Omega-3 Source Matters: Comparative Lipid Signatures and Quantitative Distribution of EPA/DHA Across Marine Resources

The marine unicellular red alga Rhodosorus marinus is a promising source of the valuable phycobiliprotein phycoerythrin and essential omega-3 polyunsaturated fatty acids (PUFAs), yet the environmental triggers for their optimal co-production remain to be fully elucidated. This study was conducted to investigate the effects of thermal and photic stress in terms of maximizing the yield of these high-value bioactive compounds. R. marinus was cultivated under a range of temperatures (18-24 °C) and light intensities (100-335 µmol photons m-2 s-1) to assess its physiological and biochemical responses, particularly focusing on lipid accumulation. This study investigates the effects of thermal (18-24 °C) and photic (100-335 µmol photons m-2 s-1) stress on the concurrent production of the valuable phycobiliprotein, phycoerythrin (PE), and essential omega-3 polyunsaturated fatty acids (PUFAs) in the marine red microalga Rhodosorus marinus. Fatty acid profiles were quantified using gas chromatography (GC), while pigment content was assessed via spectrophotometry. Statistical analyses, including one-way ANOVA and Tukey's post hoc test, were employed to determine the significance of environmental effects. Our results demonstrate that a mild hypothermic condition of 18 °C significantly enhanced the production of eicosapentaenoic acid (EPA) compared to higher temperatures. Conversely, cell density was maximized at 22 °C. Under the 18 °C thermal regime, lower light intensities (100-185 µmol photons m-2 s-1) promoted a superior synthesis of both bioactive lipids and pigments. In conclusion, the strategic application of mild hypothermia combined with moderate light intensity is an effective approach to substantially boost the metabolic yield of high-value compounds in R. marinus, highlighting its potential as a sustainable source for nutraceutical and pharmaceutical applications.

Membrane levels of docosahexaenoic acid (DHA), an essential omega-3 polyunsaturated fatty acid (ω-3 PUFA), are decreased in common neuropsychiatric disorders. DHA modulates key cell membrane properties like fluidity, thereby affecting the behaviour of transmembrane proteins like G protein-coupled receptors (GPCRs). These receptors, which have special relevance for major neuropsychiatric disorders have recently been shown to form dimers or higher order oligomers, and evidence suggests that DHA levels affect GPCR function by modulating oligomerisation. In this study, we assessed the effect of membrane DHA content on the formation of a class of protein complexes with particular relevance for brain disease: adenosine A2A and dopamine D2 receptor oligomers. Using extensive multiscale computer modelling, we find a marked propensity of DHA for interaction with both A2A and D2 receptors, which leads to an increased rate of receptor oligomerisation. Bioluminescence resonance energy transfer (BRET) experiments performed on living cells suggest that this DHA effect on the oligomerisation of A2A and D2 receptors is purely kinetic. This work reveals for the first time that membrane ω-3 PUFAs play a key role in GPCR oligomerisation kinetics, which may have important implications for neuropsychiatric conditions like schizophrenia or Parkinson’s disease.

