How HALO’s critical fatty acids improve everything from energy production to bloodflow and recovery.

by Luke Bucci, PhD CCN CNS

Introduction

In this blog installment on omega-3s, one of HALO’s most critical components, Dr. Luke Bucci takes us on a trip down cell membrane lane to explain the importance of omega-3s and why our patent-pending HALO formula uses krill oil to deliver them. He begins by explaining how cell membranes work, then he gradually unpacks their structure down to their most basic, most effective component: the all-important omega-3s. It’s a circuitous journey, as twisted as the best fatty acid structures (that’ll make sense later) and passing through cell membranes to phospholipids, fats, fatty acids, a little detour into kinky bonds, and finally arriving at omega-3s.

Don’t worry, it initially overwhelmed us, too, but you’ve got a capable guide in Dr. Bucci, and he keeps the head-exploding organic chemistry to a minimum.

All told, HALO delivers the body’s two most common omega-3s, DHA and EPA, which work in a general way to keep our bodies functioning at tip-top shape by creating cell membrane fluidity. That fluidity powers optimal efficiency of mental processes, elasticity of red blood cells (for easier circulation through capillaries), responsivity of blood vessel linings, response to tissue damage, reparative processes, and immune cell activities, among other things.

If that sounds like a greatest hits of the topics we revisit again and again in these blog posts, well, it is. That should drive home the importance of omega-3s to every aspect of an endurance lifestyle – training and competing, of course, but also recovery and just daily life with the added enormous stressors of dedicated training.

Cell Membranes

Life as we know it depends on barriers, both macro and micro. We are a collection of cells and their outputs. Cells are individual units of life that have a cell membrane that maintains cellular integrity and function. We are as healthy – and only as healthy – as our collective cell membrane health. Cell membranes are where it’s at for endurance performance, of course, but also for recovery, rest, and simply existing daily. Every tissue, every organ, even the neurotransmitters that signal our thoughts and actions – it all depends on cell membranes.

So what are cell membranes? The simplest explanation is that cell membranes use fat in an arrangement that can be easily manipulated to be semi-permeable, meaning controlling what comes in and goes out of cells. These fat membranes also make the cell organelles like the nucleus, mitochondria, Golgi apparatus, endoplasmic reticulum, lysosomes, microsomes, vacuoles, and other cell compartments, so membranes are critical to every function carried out by a human body, inside and outside of cells. They ensure every cell can communicate, eat, and remove waste – also called homeostasis.

Those bilayer fat membranes are built from a basic unit called phospholipids, which are arranged in a back-to-back (or fatty-acid-to-fatty-acid) bilayer, so that’s our first stop on the journey towards omega-3s.

Phospholipids

Essentially, a phospholipid is a fat molecule with one alteration. Fats are called triglycerides because they comprise three fatty acids fused to a single glycerol. To convert a triglyceride (fat) molecule to a phospholipid, one of the triglyceride’s three fatty acids is replaced with a phosphate group.

The phosphate group makes the entire molecule water soluble, but the two remaining fatty acids resist being in water. That polarity is the basis for our cell membranes, because oil (in this case fatty acids) and water do not mix. When immersed in watery solutions, the phospholipid molecules arrange themselves spontaneously to form a lipid bilayer. Each phospholipid’s fatty acids cling to other fatty acids on other phospholipids by mutual attraction, and the phosphate groups shield them from water. This contained layer of fat is the barrier that maintains cell integrity. Phospholipids define cell membranes – and human life itself.

For our purposes here, phospholipids are themselves defined by their two attendant fatty acids, so Fatty Acid Station is the next stop on the Omega-3 Express.

Fatty Acids

Fatty acids, the defining components of triglycerides and phospholipids, are mostly quite simple – a chain of carbons and hydrogens tailing off of a carboxylic acid group (-COOH) at one end. Most fatty acids are much more “fatty” than “acid,” and they do not dissolve in water (or your bodily fluids).

The carboxylic acid group gives a way for fatty acids to attach to other molecules, which is how they form triglycerides and, ultimately, the hydrophilic/hydrophobic structure of phospholipids. This is what makes fatty acids the backbone of each and every cell’s membrane, because they are the fat that maintains cellular integrity by keeping the external out and the internal in. Suffice it to say, fatty acids are essential for life.

