Fish oil: Difference between revisions
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imported>Robert Badgett (→Clinical effects: Added Brouwer) |
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===Clinical effects=== | ===Clinical effects=== | ||
The | The most recent [[systematic review]] concluded "significant<sup> </sup>reduction in deaths from cardiac causes but had no effect on<sup> </sup>arrhythmias or all cause mortality."<ref name="pmid19106137">{{cite journal |author=León H, Shibata MC, Sivakumaran S, Dorgan M, Chatterley T, Tsuyuki RT |title=Effect of fish oil on arrhythmias and mortality: systematic review |journal=BMJ |volume=337 |issue= |pages=a2931 |year=2008 |pmid=19106137 |pmc=2612582 |doi= |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=19106137 |issn=}}</ref> | ||
Three subsequent [[randomized controlled trial]]s not included in the above [[systematic review]]s have also had conflicting results finding both benefit (reduction on coronary events in Japanese hypercholesterolemic patients<ref name="pmid17398308">{{cite journal |author=Yokoyama M, Origasa H, Matsuzaki M, ''et al'' |title=Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis |journal=Lancet |volume=369 |issue=9567 |pages=1090–8 |year=2007 |pmid=17398308 |doi=10.1016/S0140-6736(07)60527-3}}</ref> and improvement in patients with [[heart failure]]<ref name="pmid18757090">{{cite journal |author=Gissi-Hf Investigators |title=Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial |journal=Lancet |volume= |issue= |pages= |year=2008 |month=August |pmid=18757090 |doi=10.1016/S0140-6736(08)61239-8 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61239-8 |issn=}}</ref>) | ====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 date February, 2002)<ref name="pmid16565093">{{cite journal |author=Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, Worthington HV, Durrington PN, Higgins JP, Capps NE, Riemersma RA, Ebrahim SB, Davey Smith G |title=Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review |journal=BMJ |volume=332 |issue=7544 |pages=752-60 |year=2006 |pmid=16565093 |doi=10.1136/bmj.38755.366331.2F}}</ref><ref name="pmid15495044">{{cite journal |author=Hooper L, Thompson RL, Harrison RA, ''et al'' |title=Omega 3 fatty acids for prevention and treatment of cardiovascular disease |journal=Cochrane Database Syst Rev |volume= |issue=4 |pages=CD003177 |year=2004 |pmid=15495044 |doi=10.1002/14651858.CD003177.pub2}}</ref> of [[randomized controlled trial]]s by the international [[Cochrane Collaboration]], a partially positive [[systematic review]] (search date July, 2005)<ref name="pmid16825676">{{cite journal |author=Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J |title=n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review |journal=Am. J. Clin. Nutr. |volume=84 |issue=1 |pages=5-17 |year=2006 |pmid=16825676 |doi=}} http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1a.chapter.38290</ref> by the [[Agency for Healthcare Research and Quality]] (AHRQ), and a positive [[systematic review]] (search date March, 2007)<ref name="pmid19106137">{{cite journal |author=León H, Shibata MC, Sivakumaran S, Dorgan M, Chatterley T, Tsuyuki RT |title=Effect of fish oil on arrhythmias and mortality: systematic review |journal=BMJ |volume=337 |issue= |pages=a2931 |year=2008 |pmid=19106137 |pmc=2612582 |doi= |url=http://bmj.com/cgi/pmidlookup?view=long&pmid=19106137 |issn=}}</ref>. 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 trial]]s not included in the above [[systematic review]]s have also had conflicting results finding both benefit (reduction on coronary events in Japanese hypercholesterolemic patients<ref name="pmid17398308">{{cite journal |author=Yokoyama M, Origasa H, Matsuzaki M, ''et al'' |title=Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis |journal=Lancet |volume=369 |issue=9567 |pages=1090–8 |year=2007 |pmid=17398308 |doi=10.1016/S0140-6736(07)60527-3}}</ref> and improvement in patients with [[heart failure]]<ref name="pmid18757090">{{cite journal |author=Gissi-Hf Investigators |title=Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial |journal=Lancet |volume= |issue= |pages= |year=2008 |month=August |pmid=18757090 |doi=10.1016/S0140-6736(08)61239-8 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61239-8 |issn=}}</ref>). | |||
