doi: 10.1161/01.CIR.0000038493.65177.94
(Circulation. 2002;106:2747.)
© 2002 American Heart Association, Inc.
AHA Scientific Statement |
Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease
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Key Words: AHA Scientific Statements • nutrition • fatty acids, omega-3 • fish oils • cardiovascular diseases
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Introduction |
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 Top Introduction Epidemiological and...Randomized Controlled TrialsPossible MechanismsIntake of Omega-3 Fatty...Safety of Omega-3 Fatty...Safety of FishSummaryReferences |
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Since the first AHA Science Advisory "Fish Consumption, Fish Oil, Lipids, and Coronary Heart Disease,"1 important new findings, including evidence from randomized controlled trials (RCTs), have been reported about the beneficial effects of omega-3 (or n-3) fatty acids on cardiovascular disease (CVD) in patients with preexisting CVD as well as in healthy individuals.2 New information about how omega-3 fatty acids affect cardiac function (including antiarrhythmic effects), hemodynamics (cardiac mechanics), and arterial endothelial function have helped clarify potential mechanisms of action. The present Statement will address distinctions between plant-derived (
-linolenic acid, C18:3n-3) and marine-derived (eicosapentaenoic acid, C20:5n-3 [EPA] and docosahexaenoic acid, C22:6n-3 [DHA]) omega-3 fatty acids. (Unless otherwise noted, the term omega-3 fatty acids will refer to the latter.) Evidence from epidemiological studies and RCTs will be reviewed, and recommendations reflecting the current state of knowledge will be made with regard to both fish consumption and omega-3 fatty acid (plant- and marine-derived) supplementation. This will be done in the context of recent guidance issued by the US Environmental Protection Agency and the Food and Drug Administration (FDA) about the presence of environmental contaminants in certain species of fish. |
Epidemiological and Observational Studies |
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Coronary Heart Disease
As reviewed by Stone,1 three prospective epidemiological studies within populations reported that men who ate at least some fish weekly had a lower coronary heart disease (CHD) mortality rate than that of men who ate none.3–6 More recent evidence that fish consumption favorably affects CHD mortality, especially nonsudden death from myocardial infarction (MI), has been reported in a 30-year follow-up of the Chicago Western Electric Study.7 Men who consumed 35 g or more of fish daily compared with those who consumed none had a relative risk of death from CHD of 0.62 and a relative risk of nonsudden death from MI of 0.33. In an ecological study conducted by Zhang et al,8 fish consumption was associated with a reduced risk from all-cause, ischemic heart disease and stroke mortality across 36 countries. In addition, in a study of Japanese living in Japan or Brazil, Mizushima et al9 reported a dose-response relationship between the frequency of weekly fish intake and reduced CVD risk factors (eg, obesity, hypertension, glycohemoglobin, ST-T segment change on the ECG). Until recently, little information was available about the effects of fish and omega-3 fatty acids and risk of CHD in women. A recent study conducted with women in the Nurses’ Health Study10 reported an inverse association between fish intake and omega-3 fatty acids and CHD death. Compared with women who rarely ate fish (less than once per month), the risk for CHD death was 21%, 29%, 31%, and 34% lower for fish consumption 1 to 3 times per month, once per week, 2 to 4 times per week, and >5 times per week, respectively (P for trend=0.001). Comparing the extreme quintiles of fish intake, the reduction in risk for CHD deaths seemed to be stronger for CHD death than for nonfatal MI (RR 0.55 versus 0.73).
Some studies have not reported a beneficial association of fish consumption and CHD mortality. In the Health Professionals’ Follow-up Study,11 no significant association was observed between fish intake (and omega-3 fatty acids) and risk of any CHD (ie, fatal coronary disease including sudden death, nonfatal MI, coronary artery bypass grafting, or angioplasty). Likewise, the US Physicians’ Health Study did not show an association between fish consumption (or omega-3 fatty acid intake) and reduced risk of total MI, nonsudden cardiac death, or total cardiovascular mortality.12 In contrast, however, fish consumption was related to a reduced risk of total mortality. The lack of an association between fish intake and CHD incidence and mortality also was reported from an analysis of the Seven Countries data and the EURAMIC (European Multicenter Case-Control Study on Antioxidants, Myocardial Infarction and Breast Cancer) Study.13,14 In the Seven Countries Study, although an inverse association between fish consumption and 25-year mortality from CHD across several populations was observed,13 when the confounding effects of saturated fatty acids, flavonoids, and smoking were considered, the association was not significant. In the EURAMIC Study, a large international case-control study, no evidence of a protective effect of adipose tissue DHA (a measure of long-term fish consumption) on the risk of developing MI was seen.14
Some investigators have speculated that the conflicting data from the epidemiological studies reflect differences in definitions of sudden death and the residual confounding of reference groups that had a less healthy lifestyle, 15 variability in the end points studied, experimental design or how fish intake was estimated, different study populations,16 and the possible confounding effect of an increase in hemorrhagic stroke. Albert et al12 proposed that their lack of an association may have been due to the small fraction of their study population (3.1%) reporting little to no fish consumption. Only studies including sizable non–fish-eating populations have reported an inverse association between fish consumption and coronary mortality. In the EURAMIC Study, only survivors of MI were evaluated, and it is conceivable that individuals who did not survive ate less fish. Another explanation, based on a rigorous analysis of 11 prospective cohort studies, is that the protective effect of fish consumption relates to the CHD risk status of the population studied17; this analysis concluded that fish consumption reduced CHD mortality (RR=0.4 to 0.6) in high-risk but not low-risk populations. Another consideration relates to the type of fish consumed (ie, fatty versus lean fish). Oomen et al18 reported a lower CHD mortality (RR=0.66) in populations that consumed fatty fish but not lean fish.
Finally, another explanation for the discordant results of epidemiological studies pertains to the hypothesized adverse effects of methylmercury, an environmental contaminant found in certain fish that may diminish the health benefits of omega-3 fatty acids.19 Recent studies have produced conflicting results with regard to the effects of methylmercury on CHD risk.20,21 Thus, the extent to which methylmercury in fish may mask the beneficial effects of omega-3 fatty acids requires further study.
Fish consumption has been shown to be related to reduced sudden cardiac death. In a population-based, nested, case-control study, a strong negative relationship was reported between fish intake and risk for sudden death (ie, 5.5 g of omega-3 fatty acids per month, equivalent to two fatty fish meals per week, was associated with a 50% reduced risk of primary cardiac arrest).22 In the US Physicians’ Health Study, men who consumed fish at least once weekly had a relative risk of sudden death of 0.48 (P=0.04) versus men who consumed fish less than once per month.12 A recent report from the Physicians’ Health Study23 reported an inverse relationship between blood levels of long-chain omega-3 fatty acids and risk of sudden death in men without a history of CVD. The relative risk of sudden death was significantly lower among men with levels in the third quartile (RR=0.28) and the fourth quartile (RR=0.19) compared with men whose blood levels were in the first quartile.
Further evidence for a protective effect of omega-3 fatty acids comes from two recent studies by Landmark et al24,25 who reported that chronic intake of fish or fish oil was associated with a reduction in infarct size as estimated by the frequency of Q-wave infarcts and by peak creatine kinase and lactate dehydrogenase activities after MI. In contrast to all the studies demonstrating a beneficial association, the Alpha- Tocopherol, Beta-Carotene Cancer Prevention Study found that estimated omega-3 fatty acid intake from fish was associated with a trend toward increased relative risk of coronary death after adjustment for trans, saturated, and cis-monounsaturated fatty acids.26
A growing body of evidence from recent epidemiological studies indicates that -linolenic acid is associated with a lower risk of MI and fatal ischemic heart disease in women and in men. In the EURAMIC Study, Guallar et al14 compared the highest quintile of adipose tissue -linolenic acid to the lowest and found a relative risk for MI of 0.42 (P for trend=0.02). This became nonsignificant after adjusting for classic risk factors (primarily smoking). Using a food-frequency questionnaire from a 10-year follow-up of the Nurses’ Health Study, and after controlling for standard coronary risk factors, Hu et al27 reported a dose-response relationship between -linolenic acid intake and relative risk of fatal ischemic heart disease, which was reduced by 45% in the highest quintile (P for trend=0.01). Similar findings were reported with the same methodology in the all-male Health Professionals’ Study, in which a 1% increase in -linolenic acid intake was associated with a 0.41 relative risk for acute MI (P for trend=0.01).28 Lowest-quintile intakes of -linolenic acid in these latter two trials were 0.7 to 0.8 g/d, and highest quintile intakes, 1.4 to 1.5 g/d. In the National Heart, Lung, and Blood Institute Family Heart Study, a cross-sectional study with 4584 participants, -linolenic acid was inversely related to coronary artery disease.29 The prevalence odds ratio of coronary artery disease was reduced 
40% for men in the top three quintiles of -linolenic acid intake and 50% to 70% for women. In contrast, in the Zutphen Elderly Study, a prospective epidemiological study with 667 men, ages 64 to 84 years, there was no beneficial effect of -linolenic acid intake on risk of 10-year coronary artery disease incidence.30 In the latter study, however, these negative results have been explained by the association between -linolenic acid and trans-fatty acid intake,30 as well as by limitations in the collection of the dietary data.31 Despite this latter study, a growing epidemiological database demonstrates a protective effect of -linolenic acid on coronary disease. Nonetheless, intervention studies are needed to establish a causal relationship between -linolenic acid intake and coronary disease.