A review was made of the literature concerning the metabolism of fatty acids in the dairy cow, and the potential of increasing the content of the essential fatty acids eicosapentaenoic acid (EPA; C20:5) and docosahexaenoic acid (DHA; C22:6) in cows' milk. EPA and DHA are two n-3 polyunsaturated fatty acids, which can be synthesised from a-linolenic acid (LNA, C18:3). Both EPA and DHA have anti-thrombotic and anti-carcinogenic effects. The UK Department of Health has recommended that the daily human intake of total n-3 PUFA should be 0.2 g/d, which is approximately double the current average intake. The richest source of dietary EPA and DHA is marine products, but the consumption of fish in the UK is declining. Milk fat consumption constitutes 30% of total fat consumption in the UK diet, and so enhancing the concentration of EPA and DHA in milk fat could be an effective means of increasing the consumption of these fatty acids in the UK. Grass and linseed are rich sources of LNA for dairy cows, while fish oil or marine algae are the richest sources of EPA and DHA. However, a large proportion of these fatty acids ( ca 0.9) are hydrogenated to more saturated fatty acids by the microorganisms in the rumen. The proportion of absorbed n-3 PUFA is therefore only about 7 g/kg ingested n-3 PUFA. Absorbed EPA and DHA are transported around the body as phospholipids, associated with the high-density lipoprotein fraction of the plasma. This fraction is not a good substrate for lipoprotein lipase, which is the enzyme in the mammary gland that removes fatty acids from the circulation for incorporation into milk fat. The uptake by the mammary gland of absorbed EPA and DHA is therefore extremely low. The concentration of EPA and DHA in milk fat therefore remains low even when the diet is enriched with these fatty acids. It is possible that the EPA and DHA present in the milk arise from de novo synthesis of these acids from LNA in the mammary gland. However, while EPA is synthesised from LNA, there appears to be a block on the subsequent synthesis of DHA from EPA. EPA and DHA are not stored in adipose tissue triacylglycerols, and they are not used for oxidative metabolism. There is therefore little competition for circulating EPA and DHA between the mammary gland and adipose tissue, or between secretion and oxidation. There is some potential storage of these acids in the phospholipids of muscle tissue and adipose tissue. Grass is a rich source of LNA, and the LNA content of milk can be enhanced by increasing the herbage content of the diet. This potentially provides more precursors of EPA and DHA. However, increasing the proportion of forage in the diet also tends to increase the extent of rumen biohydrogenation of PUFA as this process is encouraged by higher rumen pH and reduced propionate production. Including either fish oil or some species of marine microalgae in the diet increases the EPA and DHA content of milk. However, these oils can adversely affect rumen function, so that total dry matter intake and milk fat content are reduced. Feeding fish oils to ruminant animals may also not be a sustainable practice in the longer-term. Protecting marine oils from rumen biohydrogenation should prevent the adverse effects on rumen function. However, the evaluation of a protected marine microalgae product suggested that the protection was far from complete, and a reliable means of treating algae to protect it from rumen metabolism still awaits development. Further enhancement of the EPA and DHA content of cows' milk requires more research. Issues, which need to be addressed, are the development of a suitable oil supplement, and a reliable means of protecting it from rumen biohydrogenation. A means of transporting the absorbed EPA and DHA in the circulation so that it is readily taken up by the mammary gland for incorporation into the milk fat also needs to be developed. Changes in the marketing of milk that has been improved in this way would also be required to meet the increased cost of producing this nutritionally enhanced milk.

Deficiency in essential omega-3 polyunsaturated fatty acids (PUFAs), particularly the long-chain form of docosahexaenoic acid (DHA), has been linked to health problems in mammals, including many mental disorders and reduced cognitive performance. Insects have very low long-chain PUFA concentrations, and the effect of omega-3 deficiency on cognition in insects has not been studied. We show a low omega-6:3 ratio of pollen collected by honey bee colonies in heterogenous landscapes and in many hand-collected pollens that we analyzed. We identified Eucalyptus as an important bee-forage plant particularly poor in omega-3 and high in the omega-6:3 ratio. We tested the effect of dietary omega-3 deficiency on olfactory and tactile associative learning of the economically highly valued honey bee. Bees fed either of two omega-3-poor diets, or Eucalyptus pollen, showed greatly reduced learning abilities in conditioned proboscis-extension assays compared with those fed omega-3-rich diets, or omega-3-rich pollen mixture. The effect on performance was not due to reduced sucrose sensitivity. Omega-3 deficiency also led to smaller hypopharyngeal glands. Bee brains contained high omega-3 concentrations, which were only slightly affected by diet, suggesting additional peripheral effects on learning. The shift from a low to high omega-6:3 ratio in the Western human diet is deemed a primary cause of many diseases and reduced mental health. A similar shift seems to be occurring in bee forage, possibly an important factor in colony declines. Our study shows the detrimental effect on cognitive performance of omega-3 deficiency in a nonmammal.

