arch Intern Med. 2005;165:200-206. FREE FULL TEXT 55. Erkkila AT, Lichtenstein AH, Mozaffarian D, Herrington DM. Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease. Am J Clin Nutr. 2004;80:626-632. FREE FULL TEXT 56. Sacks FM, Stone PH, Gibson CM, Silverman DI, Rosner B, Pasternak RC, HARP Research Group. Controlled trial of fish oil for regression of human coronary atherosclerosis. J Am Coll Cardiol. 1995;25:1492-1498. ABSTRACT 57. von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H. The effect of dietary omega-3 fatty acids on coronary atherosclerosis: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1999;130:554-562. FREE FULL TEXT 58. Angerer P, Kothny W, Stork S, von Schacky C. Effect of dietary supplementation with omega-3 fatty acids on progression of atherosclerosis in carotid arteries. Cardiovasc Res. 2002;54:183-190. FREE FULL TEXT 59. Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on coronary restenosis, intima-media thickness, and exercise tolerance: a systematic review. Atherosclerosis. 2006;184:237-246. FULL TEXT | WEB OF SCIENCE | PUBMED 60. Raitt MH, Connor WE, Morris C, et al. Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial. JAMA. 2005;293:2884-2891. FREE FULL TEXT 61. Leaf A, Albert CM, Josephson M, et al. Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake. Circulation. 2005;112:2762-2768. FREE FULL TEXT 62. Brouwer IA, Zock PL, Camm AJ, et al. Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial. JAMA. 2006;295:2613-2619. FREE FULL TEXT 63. Mozaffarian D, Psaty BM, Rimm EB, et al. Fish intake and risk of incident atrial fibrillation. Circulation. 2004;110:368-373. FREE FULL TEXT 64. Frost L, Vestergaard P. n-3 Fatty acids consumed from fish and risk of atrial fibrillation or flutter: the Danish Diet, Cancer, and Health Study. Am J Clin Nutr. 2005;81:50-54. FREE FULL TEXT 65. Calo L, Bianconi L, Colivicchi F, et al. N-3 Fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial. J Am Coll Cardiol. 2005;45:1723-1728. FREE FULL TEXT 66. Mozaffarian D, Bryson CL, Lemaitre RN, Burke GL, Siscovick DS. Fish intake and risk of incident heart failure. J Am Coll Cardiol. 2005;45:2015-2021. FREE FULL TEXT 67. Charnock JS, McLennan PL, Abeywardena MY. Dietary modulation of lipid metabolism and mechanical performance of the heart. Mol Cell Biochem. 1992;116:19-25. FULL TEXT | WEB OF SCIENCE | PUBMED 68. Kenny D, Warltier DC, Pleuss JA, Hoffmann RG, Goodfriend TL, Egan BM. Effect of omega-3 fatty acids on the vascular response to angiotensin in normotensive men. Am J Cardiol. 1992;70:1347-1352. FULL TEXT | WEB OF SCIENCE | PUBMED 69. Chin JP, Gust AP, Nestel PJ, Dart AM. Marine oils dose-dependently inhibit vasoconstriction of forearm resistance vessels in humans. Hypertension. 1993;21:22-28. FREE FULL TEXT 70. Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ. Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J Hypertens. 2002;20:1493-1499. FULL TEXT | WEB OF SCIENCE | PUBMED 71. Mozaffarian D, Geelen A, Brouwer IA, Geleijnse JM, Zock PL, Katan MB. Effect of fish oil on heart rate in humans: a meta-analysis of randomized controlled trials. Circulation. 2005;112:1945-1952. FREE FULL TEXT 72. Mozaffarian D, Gottdiener JS, Siscovick DS. Intake of tuna or other broiled or baked fish vs. fried fish and cardiac structure, function, and hemodynamics. Am J Cardiol. 2006;97:216-222. FULL TEXT | WEB OF SCIENCE | PUBMED 73. Nestel PJ. Fish oil and cardiovascular disease: lipids and arterial function. Am J Clin Nutr. 2000;71:228S-231S. FREE FULL TEXT 74. Christensen JH. n-3 fatty acids and the risk of sudden cardiac death: emphasis on heart rate variability. Dan Med Bull. 2003;50:347-367. WEB OF SCIENCE | PUBMED 75. Kristensen SD, Iversen AM, Schmidt EB. n-3 polyunsaturated fatty acids and coronary thrombosis. Lipids. 2001;36(suppl):S79-S82.76. Clandinin MT, Cheema S, Field CJ, Garg ML, Venkatraman J, Clandinin TR. Dietary fat: exogenous determination of membrane structure and cell function. FASEB J. 1991;5:2761-2769. ABSTRACT 77. Feller SE, Gawrisch K. Properties of docosahexaenoic-acid-containing lipids and their influence on the function of rhodopsin. Curr Opin Struct Biol. 2005;15:416-422. FULL TEXT | WEB OF SCIENCE | PUBMED 78. Vanden Heuvel JP. Diet, fatty acids, and regulation of genes important for heart disease. Curr Atheroscler Rep. 2004;6:432-440. PUBMED 79. Harris WS. n-3 Fatty acids and serum lipoproteins: human studies. AM J Clin Nutr. 1997;65(5 suppl):1645S-1654S. FREE FULL TEXT 80. Dallongeville J, Yarnell J, Ducimetiere P, et al. Fish consumption is associated with lower heart rates. Circulation. 2003;108:820-825. FREE FULL TEXT 81. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silberschatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97:1837-1847. FREE FULL TEXT 82. Austin MA, Hokanson JE, Edwards KL. Hypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol. 1998;81:7B-12B. FULL TEXT | WEB OF SCIENCE | PUBMED 83. Kannel WB, Kannel C, Paffenbarger RS Jr, Cupples LA. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J. 1987;113:1489-1494. FULL TEXT | WEB OF SCIENCE | PUBMED 84. Jouven X, Zureik M, Desnos M, Guerot C, Ducimetiere P. Resting heart rate as a predictive risk factor for sudden death in middle-aged men. Cardiovasc Res. 2001;50:373-378. FREE FULL TEXT 85. Hu FB, Stampfer MJ, Manson JE, et al. Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women. Am J Clin Nutr. 1999;70:1001-1008. FREE FULL TEXT 86. Anderson RN, Smith LB, Division of Vital Statistics, Centers for Disease Control and Prevention. National Vital Statistics Reports: deaths: leading causes for 2002. http://www.cdc.gov/nchs/data/nvsr/nvsr53/nvsr53_17.pdf. Accessed March 29, 2006.87. Brox J, Olaussen K, Osterud B, et al. A long-term seal- and cod-liver-oil supplementation in hypercholesterolemic subjects. Lipids. 2001;36:7-13. WEB OF SCIENCE | PUBMED 88. Eritsland J, Arnesen H, Gronseth K, Fjeld NB, Abdelnoor M. Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Am J Cardiol. 1996;77:31-36. FULL TEXT | WEB OF SCIENCE | PUBMED 89. Johansen O, Brekke M, Seljeflot I, Abdelnoor M, Arnesen H, Coronary Angioplasty Restenosis Trial. N-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study. J Am Coll Cardiol. 1999;33:1619-1626. FREE FULL TEXT 90. Kaul U, Sanghvi S, Bahl VK, Dev V, Wasir HS. Fish oil supplements for prevention of restenosis after coronary angioplasty. Int J Cardiol. 1992;35:87-93. FULL TEXT | WEB OF SCIENCE | PUBMED 91. Leaf A, Jorgensen MB, Jacobs AK, et al. Do fish oils prevent restenosis after coronary angioplasty? Circulation. 1994;90:2248-2257. FREE FULL TEXT 92. Nilsen DW, Albrektsen G, Landmark K, Moen S, Aarsland T, Woie L. Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol. Am J Clin Nutr. 2001;74:50-56. FREE FULL TEXT 93. Singh RB, Niaz MA, Sharma JP, Kumar R, Rastogi V, Moshiri M. Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival—4. Cardiovasc Drugs Ther. 1997;11:485-491. FULL TEXT | WEB OF SCIENCE | PUBMED 94. Hooper L, Thompson RL, Harrison RA, et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ. 2006;332:752-760. FREE FULL TEXT 95. Cheung BM, Lauder IJ, Lau CP, Kumana CR. Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes. Br J Clin Pharmacol. 2004;57:640-651. FULL TEXT | WEB OF SCIENCE | PUBMED 96. Uauy R, Mena P, Wegher B, Nieto S, Salem N Jr. Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth. Pediatr Res. 2000;47:127-135. WEB OF SCIENCE | PUBMED 97. Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Pediatrics. 2003;111:e39-e44. FREE FULL TEXT 98. Oken E, Wright RO, Kleinman KP, et al. Maternal fish consumption, hair mercury, and infant cognition in a U.S. Cohort. Environ Health Perspect. 2005;113:1376-1380. WEB OF SCIENCE | PUBMED 99. Colombo J, Kannass KN, Shaddy DJ, et al. Maternal DHA and the development of attention in infancy and toddlerhood. Child Dev. 2004;75:1254-1267. FULL TEXT | WEB OF SCIENCE | PUBMED 100. Daniels JL, Longnecker MP, Rowland AS, Golding J. Fish intake during pregnancy and early cognitive development of offspring. Epidemiology. 2004;15:394-402. FULL TEXT | WEB OF SCIENCE | PUBMED 101. US Environmental Protection Agency. Controlling power plant emissions: emissions progress. http://www.epa.gov/mercury/control_emissions/emissions.htm. Accessed March 29, 2006, 2006.102. Office of Regulatory Affairs, US Food And Drug Administration. Compliance policy guides. http://www.fda.gov/ora/compliance_ref/cpg/cpgfod/default.htm#sc540. Accessed February 2, 2006, 2006.103. Bayarri S, Baldassarri LT, Iacovella N, Ferrara F, di Domenico A. PCDDs, PCDFs, PCBs and DDE in edible marine species from the Adriatic Sea. Chemosphere. 2001;43:601-610. PUBMED 104. Schmitt CJ, Hinck JE, Blazer VS, et al. Environmental contaminants and biomarker responses in fish from the Rio Grande and its U.S. tributaries: spatial and temporal trends. Sci Total Environ. 2005;350:161-193. FULL TEXT | PUBMED 105. Karl H, Ruoff U, Bluthgen A. Levels of dioxins in fish and fishery products on the German market. Chemosphere. 2002;49:765-773. PUBMED 106. Schecter A, Dellarco M, Papke O, Olson J. A comparison of dioxins, dibenzofurans and coplanar PCBs in uncooked and broiled ground beef, catfish and bacon. Chemosphere. 1998;37:1723-1730. PUBMED 107. Jensen E, Bolger PM. Exposure assessment of dioxins/furans consumed in dairy foods and fish. Food Addit Contam. 2001;18:395-403. FULL TEXT | WEB OF SCIENCE | PUBMED 108. Fiedler H, Cooper K, Bergek S, et al. PCDD, PCDF, and PCB in farm-raised catfish from southeast United States—concentrations, sources, and CYP1A induction. Chemosphere. 1998;37:1645-1656. PUBMED 109. Focant JF, Pirard C, De Pauw E. Levels of PCDDs, PCDFs and PCBs in Belgian and international fast food samples. Chemosphere. 2004;54:137-142. PUBMED 110. US Food And Drug Administration. Food and Drug Administration total diet study. http://vm.cfsan.fda.gov/~comm/tds-toc.html. Accessed February 1, 2006.111. Hayward DG, Holcomb J, Glidden R, Wilson P, Harris M, Spencer V. Quadrupole ion storage tandem mass spectrometry and high-resolution mass spectrometry: complementary application in the measurement of 2,3,7,8-chlorine substituted dibenzo-p-dioxins and dibenzofurans in US foods. Chemosphere. 2001;43:407-415. PUBMED 112. Gomara B, Bordajandi LR, Fernandez MA, et al. Levels and trends of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (PCBs) in Spanish commercial fish and shellfish products, 1995-2003. J Agric Food Chem. 2005;53:8406-8413. FULL TEXT | WEB OF SCIENCE | PUBMED 113. Rawn DF, Forsyth DS, Ryan JJ, et al. PCB, PCDD and PCDF residues in fin and non-fin fish products from the Canadian retail market 2002. Sci Total Environ. 2006;359:101-110. FULL TEXT | PUBMED 114. Food Safety Authority of Ireland. Summary of investigation of dioxins, furans, and PCBs in farmed salmon, wild salmon, farmed trout and fish oil capsules. March 2002. http://www.fsai.ie/surveillance/food/surveillance_food_summarydioxins.asp. Accessed March 31, 2006.115. Hites RA, Foran JA, Carpenter DO, Hamilton MC, Knuth BA, Schwager SJ. Global assessment of organic contaminants in farmed salmon. Science. 2004;303:226-229. FREE FULL TEXT 116. Jacobs MN, Covaci A, Schepens P. Investigation of selected persistent organic pollutants in farmed Atlantic salmon (Salmo salar), salmon aquaculture feed, and fish oil components of the feed. Environ Sci Technol. 2002;36:2797-2805. PUBMED 117. Easton MD, Luszniak D, Von der GE. Preliminary examination of contaminant loadings in farmed salmon, wild salmon and commercial salmon feed. Chemosphere. 2002;46:1053-1074. PUBMED 118. Bordajandi LR, Martin I, Abad E, Rivera J, Gonzalez MJ. Organochlorine compounds (PCBs, PCDDs and PCDFs) in seafish and seafood from the Spanish Atlantic Southwest Coast. Chemosphere. 2006;64:1450-1457. PUBMED 119. Kiviranta H, Hallikainen A, Ovaskainen ML, Kumpulainen J, Vartiainen T. Dietary intakes of polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls in Finland. Food Addit Contam. 2001;18:945-953. FULL TEXT | WEB OF SCIENCE | PUBMED 120. Schecter A, Cramer P, Boggess K, et al. Intake of dioxins and related compounds from food in the U.S. population. J Toxicol Environ Health A. 2001;63:1-18. FULL TEXT | WEB OF SCIENCE | PUBMED 121. Agricultural Research Service, US Department of Agriculture. USDA National Nutrient Database for Standard Reference—Release 18 (2005). Washington, DC: US Dept of Agriculture; 2006.122. US Department of Health and Human Services; US Environmental Protection Agency. Mercury levels in commercial fish and shellfish. http://www.cfsan.fda.gov/~frf/sea-mehg.html. Accessed February 2, 2006.123. Shim SM, Lasrado JA, Dorworth LE, Santerre CR. Mercury and omega-3 fatty acids in retail fish sandwiches. J Food Prot. 2005;68:633-635. WEB OF SCIENCE | PUBMED 124. DietFacts.com. Helping you choose healthful foods. http://www.dietfacts.com/. Accessed April 4, 2006.125. Office MF, US Fish and Wildlife Service. Total mercury and methylmercury in freshwater mussels from the Sudbury River Watershed, Massachusetts. http://www.fws.gov/northeast/mainecontaminants/PDF%20files/NyanMussels.PDF#search='mussel%20mercury'. Accessed July 11, 2006.126. Airas S, Duinker A, Julshamn K. Copper, zinc, arsenic, cadmium, mercury, and lead in blue mussels (Mytilus edulis) in the Bergen harbor area, Western Norway. Bull Environ Contam Toxicol. 2004;73:276-284. FULL TEXT | WEB OF SCIENCE | PUBMED 127. Food Safety and Inspection Service, US Department of Agriculture. Dioxins and dioxin-like compounds in the U.S. domestic meat and poultry supply. http://www.fsis.usda.gov/PDF/Dioxin_Report_0605.pdf. Accessed March 24, 2006.128. Liem AK, Furst P, Rappe C. Exposure of populations to dioxins and related compounds. Food Addit Contam. 2000;17:241-259. FULL TEXT | WEB OF SCIENCE | PUBMED 129. US Food And Drug Administration. Questions and answers about dioxins. http://www.cfsan.fda.gov/~lrd/dioxinqa.html#g11. Accessed February 2, 2006, 2006.130. Thannum J, Great Lakes Indian Fish & Wildlife Commission. Tribally sold Lake Superior fish easily meet FDA restrictions for chemical contaminants. http://www.glifwc.org/pub/summer00/fish_contaminants.htm. Accessed March 25, 2006.131. Gochfeld M. Cases of mercury exposure, bioavailability, and absorption. Ecotoxicol Environ Saf. 2003;56:174-179. FULL TEXT | WEB OF SCIENCE | PUBMED 132. Integrated Risk Information System, US Environmental Protection Agency. Methylmercury (MeHg) (CASRN 22967-92-6). http://www.epa.gov/iris/subst/0073.htm. Accessed May 1, 2006.133. McDowell MA, Dillon CF, Osterloh J, et al. Hair mercury levels in U.S. children and women of childbearing age: reference range data from NHANES 1999-2000. Environ Health Perspect. 