Better by far that you should forget and smile than that you should remember and be sad. Christina Rossetti

I don't know about you but this late picture of Christina, painted by her brother, suggests that she couldn't help but remember!

Heart attack prevention – the meta-analyses

 To my mind the evidence that eating oily fish, or taking a fish oil supplement, protects people from heart attacks has been strong for quite some time. Nevertheless, on April 1 2006, a meta-analysis by Dr Lee Hopper and colleagues, published in the British Medical Journal, concluded the very opposite.  In their words, “The pooled estimate showed no strong evidence of reduced risk of total mortality or combined cardiovascular events in participants taking additional omega-3 fats.” They concluded that long chain and shorter chain omega-3 fats do not have a clear effect on total mortality, combined cardiovascular events, or cancer.”

Have I been wrong in my conclusions over the years? I don’t think so. Yet I do think the study is in itself a wake-up call to governments to do sponsor additional studies, in particular a high quality double blind controlled population study that compares fish oil, and concentrated omega-3s, to aspirin in heart attack and mortality prevention.

A year earlier a meta-analysis by Mozaffarian and Rimm, published by the Journal of the American Medical Association, concluded the very opposite, concluding that eating fish, or taking fish oil, was indeed protective – and with little or no side effects.

Why the differences in the two conclusions. I think an editorial by Deckelbaum and Akabas, published in the American Journal of Clinical Nutrition to accompany a third meta-analysis of the benefits of fish or fish oil supplements, is indicative:

“The authors correctly propose that a meta-analysis of this topic is not possible because of the heterogeneity of study designs, background diets, endpoint definitions, and baseline fish or omega-3 intakes.” 

The meta-analysis referred was the 2006 study reported by Wang and colleagues, which concluded, “Most cohort studies reported that fish consumption was associated with lower rates of all-cause mortality and adverse cardiac outcomes… Evidence suggests that increased consumption of omega-3 fatty acids from fish or fish oil supplements, but not of alpha-linolenic acid [the vegetable omega-3], reduces the rates of all-cause mortality, cardiac and sudden deaths, and possibly stroke.”

I agree with the major health authorities, including the American Heart Association and the UK NICE Committe, which continue to advocate fish or fish oil in heart attack prevention.

 

 Further Reading
 

Ait-Said, Elalmy I I, et al (2003). Inhibition by eicosapentaenoic acid of IL beta-induced PGHS-2 expression in human microvascular enthothelial cells: involvement of lipoxygenase-derived metabolites and p38 MAPK pathway. Biochim Biopphys Acta 1631(1):77-84.

Albertazzi P, Coupland K, et al (2002). Polyunsaturated fatty acids. Is there a role in postmenopausal osteopororis prevention. Maturitas 42(1):13-22.
American Heart Association website at www.americanheart.org/presenter.

Balk E, Chung M, et al (2004). Effects of Omega-3 fatty acids on cardiovascular Disease. Evidence Report/Technology Assessment No. 94 (prepared by Tufts-New England Medical Center Evidence-based Practice Center. AHRQ Publication No. 04-E009-2 Agency for Healthcare Research and Quality March 2004.

Belluzzi A, Boschi S, et al (2000). Polyunsaturated fatty acids and inflammatory bowel disease. Am J Cli Nutr 71(S) : 339-42.

Burr, ML, Fehily AM, et al (1989). Effects of changes in fat, fish and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 2:757-761.

Burr ML, Sweetham PM and Fehily AM (1994). Diet and reinfarction. Eur Heart J 15:1152-1153.

Connor WE (2000). Importance of n-3 fatty acids in health and disease. Am J Clin Nutr 71(Suppl): 171S-75S.

Curtis CI, Hughes CE, et al (1999). N-3 Fatty Acids Specifically Modulate Catabolic Factors Involved in Articular Cartilage Degradation. J Biol Chem 275: 721-24.

Curtis CL, Rees SG, et al (2002). Pathologic indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids. Arthritis Rheum 46(6):1544-53.
Curtis CL, Rees SG, et al (2002). Effects of n-3 fatty acids on cartilage metabolism. Proc Nutr Soc 61(3):381-89.
Das UN (2006). Biological significance of essential fatty acids. JAPI 54: 309-19.

Damsgaard C, Lauritzen L, et al (2007). Fish Oil Supplementation Modulates Immune Function in Healthy Infants. J Nutr 137:1031-1036.  

De Lorgereil M and Salen P (2006). The Mediterranean diet in secondary prevention of coronary heart disease. Clin Invest Med 29(3):154-58.

Deckelbaum RJ and Akabas SR (2006).  N-3 fatty acids and cardiovascular disease: navigating toward recommendations.  Am J Nutr 84: 1-2.

Dietary supplementation with n-3 polyunsaturated fatty acids and Vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial (1999). Lancet354:447-455. Geusens P, Wouters C, et al (1991). Long-term Effects of Omega-3 Fatty Acid Supplementation in Active Rheumatoid Arthritis: A 12-Month, Double Blind, Controlled Study. Arthritis and Rheumatism 37: 824-29. 

Endres S, Caterina R De, et al (1995). N-3 Polyunsaturated fatty Acids: update. European J Clinical Investigation 25: 629-638. 

Geusens P, Wouters C, et al (1991). Long-term effects of omega-3 fatty acid supplementation in active rheumatoid arthritis: a 12-month, double blind, controlled study. Arthritis and Rheumatism 37: 824-829. 

Harris WS (1997). N-3 fatty acids and serum lipoproteins: human studies.  Am J Clin Nutr 65(S):1644S-54S.