* JELIS<ref name="pmid17398308">{{cite journal |author=Yokoyama M, Origasa H, Matsuzaki M, ''et al'' |title=Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis |journal=Lancet |volume=369 |issue=9567 |pages=1090–8 |year=2007 |pmid=17398308 |doi=10.1016/S0140-6736(07)60527-3}}</ref> 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]]. | * JELIS<ref name="pmid17398308">{{cite journal |author=Yokoyama M, Origasa H, Matsuzaki M, ''et al'' |title=Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis |journal=Lancet |volume=369 |issue=9567 |pages=1090–8 |year=2007 |pmid=17398308 |doi=10.1016/S0140-6736(07)60527-3}}</ref> 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]]. | ||
* Gissi-HF<ref name="pmid18757090">{{cite journal |author=Gissi-Hf Investigators |title=Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial |journal=Lancet |volume= |issue= |pages= |year=2008 |month=August |pmid=18757090 |doi=10.1016/S0140-6736(08)61239-8 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61239-8 |issn=}}</ref> 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)" | * Gissi-HF<ref name="pmid18757090">{{cite journal |author=Gissi-Hf Investigators |title=Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial |journal=Lancet |volume= |issue= |pages= |year=2008 |month=August |pmid=18757090 |doi=10.1016/S0140-6736(08)61239-8 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(08)61239-8 |issn=}}</ref> 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)" | ||
====Dysrhythmias==== | |||
* Raitt<ref name="pmid15956633">{{cite journal |author=Raitt MH, Connor WE, Morris C, ''et al'' |title=Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial |journal=JAMA |volume=293 |issue=23 |pages=2884–91 |year=2005 |pmid=15956633 |doi=10.1001/jama.293.23.2884}}</ref> 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.<ref name="pmid10465168">{{cite journal |author= |title=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 |journal=Lancet |volume=354 |issue=9177 |pages=447–55 |year=1999 |month=August |pmid=10465168 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0140673699070725 |issn=}}</ref> and the insignificant improvements in the SOFA<ref name="pmid16772624">{{cite journal |author=Brouwer IA, Zock PL, Camm AJ, ''et al'' |title=Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial |journal=JAMA |volume=295 |issue=22 |pages=2613–9 |year=2006 |month=June |pmid=16772624 |doi=10.1001/jama.295.22.2613 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=16772624 |issn=}}</ref> and FAATI<ref name="pmid16267249">{{cite journal |author=Leaf A, Albert CM, Josephson M, ''et al'' |title=Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake |journal=Circulation |volume=112 |issue=18 |pages=2762–8 |year=2005 |month=November |pmid=16267249 |doi=10.1161/CIRCULATIONAHA.105.549527 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16267249 |issn=}}</ref> trials. | |||
====Evidence table==== | |||
{| class="wikitable" align="right" | {| class="wikitable" align="right" | ||
|+ Major [[randomized controlled trial]]s of fish oils | |+ Major [[randomized controlled trial]]s of fish oils | ||
| Line 56: | Line 62: | ||
| JELIS<ref name="pmid17398308"/>|| 18,645 Japanese patients with hypcholesterolemia<br/>All received [[Hydroxymethylglutaryl-coenzyme A reductase inhibitor|statins]]<br/>20% had [[coronary heart disease]]|| 1800 mg of EPA daily for 4.6 years|| All death<br/>Major coronary event†|| 1.09 | | JELIS<ref name="pmid17398308"/>|| 18,645 Japanese patients with hypcholesterolemia<br/>All received [[Hydroxymethylglutaryl-coenzyme A reductase inhibitor|statins]]<br/>20% had [[coronary heart disease]]|| 1800 mg of EPA daily for 4.6 years|| All death<br/>Major coronary event†|| 1.09 | ||
|- | |- | ||
| Raitt|| 200 patients with an [[implantable cardioverter defibrillator]] and | | SOFA<ref name="pmid16772624"/><br/>2005|| 546 patients with an [[implantable cardioverter defibrillator]] and prior sustained ventricular dysrhythmia<br/>76% had [[coronary heart disease]]|| <font>961 mg of EPA & DHA, and 162 mg other omega-3 PUFAs for 1 year|| Any death<br/>Death or recurrent ventricular dysrhythmia†|| 0.43<br/>0.86 | ||
|- | |||