Stroke
Compared with the literature describing the effects of omega-3 fatty acids on CHD, relatively little information about the association of omega-3 fatty acids and cerebral infarctions (stroke) is available. Several epidemiological studies have examined the relationship between fish intake and stroke incidence. In the Zutphen Study, the unadjusted hazard ratio of men who consumed an average of 20 g/d of fish was 0.49 (P<0.05) compared with those who consumed less.32 Likewise, in the National Health and Nutrition Examination Survey (NHANES) Epidemiologic Follow-up Study, white females who consumed fish more than once per week had an age-adjusted stroke incidence that was only half that of women who reported not consuming fish.33 A similar protective effect was seen in both black women and men but not in white men. A trend (P=0.06) toward reduced risk for stroke with increasing reported fish consumption was also reported in the Nurses’ Health Study.34 In contrast, both the Chicago Western Electric Study35 and the Physicians’ Health Study36 failed to find any relationship between reported fish intake and reduced stroke risk.
According to the serum fatty acid profiles of subjects in the Multiple Risk Factor Intervention Trial, -linolenic acid was negatively associated with stroke incidence.37 In both the Lyon Diet Heart Study38 (testing a Mediterranean-style diet enriched with -linolenic acid) and the GISSI-Prevention Study39 (testing the effects of 850 mg of supplemental omega-3 fatty acids), there was no significant effect on the incidence of stroke.
The evidence to date is primarily for total stroke risk, and associations could differ if the data were analyzed for type-specific stroke incidence. For example, evidence exists for an inverse relationship between small intakes of fish (1 portion per week) and ischemic stroke32 and for a possible increased risk for hemorrhagic stroke with "Eskimo" intakes of omega-3 fatty acids.40 Thus, as Zhang et al8 have noted, linking fish consumption with total stroke risk is likely to underestimate the strength of the real associations between fish consumption and type-specific stroke risk.
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Randomized Controlled Trials |
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At the time of the first Advisory, the only RCT of omega-3 fatty acids in secondary prevention of CHD was the Diet And Reinfarction Trial (DART), which reported a 29% reduction in all-cause mortality over a 2-year period in male MI survivors advised to increase their intake of oily fish (200 to 400 g of fatty fish per week, which provided an additional 500 to 800 mg/d of omega-3 fatty acids).41 The greatest benefit was seen in fatal MIs, and this observation led to the hypothesis that omega-3 fatty acids might protect the myocardium against the adverse sequela of acute ischemic stress. A post hoc analysis of patients receiving fish oil capsules (900 mg/d of EPA+DHA) in DART suggested that the protective effect was attributable to omega-3 fatty acids.42
The first of three recent RCTs designed to detect the effects of supplemental EPA and DHA on clinical events was reported by Singh et al.43 Patients admitted to the hospital with suspected acute MIs were randomized to either fish oil capsules (containing 1.8 g/d of EPA+DHA), mustard oil (20 g/d providing 2.9 g -linolenic acid), or placebo. After one year, total cardiac events were 25% and 28% in the fish oil and mustard oil groups, respectively, versus 35% in the placebo group (P<0.01). As in the DART, nonfatal MIs were significantly lower in the fish oil and mustard oil groups.
The largest prospective RCT to test the efficacy of omega-3 fatty acids for secondary prevention of CHD is the GISSI-Prevention Study.39 In this study, 11 324 patients with preexisting CHD (who were receiving conventional cardiac pharmacotherapy) were randomized to either 300 mg of vitamin E, 850 mg of omega-3 fatty acid ethyl esters (as EPA and DHA), both, or neither. After 3.5 years of follow-up, the group given the omega-3 fatty acids alone experienced a 15% reduction in the primary end point of death, nonfatal MI, and nonfatal stroke (P<0.02). There was a 20% reduction in all-cause mortality (P=0.01) and a 45% reduction in sudden death (P<0.001) compared with the control group; vitamin E provided no additional benefit. Triglycerides decreased by 4% and LDL cholesterol levels increased by 2.5% after six months in the omega-3 fatty acid treatment groups compared with controls. This trial, although very large and carried out in a relatively "usual-care" setting, was not placebo controlled, and dropout rates were high (>25%). A follow-up study44 assessed the time-course of the benefit of omega-3 fatty acids on mortality in subjects in the GISSI Study and found that survival curves diverged early after randomization. Total mortality was significantly lowered after 3 months of treatment (RR=0.59), and by 4 months, risk of sudden death was reduced (RR=0.47).
In contrast to the growing body of evidence supporting a protective effect of omega-3 fatty acids in secondary prevention, a recent study reported no effect of 3.5 g/d of DHA+EPA versus corn oil on cardiac events in post-MI patients (n=300) after 1.5 years of intervention.45 The authors speculated that the lack of an omega-3 fatty acid effect may have been due to the high habitual fish intake in western Norway, which could have afforded maximal protection beyond which no additional effects would be expected. Thus, further research is needed to confirm and further define the role of omega-3 fatty acid supplements for secondary prevention of coronary disease.
The first study to explore the effects of omega-3 fatty acids on angiographic progression rates provided 59 patients either 6 g/d of omega-3 fatty acids or olive oil for 2 years.46 No benefit was observed. More recently, a larger trial using lower and more practical intakes of omega-3 fatty acids has been reported.47 Patients presenting for coronary angiography (n=223) were randomized to either placebo or omega-3 fatty acids (3 g/d for 3 months followed by 1.5 g/d for 21 months). The latter group exhibited significantly (P=0.04) less progression, more regression, and a trend toward fewer clinical events (7 versus 2, P=0.1). Finally, Eritsland et al48 reported that in 610 patients undergoing coronary artery bypass grafting, the provision of 3.4 g of omega-3 fatty acid ethyl esters lowered vein graft occlusion rates from 33% (control) to 27% (P=0.03).
Several randomized trials of fish oil were conducted over the past 10 years to test the hypothesis that omega-3 fatty acids could prevent restenosis after percutaneous transluminal coronary angioplasty. Although a meta-analysis of seven early trials concluded that supplementation was beneficial,49 more recent trials (with large study populations given 5 to 7 g/d of omega-3 fatty acids) have not supported this conclusion.50,51 Most investigators have concluded that further trials are not warranted.
The question of the efficacy of -linolenic acid in CHD prevention has been examined in four trials. The Indian Experiment of Infarct Survival43 discussed above reported a significant decrease in total cardiac events in the group assigned to mustard seed oil. The Lyon Heart Trial was a secondary prevention trial designed to test whether a Mediterranean-type diet (including increased amounts of -linolenic acid) would reduce reoccurrence rates of cardiac events compared with a prudent Western diet.38,52 Marked reductions were seen in cardiac death and nonfatal MI, major secondary end points, and minor events. The difference in intakes of -linolenic acid between groups was 0.5 versus 1.5 g/d. It is impossible, however, to ascribe the benefit unambiguously to -linolenic acid because many other dietary variables were present: Saturated fat and cholesterol decreased and monounsaturated fat increased, as did the consumption of fruits and vegetables.
Although the Indian Experiment of Infarct Survival43 and the Lyon Heart Trial38 provide clinical trial evidence in support of a beneficial effect of -linolenic acid, the Norwegian Vegetable Oil Experiment53 and the Mediterranean Alpha-Linolenic Enriched Groningen Dietary Intervention (MARGARIN) Study54 do not. The Norwegian Vegetable Oil Experiment was a double-blind RCT in which >13 000 men ages 50 to 59 with no history of MI were randomized to consume 5.5 g/d of -linolenic acid (from 10 mL of linseed oil) or 10 mL of sunflower seed oil for one year. There were 27 cases of new CHD or sudden death in each group, and 40 versus 43 deaths from any cause in the control versus the linseed oil groups. In the MARGARIN Study, free-living subjects (n=124 men and 158 women) with multiple CVD risk factors were provided with margarines high in either -linolenic acid or linoleic acid and followed up for 2 years.54 According to effects on CVD risk factors, the 10-year estimated ischemic heart disease risk decreased similarly in both groups (2.1% and 2.5%, respectively). Of note, however, was a trend toward fewer CVD events in the -linolenic acid group (1.8% versus 5.7%, P=0.20). It is important that additional studies be conducted to clarify the role of -linolenic acid in reducing CHD risk.
In aggregate, available RCTs show a beneficial effect of dietary and supplemental omega-3 fatty acids, including both EPA+DHA and -linolenic acid, on CHD. This has been summarized in a recent meta-analysis of 11 RCTs with 7951 patients in the intervention groups.55 In this meta-analysis, the risk ratio of nonfatal MI was 0.8, for fatal MI it was 0.7, and for sudden death (in 5 trials) it was 0.7.