Hjerkinn EM, Abdelnoor M, et al (2006). Effect of diet of very long chain Omega-3 fatty acids on progression of atherosclerosis, evaluated by carotid plaques, intima-media thickness and by pulse wave propagation in elerly men with hypercholesterolaemia. Eur J Cardiovasc Pre Rehabil 13(3):325-33.
Hu Frank B., et al (2003). Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women. Circulation 107: 1852-57.
Jolly CA, Muthukumar A, et al (2001). Life span is prolonged in food-restricted autoimmune-prone (NZB x NZW)F (1) mice fed a diet enriched with (n-3) fatty acids. J Nutr 131(10):2753-60.

Kahn F, Elherik K, et al (2003). The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects. Cardiovasc Res 59: 995-62.

Kettler DB (2001). Can manipulation of the ratios of essential fatty acids slow the rapid rate of postmenopausal bone loss? Altern Med Rev 6(1):61-77.

Kremer JM, Jubiz W, et al (1987). Fish-Oil Fatty Acid Supplementation in Active Rheumatoid Arthritis: A Double Blind, Controlled, Crossover Study. Ann Int Med 106: 497-502.

Kremer JM (1997). Omega-3 Fatty Acid Supplements in Rheumatoid Arthritis. ISSFAL Newsletter  4: 5-8. (An important summary of the American findings)

Kris-Etherton PM, Harris WS, et al (2002). Fish consumption, fish oil, Omega-3 fatty acids and cardiovascular disease. Circulation 106:2747.
Kruger MC and Coetzer H (1998). Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging (Milano) 10(5):385-94.
Lau, CS, Morley KD and Belch JJF (1993). Effects of Fish Oil Supplementation on Non-Steroidal Anti-Inflammatory Drug Requirements in Patients with Mild Rheumatoid Arthritis - A Double-Blind Placebo Controlled Study. Br J Rheumatology 32: 982-89. 

Lee S, Gura KM, et al (2006). Current clinical application of omega-6 and omega-3 fatty acids. Nutr Clin Practice 21(4):323-41.
Lichtenstein AH, Allel LJ, et al (2006). Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation 114: 82-86.

Maki NC, Van Elswky ME, et al (2005). Lipid responses to a dietary docosahexaenoic acide supplement in men and women with below average levels of high density lipoprotein cholesterol. J Am Coll Nutr 24(3):189-99.
Marchioli R, Barzi F, et al (2002). Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Sudio dell Sopravvivenze nell’Infarcto Mayo Clinic website at www.mayoclinic.com/health/fiosh-oil/NS-patient-fishoil. McKenney J and Sica D (2007). Prescription omega-3 fatty acids for the treatment of hypertriglyceridemia. American Journal of Health-System Pharmacy 646:595-605.

Miocardi (GISSI)-Prevenzione. Circulation 105: 1897-1903.

Mita T, Watada H, et al (2003). Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes.  Atherosclerosis 191(1): 162-167. 

Mozaffarian D, Lemaitre RN, et al (2003). Cardiac benefits of fish consumption may depend on the type of fish meal consumed: The cardiovascular health study. Circulation 107: 1372-7.

Mozaffarian D, Psaty BM (2004). Fish intake and risk of incident atrial fibrillation. Circulation 110(4):368–73.

Mozaffarian D, Bryson CL, et al (2005). Fish intake and risk of incident heart failure. J Amer Coll Cardiol 45(12): 2015-21.

Mozaffarian D and Rimm EB (2006). Fish Intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 296(15): 1885-1900.

Mozzafarian D, Longstreth WT, et al (2005). Fish consumption and stroke risk in elderly individuals. Arch Intern Med 165(2): 200-6.

Muthukumar A, Sun D, et al (2004). Age associated alterations in costimulatory and adhesion molecule expression in lupus-prone mice are attenuated by food restriction with N-6 and N-3 fatty acids. J Clin Immunol 24(5):471-80.

Nestel PJ (2000). Fish oil and cardiovascular disease: lipids and arterial function. Am J Clin Nutr 71(S): 228-31

NIH Office of Dietary Supplements website at www.dietary-supplements.info.nih.gov/Fact Sheets/Omega3fatty Acids and Health.asp See also ods.od.nih.gov and ahrq.gov.

Rupp H (2006). Omega-3 fatty acids in secondary prevention after myocardial infarct. Clin Res Cardiol 95(S6): vi12-vi16.
Sanders TAB (1993). Marine oils: metabolic effects and role in human nutrition. Proc Nutrition Society 52: 457-472. 

Simopoulos AP (2002). Omega-3 fatty acids in inflammation and autoimmune diseases. J Am College of Nutrition 21: 495-505.

Siscovick, DS, Raghunathan TE, et al (1995). Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA 274(17):1363-67.

Sun L, Tamaki L, et al (2004). Inhibitation of osteopororsis due to restricted food intake by the fish oils DHA and EPA and perilla oil in the rat. Biosci Biotechnol Biochme 68(12):2613-5.

Tempel H van der, Tulleken JE, et al (1990). Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheumatol Diseases 49: 76-80.

Von Schacky C (2000). N-3 fatty acids and the prevention of coronary atherosclerosis. Am J Clin Nutr 71(S):224-27. 

Wang C, Harris WS, et al (2006). N-3 fatty acids from fish or fish-oil supplements but not α-linoleic acid, benefit cardiovascular outcomes in primary and secondary prevention studies: a systematic review. Am J. Clin Nutr 84:5-17

Yokoyama M et al (2007). Effects of eicosapentaenoic acid on major coronary events in hypercholesterolemic patients (JELIS): a randomized open-label, blinded endpoint analysis. Lancet 369: 1090-98.



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