Beware! There are many synonyms for fatty acids, which can also confuse scientists and chemists. Here, we will stick to the most common terms, avoiding any toe-curling, head-exploding Organic Chemistry – well, avoiding as much of it as we can, anyway. We’ll also limit our focus to the longer fatty acids, which are 12+ carbon units and called, helpfully, long-chain fatty acids.

But first, let’s get to what really makes fatty acids do their thing: structure.

Double Bondage: A Structure Kink

Long-chain fatty acid molecules are pretty much a straight line in shape (linear). The simplest fatty acids are a chain of carbon-carbon units with the other atomic bonds filled by hydrogens (saturated with hydrogen), which is where the term saturated fats comes from. (Long-chain saturated fatty acids and fats made from them are solid at room temperature.) Saturated fatty acid molecules are pretty much linear in shape because they have a straightforward structure of bonds, but nature has some literal kinks to throw in our path.

Carbons prefer binding to each other instead of to hydrogen, so by kicking out a hydrogen, two carbons can form a double bond with each other, known as an unsaturated bond. This can happen once in the fatty acid molecule’s chain (monounsaturated), or more than once (polyunsaturated). Here’s the kinky part. An unsaturated fatty acid molecule has a less linear shape, ranging from a gentle bend to coiling in on itself, structurally speaking, and is less liable to form a solid at body or room temperatures.

Double bonds between two carbons are the all-important structural element that determines the shape of the fatty acid, and that shape determines the fatty acid’s function. Saturated fatty acids (lacking double bonds) are a simple straight line. Monounsaturated fatty acids (a single double carbon bond) have one kink in the middle, which makes the shape a low, wide V. Polyunsaturated fatty acids (multiple double carbon bonds) keep making kinks that start with a hook shape, until they coil into themselves, making circular, loop shapes.

Why does this matter? Easy. It’s all about enabling life in cells. Saturated fats – the straight strands with no carbon double bonds – can be densely packed and repel water, which is what our cell membranes use to keep everything in and out. But a membrane consisting only of saturated fats is hard and stiff, not fluid, and don’t allow the membrane to sprout a diversity of proteins and carbohydrate chains that makes each cell function. Membrane proteins are channels into and out of the cell, controlled to let good things (water, salts, food, signals) into cells and waste out of cells.

Those different fatty acid shapes define how our cell membranes work. And cell membranes actualize everything in our bodies by controlling everything that goes into and comes out of our cells. The shapes of mono- and polyunsaturated fatty acids spread out the spacing of fatty acids, making the membrane more fluid and less stiff. This, in turn enables membranes to easily add proteins and carbohydrates that control what comes in and goes out of a cell – life as we know it.

No fatty acid shape serves our purposes as well as certain omega-3s, which brings us at long last to…

Finally, Omega-3s

Omega-3 is a shorthand term for long-chain n3 polyunsaturated fatty acids (n3PUFAs). The omega-# term signifies how close to the tail the furthest carbon double bond from the head resides, so omega-3 fatty acids have a double bond connecting the 3rd to the 4th carbon from the tail end. There are Two Kinds of Omega-3s in foods: ALA and DHA/EPA. The latter two are paired together because they’re the important ones, so let’s knock ALA out immediately before moving on to those.

ALA is Alpha-Linolenic Acid with 18 carbons, 3 double bonds, and a J molecular shape. ALA is mostly a bridge to convert other acids to DHA/EPA, but converting is less efficient than simply getting DHA/EPA directly. There are a lot of complications and reasons that explain this – and getting plenty of ALA in your diet is a very good thing (especially for vegans and vegetarians/lacto-ovarians) – but we’re staying focused on the more critical, more effective omega-3s delivered by HALO: DHA and EPA.

The Alphas of Omega-3s: DHA & EPA

DHA and EPA in HALO are the two predominant omega-3 fatty acids in your cells. Given the right inputs, your body can make them, but the best way to get them into your system is by ingesting them directly. They have two major functions: 1) providing more membrane fluidity; and 2) serving as precursors to a bevy of powerful signaling molecules called eicosanoids, which are metabolically calming, pro-healing, and counteract signals derived from omega-6 fatty acids that are excitatory and not pro-healing.