| Raitt<br/>2005|| 200 patients with an [[implantable cardioverter defibrillator]] and prior sustained ventricular dysrhythmia<br/>73% had [[coronary heart disease]]|| 1.8 grams of EPA & DHA per day for 3 years|| Any death<br/>Recurrent ventricular dysrhythmia†|| 0.4<br/>1.10 | |||
|- | |||
| FAATI<ref name="pmid16267249"/><br/>2005|| 402 patients with an [[implantable cardioverter defibrillator]] and prior sustained ventricular dysrhythmia<br/>76% had [[coronary heart disease]]<br/>35% of patients stopped treatment|| <font>2.6 gm g of EPA & DHA for 1 year|| Any death<br/>Recurrent ventricular dysrhythmia†||Excessive dropout of patients | |||
|- | |- | ||
| GISSI-HF<ref name="pmid18757090"/><br/>2008|| 6975 patients with [[heart failure]]<br/>50% had [[coronary heart disease]]|| 850–882 mg of EPA & DHA per day for 3.9 years|| Any death || 0.91 | | GISSI-HF<ref name="pmid18757090"/><br/>2008|| 6975 patients with [[heart failure]]<br/>50% had [[coronary heart disease]]|| 850–882 mg of EPA & DHA per day for 3.9 years|| Any death || 0.91 | ||
Revision as of 11:51, 9 February 2009
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."[1]
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) |
Arachidonic acid |
| Physiology | • suppression of inflammatory cytokines | • platelet aggregation • vasoconstriction • synthesis of inflammatory cytokines |
Dietary consumption
About nine ounces per week of oily fish is equivalent to taking about 500 mg eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids per day.[3] Thus, for cardiac protection, at least 6 servings pwer week of 3 ounces of fish are needed.
Biochemistry
(PD) Image: National Library of Medicine (NLM)
Polyunsaturated fatty acids (PUFAs) metabolic pathways in humans.[2]
Polyunsaturated fatty acids (PUFAs) metabolic pathways in humans.[2]
Dietary fatty acids can be divided into saturated fatty acids and unsaturated fatty acids.[2] 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.[2] 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%.[2] 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.[4]
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.[3]
Benefit to human health
Biochemical effects
The main effect of fish oils is to reduce triglycerides.[5]
Omega-3 fatty acids may improve endothelial function[6][5] and reduce coagulation[5] but not reduce inflammation as measured by the c-reactive protein.[6][5]
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.[7]
Clinical effects
The most recent systematic review concluded "significant reduction in deaths from cardiac causes but had no effect on arrhythmias or all cause mortality."[8]
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 date February, 2002)[9][10] of randomized controlled trials by the international Cochrane Collaboration, a partially positive systematic review (search date July, 2005)[2] by the Agency for Healthcare Research and Quality (AHRQ), and a positive systematic review (search date March, 2007)[8]. 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 the above systematic reviews have also had conflicting results finding both benefit (reduction on coronary events in Japanese hypercholesterolemic patients[11] and improvement in patients with heart failure[12]).
- JELIS[11] 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.
- Gissi-HF[12] 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)"
Dysrhythmias
- Raitt[7] 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.[13] and the insignificant improvements in the SOFA[14] and FAATI[15] trials.
Evidence table
| Patients | Intervention | Outcome | Relative risk ratio | |
|---|---|---|---|---|
| GISSI-Prevenzione[13] 1999 |
11,324 patients with myocardial infarction within 3 months | 850–882 mg of EPA & DHA per day for 3.5 years | Any death | 0.9 |
| JELIS[11] | 18,645 Japanese patients with hypcholesterolemia All received statins 20% had coronary heart disease |
1800 mg of EPA daily for 4.6 years | All death Major coronary event† |
1.09 |
| SOFA[14] 2005 |
546 patients with an implantable cardioverter defibrillator and prior sustained ventricular dysrhythmia 76% had coronary heart disease |
961 mg of EPA & DHA, and 162 mg other omega-3 PUFAs for 1 year | Any death Death or recurrent ventricular dysrhythmia† |
0.43 0.86 |
| Raitt 2005 |
200 patients with an implantable cardioverter defibrillator and prior sustained ventricular dysrhythmia 73% had coronary heart disease |
