INTRODUCTION

The very-long chain (VLC) omega-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA; 20 : 5n-3) and docosahexaenoic acid (DHA; 22 : 6n-3) promote early life development, optimal physiological function and healthy ageing [1–3,4▪]. Multiple observational studies indicate that higher intake and higher status of EPA and DHA are associated with lower risk of developing and dying from cardiovascular diseases, especially coronary heart disease, as reviewed elsewhere [5,6▪]; such studies continue to be published [7,8▪,9▪] as do meta-analyses supporting the cardioprotective action of EPA and DHA [10▪]. This action occurs as a result of beneficial modification of a range of cardiovascular risk factors, as demonstrated through many randomised controlled trials [11,12]. The health benefits of EPA and DHA go well beyond the cardiovascular system. It has been known for decades that DHA is vital for visual and cognitive development in early life [2]. More recently it has emerged that EPA and DHA promote embryo quality [13] and reduce the risk of preterm birth [14,15] and gestational diabetes [16,17▪]. They are associated with lower risk of developing type-2 diabetes [18▪] and improved outcomes in patients with type-2 diabetes [19▪,20▪]. EPA and DHA influence muscle protein turnover in ways that suggest that they help to promote maintenance of muscle mass in aging, disease and times of immobilisation [21,22▪,23▪]. They may have a role in preventing cognitive decline [24▪] and promoting mental well being [25▪,26▪]. EPA and DHA have multiple anti-inflammatory actions [27] and they are now known to be substrates for the synthesis of potent pro-resolution mediators that act to switch off on-going inflammation [28▪▪]. Hence, EPA and DHA may lower the risk of diseases that have an inflammatory component and, at high doses, they may be able to help manage such conditions [29]. EPA and DHA promote hepatic metabolic homeostasis [30,31] and there are studies showing that they can be used to reduce liver fat in people with hepatic steatosis [32▪]. There is some evidence that high dose VLC omega-3 PUFAs have survival benefits in those at risk of cardiovascular mortality [33▪], although the findings of such trials are inconsistent [34▪]. A number of recent studies have reported an inverse association between intake or status of EPA and DHA and risk of infection with SARS-CoV-2 and severity of COVID-19 [35▪–37▪], as discussed elsewhere [38]. Many national and international agencies have made recommendations for daily intake of EPA and DHA, typically between 200 and 1000 mg/day (see [1]); such recommendations are based mainly on the literature around cardioprotection but are designed to promote general good health in the population in recognition of the broad range of effects of these fatty acids. Some recommendations for DHA intake are higher for pregnant and lactating women, recognizing the importance of DHA to early life development. The American Heart Association recommends 2 to 4 g of EPA plus DHA daily to treat hypertriglyceridemia [39] and supports the use of a lower intake (1 g/day) for cardioprotection [40].

EPA and DHA are also well recognized to have a role in nutrition support of hospitalized patients [41]. They have been included in many “sip feeds” (oral nutrition supplements) used to complement dietary intake in several patient groups including the elderly, the frail and those with advanced cancer and in many enteral nutrition formulas used in clinical settings. Meta-analyses suggest that enteral formulas that include the VLC omega-3 PUFAs, along with other bioactive nutrients, are important in promoting improved clinical outcomes like reduced infection risk and shorter hospital stay in patients undergoing surgery for gastrointestinal cancer [42] and in critically ill patients [43,44]. VLC omega-3 PUFAs have been included as “fish oil” in intravenous lipid emulsions used as part of parenteral nutrition [45]. Recent meta-analyses of trials of fish oil containing intravenous lipid emulsions identify clinical benefits in hospitalized adults [46,47▪] including those who are critically ill [48]. Using modelling across different healthcare systems, the clinical benefits have been suggested to result in economic benefits [49▪]. There are also roles for intravenous VLC omega-3 PUFAs in neonates [50,51] and in those who need long-term nutrition support [52,53]. 

