Part 2

By: Samuel (Jody) Stagg, M.D., F.A.C.C., F.A.C.P.
In Part 1 of my discussion on Omega-3 FA, I discussed the essential nature of Omega-3 FA and that they require an outside food source because they can’t be synthesized by the human body. They are critical in human metabolism and physiology. They are key for normal growth in children and in all organ systems. They are important in both the development of and limitation of inflammatory processes in the body.

I discussed previously the three types of Omega-3 FA involved in human physiology including ALA (alpha-linolenic acid) found in plant oils and consisting of short-chain fatty acids of which humans have a limited ability to synthesize the more important long-chain fatty acids EPA/DHA from ALA. The other two types of Omega-3 FA are principally found in marine oils, and they include EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). The EPA and DHA are found in coldwater fatty fish, krill, squid, and chicken egg oils.

I previously discussed that the ratio of Omega-3 FA to Omega-6 FA was important in health and pathology. There are pro-inflammatory metabolites of both Omega-3 and Omega-6 fatty acids. The metabolites from Omega-3 FA, however, are significantly less inflammatory and less pathologic. If there is an excess consumption of Omega-6 FA, then the production of thromboxanes, prostacyclins, and leukotrienes are all significantly enhanced, leading to an abnormal inflammatory state.

I previously discussed the relation of consumption of Omega-3 FA to cancer, inflammatory disease, developmental disorders, mental health disorders, cognitive function, and briefly touched upon the correlation of Omega-3 FA levels, consumption and cardiovascular disease.

I will next move on to a discussion primarily of the cardiovascular effects of Omega-3 FA. I will discuss their effects on coronary artery disease, sudden cardiac death, ventricular and atrial arrhythmias, heart failure, cerebrovascular accidents or strokes, hypertension, and their effects on lipid levels. Finally, I’ll discuss the recommendations for Omega-3 FA intake and supplementation.


Cardiovascular Effects of Omega-3 FA

Omega-3 FA decrease triglyceride levels and change small, dense LDL (low density lipoprotein) particles to large and fluffy (less atherogenic particles) and also decrease the level of circulating inflammatory components in our bloodstreams. So there should be a significant positive benefit on cardiovascular status from their consumption.

The first reports of beneficial effects of high fish consumption were in the Greenland Eskimo population and Okinowa Islander population. These populations were observed to have a low risk of death from coronary artery disease felt to be secondary to abundance of Omega-3 FA in their diets.1, 2, 3


Coronary Artery Disease

There are several trials that have shown beneficial effects of Omega-3 FA in primary prevention of coronary artery disease but even more so in secondary prevention of cardiovascular events following a diagnosis of coronary artery disease or prior myocardial infarction. The DART Trial4showed a 30 percent reduction in total mortality and mortality related to coronary artery disease in men with prior myocardial infarctions consuming fatty fish twice per week.

The GISSI-Prevenzione Study5 showed a substantial reduction in cardiovascular and all-cause mortality in patients supplemented with one gram per day of Omega-3 FA.

In just these first two studies there has been a benefit from consuming fatty coldwater fish on a routine basis and then having Omega-3 FA provided by a fish oil supplement.

The JELIS Trial6 showed that in Japanese patients with or without coronary artery disease, the long-term use of daily Omega-3 FA reduced the risk of major cardiac events. Omega-3 FA have been shown to have a positive impact on coronary artery disease, the most prevalent disease and life-threatening condition in Western countries.


Sudden Cardiac Death

There are several studies that have found data supporting a role of Omega-3 FA supplementation in lowering the risk of sudden cardiac death. The most compelling data comes from the GISSI study7showing a significant reduction in sudden cardiac death within four months after myocardial infarction with Omega-3 FA supplementation. Ventricular arrhythmias are the usual cause of sudden cardiac death, and a decrease in sudden cardiac death would be expected to be attributed to a decrease in life-threatening ventricular arrhythmias.


Ventricular Arrhythmias

Electrophysiologic studies have shown a decrease in ventricular arrhythmias precipitated by triggered activity in patients with prior myocardial infarction (heart attacks) with Omega-3 supplements. They have found several electrophysiologic phenomena attributed to Omega-3 FA including slowing of sodium channels,8 shortening of action potential duration9 and slowing of ventricular conduction.10 These same mechanisms can potentially cause an increase in re-entry ventricular arrhythmias in patients without coronary disease or prior myocardial infarction, but the risk of arrhythmias in patients with normal hearts is miniscule. There are many factors that affect patients with coronary artery disease, cardiomyopathy and ventricular ectopy, and the potential for Omega-3 supplements to benefit both ventricular arrhythmias and sudden cardiac death may have widespread application.


Heart Failure

The risk of heart failure has been shown to be decreased by consumption of Omega-3’s, and higher serum levels of Omega-3 FA have also been shown to be associated with a diminished risk of heart failure.11 In the GISSI trial, the reduction in sudden cardiac death was most pronounced in the patients with left ventricular systolic dysfunction (weakened heart muscle).

In the GISSI Heart Failure Investigators Trial12 there were significant reductions in heart failure admissions and heart failure deaths in patients treated with 1 gram per day of EPA and DHA Omega-3 FA.