Back to table of contents Previous article Next article Letter to the EditorFull AccessLack of Seasonal Mood Change in IcelandersJERRY COTT, PH.D., and JOSEPH R. HIBBELN, M.D., JERRY COTTSearch for more papers by this author, PH.D., and JOSEPH R. HIBBELNSearch for more papers by this author, M.D., Bethesda, Md.Published Online:1 Feb 2001https://doi.org/10.1176/appi.ajp.158.2.328AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: The finding of a lack of seasonal affective disorders in Iceland, from a study by Magnusson et al. (1), is striking, especially when compared with findings from other countries of similar latitude. One reason for this finding may be the high content of fish in the Icelandic diet (225 lb per person per year) (2). The authors noted a similar and unexpected previous finding of a low prevalence of seasonal affective disorders in Japan, which also has a high per capita intake of fish (147 lb per person per year) (2). Despite a greater exposure to light in winter, most other countries have higher rates of seasonal affective disorder. Per capita fish intake in pounds per person per year is as follows: Canada, 51; Finland, 72; Netherlands, 25; Sweden, 59; Switzerland, 30; United Kingdom, 41; and the United States, 48 (2). We suggest that the difference in the prevalence of seasonal affective disorders between Icelandic descendants and other citizens in Winnipeg may be due to a cultural tradition of fish consumption, rather than differences in genetic predisposition. Our proposition is consistent with the finding in a cross-national analysis that greater seafood consumption predicted lower prevalence rates of major depression (r=–0.84, p<0.005) (3).Seafood is rich in the omega-3 essential fatty acids eicosapentaenoic and docosahexaenoic acids. Docosahexaenoic acid is selectively concentrated in synaptic membranes, where it has a crucial role in maintaining the biophysical properties determining receptor conformation (4). Mechanisms through which eicosapentaenoic and docosahexaenoic acids may diminish depressive symptoms have recently been reviewed (5) and include modulation of serotonin turnover, phosphoinositol-mediated signal transduction, and L-type calcium channel regulation. Depletions of docosahexaenoic acid in RBC phospholipid membranes have been reported in depression (6). A placebo-controlled study in bipolar disorder (7) showed that supplementation with docosahexaenoic and eicosapentaenoic acids had marked mood-stabilizing and antidepressant activity. Thus, high levels of fish consumption should be considered a potential etiology for the finding of a lack of seasonal affective disorder among the Icelandic population.

The cyclooxygenases (COX-1 and COX-2) are membrane-associated heme-containing homodimers that generate prostaglandin H(2) from arachidonic acid (AA). Although AA is the preferred substrate, other fatty acids are oxygenated by these enzymes with varying efficiencies. We determined the crystal structures of AA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) bound to Co(3+)-protoporphyrin IX-reconstituted murine COX-2 to 2.1, 2.4, and 2.65 A, respectively. AA, EPA, and docosahexaenoic acid bind in different conformations in each monomer constituting the homodimer in their respective structures such that one monomer exhibits nonproductive binding and the other productive binding of the substrate in the cyclooxygenase channel. The interactions identified between protein and substrate when bound to COX-1 are conserved in our COX-2 structures, with the only notable difference being the lack of interaction of the carboxylate of AA and EPA with the side chain of Arg-120. Leu-531 exhibits a different side chain conformation when the nonproductive and productive binding modes of AA are compared. Unlike COX-1, mutating this residue to Ala, Phe, Pro, or Thr did not result in a significant loss of activity or substrate binding affinity. Determination of the L531F:AA crystal structure resulted in AA binding in the same global conformation in each monomer. We speculate that the mobility of the Leu-531 side chain increases the volume available at the opening of the cyclooxygenase channel and contributes to the observed ability of COX-2 to oxygenate a broad spectrum of fatty acid and fatty ester substrates.

This paper examines the process and evidence used to create the Dietary Reference Intake (DRI) of alpha-linolenic acid (ALA) and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) for Koreans. ALA (18:3n3) is an essential fatty acid, and EPA and DHA are known to have beneficial effects on cardiovascular disease risk and reduction of triglyceride levels. Various international organizations have suggested dietary recommendations for n-3 polyunsaturated fatty acids (PUFAs), including ALA, EPA, and DHA. A DRI for Koreans was established for the first time in 2020, specifically for the adequate intake (AI) of ALA and EPA + DHA. This recommendation was based on the average intake of ALA and EPA + DHA from the Korea National Health and Nutrition Examination Survey 2013–2017. For Korean infants, the AI of ALA and DHA was based on the fatty acid composition of maternal milk. Estimated average requirement and a tolerable upper intake level have not been set for n-3 PUFA due to insufficient evidence. In addition, the intake level of n-3 PUFA for prevention of chronic disease has also not been determined. Future studies and randomized controlled trials are required to establish the UL and to define the level for disease prevention.