Box 1:

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TRADITIONAL SOURCES OF VERY-LONG CHAIN OMEGA-3 PUFAS ARE NOT SUSTAINABLE

The foregoing discussion indicates that VLC omega-3 PUFAs have important roles in public and patient health and are highly relevant to both public health nutrition and clinical nutrition. The main sources of EPA and DHA for human consumption are marine organisms, especially fatty fish. The World Health Organization, as well as many other agencies, recommends consumption of fatty fish once or twice a week to assure dietary intake of VLC omega-3 PUFAs. However, despite recommendations to do so, many people do not eat fatty fish and some types of fatty fish can be contaminated. Furthermore, fish stocks are declining and are at risk due to climate change; the current stocks of both farmed and wild fish already do not meet the needs for human nutrition [54], meaning the need for new dietary sources of bioactive omega-3 fatty acids is imperative. Supplements of VLC omega-3 PUFAs are a viable alternative to fish for many consumers, but the oil (“fish oil”) used in supplements is sourced from fish; therefore, this source of EPA and DHA is also not sustainable. This also holds for the oil used in products for oral, enteral or parenteral nutrition support.

The global production of fish oil in 2022 was approximately 1.25 million metric tons, the major global producers being Vietnam, Chile, Norway and Peru [55]. About half of fish oil comes from whole wild or farmed fish and about half from fish by-products. Anchovies, sardines, herring, capelin and similar fish species are the main source of fish oil; menhaden, tuna, salmon and cod are also used but make a smaller contribution [55]. Most standard fish oils contain about 30% EPA and DHA (i.e. 1 g of fish oil contains about 300 mg of EPA plus DHA), although fish oil concentrates and high quality, highly concentrated fish oil derivatives (e.g. near pure EPA ethyl esters) are produced as supplements and for pharmaceutical uses (e.g. for triglyceride lowering). The global production of EPA plus DHA in 2022 was estimated to be about 160 000 metric tons, mostly from fish [55]. Peru was the single biggest producer of EPA and DHA, accounting for about 20% of global production. Only about 15% of fish oil is directly used for human consumption; most (about 75%) is used in aquaculture and some (about 10%) in pet food. Aquaculture is an increasing contributor to the global fish supply now accounting for almost 50% of the live weight of fisheries capture [55]. The reliance of aquaculture on fish oil has decreased over the last 20 years as plant oils have been increasingly used as a partial replacement for fish oil in aquaculture, especially for salmon farming. However, this decreased reliance is offset by the huge increase in aquaculture, so that aquaculture uses about the same proportion of the global fish oil supply that it used in 2000 [55]. It is forecast that demand for EPA and DHA by all main sectors (aquaculture, human uses, pet food) will increase year-on-year. This demand may not be met because of insufficient fisheries catch due to reduction in fish stocks from overfishing and climate change. Hence alternatives sources of EPA and DHA to fish need to be seriously considered and their potential explored. Such alternatives could be used directly for human consumption as foods, depending upon their origin, or through the oil being incorporated into functional foods or used in supplements. Alternatively, the oil could be used in aquaculture [56] or for pet food applications, sparing fish oil for human use.

WHAT ARE THE ALTERNATIVES TO FISH AS A SOURCE OF VLC OMEGA-3 POLYUNSATURATED FATTY ACIDS?

Alternative sources of EPA and DHA to fish are already available and likely more will become available in the next years. Fish do not produce much EPA and DHA themselves but acquire these fatty acids in their diet, with phytoplankton being the predominant global producers of EPA and DHA; microalgae are a type of phytoplankton. Heterotrophic microalgal species such as Schizochytrium, Aurantiochytrium, Thraustochytrium, and Crypthecodinium cohnii are essential producers of DHA. In wildtype Schizochytrium, Aurantiochytrium and Crypthecodinium cohnii strains, DHA content ranges from 43 to 55%, 24 to 53% and 24 to 54% of the total fatty acids, respectively [57]. Photosynthetic microalgae, such as Phaeodactylum tricornutum, Nannochloropsis oceanica and Dunaliella salina primarily produce EPA, which can reach up to 36%, 42%, and 46% of the total fatty acids, respectively [57,58]. Genetic engineering has been used to increase the EPA and DHA contents of different microalgae species and is discussed in detail elsewhere [59▪]. Nevertheless, many wild type microalgae produce oils that contain much more DHA than is present in fish oil (20–55% of fatty acids) and some also contain EPA. DHA-rich algal oils have been used in the infant formula industry for decades now providing DHA at a concentration similar to that seen (or present) in human breast milk and supported by research showing advantages for visual and cognitive development compared with formula not containing DHA [2]. Algal oils are also used for supplements for vegetarian or vegan consumers. Thus algal oils have the potential to at least partially replace fish oil for the wider supplement market and for uses in functional foods and products for clinical applications, such as nutrition support. The VLC omega-3 PUFAs in algal oils are readily bioavailable and increase EPA and DHA status in blood and blood cells just as fish oil does [60,61]. Algal oils also have the same impact on cardiovascular risk factors as VLC omega-3 PUFAs from fish oil; for example, a meta-analysis of 11 randomized controlled trials (RCTs) using algal oil in adults identified a significant 0.2 mmol/l reduction in fasting triglyceride concentrations with no evidence of heterogeneity [62]. The size of this reduction is similar to that seen with fish oil. There was also an increase in both low- and high-density lipoprotein cholesterol [62], effects also seen with fish oil [12] and with DHA [11].