DHA is the ultimate Omega-3. DHA has 22 carbons, 6 double bonds, and a circular molecular shape. This circular shape creates molecular openness, making it more fluid (liquid) than saturated fats. DHA phospholipids tend to cluster together in localized membrane areas, or “lipid rafts,” that contain rapidly changing receptors and other cell surface activities. Cells with very active membranes and high levels of DHA phospholipids include neurons in the brain and cells controlling immune functions. Mental processes, response to tissue damage, elasticity of red blood cells (for easier circulation through capillaries), responsivity of blood vessel linings, immune cell activities – DHA is the key player for a host of items that I’d call super critical.

EPA is the penultimate Omega-3. EPA has 20 carbons, 5 double bonds, and a half-circle molecular shape. Like with DHA, this molecular openness contributes to membrane fluidity, and EPA is no slouch at facilitating membrane function. EPA is also the direct precursor to DHA, and is necessary to make DHA by biosynthesis, but consuming DHA directly is more efficient and preserves EPA stock in cell membranes.

DHA/EPA are both also precursors for signaling molecules that restore normality (health) in a wide variety of normal, everyday situations of stress to cells (Bannenberg 2010; Levy 2010; Mas 2012; ODS 2020; Serhan 2002; Sommer 2011; Souza 2020). These signals are vital for maintenance of healthy cell, tissue and organ functions and structures. Increasing DHA/EPA levels in cell membranes makes this signaling system more efficient and stronger.

Fluidity and Rigidity – Putting it all Together

A delicate balance of polyunsaturated fatty acids (like DHA and EPA) and monounsaturated or saturated fatty acids in cell membrane bilayer phospholipids is the determining factor for optimal health.

This is where the omega-3 fatty acids, especially DHA & EPA, come into play. When phospholipids containing just one DHA or EPA fatty acid are present, they spread out the membrane, facilitating more rapid exchange of receptors. Receptors can be shuttled in and out of the membrane as the cell wishes. High fluidity allows rapid cycling of ingress and egress of water, salts, nutrients, and compounds such as neurotransmitters or intercellular signals that trigger muscle activity or healing. This allows our cells, and our whole body, to respond to our environment.

In other words, anything your cells, brain, or body do requires smooth cell membrane functioning, and omega-3s as membrane phospholipids are a huge part of that smooth functioning.

 

Enter Krill Oil

To close out this omega-3 tour, I’ll explain the importance of HALO’s use of krill oil compared to more common omega-3 sources like fish oil. The short version: they deliver complete, ready-to-use phospholipids already equipped with those all important DHA/EPA fatty acids. They skim through the digestion process unmolested and arrive ready-to-install at cell membranes. Now for the longer (although not exhaustive) version.

While they are critical for cellular health, DHA/EPA are only building blocks, and must be part of a specific form of phospholipid, phosphatidyl choline phospholipids, and installed in cell membranes in order to realize their benefits. (The most common omega-3 phospholipid in humans is called 1-palmitoyl-2-DHA phosphatidyl choline, and DHA/EPA are the critical part of that phospholipid – see the figure above, in “Phospholipids.”) Although pathways exist for biosynthesizing these phospholipids from loose DHA/EPA fatty acids, it is much less efficient than simply consuming the phospholipids whole (Burri 2015). Happily, this exact phospholipid is also the most common single omega-3 phospholipid in krill oil, identical to those in cell membranes and ready to go to work (Winther 2011).

To understand why this is a big “advantage krill” moment, let’s track triglycerides on their journey from ingestion to cells. During digestion, triglycerides are stripped of their outer two fatty acids and absorbed as monoglycerides (with some diglycerides) into intestinal cells. Inside the intestinal cells, the fats are reassembled and then sent into the bloodstream in lipoprotein particles. Next, the liver grabs these particles and starts to repackage them with cholesterol into other lipoprotein particles for delivery to all your cells. After your cells attach these particles to themselves, they suck out the fats and proceed to convert them into fatty acids and glycerol to be used for energy production, with excess stored as fat. Some are converted into phospholipids to keep the membranes running normally. Along the way, fatty acids are damaged, oxidized, lost in the stool, burned for energy, or stored away for later use. Many steps and transports are needed to feed membranes their phospholipids from Omega-3 triglycerides like fish oils.