1.8 grams of EPA & DHA per day for 3 years | Any death Recurrent ventricular dysrhythmia† |
0.4 1.10 |
| FAATI[15] 2005 |
402 patients with an implantable cardioverter defibrillator and prior sustained ventricular dysrhythmia 76% had coronary heart disease 35% of patients stopped treatment |
2.6 gm g of EPA & DHA for 1 year | Any death Recurrent ventricular dysrhythmia† |
Excessive dropout of patients |
| GISSI-HF[12] 2008 |
6975 patients with heart failure 50% had coronary heart disease |
850–882 mg of EPA & DHA per day for 3.9 years | Any death | 0.91 |
| † indicates the a prior primary outcome of the study. | ||||
References
- ↑ Anonymous (2024), Fish oil (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B, Jordan HS, Lau J (2006). "n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review". Am. J. Clin. Nutr. 84 (1): 5-17. PMID 16825676. [e] http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hstat1a.chapter.38290
- ↑ 3.0 3.1 Harris WS, Pottala JV, Sands SA, Jones PG (December 2007). "Comparison of the effects of fish and fish-oil capsules on the n 3 fatty acid content of blood cells and plasma phospholipids". Am. J. Clin. Nutr. 86 (6): 1621–5. PMID 18065578. [e]
- ↑ Iso H, Sato S, Folsom AR, et al (June 1989). "Serum fatty acids and fish intake in rural Japanese, urban Japanese, Japanese American and Caucasian American men". Int J Epidemiol 18 (2): 374–81. PMID 2767851. [e]
- ↑ 5.0 5.1 5.2 5.3 Balk E, Chung M, Lichtenstein A, Chew P, Kupelnick B, Lawrence A, DeVine D, Lau J. Effects of Omega-3 Fatty Acids on Cardiovascular Risk Factors and Intermediate Markers of Cardiovascular Disease. Evidence Report/Technology Assessment No. 93 (Prepared by Tufts-New England Medical Center Evidence-based Practice Center under Contract No. 290-02-0022). AHRQ Publication No. 04-E010-2. Rockville, MD: Agency for Healthcare Research and Quality. March 2004
- ↑ 6.0 6.1 Schiano V, Laurenzano E, Brevetti G, et al (April 2008). "Omega-3 polyunsaturated fatty acid in peripheral arterial disease: effect on lipid pattern, disease severity, inflammation profile, and endothelial function". Clin Nutr 27 (2): 241–7. DOI:10.1016/j.clnu.2007.11.007. PMID 18237823. Research Blogging.
- ↑ 7.0 7.1 Raitt MH, Connor WE, Morris C, et al (2005). "Fish oil supplementation and risk of ventricular tachycardia and ventricular fibrillation in patients with implantable defibrillators: a randomized controlled trial". JAMA 293 (23): 2884–91. DOI:10.1001/jama.293.23.2884. PMID 15956633. Research Blogging.
- ↑ 8.0 8.1 León H, Shibata MC, Sivakumaran S, Dorgan M, Chatterley T, Tsuyuki RT (2008). "Effect of fish oil on arrhythmias and mortality: systematic review". BMJ 337: a2931. PMID 19106137. PMC 2612582. [e]
- ↑ Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, Worthington HV, Durrington PN, Higgins JP, Capps NE, Riemersma RA, Ebrahim SB, Davey Smith G (2006). "Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review". BMJ 332 (7544): 752-60. DOI:10.1136/bmj.38755.366331.2F. PMID 16565093. Research Blogging.
- ↑ Hooper L, Thompson RL, Harrison RA, et al (2004). "Omega 3 fatty acids for prevention and treatment of cardiovascular disease". Cochrane Database Syst Rev (4): CD003177. DOI:10.1002/14651858.CD003177.pub2. PMID 15495044. Research Blogging.
- ↑ 11.0 11.1 11.2 Yokoyama M, Origasa H, Matsuzaki M, et al (2007). "Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis". Lancet 369 (9567): 1090–8. DOI:10.1016/S0140-6736(07)60527-3. PMID 17398308. Research Blogging.
- ↑ 12.0 12.1 12.2 Gissi-Hf Investigators (August 2008). "Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial". Lancet. DOI:10.1016/S0140-6736(08)61239-8. PMID 18757090. Research Blogging.
Cite error: Invalid
<ref>tag; name "pmid18757090" defined multiple times with different content - ↑ 13.0 13.1 (August 1999) "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 354 (9177): 447–55. PMID 10465168. [e]
- ↑ 14.0 14.1 Brouwer IA, Zock PL, Camm AJ, et al (June 2006). "Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial". JAMA 295 (22): 2613–9. DOI:10.1001/jama.295.22.2613. PMID 16772624. Research Blogging.
- ↑ 15.0 15.1 Leaf A, Albert CM, Josephson M, et al (November 2005). "Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake". Circulation 112 (18): 2762–8. DOI:10.1161/CIRCULATIONAHA.105.549527. PMID 16267249. Research Blogging.