Terrestrial plants do not typically synthesize VLC omega-3 PUFAs. However, two oilseed crops, Camelina sativa and Brasscia napus (rapeseed, also known as canola) have been successfully genetically modified for EPA and DHA production and represent a promising sustainable and clean plant source of these fatty acids. Several genetically modified C. sativa lines have been generated, some producing high EPA (up to 30% of fatty acids) and relatively little DHA, some high DHA and modest EPA (12 and 3% of fatty acids, respectively), and others producing high amounts of both (e.g. EPA 12% and DHA 14% or EPA 11% and DHA 8%) [63,64]. Genetically modified canola lines accumulating ∼7% EPA and ∼1% DHA or ∼1% EPA and ∼10% DHA have been developed [65]. Oils from genetically modified canola and camelina lines have been studied recently in humans [66–68]. In a study in healthy participants, DHA containing oil from genetically modified canola (∼1% EPA and ∼10% DHA) was shown to dose-dependently increase plasma EPA and DHA in the hours following consumption, to dose-dependently increase whole blood EPA and DHA after 4 weeks of daily consumption, and to dose-dependently increase erythrocyte EPA and DHA after 16 weeks of daily consumption [66]. In all studies, increases in DHA concentration were higher than increases in EPA concentration, reflecting the much higher content of DHA in the oil. Oil from genetically modified camelina containing 11% EPA and 8% DHA was compared with fish oil containing 14% EPA and 12% DHA in two trials [67,68]. The first trial demonstrated that the postprandial appearance of EPA and DHA into plasma lipids did not differ between fish oil and the camelina oil in either young or older adults [67], suggesting equivalent bioavailability and metabolic handling of VLC omega-3 PUFAs from the two oils. The second trial demonstrated no differences in incorporation of EPA and DHA into plasma lipids (phospholipids, triglycerides, cholesteryl esters) and erythrocytes over 8 weeks of daily supplementation with the two oils delivering 450 mg EPA+DHA per day [68]. These studies highlight the potential of the oil from genetically modified C. sativa as a sustainable alternative to fish oil.

IS THERE A ROLE FOR PRECURSOR PLANT-SOURCED OMEGA-3 POLYUNSATURATED FATTY ACIDS?

Many plants produce 18-carbon PUFAs as an end product of de novo fatty acid synthesis. Hence, α-linolenic acid (ALA; 18 : 3n-3) is found in foods of plant origin such as green leaves, seeds and nuts and in some plant oils including soybean and canola oils. Flaxseeds and flaxseed oil are a very rich source of ALA, which contributes about 55% of the fatty acids present. Chia seeds are also rich in ALA (60% of fatty acids). ALA has some biological properties in its own right; for example, it lowers total and low-density lipoprotein cholesterol [69▪] and is a precursor to oxylipins [70▪] some of which are bioactive [71▪▪]. There is a pathway by which ALA is converted to EPA and on to DHA (Fig. 1), although the extent of the activity beyond docosapentaenoic acid (i.e. to DHA) is uncertain [72]. The first step of that pathway is catalysed by delta-6 desaturase and produces stearidonic acid (SDA; 18 : 4n-3). This reaction is the rate limiting step of the pathway and is considered to have low activity in many individuals so restricting the conversion of ALA to EPA. There has been a long history of human research with ALA given as a supplement (e.g. flaxseed oil capsules) or in foods (e.g. muffins made using flaxseed oil as the fat source). This research was comprehensively reviewed several years ago [72]; the major conclusions were that increasing ALA intake results in increased levels of EPA, but not of DHA, in blood lipids and blood cells and that high intakes of ALA can mimic some of the effects of EPA+DHA but the size of the effects seen is smaller than seen with EPA and DHA. A similar conclusion was reached in a recent meta-analysis of trials that compared ALA with EPA+DHA and reported on blood lipids [73]: the analysis identified that ALA decreased low-density lipoprotein cholesterol while EPA and DHA lowered triglycerides and increased total, low-density lipoprotein and high-density lipoprotein cholesterol. Furthermore, compared with ALA, supplementation with EPA and/or DHA showed a greater reduction in triglycerides and a greater increase in high-density lipoprotein cholesterol. This difference in potency between ALA and the VLC omega-3 PUFAs probably relates to the extent of conversion of ALA to EPA and suggests that the main role of ALA is to act as a precursor for synthesis of the longer chain, more unsaturated omega-3 PUFAs. This does not rule out roles for ALA-derived oxylipins or a role for ALA in limiting the conversion of the omega-6 PUFA linoleic acid (18 : 2n-6) to its bioactive derivative arachidonic acid (20 : 4n-6). A recent meta-analysis of 41 prospective cohort studies showed that dietary ALA intake is positively associated with a reduced risk of mortality from all causes, cardiovascular disease and coronary heart disease, and that higher blood levels of ALA are positively associated with a reduced risk of all cause and coronary heart disease mortality [74▪]. It is unclear whether these effects are due to ALA itself or to EPA formed from ALA. The potential for broad ranging health impacts of ALA have been recently reviewed [75▪▪].