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Possible Mechanisms |
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TopIntroductionEpidemiological and...Randomized Controlled TrialsPossible MechanismsIntake of Omega-3 Fatty...Safety of Omega-3 Fatty...Safety of FishSummaryReferences |
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The mechanisms responsible for the observed effects of omega-3 fatty acids on cardiovascular health are not known with confidence, especially at the low intakes utilized in the DART and GISSI Prevention Study. Those possibly involved are summarized in Table 1.56
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Triglycerides
The hypotriglyceridemic effects of omega-3 fatty acids from fish oils are well established. In a comprehensive review of human studies, Harris57 reported that 4 g/d of omega-3 fatty acids from fish oil decreased serum triglyceride concentrations by 25% to 30%, with accompanying increases in LDL cholesterol of 5% to 10% and in HDL cholesterol of 1% to 3%. A dose-response relationship exists between omega-3 fatty acid intake and triglyceride lowering.57 Postprandial triglyceridemia is especially sensitive to chronic omega-3 fatty acid consumption,58,59 with quite small intakes (<2 g/d) producing significant reductions.60 The plasma lipid and lipoprotein responses to fish oil are comparable in diabetic and nondiabetic subjects.61 In addition, a recent meta-analysis of 26 trials of subjects with type 1 or type 2 diabetes mellitus reported no effects of fish oil on hemoglobin A1c,62 although fasting blood glucose levels rose slightly in the latter group.
Fish oil can have a therapeutic role in the treatment of marked hypertriglyceridemia (>750 mg/dL). Effective doses of omega-3 fatty acids range from 3 to 5 g/d, which can only be obtained consistently by supplementation. At present, it seems that both EPA and DHA have triglyceride-lowering properties.63 Patients taking >3 g of EPA+DHA from supplements should do so only under a physician’s care because the FDA has noted that an intake in excess of this level could result in excessive bleeding in some individuals.64 In contrast, cardioprotective intakes seem to be considerably lower (1 g/d), have almost no potential for adverse effects, and can be achieved by diet.
Blood Pressure
Omega-3 fatty acids seem to have a small, dose-dependent, hypotensive effect, the extent of which seems to be dependent on the degree of hypertension.65 In a meta-analysis, Morris et al66 found a significant reduction in blood pressure of -3.4/-2.0 mm Hg in studies with hypertensive subjects who consumed 5.6 g/d of omega-3 fatty acids. Likewise, Appel et al67 found that blood pressure was decreased -5.5/-3.5 mm Hg in trials of untreated hypertensives given >3 g/d of omega-3 fatty acids. DHA seems to be more effective than EPA in lowering blood pressure.68 Still, in view of the high dose required to lower blood pressure and the proven efficacy of other nutritional factors and of antihypertensive medications, an increased intake of omega-3 fatty acids has a limited role in the management of hypertension.
Thrombosis and Hemostasis
Omega-3 fatty acids decrease platelet aggregation,69,70 resulting in a modest prolongation of bleeding times (reviewed by Knapp71). Some evidence indicates that fish oil supplementation may enhance fibrinolysis.72 Although omega-3 fatty acid intake has been negatively associated with levels of fibrinogen, Factor VIII, and von Willebrand factor,73 more recent evidence from the Coronary Artery Risk Development In young Adults (CARDIA) study found no significant associations between customary intakes of fish (4 to 39 g/d) and omega-3 fatty acids (0.9 to 4.1 g/d) and these coagulation factors.74 Marckmann et al75 also found no effect of omega-3 fatty acids (0.9 g/d) on levels of Factor VII, fibrinogen, endogenous fibrinolysis, ß-thromboglobulin, and von Willebrand factor. In contrast, a recent study reported that coronary patients taking 5.1 g/d of omega-3 fatty acids for 6 months experienced a reduction in von Willebrand factor (128% versus 147% for controls) and thrombomodulin (25 versus 33 ng/mL).76 Although it seems clear that omega-3 fatty acids beneficially influence collagen-induced platelet aggregation (thereby affecting hemostasis), their effects on thrombosis remain unclear. There is little evidence to suggest that an intake <3 g/d of omega-3 fatty acids would cause clinically significant bleeding.
Arrhythmias
The possibility that omega-3 fatty acids (including -linolenic acid) may reduce risk for sudden cardiac death is based on evidence from a prospective cohort study,12 a case-control study,22 and four prospective dietary intervention trials.38,39,41,43 Proposed mechanisms to explain these observations center not on lipid or blood pressure lowering or on antithrombotic effects, but on a novel stabilizing effect of omega-3 fatty acids on the myocardium itself. Evidence for a direct effect of these fatty acids on the heart has come from several observations. First, increased heart rate variability in survivors of MI was associated with the consumption of one fish meal per week77 or fish oil supplements (4.3 g/d of omega-3 fatty acids).78 Increases in this parameter predict a lower risk of mortality due to arrhythmic events in post-MI patients. EPA and DHA also have been shown to reduce resting heart rate and increase left ventricular filling capacity.79 Animal experiments and cell culture studies have shown that fish oil has potent antiarrhythmic effects. For example, studies with rats80 and dogs81,82 have shown that pretreatment with omega-3 fatty acids reduced damage to cardiac tissue and forestalled the development of ventricular dysrhythmias when heart attacks were induced. Similar observations were made in fish oil–fed cats that were protected from cerebral damage after stroke induction.83 In vitro induction of tachyarrhythmias in cultured neonatal rat ventricular myocytes by various pharmacological agents (such as ouabain) can be prevented or abolished by the addition of omega-3 fatty acids to the culture medium (reviewed by Kang and Leaf84). This seems to be due to the ability of omega-3 fatty acids to prevent calcium overload by maintaining the activity of L-type calcium channels during periods of stress,85 and to increase the activity of cardiac microsomal Ca2+/Mg2+-ATPase.79 In addition, omega-3 fatty acids (including -linolenic acid) are potent inhibitors of voltage-gated sodium channels in cultured neonatal cardiac myocytes, which may contribute to the reduction in arrhythmia.84
Other Biological Effects
Goode et al86 showed that acetylcholine-stimulated relaxation of small arteries taken from hypercholesterolemic patients was significantly improved after three months of supplementation with 3 g/d of EPA+DHA. Fish oil feeding has also been shown to improve endothelial function (reviewed by Chin and Dart87) and to increase arterial compliance.88 These effects may be secondary to fish oil’s ability to enhance nitric oxide production89 and may be the mechanism by which fish oil elicits a small hypotensive effect.
Mechanisms to explain the antiatherogenic (inhibition of new plaque development) effect of omega-3 fatty acids have recently been proposed.48 For example, EPA and DHA seem to alter the metabolism of adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and intercellular adhesion molecule-1 (ICAM-1). Abe et al (1998)90 reported a 9% reduction in soluble ICAM-1 and a 16% reduction in soluble E-selectin but not in soluble VCAM-1 in hypertriglyceridemic subjects receiving 3.4 g/d of highly purified omega-3 fatty acid ethyl esters for 7 to 12 months. There is also in vitro evidence that DHA reduces endothelial expression of VCAM-1 and the expression of E-selectin, ICAM-1, interleukin (IL)-6, and IL-8 in stimulated cells.91,92 On the other hand, a study in male smokers with hyperlipidemia showed that six weeks of omega-3 fatty acid supplementation (4.8 g/d) increased soluble forms of E-selectin and VCAM-1.93 A subsequent study in coronary patients given supplemental omega-3 fatty acids (5.1 g/d for 6 months) found similar results.76 Fish oil also affects the metabolism of inflammatory mediators like the interleukins and tumor necrosis factor-,94 molecules also believed to play a role in atherogenesis and plaque stability.95
Another potential antiatherogenic mechanism of omega-3 fatty acids is their interference with the arachidonic acid cascade that generates a wide variety of eicosanoids (reviewed by Uauy et al96). EPA not only can replace arachidonic acid in phospholipid bilayers, but it is also a competitive inhibitor of cyclooxygenase, reducing the production of the 2-series prostaglandins, thromboxanes, and prostacyclins and the 4-series leukotrienes. The 3- and 5-series (respectively) produced from EPA are generally less biologically active. DHA, although not a direct inhibitor of arachidonic acid metabolism, nevertheless can inhibit platelet aggregation by reducing the affinity of platelet TxA2/PGH2 receptor for its ligand.97 The net effects of omega-3 fatty acids are thus to reduce inflammatory processes, vasoconstriction, and platelet aggregation, all known to be antiatherogenic.
Some studies have shown that omega-3 fatty acids may increase the susceptibility of LDL to oxidation,98,99 whereas others have not.100–102 It therefore remains to be established whether LDL oxidative status in vivo is affected by omega-3 fatty acids and, if so, whether this has any adverse clinical implications. Our current inability to identify and quantify in vivo oxidative damage and to relate it to clinical outcomes makes it difficult to draw firm conclusions about the impact of omega-3 fatty acids on these processes.
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Intake of Omega-3 Fatty Acids |
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The intake of total omega-3 fatty acids in the United States is
1.6 g/d (0.7% of energy intake).103 Of this, -linolenic acid accounts for 1.4 g/d, and only 0.1 to 0.2 g/d comes from EPA and DHA. The major food sources of -linolenic acid are vegetable oils, principally canola and soybean oils. Other food sources that are rich in -linolenic acid (Table 2)104 include flaxseed (23 g/100 g) and English walnuts (7 g/100 g). Although some -linolenic acid is converted to the longer-chain omega-3 fatty acids, the extent of this conversion is modest and controversial. For example, Emken et al105 reported a 15% conversion, whereas Pawlosky et al106 found 0.2%; both reported that the conversion to DHA was much less than that to EPA. Fish are the major food source of EPA and DHA (Table 3).104 All fish contain EPA and DHA; however, the quantities vary among species and within a species according to environmental variables such as diet and whether fish are wild or farm-raised. Farm-raised catfish tend to have less EPA and DHA than do wild catfish, whereas farm-raised salmon and trout contain similar amounts versus their wild counterparts.
