Fish oils, including omega-3 fatty acids or ω-3 fatty acids, are dietary "oils high in unsaturated fats extracted from the bodies of fish or fish parts, especially the livers. Those from the liver are usually high in vitamin A. The oils are used as dietary supplements, in soaps and detergents, as protective coatings, and as a base for other food products such as vegetable shortenings."
Classification of polyunsaturated fatty acids
|ω-3 fatty acids||ω-6 fatty acids|
|Essential fatty acid precursor||α-linolenic acid (ALA)||linoleic acid (LA)|
|Proportion of PUFAs in North American diet||9%||89%|
|Dietary source||Leafy green vegetables, canola and soybean oil flaxseed, walnuts||Cooking oils including safflower, sunflower, soy, and corn|
|Metabolic products||Eicosapentaenoic acid (EPA)
Docosahexaenoic acid (DHA)
(Fish oils contain EPA and DEA)
|Physiology||• suppression of inflammatory cytokines||• platelet aggregation|
• synthesis of inflammatory cytokines
About nine ounces per week of oily fish is equivalent to taking about 500 mg eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids per day. Thus, for cardiac protection, at least 6 servings per week of 3 ounces of fish are needed.
Dietary fatty acids can be divided into saturated fatty acids and unsaturated fatty acids. Unsaturated fatty acids can be further divided into monounsaturated and polyunsaturated fatty acids (PUFAs).
PUFAs are divided into two groups: omega-3 fatty acids and omega-6 fatty acids. Whereas omega-3 fatty acid have health benefits due to several mechanisms; omega-6 fatty acids are precursors to arachidonic acid (AA) which leads to thrombaxanes which promote platelet aggregation and vasoconstriction.
Two PUFAs, α-linolenic acid (ALA) and linoleic acid (LA) are called essential fatty acids because human function requires them, yet humans cannot synthesize then in vivo. ALA is a omega-3 fatty acid while AL is a omega-6 fatty acid. In North America, LA comprises 89% of the total PUFAs consumed, while ALA - which leads to the favorable omega-3 fatty acid pathway - comprises only 9%. LA is in many commonly used oils, including safflower, sunflower, soy, and corn oil. ALA is in leafy green vegetables and in canola and soybean oil. Fish oil consumption is 2-4 times higher (1 ounce versus 2-4 ounces) in the Japanese diet than the North American diet.
Dietary fish oils are converted to eicosapentaenoic acid (EPA) which is further converted to docosahexaenoic acid (DHA). Both EPA and HHA are omega-3 fatty acids. About nine ounces per week of oily fish is equivalent to taking about 500 mg eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids per day.
Effect on human health
Although proposed to improve membrane stabilization and thus reduce dysrhythmias, this benefit seems unlikely based on the increase in dysrhythmias in a more recent trial.
Coronary heart disease and mortality
The benefit of fish oil on coronary heart disease and mortality is controversial with conflicting conclusions reached by a negative meta-analysis (search dates April, 2011 and February, 2002) of randomized controlled trials by the international Cochrane Collaboration, a partially positive systematic review (search date July, 2005) by the Agency for Healthcare Research and Quality (AHRQ), and a positive systematic review (search date March, 2007). The AHRQ review noted differences among types of fish oils, "Evidence suggests that increased consumption of n–3 FAs from fish or fish-oil supplements, but not of α-linolenic acid, reduces the rates of all-cause mortality, cardiac and sudden death, and possibly stroke." They note that less than 5% of α-linolenic acid is converted to EPA or DHA.
Three subsequent randomized controlled trials not included in all of the above systematic reviews have also had conflicting results finding both benefit (reduction on coronary events in Japanese hypercholesterolemic patients and improvement in patients with heart failure).
- JELIS used "eicosapentaenoic acid...given at a dose of 600 mg, three times a day after meals (to a total of 1800 mg per day)." 20% of patients had prior coronary heart disease. This trial was only included in the 2007 systematic review by León.
- Gissi-HF used "one capsule per day of 1 g n-3 PUFA (850–882 mg eicosapentaenoic acid and docosahexaenoic acid as ethyl esters in the average ratio of 1:1·2)." This trial was not only included in any of the three systematic reviews above. The benefit of fish oil in this study was better than the benefit of rosuvastatin in GISSI-HF.
Raitt studied antiarrhythmic effects in patients with a history of sustained ventricular tachycardia or ventricular fibrillation (73% of patients had prior coronary heart disease) and found an increase in dysrhythmias. This result contradicts the benefit found in the GISSI-Prevenzione randomized controlled trial of patients with recent myocardial infarction who were treated for 3.5 years. and the insignificant improvements in the SOFA and FAATI trials.
The contradictory results have been hypothesized to be from omega3-PUFAs being both pro-arrhythmic or antiarrhythmic, and suppress re-entrant dysrhythmias (patients with acute ischemia or prior sustained ventricular dysrhythmia)and promote triggered dysrhythmias (patients with prior myocardial infarction).
|Patients||Intervention / duration||Outcome||Relative risk ratio|
| 2033 men with recent myocardial infarction
• None taking statins
| ≥ at least two portions (200-400 g) of fatty fish weekly
| 11,324 patients with myocardial infarction within 3 months
• 46% taking statins by study end
| 850–882 mg of EPA & DHA daily
| 200 patients with an implantable cardioverter defibrillator and prior sustained ventricular dysrhythmia
• 73% had coronary heart disease
• 46% taking statins
| 1.8 grams of EPA & DHA daily
|• Any death
• Recurrent ventricular dysrhythmia†
| 402 patients with an implantable cardioverter defibrillator and prior sustained ventricular dysrhythmia
• 78% had coronary heart disease
• 35% of patients stopped treatment
| 2.6 gm g of EPA & DHA daily
|• Any death
• Recurrent ventricular dysrhythmia†
|Excessive dropout of patients, perhaps due to high dose.|
| 546 patients with an implantable cardioverter defibrillator and prior sustained ventricular dysrhythmia
• 76% had coronary heart disease
• 46% on anticholesteremic agent
| 961 mg of EPA & DHA, and 162 mg other omega-3 PUFAs daily
|• Any death
• Death or recurrent ventricular dysrhythmia†
| 18,645 Japanese patients with hypercholesterolemia
• 20% had coronary heart disease
• 100% taking statins (average doses: pravastatin 10.0 mg/day; simvastatin 5.6 mg/day; average LDL 182 mg/dl)
|1800 mg of EPA daily
|• Any death
• Major coronary event†
| 6975 patients with heart failure
• 50% had coronary heart disease
• 23% taking statins
| 850–882 mg of EPA & DHA daily
| Alpha Omega
| 4837 patients with prior myocardial infarction within 10 years
• 100% had coronary heart disease
• 85% taking statins
| 400 mg of EPA & 2 g/d of DHA daily
|† indicates the a prior primary outcome of the study.|
‡ p< 0.05
- High doses over 2 grams per day
Gastrointestinal effects are common.
- Doses of 1 to 2 grams per day
In the JELIS study, discontinuation rates were increased - 12% in the EPA group and 7% in the control group.
- Doses less than 1 gram per day
In the GISSI-HF study, discontinuation rates were not increased - 29% in the EPA/DHA group and 30% in the control group.
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