2004;112:1165-1171. WEB OF SCIENCE | PUBMED 134. Grandjean P, Weihe P, White RF, et al. Cognitive deficit in 7-year-old children with prenatal exposure to methylmercury. Neurotoxicol Teratol. 1997;19:417-428. FULL TEXT | WEB OF SCIENCE | PUBMED 135. Grandjean P, Weihe P, White RF, Debes F. Cognitive performance of children prenatally exposed to "safe" levels of methylmercury. Environ Res. 1998;77:165-172. PUBMED 136. Kjellstrom T. Physical and Mental Development of Children With Prenatal Exposure to Mercury from Fish: Stage II: Interviews and Psychological Tests at Age 6. Stockholm, Sweden: National Swedish Environmental Protection Board; 1989.137. Crump KS, Kjellstrom T, Shipp AM, Silvers A, Stewart A. Influence of prenatal mercury exposure upon scholastic and psychological test performance: benchmark analysis of a New Zealand cohort. Risk Anal. 1998;18:701-713. WEB OF SCIENCE | PUBMED 138. Jedrychowski W, Jankowski J, Flak E, et al. Effects of prenatal exposure to mercury on cognitive and psychomotor function in one-year-old infants: epidemiologic cohort study in Poland. Ann Epidemiol. 2006;16:439-447. FULL TEXT | WEB OF SCIENCE | PUBMED 139. Palumbo DR, Cox C, Davidson PW, et al. Association between prenatal exposure to methylmercury and cognitive functioning in Seychellois children: a reanalysis of the McCarthy Scales of Children's Ability from the main cohort study. Environ Res. 2000;84:81-88. PUBMED 140. Davidson PW, Palumbo D, Myers GJ, et al. Neurodevelopmental outcomes of Seychellois children from the pilot cohort at 108 months following prenatal exposure to methylmercury from a maternal fish diet. Environ Res. 2000;84:1-11. PUBMED 141. Spurgeon A. Prenatal methylmercury exposure and developmental outcomes: review of the evidence and discussion of future directions. Environ Health Perspect. 2006;114:307-312. WEB OF SCIENCE | PUBMED 142. US Environmental Protection Agency. What you need to know about mercury in fish and shellfish. http://www.epa.gov/waterscience/fishadvice/advice.html. Accessed March 25, 2006.143. Rice DC. The US EPA reference dose for methylmercury: sources of uncertainty. Environ Res. 2004;95:406-413. PUBMED 144. Ahlqwist M, Bengtsson C, Lapidus L, Gergdahl IA, Schutz A. Serum mercury concentration in relation to survival, symptoms, and diseases: results from the prospective population study of women in Gothenburg, Sweden. Acta Odontol Scand. 1999;57:168-174. FULL TEXT | WEB OF SCIENCE | PUBMED 145. Hallgren CG, Hallmans G, Jansson JH, et al. Markers of high fish intake are associated with decreased risk of a first myocardial infarction. Br J Nutr. 2001;86:397-404. WEB OF SCIENCE | PUBMED 146. Guallar E, Sanz-Gallardo MI, van't Veer P, et al. Mercury, fish oils, and the risk of myocardial infarction. N Engl J Med. 2002;347:1747-1754. FREE FULL TEXT 147. Yoshizawa K, Rimm EB, Morris JS, et al. Mercury and the risk of coronary heart disease in men. N Engl J Med. 2002;347:1755-1760. FREE FULL TEXT 148. Virtanen JK, Voutilainen S, Rissanen TH, et al. Mercury, fish oils, and risk of acute coronary events and cardiovascular disease, coronary heart disease, and all-cause mortality in men in eastern Finland. Arterioscler Thromb Vasc Biol. 2005;25:228-233. FREE FULL TEXT 149. Joshi A, Douglass CW, Kim HD, et al. The relationship between amalgam restorations and mercury levels in male dentists and nondental health professionals. J Public Health Dent. 2003;63:52-60. WEB OF SCIENCE | PUBMED 150. Rissanen T, Voutilainen S, Nyyssonen K, Lakka TA, Salonen JT. Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk of acute coronary events: the Kuopio ischaemic heart disease risk factor study. Circulation. 2000;102:2677-2679. FREE FULL TEXT 151. Risher JF, Murray HE, Prince GR. Organic mercury compounds: human exposure and its relevance to public health. Toxicol Ind Health. 2002;18:109-160. FREE FULL TEXT 152. Risher JF. Too much of a good thing (fish): methylmercury case study. J Environ Health. 2004;67:9-14, 28. PUBMED 153. Lebel J, Mergler D, Branches F, et al. Neurotoxic effects of low-level methylmercury contamination in the Amazonian Basin. Environ Res. 1998;79:20-32. PUBMED 154. Yokoo EM, Valente JG, Grattan L, Schmidt SL, Platt I, Silbergeld EK. Low level methylmercury exposure affects neuropsychological function in adults. Environ Health. 2003;2:8. FULL TEXT | PUBMED 155. Auger N, Kofman O, Kosatsky T, Armstrong B. Low-level methylmercury exposure as a risk factor for neurologic abnormalities in adults. Neurotoxicology. 2005;26:149-157. FULL TEXT | WEB OF SCIENCE | PUBMED 156. Weil M, Bressler J, Parsons P, Bolla K, Glass T, Schwartz B. Blood mercury levels and neurobehavioral function. JAMA. 2005;293:1875-1882. FREE FULL TEXT 157. Johansson N, Basun H, Winblad B, Nordberg M. Relationship between mercury concentration in blood, cognitive performance, and blood pressure, in an elderly urban population. Biometals. 2002;15:189-195. FULL TEXT | WEB OF SCIENCE | PUBMED 158. Suzuki KT, Sasakura C, Yoneda S. Binding sites for the (Hg-Se) complex on selenoprotein P. Biochim Biophys Acta. 1998;1429:102-112. FULL TEXT | PUBMED 159. Watanabe C. Modification of mercury toxicity by selenium: practical importance? Tohoku J Exp Med. 2002;196:71-77. FULL TEXT | WEB OF SCIENCE | PUBMED 160. Raymond LJ, Ralston NV. Mercury: selenium interactions and health implications. Seychelles Med Dent J. 2004;7:72-77. 161. Chen C, Yu H, Zhao J, et al. The roles of serum selenium and selenoproteins on mercury toxicity in environmental and occupational exposure. Environ Health Perspect. 2006;114:297-301. WEB OF SCIENCE | PUBMED 162. Paulsson K, Lundbergh K. The selenium method for treatment of lakes for elevated levels of mercury in fish. Sci Total Environ. 1989;87-88:495-507.163. Seppanen K, Kantola M, Laatikainen R, et al. Effect of supplementation with organic selenium on mercury status as measured by mercury in pubic hair. J Trace Elem Med Biol. 2000;14:84-87. FULL TEXT | WEB OF SCIENCE | PUBMED 164. Buettner C. Mercury and the risk of myocardial infarction. N Engl J Med. 2003;348:2151-2154. FREE FULL TEXT 165. National Center for Environmental Assessment, US Environmental Protection Agency. PCBs: cancer dose-response assessment and application to environmental mixtures. Washington, DC: US Environmental Protection Agency; 1996.166. Hamilton MC, Hites RA, Schwager SJ, Foran JA, Knuth BA, Carpenter DO. Lipid composition and contaminants in farmed and wild salmon. Environ Sci Technol. 2005;39:8622-8629. PUBMED 167. Foran JA, Good DH, Carpenter DO, Hamilton MC, Knuth BA, Schwager SJ. Quantitative analysis of the benefits and risks of consuming farmed and wild salmon. J Nutr. 2005;135:2639-2643. FREE FULL TEXT 168. US Environmental Protection Agency. Risk Assessment and Fish Consumption Limits. 