The benefits of fish oil: fact or fiction?

IN 2002, the American Heart Association (AHA) published a scientific statement, "Fish Consumption, Fish Oil, Omega-3 Fatty Acids, and Cardiovascular Disease".

At that time, based on evidence from two large randomised controlled trials (RCTs) that demonstrated that consumption of eicosapentaenoic acid (EPA)+docosahexaenoic acid (DHA) supplements significantly reduced fatal cardiac events, the AHA recommended that patients with documented heart artery disease consume about one gram/day of EPA and DHA, preferably from oily fish, but EPA and DHA supplements could be considered in consultation with a physician.

The statement recommended that additional studies be done to confirm the findings and to further understand the potential benefits of omega-3 polyunsaturated fatty acid (PUFA) supplements in those with and without underlying heart disease.

Since then, there have been many RCTs that have been conducted to evaluate the potential benefits of omega-3 fatty acid supplements. In 2017, American Heart Association issued a new advisory on "Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease".

Fish oils and heart disease

If you are healthy and have no underlying heart disease, before you pay for that expensive fish oil supplements, you may wish to know that presently, there has been no major RCT that has examined the effect of consumption of omega-3 PUFA supplements in those with no known heart disease. Hence, there is no evidence that consumption of omega-3 PUFA supplements in a healthy person is of any benefit.

Fish oils and diabetics

Patients with diabetes or at risk of diabetes are at a higher risk of getting strokes and heart attacks. In the large ORIGIN trial (Outcome Reduction With Initial Glargine Intervention), more than 12,000 pre-diabetic or diabetic patients who were at high risk of heart attack or stroke were randomly divided to consume omega-3 PUFA supplement or placebo. The study showed that there was no benefit seen with supplementation with omega-3 PUFA in this group of patients.

A more recent large RCT, ASCEND (A Study of Cardiovascular Events in Diabetes), published in the New England Journal of Medicine in August 2018 examined the effects of omega-3 PUFA supplements on cardiovascular events in patients with diabetes without known heart disease or stroke. It found no significant difference between the omega-3 PUFA supplementation and placebo groups.

Overall, the current evidence from RCTs suggests that omega-3 PUFA supplementation in patients with or at risk of diabetes mellitus did not prevent heart attacks or stroke and there is no benefit in taking omega-3 PUFA supplements in this group of patients.

High risk of heart disease

If you are considered to be at high risk of a heart attack because you have risk factors such as diabetes mellitus, or high cholesterol levels, or if you have pre-existing conditions such as previous stroke or narrowing of your lower limb arteries, will you benefit from omega-3 PUFA supplementation?

Of the four RCT trials (including the ORIGIN trial) that looked at this matter, none showed any benefit of omega-3 PUFA supplementation in preventing heart attacks and death related to heart disease. One of the four trials, the JELIS trial (Japan EPA Lipid Intervention Study), reported that omega-3 PUFA supplementation was associated with a reduction in unstable angina, coronary artery bypass grafting, or percutaneous transluminal coronary angioplasty. However, there was also no reduction in heart attacks and death from heart disease.

As a result of the data from the JELIS trial, the 2017 American Heart Association co-authors of the advisory could not reach a consensus but the majority of the co-authors concluded that treatment with omega-3 PUFA supplementation is not indicated. However , a minority of co-authors concluded that treatment of these patients is reasonable.

Preventing sudden cardiac death

For those with pre-existing heart disease, the data suggests that omega-3 PUFA supplementation may reduce heart-related death. It is thought that this reduction in death is due mainly to a reduction in life threatening heart rhythms which occur as a result of insufficient blood flow to the heart muscle. However, the treatment does not reduce the incidence of recurrent non-life threatening heart attacks.

The reduction in heart-related death (about 10 per cent) , presumably by reducing sudden cardiac death, is a likely benefit of omega-3 PUFA supplementation. However, this beneficial effect has diminished over time.

The American Heart Association advisory committee's review of 20 studies showed a trend of earlier studies showing large reductions in heart-related and sudden cardiac deaths but later studies showing no benefit. One possible explanation is that there is a higher dietary consumption of fish by patients included in recent trials as compared to those in earlier studies. Hence, the effect of omega-3 PUFA supplementation has been attenuated in those participating in recent trials.

Another possibility is that in recent years, with the widespread implementation of optimal medical treatment of heart disease , including the use of statins, it may be possible that omega-3 PUFA supplementation has little benefit. Nevertheless, the current recommendation is that for those with pre-existing heart disease, it is considered reasonable to consume omega-3 PUFA supplements.

The postulated mechanism for the effect of omega-3 PUFA on heart related death is related to its effects on the setting of life threatening abnormal heart rhythm resulting from insufficient blood flow (ischaemia-induced) causing irritability of the heart's electrical system. It is believed that the effects include stabilisation of ischaemia-induced heart muscle cell membrane electrical signal, rather than any effects on the heart artery narrowing or on the plaque deposits in the heart artery.

The data from the trials supporting this shows that the reduction of heart related death following the use of omega-3 PUFA in those with pre-existing heart disease was attributable mainly to reduced sudden cardiac death from abnormal heart rhythms rather than other types of heart-related death.

Preventing stroke

To date there has been no RCT which has studied whether omega-3 PUFA supplements can prevent stroke in healthy individuals or in those with pre-existing stroke. Currently, there is no data to support the use of omega-3 PUFA supplementation to reduce the risk of stroke in patients without a history of stroke or in patients with a past history of stroke.

Heart failure

Based on one large RCT, heart failure patients on omega-3 PUFA supplements had reduction of death resulting from any cause, heart related-hospitalisations or death. While more studies are required to further define the benefit of omega-3 PUFA supplementation in patients with heart failure, it is reasonable to consume omega-3 PUFA supplements among patients with heart failure with impaired heart function.

Fish oil 2018

Based on all available evidence, the conclusions are as follows.

While many healthy people consume omega-3 PUFA supplements, the present data shows that the potential benefits of omega-3 PUFA supplementation are mostly seen in those with a recent heart attack. Even then, this potential effect has been diminished over time, with more recent trials showing no benefit.

This series is produced on alternate Saturdays in collaboration with Singapore Heart, Stroke & Cancer Centre.