Monographs


Omega-3 fatty acids (general)

Nutritional therapy

Download as PDF

Action

Omega-3 and omega-6 fatty acids
The polyunsaturated fatty acids are part of a group of essential nutrients. They consist of two large groups: omega-3 fatty acids (alpha-linolenic acid (ALA) and the metabolites formed from this, such as EPA and DHA) and omega-6 fatty acids (linolenic acid and metabolites such as arachidonic acid and GLA). Today’s diet contains (more than) enough omega-6 fatty acids (linolenic acid from oils and fats derived from plants, arachidonic acid from meat), whilst conversely the intake of omega-3 fatty acids (ALA from linseed oil and canola oil, EPA and DHA from fatty fish, seafood or algae) is inadequate. The ratio between omega-6 and omega-3 fatty acids in the western diet is approximately 15-25:1, whilst a ratio of approximately 5:1 to 1:1 is desirable. A high ratio between omega-6 and omega-3 fatty acids in the diet leads to (among other things) inflammations and is associated with many chronic inflammation-associated diseases.
   

The enzyme delta-6 desaturase regulates both the conversion of linolenic acid into DGLA and the conversion of ALA into (ultimately) EPA. When there is a surplus of linolenic acid, there is almost no more delta-6 desaturase available for the conversion of ALA. In addition to that, the enzyme works extremely slowly and is inhibited by all sorts of dietary factors (including trans fatty acids, saturated fats, alcohol, deficiencies in zinc, magnesium, vitamin C, vitamin B3 and/or vitamin B6) and metabolic factors (the contraceptive pill, hypercholesterolaemia, insulin-resistance, certain medicines). The question therefore arises whether the consumption of ALA leads to a sufficient rise in the levels of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). 

    
EPA and DHA are essential
Initially it was assumed that only the precursors alpha linolenic acid (omega-3 series) and linolenic acid (omega-6 series) are essential for humans, as we have enzymes (desaturases, elongases) that can metabolise these fatty acids. However, a large number of studies have revealed that the conversion from ALA to EPA and DHA (and linolenic acid to GLA) is very inefficient in humans. Only 0.3 to 8% of ALA is converted into EPA and no more than 0.5-1% into DHA, even under optimum conditions. Scientists therefore believe that EPA and DHA have to be seen as essential fatty acids and that the consumption of only ALA (from linseed oil and other plant-based sources) is inadequate for a good omega-3 fatty acid status. 

   
Supplements containing EPA and DHA
When providing fish oil supplements containing EPA and DHA, it is preferable to take EPA and DHA in the form of triglycerides (the natural form in food) and not as ethyl esters. Quite apart from the potential toxic effects, ethyl esters of DHA and EPA are less stable, oxidise faster and are less readily digested and absorbed, especially if taken during a meal containing little fat. Studies have revealed that the biological availability of DHA and EPA from triglycerides is up to 70% higher than from ethyl esters.  
In addition, it is good to opt for fish oil in the form of emulsion. EPA and DHA are absorbed significantly faster and more readily from emulsified fish oil than from ordinary fish oil. Furthermore, emulsified fish oil is tolerated better. Fish oil has to be purified to remove harmful contaminants (heavy metals, dioxins, PCBs) and contain sufficient antioxidants (mixed tocopherols) to combat oxidation.

  

Algae as a source of DHA
Algae are at the bottom of the marine food chain and can be considered to be a very pure plant-based source of EPA and DHA. Algae contain relatively high levels of DHA and, as a primary source of omega-3, a major advantage is that there is little or no contamination with toxic substances. Studies confirm that the beneficial effects of the omega-3 fatty acids from algae oil are similar to those of fish oil.
Furthermore, is particularly suitable for both vegetarians and vegans, an ever-growing group within the population. ALA-rich plant-based sources, part of the vegetarian or vegan menu, are insufficient to meet the needs for omega-3, due to the body’s inefficient conversion of ALA to EPA and DHA. Studies have shown that most people who follow these diets have significantly lower omega-3 levels than people who eat fish. DHA is the most complex fatty acid of all omega-3 fatty acids. Not only is the conversion of ALA to EPA and DHA as mentioned above very inefficient, but the route from EPA to DHA is very difficult. However, the conversion of DHA to EPA is very easy and this is converted when required by the body. Direct supplementation with DHA is therefore definitely preferable and this is more effective than EPA supplementation.