Cerebrovascular Accidents (CVA, Stroke)

A diet high in Omega-3 FA has been shown to have a carotid plaque stabilizing effect through an anti-inflammatory mechanism. Hopefully these factors will lead to less strokes, but studies are limited to date.13



There is data supporting a drop in systolic blood pressure with higher doses of Omega-3 FA supplements in particular in patients over 45 years of age.14


Atrial Fibrillation

In older patients the incidence of atrial fibrillation has been shown to be lower in those particular patients with higher levels of Omega-3’s circulating in their bloodstream.15


Lipid Levels

Omega-3 FA consistently lower triglyceride levels. Patients that have excessively high levels of triglycerides initially will require higher doses of Omega-3 FA to adequately lower the triglycerides.

Omega-3 FA change the consistency of LDL-low density lipoprotein cholesterol. At times there may be a minimal increase in the total value of LDL, but the LDL is changed from an atherogenic small, dense molecule to a much less atherogenic large, buoyant or fluffy molecule.


Omega-3 Index

A new approach to therapy with Omega-3’s has been suggested.16 It requires measuring the content of EPA and DHA in red blood cells. This is termed the “Omega-3 Index”. If the index is 8% or higher, the cardioprotection is at its maximum, and if the level is less than 4%, then the protection is minimal. In patients with a low index, then supplementation would be tailored to achieve a level of 8% or higher, giving the patients their maximum benefit.


Omega-3 FA’s Supplement Recommendations

The current American Heart Association recommendation for Omega-3 FA supplementation is supplements to include EPA/DHA:

1)             People with no history of coronary artery disease should consume oily fish or fish oils two times per week;

2)             People with coronary artery disease and a history of myocardial infarction should consume 1 gram EPA and DHA per day;

3)             People with significantly elevated triglyceride levels should consume 2 to 4 grams per day of EPA and DHA (Omega-3 FA).



Cardiovascular disease is a wide and varied disease involving all components of the cardiovascular system. It is worsened by high levels of abnormal fats and plaque-causing fats. It is also severely influenced by the level of inflammation in the body and in particular in the circulatory system. These factors can affect blockages, heart rhythm, and heart function. It affects heart disease and heart attacks, heart failure, sudden cardiac death, strokes, rhythm problems, and hypertension. There is important compelling data in multiple studies that support supplementation with Omega-3 FA, ideally with fatty fish intake but also with fish oil both in healthy subjects and more aggressively in patients with heart disease, elevated lipid levels, or a weakened heart muscle. There continues to be ongoing research into the best dosage for both healthy individuals as well as people who already have cardiovascular disease. But certainly at the present time there is ample support for supplementation with both fatty coldwater fish intake as well as supplementation in the form of fish oil.




  1. Saravanan, P et al. “Cardiovascular effects of marine Omega-3 fatty acids”: The Lancet:published on line July 16, 2010.
  2. Bang, HO et al. “Lipid metabolism and ischemic heart disease in Greenland Eskimos” Advances in Nutrition Research 1980:1-22.
  3. Kagawa, Y. “Eicosapolyenoic acids of serum lipids of Japanese islanders with low incidence of cardiovascular disease” Nutritional Science Vitaminology 1982:28:441-53.
  4. Burr, ML et al. “Effects of changes in fat, fish, and fiber intakes on death and myocardial infarction: diet and re-infarction trial (DART)” Lancet 1989; 344:757-61.
  5. GISSI-Prevenzione Investigators “Dietary supplementation with N-3 polyunsaturated fatty acids and Vitamin E after myocardial infarction” Lancet 1999; 354:447-55.
  6. Yokoyama, M et al. “Effects of eicosapentaenoic acid on major coronary events and hypercholesterolaemic patients (JELIS)” Lancet 2007; 369:1090-98.
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  8. Xiao, YF et al. “Blocking effects of polyunsaturated fatty acids on sodium channels in neonatal rat ventricular myocytes” Proc Natl Acad Science 1995; 92:11000-04.
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  10. Dhein, S et al. “Anti-arrhythmic and electrophysiologic effects of long-chain omega-3 polyunsaturated fatty acids” Naunyn-Schmiedeberg’s Archives Pharmacology 2005; 371:202-11.
  11. Mozaffarian, D et al. “Fish intake and risk of incident heart failure” JACC 2005; 45:2015-21.
  12. GISSI-HF Investigators. “Effect of N-3 polyunsaturated fatty acids in patients with chronic heart failure” Lancet 2008; 372:1223-30.
  13. Thies, F et al. “Association of N-3 polyunsaturated fatty acids with stability of atherosclerotic plaques” Lancet 2003; 361:477-85.
  14. Morris, MC et al. “Does fish oil lower blood pressure?” Circulation 1993; 88:523-33.
  15. Mozaffarian, D et al. “Fish intake and risk of incident atrial fibrillation” Circulation 2004; 110:368-73.
  16. Harris, WS et al. “The omega-3 index: a new risk factor for death from coronary heart disease” Preventive Medicine 2004; 39:212-20.