Tuesday, October 3, 2023

How omega-3 fish oil helps after a heart attack

High dose omega–3 fish oils, if given after a heart attack, improve heart function, reduce heart muscle scarring, and reduce inflammation in the heart muscles. All of these reduce risk of death in the days after heart attack.

Executive Summary

In a heart attack, some muscles of the heart die. The shape and function of the heart changes. This can lead to heart failure in near future.

High dose omega-3 fish oil capsules, 4,000 mg a day, can help reduce post–heart attack heart shape and function change.

The patients in this study, effectively, took nearly 11 standard capsules of fish oil. Such high doses should be taken under guidance and observation of doctors only.

Fish oil softgels reduced scarring in the undamaged heart muscles, which further compromise heart functioning.

Fish oils capsules reduced inflammation in the heart tissue, which is, perhaps, how they lead to the improvements.

Since the above damages lead to heart failure, and subsequent death, in a few months after a heart attack, omega–3 fish oils reduced the post–heart attack mortality significantly.

The full article explains the mechanism of this heart failure. It also discusses aspects of fish oil capsules that people don’t know about, including the USA and the European safety guidelines.

Omega–3 fish oils are known to help heart. They have been used for decades to lower blood pressure, decrease inflammation, slow the progression of artery–clogging plaque, decrease clotting tendencies, and lower the chance of irregular heartbeats.

However, the trials to find if omega–3 fish oils benefit patients, who have had a heart attack, have shown inconsistent results. Some have shown benefits; some others have shown no benefit, although none have shown any harm.

What happens after a heart attack

After a heart attack, some muscles of the heart die. Thus, the heart cannot function exactly as before. Its shape, as well as the function, changes after a heart attack. This is a medical condition called post–heart attack remodeling.

Remodeling means reshaping, or reconfiguration. This change in the heart functioning can lead to heart failure in near future. It is also linked to poor patient survival in the months after the heart attack.

The heart’s shape and function can be altered after a heart attack, a condition known as post-heart attack remodeling and it is linked with poor patient outcomes and could lead to heart failure.

Mostly, after the heart attack, the left ventricle (LV) of the heart undergoes change in shape and function. It is our heart’s main pumping chamber.

There is also a reduction in something called ejection fraction of the left ventricle (LVEF). This is percentage of blood in the left ventricle that is pumped out. For example, the normal LVEF is 55% to 70%. That means, 55–70% of the blood in the left ventricle is pumped out into the body with each heartbeat.

After a heart attack, this LVEF may fall. If it goes below 35%, heartbeats can become irregular. That can lead to heart failure, and sudden cardiac death.

Also, the heart tissue that was not affected in the heart attack, starts developing scarring or thickening. This is called fibrosis, and in technical terms, it is called non–infarct myocardial fibrosis. Non–infarct means ‘the one not directly affected by the heart attack’. Myocardial means ‘of the heart muscle’.

The test used for measuring the extent of these damages is cardiac MRI, where an MRI scan of the heart is done. It gives a measurement called left ventricular end-systolic volume indexed to body surface area (LVESVI, mL/m2). Phew! This measurement is usually obtained at the beginning and the end of the therapy. The changes tell us if the heart has improved or worsened during the treatment.

There are no good treatments that can improve healing of the heart, or prevent its wrong reconfiguration. So, scientists are keen to explore if omega–3 fatty acids can help in this remodeling.

Earlier studies

One earlier study published in 2002 used 1000 mg/day of fish oil on 11000 plus patients and found 20% reduction in deaths (mortality) compared to patients who were given a placebo.

However, as the patient care for acute heart attack improved over the years, this benefit became less pronounced, and statistically insignificant. A subsequent study did not show any improvement, as per a 2010 paper.

New study

A paper published in Aug 2016 in the journal Circulation tried answering if, and how, fish oils can help heart remodeling.

It showed that fish oils helped improve the healing of the heart. The heart attack patients were given a high dose of omega–3 fish oils, daily for six months after the heart. It improved the function of their heart. It also reduced the scarring that follows a heart attack in the undamaged muscles of the heart.

Trial details

The scientists used 4000 mg/day, four times the previously tested dose of omega–3 fish oils.

Note that a standard capsule of fish oil contains 1000–1500 mg of fish oil, which contains 300 mg of omega-3 fatty acids, DHA and EPA, taken together. Fish oil is not the same as omega–3 fatty acids. Fish oil contains many other ingredients than omega–3 fatty acids. As you can see, in a standard fish oil, 30% is the omega–3 fatty acid component.