So it’s a whole process of dissasembly and reassembly. Now let’s look at ingesting phospholipids, instead.

When ingested, phospholipids readily mix with water and are absorbed by your gut pretty much the way they were swallowed. Some are reassembled, but highly desired phospholipids – like our 1-palmitoyl-2-DHA phosphatidyl choline – are given a free pass to move in and out of membranes, being handed over to neighboring cells until they reach the bloodstream, where they dive into red blood cell membranes and are carried everywhere. When a tissue or cell needs one, it simply sucks it out of the red blood cells and also the stash that is dissolved in your blood. Our bodies have ways to get DHA/EPA phospholipids quickly and with less loss than from fats.

In short, when they’re consumed whole, phospholipids are absorbed more easily and completely than fatty acids in fat (triglycerides), such as fish oil (Burri 2015). Krill oil is like a preformed, cell membrane-ready, DHA/EPA-infused phospholipid source. It skips the entire process of deconstructing/reconstructing and just gives membranes what they need to upgrade their function.

There is another advantage to krill oil over other omega-3 fat sources: built-in antioxidant protection from astaxanthin. Because of the prevalence of carbon-carbon double bonds, all polyunsaturated fatty acids – including omega-3s – are susceptible to oxidation (adding oxygen and small oxygen-containing compounds). Oxidation causes the molecules to form aberrant structures that ruin the effects of their shapes and cause a cascade of membrane damage. Since omega-3s’ shape is what makes them function, this effectively deactivates them. Lipid-soluble antioxidants like astaxanthin are helpful to keep oxidation from damaging those precious omega-3s, keeping them active. Even adding Vitamin E to fish and plant oils – a common practice – is not as successful as HALO’s krill oil with its built-in astaxanthin activity.

Advantages of Krill Oil Over Fish Oil

1. Cell-membrane-identical phospholipid DHA forms.
2. Efficient delivery and integration of DHA into cell membranes.
3. Less digestion & metabolism required for use by the body.
4. Built-in antioxidant protection from naturally-occurring astaxanthin.
5. Soluble in water (body fluids).
6. Sustainable & eco-friendly.
7. No environmental contaminant concerns (mercury, heavy metals, pollutants).
8. No heat during processing keeps molecular integrity of oil.
9. No ill effects on the food chain by a large margin.
   
   

References

American Heart Association. Fish and omega-3 fatty acids.2017 Mar23: https://www.heart.org/en/healthy-living/healthy-eating/eat-smart/fats/fish-and-omega-3-fatty-acids. 

Anzalone A, Carbuhn C, Jones L, Gallop A, Smith A, Johnson P, Swearingen L, Moore C, Rimer E, McBeth J, Harris W, Kirk KM, Gable D, Askow A, Jennings W, Oliver JM. The Omega-3 Index in National Collegiate Athletic Association Division I collegiate football athletes. J Athl Train. 2019 Jan;54(1):7-11.

Avila-Gande V, Torregrosa-Garcia A, Luque-Rubia AJ, Abellan-Ruiz MS, Victoria-Montesinos D, Lopez-Roman FJ. Re-esterified DHA improves ventilatory threshold 2 in competitive amateur cyclists. J Int Soc Sports Nutr. 2020 Oct21;17(1):51.

Baker KR, Matthan NR, Lichtenstein AH, Niu J, Guermazi A, Roemer F, Grainger A, Nevitt MC, Clancy M, Lewis CE, Torner JC, Felson DT. Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee: the MOST study. Osteoarthritis Cartilage. 2012 May;20(5):382-7.

Bannenberg G, Serhan CN. Specialized pro-resolving lipid mediators in the inflammatory response: an update. Biochim Biophys Acta. 2010 Dec;1801(12):1260-73.

Baumert P, Lake MJ, Stewart CE, Drust B, Erskine RM. Genetic variation and exercise-induced muscle damage: implications for athletic performance, injury and ageing. Eur J Appl Physiol. 2016 Sep;116(9):1595-625.

