pidemiological studies suggest that consuming fish is associated with a decreased risk of cardiovascular disease. Fish may be protective of cardiovascular disease because of the long-chain fatty acids contained within it. Fish oil accumulates in the skin of some species of cold water fish, and tuna, mackerel, pilchards, trout and salmon all display this characteristic. However, some fish store oil in their livers, cod being a good example. This oil is a rich source of the omega 3 (n-3) fatty acids eicosapentanoic acid (EPA, C:20:5 (n-3)), docosahexanoic acid (DHA, C22:6 (n-3)), docosapentanoic acid (DPA, C22:5 (n-3)) and stearidonic acid (SDA, C18:4 (n-3)), which are almost exclusively derived from marine sources. These fatty acids all share a common metabolic pathway (figure 1) beginning with α-linolenic acid (ALA, C18:3 (n-3)). The precursor fatty acid ALA is essential because it cannot be synthesised from other substances in humans.
Figure 1. The metabolism of n-3 fatty acids in humans.
The n-3 long-chain marine fatty acids accumulate in cell membranes of humans where they increase membrane fluidity. This characteristic to increase membrane fluidity derives from the numerous double bonds in their hydrocarbon tails. The cis-configuration of the bonds gives the molecule a pronounced kink and this increases inter-phospholipid space, thereby increasing the fluidity of the membrane. The cell also uses the cell membrane accumulated EPA and DHA to produce a number of short-lived hormone-like compounds that regulate cell function. Membrane bound EPA and DHA are converted to Eicosanoids and docosanoids, respectively and these can have anti-inflammatory effects primarily through the inhibition of pro-inflammatory eicosanoids. Such pro-inflammatory eicosanoids are derived from arachidonic acid (AA, C20:4 (n-6)), also present in the membranes of cells, and the ratio of the EPA and DHA to AA within the membrane therefore influences cellular function.
Because high intakes of fish increase the ratio of EPA and DHA to AA in cell membranes they have anti-inflammatory effects. This is likely the primary mechanism of action of fish oils in protecting from cardiovascular disease. Both SDA and DPA are also protective because they feed into the same pathway and increase cell membrane levels of EPA and DHA, thus also having a pronounced anti-inflammatory effect. The plant derived α-linolenic acid (ALA, C18:3 (n-3)) is often suggested as a vegetarian alternative to fish oils because it is part of the same metabolic pathway. And it is true that ALA will increase cell membrane levels of EPA and DHA somewhat. However, the conversion in humans is very inefficient due to low activity of the delta 6-desatuase enzyme. As a result ALA cannot raise cell membrane levels of EPA and DHA to the same degree as fish sources of these oils.
It is questionable therefore if ALA is cardioprotective. This is confirmed from studies showing that ALA is preferentially oxidised, rather than being converted to EPA or DHA. Cardioprotective effect of n-3 oils must therefore come from marine sources. In this regard the cardioprotective effects of long-chain fatty acids have been well researched. Both EPA and DHA consumption have been shown to reduce levels of very-low density lipoprotein (triglycerides), possibly through a beneficial effect on insulin sensitivity. In addition, EPA and DHA may raise high density lipoprotein and lower low density lipoprotein. High concentrations of EPA and DHA may also lower blood pressure. Fish oils also improve endothelial function, possibly because they decrease inflammation, which decreases oxidative stress, and this in turn increases nitric oxide synthesis. Evidence also suggests that high intakes of fish oils may decrease cardiac arrhythmias and prevent myocardial infarction.
High intakes of EPA and DHA can also decrease platelet aggregation and decrease the risk of blood clot formation. Increasing levels of EPA and DHA in cell membranes increase production of the eicosanoid hormone prostaglandin E3, thromboxane A3 and leukotriene B5. Prostaglandin E3 is a strong vasodilator and inhibitor of platelet aggregation, and so its action is to decrease the risk of forming blood clots. Although thromboxane A3 weakly increase vasoconstriction and inflammation, it also has an overall beneficial effect because its production inhibits the action of thromboxane A2 from AA. Thromboxane A2 is a strong vasoconstrictor and platelet aggregator and by inhibiting its action, beneficial effects on platelet aggregation are seen. Likewise, the weak inflammatory effects of leukotriene B5 counters stronger inflammatory effects of the AA derived leukotriene B4. Research also suggests that EPA and DHA may decrease platelet production directly, and may decrease adhesion molecule expression.
However, while fish may have multiple beneficial mechanisms by which it is protective of cardiovascular disease, doubt persist about the long term consumption of fish. Farmed fish is high in antibiotic and other drug residues, used to keep the fish parasite free in their keep nets. Wild fish are contaminated with mercury and organochloride compounds such as polychlorinated biphenyls (PCBs). Some limitations have already been recommended to vulnerable groups such as pregnant women in order to prevent accumulation of these carcinogenic, cardiotoxic and neurotoxic agents. Some organochlorides are resistant to degradation in the environment and bioaccumulate, which explains their high concentrations in some fish. That they have cardiotoxic effects suggests that organochlorides in fish might negate some of the beneficial effects of fish consumption. Because of the possible risk associated with fish supplementation of fish oils are increasingly being seen as a viable alternative1.
For example, one group of researchers1 investigated the concentrations of polychlorinated biphenyl (PCBs) and other organochlorides (α-chlordane, dieldrin, γ-chlodane, 1,1-dichloro-2,2-bis(ρ-chlorophenyl)ethane [DDD], dichlorodiphenyldichloroethane [DDE], lindane, dichlorodiphenyltrichloroethane [DDT], heptachlor, heptachlorepoxide, hexachlorobenzene, methoxychlor, oxychlordane, polybrominated biphenyls (PBBs), trans-nonachlor) in 5 over the counter fish oil supplements. All chemical were below the level of detection indicating that supplements would be safe for long-term consumption. In addition, some fish oils are available that have been treated to remove contaminants, thus producing purer products that may eliminate any cardiotoxic compounds. Therefore, unless uncontaminated fish can be obtained from a reliable source, fish oil capsules provide a safe alternative to benefit from consumption of the long-chain marine fatty acids.
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