MICROgenics^® Reflux Free Fish Oil

Inflammation

Inflammation is a response to tissue damage or other perceived threat, characterised by swelling, heat, redness, and pain. These symptoms are due to immune activity and the release of inflammatory chemicals. Blood flow is increased to deliver immune cells and nutrients to the area affected to protect against infection and heal damaged tissue.

Chronic inflammation

Chronic inflammation is a long-term reaction maintained by continued production of inflammatory compounds which damage tissue in the affected area and cause chronic pain, and swelling, and may lead to loss of function. Causes may include genetic factors, injuries, infections, toxins, allergic reactions, or nutritional deficiencies or imbalances. Chronic inflammation is believed to be a contributing factor to diseases such as osteoarthritis, eczema, dermatitis, asthma, heart disease, Alzheimer’s disease, cancer, and autoimmune disorders, such as multiple sclerosis and rheumatoid arthritis.

Polyunsaturated fats in cell membranes regulate chronic inflammation

Cell membranes contain a mix of omega-3  omega-6 polyunsaturated fats. The omega-6 fatty acid, linoleic acid, and the omega-3 fatty acid, alpha-linolenic acid, are both essential in the diet because they cannot be made in the body. They are the starting materials for making pro- and anti-inflammatory eicosanoids, comprising prostaglandins (PG), thromboxanes and leukotrienes. Eicosanoids act like local hormones to regulate cell functions and are produced as required from the breakdown of omega-3 and omega-6 fats in cell membranes.

The correct balance between omega-3  omega-6 fats is vital for keeping inflammation under control. Modern diets are overloaded with omega-6 fats that form eicosanoids with powerful inflammatory effects. In normal conditions, the enzyme COX-1 helps convert fatty acids to eicosanoids for short-term use in immune defence and healing but in chronic inflammation a variant enzyme, COX-2, is expressed that drives ongoing production of inflammatory eicosanoids, especially PGE2 from the omega-6 fatty acid arachidonic acid, that can cause damage to body tissues. If sufficient omega-3 fats are eaten, they will replace omega-6 fats in cell membranes and be used preferentially to make eicosanoids that are less inflammatory.

Omega-3 fats have anti-inflammatory activity¹

Step 1. The essential omega-3 fatty acid, alpha-linolenic acid, found in foods such as fatty fish, seafood, fish oil, flaxseed oil, canola oil, and green leafy vegetables, is incorporated into cell membranes and converted to eicosapentaenoic acid (EPA). EPA can also be obtained from fatty fish, seafood, and fish oil, but not from plant foods.

Step 2. EPA in cell membranes is then converted to DHA and pro- and anti-inflammatory eicosanoids by the same enzymes that work on the omega-6 pathway. Prostaglandin I3 is strongly anti-inflammatory but the inflammatory eicosanoids produced are relatively weak compared to those produced from omega-6 fats, and the overall effect is to reduce inflammation. PGE2 and PGE3 both induce COX-2 gene expression but PGE3 is significantly weaker in effect.²

Fish oil is a source of alpha-linolenic acid as well as preformed EPA and DHA

Unlike plant sources of omega-3 fats, fatty fish and fish oil contain preformed EPA and DHA. Research has shown that, in humans, alpha-linolenic acid has relatively poor conversion to EPA and even poorer conversion to DHA.³ If the diet is high in saturated fat, only 6% of a given dose of alpha-linolenic acid is converted to EPA and only 3.8% to DHA, and a diet high in omega-6 fats reduces conversion by 40-50%. EPA and DHA inhibit arachidonic acid metabolism to inflammatory eicosanoids. EPA produces less inflammatory eicosanoids and both EPA and DHA produce resolvins and protectins that help switch off inflammation.⁴ Fish oil modulates antigen presentation, T-cell reactivity, and production of NF kappaB, interleukins, tumour necrosis factor and inflammatory cytokines, creating a net anti-inflammatory effect.⁵

Fish oil protects against cardiovascular disease (CVD)

Omega-3 fats have blood thinning activity, stabilise heart rhythm, lower blood pressure, reduce triglyceride levels and lower the secretion of very low density lipoproteins (VLDL), as well as increasing triglyceride removal from VLDL and chylomicron particles by upregulating enzymes such as lipoprotein lipase.