Berdeaux O, Juaneda P, Martine L, Cabaret S, Bretillon L, Acar N. Identification and quantification of phosphatidylcholines containing very-long-chain polyunsaturated fatty acid in bovine and human retina using liquid chromatography/tandem mass spectrometry. J Chromatogr A. 2010 Dec3;1217(49):7738-48.

Black KE, Witard OC, Baker D, Healey P, Lewis V, Tavares F, Christensen S, Pease T, Smith B. Adding omega-3 fatty acids to a protein-based supplement during pre-season training results in reduced muscle soreness and the better maintenance of explosive power in professional Rugby Union players. Eur J Appl Physiol. 2018 Nov;18(10):1357-67.

Bradbury J. Docosahexaenoic acid (DHA): an ancient nutrient for the modern human brain. Nutrients. 2011 May;3(5):529-54.

Buckley JD, Burgess S, Murphy KJ, Howe PRC. DHA-rich fish oil lowers heart rate during submaximal exercise in elite Australian Rules footballers. J Med Sci Sport. 2009 Jul;12(4):503-7.

Calder PC. Polyunsaturated fatty acids and inflammatory processes: new twists in an old tale. Biochime. 2009;91:791-5.

Chen GC, Yang J, Eggersdorfer M, Zhang W, Qin LQ. N-3 long-chain polyunsaturated fatty acids and risk of all-cause mortality among general populations: a meta-analysis. Sci Rep. 2016 Jun16;6:28165.

Cheung K, Hume P, Maxwell L. Delayed onset muscle soreness: treatment strategies and performance factors. Sports Med. 2003;33(2):145-64.

Clarkson PM, Hubal MJ. Exercise-induced muscle damage in humans. Am J Phys Med Rehabil. 2002 Nov;81(11 Suppl):S52-69.

Cox MJ, Candy S, de la Mare WK, Nicol S, Kawaguchi S, Gales N. No evidence for a decline in the density of Antarctic krill Euphasia superba) Dana, 1850, in the Southwest Atlantic sector between 1976 and 2016.  J Crustacean Biol. 2018;38(6):656-61.

Danaei G, Ding EL, Mozaffarian D, Taylor B, Rehm J, Murray CJ, Ezzati M. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle and metabolic risk factors. PLoS Med. 2009 Apr28;6(4):e1000058.

Daniells S. Aker’s chief scientist: let’s stop talking about bioavailability & focus on what happens to omega-3 in the body. Nutraingredients. 2015 Sep15.

Davinelli S, Corbi G, Righetti S, Casiraghi E, Chiappero F, Martegani S, Pina R, De Vivo I, Simopoulos AP, Scapagnini G. Relationship between distance run per week, Omega-3 Index, and arachidonic acid (AA)/Eicosapentaenoic acid (EPA) ratio: An observational retrospective study in non-elite runners. Front Physiol. 2019;10:487.

Del Gobbo LC, Imamura F, Aslibekyan S, Marklund M, Virtanen JK, Wennberg M, Yakoob MY, Ciuve SE, Dela Cruz L, Frazier-Wood AC, Fretts AM, Guallar E, Matsumoto C, Prem K, Tanaka T, Wu JHY, Zhou X, Helmer C, Ingelsson E, Yuan JM, Barberger-Gateau P, Campos H, Chaves PHM, Djousse L, Giles GG, Gomez-Aracena J, Hodge AM, Hu FB, Jansson JH, Johansson I, Khaw JT, Koh WP, Lemaitre RN, Lind L, Luben RN, Rimm EB, Riserus U, Samieri C, Franks PW, Siscovick DS, Stampfer M, Steffen LM, Steffen BT, Tsai MY, van Dam RM, Voutilainen S, Willett WC, Woodward M, Mozaffarian D, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Fatty Acids and Outcomes Research Consortium (FORCe). Omega-3 polyunsaturated fatty acid biomarkers and coronary heart disease: pooling project of 19 cohort studies. JAMA Intern Med. 2016 Aug1;176(8):1155-66.

Derbyshire E. Brain health across the lifespan: a systematic review on the role of omega-3 fatty acid supplements. Nutrients. 2018 Aug15;10:1094.

Dolecek TA, Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the multiple risk factor intervention trial. Proc Soc Exp Biol Med. 1992 Jun;200(2):177-82.