FIGURE 1:

Pathway of conversion of α-linolenic acid to docosahexaenoic acid, showing sites of entry of preformed omega-3 fatty acids from foods or supplements. ALA, α-linolenic acid; DHA, docosahexaenoic acid; DPA, docosapentaenoic acid; EPA, eicosapentaenoic acid; ETA, eicosatetraenoic acid; SDA, stearidonic acid; Italicised names in parentheses after enzyme names are the genes encoding the protein.

If the main reason for limited biological action of ALA is low activity of delta-6 desaturase, then the omega-3 product of that enzyme, SDA, could be a superior alternative as a plant-based health-promoting omega-3 PUFA. Certainly, SDA is a better precursor for EPA synthesis than ALA; this was demonstrated many years ago by James et al.[76] who showed that 1.5 g SDA per day for 6 weeks increased plasma and red blood cell EPA to a greater extent (approximately 5-fold) than 1.5 g ALA per day. Some plant seed oils naturally contain SDA including those from Echium plantagineum, where SDA makes up about 12% of fatty acids, and from Buglossoides arvensis, now commercially known as Ahiflower, where SDA makes up about 20% of fatty acids. These oils also contain quite a lot of ALA (about 33% and 45% of fatty acids, respectively) as well as the omega-6 PUFA γ-linolenic acid (GLA; 18 : 3n-6). Older studies with Echium oil or near-pure SDA reported qualitatively similar but quantitatively weaker effects than those reported for EPA+DHA (reviewed in [77,78]), again suggesting that SDA acts largely through conversion to EPA. However, there are likely to be novel oxylipins produced from SDA that have biological activity [79]. There has been recent interest in Ahiflower oil. In a study in C57Bl6 mice diets rich in flaxseed oil, Ahiflower oil or fish oil all attenuated colitis-induced mucosal inflammation and induced pro-resolution mediators with the pattern of the latter being different according to the oil fed [80]. A human trial involving different doses of Ahiflower oil showed dose-dependent increases in SDA, its derivative eicosatetraenoic acid (20 : 4n-3) and EPA in plasma and in blood mononuclear cells, but no increase in DHA [81]. Production of the anti-inflammatory cytokine interleukin 10 by lipopolysaccharide stimulated whole blood was enhanced by Ahiflower oil; other cytokines were unaffected [81]. Incubation of M2 macrophages with SDA, eicosatetraenoic acid or EPA resulted in increased interleukin 10 production [81]. Intravenous infusion of an experimental lipid emulsion comprising Ahiflower oil, olive oil and coconut oil (50 : 25:25 vol/vol/vol) was tested in C57Bl6 mice with the comparators being commercially available 100% soybean oil and 100% fish oil emulsions [82▪▪]. The infusion period was 7 days and the outcomes were tissue cytokines, markers of whole-body and hepatic glucose metabolism, immune cells, lipid mediators and intestinal microbiota. Remarkably, the effects of the Ahiflower oil containing lipid emulsion were greater than those of the fish oil emulsion. Liver and muscle interleukin 10 and the ratio of interleukin 10 to interleukin 6 were higher with Ahiflower oil than with either soybean oil or fish oil. Both Ahiflower and fish oils resulted in greater hepatic insulin receptor abundance and in similar HOMA-IR, a marker of insulin resistance. Ahiflower oil resulted in greater hepatic insulin receptor substrate 2 expression and maintained normal hepatic glycogen content. The percentages of liver helper T cells expressing interferon-γ and interleukin 17 were higher with Ahilflower oil and liver macrophages had phenotypes indicative of immune priming. Ahiflower oil lipid emulsion resulted in elimination of the microinvasive bacterium Akkermansia muciniphila from the intestinal mucosa. Hepatic lipid mediators were altered according to the lipid emulsion used, with Ahiflower oil lipid emulsion resulting in higher 9(S)-hydroxy-octadecatrienoic acid, a 15-lipoxygenase metabolite of ALA. In an interesting experiment, co-administration of 9(S)- and 13(S)-hydroxy-octadecatrienoic acids along with the soybean oil lipid emulsion mimicked many of the immunomodulatory effects of the Ahiflower oil containing lipid emulsion, suggesting that oxylipins are responsible for mediating the effects seen [82▪▪]. Recent in vitro experiments with human T cells identified that having a lower ratio of linoleic acid to ALA in the culture medium favoured production of ALA- and EPA-derived oxylipins including both 9(S)- and 13(S)-hydroxy-octadecatrienoic acid [83▪].