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A number of countries (Canada, Sweden, United Kingdom, Australia, Japan) as well as the World Health Organization and North Atlantic Treaty Organisation have made formal population-based dietary recommendations for omega-3 fatty acids. Typical recommendations are 0.3 to 0.5 g/d of EPA+DHA and 0.8 to 1.1 g/d of -linolenic acid. Recently, the Food and Nutrition Board, Institute of Medicine, and The National Academies, in collaboration with Health Canada, released the Dietary Reference Intakes for Energy and Macronutrients.107 The Acceptable Macronutrient Distribution Range (AMDR) for -linolenic acid is estimated to be 0.6% to 1.2% of energy, or 1.3 to 2.7 g/d on the basis of a 2000-calorie diet. This is 10 times the current intake of EPA+DHA. The lower boundary of the range is based on an Adequate Intake set for -linolenic acid, which represents median intake levels that prevent an essential fatty acid deficiency. The upper boundary corresponds to the highest -linolenic acid intakes from foods consumed by individuals in the United States and Canada. Thus, the intent of the AMDR range for omega-3 fatty acids is to provide guidance for healthy people, not to prevent chronic disease. These recommendations can easily be met by following the AHA Dietary Guidelines to consume two fish meals per week, with an emphasis on fatty fish (ie, salmon, herring, and mackerel), and by using liquid vegetable oils containing -linolenic acid. Commercially prepared fried fish (eg, from restaurants and fast food establishments, as well as many frozen, convenience-type fried fish products) should be avoided because they are low in omega-3 and high in trans-fatty acids.
Patients with CHD should be encouraged to increase their consumption of EPA and DHA to 1 g/d, which is the dose used in the GISSI-Prevention Study. Table 3 presents omega-3 fatty acid content of various fish and supplements as well as the amount required each day to provide 1 g/d of EPA+DHA. Although this level of EPA and DHA intake potentially can be attained through fish consumption, the requisite amount of fish intake may be difficult to achieve and sustain over the long term. For those individuals who do not eat fish, have limited access to a variety of fish, or cannot afford to purchase fish, a fish oil supplement may be considered. Depending on the preparation, up to three 1-g fish oil capsules per day will be necessary to provide 1 g/d of omega-3 fatty acids. The most common fish oil capsules in the United States today provide 180 mg of EPA and 120 mg DHA per capsule. It is important that consumers read the nutrition label to determine EPA and DHA levels in the fish oil capsule.
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Safety of Omega-3 Fatty Acids |
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Omega-3 fatty acids have been a part of the human diet for millennia. It has been estimated that the ratio of omega-6 to omega-3 fatty acids in the diet of early humans was 1:1.108 The ratio in the United States today has risen to
10:1 because of the combination of reduced omega-3 fatty acid intake and the widespread use of vegetable oils rich in linoleic acid.103 Because of the well-known competition between the omega-6 linoleate and the omega-3 -linolenate for metabolic conversion to longer-chain, physiologically active metabolites, reducing the former while increasing the latter (or simply increasing the latter) is a strategy for increasing tissue levels of omega-3 fatty acids.109 Another obvious strategy is to simply consume more EPA and DHA, an approach that minimizes the significance of the ratio. Since the first omega-3 fatty acid advisory,1 the FDA has ruled that intakes of up to 3 g/d of marine omega-3 fatty acids are GRAS (Generally Recognized As Safe) for inclusion in the diet.110 This ruling included specific consideration of the reported effects of omega-3 fatty acids on glycemic control in patients with diabetes, on bleeding tendencies, and on LDL cholesterol. Moreover, the FDA recently has approved a qualified health claim for EPA and DHA omega-3 fatty acids in dietary supplements.64
Although the safety of low intakes does not seem to be an issue, and supplements are essentially mercury free, some side effects of omega-3 fatty acid supplementation do occur (Table 4).111 Perhaps the most common is a fishy aftertaste. In the GISSI Prevention study, which provided 0.85 g of omega-3 fatty acids per day for 3.5 years, 3.8% of patients discontinued taking their supplements (compared with 2.1% for the vitamin E group). Gastrointestinal disturbances and nausea were the most commonly reported side effects, with 4.9% and 1.4% reported, respectively, compared with 2.9% and 0.4% in the vitamin E group. When 12 capsules containing 6 g of omega-3 fatty acids were fed to 41 patients for 2.4 years, three patients dropped from the study claiming intolerance to the capsules.46 In a 6-month trial providing 275 patients with 6.9 g of EPA+DHA in 10 capsules daily, there was no difference between the fish oil and corn oil control groups for any adverse event.112 Gastrointestinal upset was reported by 8% of the latter and 7% of the former. Finally, although refined and concentrated omega-3 fatty acid products contain virtually no methylmercury and are very low in organochloride contaminants,113 less well-controlled preparations can contain appreciable amounts.114
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Safety of Fish |
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TopIntroductionEpidemiological and...Randomized Controlled TrialsPossible MechanismsIntake of Omega-3 Fatty...Safety of Omega-3 Fatty...Safety of FishSummaryReferences |
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Some species of fish may contain significant levels of methylmercury, polychlorinated biphenyls (PCBs), dioxins, and other environmental contaminants. These substances are present at low levels in fresh waters and oceans, and they bioconcentrate in the aquatic food chain such that levels are generally highest in older, larger, predatory fish and marine mammals.
Fish and seafood are a major source of human exposure to these contaminants. PCBs and methylmercury have long half-lives in the body and can accumulate in people who consume contaminated fish on a frequent basis. Consumers can reduce their exposure to PCBs by removing the skin and fat from these fish before cooking them; however, because methylmercury is distributed throughout the muscle, skinning and trimming does not significantly reduce mercury concentrations in filets.
The responsibility for regulating the quality of the fish for human consumption is shared by the states and two federal agencies. The Environmental Protection Agency regulates sport-caught fish, whereas the FDA regulates all commercial fish—including farm-raised, imported, and marine fish. The Environmental Protection Agency’s 2000 National Listing of Fish and Wildlife Advisories may be found on the Environmental Protection Agency web site.115 The Environmental Protection Agency advises women who are pregnant or may become pregnant and nursing mothers to limit their consumption of sport-caught fish to one 6-ounce meal per week.116 The Environmental Protection Agency also recommends that young children consume 
2 ounces of sport-caught fish per week. The FDA recommends that women who are pregnant or nursing and young children eliminate shark, swordfish, king mackerel in the mackerel family, and tilefish (also referred to as golden bass or golden snapper) from their diets completely and limit their consumption of other fish to 12 ounces per week (3 to 4 servings/wk) to minimize exposure to methylmercury.117 The FDA has concluded that persons other than pregnant women and women who may become pregnant can consume up to 7 ounces per week of fish with methylmercury levels around 1 ppm (eg, shark, swordfish, king mackerel, tilefish) and 14 ounces per week of fish with mercury levels averaging 0.5 ppm (eg, fresh tuna, orange roughy, marlin, red snapper).118 In July 2002, an FDA Scientific Committee advised the FDA to conduct a more detailed analysis of the contribution of methylmercury from tuna (with emphasis on large tuna consumed as steaks rather than canned tuna) to total methylmercury levels in women and children. Although more data are needed, information currently available about the methylmercury content of selected fish can be found on the FDA web site.119
In summary, consumers need to be aware of both the benefits and risks of fish consumption for their particular stage of life. Children and pregnant and lactating women may be at increased risk for mercury intoxication from fish consumption but also are at low risk for CHD. Thus, avoidance of potentially contaminated fish is a higher priority for this group. For middle-aged and older men and postmenopausal women, the benefits of fish consumption far outweigh the risks within the guidelines established by the FDA and Environmental Protection Agency. Consumption of a wide variety of species within the guidelines is the best approach to both minimizing mercury exposure and increasing omega-3 fatty acid intake.
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Summary |
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TopIntroductionEpidemiological and...Randomized Controlled TrialsPossible MechanismsIntake of Omega-3 Fatty...Safety of Omega-3 Fatty...Safety of FishSummaryReferences |
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Omega-3 fatty acids have been shown in epidemiological and clinical trials to reduce the incidence of CVD. Large-scale epidemiological studies suggest that individuals at risk for CHD benefit from the consumption of plant- and marine-derived omega-3 fatty acids, although the ideal intakes presently are unclear. Evidence from prospective secondary prevention studies suggests that EPA+DHA supplementation ranging from 0.5 to 1.8 g/d (either as fatty fish or supplements) significantly reduces subsequent cardiac and all-cause mortality. For
-linolenic acid, total intakes of 1.5 to 3 g/d seem to be beneficial.
Collectively, these data are supportive of the recommendation made by the AHA Dietary Guidelines to include at least two servings of fish per week (particularly fatty fish). In addition, the data support inclusion of vegetable oils (eg, soybean, canola, walnut, flaxseed) and food sources (eg, walnuts, flaxseeds) high in -linolenic acid in a healthy diet for the general population (Table 5). The fish recommendation must be balanced with concerns about environmental pollutants, in particular PCB and methylmercury, described in state and federal advisories. Consumption of a variety of fish is recommended to minimize any potentially adverse effects due to environmental pollutants and, at the same time, achieve desired CVD health outcomes.