Drobnic F, Rueda F, Pons V, Banquells M, Crodobilla B, Domngo JC. Erythrocyte Omega-3 fatty acid content in elite athletes in response to omega-3 supplementation: a dose-response pilot study. J Lipids. 2017;2017:1472719.

Fatouros IG, Jamurtas AZ. Insights into the molecular etiology of exercise-induced inflammation: opportunities for optimizing performance. J Inflamm Res 2016 Oct21;9:175-86.

Fats of Life. Brain Health Benefits. https://www.fatsoflife.com, 2020.

Fenton JI, Gurzell EA, Davidson EA, Harris WS. Red blood cell PUFAs reflect the phospholipid PUFA composition of major organs. Prostaglandins Leukot Essent Fatty Acids. 2016 Sep;112:12-23.

Gammone MA, Riccioni G, Parrinello G, D’Orazio N. Omega-3 polyunsaturated fatty acids: benefits and endpoints in sports. Nutrients. 2018 Dec27;11(1):46.

Gollasch B, Dogan I, Rothe M, Gollasch M, Luft FC. Maximal exercise and erythrocyte fatty-acid status: a lipidomics study. Physiol Rep. 2019 Apr;7(8):e14040.

Grant R, Guest J. Role of omega-3 PUFAs in neurobiological health. Adv Neurol. 2016;12:247-74.

Guzman JF, Esteve H, Pablos C, Pablos A, Villegas JA. DHA-rich fish oil improves complex reaction time in female elite soccer players. J Sports Sci Med. 2011;10:301-5.

Harris WS, Polreis J. Measurement of the omega-3 index in dried blood spots. Ann Clin Lab Res. 2016;4(4):137-44.

Harty PS, Cottet ML, Malloy JK, Kerksick CM. Nutritional and supplementation strategies to prevent an attenuate exercise-induced muscle damage: a brief review. Sports Medicine Open. 2019 Jan7;5(1):1.

Hingley L, Macartney MJ, Brown MA, McLennan PL, Peoples GE. DHA-rich fish oil increases the Omega-3 Index and lowers the oxygen cost of physiologically stressful cycling in trained Individuals. Int J Sports Nutr Exer Metab. 2017 Aug;27(4):335-343.

Hotfiel T, Friewald J, Hoppe MW, Lutter C, Forst R, Grim C, Bloch W, Huttel M, Heiss R. Advances in delayed-onset muscle soreness (DOMS): Part I: Pathogenesis and diagnostics.  Sportverletz Sportschaden. 2018 Dec;32(4):243-50.

Heiss R, Lutter C, Friewald J, Hoppe MW, Grim C, Poettgen K, Forst R, Bloch W, Huttel M, Hotfiel T. Advances in delayed-onset muscle soreness (DOMS): Part II: Treatment and prevention.  Sportverletz Sportschaden. 2019a Mar;33(1):21-9.

Hotfiel T, Mayer I, Huettel M, Hoppe MW, Engelhardt M, Lutter C, Pöttgen K, Heiss R, Kastner T, Grim C. Accelerating recovery from exercise-induced muscle injuries in triathletes: considerations for Olympic distance races. Sports. 2019b;7:143.

Hu Y, Hu FB, Manson JE. Marine omega-3 supplementation and cardiovascular disease: an updated meta-analysis of 13 randomized controlled trials involving 127477 participants. J Am Heart Assoc. 2019 Oct;8(19):e013543.

Janssen CI, Kiliaan AJ. Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aghing, and neurodegeneration. Prog Lipid Res, 2014 Jan;53:1-17.

Joint WHO/FAO Expert Consultation. Diet, nutrition and the prevention of chronic diseases. WHO Technical Report Series 916. World Health Organization, Geneva, Switzerland, 2003.

Le Grandois J, Marchioni E, Giuffrida F, Ennahar S, Bindler F. Investigation of natural phosphatidylcholine sources: separation and identification by liquid chromatography-electrospray ionization – tandem mass spectrometry (LC-ESI-MS2) of molecular species. J Agric Food Chem. 2009 Jul22;57(14):6014-20.

Lembke P, Capodice J, Hebert K, Swenson T., Influence of n-3 omega-3 PUFA (n3) index on performance and wellbeing in young adults after heavy eccentric exercise. J Sports Sci Med. 2014;13:151-6.

