Docosahexaenoic acid

About: Docosahexaenoic acid is a research topic. Over the lifetime, 14412 publications have been published within this topic receiving 620852 citations. The topic is also known as: all-cis-DHA & all-cis-docosa-4,7,10,13,16,19-hexaenoic acid.

Suppression of voltage-gated L-type Ca2+ currents by polyunsaturated fatty acids in adult and neonatal rat ventricular myocytes

Abstract: Our recent data show that in cardiac myocytes polyunsaturated fatty acids (PUFAs) are antiarrhythmic. They reduce INa, shorten the action potential, shift the threshold for excitation to more positive potentials, and prolong the relative refractory period. In this study we use patch-clamp techniques in whole-cell mode and confocal Ca2+ imaging to examine the effects of PUFAs on the voltage-gated L-type Ca2+ current (ICa,L), elementary sarcoplasmic reticulum Ca2+-release events (Ca2+-sparks), and [Ca2+]i transients in isolated rat ventricular myocytes. Extracellular application of eicosapentaenoic acid (EPA; C20:5 n − 3) produced a prompt and reversible concentration-dependent suppression of ICa,L. The concentration of EPA to produce 50% inhibition of ICa was 0.8 μM in neonatal rat heart cells and 2.1 μM in adult ventricular myocytes. While the EPA induced suppression of ICa,L, it did not significantly alter the shape of the current–voltage relation but did produce a small, but significant, negative shift of the steady-state inactivation curve. The inhibition of ICa,L was voltage- and time-dependent, but not use- or frequency-dependent. Other PUFAs, such as docosahexaenoic acid, arachidonic acid, linolenic acid, linoleic acid, conjugated linoleic acid, and eicosatetraynoic acid had similar effects on ICa,L as EPA. All-trans-retinoic acid, which had been shown to suppress induced arrhythmogenic activity in rat heart cells, also produced a significant inhibition of ICa,L. The saturated stearic acid and the monounsaturated oleic acid had no effect on ICa,L. Because both ICa,L and sarcoplasmic reticulum Ca2+-release underlie many cardiac arrhythmias, we examined the effects of EPA on ICa,L and Ca2+-sparks. While EPA suppressed both, it did not change the temporal or spatial character of the Ca2+-sparks, nor did it alter the ability of ICa,L to trigger Ca2+-sparks. We conclude that PUFAs may act as antiarrhythmic agents in vivo in normal and Ca2+-overloaded cells principally because they reduce Ca2+ entry by blocking ICa,L. Furthermore, PUFAs act directly to decrease INa and ICa,L, but indirectly to reduce the [Ca2+]i transients and [Ca2+]i-activated membrane current. Although a negative inotropic action is associated with application of PUFAs, it is clear that by reducing ICa,L, INa and Ca2+-sparks, PUFAs can reduce spontaneous extrasystoles in the heart. The mechanisms by which PUFAs act are discussed.

Differential Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Vascular Reactivity of the Forearm Microcirculation in Hyperlipidemic, Overweight Men

Abstract: Background—Recent evidence supports differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the 2 major ω3 fatty acids of marine origin, on blood pressure in humans and vascular reactivity in adult spontaneously hypertensive rats. We investigated possible differences in the effects of purified EPA or DHA on forearm vascular reactivity in overweight hyperlipidemic men that might contribute to the blood pressure–lowering effects of fish oils. Methods and Results—With a double-blind, placebo-controlled trial of parallel design, 59 overweight, mildly hyperlipidemic men were randomized to receive 4 g/d purified EPA, DHA, or olive oil (placebo) capsules while continuing their usual diets for 6 weeks. Forearm blood flow (FBF) was measured with venous occlusion, strain-gauge plethysmography during the sequential intra-arterial administration of acetylcholine (7.5, 15, and 30 μg/min), sodium nitroprusside (1.5, 3, and 10 μg/min), norepinephrine (10, 20, and 40 ng/min), a single-dose inf...