There are clear epidemiological signs that a chronic DHA deficiency can lead to depression and cognitive deterioration. Already at a relatively low dose, the intake of DHA from algae oil increases the DHA levels and omega-3 index, therefore decreasing the risk of these adverse deficiency effects. It remains unclear to what extent DHA supplementation has the same beneficial cardiovascular health effects as those found in meat-eaters.

Another (ethical) and important benefit of using algae as a source of DHA is that this curbs overfishing and deterioration of fish stocks. This also means that algae oils are a very good alternative for fish and fish oil. Through additional supplementation, the needs for omega-3 can be adequately met, which doesn’t only apply to vegetarians and vegans, but also to non-fish-eaters or to anyone suffering from a fish allergy.

Effects of EPA and DHA
The long chain omega-3 fatty acids (EPA, DHA):

  • Play an important role in the structure (double layer of phospholipids) and function of cell membranes and intracellular membranes 
  • Regulate gene expression and are important for signal transfer in cells;
  • Regulate cell division, cell differentiation and cell apoptosis
  • Regulate the immune system
  • Are precursors of eicosanoids, docosanoids, lipoxins, resolvins, protectins and maresins with anti-inflammatory activity (and inhibit eicosanoids from arachidonic acid that are conducive to inflammation, thrombosis and vascular construction) 
  • In nerve tissue they are precursors of neuroprotectins and resolvins that combat pain, including pain caused by inflammation
  • In the brain they have a positive effect on the mood, behaviour and mental capacity (DHA and EPA) and are essential for good neurological and visual development during the foetal phase and early childhood (particularly DHA)
  • Change the adipokine synthesis into adipose tissue (with a decrease in adipokines that are conducive to insulin resistance, inflammation and atherosclerosis and an increase in protective adipokines such as adiponectin)
  • Inhibit atherosclerosis, improve endothelial function, reduce arterial stiffness, lower the blood pressure, reduce the heart rate, combat thrombosis, reduce the triglycerides and atherogenic LDL cholesterol levels and increase the HDL cholesterol levels
  • In combination with resistance training, strengthen the neuromuscular system in the elderly, with an increase in muscular strength and functional capacity

Indications

  • Cardiovascular diseases (atherosclerosis, coronary artery disease, cardiac infarction, stroke, cardiomyopathy, high blood pressure, cardiac rhythm disorders, cardiac failure)
  • Psychiatric disorders (schizophrenia, depression, post-natal depression, bipolar disorder, winter depression, anxiety disorder, borderline personality disorder, aggression) 
  • Psychological stress
  • Neurocognitive disorders in children (ADD, ADHD, autism, dyslexia, dyspraxia)
  • Prevention of cognitive deterioration
  • Neurodegenerative disorders (multiple sclerosis, Parkinson’s disease, Alzheimer’s disease)
  • Pregnancy and the growth of babies and young children (particularly DHA)
  • Skin diseases (psoriasis, neurodermatitis, atopic eczema, acne vulgaris)
  • Rheumatic diseases (arthrosis, Bechterew’s disease, rheumatoid arthritis)
  • Chronic non-specific neck ache and lower backache
  • Osteoporosis (prevention)
  • Improvement in muscular strength in the elderly (in combination with resistance training)
  • Chronic inflammatory bowel disorders (Crohn’s disease, ulcerative colitis)
  • COPD (asthma, bronchitis, emphysema)
  • Allergies
  • Auto-immune diseases 
  • Reduced resistance
  • Premenstrual syndrome (PMS)
  • Menopausal flushes
  • Hypertriglyceridaemia
  • Metabolic syndrome, (prevention) of type 2 diabetes
  • Obesity
  • Non-alcoholic fatty liver disease
  • Wound healing
  • Chronic periodontitis
  • Sickle cell anaemia
  • Prevention of age-related macular degeneration

Contra-indications

At the prescribed dose, no contra-indications are known.

