Journal Name:
Biochem. Pharmacol.
Article Title:
Dietary n-6 and n-3 polyunsaturated fatty acids: From biochemistry to clinical implications in cardiovascular prevention
Date Written:
2008
Volume:
Oct.
Number:
NA
Page:
1
Author(s):
Russo G.L.
Article:
This review critically reviews the most significant epidemiological and interventional studies on the cardioprotective activity of PUFAs, linking their biological functions to biochemistry and metabolism. The controversial origin and clinical role of the n-6/n-3 ratio as a potential risk factor in cardiovascular diseases is also examined. This review highlights the important cardioprotective effect of n-3 in the secondary prevention of sudden cardiac death due to arrhythmias, but suggests caution to recommend dietary supplementation of PUFAs to the general population, without considering, at the individual level, the intake of total energy and fats.
Omega 3 FAs decrease triglycerides and very low density lipoproteins (VLDL) and result in a moderate rise in high density lipoproteins (HDL), whereas omega 6 FAs do not show these effects. Overall, omega 3 FAs do not seem to have a very significant effect neither in lowering blood lipids, nor fibrinolysis and plasminogen activator inhibitor-1, which yield the question as to the exact mechanisms of their protective effects against CHD. Epidemiological and interventional approaches clearly demonstrate that individuals with a diet rich in fish (30–35 g/day, or, alternatively, one fish meal per week), or supplemented with EPA and DHA (up to 665 mg/day) showed a 30–50% reduction in CHD and CHD-related mortality compared to those who ate no fish. Prevention trials support the antiarrhythmic effects of ALA, EPA and DHA. In epidemiological studies, ALA consumption is associated with significant reductions in the incidence of recurrent non-fatal MI. Fish oil capsules (1.08 g/day EPA plus 0.72 g/day DHA) and mustard seed oil (2.9 g/day ALA) behaved similarly in reducing total cardiac death and risk of cardiac arrhythmias in patients treated for 1 year starting 24 h after a first episode of MI.
Data from animal models and cultured cardiomyocytes suggest that the anti-arrhythmic effects of omega 3 FAs are due to the ability of ALA and EPA/DHA to influence the activity of myocyte sarcolemma ion channels (sodium and L-type calcium). These EFAs/PUFAs are able to: (i) increase the threshold of ventricular fibrillation; (ii) increase heart rate variability; and (iii) reduce ischemic damage. Further, omega 3 FA treatments are well tolerated and have no serious side effects during the trials.
More controversial is the role of omega 6 FAs in cardiovascular disease prevention. Earlier studies have shown that LA improves lipid profile by lowering total cholesterol and LDL cholesterol and slightly increasing HDL-cholesterol, whereas more recent research contradicts these conclusions. Some evidence has been assembled in favor of the importance of the omega 6/omega 3 FA ratio. The arachidonic acid (AA)-derived eicosanoids if formed in large amounts, increase the ratio and contribute to the formation of thrombus and atheromas, allergic and inflammatory disorders and abnormal cell proliferation. Several clinical intervention studies support the view that decreasing the ratio results in an increased protection against degenerative diseases. For example, replacing corn oil (high in LA) with olive and canola oil (low in LA) to reach a 4:1 ratio of LA/ALA, resulted in a 70% decrease in total mortality.
Clinical and nutritional studies largely agree on the importance of the balance in a healthy diet between saturated FAs, MUFAs and PUFAs and their role in LDL/HDL composition and oxidation, with MUFA being the most efficacious. Oleic acid when substituted for saturated FAs, lowers LDLs and increases their resistance to oxidation. The mechanism whereby incorporation of PUFAs into LDLs enhances susceptibility of LDL oxidation has been studied extensively. However, diets rich in omega 6 FAs increases the PUFA content of LDL particles and increases their susceptibility to oxidation, which in turn leads to atherosclerosis and CVD.
Recent estimations of PUFA consumption in the food chain in Europe and United States indicate that the ratio of omega 6/ omega 3 FAs is still much higher than that recommended (4:1 to 10:1). Favorable changes in the omega 6/ omega 3 FA ratio can be achieved more easily by decreasing total fats and omega 6 FAs intake, this does not necessarily mean that EPA/DHA will increase accordingly. Chronically increased consumption of ALA results in an increased EPA concentration in plasma and cell pools, but an insufficient conversion to DHA.
The reviewer concludes that the most significant effect of EFAs/PUFAs in terms of human health is the omega 3 FA protection in the secondary prevention of sudden cardiac death due to arrhythmias. He notes that dietary recommendations should distinguish between ALA and EPA/DHA and made on a mass basis (g/day) of omega 3 FAs to be consumed, and consider at an individual level, the intake of total energy, total fats and omega 6 FA intakes. Further it is recommended that it is necessary to intensify the scientific efforts in order to clarify many controversial aspects of EFA/PUFA (particular the role of dietary omega 6 FAs) consumption in order to make human diet healthier.
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