Introduction
Omega-3 fatty acids are one of the Polyunsaturated Fatty Acids (PUFA) subgroups. Belonging to the omega-3 family include alpha-linolenic acid (ALA) which is also the main derivative of other omega-3 PUFAs like eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) (Angelo 2014). Omega-3 fatty acids are essential nutrients that contribute greatly to the human health like playing important roles in functions of the brain and eye, help preventing inflammation and they also have been associated in cardiovascular protection (Ruxton 2004).
Structure
The general chemical structure of an omega-3 PUFA includes a chain of carbon atoms with two ends being a carboxylic acid (referred to as the alpha end) and a methyl group (referred to as the omega end). It is a Polyunsaturated Fatty Acid as it has more than one cis double bond and its omega group is designated according to the location of the first double bond in relation to the terminal methyl end group, which is on the third carbon as shown in Figures 1a, 2a, 2b and 2c (PubChem 2018).
Plant omega-3
Alpha-linolenic acid (ALA) is an omega-3 fatty acid found in plants.
Figure 1a. Chemical structure of ALA with 18 carbons and 3 cis double bonds on carbons numbered 9, 12 and 15 from the alpha end. Its first double bond is located at the third carbon atom in relation to the methyl group, hence it is an omega-3 PUFA and is called 18:3 (n-3) in many scientific literature, with n being omega. Adapted from PubChem (2018).
Animal omega-3
Animal omega-3 fatty acids include EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid) and DPA (docosapentaenoic acid). Their structures differ in the number of carbon atoms and double bonds as well as the location of those double bonds in the chains as illustrated in Figures 2a, 2b and 2c (PubChem 2018).
1. Eicosapentaenoic acid (EPA)
Figure 2a: Chemical structure of 20:5, n-3; EPA with 20 carbons and 5 double bonds on carbons numbered 5, 8, 11, 14 and 17 form the alpha end. Adapted from PubChem (2018).
2. Docosahexaenoic acid (DHA)
Figure 2b: Chemical structure of 22:6, n-3; DHA with 22 carbons and 6 double bonds on carbons numbered 4, 7, 10, 13, 16 and 19 from the alpha end. Adapted from PubChem (2018).
3. Docosapentaenoic acid (DPA)
Figure 2c: Chemical structure of 22:5, n-3; DPA with 22 carbons and 5 double bonds on carbons numbered 7, 10, 13, 16 and 19. Adapted from PubChem (2018).
Mechanism of action
1. Conversion of ALA to other PUFAs
Mammals are unable to synthesise omega-3 fatty acids on their own due to the lack of appropriate enzymes to insert a cis double bond at the n-3 position of the fatty acid (PubChem 2018). Despite that, mammals can obtain ALA from their dietary intake of plants and other animals and convert it into EPA, and then to DPA, and ultimately to DHA through desaturation and elongation processes as interpreted in Figure 3 (Bos et al. 2016).
Figure 3: Conversion of ALA to DHA involves elongation to add more carbon atoms to the chain using elongase enzymes and desaturation to add double bonds using appropriate desaturase enzymes at particular carbon atoms (n-6 desaturase for example indicates a double bond to be added, and only, at carbon numbered 6 (counted from the alpha end)). Adapted from Bos et al. (2016).
However, studies generally agree that this conversion process of ALA to DHA has below 5% efficiency in humans and this value can vary according to other fatty acids intakes like omega-6 PUFAs which may interfere with the process (Brenna 2000). Hence, omega-3 PUFAs are regarded as essential nutrients and reaching daily dietary intake of ALA alone is not enough to fulfil the recommended daily amounts of DHA, EPA and DPA. As a consequence, the recommended daily intakes are also established for the latter three (Table 1, Nutrient Reference Values for Australia and New Zealand 2014).
Table 1: Recommended daily intake of Linoleic acid (precursor for omega-6 fatty acids), alpha-linolenic acid and Long chains of omega-3 fatty acids (DHA+EPA+DPA) for children, adolescents & adults at different life stages, excluding pregnant women. Adapted from Nutrient Reference Values for Australia and New Zealand (2014).