Side effects

Aside from the effect on the coagulation, as listed under interactions, there is a risk of diarrhoea, nausea and belching especially when high doses of fish oil are taken (more than 5 grams of EPA+DHA a day).  

Interactions

Because omega-3 fatty acids combat blood clotting, a vitamin K deficiency can occur in patients who use blood thinners or who use other medicines that inhibit blood coagulation (aspirin), internal bleeds can occur when high doses of omega-3 fatty acids are taken (more than 5 grams of EPA+DHA). Maximum effects are achieved with omega-3 on coagulation after 6 weeks of treatment. Other interactions with mainstream or natural medicines are possible. Consult an expert about this

Dosage

For a daily maintenance dose, approximately 300-1000 mg of EPA+DHA can be taken each day. The optimum therapeutic dose of omega-3 fatty acids varies from disease to disease and can amount to 5 to 10 grams a day. If required, fish oil can be used in salads, yoghurt or fruit juices.

Synergism

To combat the oxidation of omega-3 fatty acids in the body, simultaneous use of a vitamin E supplement (complex of tocopherols) at approximately 400 IE a day is recommended. Flavonoids increase the absorption of EPA and DHA. 

References


  1.     Bradbury J, Brooks L, Myers SP. Are the Adaptogenic Effects of Omega 3 Fatty Acids Mediated via Inhibition of Proinflammatory Cytokines? Evidence-Based Complementary and Alternative Medicine. 2012; 209197
  2. Bradbury J. Docosahexaenoic Acid (DHA): An Ancient Nutrient for the Modern Human Brain. Nutrients. 2011;3(5):529-554
  3.     Brenna JT, Salem N Jr, Sinclair AJ et al; International Society for the Study of Fatty Acids and Lipids, ISSFAL. alpha-Linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids 2009;80:85-91.
  4.     Carter JR, Schwartz CE, Yang H et al. Fish oil and neurovascular reactivity to mental stress in humans. Am J Physiol Regul Integr Comp Physiol. 2013;304(7):R523-30.
  5.     Chang CL, Deckelbaum RJ. Omega-3 fatty acids: mechanisms underlying 'protective effects' in atherosclerosis. Curr Opin Lipidol. 2013;24(4):345-50.
  6.     Chong EW, Robman LD, Simpson JA et al. Fat consumption and its association with age-related macular degeneration. Arch Ophthalmol. 2009;127(5):674-80.
  7.     Daak AA, Ghebremeskel K, Hassan Z et al. Effect of omega-3 (n−3) fatty acid supplementation in patients with sickle cell anemia: randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2013;97:37-44.
  8. Daniells S. Harvard meta-analysis supports benefits of algal DHA omega-3. Nutraingredients USA. 2011;12(16):1-2
  9.     de Batlle J, Sauleda J, Balcells E et al. PAC-COPD Study Group. Association between Ω3 and Ω6 fatty acid intakes and serum inflammatory markers in COPD. J Nutr Biochem. 2012;23(7):817-21.
  10.     Dyerberg J, Madsen P, Møller JM et al. Bioavailability of marine n-3 fatty acid formulations. Prostaglandins Leukot Essent Fatty Acids 2010;83:137-141.
  11. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). EFSA Journal. 2014;12(10):3843
  12.     Elkhouli AM. The efficacy of host response modulation therapy (omega-3 plus low-dose aspirin) as an adjunctive treatment of chronic periodontitis. J Periodontal Res. 2011;46(2):261-8.