3rd ed. Washington, DC: US Environmental Protection Agency; 2003. Guidance for Assessing Chemical Contaminant Data for Use in Fish Advisories; vol 2.169. Hoyert DL, Heron MP, Murphy SL, Kung HC, Division of Vital Statistics. National Vital Statistics Report: deaths: final data for 2003. http://www.cdc.gov/nchs/data/nvsr/nvsr54/nvsr54_13.pdf. 2006. Accessed May 2, 2006.170. MacLean CH, Newberry SJ, Mojica WA, et al. Effects of omega-3 fatty acids on cancer risk: a systematic review. JAMA. 2006;295:403-415. FREE FULL TEXT 171. Jacobson JL, Jacobson SW. Intellectual impairment in children exposed to polychlorinated biphenyls in utero. N Engl J Med. 1996;335:783-789. FREE FULL TEXT 172. Patandin S, Lanting CI, Mulder PG, Boersma ER, Sauer PJ, Weisglas-Kuperus N. Effects of environmental exposure to polychlorinated biphenyls and dioxins on cognitive abilities in Dutch children at 42 months of age. J Pediatr. 1999;134:33-41. FULL TEXT | WEB OF SCIENCE | PUBMED 173. Grandjean P, Weihe P, Burse VW, et al. Neurobehavioral deficits associated with PCB in 7-year-old children prenatally exposed to seafood neurotoxicants. Neurotoxicol Teratol. 2001;23:305-317. FULL TEXT | WEB OF SCIENCE | PUBMED 174. Ribas-Fito N, Sala M, Kogevinas M, Sunyer J. Polychlorinated biphenyls (PCBs) and neurological development in children: a systematic review. J Epidemiol Community Health. 2001;55:537-546. FREE FULL TEXT 175. Stewart PW, Reihman J, Lonky EI, Darvill TJ, Pagano J. Cognitive development in preschool children prenatally exposed to PCBs and MeHg. Neurotoxicol Teratol. 2003;25:11-22. FULL TEXT | WEB OF SCIENCE | PUBMED 176. Schantz SL, Widholm JJ, Rice DC. Effects of PCB exposure on neuropsychological function in children. Environ Health Perspect. 2003;111:357-576. WEB OF SCIENCE | PUBMED 177. Nakajima S, Saijo Y, Kato S, et al. Effects of prenatal exposure to polychlorinated biphenyls and dioxins on mental and motor development in Japanese children at 6 months of age. Environ Health Perspect. 2006;114:773-778. WEB OF SCIENCE | PUBMED 178. Daniels JL, Longnecker MP, Klebanoff MA, et al. Prenatal exposure to low-level polychlorinated biphenyls in relation to mental and motor development at 8 months. Am J Epidemiol. 2003;157:485-492. FREE FULL TEXT 179. Gray KA, Klebanoff MA, Brock JW, et al. In utero exposure to background levels of polychlorinated biphenyls and cognitive functioning among school-age children. Am J Epidemiol. 2005;162:17-26. FREE FULL TEXT 180. Judd N, Griffith WC, Faustman EM. Contribution of PCB exposure from fish consumption to total dioxin-like dietary exposure. Regul Toxicol Pharmacol. 2004;40:125-135. FULL TEXT | WEB OF SCIENCE | PUBMED 181. Peapod by Stop & Shop. http://www.peapod.com/ Accessed July 11, 2006.182. Great Alaska Seafood. Fresh wild Alaska salmon. http://www.great-alaska-seafood.com/fresh-alaska-salmon.htm#alaska-king-salmon. Accessed July 11, 2006.183. Ed's Kasilof Seafoods. Alaska wild salmon. http://www.kasilofseafoods.com/seafood-gifts/wild-salmon.htm. Accessed July 12, 2006.184. Wild Pacific Salmon. Wild salmon products. http://www.wildpacificsalmon.com/site/680079/page/45031. Accessed July 12, 2006.185. Chee KM, Gong JX, Rees DM, et al. Fatty acid content of marine oil capsules. Lipids. 1990;25:523-528. WEB OF SCIENCE | PUBMED 186. Center for Drug Evaluation and Research, US Food And Drug Administration. Omacor: consumer drug information sheet—approval label. http://www.fda.gov/cder/foi/label/2004/21654lbl.pdf. Accessed April 5, 2006.187. Foran SE, Flood JG, Lewandrowski KB. Measurement of mercury levels in concentrated over-the-counter fish oil preparations: is fish oil healthier than fish? Arch Pathol Lab Med. 2003;127:1603-1605. WEB OF SCIENCE | PUBMED 188. Storelli MM, Storelli A, Marcotrigiano GO. Polychlorinated biphenyls, hexachlorobenzene, hexachlorocyclohexane isomers, and pesticide organochlorine residues in cod-liver oil dietary supplements. J Food Prot. 2004;67:1787-1791. WEB OF SCIENCE | PUBMED 189. Jimenez B, Wright C, Kelly M, Startin JR. Levels of PCDDs, PCDFs and non-ortho PCBs in dietary supplement fish oil obtained in Spain. Chemosphere. 1996;32:461-467. PUBMED 190. Patch CS, Tapsell LC, Mori TA, et al. The use of novel foods enriched with long-chain n-3 fatty acids to increase dietary intake: a comparison of methodologies assessing nutrient intake. J Am Diet Assoc. 2005;105:1918-1926. FULL TEXT | WEB OF SCIENCE | PUBMED 191. Warner K. Impact of high-temperature food processing on fats and oils. Adv Exp Med Biol. 1999;459:67-77. PUBMED 192. Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr. 1999;70:560S-569S. FREE FULL TEXT 193. Kris-Etherton PM, Taylor DS, Yu-Poth S, et al. Polyunsaturated fatty acids in the food chain in the United States. Am J Clin Nutr. 2000;71:179S-188S. FREE FULL TEXT 194. Hu FB, Stampfer MJ, Manson JE, et al. Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women. Am J Clin Nutr. 1999;69:890-897. FREE FULL TEXT 195. Naylor RL, Goldburg RJ, Primavera JH, et al. Effect of aquaculture on world fish supplies. Nature. 2000;405:1017-1024. FULL TEXT | PUBMED 196. Pauly D, Watson R, Alder J. Global trends in world fisheries: impacts on marine ecosystems and food security. Philos Trans R Soc Lond B Biol Sci. 2005;360:5-12. FREE FULL TEXT 197. Devine JA, Baker KD, Haedrich RL. Fisheries: deep-sea fishes qualify as endangered. Nature. 2006;439:29. FULL TEXT | PUBMED 198. National Marine Fisheries Service. Fisheries of the United States, 2004. Silver Spring, Md: US Dept of Commerce; 2005.199. Garcia SM, Grainger RJ. Gloom and doom? the future of marine capture fisheries. Philos Trans R Soc Lond B Biol Sci. 2005;360:21-46. FREE FULL TEXT 200. World Resources Institute. Millennium Ecosystem Assessment: Ecosystems and Human Well-Being—Synthesis Report. Washington, DC: Island Press; 2005.201. Williams CM, Burdge G. Long-chain n-3 PUFA: plant v. marine sources. Proc Nutr Soc. 2006;65:42-50. FULL TEXT | WEB OF SCIENCE | PUBMED 202. Mozaffarian D. Does alpha-linolenic acid intake reduce the risk of coronary heart disease? a review of the evidence. Altern Ther Health Med. 2005;11:24-30, 31, 79. WEB OF SCIENCE | PUBMED 203. Brown AJ, Pang E, Roberts DC. Persistent changes in the fatty acid composition of erythrocyte membranes after moderate intake of n-3 polyunsaturated fatty acids: study design implications. Am J Clin Nutr. 1991;54:668-673. FREE FULL TEXT 204. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106:2747-2757. FREE FULL TEXT 205. Van de Werf F, Ardissino D, Betriu A, et al, Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2003;24:28-66. FREE FULL TEXT 206. Schober SE, Sinks TH, Jones RL, et al. Blood mercury levels in US children and women of childbearing age, 1999-2000. JAMA. 2003;289:1667-1674. FREE FULL TEXT 207. Oken E, Kleinman KP, Berland WE, Simon SR, Rich-Edwards JW, Gillman MW. Decline in fish consumption among pregnant women after a national mercury advisory. Obstet Gynecol. 2003;102:346-351. FULL TEXT | WEB OF SCIENCE | PUBMED

