a 28% reduced risk of death from any cause, driven mainly by
a 45% reduced risk of sudden cardiac death. The differences
between the groups remained significant throughout the 3. 5
years of the study.
The Japan EPA Lipid Intervention Study (JELIS) demonstrated that EPA supplementation alone could have beneficial effects, even in a population that has a high background
consumption of fish (Yokoyama, M., et al., http://dx.doi.
org/10.1016/S0140-6736(07)60527-3, 2007). JELIS followed
18,645 patients with hypercholesterolemia, who were assigned
to groups receiving statin treatment alone, or a combination
of statin and 1.8g EPA. After five years, the combination
treatment was associated with a 19% reduced risk of major
coronary events in patients with a history of CAD compared
with the statin-only group. In contrast, EPA treatment was not
associated with a reduced risk of sudden cardiac death.
Another study has shown that the risk of sudden cardiac
death increases with decreasing blood levels of omega-3s
(Albert, C. M., et al., N. Engl. J. Med., 2002). Moreover, the
amount of DHA in plasma and cellular phospholipids, which
closely correlates with the amount of DHA in heart muscle, is
inversely related to the risk of CAD events (Harris, W. S.,
Pharmacol. Res., 2007). As a result of these findings, Harris has
proposed a new marker for cardiovascular risk—the omega- 3
index—that reflects the proportion of omega- 3 fatty acids in
the membranes of red blood cells. An omega- 3 index greater
than 8% is associated with the lowest risk of cardiovascular
events, whereas an index less than 4% is typically found in
Because most clinical trials have focused on patients who
already have a history of cardiovascular disease or are at
high risk, evidence for benefits of omega- 3 fatty acids is
stronger for secondary prevention than primary prevention.
The American Heart Association (AHA) recommends two
servings of fatty coldwater fish per week for people with no
history of CAD, or one serving per day for people with CAD.
In 2002, the AHA endorsed omega- 3 supplements for the
secondary prevention of heart disease (HD), while stating that a
food-based approach (i.e., eating fatty fish) is preferable
(Kris-Etherton, P. M., et al., Circulation, 2002). In terms of
omega- 3 amounts, 300–600 mg/day combined DHA/EPA are
recommended for people without a history of CAD, 900– 1,200
mg/day for people with a CAD history, and 3,000– 4,000 mg/
day for triglyceride lowering. Different dosages of DHA/EPA
may confer different cardiovascular benefits (Lee, J. H., et al.,
http://dx.doi.org/10.4065/83.3.324, 2008) (Table 1). For exam-
ple, low doses (0. 5–1.0 g/day DHA/EPA) can lower the risk of
sudden cardiac death in people with CAD, while very high
doses (8.0 g/day) can reduce inflammation and decrease
body fat in patients with heart failure. In addition, the time
course of different benefits may vary. With the appropriate
dose of DHA + EPA, patients can achieve strong antiarrhythmic
benefits in a matter of weeks, compared with months to
years for triglyceride or blood pressure lowering.
Relatively high doses ( 3–4 g/day) of omega-3s can lower
triglyceride levels by 30–50% (Lee, J. H., et al., http://dx.doi.
org/10.4065/83.3.324, 2008). When added to statin therapy,
DHA + EPA reduces triglycerides by an additional 23–29% compared with statins alone. The US Food and Drug Administration
(FDA) has approved three prescription drugs that deliver concentrated fish oil for the treatment of very high triglycerides.
Beginning in the mid-2000s, various clinical trials and meta-analyses failed to confirm the earlier successes of DART, GISSI-Prevenzione, and JELIS. Between 2005 and 2012, more than 24
studies of fish oil supplements were published in respected
medical journals, most examining whether fish oil could prevent cardiovascular disease in people at high risk (O’Connor, A.,
The New York Times, 2015). All but two of the studies found
no benefit of fish oil compared with placebo.
In 2012, a meta-analysis of 20 fish oil trials including a total
of 68,680 patients found no association between omega- 3
supplementation and lowered risk of all-cause mortality, cardiac death, sudden death, myocardial infarction, or stroke
(Rizos, E. C., et al., http://dx.doi.org/10.1001/2012.jama.11374).
Similarly, a 2013 randomized controlled trial of 12,513 people
found that 1.0 g/day of fish oil did not reduce the rate of death
from cardiovascular disease or the risk of hospitalization from
tAblE 1. Doses of omega- 3 fatty acids shown to have cardioprotective effects
Effect Dose of omega- 3
Reduced risk of sudden cardiac death in 0. 5–1.0 g/day of DHA + EPA*
people with CAD
Decreased resting heart rate, increased 0.81 g/day of DHA + EPA
post-exercise heart rate recovery in
people with CAD
Increased level of adiponectin in obese 1.8 g/day EPA
Antiplatelet, anti-inflammatory, 3.0– 4.0 g/day of DHA + EPA
Reduced systolic and diastolic 4.0 g/day DHA + EPA
Anti-inflammatory effects, improved body 8.0 g/day DHA + EPA
composition in people with heart failure
*Refers to combined dose of DHA and EPA.
Credit: Adapted from information in Lee, J. H., http://dx.doi.org/10.4065/83.3.324, 2008.