Lentjes MAH, Keogh RH, Welch AA, Mulligan AA, Luben RN, Wareham NJ, Kha KT. Longitudinal associations between marine omega-3 supplement users and coronary heart disease in a UK population-based cohort. BMJ Open. 2017;7:e017471.

Levy BD. Resolvins and protectins: natural pharmacophores for resolution biology. Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):327-32.

Liu A, Terry R, Lin Y, Nelson , Bernstein PS. Comprehensive and sensitive quantification of long-chain and very long-chain polyunsaturated fatty acids in small samples of human and mouse retina. J Chromatogr A. 2013 Sep13;1307:191-200.

Ma S, Suzuki K. Keto-adaptation and endurance exercise capacity, fatigue recovery, and exercise-induced muscle and organ damage prevention: a narrative review. Sports. 2019 Feb13;7(2):40.

Macartney MJ, Hingley L, Brown MA, Peoples GE, McLennan PL. Intrinsic heart rate recovery after dynamic exercise is improved with an increased omega-3 index in healthy males. Br J Nutr. 2014 Dec28;112(12):1984-92.

Mas E, Croft KD, Zahra P, Barden A, Mori TA. Resolvins D1, D2, and other mediators of self-limited resolution of inflammation in human blood following n-3 fatty acid supplementation. ClinChem. 2012 )ct;58(10):1476-84.

Mickelborough TD. Omega-3 polyunsaturated fatty acids in physical performance optimization. Int J Sport Nutr Exer Metab. 2013 Feb;23(1):83-96.

Mozaffarian D, Lemaitre RN, King IB, Song X, Huang H, Sacks FM, Rimm EB, Wang M, Siscovick DS. Plasma phospholipid long-chain omega-3 fatty acids and total and cause-specific mortality in older adults: a cohort study. Ann Intern Med. 2013 Apr2;158(7):515-25.

Muskiet FAJ, Fokkema MR, Schaafsma A, Boersma ER, Crawford MA. Is docosahexaenoic acid (DHA) essential? Lessons from DHA status regulation, our ancient diet, epidemiology and randomized clinical trials. J Nutr, 2004 Jan;134(1):183-6.

Nicol S, Brierley AS. Through a glass less darkly – new approaches for studying the distribution, abundance and biology of Euphausiids. Deep Sea Res. II. 2010;57(7):496-507.

Nikolaidis MG, Mougios V. Effects of exercise on the fatty-acid composition of blood and tissue lipids. Sports Med. 2004;34(15):1051-76.

Office of Dietary Supplements, National Institutes of Health. Omega-3 fatty acids fact sheet for consumers. 2020 Oct.1: https://ods.od.nih.gov/pdf/factsheets/Omega3FattyAcids-Consumer.pdf 

Oliver JM. Omega-3 fatty acids and student-athletes: is it time for better education and a policy change? J Athl Train. 2019;54(1):5-6.

Owens DJ, Twist C, Cobley JN, Howatson G, Close GL. Exercise-induced muscle damage: what is it. What causes it and what are the nutritional solutions? Eur J Sport Sci. 2019 Feb;19(1):71-85.

Paulsen G, Mikkelsen UR, Raastad T, Peake JM. Leucocytes, cytokines and satellite cells: what role do they play in muscle damage and regeneration following eccentric exercise? Exerc Immunol Rev. 2012;18:42-97.

Pocobelli G, Kristal AR, Patterson RE, Potter JD, Lampe JW, Kolar A, Evans I, White E. Total mortality risk in relation to use of less-common dietary supplements. Am J Clin Nutr. 2010 Jun;91(6):1791-800.

Qi K, Hall M, Deckelbaum RJ. Long-chain polyunsaturated fatty acid accretion in brain. Curr Opin Clin Nutr Metab Care. 2002 Mar;5(2):133-8.

Ritz PP, Rogers MB, Zabinsky JS, Hedrick VE, Rockwell JA, Rimer EG, Kostelnik SB, Hulver MW, Rockwell MS. Dietary and biological assessment of the omega-3 status of collegiate athletes: a cross-sectional analysis. PLoS ONE. 2020 Apr29;15(4):e0228834.