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Long-chain omega-3 fatty acids, fish intake, and the risk of type 2 diabetes mellitus
Kaushik et al.
Am. J. Clin. Nutr. 2009;90:613-620.
ABSTRACT | FULL TEXT  

Omega-3 polyunsaturated fatty acids and cardiovascular diseases.
Lavie et al.
J Am Coll Cardiol 2009;54:585-594.
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Dietary fish and meat intake and dementia in Latin America, China, and India: a 10/66 Dementia Research Group population-based study
Albanese et al.
Am. J. Clin. Nutr. 2009;90:392-400.
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Adherence to 2005 Dietary Guidelines for Americans is associated with a reduced progression of coronary artery atherosclerosis in women with established coronary artery disease
Imamura et al.
Am. J. Clin. Nutr. 2009;90:193-201.
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The Effect of a Plant-Based Low-Carbohydrate ("Eco-Atkins") Diet on Body Weight and Blood Lipid Concentrations in Hyperlipidemic Subjects
Jenkins et al.
Arch Intern Med 2009;169:1046-1054.
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Fish consumption, marine omega-3 fatty acids, and incidence of heart failure: a population-based prospective study of middle-aged and elderly men
Levitan et al.
Eur Heart J 2009;30:1495-1500.
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High Dietary Taurine Reduces Apoptosis and Atherosclerosis in the Left Main Coronary Artery: Association With Reduced CCAAT/Enhancer Binding Protein Homologous Protein and Total Plasma Homocysteine but not Lipidemia
Zulli et al.
Hypertension 2009;53:1017-1022.
ABSTRACT | FULL TEXT  

