Why Omega-3 Fatty Acids Still May Reduce the Risk of Cardiovascular Disease

Recently a meta analysis of omega-3 studies concluded “omega-3 PUFA supplementation was not associated with a lower risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke based on relative and absolute measures of association” (18). News outlets reported on this study and the public opinion of fish fat as a beneficial compound for preventing cardiovascular disease likely suffered. I won’t get into my problem with meta analysis studies like this (or this one in particular), but I will say I think there is convincing evidence that omega-3’s will reduce the risk of CVD.

A number of small trials have been conducted with favorable findings for omega-3 supplements on cardiovascular disease (1-5). However, a number of other small trials found no such benefit or even a negative effect (6-13).

Among these trials, two compared the short chain (plant derived) omega-3 fatty acid ALA to the long chain (fish derived) omega-3 fatty acids. One of these studies found a greater benefit with the fish derived form (2), while the other found a greater benefit to ALA (10).

Thus, for both of these issues it seems we must focus our attention on larger trials with greater ability to find a statistically significant effect.

The Diet and Reinfarction Trail (or DART) (14) recruited 2033 subjects who had previously had a heart attack and had half of them start eating more fatty fish (2 weekly portions of 200-400 grams per week) or fish oil (0.5 grams EPA per day). After 2 years this diet change resulted in a 25% reduction in cardiovascular events and a 29% reduction in mortality.

The GISSI trial (15) randomized heart attack survivors into different groups, 2828 into a control group and 2836 into an intervention group who took a 1 gram omega-3 supplement for 3.5 years. This study found that taking these omega-3 supplements resulted in an 11% reduction in cardiovascular events and a 14% reduction in mortality.

Unfortunately, the only study testing ALA using a comparatively large sample size was not able to find a significant effect, perhaps because it only lasted 1 year (16). Roughly 5 grams of ALA were given to 6716 subjects while 6690 subjects acted as a control group. All subjects had previously suffered a myocardial infarction. The number of cardiovascular events and deaths were both non-significantly greater in the ALA group.

So while this study may not have lasted long enough to prove the benefits of ALA, there simply exists less evidence demonstrating its benefits than the long chain (fish derived) omega-3 fatty acids.

Ultimately, the results of the DART and GISSI trial should lend decent support to the idea that omega-3 fatty acids are good for your heart and your soul (okay, just the first one).


1. von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999;130:554-62

2. Singh RB, Niaz MA, Sharma JP, Kumar R, Rastogi V, Moshiri M Randomized, double-blind, placebo-controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction: the Indian experiment of infarct survival–4. Cardiovasc Drugs Ther 1997;11:485-91

3. Bairati I, Roy L, Meyer F Double-blind, randomized, controlled trial of fish oil supplements in prevention of recurrence of stenosis after coronary angioplasty. Circulation 1992

4. Dehmer GJ, Popma JJ, van den Berg EK, Eichhorn EJ, Prewitt JB, Campbell WB, Jennings L, Willerson JT, Schmitz JM Reduction in the rate of early restenosis after coronary angioplasty by a diet supplemented with n-3 fatty acids. N Engl J Med 1988 Sep 22;319:733-40

5. Nye ER, Ablett MB, Robertson MC, Ilsley CD, Sutherland WH Effect of eicosapentaenoic acid on restenosis rate, clinical course and blood lipids in patients after percutaneous transluminal coronary angioplasty. Aust N Z J Med 1990 Aug;20:549-52

6. Johansen O, Brekke M, Seljeflot I, Abdelnoor M, Arnesen H N-3 fatty acids do not prevent restenosis after coronary angioplasty: results from the CART study. Coronary Angioplasty Restenosis Trial. J Am Coll Cardiol 1999;33:1619-26

7. Nilsen DW, Albrektsen G, Landmark K, Moen S, Aarsland T, Woie L Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol. Am J Clin Nutr 2001 Jul;74:50-6

8. Leaf A, Jorgensen MB, Jacobs AK, Cote G, Schoenfeld DA, Scheer J, Weiner BH, Slack JD, Kellett MA, Raizner AE Do fish oils prevent restenosis after coronary angioplasty? Circulation 1994 Nov;90:2248-57

9. Reis GJ, Boucher TM, Sipperly ME, Silverman DI, McCabe CH, Baim DS, Sacks FM, Grossman W, Pasternak RC Randomised trial of fish oil for prevention of restenosis after coronary angioplasty. Lancet 1989 Jul 22;2:177-81

10. Kromhout D, Giltay EJ, Geleijnse JM n-3 Fatty Acids and Cardiovascular Events after Myocardial Infarction. N Engl J Med 2010 Nov 18;363:2015-2026

11. Sacks FM, Stone PH, Gibson CM, Silverman DI, Rosner B, Pasternak RC Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. J Am Coll Cardiol 1995 Jun;25:1492-8

12. Bellamy CM, Schofield PM, Faragher EB, Ramsdale DR Can supplementation of diet with omega-3 polyunsaturated fatty acids reduce coronary angioplasty restenosis rate? Eur Heart J 1992 Dec;13:1626-31

13. Senges Randomized Trial of Omega-3 Fatty Acids on Top of Modern Therapy After Acute Myocardial Infarction: The OMEGA Trial ACC.09/i2, Orlando, FL, March 2009 [0] Rauch B, Schiele R, Schneider S, Diller F, Victor N, Gohlke H, Gottwik M, Steinbeck G, Del Castillo U, Sack R, Worth H, Katus H, Spitzer W, Sabin G, Senges J OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified omega-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction. Circulation 2010;122:2152-9

14. Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, Elwood PC, Deadman NM Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989 Sep 30;2:757-61

15. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet 1999 Aug 7;354:447-55

16. Natvig H, Borchgrevink CF, Dedichen J, Owren PA, Schiotz EH, Westlund K. A controlled trial of the effect of linolenic acid on incidence of coronary heart disease. The Norwegian vegetable oil experiment of 1965-66. Scand J Clin Lab Invest Suppl. 1968;105:1-2

17. Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA. 2012 Sep 12;308(10):1024-33. doi: 10.1001/2012.jama.11374. Review


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