The Fish Oil Story

In the 1970s, investigators discovered that Eskimos, particularly Greenland Inuit, and other populations, such as the Japanese, had very low rates of myocardial infarction and other coronary events, despite consuming large amounts of fat derived from fish.¹

This was in the middle of a low-fat diet craze. Cardiologists were stating that high-fat diets could potentially accelerate cardiovascular disease, so even healthy people were avoiding fats and oils and instead consuming artificial butters and high-carbohydrate foods.²

That led to articles and studies in the 1990s claiming that if people took fish oil pills under those circumstances, their heart health would improve. The GISSI study, which was published in 1999, had the results to prove it.³ Soon the effects of the fish oil pills became exaggerated, and they were touted as miracle pills.

People started eating more fish and healthy oils. The Mediterranean diet results became available, promoting olive oil consumption. Also, the use of statins increased, and artificial margarines and low-fat diets fell out of favor.

Results from more recent studies show that there are no benefits to taking fish oil pills, probably because many people now get healthy oils from their diets⁴

In a recent meta-analysis, investigators set out to shed light on what is going on, looking at 10 large, randomized control trials (Table 1).

All participants were high risk for cardiovascular disease. Among the participants, 61.4% were men, and the mean age at entry was 64 years. The trials lasted a mean of 4.4 years. Various dosages of fish oil were used, with eicosapentaenoic acid (EPA) levels in the range of 226 to 1800 mg/day.

The investigators looked at whether fish oils prevented all-cause mortality, fatal coronary heart disease, major vascular events, nonfatal myocardial infarction, and strokes. They concluded that omega-3 fatty acids had no significant association with fatal or nonfatal coronary heart disease or any major vascular events. The study results provide no support for current recommendations for the use of such supplements in people with a history of coronary heart disease.

No matter how the investigators analyzed and dissected the data, they found that no one really benefited from fish oil use in terms of heart health. That population included people with prior coronary heart disease, diabetes, elevated lipid levels, or statin use. Unfortunately, the investigators did not have data to analyze whether fish oils helped smokers but provided limited analysis on subgroups based on the available data.

The JELIS study used only EPA and not docosahexaenoic acid (DHA). That study had such positive results that the data were excluded from this meta-analysis.⁵ EPA has been isolated and shown promise for lowing triglycerides.⁶ Icosapent, an EPA-only drug, is already FDA approved to cut triglycerides in patients with levels above 500 mg/dL, triple the normal level.⁶

Mixtures containing both DHA and EPA can increase low-density lipoprotein cholesterol in patients with severe hypertriglyceridemia. However, results from studies have suggested that EPA alone does not produce that negative effect.^7,8

Future studies will show whether triglycerides are only markers of good health or whether lowering triglycerides to normal levels will yield better health outcomes, fewer heart attacks and strokes, and a longer life.

Fish oils are a type of polyunsaturated fatty acids (PUFAs). They are the omega-3 and omega-6 fatty acids. Regarding heart health, the active ingredients in fish oils are DHA and EPA. The hypothesis is that omega-3s offer protection from cardiovascular disease by reducing the heart’s susceptibility to arrhythmias, decreasing platelet aggregation and lowering blood pressure and triglyceride levels (Table 2). ⁹

The role of all PUFAs in disease prevention and overall good health is being studied. In the future, practitioners can expect medical research looking at the effect of PUFA on the following health conditions: age-related macular degeneration, Alzheimer disease, cognitive function and dementia, attention-deficit/hyperactivity disorder, cancer prevention through anti-inflammatory effects, childhood allergies, cystic fibrosis, depression, dry eye disease, infant health and neurodevelopment, inflammatory bowel disease, and rheumatoid arthritis.

Gunda Siska, PharmD, is a staff hospital pharmacist assisting doctors and nurses with drug administration, dispensing, and prescribing, as well as independently dosing and monitoring highly dangerous and toxic drugs.

References

• Harris WS. Omega-3 fatty acids. In: Coates PM, Betz JM, Blackman MR, et al., eds. Encyclopedia of Dietary Supplements. 2nd ed. London, United Kingdom, and New York, NY: Informa Healthcare; 2010:577-586.
• Temple NJ. Fat, sugar, whole grains and heart disease: 50 years of confusion. Nutrients. 2018;10(1):E39. doi: 10.3390/nu10010039.
• 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;354(9177):447-455.
• Aung T, Halsey J, Kromhout D, et al; Omega-3 Treatment Trialists’ Collaboration. Associations of omega-3 fatty acid supplement use with cardiovascular disease risks meta-analysis of 10 trials involving 77,917 individuals. JAMA Cardiol. 2018;3(3):225-234. doi:10.1001/jamacardio.2017.5205.
• Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090-1098. doi: 10.1016/S0140-6736(07)60527-3.
• Vascepa [prescribing information]. Bedminster, NJ: Amarin Pharma Inc; 2012. vascepa.com/assets/pdf/Vascepa_PI.pdf. Accessed October 26, 2018.
• Bays HE, Ballantyne CM, Kastelein JJ. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the multi-center, placebo-controlled, randomized, double-blind, 12-week study with an open-label extension [MARINE] trial). Am J Cardiol. 2011;108(5):682-690. doi: 10.1016/j.amjcard.2011.04.015.
• Miller M, Stone NJ, Ballantyne, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123(20):2292-2333. doi: 10.1161/CIR.0b013e3182160726.
• National Institutes of Health. Omega-3 fatty acids fact sheet for health professionals. US Department of Health & Human Services website. ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional/. Updated June 6, 2018. Accessed October 26, 2018.