  13.     Escolano-Margarit MV, Ramos R, Beyer J, Csábi G, Parrilla-Roure M, Cruz F et al. Prenatal DHA status and neurological outcome in children at age 5.5 years are positively associated. J Nutr. 2011 Jun;141(6):1216-23
  14.     Garaiova I, Guschina IA, Plummer SF et al. A randomised cross-over trial in healthy adults indicating improved absorption of omega-3 fatty acids by pre-emulsification. Nutr J. 2007;6:4.
  15.     Gregory MK, Gibson RA, Cook-Johnson RJ et al. Elongase reactions as control points in long-chain polyunsaturated fatty acid synthesis. PLoS One 2011;6:e29662.
  16.     Harris WS, Mozaffarian D, Lefevre M et al. Towards establishing dietary reference intakes for eicosapentaenoic and docosahexaenoic acids. J Nutr. 2009;139(4):804S-19S.
  17.     Hurst S, Zainal Z, Caterson B et al. Dietary fatty acids and arthritis. Prostaglandins Leukot Essent Fatty Acids. 2010;82(4-6):315-8.
  18.     Hussey EK, Portelli S, Fossler MJ, Gao F, Harris WS, Blum RA. Relative Bioavailability of an Emulsion Formulation for Omega-3-Acid Ethyl Esters Compared to the Commercially Available Formulation: A Randomized, Parallel-Group, Single-Dose Study Followed by Repeat Dosing in Healthy Volunteers. Clinical Pharmacology in Drug Development 2012 1: 14
  19.     Lavie CJ, Milani RV, Mehra MR et al. Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol. 2009;54(7):585-94.
  20.     Layé S. Polyunsaturated fatty acids, neuroinflammation and well being. Prostaglandins Leukot Essent Fatty Acids. 2010;82(4-6):295-303.
  21.     Lucas M, Asselin G, Mérette C et al. Effects of ethyl-eicosapentaenoic acid omega-3 fatty acid supplementation on hot flashes and quality of life among middle-aged women: a double-blind, placebo-controlled, randomized clinical trial. Menopause. 2009;16(2):357-66.
  22.     Maroon JC, Bost JW. Omega-3 fatty acids (fish oil) as an anti-inflammatory: an alternative to nonsteroidal anti-inflammatory drugs for discogenic pain. Surg Neurol. 2006;65(4):326-31.
  23.     Martin D, Nieto-Fuentes JA, Señoráns FJ et al. Intestinal digestion of fish oils and ω-3 concentrates under in vitro conditions. Eur J Lipid Sci Technol. 2010;112:1315-1322.
  24.     Masterton GS, Plevris JN, Hayes PC. Review article: omega-3 fatty acids - a promising novel therapy for non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2010;31(7):679-92.
  25.     McDaniel JC et al. Fish oil supplementation alters levels of lipid mediators of inflammation in microenvironment of acute human wounds. Wound Repair Regen. 2011;19(2):189-200.
  26. Meeusen J. Essentiële vetzuren uit algen. Leef Nu. 2008;5(41):6-7
  27.     Miller PE, Van Elswyk M, Alexander DD. Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials. Am J Hypertens. 2014 Jul;27(7):885-96
  28.     Mostowik M, Gajos G, Zalewski J et al. Omega-3 polyunsaturated fatty acids increase plasma adiponectin to leptin ratio in stable coronary artery disease. Cardiovasc Drugs Ther. 2013;27:289-295.
  29.     Naqvi AZ, Hasturk A, Mu L, Phillips RS, Davis RB, Halem S et al. Docosahexaenoic Acid and Periodontitis in Adults: A Randomized Controlled Trial. J Dent Res. 2014 Jun 26;93(8):767-773