Vitamin D, outdoor happiness, and the meaning of deficiency.
Mozaffarian
J Am Coll Cardiol 2009;53:2011-2012.
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Association between n-3 fatty acid consumption and ventricular ectopy after myocardial infarction
Smith et al.
Am. J. Clin. Nutr. 2009;89:1315-1320.
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Omega-3-enriched broiler meat: 1. Optimization of a production system
Zuidhof et al.
Poult. Sci. 2009;88:1108-1120.
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n-3 Fatty Acids Reduce Arterial LDL-Cholesterol Delivery and Arterial Lipoprotein Lipase Levels and Lipase Distribution
Chang et al.
Arterioscler. Thromb. Vasc. Bio. 2009;29:555-561.
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Towards Establishing Dietary Reference Intakes for Eicosapentaenoic and Docosahexaenoic Acids
Harris et al.
J. Nutr. 2009;139:804S-819S.
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Are dietary recommendations for the use of fish oils sustainable?
Jenkins et al.
CMAJ 2009;180:633-637.
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Mediterranean Diet and Incidence of and Mortality From Coronary Heart Disease and Stroke in Women
Fung et al.
Circulation 2009;119:1093-1100.
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(n-3) Fatty Acid Content of Red Blood Cells Does Not Predict Risk of Future Cardiovascular Events following an Acute Coronary Syndrome
Aarsetoey et al.
J. Nutr. 2009;139:507-513.
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Omega-6 Fatty Acids and Risk for Cardiovascular Disease: A Science Advisory From the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention
Harris et al.
Circulation 2009;119:902-907.
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Ethyl-eicosapentaenoic acid for the treatment of psychological distress and depressive symptoms in middle-aged women: a double-blind, placebo-controlled, randomized clinical trial
Lucas et al.
Am. J. Clin. Nutr. 2009;89:641-651.
ABSTRACT | FULL TEXT  