The United States FDA says one can safely take 3000 mg of DHA + EPA (10 standard capsules) a day. The European Food Safety Authority (EFPA) says taking 5000 mg of DHA + EPA daily (16 standard capsules) is safe.

Of course, note that these are higher limits to the consumption. Do not take this amount of omega–3 fish oil without your doctor’s approval and monitoring. You run a severe risk of internal or external bleeding, with almost no clotting to stop that. The advisory is 1600 mg of DHA + EPA for men and 1100 mg of DHA + EPA for women, per day.

The study above is talking about 4000 mg of fish oil. However, if you read the actual paper, you will find that the scientists used a highly purified form of fish oil, a branded product called Lovaza, from Glaxosmithkline. Each 1000 mg capsule of Lovaza contained 375 mg DHA and 465 mg EPA, a total of 840 mg of omega–3 fatty acids.

Thus, this product has 84% omega–3 fatty acids, unlike 30% in the normal fish oils. The patients were told to take 4 capsules a day, meaning 3360 mg of DHA + EPA. In other words, the patients were taking 11 standard capsules worth of fish oils daily. But all this was under the strict monitoring of scientists. Don’t try it yourself.

Incidentally, this high dose of DHA + EPA was equivalent of the doses tried in earlier animal trials which had shown benefits of taking fish oil for heart disease.

Trial outcomes

Taking 4000 mg of fish oil daily for six months after a heart attack improved the function of the heart by 6%. It also reduced the scarring in the undamaged heart muscle by 6%.

Researchers said these results suggests that omega-3 fatty acids allow the heart to contract better, and reduce the fibrosis (scarring) in the heart region that is not damaged.

The researchers also observed a reduction in biomarkers for inflammation, suggesting that omega-3 fatty acids have some anti-inflammatory properties.

The study did not test for improvement in mortality, post–heart attack. However, it noted that many studies have found that improvement of LVESVI (explained above) in the period after a heart attack, remains the strongest favorable risk predictor of heart failure. If you find reduction in LVESVI, you will find reduction in heart failure rates, post–heart attack. But how much will be the reduction in mortality?

In a trial called SAVE (Survival and Ventricular Enlargement), the improvement in LVESVI was 4%, and reduction in mortality was 45%.

In a trial called CAPRICORN (Carvedilol Post–infarct Survival Control in Left Ventricular Dysfunction), the improvement in LVESVI was 5.9% and reduction in mortality was 20%.

In this trial called OMEGA—REMODEL, the improvement in LVESVI was 5.7%. So, the possible reduction in mortality should be substantial, and statistically significant.

In fact, they found that the top 25% of the patients (called top quartile), who had the most improvement in the levels of omega–3 fatty acids in their red blood cells (a good marker for omega–3 levels in the body), had as much as 12% improvement in their LVESVI.

Comments by the researchers (for medical professionals)

The acute loss of myocardium post-MI leads to a complex set of neurohormonal, genetic, and mechanical factors that can trigger adverse LV remodeling within remote non–infarcted myocardium. In the early period after MI, inflammatory changes within the noninfarcted myocardium contribute to fibrotic changes, whereas increased wall stress and bio–mechanical strain in later phases contribute to additional myocyte hypertrophy and extracellular matrix expansion.

The results of this trial demonstrate potential mechanisms by which omega–3 fish oils (O-3FA) may attenuate these adverse processes. Our observation that O-3FA treatment was associated with a reduction of inflammation are consistent with translational studies that have shown a reduction of inflammatory cytokines by O-3FA exposure in animal and human myocardium post–infarction.

Furthermore, O-3FA treatment in this study reduced levels of serum ST, a biomarker that is upregulated in conditions of myocardial necrosis and dysfunction. ST2 antagonizes upregulation of interleukin-33, which has antihypertrophic and antifibrotic effects.

O-3FA treatment also has been shown to block directly cardiac fibroblast transformation, proliferation, and collagen synthesis through activation of the cyclic GMP / protein kinase G pathway. These mechanisms collectively may explain the attenuation of post-MI non–infarct myocardial fibrosis and adverse LV remodeling by high-dose O-3FA treatment found in this trial.

Aren’t you glad you did not have to read the whole paper? 🙂

In conclusion

High dose omega-3 fish oil capsules can help reduce post–heart attack heart shape and function change.

They can reduce the scarring in the undamaged heart muscles, which further compromise heart functioning.

They reduce inflammation in the heart tissue, which is, perhaps, how they lead to the improvements.

Since the above damages lead to heart failure, and subsequent death, in a few months after a heart attack, omega–3 fish oils may help reduce the post–heart attack mortality significantly.

First published on: 2nd August, 2016

Image credit: Ewa Urban from Pixabay



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