  30.     Neubronner J, Schuchardt JP, Kressel G et al. Enhanced increase of omega-3 index in response to longterm n-3 fatty acid supplementation from triacylglycerides versus ethyl esters. Eur J Clin Nutr 2011;65:247-254.
  31. Norris J. Omega-3 Fatty Acid Recommendations for Vegetarians. VeganHealth.org/articles/omega3. 2014;1-13
  32.     Querqes G, Forte R,Souied EH. Retina and Omega-3. Journal of Nutrition and Metabolism. 2011;748361 
  33.     Raatz SK, Redmon JB, Wimmergren N et al. Enhanced absorption of n-3 fatty acids from emulsified compared with encapsulated fish oil. J Am Diet Assoc. 2009;109(6):1076-81.
  34.     Rodacki CL, Rodacki AL, Pereira G et al. Fish-oil supplementation enhances the effects of strength training in elderly women. Am J Clin Nutr. 2012;95:428-36.
  35. Sarter B, Kelsey KS, Schwartz TA, Harris WS. Blood docosahexaenoic acid and eicosapentaenoic acid in vegans: Associations with age and gender and effects of an algal-derived omega-3 fatty acid supplement. Clin Nutr. 2015;34(2):212-218
  36.     Schuchardt JP, Huss M, Stauss-Grabo M et al. Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children. Eur J Pediatr. 2010;169(2):149-64.
  37.     Sekikawa A, Shin C, Masaki KH et al. Association of total marine fatty acids, eicosapentaenoic and docosahexaenoic acids, with aortic stiffness in Koreans, whites, and Japanese Americans. Am J Hypertens. 2013 Jul 2.
  38.     Sijben JW, Calder PC. Differential immunomodulation with long-chain n-3 PUFA in health and chronic disease. Proc Nutr Soc. 2007;66(2):237-59.
  39.     Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Med. 2008;233:674-688.
  40.     Sohrabi N, Kashanian M, Ghafoori SS et al. Evaluation of the effect of omega-3 fatty acids in the treatment of premenstrual syndrome: "a pilot trial". Complement Ther Med. 2013;21(3):141-6.
  41.     Stirban A, Nandrean S, Götting C et al. Effects of n-3 fatty acids on macro- and microvascular function in subjects with type 2 diabetes mellitus. Am J Clin Nutr. 2010;91(3):808-13.
  42. Swanson D, Block R, Mousa SA. Omega-3 Fatty Acids EPA and DHA: Health Benefits Throughout Life. Adv Nutr. 2012;3(1):1-7
  43.     Swanson D, Block R, Mousa SA. Omega-3 Fatty Acids EPA and DHA: Health Benefits Throughout Life. Adv. Nutr. 3: 1–7, 2012
  44.     Toufektsian MC, Salen P, Laporte F, Tonelli C, de Lorgeril M. Dietary flavonoids increase plasma very long-chain (n-3) fatty acids in rats. J Nutr. 2011;141(1):37-41.
  45.     Transler C, Eilander A, Mitchell S et al. The impact of polyunsaturated fatty acids in reducing child attention deficit and hyperactivity disorders. J Atten Disord. 2010;14(3):232-46.
  46.     Xu ZZ, Zhang L, Liu T et al. Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions. Nature Med. 2010;16:592-597.
  47.     Yanai R et al. Cytochrome P450-generated metabolites derived from omega-3 fatty adids attenuate neovascularization. PNAS 2014, epub June 16
  48.     Yoshii H, Furuta T, Siga H et al. Autoxidation kinetic analysis of docosahexaenoic acid ethyl ester and docosahexaenoic triglyceride with oxygen sensor. Biosci Biotechnol Biochem 2002;66:749-753.
  49.     Zheng JS, Huang T, Yang J et al. Marine N-3 polyunsaturated fatty acids are inversely associated with risk of type 2 diabetes in Asians: a systematic review and meta-analysis. PLoS One. 2012;7(9):e44525.