The idea that long-chain marine omega-3s can prevent cardiovascular disease is old and started with the Inuit of Greenland, who were found to have a lower risk of cardiovascular disease. Indeed, Inuit, with high omega-3 intake, have been observed to have lower platelet counts, reduced platelet reactivity, prolonged bleeding times, and a lower ratio of aggregated thromboxane to anticoagulant prostacyclin.
Clinical studies in humans clearly show that marine omega-3s provide antiplatelet results, and a meta-analysis of 15 randomized controlled trials (RCTs) in humans confirmed that omega-3 polyunsaturated fatty acids (PUFAs) inhibit the accumulation of overcome aspirin resistance.
In healthy marginally overweight men, 3 g of omega-3 PUFAs for 4 weeks reduced fibrinogen, thrombin and factor V levels. These benefits occurred mainly in individuals with high fibrinogen. Marine omega-3s also have the ability to reduce von Willebrand factor (vWF, a platelet activating factor), blood viscosity and can improve red blood cell elasticity (deformation). In a double-blind, placebo-controlled, 5-week study in 30 healthy individuals, 2.52 g / day omega-3 PUFA compared with 1.26 g / day significantly reduced plasma viscosity, red stiffness blood cells and systolic blood pressure.
High doses of omega-3s have more effective anticoagulant benefits. A study in healthy adults found that fish oil (providing 6 g of eicosapentaenoic acid (EPA) / day) reduced platelet adhesion. In another study, supplementation with 3.6 g omega-3 PUFA from fish oil reduced platelet aggregation. The omega-6 / omega-3 ratio in platelets is also positively correlated with platelet adhesion at rest and then, by ADP and thrombin, platelet stimulation. Another study found that plasminogen activator inhibitor-1 (PAI-1, a fibrinolysis inhibitor) may be reduced in those who consume fish oil, suggesting a reduced risk of thrombosis.
Generally, they need about 2-4 g EPA / docosahexaenoic acid (DHA) per day to reap the full benefits of atherosclerotic, anti-inflammatory and antiplatelet. Even plant omega-3s seem to have some benefit in this regard, while omega-6s can have a detrimental effect. In 24 healthy young men, a Mediterranean diet has been found to reduce thrombotic status (reduced plasma vWF, tissue factor pathway inhibitor, and PAI-1 tissue).
A Mediterranean diet high in MUFA reduces vWF (derived from the endothelium and important in the coagulation process during a platelet clot) and PAI-1. Platelet accumulation in response to collagen decreases in just 6 days after net consumption of EPA, but platelet response to ADP decreases only after at least 4 weeks of uptake. However, inhibition of platelet aggregation with DHA (6 g / day) in both stimuli occurs in just 6 days. Both EPA and DHA inhibit platelet aggregation, however, DHA has a faster onset of action than inhibiting ADP-induced platelet aggregation.
Both EPA and DHA are incorporated into platelet phospholipids to the detriment of arachidonic acid (AA), which can help reduce platelet aggregation by reducing platelet aggregation metabolites. In addition, EPA competes with AA for cyclooxygenase {COX νοντας by reducing its activity in AA. EPA / DHA is also incorporated into neutrophils and red blood cells to the detriment of both LA {linoleic acid.
The incorporation of omega-3 into red blood cells appears to reduce whole blood viscosity and increase red blood cell flexibility, thus reducing the risk of thrombosis. Daily supplementation with 3 g EPA / DHA for 12 weeks, and especially after 18 weeks, inhibits the activity of tissue factor in adherent monocytes (catalyst in coagulation cascade). This benefit also appears after 24 weeks in people with hypertriglyceridemia. Thus, the anticoagulant effects of omega-3 in clinical trials may need to be considered for at least 18 weeks in healthy patients and even more (for 24 weeks) in those with hypertriglyceridemia. Interestingly, supplementing the diet with olive oil or eating more than one MUFA-fortified fish has been found to reduce PAI-1.
A double-blind placebo-controlled trial in 59 hypertensive patients with type 2 diabetes compared with 4 g / day EPA, 4 g / day DHA or 4 g / day olive oil (“placebo”) for 6 weeks. DHA, but not EPA, significantly reduced collagen accumulation and TXB2 versus placebo, with the authors concluding that DHA is a more effective anticoagulant than EPA. Thus, supplementation of patients with type 2 diabetes with 4 g DHA per day is particularly effective in rapidly reducing platelet aggregation, reversing fibrinolysis disorder, and improving endothelial dysfunction. One study found a significant reduction in cardiovascular events in high-risk patients using 4 g of EPA per day. Endothelial production of nitric oxide, prostacyclin and tissue-plasminogen activator is very important to prevent platelet aggregation and acute cardiovascular events.
Damaging the endothelium, consuming LA {linoleic acid} can actually cause hypercoagulability, while fish oil has been shown to improve endothelial function and enhance fibrinolytic activity. DHA, but not EPA, has been found to improve endothelial function, which may be why DHA has better antihypertensive effects. Importantly, in healthy patients, a DHA dose of 6 g / day may be required to significantly reduce platelet aggregation as 1.62 and 1.68 g DHA / day have been found to be ineffective in this regard.
Supplementing the diet with 500 g of fatty fish per week for 4 weeks significantly reduces platelet aggregates by 35% compared to the control, which returned to baseline 4 weeks after cessation. Platelet aggregates can promote atherosclerosis and cause inflammatory cytokines, chemokines and expression of adhesion molecules. EPA has also been found to reduce P-selectin, oxidized LDL and glycoprotein IIb / IIIa in platelets, suggesting a decrease in platelet activation.
In terms of safety and omega-3 bleeding, in major surgeries the risk of clinically significant bleeding was virtually non-existent. Ω3 supplements do not increase the risk of clinically significant bleeding, even in patients treated with antiplatelet or anticoagulant drugs. Omega-3 and omega-6 PUFAs are supposed to balance with each other when consumed in the diet in a ratio of about 1 to 1, however, increasing the omega-6 / omega-3 ratio causes a pro-inflammatory / cumulative condition.
Despite LA’s ability to lower LDL levels, it can cause peroxidation and therefore increase the risk of coronary heart disease as LDL peroxidation is considered one of the first promoters of atherosclerosis. Most importantly, the oxidized metabolites of LA can increase thrombosis and vasoconstriction by decreasing prostacyclin in the vascular wall and increasing TXA2.
In addition, consuming LA from industrial seed oils may even increase susceptibility to fatal arrhythmias. In summary, EPA and DHA have antiplatelet effects, but do not increase the risk of clinically significant bleeding and may even reduce the risk of bleeding in the surgical setting, while omega-6 PUFA {LA} has little effect on reducing platelet aggregation and in some cases it may even increase platelet activation.
Omega-6 industrial seed oils may increase the risk of thrombotic cardiovascular events {from many randomized clinical trials in humans}.
SOURCE: {BMJ Journal 2019}