Rokke KI, Leithe HJ, Ernsten R. Floating trawl methods and arrangements. US2010/0139147A1. Jun.10, 2010.

Schoenfeld BJ. Does exercise-induced muscle damage play a role in skeletal muscle hypertrophy? J Strength Cond Res. 2012 May;26(5):1441-53.

Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac RL. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med. 2002 Oct21;196(8):1025-37.

Shearer GC, Harris WS, Pedersen TL, Newman JW. Detection of omega-3 oxylipins in human plasma and response to treatment with omega-3 acid ethyl esters.  J Lipid Res. 2010 Aug;51(8):2074-81.

Shei RJ, Lindley MR, Mickelborough TD. Omega-3 polyunsaturated fatty acids in the optimization of physical performance. Mil Med. 2014;179(11):144-56.

Sibille KT, King C, Garrett TJ, Glover TL, Zhang H, Chen H, Reddy D, Goodin BR, Sotolongo A, Petrov ME, Cruz-Almeida Y, Herbert M, Bartley EJ, Edberg JC, Staud R, Redden DT, Bradley LA, Fillingim RB. Omega-6:Omega-3 PUFA ratio, pain functioning, and distress in adults with knee pain.  Clin J Pain. 2018 Feb;34(2):182-9.

Siegel V, Watkins JL. Distribution, biomass and demography of Antarctic krill, Euphausia superba, in Biology and Ecology of Antarctic Krill. Advances in Polar Ecology, Siegel V, Ed., Springer, Cham, 2016, pp.21-100.

Sommer C, Birklein F. Resolvins and inflammatory pain. F1000 Medicine Reports. 2011 Oct03;3:19.

Sousa M, Teixeira VH, Soares J. Dietary strategies to recover from exercise-induced muscle damage. Int J Food Sci Nutr. 2014 Mar;65(2):151-63. Circ Res. 2020 Jan3;126:75-90.

Souza PR, Marques RM, Gomez EA, Colas RA, De Matteis R, Zak A, Patel M, Collier DJ, Dalli J. Enriched marine oil supplements increase peripheral blood specialized pro-resolving mediators concentrations and reprogram host immune responses. Circ Res. 2020 Jan3;126(1):75-90.

Stark KD, Van Elswyk ME, Higgins MR, Weatherford CA, Salem N. Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults. Prog Lipid Res. 2016 Jul;63:132-52.

Tee JC, Bosch AN, Lambert MI. Metabolic consequences of exercise-induced muscle damage. Sports Med. 2007;37(10):827-36.

Vannice G, Rasmussen H. Position of the Academy of Nutrition and Dietetics: dietary fatty acids for healthy adults. J Acad Nutr Diet. 2014 Apr;114(1):136-53.

Von Schacky C, Kemper M, Haslbauer R, Halle M. Low Omega-3 Index in 106 German elite winter endurance athletes: a pilot study. Int J Sports Nutr Exerc Metab. 2014 Oct, 24(5):559-64.

Walker RE, Jackson KH, Tintle NL, Shearer GC, Bernasconi A, Masson S, Latini R, Heydari B, Kwong RY, Flock M, Kris-Etherton PM, Hedengran A, Carney RM, Skulas-Ray A, Gidding SS, Dewell A, Gardner CD, Grenon SM, Sarter B, Newman JW, Pedersen TL, Larson MK, Harris WS. Predicting effects of supplemental EPA and DHA on the omega-3 index. Am J Clin Nutr. 2019 Oct1;110(4):1034-40.

Wilson PB, Madrigal LA. Associations between whole blood and dietary omega-3 polyunsaturated fatty acid levels in collegiate athletes. Int J Sport Nutr Exerc Metab. 2016 Dec;26(6):497-505.

Winther B, Hoem N, Berge K, Reubsaet L. Elucidation of phosphatidylcholine composition in krill oil extracted from Euphasia superba. Lipids. 2011 Jan;46(1):25-36.

Yang G, Atkinson A, Hill SL, Gugliemo L, Granata A, Li C. Changing circumpolar distributions and isoscapes of Antarctic krill: Indo-Pacific habitat refuges counter long-term degradation of the Atlantic sector. Limnology Oceanography. 2021 Jan;66(1):272-87.