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RCTs have demonstrated that omega-3 fatty acid supplements can reduce cardiac events (eg, death, nonfatal MI, nonfatal stroke) and decrease progression of atherosclerosis in coronary patients. However, additional studies are needed to confirm and further define the health benefits of omega-3 fatty acid supplements for both primary and secondary prevention. For example, placebo-controlled, double-blind RCTs are needed to document both the safety and efficacy of omega-3 fatty acid supplements in both high-risk patients (eg, patients with type 2 diabetes, dyslipidemia, and hypertension, and smokers) and coronary patients on drug therapy. Mechanistic studies on their apparent effects on sudden death are also needed.
A dietary (ie, food-based) approach to increasing omega-3 fatty acid intake is preferable. Still, for patients with coronary artery disease, the dose of omega-3 (1 g/d) may be greater than what can readily be achieved through diet alone (Table 5). These individuals, in consultation with their physician, could consider supplements for CHD risk reduction. Supplements also could be a component of the medical management of hypertriglyceridemia, a setting in which even larger doses (2 to 4 g/d) are required (Table 5). The availability of high-quality omega-3 fatty acid supplements, free of contaminants, is an important prerequisite to their extensive use.
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Acknowledgments |
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The authors thank Drs Lynda Knobeloch, Neil Stone, Robert Eckel, Frank Hu, Margo Denke, Diane Tribble, Henry Ginsberg, Michael Lefevre, Sheila Innis, and Thomas Pearson for reviewing this manuscript.
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Footnotes |
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The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.
This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on May 28, 2002.
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References |
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TopIntroductionEpidemiological and...Randomized Controlled TrialsPossible MechanismsIntake of Omega-3 Fatty...Safety of Omega-3 Fatty...Safety of FishSummaryReferences |
|---|
1. Stone NJ. Fish consumption, fish oil, lipids, and coronary heart disease. Circulation. 1996; 94: 2337–2340.
2. Krauss RM, Eckel RH, Howard B, et al. AHA Dietary Guidelines: revision 2000: a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation. 2000; 102: 2284–2299.
3. 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]
4. 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.
5. Shekelle RB, Missell L, Paul O, et al. Fish consumption and mortality from coronary heart disease. N Engl J Med. 1985; 313: 820.Letter.[Medline] [Order article via Infotrieve]
6. 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.[Medline] [Order article via Infotrieve]
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.
8. Zhang J, Sasaki S, Amano K, et al. Fish consumption and mortality from all causes, ischemic heart disease, and stroke: an ecological study. Prev Med. 1999; 28: 520–529.[CrossRef][Medline] [Order article via Infotrieve]
9. Mizushima S, Moriguchi EH, Ishikawa P, et al. Fish intake and cardiovascular risk among middle-aged Japanese in Japan and Brazil. J Cardiovasc Risk. 1997; 4: 191–199.[CrossRef][Medline] [Order article via Infotrieve]
10. 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.
11. Ascherio A, Rimm EB, Stampfer MJ, et al. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med. 1995; 332: 977–982.
12. Albert CM, Hennekens CH, O’Donnell CJ, et al. Fish consumption and risk of sudden cardiac death. JAMA. 1998; 279: 23–28.
13. Kromhout D, Bloemberg BP, Feskens EJ, et al. Alcohol, fish, fibre and antioxidant vitamins intake do not explain population differences in coronary heart disease mortality. Int J Epidemiol. 1996; 25: 753–759.
14. Guallar E, Aro A, Jimenez FJ, et al. Omega-3 fatty acids in adipose tissue and risk of myocardial infarction: the EURAMIC study. Arterioscler Thromb Vasc Biol. 1999; 19: 1111–1118.
15. Kromhout D. Fish consumption and sudden cardiac death. JAMA. 1998; 279: 65–66.
16. Sheard NF. Fish consumption and risk of sudden cardiac death. Nutr Rev. 1998; 56: 177–179.[Medline] [Order article via Infotrieve]
17. Marckmann P, Grønbæk M. Fish consumption and coronary heart disease mortality: a systematic review of prospective cohort studies. Eur J Clin Nutr. 1999; 53: 585–590.[CrossRef][Medline] [Order article via Infotrieve]
18. 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.
19. Rissanen T, Voutilainen S, Nyyssonen K, et al. 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.
20. Salonen JT, Seppanen K, Lakka TA, et al. Mercury accumulation and accelerated progression of carotid atherosclerosis: a population-based prospective 4-year follow-up study in men in eastern Finland. Atherosclerosis. 2000; 148: 265–273.[CrossRef][Medline] [Order article via Infotrieve]
21. Ahlqwist M, Bengtsson C, Lapidus L, et al. 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.[CrossRef][Medline] [Order article via Infotrieve]
22. 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.
23. 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.
24. Landmark K, Abdelnoor M, Kilhovd B, et al. Eating fish may reduce infarct size and the occurrence of Q wave infarcts. Eur J Clin Nutr. 1998; 52: 40–44.[CrossRef][Medline] [Order article via Infotrieve]
25. Landmark K, Abdelnoor M, Urdal P, et al. Use of fish oils appears to reduce infarct size as estimated from peak creatine kinase and lactate dehydrogenase activities. Cardiology. 1998; 89: 94–102.[CrossRef][Medline] [Order article via Infotrieve]
26. Pietinen P, Ascherio A, Korhonen P, et al. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Epidemiol. 1997; 145: 876–887.
27. 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.
28. Ascherio A, Rimm EB, Giovannucci EL, et al. Dietary fat and risk of coronary heart disease in men: cohort follow up study in the United States. BMJ. 1996; 313: 84–90.
29. Djousse L, Pankow JS, Eckfeldt JH, et al. Relation between dietary linolenic acid and coronary artery disease in the National Heart, Lung, and Blood Institute Family Heart Study. Am J Clin Nutr. 2001; 74: 612–619.
30. Oomen CM, Ocke MC, Feskens EJ, et al. alpha-Linolenic acid intake is not beneficially associated with 10-y risk of coronary artery disease incidence: the Zutphen Elderly Study. Am J Clin Nutr. 2001; 74: 457–463.
31. Visioli F, Galli C. Alpha-linolenic acid and cardiovascular disease. Am J Clin Nutr. 2002; 75: 1121.Letter.
32. Keli SO, Feskens EJ, Kromhout D. Fish consumption and risk of stroke: the Zutphen Study. Stroke. 1994; 25: 328–332.[Abstract]
33. Gillum RF, Mussolino ME, Madans JH. The relationship between fish consumption and stroke incidence: the NHANES I Epidemiologic Follow-up Study (National Health and Nutrition Examination Survey). Arch Intern Med. 1996; 156: 537–542.
34. Iso H, Rexrode KM, Stampfer MJ, et al. Intake of fish and omega-3 fatty acids and risk of stroke in women. JAMA. 2001; 285: 304–312.
35. Orencia AJ, Daviglus ML, Dyer AR, et al. Fish consumption and stroke in men: 30-year findings of the Chicago Western Electric Study. Stroke. 1996; 27: 204–209.
36. Morris MC, Manson JE, Rosner B, et al. Fish consumption and cardiovascular disease in the Physicians’ Health Study: a prospective study. Am J Epidemiol. 1995; 142: 166–175.
37. Simon JA, Fong J, Bernert JT Jr, et al. Serum fatty acids and the risk of stroke. Stroke. 1995; 26: 778–782.
38. de Lorgeril M, Salen P, Martin JL, et al. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation. 1999; 99: 779–785.
39. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999; 354: 447–455.[CrossRef][Medline] [Order article via Infotrieve]
40. Kromann N, Green A. Epidemiological studies in the Upernavik District, Greenland. Acta Med Scand. 1980; 208: 401–406.[Medline] [Order article via Infotrieve]
41. 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.[Medline] [Order article via Infotrieve]
42. Burr ML, Sweetham PM, Fehily AM. Diet and reinfarction. Eur Heart J. 1994; 15: 1152–1153.
43. Singh RB, Niaz MA, Sharma JP, et al. 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.[CrossRef][Medline] [Order article via Infotrieve]
44. Marchioli R, Barzi F, Bomba E, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation. 2002; 105: 1897–1903.
45. Nilsen DW, Albrektsen G, Landmark K, et al. 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.
46. Sacks FM, Stone PH, Gibson CM, et al. Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. J Am Coll Cardiol. 1995; 25: 1492–1498.[Abstract]
47. von Schacky C, Angerer P, Kothny W, et al. 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.
48. Eritsland J, Arnesen H, Gronseth K, et al. Effect of dietary supplementation with n-3 fatty acids on coronary artery bypass graft patency. Am J Cardiol. 1996; 77: 31–36.[CrossRef][Medline] [Order article via Infotrieve]
49. Gapinski JP, VanRuiswyk JV, Heudebert GR, et al. Preventing restenosis with fish oils following coronary angioplasty: a meta-analysis. Arch Intern Med. 1993; 153: 1595–1601.
50. Cairns JA, Gill J, Morton B, et al. Fish oils and low-molecular-weight heparin for the reduction of restenosis after percutaneous transluminal coronary angioplasty. The EMPAR Study. Circulation. 1996; 94: 1553–1560.
51. Johansen O, Brekke M, Seljeflot I, et al. N-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study. Coronary Angioplasty Restenosis Trial. J Am Coll Cardiol. 1999; 33: 1619–1626.