Heart Disease and Stroke Statistics--2009 Update: A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee
WRITING GROUP MEMBERS et al.
Circulation 2009;119:e21-e181.
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Fish oil and secondary prevention of cardiovascular disease
Brunner and Iso
BMJ 2008;337:a2541-a2541.
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Effect of fish oil on arrhythmias and mortality: systematic review
Leon et al.
BMJ 2008;337:a2931-a2931.
ABSTRACT | FULL TEXT  

Fish consumption and risk of major chronic disease in men
Virtanen et al.
Am. J. Clin. Nutr. 2008;88:1618-1625.
ABSTRACT | FULL TEXT  

Differences between Dietary Supplement and Prescription Drug Omega-3 Fatty Acid Formulations: A Legislative and Regulatory Perspective
Collins et al.
J. Am. Coll. Nutr. 2008;27:659-666.
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Frequency and Type of Seafood Consumed Influence Plasma (n-3) Fatty Acid Concentrations
Chung et al.
J. Nutr. 2008;138:2422-2427.
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Linking Exposure to Polychlorinated Biphenyls With Fatty Fish Consumption and Reduced Fetal Growth Among Danish Pregnant Women: A Cause for Concern?
Halldorsson et al.
Am J Epidemiol 2008;168:958-965.
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Direct Determinations of the Fatty Acid Composition of Daily Dietary Intakes Incorporating Nutraceuticals and Functional Food Strategies to Increase n-3 Highly Unsaturated Fatty Acids
Patterson and Stark
J. Am. Coll. Nutr. 2008;27:538-546.
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Mortality in a cohort with high fish consumption
Turunen et al.
Int J Epidemiol 2008;37:1008-1017.
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Fish, {omega}-3 Polyunsaturated Fatty Acids, and Mortality From Cardiovascular Diseases in a Nationwide Community-Based Cohort of Japanese Men and Women: The JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study
Yamagishi et al.
J Am Coll Cardiol 2008;52:988-996.
ABSTRACT | FULL TEXT  

Effect of sex and genotype on cardiovascular biomarker response to fish oils: the FINGEN Study
Caslake et al.
Am. J. Clin. Nutr. 2008;88:618-629.
ABSTRACT | FULL TEXT  

Long-chain n-3 fatty acids and mortality in elderly patients
Lindberg et al.
Am. J. Clin. Nutr. 2008;88:722-729.
ABSTRACT | FULL TEXT  

Marine-Derived n-3 Fatty Acids and Atherosclerosis in Japanese, Japanese-American, and White Men: A Cross-Sectional Study
Sekikawa et al.
J Am Coll Cardiol 2008;52:417-424.
ABSTRACT | FULL TEXT  

Fish consumption and risk of subclinical brain abnormalities on MRI in older adults
Virtanen et al.
Neurology 2008;71:439-446.
ABSTRACT | FULL TEXT  

Long-term fish consumption and n-3 fatty acid intake in relation to (sudden) coronary heart disease death: the Zutphen study
Streppel et al.
Eur Heart J 2008;29:2024-2030.
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RE: "MATERNAL FISH INTAKE DURING PREGNANCY, BLOOD MERCURY LEVELS, AND CHILD COGNITION AT AGE 3 YEARS IN A US COHORT"
Groth
Am J Epidemiol 2008;168:236-236.
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Blood concentrations of individual long-chain n-3 fatty acids and risk of nonfatal myocardial infarction
Sun et al.
Am. J. Clin. Nutr. 2008;88:216-223.
ABSTRACT | FULL TEXT  