Determination of three Unsaturated Fatty Acids in Pressure Ulcer Rats Using A UPLC-MS/MS Method

Association of Polyunsaturated Fatty Acids and Vitamin B6 with Inflammation in Adults from the National Health and Nutrition Examination Survey (NHANES) 2003–2004

Supplementation with monounsaturated or ω-3 polyunsaturated fatty acids ( n-3 PUFA) can lower resting blood pressure (BP) and reduce the risk of cardiovascular events. The independent contributions of the n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on BP, and the mechanisms responsible, are unclear. We tested whether EPA, DHA, and olive oil (OO), a source of monounsaturated fat, differentially affect resting hemodynamics and muscle sympathetic nerve activity (MSNA). Eighty-six healthy young men and women were recruited to participate in a 12-wk, randomized, double-blind trial examining the effects of orally supplementing ~3 g/day of EPA ( n = 28), DHA ( n = 28), or OO ( n = 30) on resting hemodynamics; MSNA was examined in a subset of participants ( n = 31). Both EPA and DHA supplements increased the ω-3 index ( P < 0.01). Reductions in systolic BP were greater [adjusted intergroup mean difference (95% confidence interval)] after DHA [-3.4 mmHg (-0.9, -5.9), P = 0.008] and OO [-3.0 mmHg (-0.5, -5.4), P = 0.01] compared with EPA, with no difference between DHA and OO ( P = 0.74). Reductions in diastolic BP were greater following DHA [-3.4 mmHg (-1.3,-5.6), P = 0.002] and OO [-2.2 mmHg (0.08,-4.3), P = 0.04] compared with EPA. EPA increased heart rate compared with DHA [4.2 beats/min (-0.009, 8.4), P = 0.05] and OO [4.2 beats/min, (0.08, 8.3), P = 0.04]. MSNA burst frequency was higher after DHA [4 bursts/min (0.5, 8.3), P = 0.02] but not OO [-3 bursts/min (-6, 0.6), P = 0.2] compared with EPA. Overall, DHA and OO evoked similar responses in resting BP; however, DHA, but not OO, increased peripheral vasoconstrictor outflow. These findings may have implications for fatty acid supplementation in clinical populations characterized by chronic high BP and sympathetic overactivation. NEW & NOTEWORTHY We studied the effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and olive oil supplementation on blood pressure (BP) and muscle sympathetic nerve activity (MSNA). After 12 wk of 3 g/day supplementation, DHA and olive oil were associated with lower resting systolic and diastolic BPs than EPA. However, DHA increased MSNA compared with EPA. The reductions in BP with DHA likely occur via a vascular mechanism and evoke a baroreflex-mediated increase in sympathetic activity.

Food for thought: essential fatty acid protects against neuronal deficits in transgenic mouse model of AD.

Objective Dietary eicosapentaenoicacid (EPA) and docosahexaenoic acid (DHA) are found in the highest concentrations in fish and seafood. As important nutrients for brain and eye development and function, their consumption levels are of public health interest, especially in children. This study was conducted toexamine children’sreported consumption of fish and shellfish as well as EPA and DHA intake. Methods Secondary analysis of dietary intake (24-hour recall) and Food Frequency Questionnaire (FFQ) data ascertaining habitual fish and seafood intake of 2-18 year olds (N=13,441) participating in the 2003-2004, 2005-2006, 2007-2008, and 2009-2010 National Health and Nutrition Examination Survey (NHANES). All analyses were survey design corrected and weighted (one-day dietary intake weight) and conducted for the total sample by age group (2-5, 6-11, 12-18 year olds); analysis was conducted for EPA and DHA combined. Results Less than 50% of the children consumed fish (49.0%) or shellfish (35.9%) and only 0.3% of the population consumed fish high in EPA and DHA. Children consumed, on average, less than 25% of the recommended amount of EPA and DHA. The foods that contributed the highest average of EPA and DHA to the diet were canned sardines, cooked salmon, and fried carp. The EPA and DHA-containing foods consumed by at least one child in the population with the highest EPA and DHA densities were sturgeon roe, baked/broiled mackerel, and sardines. Conclusions Results of this nationally representative study of 2-18 year olds show that children had suboptimal consumption of fish and shellfish, and EPA and DHA reported intakes were much below the recommended amounts. Further research is needed to examine the barriers to higher fish and shellfish consumption and to develop effective ways to increase children’s dietary intake of EPA and DHA. Introduction The human body has the ability to elongate and desaturate alphalinolenic acid (ALA) to the long chain omega-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) [1-3]. However, Western diets are low in n-3 PUFAs, specifically ALA found in plant oils and EPA and DHA found in oily fish [4-6]. In the United States (US), the mean intake of n-3 PUFAs is 0.7% of total energy consumed [7], and intake in adults is very low with a median intake of EPA and DHA only contributing 0.05% of total dietary energy[7, 8]. Even individuals with low fish consumption have greater n-3 PUFA status than those individuals who do not consume any fish [9]. Western diets low in n-3 PUFAs and high in n-6 PUFAs contribute to poor brain development and function [4, 10]. It is uncertain if the rate of DHA synthesis in the human body is sufficient to support optimal brain and retinal development, and these PUFA swould ideally be provided in the diet [11]. DHA is the major n-3 PUFA esterified in glycerophospholipids through the action of acyl-CoA synthases and acyl-CoA:lysophospholipid acyltransferases [12], that forms the structural matrix of brain grey matter and retinal membranes [13, 14]. In addition, dietary intake of n-6 PUFAs play a role since n-6 PUFAs interact and compete with n-3 PUFAs in the fatty acid metabolic pathway [15-21].

