(23-09-06) Are EPA and DHA Similar in Protecting Heart Health?

Consumption of fish or fish oil is associated with significantly lower risk of heart disease, coronary heart disease mortality and sudden death, and risk of a second heart attack in many, but not all studies. Whether the two principal omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFAs) in fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), act similarly in cardiovascular protection is uncertain. Answering this question may be important for treating certain types of patients and choosing appropriate supplements from an array of n-3 PUFA products.

If EPA and DHA have similar effects on cardiovascular health, it makes little difference which fatty acid is consumed for this purpose. However, if there are biologically significant differences in their effects, especially among different groups of people, such as survivors of a heart attack or type 2 diabetic patients, it may be important to ensure adequate intake of the most effective n-3 LC-PUFAs. Fish and shellfish have both fatty acids, but not all n-3 PUFA supplements do. Another implication is the potential enrichment of foods with stearidonic acid, an n-3 PUFA precursor readily converted EPA, but not in appreciable amounts to DHA. To sort out the different effects of EPA and DHA in heart health, Mori and Woodman reviewed the literature, emphasizing controlled studies and highlighting the differences between the two n-3 LC-PUFAs in studies where purified fatty acids were consumed.

Both EPA and DHA reduce plasma triglyceride concentrations about 20% to 25%, respectively, with the greatest effect occurring in patients having the highest levels. Reductions are modest in people with normal triglycerides. Detailed reviews of clinical trials have concluded that n-3 LCPUFAs have little effect on total and low-density lipoprotein cholesterol levels in plasma, although increased LDL levels have been reported. However, individually, their effects on high-density lipoprotein (HDL or ?good? cholesterol) concentrations differ. EPA has little effect on HDL levels in patients with dyslipidemia or type 2 diabetes. In contrast, DHA consumption is associated with increased HDL concentrations of about 20% in dyslipidemic and type 2 diabetic patients, with increases ranging from 4% to 37%. Increases occurred only in the HDL2 subfraction (desirable) and if relatively high doses of DHA were consumed (2-6 gm/day). DHA, but not EPA, was more likely to increase LDL particle size, an additional potentially anti-atherogenic effect.

n-3 LC-PUFA intake is associated with lower blood pressure, mostly in people with hypertension. Mori and colleagues have shown that DHA is more effective than EPA or a combination of EPA and DHA in reducing blood pressure, but large doses are needed (4 gm/day).

Both EPA and DHA are associated with improved endothelial function, but DHA was more effective than EPA in improving forearm blood flow in overweight hypertensive patients. EPA and DHA improved arterial compliance in dyslipidemic patients, while EPA improved vasomotion (rhythmic change in vessel diameter) in coronary arteries. Fish oil and DHA have been associated with lower heart rate, but EPA has no such effect.

EPA reduced platelet aggregation, one of the earliest targets of n-3 LC-PUFA investigation, in uncontrolled studies, but not in a controlled study of type 2 diabetics. In contrast, DHA reduced platelet aggregation in these patients. Increased platelet aggregation is a characteristic of type 2 diabetes and an important therapeutic target. In healthy people, very high doses of DHA (6 gm/day) for 3 months reduced platelet aggregation, but low doses in uncontrolled studies had no significant effect. The effect of DHA may be due to its inhibitory effect on thromboxane A2 production, whereas EPA leads to production of the weakly aggregatory 3-series of thromboxanes.

n-3 LC-PUFAs modify immune responses and have anti-inflammatory effects, but differences between the two fatty acids are unclear and may be dose-dependent. In general, these fatty acids reduce the production of inflammatory cytokines and cell-adhesion molecules. In vitro DHA, but not EPA, reduced the expression of inflammatory cytokines and cell-adhesion molecules. DHA was more effective in inhibiting the expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. In doses up to 2 gm/day, EPA plus DHA reduced the production of the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 in healthy volunteers. In a recent report, EPA was more potent than DHA in reducing TNF-alpha-mediated activation of two protein kinases (p38 and JNK) in human endothelial cells in vitro, but both counteracted the TNF-alpha-mediated deactivation of a third kinase, ERK1/2. DHA but not EPA reduced the TNF-alpha-induced expression of JNK messenger RNA. These varied observations suggest that both EPA and DHA affect immune responses in endothelial cells, but the effects differ with the particular regulatory molecule and may be more pronounced with DHA in some circumstances.

Mori and Woodman conclude that EPA and DHA likely have different anti-atherogenic properties and that for several parameters?increased HDL, larger LDL particle size, lower blood pressure, reduced heart rate, lower platelet aggregation and reduced endothelial cytokine production?DHA is considerably more effective than EPA. Both fatty acids lower blood triglycerides, reduce oxidative stress, and weaken inflammatory cytokine production. Some of these effects may depend on the particular patient population as well. What we do not know is whether the reported differences between DHA and EPA would be observed at lower doses more reflective of recommended intakes of fatty fish.
Source: Mori TA, Woodman RJ. The independent effects of eicosapentaenoic acid and docosahexaenoic acid on cardiovascular risk factors in human.

Curr Opin Clin Nutr Metab Care 2006;9:95-104. [PubMed]

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