52. de Lorgeril M, Renaud S, Mamelle N, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet. 1994; 343: 1454–1459.[CrossRef][Medline] [Order article via Infotrieve]
53. Natvig H, Borchgrevink CF, Dedichen J, et al. A controlled trial of the effect of linolenic acid on the incidence of coronary heart disease. Scand J Clin Lab Med. 1968; 105 (suppl): 1–20.
54. Bemelmans WJ, Broer J, Feskens EJ, et al. Effect of an increased intake of alpha-linolenic acid and group nutritional education on cardiovascular risk factors: the Mediterranean Alpha-linolenic Enriched Groningen Dietary Intervention (MARGARIN) study. Am J Clin Nutr. 2002; 75: 221–227.
55. Bucher HC, Hengstler P, Schindler C, et al. N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med. 2002; 112: 298–304.[CrossRef][Medline] [Order article via Infotrieve]
56. Connor WE. Importance of n-3 fatty acids in health and disease. Am J Clin Nutr. 2000; 71 (1 Suppl): 171S–175S.
57. Harris WS. n-3 Fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997; 65 (5 Suppl): 1645S–1654S.
58. Sanders TA, Oakley FR, Miller GJ, et al. Influence of n-6 versus n-3 polyunsaturated fatty acids in diets low in saturated fatty acids on plasma lipoproteins and hemostatic factors. Arterioscler Thromb Vasc Biol. 1997; 17: 3449–3460.
59. Harris WS, Connor WE, Alam N, et al. Reduction of postprandial triglyceridemia in humans by dietary n-3 fatty acids. J Lipid Res. 1988; 29: 1451–1460.[Abstract]
60. Roche HM, Gibney MJ. Postprandial triacylglycerolaemia: the effect of low-fat dietary treatment with and without fish oil supplementation. Eur J Clin Nutr. 1996; 50: 617–624.[Medline] [Order article via Infotrieve]
61. Montori VM, Farmer A, Wollan PC, et al. Fish oil supplementation in type 2 diabetes: a quantitative systematic review. Diabetes Care. 2000; 23: 1407–1415.
62. Friedberg CE, Janssen MJ, Heine RJ, et al. Fish oil and glycemic control in diabetes: a meta-analysis. Diabetes Care. 1998; 21: 494–500.[Abstract]
63. Grimsgaard S, Bonaa KH, Hansen JB, et al. Highly purified eicosapentaenoic acid and docosahexaenoic acid in humans have similar triacylglycerol-lowering effects but divergent effects on serum fatty acids. Am J Clin Nutr. 1997; 66: 649–659.
64. Office of Nutritional Products, Labeling, and Dietary Supplements, Center for Food Safety and Applied Nutrition, US Food and Drug Administration. Letter responding to a request to reconsider the qualified claim for a dietary supplement health claim for omega-3 fatty acids and coronary heart disease. Docket No. 91N-0103. February 8, 2002. Available at: http://www.cfsan.fda.gov/~dms/ds-ltr28.html. Accessed October 3, 2002.
65. Howe PR. Dietary fats and hypertension: focus on fish oil. Ann N Y Acad Sci. 1997; 827: 339–352.[Medline] [Order article via Infotrieve]
66. Morris MC, Sacks F, Rosner B. Does fish oil lower blood pressure? A meta-analysis of controlled trials. Circulation. 1993; 88: 523–533.
67. Appel LJ, Miller ER3rd, Seidler AJ, et al. Does supplementation of diet with ‘fish oil’ reduce blood pressure? A meta-analysis of controlled clinical trials. Arch Intern Med. 1993; 153: 1429–1438.
68. Mori TA, Watts GF, Burke V, et al. Differential effects of eicosapentaenoic acid and docosahexaenoic acid on vascular reactivity of the forearm microcirculation in hyperlipidemic, overweight men. Circulation. 2000; 102: 1264–1269.
69. Agren JJ, Vaisanen S, Hanninen O, et al. Hemostatic factors and platelet aggregation after a fish-enriched diet or fish oil or docosahexaenoic acid supplementation. Prostaglandins Leukot Essent Fatty Acids. 1997; 57: 419–421.[CrossRef][Medline] [Order article via Infotrieve]
70. Mori TA, Beilin LJ, Burke V, et al. Interactions between dietary fat, fish, and fish oils and their effects on platelet function in men at risk of cardiovascular disease. Arterioscler Thromb Vasc Biol. 1997; 17: 279–286.
71. Knapp HR. Dietary fatty acids in human thrombosis and hemostasis. Am J Clin Nutr. 1997; 65 (5 Suppl): 1687S–1698S.[Medline] [Order article via Infotrieve]
72. Barcelli U, Glas-Greenwalt P, Pollak VE. Enhancing effect of dietary supplementation with omega-3 fatty acids on plasma fibrinolysis in normal subjects. Thromb Res. 1985; 39: 307–312.[CrossRef][Medline] [Order article via Infotrieve]
73. Shahar E, Folsom AR, Wu KK, et al. Associations of fish intake and dietary n-3 polyunsaturated fatty acids with a hypocoagulable profile. The Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb. 1993; 13: 1205–1212.
74. Archer SL, Green D, Chamberlain M, et al. Association of dietary fish and n-3 fatty acid intake with hemostatic factors in the coronary artery risk development in young adults (CARDIA) study. Arterioscler Thromb Vasc Biol. 1998; 18: 1119–1123.
75. Marckmann P, Bladbjerg EM, Jespersen J. Dietary fish oil (4 g daily) and cardiovascular risk markers in healthy men. Arterioscler Thromb Vasc Biol. 1997; 17: 3384–3391.
76. Johansen O, Seljeflot I, Hostmark AT, et al. The effect of supplementation with omega-3 fatty acids on soluble markers of endothelial function in patients with coronary heart disease. Arterioscler Thromb Vas Biol. 1999; 19: 1681–1686.
77. Christensen JH, Korup E, Aaroe J, et al. Fish consumption, n-3 fatty acids in cell membranes, and heart rate variability in survivors of myocardial infarction with left ventricular dysfunction. Am J Cardiol. 1997; 79: 1670–1673.[CrossRef][Medline] [Order article via Infotrieve]
78. Christensen JH, Gustenhoff P, Korup E, et al. Effect of fish oil on heart rate variability in survivors of myocardial infarction: a double blind randomised controlled trial. BMJ. 1996; 312: 677–678.
79. Grimsgaard S, Bonaa KH, Hansen JB, et al. Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on hemodynamics in humans. Am J Clin Nutr. 1998; 68: 52–59.[Abstract]
80. Pepe S, McLennan PL. Dietary fish oil confers direct antiarrhythmic properties on the myocardium of rats. J Nutr. 1996; 126: 34–42.
81. Kinoshita I, Itoh K, Nishida-Nakai M, et al. Antiarrhythmic effects of eicosapentaenoic acid during myocardial infarction–enhanced cardiac microsomal (Ca2+-Mg2+)-ATPase activity. Japan Circ J. 1994; 58: 903–912.[Medline] [Order article via Infotrieve]
82. Billman GE, Kang JX, Leaf A. Prevention of ischemia-induced cardiac sudden death by n-3 polyunsaturated fatty acids in dogs. Lipids. 1997; 32: 1161–1168.[Medline] [Order article via Infotrieve]
83. Black KL, Culp B, Madison D, et al. The protective effects of dietary fish oil on focal cerebral infarction. Prostaglandins Med. 1979; 3: 257–268.[CrossRef][Medline] [Order article via Infotrieve]
84. Kang JX, Leaf A. Antiarrhythmic effects of polyunsaturated fatty acids: recent studies. Circulation. 1996; 94: 1774–1780.
85. Hallaq H, Smith TW, Leaf A. Modulation of dihydropyridine-sensitive calcium channels in heart cells by fish oil fatty acids. Proc Natl Acad Sci U S A. 1992; 89: 1760–1764.
86. Goode GK, Garcia S, Heagerty AM. Dietary supplementation with marine fish oil improves in vitro small artery endothelial function in hypercholesterolemic patients: a double-blind placebo-controlled study. Circulation. 1997; 96: 2802–2807.
87. Chin JP, Dart AM. How do fish oils affect vascular function? Clin Exp Pharmacol Physiol. 1995; 22: 71–81.[Medline] [Order article via Infotrieve]
88. McVeigh GE, Brennan GM, Cohn JN, et al. Fish oil improves arterial compliance in non-insulin-dependent diabetes mellitus. Arterioscler Thromb. 1994; 14: 1425–1429.
89. Harris WS, Rambjor GS, Windsor SL, et al. N-3 fatty acids and urinary excretion of nitric oxide metabolites in humans. Am J Clin Nutr. 1997; 65: 459–464.
90. Abe Y, El-Masri B, Kimball KT, et al. Soluble cell adhesion molecules in hypertriglyceridemia and potential significance on monocyte adhesion. Arterioscler Thromb Vasc Biol. 1998; 18: 723–731.
91. De Caterina R, Libby P. Control of endothelial leukocyte adhesion molecules by fatty acids. Lipids. 1996; 31: S57–S63.[CrossRef][Medline] [Order article via Infotrieve]
92. De Caterina R, Liao JK, Libby P. Fatty acid modulation of endothelial activation. Am J Clin Nutr. 2000; 71 (1 Suppl): 213S–223S.