Although Echium and Ahiflower oils naturally contain SDA, soybean has been genetically modified to produce an oil that contains about 20% SDA; this oil also contains about 6.5% GLA which is absent from wild type canola oil. Older studies demonstrated that this oil increases erythrocyte EPA and omega-3 index in humans, but does not increase DHA [84,85].

IS THERE A ROLE FOR POLYUNSATURATED FATTY ACIDS OTHER THAN OMEGA-3 POLYUNSATURATED FATTY ACIDS?

The foregoing discussion has focussed on plant sources of EPA and DHA or of the precursor omega-3 PUFAs ALA and SDA. However, it may be that PUFAs other than omega-3s have similar effects and therefore could have similar roles in promoting health and managing disease if they can be made available and consumed in sufficiently high amounts. As mentioned above SDA-rich oils also contain GLA; however, there are even richer sources of GLA, including evening primrose (Oenothera biennis) oil and borage (sometimes called Starflower) (Borago officinalis) oil, which contain 12% and 25% GLA, respectively. There is a history of research on GLA as reviewed elsewhere [86] and it, and its metabolic derivative dihomo-γ-linolenic acid (20 : 3n-6), have potential applications to health and well being [86,87▪].

Another PUFA of interest is pinolenic acid (PLA), an unusual delta-5-nonmethylene-interrupted fatty acid found in pine nut oil (PNO). PLA comprises 14–19% of total fatty acids in many PNOs (see [88▪] for details). PLA is metabolised to delta-7 eicosatrienoic acid (ETA). The literature on PNO, PLA and ETA was recently comprehensively reviewed [88▪]. PNO, PLA and ETA have all been shown to have anti-inflammatory actions with qualitatively similar effects to EPA and DHA and with similar mechanisms of action involving decreased activity of the pro-inflammatory transcription factor NF-κB and decreased production of prostaglandin E2 (see [88▪] for references). A recent cell culture study indicated that the anti-inflammatory effects of PLA in endothelial cells are mediated by its conversion to ETA, since these effects were mitigated by silencing the elongase gene that encodes the enzyme that converts PLA to ETA [89]. Other research involving cell culture, animal feeding studies and a limited number of human trials indicates that PNO and PLA improve blood lipids and insulin sensitivity, modulate immune function, and control appetite and body weight (see [88▪] for references). PLA is most likely also a substrate for oxylipins. Thus, PNO and its bioactive PUFA constituent PLA, may be sustainable plant-sourced alternatives to VLC omega-3 PUFAs for human health promotion and disease management. More research on this is needed. There are also other plant-sourced, nonomega-3 PUFAs of interest; some of these are discussed elsewhere [88▪].