Beyond Established and Novel Risk Factors: Lifestyle Risk Factors for Cardiovascular Disease
Mozaffarian et al.
Circulation 2008;117:3031-3038.
FULL TEXT  

Role of n-3 fatty acids in the treatment of hypertriglyceridemia and cardiovascular disease
Jacobson
Am. J. Clin. Nutr. 2008;87:1981S-1990S.
ABSTRACT | FULL TEXT  

Fish and n-3 fatty acids for the prevention of fatal coronary heart disease and sudden cardiac death
Mozaffarian
Am. J. Clin. Nutr. 2008;87:1991S-1996S.
ABSTRACT | FULL TEXT  

n-3 Fatty acids and cardiovascular disease: mechanisms underlying beneficial effects
Jung et al.
Am. J. Clin. Nutr. 2008;87:2003S-2009S.
ABSTRACT | FULL TEXT  

Conclusions and recommendations from the symposium, Beyond Cholesterol: Prevention and Treatment of Coronary Heart Disease with n-3 Fatty Acids
Deckelbaum et al.
Am. J. Clin. Nutr. 2008;87:2010S-2012S.
ABSTRACT | FULL TEXT  

n-3 fatty acids and cardiovascular disease
Grundt and Nilsen
haematol 2008;93:807-812.
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Heterogeneity in Randomized Controlled Trials of Long Chain (Fish) Omega-3 Fatty Acids in Restenosis, Secondary Prevention and Ventricular Arrhythmias
Jenkins et al.
J. Am. Coll. Nutr. 2008;27:367-378.
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Fish Oil in Combination with High or Low Intakes of Linoleic Acid Lowers Plasma Triacylglycerols but Does Not Affect Other Cardiovascular Risk Markers in Healthy Men
Damsgaard et al.
J. Nutr. 2008;138:1061-1066.
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Red Blood Cell Docosahexaenoic Acid and Eicosapentaenoic Acid Concentrations Are Positively Associated with Socioeconomic Status in Patients with Established Coronary Artery Disease: Data from the Heart and Soul Study
Cohen et al.
J. Nutr. 2008;138:1135-1140.
ABSTRACT | FULL TEXT  

Effect of the administration of n-3 polyunsaturated fatty acids on circulating levels of microparticles in patients with a previous myocardial infarction
Turco et al.
haematol 2008;93:892-899.
ABSTRACT | FULL TEXT  

Generic and Product-Specific Health Claim Processes for Functional Foods across Global Jurisdictions
Jew et al.
J. Nutr. 2008;138:1228S-1236S.
ABSTRACT | FULL TEXT  

Review of Food Policy and Consumer Issues of Mercury in Fish
Hughner et al.
J. Am. Coll. Nutr. 2008;27:185-194.
ABSTRACT | FULL TEXT  

Dietary Fish and {omega}-3 Fatty Acid Consumption and Heart Rate Variability in US Adults
Mozaffarian et al.
Circulation 2008;117:1130-1137.
ABSTRACT | FULL TEXT  

Omega-3 Fatty Acids for Cardioprotection
Lee et al.
Mayo Clin Proc. 2008;83:324-332.
ABSTRACT | FULL TEXT  

Hypertriglyceridemia.
Oh et al.
NEJM 2008;358:310-310.
FULL TEXT  

Fish-oil supplementation in patients with implantable cardioverter defibrillators: a meta-analysis
Jenkins et al.
CMAJ 2008;178:157-164.
ABSTRACT | FULL TEXT  

The Molecular Basis for Inhibition of BphD, a C-C Bond Hydrolase Involved in Polychlorinated Biphenyls Degradation: LARGE 3-SUBSTITUENTS PREVENT TAUTOMERIZATION
Bhowmik et al.
J. Biol. Chem. 2007;282:36377-36385.
ABSTRACT | FULL TEXT  

Comparison of the effects of fish and fish-oil capsules on the n 3 fatty acid content of blood cells and plasma phospholipids
Harris et al.
Am. J. Clin. Nutr. 2007;86:1621-1625.
ABSTRACT | FULL TEXT  

Role of Docosahexaenoic Acid in Modulating Methylmercury-Induced Neurotoxicity
Kaur et al.
Toxicol Sci 2007;100:423-432.
ABSTRACT | FULL TEXT  

Fish Oil and Prevention of Atrial Fibrillation
Mozaffarian
J Am Coll Cardiol 2007;50:1513-1514.
FULL TEXT  

Clinicians' Corner: A Lifestyle Medicine: Approach to Anxiety and Depression in Primary Care
Greenstone
AMERICAN JOURNAL OF LIFESTYLE MEDICINE 2007;1:167-170.
ABSTRACT  

Combining fish-oil supplements with regular aerobic exercise improves body composition and cardiovascular disease risk factors
Hill et al.
Am. J. Clin. Nutr. 2007;85:1267-1274.
ABSTRACT | FULL TEXT  

Statin Use and Risks for Death and Hospitalization in Chronic Heart Failure
Gerard and Gerard
JAMA 2007;297:1057-1058.
FULL TEXT  

A Commentary on Lifestyle Medicine Strategies for Risk Factor Reduction, Prevention, and Treatment of Coronary Artery Disease
Greenstone
AMERICAN JOURNAL OF LIFESTYLE MEDICINE 2007;1:91-94.
ABSTRACT  

Risks and Benefits of Fish Intake
Lucas and Harris
JAMA 2007;297:585-585.
FULL TEXT  

Risks and Benefits of Fish Intake
Tuomainen et al.
JAMA 2007;297:585-586.
FULL TEXT  

Recommending Omega-3 Oils for Patients With Heart Risks
DOC News 2007;4:4-4.
FULL TEXT  

Fish Intake: Benefits vs. Risks
Journal Watch Cardiology 2006;2006:2-2.
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