93. Seljeflot I, Arnesen H, Brude IR, et al. Effects of omega-3 fatty acids and/or antioxidants on endothelial cell markers. Eur J Clin Invest. 1998; 28: 629–635.[CrossRef][Medline] [Order article via Infotrieve]
94. Endres S, von Schacky C. n-3 polyunsaturated fatty acids and human cytokine synthesis. Curr Opin Lipidol. 1996; 7: 48–52.[Medline] [Order article via Infotrieve]
95. Lee RT, Libby P. The unstable atheroma. Arterioscler Thromb Vasc Biol. 1997; 17: 1859–1867.
96. Uauy R, Mena P, Valenzuela A. Essential fatty acids as determinants of lipid requirements in infants, children and adults. Eur J Clin Nutr. 1999; 53 (Suppl 1): S66–S77.[CrossRef][Medline] [Order article via Infotrieve]
97. Bayon Y, Croset M, Daveloose D, et al. Effect of specific phospholipid molecular species incorporated in human platelet membranes on thromboxane A2/prostaglandin H2 receptors. J Lipid Res. 1995; 36: 47–56.[Abstract]
98. Hau MF, Smelt AH, Bindels AJ, et al. Effects of fish oil on oxidation resistance of VLDL in hypertriglyceridemic patients. Arterioscler Thromb Vasc Biol. 1996; 16: 1197–1202.
99. Sorensen NS, Marckmann P, Hoy CE, et al. Effect of fish-oil-enriched margarine on plasma lipids, low-density-lipoprotein particle composition, size, and susceptibility to oxidation. Am J Clin Nutr. 1998; 68: 235–241.[Abstract]
100. Brude IR, Drevon CA, Hjermann I, et al. Peroxidation of LDL from combined-hyperlipidemic male smokers supplied with omega-3 fatty acids and antioxidants. Arterio Thromb Vasc Biol. 1997; 17: 2576–2588.
101. Bonanome A, Biasia F, De Luca M, et al. n-3 fatty acids do not enhance LDL susceptibility to oxidation in hypertriacylglycerolemic hemodialyzed subjects. Am J Clin Nutr. 1996; 63: 261–266.
102. Higdon JV, Du SH, Lee YS, et al. Supplementation of postmenopausal women with fish oil does not increase overall oxidation of LDL ex vivo compared to dietary oils rich in oleate and linoleate. J Lipid Res. 2001; 42: 407–418.
103. 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 (1 Suppl): 179S–188S.
104. USDA Nutrient Data Laboratory. Available at: http://www.nalusda.gov/fnic/foodcomp./ Accessed October 3, 2002.
105. Emken EA, Adlof RO, Gulley RM. Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. Biochim Biophys Acta. 1994; 1213: 277–288.[Medline] [Order article via Infotrieve]
106. Pawlosky RJ, Hibbeln JR, Novotny JA, et al. Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. J Lipid Res. 2001; 42: 1257–1265.
107. Institute of Medicine (IOM). Dietary Reference Intakes for Energy and Macronutrients. Washington, DC: National Academy Press; 2002.
108. Simopoulos AP. Evolutionary aspects of omega-3 fatty acids in the food supply. Prostaglandins Leukot Essent Fatty Acids. 1999; 60: 421–429.[CrossRef][Medline] [Order article via Infotrieve]
109. Lands WE. Biochemistry and physiology of n-3 fatty acids. FASEB J. 1992; 6: 2530–2536.[Abstract]
110. Department of Health and Human Services, US Food and Drug Administration. Substances affirmed as generally recognized as safe: menhaden oil. Federal Register. June 5, 1997. Vol. 62, No. 108: pp 30751–30757. 21 CFR Part 184 [Docket No. 86G-0289]. Available at: http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=1997_register&docid=fr05jn97-5. Accessed October 3, 2002.
111. Harris WS, Ginsberg HN, Arunakul N, et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk. 1997; 4: 385–391.[CrossRef][Medline] [Order article via Infotrieve]
112. Leaf A, Jorgensen MB, Jacobs AK, et al. Do fish oils prevent restenosis after coronary angioplasty? Circulation. 1994; 90: 2248–2257.
113. Hilbert G, Lillemark L, Balchen S, et al. Reduction of organochlorine contaminants from fish oil during refining. Chemosphere. 1998; 37: 1241–1252.[Medline] [Order article via Infotrieve]
114. Jacobs MN, Santillo D, Johnston PA, et al. Organochlorine residues in fish oil dietary supplements: comparison with industrial grade oils. Chemosphere. 1998; 37: 1709–1721.[Medline] [Order article via Infotrieve]
115. US Environmental Protection Agency. Fish Advisories web page. Available at: http://www.epa.gov/waterscience/fish./ Accessed October 3, 2002.
116. Office of Water, US Environmental Protection Agency. Consumption Advice Fact Sheet. National advice on mercury in fish caught by family and friends: for women who are pregnant or may become pregnant, nursing mothers, and young children. January 2001. EPA-823-F-01-004. Available at: http://www.epa.gov/waterscience/fishadvice/factsheet.html. Accessed October 7, 2002.
117. Center for Food Safety and Applied Nutrition, US Food and Drug Administration. Consumer advisory: an important message for pregnant women and women of childbearing age who may become pregnant about the risks of mercury in fish. March 2001. Available at: http://www.cfsan.fda.gov/~dms/admehg.html. Accessed October 7, 2002.
118. US Food and Drug Administration. Mercury in fish: cause for concern? FDA Consumer. 1994;28(September). Revised May 1995. Available at: http://www.fda.gov/fdac/reprints/mercury.html. Accessed October 7, 2002.
119. US Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Seafood. Mercury Levels in Seafood Species. May 2001. Available at: http://www.cfsan.fda.gov/~frf/sea-mehg.html. Accessed October 3, 2002.
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|
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|
|
|
|
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|
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|
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|
|
|
|
|
|
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|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 I. Romieu, F. Castro-Giner, N. Kunzli, and J. Sunyer Air pollution, oxidative stress and dietary supplementation: a review Eur. Respir. J., January 1, 2008; 31(1): 179 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 American Diabetes Association Nutrition Recommendations and Interventions for Diabetes: A position statement of the American Diabetes Association Diabetes Care, January 1, 2008; 31(Supplement_1): S61 - S78. [Full Text] [PDF]
|
|
|
|
|
|
W. S Harris, J. V Pottala, S. A Sands, and P. G Jones Comparison of the effects of fish and fish-oil capsules on the n 3 fatty acid content of blood cells and plasma phospholipids Am. J. Clinical Nutrition, December 1, 2007; 86(6): 1621 - 1625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Saifullah, B. A. Watkins, C. Saha, Y. Li, S. M. Moe, and A. N. Friedman Oral fish oil supplementation raises blood omega-3 levels and lowers C-reactive protein in haemodialysis patients a pilot study Nephrol. Dial. Transplant., December 1, 2007; 22(12): 3561 - 3567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Barberger-Gateau, C. Raffaitin, L. Letenneur, C. Berr, C. Tzourio, J. F. Dartigues, and A. Alperovitch Dietary patterns and risk of dementia: The Three-City cohort study Neurology, November 13, 2007; 69(20): 1921 - 1930. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ghosh, E. M. Novak, and S. M. Innis Cardiac proinflammatory pathways are altered with different dietary n-6 linoleic to n-3 {alpha}-linolenic acid ratios in normal, fat-fed pigs Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2919 - H2927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
B. London, C. Albert, M. E. Anderson, W. R. Giles, D. R. Van Wagoner, E. Balk, G. E. Billman, M. Chung, W. Lands, A. Leaf, et al. Omega-3 Fatty Acids and Cardiac Arrhythmias: Prior Studies and Recommendations for Future Research: A Report from the National Heart, Lung, and Blood Institute and Office of Dietary Supplements Omega-3 Fatty Acids and Their Role in Cardiac Arrhythmogenesis Workshop Circulation, September 4, 2007; 116(10): e320 - e335. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Itoh, T. Suganami, N. Satoh, K. Tanimoto-Koyama, X. Yuan, M. Tanaka, H. Kawano, T. Yano, S. Aoe, M. Takeya, et al. Increased Adiponectin Secretion by Highly Purified Eicosapentaenoic Acid in Rodent Models of Obesity and Human Obese Subjects Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 1918 - 1925. [Abstract] [Full Text] [PDF]
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|
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|
|
|
|
 |
|
 M. F. Muldoon, R. H. Mackey, K. Sutton-Tyrrell, J. D. Flory, B. G. Pollock, and S. B. Manuck Lower Central Serotonergic Responsivity Is Associated With Preclinical Carotid Artery Atherosclerosis Stroke, August 1, 2007; 38(8): 2228 - 2233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Burns, D. W. Dockery, L. M. Neas, J. Schwartz, B. A. Coull, M. Raizenne, and F. E. Speizer Low Dietary Nutrient Intakes and Respiratory Health in Adolescents Chest, July 1, 2007; 132(1): 238 - 245. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 N. Szentandrassy, M. R. Perez-Bido, E. Alonzo, N. Negretti, and S. C. O'Neill Protein kinase A is activated by the n-3 polyunsaturated fatty acid eicosapentaenoic acid in rat ventricular muscle J. Physiol., July 1, 2007; 582(1): 349 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M Malinowski and K. Metka Elevation of Low-Density Lipoprotein Cholesterol Concentration with Over-the-Counter Fish Oil Supplementation Ann. Pharmacother., July 1, 2007; 41(7): 1296 - 1300. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Chrysohoou, D. B Panagiotakos, C. Pitsavos, J. Skoumas, X. Krinos, Y. Chloptsios, V. Nikolaou, and C. Stefanadis Long-term fish consumption is associated with protection against arrhythmia in healthy persons in a Mediterranean region--the ATTICA study Am. J. Clinical Nutrition, May 1, 2007; 85(5): 1385 - 1391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. van Gelder, M. Tijhuis, S. Kalmijn, and D. Kromhout Fish consumption, n-3 fatty acids, and subsequent 5-y cognitive decline in elderly men: the Zutphen Elderly Study Am. J. Clinical Nutrition, April 1, 2007; 85(4): 1142 - 1147. [Abstract] [Full Text] [PDF]