A Double-Blind, Placebo-Controlled Study of the Omega-3 Fatty Acid Docosahexaenoic Acid in the Treatment of Major Depression

Abstract: OBJECTIVE: This study was an evaluation of the omega-3 fatty acid docosahexaenoic acid (DHA) for the treatment of major depression. METHOD: Thirty-six depressed patients were randomly assigned to receive DHA, 2 g/day, or placebo for 6 weeks. Response was defined a priori as a ≥50% reduction in the score on the Montgomery-Asberg Depression Rating Scale. Thirty-five participants were evaluable; 18 received DHA, and 17 received placebo. RESULTS: Response rates were 27.8% in the DHA group and 23.5% in the placebo group. The difference in response rates between groups did not reach statistical significance. CONCLUSIONS: This trial failed to show a significant effect of DHA monotherapy in subjects with major depression.

Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials.

Abstract: Background: Although previous randomized, doubleblind, placebo-controlled trials reported the efficacy of omega-3 fatty acid supplements in the secondary prevention of cardiovascular disease (CVD), the evidence remains inconclusive. Using a meta-analysis, we investigated the efficacy of eicosapentaenoic acid and docosahexaenoic acid in the secondary prevention of CVD. Methods: We searched PubMed, EMBASE, and the Cochrane Library in April 2011. Two of us independently reviewed and selected eligible randomized controlled trials. Results: Of 1007 articles retrieved, 14 randomized, double-blind, placebo-controlled trials (involving 20 485 patients with a history of CVD) were included in the final analyses. Supplementation with omega-3 fatty acids did not reduce the risk of overall cardiovascular events (relative risk, 0.99; 95% CI, 0.89-1.09), all-cause mortality, sudden cardiac death, myocardial infarction, congestive heart failure, or transient ischemic attack and stroke. There was a small reduction in cardiovascular death (relative risk, 0.91; 95% CI, 0.84-0.99), which disappeared when we excluded a study with major methodological problems. Furthermore, no significant preventive effect was observed in subgroup analyses by the following: country location, inland or coastal geographic area, history of CVD, concomitant medication use, type of placebo material in the trial, methodological quality of the trial, duration of treatment, dosage of eicosapentaenoic acid or docosahexaenoic acid, or use of fish oil supplementation only as treatment. Conclusion: Our meta-analysis showed insufficient evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular events among patients with a history of cardiovascular disease.

Brain Cortical Fatty Acids and Phospholipids During and Following Complete and Severe Incomplete Ischemia

Abstract: To explore the possibility that peroxtdative degradation of brain tissue lipid constituents is an important mechanism of irreversible ischemic damage, we measured cortical fatty acids and phospholipids during reversible brain ischemia in the rat. Neither complete nor severe incomplete ischemia (5 and 30 min) caused any measurable breakdown of total or individual fatty acids or phospholipids. Except for a small (and reversible) decrease of inositol plus serine phosphoglycerides in the early postischemic period following 30 min of incomplete ischemia, there were no significant losses of fatty acids or phospholipids during recirculation. Since peroxidation, induced in brain cortical tissue in vitro, characteristically involves degradation of polyenoic fatty acids (arachidonic and docosahexaenoic acids) and of ethanolamine phosphoglycerides, the present in vivo results fail to support the hypothesis that peroxidation of membrane lipids is of primary importance for ischemic brain cell damage. Both complete and severe incomplete ischemia caused a similar increase in the tissue content of free fatty acids (FFA). Thus the FFA pool increased by about 10 times during a 30-min ischemic period, to constitute 1 - 2% of the total fatty acid pool. Since there was a relatively larger increase in polyenoic FFA (especially in arachidonic acid) than in saturated FFA, the release of FFA may be the result of activation of a phospholipase A2 unbalanced by reesterification. Increased levels of FFA persisted during the initial recirculation period, but a gradual normalization occurred and the ischemic changes were essentially reversed at 30 min after restoration of circulation. The pathophysiological implications of the changes in FFA are discussed with respect to mitochondrial dysfunction, formation of cellular edema and prostaglandin-mediated deterioration of postischemic circulation.