There is good evidence for the effectiveness of fish oil in reducing the risk of CVD and CVD mortality. Meta-analyses of clinical trials show that fish oil, in doses averaging 3 g of omega-3 fatty acids a day, can reduce blood pressure in hypertensive people by up to 5.5/3.5 mm Hg.⁶ At least one fish meal a week is associated with a 52% reduction in sudden cardiac death.⁷ In a large-scale Italian trial, men with a previous myocardial infarction (MI) who took fish oil had a 30% reduction in cardiac mortality and a 45% reduction in sudden death.⁸

A systematic review found that fish oil supplementation has potent triglyceride-lowering activity.⁹ Fish oil can also reduce VLDL, chylomicrons, remnants, LDL, apo B, and apo E levels. Fish and fish oil had profound hypolipidaemic effects in normal subjects and in hypertriglyceridaemic patients with combined hyperlipidaemia (type II-b) and hyperlipidaemia type IV and V.¹⁰ As little as 210 mg EPA and 120 mg DHA a day has been found to significantly reduce serum triglycerides in patients with elevated levels.¹¹

Fish oil is now mainstream medicine for heart disease

The American Heart Association recommends 1000 mg of EPA and DHA from oily fish daily for all patients with heart disease, obtained through diet or fish oil supplementation.¹² Recently, the National Heart Foundation (NHF) of Australia released a position statement recommending that all adults have 500 mg of combined EPA and DHA daily (approx. 2 standard fish oil caps/day) to help reduce the risk of heart disease.¹³ The NHF recommends that all patients with heart disease consume 1,000 mg/day of combined EPA and DHA through oily fish or fish oil supplements (approx. 3 standard fish oil caps/day), and 2,000 mg/d of alpha-linolenic acid daily. The NHF also recommends that all patients with elevated triglycerides should take as first-line therapy 1,200 mg/day of combined EPA and DHA (4 standard fish oil caps/day), increasing to 4,000 mg/day as required (approx. 13 fish oil caps/day). The NHF also recommends the inclusion of fish oil in the Pharmaceutical Benefits Scheme to encourage fish oil prescribing.

Fish oil is anti-inflammatory in rheumatoid arthritis (RA)

More than fifteen clinical trials and two meta-analyses have found fish oil of benefit in patients with RA.⁶ A meta-analysis of the use of omega-3 fats for joint pain, including RA, found that supplementation for three to four months reduces patient-reported joint pain intensity, duration of morning stiffness, number of painful and/or tender joints, and non-steroidal anti-inflammatory drug (NSAID) consumption.¹⁴ A study of daily supplementation with 2.6 g of omega-3 relieved pain and reduced the need for pain-relieving medication in subjects with RA.¹⁵ It is recommended that people with RA take a supplement providing 3-6 g of omega-3 fats daily for at least 12 weeks.¹⁶ A key benefit is the potential to reduce or eliminate NSAID use in people with RA.

References

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• Bagga D et al. Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1751-6.
• Gerster H. Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)? Int J Vitam Nutr Res. 1998;68(3):159-73.
• Serhan CN, Yacoubian S, Yang R. Anti-inflammatory and proresolving lipid mediators. Annu Rev Pathol. 2008;3:279-312.
• Calder PC. Session 3: Joint Nutrition Society and Irish Nutrition and Dietetic Institute Symposium on 'Nutrition and autoimmune disease' PUFA, inflammatory processes and rheumatoid arthritis. Proc Nutr Soc. 2008 Nov;67(4):409-18.
• Howe PR. Dietary fats and hypertension. Focus on fish oil. Ann N Y Acad Sci. 1997 Sep 20;827:339-52.
• Oh R. Practical applications of fish oil (Omega-3 fatty acids) in primary care. J Am Board Fam Pract. 2005 Jan-Feb;18(1):28-36.
• Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI Prevenzione trial. Lancet 1999;354:447–55.
• Phillipson BE, Rothrock DW, Connor WE, et al. Reduction of plasma lipids, lipoproteins, and apoproteins by dietary fish oils in patients with hypertriglyceridemia. N Engl J Med 1985;312:1210–6.
• Connor WE, DeFrancesco CA, Connor SL. N-3 fatty acids from fish oil. Effects on plasma lipoproteins and hypertriglyceridemic patients. Ann N Y Acad Sci. 1993 Jun 14;683:16-34.
• Weber P, Raederstorff D. Triglyceride-lowering effect of omega-3 LC-polyunsaturated fatty acids--a review. Nutr Metab Cardiovasc Dis. 2000 Feb;10(1):28-37.
• Kris-Etherton PM, Harris WS, Appel LJ. AHA scientific statement: fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002;106:2747–57.
• National Heart Foundation. Position statement: fish, fish oils, n-3 polyunsaturated fatty acids and cardiovascular health. 2008. National Heart Foundation of Australia.
• Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007 May;129(1-2):210-23. Epub 2007 Mar 1.
• Geusens P et al. Long-term effect of omega-3 fatty acid supplementation in active rheumatoid arthritis: a 12-month, double-blind, controlled study. Arthritis Rheum. 1994;37(6):824-29.
• Kremer JM. n-3 fatty acid supplements in rheumatoid arthritis. Am J Clin Nutr. 2000 Jan;71(1 Suppl):349S-51S.