2. Eicosanoids
EPA acts as a precursor for chemical messengers called eicosanoids. EPA derived eicosanoids play critical roles in the body such as cell signalling, inhibiting platelet aggregation and anti-inflammation (Angelo 2014). In a parallel cascade, as illustrated in Figure 4 (Oliver et al. 2010), Arachidonic acid, derived from the Omega-6 fatty acids, compete in the same pathway as EPA for the enzymes in the production of eicosanoids and these Arachidonic acid eicosanoids usually promotes inflammation (Oliver et al. 2010). Hence, eicosanoids from EPA and Arachidonic acids are said to be direct antagonists of each other and a balanced dietary intake of omega-3 and omega-6 is believed to be ideal in order for both pathways to synthesise their respective lipid mediators sufficiently.
Figure 4: Mechanisms of both omega-3 and omega-6 PUFA and their eicosanoids synthesis, one of which can be competitively inhibited by the other due to the competition for the same enzymes. Adapted from Oliver et al. (2010).
Health aspects of omega-3 fatty acids
1. Role of omega-3 in modern inflammatory diseases
Over the past decade, the intake of omega-6 (n-6) and omega-3 (n-3) PUFAs showed a significant increase in the (n-6) to (n-3) ratio of (~15 : 1), there being an increase in metabolism of omega-6 leading to more pro-inflammatory products (Patterson et al. 2012). This meant that our modern Western diet, which is geared towards a higher consumption of omega-6, proved to be the source of the pandemic increase in inflammatory disease like non-alcoholic fatty liver disease, obesity and rheumatoid arthritis as prevalence of these disease coincides with the increase in the ratio of (n-6) : (n-3) (Patterson et al. 2012). Thus, increasing omega-3 intake may reduce the incidence of these modern inflammatory diseases as they yield anti-inflammatory mediators.
2. Role of omega-3 in the brain and visual functions
Polyunsaturated Fatty Acids are important for the development and functioning of the brain and visual system. DHA acts as the predominant structural fatty acids in the phospholipids of cell membrane especially in the central nervous system and retina (Weiser, Butt and Mohajeri 2016). Because of its importance in the brain development and function, pregnant and nursing women are recommended to consume large amounts of DHA especially during their last trimester of pregnancy due to the rapid growth of the fetus’ brain (Weiser, Butt and Mohajeri 2016). Whilst in adults, studies have shown that the modern diet is lacking DHA and maintaining high levels of DHA is optimum as it has been suggested to have beneficial impacts on cognitive abilities (Weiser, Butt and Mohajeri 2016).
3. Role of omega-3 in cardiovascular disease
In the past, there was emerging evidence of the use of omega-3 fatty acids in the prevention of cardiovascular diseases due to observations of Eskimos’ and hunter-gathers’ high Omega-3 diet (from wild fishes and red meat) and their low incidence of cardiovascular disease (O'Keefe and Harris, 2000). In theory, this can be explained by the anti-inflammatory nature of omega-3 eicosanoids (Figure 4, Oliver et al. 2010). However, it raised questions to scientists and health professionals when randomised clinical trials provided no support for the hypothesis that fish oil supplements (which are high in omega-3) help in preventing cardiovascular disease, as seen in a meta-analysis conducted by Myung, Kwak and Lee (2012).
A study carried out on Inuit Greenlanders (Fumagalli et al. 2015), whose diets were rich in fat, particularly omega-3 PUFAs, suggested that the Inuit have developed genetic adaptations in metabolizing fatty acids. Thus, this evolutionary advantage may presumably be the reason why they are less susceptible to cardiovascular disease as Sanders (2015) suggested that the genetic adaptation has counteracted their significantly higher intakes of fatty acids.
Conclusion
Omega-3 Polyunsaturated Fatty Acids indeed play important roles in our bodies ranging from the functioning of the brain and eyes to producing important chemical messengers called eicosanoids. A balanced intake of omega-3 and omega-6 is important to ensure these mediators are synthesised sufficiently from both pathways whilst neither inhibits another and increasing omega-3 intake may reduce the incidence of inflammatory diseases. However, it is still debatable whether omega-3 PUFAs are the panacea of cardiovascular diseases once hoped.