Long-Chain Polyunsaturated Fatty Acids and Cardiovascular Disease

Fat is an essential component of the diet, and the fatty acids have different roles in the human body. In the 1970s, Danish researchers discovered that Greenland Inuits, who consume large amounts of marine lipids as part of their native lifestyle, had a much lower cardiovascular mortality (10±30 per cent) compared with the Danes, who consume much lower levels of these lipids. These findings triggered new research on the role of the long-chain polyunsaturated fatty acids (LC PUFA) in the development of cardiovascular disease and on the possibilities of utilising the beneficial effects of n-3 LC PUFA by incorporating marine lipids into foods. This post will summarise the latest evidence for the positive effects of n-3 LC PUFA on the prevention of cardiovascular diseases and the proposed mechanisms behind the protective effect of n-3 LC PUFAs. Moreover, the problems associated with using marine oil in foods, especially the problems related to off-flavour formation, will be discussed together with examples of how such problems can be solved.

There are two distinct families of PUFA that cannot be interconverted. The parent fatty acids of the n-6 (linoleic acid) and n-3 (a-linolenic acid) families are essential fatty acids as they cannot be synthesised by the human body. The body is able to synthesise the LC PUFA from the parent fatty acids. However, linoleic acid and a-linolenic acid are competing for the same enzyme systems for the synthesis and, therefore, it is important that there is the right balance between the intake of n-6 and n-3 fatty acids.

The n-6 PUFA are found mainly in vegetable products. The parent n-3 fatty acid a-linolenic acid, is also present in some vegetables (rapeseed, soybean and nut oils), but fish and marine animals are the best sources of the n-3 LC PUFA eicosapentanoic acid (EPA) and docosahexanoic acid (DHA). Low levels of n-3 LC PUFA are also found in meat. The current intake of n-3 PUFA in industrialised countries is only 4±10 per cent of the intake of n-6 PUFA, compared with an estimated ratio of 1:1 about 150 years ago. Therefore, several bodies have issued PUFA guidelines to encourage a more balanced ratio of n-6/ n-3 fatty acids that would optimise the benefits of both fatty acids.

Several large-scale epidemiological studies have demonstrated a negative association between fish consumption and cardiovascular and/or overall mortality. The cardioprotective effect of fish consumption seems to be more prevalent in high-risk populations. Intervention studies in cardiac patients have shown that fish or fish oil supplementation vs. placebo reduced the mortality risk up to 45 per cent. Apparently, fish or fish lipids do not reduce the risk of a new cardiovascular incident, but fewer incidents are fatal. At least half the deaths from coronary artery disease are sudden cardiac deaths with fatal arrhythmia caused by ventricular fibrillation. A number of studies have shown that n-3 LC PUFA prevent arrhythmias and this seems to be an important property of these fatty acids.

Several mechanisms have been suggested to explain the preventive effect of n-3 LC PUFA on cardiovascular diseases. It is now well established that n-3 LC PUFA reduce triglyceride levels by lowering hepatic triglyceride synthesis and by decreasing the release of triglyceride-rich very low-density lipoproteins (VLDLs) into the blood. A high plasma triglyceride level is a cardiovascular risk factor. Hypertension is another important cardiovascular risk factor. High doses of n-3 LC PUFA have been shown to reduce hypertension, probably by influencing membrane fluidity and the balance of the prostanoids that control the constriction and dilation of the small arteries and arterioles.

Numerous studies have shown that n-3 LC PUFA have antiaggregant activity. This is probably due to EPA’s role in the eicosanoid synthesis and its ability to reduce the levels of arachidonic acid (AA) in the membrane. EPA is a precursor of the 3-series prostanoids TXA3 and PGI3 while AA is a precursor of TXA2 and PGI2. TXA2 and TXA3 are both prothrombotic, but TXA3 is less prothrombotic than TXA2. In contrast, PGI2 and PGI3 are equally antithrombotic. Moreover, it seems that EPA and DHA reduce the gene expression of the enzymes involved in eicosanoid synthesis.

The ability of EPA and especially DHA to prevent arrhythmias may be due to their effect on (i) the ion channel (modulation of the ionic currents in heart cells), (ii) adrenoreceptors (DHA decreases the production of the main 0­ adrenic messenger, cyclic AMP, which transmits the message from catecholamins to the heart about the rhythm and force of contraction, (iii) prostaglandins (prostaglandins from EPA are less effective in promoting arrhythmias than prostaglandins from AA5), and (iv) energy production (EPA produces energy at a lower oxygen cost than other fatty acids and this is important in ischaemia where the tissue is deprived of oxygen).

EPA and DHA have inflammatory properties and are similar in action to certain anti-inflammatory agents by inhibiting the production of inflammatory mediators such as prostaglandin E2 and leukotrine B4 derived from leuckocyte and macrophage activation. Because of these properties, n-3 LC PUFA may help to prevent or reduce the symptoms of rheumatoid arthritis and Crohn’s disease. There is also some evidence that n-3 LC PUFA may prevent certain cancer forms, but more research is necessary to support this hypothesis.

The n-3 LC PUFA have a very important role in the brain, retina and nervous tissue as DHA constitutes up to 50 per cent of the phospholipid fatty acids. Therefore, the brain and retina are dependent on a continuous DHA supply for optimal function. DHA is particularly important during the development of the central nervous system in the foetus in the last trimester of the pregnancy, in pre-term infants and also during childhood. Maternal LC PUFA intake under the present dietary conditions seems to be inadequate to keep up with the increased demand for n-3 LC PUFA during pregnancy. Therefore, it has been suggested that pregnant women should increase their intake of DHA and that infant formulas for both pre-term and term infants should contain DHA. Infant formulas with DHA are now available in several countries.

 PUFA recommended dietary allowancesScientific Review Committee Canada, 1990British Nutrition Task Force, 1992Scientific Committee for Food, EU, 1993FAO/WHO Expert Committee, 1994Committee on Medical Aspects of Food Policy, 1991, 1994National Nutrition Council, Norway, 1996The Japanese Society of Nutrition and Food Science, RDA for theHealth Council of the Netherlands0-5 months: 80 mg/kg day above 5 months 1%*0-5 months: 20 mg/kg day DHA above 5 months

*% energy intake.

Source: Anselmino and Hornstra, http://www.nutrivit. co. uk/professional/PDFs/Omega_3%20book.pdf.