A feeding experiment was conducted to compare the essential fatty acid (EFA) efficiency between eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) for juvenile striped jack.The fish fed an EFA-deficient diet began to show a high mortality together with poor appetite and swimming activity around 10 days after feeding, although there was no marked external deficiency sign. The growth and feed efficiency were improved by addition of EPA and DHA to the diet. However, the supplementation of EPA alone was not effective in preventing high mortality or improving the growth rate of the fish. A replacement of one half of EPA with DHA effectively improved the growth and feed efficiency as well as reducing mortality. On the other hand, the growth and feed efficiency were highest in the fish fed the diet containing DHA and the mortality due to the EFA-deficiency was almost completely prevented by DHA alone. The fatty acid analyses of whole body lipids have shown that EPA is converted to 22:5n-3, but not to DHA, and that DHA is not retroconverted to 22:5n-3 and EPA.

Different metabolism of EPA, DPA and DHA in humans: A double-blind cross-over study

Human beings evolved consuming a diet that contained approximately equal amounts of omega‐6 and omega‐3 essential fatty acids. Over the past 100−150 years there has been an enormous increase in the consumption of omega‐6 fatty acids due to the increased intake of vegetable oils from seeds of corn, sunflower, safflower, cotton and soybeans. Today, in Western diets, the ratio of omega‐6 to omega‐3 fatty acids ranges from 10 to 20:1 instead of the traditional range of 1−2:1. Studies indicate that a high intake of omega‐6 fatty acids shifts the physiologic state to one that is prothrombotic and proaggregatory, characterized by increases in blood viscosity, vasospasm, and vasoconstriction and decreases in bleeding time, whereas omega‐3 fatty acids have anti‐inflammatory, antithrombotic, anti‐arrhythmic, hypolipidemic, and vasodilatory properties. These beneficial effects of omega‐3 fatty acids have been shown in the secondary prevention of coronary heart disease and hypertension, as for example, in the Lyon Heart Study, the GISSI Prevenzione Trial, and in the The Dietary Approaches to Stop Hypertension Study. Most of the studies have been carried out with fish oils (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)). However, α‐linolenic acid (ALA), found in green leafy vegetables, flaxseed, rapeseed, and walnuts, desaturates and elongates in the body to EPA and DHA and by itself may have beneficial effects in health and in the control of chronic diseases. The present paper identifies multiple sources of ALA from plants, legumes, nuts and seeds and emphasizes the importance of the ratio of omega‐6 to omega‐3 fatty acids for proper desaturation and elongation of ALA into EPA and DHA. α‐linolenic acid is not equivalent in its biological effects to the long‐chain omega‐3 fatty acids found in marine oils. Eicosapentaenoic acid and DHA are more rapidly incorporated into plasma and membrane lipids and produce more rapid effects than does ALA. Relatively large reserves of linoleic acid in body fat, as are found in vegans or in the diet of omnivores in Western societies, would tend to slow down the formation of long‐chain omega‐3 fatty acids from ALA. Therefore, the role of ALA in human nutrition becomes important in terms of long‐term dietary intake. One advantage of the consumption of ALA over omega‐3 fatty acids from fish is that the problem of insufficient vitamin E intake does not exist with high intake of ALA from plant sources.