expert opinion

Omega-3 fatty acids in disease prevention: a general overview

May 1, 2013

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Philip C. Calder, Professor of Nutritional Immunology, University of Southampton, UK

Omega-3 fatty acids are a family of naturally occurring polyunsaturated fatty acids. The omega-3 family includes alpha-linolenic (ALA), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA). These fatty acids have different structures, different dietary sources and different functions, but they are metabolically related to one another. ALA cannot be synthesized by animals, including humans, but is synthesized by plants (particularly flaxseeds). In the human body ALA can be converted into EPA and DHA, although the extent of this conversion, especially to the end product DHA, seems to be quite poor, may be greater in women than in men and may be partly determined by genetics (1). Increased intake of ALA can increase the amount of EPA in the blood and in blood cells. However, conversion of ALA to EPA is decreased if intake of the essential omega-6 fatty acid linoleic acid (LA) is high, because of metabolic competition between the two fatty acids. EPA and DHA are found in seafood and in the greatest amounts in ‘fatty’ or ‘oily’ fish like salmon, mackerel and sardines. In the absence of a significant consumption of oily fish, ALA is the major omega-3 fat in the diet; adults in the UK typically consume about one gram of ALA each day, this constituting about 90 percent of their dietary requirement of omega-3 fatty acids. Intake of the omega-6 fatty acid linoleic acid is about 10 times greater than this.

In non-fish consumers, intake of EPA+DHA is likely to be less than 0.1 gram per day. One meal of oily fish can provide one to three grams of EPA+DHA, depending upon the type of fish, so eating oily fish can greatly increase intake of EPA and DHA. Regular fish consumers have a higher content of these two fatty acids in their blood, blood cells and tissues compared with non-fish eaters. In the UK less than 25 percent of adults eat oily fish on a regular basis (2). Fish oil supplements provide both EPA and DHA, which constitute about one third of the fatty acids in a standard fish oil capsule. Thus, a standard one gram capsule would provide about 0.3 grams of EPA+DHA. More concentrated fish oils are available, which have a higher content of EPA and DHA, and there is a pharmaceutical grade omega-3 preparation which is highly concentrated, being made up of approximately 90 percent EPA+DHA. Fish oil supplements can substantially increase intake of EPA and DHA and people who regularly use these supplements have a higher content of these two fatty acids in their blood, blood cells and tissues than those who do not use supplements and do not eat fish. As far as human health is concerned, EPA and DHA are the most important omega-3 fatty acids, although ALA is important in those who do not consume pre-formed EPA from fish or supplements.

Interest in the health benefits of omega-3 fats can be traced back to epidemiological studies on Greenland Inuits, where the very low rate of mortality from coronary heart disease that was observed was ascribed to a high intake of EPA and DHA from seal, whale and fish. This link was confirmed by studies on the Japanese and has also been demonstrated across the range of habitual intakes in Western populations (3). The expla-nation for the cardio-protective effect of EPA+DHA is beneficial modification in the profile of cardiovascular risk factors such as serum triglycerides, blood pressure, endothelial dysfunction, inflammation and thrombo-sis (4). The efficacy of EPA+DHA in lowering serum triglycerides is such that some formulations are licensed as triglyceride -lowering medications. The improved risk profile for cardiovascular disease that occurs with increased intake of EPA+DHA most likely slows or limits the process of atherosclerosis, the build-up of fatty plaque within the blood vessel wall. A small number of large secondary prevention trials have demonstrated that EPA+DHA reduces mortality, especially as a result of myocardial infarction, in people with existing ad-vanced atherosclerosis (5).This has focused attention on the actions of EPA and DHA in heart cell electro-physiology and in atherosclerotic plaque stability as likely mechanisms at play in people with existing di-sease. Some recent trials have failed to reproduce the previously documented protective effects of EPA+DHA on mortality; the reason for this is not clear, but may relate to some significant differences between recent and earlier trials and some failures in the design of recent trials (6).

Omega-3 fatty acids have an anti-inflammatory action that may be useful in treating some chronic diseases where inflammation is part of the pathology (7). The anti-inflammatory effect of EPA+DHA stems from their ability to interfere with the production of the classic pro-inflammatory eicosanoids (prostaglandins and leukotrienes) produced from omega-6 arachidonic acid (AA). In addition, EPA yields eicosanoids that are typically biologically weak, while resolvins produced from EPA and DHA and protectins produced from DHA seem to be very potent inflammation-resolving agents. Thus increased exposure to EPA and DHA results in an environment that is not only less inflammatory, but which favors the resolution (‘turning off’) of inflam-mation.