|
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H. M. Den Ruijter, G. Berecki, T. Opthof, A. O. Verkerk, P. L. Zock, and R. Coronel Pro- and antiarrhythmic properties of a diet rich in fish oil Cardiovasc Res, January 15, 2007; 73(2): 316 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. PARKER Dr. Parker Replies Am J Psychiatry, November 1, 2006; 163(11): 2018 - 2019. [Full Text] [PDF]
|
|
|
|
|
|
L. K Nies, A. A Cymbala, S. L Kasten, D. G Lamprecht, and K. L Olson Complementary and Alternative Therapies for the Management of Dyslipidemia Ann. Pharmacother., November 1, 2006; 40(11): 1984 - 1992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Mozaffarian and E. B. Rimm Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA, October 18, 2006; 296(15): 1885 - 1899. [Abstract] [Full Text] [PDF]
|
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|
 |
|
 G. P. Zaloga, K. A. Harvey, W. Stillwell, and R. Siddiqui Trans Fatty Acids and Coronary Heart Disease Nutr Clin Pract, October 1, 2006; 21(5): 505 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Lichtenstein, L. J. Appel, M. Brands, M. Carnethon, S. Daniels, H. A. Franch, B. Franklin, P. Kris-Etherton, W. S. Harris, B. Howard, et al. Summary of American Heart Association Diet and Lifestyle Recommendations Revision 2006 Arterioscler. Thromb. Vasc. Biol., October 1, 2006; 26(10): 2186 - 2191. [Full Text] [PDF]
|
|
|
|
|
|
N. O'Kennedy, L. Crosbie, M. van Lieshout, J. I Broom, D. J Webb, and A. K Duttaroy Effects of antiplatelet components of tomato extract on platelet function in vitro and ex vivo: a time-course cannulation study in healthy humans. Am. J. Clinical Nutrition, September 1, 2006; 84(3): 570 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Oh, S. A. A. Beresford, and W. E. Lafferty The Fish in Secondary Prevention of Heart Disease (FISH) Survey--Primary Care Physicians and {omega}3 Fatty Acid Prescribing Behaviors J Am Board Fam Med, September 1, 2006; 19(5): 459 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
American Diabetes Association Nutrition Recommendations and Interventions for Diabetes-2006: A position statement of the American Diabetes Association. Diabetes Care, September 1, 2006; 29(9): 2140 - 2157. [Full Text] [PDF]
|
|
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|
|
I. G.E. Zarraga and E. R. Schwarz Impact of Dietary Patterns and Interventions on Cardiovascular Health Circulation, August 29, 2006; 114(9): 961 - 973. [Full Text] [PDF]
|
|
|
|
|
|
A. H. Lichtenstein Thematic review series: Patient-Oriented Research. Dietary fat, carbohydrate, and protein: effects on plasma lipoprotein patterns J. Lipid Res., August 1, 2006; 47(8): 1661 - 1667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Lichtenstein, L. J. Appel, M. Brands, M. Carnethon, S. Daniels, H. A. Franch, B. Franklin, P. Kris-Etherton, W. S. Harris, B. Howard, et al. Diet and Lifestyle Recommendations Revision 2006: A Scientific Statement From the American Heart Association Nutrition Committee Circulation, July 4, 2006; 114(1): 82 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J Deckelbaum and S. R Akabas n-3 Fatty acids and cardiovascular disease: navigating toward recommendations Am. J. Clinical Nutrition, July 1, 2006; 84(1): 1 - 2. [Full Text] [PDF]
|
|
|
|
|
|
C. Wang, W. S Harris, M. Chung, A. H Lichtenstein, E. M Balk, B. Kupelnick, H. S Jordan, and J. Lau 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. Clinical Nutrition, July 1, 2006; 84(1): 5 - 17. [Abstract] [Full Text] [PDF]
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 |
|
 M. Svensson, E. B. Schmidt, K. A. Jorgensen, J. H. Christensen, and on behalf of the OPACH Study Group N-3 Fatty Acids as Secondary Prevention against Cardiovascular Events in Patients Who Undergo Chronic Hemodialysis: A Randomized, Placebo-Controlled Intervention Trial Clin. J. Am. Soc. Nephrol., July 1, 2006; 1(4): 780 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L Breslow n-3 Fatty acids and cardiovascular disease Am. J. Clinical Nutrition, June 1, 2006; 83(6): S1477 - 1482S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R Hibbeln, L. R. Nieminen, T. L Blasbalg, J. A Riggs, and W. E. Lands Healthy intakes of n-3 and n-6 fatty acids: estimations considering worldwide diversity Am. J. Clinical Nutrition, June 1, 2006; 83(6): S1483 - 1493S. [Abstract] [Full Text] [PDF]
|
|
|
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|
|
E. J Johnson and E. J Schaefer Potential role of dietary n-3 fatty acids in the prevention of dementia and macular degeneration Am. J. Clinical Nutrition, June 1, 2006; 83(6): S1494 - 1498S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K Gebauer, T. L Psota, W. S Harris, and P. M Kris-Etherton n-3 Fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits Am. J. Clinical Nutrition, June 1, 2006; 83(6): S1526 - 1535S. [Abstract] [Full Text] [PDF]
|
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|
|
|
|
L. Gao, H. Yin, G. L. Milne, N. A. Porter, and J. D. Morrow Formation of F-ring Isoprostane-like Compounds (F3-Isoprostanes) in Vivo from Eicosapentaenoic Acid J. Biol. Chem., May 19, 2006; 281(20): 14092 - 14099. [Abstract] [Full Text] [PDF]
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|
|
S. C. Smith Jr, J. Allen, S. N. Blair, R. O. Bonow, L. M. Brass, G. C. Fonarow, S. M. Grundy, L. Hiratzka, D. Jones, H. M. Krumholz, et al. AHA/ACC Guidelines for Secondary Prevention for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2006 Update: Endorsed by the National Heart, Lung, and Blood Institute J. Am. Coll. Cardiol., May 16, 2006; 47(10): 2130 - 2139. [Full Text] [PDF]
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|
|
|
S. C. Smith Jr, J. Allen, S. N. Blair, R. O. Bonow, L. M. Brass, G. C. Fonarow, S. M. Grundy, L. Hiratzka, D. Jones, H. M. Krumholz, et al. AHA/ACC Guidelines for Secondary Prevention for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2006 Update: Endorsed by the National Heart, Lung, and Blood Institute Circulation, May 16, 2006; 113(19): 2363 - 2372. [Full Text] [PDF]
|
|
|
|
 |
|
 N.P. Jenkins, N.C. Davidson, and D.H. Bennett Successful treatment of drug refractory ventricular tachycardia by omega-3 fatty acid supplementation Europace, May 1, 2006; 8(5): 330 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Wigle and K. K. Birtcher What's New? Guidelines and Goals Journal of Pharmacy Practice, April 1, 2006; 19(2): 103 - 112. [Abstract] [PDF]
|
|
|
|
|
|
S. S. AbuMweis, C. A. Vanstone, N. Ebine, A. Kassis, L. M. Ausman, P. J. H. Jones, and A. H. Lichtenstein Intake of a Single Morning Dose of Standard and Novel Plant Sterol Preparations for 4 Weeks Does Not Dramatically Affect Plasma Lipid Concentrations in Humans J. Nutr., April 1, 2006; 136(4): 1012 - 1016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D Kark, R. Fink, B. Adler, N. Goldberger, and S. Goldman The incidence of coronary heart disease among Palestinians and Israelis in Jerusalem Int. J. Epidemiol., April 1, 2006; 35(2): 448 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Friedman and S. Moe Review of the Effects of Omega-3 Supplementation in Dialysis Patients Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 182 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. V. Howard, L. Van Horn, J. Hsia, J. E. Manson, M. L. Stefanick, S. Wassertheil-Smoller, L. H. Kuller, A. Z. LaCroix, R. D. Langer, N. L. Lasser, et al. Low-Fat Dietary Pattern and Risk of Cardiovascular Disease: The Women's Health Initiative Randomized Controlled Dietary Modification Trial JAMA, February 8, 2006; 295(6): 655 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. M. Anderson and L. J. Appel Dietary Modification and CVD Prevention: A Matter of Fat JAMA, February 8, 2006; 295(6): 693 - 695. [Full Text] [PDF]
|
|
|
|
|
|
D. Rees, E. A Miles, T. Banerjee, S. J Wells, C. E Roynette, K. W. Wahle, and P. C Calder Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men Am. J. Clinical Nutrition, February 1, 2006; 83(2): 331 - 342. [Abstract] [Full Text] [PDF]
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|
|
|
|
J. Dwyer Starting down the right path: nutrition connections with chronic diseases of later life Am. J. Clinical Nutrition, February 1, 2006; 83(2): 415S - 420S. [Abstract] [Full Text] [PDF]
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