SUMMARY AND CONCLUSION

The VLC omega-3 PUFAs EPA and DHA act through multiple interlinking mechanisms to influence cell function and tissue physiology. In general, these actions serve to promote optimal development, optimal function and healthy ageing. EPA and DHA decrease the risk for common noncommunicable diseases and have a role in management of some diseases and in artificial nutrition support of various patient groups. EPA and DHA are sourced mainly from fish. This is not sustainable due to declining fish stocks and climate change. Furthermore, human uses for fish oil compete with uses in aquaculture, which is the main application, and pet food, both of which will increase in coming years. Therefore, there is an immediate need to identify nonfish, sustainable sources of EPA and DHA. The two most likely alternatives are algal oils and oils from genetically modified terrestrial plants. Algal oils with significant amounts of EPA and/or DHA are available and have been used in the infant formula industry for decades and more recently as VLC omega-3 PUFA supplements for vegetarian and vegan consumers. Human trials show that such algal oils mimic the effects of fish oils on health-related biomarkers. Clearly there is a place for such oils in further human applications. Canola and camelina have been genetically modified to produce VLC omega-3 PUFAs; the amounts of EPA and DHA present in the oil from some camelina lines are similar to the amounts present in standard fish oils. Human trials with oils from genetically modified canola and camelina demonstrate acute and chronic increments in EPA and DHA in blood pools similar those seen with fish oil providing similar amounts of EPA and DHA. As such, these oils would be expected to have the same biological and health impacts as EPA and DHA from fish oils. Thus, both algal oils and oils from genetically modified plants are potential alternatives to marine-sourced EPA and DHA. Barriers to use of the oils from the genetically modified plants include cost, regulatory issues and acceptability by the public, at least in some geographies [90].

As an alternative strategy to nonfish sourced oils containing EPA and DHA, the endogenous pathway of EPA (and DHA) synthesis could be used to enhance EPA and possibly DHA status through increased supply of plant-sourced precursor omega-3 PUFAs. Increased intake of ALA does increase EPA levels in blood pools and results in qualitatively similar biological effects to those of EPA and combinations of EPA and DHA. These are quantitatively smaller effects, most likely due to the limited conversion of ALA to EPA, even at high ALA intakes. ALA conversion to EPA is increased in humans by lowering linoleic acid intake [91], so one strategy to maximize the effect of increased ALA intake would be to simultaneously lower linoleic acid intake. Judicious use of various plant oils in the diet could help to achieve this, and the important role of ALA as a precursor for EPA should not be dismissed. ALA is also a precursor of bioactive oxylipins so it may have effects and benefits separate from its conversion to EPA. It is important to recognize that even significantly increased intake of ALA does not appear to result in enhanced DHA status, at least in the population sub-groups studied, and therefore ALA may not be a real alternative for roles held exclusively by DHA, such as in early life visual and cognitive development. There are plant seed oils naturally rich in SDA, the product of delta-6 desaturation of ALA. SDA increases EPA status much more than ALA when given to humans at the same dose, but, like ALA, does not increase DHA status. SDA has qualitatively similar effects to EPA and combinations of EPA and DHA, but these are greater than the effects of ALA (at the same intake level). Recent experimental studies with oil from a commercially grown crop that is rich in SDA, Ahiflower oil, have reported remarkable effects which might result from its high content of ALA, SDA and GLA. The foregoing discussion has focussed on nonfish alternative sources of EPA and DHA and on plants as sources of the precursor omega-3 PUFAs ALA and SDA. Although there is an obvious emphasis on finding plant-sourced omega-3 PUFAs as an alternative to fish-sourced, it may be that PUFAs from other families have desirable functional properties that would establish them as potential alternatives. GLA has already been mentioned. PNO and its constituent PUFA PLA, which is not an omega-3 PUFA, have similar functional effects to VLC omega-3 PUFAs in cell and animal models and in human studies and there are other possibilities [88▪].

More research on algal oils, oils from genetically modified seed crops, Ahiflower oil and other sources of SDA, and nonomega-3 oils including PNO, and on their constituent fatty acids, is needed in order to fully appreciate the spectrum of possibilities for multiple plant-sourced, sustainable and clean alternatives to fish-sourced VLC omega-3 PUFAs.

Acknowledgements

E.J.B. is funded by the NIHR Southampton Biomedical Research Centre. E.J.B. wishes to thank Prof. Philip Calder for a discussion on the content of this article.

Financial support and sponsorship

None.

Conflicts of interest

E.J.B. has no conflicts of interest to declare.

REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

▪ of special interest

▪▪ of outstanding interest

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