Some regions of the brain and the eye have a very high content of DHA which plays specific roles in membrane structure, enabling appropriate signaling mechanisms to operate, for example when the eye receives a visual stimulus. Because the brain and eye develop early in life, it is essential that a baby receives sufficient DHA from its mother before birth (i.e. across the placenta) and after birth (i.e. in breast milk) in order to optimize visual and neurological function (8). There is some evidence that the importance of omega-3 fats for aspects of brain function goes beyond these very early fundamental developmental aspects. For example, a small number of studies have highlighted the potential for omega-3 fatty acids to contribute to enhanced mental development (9) and improved childhood learning and behavior (10), and to reduce the burden of psychiatric illnesses in adults (11), although these remain less certain areas of possible action which require more scientific support. There may also be a role for omega-3 fatty acids, DHA in parti-cular, in preventing neurodegenerative disease as a consequence of ageing (12).

Another area that has emerged where omega-3 fatty acids may have an important role is in nutrition support, either enterally or parenterally. Lipids traditionally used in nutrition support are based on soybean oil, which is rich in the omega-6 fatty acid LA. This may not be optimal and one alternative is the partial replacement of soybean oil by fish oil. Parenteral fish oil has proven to be beneficial for neonates with liver failure, adults having undergone surgery (mainly gastrointestinal) and, in some studies, critically ill adults (13). Fish oil has been included in combination with other nutrients in various enteral formulae which have benefits for post-surgical patients, for patients with mild sepsis or trauma and for patients with acute respiratory distress syndrome, acute lung injury or severe sepsis (13).

Much progress is being made in terms of our understanding of the effects of omega-3 fatty acids and the mechanisms of action involved (14). It is likely that the coming years will see significant progress in this area, with new actions being discovered and existing actions being increasingly understood.”

Based on: Calder P. C. Omega-3 fatty acids in health and disease: the science behind the headlines. NHD Magazine. 2013; 83:18-19.

References

  1. Burdge G. C. and Calder P. C. Dietary alpha-linolenic acid and health-related outcomes: a metabolic perspective. Nutrition Research Reviews. 2006; 19:26-52.
  2. Scientific Advisory Committee on Nutrition/Committee on Toxicity. Advice on Fish Consumption: Benefits and Risks. London: TSO. 2004.
  3. Calder P. C. N-3 fatty acids and cardiovascular disease: evidence explained and mechanisms explored. Clinical Science. 2004; 107:1-11.
  4. Saravanan P. et al. Cardiovascular effects of marine omega-3 fatty acids. Lancet. 2010; 376:540-550.
  5. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated atty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999; 354:447-455.
  6. Calder P. C. and Yaqoob P. Marine omega-3 fatty acids and coronary heart disease. Current Opinion in Cardiology. 2012; 27:412-419.
  7. Miles E. A. and Calder P. C. Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis. British Journal of Nutrition. 2012; 107:171-184.
  8. SanGiovanni J. P. et al. Meta-analysis of dietary essential atty acids and long-chain polyunsaturated fatty acids as they relate to visual resolution acuity in healthy preterm infants. Pediatrics. 2000; 105:1292-1298.
  9. Helland I. B. et al. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children’s IQ at 4 years of age. Pediatrics. 2003; 111:39-44.
  10. Richardson A. J. Clinical trials of fatty acid treatment in ADHD, dyslexia, dyspraxia and the autistic spectrum. Prostaglandins Leukotrienes and Essential Fatty Acids. 2004; 70:383-390.
  11. Freeman M. P. et al. Omega-3 fatty acids: evidence basis for treatment and future research in psychiatry. Journal of Clinical Psychiatry. 2006; 67:1954-1967.
  12. Solfrizzi V. et al. Dietary fatty acids in dementia and predementia syndromes: epidemiological evidence and possible underlying mechanisms. Ageing Research Reviews. 2010; 9:184-199.
  13. Calder P. C. Rationale and use of n-3 fatty acids in artificial nutrition. Proceedings of the Nutrition Society. 2010; 69:565-573.
  14. Calder P. C. Mechanisms of action of (n-3) fatty acids. Journal of Nutrition. 2012; 142:592-599.